Gallbladder cancer incidence in Gwalior district of India: Five-year trend based on the registry of a regional cancer center.

BACKGROUND: We have reported here the 5-year incidence (2004-2008) of gallbladder cancer (GBC) in North Central India along with its descriptive epidemiology. This provides potential clues for better prevention. The present study has also evaluated the association of ABO blood groups with GBC. PATIENTS AND METHODS: The study comprised 742 GBC cases referred to the regional cancer hospital, Gwalior, during 2004-2008. The demographic statistics of Gwalior district was considered to calculate the relative risk and incidence rates. ABO blood group distribution amongst 90,000 healthy subjects registered in the local blood bank during 2002-2007 was taken as controls to study the association of blood groups with GBC. RESULTS: The age-standardized total incidence rate of GBC was calculated to be 7.16/1,00,000. The relative risk of females getting GBC was 2.693 at 95% confidence interval of 2.304-3.151 (P < 0.0001). The females formed 69.5% of total cancer cases, with age-standardized incidence rate of 10/1,00,000. The mean age of male and female GBC cases was found to be 55.4 years (SD = 13, SE = 0.77) and 51.5 years (SD = 12.3, SE = 0.50), respectively. The blood groups A (P = 0.0022) and AB (P < 0.0001) had a positive association with GBC with significant level of differences in comparison to controls. CONCLUSION: Our study provided an estimate of a 5-year incidence of GBC in North Central India for the first time. With regard to the association of risk factors like obesity, age, and urban living with GBC, the findings of the present study are contradictory to the general opinion. Blood groups A and AB were found to be associated with GBC, which would be provisional for further investigations.

Central pontine and extrapontine myelinolysis: a systematic review.

The purpose was to perform a systematic review of studies on central pontine and extrapontine myelinolysis [forms of osmotic demyelination syndrome (ODS)] and define the spectrum of causes, risk factors, clinical and radiological presentations, and functional outcomes of this disorder. A thorough search of the literature was conducted using multiple databases (PubMed, Ovid Medline and Google) and bibliographies of key articles to identify all case series of adult patients with ODS published from 1959 to January 2013. Only series with five or more cases published in English were considered. Of the 2602 articles identified, 38 case series were included comprising a total of 541 patients who fulfilled our inclusion criteria. The most common predisposing factor was hyponatremia (78%) and the most common presentation was encephalopathy (39%). Favorable recovery occurred in 51.9% of patients and death in 24.8%. Liver transplant patients with ODS had a combined rate of death and disability of 77.4%, compared with 44.7% in those without liver transplantation (P < 0.001). ODS is found to have a good recovery in more than half of cases and its mortality has decreased with each passing decade. Favorable prognosis is possible in patients of ODS, even with severe neurological presentation. Further research is required to confirm the differences found in liver transplant recipients.

The liver function test enzymes and glucose level are positively correlated in gallbladder cancer: a cancer registry data analysis from north central India.

AIM OF STUDY: To investigate the trend of expression of liver function test enzymes and other biochemical changes during gallbladder carcinogenesis. MATERIALS AND METHODS: Eight hundred and seventy-eight gallbladder disease patients were selected to study the liver function test enzymes and routine blood biochemical changes in the last five years (2004-08). Statistical analysis was performed using Graph Pad prism 5.02 software. RESULTS: The liver function test enzymes showed significant correlations among themselves, and with glucose in gallbladder cancer and gallstone disease patients (N = 878). Out of 878 gallbladder cases, 46 (5.24%) showed significantly higher glucose level of 216.66 mg/dL (P < 0.0001). All the three pathological conditions of gallbladder, gallbladder cancer with stones (GBCS), gallbladder cancer without stones (GBC) and calculus cholecystitis (CC), showed highly significant positive correlation (Pearson) between Serum Glutamic Oxaloactetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) [P < 0.0001, (GBCS); P < 0.0001, (GBC), and P < 0.0001, (CC)]. SGOT and SGPT also showed positive correlation with higher glucose level independently, in both GBCS and CC (P < 0.0001 and P < 0.0001), respectively. CONCLUSION: Simultaneous elevation of glucose and liver function test enzymes in GBC makes the diagnosis complex. Any patient of gallbladder diseases with higher level of glucose may have the possibility of developing gallbladder cancer.

