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Postlaminectomy ossified extradural pseudocyst. Case report. A large ossified spurious meningocele accompanied by recurrent lumbar disc herniation occurred 7 years after posterior intervention for laminectomy and discectomy in a 53-year-old man. The cyst wall, histologically composed of mature bone tissue, was sparsely covered with connective tissue and lined with fibrocyte- or fibroblast-like cells on the inside. The ossified pseudocyst was presumed to have originated from a minute defect in the dura mater which occurred at the time of the first operation.

Optimizing heparin utilization in angiographic flush solutions. Various concentrations of heparin in angiographic flush solutions are employed during angiography. In an effort to determine whether differences in outcome are seen when either high or low concentrations of heparin in angiographic flush solutions are utilized, two groups of patients were evaluated. There was no difference in outcome and a small systemic effect from heparin was seen in both groups. Use of a low concentration of heparin is suggested for routine angiography.

Locally recurrent endometrioid adenocarcinoma of the prostate after radical prostatectomy. Endometrioid carcinoma of the prostate is considered a variant of classical prostatic ductal carcinoma. Endometrioid carcinoma variant often has the unique clinical presentation of gross hematuria. The propensity of this tumor to spread within the urothelium makes local failure of curative therapy commonplace. We present 2 representative cases with a review of followup surveillance procedures and treatment options for the local recurrence once identified.

Upper-extremity deep venous thrombosis and pulmonary embolism. A prospective study. We prospectively evaluated the prevalence of pulmonary embolism (PE) in 30 consecutive patients with proved deep venous thrombosis (DVT) of the upper extremity. Ten patients (seven male and three female; mean age, 43 years) had primary DVT, and 20 patients (14 male and six female; mean age, 52 years) had catheter-related DVT. Ventilation-perfusion lung scans were routinely performed at the time of hospital admission to all but one patient (one patient was critically ill, and he died four days after DVT diagnosis because of massive PE). Lung scan findings were normal in nine of ten patients with primary DVT, and they were indetermine in the remaining patient. By contrast, perfusion defects were considered highly suggestive of PE in four patients with catheter-related DVT; two patients had indeterminate lung scans, and 13 patients had normal scans. We conclude that PE is not a rare complication in upper extremity DVT, and that patients with catheter-related DVT seem to be at a higher risk.

Rapid inactivation and phosphorylation of pyroglutamyl peptidase II in Y-79 human retinoblastoma cells after exposure to phorbol ester. Pyroglutamyl peptidase II (EC 3.4.19.-), a membrane-bound metalloproteinase, is a highly specific TRH-degrading enzyme. Exposure of Y-79 human retinoblastoma cells to 12-0-tetradecanoyl phorbol 13-acetate (TPA) decreased the activity of this enzyme in a time- and concentration-dependent manner (IC50 5 x 10(-9) M). After 15 min of TPA treatment, only 10% of pyroglutamyl peptidase II activity remained. TPA treatment did not affect the activity of the cytosolic enzyme pyroglutamyl peptidase I (EC 3.4.19.3) or the membrane-bound enzyme dipeptidyl peptidase IV (EC 3.4.19.3). Pretreatment of the cells with the protein kinase C inhibitors H-7 or sphingosine prevented the inactivation of pyroglutamyl peptidase II by TPA. The time course of the TPA-mediated effect paralleled the time course of translocation and activation of protein kinase C in this cell line. Immunoblot analysis demonstrated that inactivation of pyroglutamyl peptidase II was not due to dissociation or internalization of this enzyme molecule. Incubation of TPA-activated Y-79 cell membranes with gamma-[32P]-ATP followed by immunoprecipitation revealed a time-dependent phosphorylation of a 48 kilodalton subunit of pyroglutamyl peptidase II. These studies indicate that the phorbol ester effect is mediated by protein kinase C, and reveal a mechanism of potentiation of the action of TRH at its target sites.

The role of antibiotic therapy in the prevention of empyema in patients with an isolated chest injury (ISS 9-10): a prospective study. The purpose of this study was to determine the impact of an antibiotic regimen on the incidence of empyema in patients admitted with isolated chest trauma (ISS 9/10) and hemopneumothorax requiring tube thoracostomy. All patients with isolated chest trauma and hemopneumothorax (estimated ISS 9 or 10) seen in our trauma center were considered eligible for this study. Patients were excluded for the following reasons: age less than 18 years, presence of shock at the time of initial resuscitation, ongoing antibiotic therapy for unrelated disease, documented pre-existing infection or documented abnormal immune status. Ninety patients were randomized to two treatment limbs: antibiotics and tube thoracostomy or tube thoracostomy alone. All patients had the procedure performed in the trauma center in a standard fashion. Wound care and tube care were identical. Antibiotic therapy consisted of a first-generation cephalosporin (cefazolin), one dose given just before the procedure and then q 6 h into the tube removal. Injury Severity Scores were established as described by Schwab after the manner of Baker. Statistical analysis was performed using Fisher's exact test of binary outcome. In this study, antibiotics were able to reduce the incidence of empyema in patients with isolated chest trauma and for such patients antibiotic treatment appears justified. Further work is required to determine the effect on patients with more severe injury and multisystem involvement.

Rib infarcts and acute chest syndrome in sickle cell diseases. In the absence of evidence for pneumonia or pulmonary embolus, primary pulmonary infarction has been assumed to be the cause of the syndrome of chest pain, fever, and pulmonary infiltrate on chest X-ray that commonly complicates sickle cell anaemia. To find out whether the syndrome might be due to rib infarction, 99mTc-diphosphonate bone scans were done. In the eleven episodes thus investigated (10 patients) the scans showed segmental areas of increased radionuclide uptake in ribs, indicative of bone infarction. A possible sequence of events is that the rib infarcts are primary and cause bone pain, followed by soft tissue reaction, pleuritis, and splinting. The resultant hypoventilation leads to atelectasis and subsequent development of the radiographic changes of the acute chest syndrome. Prevention of hypoventilation and treatment of bone pain are important therapeutic goals.

Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy. The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy.

Prostate tumour markers and differentiation grade in prostatic cancer. Serum acid phosphatase activity, prostate specific phosphatase and prostate specific antigen were measured in 100 patients with prostatic cancer. The patients were divided according to the differentiation grade into 3 groups: G1 (well), G2 (moderately) and G3 (poorly differentiated) carcinoma. Bone metastases were identified by scintigraphy. Among the 76 M0 patients the mean levels of all 3 markers were slightly higher in patients with moderately differentiated prostatic carcinoma. Among the 24 M1 patients the primary tumour was either G2 (18 patients) or G3 (6 patients); none had G1 lesions. Significantly higher serum ACP and PAP levels were found in patients with G2 tumours than in those with G3 lesions. It was concluded that the histological differentiation grade of prostatic carcinoma did affect serum levels of prostatic tumour markers; the tendency towards higher levels in the G2 group was noticeable in both non-metastatic and metastatic cases despite the limited number of patients in the latter category. In clinical practice this information may be an important additional tool in staging prostatic cancer.

Effects of inosine on glycolysis and contracture during myocardial ischemia. The effects of inosine (INO) on substrate metabolism and rigor formation in ischemic myocardium were examined in isolated rabbit hearts. Metabolite content was assessed in tissue extracts by chemical analysis and in the whole heart by 13C and 31P nuclear magnetic resonance spectroscopy. In ischemic hearts metabolizing either [3-13C]pyruvate or [1-13C]glucose, 1 mM INO increased both total and 13C-labeled alanine content; lactate content was unaffected. At 3 minutes of ischemia, tissue alanine was 1.81 +/- 0.11 microM/g wet wt (mean +/- SEM) in hearts perfused with pyruvate+INO versus 1.23 +/- 0.15 microM/g wet wt in hearts perfused with pyruvate alone (p less than 0.05). INO reduced tissue glycogen during ischemia in pyruvate-perfused hearts. Tissue alanine content in ischemic hearts that were supplied glucose+INO (1.29 +/- 0.13 microM/g wet wt) was greater than in ischemic hearts supplied glucose alone (0.65 +/- 0.14 microM/g wet wt). Alanine was found to originate from pyruvate and was a glycolytic end product in glucose-perfused hearts. INO raised the [3-13C]alanine/[3-13C]lactate ratio in ischemic, intact hearts (glucose = 0.24 +/- 0.07 versus glucose+INO = 0.60 +/- 0.09; pyruvate = 0.49 +/- 0.08 versus pyruvate+INO = 0.89 +/- 0.08). At 7 minutes of ischemia, ATP content fell to 70 +/- 3% with glucose+INO versus 58 +/- 5% with glucose alone. Rigor (stone heart) was delayed from 14.7 +/- 1.3 to 23.2 +/- 1.6 minutes with INO. INO did not change ATP content in ischemic hearts that were supplied pyruvate but delayed rigor (pyruvate = 9.9 +/- 1.2 minutes; pyruvate+INO = 15.6 +/- 1.0 minutes), possibly at the expense of glycogen. Supplemental glucose improved the effectiveness of INO with pyruvate to preserve ATP (pyruvate+glucose = 42 +/- 6%; pyruvate+glucose+INO = 72 +/- 6%) and further delayed rigor (pyruvate+glucose = 13.3 +/- 1.5 minutes; pyruvate+glucose+INO = 20.3 +/- 1.8 minutes). Glucose metabolism supported improved energetic and contractile states in ischemic hearts treated with INO. Thus, cardioprotection of the ischemic heart by INO was associated with preservation of functional integrity and improved energy production due to increased glycolytic activity. Activation of glycolysis in the presence of INO was accommodated by augmented alanine production without the additional accumulation of lactate.

Traumatic rupture of the aorta--critical decisions for trauma surgeons. The diagnosis and initial stabilization of patients with traumatic rupture of the aorta (TRA) is performed by trauma surgeons. The resuscitations of 54 TRA patients at a Level I trauma center are reviewed. Although the survival of patients who underwent attempted repair was good (75%), 21/27 (78%) deaths occurred during phases of treatment controlled by a trauma surgeon. The techniques and sequencing of resuscitation can affect outcome. Pneumatic antishock garments were not beneficial in the prehospital setting for patients with TRA. In fact, PASG were on and inflated in all patients who presented in cardiac arrest. Awake, unanesthetized intubation caused fatal aortic rupture in three patients. Pharmacologic control of blood pressure during intubation is necessary. The amount of fluid, blood transfusion, and changes in blood pressure secondary to therapy did not statistically affect outcome. The average time from arrival in the ER to angiogram was 64.7 minutes. The average time ER to operating room was 159.7 minutes. Seven cases of TRA had delayed diagnosis usually for a misinterpreted CXR (5/7). Delay in diagnosis did not directly contribute to any deaths. Associated abdominal injuries are a common cause of preventable deaths. Fourteen patients with combined abdominal injuries and TRA were identified. Four of six deaths occurred with potentially reparable injuries. Operative and diagnostic sequences must be adjusted to allow rapid control of all potentially fatal injuries.

Crystalluria, medullary matrix crystal deposits and bladder calculi associated with an acutely induced renal papillary necrosis. A single (100 mg/kg) intraperitoneal dose of 2-bromoethanamine hydrobromide induced renal papillary necrosis (RPN) acutely in rodents and caused a transient crystalluria between 4 and 8 h after dosing. These crystals comprised struvite or magnesium ammonium phosphate (MAP) as assessed by shape, solubility, infra-red spectrum and X-ray microprobe analysis. Acid-soluble, bi-refringent crystals were also present within the renal medullary matrix during the same time period as the crystalluria. The presence of the MAP was associated with loss of the anionic renal medullary mucopolysaccharides staining. A total of 5/64 rats with a 2-bromoethanamine-induced renal papillary necrosis and monitored for up to 160 days had bladder calculi that were predominantly MAP. These data suggest that medullary mucopolysaccharide matrix disruption associated with RPN leads to a release of previously bound cations, super-saturation and the nucleation of crystalline MAP. These processes could also be implicated in the formation of MAP bladder calculi.

