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Biomedical subjects

V Thakur

Publications and source records attributed to V Thakur.

At least 19 recordsLinked to original sources
PubMed2006

Uterine choriocarcinoma in a postmenopausal woman.

Uterine choriocarcinoma developing in patients beyond reproductive age is a rare occurrence. We report a case of choriocarcinoma of uterine corpus in a 54-yr-old woman after 7 yr of menopause and 25 yr after last child birth. She presented with pain in the abdomen, and on radiological investigation a left uterine adnexal mass of 3.4 x 2.8 cm size was detected. Her serum CA125 level was 40 mIU/mL (normal up to 35 mIU/mL). Hysterectomy revealed an intramural growth in left uterine cornu measuring 3.5 x 3.0 x 2.5 cm. Histological features of the tumor were consistent with choriocarcinoma, and immunohistochemistry detected strong reactivity for beta-hCG in the tumor cells. Serum beta-hCG level 4 wk after surgery was 1345 mIU/mL. The patient was put on combination chemotherapy (EMACO). She achieved serological remission but showed a rise in serum beta-hCG level 4 wk after completion of chemotherapy. We conclude that a high level of suspicion may help in preoperative diagnosis of uterine choriocarcinoma in the postmenopausal age group. However, the response to chemotherapy in these cases may not be as encouraging as in choriocarcinoma of reproductive age.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

The value of uterine artery Doppler in the prediction of uteroplacental complications in multiparous women.

OBJECTIVE: To investigate the value of second-trimester uterine artery Doppler in the prediction of complications resulting from uteroplacental insufficiency in low- and high-risk multiparous women. METHODS: Color flow pulsed Doppler imaging of both uterine arteries at 20 weeks' gestation was performed on 628 multiparous women; 458 of them had no known risk factors and 170 had clinically identifiable high-risk factors at booking. An abnormal result was defined as bilateral notches and a mean resistance index (RI) >/= 0.55 (50th centile) or unilateral notches and a mean RI >/= 0.65 (80th centile). The main outcome measure was adverse pregnancy outcome defined as any case of pre-eclampsia, small-for-gestational age birth weight (< 5th centile), placental abruption, stillbirth or early neonatal death. RESULTS: There was an adverse outcome in 30 women (6.6%) in the low-risk group and 48 (28.2%) women in the high-risk group. In the high-risk group the sensitivity to predict adverse pregnancy outcome in screen-positive women was 81.4% for a specificity of 89.0%, a positive predictive value of 71.4% and a negative predictive value of 93.4%. Normal Doppler studies in the high-risk group conferred a risk of adverse perinatal outcome of 6.6%, similar to the risk of adverse outcome in the low-risk population (6.6%). In the low-risk group the sensitivity for an adverse outcome in screen-positive women was 33.3% for a specificity of 92.8% and a positive predictive value of 24.4%. CONCLUSION: In high-risk multiparous women, persistent bilateral notches with mean RI >/= 0.55 and unilateral notches with mean RI >/= 0.65 at 20 weeks' gestation identifies the vast majority of women who will subsequently develop complications secondary to uteroplacental insufficiency. Normal uterine artery Doppler studies in these women confers a risk of adverse outcome similar to that of women with an uncomplicated obstetric history. In low-risk women, the screening efficacy of uterine artery Doppler for adverse perinatal outcome is poor and does not justify routine screening.

Arteries↗
PubMed2004

Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease patients in India.

