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Biomedical subjects

S R Nair

Publications and source records attributed to S R Nair.

At least 19 recordsLinked to original sources

Methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia as a risk factor for coronary heart disease in the Indian population.

OBJECTIVE: The screening and therapeutic guidelines for the management of lipid abnormalities are reasonably well established. However, other risk factors like hyperhomocysteinemia (HCA) and single nucleotide polymorphisms involving the angiotensin converting enzyme (ACE) and angiotensinogen genes, various clotting factors etc., have yet to be established firmly as other causative factors of atherothrombotic disease. Our study was aimed at finding the relationship between HCA, folate, vitamins B12 levels, and mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes. METHODS: We studied 230 subjects, which included patients with angiographically documented coronary heart disease (CHD) (n=115) and controls (n=115) with no history of CHD. RESULTS: Elevated levels of plasma homocysteine, above 18 nmoles/ml, were detected in 19.13% and 18.26% of our patients and controls, respectively. Homocysteine was significantly correlated to Apo A1 (r=0.51, p < 0.05) and Apo B (r=0.49, p < 0.05). The heterozygous MTHFR mutation was found to be 54.5% (12/22) in our patients with HCA. Of these, 31.8% (7/22) were deficient for plasma folate. Heterozygosity for T833C mutation in the CBS gene was observed in 9.99% (2/22) of our patients with HCA. Both these patients were also deficient for plasma folate and vitamin B12. CONCLUSION: In our study, heterozygosity for the thermolabile MTHFR mutation was found to be associated with hyperhomocysteinemia (HCA). This genetic predisposition to HCA could be risk factor for CHD and can be correlated with vitamin supplementation. To the best of our knowledge this is the first report from India on plasma homocysteine levels and its genetic aspect in patients with CHD.

Adult↗

Post-thymectomy murine experimental autoimmune oophoritis is associated with reduced natural killer cell activity.

PROBLEM: Natural killer (NK) cells can influence the immune response by secreting potent lymphokines. It has been suggested that NK cells have a suppressive action on B cells, and that impaired NK cell activity may play a role in some types of autoimmunity. NK cell abnormalities have been reported in women with premature ovarian failure. We therefore examined NK cell activity during the development of murine experimental autoimmune oophoritis, which serves as a model for autoimmune ovarian failure in women. METHOD OF STUDY: Neonatally thymectomized and sham-operated C57B1/6 x A/J (B6A) mice were prepared and sacrificed at 4, 6, 8, and 10 weeks after surgery. Splenic NK cell activity was determined in groups of five or more mice by measuring the percent specific lysis of target YAC-1 lymphoma cells using a standard 4-hr chromium release cytotoxicity assay. The number of splenic NK cells in neonatally thymectomized and sham-operated animals was also compared using flow cytometry. In a subsequent experiment, interleukin 12 (IL-12; NK cell-stimulating factor) was administered to neonatal mice before neonatal thymectomy. RESULTS: Neonatally thymectomized mice with associated autoimmune oophoritis had a 75% reduction in the number of splenic NK cells, and 50% or greater reduction in splenic NK cell activity at 4, 6, and 8 weeks after surgery. IL-12 treatment before neonatal thymectomy maintained NK cell activity and was shown to ameliorate the associated autoimmune oophoritis. CONCLUSION: Murine post-thymectomy autoimmune oophoritis is associated with reduced NK cell number and impaired NK cell activity, and in these respects the model is similar to premature ovarian failure in women. Research to define the relationship between NK cell abnormalities and the mechanism of ovarian failure in this model might lend insight into the pathogenesis of premature ovarian failure in women.

Animals↗

Concentrations of cefotaxime and the desacetyl metabolite in serum and CSF of patients with meningitis.

Thirty-two cases of meningitis (20 caused by Gram-positive or -negative cocci, 7 by Gram-negative bacilli or listeria, and 5 with aseptic meningitis) received cefotaxime, 2 g 8-hourly, in addition to routine therapy. The concentrations of cefotaxime and its desacetyl metabolite in serum and CSF were determined by a high pressure liquid chromotography. Mean concentration of cefotaxime in CSF ranged from 0.8 mg/l (aseptic meningitis), to 6.4 mg/l (Gram-negative and listeria meningitis), and from 0.5 to 5.4 mg/l for the metabolite. The concentrations of both cefotaxime and the derivative demonstrated a correlation with the degree of inflammation (i.e., cell count and protein concentration) and were higher at 3 h after an infusion of antibiotic than at one and two hours. The concentration showed no marked decline on day 10 when signs of inflammation had largely resolved. The concentrations of both the parent compound and the metabolite 3 h after the infusion suggest that, considering the activity and half life of both the dosing might be spaced at 6-8 h intervals.

Cefotaxime↗

Madura Foot: a case report.

Mycetoma or Madura foot is a chronic infection of the foot characterized by swelling and multiple sinuses. The sinuses discharge pus composed of colored granules which contain the infecting organism. Although this entity is still rare in the United States, an increasing immigrant population and rapid air transportation have resulted in a greater number of cases being reported. A case of Madura foot is presented in which initial cultures yielded Staphylococcus aureus. Dicloxacillin was prescribed and this led to some improvement in the condition. Later, a gram-stained specimen of exudate from an inguinal site showed actinomycetes. Because of this finding, amoxicillin was then administered. As a result, the condition dramatically improved with subsequent healing of the involved bone.

Actinomycetales Infections↗

Abnormal neutrophil chemotaxis and random migration induced by aminoglycoside antibiotics.

