Biomedical subjects
Publications and source records attributed to A K Khanna.
Hydatid disease usually affects liver and lungs, but may affect any organ, posing a diagnostic and therapeutic dilemma. We analysed 110 patients with hydatid cyst over 21 years in our general surgical unit, which included 24 cases in unusual sites. The spleen was the most common, followed by skin and soft tissues.
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Sir Astley Paston Cooper stated in 1804 that a sound knowledge of proper anatomy of hernia is vital. But even in the succeeding two centuries, the confusion has only multiplied by varied and overly enthusiastic descriptions, some speculative and others real, by different workers. An attempt has been made to highlight the size of the controversies surrounding the anatomical structures forming the inguinal canal and groin. The inguinal and femoral hernias should be viewed collectively as one entity and together be called groin hernias. Therefore, the passage for their superficial emergence through the anterior abdominal wall is redefined and is called pubomyoaponeurotic foramen. It is uniformly accepted that the strong posterior wall of the groin area is the only preventive factor towards the emergence of hernia; it has been renamed as posterior groin plait. Therefore, proper understanding of its structure towards effective repair and reinforcement is the only safe method, whether the procedure is carried out by anterior or posterior route or laparoscopically. Hence, an attempt has been made to elucidate its true structure. In spite of so many descriptions, the exact anatomy of hernia is yet to be resolved.
Fenofibrate is the ligand for PPARalpha subtype that mediates the action of its agonists' in lipid metabolism. How fibrate exerts hypolipidemic effect? The mechanism is studied in a newly developed high-fat fructose enriched diet induced dyslipidemia-diabetic hamster model. Fenofibrate lowered the basal plasma lipids like TC, TG, PL, FFA, glycerol, VLDL, and LDL, but HDL was increased. The activity of lipoprotein lipase in liver, adipose tissue, and small intestine was upregulated. However, that of triglyceride lipase was downregulated in liver. It has also improved the insulin secretion and plasma glucose lowering, caused by impairment in insulin secretion due to high-fat load. The drug was found effective in reducing body weight and diet due to rise in leptin level. Fenofibrate also enhanced the fecal excretion of total lipids, cholic acid, and deoxycholic acid probably by the activation of 7alpha cholesterol hydroxylase enzyme. Thus, causing broad-spectrum lipid lowering along with inhibition of hepatic lipid biosynthesis and maintaining lipid-glucose homeostasis.
With an aim to evaluate the antifibrotic action of colchicine in experimental model of pulmonary silicosis, the effect of colchicine on developing and developed pulmonary silicosis induced by quartz was studied in rats in vivo and on alveolar macrophages exposed to quartz particulates in vitro. A progressive increase in wet and dry weight of lungs exposed to quartz dust alone, and quartz dust and colchicine injected orally was investigated. An increase in collagen contents, with lapse in time, in animals exposed intratracheally to quartz dust, or exposed similarly to quartz dust but receiving colchicine simultaneously through oral route was observed. A blindfold evaluation of histological sections of lungs of silicotic animals with or without colchicine administration during development of lesions did not reveal any difference between two groups of silicotic rats. Administration of colchicine for 4 weeks after the lesions were developed neither inhibited nor retarded the laying down of collagen. The studies were extended to investigate the effect of colchicine on quartz-induced alveolar macrophage cytotoxicity. The presence of varying concentrations of colchicine in the culture medium did not significantly alter cytotoxic potential of quartz. The results reveal that colchicine administration during the development of and on developed silicosis does not significantly alter pathogenesis of silicotic lesions. At the cellular level colchicine does not modulate quartz-induced alveolar macrophage cytotoxicity, believed to be a significant event for the onset of pulmonary silicotic fibrogenesis.
