Tricuspid valve regurgitation and lithium carbonate toxicity in a newborn infant.

A newborn with massive tricuspid regurgitation, atrial flutter, congestive heart failure, and a high serum lithium level is described. This is the first patient to initially manifest tricuspid regurgitation and atrial flutter, and the 11th described patient with cardiac disease among infants exposed to lithium compounds in the first trimester of pregnancy. Sixty-three percent of these infants had tricuspid valve involvement. Lithium carbonate may be a factor in the increasing incidence of congenital heart disease when taken during early pregnancy. It also causes neurologic depression, cyanosis, and cardiac arrhythmia when consumed prior to delivery.

Tricuspid valve regurgitation

lithium carbonate

toxicity

tricuspid regurgitation

atrial flutter

congestive heart failure

lithium

tricuspid regurgitation

atrial flutter

cardiac disease

lithium

Lithium carbonate

congenital heart disease

neurologic depression

cyanosis

cardiac arrhythmia


Phenobarbital-induced dyskinesia in a neurologically-impaired child.

A 2-year-old child with known neurologic impairment developed a dyskinesia soon after starting phenobarbital therapy for seizures. Known causes of movement disorders were eliminated after evaluation. On repeat challenge with phenobarbital, the dyskinesia recurred. Phenobarbital should be added to the list of anticonvulsant drugs that can cause movement disorders.

Phenobarbital

dyskinesia

neurologically-impaired

neurologic impairment

dyskinesia

phenobarbital

seizures

movement disorders

phenobarbital

dyskinesia

Phenobarbital

movement disorders


Acute changes of blood ammonia may predict short-term adverse effects of valproic acid.

Valproic acid (VPA) was given to 24 epileptic patients who were already being treated with other antiepileptic drugs. A standardized loading dose of VPA was administered, and venous blood was sampled at 0, 1, 2, 3, and 4 hours. Ammonia (NH3) was higher in patients who, during continuous therapy, complained of drowsiness (7 patients) than in those who were symptom-free (17 patients), although VPA plasma levels were similar in both groups. By measuring VPA-induced changes of blood NH3 content, it may be possible to identify patients at higher risk of obtundation when VPA is given chronically.

ammonia

valproic acid

Valproic acid

VPA

epileptic

VPA

Ammonia

drowsiness

VPA

VPA

VPA


Effects of calcitonin on rat extrapyramidal motor system: behavioral and biochemical data.

The effects of i.v.c. injection of human and salmon calcitonin on biochemical and behavioral parameters related to the extrapyramidal motor system, were investigated in male rats. Calcitonin injection resulted in a potentiation of haloperidol-induced catalepsy and a partial prevention of apomorphine-induced hyperactivity. Moreover calcitonin induced a significant decrease in nigral GAD activity but no change in striatal DA and DOPAC concentration or GAD activity. The results are discussed in view of a primary action of calcitonin on the striatonigral GABAergic pathway mediating the DA-related behavioral messages of striatal origin.

haloperidol

catalepsy

apomorphine

hyperactivity

DA

DOPAC

DA


Development of isoproterenol-induced cardiac hypertrophy.

The development of cardiac hypertrophy was studied in adult female Wistar rats following daily subcutaneous injections of isoproterenol (ISO) (0.3 mg/kg body weight). A time course was established for the change in tissue mass, RNA and DNA content, as well as hydroxyproline content. Heart weight increased 44% after 8 days of treatment with a half time of 3.4 days. Ventricular RNA content was elevated 26% after 24 h of a single injection and reached a maximal level following 8 days of therapy. The half time for RNA accumulation was 2.0 days. The total content of hydroxyproline remained stable during the first 2 days of treatment but increased 46% after 4 days of therapy. Ventricular DNA content was unchanged during the early stage (1-4 days) of hypertrophic growth but increased to a new steady-state level 19% above the controls after 8 days of treatment. Intraventricular pressures and coronary flow measures were similar for control and experimental animals following 4 days of developed hypertrophy. However, dP/dt in the ISO-treated hearts was slightly but significantly (P less than 0.05) elevated. These data indicate that the adaptive response to ISO shows an early hypertrophic phase (1-4 days) characterized by a substantial increase in RNA content and cardiac mass in the absence of changes in DNA. However, prolonged stimulation (8-12 days) appears to represent a complex integration of both cellular hypertrophy and hyperplasia within the heart.

isoproterenol

cardiac hypertrophy

cardiac hypertrophy

isoproterenol

ISO

hydroxyproline

hydroxyproline

hypertrophic

hypertrophy

ISO

ISO

hypertrophic

hypertrophy

hyperplasia


Co-carcinogenic effect of retinyl acetate on forestomach carcinogenesis of male F344 rats induced with butylated hydroxyanisole.

The potential modifying effect of retinyl acetate (RA) on butylated hydroxyanisole (BHA)-induced rat forestomach tumorigenesis was examined. Male F344 rats, 5 weeks of age, were maintained on diet containing 1% or 2% BHA by weight and simultaneously on drinking water supplemented with RA at various concentrations (w/v) for 52 weeks. In groups given 2% BHA, although marked hyperplastic changes of the forestomach epithelium were observed in all animals, co-administration of 0.25% RA significantly (P less than 0.05) increased the incidence of forestomach tumors (squamous cell papilloma and carcinoma) to 60% (9/15, 2 rats with carcinoma) from 15% (3/20, one rat with carcinoma) in the group given RA-free water. In rats given 1% BHA, RA co-administered at a dose of 0.05, 0.1, 0.2 or 0.25% showed a dose-dependent enhancing effect on the development of the BHA-induced epithelial hyperplasia. Tumors, all papillomas, were induced in 3 rats (17%) with 0.25% RA and in one rat (10%) with 0.05% RA co-administration. RA alone did not induce hyperplastic changes in the forestomach. These findings indicate that RA acted as a co-carcinogen in the BHA forestomach carcinogenesis of the rat.

carcinogenic

retinyl acetate

forestomach carcinogenesis

butylated hydroxyanisole

retinyl acetate

RA

butylated hydroxyanisole

BHA

forestomach tumorigenesis

BHA

RA

BHA

RA

forestomach tumors

squamous cell papilloma

carcinoma

carcinoma

carcinoma

RA

BHA

RA

BHA

epithelial hyperplasia

Tumors

papillomas

RA

RA

RA

RA

BHA

forestomach carcinogenesis


Ketanserin pretreatment reverses alfentanil-induced muscle rigidity.

Systemic pretreatment with ketanserin, a relatively specific type-2 serotonin receptor antagonist, significantly attenuated the muscle rigidity produced in rats by the potent short-acting opiate agonist alfentanil. Following placement of subcutaneous electrodes in each animal's left gastrocnemius muscle, rigidity was assessed by analyzing root-mean-square electromyographic activity. Intraperitoneal ketanserin administration at doses of 0.63 and 2.5 mg/kg prevented the alfentanil-induced increase in electromyographic activity compared with animals pretreated with saline. Chlordiazepoxide at doses up to 10 mg/kg failed to significantly influence the rigidity produced by alfentanil. Despite the absence of rigidity, animals that received ketanserin (greater than 0.31 mg/kg i.p.) followed by alfentanil were motionless, flaccid, and less responsive to external stimuli than were animals receiving alfentanil alone. Rats that received ketanserin and alfentanil exhibited less rearing and exploratory behavior at the end of the 60-min recording period than did animals that received ketanserin alone. These results, in combination with previous work, suggest that muscle rigidity, a clinically relevant side-effect of parenteral narcotic administration, may be partly mediated via serotonergic pathways. Pretreatment with type-2 serotonin antagonists may be clinically useful in attenuating opiate-induced rigidity, although further studies will be necessary to assess the interaction of possibly enhanced CNS, cardiovascular, and respiratory depression.

Ketanserin

alfentanil

muscle rigidity

ketanserin

serotonin

muscle rigidity

alfentanil

rigidity

ketanserin

alfentanil

Chlordiazepoxide

rigidity

alfentanil

rigidity

ketanserin

alfentanil

alfentanil

ketanserin

alfentanil

ketanserin

muscle rigidity

serotonin

rigidity

cardiovascular depression

respiratory depression


Glycopyrronium requirements for antagonism of the muscarinic side effects of edrophonium.

We have compared, in 60 adult patients, the cardiovascular effects of glycopyrronium 5 micrograms kg-1 and 10 micrograms kg-1 given either simultaneously or 1 min before edrophonium 1 mg kg-1. Significant differences between the four groups were detected (P less than 0.001). Both groups receiving 10 micrograms kg-1 showed increases in heart rate of up to 30 beat min-1 (95% confidence limits 28-32 beat min-1). Use of glycopyrronium 5 micrograms kg-1 provided greater cardiovascular stability and, given 1 min before the edrophonium, was sufficient to minimize early, edrophonium-induced bradycardias. This low dose of glycopyrronium provided good control of oropharyngeal secretions.

Glycopyrronium

edrophonium

glycopyrronium

edrophonium

glycopyrronium

edrophonium

edrophonium

bradycardias

glycopyrronium


Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat.

