Drug-induced Stevens-Johnson syndrome in Indian population: A multicentric retrospective analysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening hypersensitivity reactions mainly caused by drugs. Data on incubation period, hospital stay, and outcome for HIV-positive patients are sparse. Role of corticosteroids in their management is still controversial. METHODS: Indoor cases of SJS, SJS-TEN overlap, and TEN were analyzed for causative drugs, incubation period, a severity-of-illness score for toxic epidermal necrolysis (SCORTEN) score, HIV status, treatment, and outcome. Comparison of parameters between HIV and non-HIV cases was done. Utilization pattern of corticosteroids and their role in outcome were evaluated. RESULTS: Four SJS, 15 SJS-TEN overlap, and 21 TEN cases were evaluated. Antimicrobials (27.1%), antiviral (23%), antiseizure drugs (8.4%), and analgesics (8.4%) were commonly associated drugs. Among 12 (30%) HIV-reactive cases, nevirapine (97.6%) and cotrimoxazole (41.6%) were common causative drugs. Males (75%) were affected more than females (25%) among HIV-positive individuals. Incubation period was significantly higher in HIV-reactive patients. Total 30 (75%) patients were treated with corticosteroids. Dexamethasone (90%) and prednisolone (26.6%) were most commonly used. No significant difference was found among cases treated with or without corticosteroids. CONCLUSIONS: Antimicrobial drugs are common to cause SJS/TEN. Among HIV-reactive patients, male have more risk, incubation period is more and severity of reaction is less. Effectiveness of corticosteroids for treatment of SJS/TEN is inconclusive.

Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model.

Trabecular bone volume fraction assessments are likely sensitive to the analysis method and selection of the region of interest. Currently, there are several methods for selecting the region of interest to analyze trabecular bone in animal models of post-traumatic osteoarthritis. The objective of this study was to compare three published methods for determining the trabecular bone volume fraction of the medial tibial epiphyses in ACL transected and contralateral ACL intact knees. Micro-computed tomography images of both knees were obtained five weeks post-operatively and evaluated using three methods: (1) the Whole Compartment Method that captured the entire medial compartment, (2) the centrally located Single Core Method, and (3) the Triplet Core Method that averaged focal locations in the anterior, central, and posterior regions. The Whole Compartment Method detected significant bone loss in the ACL transected knee compared to the ACL intact knee (p<0.001), with a loss of 15.2±3.9%. The Single Core and the Triplet Core Methods detected losses of 7.5±10.5% (p=0.061) and 14.1±13.7%(p=0.01), respectively. Details regarding segmentation methods are important for facilitating comparisons between studies, and for selecting methods to document trabecular bone changes and treatment outcomes. Based on these findings, the Whole Compartment Method is recommended, as it was least variable and more sensitive for detecting differences in the bone volume fraction in the medial compartment.

Effect of Zidovudine and its interaction with rocuronium on neuromuscular transmission.

Neuromuscular weakness is often found in patients receiving zidovudine therapy due to mitochondrial damage. Effect of zidovudine was evaluated in indirectly and directly stimulated isolated rat phrenic nerve hemidiaphragm preparations, by cumulative dose response curve with square wave pulses, 0.5 ms duration of 2 Hz at every 10 s. To understand the observed effect of zidovudine, interaction studies were carried out with rocuronium. Dose response curve of rocuronium was compared in the absence and in the presence of 1.2 and 12 mmol/ml zidovudine. In another set of experiment, intact animals were treated with zidovudine 50 and 100 mg/kg for 15 days and phrenic nerve hemidiaphragm was obtained for in vitro experiment. Effect of zidovudine (30 mmol/ml) on twitch responses inhibited by dantrolene 50 µmol/ml, magnesium chloride 8 mmol/ml, rocuronium 10 µmol/ml, succinylcholine 25 µmol/ml and lignocaine 600 µmol/ml was studied. Zidovudine (3-30 mmol/ml) significantly augmented the twitch responses up to 80 and 40% in indirectly and directly stimulated preparations, respectively (P<0.05). Zidovudine did not show significant interaction with rocuronium in any group as per dose response curve and inhibitory concentration 5%, inhibitory concentration 50% and inhibitory concentration 95% of rocuronium. Zidovudine (30 mmol/ml) augmented the twitch responses inhibited by dantrolene, magnesium chloride and rocuronium. It reduced the time for complete block of succinylcholine (P<0.05). Zidovudine affects the neuromuscular transmission. No conclusive interaction between rocuronium and zidovudine was found.

Neuromuscular blocking effect of fluoxetine and its interaction with rocuronium.