Prevalence of smear-positive pulmonary tuberculosis in different ethnic groups in India: evaluation of public health.

OBJECTIVE: To estimate the prevalence of pulmonary tuberculosis (TB) in a high-risk rural area of central India. STUDY DESIGN: Retrospective analysis of primary data. METHODS: In total, 10,963 sputum smears were screened from Hindu tribes (n = 4032), Hindu non-tribal (n = 5445) and Muslim communities (n = 1486) between 2004 and 2009. Smears were recorded as positive or negative for tubercle bacilli following staining with acid-fast bacilli, in accordance with the guidelines of the World Health Organization. Age- and gender-specific prevalence rates and relative risks (RR) were calculated using Statistical Package for the Social Sciences Version 13.0. RESULTS: The prevalence of TB was found to be significantly higher in Hindu tribes compared with Hindu castes and Muslims (P < 0.005). The overall RR of developing smear-positive disease was 1.4-fold higher (95% confidence interval 1.1-1.7; P < 0.005) in males than females in all the study groups. The highest prevalence of TB was observed in subjects aged 15-34 years. CONCLUSIONS: Hindu tribes and males of working age are still at high risk of smear-positive TB.

Role of nitric oxide in the diuresis and natriuresis occurring in patients with obstructive sleep apnoea syndrome.

OBJECTIVE: To determine whether nitric oxide (NO) has any role in the diuresis and natriuresis observed in patients with obstructive sleep apnoea syndrome (OSAS). METHODS: We measured 12-hour urine volume in the day and in the night in patients with OSAS (n=20) and determined the concentrations of urinary sodium and nitrate. The frequency of urination in the night was also noted. The measurements were done again after two nights of continuous positive airway pressure (CPAP) therapy and after putting the patients on oral anti-oxidant treatment (vitamin C-100 mg BD and vitamin E-400 IU BD) for 45 days. Ten healthy normal subjects underwent the same protocol except the CPAP therapy. RESULTS: In patients with OSAS, the night urine volume and sodium concentration were similar and the nitrate levels were higher compared to those in the day. After CPAP therapy, while the urine volume and sodium concentration decreased, the nitrate level became similar to that in the day. Such effects were not observed after anti-oxidant treatment. The frequency of urination was decreased in both the instances. The effects observed after CPAP therapy were similar to those observed in control subjects with or without anti-oxidant treatment. CONCLUSION: Renal NO promotes diuresis and natriuresis in patients with OSAS.

A new benzylisoquinoline alkaloid from Argemone mexicana.

A new benzylisoquinoline alkaloid, argemexirine, together with two known protoberberine alkaloids, dl-tetrahydrocoptisine and dihydrocoptisine, have been isolated from the methanolic extract of the whole plant of Argemone mexicana L. The compounds were identified by spectral and chemical evidence. This is the first report of these alkaloids in this plant species.

Oxidative stress and obstructive sleep apnoea syndrome.

RATIONALE: Even though oxidative stress has been proposed as an underlying mechanism for the symptoms in patients with obstructive sleep apnoea syndrome (OSAS), little information is available on the effects of anti-oxidant treatment on their improvement. OBJECTIVES: To observe the effects of anti-oxidant treatment on polysomnographic parameters and oxidative stress markers in OSAS patients. METHODS: Polysomnography (PSG) was performed on 20 male patients. They were administered continuous positive airway pressure (CPAP) therapy for two nights followed by oral intake of vitamin C (100 mg BD) [DOSAGE ERROR CORRECTED] and vitamin E (400 IU BD) for 45 days and a repeat PSG was done. Ten healthy normal subjects underwent the same protocol excepting the CPAP therapy. RESULTS: In OSAS patients, plasma lipid peroxidation increased significantly and whole blood reduced glutathione decreased significantly. The CPAP therapy as well as anti-oxidant treatment reduced the lipid peroxidation and restored the reduced glutathione concentrations. After anti-oxidant intake, OSAS patients slept better with decrease in Epworth sleepiness score and the number of apnoeic episodes. They spent more time in stages 3 and 4 of sleep. The optimum pressure of CPAP device was significantly lowered also. CONCLUSIONS: Oxidative stress contributes to sleep behaviour in OSAS patients, and anti-oxidant intake improves the quality of sleep in them.

