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Biomedical subjects

V K Sharma

Publications and source records attributed to V K Sharma.

At least 19 recordsLinked to original sources

Parthenium dermatitis presenting as photosensitive lichenoid eruption. A new clinical variant.

Parthenium hysterophorus is the commonest cause of airborne contact dermatitis (ABCD) in India. The disease usually manifests as itchy erythematous, papular, papulovesicular and plaque lesions on exposed areas of the body. Rarely, however, the disease may present as actinic reticuloid or photocontact dermatitis. We have observed a different clinical variant of this disease where certain patients with Parthenium dermatitis have presented with discrete, flat, violaceous papules and plaques on exposed areas of the body closely simulating photosensitive lichenoid eruption. We had 8 patients, 6 males and 2 females between 30 and 62 years of age, with itchy, violaceous, papules and plaques on the face, neck, ears, upper chest and dorsa of the hands for 6 months to 6.5 years. Four of these patients had a history of improvement of the lesions up to 30% in winter and aggravation of lesions on exposure to sunlight. There was no personal or family history of atopy. Cutaneous examination in all patients revealed multiple flat, violaceous, mildly erythematous papules and plaques on the forehead, sides and nape of neck, ears, 'V' area of the chest, and extensor aspects of the forearms and hands. Skin biopsies from these lesions showed features of chronic non-specific dermatitis. Patch testing with standardized plant antigens showed a positive patch test reaction to Parthenium hysterophorus in all patients, with a titre of contact hypersensitivity (TCH) varying from undiluted to 1 : 100. We conclude that Parthenium dermatitis may occasionally present with lesions very similar to the lesions of photosensitive lichenoid eruption in morphology and distribution. This clinical presentation of Parthenium dermatitis needs to be recognized to avoid misdiagnosis.

Adult↗

Meta-analysis: the efficacy of intravenous H2-receptor antagonists in bleeding peptic ulcer.

BACKGROUND: Although a previous meta-analysis found that intravenous H2-receptor antagonists were only weakly beneficial in bleeding gastric ulcer and of no benefit in bleeding duodenal ulcer, patients with ulcer bleeding continue to receive such treatment. AIM: To re-evaluate the efficacy of intravenous H2-receptor antagonists in ulcer re-bleeding, surgery and mortality by updating the previous meta-analysis. METHODS: After two independent literature searches, randomized, placebo-controlled trials of intravenous H2-receptor antagonists in bleeding ulcer published between 1984 and 2000 were added to those from the initial meta-analysis. Pooled rates of re-bleeding, surgery and death were re-calculated, together with the relative risk reduction, absolute risk reduction, number needed to treat and Mantel-Haenszel odds ratio. RESULTS: Intravenous H2-receptor antagonists did not significantly reduce re-bleeding, surgery or death in bleeding duodenal ulcer. There were small but significant reductions in re-bleeding, surgery and death in bleeding gastric ulcer; the absolute risk reductions were 7.2%, 6.7% and 3.2%, respectively. CONCLUSIONS: Intravenous H2-receptor antagonists are of no value in bleeding duodenal ulcer, although they may be mildly beneficial in bleeding gastric ulcer. Because proton pump inhibitors have a greater inhibitory effect on gastric acid secretion than H2-receptor antagonists, they may be more effective in ulcer bleeding and should be further evaluated for that indication.

Histamine H2 Antagonists↗

Mitochondria regulate inactivation of L-type Ca2+ channels in rat heart.

1. L-type Ca2+ channels play an important role in vital cell functions such as muscle contraction and hormone secretion. Both a voltage-dependent and a Ca2+-dependent process inactivate these channels. Here we present evidence that inhibition of the mitochondrial Ca2+ import mechanism in rat (Sprague-Dawley) ventricular myocytes by ruthenium red (RR), by Ru360 or by carbonyl cyanide m-chlorophenylhydrazone (CCCP) decreases the magnitude of electrically evoked transient elevations of cytosolic Ca2+ concentration ([Ca2+]c). These agents were most effective at stimulus rates greater than 1 Hz. 2. RR and CCCP also caused a significant delay in the recovery from inactivation of L-type Ca2+ currents (I(Ca)). This suggests that sequestration of cytosolic Ca2+, probably near the mouth of L-type Ca2+ channels, into mitochondria during cardiac contractile cycles, helps to remove the Ca2+-dependent inactivation of L-type Ca2+ channels. 3. We conclude that impairment of mitochondrial Ca2+ transport has no impact on either L-type Ca2+ currents or SR Ca2+ release at low stimulation frequencies (e.g. 0.1 Hz); however, it causes a depression of cytosolic Ca2+ transients attributable to an impaired recovery of L-type Ca2+ currents from inactivation at high stimulation frequencies (e.g. 3 Hz). The impairment of mitochondrial Ca2+ uptake and subsequent effects on Ca2+ transients at high frequencies at room temperature could be physiologically relevant since the normal heart rate of rat is around 5 Hz at body temperature. The role of mitochondria in clearing Ca2+ in the micro-domain near L-type Ca2+ channels could be impaired during high frequencies of heart beats such as in ventricular tachycardia, explaining, at least in part, the reduction of muscle contractility.

