Famotidine-associated delirium. A series of six cases.

Famotidine is a histamine H2-receptor antagonist used in inpatient settings for prevention of stress ulcers and is showing increasing popularity because of its low cost. Although all of the currently available H2-receptor antagonists have shown the propensity to cause delirium, only two previously reported cases have been associated with famotidine. The authors report on six cases of famotidine-associated delirium in hospitalized patients who cleared completely upon removal of famotidine. The pharmacokinetics of famotidine are reviewed, with no change in its metabolism in the elderly population seen. The implications of using famotidine in elderly persons are discussed.

Famotidine

delirium

Famotidine

ulcers

delirium

famotidine

famotidine

delirium

famotidine

famotidine

famotidine


Indomethacin induced hypotension in sodium and volume depleted rats.

After a single oral dose of 4 mg/kg indomethacin (IDM) to sodium and volume depleted rats plasma renin activity (PRA) and systolic blood pressure fell significantly within four hours. In sodium repleted animals indomethacin did not change systolic blood pressure (BP) although plasma renin activity was decreased. Thus, indomethacin by inhibition of prostaglandin synthesis may diminish the blood pressure maintaining effect of the stimulated renin-angiotensin system in sodium and volume depletion.

Indomethacin

hypotension

sodium

indomethacin

IDM

sodium

sodium

indomethacin

indomethacin

prostaglandin

angiotensin

sodium


Late-onset scleroderma renal crisis induced by tacrolimus and prednisolone: a case report.

Scleroderma renal crisis (SRC) is a rare complication of systemic sclerosis (SSc) but can be severe enough to require temporary or permanent renal replacement therapy. Moderate to high dose corticosteroid use is recognized as a major risk factor for SRC. Furthermore, there have been reports of thrombotic microangiopathy precipitated by cyclosporine in patients with SSc. In this article, we report a patient with SRC induced by tacrolimus and corticosteroids. The aim of this work is to call attention to the risk of tacrolimus use in patients with SSc.

scleroderma renal crisis

tacrolimus

prednisolone

Scleroderma renal crisis

SRC

systemic sclerosis

SSc

corticosteroid

SRC

thrombotic microangiopathy

cyclosporine

SSc

SRC

tacrolimus

corticosteroids

tacrolimus

SSc


The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia.

OBJECTIVE: The objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. METHODS: This was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. RESULTS: Of 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612-19.708), bipolar disorder (OR=13.807, 95 CI=5.194-36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702-23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154-7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375-7.914) were the only factors associated with current psychosis. CONCLUSION: There was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms.

methamphetamine

psychosis

methamphetamine

methamphetamine

psychosis

methamphetamine

methamphetamine

psychosis

methamphetamine

methamphetamine

psychosis

psychiatric disorders

psychotic symptoms

psychotic symptoms

depressive disorder

bipolar disorder

antisocial personality disorder

methamphetamine

methamphetamine

psychosis

Major depressive disorder

antisocial personality disorder

psychosis

psychosis

methamphetamine

affective disorder

antisocial personality

methamphetamine

methamphetamine

psychotic symptoms


Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson's disease: clues from dyskinetic patients.

The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently reported in young healthy subjects that inhibitory cerebellar stimulation enhanced the sensorimotor plasticity of M1 that was induced by paired associative stimulation (PAS). This study demonstrates that the deficient sensorimotor M1 plasticity in 16 patients with LIDs could be reinstated by a single session of real inhibitory cerebellar stimulation but not sham stimulation. This was evident only when a sensory component was involved in the induction of plasticity, indicating that cerebellar sensory processing function is involved in the resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on LIDs is known. To explore whether this benefit is linked to the restoration of sensorimotor plasticity of M1, we conducted an additional study looking at changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral, real inhibitory cerebellar stimulation or sham stimulation. Only real and not sham stimulation had an antidyskinetic effect and it was paralleled by a resurgence in the sensorimotor plasticity of M1. These results suggest that alterations in cerebellar sensory processing function, occurring secondary to abnormal basal ganglia signals reaching it, may be an important element contributing to the maladaptive sensorimotor plasticity of M1 and the emergence of abnormal involuntary movements.

Parkinson's disease

dyskinetic

Parkinson's disease

PD

levodopa

dyskinesias

LIDs

LIDs

LIDs

LIDs

abnormal involuntary movements


The function of P2X3 receptor and NK1 receptor antagonists on cyclophosphamide-induced cystitis in rats.

PURPOSE: The purpose of the study is to explore the function of P2X3 and NK1 receptors antagonists on cyclophosphamide (CYP)-induced cystitis in rats. METHODS: Sixty female Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the control group were intraperitoneally (i.p.) injected with 0.9% saline (4 ml/kg); the rats in the model group were i.p. injected with CYP (150 mg/kg); and the rats in the intervention group were i.p. injected with CYP with subsequently perfusion of bladder with P2X3 and NK1 receptors' antagonists, Suramin and GR 82334. Spontaneous pain behaviors following the administration of CYP were observed. Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder. RESULTS: Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (X(2) = 7.619, P = 0.007) and control group (X(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower. CONCLUSIONS: In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder function.

cyclophosphamide

cystitis

cyclophosphamide

CYP

cystitis

CYP

CYP

Suramin

GR 82334

pain

CYP

Cyclophosphamide

pain

edema

CYP

cystitis


Acute hepatitis associated with clopidogrel: a case report and review of the literature.

Drug-induced hepatotoxicity is a common cause of acute hepatitis, and the recognition of the responsible drug may be difficult. We describe a case of clopidogrel-related acute hepatitis. The diagnosis is strongly suggested by an accurate medical history and liver biopsy. Reports about cases of hepatotoxicity due to clopidogrel are increasing in the last few years, after the increased use of this drug. In conclusion, we believe that physicians should carefully consider the risk of drug-induced hepatic injury when clopidogrel is prescribed.

hepatitis

clopidogrel

hepatotoxicity

hepatitis

clopidogrel

hepatitis

hepatotoxicity

clopidogrel

hepatic injury

clopidogrel


Bortezomib and dexamethasone as salvage therapy in patients with relapsed/refractory multiple myeloma: analysis of long-term clinical outcomes.

Bortezomib (bort)-dexamethasone (dex) is an effective therapy for relapsed/refractory (R/R) multiple myeloma (MM). This retrospective study investigated the combination of bort (1.3 mg/m(2) on days 1, 4, 8, and 11 every 3 weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment in 85 patients with R/R MM after prior autologous stem cell transplantation or conventional chemotherapy. The median number of prior lines of therapy was 2. Eighty-seven percent of the patients had received immunomodulatory drugs included in some line of therapy before bort-dex. The median number of bort-dex cycles was 6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the patients achieved at least partial response, including 19 % CR and 35 % achieved at least very good partial response. Median durations of response, time to next therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively. The most relevant adverse event was peripheral neuropathy, which occurred in 78 % of the patients (grade II, 38 %; grade III, 21 %) and led to treatment discontinuation in 6 %. With a median follow up of 22 months, median time to progression, progression-free survival (PFS) and overall survival (OS) were 8.9, 8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was an effective salvage treatment for MM patients, particularly for those in first relapse.

Bortezomib

dexamethasone

multiple myeloma

Bortezomib

bort

dexamethasone

dex

multiple myeloma

MM

bort

dex

bort

MM

bort

dex

bort

dex

peripheral neuropathy

bort

dex

Bort

dex

MM


Pubertal exposure to Bisphenol A increases anxiety-like behavior and decreases acetylcholinesterase activity of hippocampus in adult male mice.