Due to similarities in lipid metabolism to those in humans, hamster is considered as a good model for the study of regulatory mechanisms of plasma lipoproteins in response to cholesterol or fatty acid-enriched diet. This model of hyperlipidemia has been modified to produce dyslipidedmia with diabetes complexities by feeding with high fat diet added with 9% (w/w) fructose. Feeding this diet to hamster for 10 days markedly increases plasma levels of triglyceride, cholesterol, fatty acids followed by a significant increase in glycerol, beta lipoproteins, high density lipoprotein, glucose and glycosylated proteins. This model is being used for research and development of lipid lowering drugs with hypoglycemic activity in collaboration with Novo Nordisk, Denmark. The modified high fat diet formulation has now been prepared (Research diet D.99122211) and supplied by Research Diets Inc, Burnswick USA.
The lipid lowering activity (LLA) of Phyllanthus niruri has been studied in triton and cholesterol fed hyperlipemic rats. Serum lipids were lowered by P. niruri extract orally fed (250 mg/kg b.w.) to the triton WR-1339 induced hyperlipemic rats. Chronic feeding of this drugs (100 mg/kg b.w.) in animals simultaneously fed with cholesterol (25 mg/kg b.w.) for 30 days caused lowering in the lipids and apoprotein levels of VLDL and LDL in experimental animals. The LLA of this drug is mediated through inhibition of hepatic cholesterol biosynthesis, increased faecal bile acids excretion and enhanced plasma lecithin: cholesterol acyltransferase activity.
OBJECTIVE: To estimate the value of estrogen receptor (ER) in benign breast diseases and to find out if the response of benign breast diseases to danazol depends on the ER status of the tissue. DESIGN: Prospective study. SETTING: University hospital, India. MATERIAL: Samples of tissue from benign breast lesions, 40 fibrocystic disease and 10 fibroadenomas. INTERVENTIONS: Enzyme immunoassay for the presence of cytosolic ER. MAIN OUTCOME MEASURES: ER concentrations, and correlation with effect of treatment with danazol. RESULTS: Fibrocystic disease and fibroadenomas showed 30% and 40% ER positivity, respectively. The mean (SD) ER concentration was significantly higher in premenopausal than postmenopausal patients 14.75 (3.79) fmol/mgm compared with 6.2 (1.59) fmol/mg (p < 0.05). All ten patients with mastalgia who had ER-positive lesions (n = 26) responded to danazol, compared with 6 of 16 patients who had ER-negative lesions (p < 0.05). Lesions with diffuse fibrosis (n = 14) and five with lymphocytic infiltration on histology were all ER-negative. CONCLUSION: The patients with ER positive breast disease responded better to danazol than patients with ER negative breast disease.
Fifty two cases of tuberculosis of the breast encountered over a 15 year period and accounting for 3% of all breast lesions are reported. The classic presentation was a breast lump with associated sinus in 39%, isolated breast lump in 23%, sinus without lump in 12%, and tender nodularity in 23% of the patients. Associated axillary lymphadenopathy was found in 41%. Diagnosis was confirmed by fine needle aspiration cytology or histology in all the cases and antitubercular therapy formed the mainstay of treatment.
Intravaginal foreign body rarely causes bowel obstruction. A 60-year-old female presented with pain in lower abdomen. On examination, her abdomen was found distended with muscle guard. Per rectal examination revealed a hard mass 3-4 cm away from the anal verge. There was leucocytosis and straight x-ray showed features of large bowel obstruction. Exploratory laparatomy was performed. The large bowel was distended with a hard mass felt in the pelvis. On manipulation the mass of about 15 cm x 12 cm x 12 cm size came out of the vagina and it happended to be a brick. The recovery was uneventful.
