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Biomedical subjects

K Bhargava

Publications and source records attributed to K Bhargava.

At least 19 recordsLinked to original sources

Endothelium-dependent brachial artery flow mediated vasodilatation in patients with diabetes mellitus with and without coronary artery disease.

AIM OF THE STUDY: Endothelial function as assessed by brachial artery flow mediated vasodilatation (FMD) has been shown to be impaired in patients with coronary artery disease (CAD). Since diabetes mellitus (DM) has been considered to be CAD risk-equivalent, we sought to determine whether endothelial dysfunction is present in patients with DM independent of presence of CAD. METHODOLOGY: One hundred and ninety eight individuals were included in the study and divided into four groups: Group 1--patients with risk factors for CAD, but no DM or CAD; Group 2--patients with DM but no CAD; Group 3--patients with CAD but no DM and Group 4--patients with both DM and CAD. Brachial artery FMD assessment was performed once in all subjects and FMD was calculated as percentage increase in brachial artery diameter in response to increase in brachial artery flow. RESULTS: Mean FMD was significantly higher in Group 1 (7.03 +/- 2.87%) compared to the other three groups. Mean FMD in Group 2 (5.51 +/- 2.12%) was similar to that in Group 3 (4.56 +/- 2.70%; p value 0.195) but significantly higher than that in Group 4 (4.26 +/- 1.93%; p value 0.038). There was no statistically significant difference in mean FMD in Group 3 and Group 4 (p value 0.65). CONCLUSION: Endothelial function as assessed by FMD is significantly impaired in diabetics compared to non-diabetics in absence of CAD. In addition, similar degree of impairment in endothelial function is seen in diabetics without CAD and non-diabetic patients having CAD, implying CAD risk-equivalence of diabetes.

Arm↗

Insect neuropeptide antagonist. Part II. Synthesis and biological activity of backbone cyclic and precyclic PBAN antagonists.

A new approach for the design and synthesis of pheromone biosynthesis activating neuropeptide (PBAN) agonists and antagonists using the backbone cyclization and cycloscan concepts is described. Two backbone cyclic (BBC) libraries were synthesized: library I (Ser library) was based on the active C-terminal hexapeptide sequence Tyr-Phe-Ser-Pro-Arg-Leu-NH2 of PBAN1-33NH2; whereas library II (D-Phe library) was based on the sequence of the PBAN lead linear antagonist Arg-Tyr-Phe-d-Phe-Pro-Arg-Leu-NH2. In both libraries the Pro residue was replaced by the BBC building unit Nalpha-(omega-aminoalkyl) Gly having various lengths of alkyl chain. The peptides of the two libraries were tested for agonistic and antagonistic activity. Four precyclic peptides based on two of the BBC antagonists were also synthesized; their activity revealed that a negative charge at the N-terminus of the peptide abolished antagonistic activity. We also describe the use of the reagent SiCl3I for selective deprotection of the Boc group from the building unit prior to on-resin amino-end to backbone-nitrogen (AE-BN) cyclization, during solid-phase synthesis with Fmoc chemistry.

Animals↗

Myoglobinuria and transient acute renal failure in a patient revealing hypothyroidism.

Muscle involvement in hypothyroidism commonly manifests as fatigue, myalgias, stiffness and slowed reflexes. We report a case of transient acute renal failure related to rhabdomyolysis and myoglobinuria in a 40 year old man that revealed the diagnosis of hypothyroidism with myopathy. The patient had proximal muscle weakness and tenderness, markedly raised muscle enzymes and deranged renal functions that normalised with thyroid replacement therapy. Hypothyroidism, though rare, should be considered a definite and authentic cause of rhabdomyolysis.

Acute Kidney Injury↗

Effects of a hybrid recombinant human alpha interferon (A/D) on in vitro cytotoxicity and in vivo localization of monoclonal antibody L6-cytosine deaminase conjugate in a colon cancer model.