The negative effects of Bisphenol A (BPA) on neurodevelopment and behaviors have been well established. Acetylcholinesterase (AChE) is a regulatory enzyme which is involved in anxiety-like behavior. This study investigated behavioral phenotypes and AChE activity in male mice following BPA exposure during puberty. On postnatal day (PND) 35, male mice were exposed to 50mg BPA/kg diet per day for a period of 35 days. On PND71, a behavioral assay was performed using the elevated plus maze (EPM) and the light/dark test. In addition, AChE activity was measured in the prefrontal cortex, hypothalamus, cerebellum and hippocampus. Results from our behavioral phenotyping indicated that anxiety-like behavior was increased in mice exposed to BPA. AChE activity was significantly decreased in the hippocampus of mice with BPA compared to control mice, whereas no difference was found in the prefrontal cortex, hypothalamus and cerebellum. Our findings showed that pubertal BPA exposure increased anxiety-like behavior, which may be associated with decreased AChE activity of the hippocampus in adult male mice. Further studies are necessary to investigate the cholinergic signaling of the hippocampus in PBE induced anxiety-like behaviors.

Bisphenol A

anxiety

Bisphenol A

BPA

anxiety

BPA

BPA

anxiety

BPA

BPA

BPA

anxiety

anxiety


Biochemical effects of Solidago virgaurea extract on experimental cardiotoxicity.

Cardiovascular diseases (CVDs) are the major health problem of advanced as well as developing countries of the world. The aim of the present study was to investigate the protective effect of the Solidago virgaurea extract on isoproterenol-induced cardiotoxicity in rats. The subcutaneous injection of isoproterenol (30 mg/kg) into rats twice at an interval of 24 h, for two consecutive days, led to a significant increase in serum lactate dehydrogenase, creatine phosphokinase, alanine transaminase, aspartate transaminase, and angiotensin-converting enzyme activities, total cholesterol, triglycerides, free serum fatty acid, cardiac tissue malondialdehyde (MDA), and nitric oxide levels and a significant decrease in levels of glutathione and superoxide dismutase in cardiac tissue as compared to the normal control group (P < 0.05). Pretreatment with S. virgaurea extract for 5 weeks at a dose of 250 mg/kg followed by isoproterenol injection significantly prevented the observed alterations. Captopril (50 mg/kg/day, given orally), an inhibitor of angiotensin-converting enzyme used as a standard cardioprotective drug, was used as a positive control in this study. The data of the present study suggest that S. virgaurea extract exerts its protective effect by decreasing MDA level and increasing the antioxidant status in isoproterenol-treated rats. The study emphasizes the beneficial action of S. virgaurea extract as a cardioprotective agent.

cardiotoxicity

Cardiovascular diseases

CVDs

isoproterenol

cardiotoxicity

isoproterenol

lactate

creatine

alanine

aspartate

angiotensin

cholesterol

triglycerides

fatty acid

malondialdehyde

MDA

nitric oxide

glutathione

superoxide

isoproterenol

Captopril

angiotensin

MDA

isoproterenol


"Real-world" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group.

Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the "real world" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (>PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2(nd)-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease.

lenalidomide

dexamethasone

multiple myeloma

Myeloma

Lenalidomide

dexamethasone

RD

multiple myeloma

RRMM

RRMM

RD

RD

thalidomide

bortezomib

RD

myelosuppression

Peripheral neuropathy

deep vein thrombosis

lenalidomide

RD

RRMM


The cytogenetic action of ifosfamide, mesna, and their combination on peripheral rabbit lymphocytes: an in vivo/in vitro cytogenetic study.

Ifosfamide (IFO) is an alkylating nitrogen mustard, administrated as an antineoplasmic agent. It is characterized by its intense urotoxic action, leading to hemorrhagic cystitis. This side effect of IFO raises the requirement for the co-administration with sodium 2-sulfanylethanesulfonate (Mesna) aiming to avoid or minimize this effect. IFO and Mesna were administrated separately on rabbit's lymphocytes in vivo, which were later developed in vitro. Cytogenetic markers for sister chromatid exchanges (SCEs), proliferation rate index (PRI) and Mitotic Index were recorded. Mesna's action, in conjunction with IFO reduces the frequency of SCEs, in comparison with the SCEs recordings obtained when IFO is administered alone. In addition to this, when high concentrations of Mesna were administered alone significant reductions of the PRI were noted, than with IFO acting at the same concentration on the lymphocytes. Mesna significantly reduces IFO's genotoxicity, while when administered in high concentrations it acts in an inhibitory fashion on the cytostatic action of the drug.

ifosfamide

mesna

Ifosfamide

IFO

nitrogen

hemorrhagic cystitis

hemorrhagic

cystitis

IFO

sodium 2-sulfanylethanesulfonate

Mesna

IFO

Mesna

Mesna

IFO

IFO

Mesna

IFO

Mesna

IFO

genotoxicity


Risk factors and predictors of levodopa-induced dyskinesia among multiethnic Malaysians with Parkinson's disease.

Chronic pulsatile levodopa therapy for Parkinson's disease (PD) leads to the development of motor fluctuations and dyskinesia. We studied the prevalence and predictors of levodopa-induced dyskinesia among multiethnic Malaysian patients with PD. METHODS: This is a cross-sectional study involving 95 patients with PD on uninterrupted levodopa therapy for at least 6 months. The instrument used was the UPDRS questionnaires. The predictors of dyskinesia were determined using multivariate logistic regression analysis. RESULTS: The mean age was 65.6 + 8.5 years. The mean onset age was 58.5 + 9.8 years. The median disease duration was 6 (7) years. Dyskinesia was present in 44% (n = 42) with median levodopa therapy of 3 years. There were 64.3% Chinese, 31% Malays, and 3.7% Indians and other ethnic groups. Eighty-one percent of patients with dyskinesia had clinical fluctuations. Patients with dyskinesia had lower onset age ( p < 0.001), longer duration of levodopa therapy ( p < 0.001), longer disease duration ( p < 0.001), higher total daily levodopa dose ( p < 0.001), and higher total UPDRS scores ( p = 0.005) than patients without dyskinesia. The three significant predictors of dyskinesia were duration of levodopa therapy, onset age, and total daily levodopa dose. CONCLUSIONS: The prevalence of levodopa-induced dyskinesia in our patients was 44%. The most significant predictors were duration of levodopa therapy, total daily levodopa dose, and onset age.

levodopa

dyskinesia

Parkinson's disease

levodopa

Parkinson's disease

PD

dyskinesia

levodopa

dyskinesia

PD

PD

levodopa

dyskinesia

Dyskinesia

levodopa

dyskinesia

dyskinesia

levodopa

levodopa

dyskinesia

dyskinesia

levodopa

levodopa

levodopa

dyskinesia

levodopa

levodopa


An unexpected diagnosis in a renal-transplant patient with proteinuria treated with everolimus: AL amyloidosis.

Proteinuria is an expected complication in transplant patients treated with mammalian target of rapamycin inhibitors (mTOR-i). However, clinical suspicion should always be supported by histological evidence in order to investigate potential alternate diagnoses such as acute or chronic rejection, interstitial fibrosis and tubular atrophy, or recurrent or de novo glomerulopathy. In this case we report the unexpected diagnosis of amyloidosis in a renal-transplant patient with pre-transplant monoclonal gammapathy of undetermined significance who developed proteinuria after conversion from tacrolimus to everolimus.

proteinuria

everolimus

AL

amyloidosis

Proteinuria

rapamycin

fibrosis

atrophy

glomerulopathy

amyloidosis

proteinuria

tacrolimus

everolimus


An investigation of the pattern of kidney injury in HIV-positive persons exposed to tenofovir disoproxil fumarate: an examination of a large population database (MHRA database).

The potential for tenofovir to cause a range of kidney syndromes has been established from mechanistic and randomised clinical trials. However, the exact pattern of kidney involvement is still uncertain. We undertook a descriptive analysis of Yellow Card records of 407 HIV-positive persons taking tenofovir disoproxil fumarate (TDF) as part of their antiretroviral therapy regimen and submitted to the Medicines and Healthcare Products Regulatory Agency (MHRA) with suspected kidney adverse effects. Reports that satisfy defined criteria were classified as acute kidney injury, kidney tubular dysfunction and Fanconi syndrome. Of the 407 Yellow Card records analysed, 106 satisfied criteria for TDF-related kidney disease, of which 53 (50%) had features of kidney tubular dysfunction, 35 (33%) were found to have features of glomerular dysfunction and 18 (17%) had Fanconi syndrome. The median TDF exposure was 316 days (interquartile range 120-740). The incidence of hospitalisation for TDF kidney adverse effects was high, particularly amongst patients with features of Fanconi syndrome. The pattern of kidney syndromes in this population series mirrors that reported in randomised clinical trials. Cessation of TDF was associated with complete restoration of kidney function in up half of the patients in this report.

kidney injury

tenofovir disoproxil fumarate

tenofovir

tenofovir disoproxil fumarate

TDF

acute kidney injury

kidney tubular dysfunction

Fanconi syndrome

TDF

kidney disease

kidney tubular dysfunction

glomerular dysfunction

Fanconi syndrome

TDF

TDF

Fanconi syndrome

TDF


Incidence of postoperative delirium is high even in a population without known risk factors.

