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Biomedical subjects

A K Sharma

Publications and source records attributed to A K Sharma.

At least 199 records · Page 11Linked to original sources

Clinical and demographic features of Meige's syndrome.

Fifty five patients with Meige's syndrome were examined for clinical and demographic features. The mean age of onset was 52.3 years. The peak age of onset was in the sixth decade with a male to female ratio of 1.11:1. The mean duration of illness was 3.7 years. Commonest initial symptom was increased blinking, seen in 30 cases (54.5%). Twenty five patients (45.4%) had complete syndrome of blepharospasm with oromandibular dystonia, whereas 24 patients (43.6%) had blepharospasm alone and the rest (6 patients, 10.9%) had oromandibular dystonia. The extension of spasm beyond cranial muscles was observed in 10 patients (18.1%). Eleven patients had family history of dystonia or other extrapyramidal disorders. Incidence of depression was high in these cases.

Adult↗

A cautionary note regarding the application of Ki-67 antibodies to paraffin-embedded breast cancers.

Immunocytochemical studies examining the Ki-67 proliferation marker in paraffin-embedded material have recently been made possible by the availability of several antibodies, notably MIB-1, which are readily applicable to microwaved sections. Using breast cancer material, the present study examines correlations shown by these new paraffin assays and also by PCNA (proliferating cell nuclear antigen), an existing marker of proliferation, with the established Ki-67 cryosection assay. Paraffin sections were microwaved prior to incubation with Ki-67 or MIB-1 antibodies. Signal detection was carried out with a biotinylated secondary antibody, peroxidase-conjugated streptavidin, and DAB/H2O2 chromogen. The results suggest that caution is required when studying proliferation in paraffin-embedded breast cancers by immunostaining using Ki-67 antibodies. Nuclear staining in wax sections (Ki-Par, MIB-1, PCNA) greatly exceeded that in cryosections (Ki-Froz) and thus correlations were notably absent between Ki-Par or PCNA immunostaining and the routine Ki-Froz assay. Immunostaining with MIB-1 or PCNA may, however, be useful to assess proliferation if cut-offs are applied to eliminate weak immunostaining associated with wax sections. Thus, an approximately linear relationship was seen between MIB-1/Ki-Froz, which was improved if only moderately or moderately/strongly MIB-1-positive cells were scored. Similarly, a significant correlation was also revealed between PCNA/Ki-Froz if such a cut-off was applied.

Antibodies, Monoclonal↗

The role of endoscopic retrograde cholangiopancreatography in the management of choledochal cysts in children.

Endoscopic retrograde cholangiopancreatography (ERCP) was performed in eight consecutively treated patients with choledochal cyst to assess its technical feasibility and complications. Satisfactory visualization of the complete anatomy of the biliary tract was possible in seven patients. Four patients had a type IV choledochal cyst and three had type I. In one patient, the procedure showed a congenital web in the lower end of the common bile duct; in another, there was complete membranous block of the lower end of the common bile duct. The findings of ERCP and intraoperative cholangiography were concordant for six patients. Only one patient had exacerbation of preexisting cholangitis. The authors conclude that ERCP is an essential investigative method in the management of choledochal cysts in children.

Anastomosis, Roux-en-Y↗

Anal agenesis associated with rectal atresia.

The authors report an unusual case of anal agenesis associated with rectal atresia. Such an anomaly has been reported only once before. Coincidentally, this patient also had a rarely encountered skeletal anomaly--unilateral cleft foot.

Abnormalities, Multiple↗

Addition of immunotherapy with Mycobacterium w vaccine to multi-drug therapy benefits multibacillary leprosy patients.