Whereas muscular rigidity is a well-known side effect that is associated with high-dose fentanyl anesthesia, a paucity of information exists with regard to its underlying mechanism(s). We investigated in this study the possible engagement of locus coeruleus of the pons in this phenomenon, using male Sprague-Dawley rats anesthetized with ketamine. Under proper control of respiration, body temperature and end-tidal CO2, intravenous administration of fentanyl (50 or 100 micrograms/kg) consistently promoted an increase in electromyographic activity recorded from the gastrocnemius and abdominal rectus muscles. Such an induced muscular rigidity by the narcotic agent was significantly antagonized or even reduced by prior electrolytic lesions of the locus coeruleus or pretreatment with the alpha-adrenoceptor blocker, prazosin. Microinjection of fentanyl (2.5 micrograms/50 nl) directly into this pontine nucleus, on the other hand, elicited discernible electromyographic excitation. It is speculated that the induction of muscular rigidity by fentanyl may involve the coerulospinal noradrenergic fibers to the spinal motoneurons.

fentanyl

muscular rigidity

muscular rigidity

fentanyl

ketamine

fentanyl

muscular rigidity

prazosin

fentanyl

muscular rigidity

fentanyl


Cerebral sinus thrombosis as a potential hazard of antifibrinolytic treatment in menorrhagia.

We describe a 42-year-old woman who developed superior sagittal and left transverse sinus thrombosis associated with prolonged epsilon-aminocaproic acid therapy for menorrhagia. This antifibrinolytic agent has been used in women with menorrhagia to promote clotting and reduce blood loss. Although increased risk of thromboembolic disease has been reported during treatment with epsilon-aminocaproic acid, cerebral sinus thrombosis has not been previously described. Careful use of epsilon-aminocaproic acid therapy is recommended.

Cerebral sinus thrombosis

menorrhagia

sagittal
sinus thrombosis

left transverse sinus thrombosis

epsilon-aminocaproic acid

menorrhagia

menorrhagia

blood loss

thromboembolic disease

epsilon-aminocaproic acid

cerebral sinus thrombosis

epsilon-aminocaproic acid


Hemorrhagic cystitis complicating bone marrow transplantation.

Hemorrhagic cystitis is a potentially serious complication of high-dose cyclophosphamide therapy administered before bone marrow transplantation. As standard practice at our institution, patients who are scheduled to receive a bone marrow transplant are treated prophylactically with forced hydration and bladder irrigation. In an attempt to obviate the inconvenience of bladder irrigation, we conducted a feasibility trial of uroprophylaxis with mesna, which neutralizes the hepatic metabolite of cyclophosphamide that causes hemorrhagic cystitis. Of 97 patients who received standard prophylaxis, 4 had symptomatic hemorrhagic cystitis. In contrast, two of four consecutive patients who received mesna uroprophylaxis before allogeneic bone marrow transplantation had severe hemorrhagic cystitis for at least 2 weeks. Because of this suboptimal result, we resumed the use of bladder irrigation and forced hydration to minimize the risk of hemorrhagic cystitis.

Hemorrhagic cystitis

Hemorrhagic

cystitis

Hemorrhagic cystitis

Hemorrhagic

cystitis

cyclophosphamide

mesna

cyclophosphamide

hemorrhagic cystitis

hemorrhagic

cystitis

hemorrhagic cystitis

hemorrhagic

cystitis

mesna

hemorrhagic cystitis

hemorrhagic

cystitis

hemorrhagic cystitis

hemorrhagic

cystitis


Reversal of central benzodiazepine effects by flumazenil after intravenous conscious sedation with diazepam and opioids: report of a double-blind multicenter study. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group II.

The efficacy and safety of a new benzodiazepine antagonist, flumazenil, were assessed in a double-blind multicenter study. Flumazenil (mean dose, 0.76 mg) or placebo (mean dose, 8.9 ml) was administered intravenously to 130 and 67 patients, respectively, who had been given diazepam in conjunction with an opioid (fentanyl, meperidine, or morphine) for the induction and maintenance of intravenous conscious sedation for diagnostic or therapeutic surgical procedures. The group assessable for efficacy comprised 122 patients treated with flumazenil and 64 patients given placebo. After 5 minutes, 80/115 (70%) flumazenil-treated patients, compared with 21/63 (33%) placebo-treated patients, were completely awake and alert, as indicated by a score of 5 on the Observer's Assessment of Alertness/Sedation Scale. Ninety-five percent of patients in each group who attained a score of 5 at the 5-minute assessment showed no loss of alertness throughout the 180-minute assessment period. Flumazenil-treated patients also performed significantly better on the Finger-to-Nose Test and the recall of pictures shown at the 5-minute assessment. Flumazenil was well tolerated, with no serious adverse effects reported. Thirty-nine (30%) of flumazenil-treated patients, compared with 17 (25%) of placebo-treated patients had one or more drug-related adverse experiences. The most common adverse effects were nausea and vomiting in the flumazenil group and nausea and injection-site pain in the placebo group. Flumazenil was found to promptly reverse sedation induced by diazepam in the presence of opioids.

benzodiazepine

flumazenil

diazepam

Flumazenil

Diazepam

benzodiazepine

flumazenil

Flumazenil

diazepam

fentanyl

meperidine

morphine

flumazenil

flumazenil

Flumazenil

Flumazenil

flumazenil

nausea

vomiting

flumazenil

nausea

pain

Flumazenil

diazepam


Hepatic adenomas and focal nodular hyperplasia of the liver in young women on oral contraceptives: case reports.

Two cases of hepatic adenoma and one of focal nodular hyperplasia presumably associated with the use of oral contraceptives, are reported. Special reference is made to their clinical presentation, which may be totally asymptomatic. Liver-function tests are of little diagnostic value, but valuable information may be obtained from both liver scanning and hepatic angiography. Histologic differences and clinical similarities between hepatic adenoma and focal nodular hyperplasia of the liver are discussed.

adenomas

focal nodular hyperplasia

oral contraceptives

adenoma

focal nodular hyperplasia

oral contraceptives

adenoma

focal nodular hyperplasia


Arterial thromboembolism in patients receiving systemic heparin therapy: a complication associated with heparin-induced thrombocytopenia.

Arterial thromboembolism is a recognized complication of systemic heparin therapy. Characteristic of the entity is arterial occlusion by platelet-fibrin thrombi with distal ischemia occurring four to twenty days after the initiation of heparin therapy, preceded by profound thrombocytopenia with platelet counts in the range of 30,000 to 40,000 per cubic millimeter. The clinically apparent occlusion may be preceded by gastrointestinal and musculoskeletal symptoms that appear to be ischemic in origin, and might serve to warn the clinician of these complications. Previous reports of these phenomena as well as recent studies of the effect of heparin are reviewed. The common factor relating thromboembolism and thrombocytopenia is heparin-induced platelet aggregation. Appropriate treatment consists of discontinuation of heparin, and anticoagulation with sodium warfarin if necessary. Vascular procedures are performed as indicated.

thromboembolism

heparin

heparin

thrombocytopenia

thromboembolism

heparin

arterial occlusion

thrombi

ischemia

heparin

thrombocytopenia

gastrointestinal symptoms

musculoskeletal symptoms

ischemic

heparin

thromboembolism

thrombocytopenia

heparin

platelet aggregation

heparin

sodium warfarin


Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure.

BACKGROUND: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown. AIM: To examine whether paracetamol-induced acute liver failure increases long-term mortality. METHODS: We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984-2004. We compared age-specific mortality rates from 1 year post-discharge through 2008 between those in whom the liver injury led to an acute liver failure and those in whom it did not. RESULTS: We included 641 patients. On average, age-specific mortality rates were slightly higher for the 101 patients whose paracetamol-induced liver injury had caused an acute liver failure (adjusted mortality rate ratio = 1.70, 95% CI 1.02-2.85), but the association was age-dependent, and no survivors of acute liver failure died of liver disease, whereas suicides were frequent in both groups. These observations speak against long-term effects of acute liver failure. More likely, the elevated mortality rate ratio resulted from incomplete adjustment for the greater prevalence of substance abuse among survivors of acute liver failure. CONCLUSIONS: Paracetamol-induced acute liver failure did not affect long-term mortality. Clinical follow-up may be justified by the cause of the liver failure, but not by the liver failure itself.

paracetamol

acute liver failure

paracetamol

acute liver failure

paracetamol

acute liver failure

paracetamol

acute liver injury

liver injury

acute liver failure

paracetamol

liver injury

acute liver failure

acute liver failure

liver disease

acute liver failure

substance abuse

acute liver failure

Paracetamol

acute liver failure

liver failure

liver failure


Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population.

BACKGROUND: Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for psychotic disorders such as schizophrenia. The serotonin 6 (5-HT6) receptor is therapeutically targeted by several second generation antipsychotics, such as clozapine and olanzapine, and d-amphetamine-induced hyperactivity in rats is corrected with the use of a selective 5-HT6 receptor antagonist. In addition, the disrupted prepulse inhibition induced by d-amphetamine or phencyclidine was restored by 5-HT6 receptor antagonist in an animal study using rats. These animal models were considered to reflect the positive symptoms of schizophrenia, and the above evidence suggests that altered 5-HT6 receptors are involved in the pathophysiology of psychotic disorders. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an analysis of the association of the 5-HT6 gene (HTR6) with METH-induced psychosis. METHOD: Using five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. RESULTS: rs6693503 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this association remained significant after Bonferroni correction. In the haplotype-wise analysis, we detected an association between two markers (rs6693503 and rs1805054) and three markers (rs6693503, rs1805054 and rs4912138) in HTR6 and METH-induced psychosis patients, respectively. CONCLUSION: HTR6 may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population.

Serotonin

methamphetamine

psychosis

psychotic disorders

schizophrenia

serotonin

clozapine

olanzapine

d-amphetamine

hyperactivity

d-amphetamine

phencyclidine

schizophrenia

psychotic disorders

methamphetamine

METH

psychosis

paranoid type schizophrenia

METH

psychosis

METH

psychosis

methamphetamine

METH

psychosis

METH

psychosis

METH

psychosis


Effect of increasing intraperitoneal infusion rates on bupropion hydrochloride-induced seizures in mice.