OBJECTIVE: To study the argyrophilic nucleolar organizer region (AgNOR) count and subjective AgNOR pattern assessment (SAPA) score in cytologic and histologic specimens of various skin tumors. STUDY DESIGN: The study group consisted of 37 patients (14 benign and 23 malignant) of various skin tumors. In all cases, cytology by fine needle aspiration cytology (FNAC), and histological specimens were studied by conventional staining and silver staining for AgNOR. RESULTS: The mean count in benign tumors in cytologic specimens was 2.08 +/- 0.01, compared with 5.50 +/- 1.12 in malignant tumors (P<0.001). In histologic specimens, mean count was 2.13 +/- 0.51 in benign, compared with 5.38 +/- 1.10 in malignant tumors (P<0.001). The SAPA score in benign tumors (P<0.001) in cytologic specimens, was 6.07 +/- 0.83, compared with 10.65 +/- 1.27 in malignant tumors, and in histology, it was 6.07 +/- 0.87 in benign, compared with 10.83 +/- 1.15 in malignant tumors (P < 0.001). Melanoma showed the higher AgNOR count compared with squamous cell carcinoma and basal cell carcinoma. The parameters were statistically significant between the grade of tumor in squamous cell carcinoma and the positivity of lymph nodes as demonstrated by SAPA score. No correlation was found between the clinical stage and Clark level of melanoma. Although, AgNOR count and SAPA score showed similar results, the indicators of validity were higher in SAPA than AgNOR count. CONCLUSION: Although, AgNOR count and SAPA score gave similar results, but the indicators of validity were higher in SAPA score than AgNOR count.
A new series of compounds belonging to N,N'- [bis (1-aryl-6-hydroxy-hex-2-ene-1-one-3-yl)-1,n-alkanediamines (2-5a-f) have been synthesized and evaluated for antioxidant and hypolipidemic activities. Amongst all the synthesized compounds, seven compounds namely 2c, 2e, 4c, 5b, 5c, 5e and 5f exhibit potent antioxidant activity. These compounds have also been evaluated for hypolipidemic activity.
Rats were exposed for 1 h to increasing concentrations of cadmium (Cd) through inhalation of cadmium chloride aerosol using nose-only inhalation chambers and depositions of Cd in lungs, liver and kidneys were measured. Changes in spontaneous locomotor activities were recorded 2 and 7 d after cessation of exposure. A concentration dependent increase in Cd in lungs, liver and kidneys was accompanied by significant alterations in spontaneous locomotor response that was dependent on the air Cd concentrations and the postexposure duration. The study shows decreased spontaneous locomotor activity due to Cd accumulation in tissues.
OBJECTIVE: To find the correlation of argyrophilic nucleolar organizer region (AgNOR) count and subjective AgNOR pattern assessment (SAPA) score in cytology and histology of breast lumps. STUDY DESIGN: The study group consisted of 73 patients (46 malignant, 27 benign) with breast lumps. In all cases, fine needle aspiration cytology (FNAC) samples and histologic specimens were studied by conventional and silver staining for AgNORs. RESULTS: AgNOR count and SAPA score were helpful in differentiating benign from malignant tumors in both the cytologic smear and histologic specimen. AgNOR count was 6.94+/-2.74 in FNAC and 6.57+/-2.73 in histology of malignant tumors, while in benign tumors it was 2.75+/-0.74 in FNAC and 2.68+/-0.77 in histology. SAPA score was 9.02+/-4.60 in FNAC and 8.76+/-2.34 in histology in malignant tumors and 5.87+/-0.93 in FNAC and 5.82+/- 0.83 in histology in benign tumors. CONCLUSION: Both AgNOR count and SAPA score gave similar results, but SAPA score is a more convenient, reproducible and rapid method of AgNOR evaluation.
Majority of patients with advanced carcinoma gall bladder have irresectable disease and require palliation for jaundice, pruritus and cholangitis. These cases presenting with jaundice are usually high risk cases to undergo any major surgical procedure like segment-III hepaticodochojejunostomy. So intra-operative tube stenting was attempted in 6 patients of carcinoma gall bladder but technically, it was possible in 4 cases only. In 2 cases because of massive locoregional disease it was not possible to cannulate the proximal part of the bile duct. The distal end of the tube was passed either in the duodenum or proximal part of the jejunum. Patients were followed up, showed good recovery from jaundice and pruritus.
