PubMed Health⌕ Search

Biomedical subjects

A Swaminathan

Publications and source records attributed to A Swaminathan.

12 recordsLinked to original sources

Fulminant methicillin-sensitive Staphylococcus aureus infection in a healthy adolescent, highlighting 'Panton-Valentine leucocidin syndrome'.

A 14-year-old immunocompetent adolescent presented systemically unwell with left knee septic arthritis. Within several days, disseminated bone and soft tissue collections became evident, associated with deep venous thrombosis and pulmonary involvement. Methicillin-sensitive Staphylococcus aureus was isolated, harbouring Panton-Valentine leucocidin genes. Aggressive antibiotic and surgical therapies eventually lead to recovery. Intrafamilial spread of the pathogenic isolate was shown by household screening. This presentation is consistent with 'PVL Syndrome' and is typical of severe S. aureus infection emerging in young populations globally.

Adolescent↗

Oliguric acute renal failure in mycosis fungoides with lymphomatous infiltrates in the kidneys.

OBJECTIVE: To present the clinical picture of acute renal failure in patients with mycosis fungoides (MF) and renal lymphomatous infiltrates. To analyze the pathogenesis of renal failure. METHODS: Correlation of clinical picture, urinary findings, imaging reports and autopsy findings in two patients with long-standing MF who died with renal failure. CASE SUMMARIES: Both subjects had sustained oliguria in the last 2 weeks. One patient had persistent hypotension, normal urinalysis, normal renal sonogram, and scarce interstitial lymphomatous infiltrates with preservation of renal parenchymal architecture. He was thought to have ischemic acute renal failure not directly linked to the lymphomatous infiltrates. The second patient developed hypertension one month prior to death, and had moderate proteinuria, hematuria, pyuria, grossly enlarged kidneys with hypoechoic masses, and extensive replacement of the renal parenchyma by lymphomatous infiltrates. This picture is typical of renal failure secondary to lymphomatous replacement of the kidneys. CONCLUSIONS: The development of oliguric renal failure in MF with renal lymphomatous infiltrates may have varying clinical and imaging manifestations and pathogeneses. Potentially reversible pathogenic mechanisms should be systematically investigated, particularly if the overall clinical picture is not characteristic of renal failure secondary to lymphomatous replacement of the parenchyma.

Acute Kidney Injury↗

Cloning and functional expression of human retinal kir2.4, a pH-sensitive inwardly rectifying K(+) channel.

To identify novel potassium channel genes expressed in the retina, we screened a human retina cDNA library with an EST sequence showing partial homology to inwardly rectifying potassium (Kir) channel genes. The isolated cDNA yielded a 2,961-base pair sequence with the predicted open reading frame showing strong homology to the rat Kir2. 4 (rKir2.4). Northern analysis of mRNA from human and bovine tissues showed preferential expression of Kir2.4 in the neural retina. In situ hybridization to sections of monkey retina detected Kir2.4 transcript in most retinal neurons. Somatic hybridization analysis and dual-color in situ hybridization to metaphase chromosomes mapped Kir2.4 to human chromosome 19 q13.1-q13.3. Expression of human Kir2. 4 cRNA in Xenopus oocytes generated strong, inwardly rectifying K(+) currents that were enhanced by extracellular alkalinization. We conclude that human Kir2.4 encodes an inwardly rectifying K(+) channel that is preferentially expressed in the neural retina and that is sensitive to physiological changes in extracellular pH.

Amino Acid Sequence↗

Metabolism of tacrolimus (FK 506) in rat liver microsomes. Effect of rifampin and dexamethasone.