BACKGROUND: It is not known if there is a relationship between input rate and incidence of bupropion-induced seizures. This is important, since different controlled release formulations of bupropion release the active drug at different rates. METHODS: We investigated the effect of varying the intraperitoneal infusion rates of bupropion HCl 120 mg/kg, a known convulsive dose 50 (CD50), on the incidence and severity of bupropion-induced convulsions in the Swiss albino mice. A total of 69 mice, approximately 7 weeks of age, and weighing 21.0 to 29.1 g were randomly assigned to bupropion HCl 120 mg/kg treatment by intraperitoneal (IP) administration in 7 groups (9 to 10 animals per group). Bupropion HCl was infused through a surgically implanted IP dosing catheter with infusions in each group of 0 min, 15 min, 30 min, 60 min, 90 min, 120 min, and 240 min. The number, time of onset, duration and the intensity of the convulsions or absence of convulsions were recorded. RESULTS: The results showed that IP administration of bupropion HCl 120 mg/kg by bolus injection induced convulsions in 6 out of 10 mice (60% of convulsing mice) in group 1. Logistic regression analysis revealed that infusion time was significant (p = 0.0004; odds ratio = 0.974) and increasing the IP infusion time of bupropion HCl 120 mg/kg was associated with a 91% reduced odds of convulsions at infusion times of 15 to 90 min compared to bolus injection. Further increase in infusion time resulted in further reduction in the odds of convulsions to 99.8% reduction at 240 min. CONCLUSION: In conclusion, the demonstration of an inverse relationship between infusion time of a fixed and convulsive dose of bupropion and the risk of convulsions in a prospective study is novel.

bupropion hydrochloride

seizures

bupropion

seizures

bupropion

bupropion HCl

convulsive

bupropion

convulsions

bupropion HCl

Bupropion HCl

convulsions

convulsions

bupropion HCl

convulsions

bupropion HCl

convulsions

convulsions

convulsive

bupropion

convulsions


Detailed spectral profile analysis of penicillin-induced epileptiform activity in anesthetized rats.

Penicillin model is a widely used experimental model for epilepsy research. In the present study we aimed to portray a detailed spectral analysis of penicillin-induced epileptiform activity in comparison with basal brain activity in anesthetized Wistar rats. Male Wistar rats were anesthetized with i.p. urethane and connected to an electrocorticogram setup. After a short period of basal activity recording, epileptic focus was induced by injecting 400IU/2 microl penicillin-G potassium into the left lateral ventricle while the cortical activity was continuously recorded. Basal activity, latent period and the penicillin-induced epileptiform activity periods were then analyzed using both conventional methods and spectral analysis. Spectral analyses were conducted by dividing the whole spectrum into different frequency bands including delta, theta (slow and fast), alpha-sigma, beta (1 and 2) and gamma (1 and 2) bands. Our results show that the most affected frequency bands were delta, theta, beta-2 and gamma-2 bands during the epileptiform activity and there were marked differences in terms of spectral densities between three investigated episodes (basal activity, latent period and epileptiform activity). Our results may help to analyze novel data obtained using similar experimental models and the simple analysis method described here can be used in similar studies to investigate the basic neuronal mechanism of this or other types of experimental epilepsies.

penicillin

epileptiform activity

Penicillin

epilepsy

penicillin

epileptiform activity

urethane

epileptic

penicillin-G potassium

penicillin

epileptiform activity

epileptiform activity

epileptiform activity

epilepsies


High dose dexmedetomidine as the sole sedative for pediatric MRI.

OBJECTIVE: This large-scale retrospective review evaluates the sedation profile of dexmedetomidine. AIM: To determine the hemodynamic responses, efficacy and adverse events associated with the use of high dose dexmedetomidine as the sole sedative for magnetic resonance imaging (MRI) studies. BACKGROUND: Dexmedetomidine has been used at our institution since 2005 to provide sedation for pediatric radiological imaging studies. Over time, an effective protocol utilizing high dose dexmedetomidine as the sole sedative agent has evolved. METHODS/MATERIALS: As part of the ongoing Quality Assurance process, data on all sedations are reviewed monthly and protocols modified as needed. Data were analyzed from all 747 consecutive patients who received dexmedetomidine for MRI sedation from April 2005 to April 2007. RESULTS: Since 2005, the 10-min loading dose of our dexmedetomidine protocol increased from 2 to 3 microg.kg(-1), and the infusion rate increased from 1 to 1.5 to 2 microg.kg(-1).h(-1). The current sedation protocol progressively increased the rate of successful sedation (able to complete the imaging study) when using dexmedetomidine alone from 91.8% to 97.6% (P = 0.009), reducing the requirement for adjuvant pentobarbital in the event of sedation failure with dexmedetomidine alone and decreased the mean recovery time by 10 min (P < 0.001). Although dexmedetomidine sedation was associated with a 16% incidence of bradycardia, all concomitant mean arterial blood pressures were within 20% of age-adjusted normal range and oxygen saturations were 95% or higher. CONCLUSION: Dexmedetomidine in high doses provides adequate sedation for pediatric MRI studies. While use of high dose dexmedetomidine is associated with decreases in heart rate and blood pressure outside the established 'awake' norms, this deviation is generally within 20% of norms, and is not associated with adverse sequelae. Dexmedetomidine is useful as the sole sedative for pediatric MRI.

dexmedetomidine

dexmedetomidine

dexmedetomidine

Dexmedetomidine

dexmedetomidine

dexmedetomidine

dexmedetomidine

dexmedetomidine

pentobarbital

dexmedetomidine

dexmedetomidine

bradycardia

oxygen

Dexmedetomidine

dexmedetomidine

Dexmedetomidine


Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness.

Aggressive behaviors have been reported in patients who suffer from some psychiatric disorders, and are common in methamphetamine (METH) abusers. Herein, we report that multiple (but not single) injections of METH significantly increased aggressiveness in male CD-1 mice. This increase in aggressiveness was not secondary to METH-induced hyperactivity. Analysis of protein expression using antibody microarrays and Western blotting revealed differential changes in MAP kinase-related pathways after multiple and single METH injections. There were statistically significant (p<0.05) decreases in MEK1, Erk2p, GSK3alpha, 14-3-3e, and MEK7 in the striata of mice after multiple injections of METH. MEK1 was significantly decreased also after a single injection of METH, but to a much lesser degree than after multiple injections of METH. In the frontal cortex, there was a statistically significant decrease in GSK3alpha after multiple (but not single) injections of METH. These findings suggest that alterations in MAP kinase-related pathways in the prefronto-striatal circuitries might be involved in the manifestation of aggressive behaviors in mice.

Methamphetamine

aggressiveness

Aggressive behaviors

psychiatric disorders

methamphetamine

METH

METH

aggressiveness

aggressiveness

METH

hyperactivity

METH

METH

METH

METH

METH

aggressive behaviors


Lamotrigine associated with exacerbation or de novo myoclonus in idiopathic generalized epilepsies.

Five patients with idiopathic generalized epilepsies (IGE) treated with lamotrigine (LTG) experienced exacerbation or de novo appearance of myoclonic jerks (MJ). In three patients, LTG exacerbated MJ in a dose-dependent manner with early aggravation during titration. MJ disappeared when LTG dose was decreased by 25 to 50%. In two patients, LTG exacerbated MJ in a delayed but more severe manner, with myoclonic status that only ceased after LTG withdrawal.

Lamotrigine

myoclonus

idiopathic generalized epilepsies

idiopathic generalized epilepsies

IGE

lamotrigine

LTG

myoclonic jerks

MJ

LTG

MJ

MJ

LTG

LTG

MJ

myoclonic status

LTG


rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease.

The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase.

dyskinesias

Parkinson disease

levodopa

dyskinesia

Parkinson disease

dyskinetic

apomorphine

drug-induced dyskinesias


Assessment of the onset and persistence of amnesia during procedural sedation with propofol.

OBJECTIVES: To assess patients' ability to repeat and recall words presented to them while undergoing procedural sedation with propofol, and correlate their recall with their level of awareness as measured by bispectral index (BIS) monitoring. METHODS: This was a prospective, single-intervention study of consenting adult patients undergoing procedural sedation with propofol between December 28, 2002, and October 31, 2003. BIS monitoring was initiated starting 3 minutes before the procedure and continuing until the patient had regained baseline mental status. At 1-minute intervals during the procedural sedation, until the patient regained baseline mental status at the end of the procedure, a word from a standardized list was read aloud, and the patient was asked to immediately repeat the word to the investigator. The BIS score at the time the word was read and the patient's ability to repeat the word were recorded. After the procedure, the patient was asked to state all of the words from the list that he or she could recall, and to identify the last word recalled from prior to the start of the procedure and the first word recalled from after the procedure was completed. RESULTS: Seventy-five consenting patients were enrolled; one patient was excluded from data analysis for a protocol violation. No serious adverse events were noted during the procedural sedations. The mean (+/-standard deviation) time of data collection was 16.4 minutes (+/-7.1; range 5 to 34 minutes). The mean initial (preprocedure) BIS score was 97.1 (+/-2.3; range 92 to 99). The mean lowest BIS score occurring during these procedural sedations was 66.9 (+/-14.4; range 33 to 91). The mean lowest BIS score corresponding to the ability of the patient to immediately repeat words read from the list was 77.1 (95% CI = 74.3 to 80.0). The mean highest BIS score corresponding to the inability to repeat words was 81.5 (95% CI = 78.1 to 84.8). The mean BIS score corresponding to the last word recalled from prior to the initiation of the sedation was 96.7 (+/-2.4; range 84 to 98). The mean BIS score corresponding to the first word recalled after the procedure was completed was 91.2 (95% CI = 88.1 to 94.3). All patients recalled at least one word that had been read to them during the protocol. The mean lowest BIS score for any recalled word was 91.5 (+/-11.1; range 79 to 98), and no words were recalled when the corresponding BIS score was less than 90. CONCLUSIONS: There is a range of BIS scores during which sedated patients are able to repeat words read to them but are not able to subsequently recall these words. Furthermore, patients had no recall of words repeated prior to procedural sedation in BIS ranges associated with recall after procedural sedation, suggestive of retrograde amnesia.

amnesia

propofol

propofol

propofol

inability to repeat words

retrograde amnesia


Assessment of perinatal hepatitis B and rubella prevention in New Hampshire delivery hospitals.

