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Biomedical subjects

V K Shukla

Publications and source records attributed to V K Shukla.

At least 55 records · Page 3Linked to original sources

Fatty acids, biliary bile acids, lipid peroxidation products and gallbladder carcinogenesis.

Secondary bile acids, by virtue of their lipophilic action, change the membrane composition of hepatocyte mitochondria, the inner membranes of which harbour the cytochrome P450 oxido-reductase system. The changes in the membrane fatty acid composition decreases the activity of the mitochondrial enzyme system, thereby making them incapable of handling free radicals generated during the normal process of energy production and detoxification. These free radicals in turn may attack membrane polyunsaturated fatty acids to initiate and propagate lipid peroxidation, leading to formation of aldehydic lipid peroxidation products. Notably among these is 4-hydroxynonenal, which has a high genotoxic and neoplastic potential. Disorders of gallbladder contractility further lead to accumulation of these toxic substances normally excreted in bile, and if retained for long time in the gallbladder they may induce gallbladder carcinogenesis.

Bile Acids and Salts↗

Histoplasmosis: an unusual presentation.

Histoplasma capsulatum (HC) infection is rare in India. We document a case of unilateral adrenal histoplasmosis in a 56 year male. The patient presented with hepatosplenomegaly, unilateral adrenal mass and significant weight loss. Since FNAC of adrenal mass was inconclusive, he underwent splenectomy, adrenalectomy and liver biopsy, histology of these specimens revealed HC only in adrenal mass. Subsequently, histoplasmin test was also performed which was also found to be positive. He responded well to parenteral amphotericin B and is under regular follow-up with no complaints now.

Adrenal Gland Diseases↗

Activation tagging of the floral inducer FT.

FLOWERING LOCUS T (FT), which acts in parallel with the meristem-identity gene LEAFY (LFY) to induce flowering of Arabidopsis, was isolated by activation tagging. Like LFY, FT acts partially downstream of CONSTANS (CO), which promotes flowering in response to long days. Unlike many other floral regulators, the deduced sequence of the FT protein does not suggest that it directly controls transcription or transcript processing. Instead, it is similar to the sequence of TERMINAL FLOWER 1 (TFL1), an inhibitor of flowering that also shares sequence similarity with membrane-associated mammalian proteins.

Alleles↗

Induction of zidovudine glucuronidation and amination pathways by rifampicin in HIV-infected patients.

AIMS: The objective of the study was to determine the effect of multiple doses of rifampicin on the steady-state pharmacokinetics of zidovudine and its 5'-glucuronosyl (GZDV) and 3'-amino (AMT) metabolites. METHODS: Eight asymptomatic HIV-infected patients (seven male, one female) participated in this three-period longitudinal study. Each patient received zidovudine (200 mg every 8 h) for 14 days (period 1), followed by rifampicin (600 mg every 24 h) with zidovudine for 14 days (period 2), and then zidovudine alone for a further 14 days (period 3). Blood and urine samples were collected over 6 h on the last day of each period for measurements of zidovudine and GZDV by h.p.l.c.-u.v. and AMT by h.p.l.c.-m.s-m.s. RESULTS: Compared with zidovudine-alone values in period 1, 14 days of coadministration with rifampicin significantly increased zidovudine oral clearance (89%) and formation clearances to GZDV (100%) and AMT (82%). Correspondingly, there were decreases in maximum plasma concentration (43%), AUC (47%) and urine recovery (37%) of zidovudine. GZDV/zidovudine and AMT/zidovudine AUC ratios increased by 99% and 36%, respectively, despite a significant 29% decrease in AMT AUC. After stopping rifampicin for 14 days, values of these pharmacokinetic parameters returned to within 26% of baseline. Over the three periods AMT plasma levels were <18 ng ml-1 (n=6) and <40 ng ml-1 (n=2), and molar AMT/zidovudine AUC ratios ranged from 1.7% to 4.5%. CONCLUSIONS: Rifampicin induced zidovudine glucuronidation and amination pathways resulting in decreased plasma and urine exposures to zidovudine. AMT plasma exposure decreased because induction was more pronounced for the major GZDV metabolite. The magnitude of the residual inductive effect was minimal at 14 days after stopping rifampicin.

Adult↗

Malignancy load on general surgeons: the need to change the general surgical training curriculum.