PURPOSE: Postoperative delirium is a recognized complication in populations at risk. The aim of this study is to assess the prevalence of early postoperative delirium in a population without known risk factors admitted to the ICU for postoperative monitoring after elective major surgery. The secondary outcome investigated is to identify eventual independent risk factors among demographic data and anesthetic drugs used. METHODS: An observational, prospective study was conducted on a consecutive cohort of patients admitted to our ICU within and for at least 24 h after major surgical procedures. Exclusion criteria were any preexisting predisposing factor for delirium or other potentially confounding neurological dysfunctions. Patients were assessed daily using the confusion assessment method for the ICU scale for 3 days after the surgical procedure. Early postoperative delirium incidence risk factors were then assessed through three different multiple regression models. RESULTS: According to the confusion assessment method for the ICU scale, 28 % of patients were diagnosed with early postoperative delirium. The use of thiopentone was significantly associated with an eight-fold-higher risk for delirium compared to propofol (57.1% vs. 7.1%, RR = 8.0, X2 = 4.256; df = 1; 0.05 < p < 0.02). CONCLUSION: In this study early postoperative delirium was found to be a very common complication after major surgery, even in a population without known risk factors. Thiopentone was independently associated with an increase in its relative risk.

postoperative delirium

Postoperative delirium

postoperative delirium

delirium

neurological dysfunctions

confusion

postoperative delirium

postoperative delirium

thiopentone

delirium

propofol

postoperative delirium

Thiopentone


A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice.

Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis.

neurotoxic

methamphetamine

depressive

Methamphetamine

METH

METH

depressive symptoms

METH

depressive

depressive

METH

METH

METH

depressive

METH

dopamine

DOPAC

HVA

tyrosine

serotonin

depression

METH

depressive


Linezolid-induced optic neuropathy.

Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.

Linezolid

optic neuropathy

loss of vision

linezolid

linezolid

ethambutol

extensively drug-resistant tuberculosis

XDR-TB

loss of vision

optic disc edema

Ethambutol

toxic optic neuropathy

ethambutol

Deterioration of vision

ethambutol

linezolid

linezolid


Resuscitation with lipid, epinephrine, or both in levobupivacaine-induced cardiac toxicity in newborn piglets.

BACKGROUND: The optimal dosing regimens of lipid emulsion, epinephrine, or both are not yet determined in neonates in cases of local anaesthetic systemic toxicity (LAST). METHODS: Newborn piglets received levobupivacaine until cardiovascular collapse occurred. Standard cardiopulmonary resuscitation was started and electrocardiogram (ECG) was monitored for ventricular tachycardia, fibrillation, or QRS prolongation. Piglets were then randomly allocated to four groups: control (saline), Intralipid( ) alone, epinephrine alone, or a combination of Intralipd plus epinephrine. Resuscitation continued for 30 min or until there was a return of spontaneous circulation (ROSC) accompanied by a mean arterial pressure at or superior to the baseline pressure and normal sinus rhythm for a period of 30 min. RESULTS: ROSC was achieved in only one of the control piglets compared with most of the treated piglets. Mortality was not significantly different between the three treatment groups, but was significantly lower in all the treatment groups compared with control. The number of ECG abnormalities was zero in the Intralipid only group, but 14 and 17, respectively, in the epinephrine and epinephrine plus lipid groups (P<0.05). CONCLUSIONS: Lipid emulsion with or without epinephrine, or epinephrine alone were equally effective in achieving a return to spontaneous circulation in this model of LAST. Epinephrine alone or in combination with lipid was associated with an increased number of ECG abnormalities compared with lipid emulsion alone.

epinephrine

levobupivacaine

cardiac toxicity

epinephrine

toxicity

levobupivacaine

cardiovascular collapse

ventricular tachycardia

fibrillation

epinephrine

epinephrine

epinephrine

epinephrine

epinephrine

epinephrine

Epinephrine


Incidence of heparin-induced thrombocytopenia type II and postoperative recovery of platelet count in liver graft recipients: a retrospective cohort analysis.

BACKGROUND: Thrombocytopenia in patients with end-stage liver disease is a common disorder caused mainly by portal hypertension, low levels of thrombopoetin, and endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type II (HIT type II) as a cause of thrombocytopenia after liver transplantation is not yet understood, with few literature citations reporting contradictory results. The aim of our study was to demonstrate the perioperative course of thrombocytopenia after liver transplantation and determine the occurrence of clinical HIT type II. METHOD: We retrospectively evaluated the medical records of 205 consecutive adult patients who underwent full-size liver transplantation between January 2006 and December 2010 due to end-stage or malignant liver disease. Preoperative platelet count, postoperative course of platelets, and clinical signs of HIT type II were analyzed. RESULTS: A total of 155 (75.6%) of 205 patients had thrombocytopenia before transplantation, significantly influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The platelet count exceeded 100,000/uL in most of the patients (n = 193) at a medium of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of HIT type II. CONCLUSIONS: The incidence of HIT in patients with end-stage hepatic failure is, with about 1.95%, rare. For further reduction of HIT type II, the use of intravenous heparin should be avoided and the prophylactic anticoagulation should be performed with low-molecular-weight heparin after normalization of platelet count.

heparin

thrombocytopenia type II

Thrombocytopenia

end-stage liver disease

portal hypertension

endotoxemia

heparin

thrombocytopenia type II

HIT type II

thrombocytopenia

thrombocytopenia

HIT type II

end-stage or malignant liver disease

end-stage
liver disease

malignant liver disease

HIT type II

thrombocytopenia

End-Stage Liver Disease

liver cirrhosis

HIT II

HIT type II

HIT

end-stage hepatic failure

HIT type II

heparin

heparin


Takotsubo syndrome (or apical ballooning syndrome) secondary to Zolmitriptan.

Takotsubo syndrome (TS), also known as broken heart syndrome, is characterized by left ventricle apical ballooning with elevated cardiac biomarkers and electrocardiographic changes suggestive of an acute coronary syndrome (ie, ST-segment elevation, T wave inversions, and pathologic Q waves). We report a case of 54-year-old woman with medical history of mitral valve prolapse and migraines, who was admitted to the hospital for substernal chest pain and electrocardiogram demonstrated 1/2 mm ST-segment elevation in leads II, III, aVF, V5, and V6 and positive troponin I. Emergent coronary angiogram revealed normal coronary arteries with moderately reduced left ventricular ejection fraction with wall motion abnormalities consistent with TS. Detailed history obtained retrospectively revealed that the patient took zolmitriptan sparingly only when she had migraines. But before this event, she was taking zolmitriptan 2-3 times daily for several days because of a persistent migraine headache. She otherwise reported that she is quite active, rides horses, and does show jumping without any limitations in her physical activity. There was no evidence of any recent stress or status migrainosus. Extensive literature search revealed multiple cases of coronary artery vasospasm secondary to zolmitriptan, but none of the cases were associated with TS.

Takotsubo syndrome

apical ballooning syndrome

Zolmitriptan

Takotsubo syndrome

TS

broken heart syndrome

acute coronary syndrome

mitral valve prolapse

migraines

chest pain

TS

zolmitriptan

migraines

zolmitriptan

migraine headache

status migrainosus

coronary artery vasospasm

zolmitriptan

TS


Depression, impulsiveness, sleep, and memory in past and present polydrug users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).