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w, was given in addition to standard chemotherapy (multidrug therapy (MDT)) to 93 multibacillary (MB) leprosy patients. One hundred and seven patients with similar types of disease served as controls and received MDT + placebo injections. The study was a double-blind randomised trial. On opening the codes, results obtained were in concordance with those in a single-blind trial which has been extensively reported. Bacteriological clearances were significantly more rapid in vaccinated patients (p < 0.03). Thirty-five LL or BL patients with a high bacterial index (BI) of 6 were completely cleared of acid-fast bacilli (AFB) after eight doses of vaccine. Only 8 patients in the control group became bacteriologically negative in the same time period. They all had BIs < 4. Associated with decreasing BI was accelerated clinical regression of lesions after vaccination and lepromin conversion rates of 100% for BB, 71% for BL and 70% for LL. A significant number of immunised patients showed histological improvement (p < 0.004). Thirty-six showed a complete disappearance of dermal granulomas and a picture of non-specific infiltration. The vaccine did not precipitate neuritis or deformities; episodes were noted in vaccinated patients as were incidences of Type 2 reaction. The overall improvement was reflected by a shorter duration of treatment and faster release of vaccinated patients.

Bacterial Vaccines↗

MnPcS4: a new MRI contrast enhancing agent for tumor localisation in mice.

Manganese-tetrasulfonated phthalocyanine (MnPcS4) has been evaluated as a potential contrast agent in Magnetic resonance imaging (MRI) for tumor localisation in mice. MnPcS4 showed favourable molar relaxivity, much better than Gd-DTPA and comparable to tetrasulfonated manganese complex of porphyrin (TPPS4). Tumors showed selective retention of the metal complex (dye) with the peak value reached at 24 hours following intravenous administration. Dye concentration in tumors remained consistently higher than either kidney or muscle tissue both at 1 and 24 hours and a 10-fold increase in tumor-to-muscle ratio over the control was seen at 24 hr. Normal liver tissue, however, showed higher concentration than tumor at all times during the study. A linear correlation was found between longitudinal relaxation rate (1/T1) and the corresponding concentration of MnPcS4 in various tissues. MR imaging done in animals using 1.5 T superconducting clinical imager showed a mean percent increase in signal intensity of 131.8% (SD +/- 32.86) in the tumor and a 70% increase in tumor-to-muscle ratio over the pretreatment value, at 24 hr. The results suggest that MnPcS4 is a potential tumor-selective contrast agent in MRI.

Animals↗

Physical characteristics of photon and electron beams from a dual energy linear accelerator.

Clinically pertinent data of the photon beams of nominal energy 6 MV and 18 MV from a dual photon energy linear accelerator are measured using a radiation field analyser with semiconductor diodes and ionisation chambers. Percentage depth dose values are compared with available data from other linacs and BJR-17. Measurements made in the buildup region using a parallel plate chamber show a marked increase in the surface dose and dmax shifts by 3 mm and 14 mm for 6 MV and 18 MV photons, respectively as the field size is increased from 4 x 4 cm2 to the maximum. Variations of wedge angles with energy and field size are also determined up to wedge widths of 15 cm for all the four available wedge angles. Isodose plots of both the energies are plotted using semiconductor diodes in a RFA-3 system. Output factors, wedge transmission factors, and shielding tray factors were also measured in clear polystyrene phantom for both the photon energies at the depths of maximum ionisation. Beam characteristics of the electron beams of energies 6, 9, 12, 16, and 20 MeV produced by the Clinac-1800 have also been studied. The characteristics include percentage depth dose, isodose distribution, depth of maximum dose, surface dose, photon contamination, uniformity index, and penumbra. Most of the measurements were carried out using semiconductor detectors, whereas small volume ionization chambers and a plane-parallel chamber were kept as standards for comparison. Isodose distributions were drawn from the film densitometry method. Range-energy parameters are obtained from the observed depth dose data. These parameters vary from machine to machine and must be ascertained for individual units. The parameters differ to a considerable extent from their theoretically predicted values but generally follow the trend, experimentally observed by others, for similar types of units.

Electrons↗

Microvascular response to tissue injury and capillary ultrastructure in the foot skin of type I diabetic patients.