OBJECTIVE: To evaluate current performance on recommended perinatal hepatitis B and rubella prevention practices in New Hampshire. METHODS: Data were extracted from 2021 paired mother-infant records for the year 2000 birth cohort in New Hampshire's 25 delivery hospitals. Assessment was done on the following: prenatal screening for hepatitis B and rubella, administration of the hepatitis B vaccine birth dose to all infants, administration of hepatitis B immune globulin to infants who were born to hepatitis B surface antigen-positive mothers, rubella immunity, and administration of in-hospital postpartum rubella vaccine to rubella nonimmune women. RESULTS: Prenatal screening rates for hepatitis B (98.8%) and rubella (99.4%) were high. Hepatitis B vaccine birth dose was administered to 76.2% of all infants. All infants who were born to hepatitis B surface antigen-positive mothers also received hepatitis B immune globulin. Multivariate logistic regression showed that the month of delivery and infant birth weight were independent predictors of hepatitis B vaccination. The proportion of infants who were vaccinated in January and February 2000 (48.5% and 67.5%, respectively) was less than any other months, whereas the proportion who were vaccinated in December 2000 (88.2%) was the highest. Women who were born between 1971 and 1975 had the highest rate of rubella nonimmunity (9.5%). In-hospital postpartum rubella vaccine administration was documented for 75.6% of nonimmune women. CONCLUSION: This study documents good compliance in New Hampshire's birthing hospitals with national guidelines for perinatal hepatitis B and rubella prevention and highlights potential areas for improvement.

hepatitis B

rubella

hepatitis B

rubella

hepatitis B

rubella

hepatitis B

hepatitis B

hepatitis B surface antigen

rubella

rubella

rubella

hepatitis B

rubella

Hepatitis B

hepatitis B surface antigen

hepatitis B

hepatitis B

rubella

rubella

hepatitis B

rubella


Expression of p300 protects cardiac myocytes from apoptosis in vivo.

Doxorubicin is an anti-tumor agent that represses cardiac-specific gene expression and induces myocardial cell apoptosis. Doxorubicin depletes cardiac p300, a transcriptional coactivator that is required for the maintenance of the differentiated phenotype of cardiac myocytes. However, the role of p300 in protection against doxorubicin-induced apoptosis is unknown. Transgenic mice overexpressing p300 in the heart and wild-type mice were subjected to doxorubicin treatment. Compared with wild-type mice, transgenic mice exhibited higher survival rate as well as more preserved left ventricular function and cardiac expression of alpha-sarcomeric actin. Doxorubicin induced myocardial cell apoptosis in wild-type mice but not in transgenic mice. Expression of p300 increased the cardiac level of bcl-2 and mdm-2, but not that of p53 or other members of the bcl-2 family. These findings demonstrate that overexpression of p300 protects cardiac myocytes from doxorubicin-induced apoptosis and reduces the extent of acute heart failure in adult mice in vivo.

Doxorubicin

tumor

Doxorubicin

doxorubicin

doxorubicin

Doxorubicin

doxorubicin

heart failure


Mitochondrial DNA and its respiratory chain products are defective in doxorubicin nephrosis.

BACKGROUND: Doxorubicin induces a self-perpetuating nephropathy characterized by early glomerular and late-onset tubular lesions in rats. We investigated the potential role of mitochondrial injury in the onset of these lesions. METHODS: Rats were treated with intravenous doxorubicin (1 mg kg(-1) week(-1)) for 7 weeks and were sacrificed either 1 week ('short-term') or 30 weeks ('long-term') following the last dose. Additional rats received a single dose either 6 days or 2 h prior to euthanasia. All rats were killed at 48 weeks of age. Glomerular and tubular injury was monitored and correlated to the activity or expression of respiratory chain components. Finally, we quantified both nuclear and mitochondrial DNA (mtDNA) as well as superoxide production and the 4834 base pair 'common' mtDNA deletion. RESULTS: The 'long-term' group had significant glomerular and tubular lesions, depressed activities of mtDNA-encoded NADH dehydrogenase and cytochrome-c oxidase (COX) and increased citrate synthase activity. In addition, expression of the mtDNA-encoded COX subunit I was reduced and mtDNA levels were decreased. In 'short-term' rats, there were fewer tubular lesions, but similar numbers of glomerular lesions activity. Among all animals, glomerular and tubular injury were inversely correlated with mtDNA levels, mtDNA-encoded respiratory chain activities and with the expression of the mtDNA-encoded respiratory chain subunit COX-I. Injury was positively correlated with superoxide production and the activities of nucleus-encoded mitochondrial or cytoplasmic enzymes. Kidneys from the 'long-term' group showed more mtDNA deletions than in 'short-term' animals and these were not observed in the other groups. CONCLUSIONS: These results suggest an important role for quantitative and qualitative mtDNA alterations through the reduction of mtDNA-encoded respiratory chain function and induction of superoxide in doxorubicin-induced renal lesions.

doxorubicin

nephrosis

Doxorubicin

nephropathy

mitochondrial injury

doxorubicin

Glomerular and tubular injury

superoxide

glomerular and tubular lesions

citrate

tubular lesions

glomerular lesions

glomerular and tubular injury

superoxide

superoxide

doxorubicin

renal lesions


Amphotericin B-induced seizures in a patient with AIDS.

OBJECTIVE: To report a case of multiple episodes of seizure activity in an AIDS patent following amphotericin B infusion. CASE SUMMARY: A 46-year-old African-American man experienced recurrent grand mal seizures during intravenous infusion of amphotericin B, then petit mal seizures as the infusion was stopped and the drug concentrations decreased with time. The patients concurrent medications included didanosine, hydroxyzine, promethazine, hydrocortisone, and prochlorperazine. Despite administration of phenytoin and lorazepam, the seizures persisted and occurred only during amphotercin B administration. DISCUSSION: AIDS and cryptococcal meningitis, both of which the patient had, can potentially cause seizures. The patient had a history of alcohol abuse; alcohol intake as well as withdrawal can also cause seizures. Didanosine also has a potential for inducing seizures. However, these other potential causes of seizure were ruled out. The time course of events suggested that amphotericin B was the cause of the seizures in this AIDS patient. CONCLUSIONS: Amphotericin B seems to be the probable cause of the seizures. To date, only three cases of seizures associated with amphotericin B have been reported in the literature, but healthcare providers should be aware of the potential for this rare adverse effect.

Amphotericin B

seizures

AIDS

seizure

AIDS

amphotericin B

grand mal seizures

amphotericin B

seizures

didanosine

hydroxyzine

promethazine

hydrocortisone

prochlorperazine

phenytoin

lorazepam

seizures

amphotercin B

AIDS

cryptococcal meningitis

seizures

alcohol abuse

alcohol

seizures

Didanosine

seizures

seizure

amphotericin B

seizures

AIDS

Amphotericin B

seizures

seizures

amphotericin B


Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.

OBJECTIVE: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. MATERIALS AND METHODS: Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. RESULTS: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. CONCLUSION: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.

tobramycin

tobramicyn

toxicity

tobramycin

tobramycin

Tobramycin

creatinine

nephrotoxicity

decreased auditory function

auditory loss

decreased auditory function

tobramycin


Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs.

This study was designed to investigate the chronic cardiotoxic potential of SM-5887 and a possible deteriorating effect of SM-5887 on low-grade cardiotoxicity pre-induced by doxorubicin in beagle dogs. In the chronic treatment, beagle dogs of each sex were given intravenously once every 3 weeks, either a sublethal dose of doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg). The experiment was terminated 3 weeks after the ninth dosing. Animals which received over six courses of doxorubicin demonstrated the electrocardiogram (ECG) changes, decrease of blood pressure and high-grade histopathological cardiomyopathy, while animals which were terminally sacrificed after the SM-5887 administration did not show any changes in ECG, blood pressure and histopathological examinations. To examine a possibly deteriorating cardiotoxic effect of SM-5887, low-grade cardiomyopathy was induced in dogs by four courses of doxorubicin (1.5 mg/kg). Nine weeks after pre-treatment, dogs were given four courses of either doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg) once every 3 weeks. The low-grade cardiotoxic changes were enhanced by the additional doxorubicin treatment. On the contrary, the SM-5887 treatment did not progress the grade of cardiomyopathy. In conclusion, SM-5887 does not have any potential of chronic cardiotoxicity and deteriorating effect on doxorubicin-induced cardiotoxicity in dogs.

anthracycline

doxorubicin

cardiomyopathy

cardiotoxic

cardiotoxicity

doxorubicin

doxorubicin

doxorubicin

cardiomyopathy

cardiotoxic

cardiomyopathy

doxorubicin

doxorubicin

cardiotoxic

doxorubicin

cardiomyopathy

cardiotoxicity

doxorubicin

cardiotoxicity


Posteroventral medial pallidotomy in advanced Parkinson's disease.