BACKGROUND AND AIM: Hereditary hemochromatosis (HHC) is an autosomal recessive disorder causing primary iron overload syndrome and chronic liver disease (CLD). This genetic disease is commonly associated with C282Y mutation of the HFE gene, commonly seen in the Northern European population. Minor reports on HHC are available from Asia, however, so far no genetic study is available from India. We prospectively studied the prevalence of C282Y mutation in CLD patients and healthy subjects in a tertiary care referral center in India. METHODS: A total of 249 consecutive biopsy proven CLD (HBV = 112, HCV = 72, cryptogenic = 65) patients and 134 age matched healthy controls were included. Cases of secondary iron overload, pregnancy, chronic alcoholism, age < 30 years and hepatocellular carcinoma (HCC) were excluded. A transferrin saturation index (TSI) of >60% was suggestive of a phenotypic presentation of HHC. C282Y mutation was studied by restriction fragment length polymorphism (RFLP) using genomic DNA. The 387 bp fragment obtained after polymerase chain reaction was digested with 10 units of endonuclease Rsa1. The mutation was detected by creation of an additional restriction site, giving rise to fragments of 247 111 and 29 bp. RESULTS: While the mean TSI was comparable, serum ferritin was significantly higher in CLD patients compared to controls (38 +/- 16%vs 28 +/- 13%; p = not significant (NS), and 125 +/- 18 vs 42 +/- 25 ng/mL; p < 0.001). A TSI of >60% was detected in 24 (9.64%) patients. Only one restriction site was found for endonuclease Rsa1, giving rise to two fragments of 247 and 140 bp, suggesting absence of C282Y mutation in the HFE gene in all patients. CONCLUSIONS: Almost 10% of nonalcoholic CLD patients in India have iron overload, but this is independent of C282Y mutation of the HFE gene. Large population based studies are recommended to investigate the prevalence of this rare disorder in India.

Adult↗
PubMed2002

Renal and cardiovascular considerations for the nonpharmacological and pharmacological therapies of obesity-hypertension.

Obesity-associated hypertension is a common disease that involves a complex pathogenesis. Failure to control hypertension (HTN) in obese subjects provides a great threat to their renal and cardiovascular functions. The treatment of obesity-associated HTN is often difficult, and requires nonpharmacological and/or pharmacological approaches. Weight reduction is the cornerstone of the therapies of obesity-HTN, as it reverses the multiple components of its pathogenesis. When weight loss cannot be sustained or fails, pharmacological means should then be used. Angiotensin-converting enzyme inhibitors (ACEI) are the drug of choice: they can reduce blood pressure, protect the kidney and heart, and improve the metabolic abnormalities in obese subjects. Angiotensin-2 type-1 receptor blockers have a renoprotective benefit similar to ACEI, and they provide an important alternative to the use of ACEI. Diuretics are very effective in African-American obese hypertensives, but small doses should be used to avoid adverse effects on metabolic profiles. Long-acting calcium channel blockers are also effective and have the advantage of no adverse metabolic effects. Nondihydropyridine calcium channel blockers may provide additional renal and cardiovascular protective effects. The beta-adrenergic receptor blockers can cause further weight gain and metabolic abnormalities in obese subjects; therefore, careful monitoring is needed. There are few clinical data that support the efficacy and benefit of centrally acting alpha-2 agonists and alpha-adrenergic receptor antagonists in the treatment of obesity-HTN.

Cardiovascular Physiological Phenomena↗
PubMed2002

Correlation between serum magnesium and blood cyclosporine A concentrations in renal transplant recipients.

BACKGROUND: Low total serum magnesium concentration has been reported in renal transplant recipients on cyclosporine therapy, and this is a risk factor for hypertension and cardiac death. No study is yet available from the Indian subcontinent on the relationship between total serum magnesium and cyclosporine A concentration. METHODS: Blood cyclosporine A and total serum magnesium concentrations were estimated in 31 post renal transplant patients. Sixteen chronic renal failure patients who had not yet received a transplant served as controls. RESULTS: The mean total serum magnesium in post-transplant patients was 0.64+/-0.11 mmol/L (n = 31), which was significantly lower (P <0.001) than in the controls (1.0+/-0.16 mmol/L). An inverse correlation was found between total serum magnesium and blood cyclosporine A concentration (r = -0.532). Systolic and diastolic blood pressures were also higher in the cyclosporine-treated patients. CONCLUSIONS: We conclude that serum magnesium should be monitored regularly in patients receiving cyclosporine A.

Adult↗
PubMed2002

Clinical implications of viral activity in dual infection with hepatitis B and C in chronic liver disease.