RATIONALE: Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide recreational drug of abuse. Unfortunately, the results from human research investigating its psychological effects have been inconsistent. OBJECTIVES: The present study aimed to be the largest to date in sample size and 5HT-related behaviors; the first to compare present ecstasy users with past users after an abstinence of 4 or more years, and the first to include robust controls for other recreational substances. METHODS: A sample of 997 participants (52 % male) was recruited to four control groups (non-drug (ND), alcohol/nicotine (AN), cannabis/alcohol/nicotine (CAN), non-ecstasy polydrug (PD)), and two ecstasy polydrug groups (present (MDMA) and past users (EX-MDMA). Participants completed a drug history questionnaire, Beck Depression Inventory, Barratt Impulsiveness Scale, Pittsburgh Sleep Quality Index, and Wechsler Memory Scale-Revised which, in total, provided 13 psychometric measures. RESULTS: While the CAN and PD groups tended to record greater deficits than the non-drug controls, the MDMA and EX-MDMA groups recorded greater deficits than all the control groups on ten of the 13 psychometric measures. Strikingly, despite prolonged abstinence (mean, 4.98; range, 4-9 years), past ecstasy users showed few signs of recovery. Compared with present ecstasy users, the past users showed no change for ten measures, increased impairment for two measures, and improvement on just one measure. CONCLUSIONS: Given this record of impaired memory and clinically significant levels of depression, impulsiveness, and sleep disturbance, the prognosis for the current generation of ecstasy users is a major cause for concern.

Depression

impulsiveness

MDMA

ecstasy

Ecstasy

MDMA

ecstasy

alcohol

nicotine

AN

cannabis

alcohol

nicotine

CAN

ecstasy

ecstasy

MDMA

MDMA

Depression

Impulsiveness

CAN

MDMA

MDMA

ecstasy

ecstasy

impaired memory

depression

impulsiveness

sleep disturbance

ecstasy


Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients.

Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER1 gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR)=0.615, 95% confidence interval (CI) 0.426-0.887, P=0.009) and visual hallucinations (PR=0.515, 95% CI 0.295-0.899, P=0.020). Our data suggest that HOMER1 rs4704559 G allele has a protective role for the development of levodopa adverse effects.

levodopa

Parkinson's disease

Levodopa

Parkinson's disease

dyskinesia

visual hallucinations

glutamate

levodopa

idiopathic Parkinson's disease

dyskinesia

visual hallucinations

levodopa


Crocin improves lipid dysregulation in subacute diazinon exposure through ERK1/2 pathway in rat liver.

INTRODUCTION: Diazinon Yis one of the most broadly used organophosphorus insecticides in agriculture. It has been shown that exposure to diazinon may interfere with lipid metabolism. Moreover, the hypolipidemic effect of crocin has been established. Earlier studies revealed the major role of Extracellular signal-regulated kinase (ERK) pathways in low-density lipoprotein receptor (LDLr) expression. The aim of this study was to evaluate changes in the regulation of lipid metabolism, ERK and LDLr expression in the liver of rats exposed to subacute diazinon. Furthermore ameliorating effect of crocin on diazinon induced disturbed cholesterol homeostasis was studied. METHODS: 24 Rats were divided into 4 groups and received following treatments for 4 weeks; Corn oil (control), diazinon (15mg/kg per day, orally) and crocin (12.5 and 25mg/kg per day, intraperitoneally) in combination with diazinon (15 mg/kg). The levels of cholesterol, triglyceride and LDL in blood of rats were analyzed. Moreover mRNA levels of LDLr and ERK1/2 as well as protein levels of total and activated forms of ERK1/2 in rat liver were evaluated by Western blotting and quantitative real time polymerase chain reaction analysis. RESULTS: Our data showed that subacute exposure to diazinon significantly increased concentrations of cholesterol, triglyceride and LDL. Moreover diazinon decreased ERK1/2 protein phosphorylation and LDLr transcript. Crocin reduced inhibition of ERK activation and diazinon-induced hyperlipemia and increased levels of LDLr transcript. CONCLUSIONS: Crocin may be considered as a novel protective agent in diazinon-induced hyperlipemia through modulating of ERK pathway and increase of LDLr expression.

Crocin

diazinon

Diazinon

organophosphorus

diazinon

crocin

diazinon

crocin

diazinon

cholesterol

diazinon

crocin

diazinon

cholesterol

triglyceride

diazinon

cholesterol

triglyceride

diazinon

Crocin

diazinon

hyperlipemia

Crocin

diazinon

hyperlipemia


GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m(2) day (D)1, D8 and D15; methylprednisolone 1,000 mg D1-5; and cisplatin 100 mg/m(2) D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1-6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30-62 %) and 5-year overall survival was 59 % (95 % CI, 43-74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.

GEM

Hodgkin lymphoma

Hodgkin lymphoma

HL

malignancy

toxicity

Gemcitabine

cisplatin

HL

toxicity

HL

gemcitabine

methylprednisolone

cisplatin

GEM

toxicity

GEM

GEM

GEM

toxicities

neutropenia

thrombocytopenia

GEM

GEM

GEM

HL


Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users.

RATIONALE: Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. OBJECTIVES: The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. METHOD: Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. RESULTS: Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. CONCLUSIONS: The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.

ecstasy

Ecstasy

MDMA

psychobiological dysfunction

ecstasy

cortisol

ecstasy

ecstasy

cortisol

anxiety

depression

cortisol

ecstasy

cortisol

cortisol

anxiety

depression

ecstasy

cortisol

ecstasy


Ifosfamide related encephalopathy: the need for a timely EEG evaluation.

BACKGROUND: Ifosfamide is an alkylating agent useful in the treatment of a wide range of cancers including sarcomas, lymphoma, gynecologic and testicular cancers. Encephalopathy has been reported in 10-40% of patients receiving high-dose IV ifosfamide. OBJECTIVE: To highlight the role of electroencephalogram (EEG) in the early detection and management of ifosfamide related encephalopathy. METHODS: Retrospective chart review including clinical data and EEG recordings was done on five patients, admitted to MD Anderson Cancer Center between years 2009 and 2012, who developed ifosfamide related acute encephalopathy. RESULTS: All five patients experienced symptoms of encephalopathy soon after (within 12 h-2 days) receiving ifosfamide. Two patients developed generalized convulsions while one patient developed continuous non-convulsive status epilepticus (NCSE) that required ICU admission and intubation. Initial EEG showed epileptiform discharges in three patients; run of triphasic waves in one patient and moderate degree diffuse generalized slowing. Mixed pattern with the presence of both sharps and triphasic waves were also noted. Repeat EEGs within 24_h of symptom onset showed marked improvement that was correlated with clinical improvement. CONCLUSIONS: Severity of ifosfamide related encephalopathy correlates with EEG changes. We suggest a timely EEG evaluation for patients receiving ifosfamide who develop features of encephalopathy.

Ifosfamide

encephalopathy

Ifosfamide

cancers

sarcomas

lymphoma

gynecologic and testicular cancers

Encephalopathy

ifosfamide

ifosfamide

encephalopathy

Cancer

ifosfamide

encephalopathy

encephalopathy

ifosfamide

convulsions

non-convulsive status epilepticus

NCSE

ifosfamide

encephalopathy

ifosfamide

encephalopathy


Incidence of contrast-induced nephropathy in hospitalised patients with cancer.

OBJECTIVES: To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer. METHODS: Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast-enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated. RESULTS: CIN was detected in 18/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P = 0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P = 0.005); it was also an independent risk factor (P = 0.017). CIN was significantly more after treatment with bevacizumab/irinotecan (P = 0.021) and in patients with hypertension (P = 0.044). CONCLUSIONS: The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab/irinotecan may be additional risk factors for CIN development. KEY POINTS: . Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. . CIN occurs more often when CT is performed <45 days after chemotherapy. . Hypertension and treatment with bevacizumab appear to be additional risk factors.

contrast

nephropathy

cancer

contrast

nephropathy

cancer

acute renal failure

contrast

creatinine

Cr

Cr

bevacizumab

irinotecan

hypertension

cancer

Hypertension

bevacizumab

irinotecan

Contrast

nephropathy

Hypertension

bevacizumab


Syndrome of inappropriate antidiuretic hormone secretion associated with desvenlafaxine.