Pachyonychia congenita complicated by hidradenitis suppurativa: a family study. A family is described in which five of the six members with the Jackson-Lawler type of pachyonychia congenita also had varying degrees of hidradenitis suppurativa. We suggest an association between this type of pachyonychia congenita and hidradenitis suppurativa.

Surgical treatment for severe slipping of the upper femoral epiphysis. We have used a modified technique of cervical osteotomy to treat a consecutive series of 23 patients with chronic slip of the upper femoral epiphysis. It has been successful in correcting both moderate and severe deformities with a low incidence of avascular necrosis, comparable to that seen after subtrochanteric osteotomies. We describe the operative details and discuss the features which make cervical osteotomy technically superior to intertrochanteric and subtrochanteric procedures.

Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously (iv) every 24 h (n = 17), or cefotaxime, 2 g iv every 8 h (n = 16). Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy. Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period. At follow-up examinations after a mean of 8.1 months, 17 of 27 patients examined were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid (CSF) 7.5 months after ceftriaxone therapy. CSF antibiotic concentrations were above the MIC 90 level for B. burgdorferi in nearly all patients examined. Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime. However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary.

Acquired benign esophagorespiratory fistula: report of 16 consecutive cases. Sixteen cases of acquired benign esophagorespiratory fistula were treated in a 20-year period. A delay in diagnosis was usual, and most patients were first seen with a pulmonary infection already developed. Contrast esophageal x-ray studies established the diagnosis in all patients. There were seven esophagotracheal and nine esophagobronchial fistulas. A fistula between the esophageal diverticulum and a bronchus considered to be of inflammatory origin developed in 7 patients. A fistula as the consequence of trauma developed in 9 patients, and these fistulas were situated at a higher level of the respiratory tree. All patients underwent surgical treatment; in 12 it was definitive, and in 4 temporary gastrostomy was performed to improve nutrition before definite repair. The definitive repair consisted of eventual diverticulectomy, division of the fistula, and suture of both esophageal and respiratory defects. Two patients required esophageal resection and later reconstruction with colon interposition. One patient died, creating an operative mortality of 8.3% in the definitive-repair group. The remaining 11 patients had a gratifying long-term result. There were two deaths in the gastrostomy group due to an extremely poor condition of patients and debilitating pulmonary infection. Early diagnosis of this rare condition is necessary if severe pulmonary complications are to be avoided. Early direct repair gives excellent results.

The association of selected cancers with service in the US military in Vietnam. II. Soft-tissue and other sarcomas. The Selected Cancers Cooperative Study Group As part of a series of investigations into the health of Vietnam veterans, we conducted a population-based, case-control study of soft-tissue and other sarcomas between 1984 and 1988. All men born between 1929 and 1953 and diagnosed in an area covered by eight cancer registries were considered eligible. Controls were selected by random-digit dialing. Analyses of 342 men with pathologically confirmed sarcoma and 1776 controls showed that Vietnam veterans had a relative risk of 1.0 for sarcoma in comparison with men who did not serve in Vietnam (95% confidence interval, 0.6 to 1.6). Restriction of the analysis to the 254 men with soft-tissue sarcoma yielded a relative risk of 0.9 (95% confidence interval, 0.5 to 1.6). Several attributes of military service in Vietnam (eg, branch, duration of service, military region, and other characteristics that may have been associated with the use of Agent Orange) were examined, and none was associated with an increased risk for the development of sarcoma. Furthermore, no morphologic type of sarcoma was overrepresented among Vietnam veterans. Results were unchanged if Vietnam veterans were compared with (1) other veterans or (2) men who never served in the military. This study, which had 97% power to detect a relative risk of 2.0 for all sarcomas, provides no evidence that the risk for the development of soft-tissue or other sarcomas is increased among veterans 15 to 25 years following service in Vietnam.

Optimal interpretation of the supine exercise electrocardiogram in patients with right bundle branch block. A detailed analysis of the exercise ECG was performed in 82 patients with right bundle branch block who underwent supine exercise equilibrium radionuclide angiography. The sensitivity and specificity of each individual electrocardiographic lead for the detection of a positive radionuclide angiogram was determined. Leads V5 and V6 had a sensitivity of 58 percent and a specificity of 89 percent. The limb leads and lead V4 had a lower sensitivity, but an equivalent specificity. Leads V1 and V3 each had a clearly lower specificity that ranged from 56 to 67 percent. Receiver operating characteristic curve analysis demonstrated that the optimal interpretation of the exercise ECG included the limb leads and V4 to V6, but not V1 to V3. The results of coronary angiography in the subset of 16 patients who underwent this procedure confirmed these findings.

An echocardiographic assessment of atrial mechanical behaviour. Relations between movement of the atrioventricular ring and changes in left atrial and ventricular dimensions were studied by echocardiography and compared with apexcardiography and Doppler mitral flow velocity traces in 20 healthy controls and in patients with left ventricular hypertrophy (n = 28) or dilatation (n = 16). During left ventricular systole the atrioventricular ring, a structure common to ventricle and atrium, moved towards the ventricular apex, thus increasing left atrial volume. This action matched pulmonary venous return because it was in phase with the transverse left atrial dimension measured from aortic root to posterior left atrial wall. During early diastole, the mitral ring moved rapidly towards the atrium as transmitral flow accelerated. This requires a force directed from ventricle to atrium, likely to be the result of elastic recoil arising from compression of the ventricular myocardium or stretching of the atrial myocardium during ventricular systole. Two additional mechanisms of ventricular filling with atrial systole were recognised: (a) an increase in ventricular volume as the atrioventricular ring moved upwards and (b) transverse left ventricular expansion by pressure driven transmitral flow. The former is undetectable by Doppler from the apex; it accounted for 10% of ventricular filling in the healthy controls, but for significantly less in those with ventricular dilatation. In left ventricular hypertrophy, left ventricular filling was maintained by both mechanisms compensating for the reduced increase in volume early in diastole. Interactions between the atrium and ventricle are functionally important during ventricular systole, early diastole, and in atrial systole. They are not included in the traditional separation of atrial function into reservoir, conduit, and pump functions.

Developing improved observational methods for evaluating therapeutic effectiveness. Therapeutic efficacy is often studied with observational surveys of patients whose treatments were selected nonexperimentally. The results of these surveys are distrusted because of the fear that biased results occur in the absence of experimental principles, particularly randomization. The purpose of the current study was to develop and validate improved observational study designs by incorporating many of the design principles and patient assembly procedures of the randomized trial. The specific topic investigated was the prophylactic effectiveness of beta-blocker therapy after an acute myocardial infarction. To accomplish the research objective, three sets of data were compared. First, we developed a restricted cohort based on the eligibility criteria of the randomized clinical trial; second, we assembled an expanded cohort using the same design principles except for not restricting patient eligibility; and third, we used the data from the Beta Blocker Heart Attack Trial (BHAT), whose results served as the gold standard for comparison. In this research, the treatment difference in death rates for the restricted cohort and the BHAT trial was nearly identical. In contrast, the expanded cohort had a larger treatment difference than was observed in the BHAT trial. We also noted the important and largely neglected role that eligibility criteria may play in ensuring the validity of treatment comparisons and study outcomes. The new methodologic strategies we developed may improve the quality of observational studies and may be useful in assessing the efficacy of the many medical/surgical therapies that cannot be tested with randomized clinical trials.

Pelvic pain: lessons from anatomy and physiology. Pelvic pain is often a difficult differential diagnosis in the emergency department. For physiologic reasons, pain in the pelvis is difficult to localize to a specific organ, and pelvic peritonitis is hard to recognize. On the other hand, differences in types of pain can be very useful in arriving at a correct diagnosis. The clinician must learn to recognize superficial and deep somatic pain, and differentiate between various types of visceral pain which originate from inflammation, ischemia, or colic. A review of the anatomy and physiology of pelvic pain helps identify some of the problems as well as potential aids in approaching the patient with pelvic pain.

Demographic, social and stress correlates of hypertension among the urban poor. The relationship of demographic, social, and psychological variables to the diagnosis of hypertension in a population of urban, poor, predominantly black out-patients is reported. Subjects were 182 patients presenting for health care at Wayne State University Family Practice Clinic. Age, race, marital status, attendance at religious services, education, employment status, income, source of income and interpersonal stress were significantly related to a diagnosis of hypertension in this sample. Of those characteristics found to be significantly related to hypertension, discriminative analysis showed that age, race, education and frequency of church attendance were most important in predicting a diagnosis of hypertension among this out-patient sample of the urban poor. Implications for clinical care and for future research needs are considered.

Abdominal aneurysms in childhood: report of a case and review of the literature. Abdominal aneurysms are rare in children and are usually found in association with congenital cardiac or aortic malformations, connective tissue disorders, trauma, or previous arterial catheter placement. A 4-year-old girl who had a common iliac artery aneurysm, who had no history of arterial catheter placement or trauma, and who had no evidence of Marfan's or Ehlers-Danlos syndrome, arteritis, coarctation of the aorta, or other diseases associated with childhood aneurysms is presented. Resection of the aneurysm and arterial reconstruction were performed without the use of prosthetic material or vein graft. Pathologic examination showed no evidence of inflammation or medial degeneration in any of the layers of the arterial wall. This is the fourth report found in the literature of documented idiopathic abdominal aneurysm in a child. The conditions associated with abdominal aneurysms in childhood are discussed, and the literature is reviewed.

Hamman-Rich syndrome revisited In this article, we retrospectively review 29 cases of Hamman-Rich syndrome. As in some other recent reports, we have used the term "acute interstitial pneumonia" to emphasize the clinical and pathologic features of these cases and to distinguish them from the more common chronic interstitial pneumonias, particularly idiopathic pulmonary fibrosis. Of the 29 patients, 12 survived, some after a long and complicated hospitalization. The histologic features were those of organizing diffuse alveolar damage, and some patients, including survivors, had extensive fibroblastic distortion of lung parenchyma. The overall survival among these patients was not appreciably different from the survival of patients with the adult respiratory distress syndrome in general.

Clinicopathological experience with pineocytomas: report of five surgically treated cases. The clinicopathological experience associated with five cases of pineocytoma is presented. All patients were treated by surgical removal without postoperative radiotherapy. In three individuals, 2000 cGy was administered to the tumor as a presurgical diagnostic test, with no evidence of response. All cases demonstrated histological features of pineocytoma, according to the criteria of Borit et al., and of the so-called "pineocytoma with neuronal differentiation," according to the criteria of Rubinstein. The experience obtained from the present series reveals that these tumors can occur in the initial decades of life, that a cystic appearance and the presence of calcifications are distinctive features of their radiological evaluation, and that they have a good prognosis after surgical removal, even when the histological data indicate local invasion. The convenience of reserving the term "pineocytoma" for these tumors, and of including the so-called "pineocytomas without further differentiation" within the group of pineoblastomas, is suggested in order to achieve a practical clinicopathological assessment of parenchymatous pineal tumors.

Occult inferior vena cava thrombosis: diagnosis by sonography--case reports. Ultrasound has become an effective tool for evaluating the inferior vena cava. The authors report 3 cases that illustrate the difficulty in diagnosing partially adherent clots, which may have a high propensity for pulmonary embolism.