NR2B downregulation in a forebrain region required for avian vocal learning is not sufficient to close the sensitive period for song learning.

The neural changes that limit the sensitive period for avian song development are unknown, but neurons in a forebrain region critical for song learning, the lMAN, exhibit experience-driven changes in NMDAR subunit expression that could regulate sensitive period closure. Specifically, NR2B levels in lMAN decrease during song acquisition, potentially reducing synaptic plasticity by decreasing NMDAR EPSC duration and/or affecting NMDAR-coupled intracellular cascades. While rearing birds in isolation extends the sensitive period and also delays the developmental changes in NR2B expression and NMDAR physiology, recent work indicates that a transition to faster NMDAR currents does not preclude further song learning. However, NR2B mRNA expression in isolates remains elevated beyond the age at which NMDAR currents shorten, leaving open the possibility that NR2B levels regulate closure of the sensitive period through effects other than those mediated by NMDAR current duration. To determine whether the experience-driven decrease in NR2B expression in lMAN closes the sensitive period, we promoted this change in gene expression either by treating isolation-reared zebra finches briefly with testosterone (T-isolates) or by allowing males limited access to conspecific song (pre-exposed isolates). We then assessed if these birds could acquire song from tutors after the normal close of the sensitive period. Despite a normal decline in NR2B expression, T-isolate and pre-exposed isolate birds learned tutor songs heard from d65-90, while normally reared birds did not. These findings suggest that the normal decline in NR2B expression with lMAN is not sufficient for sensitive period closure.

Developmental and hormonal regulation of NR2A mRNA in forebrain regions controlling avian vocal learning.

Developmental changes in the composition of NMDA receptors can alter receptor physiology as well as intracellular signal transduction cascades, potentially shifting thresholds for neural and behavioral plasticity. During song learning in zebra finches, NMDAR currents become faster, and transcripts for the modulatory NR2B subunit of this receptor decrease in lMAN, a region in which NMDAR activation is critical for vocal learning. Using in situ hybridization, we found that NR2A transcripts change reciprocally, increasing significantly in both lMAN (59%) and in another song region, Area X (38%), between posthatch day (PHD) 20 and 40, but not changing further at PHD60 or 80. In adjacent areas not associated with song learning, NR2A mRNA did not change between PHD20-80. Although early song deprivation (which extends the sensitive period for song learning) delays changes in NR2B gene expression and NMDAR physiology within the lMAN, it did not alter NR2A mRNA levels measured at PHD40, 45, or 60. Early testosterone (T) treatment, which disrupts vocal development and accelerates the maturation of both NR2B levels and NMDAR physiology in lMAN, also significantly increased NR2A transcripts measured at PHD35 in lMAN. In Area X, a similar effect of T approached significance. Together with our previous studies, these results show that in a pathway critical for vocal plasticity, the ratio of NR2A:NR2B mRNA rises abruptly early during the sensitive period for song learning. Furthermore, androgen regulation of NMDAR gene expression may alter thresholds for experience-dependent synaptic change.

Puetz-Jeghers syndrome involving appendix.

Puetz-Jegher's syndrome is an autosomal dominant hereditary disease, which is characterized by hamartomatous polyposis and mucocutaneous pigmentation mainly over the circum-oral region. Patients with Peutz-Jeghers syndrome seek medical attention whenever there are complications such as intussusception, bleeding from the polyps, etc. Occasionally, gastrointestinal tract malignancies have been reported in Peutz-Jeghers syndrome. In this paper, we report a patient with Peutz-Jeghers syndrome who had multiple complications and polyposis involving the appendix, because involvement of the appendix is extremely rare in Peutz-Jeghers syndrome.