BACKGROUND: There is limited information on the clinical and biochemical profile of chronic liver disease due to dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. There are variable reports on the severity of liver disease in dual infections. This is important, from clinical and therapeutic point of view. The present study analyzes liver disease in dual infections as compared to HBV and HCV infection present alone. MATERIAL AND METHODS: Out of 186 histologically proven non-alcoholic chronic liver disease patients, 30 (16.1%) were serologically diagnosed to be HBV and HCV dual infection (Group A, n=30). The clinical profile of these patients was compared with consecutively seen HBV related (Group B, n=30) and HCV related chronic liver disease (Group C, n=30) patients. Patients with dual infection were further grouped based on predominant HBV or HCV viral activity. RESULTS: Patients with dual infection were younger than those with chronic HCV infection (38.4 +/- 14.4 vs. 45.9 +/- 14.7 years, p < 0.05); with male predominance (p=0.06). Patients with chronic HCV infection more often presented with low-grade fever than dual infection group (60% vs. 30%, p < 0.05). Ascites and variceal bleeding were common presentations of HBV related cirrhosis. Patients with dual infection had significantly more deranged liver functions. The duration of illness was shorter in these patients compared with chronic HCV (2.9 +/- 1.6 vs. 7.3 +/- 1.4 year, p < 0.05). When patients with dual infection were subgrouped on HBV DNA and HCV RNA positivity, there was a tendency for increased biochemical derangement with active HBV infectionity. CONCLUSIONS: Our results highlight the fact that patients with HBV and HCV dual infection related chronic liver disease have a more aggressive course. There is a tendency for a more severe liver disease when HBV is active in the dual infection group.

Adult↗
PubMed2002

High seroprevalence and clinical significance of hepatitis B and C infection in hospitalized patients with alcoholic cirrhosis.

OBJECTIVES: Patients with alcoholic cirrhosis (AC) are frequently infected with hepatotropic viruses which could alter the clinical spectrum of the disease. We studied the seroprevalence of hepatitis B (HBV) and hepatitis C virus (HCV) and their impact on the clinical profile of patients with AC. METHODS: Two hundred and ten hospitalized patients of AC were studied and screened for markers of HBV and HCV infection. Clinical, biochemical and virological correlation was done. RESULTS: One hundred and forty (66.6%) patients had no viral infection Group I, 50 (23.8%) were positive for HBsAg Group II and 20 (9.5%) for anti-HCV Group III. All patients were males with comparable ages (43.9 years, 44 years and 45.9 years respectively). The amount of alcohol consumed by patients in Group III (130 +/- 115 g/d) was significantly less than Group II (204 +/- 130 g/d, P < 0.05) and Group I (281 +/- 188 g/d, p < 0.001). The duration of alcohol abuse was shorter in Group II and III, although not statistically significant. Presentation as jaundice was common in Group II and III (p < 0.05). The AST and ALT values (IU/L) were significantly higher in Group II (239 +/- 351, 197 +/- 266) and III (157 +/- 170, 86 +/- 52) than Group I (89 +/- 78, 66 +/- 54) (P < 0.05). The serum alkaline phosphatase (IU/L) was higher in Group III (349 +/- 223) as compared to Group II (263 +/- 186) and Group I (162 +/- 62) (P < 0.05). There was however, no difference in Child's grade or the discriminant function between the three groups of patients. CONCLUSIONS: (i) One-third of the hospitalized patients with AC are infected with HBV or HCV infection, (ii) these infections hasten clinical presentation of patients with alcoholic liver disease, with lesser amount of alcohol consumption and (iii) jaundice, raised ALT/AST and alkaline phosphatase are more common with superadded viral infection.

Adult↗
PubMed2001

Seizure activity results in increased tyrosine phosphorylation of the N-methyl-D-aspartate receptor in the hippocampus.

Systemic administration of kainic acid (KA) induces status epilepticus (SE) that causes neurodegeneration and may subsequently lead to spontaneous recurrent seizures. We investigated the effects of KA-induced SE on tyrosine phosphorylation and solubility properties of the NMDA receptor. Following 1 h of SE, total protein tyrosine phosphorylation was elevated in both the hippocampus and frontal cortex relative to controls. Tyrosine phosphorylation of the NMDA receptor subunits NR2A and NR2B was also enhanced following SE. Animals that received KA but did not develop SE, did not exhibit increased tyrosine phosphorylation. SE resulted in a decrease in the solubility of NMDA receptor subunits and of PSD-95 in 1% deoxycholate. In contrast, the detergent solubility of AMPA and kainate receptors was not affected. These findings demonstrate that SE alters tyrosine phosphorylation of the NMDA receptor, and indicate that the interaction of the NMDA receptor with other components of the NMDA receptor complex are altered as a consequence of seizure activity.

Animals↗
PubMed2001

Subtotal hysterectomy for uterine rupture.