BACKGROUND: Posteroventral medial pallidotomy sometimes produces striking improvement in patients with advanced Parkinson's disease, but the studies to date have involved small numbers of patients and short-term follow-up. METHODS: Forty patients with Parkinson's disease underwent serial, detailed assessments both after drug withdrawal ("off" period) and while taking their optimal medical regimens ("on" period). All patients were examined preoperatively and 39 were examined at six months; 27 of the patients were also examined at one year, and 11 at two years. RESULTS: The percent improvements at six months were as follows: off-period score for overall motor function, 28 percent (95 percent confidence interval, 19 to 38 percent), with most of the improvement in the contralateral limbs; off-period score for activities of daily living, 29 percent (95 percent confidence interval, 19 to 39 percent); on-period score for contralateral dyskinesias, 82 percent (95 percent confidence interval, 72 to 91 percent); and on-period score for ipsilateral dyskinesias, 44 percent (95 percent confidence interval, 29 to 59 percent). The improvements in dyskinesias and the total scores for off-period parkinsonism, contralateral bradykinesia, and rigidity were sustained in the 11 patients examined at two years. The improvement in ipsilateral dyskinesias was lost after one year, and the improvements in postural stability and gait lasted only three to six months. Approximately half the patients who had been dependent on assistance in activities of daily living in the off period before surgery became independent after surgery. The complications of surgery were generally well tolerated, and there were no significant changes in the use of medication. CONCLUSIONS: In late-stage Parkinson's disease, pallidotomy significantly reduces levodopa-induced dyskinesias and off-period disability. Much of the benefit is sustained at two years, although some improvements, such as those on the ipsilateral side and in axial symptoms, wane within the first year. The on-period symptoms that are resistant to dopaminergic therapy do not respond to pallidotomy.

Parkinson's disease

Parkinson's disease

Parkinson's disease

dyskinesias

dyskinesias

dyskinesias

parkinsonism

bradykinesia

rigidity

dyskinesias

Parkinson's disease

levodopa

dyskinesias


Neuropeptide-Y immunoreactivity in the pilocarpine model of temporal lobe epilepsy.

Neuropeptide-Y (NPY) is expressed by granule cells and mossy fibres of the hippocampal dentate gyrus during experimental temporal lobe epilepsy (TLE). This expression may represent an endogenous damping mechanism since NPY has been shown to block seizure-like events following high-frequency stimulation in hippocampal slices. The pilocarpine (PILO) model of epilepsy is characterized by an acute period of status epilepticus followed by spontaneous recurrent seizures and related brain damage. We report peroxidase-antiperoxidase immunostaining for NPY in several brain regions in this model. PILO-injected animals exhibited NPY immunoreactivity in the region of the mossy fibre terminals, in the dentate gyrus inner molecular layer and, in a few cases, within presumed granule cells. NPY immunoreactivity was also dramatically changed in the entorhinal cortex, amygdala and sensorimotor areas. In addition, PILO injected animals exhibited a reduction in the number of NPY-immunoreactive interneurons compared with controls. The results demonstrate that changes in NPY expression, including expression in the granule cells and mossy fibres and the loss of vulnerable NPY neurons, are present in the PILO model of TLE. However, the significance of this changed synthesis of NPY remains to be determined.

pilocarpine

temporal lobe epilepsy

temporal lobe epilepsy

TLE

seizure

pilocarpine

PILO

epilepsy

status epilepticus

seizures

brain damage

PILO

PILO

PILO

TLE


Effect of myopic excimer laser photorefractive keratectomy on the electrophysiologic function of the retina and optic nerve.

PURPOSE: To assess by electrophysiologic testing the effect of photorefractive keratectomy (PRK) on the retina and optic nerve. SETTING: Eye Clinic, S. Salvatore Hospital, L'Aquila University, Italy. METHODS: Standard pattern electroretinograms (P-ERGs) and standard pattern visual evoked potentials (P-VEPs) were done in 25 eyes of 25 patients who had myopic PRK for an attempted correction between 5.00 and 15.00 diopters (D) (mean 8.00 D). Testing was done preoperatively and 3, 6, 12, and 18 months postoperatively. The contralateral eyes served as controls. During the follow-up, 3 patients (12%) developed steroid-induced elevated intraocular pressure (IOP) that resolved after corticosteroid therapy was discontinued. RESULTS: No statistically significant differences were seen between treated and control eyes nor between treated eyes preoperatively and postoperatively. CONCLUSION: Myopic excimer laser PRK did not seem to affect the posterior segment. The transient steroid-induced IOP rise did not seem to cause functional impairment.

steroid

elevated intraocular pressure

corticosteroid

steroid

IOP rise


Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study.

We report a non-randomized Phase II clinical trial to assess the efficacy and safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were entered in the trial. Changes in size, colour and associated oedema of selected 'target' lesions were measured. Clinical, biochemical and haematological toxicities were assessed. Ten subjects were evaluated. A partial response was achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's sarcoma occurred in the remaining six, maintained until the end of the trial period in four. The drug was generally well tolerated, with few mild symptoms of toxicity. The main problem encountered was haematological toxicity, with three subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)/l). There was no evidence of cardiotoxicity. In this small patient sample, liposomal daunorubicin was an effective and well tolerated agent in the treatment of Kaposi's sarcoma.

daunorubicin

Kaposi's sarcoma

daunorubicin

AIDS

Kaposi's sarcoma

Kaposi's sarcoma

oedema

toxicities

Kaposi's sarcoma

toxicity

toxicity

neutropenia

cardiotoxicity

daunorubicin

Kaposi's sarcoma


Failure of ancrod in the treatment of heparin-induced arterial thrombosis.

The morbidity and mortality associated with heparin-induced thrombosis remain high despite numerous empirical therapies. Ancrod has been used successfully for prophylaxis against development of thrombosis in patients with heparin induced platelet aggregation who require brief reexposure to heparin, but its success in patients who have developed the thrombosis syndrome is not well defined. The authors present a case of failure of ancrod treatment in a patient with heparin-induced thrombosis.

heparin

thrombosis

heparin

thrombosis

thrombosis

heparin

platelet aggregation

heparin

thrombosis

heparin

thrombosis


Seizure after flumazenil administration in a pediatric patient.

Flumazenil is a benzodiazepine receptor antagonist used to reverse sedation and respiratory depression induced by benzodiazepines. Seizures and cardiac arrhythmias have complicated its use in adult patients. Overdose patients who have coingested tricyclic antidepressants have a higher risk of these complications. Little information exists concerning adverse effects of flumazenil in children. We report the occurrence of a generalized tonic-clonic seizure in a pediatric patient following the administration of flumazenil.

Seizure

flumazenil

Flumazenil

benzodiazepine

respiratory depression

benzodiazepines

Seizures

cardiac arrhythmias

Overdose

flumazenil

tonic-clonic seizure

flumazenil


Remodelling of nerve structure in experimental isoniazid neuropathy in the rat.

The neuropathy caused by a single dose of isoniazid in rats was studied with a computer-assisted morphometric method. Scatter diagrams of the g ratio (quotient fibre diameter/axon diameter) define regenerating fibres as a distinct population, distinguishable from the surviving fibres by reduced sheath thickness and reduced axon calibre. There was also evidence of a subtle direct toxic effect on the entire fibre population, causing axon shrinkage masked by readjustment of the myelin sheath.

isoniazid

neuropathy

neuropathy

isoniazid


Selective injection of iopentol, iohexol and metrizoate into the left coronary artery of the dog. Induction of ventricular fibrillation and decrease of aortic pressure.

In twenty beagle dogs selective injections were made into the left coronary artery with iopentol, iohexol and metrizoate in doses of 4 ml, 8 ml and 16 ml. Thirty-six iopentol injections, 35 iohexol injections and 37 metrizoate injections were made. Frequencies of ventricular fibrillation were significantly lower (p less than 0.05) after iopentol (0%) and iohexol (3%) than after metrizoate (22%). Iopentol and iohexol also produced significantly less decrease in aortic blood pressure than metrizoate at the different doses.

iopentol

iohexol

metrizoate

ventricular fibrillation

iopentol

iohexol

metrizoate

iopentol

iohexol

metrizoate

ventricular fibrillation

iopentol

iohexol

metrizoate

Iopentol

iohexol

metrizoate


Magnetic resonance imaging of cerebral venous thrombosis secondary to "low-dose" birth control pills.

The clinical and radiographic features of cerebral deep venous thrombosis in a 21-year-old white woman are presented. This nulliparous patient presented with relatively mild clinical symptoms and progressing mental status changes. The only known risk factor was "low-dose" oral contraceptive pills. The magnetic resonance image (MRI) showed increased signal intensity from the internal cerebral veins, vein of Galen, and straight sinus. The diagnosis was confirmed by arterial angiography.

venous thrombosis

deep venous thrombosis

oral contraceptive


Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: correlation with thallium-201 single-photon emission tomography.

It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT.

coronary stenosis

thallium

coronary occlusion

coronary stenoses

hyperemic

coronary stenosis

thallium

coronary occlusion

dipyridamole

hyperemia

coronary stenosis

dipyridamole

hyperemia

Thallium

dipyridamole

hyperemia

coronary stenosis

thallium


Potential deleterious effect of furosemide in radiocontrast nephropathy.

