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Biomedical subjects

S Srinivasan

Publications and source records attributed to S Srinivasan.

At least 145 records · Page 8Linked to original sources
PubMed1998

Pyogenic liver abscess in children--South Indian experiences.

PURPOSE: Eighteen cases of pyogenic liver abscess (PLA) admitted at JIPMER hospital, South India, over a 6-year period were analyzed to document the clinical profile and to evaluate the management of PLA among children. METHODS: Records of all these patients were reviewed for presenting signs and symptoms, any associated condition, investigative results, management, and follow-up findings. RESULTS: The overall incidence of PLA was 78.9 per 100,000 pediatric (under 12 years) admissions. One patient had aplastic anemia and was on long-term steroid therapy, whereas another had measles in recent past. Moderate to severe malnutrition was present in five (27.8%) and ascariasis in seven (38.9%) children. Common presentations were fever (100%), abdominal pain (76.9%), and tender hepatomegaly (83.3%). Ultrasonography results were positive in all cases. Fourteen patients (77.8%) had solitary liver abscess, and four had multiple abscesses. Organism was isolated in 11 cases (63.6%), and Staphylococcus aureus was the commonest isolate (66.7%). All patients received antibiotics. Twelve cases were managed conservatively with antibiotics alone, of these only two (16.7%) required drainage later on. Percutaneous aspiration was also undertaken in four additional (22.2%) cases and open drainage in two (11.1%), at presentation. The overall mortality rate was 11.1%. Time taken for complete resolution ranged from 10 days to 40 days. CONCLUSIONS: Any child presenting with fever, abdominal pain, and tender hepatomegaly should be subjected to ultrasound scan for early detection of PLA. S aureus is the commonest causative agent. Enterobacteriaceae contribute significantly during infancy. A combination of cloxacillin and gentamicin or a third generation cephalosporine and gentamicin, especially in infants, is a satisfactory initial coverage. Therapeutic drainage is not a must in all cases of PLA. When required, percutaneous needle aspiration is safe and effective. Resolution and significant reduction in mortality has been made possible by early detection and optimum antibiotics therapy.

Child↗
PubMed1998

Study of ethmoid sinus involvement in multibacillary leprosy.

The nasal mucosal involvement in lepromatous leprosy is well recognized. Currently interest has centred around the involvement of paranasal sinuses in leprosy. They act as a reservoir and constant source of reinfection to the nasal mucosa. In the present prospective study 25 untreated patients with multi-bacillary leprosy were included. Clinical examination, computed tomography (CT) scan of paranasal sinuses, ethmoid sinus endoscopy and biopsy were carried out in all patients, to investigate the involvement of the paranasal sinuses in leprosy. Ethmoid sinus involvement was noted in 20 patients on CT scan. Bilateral involvement was more common (65 per cent). Anterior ethmoids were more commonly affected (65 per cent). On ethmoid sinus endoscopy abnormal mucosa was noted in 17 patients (68 per cent). Ethmoid sinus biopsy was confirmative in 16 patients (64 per cent). Statistically significant correlation was found between CT findings, sinus endoscopy and sinus biopsy findings.

Adolescent↗
PubMed1998

Interleukin-1 receptor (IL-1R) liquid formulation development using differential scanning calorimetry.

PURPOSE: To elucidate the solution conditions that confer stability of aqueous IL-1R using differential scanning calorimetry (DSC). METHODS: Optimal pH conditions were determined by monitoring degradation products encountered during accelerated studies (at elevated temperatures) using SDS-PAGE. At the pH optimum, DSC screened for excipients that enhanced thermal stability by shifting the Tm to higher values. Using SEC the relationship between thermal unfolding and stability was investigated by considering if lower Tm's in the presence of preservatives correlated with degradation products at 37 degrees C over time. The degree of aggregation relative to that of a control determined the level of stability achieved. RESULTS: Circular dichroism (CD) measurements confirmed molecular modeling studies showing IL-1R to be about 39% beta-sheet. Two major transitions characterized the DSC data with Tm's observed near 47 degrees C and 66 degrees C. Among 21 excipients screened, NaCl exhibited the greatest stabilizing influences based on shifting the low temperature transition to 53 degrees C. The low temperature transition was later found to comprise two transitions, yielding a total of three melting transitions for IL-1R. High Tm's arising from the presence of preservatives correlated with the order of stability (i.e., 0.065% phenol > 0.1% m-Cresol > 0.9% benzyl alcohol). CONCLUSIONS: The three melting transitions are consistent in origin with the cooperative unfolding of three unique immunoglobulin-like domains of IL-1R. Optimal stability was achieved in 20 mM sodium citrate at pH 6 with sufficient NaCl to attain the tonicity of human serum. A correlation between the predicted ranking of stability and the extent of aggregation was demonstrated using DSC.

