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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 37 records · Page 2Linked to original sources

Platelet activating factor inhibition reduces lung injury after cardiopulmonary bypass.

Because cardiopulmonary bypass (CPB) produces a diffuse inflammatory reaction that may injure multiple organs and complicate cardiac surgical procedures, we examined the use of a competitive inhibitor of platelet activating factor (SDZ HUL-412) in a porcine model of CPB as a means to ameliorate pulmonary injury after CPB. Thirteen pigs (35 to 40 kg) underwent CPB at 28 degrees C for 2 hours, followed by 2 hours of observation. Group I (n = 6) received SDZ HUL-412 (a quinolinium compound) intravenously (3 mg/kg loading dose and 2 mg.kg-1.h-1 continuous infusion) starting before sternotomy. Group II (n = 7) received a saline vehicle. Peak airway pressure, pulmonary arterial pressure, left atrial pressure, and arterial blood gases were measured and flow cytometry evaluated surface expression of adhesion molecule subunit CD18 on circulating neutrophils. Pulmonary function was significantly improved in group I. Fifteen minutes after CPB, dynamic lung compliance in group I was 91% +/- 12% of baseline versus 49% +/- 5.2% in group II (p = 0.06 by analysis of variance). After CPB, the arterial oxygen pressure was also significantly better in group I than in group II (425 +/- 61 versus 234 +/- 76 mm Hg) (p < 0.05). The rise in pulmonary vascular resistance after CPB was less in group I (p < 0.05) (323 +/- 55 to 553 +/- 106 dynes.s.cm-5) than in group II (531 +/- 177 to 884 +/- 419 dynes.s.cm-5) at the end of the observation period. CD18 up-regulation increased similarly in the two groups during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate

Thalidomide as replacement for steroids in immunosuppression after lung transplantation.

Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (alpha-phthalimidoglutarimide), a sedative drug with known immunomodulatory properties, was used to replace corticosteroids after canine lung transplantation. Fifteen mongrel dogs underwent single-lung transplantation: group I (n = 5) received cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Group II (n = 5) received standard immunosuppression of cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and prednisone (2 mg/kg once a day), and group III (n = 5) received cyclosporin A (10 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Open lung biopsy and bronchoscopy were performed weekly until sacrifice on day 28. Serum thalidomide and cyclosporin A levels were followed up weekly. Group I showed essentially no rejection until week 2 and minimal rejection (grade 1) until day 28. Group II had moderate rejection (grade 2) of the graft at all time points. Group III animals had moderate to severe rejection (grades 3 to 4) after 21 days (p < 0.05 for group I versus groups II and III). The number of clinically evident episodes of pneumonia was also significantly lower in group I than in groups II and III (p < 0.05). We conclude that thalidomide appears to replace corticosteroids effectively in early postoperative immunosuppression after lung transplantation and is associated with a decreased incidence of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Mutagenicity of nitrobenzyl derivatives: potential bioreductive anticancer agents.

Ortho-, meta- and para-nitrobenzyl bromides, alcohols, ethers and esters were synthesised and tested for their mutagenicity toward Salmonella typhimurium TA100, TA100NR (nitroreductase deficient) and TA98 in absence of S9 mix and in TA100 with S9 mix. Compounds of the ortho- and meta-series were non mutagenic with and without S9 mix. Except for the alcohol and ether, the compounds of the para-series were mutagenic in TA100 with activity sequence propionate > butyrate > benzoate > acetate > bromide and this specific activity was reduced considerably by S9 mix. The Ames Salmonella test system does not seem to be an appropriate model to evaluate mutagenicity of o-nitrobenzyls. However, further work is in progress to test all the compounds for mutagenicity in mammalian system.

Alcohols

Modulation of wound healing in Swiss albino mice by different doses of gamma radiation.

Changes in wound healing were studied using artificial wounds created either by surgical excision of full thickness skin or partial skin thickness dermabrasion of dorsal skin of Swiss albino mice exposed to 2, 4 and 6 Gy of gamma radiation. There was a significant delay in the wound healing process after exposure to 2 Gy when compared to the controls. With increasing doses of radiation wound healing time was also delayed. However, the differences in wound healing times between all three doses were not significant. The irradiation resulted in a dose-dependent delay in the wound contraction and mean wound healing time. The abrasion group was followed until complete epithelialization in the animals exposed to 2, 4 and 6 Gy of gamma radiation. However, no significant difference was observed in the healing time with respect to non-irradiated controls for all the exposure doses used in the present study.