The management of aneurysms and arterio-venous fistulae of the popliteal artery arising from war trauma. Emphasis on sigmoid operative approach. Between 1986-1988, 600 vascular cases arising from the Iran-Iraq conflict were dealt with within an 18 month period and 60 cases of popliteal artery and/or venous disruption were encountered presenting at variable times after injury. A policy of management between the forward and base hospital surgical teams was introduced, observing the following broad categorizations: (a) assessment/referral, (b) assessment/fasciotomy/referral, (c) immediate operation/referral for further operation/review/management. Two types of incision were used to enter the popliteal fossa: (a) a medial incision and (b) a sigmoid posterior incision (which we now favor). The results of this strategy of management and operative technique (when compared with our previous experience within the same time frame) suggested an improved outcome. Fifty-four out of 60 cases had a satisfactory operative result with below-knee amputation being required in only four cases and higher amputations in two others. No operative or postoperative deaths occurred. The implementation of this "vetting policy" at the front line appeared to reduce the number of amputations and assisted the clarification of management criteria in assessing limb viability at the forward hospital when a large number of casualties were being received. Operative access using the sigmoid posterior incision was not associated with any complications, offered better exposure than the medial incision and was technically easier for the surgeon to perform.

Outbreak of diarrhoea due to Escherichia coli O111:B4 in schoolchildren and adults: association of Vi antigen-like reactivity. During six days in November, 1987, 611 pupils (age range 7-19 years) and 39 adults (23-57) at a school complex in southern Finland had diarrhoea due to Escherichia coli O111:B4. Diarrhoea developed in 137 other household members during the two weeks after the school outbreak. The source of the organism remains unknown. The outbreak strains, when incubated at 22 degrees C or exposed to ampicillin, lost the lipopolysaccharide O antigen and began to react with antisera against Salmonella typhi Vi antigen. The Vi antigen-like reactivity increased the adherence of the organisms to Hep-2 cells. These results indicate that E coli O111:B4, and possibly other enteropathogenic E coli strains, should be considered in the diagnosis of all diarrhoea cases and not only in infantile diarrhoea. Expression of Vi antigen in E coli may play a part in virulence by enhancing adherence to the intestinal epithelium.

Inflammatory pseudosarcoma (pseudotumor) of the bladder. Inflammatory pseudosarcoma of the bladder is a rare benign entity that cannot be differentiated from malignant tumor at radiologic examination alone. Only pathologic examination can enable a definitive diagnosis. The authors report two cases of these benign tumors in patients with no history of bladder disease or trauma; the tumors were large, demonstrated invasion into local tissues, and recurred in one case after incomplete transurethral resection.

Fundoplication and gastrostomy in familial dysautonomia. Fundoplication with gastrostomy has become a frequent treatment for patients with familial dysautonomia, so we evaluated the use of both procedures in 65 patients. Although patients differed widely in presenting signs and age, from 5 weeks to 40 years, gastroesophageal reflux was documented in 95% of patients by cineradiography or pH monitoring. Panendoscopy was a useful adjunct. Preoperative symptoms of gastroesophageal reflux included vomiting, respiratory infections, and exaggerated autonomic dysfunction. Severe oropharyngeal incoordination frequently coexisted and resulted in misdirected swallows with aspiration, dependence on gavage feedings, or poor weight gain and dehydration. Follow-up after surgical correction ranged from 3 months to 11 years; 55 patients (85%) were available for a 1-year postoperative assessment. We had no instances of surgical death. The long-term mortality rate was 14%, primarily related to severe preexisting respiratory disease. Beyond the first postoperative year, 30 patients had pneumonia attributed to continued aspiration, exacerbation of preexisting lung disease, or recurrence of gastroesophageal reflux. Of 11 patients who vomited postoperatively, six had recurrence of reflux. Recurrence of gastroesophageal reflux was documented in eight patients (12%), and we revised the fundoplication in three patients. The number of patients with cyclic crises was reduced from 18 to 7; retching replaced overt vomiting in all but two of these seven patients, neither of whom had recurrence of reflux. Because oropharyngeal incoordination was prominent, concomitant use of gastrostomy and an antireflux procedure was especially effective in the treatment of younger patients with familial dysautonomia, before the development of severe respiratory disease. Despite the development of severe morning nausea in 15 patients, the combination procedure resulted in significantly improved nutritional status, decreased vomiting, and decreased respiratory problems. Appropriate use of gastrostomy feedings also contributed to success of the operation. The generally good outcome of fundoplication with gastrostomy confirms the benefit of this procedure in familial dysautonomia.

A distinctive triad of malformations of the central nervous system in the Meckel-Gruber syndrome. A distinct triad of central nervous system (CNS) malformations (prosencephalic dysgenesis, occipital exencephalocele and rhombic roof dysgenesis) was present in seven cases of the Meckel-Gruber syndrome examined at autopsy. We compared our findings with those previously described. Microcephaly, sloping forehead, posterior occipital exencephalocele, cerebellar hypoplasia, Chiari malformation, hydrocephalus, polymicrogyria, arhinencephaly, holoprosencephaly and anencephaly constituted a broad spectrum of the reported CNS anomalies. Few reports contained a comprehensive description of the observed CNS malformations. In those reports, and in our cases, features of prosencephalic dysgenesis included agenesis of olfactory bulbs and tracts (arhinencephaly), hypoplasia of optic nerves and chiasm, agenesis of corpus callosum, fused thalami or complete holoprosencephaly. The occipital encephalocele has consisted of a displacement of rhombic roof elements, including caudal third ventricle, cerebellar vermis and fourth ventricle, extruded through an enlarged posterior fontanelle rather than through an occipital cranium bifidum and is thus more precisely labeled an exencephalocele. Different degrees of dysgenesis of posterior fossa structures, described by some as a variant of Dandy-Walker cyst with features of a Chiari malformation, were often associated with this occipital exencephalocele. This pattern of CNS anomalies represents a triad of malformations probably associated with defective ventral induction of the developing CNS by the prechordal mesoderm.

Adenocarcinoma arising in Barrett's esophagus after total gastrectomy A 64-yr-old Japanese male who underwent a partial gastrectomy for a duodenal ulcer at the age of 21, a total resection of the remnant stomach for a stomal ulcer at age 25, and in whom Barrett's esophagus was diagnosed at age 47, was found to have a tumor at the distal esophagus and was operated on by thoracic esophagectomy. The tumor was a well to moderately differentiated adenocarcinoma invading down to the muscularis propria. The entire esophageal mucosa in the resected specimen was lined by columnar epithelium. This tumor was thought to derive from the Barrett's esophageal epithelium.

Retinal vasculitis as a complication of rheumatoid arthritis. Two middle-aged women developed retinal vasculitis in the moderately active phase of classical rheumatoid arthritis. Fluorescein angiography disclosed diffuse leakage from the retinal capillaries and cystoid macular edema, which subsided in response to oral steroid. They did not show any clinical signs of vasculitis in other parts of the body. Retinal vasculitis should be included in the list of complications observed in rheumatoid arthritis.

A combined electromyographic and cineradiologic investigation in patients with defecation disorders. Records from 20 patients on whom defecography and electromyography were performed simultaneously because of defecation disorders were analyzed. According to the electromyographic investigation, the patients could be divided into three main groups: 1) normal sphincter reaction; 2) paradoxical sphincter reaction; and 3) combined reaction. Group A was characterized by a marked reduction of muscular activity during emptying and a pronounced closing reflex after emptying. This was followed by return of normal tonic activity. Patients in group B had no relaxation of the sphincters during emptying but a pronounced increased activity in the external sphincter and the puborectalis muscle. They also had severe emptying difficulties at defecography. No closing reflex was seen. In group C the electrical activity in the sphincters increased during moderate straining and when emptying was complete a clear closing reflex was seen. In this study, a dynamic visualization of the defecation together with a registration of electromyographic activity in the striated anal sphincters was performed. It was shown that patients with paradoxical sphincter reaction were lacking a closing reflex after emptying was complete. This has not been reported previously and is important evidence for the paradoxical defecation pattern. It was also shown that the patients with rectoceles had paradoxical sphincter reaction.

Colonic polyamine content and ornithine decarboxylase activity as markers for adenomas. Polyamine content (putrescine, spermidine, and spermine) or ornithine decarboxylase (ODC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonoscopy. Comparisons were made between those with and those without adenomatous polyps. Colonic mucosal polyamine content was measured in 44 persons. Mean putrescine content was 1.25 +/- 0.26 (SE) nmol/mg protein in 22 patients with adenomatous polyps compared with 0.53 +/- 0.12 nmol/mg protein in patients without polyps (P less than 0.02). Tissue content of spermidine and spermine did not differ between these two groups. Ornithine decarboxylase activity was measured in tissue from 45 patients. Mean ODC activity was 2.84 +/- 0.73 pmol/hr/mg protein in 23 persons with adenomatous polyps compared with 1.15 +/- 0.18 pmol/hr/mg protein in persons without polyps (P less than 0.05). Mucosal putrescine and ODC activity are elevated in patients with adenomatous polyps compared with patients without polyps. These biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps.

Modifying the translabyrinthine approach to preserve hearing during acoustic tumour surgery. Removing an acoustic schwannoma using the translabyrinthine approach has previously been considered incompatible with hearing preservation. By modifying the approach and preventing the loss of endolymph, we have successfully removed an intracanalicular acoustic schwannoma, which originated from the inferior vestibular nerve, and preserved hearing in the operated ear. This report represents the preliminary findings using this particular technique in the management of an intracanalicular acoustic tumour.

Myofibroblastoma of the tongue. An immunohistochemical, ultrastructural, and flow cytometric study. A case of myofibroblastoma arising in the tongue of a 77-year-old man is described. The patient presented with a submucosal tongue mass without other associated symptoms. The tumor was 2 cm in diameter, well circumscribed, and composed of uniform spindle cells arranged in fascicles. Electron microscopic examination and immunohistochemistry demonstrated a myofibroblastic origin for the tumor cells. DNA flow cytometric analysis showed a diploid DNA content of this tumor. To the authors' knowledge, this is the first report of myofibroblastoma occurring in the tongue.

Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom. To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes. In female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3.7. A screening programme based on estimated risks could be offered to first-degree relatives of index patients with Lynch type II cancer family syndrome.

Cerebral vein thrombosis shown by MRI. A 46 year old man with a short history of left facial pain and numbness, and subsequently headaches, had a normal physical examination and a normal CT scan of head. Lumbar puncture yielded normal CSF under increased pressure. MRI showed thrombosis of the superior sagittal sinus, subsequently confirmed by angiography. MRI is a sensitive test for detecting intracranial venous thrombosis, and may be the investigation of choice when this disorder is suspected.

Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat. Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B2 when compared with normotensive (LN) and low blood pressure (LL) controls. Therefore, the effects of norepinephrine (1.2 x 10(-8) to 9.6 x 10(-7) M) and of phenylephrine (5 x 10(-8) to 1.9 x 10(-6) M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed before and during thromboxane A2/prostaglandin H2 receptor blockade by AH23848 (4 x 10(-6) M). Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E2 and F2 alpha, of 6-ketoprostaglandin F1 alpha, and of thromboxane B2 was similar in the three strains. The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced. Norepinephrine and phenylephrine induced a 10- to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B2 only. AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys.

Primary carcinoma of the gallbladder. Seventy-four patients with primary carcinoma of the gallbladder, diagnosed over 18 years from 1969 to 1987, were studied retrospectively. The most common presenting complaint was abdominal pain, followed by jaundice and weight loss. Surgery was performed in 61 patients and of these patients, only two had accurate preoperative diagnosis which was made by ultrasonography. Twelve of the 13 patients who were treated medically had the disease diagnosed at autopsy. One of the 13 patients had the diagnosis of gallbladder cancer by the findings of ultrasonography and abdominal computed tomography (CT) scanning. The resectability of the surgically managed group was 36.1%, and the majority of patients with advanced tumors (82.2%) were deemed unresectable. The most common histologic type was adenocarcinoma. Liver was the organ most commonly invaded (76.5%) by direct extension and/or metastases, followed by regional lymph nodes (52.9%). The overall 5-year survival rate was 5.4%. A high index of suspicion of the disease, intraoperative examination of gallbladder specimen, and earlier, more aggressive surgical treatment may improve patient survival.