Phaeochromocytoma at the root of the mesentery.

A 65-year-old male reported with a freely mobile abdominal lump and hypertension. Though pre-operatively and intra-operatively, we have suspected the lump to be a mesenteric cyst, postoperative histopathological examination revealed it to be phaeochromocytoma which is rare. In view of its extra-adrenal site of presentation and rarity, this case is reported herein.

Early sensory and hormonal experience modulate age-related changes in NR2B mRNA within a forebrain region controlling avian vocal learning.

Male zebra finches are most apt to mimic songs heard between posthatch days (PHD) 35 and 65, and this vocal learning depends, in part, on the activation of N-methyl-D-aspartate receptors (NMDAR) within a discrete forebrain circuit that includes the lateral magnocellular nucleus of the anterior neostriatum (lMAN) and area X. Using in situ hybridization, we show that transcripts for both the constitutive NMDAR subunit NR1 and the modulatory subunit NR2B decrease abruptly in the lMAN between PHD20 and 40. This downregulation corresponds to the onset of song learning and a transition from slow to faster NMDAR currents in lMAN neurons. In area X, NR1 mRNA increases as NR2B mRNA decreases during song development. To understand how these changes in NMDAR mRNA might regulate song learning, we next investigated how manipulations that influence song development affect NMDAR mRNA expression. Early isolation from conspecific song (which delays closure of the sensitive period for song learning) selectively increases NR2B, but not NR1 mRNA, within lMAN at PHD60. In contrast, exposure to testosterone beginning at PHD20 (which impairs song development and hastens the developmental transition to faster NMDAR current kinetics within lMAN) accelerates the decline in NR2B mRNA in lMAN, again without affecting NR1 transcript levels. Neither manipulation significantly effects NR1 or NR2B mRNA levels in area X. Our data suggest that developmental changes in the expression of specific NMDAR subunits may regulate periods of neural and behavioral plasticity and that flexibility in the timing of these sensitive periods may be achieved through experience and/or hormone-dependent modulation of NMDAR gene expression.

Developmental regulation and effect of early undernutrition on phosphorylation of rat cortical synaptic membrane proteins.

Undernutrition during early postnatal life was employed in rats by restricting the feeding time. The synaptic membrane fraction from cerebral cortex of normal and undernourished rats of various ages was prepared and endogenous protein phosphorylation studied. Many of the synaptic membrane proteins were found to be phosphorylated in an age-dependent manner. Early undernutrition affects the phosphorylation of various proteins in a complex way; most affected were 48-, 52-, 61- and 74-kDa proteins. These proteins were found to have phosphorylations mainly at tyrosine residues. This finding indicates that tyrosine phosphorylations may be affected most by early undernutrition. Adequate nutrition after early undernutrition removes most of the effects of undernutrition on synaptic protein phosphorylation. To address the question of how undernutrition may affect protein phosphorylation, we studied the lipid content of synaptic membrane fraction as it can affect membrane properties, including the fluidity. We found that undernutrition affects phosphorylation of most of the synaptic membrane proteins in the same manner in which it affects the cholesterol-phospholipid ratio of synaptic membrane and, hence, the fluidity of the membrane. This indicates that lipid biosynthesis is one of the ways by which undernutrition can affect synaptic membrane protein phosphorylation.

Developmental regulation of NMDA receptor 2B subunit mRNA and ifenprodil binding in the zebra finch anterior forebrain.