As selective serotonin reuptake inhibitors have an inhibitory effect on nicotinic acetylcholine receptors, they may affect the neuromuscular transmission and interact with neuromuscular blockers. This study was designed to observe the effect of fluoxetine on neuromuscular transmission and its interaction with rocuronium using the rat phrenic nerve hemidiaphragm and rabbit head drop methods. Rat phrenic nerve hemidiaphragms were mounted and stimulated using a train of four pulses (TOF). The effect of fluoxetine was studied on both indirectly and directly stimulated basal twitch responses by plotting cumulative dose response curves (DRCs). DRCs of rocuronium were obtained in the absence, and presence of 5 µm and 20 µm fluoxetine to study its interaction. ED5 , ED50 and ED95 values of rocuronium DRCs in absence and presence of fluoxetine were calculated. Fluoxetine significantly inhibited twitch responses in both indirect and directly stimulated preparations. Fluoxetine (20 µm) caused an increase in the potency of rocuronium such that the ED50 and ED95 values of rocuronium DRCs were significantly decreased. Partially inhibited twitch responses by fluoxetine (100 µm) were not reversed by neostigmine (3.3 µm) or 3,4 diaminopyridine (0.25 µm). Rabbits were given fluoxetine 0.25 mg kg(-1) and 1 mg kg(-1) orally for 15 days, and on 15th day, rocuronium infusion was given, and time for head drop was recorded. The time of head drop was significantly reduced in fluoxetine pretreated as compared to control group. Fluoxetine blocks the neuromuscular transmission and increases the potency of rocuronium-induced neuromuscular block.

Montmorillonite Poly-L-Lactide Microcomposites of Procainamide for controlled drug delivery: In vitro and In vivo evaluation.

The research work reported in this paper is extension of our previous findings related to intercalation of procainamide hydrochloride, an antiarrythmia drug in interlayer gallery of Na(+)-clay (montmorillonite). The microcomposite particles prepared from procainamide-montmorillonite hybrid and poly L-lactide were characterised by scanning electron microscope and atomic force microscopy analysis. In vitro drug release study in simulated intestinal fluid showed controlled release pattern up to ~72 h and significant reduction in the drug release in gastric environment. In vivo pharmacokinetics and biodistribution in rats showed that the plasma/tissue drug levels were within therapeutic window as compared with free drug. The data from toxicity biomarker estimations and clinical biochemistry/haematological parameters showed significant reduction in drug toxicity when formulated in montmorillonite/poly L-lactide as compared with free drug, which is of considerable value in achieving improved therapy with reduced side effects.

Differential diagnosis of an unusual shoulder articular lesion in an ancient domestic dog (Canis lupus familiaris L., 1758).

A proximal humeral articular surface from an ancient domestic dog deliberate burial was examined during survey of small mammal bones from a prehistoric early Late Woodland archeological site. An unusual lesion on the caudolateral articular surface prompted micro-computed tomography to define detailed structure. Results indicate cortical or immature woven bone arising subchondrally, replacing normal trabeculae, extending through a breach in the cortical surface, and having sharp transition with surrounding normal bone. Organized bone within the lesion indicates that the dog lived for months-to-years following insult. Differential diagnoses initially included: sharp penetrating trauma; intrinsic or extrinsic blunt fracturing force; osteochondrosis or complication of an osteochondral lesion; unusual osteoarthritis; and neoplasia. Computed tomography ruled out normal or unusual osteoarthritis, and neoplasia. The nature and small size of the lesion, relatively small size of the dog, and lack of evidence for complicating infection, suggest against sharp penetrating trauma as a sole cause. The most plausible differential diagnoses include: uncommon fracture-producing force in a companion animal, and blunt intrinsic or extrinsic force causing fracture at a weak point, such as an early osteochondral lesion, that was obliterated by healing. Combined gross examination, micro-computed tomography, and archeological-anthropological influences facilitated refinement of differential diagnosis.

Pharmacodynamic interaction between pantoprazole and vecuronium at neuromuscular junction.