OBJECTIVE: To report a case of syndrome of inappropriate anti-diuretic hormone (SIADH) secretion associated with desvenlafaxine. CASE SUMMARY: A 57-year old female with hyponatraemia. Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion. The serum sodium at this time was 120 mmol/L, serum osmolality was 263 mosmol/kg, urine osmolality 410 mosmol/kg and urine sodium 63 mmol/L, consistent with a diagnosis of SIADH. Desvenlafaxine was ceased and fluid restriction implemented. After 4 days the sodium increased to 128 mmol/L and fluid restriction was relaxed. During her further 3 weeks inpatient admission the serum sodium ranged from 134 to 137 mmol/L during treatment with mirtazapine. DISCUSSION: SIADH has been widely reported with a range of antidepressants. This case report suggests that desvenlafaxine might cause clinically significant hyponatremia. CONCLUSIONS: Clinicians should be aware of the potential for antidepressants to cause hyponatremia,and take appropriate corrective action where necessary.

desvenlafaxine

SIADH

desvenlafaxine

hyponatraemia

desvenlafaxine

nausea

anxiety

confusion

sodium

sodium

SIADH

Desvenlafaxine

sodium

sodium

mirtazapine

SIADH

desvenlafaxine

hyponatremia

hyponatremia


Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin.

The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial. Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly assigned to 2 experimental protocols: (1) rats were killed before (-24 h, n = 8) and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg/kg body weight) to determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX (4 mg/kg body weight/week) and were killed before the first injection (M0) and 1 week after each injection (M1, M2, M3, and M4) to determine the chronological effects. Animals used at M0 (n = 8) were also used at moment -24 h of acute study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology analyses were carried out at each time point. Single dose of DOX was associated with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed an effect of a cumulative dose on body weight (R = -0.99, p = 0.011), necrosis (R = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = -0.95, p = 0.049). DNA SBs damage was negatively associated with TAP (R = -0.98, p = 0.018), and necrosis (R = -0.97, p = 0.027). Our results suggest that oxidative damage is associated with acute cardiotoxicity induced by a single dose of DOX only. Increased resistance to the oxidative stress is plausible for the multiple dose of DOX. Thus, different mechanisms may be involved in acute toxicity versus chronic toxicity.

cardiotoxicity

doxorubicin

doxorubicin

DOX

cardiotoxicity

DOX

DOX

DOX

DOX

DOX

cardiac disarrangement

necrosis

necrosis

necrosis

cardiotoxicity

DOX

DOX

toxicity

toxicity


Tacrolimus-related seizure after pediatric liver transplantation--a single-center experience.

To identify the risk factors for new-onset seizures after pediatric LT and to assess their clinical implications and long-term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non-seizures group. Pre-operative, intra-operative, and post-operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic-clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end-stage liver disease score before surgery, Child-Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure-free without anti-epileptic drugs over a mean follow-up period of 33.7 + 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post-operative period after pediatric LT. High PELD and Child-Pugh scores before LT and high post-operative serum Tbil may be contributory risk factors for TAC-related seizures.

Tacrolimus

seizure

seizures

seizures

seizures

Seizures

tonic-clonic seizures

seizures

end-stage liver disease

bilirubin

TAC

TAC

seizures

seizures

seizure

epileptic

TAC

seizures

TAC

seizures


The flavonoid apigenin delays forgetting of passive avoidance conditioning in rats.

The present experiments were performed to study the effect of the flavonoid apigenin (20 mg/kg intraperitoneally (i.p.), 1 h before acquisition), on 24 h retention performance and forgetting of a step-through passive avoidance task, in young male Wistar rats. There were no differences between saline- and apigenin-treated groups in the 24 h retention trial. Furthermore, apigenin did not prevent the amnesia induced by scopolamine (1mg/kg, i.p., 30 min before the acquisition). The saline- and apigenin-treated rats that did not step through into the dark compartment during the cut-off time (540 s) were retested weekly for up to eight weeks. In the saline treated group, the first significant decline in passive avoidance response was observed at four weeks, and complete memory loss was found five weeks after the acquisition of the passive avoidance task. At the end of the experimental period, 60% of the animals treated with apigenin still did not step through. These data suggest that 1) apigenin delays the long-term forgetting but did not modulate the 24 h retention of fear memory and 2) the obtained beneficial effect of apigenin on the passive avoidance conditioning is mediated by mechanisms that do not implicate its action on the muscarinic cholinergic system.

flavonoid

apigenin

flavonoid

apigenin

apigenin

apigenin

amnesia

scopolamine

apigenin

memory loss

apigenin

apigenin

apigenin


Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats.

Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1ug, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1ug, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10ug, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10ug, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.

Cholecystokinin-octapeptide

morphine

Cholecystokinin-octapeptide

morphine

amnesia

morphine

morphine

morphine

morphine

morphine

morphine

memory impairment


Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats.

In the present study the role of glial activation and post synaptic toxicity in ICV Streptozotocin (STZ) induced memory impaired rats was explored. In experiment set up 1: Memory deficit was found in Morris water maze test on 14-16 days after STZ (ICV; 3mg/Kg) administration. STZ causes increased expression of GFAP, CD11b and TNF-a indicating glial activation and neuroinflammation. STZ also significantly increased the level of ROS, nitrite, Ca(2+) and reduced the mitochondrial activity in synaptosomal preparation illustrating free radical generation and excitotoxicity. Increased expression and activity of Caspase-3 was also observed in STZ treated rat which specify apoptotic cell death in hippocampus and cortex. STZ treatment showed decrease expression of post synaptic markers CaMKIIa and PSD-95, while, expression of pre synaptic markers (synaptophysin and SNAP-25) remains unaltered indicating selective post synaptic neurotoxicity. Oral treatment with Memantine (10mg/kg) and Ibuprofen (50 mg/kg) daily for 13 days attenuated STZ induced glial activation, apoptotic cell death and post synaptic neurotoxicity in rat brain. Further, in experiment set up 2: where memory function was not affected i.e. 7-9 days after STZ treatment. The level of GFAP, CD11b, TNF-a, ROS and nitrite levels were increased. On the other hand, apoptotic marker, synaptic markers, mitochondrial activity and Ca(2+) levels remained unaffected. Collective data indicates that neuroinflammatory process and oxidative stress occurs earlier to apoptosis and does not affect memory function. Present study clearly suggests that glial activation and post synaptic neurotoxicity are the key factors in STZ induced memory impairment and neuronal cell death.

neurotoxicity

Streptozotocin

memory impairment

toxicity

Streptozotocin

STZ

memory impaired

Memory deficit

STZ

STZ

neuroinflammation

STZ

nitrite

Ca

excitotoxicity

STZ

STZ

neurotoxicity

Memantine

Ibuprofen

STZ

neurotoxicity

STZ

nitrite

Ca

neuroinflammatory

neurotoxicity

STZ

memory impairment


Comparison of effects of isotonic sodium chloride with diltiazem in prevention of contrast-induced nephropathy.