The in vitro metabolism of tacrolimus (TAC, FK 506) was investigated in the liver microsomes prepared from normal rats as well as rats treated with dexamethasone (DEX) and rifampin (RIF). The rate of tacrolimus metabolism was similar in control and RIF treated rat liver microsomes, whereas it significantly increased in microsomes obtained from dexamethasone treated rats. Seven different possible metabolites were identified in the microsomal preparations from rats treated with rifampin or dexamethasone whereas the microsomes from the control rats failed to produce the mono-demethylated and monohydroxylated metabolite of TAC (TAC+2, m/z = 805.5). There was an apparent difference in the amount of individual metabolites formed in different groups. This indicates quantitative differences in the induction of cytochrome P450 3A, an enzyme sub family known to be primarily responsible for tacrolimus metabolism. Lack of induction of tacrolimus metabolism by rifampin can be attributed to the lack of effect of rifampin in inducing cytochrome P450 3A in rats.

Animals↗

Clinical pharmacokinetics of tacrolimus.

Tacrolimus, a novel macrocyclic lactone with potent immunosuppressive properties, is currently available as an intravenous formulation and as a capsule for oral use, although other formulations are under investigation. Tacrolimus concentrations in biological fluids have been measured using a number of methods, which are reviewed and compared in the present article. The development of a simple, specific and sensitive assay method for measuring concentrations of tacrolimus is limited by the low absorptivity of the drug, low plasma and blood concentrations, and the presence of metabolites and other drugs which may interfere with the determination of tacrolimus concentrations. Currently, most of the pharmacokinetic data available for tacrolimus are based on an enzyme-linked immunosorbent assay method, which does not distinguish tacrolimus from its metabolites. The rate of absorption of tacrolimus is variable with peak blood or plasma concentrations being reached in 0.5 to 6 hours; approximately 25% of the oral dose is bioavailable. Tacrolimus is extensively bound to red blood cells, with a mean blood to plasma ratio of about 15; albumin and alpha 1-acid glycoprotein appear to primarily bind tacrolimus in plasma. Tacrolimus is completely metabolised prior to elimination. The mean disposition half-life is 12 hours and the total body clearance based on blood concentration is approximately 0.06 L/h/kg. The elimination of tacrolimus is decreased in the presence of liver impairment and in the presence of several drugs. Various factors that contribute to the large inter- and interindividual variability in the pharmacokinetics of tacrolimus are reviewed here. Because of this variability, the narrow therapeutic index of tacrolimus, and the potential for several drug interactions, monitoring of tacrolimus blood concentrations is useful for optimisation of therapy and dosage regimen design.

Drug Interactions↗

Preoperative intra-arterial infusion chemotherapy for advanced squamous cell carcinoma of the mouth and oropharynx.

Twelve patients with advanced locoregional (Stage III and IV) squamous cell carcinoma of the oral cavity and oropharynx underwent treatment with cisplatin, vinblastine, bleomycin, and 5-fluorouracil, given by intra-arterial infusion, as primary adjuvant therapy, in preparation for radiation therapy and surgery. Responses were observed during or immediately after infusion therapy in 8 of 12 (67%) of patients (1 complete response, 7 partial responses). Infusion chemotherapy was followed by radiation therapy alone in five patients and by radiation and surgery in six patients. The protocol was initiated in August 1981, and six patients are now free of their primary cancer, at 21 to 36 months, whereas six have died with disease. Arterial infusion of a combination of effective antineoplastic agents is a promising method for the preparation of selected patients for radiation therapy and surgery, as it is less likely to produce serious systemic toxicity and it requires a shorter period than systemic neoadjuvant chemotherapy.

Aged↗

Mental health initiatives as peace initiatives in Sri Lankan schoolchildren affected by armed conflict.

The Health Reach Sri Lanka project (1993-96) is described. It was a school-based assessment of children's exposure to war-related events and the presence of psychological distress, undertaken in six communities in parts of Sri Lanka variously affected by armed conflict. Its objectives, methods and results are presented. The research project aimed to raise national awareness of the psychosocial effects of armed conflict on children, using a community-development approach to local capacity building, based on the 'health initiative as peace initiative' model. As a follow-up to the study, a locally run programme, based on creative play and trauma-healing, was established, initially for the children involved in the study. This was later extended to other children in the district affected by armed conflict.

Child↗