1 The effect of pantoprazole on vecuronium-induced neuromuscular blockade in in vivo has not been clearly defined. In this study, we demonstrate that chronic administration, but not acute administration, of pantoprazole alters the pattern of vecuronium-induced neuromuscular blockade. 2 This study was designed to evaluate the effect of acute and chronic administration of pantoprazole on vecuronium-induced neuromuscular blockade using the rat in vivo sciatic nerve-stimulated gastrocnemius preparation. 3 Vecuronium was administered as a slow intravenous infusion (29.41 µg kg(-1) min(-1)) until the gastrocnemius twitch response to sciatic nerve stimulation was completely abolished. The effect of acute (single dose, i.v.) and chronic administration (per oral for 21 days) of pantoprazole (3.64 mg kg(-1)) on vecuronium-induced blockade was assessed by comparing ED50 values, time required for 50% block, ED95 values, block duration and percentage of recovery with respect to control. 4 Acute administration of pantoprazole had no significant effect on any parameter of vecuronium-induced neuromuscular blockade. Chronic administration of pantoprazole significantly reduced vecuronium ED50 value, time for 50% block, ED95 value and percentage recovery from blockade compared with the control group (P<0.05). Reduction in the duration of vecuronium-induced blockade was not significantly affected by chronic treatment with pantoprazole compared with control. 5 On chronic administration, pantoprazole may produce earlier block, quick relaxation and reduces the recovery of vecuronium without affecting its duration of action.

Tetany: possible adverse effect of bevacizumab.

BACKGROUND: Bevacizumab a recombinant humanized monoclonal antibody was approved in 2004 by US FDA for metastatic colorectal cancer. It is reported to cause potentially serious toxicities including severe hypertension, proteinuria, and congestive heart failure. AIM: To correlate adverse event tetany with the use of bevacizumab. MATERIALS AND METHODS: World Health Organization's Uppsala Monitoring Centre, Sweden, for reporting of adverse drug reactions from all over the world, identified 7 cases with tetany-related symptoms to bevacizumab from four different countries. These 7 patients reported to UMC database developed adverse events described as musculoskeletal stiffness (1), muscle spasm (1), muscle cramps (1), lock jaw or jaw stiffness (4), and hypertonia (1), with hypocalcaemia. RESULTS: After detailed study of the possible mechanism of actions of bevacizumab and factors causing tetany, it is proposed that there is a possibility of tetany by bevacizumab, which may occur by interfering with calcium metabolism. Resorption of bone through osteoclasts by affecting VEGF may interfere with calcium metabolism. Another possibility of tetany may be due to associated hypomagnesaemia, hypokalemia, or hyponatremia. CONCLUSIONS: Tetany should be considered as a one of the signs. Patient on bevacizumab should carefully watch for tetany-related symptoms and calcium and magnesium levels for their safety.

Protective Effect of Ethanol Extract of Gymnosporia montana (Roth) Bemth. in Paracetamol-induced Hepatotoxicity in Rats.

The aim of the present study was to explore the hepatoprotective activity of the ethanol extract of leaves of Gymnosporia montana (Roth) Bemth. (Family: Celastraceous) against paracetamol-induced hepatotoxicity. Hepatotoxicity in Wistar rats was induced by a single intraperitoneal dose of 500 mg/kg of paracetamol and studied by comparing parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase and histopathological examination of liver. Pre and post-treatment with ethanol extract of Gymnosporia montana (Roth) Bemth. at doses of 50 and 100 mg/kg was studied by comparing the above mentioned parameters with silymarin (100 mg/kg) as standard. Both doses of ethanol extract of Gymnosporia montana (Roth) Bemth. were found to be hepatoprotective. Extract at the dose of 100 mg/kg produced effects comparable to those of silymarin. The present study indicates that alcohol extract of Gymnosporia montana (Roth) Bemth. possessed significant hepatoprotective activity.

Verbal and affective laterality effects in P-dyslexic, L-dyslexic and normal children.

Lateralization of verbal and affective processes was investigated in P-dyslexic, L-dyslexic and normal children with the aid of a dichotic listening task. The children were asked to detect either the presence of a specific target word or of words spoken in a specific emotional tone of voice. The number of correct responses and reaction time were recorded. For monitoring words, an overall right ear advantage was obtained. However, further tests showed no significant ear advantage for P-types, and a right ear advantage for L-types and controls. For emotions, an overall left ear advantage was obtained that was less robust than the word-effect. The results of the word task are in support of previous findings concerning differences between P- and L-dyslexics in verbal processing according to the balance model of dyslexia. However, dyslexic children do not differ from controls on processing of emotional prosody although certain task variables may have affected this result.

Unsuccessful deflation of a bifoil balloon during percutaneous mitral valvuloplasty.

A middle-aged woman was subjected to balloon mitral valvuloplasty using a bifoil balloon catheter. After inflation the balloon failed to deflate in spite of negative suction, probably due to a kink. The balloon was perforated with a transseptal puncture needle in order to deflate it and save open heart surgery.

Tricuspid balloon valvuloplasty: a more simplified approach using inoue balloon.