INTRODUCTION AND OBJECTIVE: Contrast-induced nephropathy (CIN) significantly increases the morbidity and mortality of patients. The aim of this study is to investigate and compare the protective effects of isotonic sodium chloride with sodium bicarbonate infusion and isotonic sodium chloride infusion with diltiazem, a calcium channel blocker, in preventing CIN. MATERIALS AND METHODS: Our study included patients who were administered 30-60 mL of iodinated contrast agent for percutaneous coronary angiography (PCAG), all with creatinine values between 1.1 and 3.1 mg/dL. Patients were divided into three groups and each group had 20 patients. The first group of patients was administered isotonic sodium chloride; the second group was administered a solution that of 5% dextrose and sodium bicarbonate, while the third group was administered isotonic sodium chloride before and after the contrast injection. The third group received an additional injection of diltiazem the day before and first 2 days after the contrast injection. All of the patients' plasma blood urea nitrogen (BUN) and creatinine levels were measured on the second and seventh day after the administration of intravenous contrast material. RESULTS: The basal creatinine levels were similar for all three groups (p > 0.05). Among a total of 60 patients included in the study, 16 patients developed acute renal failure (ARF) on the second day after contrast material was injected (26.6%). The number of patients who developed ARF on the second day after the injection in the first group was five (25%), in the second group was six (30%) and the third group was five (25%) (p > 0.05). CONCLUSION: There was no significant difference between isotonic sodium chloride, sodium bicarbonate and isotonic sodium chloride with diltiazem application in prevention of CIN.

sodium chloride

diltiazem

contrast

nephropathy

Contrast

nephropathy

sodium chloride

sodium bicarbonate

sodium chloride

diltiazem

calcium

contrast

creatinine

sodium chloride

dextrose

sodium bicarbonate

sodium chloride

contrast

diltiazem

contrast

blood urea nitrogen

BUN

creatinine

contrast

creatinine

acute renal failure

ARF

contrast

ARF

sodium chloride

sodium bicarbonate

sodium chloride

diltiazem


Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children's Oncology Group.

Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with "standard-risk" acute lymphoblastic leukemia, 1.00 to 9.99 years at diagnosis, without evidence of CNS leukemia at diagnosis were enrolled on ACCL0131: 28 from P9201 and 38 from P9605. Magnetic resonance imaging scans and standard neuropsychological tests were performed >2.6 years after the end of treatment. Significantly more P9605 patients developed leukoencephalopathy compared with P9201 patients (68%, 95% confidence interval 49%-83% vs. 22%, 95% confidence interval 5%-44%; P=0.001) identified as late as 7.7 years after the end of treatment. Overall, 40% of patients scored <85 on either Verbal or Performance IQ. Children on both studies had significant attention problems, but P9605 children scored below average on more neurocognitive measures than those treated on P9201 (82%, 14/17 measures vs. 24%, 4/17 measures). This supports ongoing concerns about intensive MTX exposure as a major contributor to CNS late effects.

acute lymphoblastic leukemia

methotrexate

methotrexate

MTX

neurotoxicity

MTX

acute lymphoblastic leukemia

leukoencephalopathy

acute lymphoblastic leukemia

leukemia

leukoencephalopathy

attention problems

MTX


Tranexamic acid overdosage-induced generalized seizure in renal failure.

We report a 45-year-old lady with chronic kidney disease stage 4 due to chronic tubulointerstial disease. She was admitted to our center for severe anemia due to menorrhagia and deterioration of renal function. She was infused three units of packed cells during a session of hemodialysis. Tranexamic acid (TNA) 1 g 8-hourly was administered to her to control bleeding per vaginum. Two hours after the sixth dose of TNA, she had an episode of generalized tonic clonic convulsions. TNA was discontinued. Investigations of the patient revealed no biochemical or structural central nervous system abnormalities that could have provoked the convulsions. She did not require any further dialytic support. She had no further episodes of convulsion till dis-charge and during the two months of follow-up. Thus, the precipitating cause of convulsions was believed to be an overdose of TNA.

Tranexamic acid

seizure

renal failure

chronic kidney disease

tubulointerstial disease

anemia

menorrhagia

deterioration of renal function

Tranexamic acid

TNA

bleeding

TNA

tonic clonic convulsions

TNA

nervous system abnormalities

convulsions

convulsion

convulsions

overdose

TNA


Pre-treatment of bupivacaine-induced cardiovascular depression using different lipid formulations of propofol.

BACKGROUND: Pre-treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine-induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine-induced cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0.5 mg/kg/min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg/kg/min bupivacaine 0.5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole. RESULTS: The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C. CONCLUSION: We conclude that pre-treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine-induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice.

bupivacaine

cardiovascular depression

propofol

bupivacaine

propofol

bupivacaine

cardiotoxicity

propofol

bupivacaine

cardiotoxicity

ketamine

propofol

propofol

bupivacaine

dysrhythmia

asystole

bupivacaine

asystole

dysrhythmia

asystole

bupivacaine

bupivacaine

Bupivacaine

propofol

propofol

bupivacaine

cardiotoxic

bupivacaine

bupivacaine

propofol


Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.

Although statins are generally well-tolerated drugs, recent cases of drug-induced liver injury associated with their use have been reported. A 52-year-old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.

Drug-Induced Acute Liver Injury

Fluvastatin

statins

drug-induced liver injury

liver damage

fluvastatin

nausea

anorexia

abdominal pain

creatine

fluvastatin

hepatic damage


Fluconazole associated agranulocytosis and thrombocytopenia.

CASE: We describe a second case of fluconazole associated agranulocytosis with thrombocytopenia and recovery upon discontinuation of therapy. The patient began to have changes in white blood cells and platelets within 48 h of administration of fluconazole and began to recover with 48 h of discontinuation. This case highlights that drug-induced blood dyscrasias can occur unexpectedly as a result of treatment with a commonly used drug thought to be "safe". CONCLUSION: According to Naranjo's algorithm the likelihood that our patient's agranulocytosis and thrombocytopenia occurred as a result of therapy with fluconazole is probable, with a total of six points. We feel that the weight of the overall evidence of this evidence is strong. In particular the temporal relationship of bone marrow suppression to the initiation of fluconazole and the abatement of symptoms that rapidly reversed immediately following discontinuation.

Fluconazole

agranulocytosis

thrombocytopenia

fluconazole

agranulocytosis

thrombocytopenia

fluconazole

blood dyscrasias

agranulocytosis

thrombocytopenia

fluconazole

bone marrow suppression

fluconazole


Two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine-based chemotherapy.

AIMS: To investigate whether alterations of myocardial strain and high-sensitive cardiac troponin T (cTnT) could predict future cardiac dysfunction in patients after epirubicin exposure. METHODS: Seventy-five patients with non-Hodgkin lymphoma treated with epirubicin were studied. Blood collection and echocardiography were performed at baseline, 1 day after the third cycle, and 1 day after completion of chemotherapy. Patients were studied using echocardiography during follow-up. Global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were calculated using speckle tracking echocardiography. Left ventricular ejection fraction was analysed by real-time 3D echocardiography. Cardiotoxicity was defined as a reduction of the LVEF of >5% to <55% with symptoms of heart failure or an asymptomatic reduction of the LVEF of >10% to <55%. RESULTS: Fourteen patients (18.67%) developed cardiotoxicity after treatment. GLS (-18.48 + 1.72% vs. -15.96 + 1.6%), GCS (-20.93 + 2.86% vs. -19.20 + 3.21%), and GRS (39.23 + 6.44% vs. 34.98 + 6.2%) were markedly reduced and cTnT was elevated from 0.0010 + 0.0020 to 0.0073 + 0.0038 ng/mL (P all < 0.01) at the completion of chemotherapy compared with baseline values. A >15.9% decrease in GLS [sensitivity, 86%; specificity, 75%; area under the curve (AUC) = 0.815; P = 0.001] and a >0.004 ng/mL elevation in cTnT (sensitivity, 79%; specificity, 64%; AUC = 0.757; P = 0.005) from baseline to the third cycle of chemotherapy predicted later cardiotoxicity. The decrease in GLS remained the only independent predictor of cardiotoxicity (P = 0.000). CONCLUSIONS: GLS combined with cTnT may provide a reliable and non-invasive method to predict cardiac dysfunction in patients receiving anthracycline-based chemotherapy.

cardiotoxicity

epirubicine

myocardial strain

cardiac dysfunction

epirubicin

non-Hodgkin lymphoma

epirubicin

Cardiotoxicity

heart failure

cardiotoxicity

cardiotoxicity

cardiotoxicity

cardiac dysfunction

anthracycline


Prevention of etomidate-induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study.