Calorimetry, Differential Scanning↗
PubMed1998

Timing of HIV interventions on reductions in sexual risk among adolescents.

Examined the effectiveness of an HIV intervention program among 151 adolescents ages 13 to 24 years who were randomly assigned to (a) seven sessions of 1.5 hr each (10.5 hr); (b) three sessions of 3.5 hr each (10.5 hr); or (c) a no-intervention condition. Using cognitive-behavioral intervention strategies, social skills and HIV-related beliefs, perceptions, and norms were targeted in both the three- and seven-session, small-group intervention conditions. Regression analysis indicated that over 3 months, the number of unprotected risk acts and the number of sexual partners were lower in the seven-session condition compared to the other conditions. Factors mediating risk acts changed in a complex manner. For example, perceived vulnerability increased for those with initially lower vulnerability scores among youths in the seven-session condition compared to others. Self-approval of condom use was also higher for those with initially low scores in the seven-session compared to the three-session condition. Self-efficacy for risk avoidance and condom use was significantly higher in the three-session condition for those with initially low scores compared to other groups. On the role-play measure, those with higher baseline scores in the low-pressure situation improved significantly only in the three-session intervention; in the high-pressure situation, the participants reported significantly higher scores in the seven-session intervention, and those with higher scores improved the most. Results suggest the importance of multisession HIV intervention programs to be delivered with fidelity in community settings.

Adolescent↗
PubMed1998

A brief HIV intervention for adolescents and young adults.

The delivery format of an HIV prevention program that had been efficacious with youths at high risk was modified from seven relatively short sessions over a one- to two-month period to three longer sessions over a one- to two-week period. In contrast to youths in the seven-session program, no change in sexual behavior was observed among those in the redesigned program at three-month follow-up. However, change was apparent in the mediators of high-risk behavior over the same period.

Adolescent↗
PubMed1998

Extracellular signal molecule(s) involved in the carbon starvation response of marine Vibrio sp. strain S14.

The role of exogenous metabolites as putative signal molecules mediating and/or regulating the carbon starvation adaptation program in Vibrio sp. strain S14 was investigated. Addition of the stationary-phase supernatant extract (SSE) of Vibrio sp. strain S14 to logarithmic-phase cells resulted in a significant number of carbon starvation-induced proteins being up-regulated. Halogenated furanones, putative antagonists of acylated homoserine lactones (AHLs), inhibited the synthesis of proteins specifically induced upon carbon starvation. The effect of the furanone was the opposite of that caused by SSE with respect to the up- and down-regulation of protein expression, indicating that both the furanone and the putative signalling molecules were acting on the same regulatory pathway. Culturability was rapidly lost when Vibrio sp. strain S14 was starved in the presence of the furanone at a low concentration. The furanone also had a negative effect on the ability of carbon-starved cells to mount resistance against UV irradiation and hydrogen peroxide exposure. The SSE of Vibrio sp. strain S14 had the ability to provide cross-protection against the loss in viability caused by the furanone. We have further demonstrated that the SSE taken from low- as well as high-cell-density cultures of Vibrio sp. strain S14 induced luminescence in Vibrio harveyi. Taken together, the results in this report provide evidence that Vibrio sp. strain S14 produces extracellular signalling metabolites during carbon and energy starvation and that these molecules play an important role in the expression of proteins crucial to the development of starvation- and stress-resistant phenotypes.

Bacterial Proteins↗
PubMed1998

Serum from diabetic BB/W rats enhances calcium currents in primary sensory neurons.