BACKGROUND: The combination of rapamycin with Cyclosporine has demonstrated beneficial effects in organ transplantation; however, the mechanism of this combination immunosuppression is not fully understood. The mechanism of action of cyclosporine and tacrolimus has been explained on the basis of their inhibition of interleukin-2 (IL-2), and induction of transforming growth factor-beta (TGF-beta). In this study, we explored the effects of rapamycin in combination with either tacrolimus or cyclosporine on lymphocyte proliferation, and expression of interleulin-2 (IL-2) and TGF-beta METHODS: Peripheral blood mononuclear cells/lymphocytes were isolated from buffy coats obtained from blood center, and activated with phytohemagglutinin (PHA) in the presence or absence of rapamycin, cyclo sporine, and tacrolimus alone or in various combinations. The activation was quantified by 3H-thymidine uptake assay and using reverse transcriptase assisted polymerase chain reaction and ELISA, we studied the TGF-beta and IL-2 mRNA and protein expression, respectively. RESULTS: In this study, we report that rapamycin in combination with either tacrolimus or cyclosporine significantly inhibited the lymphocyte proliferation, IL-2 expression, and induced TGF-beta, compared with these drugs alone. The levels of TGF-beta and IL-2 correlated positively and negatively, respectively, with inhibition of lymphocyte proliferation. CONCLUSIONS: These novel findings provide the mechanism as well as the rationale to use these drugs in combination at subclinical dosages in organ transplantation.
Cyclosporine has potent antiproliferative properties, some of which may be via the induction of the cyclin inhibitor p21. In this study, we describe the effects of in vitro and in vivo transfection of p21 in lymphoid and nonlymphoid cells. For in vitro studies, p21 sense plasmid DNA was transfected in A-549 cells (lung adenocarcinoma cell line) and Jurkat cells (human lymphoid cell line). This in vitro transfection of p21 resulted in the inhibition of spontaneous and mitogen-induced cellular proliferation ([3H]thymidine uptake) and also augmented the antiproliferative effects of cyclosporine. In vivo transfection of p21 was accomplished in mice via the i.m. injection of p21 sense plasmid DNA complexed with cationic lipids. As was the case in the cell lines, p21 mRNA was augmented in heart, lung, liver, and spleen 7 days after i.m. injection of p21 sense plasmid DNA. The mitogen (anti-CD3)-induced proliferation of splenocytes from p21-overexpressing mice was significantly decreased, and again this effect was augmented by cotreatment with cyclosporine. These novel findings demonstrate the potential of targeting the cell cycle directly to inhibit alloimmune activation in organ transplantation. This may serve as an alternate strategy to induce immunosuppression, perhaps with less toxicity than that which is seen with conventional immunosuppressive agents.
BACKGROUND: The impact of acute rejection, immunosuppression, and infection, specifically cytomegalovirus infection, on the development of chronic rejection in the cardiac allograft, has been the subject of a large number of investigations. One of the difficulties in finding associations has been the marked immunologic heterogeneity of the patient population coupled with the lack of the ability to HLA match. Furthermore, the ideal animal model, which duplicates as well as controls for this immunologic heterogeneity, is lacking. METHODS: To try to simulate differences in HLA matching, immunosuppression regiments and cytomegalovirus infection, heterotopic heart transplantation was performed in two separate, complete MHC mismatch, rat strain combinations (WF-LEW, BN-LEW) requiring chronic immunosuppression and employing four separate immunosuppression/infection protocols. Animals were followed for 6 months, killed, and rejection and vascular changes were scored blinded to the group. RESULTS: The mean vascular and acute rejection scores were not significantly different between treatment regiments for either specific strain combination. There was a trend for the subtherapeutic groups to have higher vascular scores. Overall, there were no significant differences in vascular scores between the WF-LEW and BN-LEW groups (1.25+/-0.18 vs. 1.13+/-0.20, P=NS). Similar numbers of WF-LEW and BN-LEW exhibited cellular infiltration and necrosis of the allograft, but the intensity of the response (rejection score) was more severe in the WF-LEW combination (4.54+/-0.22 vs. 3.92+/-0.21, P=0.052) when limiting the analysis to those with myocyte necrosis. There was no significant correlation between acute rejection and vascular lesion severity in the WF-LEW combination (r=0.22, P=NS) but a high correlation between these parameters in the BN-LEW combination (r=0.74, P<0.0001). CONCLUSIONS: These data suggest that, although acute rejection and chronic rejection are related, MHC matching may influence their interdependence. These data also may explain why the clinical association between acute and chronic rejection is difficult to demonstrate.