1. Microvascular blood flow responses to injury and capillary ultrastructure were assessed by laser Doppler flowmetry and detailed light and electron microscopy respectively in skin biopsied from 28 patients with insulin-dependent diabetes and 17 control subjects. 2. The hyperaemic response induced by biopsy (P < 0.001) and heating to 44 degrees C (P < 0.001) was significantly lower in the diabetic patients and showed progressive impairment with the severity of complications (P < 0.001). 3. Skin capillary basement membrane thickness was significantly increased in the diabetic patients (P < 0.001) and also increased with the severity of complications (P < 0.002). Both the luminal area (P < 0.001) and the endothelial cell outer perimeter (P < 0.002), measures of luminal and capillary size, respectively, were significantly reduced in all diabetic patients. 4. Basement membrane thickness was related significantly to the impaired hyperaemic response to both biopsy (P < 0.01) and thermal injury (P < 0.01). 5. Our findings support the hypothesis that structural abnormalities, which are characterized by an early reduction in capillary size and later thickening of basement membrane, form an important mechanism for the impaired hyperaemic response in diabetic patients.

Adult↗

Cell-mediated immune responses of lambs to challenge with bovine respiratory syncytial virus.

The lamb is a good model to study the pathogenesis and immune responses to infections with respiratory syncytial virus (RSV) as lambs experimentally infected with bovine or human RSV may develop overt clinical disease. In the present study the development of cellular cytotoxic responses was studied in splenic, pulmonary and peripheral blood mononuclear cells obtained from lambs after primary and secondary infection with bovine RSV. Infection with bovine RSV was followed by the appearance of cytotoxic cells in the peripheral blood, the spleen and lung lavage fluids. These effector cells lysed virus-infected targets in a self-restricted manner. Depletion techniques revealed that cytotoxic activity was largely due to OvCD8+ cells. When effector cells obtained from primed lambs were stimulated with inactivated bovine RSV or with virus-infected cells in vitro, virus-specific cytotoxicity was significantly increased.

Animals↗

Non-islet cell tumour induced hypoglycaemia with acromegaloid facial and acral swelling.

The syndrome of non-islet cell tumour hypoglycaemia (NICTH) has been linked with the synthesis and secretion of 'big' IGF-II. We report a patient with a large pelvic clear cell sarcoma who developed recurrent severe hypoglycaemia and in addition presented with severe soft tissue facial swelling, skin tags and nuchal hyperpigmentation. After resection of the tumour serum 'big' IGF-II returned to normal and the acromegaloid skin changes remitted.

Acromegaly↗

Altered expression of matrix metalloproteinase-2, TIMP, and TIMP-2 in obstructive nephropathy.

We have previously characterized the evolution of renal cortical interstitial fibrosis in the rabbit model of unilateral ureteral obstruction (UUO). In our earlier report, we examined the extracellular matrix protein composition of the interstitial space. Of note, UUO was associated with the acquisition of prominent interstitial collagen IV immunoreactivity. Interstitial collagens I and III were also increased. In situ hybridization localized increased expression of collagens I and IV to cells of the interstitial space. In the current study, we examine metalloproteinase and metalloproteinase inhibitor expression in the obstructed renal cortex. Matrix metalloproteinase-2 is a metalloproteinase with activity against both collagen IV and denatured collagen I. At day 3 of UUO, both transcripts were significantly increased, although expression of these mRNAs was not different from controls after 7 and 16 days of UUO. Expression of mRNA of tissue inhibitor of the metalloproteinases (TIMP) was significantly increased in the UUO samples at all times, although it was maximal at day 3. Immunohistochemically, increased TIMP reactivity localized to the interstitial space, and TIMP mRNA expression was seen to parallel the interstitial macrophage infiltration that accompanies ureteteral obstruction. In contrast, TIMP-2 mRNA expression appeared to be biphasic, with peaks at both day 3 and day 16 of UUO. At day 7, expression was not different from controls. These data suggest a role for impaired matrix degradation in the development of interstitial fibrosis in the obstructed kidney, particularly at late times when collagen mRNA expression has returned to control values.

Animals↗

Carcinoma in Graves' disease.

Association of thyroid carcinoma in thyrotoxicosis is uncommon. Preoperative diagnosis of such association is difficult. In a retrospective study of 49 operated cases of Graves' disease (GD) such an association was found in four patients. Findings of a palpable nodule, calcification and a cold nodule on scanning in Graves' disease should increase suspicion for such an association and a frozen section study should be underken in all these cases during surgery to exclude possible co-existing malignancy.

Adenocarcinoma, Follicular↗