AIMS: With the advent of newer diagnostic modalities more and more cancer patients are being diagnosed each year. The rising detection rate and greater public awareness have immensely increased the load on already overburdened and increasingly fewer surgical oncology units. As a result a large number of these cases are being dealt with by general surgeons. METHODS: We have used a retrospective case count from a single surgical unit, based at the University Hospital, Varanasi, and data from the Hospital Based Cancer Registry (HBCR), Regional Cancer Centre (RCC), Trivandrum, from 1990 to 1994, to define the malignancy load on general surgical units and to define the number and sites of malignancies commonly encountered by general surgeons. RESULTS: A total of 28,136 patients were registered at the RCC, the commonest malignancy being oral cavity (16.35%), followed by lung (12.7%) and breast (23.8%) among men and women, respectively. On the other hand, in the 2123 patients with malignancy who were treated at the Medical College (MCH) in Trivandrum, the commonest sites encountered were stomach (11.68%), thyroid (10.31%) and colorectal (9.5%). This was quite similar to the frequencies observed at Varanasi, where colorectal cancer constituted 10.26% and stomach 6.98%. Only 13.6% of the patients reporting to RCC were treated by surgery alone or in combination, while this figure was 48. 1% for MCH. Similarly 2056 (7.3%) patients presenting to RCC had completed treatment prior to being referred to RCC; almost all of these patients were treated by surgery at referral institutions by general surgeons. CONCLUSIONS: The results clearly indicate an increased demand on the surgical oncology units, or alternatively an urgent need to redefine the postgraduate curriculum for the better training of general surgeons in understanding malignant disease, especially in the developing countries. We recommend a minimum of 6 months training in surgical oncology for each general surgery postgraduate.

Cancer Care Facilities↗

Malignant fibrous histiocytoma of the rectum.

Malignant fibrous histiocytoma (MFH) of the gastrointestinal tract is a rare occurrence. We report a case of MFH of the rectum in a 55-year-old man. Ultrasound examination revealed thickening of the rectal wall and the biopsy study indicated MFH. The patient underwent abdominoperineal resection and chemoradiation and is doing well after 46 months. A high index of suspicion for colorectal MFH should be taken into account in order to avoid histological misdiagnosis.

Histiocytoma, Benign Fibrous↗

Appendicectomy under local anaesthesia.

OBJECTIVE: To analyse our results of appendicetomy under local anaesthesia. DESIGN: Prospective study. SETTING: University hospital, India. SUBJECTS: 165 patients who presented with appendicitis between January 1996 and December 1997. INTERVENTION AND MAIN OUTCOME MEASURES: Appendicectomy after infiltration of local anaesthetic. No patient required general or spinal anaesthesia. RESULT: Five patients (3%) developed postoperative wound infections. Mean operating time was 20 minutes (range 15-30) and median hospital stay 2 days (range 1-3). CONCLUSION: Appendicectomy under local anaesthesia is quick, cost-effective and carries little morbidity. It can be safely used for all age groups.

Adolescent↗

Hepatic duct stones masquerading as Klatskin tumour.

We report woman who presented with painless progressive jaundice following cholecystectomy. Radiological investigations indicated proximal bile duct obstruction suggestive of hilar malignancy. Exploratory laparatomy revealed bilateral hepatic duct stone causing obstruction.

Bile Duct Neoplasms↗

Erythrocyte membrane stearic to oleic acid ratio in carcinoma of the gallbladder: a preliminary study.

AIMS: The role of erythrocyte membrane stearic to oleic acid ratio (saturation index) as a marker of malignancy is still unclear, though an association has been found in colorectal carcinoma, bronchogenic carcinoma, leukaemia, lymphoma and in hepatic malignancies. This study aims to investigate the role of the saturation index in primary carcinoma of the gallbladder. METHODS: This paper describes the results of the stearic to oleic acid ratio determination in 26 subjects with either cholelithiasis or carcinoma of the gallbladder, also including a group of age- and sex-matched controls, using gas chromatography. This is the first report of the saturation index in carcinoma of the gallbladder. RESULTS: A significantly lower saturation index was observed in patients with carcinoma of the gallbladder than with cholelithiasis (t = 2.19, P = 0.043, T = 47, P < 0.05, Wilcoxon P < 0.001, F = 2192.23, P < 0.001; 95% CI 18.45-30.44) and controls (t = 2.5, P = 0.024, T = 36, P < 0.05, F = 10904.11, P < 0.001, Wilcoxon P < 0.001; 95% CI 52.42-63.39). Among the carcinoma patients a further lowering was noted in stage IV disease compared with stage III (T = 6, P < 0.05). CONCLUSIONS: These changes are probably due to a marked increase in oleic acid content at the expense of stearic acid. This lowering of the saturation index in carcinoma of the gallbladder is similar to that observed previously in the other malignancies.

Carcinoma↗

Carcinoma of the gallbladder presenting as scalp tumour.

Carcinoma of the gallbladder is characterized by rapid tumour growth associated with lymphatic and local tumour invasion. The peritoneum, GIT and lungs are common sites of seeding. Distant metastasis to bone rarely occurs. Here we document a case of silent gallbladder carcinoma presenting as scalp tumour with improved survival.

Carcinoma↗

Xanthogranulomatous cholecystitis.