Animals↗

Persistence of oviposition rhythm in individuals of Drosophila melanogaster reared in an aperiodic environment for several hundred generations.

The oviposition rhythm of individual flies of Drosophila melanogaster from a population maintained in an aperiodic environment (with light, temperature, humidity, and other factors which could provide time cues, kept constant) for several hundred generations was assayed in constant light (LL), in light/dark (LD 12:12 hr) cycle, and in constant darkness (DD). More than 50% of the flies assayed exhibited rhythmicity in oviposition in all three light regimes. The results indicate that the phenomenon of egg laying is rhythmic in individual D. melanogaster females and is controlled by an endogenous time keeping mechanism. The persistence of the oviposition rhythm in a large proportion of individuals in the population after several hundred generations of rearing in a constant environment strengthens the view that possessing biological clocks may confer some intrinsic fitness advantage even to organisms living in aperiodic environments. J. Exp. Zool. 290:541-549, 2001.

Animals↗

Identification of a ryanodine receptor in rat heart mitochondria.

Recent studies have shown that, in a wide variety of cells, mitochondria respond dynamically to physiological changes in cytosolic Ca(2+) concentrations ([Ca(2+)](c)). Mitochondrial Ca(2+) uptake occurs via a ruthenium red-sensitive calcium uniporter and a rapid mode of Ca(2+) uptake. Surprisingly, the molecular identity of these Ca(2+) transport proteins is still unknown. Using electron microscopy and Western blotting, we identified a ryanodine receptor in the inner mitochondrial membrane with a molecular mass of approximately 600 kDa in mitochondria isolated from the rat heart. [(3)H]Ryanodine binds to this mitochondrial ryanodine receptor with high affinity. This binding is modulated by Ca(2+) but not caffeine and is inhibited by Mg(2+) and ruthenium red in the assay medium. In the presence of ryanodine, Ca(2+) uptake into isolated heart mitochondria is suppressed. In addition, ryanodine inhibited mitochondrial swelling induced by Ca(2+) overload. This swelling effect was not observed when Ca(2+) was applied to the cytosolic fraction containing sarcoplasmic reticulum. These results are the first to identify a mitochondrial Ca(2+) transport protein that has characteristics similar to the ryanodine receptor. This mitochondrial ryanodine receptor is likely to play an essential role in the dynamic uptake of Ca(2+) into mitochondria during Ca(2+) oscillations.

Adenosine Triphosphate↗

Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine.

BACKGROUND: Acute rejection is a serious and frequent complication of renal transplantation, and its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for rejection could improve the outcome of transplantation. METHODS: We obtained 24 urine specimens from 22 renal-allograft recipients with a biopsy-confirmed episode of acute rejection and 127 samples from 63 recipients without evidence of acute rejection. RNA was isolated from the urinary cells. Messenger RNA (mRNA) encoding the cytotoxic proteins perforin and granzyme B and a constitutively expressed cyclophilin B gene were measured with the use of a competitive, quantitative polymerase chain reaction, and the level of expression was correlated with allograft status. RESULTS: The log-transformed mean (+/-SE) levels of perforin mRNA and granzyme B mRNA, which encode cytotoxic proteins, but not the levels of constitutively expressed cyclophiiin B mRNA, were higher in the urinary cells from the 22 patients with a biopsy-confirmed episode of acute rejection than in the 63 recipients without an episode of acute rejection (perforin, 1.4+/-0.3 vs. -0.6+/-0.2 fg per microgram of total RNA; P<0.001; and granzyme B, 1.2+/-0.3 vs. -0.9+/-0.2 fg per microgram of total RNA; P<0.001). Analysis involving the receiver-operating-characteristic curve demonstrated that acute rejection can be predicted with a sensitivity of 83 percent and a specificity of 83 percent with the use of a cutoff value of 0.9 fg of perforin mRNA per microgram of total RNA, and with a sensitivity of 79 percent and a specificity of 77 percent with the use of a cutoff value of 0.4 fg of granzyme B mRNA per microgram of total RNA. Sequential urine samples were obtained from 37 patients during the first nine days after transplantation; and measurements of the levels of mRNA that encoded cytotoxic proteins identified those in whom acute rejection developed. CONCLUSIONS: Measurement of mRNA encoding cytotoxic proteins in urinary cells offers a noninvasive means of diagnosing acute rejection of renal allografts.