Gentamicin and amikacin, administered in therapeutic doses to normal healthy adults, caused a transient decrease in chemotactic migration of their PMNs. In contrast, RM of leukocytes obtained from these individuals was increased significantly. The magnitude of these changes did not correlate with the serum antibiotic concentrations. Separate in vitro experiments with gentamicin, however, revealed an inverse dose-response relationship with chemotactic suppression. The mechanism(s) involved in modifications of these leukocyte functions is not well understood. These findings may be of clinical significance in patients, especially those with altered host defense mechanisms, who require therapy with these aminoglycoside antimicrobial agents.

Adult↗

Persistent nocardemia following renal transplantation. Association with pulmonary nocardiosis.

Pulmonary nocardiosis occurred in a renal homotransplant patient and was diagnosed by persistently positive blood cultures. Infection developed at a time when efforts were being made with moderate dosages of immunosuppressive drugs to prevent rejection of the transplant. The subsequent nocardemia lasted for one week. The remaining kidney function was preserved, and the patient had a very favorable outcome because of early diagnosis and prompt treatment with sulfisoxazole.

Adult↗

Clindamycin in infective endocarditis.

Because of problems of penicillin allergy or lack of veins for intravenous administration of antibiotics, nine patients with endocarditis were treated with clindamycin, administered intramuscularly. Five patients were heroin addicts with staphylococcal endocarditis and four had alpha-streptococcal endocarditis. The only therapeutic failure occurred in a patient with a strain of Staphylococcus aureus that became resistant to clindamycin in vivo. Such resistance has been reported to occur in vitro, and testing for it should prove useful in proper selection of cases for treatment with clindamycin, an agent that appears to be effective in selected cases of endocarditis.

Clindamycin↗

Use of cefoxitin, new cephalosporin-like antibiotic, in the treatment of aerobic and anaerobic infections.

Forty-two patients were treated with intravenous cefoxitin, a new cephamycin antibiotic. These patients had postoperative abdominal sepsis (26), intrathoracic infections (6), urinary tract infections (5), gram-negative bacterial meningitis (2), septic arthritis (1), epidural abscess (1) and isolated septicemia (1). The antibacterial spectrum of cefoxitin was found to be one which included all gram-positive organisms except enterococci, most gram-negative organisms except Pseudomonas aeruginosa, and almost all of the important anaerobic organisms. The only five treatment failures included one patient with empyema and one with septic arthritis, both caused by Serratia marcescens, initially only moderately susceptible to cefoxitin, which subsequently developed increased resistance, two patients with contaminated intravenous catheters, and one patient with epidural abscess and cerebritis, who was treated late in the course. There was one serious clinical superinfection with P. aeruginosa. The drug levels noted in the pus and joint fluid were half to two-thirds of the simultaneous serum level. In inflamed meninges, up to 30% of the serum level was noted in the cerebrospinal fluid, and as the process resolved, 10 to 15% was noted. Toxicity of cefoxitin was mild and constituted skin rash in three patients (7%) and phlebitis in eight (19%).

Adolescent↗

Medical treatment of Serratia arthritis with trimethoprim-sulfamethoxazole.

A patient with moderately severe rheumatoid arthritis and diabetes mellitus receiving steroids developed septic arthritis due to Serratia marcescens. Treatment with a new cephalosporin analogue, intra-articular and intramuscular gentamicin, and chloramphenicol alone and in combination proved ineffective. Finally, trimethoprim-sulfamethoxazole therapy, given for a protracted period, eradicated the infection without the need for surgical drainage.

Arthritis, Infectious↗

Pyle's disease.

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Adolescent↗

Penetration of cefoxitin into cerebrospinal fluid and treatment of meningitis caused by gram-negative bacteria.

Two patients with meningitis caused by antibiotic-resistant Escherichia coli and Klebsiella pneumoniae were treated successfully with intravenous cefoxitin plus oral probenecid. A total of 25 patients with central nervous system disorders that required a diagnostic spinal tap were also given cefoxitin, with or without probenecid, for determination of the degree of penetration into cerebrospinal fluid. In patients with uninflamed meninges, little or no cefoxitin entered after a single dose of 4-6 g. After three doses of 4 g each over a 6-8-hr period, penetration was considerable (average, 7% of the simultaneous serum level). In patients with inflamed meninges, a similar concentration was achieved rapidly after a single 2-g dose. After a day of therapy, cerebrospinal fluid levels equivalent to 30%-70% of the simultaneous serum levels were found; as the inflammation subsided, cerebrospinal fluid levels fell to around 15% of those in serum. Probenecid did not appear to influence greatly the degree of penetration.

Adolescent↗

Treatment of gram-negative bacillary meningitis: role of the new cephalosporin antibiotics.

Results of the treatment of gram-negative bacillary meningitis have been disappointing: mortality is extremely high, and treatment with chloramphenicol has shown a high failure rate. This failure rate for chloramphenicol is consistent with the wide gap between minimal inhibitory concentration and minimal bactericidal concentration of this drug for Escherichia coli, Klebsiella, and other Enterobacteriaceae. Cefotaxime, a new cephalosporin, is cidal for most gram-negative bacteria at concentrations of less than 0.25 microgram/ml. By late 1981, 137 patients with meningitis due to a variety of bacteria had been treated with this agent. Bacteriologic cure rates were 93% for meningitis due to Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae and 88% for meningitis due to gram-negative bacteria (94.4% for meningitis due to E. coli and Klebsiella). This new antibiotic shows considerable promise in the treatment of these forms of meningitis.

Adult↗