Does percutaneous transluminal coronary angioplasty accelerate atherosclerotic lesions? Recent reports have suggested that angioplasty may cause or accelerate coronary arterial stenoses secondary to traumatic injury. Ninety-four coronary angiograms performed in a 1 yr period were reviewed in patients who had successful coronary angioplasty 6 to 30 mo (mean 10.7) prior to restudy. Restenosis was found in 43 of 140 dilated lesions (31%) and in 41 of 94 patients (44%). Thirty-three (35%) patients had new or progressive lesions outside the angioplasty site. New or progressive lesions occurred with similar frequency in the arteries that did not have angioplasty (23/155 = 15%) as in the arteries that did (13/127 = 10%; chi-square n.s.). In the arteries which underwent angioplasty, new or progressive lesions occurred as commonly proximal to the PTCA site (7/14, 50%) as distal (6/13, 46%). New or progressive lesions occurred in 29% of patients with concomitant restenosis, and 40% of those without restenosis (chi-square n.s.). No clinical, angiographic, or procedural factors distinguished patients with new and progressive lesions in target vessels from those without these lesions in target vessels. Patients with progressive lesions anywhere in the coronary tree were more likely to have had a shorter duration of anginal symptoms before angioplasty and a family history of coronary disease when compared with patients without progressive atherosclerosis. In conclusion, new and progressive lesions outside the angioplasty site occur after the procedure but appear unrelated to the restenosis process or traumatic injury by angioplasty instrumentation.

Prognostic significance of exercise versus resting blood pressure in hypertensive men. The outcome of 143 male hypertensive patients, investigated in the period 1972-1982, was ascertained in 1989 to determine if brachial artery pressure measured during a progressive graded exercise test on the bicycle ergometer is a better predictor of mortality and cardiovascular events than pressure at rest. During the total follow-up time of 1,573 patient years, 27 patients suffered at least one fatal or nonfatal cardiovascular event and 13 patients died. Using the Cox regression model, the age-adjusted relative hazard rates of systolic pressure at supine rest, at 50 W, at peak work load, and at 50% of peak exercise capacity were significant for total mortality (p less than or equal to 0.01) and for cardiovascular events (p less than or equal to 0.03). Pressure during exercise, however, did not significantly (p = 0.11-0.97) predict the outcome of the patients when age and pressure at rest were taken into account. The results were similar for diastolic pressure. In conclusion, intra-arterial pressures at rest and during submaximal and peak exercise significantly predict mortality and the incidence of cardiovascular events in hypertensive men, independent of age. However, there is no additional prognostic precision of the exercise pressures when age and the rest pressure are taken into account.

Simulated left ventricular aneurysm and aneurysm repair in swine. Patch reconstruction of left ventricular aneurysm may be superior to linear closure, but this hypothesis has not been tested experimentally. Accordingly, six anesthetized domestic pigs were instrumented to measure regional left ventricular wall thickening, stroke volume, systolic left ventricular pressure, and myocardial oxygen consumption. With total bypass and cardioplegia, a 6 by 8 cm Dacron patch was inserted into the anteroapical left ventricle. Simulations were as follows: left ventricular aneurysm, patch open; patch reconstruction, 50% patch plication; standard repair, ventriculotomy edges approximated. Global function, from stroke work (stroke volume x integral of left ventricular pressure)-left ventricular end-diastolic pressure curves, was depressed in all three simulations compared with control. A tendency for stroke work to be greater for standard repair than for left ventricular aneurysm and patch reconstruction at higher preloads was not statistically significant. Mechanical efficiency, from stroke work/myocardial oxygen consumption (joules per milliliter oxygen per beat), was 2.43 +/- 0.52 (mean +/- standard error of the mean) (control), 2.22 +/- 0.94 (standard repair), 1.27 +/- 0.39 (patch reconstruction), and 1.09 +/- 0.37 (left ventricular aneurysm) (no significant differences). Regional work was calculated as regional left ventricular wall thickening x integral of left ventricular pressure. The slope of the regional work-end-diastolic wall thickness relation decreased in the posterior wall 14.0 +/- 2.9 (control) versus 8.4 +/- 2.0 (left ventricular aneurysm), 6.9 +/- 1.4 (patch reconstruction), and 7.4 +/- 1.4 (standard repair) (p less than 0.05). In the anterior wall, contractility did not change significantly (7.4 +/- 1.2, control; 7.8 +/- 2.7, left ventricular aneurysm; 5.0 +/- 0.4, patch reconstruction; and 5.3 +/- 0.4, standard repair). Decreased end-diastolic wall thinning anteriorly suggested tethering. These results in the normal left ventricle suggest that patch ventriculoplasty is of no greater benefit than linear repair. Either repair may impede function of adjacent myocardium through restriction of regional diastolic lengthening.

Unusual malignant neoplasms of the esophagus. Oat cell carcinoma, melanoma, and sarcoma. Primary noncarcinomatous malignant neoplasms of the esophagus are uncommon and data concerning treatment and results are sparse. To evaluate the results of therapy in this group, we reviewed the records of 32 patients with primary esophageal malignant tumors of unusual histologic type. Thirteen patients (41%) had sarcoma, eight (25%) melanoma, and 11 (34%) had oat cell carcinoma. Dysphagia was present in 78% (25/32) of the patients for a median of 13 weeks before diagnosis. Location of the esophageal primary tumor was upper third in four patients (12%), middle third in 12 (38%), and lower third in 16 (50%). Treatment consisted of esophagectomy in 10 of 13 patients with sarcoma (77%), seven of eight with melanoma (88%), and three of 11 with oat cell carcinoma (27%). Patients not undergoing resection received chemotherapy or radiation therapy, or both. The 3- and 5-year survival rates were 46% and 23% for sarcoma (median 20 months), 13% and 0% for melanoma (median 5 months), and 0% and 0% for oat cell carcinoma (median 5 months), respectively. Distant disease was the initial form of recurrence in 73% (11/15) of patients undergoing curative therapy. Surgical resection appears indicated for localized primary esophageal sarcoma. Optimum treatment of primary esophageal melanoma is less clear, but surgical resection may be of benefit in selected patients. Esophageal oat cell carcinoma is a systemic disease necessitating systemic therapy with local therapy reserved for palliation of dysphagia.

Functional heart replacement with the spindle pump: first results. The spindle pump is a nonpulsatile blood pump with a double function, i.e., it works centrifugally and represses simultaneously. The first experiences with this type of pump used as a biventricular assist device in four short-term animal experiments (up to 13 hours) are described. It can be demonstrated that in cases of a normally beating heart, this BVAD decompresses both ventricles by 60-70%, while the aortic pressure is slightly increased; on the other hand, in case of ventricular fibrillation, the BVAD with two spindle pumps maintained the entire circulation, at an arterial pressure between 80 and 90 mmHg with a flow volume between 3.5 and 4 L/min.

Arterial protection: a neglected but crucial therapeutic goal. Hypertension is accompanied by 2 major types of arterial pathologic conditions: smooth muscle hypertrophy of arteriolar resistance vessels and atherosclerosis, primarily involving the larger arteries. Smooth muscle hypertrophy may develop either as a secondary defense against elevated intravascular pressure or as a primary defect responsible for the increased pressure. Insulin and a number of other trophic stimuli may play a pathogenetic role in vascular hypertrophy. Reducing blood pressure and trophic stimuli may cause hypertrophy to be reversed. Because atherosclerosis may be markedly accelerated by hypertension, especially in the presence of concomitant risk factors, such as hypercholesterolemia, cigarette smoking and diabetes mellitus, antihypertensive treatment may attenuate or even reverse the extent of atherosclerosis, but only when the causative factors are also corrected. Some commonly used antihypertensive agents, e.g., diuretics and beta blockers without intrinsic sympathomimetic activity, often aggravate hypercholesterolemia and glucose intolerance, thereby diminishing their potential protective value. Other types of drug therapy, such as alpha blockers, beta blockers with intrinsic sympathomimetic activity or other vasodilator activity, angiotensin-converting enzyme inhibitors and calcium entry blockers that may not induce biochemical changes, should provide better control of multiple risks and thereby better protection against atherosclerosis. With a better understanding of how hypertension induces arterial damage, clinicians will be able to provide more appropriate treatment and, it is hoped, alleviate such damage.

Endothelium-derived relaxing factors. A perspective from in vivo data. We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions.

Social environment and social support. Research on the relevance of social support to cancer has been plentiful since the first American Cancer Society workshop on methodological issues in behavioral and psychosocial science. Nonetheless, critical shortcomings continue to characterize the attempt empirically to establish such things as the extent to which social support predicts adjustment to cancer diagnosis and treatment. Prominent among these is the failure to adequately address large elements of the social structure, such as social class and urbanization, and to investigate how they shape the well being of persons with or at risk for cancer and their caregivers. We recommend that more psychosocial research on the link between social support and cancer be conducted within populations beset by poverty and without adequate access to health care. Funding is needed for the training and maintenance of multidisciplinary and multicultural teams of researchers working within community-based organizations and hospitals serving the underserved.

Lower leg subcutaneous blood flow during walking and passive dependency in chronic venous insufficiency. The blood flow in the subcutaneous adipose tissue of the lower leg of eight normal subjects and 19 patients with chronic venous insufficiency was measured. The 133Xe-washout technique was used with portable CdT1(C1) detectors and a data storage unit. Only those patients with ulcers and a systolic blood pressure at the toe of greater than or equal to 60 mm were investigated. In the controls the relative blood flow during sitting was 0.61 (range 0.35-0.80). In the patients it was 0.46 (range 0.22-0.87). This difference was not significant. During walking the blood flow increased in controls as well as in the patients compared to the value determined in the sitting position (P = 0.0078 and P = 0.0028, respectively, Wilcoxon matched-pairs test). The relative blood-flow rate during walking was 0.96 (range 0.60-1.58) in the controls, and 1.04 (range 0.49-1.46) in the patients. The difference between the normal subjects and the patients was not significant (P = 0.79). We conclude from our studies that patients with venous insufficiency are able to increase their blood flow during walking to the same extent as normal controls.

Comparison of medical and surgical therapy for uncomplicated descending aortic dissection. To guide the choice of medical versus surgical therapy for patients with descending (type B) aortic dissection (tear in the descending aorta without involvement of the ascending aorta), multivariate survival analysis was applied to 136 patients admitted to two medical centers between 1975 and 1988 with acute (n = 89) or chronic (n = 47) descending dissection: group 1, all 136 patients; group 2, 106 patients without rupture, pulse loss, or visceral organ compromise; and group 3, 56 patients from group 2 without major cardiac or renal disease (23 surgical and 33 medical). Group 3 medical and surgical subgroups were well matched for baseline characteristics and were potential candidates for either mode of therapy. By Cox model analysis, significant predictors of mortality were pleural rupture, other dissection complications, increasing age, and cardiac disease (all p less than 0.01). Surgical versus medical therapy was not an independent determinant of survival in any of the three groups for acute or chronic dissection. Survival probabilities for all group 3 patients at 1, 5, and 10 years were 0.94, 0.87, and 0.32 (medical) and 0.90, 0.80, and 0.50 (surgical). Despite the limitations of this retrospective study (including the possibility of undefined treatment selection biases), these data suggest that medical or early surgical therapy is associated with equivalent outcome in selected patients with uncomplicated acute or chronic descending aortic dissection.