L6 is an IgG2a murine monoclonal antibody which we have demonstrated binds well to HT29 human colon carcinoma cells by flow cytometry, whole cell ELISA, and mixed hemadsorption. In vitro cytotoxicity studies revealed that the monoclonal antibody L6-cytosine deaminase (L6-CD) immunoconjugate plus the nontoxic prodrug, 5-fluorocytosine (5-FC), is equivalent to 5-fluorouracil (5-FU) in its ability to kill HT29 cells. Human alpha-interferon (A/D) was able to enhance this cytotoxic effect. The I.C.50's revealed that very small amounts of L6-CD are needed for this cytotoxic effect (approximately, 5 pg/ml resulted in 50% viability). The limiting factor was the amount of 5-FC employed with L6-CD (3 microM yielded 50% cell viability). alpha-Interferon (A/D) lowered the requirement of 5-FC to 1 microM to achieve 50% cell lethality. In vivo biodistribution experiments indicated that 1 microgram of L6-CD is nonspecifically taken up by the liver and spleen and cleared rapidly from the blood. Significant localization of L6-CD to HT29 tumors occurred only when 99 micrograms of unlabeled L6-CD was added to 1 microgram of 125I-labeled immunoconjugate injected intravenously. Further augmentation of tumor/blood ratios without reduction in percent injected dose per gram of tumor was possible with the intravenous injection of 100 micrograms of anti-idiotypic monoclonal antibody 13B, 24 hours after L6-CD, which bound unreacted L6-CD and cleared it from the blood. The addition of 100,000 U of alpha-interferon (A/D) given intraperitoneally every day increased the clearance of L6-CD by the liver and spleen, but impaired tumor localization (percent injected dose per gram). These studies demonstrated that in vivo localization of the L6-CD conjugate to HT29 tumors could be optimized by injecting excess L6-CD followed by an equal amount of L6 anti-idiotype mAb 13B, 24 hours after L6-CD.

Adenosine Deaminase↗

Pedicled omental transfer for ischaemic limbs--a 5-year experience.

Chronic occlusive arterial diseases form a single largest entity amongst the peripheral vascular diseases. Current operative methods available for improving circulation often elicit poor results and the patient has to undergo an amputation. The technique of pedicled omental transfer has given hope of saving such unsalvageable limbs. Although symptomatic and clinical improvement has been reported by this method of "biological by-pass revascularisation", there are no simple, objective and easily reproducible tests to assess improvement in circulation. In this study pulse oximetry and stress testing have been used to assess revascularisation. This study comprised 56 patients (78 limbs) suffering from chronic occlusive arterial disease, spanning a period of 5 years. Patients were investigated and subjected to pedicled omental transplantation (omentopexy). Symptomatological assessment showed improvement in intermittent claudication in about 85% of patients, relief from rest pain in 86% and healing of chronic ulcers in 73% of patients. Objective tests of stress testing and pulse oximetry also showed improvement in circulation. Relief from ischaemia was more in cases of Buerger's disease (TAO) than in cases of atherosclerosis obliterans (ASO).

Adult↗

A cephalometric study comparing the occlusal plane in dentulous and edentulous subjects in relation to the maxillomandibular space.

This study examines the validity of Camper's plane as a guide to determine the occlusal plane in edentulous subjects. Based on the data collected from the cephalometric tracings of 40 dentulous and edentulous patients and with the use of the significant correlations of the variables of the maxillomandibular space established from the dentulous group, the dentulous and edentulous groups were classified into four subdivisions based on length and maxillomandibular angle. The occlusal plane/maxillary plane angles and the occlusal plane/mandibular plane angles were then compared to check for similarities in the two groups.

Analysis of Variance↗

Anisakiasis of the tonsils.

A six-year-old Indian girl presenting with clinical features of chronic recurrent tonsillitis, had a tonsillectomy. Histopathology revealed a cross-section of an Anisakis worm in the tonsil. This report documents a new location in the human host for this rare parasite.