We report a more simplified technique of the balloon tricuspid valvuloplasty using inoue balloon set in a patient suffering from severe rheumatic tricuspid stenosis. We believe that this technique may be useful in a difficult case of tricuspid valvuloplasty.

Percutaneous transvenous mitral commissurotomy using Inoue balloon catheter: a left femoral vein approach.

Percutaneous transvenous mitral commissurotomy by the Inoue technique is usually recommended from right femoral vein approach only. We report an unusual patient in whom the left femoral vein approach was used successfully. We believe that the left femoral vein approach can be reserved as a last resort in certain cases.

Difficult mitral valvuloplasty: an "over the wire" modification of Inoue technique.

Failure to cross the mitral valve remains an important cause of the technical failure in performing mitral valvuloplasty with the Inoue technique, especially during initial experience of the operator. We report two such cases where conventional methods failed and an "over the wire" modification of the Inoue technique had to be utilized. This particular modification can be beneficial in the rare cases where negotiating the Inoue balloon across the mitral valve is particularly difficult.

Left ventricular mass and function in children with severe protein energy malnutrition.

We studied 25 children, aged 1-5 years (mean 2.65 +/- 0.8 years) with severe protein energy malnutrition, and compared their left ventricular mass and function to those of 26 healthy, age- and sex-matched normal children. The mean left ventricular mass in the patients was lower than that in the controls (25.75 +/- 8.09 g vs. 32.44 +/- 11.64 g; P less than 0.05, C.I. 2.08 to 11.30). However, left ventricular mass (g)/kg body weight was significantly increased in the patients (4.44 +/- 1.45 vs. 2.42 +/- 0.87; P less than 0.001, C.I. 1.28 to 2.76) suggesting relative cardiac "sparing". The systolic function indices like ejection fraction, percentage fractional shortening, and velocity of circumferential fiber shortening were not significantly different in the patients and in the normal children. The left ventricular end-diastolic volume, stroke volume and cardiac output were reduced in proportion to decrease in body size in the patients, so that the cardiac index was not reduced but slightly increased in the patients. (5.95 +/- 1.9 l/min/m2 in patients, 4.97 +/- 1.4 l/min/m2 in controls; P less than 0.05, C.I. 0.04 to 1.92). There was no significant difference in any of these parameters of left ventricular function or mass in patients with marasmus, as compared to those of patients with marasmic kwashiorkor. Amongst the 25 patients, however, 5 patients (20%) had an ejection fraction of less than 50%. Compared to the other 20 patients, these 5 patients had lower left ventricular mass (18.4 +/- 4.3 g vs. 27.5 +/- 7.8 g, P less than 0.05 C.I. 1.63 to 16.75), lower left ventricular mass (g)/kg body weight and a worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

T-U wave alternans. A case report and review of the literature.

A patient with severe hypertension, hypokalemia and marked T-U wave alternans on electrocardiogram is reported for its rarity. Relevant literature is reviewed. Recent data indicate that electric alternans is related to changes in action potential configuration, and that it may be a marker of cardiac electrical instability.

Noninvasive assessment of left ventricular function in asymptomatic diabetics and its relation to metabolic control and microangiopathy.

Fifty otherwise healthy patients with diabetes mellitus (37 males, 13 females; mean age: 53 +/- 10 years) of more than five year duration were compared with twenty six healthy age and sex matched controls. Detailed echocardiographic evaluation was done in all and systolic time intervals (STI) were measured. In diabetics, metabolic control and presence of microangiopathy were evaluated. PEP Index (patients: 146.23 +/- 17.04; controls: 121.99 +/- 5.15; p less than 0.001), PEP/LVET ratio (patients: 0.38 +/- 0.07; controls: 0.32 +/- 0.02; p less than 0.001), LVEF% (patients: 54.1 +/- 10.56; controls: 64.71 +/- 6.33; p less than 0.001), all were significantly altered in diabetics suggesting left ventricular dysfunction. The left ventricular posterior wall thickness (patients: 0.96 +/- 0.23 cm; controls: 0.85 +/- 0.12 cm; p less than 0.01) and interventricular septal thickness (patients: 1.2 +/- 0.24 cm; controls: 0.87 +/- 0.25 cm; p less than 0.001) in diastole were increased in diabetics. The PEPI correlated with day-to-day control but not with chronic glycemic control of diabetes mellitus. The PEP/LVET was significantly increased in patients with severe, as compared to those with none or mild microangiopathy (p less than 0.05). Thus, significant left ventricular dysfunction is evident in asymptomatic, otherwise healthy diabetics. Both metabolic control and microangiopathy may be responsible for the abnormalities.