Autoimmune enteropathy and colitis: is there a generalised autoimmune gut disorder? Children with protracted diarrhoea, circulating enterocyte autoantibodies, and an enteropathy showing features of inappropriate HLA molecule expression on the jejunal crypt epithelium, often present with persistent blood and mucus in their stools. Eight children with autoimmune enteropathy were investigated for the presence of associated colonic disease. Six children with protracted diarrhoea, no circulating autoantibodies, and an enteropathy (in five of them) undergoing colonoscopy were used as control subjects. In all eight patients, but not in the control subjects, there was macroscopic and microscopic evidence of an accompanying colitis of variable severity, thus indicating that a more generalised intestinal disorder was present, which might affect the whole intestine. Aberrant expression of DR molecules on the colonic surface and crypt epithelium was also detected. Autoimmunity may play a role in the colitis.

Gilles de la Tourette syndrome is not linked to D2-dopamine receptor. Gilles de la Tourette syndrome has an important genetic component; the pathophysiology of this disorder may involve the dopamine system. We tested a D2-dopamine receptor (locus DRD2, recognized by probe hD2G1) for genetic linkage with Gilles de la Tourette syndrome. Using a genetic linkage map of the region of DRD2 on the long arm of chromosome 11 and restriction fragment length polymorphism data from a total of four markers (DRD2 itself, D11S84, D11S29, and PBGD), we were able to exclude linkage of this candidate gene and Gilles de la Tourette syndrome in two extended kindreds segregating for Gilles de la Tourette syndrome. This rules out causation of Gilles de la Tourette syndrome by mutation in DRD2 in the kindreds studied under the genetic assumptions we employed; use of the map and multipoint linkage analyses also allowed us to exclude a Gilles de la Tourette syndrome susceptibility locus from a larger genetic region.

Management of recurrent malignant pleural effusion in the United Kingdom: survey of clinical practice. Malignant pleural effusions are often symptomatic and tend to recur after simple aspiration. Pleurodesis may prevent recurrence of the effusion; many agents and techniques have been described. A questionnaire was sent to 448 clinicians in the United Kingdom to determine how pleurodesis is performed in practice. There was a 56% overall response, with replies from 101 respiratory physicians, 88 general physicians, 29 thoracic surgeons, and 35 general surgeons. General surgeons saw few cases of malignant pleural effusion and rarely performed pleurodesis. A patient with recurrent malignant pleural effusion would usually be managed with pleurodesis by 76 (76%) respiratory physicians, 26 (30%) general physicians, and 23 (81%) thoracic surgeons; a further 29 (33%) general physicians would refer such patients to another specialist. Most medical pleurodesis were performed by junior staff, whereas consultant thoracic surgeons were more likely to be concerned with the procedure. All the thoracic surgeons used an intercostal tube drain, usually with suction. An intercostal tube drain was used routinely by only 54 (54%) of the respiratory physicians and 28 (32%) general physicians. Thoracic surgeons preferred talc for pleurodesis whereas physicians most commonly used tetracycline. The variety of methods in use supports the need for randomised, controlled studies to determine the most effective technique of pleurodesis.

Facial nerve injury and hemifacial spasm. We studied evidence of facial nerve damage in patients with hemifacial spasm. Three types of evidence of nerve damage were analyzed: objectively measured weakness in eyelid protractor strength, clinically evident weakness of muscles innervated by the seventh nerve, and clinically evident aberrant seventh nerve regeneration. Of the 60 patients in the study, 54 (90%) had at least one of these features of seventh nerve damage. Objectively measured eyelid protractor weakness was noted in 27 of 58 patients (47%) who were tested. Clinically apparent weakness of at least one of four facial muscle groups was noted in 42 of 60 patients (70%). Aberrant seventh nerve regeneration was documented in 25 of 60 patients (42%). These findings indicate that facial nerve damage is common in patients with hemifacial spasm.

Effect of indomethacin on gastric mucosal blood flow around acetic acid-induced gastric ulcers in rats. Repeated administration of indomethacin markedly delays spontaneous healing of experimental gastric ulcers induced in rats. To elucidate the underlying mechanism, the effect of indomethacin on the gastric mucosal blood flow around ulcers was examined. Gastric ulcers were induced 5 days after submucosal injection of an acetic acid solution into the stomachs of rats. Blood flow was determined by the hydrogen gas clearance method. The blood flow around ulcers was significantly higher than that in rats without ulcers up to 2 weeks after ulceration but had returned to within the normal range 3 or 4 weeks later. Indomethacin, administered SC at 1 mg/kg once or repeatedly for 1-4 weeks, had little or no effect on the blood flow in normal rats. However, such treatment significantly reduced the blood flow by 20%-30% of the corresponding control levels in rats with ulcers. Prostaglandin E2, administered SC at 3 mg/kg once, markedly prevented the reduction in the blood flow due to indomethacin. The administration of prostaglandin E2, with indomethacin for 4 weeks resulted in a significantly higher blood-flow level than the control and prevented the delay in ulcer healing. Omeprazole, administered SC at 30 mg/kg once or repeatedly with indomethacin for 4 weeks, had an insignificant effect on the blood flow around ulcers but prevented the delay in ulcer healing. In conclusion, the delayed ulcer healing caused by indomethacin might be partly related to the reduced blood flow around the ulcers.

Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies. The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas.

Safe performance of difficult laparoscopic cholecystectomies. Laparoscopic cholecystectomy has been advocated for the treatment of uncomplicated symptomatic gallstone disease, but has not been widely advocated for the management of more complicated gallbladder disease such as acute cholecystitis, previous surgery, or common duct stones. During the last 9 months, 360 patients underwent laparoscopic removal of their gallbladder. A total of 138 had a complicated presentation, making surgery more difficult. This article discusses the management of these patients with acute cholecystitis, previous surgery, or common duct disease. Using the described techniques, there were no complications or mortality. Laparoscopic management of difficult gallbladder problems is safe and effective.

Traction injury in the internal mammary artery. Report of a case and review of the literature. The internal mammary artery (IMA) is now used routinely along with saphenous vein for myocardial revascularization procedures. We have documented a particular form of non-perforating injury which may reduce blood flow during operation or may lead to early closure of the IMA bypass graft. Traction injury to the intima is well documented in other vessles but has not been previously reported in the IMA. We present a potentially disastrous example of traction injury to the IMA.

Basement membrane of cervical adenocarcinoma: an immunoperoxidase study of laminin and type IV collagen. The basement membrane components type IV collagen and laminin were examined immunohistochemically in 14 cases of adenocarcinoma of the cervix. The patterns of staining in adenocarcinoma in situ, invasive adenocarcinoma, and early invasive adenocarcinoma were compared to see whether characteristic patterns could be delineated. Adenocarcinoma in situ had a uniform intact basement membrane, whereas the basement membrane of invasive adenocarcinoma was fragmented and irregular. Cases of early stromal invasion showed early gland buds and outpouchings with defective basement membrane staining. The degree of histologic differentiation of the tumor was not clearly related to the amount of basement membrane component staining. The concept of early stromal invasion in cervical adenocarcinoma, as supported by our immunohistochemical studies, is discussed as it relates to a possible pathogenic mechanism in early invasion and infiltration of adenocarcinoma of the cervix.

Hilar malignancy: treatment with an expandable metallic transhepatic biliary stent. An expandable metallic transhepatic biliary endoprosthesis was used to treat 20 patients with hilar malignancy and isolated right and left intrahepatic ducts. In 12 patients, only one intrahepatic ductal system was drained; in eight patients, both systems were drained. In five patients, both systems were drained through a single transhepatic track by arrangement of two stents in a T configuration. The initial technical success rate in placing the stents and achieving internal drainage was 100%. Complications necessitating further intervention occurred in two of the 20 patients. Short-term clinical follow-up was available for 19 of the 20 patients. Two months after stent insertion, two patients complained of persistent jaundice, two patients died without jaundice, and 15 patients were free of symptoms of biliary obstruction. A variety of geometric configurations are possible with this endoprosthesis. The relative merits of these stent arrangements are discussed, and a new technique for placing the stents in a T configuration is described.

A prospective, randomized study of three surgical techniques for treatment of acute ruptures of the anterior cruciate ligament. Treatment of ACL tears is controversial. Recent reports on nonoperative treatment have shown poor results. Results after primary repair have deteriorated with time, leading to augmentation procedures that seem to have improved the results. However, there have been few prospective, randomized studies in this field. Our goal was to compare primary repair with a bone-patellar tendon-bone augmentation method and with a new method using the Kennedy Ligament Augmentation Device. One hundred fifty patients aged 16 to 50, all of whom had acute ACL tears, were randomized with the closed envelope method to one of three groups treated with open surgical methods. Fifty patients were treated with primary repair, 50 patients with patellar tendon augmentation, and 50 patients were augmented with the Kennedy Ligament Augmentation Device. All patients were operated on within 10 days of injury. The rehabilitation protocol was identical, consisting of a long leg cast for 2 weeks, followed by a brace with no weight-bearing and limited motion for 6 weeks. The patients were followed prospectively by one surgeon (LE) using the Lysholm functional score, Tegner activity level score, clinical evaluation and KT-1000 arthrometer at 6 months, 1, and 2 years. Three patients were lost to followup. There was no age or activity level difference between the groups. Sport activities led to 85% of the injuries, with skiing, soccer, and European handball representing 80% of injuries. All three groups reduced their activity level the 1st year. The repair group remained at the same level after 2 years.

Effect of epinephrine and lidocaine therapy on outcome after cardiac arrest due to ventricular fibrillation. One hundred ninety-nine patients with out-of-hospital cardiac arrest persisted in ventricular fibrillation after the first defibrillation attempt and were then randomly assigned to receive either epinephrine or lidocaine before the next two shocks. The resulting electrocardiographic rhythms and outcomes for each group of patients were compared for each group and also compared with results during the prior 2 years, a period when similar patients primarily received sodium bicarbonate as initial adjunctive therapy. Asystole occurred after defibrillation with threefold frequency after repeated injection of lidocaine (15 of 59, 25%) compared with patients treated with epinephrine (four of 55, 7%) (p less than 0.02). There was no difference in the proportion of patients resuscitated after treatment with either lidocaine or epinephrine (51 of 106, 48% vs. 50 of 93, 54%) and in the proportion surviving (18, 19% vs. 21, 20%), respectively. Resuscitation (64% vs. 50%, p less than 0.005) but not survival rates (24% vs. 20%) were higher during the prior 2-year period in which initial adjunctive drug treatment for persistent ventricular fibrillation primarily consisted of a continuous infusion of sodium bicarbonate. The negative effect of lidocaine or epinephrine treatment was explained in part by their influence on delaying subsequent defibrillation attempts. Survival rates were highest (30%) in a subset of patients who received no drug therapy between shocks. We conclude that currently recommended doses of epinephrine and lidocaine are not useful for improving outcome in patients who persist in ventricular fibrillation.

Managing geriatric arrhythmias, I: General considerations. Cardiac arrhythmias become increasingly common as people age, but they are not always clinically significant. Sinus node dysfunction, AV conduction disturbances, and ventricular and supraventricular arrhythmias will be found but are not always symptomatic. Treatment of asymptomatic arrhythmias is controversial and probably not indicated, but in symptomatic elderly, therapy is indicated, since even the very elderly have been found to benefit from it as much as younger patients. There are specific guidelines, however, that apply to this age group based on its susceptibility to side effects.

Endoscopic retrograde cannulation of the gallbladder: direct dissolution of gallstones. Percutaneous transhepatic catheterization of the gallbladder for dissolution of cholesterol stones by instillation of methyl tert-butyl ether (MTBE) is an invasive therapeutic procedure. The only non-invasive alternative available to now, endoscopic retrograde cannulation of the cystic duct, was difficult because of the cystic duct's tortuosity and spiral valves. We therefore developed a catheter system which, using conventional duodenoscopes during a routine endoscopic retrograde cholangiography (ERC) procedure, permits reliable and safe catheterization of the gallbladder without the need for endoscopic sphincterotomy. In 18 of 22 patients (82%) we were able to place a cysto-nasal catheter, and in 14 patients MTBE dissolution therapy was then performed. Eight patients (57%) were completely free of stones after treatment; the other six (43%) had residual debris. In 4 of 22 patients (18%) cannulation attempts failed, in 3 patients due to cystic duct blockage by a calculus. Endoscopic retrograde cannulation of the gallbladder (ERCG) represents a promising alternative to the invasive percutaneous transhepatic catheterization procedure.