BACKGROUND: In this retrospective comparative study, we aimed to compare the effectiveness of fentanyl, midazolam, and a combination of fentanyl and midazolam to prevent etomidate-induced myoclonus. MATERIAL AND METHODS: This study was performed based on anesthesia records. Depending on the drugs that would be given before the induction of anesthesia with etomidate, the patients were separated into 4 groups: no pretreatment (Group NP), fentanyl 1 ug.kg-1 (Group F), midazolam 0.03 mg.kg-1 (Group M), and midazolam 0.015 mg.kg-1 + fentanyl 0.5 ug.kg-1 (Group FM). Patients who received the same anesthetic procedure were selected: 2 minutes after intravenous injections of the pretreatment drugs, anesthesia is induced with 0.3 mg.kg-1 etomidate injected intravenously over a period of 20-30 seconds. Myoclonic movements are evaluated, which were observed and graded according to clinical severity during the 2 minutes after etomidate injection. The severity of pain due to etomidate injection, mean arterial pressure, heart rate, and adverse effects were also evaluated. RESULTS: Study results showed that myoclonus incidence was 85%, 40%, 70%, and 25% in Group NP, Group F, Group M, and Group FM, respectively, and were significantly lower in Group F and Group FM. CONCLUSIONS: We conclude that pretreatment with fentanyl or combination of fentanyl and midazolam was effective in preventing etomidate-induced myoclonus.

etomidate

myoclonus

Fentanyl

midazolam

fentanyl

midazolam

fentanyl

midazolam

etomidate

myoclonus

etomidate

fentanyl

midazolam

midazolam

fentanyl

etomidate

Myoclonic movements

etomidate

pain

etomidate

myoclonus

fentanyl

fentanyl

midazolam

etomidate

myoclonus


Cholestatic presentation of yellow phosphorus poisoning.

Yellow phosphorus, a component of certain pesticide pastes and fireworks, is well known to cause hepatotoxicity. Poisoning with yellow phosphorus classically manifests with acute hepatitis leading to acute liver failure which may need liver transplantation. We present a case of yellow phosphorus poisoning in which a patient presented with florid clinical features of cholestasis highlighting the fact that cholestasis can rarely be a presenting feature of yellow phosphorus hepatotoxicity.

Cholestatic

phosphorus

poisoning

phosphorus

hepatotoxicity

Poisoning

phosphorus

acute hepatitis

acute liver failure

phosphorus

poisoning

cholestasis

cholestasis

phosphorus

hepatotoxicity


Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for pediatric procedural sedation.

We report syncope and bradycardia in an 11-year-old girl following administration of intranasal dexmedetomidine for sedation for a voiding cystourethrogram. Following successful completion of VCUG and a 60-min recovery period, the patient's level of consciousness and vital signs returned to presedation levels. Upon leaving the sedation area, the patient collapsed, with no apparent inciting event. The patient quickly regained consciousness and no injury occurred. The primary abnormality found was persistent bradycardia, and she was admitted to the hospital for telemetric observation. The bradycardia lasted ~2 h, and further cardiac workup revealed no underlying abnormality. Unanticipated and previously unreported outcomes may be witnessed as we expand the use of certain sedatives to alternative routes of administration.

Vasovagal syncope

bradycardia

dexmedetomidine

syncope

bradycardia

dexmedetomidine

bradycardia

bradycardia


Paradoxical severe agitation induced by add-on high-doses quetiapine in schizo-affective disorder.

We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.

agitation

quetiapine

schizo-affective disorder

schizo-affective disorder

zuclopenthixol

lithium

lithium

personality disorder

antisocial disorder

substance abuse disorder

quetiapine

agitation

aggressiveness

personality disorder

manic

akathisia

quetiapine

agitation

agitation

quetiapine


Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension in rat.

Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30  u g/kg/day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300 mg/kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail-cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered (P < 0.01) and dose dependently prevented (P < 0.001) Dex-induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex-induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF.

dexamethasone

hypertension

Dexamethasone

Dex

hypertension

iron

hypertension

Dex

Dex

Dex

hydrogen peroxide

Dexamethasone

Dex

hypertension

weight loss

Dex

hypertension


The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients.

Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in-hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26 (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative seizures.

tranexamic acid

convulsive

seizures

seizures

convulsive

seizure

abnormal involuntary motor movements

seizures

convulsive

seizures

Generalised and focal seizures

seizure

seizures

congestive heart failure

hypothermic

tranexamic acid

tranexamic acid

seizures

convulsive

seizures

convulsive

seizures

convulsive

seizures

seizures

Convulsive

seizures

postoperative complication

tranexamic acid

seizures


Dysfunctional overnight memory consolidation in ecstasy users.

Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naive healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users.

Dysfunctional overnight memory

ecstasy

ecstasy

sleep-related impairments

ecstasy

Ecstasy

impaired overnight memory

ecstasy

ecstasy

memory impairments

ecstasy


Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?

A 77-year-old woman presented with subacute onset progressive confusion, aggression, auditory hallucinations and delusions. In the preceding months, the patient had a number of admissions with transient unilateral hemiparesis with facial droop, and had been started on valproate for presumed hemiplegic migraine. Valproate was withdrawn soon after admission and her cognitive abilities have gradually improved over 3 months of follow-up. Valproate levels taken prior to withdrawal were subtherapeutic and the patient was normoammonaemic. EEG undertaken during inpatient stay showed changes consistent with encephalopathy, and low titre N-methyl-D-aspartate (NMDA) receptor antibodies were present in this patient. The possible aetiologies of valproate-induced encephalopathy and NMDA receptor-associated encephalitis present a diagnostic dilemma. We present a putative combinatorial hypothesis to explain this patient's symptoms.

encephalopathy

valproate

confusion

aggression

auditory hallucinations

delusions

hemiparesis

valproate

hemiplegic migraine

Valproate

Valproate

encephalopathy

N-methyl-D-aspartate

NMDA

valproate

encephalopathy

NMDA

encephalitis


Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine.

Pethidine is an opioid that gains its popularity for the effective pain control through acting on the opioid-receptors. However, rapid pain relief sometimes brings about unfavourable side effects that largely limit its clinical utility. Common side effects include nausea, vomiting and hypotension. In patients with impaired renal and liver function, and those who need long-term pain control, pethidine may cause excitatory central nervous system (CNS) effects through its neurotoxic metabolite, norpethidine, resulting in irritability and seizure attack. On the contrary, though not clinically apparent, pethidine potentially causes inhibitory impacts on the CNS and impairs normal cerebellar and oculomotor function in the short term. In this case report, we highlight opioid's inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity.

Cerebellar and oculomotor dysfunction

Cerebellar dysfunction

oculomotor dysfunction

pethidine

Pethidine

pain

pain

nausea

vomiting

hypotension

impaired renal and liver function

impaired renal
function

impaired
liver function

pain

pethidine

neurotoxic

norpethidine

irritability

seizure

pethidine

dysmetria

dysarthria


Baboon syndrome induced by ketoconazole.

A 27-year-old male patient presented with a maculopapular eruption on the flexural areas and buttocks after using oral ketoconazole. The patient was diagnosed with drug-induced baboon syndrome based on his history, which included prior sensitivity to topical ketoconazole, a physical examination, and histopathological findings. Baboon syndrome is a drug- or contact allergen-related maculopapular eruption that typically involves the flexural and gluteal areas. To the best of our knowledge, this is the first reported case of ketoconazole-induced baboon syndrome in the English literature.

Baboon syndrome

ketoconazole

maculopapular eruption

ketoconazole

baboon syndrome

ketoconazole

Baboon syndrome

maculopapular eruption

ketoconazole

baboon syndrome


A Case of Sudden Cardiac Death due to Pilsicainide-Induced Torsades de Pointes.

An 84-year-old male received oral pilsicainide, a pure sodium channel blocker with slow recovery kinetics, to convert his paroxysmal atrial fibrillation to a sinus rhythm; the patient developed sudden cardiac death two days later. The Holter electrocardiogram, which was worn by chance, revealed torsade de pointes with gradually prolonged QT intervals. This drug is rapidly absorbed from the gastrointestinal tract, and most of it is excreted from the kidney. Although the patient's renal function was not highly impaired and the dose of pilsicainide was low, the plasma concentration of pilsicainide may have been high, which can produce torsades de pointes in the octogenarian. Although the oral administration of class IC drugs, including pilsicainide, is effective to terminate atrial fibrillation, careful consideration must be taken before giving these drugs to octogenarians.