Anisakiasis↗

Expression of human tumor mucin-associated carbohydrate epitopes, including sialylated Tn, and localization of murine monoclonal antibodies CC49 and B72.3 in a syngeneic rat colon carcinoma model.

Using immunohistochemical techniques and whole-cell enzyme-linked immunosorbent assay, we have determined that monoclonal antibodies (mAbs) B72.3 and CC49, which are widely used in the diagnosis and treatment of several human epithelial cancers, are expressed in a transplantable rat colon carcinoma cell line, K12-TRb. MAbs B72.3 and CC49 react with tumor-associated glycoprotein-72 (TAG-72) which is a carcinoma mucin molecule expressed in colon, breast, pancreatic, ovarian, lung, and gastric cancers. The carbohydrate epitope for mAb B72.3 is sialylated Tn (sTn), whereas CC49 reacts with an unknown carbohydrate epitope. K12-TRb is a transplantable rat colon carcinoma cell line derived from a dimethylhydrazine tumor which grows as progressive tumors in syngeneic BD IX rats. We found that the carbohydrate epitopes for mAbs B72.3 and CC49, including sTn, were more tumor-restricted in the rat than in humans. The only binding these had mAbs to normal rat tissue was to small-intestinal mucosa. MAbs B72.3 and CC49 were radiolabeled with iodine-125 (125I) and injected intravenously into BD IX rats containing subcutaneously grown syngeneic K12-TRb tumors. Biodistribution experiments were conducted by dissecting groups of three rats on days 2, 4, 7, and 14 after injection of radiolabeled mAbs. These experiments confirmed that maBs B72.3 and CC49 localize to K12-TRb tumors in vivo, and that the higher affinity mAb CC49 localized better than mAb B72.3. Gamma-camera imaging of subcutaneous K12-TRb tumors was successfully performed using 125I-labeled mAb CC49. The importance of this model is that mAbs B72.3 and CC49, immunoconjugates of these mAbs, and vaccines containing their corresponding carbohydrate epitopes, including sTn, can be studied in a relevant immunocompetent syngeneic rat colon carcinoma model.

Animals↗

Lactate turnover at rest and during submaximal exercise in patients with heart failure.

Systemic and lower limb skeletal muscle lactate metabolism was studied in 10 men with congestive heart failure by use of a primed continuous intravenous infusion of L-(+)-[U-14C]lactate. Arterial and deep femoral venous blood samples were obtained at rest and during 30 min of submaximal exercise. Systemic lactate metabolic turnover rate (Rd) was determined using Steele's isotopic steady-state equation (Rd = isotopic infusion rate/arterial specific activity). Plasma lactate concentrations in the artery and deep femoral vein did not change significantly from resting values during exercise (1.11 +/- 0.13 vs. 1.26 +/- 0.12 and 1.27 +/- 0.12 vs. 1.30 +/- 0.12 mM, respectively), whereas Rd increased from 22.5 +/- 1.8 to 41.6 +/- 4.8 mumol.kg-1.min-1 (P < 0.005). Rd did not significantly correlate with arterial lactate concentration during rest or exercise. Because of simultaneous uptake and release of lactate in skeletal muscle, arterial and deep femoral venous lactate concentrations are not closely related to either systemic or lower limb skeletal muscle lactate metabolism in patients with congestive heart failure.

Aged↗

Immobilization of active urokinase on albumin microspheres: use of a chemical dehydrant and process monitoring.

A method of immobilizing urokinase on albumin microspheres has been developed. Laser scattering, which was used to follow particle size from the initial emulsification stage to the final aqueous resuspension of the microsphere stage, showed that particle coalescence and crosslinking were critical parameters in manufacturing the microspheres. Chemical dehydration with 2,2-dimethoxypropane was used to convert an albumin emulsion into an albumin suspension and to reduce coalescence. An optimal amount of dehydrant produced 0.3-micron particles which resisted a 50 degrees C temperature challenge. Since oil/glutaraldehyde emulsion resulted in large particles with no urokinase activity, the cross-linking concentration of glutaraldehyde was reduced by solubilizing 25% (w/v) glutaraldehyde in the oil phase with n-propanol. A concentration of 0.015% (v/v) glutaraldehyde effectively immobilized urokinase and stabilized albumin microspheres. Amidolytic activity using the specific chromogenic substrate for urokinase, S-2444, showed that enzyme activity could be retained during this glutaraldehyde cross-linking.