Monozygotic twins discordant for partial trisomy 1. A 25-year-old primigravida delivered monozygotic twins discordant for multiple anomalies and partial trisomy 1 mosaicism. The phenotype of partial trisomy 1 includes craniofacial, central nervous system, and ocular anomalies. The most likely explanation for these findings is that the translocation occurred after twinning occurred. This observation emphasizes that monozygotic twins are not necessarily genetically identical. They are identical at conception, but subsequent mutation and rearrangement of the genome may cause substantial phenotypic differences.

Neuropathy caused by spontaneous intraneural hemorrhage: case report. A case of ulnar neuropathy at the elbow produced by spontaneous intraneural hemorrhage in a patient with acquired immunodeficiency syndrome and thrombocytopenia is reported. Intraneural hemorrhage in patients with bleeding disorders occurs infrequently. It consists of acute intrafascicular bleeding, presumably producing very high elevations of endoneurial fluid pressure. The clinical features and treatment of this condition are considered, the pertinent literature is reviewed, and the involved pathophysiological mechanisms are discussed.

Intraosseous lipomatosis. A case report. We report a case of systemic intraosseous lipomatosis involving the proximal femur, both ends of the tibia, and the tarsal and metatarsal bones. The lesions progressed during a five-year follow-up with a pathological fracture of the tibial plateau. CT scans were characteristic and helpful in diagnosis but MR imaging added little information. Intraosseous lipomatosis is a hamartomatous malformation due to hyperplasia of adipose tissue, and is fundamentally different from solitary benign intraosseous lipoma. Management involves reconstruction of any pathological fracture. Large progressive lesions should be treated by curettage and grafting in an attempt to prevent such fractures.

Sudden infant death syndrome in infants of substance-abusing mothers. A population-based study was performed to determine whether substance abuse during the perinatal period may be a risk factor for sudden infant death syndrome (SIDS). The incidence of SIDS was studied in 2143 infants of substance-abusing mothers (ISAM) born in Los Angeles County during 1986 and 1987 who were reported to the Los Angeles County Department of Health Services because of a history of drug exposure or positive urine test results in the mother, infant, or both. By comparing the ISAM birth reports with records of autopsy-proven SIDS in Los Angeles County, we found 19 SIDS cases in the population of 2143 ISAM, a SIDS rate of 8.87 cases per 1000 ISAM (95% confidence interval 5.3 to 13.8). This was significantly higher than the SIDS rate for the non-ISAM general population: 396 SIDS deaths among 325,372 live births, an incidence rate of 1.22 cases per 1000 births, p less than 0.00001. The age of ISAM at death was 99 +/- 63 (mean +/- SD) days compared with 91 +/- 52 days for the non-ISAM population (not significant). The incidence of SIDS was significantly greater in male infants, during the winter months, in black infants, and in non-Hispanic white infants in the non-ISAM population. Such differences were not observed in the ISAM group. A greater incidence of symptomatic apnea was reported before SIDS for the ISAM than for the non-ISAM population (22% vs 5.4%, p = 0.022). We conclude that ISAM have a higher incidence of SIDS than the non-ISAM general population. However, it was not possible to separate maternal substance abuse from other confounding variables that may also have had an impact on SIDS risk in the ISAM group.

Prolonged response to carboplatin in an infant with brain stem glioma. Adults and children with brain stem gliomas have a mean survival time of 15 months after radiation therapy (XRT). Infants with this tumor present additional complexities for treatment because of possible neurotoxicity of the radiation to the developing brain. We report a 15-month-old child with biopsy-proven brain stem glioma with clinical and radiographic evidence of disease progression. She was treated with 24 monthly courses of carboplatin without radiation therapy and has had a 39+ month response. The clinical response started after 3 months and the radiographic evidence was documented at 10 months by magnetic resonance imaging. The toxicity was minimal. Longitudinal neuropsychological assessment demonstrated continued improvement at 36 months post diagnosis but with some motor functioning below expected age levels. Cervico-medullary astrocytoma in a young patient may be the appropriate clinical setting for future trials of chemotherapy without XRT.

Pathologic bronchial vasculature in a case of massive hemoptysis due to chronic bronchitis. The cause of bleeding in a patient with recurrent massive hemoptysis was not apparent after bronchoscopy and gross examination of the lobectomy specimen. Histologic submission of all major bronchi uncovered dilated, tortuous bronchial arteries just below the bronchial mucosa with sites of both current and healing arterial rupture. This bronchial arterial abnormality is common to several chronic pulmonary diseases, but is rarely diagnosed as a cause of massive hemoptysis. Careful pathologic examination of major bronchi in the setting of hemoptysis of unknown causation is recommended.

Primary neuroendocrine carcinoma of the skin. Clinicopathologic study of 18 cases. The clinical and pathologic features of primary neuroendocrine carcinoma of the skin in 18 elderly patients are reported. The carcinomas arose in the dermis and subcutaneous tissues, particularly on the head and the upper extremities. One tumor occurred in an irradiated area. Using Gould's clinicopathologic classification, we have found four trabecular types, eleven intermediate cell types, and two small cell types. One tumor could not be classified. Other noteworthy pathologic features were association with invasive squamous cell carcinoma, lentiginous melanocytic hyperplasia, and presence of intratumoral melanocytes. Immunoreactivity for cytokeratins (56 kD), neurofilaments, neuron-specific enolase, and epithelial membrane antigen was observed. The paranuclear globular staining pattern of cytokeratins and neurofilaments was conspicuous. The ultrastructural features revealed paranuclear intermediate filament aggregates (fibrous bodies), neurosecretory granules, and cell junctions. In two metastatic tumors, high levels of catecholamines were found. The trabecular types were characterized by localized disease and a good prognosis. The patients with the small cell types died of distant metastases. Postoperative radiotherapy seemed to reduce the rate of local recurrences.

Everted cervical vein for carotid patch angioplasty. Because of the theoretic benefits of autologous vein we undertook an investigation to evaluate cervical veins (facial, external jugular) as patch material after carotid endarterectomy. A device that stimulated both circumferential fixation by sutures and radial tension exerted on in vivo patches was constructed to measure burst strength of tissue. Mean bursting pressure for groin saphenous vein (n = 10) was 94.5 +/- 15.1 pounds per square inch (psi), 75.5 +/- 8.9 psi for ankle saphenous vein (n = 10), 83.3 +/- 14.5 psi for everted (double layer) cervical vein (n = 5) and 10 +/- 3.3 psi for single layer cervical vein (n = 5). No significant differences between saphenous vein at any level and everted (double layer) cervical vein, but all were significantly different from single layer cervical vein (p less than 0.05). From June 1987 through November 1989, 19 patients underwent 21 carotid endarterectomies complemented with adjunctive everted cervical vein patch angioplasty. Indications for surgery were asymptomatic stenosis (53%), transient ischemic attack (29%), and cerebrovascular accident with recovery (18%). All patients were studied after surgery with duplex scanning. Asymptomatic recurrent stenosis was observed in one patient. Transient hypoglossal nerve dysfunction occurred in one other patient. One postoperative death occurred as a result of massive aspiration. These results indicate that everted cervical vein is comparable to the saphenous vein in resistance to bursting and can yield similar results as patch material after carotid endarterectomy. Accordingly, saphenous vein can be spared and lower extremity incisions avoided.

Progress in cardioprotection: the role of calcium antagonists. Calcium antagonists are now widely used for the treatment of clinical hypertension and angina pectoris. They are efficacious for the treatment of vasospastic, fixed atherosclerotic and mixed angina; they reduce the incidence of silent ischemia; and they have been shown to reduce postmyocardial infarct angina. Experimental data suggest that they may have certain cardioprotective properties in cases of acute myocardial ischemia and infarction, stunned myocardium, diastolic dysfunction, left ventricular hypertrophy and atherosclerosis. Moreover, they have been shown to improve exercise performance, as well as the diastolic abnormalities in patients with hypertrophic cardiomyopathy. In animals, they may delay or reduce the extent of myocardial necrosis after coronary occlusion or coronary occlusion followed by reperfusion, and in low doses that do not alter the hemodynamic profile, they have been shown to enhance the return of ventricular function in animals with stunned myocardium. However, the early first-generation calcium antagonists (nifedipine, verapamil, diltiazem) have not been shown to reduce myocardial infarct size or to enhance survival in patients with acute myocardial infarction. There now are clinical studies that suggest that, unlike beta blockers or nitrates, nifedipine may slow the development of atherosclerotic progression in humans over a 2-year period, and it seems likely that in the 1990s there will be further expansion of the use of calcium antagonists for not only angina and hypertension but also for aspects of cardioprotection. That calcium antagonists may delay, prevent or possibly regress atherosclerotic lesions is an exciting possibility.

Potential role of IgG avidity for diagnosing toxoplasmosis. Sera from 20 cases of toxoplasmic lymphadenopathy were examined by an enzyme linked immunosorbent assay toxoplasma IgG avidity (ELISA) at two laboratories. The results obtained were largely in agreement and showed that sera from patients with acute infection had low avidity IgG (30% or less), whereas sera from patients with chronic infection had high avidity IgG (40% or more). It is suggested that this type of assay could have a useful complementary role in antenatal testing for toxoplasmosis.

Early and late effects of captopril treatment after large myocardial infarction in rats. The early (after 21 days) and late (after 4 months) effects of continuous treatment with captopril on left ventricular performance, weight and volumes were studied in rats with myocardial infarction. Early effects were examined in rats subjected to coronary ligation and randomized to either immediate treatment with captopril (2 g/liter drinking water) starting 2 h after surgery or no treatment. After 21 days, the treated group showed reductions in mean arterial, left ventricular systolic and left ventricular end-diastolic pressures compared with untreated rats. Right and left ventricular weight and left ventricular volumes were decreased and the ejection fraction index was increased by captopril treatment. To study the late effects of captopril, a second group of rats was randomized to immediate captopril treatment (starting 2 h after surgery), delayed captopril treatment (starting 21 days after surgery) or no treatment. When studied after 4 months of treatment, rats started on captopril treatment 2 h after infarction showed no differences compared with rats started on treatment 21 days after infarction. Treatment with captopril for 4 months produced changes that were similar to those in rats treated for 21 days. Captopril treatment improved hemodynamic function after myocardial infarction in rats examined after either 21 days or 4 months of treatment. The extent of the benefit was similar in the two treatment periods. Initiation of captopril therapy immediately after infarction did not appear to produce a greater effect than treatment started at 21 days after infarction in rats studied after the drug had been administered for 4 months.

Surgical management of cervical soft disc herniation. A comparison between the anterior and posterior approach. Anterior cervical fusion was initially described in the 1950s for cervical spondylotic radiculopathy. The indications for this procedure in the management of soft disc herniation have not been clearly defined. In addition, controversy exists as to whether a cervical soft herniation should be managed by an anterior approach or a posterior cervical laminotomy-foraminotomy. The authors report the results of a prospective study comparing anterior discectomy and fusion to posterior laminotomy-foraminotomy for the management of soft cervical disc herniation. Twenty-eight patients underwent anterior discectomy and fusion (Robinson horseshoe graft) while 16 patients underwent posterior laminotomy-foraminotomy. The disc herniations were classified into two types. Type I were single level anterolateral herniations (33 patients) while type II were central soft disc herniations (11 patients). Clinically, patients with type I herniations manifested signs and symptoms of radiculopathy while patients with type II herniations manifested signs of myelopathy or neck pain and bilateral upper extremity paresthesias in 4 patients. Confirmatory studies were myelography in 12 patients, myelography combined with computed tomography (CT) in 26 patients, and magnetic resonance imaging (MRI) in 6 patients. For type I herniations, 17 patients underwent anterior fusion while 16 patients had a posterior laminotomy-foraminotomy. The 11 patients classified as type II herniation all underwent anterior discectomy and fusion. There were 27 men and 17 women. The age range was 21 to 52 years (mean, 41 years). The follow-up was 1.6 to 8.2 years (mean, 4.2 years).