Acute Disease↗

Oral hyposensitization in patients with contact dermatitis from Parthenium hysterophorus.

Parthenium hysterophorus is the commonest cause of airborne contact dermatitis in northern India. Treatment is mostly palliative and consists of repeated courses of antihistamines and topical and/or systemic corticosteroids. We have evaluated the effect of oral hyposensitization as an alternative therapeutic modality. In 70% of those patients who completed the study, there was a gradual improvement in their clinical status, as evident from a fall in their clinical severity score for eczema. 30% of patients had an exacerbation during the course of the study and hence hyposensitization in them was stopped. Patients tolerated therapy well and no significant side-effects were seen, except for abdominal pain, 'heartburn' and cheilitis.

Administration, Oral↗

Meta-analysis of randomized controlled trials comparing standard clinical doses of omeprazole and lansoprazole in erosive oesophagitis.

BACKGROUND: Omeprazole and lansoprazole are used to treat erosive oesophagitis in the respective daily doses of 20 and 30 mg. AIM: To investigate, by meta-analysis, whether treatment with lansoprazole 30 mg increases erosive oesophagitis healing rates over omeprazole 20 mg. METHODS: We searched for randomized, double-blind trials comparing omeprazole 20 mg and lansoprazole 30 mg in endoscopically diagnosed erosive oesophagitis. After assessing for homogeneity, non-heterogeneous trials were combined and pooled healing rates derived. We calculated the relative benefit increase, absolute benefit increase and number needed to treat. RESULTS: Six trials without significant heterogeneity met predetermined inclusion criteria. By per protocol analysis, pooled healing rates for omeprazole 20 mg and lansoprazole 30 mg were, respectively, 74.7% and 77.7% after 4 weeks and 87.0% and 88.7% after 8 weeks. The corresponding figures by intention-to-treat analysis were 70.8% and 72.7% after 4 weeks and 81.8% and 83.3% after 8 weeks. In each analysis the absolute benefit increase for lansoprazole was small and its 95% confidence interval encompassed zero. CONCLUSION: Lansoprazole 30 mg produces healing rates in erosive oesophagitis that are not statistically significantly different to those of omeprazole 20 mg.

2-Pyridinylmethylsulfinylbenzimidazoles↗

A comparison of simplified lansoprazole suspension administered nasogastrically and pantoprazole administered intravenously: effects on 24-h intragastric pH.

AIM: To compare the 24-h intragastric pH effects of simplified lansoprazole suspension, 30 mg, administered nasogastrically, with pantoprazole, 40 mg, administered intravenously. METHODS: Thirty-six healthy adults were enrolled and given simplified lansoprazole suspension, 30 mg (nasogastrically), or pantoprazole, 40 mg (intravenously), once daily for five consecutive days in a cross-over fashion. Intragastric pH was monitored at baseline and on Days 1 and 5 of each treatment period. The pharmacokinetic parameters of lansoprazole and pantoprazole were also determined on Days 1 and 5. RESULTS: No statistically significant changes in pharmacokinetic parameters occurred between Days 1 and 5 with either regimen, except for pantoprazole Cmax. On Days 1 and 5, significantly higher mean 24-h intragastric pH values were observed with 30 mg simplified lansoprazole suspension compared with 40 mg intravenous pantoprazole (Day 1, 3.13 vs. 2.67; Day 5, 3.95 vs. 3.61, respectively; P < 0.05). Additionally, 30 mg simplified lansoprazole suspension produced significantly (P < 0.05) higher percentages of time intragastric pH was above 3, 4, 5 or 6 as compared with 40 mg intravenous pantoprazole throughout Days 1 and 5. CONCLUSIONS: A 30 mg dose of simplified lansoprazole suspension administered nasogastrically was consistently more effective at controlling intragastric pH than pantoprazole, 40 mg, administered intravenously.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Helicobacter pylori eradication is superior to ulcer healing with or without maintenance therapy to prevent further ulcer haemorrhage.