In passerine songbirds, song learning often is restricted to an early sensitive period and requires the participation of several discrete regions within the anterior forebrain. Activation of N-methyl-D-aspartate (NMDA) receptors is implicated in song learning and in one forebrain song region, the lateral magnocellular nucleus of the anterior neostriatum (IMAN), NMDA receptors decrease in density, their affinity for the antagonist MK-801 increases, and their currents decay more quickly as young male zebra finches lose the ability to imitate new song elements. These developmental changes in NMDA receptor pharmacology and physiology suggest that the subunit composition of NMDA receptors changes developmentally. Here, we have used in situ hybridization and [3H]ifenprodil receptor autoradiography to study the developmental regulation of the NMDA receptor 2B subunit (NR2B) within the anterior forebrain of male zebra finches. NR2B mRNA expression within the IMAN was twice as great in 30-day-old males (early in the sensitive period for song learning) as in adult males, and this developmental decrease in NR2B mRNA expression was mirrored by a decrease in high-affinity (NR2B-associated) [3H]ifenprodil binding within this song region. In another anterior forebrain song region, Area X, NR2B mRNA also declined significantly after 30 days posthatch, but this decline was not accompanied by a significant decrease in [3H]ifenprodil binding. The results are consistent with the hypothesis that developmental changes in NMDA receptor function mediated by regulation of subunit composition contribute to the sensitive period for vocal learning in birds.

Lithium regulation of protein phosphorylation in rat cerebral cortex slices in vitro.

The aim of the present study was to evaluate the direct effect of Li+ and Na+-Li+ exchange on protein phosphorylation in rat cerebral cortex slices incubated in Krebs Ringer medium. When Na+ concentration was varied in the incubation medium, either by replacement with Li+ or sucrose, a variable effect on [32P] phosphate incorporation into proteins was observed. Protein phosphorylation in cerebral cortex slices was very low in the absence of Na+, and some dependence of phosphorylating system of neural tissue on extra cellular concentration of Na+ was evident. Lithium was not able to replace sodium as far as protein phosphorylation in cortical slices is concerned. Ouabain was more effective in a Li+ containing medium in inhibiting protein phosphorylation, presumably due to improper functioning of the sodium pump.

BDNF and trkB mRNA expression in neurons of the neonatal mouse barrel field cortex: normal development and plasticity after cauterizing facial vibrissae.

Development of the central somatosensory system is profoundly modulated by the sensory periphery. Cauterization of facial whiskers alters the segregation pattern of barrels in rodents only during a few days just after birth (critical period). Although a molecular basis of the segregation of barrel neurons and the critical period for the anatomical plasticity observed in layer IV barrel neuron is not clear yet, the accumulating evidence suggests that neurotrophins modulate synaptic connections including central nervous system. In this study, we showed by in situ hybridization that mouse barrel side neurons express brain-derived neurotrophic factor (BDNF) mRNA and both catalytic and non-catalytic forms of trkB mRNA. Cautery of row C vibrissae on the right side of the face within 24 h after birth (post natal day 0, PND0) reduced the expression of BDNF and trkB mRNA from the division region between the contralateral row C barrels at PND7. The vibrissae in row A, C, and E were cauterized at PND0 followed by quantitative RT-PCR for BDNF and trkB mRNA with total RNA isolated from the barrel region at PND7. The result showed that BDNF, but not trkB, mRNA was increased several-fold in the contralateral barrel region. These data suggest that the expression of BDNF mRNA is differentially regulated between injured barrels and actively innervated barrels. The differential expression of the mRNA encoding neurotrophins and their receptors may be important in regulating the injury-dependent re-segregation of barrels.

An anesthetic for the adult patient with congenital tracheoesophageal fistula: a case report.

A 20-year-old male with a history of recurrent pneumonia was diagnosed as having an N-type tracheoesophageal fistula. A general anesthetic was planned to facilitate the repair of the tracheoesophageal fistula using a left anterior cervical approach. Intraoperatively, the surgeons were unable to identify the defect after surgical exposure. To facilitate location of the tracheoesophageal fistula, a flexible pediatric fiberoptic bronchoscope was passed through an elbow adapter connected to the endotracheal tube. The scope was then visually passed via the trachea through the defect into the esophagus. The surgeons were able to palpate the fistula with the bronchoscope passed through the defect. Ease of identification allowed the tracheoesophageal fistula to be quickly repaired. At the completion of the surgery, the patient was extubated, and recovery was uneventful. The patient was discharged 48 hours postoperatively.