The purpose of the study was to determine the efficacy of furosemide in addition to intravenous fluids in the prevention of radiocontrast nephropathy. 18 patients, referred to a radiocontrast study, considered at risk because of preexisting renal insufficiency, were enrolled in a prospective, randomized, controlled trial, performed at the secondary care center of a 1,100-bed private university hospital. In addition to fluids, the treatment group received furosemide (mean dose 110 mg) intravenously 30 min prior to the injection of contrast material. The control group received fluids (mean 3 liters). Radiological studies were mostly angiographies performed with both ionic and non-ionic contrast material, at an average dose of 245 ml. Renal function significantly deteriorated in the group pretreated with furosemide (p < 0.005 by ANOVA), with a rise in serum creatinine from 145 +/- 13 to 182 +/- 16 mumol/l at 24 h, while no change occurred in the control group (from 141 +/- 6 to 142 +/- 7 mumol/l). Renal failure was associated with weight loss in the furosemide-treated group. Furosemide may be deleterious in the prevention of radiocontrast nephropathy.

furosemide

nephropathy

furosemide

nephropathy

renal insufficiency

furosemide

furosemide

creatinine

Renal failure

weight loss

furosemide

Furosemide

nephropathy


The renal pathology in a case of lithium-induced diabetes insipidus.

A case of lithium-induced diabetes insipidus is reported. At necropsy microscopy shoed unique and extensive damage to cells lining the distal nephron. It is suggested that these changes represent a specific toxic effect of lithium, reported here for the first time in man.

lithium

diabetes insipidus

lithium

diabetes insipidus

lithium


Etiologic factors in the pathogenesis of liver tumors associated with oral contraceptives.

Within the last several years, previously rare liver tumors have been seen in young women using oral contraceptive steroids. The Registry for Liver Tumors Associated with Oral Contraceptives at the University of California, Irvine, has clearly identified 27 cases. The recent literature contains 44 case reports. Common to these 71 cases has been a histopathologic diagnosis of focal nodular hyperplasia, adenoma, hamartoma, and hepatoma. Significant statistical etiologic factors include prolonged uninterrupted usage of oral contraceptive steroids. Eight deaths and liver rupture in 18 patients attest to the seriousness of this new potentially lethal adverse phenomenon.

liver tumors

oral contraceptives

liver tumors

oral contraceptive

steroids

Liver Tumors

Oral Contraceptives

focal nodular hyperplasia

adenoma

hamartoma

hepatoma

oral contraceptive

steroids

rupture


Graft-versus-host disease prophylaxis with everolimus and tacrolimus is associated with a high incidence of sinusoidal obstruction syndrome and microangiopathy: results of the EVTAC trial.

A calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens.

Graft-versus-host disease

everolimus

tacrolimus

sinusoidal obstruction syndrome

microangiopathy

methotrexate

graft-versus-host disease

GVHD

Everolimus

sirolimus

everolimus

tacrolimus

myelodysplastic syndrome

MDS

acute myeloid leukemia

AML

mucositis

GVHD

GVHD

TMA

acute renal failure

sinusoidal obstruction syndrome

SOS

GVHD

TMA

SOS


Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or clonazepam in amygdala-kindled rats.

Loreclezole (5 mg/kg) exerted a significant protective action in amygdala-kindled rats, reducing both seizure and afterdischarge durations. The combinations of loreclezole (2.5 mg/kg) with valproate, clonazepam, or carbamazepine (applied at their subprotective doses) also exhibited antiseizure effect in this test. However, only two first combinations occurred to be of pharmacodynamic nature. Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k-8644 (the opener of L-type calcium channels) reversed the protective activity of loreclezole alone and its combination with valproate. On the other hand, bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of loreclezole combined with clonazepam. The results support the hypothesis that the protective activity of loreclezole and its combinations with other antiepileptics may involve potentiation of GABAergic neurotransmission and blockade of L-type of calcium channels.

loreclezole

valproate

clonazepam

Loreclezole

seizure

loreclezole

valproate

clonazepam

carbamazepine

bicuculline

N-methyl-D-aspartic acid

BAY k-8644

calcium

loreclezole

valproate

bicuculline

aminophylline

BAY k-8644

loreclezole

clonazepam

loreclezole

calcium


Acute liver failure with concurrent bupropion and carbimazole therapy.

OBJECTIVE: To report a case of fatal liver failure possibly associated with concurrent use of bupropion and carbimazole. CASE SUMMARY: A 41-year-old Chinese man with a history of hyperthyroidism had been treated with carbimazole and propranolol for the past 5 years. He received a 10-day course of bupropion as an aid for smoking cessation 10 weeks prior to presentation. He developed acute liver failure with rapid deterioration of renal function. Liver biopsy showed evidence of nonspecific drug-induced acute liver injury. His condition was further complicated by sepsis and coagulopathy. Death resulted 19 days after the onset of symptoms. The likelihood that bupropion induced hepatotoxicity in our patient was possible, based on the Naranjo probability scale. DISCUSSION: Although there is increasing evidence of hepatotoxicity induced by bupropion, this is the first case of fatality that could have resulted from acute liver failure in a patient receiving bupropion while on concomitant treatment with carbimazole. CONCLUSIONS: Clinicians should be aware of the possibility of acute liver insult induced by bupropion given concurrently with other hepatotoxic drugs.

Acute liver failure

bupropion

carbimazole

liver failure

bupropion

carbimazole

hyperthyroidism

carbimazole

propranolol

bupropion

acute liver failure

drug-induced acute liver injury

sepsis

coagulopathy

bupropion

hepatotoxicity

hepatotoxicity

bupropion

acute liver failure

bupropion

carbimazole

acute liver insult

bupropion

hepatotoxic


Long term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms and has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of the original Cochrane review first published in 2005. OBJECTIVES: To assess the effect of long-term HT on mortality, cardiovascular outcomes, cancer, gallbladder disease, cognition, fractures and quality of life. SEARCH STRATEGY: We searched the following databases to November 2007: Trials Register of the Cochrane Menstrual Disorders and Subfertility Group, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Biological Abstracts. Also relevant non-indexed journals and conference abstracts. SELECTION CRITERIA: Randomised double-blind trials of HT versus placebo, taken for at least one year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via oral, transdermal, subcutaneous or transnasal routes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Nineteen trials involving 41,904 women were included. In relatively healthy women, combined continuous HT significantly increased the risk of venous thrombo-embolism or coronary event (after one year's use), stroke (after three years), breast cancer and gallbladder disease. Long-term oestrogen-only HT significantly increased the risk of venous thrombo-embolism, stroke and gallbladder disease (after one to two years, three years and seven years' use respectively), but did not significantly increase the risk of breast cancer. The only statistically significant benefits of HT were a decreased incidence of fractures and (for combined HT) colon cancer, with long-term use. Among women aged over 65 who were relatively healthy (i.e. generally fit, without overt disease) and taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thrombo-embolism.One trial analysed subgroups of 2839 relatively healthy 50 to 59 year old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thrombo-embolism in women taking combined continuous HT: their absolute risk remained low, at less than 1/500. However, this study was not powered to detect differences between groups of younger women. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.

cardiovascular disease

osteoporosis

dementia

cancer

gallbladder disease

fractures

Menstrual Disorders

oestrogens

progestogens

venous thrombo-embolism

stroke

breast cancer

gallbladder disease

oestrogen

venous thrombo-embolism

stroke

gallbladder disease

breast cancer

fractures

colon cancer

dementia

cardiovascular disease

venous thrombo-embolism

oestrogen

venous thrombo-embolism


Passage of mannitol into the brain around gliomas: a potential cause of rebound phenomenon. A study on 21 patients.

AIM: Widespread use of mannitol to reduce brain edema and lower elevated ICP in brain tumor patients continues to be afflicted by the so-called rebound phenomenon. Leakage of mannitol into the brain parenchyma through an altered BBB and secondary reversal of osmotic gradient is considered the major cause of rebound . This has only been demonstrated experimentally in animals. As a contribution to this issue we decided to research the possible passage of mannitol into the brain after administration to 21 brain tumor patients. METHODS: Mannitol (18% solution; 1 g/kg) was administered as a bolus to patients (ten had malignant glioma, seven brain metastases and four meningioma) about 30 minutes before craniotomy. During resection, a sample of the surrounding edematous white matter was taken at the same time as a 10 ml venous blood sample. Mannitol concentrations were measured in plasma and white matter by a modified version of the enzyme assay of Blonquist et al. RESULTS: In most glioma patients, mannitol concentrations in white matter were 2 to 6 times higher than in plasma (mean 3.5 times). In meningioma and metastases patients plasma concentrations of mannitol were higher than white matter concentrations except in three cases with infiltration by neoplastic cells. CONCLUSIONS: The results of our study show that even after a single bolus, mannitol may leak through the altered BBB near gliomas, reversing the initial plasma-to-blood osmotic gradient, aggravating peritumoral edema and promoting rebound of ICP.

mannitol

gliomas

mannitol

brain edema

elevated ICP

brain tumor

mannitol

mannitol

brain tumor

Mannitol

malignant glioma

metastases

meningioma

edematous

Mannitol

glioma

mannitol

meningioma

metastases

mannitol

mannitol

gliomas

edema


Can lidocaine reduce succinylcholine induced postoperative myalgia?