Oxygen supply and utilization relationships. A reevaluation. The relationship between oxygen transport (TO2) and oxygen consumption (VO2) has been studied in patients with a number of acute and chronic disorders. Many of these patients have been shown to have a linear relationship between these two variables over a wide range of TO2, which has been considered as evidence of pathologic supply dependency. This supply dependency contrasts with animal studies that have clearly demonstrated a biphasic relationship between TO2 and VO2. This review of the available data concerning the relationship between oxygen transport and supply under conditions of increased oxygen requirements and reduced oxygen transport suggests the possibility that the observed interaction in patients may, in many cases, represent the normal physiologic behavior of the system rather than an abnormal manifestation of impaired oxygen extraction.

Increased sensitivity to endotoxemia by tissue necrosis. In this study the interaction of endotoxemia and ischemic organ injury was investigated in a rat model. Animals received lipopolysaccharide to induce endotoxemia and were simultaneously subjected to renal ischemia. If only renal ischemia was induced, moderate azotemia occurred and all animals survived. Lipopolysaccharide treatment caused neither renal failure nor death. However, rats with both endotoxemia and renal ischemia showed severe azotemia, and 50% of the animals died within 48 hours. The observed mortality rate is unlikely related to renal failure since animals subjected to bilateral nephrectomy did not die within 48 hours after treatment with lipopolysaccharide. To further exclude the role of renal failure in the enhanced effect of endotoxemia, experiments were performed in which ischemic kidneys were excised from littermates and were placed in the abdomens of lipopolysaccharide-treated animals. A similar effect was observed: 50% of the animals died within 48 hours. Azotemia did not occur. Since tumor necrosis factor (TNF) is an important cytokine involved in endotoxemia-induced morbidity and death, we studied the role of TNF in our model. Plasma levels of TNF were increased during endotoxemia. Concomitant renal ischemic injury did not influence the concentration of TNF. When animals were treated with recombinant TNF and were subsequently subjected to renal ischemic injury, again a 50% mortality was observed, a rate similar to that in lipopolysaccharide-treated animals. We conclude that the sensitivity to endotoxemia is enhanced by tissue necrosis and may lead to death in the experimental model used in this study.

Quantification of leakage pressures after durotomy repairs in the canine. This study was undertaken to investigate the relative strengths of dural repair using standard suture techniques, suture supplemented with tissue adhesive, and tissue adhesive alone. Uniform 2 mm dural defects were created in adult beagles, repaired, and then subjected to pressurization testing. Defects repaired with suture alone initially leaked within the range of physiologic pressurization, while those supplemented with tissue adhesive or repaired with tissue adhesive alone failed at higher pressurization levels. Histologic sections obtained from the dura treated with fibrin adhesive sealant demonstrated minimal inflammatory response not significantly different than those sections examined at sites repaired by suture alone. A new substance, fibrin adhesive sealant, appears to be useful in effecting dural repair due to its ability to withstand pressures greater than those obtained with suture alone.

Evidence for hypomotility in non-ulcer dyspepsia: a prospective multifactorial study. A prospective multifactorial study of symptoms and disturbance of gastrointestinal function has been undertaken in 50 patients with non-ulcer dyspepsia. Objective tests including solid meal gastric emptying studies, gastric acid secretion, E-HIDA scintiscan for enterogastric bile reflux, and hydrogen breath studies were carried out in all patients and validated against control data. Gastroscopy and biopsy were carried out in non-ulcer dyspepsia patients only. Non-ulcer dyspepsia patients were categorised on the basis of predominant symptoms as: dysmotility-like dyspepsia (n = 22); essential dyspepsia (n = 14), gastro-oesophageal reflux-like dyspepsia (n = 11); and ulcer-like dyspepsia (n = 3). In the total non-ulcer dyspepsia population, solid meal gastric emptying was delayed (T50 mean (SEM) = 102 (6) minutes (patients) v 64 (6) minutes (controls), (p less than 0.01) and high incidences of gastritis (n = 26) and Helicobacter pyloridis infection (n = 18) were found. An inverse correlation was observed between solid meal gastric emptying and fasting peak acid output (r = -0.4; p less than 0.01). Indeed gastric emptying was particularly prolonged in eight patients (T50 mean (SEM) = 139 (15) minutes) with hypochlorhydria. In the non-ulcer dyspepsia population oral to caecal transit time of a solid meal was delayed (mean SEM = 302 (14) minutes (patients) v 244 (12) minutes (controls) (p less than 0.01]. Seven patients had a dual peak of breath hydrogen suggestive of small bowel bacterial overgrowth. No association was observed between symptoms and any of the objective abnormalities.

Integrated magnetic resonance imaging and phosphorus spectroscopy of soft tissue tumors. Eighteen patients with soft tissue masses underwent integrated magnetic resonance imaging (MRI) and phosphorus spectroscopy (31P-MRS) to evaluate benign and malignant tumor morphology and metabolism. Spectra from soft tissue tumors had a significantly higher proportion of phosphate in the low-energy portion of the 31P spectrum (P less than 0.001) with a concomitant decrease in phosphocreatine (P less than 0.01) compared with 31P spectra from normal muscle. Malignant tumors had a mean pH of 7.35 +/- 0.13 which was greater than that of muscle tissue with a mean pH of 7.08 +/- 0.07 (P less than 0.001). All tumors had greater relative levels of phosphomonoesters, inorganic phosphate, and phosphodiesters compared with those in muscle tissue but considerable variability among tumors was noted due to tumor size, extent of tumor necrosis, and muscle contamination. Integrated MRI/MRS studies are necessary to provide exact localization of the tumor and a more correct interpretation of the 31P-MRS data.

Enterogenous cyst of the cerebellopontine angle cistern: case report. A case of an enterogenous cyst located in the cerebellopontine angle cistern is presented. These cysts have usually been found in the spinal canal, and their intracranial occurrence is exceptional. In the present case, the cyst was lined histologically by a single epithelial layer of cuboidal cells with some glandular structures resembling the fundic glands of the stomach. The unusual location of the cyst and its histological features are discussed.

1,25-Dihydroxyvitamin D3 receptor RNA: expression in hematopoietic cells. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] induces differentiation and inhibits proliferation of myeloid leukemic cells from various lines and patients; these effects are probably mediated through the 1,25(OH)2D3 receptor. Little is known of expression of 1,25(OH)2D3 receptor RNA in hematopoietic cells. We examined the expression and modulation of expression of 1,25(OH)2D3 receptor RNA in various proliferating and nonproliferating hematopoietic cells. Constitutive expression of 1,25(OH)2D3 receptor RNA was detected in various kinds of hematopoietic cells, including macrophages and activated T lymphocytes, as well as in cell lines KG-1 (myeloblasts), HL-60 (promyelocytes), ML-3 (myelomonoblasts), U937, THP-1 (monoblasts), K562 (erythroblasts), and S-LB1 (HTLV-1-transfected T lymphocytes). Receptor transcripts were 4.6 kilobases (kb), and no variant sizes were observed. All cell lines examined in this group also expressed 1,25(OH)2D3 receptors. Most B lymphocyte lines expressed negligible levels of 1,25(OH)2D3 receptor RNA and protein; however; analysis of a lymphoid/myeloid somatic hybrid suggested that suppression of expression of 1,25(OH)2D3 receptor RNA in B lymphocytes may be a dominant characteristic. HL-60 cells were cultured with 10(-7) mol/L 1,25(OH)2D3 for 24 to 72 hours, and levels of expression of 1,25(OH)2D3 receptor and its RNA were examined. Levels of RNA coding for the receptor were not modulated by exposure to high levels of ligand. Levels of occupied 1,25(OH)2D3 receptor protein increased in these HL-60 cells; but the total number of 1,25(OH)2D3 receptors decreased about 50% at 24 hours and returned toward normal at 72 hours. Steady-state levels of 1,25(OH)2D3 receptor RNA were not affected by terminal differentiation of HL-60 toward either granulocytes or macrophages. Nondividing macrophages from normal individuals also expressed 1,25(OH)2D3 receptor RNA. In contrast, nondividing peripheral blood lymphocytes from normal individuals did not express 1,25(OH)2D3 receptor RNA; with stimulation of proliferation of these cells, accumulation of 1,25(OH)2D3 receptor RNA increased markedly. Half-life (t1/2) of 1,25(OH)2D3 receptor RNA in T lymphocytes was short (1 hour) as determined by measuring decay of the message after addition of actinomycin D. Consistent with this short t1/2, accumulation of 1,25(OH)2D3 receptor RNA increased in cells as their protein synthesis was inhibited. Further studies are required to understand the physiologic role of 1,25(OH)2D3 receptors in myeloid cells and proliferating T lymphocytes.

Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.

Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients. Insulinlike growth factor I (IGF-I) has been shown to be a potent mitogen for breast cancer cells in vitro, and IGF-I receptors have been demonstrated on human primary breast neoplasms. In a randomized, placebo-controlled study, we document that administration of the antiestrogen tamoxifen to patients with breast cancer was associated with a statistically significant (P = .002) reduction in the serum level of IGF-I. The mean IGF-I level was 1.4 U/mL in the placebo-treated group and 0.9 U/mL in the tamoxifen-treated group. Because serum IGF-I level is growth hormone (GH) dependent and because data suggest that the pubertal surge in GH and IGF-I levels is sex steroid dependent, we speculate that the mechanism underlying our observation may involve blockade by tamoxifen of estrogen action in the hypothalamic-pituitary axis. We conclude that tamoxifen treatment reduces IGF-I levels and that this reduction may contribute to the therapeutic effect of the drug.

Hepatitis B virus integration in hepatitis B virus-related hepatocellular carcinoma in childhood. In Taiwan, hepatocellular carcinoma is one of the major malignancies in children between 5 and 14 yr of age. We studied the status of hepatitis B virus DNA in the hepatocellular carcinoma and nontumorous liver tissues of eight children with positive serum HBsAg and maternal HBsAg. The hepatocellular carcinoma tissues from five of the eight children showed integration of hepatitis B virus DNA into host cellular DNA sequences. A pattern of single-site integration in four children and a multiple-site integration pattern in one child were demonstrated. In the remaining three children, hepatitis B virus DNA could not be demonstrated in the tumor tissues. Using subgenomic fragments of the hepatitis B virus genome as probes, we found that the X gene fragment and the surface antigen gene fragment were the most conserved sequences. The single-site integration of hepatitis B virus DNA in childhood hepatocellular carcinoma may have hit the critical region, resulting in insertional mutagenesis and early development of hepatocellular carcinoma. With a short incubation period and less exposure to environmental carcinogens during early life, childhood hepatocellular carcinoma may provide a good model to study the carcinogenic potential of hepatitis B virus.