Animals

Reduction of FK-506 requirements by combination with polyethylene glycol superoxide dismutase in orthotopic rat liver transplantation.

Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Plasma immunoreactive endothelin-1 concentration in cord blood of normal term neonates.

Plasma immunoreactive endothelin-1 (ir-ET-1) concentrations in cord blood of 20 term infants were measured by radioimmunoassay. The mean (+/- SEM) ir-ET-1 concentration was 1.04 +/- 0.29 pg/mL. There was no relationship between ir-ET-1 concentrations and race, sex, mode of delivery, and prenatal characteristics, such as cocaine exposure. The current methodologies were reviewed in an effort to explain the differences in ET-1 concentrations reported in various studies.

Apgar Score

Pentoxifylline impairs macrophage defense against Mycobacterium avium complex.

Pentoxifylline, a tumor necrosis factor-alpha (TNF) inhibitor, is being tested as a treatment adjunct in human immunodeficiency virus (HIV)-infected patients. However, TNF is important in cellular defense. The effect of pentoxifylline on Mycobacterium avium complex (MAC) growth in exogenously infected macrophages was compared with the effect of dexamethasone. Pentoxifylline, in a concentration that decreased MAC-induced TNF by 48.1%, enhanced MAC growth by 1.9- to 19.6-fold and 1.82- to 4.46-fold in macrophages from normal and HIV-infected patients, respectively. It also induced interleukin-6 (IL-6) in infected macrophages. IL-6 induction correlated with the increase in MAC growth (y = 0.89 + 0.266x, P = .025). Dexamethasone in an equivalent TNF-suppressing concentration also increased MAC growth but was less effective. Unlike pentoxifylline, dexamethasone suppressed IL-6 and the suppression correlated inversely with MAC growth (y = 0.248 + 9.942x, P = .003). Thus, TNF and IL-6 are important in macrophage defense against MAC. Pentoxifylline and dexamethasone should be used with caution in AIDS patients.

CD4 Lymphocyte Count

Ultrasonography, computed tomography and percutaneous intervention in acute pancreatitis: a serial study.

Fifty-seven patients (45 males, 12 females) with a clinical diagnosis of acute pancreatitis were serially evaluated by ultrasonography (US) and computed tomography (CT). Thirty patients had a single study, 18 had one follow-up study while 9 had two follow-up studies. The aetiology was gallstone disease in 26% of patients and a history of chronic alcohol abuse in only 16%. No cause could be identified in 47% of patients; 22% of US scans were unsatisfactory for the evaluation of pancreas whereas CT was uniformly satisfactory. Peripancreatic inflammation was detected in only 29% patients on US compared with 91% on CT. Pancreatic abscesses were detected in 8 patients on CT and gas was present in all of them. Fourteen patients underwent guided interventional procedures (US, 12; CT, 2). On follow up after 3 months, worsening of inflammation was detected in 11% patients on CT, which was not detected on US. It is concluded from this study that CT is far superior to US in the evaluation of acute pancreatitis, detection of peripancreatic inflammation and its extension into the retroperitoneal compartments and mesentery, and also for the evaluation of fluid collections, haemorrhage and abscesses. However, US provides easy guidance for percutaneous interventional procedures and can be used for follow-up scans.

Abscess

Role of routine lumbar puncture in neonatal sepsis.

OBJECTIVE: To evaluate the utility of lumbar puncture done routinely as part of complete workup in neonatal sepsis. METHODOLOGY: Two hundred and nine consecutive lumbar punctures performed in 169 neonates were prospectively evaluated for the diagnosis of meningitis over a 6 month period in a tertiary care referral neonatal unit. RESULTS: Among babies with 'suspected clinical sepsis', five (3.3%) were diagnosed to have meningitis. None of the clinically normal babies with high risk obstetric factors alone had meningitis. The lumbar puncture was traumatic in 22.9%, and in 26.3% the fluid obtained was inadequate for complete analysis. The results were inconclusive in 37% of the cases. CONCLUSION: Based on this study, routine lumbar puncture may not be required in clinically normal newborns with adverse obstetric factors. In babies with clinical sepsis, though the yield is not very high; there are no reliable clinical or laboratory markers to predict which babies will have meningitis and hence these babies would warrant a lumbar puncture.