This study was undertaken to determine the effect of lidocaine pretreatment on reduction of succinylcholine-induced myalgia in patients undergoing general anesthesia for gynecological surgery. One hundred and thirty-five patients were assigned to one of three groups in a prospective, double blind, randomized manner. Group PS, the control group, received normal saline and succinylcholine 1.5 mg x kg(-1); Group LS, lidocaine 1.5 mg x kg(-1) and succinylcholine 1.5 mg x kg(-1); Group PR, normal saline and rocuronium 0.6 mg x kg(-1). Morphine 0.1 mg x kg(-1) iv was given for premedication and all patients were monitored with a noninvasive blood pressure monitor, ECG and pulse oximetry. Anesthesia was induced with 5 mg.kg(-1) thiopental iv. followed by succinylcholine (Group PS, LS) or rocuronium (Group PR) for tracheal intubation. Following administration of these agents, the presence, and degree of fasciculation were assessed visually on a four point scale by one investigator who was blinded to the drug administered. The blood pressure and heart rate of each patient were monitored on nine occasions. Twenty-four hours later, any myalgia experienced was assessed according to a structured questionaire and graded by a four point scale by one investigator blinded to the intraoperative management. The results indicate that muscle fasciculation was not found in Group PR while the patients in Group LS had a lower incidence of muscle fasciculation than those in Group PS (p < 0.001). At 24 h, the incidence of myalgia was higher in Group PS than in Group LS and PR (p < 0.05). A correlation was not found between the incidence of myalgia and the occurrence of muscle fasciculation. The changes in systolic and diastolic blood pressure and heart rate were not significant among the three groups. In conclusion, where succinylcholine is used, lidocaine is proven to be the useful pretreatment agent for the reduction of postoperative myalgia.

lidocaine

succinylcholine

postoperative myalgia

lidocaine

succinylcholine

myalgia

succinylcholine

lidocaine

succinylcholine

rocuronium

Morphine

thiopental

succinylcholine

rocuronium

fasciculation

myalgia

muscle fasciculation

muscle fasciculation

myalgia

myalgia

muscle fasciculation

succinylcholine

lidocaine

postoperative myalgia


Open-label assessment of levofloxacin for the treatment of acute bacterial sinusitis in adults.

PURPOSE: To evaluate the efficacy and safety of levofloxacin (500 mg orally once daily for 10 to 14 days) in treating adult outpatients with acute bacterial sinusitis. PATIENTS AND METHODS: A total of 329 patients enrolled in the study at 24 centers. All patients had a pre-therapy Gram's stain and culture of sinus exudate obtained by antral puncture or nasal endoscopy. Clinical response was assessed on the basis of signs and symptoms and sinus radiograph or computed tomography results. Microbiologic cure rates were determined on the basis of presumed plus documented eradication of the pre-therapy pathogen(s). RESULTS: The most common pathogens were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Moraxella catarrhalis. Of 300 clinically evaluable patients, 175 (58%) were cured and 90 (30%) were improved at the post-therapy evaluation, resulting in a clinical success rate of 88%. Thirty-five patients (12%) clinically failed treatment. The microbiologic eradication rate (presumed plus documented) among 138 microbiologically evaluable patients was 92%. Microbiologic eradication rates (presumed plus documented) of the most common pathogens ranged from 93% (M. catarrhalis) to 100% (S. pneumoniae) at the post-therapy visit. All but one of the 265 patients who were cured or improved at post-therapy returned for a long-term follow-up visit; 243 (92%) remained well 4 to 6 weeks after therapy; and 21 (8%) had a relapse of symptoms. Adverse events considered to be related to levofloxacin administration were reported by 29 patients (9%). The most common drug-related adverse events were diarrhea, flatulence, and nausea; most adverse events were mild to moderate in severity. CONCLUSION: The results of this study indicate that levofloxacin 500 mg once daily is an effective and safe treatment for acute bacterial sinusitis.

levofloxacin

sinusitis

levofloxacin

sinusitis

levofloxacin

diarrhea

flatulence

nausea

levofloxacin

sinusitis


Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol.

Among various oral antiplatelets, a combination of a novel prostacyclin analogue beraprost (BPT) and a potent phosphodiesterase inhibitor cilostazol (CLZ) may result in untoward clinical effects due to possible synergistic elevation of intracellular cAMP (cyclic adenosine 3',5'-monophosphate). Thereby, a clinical study of the combined administration of the two agents was attempted. Twelve healthy volunteers were assigned to take BPT/CLZ in the following schedule; BPT: 40 micrograms at day 1 and 120 micrograms t.i.d. from day 7 to 14, CLZ: 200 mg t.i.d. from day 3 to 14. At various time intervals, physical examination and blood collection for ex vivo platelet aggregation and determination of intraplatelet cAMP were performed. Throughout the observation period, no significant alteration in vital signs was observed. Seven out of 12 subjects experienced headache of a short duration accompanying facial flush in one and nausea in one, especially after ingestion of CLZ. All of these symptoms, probably caused by the vasodilating effect of the two agents, were of mild degree and no special treatment was required. Intraplatelet cAMP content was gradually but significantly increased to 9.84 +/- 4.59 pmol per 10(9) platelets at day 14 in comparison with the initial value (6.87 +/- 2.25 pmol). The platelet aggregability was significantly suppressed at various time intervals but no additive or synergistic inhibitory effect by the combined administration was noted. In conclusion, the combined administration of BPT/CLZ is safe at doses used in the study, though the beneficial clinical effect of the combined administration has yet to be elucidated.

prostacyclin

beraprost

cilostazol

prostacyclin

beraprost

BPT

cilostazol

CLZ

cAMP

cyclic adenosine 3',5'-monophosphate

BPT

CLZ

BPT

CLZ

platelet aggregation

cAMP

headache

facial flush

nausea

CLZ

cAMP

BPT

CLZ


Gastrointestinal tolerability of etoricoxib in rheumatoid arthritis patients: results of the etoricoxib vs diclofenac sodium gastrointestinal tolerability and effectiveness trial (EDGE-II).

OBJECTIVE: A randomised, double-blind study to compare the gastrointestinal (GI) tolerability, safety and efficacy of etoricoxib and diclofenac in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 4086 patients (mean age 60.8 years) diagnosed with RA were enrolled and received etoricoxib 90 mg daily (n = 2032) or diclofenac 75 mg twice daily (n = 2054). Use of gastroprotective agents and low-dose aspirin was allowed. The prespecified primary end point consisted of the cumulative rate of patient discontinuations due to clinical and laboratory GI adverse experiences (AEs). General safety was also assessed, including adjudicated thrombotic cardiovascular event data. Efficacy was evaluated using the Patient Global Assessment of Disease Status (PGADS; 0-4 point scale). RESULTS: Mean (SD; maximum) duration of treatment was 19.3 (10.3; 32.9) and 19.1 (10.4; 33.1) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AEs was significantly lower with etoricoxib than diclofenac (5.2 vs 8.5 events per 100 patient-years, respectively; hazard ratio 0.62 (95% CI: 0.47, 0.81; p<or=0.001)). The incidence of discontinuations for hypertension-related and oedema-related AEs were significantly higher with etoricoxib (2.5% and 1.1% respectively) compared with diclofenac (1.5% and 0.4% respectively; p<0.001 for hypertension and p<0.01 for oedema). Etoricoxib and diclofenac treatment resulted in similar efficacy (PGADS mean changes from baseline -0.62 vs -0.58, respectively). CONCLUSIONS: Etoricoxib 90 mg demonstrated a significantly lower risk for discontinuing treatment due to GI AEs compared with diclofenac 150 mg. Discontinuations from renovascular AEs, although less common than discontinuations from GI AEs, were significantly higher with etoricoxib.

etoricoxib

rheumatoid arthritis

etoricoxib

diclofenac sodium

etoricoxib

diclofenac

rheumatoid arthritis

RA

RA

etoricoxib

diclofenac

aspirin

thrombotic cardiovascular

etoricoxib

diclofenac

GI AEs

etoricoxib

diclofenac

hypertension

oedema

etoricoxib

diclofenac

hypertension

oedema

Etoricoxib

diclofenac

Etoricoxib

GI AEs

diclofenac

GI AEs

etoricoxib


Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania.

OBJECTIVES: To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania. METHODS: Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage. RESULTS: The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo. CONCLUSIONS: In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo.

extrapyramidal symptoms

EPS

quetiapine

bipolar mania

extrapyramidal symptoms

EPS

akathisia

quetiapine

bipolar mania

quetiapine

lithium

haloperidol

quetiapine

lithium

divalproex

QTP

Li

DVP

Li

DVP

Extrapyramidal symptoms

EPS

akathisia

quetiapine

EPS

QTP

Li

DVP

Li

DVP

EPS

haloperidol

lithium

EPS

akathisia

quetiapine

QTP

Li

DVP

Li

DVP

Lithium

tremor

quetiapine

tremor

lithium

tremor

lithium

Haloperidol

akathisia

tremor

extrapyramidal syndrome

quetiapine

quetiapine

quetiapine

bipolar mania

EPS

akathisia

quetiapine


Contribution of the sympathetic nervous system to salt-sensitivity in lifetime captopril-treated spontaneously hypertensive rats.