Albumins↗

Experience with oral morphine for cancer pain relief.

The authors report a prospective survey of 88 patients with cancer pain who were treated with oral morphine solution during a period of 140 days at the Pain Relief Unit, Kidwai Memorial Institute of Oncology, Bangalore. A high percentage of pain relief was achieved at the end of the first week of titrated therapy; relief was maintained at satisfactory levels throughout the study period in a majority of patients (86%). Interruption of oral morphine administration was necessitated by intractable vomiting in two patients. The majority of patients (65%) did not manifest any side effects, and appropriate medication successfully managed those who did. Oral morphine therapy for cancer pain offers effective pain relief with minimal side effects in the majority of patients.

Administration, Oral↗

An evaluation of cross-bite ridge relationships. A study of articulated jaw records of 150 edentulous patients.

Data were collected from 150 men and women complete-denture patients. Their jaw records were evaluated with a specially designed instruments. The extent of deviation of the maxillary and the mandibular ridges in the horizontal plane was calculated at various interridge distances, at a constant interalveolar crest-line angle of 80 degrees. It was found that: 1. Most patients of both sexes revealed a normal horizontal ridge relationship. 2. Next to the normal ridge relationship, there was a tendency for a unilateral cross-bite ridge relationship on the left sides of those patients who had recent extractions (up to 6 months previously). 3. True bilateral cross-bite ridge relationships were found only in those patients who gave a history of prolonged edentulousness. 4. The decision to arrange the posterior teeth in normal or cross-bite ridge relationship should take into consideration the deviations in the ridge relationship as well as the interridge distance. A method of evaluating interridge deviations in the horizontal plane in the posterior region of articulated jaw records of edentulous patients was developed.

Adult↗

Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India.

In Gujarat, India, 6718 industrial workers, over 35 years of age, with oral leukoplakia (confirmed clinically and microscopically), were studied. After 2 years, 4762 (71%) of the individuals were re-examined. The buccal mucosa was the most common site of occurrence; 98.3% of these individuals had oral habits, with smoking alone or smoking in combination with "pan" or "supari" chewing accounting for 74.9% of the habit forms. Six individuals (0.13%) with oral leukoplakia developed oral carcinomas within 2 years. This incidence of malignant transformation was equivalent to 63/100,000 per year, which far exceeds that of new oral cancers expected even in high-risk populations. While 57.3% the leukoplakic lesions remained unchanged during a 2-year interval, 31.6% disappeared and 11% had an altered appearance. This study confirmed the precancerous nature of oral leukoplakia.

Adult↗

A histologic comparison of palatal mucosa before and after wearing complete dentures.

A histologic investigation to study the tissue changes occurring under complete dentures was done. Biopsies were obtained from 40 patients from the area of left side of the hard palate at the first molar region, midway between the median raphe and the residual ridge. The same patients were examined 3 months after placement of well-fitted dentures. Thirty of the 40 patients responded. A second biopsy was taken from the same area on the right side of these patients. On the basis of the microscopic examination, the following conclusions were drawn. 1. The average thickness of the palatal epithelium of edentulous non-denture wearers was 0.222 mm. in the rete peg region. 2. There was a general increase in the thickness of the palatal epithelium following 3 months of wearing complete dentures. 3. The increase in the palatal epithelium was more marked in the rete peg region than in the inter-rete peg region. 4. There was an increase in the thickness of the keratin layer in most patients. 5. No significant changes were found in the granular-cell layer or the prickle-cell layer. 6. The oral mucous membrane responded favorably to well-fitted dentures.

Adult↗