Birth Weight

Effect of inhaled aerosol of 1-chloroacetophenone (CN) and Dibenz (b,f)-1,4 oxazepine (CR) on lung mechanics and pulmonary surfactants in rats.

Inhalation toxicity following exposure to 1-Chloroacetophenone (CN) and Dibenz(b,f)-1,4 oxazepine (CR) aerosols for 60 min at sublethal concentrations were studied in rats. The dynamic surface tension (gamma max and stability ratio) of lung homogenate increased significantly on CN exposure. The lung mechanics studies revealed a significant increase in compliance in CN exposed rats. CR, on the other hand did not influence any of the above variables except for a decrease in compliance. Total lung phospholipids and sphingomyelin contents decreased significantly following exposure to CN, while CR exposure produced an increase in sphingomyelin, reduction in phosphatidylcholine and ethanolamine, with no change in total phospholipid contents. Histomorphological observations indicated cellular degeneration in the epithelium of the bronchiole and alveolar septal-wall thickening due to the presence of an increased number of mononuclear cells in CN exposed rats. However, CR induced inflammatory reaction and enlargement of respiratory air spaces. It is concluded that of the two sensory irritants (tear gases) examined, CN is potentially more toxic compared to CR in rats.

Administration, Inhalation

Quality of life in octogenarians after open heart surgery.

OBJECTIVES: To determine the quality of life in octogenarians after open heart surgery. BACKGROUND: Despite an increasing number of cardiac operations on octogenarians, the outcome as measured by functional status, independence of living, and psychological parameters of quality of life remain unproved. METHODS: Two groups of octogenarians (group 1, undergoing operation in 1986; group 2 in 1991) were reviewed retrospectively to determine operative mortality and functional results. RESULTS: Group 1 (n = 15, mean age of 83.2 years) and group 2 (n = 53, mean age 83.0 years) were studied. Operations included isolated coronary artery bypass grafting (group 1, 10; group 2, 29) and valve replacements +/- coronary artery bypass grafting +/- other procedures (group 1: 5; group 2, 24). Group 1 had 9% hospital mortality and 53% actuarial survival after a mean follow-up of 6.3 years. Group 2 had 17% hospital mortality and 72% actuarial survival after a mean follow-up of 1.5 years. At follow-up, significant improvements were observed in New York Heart Association (NYHA) angina class, congestive cardiac failure class, number of cardiovascular symptoms, and indices for satisfaction with overall life and general affect in both groups. Further, group 2 also showed significant improvements in independence of living, ease of life, and Karnofsky dependency category, but these improvements were less evident in group 1 after a longer period of follow-up. At follow-up, 75% of group 1 and 84% of group 2 octogenarians would definitely have made the same decision to undergo open heart surgery in retrospect. CONCLUSION: This study demonstrates improved quality of life after open heart surgery in octogenarians.

Activities of Daily Living

In vitro antifungal susceptibility of Candida.

To develop a simple, standardised procedure for antifungal susceptibility of yeasts, disc diffusion test was evaluated in comparison to agar dilution and the macrobroth dilution procedure of the National Committee for Clinical Laboratory Standards USA. One hundred Candida strains isolated from clinical material were used against four antifungal agents (amphotericin B, 5-flucytosine, ketoconazole and fluconazole). Inoculum size of 10(6) yeasts/ml just failed to produce confluent colonies at 37 degrees C after 48 h on yeast nitrogen-glucose-agar with or without asparagine medium. The zones of inhibition were correlated with both broth and agar dilution minimum inhibitory concentrations (MICs). The results were found to correlate well using amphotericin B, 5-flucytosine and fluconazole (with broth dilution only). But there was no significant correlation using ketoconazole. Therefore, disc diffusion susceptibility testing of Candida strains appears to be generally applicable except for azoles where broth dilution test would confirm the resistant isolates.

Antifungal Agents

Inhalation challenge effects of perfume scent strips in patients with asthma.