OBJECTIVE: To test the hypothesis that, in lifetime captopril-treated spontaneously hypertensive rats (SHR), the sympathetic nervous system contributes importantly to the hypertensive effect of dietary sodium chloride supplementation. METHODS: Male SHR (aged 6 weeks) that had been treated from conception onward with either captopril or vehicle remained on a basal sodium chloride diet or were fed a high sodium chloride diet. After 2 weeks, the rats were subjected to ganglionic blockade and 2 days later, an infusion of clonidine. RESULTS: Lifetime captopril treatment significantly lowered mean arterial pressure in both groups. Intravenous infusion of the ganglionic blocker hexamethonium resulted in a rapid decline in MAP that eliminated the dietary sodium chloride-induced increase in MAP in both groups. Infusion of the central nervous system alpha2-adrenergic receptor agonist clonidine also resulted in a greater reduction in MAP in both groups of SHR that were fed the high (compared with the basal) sodium chloride diet. CONCLUSIONS: In both lifetime captopril-treated and control SHR, the sympathetic nervous system contributes to the pressor effects of a high sodium chloride diet.

captopril

hypertensive

captopril

hypertensive

hypertensive

dietary sodium chloride

captopril

sodium chloride

sodium chloride

clonidine

captopril

hexamethonium

dietary sodium chloride

increase in MAP

alpha2-adrenergic receptor agonist

clonidine

sodium chloride

captopril

sodium chloride


Dose-related beneficial and adverse effects of dietary corticosterone on organophosphorus-induced delayed neuropathy in chickens.

Tri-ortho-tolyl phosphate (TOTP), 360 mg/kg, po, and 0,0'-diisopropyl phosphorofluoridate (DFP), 1 mg/kg sc, were administered to adult White Leghorn chickens 24 hr after they were placed on diets containing 0 to 300 ppm corticosterone. Supplemented diets were continued until clinical signs and lesions of delayed neuropathy appeared. Although low concentrations (less than or equal to 50 ppm) of corticosterone had beneficial effects on TOTP-induced neuropathy, greater than or equal to 200 ppm exacerbated clinical signs in chickens given either TOTP or DFP. Neurotoxic esterase activities 24 hr after TOTP or DFP were less than 20% of values measured in chickens not given organophosphorous compounds. Chickens given 200 ppm corticosterone without TOTP or DFP had significantly elevated activity of plasma cholinesterase and significantly inhibited activity of liver carboxylesterase. Degenerating myelinated fibers were also evident in distal levels of the peripheral nerves of chickens given TOTP or DFP.

corticosterone

organophosphorus

neuropathy

Tri-ortho-tolyl phosphate

TOTP

0,0'-diisopropyl phosphorofluoridate

DFP

corticosterone

neuropathy

corticosterone

TOTP

neuropathy

TOTP

DFP

Neurotoxic

TOTP

DFP

organophosphorous

corticosterone

TOTP

DFP

Degenerating myelinated fibers

TOTP

DFP


In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease.

The in vivo characterization of a dual adenosine A(2A)/A(1) receptor antagonist in several animal models of Parkinson's disease is described. Discovery and scale-up syntheses of compound 1 are described in detail, highlighting optimization steps that increased the overall yield of 1 from 10.0% to 30.5%. Compound 1 is a potent A(2A)/A(1) receptor antagonist in vitro (A(2A) K(i) = 4.1 nM; A(1) K(i) = 17.0 nM) that has excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse model of reserpine-induced akinesia, rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation, and MPTP-treated non-human primate model.

adenosine A2A/A1 receptor antagonist

Parkinson's disease

Parkinson's disease

Parkinson's disease

haloperidol

catalepsy

reserpine

akinesia

MPTP


An extremely rare case of delusional parasitosis in a chronic hepatitis C patient during pegylated interferon alpha-2b and ribavirin treatment.

During treatment of chronic hepatitis C patients with interferon and ribavirin, a lot of side effects are described. Twenty-three percent to 44% of patients develop depression. A minority of patients evolve to psychosis. To the best of our knowledge, no cases of psychogenic parasitosis occurring during interferon therapy have been described in the literature. We present a 49-year-old woman who developed a delusional parasitosis during treatment with pegylated interferon alpha-2b weekly and ribavirin. She complained of seeing parasites and the larvae of fleas in her stools. This could not be confirmed by any technical examination. All the complaints disappeared after stopping pegylated interferon alpha-2b and reappeared after restarting it. She had a complete sustained viral response.

delusional parasitosis

chronic hepatitis C

pegylated interferon alpha-2b

ribavirin

chronic hepatitis C

ribavirin

depression

psychosis

psychogenic parasitosis

delusional parasitosis

pegylated interferon alpha-2b

ribavirin

pegylated interferon alpha-2b


Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam.

A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165/90 and 130/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU/L), aspartate aminotransferase (134 IU/L), alanine aminotransferase (78 IU/L), and BUN (27.9 mg/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression.

neuroleptic malignant syndrome

paroxetine

alprazolam

depressive symptoms

psychiatric

insomnia

loss of appetite

agitation

paroxetine

alprazolam

paroxetine

alprazolam

psychomotor retardation

muscle rigidity

tremors

fever

extrapyramidal symptoms

creatine

aspartate

alanine

bromocriptine

diazepam

fever

neuroleptic malignant syndrome

NMS

NMS

paroxetine

alprazolam

NMS

NMS

depressive

dehydration

agitation

malnutrition

depression


Pilocarpine seizures cause age-dependent impairment in auditory location discrimination.

Children who have status epilepticus have continuous or rapidly repeating seizures that may be life-threatening and may cause life-long changes in brain and behavior. The extent to which status epilepticus causes deficits in auditory discrimination is unknown. A naturalistic auditory location discrimination method was used to evaluate this question using an animal model of status epilepticus. Male Sprague-Dawley rats were injected with saline on postnatal day (P) 20, or a convulsant dose of pilocarpine on P20 or P45. Pilocarpine on either day induced status epilepticus; status epilepticus at P45 resulted in CA3 cell loss and spontaneous seizures, whereas P20 rats had no cell loss or spontaneous seizures. Mature rats were trained with sound-source location and sound-silence discriminations. Control (saline P20) rats acquired both discriminations immediately. In status epilepticus (P20) rats, acquisition of the sound-source location discrimination was moderately impaired. Status epilepticus (P45) rats failed to acquire either sound-source location or sound-silence discriminations. Status epilepticus in rat causes an age-dependent, long-term impairment in auditory discrimination. This impairment may explain one cause of impaired auditory location discrimination in humans.

Pilocarpine

seizures

status epilepticus

seizures

status epilepticus

deficits in auditory discrimination

status epilepticus

pilocarpine

Pilocarpine

status epilepticus

status epilepticus

seizures

seizures

status epilepticus

Status epilepticus

Status epilepticus

impairment in auditory discrimination


Cardiovascular risk with cyclooxygenase inhibitors: general problem with substance specific differences?

Randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during treatment with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly, but not exclusively, in patients with concomitant risk factors. Cyclooxygenase inhibitors cause complex changes in renal, vascular and cardiac prostanoid profiles thereby increasing vascular resistance and fluid retention. The incidence of cardiovascular adverse events tends to increase with the daily dose and total exposure time. A comparison of individual selective and unselective cyclooxygenase inhibitors suggests substance-specific differences, which may depend on differences in pharmacokinetic parameters or inhibitory potency and may be contributed by prostaglandin-independent effects. Diagnostic markers such as N-terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive protein might help in the early identification of patients at risk, thus avoiding the occurrence of serious cardiovascular toxicity.

cyclooxygenase inhibitors

myocardial infarction

stroke

hypertension

heart failure

cyclooxygenase inhibitors

Cyclooxygenase inhibitors

cyclooxygenase inhibitors

prostaglandin

NT-proBNP

cardiovascular toxicity


Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD)

BACKGROUND: Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. OBJECTIVE: To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD: We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. RESULTS: Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). CONCLUSIONS: Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy.

decreased renal function

heart failure

angiotensin

left ventricular dysfunction

angiotensin

congestive heart failure

CHF

decreased renal function

reduction in renal function

CHF

angiotensin

Left Ventricular Dysfunction

enalapril

CHF

enalapril

Decreased renal function

creatinine

creatinine

hypertension

diabetes

diuretic

enalapril

decreased renal function

enalapril

diuretic

diabetes

decreased renal function

decreased renal function

enalapril

enalapril

enalapril

Diuretic

decreased renal function

enalapril

enalapril

diabetes

renal impairment

Enalapril

decreased renal function

CHF

Diuretic

Diabetes

renal impairment

CHF

enalapril


Pemoline induced acute choreoathetosis: case report and review of the literature.

BACKGROUND: Pemoline is an oxazolidine derivative that is structurally different from amphetamines and used in the treatment of attention deficit disorder. Pemoline has not been commonly associated in the literature as a cause of acute movement disorders. The following case describes two children acutely poisoned with pemoline who experienced profound choreoathetosis. CASE REPORT: Two, 3-year-old male, identical twin siblings presented to the emergency department after found playing with a an empty bottle of pemoline originally containing 59 tablets. The children had a medical history significant for attention deficit disorder previously treated with methylphenidate without success. This was their first day of pemoline therapy. The choreoathetoid movements began 45 min to 1 h after ingestion. The children gave no history of prior movement disorders and there was no family history of movement disorders. The children received gastrointestinal decontamination and high doses of intravenous benzodiazepines in an attempt to control the choreoathetoid movements. Despite treatment, the children continued to have choreoathetosis for approximately 24 hours. Forty-eight hours after admission, the children appeared to be at their baseline and were discharged home. CONCLUSION: Pemoline associated movement disorder has been rarely reported in the acute toxicology literature. The possibility of choreoathetoid movements should be considered in patients presenting after pemoline overdose.

Pemoline

choreoathetosis

Pemoline

oxazolidine

amphetamines

attention deficit disorder

Pemoline

movement disorders

pemoline

choreoathetosis

pemoline

attention deficit disorder

methylphenidate

pemoline

choreoathetoid

movement disorders

movement disorders

benzodiazepines

choreoathetoid

choreoathetosis

Pemoline

movement disorder

choreoathetoid

pemoline

overdose