Sudden Cardiac Death

Pilsicainide

Torsades de Pointes

pilsicainide

sodium

atrial fibrillation

sudden cardiac death

torsade de pointes

pilsicainide

pilsicainide

torsades de pointes

pilsicainide

atrial fibrillation


All-trans retinoic acid-induced inflammatory myositis in a patient with acute promyelocytic leukemia.

All-trans retinoic acid (ATRA), a component of standard therapy for acute promyelocytic leukemia (APL), is associated with potentially serious but treatable adverse effects involving numerous organ systems, including rare skeletal muscle involvement. Only a handful of cases of ATRA-induced myositis in children have been reported, and none in the radiology literature. We present such a case in a 15-year-old boy with APL, where recognition of imaging findings played a crucial role in making the diagnosis and facilitated prompt, effective treatment.

All-trans retinoic acid

myositis

acute promyelocytic leukemia

All-trans retinoic acid

ATRA

acute promyelocytic leukemia

APL

ATRA

myositis

APL


Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma.

This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg + 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg + 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.

lomustine

cyclophosphamide

lymphoma

toxicity

lomustine

CCNU

cyclophosphamide

CTX

lymphoma

CCNU

CTX

Neutropenia

neutropenia

CCNU

CTX

neutropenia

neutropenia

hepatotoxicity

renal toxicity

hemorrhagic cystitis

hemorrhagic

cystitis

CCNU

CTX

tumor


Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature.

Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal (IT) chemotherapy is reported. A 37-year-old Caucasian woman with a history of T-cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally treated with induction chemotherapy followed by an autologous transplant. She developed relapsed disease 10 months later with leukemic involvement. She was re-induced with nelarabine 1500 mg/m(2) on days 1, 3, and 5 with 1 dose of IT cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the time of treatment, she was on continuous renal replacement therapy due to sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a complete remission, and recovered her renal function. She received a second cycle of nelarabine without additional IT prophylaxis one month later. A week after this second cycle, she noted numbness in her lower extremities. Predominantly sensory, though also motor and autonomic, peripheral neuropathy started in her feet, ascended proximally to the mid-thoracic region, and eventually included her distal upper extremities. A magnetic resonance imaging (MRI) of her spine demonstrated changes from C2 to C6 consistent with subacute combined degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy stabilized and showed slight improvement and ultimately received an unrelated, reduced-intensity allogeneic transplant while in complete remission, but relapsed disease 10 weeks later. She is currently being treated with best supportive care. To our knowledge, this is the first published case report of severe neurotoxicity caused by nelarabine in a patient who received concurrent IT chemotherapy.

Nelarabine

neurotoxicity

nelarabine

neurotoxicity

T-cell lymphoblastic lymphoma

leukemic

nelarabine

cytarabine

tumor lysis syndrome

TLS

nelarabine

peripheral neuropathy

Nelarabine

neuropathy

neurotoxicity

nelarabine


Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient.

Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.

Valproate

hyperammonemic

encephalopathy

Neurological complications

Valproate

hyperammonemic

encephalopathy

valproate

valproate

epilepsy

impaired consciousness

hyperammonemia

valproate

valproate


Necrotising fasciitis after bortezomib and dexamethasone-containing regimen in an elderly patient of Waldenstrom macroglobulinaemia.

Bortezomib and high-dose dexamethasone-containing regimens are considered to be generally tolerable with few severe bacterial infections in patients with B-cell malignancies. However, information is limited concerning the safety of the regimen in elderly patients. We report a case of a 76-year-old man with Waldenstrom macroglobulinaemia who suffered necrotising fasciitis without neutropenia after the combination treatment with bortezomib, high-dose dexamethasone and rituximab. Despite immediate intravenous antimicrobial therapy, he succumbed 23 h after the onset. Physicians should recognise the possibility of fatal bacterial infections related to bortezomib plus high-dose dexamethasone in elderly patients, and we believe this case warrants further investigation.

Necrotising fasciitis

bortezomib

dexamethasone

Waldenstrom macroglobulinaemia

Bortezomib

dexamethasone

bacterial infections

malignancies

Waldenstrom macroglobulinaemia

necrotising fasciitis

neutropenia

bortezomib

dexamethasone

bacterial infections

bortezomib

dexamethasone


An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity.

Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.25 mg/kg DOX weekly for 8 weeks followed by a 4 week off-dosing "recovery" period. Electron microscopy of the myocardium revealed subcellular degeneration and marked mitochondrial changes after a single dose. Histopathological analysis revealed progressive cardiomyocyte degeneration, hypertrophy/cytomegaly, and extensive vacuolation after two doses. Extensive replacement fibrosis (quantified by Sirius red staining) developed during the off-dosing period. Functional indices assessed by cardiac MRI (including left ventricular ejection fraction (LVEF), cardiac output, and E/A ratio) declined progressively, reaching statistical significance after two doses and culminating in "clinical" LV dysfunction by 12 weeks. Significant increases in peak myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged after eight doses, importantly preceding the LVEF decline to <50%. Troponin I levels positively correlated with delayed and peak gadolinium contrast enhancement, histopathological grading, and diastolic dysfunction. In summary, subcellular cardiomyocyte degeneration was the earliest marker, followed by progressive functional decline and histopathological manifestations. Myocardial contrast enhancement and elevations in cTnI occurred later. However, all indices predated "clinical" LV dysfunction and thus warrant further evaluation as predictive biomarkers.

doxorubicin

cardiotoxicity

cancer

doxorubicin

DOX

cardiomyopathy

toxicity

DOX

subcellular degeneration

cardiomyocyte degeneration

hypertrophy

fibrosis

LV dysfunction

gadolinium

diastolic dysfunction

cardiomyocyte degeneration

LV dysfunction


Intradermal glutamate and capsaicin injections: intra- and interindividual variability of provoked hyperalgesia and allodynia.

Intradermal injections of glutamate and capsaicin are attractive to use in human experimental pain models because hyperalgesia and allodynia mimic isolated aspects of clinical pain disorders. The aim of the present study was to investigate the reproducibility of these models. Twenty healthy male volunteers (mean age 24 years; range 18-38 years) received intradermal injections of glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick hyperalgesia and brush-evoked allodynia were investigated using von Frey filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary hyperalgesia and allodynia were quantified immediately after injection and after 15, 30 and 60 min. Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter- and intra-individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71). Intra-individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena.

glutamate

capsaicin

hyperalgesia

allodynia

glutamate

capsaicin

pain

hyperalgesia

allodynia

pain disorders

glutamate

capsaicin

hyperalgesia

allodynia

secondary hyperalgesia

allodynia

hyperalgesia

glutamate

capsaicin

hyperalgesia

Glutamate

Capsaicin

secondary hyperalgesia

allodynia

secondary hyperalgesia

allodynia

glutamate

capsaicin

hyperalgesic

allodynic


Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma.

Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma.

glaucoma

glaucoma

ocular hypertension

glaucoma

primary open-angle glaucoma

POAG

glaucoma

glaucoma

glaucoma

dexamethasone

retinal ganglion

axonal degeneration

glaucoma

dexamethasone

ocular hypertension

dexamethasone

Dexamethasone

dexamethasone

ocular hypertension

sodium 4-phenylbutyrate

dexamethasone

ocular hypertension

ocular hypertension

glaucoma


Effects of ginsenosides on opioid-induced hyperalgesia in mice.

Opioid-induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid-induced writhing test. Re (300 mg/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.

ginsenosides

hyperalgesia

hyperalgesia

OIH

OIH

opioid addiction

Re, Rg1, and Rb1 ginsenosides

Re ginsenosides

ginsenosides

Rb1 ginsenosides

OIH

OIH

morphine

Re

acetic acid

Re

OIH

acetic acid

Rg1 and Rb1 ginsenosides

ginsenosides

Rb1 ginsenosides

OIH

OIH

acetic acid

ginsenoside Re

OIH