OBJECTIVE: The aim of this paper was to stratify patients with uterine rupture in extremis (with hypotension, change in vital organ function, and altered mental status) and evaluate outcome for patients undergoing subtotal hysterectomy (STH) vs. uterine repair (UR). METHODS: Of 39667 hospital deliveries between 1993 and 1998 at a university hospital, 367 presented with uterine rupture. Of these, 96 presented in extremis and had an irregularly torn uterus found at operation. Charts were retrospectively reviewed to stratify patient population with uterine rupture and their outcome. Results were analyzed using Fisher's exact test. RESULTS: Patients with uterine rupture were 31-35 years old, para> or =3, had received no antenatal care, and presented with rupture in the lower uterine segment. Sixty-one patients underwent STH while 35 underwent UR. The groups were similar with respect to patient age, parity, cause of rupture, and clinical condition at the time of evaluation (P=0.2). The operative time for STH was significantly less than UR, 35 min vs. 75 min (P<0.01). Maternal mortality was significantly higher in patients undergoing UR vs. STH, 46% vs. 20% (P=0.01). Maternal morbidity occurred in 30% of patients undergoing STH vs. 50% in patients undergoing UR (P=0.01). The time to discharge was significantly less in patients undergoing STH compared to UR, 14.5 days vs. 27 days (P<0.01). CONCLUSIONS: Patients with uterine rupture in extremis tend to be young, multiparous, receive no antenatal care, and have uterine rupture of the lower segment. STH significantly lowered operative time, morbidity, time to discharge, and mortality than UR in patients in extremis with uterine rupture.

Adult↗
PubMed2001

Base-pair alterations in the epsilon-lower stem due to a novel double substitution in the precore gene of HBV-e negative variant were recovered by secondary mutations.

The HBe negative phenotype, a natural precore mutant (G1896A/G1897A) of HBV with aborted HBeAg expression is known to cause chronic hepatitis. The destabilized C : G base-pairing in the lower stem of epsilon-hairpin due to G1896A substitution is reportedly compensated by a second C1858T mutation and suggested to play an important role in enhanced selection of the HBe negative variant. We undertook to investigate presence of such compensatory mutations at other positions by analyzing epsilon-sequences (nts. 1847-1907) as well as to look for their effect(s), if any, on the consensus sequence of the overlapping core-initiator of HBe negative HBV variants in CLD patients. Three of the 5 HBe negative patients had classical G1896A mutation having a second compensatory mutation at nt. 1858. One patient showed an additional G1897A substitution, presenting as a novel precore stop codon mutation (UGG-->UAA), followed by a compensatory mutation at position 1857. In the third patient, a G1899A substitution was seen which compensated the impaired U at position 1855. Other substitution and deletion mutations were also observed in the remaining epsilon-hairpin, which however, did not produce any compensatory mutation. Further, all the precore variants showed a conserved G at position 1904, important for the optimal context of their core-initiator which however, remained impaired with A (nt. 1850). Our results suggest that the nts. 1851-1859 and nts. 1895-1904 in the lower stem, and restoration of authentic base-pairings therein, maintain the structural integrity and stability of the epsilon-hairpin. This may have a role in the enhanced selection of the HBe negative variants and persistence of HBV infection in chronic liver disease patients.

Base Pairing↗
PubMed2001

Profile of hepatocellular carcinoma in India: an insight into the possible etiologic associations.

BACKGROUND: Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent. METHODS: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. RESULTS: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 +/- 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg - ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. CONCLUSIONS: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.

Aflatoxin B1↗
PubMed2001

Gene transfer to the embryo: strategies for the delivery and expression of proteins at 48 to 56 hours postfertilization.