BACKGROUND: Helicobacter pylori eradication decreases ulcer recurrence and should prevent recurrent ulcer haemorrhage. AIM: By meta-analysis, to compare treatment of H. pylori infection with other approaches to prevent recurrent ulcer haemorrhage and, by cost minimization analysis, to determine the least costly strategy. METHODS: We searched for randomized, controlled trials comparing treatment of H. pylori infection with ulcer healing alone or with maintenance therapy in preventing recurrent ulcer haemorrhage. We calculated the relative and absolute risk reductions and numbers needed to treat. RESULTS: Treatment of H. pylori infection decreased recurrent bleeding by 17% (numbers needed to treat=6) compared with ulcer healing treatment alone. Compared with ulcer healing treatment followed by maintenance therapy, recurrent bleeding was decreased by 4% (numbers needed to treat=25). Decision model-based cost minimization analysis demonstrated that treatment of H. pylori infection was the least costly strategy unless the incidence of complicated recurrences after treatment was over 6%, or the cost of confirming eradication was over $741. CONCLUSIONS: Treatment of H. pylori infection is superior to ulcer healing treatment with or without maintenance therapy in preventing recurrent ulcer haemorrhage. All patients with ulcer bleeding should be tested for H. pylori infection and appropriately treated if positive.

Anti-Bacterial Agents↗

Ehlers-Danlos syndrome with bladder diverticula.

We describe an Indian man with the unusual association of classical cutaneous features of Ehlers-Danlos syndrome, a marfanoid habitus, bladder diverticula and multiple emphysematous bullae.

Diverticulum↗

Does the difference in the timing of eclosion of the fruit fly Drosophila melanogaster reflect differences in the circadian organization?

The eclosion rhythm of a laboratory population of Drosophila melanogaster was studied under 12h light, 12h dark (LD 12:12) cycles. Although most of the flies were found to eclose just after "lights on" in LD 12:12, termed within gate (WG) flies, a few flies were found to eclose nearly 10h after peak eclosion, termed outside gate (OG) flies. The circadian parameters of the clocks controlling oviposition rhythms in the WG and the OG flies were estimated to understand the cause of such differences in the timing of eclosion. The distribution of the fraction of individual flies exhibiting single, multiple, and no significant period in the WG flies was significantly different from distribution in the OG flies. Compared to the WG flies, more OG flies were found to exhibit oviposition rhythm with multiple periodicity, whereas more WG flies exhibited an oviposition rhythm with a single significant period. The fraction of flies with arrhythmic oviposition was similar in both the WG and the OG flies. Free-running period tau in constant darkness (DD) and the phase angle difference psi in LD 12:12 for the oviposition rhythm of WG and OG flies were significantly different. These results suggest that the differences in the time of eclosion between the flies eclosing within the gate and outside the gate of eclosion are probably due to differences in the circadian system controlling eclosion, which is reflected by the differences in their oviposition rhythm.

Animals↗

Changing trends in gastric carcinoma at a university medical center: a twelve-year retrospective analysis.

Over the past 60 years, the epidemiology of gastric adenocarcinoma has changed considerably. The most striking change in the epidemiology of gastric adenocarcinoma has been the rapid increase in cancers of the proximal stomach. We performed a retrospective analysis of all gastric adenocarcinomas diagnosed at two hospitals in Little Rock, Arkansas, U.S.A., between 1985 and 1996. Two hundred seventeen patients were diagnosed with gastric adenocarcinoma. Patients were divided into three 4-year cohorts. We found that the proportions of gastric cardia adenocarcinoma in cohorts 1, 2, and 3 were 31%, 36%, and 42%, respectively (p = 0.52). Median survival in the three cohorts was 5, 8, and 8 months, respectively (p = 0.22). Median survival (stages 1-4) was 41.5, 11.5, 10, and 3 months, respectively (p < 0.0001). Well-, moderately-, and poorly- differentiated adenocarcinoma had median survivals of 18, 7.5, and 6 months, respectively (p = 0.07). We concluded that patients with gastric adenocarcinoma continue to be diagnosed at late stages. There has been a trend toward an increasing proportion of cardia adenocarcinoma. Stage at presentation was the only significant predictor of survival.

Adenocarcinoma↗