Relevance of intrinsic sympathomimetic activity for beta blockers. Intrinsic sympathomimetic activity (ISA) characterizes a group of beta blockers that are able to stimulate beta-adrenergic receptors (agonist effect) and to oppose the stimulating effects of catecholamines (antagonist effect) in a competitive way. Partial agonists are ligands that elicit a submaximal response when bound to beta receptors at maximal occupancy. In the isolated rat atrium, acebutolol produces a maximal stimulatory effect that is only 17 +/- 8% of the maximal effect induced by the full beta agonist isoproterenol. The presence of ISA results in less resting bradycardia and less of a reduction in cardiac output than is observed with beta blockers without ISA. In the long term, partial beta agonists may produce arterial vasodilation and increase arterial compliance, possibly leading to additional beneficial effects in the treatment of hypertension. beta blockers with ISA do not have adverse effects on plasma lipoproteins during long-term treatment; in addition, the presence of ISA could counteract the up-regulation of beta adrenoceptors often observed with beta blockers without ISA. Finally, the presence of ISA has been a conflicting issue for the use of such beta blockers in secondary prevention after myocardial infarction. However, the impressive results of the Acebutolol Prevention of Secondary Infarction trial in high-risk patients after myocardial infarction show that acebutolol, a beta blocker with moderate partial agonist activity, can be effective in decreasing the postinfarction mortality rate. By exhibiting a strikingly different hemodynamic profile from that of beta blockers without ISA, the partial beta agonists form an intriguing pharmacologic class of drugs for which prospective clinical trials should be extensively pursued.

Perioperative myocardial ischemia in patients undergoing noncardiac surgery--II: Incidence and severity during the 1st week after surgery. The Study of Perioperative Ischemia (SPI) Research Group. Because of the importance of postoperative myocardial ischemia and because substantial physiologic changes can occur for prolonged periods postoperatively, the incidence, severity and temporal course of myocardial ischemia were studied in 100 high risk patients during the 1st week after major noncardiac surgery. Electrocardiographic (ECG) changes consistent with ischemia were continuously monitored using ambulatory solid state ECG in the 100 patients with or at risk for coronary artery disease. Ischemic episodes were defined as reversible ST segment depression greater than or equal to 1 mm or elevation greater than or equal to 2 mm above the baseline value, with the baseline adjusted for respiratory and positional variation and temporal drift. All ischemic episodes were confirmed by three independent blinded investigators using hard-copy recordings. Total ECG monitoring time was 10,445 h. Twenty-seven patients (27%) developed 437 episodes of ischemia during the 1st week after surgery. The total duration of ischemia was 18,658 min, or 1.8 min of ischemia/h monitored. Ischemia was most severe during the early (days 0 to 3) versus late (days 4 to 7) postoperative period: 284 versus 153 episodes; 2.2 versus 1.2 min of ischemia/h. The greatest severity occurred on postoperative day 3: 109 episodes, 3.4 min of ischemia/h monitored, 1.5 mm mean ST change and 130 min mean duration. However, in 8% of patients, severe episodes also occurred late: postoperative day 6 = 44 episodes, 1.7 min of ischemia/h monitored, 1.3 mm mean ST change (59% greater than or equal to 2 mm) and 92 min mean duration. Most ischemic episodes (57%) were associated with tachycardia.

Strokes in African-Americans. Hypertension is the most important risk factor for stroke, especially in African-Americans. Improved control of high blood pressure nationwide is a key factor in the recent dramatic decline in stroke frequency, most notably in African-American women. Hypertension control programs must be adequately funded and expanded. African-Americans have a disproportionately high incidence of risk factors for stroke, including hypertension. There is evidence that the cerebral vessels involved in ischemic stroke in African-Americans may differ from those of Caucasians. There is an urgent need for more research on stroke in general, risk factor relations in particular, and mechanisms in the pathogenesis of stroke in African-Americans.

Helicobacter pylori infection in pernicious anemia: a prospective controlled study. Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process.

Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia. Vitamin B12 and folate concentrations were measured in serum and cerebrospinal fluid (CSF) in 293 neurological patients. Serum and CSF vitamin B12 concentrations showed a positive correlation. In individual patients CSF B12 concentrations varied considerably for a given serum concentration. The median serum vitamin B12 concentration of the Alzheimer's type dementia group was significantly lower compared with that of a control group. Lower median CSF vitamin B12 concentrations were found in groups of patients with multiple sclerosis and Alzheimer's type dementia. Five patients with heterogeneous clinical pictures had unexplained low serum and CSF B12 concentrations without macrocytosis. Two patients had very high serum B12 and low-normal CSF concentrations which could be explained by a blood-brain barrier transport defect. Serum and CSF folate concentrations did not show significant differences between the various groups.

Comparison of early versus late experience with percutaneous mitral balloon valvuloplasty. The immediate outcome of the first 150 patients (Group 1) and the last 161 patients (Group 2) who underwent percutaneous mitral balloon valvuloplasty was compared. There was no difference between the two groups in age, gender, New York Heart Association functional class, presence of calcification, atrial fibrillation, degree of mitral regurgitation, mean pulmonary artery pressure, left atrial pressure, cardiac output, pulmonary vascular resistance, mitral valve gradient and mitral valve area. Fewer patients in Group 1 than Group 2 had an echocardiographic score less than or equal to 8 (62% versus 69%, respectively, p = 0.02). The atrial septum was dilated with an 8 mm balloon in 74% of patients in Group 1 and with a 5 mm balloon in all patients in Group 2. Ratio of effective balloon dilating area to body surface area was larger in Group 1 than in Group 2 (4.05 +/- 0.07 versus 3.7 +/- 0.03 cm2/m2, p = 0.0001). A good result (mitral valve area greater than or equal to 1.5 cm2) was obtained in 77% and 75% in Groups 1 and 2, respectively (p = NS). After percutaneous mitral valvuloplasty, a greater than or equal to 2 grade increase in mitral regurgitation was noted in 12% of Group 1 and 6% of Group 2 (p = 0.02) and a left to right shunt was detected in 22% of Group 1 and 11% of Group 2 (p = 0.0001). There were three procedure-related deaths in Group 1, but none in Group 2.

The effect of improved cementing techniques on component loosening in total hip replacement. An 11-year radiographic review. Improved cementing techniques have been shown to decrease the rate of aseptic loosening of femoral components of cemented total hip replacements at five to seven years. We now report our results in 105 hips in 93 patients at 10 to 12.7 years (mean 11.2). The improved techniques included use of a medullary plug, a cement gun, a doughy mix of Simplex P and a collared stem of chrome cobalt. Only three femoral components had definitely loosened, none were probably loose and 24 were graded as possibly loose. In contrast, the incidence of radiographic loosening on the acetabular side was 42%. Improved cementing techniques have produced a marked reduction in the rate of aseptic loosening of the femoral component, but the incidence of acetabular loosening is unchanged.

Postoperative pancreatic abscess due to Plesiomonas shigelloides. Plesiomonas shigelloides is being recognized with increasing frequency as a human pathogen. The organism is ubiquitous in fresh and brackish water, and clinical illness has been associated with foreign travel and ingestion of inadequately cooked seafood. We describe a 64-year-old Filipino woman who presented 2 weeks after elective cholecystectomy and pancreatic biopsy with left upper quadrant pain, abdominal distention, and fever. Computerized tomography of the abdomen revealed an abscess in the tail of the pancreas with fluid accumulation in the lesser omental sac. Percutaneous aspiration yielded purulent material, and P. shigelloides was recovered in pure culture. To our knowledge, this is the first reported case of pancreatic abscess due to P. shigelloides.

Sleep apnoea syndrome associated with maxillofacial abnormalities. Four cases with Obstructive Sleep Apnoea Syndrome (OSAS) are presented. They consisted of two cases with TMJ ankylosis with micrognathia, one case with Treacher Collins Syndrome, and one case with the Long Face Syndrome. Standard and specific cephalometric parameters were obtained to detect the site of the obstruction. Polysomnographic studies yielded information regarding the patient's sleep-wake state, respiratory and cardiac functioning, pre- and post-operatively. A temporary tracheostomy corrected the symptoms in one patient but the syndrome recurred when it was closed. Surgical correction of the maxillofacial anomalies will re-establish normal sleep patterns preventing OSAS.

Gallium uptake in tryptophan-related pulmonary disease. We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking "high doses" of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.

Percutaneous balloon pulmonic valvuloplasty following treated endocarditis in a patient with congenital pulmonary valve stenosis. A 36-year-old woman with congenital pulmonary valve stenosis developed the rare complication of endocarditis of the valve. After successful sterilization of the valve, the patient underwent percutaneous balloon pulmonic valvuloplasty at a later date. The procedure successfully reduced the peak pulmonary valve gradient from 94 to 45 mm Hg. Percutaneous balloon valvuloplasty is the procedure of choice for treatment of congenital pulmonary valvular stenosis, even in the unusual patient who has healed endocarditis of the pulmonary valve.

Long-term cardiopulmonary bypass by peripheral cannulation in a model of total heart failure. The decompression of the left heart through a percutaneous helical spring positioned within the lumen of the tricuspid and pulmonary artery valves. We performed long-term closed-chest cardiopulmonary bypass in an animal model of total heart failure (induced ventricular fibrillation). The extracorporeal system included a venous reservoir, a roller pump, a membrane lung, and a blood pulsator system. We cannulated the right external jugular vein for venous drainage and the right subclavian artery for arterial return. To decompress the left heart we passed by percutaneous cannulation a special helical spring mounted on a Swan-Ganz catheter (Baxter Edwards Divisions, Irvine, Calif.) and positioned it to rest within the pulmonary artery and tricuspid valves, which rendered them partly incompetent. After induced ventricular fibrillation, blood flow was raised to keep the central venous pressure at baseline values. The lungs were ventilated with 5% carbon dioxide in room air. During bypass, mean pulmonary artery pressure was 10.0 +/- 1.7 mm Hg, mean wedge pressure 11.9 +/- 1.8 mm Hg, and mean blood pressure 95.2 +/- 5.6 mm Hg. After 2 days (four animals) and 3 days (two animals) the hearts were defibrillated. There was immediate ejection from both sides of the heart. All sheep were weaned from bypass within 29 +/- 11 minutes and their lungs were ventilated with room air within 42 +/- 34 minutes. At autopsy hearts and lungs grossly appeared normal. We conclude that the percutaneous helical spring resting within right heart valves provided excellent decompression throughout the study, with full recovery of heart and lung function on defibrillation.

Hyponatremia-induced inhibition of magnocellular neurons causes stressor-selective impairment of stimulated adrenocorticotropin secretion in rats. Chronically hyponatremic rats were subjected to various stressors in order to evaluate the possible contribution of magnocellular neurons to the regulation of ACTH secretion, since such rats have markedly inhibited secretion and synthesis of magnocellular arginine vasopressin (AVP) and oxytocin (OT). Stress caused by a novel environment or by insulin-induced hypoglycemia resulted in moderate increases in plasma ACTH, which were of similar magnitude in both hyponatremic and normonatremic rats, and these stressors caused no increase in plasma AVP and OT levels in either group of rats. However, when exposed to ether, hyponatremic rats exhibited a significantly blunted ACTH response compared to normonatremic controls (331 +/- 49 vs. 740 +/- 124 pg/ml; P less than 0.01, respectively), and plasma AVP levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. Intravenous infusion of 2 M NaCl also caused an ACTH release in hyponatremic rats that was significantly smaller than that in their normonatremic counterparts (228 +/- 52 vs. 479 +/- 85 pg/ml; P less than 0.05, respectively), and in this case both plasma AVP and OT levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. However, hyponatremic rats exhibited greatly increased plasma ACTH levels 2 and 96 h after adrenalectomy (ADX), which were statistically equivalent to the increases in ACTH levels in normonatremic rats after ADX. Seven days after ADX parvocellular neurons of the paraventricular nucleus showed strongly increased CRF-41 and AVP-neurophysin, but not OT-neurophysin, immunoreactivities in both normonatremic and hyponatremic rats. These results show that parvocellular CRF-41/AVP-producing neurons in the paraventricular nucleus are not inhibited by chronic hyponatremia, in contrast to magnocellular neurons, and suggest that ACTH secretion induced by ether or hypertonic saline, but not by novel environment or insulin-induced hypoglycemia, is partially mediated by magnocellular AVP and/or OT.