BACKGROUND/PURPOSE: Although gene and protein transfer may potentiate the cure of genetic disease, current strategies involving fetal gene therapy remain nonfocal and confounded by the lack of imaging techniques and in vivo markers for precise gene transfer. METHODS: Fourteen white Leghorn chick eggs were incubated for 48 to 56 hours postfertilization until they reached stages 11 to 16, about 3 mm in size. In 7 chick embryos, a glass needle was placed at the midbrain/hindbrain level and 1 x 10(7) pfu of an adenovirus containing the green fluorescent protein (GFP) reporter gene was injected into the lateral head. In another 7 chicken embryos, colored agarose beads coated with Sonic hedgehog (Shh) protein were implanted at the level of the hindbrain under direct microscopy. The eggs were then sealed, incubated at 37 degrees C for 24 hours, and reimaged using fluorescent microscopy and confocal laser microscopy. RESULTS: At 24 hours postinjection, all embryos were alive and were imaged in vivo. Fluorescent microscopic imaging showed green fluorescence in the region of the injection site in all the embryos. In embryos that underwent bead placement, the beads were visualized under microscopy in the lateral hindbrain of all embryos, and the presence of the Shh protein was confirmed using fluorescein isothiocyanate (FITC)-conjugated secondary antibody. CONCLUSIONS: This study shows that embryonic 3-mm chick embryos survive adenoviral transduction or agarose bead implantation in a focal manner in vivo and that this delivery results in production of imageable levels of protein. This may be used in mammalian systems, including humans, to introduce genes and proteins.

Animals↗
PubMed2001

Enhanced immunogenicity of recombinant hepatitis B vaccine in exposed family contacts of chronic liver disease patients.

Close family contacts of hepatitis B virus (HBV)-related chronic liver disease patients have a high risk of exposure to HBV. Variable responses to vaccination have been reported in family contacts, especially in previously exposed contacts (IgG antiHBc-positive). Seventy-nine healthy family contacts, who were HBsAg-negative with normal alanine amino-transferase level and no evidence of liver disease, were vaccinated using a recombinant HBV vaccine, irrespective of past exposure status. A significantly higher number of previously exposed subjects (n = 25; Group I) developed early seroprotective anti-HBs titers with 2 initial doses of vaccine compared to the unexposed contacts (Group II; n = 54) (64% vs. 33%, respectively; P < 0.05). However, the responses were comparable on completion of the schedule (96% vs. 94%, respectively). HBV DNA was detected in 11 of 25 (44%) exposed and none of the unexposed contacts at baseline. Post-vaccination, 3 of 11 (27%) subjects became HBV DNA-negative and remained negative for the next 12 months. These results suggest that exposed family contacts achieve efficient seroprotection after HBV vaccination, irrespective of the IgG anti-HBc status. The response to vaccination resembles an anamnestic reaction and possibly demonstrates a therapeutic effect.

Adolescent↗
PubMed2001

Obesity, hypertension, and the heart.

Hypertension occurs more commonly in obese than in lean persons at virtually every age. A variety of endocrine, genetic, and metabolic mechanisms have been linked to the development of obesity hypertension. These include insulin resistance and hyperinsulinemia, increased serum aldosterone levels, salt sensitivity and expanded plasma volume in the presence of increased peripheral vascular resistance, a genetic predisposition, and possibly increased leptin levels. Pressure and volume overload are present in obese hypertensives. This leads to a mixed eccentric-concentric form of left ventricular hypertrophy and increases the predisposition to congestive heart failure. Weight loss, even in modest decrements, is effective in reducing obesity-hypertension, possibly by ameliorating several of the proposed pathophysiologic mechanisms. There are currently no specific recommendations concerning pharmacotherapy of obesity-hypertension because each drug group has pros and cons.

Antihypertensive Agents↗
PubMed2001

Elevated serum cancer antigen 125 levels in advanced abdominal tuberculosis.

A 48-yr-old female presented with a 1-yr history of pain in the hypochondrium and epigastrium. All routine investigations and computed tomography (CT) of the abdomen were done. CT findings revealed a well-defined cystic mass in the right ovary, and ascitis with features suggestive of secondaries over the omentum and peritoneal surface. The serum CA125 was 1255 U/mL (normal range 0-35 U/mL), which was indicative of ovarian malignancy. An exploratory laparotomy was performed. Histopathological examination of organs revealed the presence of granuloma. The patient was advised to undergo antitubercular treatment (ATT) and follow-up every month. After 1 mo of ATT, the CA125 level came down to 42 U/mL, which was near normal. As tuberculosis requires only a conservative management, we suggest that in cases of abdominopelvic mass with or without ascitis, high serum CA125 should always raise a suspicion of tuberculosis and a laparoscopy combined with peritoneal biopsy should be performed to confirm the diagnosis. This will prevent unnecessary laparotomies. Moreover, serum CA125 can be used to monitor the response of disease to antitubercular treatment.

Adnexal Diseases↗