BACKGROUND: Perfume- and cologne-scented advertisement strips are widely used. There are, however, very few data on the adverse effects of perfume inhalation in asthmatic subjects. OBJECTIVES: This study was undertaken to determine whether perfume inhalation from magazine scent strips could exacerbate asthma. METHODS: Twenty-nine asthmatic adults and 13 normal subjects were included in the study. Histories were obtained and physical examinations performed. Asthma severity was determined by clinical criteria of the National Heart, Lung, and Blood Institute (NHLBI). Skin prick tests with common inhalant allergens and with the perfume under investigation were also performed. Four bronchial inhalation challenges were performed on each subject using commercial perfume scented strips, filter paper impregnated with perfume identical to that of the commercial strips, 70% isopropyl alcohol, and normal saline, respectively. Symptoms and signs were recorded before and after challenges. Pulmonary function studies were performed before and at 10, 20, and 30 minutes after challenges. RESULTS: Inhalational challenges using perfume produced significant declines in FEV1 in asthmatic patients when compared with control subjects. No significant change in FEV1 was noted after saline (placebo) challenge in asthmatic patients. The percent decline in FEV1 was significantly greater after challenge in severely asthmatic patients as compared with those with mild asthma. Chest tightness and wheezing occurred in 20.7% of asthmatic patients after perfume challenges. Asthmatic exacerbations after perfume challenge occurred in 36%, 17%, and 8% of patients with severe, moderate, and mild asthma, respectively. Patients with atopic asthma had greater decreases in FEV1 after perfume challenge when compared with patients with nonallergic asthma. CONCLUSIONS: Perfume-scented strips in magazines can cause exacerbations of symptoms and airway obstruction in asthmatic patients. Severe and atopic asthma increases risk of adverse respiratory reactions to perfumes.

Administration, Inhalation

Synthesis and cytotoxic evaluation of mesna adducts of some 1-aryl-4,4-dimethyl-5-(1-piperidino)-1-penten-3-one hydrochlorides.

Reaction of 1-(4-bromophenyl)-4,4-dimethyl-5-(1-piperidino)-1-penten-3-one hydrochloride (1f) with sodium 2-mercaptoethanesulphonate (mesna) gave rise to the thiol adduct. 3. Recrystallization of this compound led to the formation of the corresponding zwitterion 4f. A series of analogues of 4f were prepared and the structure of a representative compound was confirmed by X-ray crystallography. In general, the thiol adducts had similar activity towards P388 cells and human tumour cell lines as the precursor enones 1 although greater selectivity to malignant diseases was found with the thiol adducts. A stability study of representative compounds conducted by 1H NMR spectroscopy revealed that the thiol adducts decomposed in solution. In one case regeneration of the ketone was noted while for the other compounds, the decomposition products were not identified.

Animals

Effect of oral water soluble vitamin K on PIVKA-II levels in newborns.

Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost, pain, anxiety to parents and risk of transmission of infection. Oral route is a better alternative. Oral absorption of vitamin K has been shown to be equally good using special oral preparations. However, this preparation is not available in India. A prospective study was carried out on 51 full term, healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K (menadione sodium bisulphite) could be as effective. Fourteen babies received 1 mg vitamin K intramuscularly, 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth. PIVKA-II levels were measured in cord blood and at 72-78 hours of age in all babies as a marker of vitamin K deficiency. The overall PIVKA-II prevalence in cord blood was 64.7%. At 72-78 hours, PIVKA-II was present in 50% of babies in IM group, 58.3% of babies in oral group and in 76.9% of babies in 'no vitamin K' group (p > 0.05). The PIVKA-II levels decreased or did not change at 72-78 hours in 91.6% of babies in oral group versus 92.8% of babies in IM group (p > 0.05). On the other hand, PIVKA-II levels increased in 30.7% of babies who did not receive vitamin K as against in 7.8% of babies receiving vitamin K in either form (p < 0.05). Hence, vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K (menadione sodium bisulphite) given orally to term healthy babies is effective in preventing vitamin K deficiency state.

Administration, Oral

Carbohydrate induced modulation of cell membrane. I. Interaction of sialic acid with peripheral blood lymphocytes: a spin label study.

Sialic acid is now known to serve as ligand for lymphocyte lectins known as selectins. Although its role as a ligand for adhesion molecules has been studied extensively, no studies have been performed to determine the physiological changes in lymphocytes after binding of sialic acid to lymphocyte lectin. We report for the first time that interaction of lymphocytes with sialic acid severely restricts the rotational mobility of the cell surface proteins as well as membrane lipids, as studied by EPR spectroscopy using spin probes. Binding of mucin totally immobilizes the lymphocyte membrane. Surprisingly the binding of sialic acid or mucin also immobilized the aqueous probe TEMPO, indicating an appreciable increase in cytoplasmic viscosity.

Animals