Xanthogranulomatous cholecystitis exists in a small but significant proportion of routine cholecystectomy specimens. A few recent reports have shown a possible association of this disease with carcinoma of the gallbladder. All cholecystectomized specimens were prospectively evaluated over a period of two and half years in a single surgical unit to examine the incidence of xanthogranulomatous cholecystitis and its association, if any, with carcinoma of the gallbladder in an area that is prone to gallbladder diseases. A total of 460 cholecystectomies were performed for various gallbladder diseases. Histological confirmation revealed chronic cholecystitis in 311 (67.6%) cases, carcinoma of the gallbladder in 62 (13.5%), acute cholecystitis in 29 (6.3%), xanthogranulomatous cholecystitis in 41 (8.9%), and xanthogranuloma and carcinoma of the gallbladder in one case (0.2%) only. Almost all cases were suspected to have chronic cholecystitis on clinical and ultrasonographic features. Two specimens on gross examination showed mass lesions, and hence were suspected to be carcinoma of the gallbladder. Subsequent frozen section and histopathology demonstrated xanthogranulomatous cholecystitis. Only one case of xanthogranuloma was found to be associated with carcinoma of the gallbladder but no firm association could be established between xanthogranulomatous cholecystitis and carcinoma of the gallbladder.

Acute Disease↗

Metallothionein expression in carcinoma of the gallbladder.

AIMS: Metallothioneins (MT) are sulphur-rich, low molecular-weight, intracellular metal-binding proteins with a possible role in carcinogenesis of some human tumours. Metallothionein expression in gallbladder cancer has not been studied previously. METHODS AND RESULTS: Immunohistochemical expression of metallothionein was studied in 42 gallbladders (27 cases of carcinoma of the gallbladder, eight chronic cholecystitis and seven cases of normal gallbladder). Metallothionein expression was significantly higher in cases with carcinoma of the gallbladder (70.37%) as compared to chronic cholecystitis (25%) and normal gallbladders (0%). There was a trend suggestive of increasing MT expression with increasing histological dedifferentiation of carcinoma of the gallbladder. CONCLUSIONS: The increased expression of MT in cases of carcinoma of the gallbladder may represent an increased exposure to heavy metals, which are known carcinogens, and may have a role in gallbladder carcinogenesis. Metallothionein over-expression in carcinoma of the gallbladder may be relevant to the poor prognosis and chemoresistance seen in these cases.

Adult↗

Cardiff repair of incisional hernia: a university hospital experience.

OBJECTIVE: To analyse our results of the "Cardiff' (far and near) repair in incisional hernias. DESIGN: Prospective study. SETTING: University hospital, Varanasi, India. SUBJECTS: 50 patients who presented with incisional hernias between January 1990 and December 1994. INTERVENTION: Interrupted far-and-near sutures inserted after excision of the sac. The contents were pushed into the abdomen and the peritoneum sutured with non-absorbable polypropylene (prolene). MAIN OUTCOME MEASURES: Early and late morbidity. Six patients developed postoperative complications (wound infection, n=3; flap necrosis, n=2; and wound sinus, n=1). No patient has been lost to follow up and there have been no signs of recurrence after a mean follow up of 52 months. CONCLUSION: The meticulous application of this simple surgical technique has low morbidity and is cost effective. We recommend it for small and medium size defects.

Adolescent↗

Water transport activity of the plasma membrane aquaporin PM28A is regulated by phosphorylation.

PM28A is a major intrinsic protein of the spinach leaf plasma membrane and the major phosphoprotein. Phosphorylation of PM28A is dependent in vivo on the apoplastic water potential and in vitro on submicromolar concentrations of Ca2+. Here, we demonstrate that PM28A is an aquaporin and that its water channel activity is regulated by phosphorylation. Wild-type and mutant forms of PM28A, in which putative phosphorylation sites had been knocked out, were expressed in Xenopus oocytes, and the resulting increase in osmotic water permeability was measured in the presence or absence of an inhibitor of protein kinases (K252a) or of an inhibitor of protein phosphatases (okadaic acid). The results indicate that the water channel activity of PM28A is regulated by phosphorylation of two serine residues, Ser-115 in the first cytoplasmic loop and Ser-274 in the C-terminal region. Labeling of spinach leaves with 32P-orthophosphate and subsequent sequencing of PM28A-derived peptides demonstrated that Ser-274 is phosphorylated in vivo, whereas phosphorylation of Ser-115, a residue conserved among all plant plasma membrane aquaporins, could not be demonstrated. This identifies Ser-274 of PM28A as the amino acid residue being phosphorylated in vivo in response to increasing apoplastic water potential and dephosphorylated in response to decreasing water potential. Taken together, our results suggest an active role for PM28A in maintaining cellular water balance.

Animals↗