We examined the hypothesis that exposure of nondiabetic rat dorsal root ganglion (DRG) neurons to sera from diabetic BB/W rats would produce an increase in calcium currents associated with impaired regulation of the inhibitory G protein-calcium channel complex. Acutely dissociated rat DRGs were incubated for 18-24 h in medium supplemented with sera (10% vol/vol) from either diabetic rats with neuropathy or age-matched, nondiabetic controls. Exposure of DRG neurons to sera from diabetic BB/W rats resulted in a surface membrane immunofluorescence pattern when treated with an anti-rat light-chain antibody that was not observed in neurons exposed to control sera. Calcium current density (IDCa) was assessed with the use of the whole cell variation of the patch-clamp technique. IDCa in neurons exposed to diabetic sera was significantly increased compared with neurons exposed to control sera. Guanine nucleotide-binding (G) protein regulation of calcium channel function was examined with the use of a two-pulse "facilitation" or IDCa enhancement protocol in the presence of activators [guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)] or antagonists [guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and pertussis toxin (PTX)] of G protein function. Facilitation was significantly decreased in neurons exposed to diabetic sera. Intracellular diffusion of neurons with GDP beta s blocked facilitation, whereas dialysis with GTP gamma s increased facilitation to a similar magnitude in neurons exposed to either diabetic or control sera. Treatment with PTX resulted in a significant increase in IDCa and approximately 50% decrease in facilitation in neurons treated with control sera but no significant changes in neurons exposed to diabetic sera. We conclude that serum from diabetic BB/W rats with neuropathy contains an autoimmune immunoglobulin that impairs regulation of the inhibitory G protein-calcium channel complex, resulting in enhanced calcium influx. Regulation of the inhibitory G protein-calcium channel complex involves PTX-sensitive and -insensitive G proteins.

Animals↗
PubMed1998

Frequency, causes, and outcome of home ventilator failure.

STUDY OBJECTIVES: The safety of home ventilators has been questioned. We collected data to study the following: frequency of home ventilator failure, apparent causes for the failure or malfunction, and adverse consequences following the failure. STUDY DESIGN: Information on all requests to correct home ventilator failures reported to a home respiratory equipment vendor was collected prospectively between November 1991, and November 1992. PATIENTS: There were 150 ventilator-assisted patients aged 2 to 77 years; 44 were < or = 18 years. They received 841,234 h of home mechanical ventilation (average, 15.4 h/d per ventilator-assisted patient). RESULTS: There were 189 reports of home ventilator failure. Defective equipment or mechanical failure was found in only 39% (73 reports), equivalent to one home ventilator failure for every 1.25 years of continuous use. Other causes of ventilator failure included the following: improper care, damage, or tampering with the ventilator by caregivers (13%), functional equipment improperly used by caregivers (30%), and equipment functional but the patient's condition changed, mimicking ventilator failure (3%). No problem could be identified in 16%. The following actions were required: ventilator replacement (44%), repair of a defective part (6%), replacement of a functioning ventilator for psychological comfort (14%), ventilator adjustments made (21%), caregiver reeducation (7%), caregiver anxiety or distress reduced (3%), and no action required (4%). Hospitalization was required only in two cases (1%). No adverse outcomes, deaths, or serious injuries were associated with home ventilator failure. CONCLUSIONS: We conclude that in 150 patients requiring home mechanical ventilation, ventilator failure occurred relatively infrequently, and there were no adverse outcomes as a result of equipment failure at home. We speculate that equipment failure is not a frequent or serious problem for ventilator-assisted patients treated at home.

Adolescent↗
PubMed1998

Physician, do no harm.

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Controlled Clinical Trials as Topic↗
PubMed1997

Differences in HDL cholesterol concentrations in Japanese, American, and Australian children.

BACKGROUND: Mortality from coronary heart disease is relatively low in Japan compared with other developed countries and has remained low despite an increasing standard of living and an apparent increase in mean plasma cholesterol concentration in adults over the past three decades. Important differences in childhood plasma lipoprotein profile might contribute to some of the difference in coronary heart disease mortality seen between Japan and both Australia and North America. METHODS AND RESULTS: Plasma HDL cholesterol and total cholesterol were surveyed in representative populations of schoolchildren in Australia, Japan, and Bogalusa, La. The mean concentration of plasma HDL cholesterol (but not total cholesterol) was higher for Japanese schoolchildren than for Australian or US schoolchildren (P<.001). In addition, the difference in plasma HDL cholesterol between the ages of 8 to 10 years and 12 to 15 years was much greater for Australian (boys, 15.2%; girls, 2.6%) and US (boys, 9.1%; girls, 2.7%) children than for their Japanese counterparts (boys, 4.2%; girls, 1.9%). An examination of potential explanatory factors revealed little difference in body mass index between samples, higher physical activity levels for the Japanese compared with the Australians, and substantial differences in dietary intake between Japanese and Australian schoolchildren. CONCLUSIONS: The relatively high ratio of plasma HDL cholesterol to total cholesterol in Japanese schoolchildren and the relatively small negative difference of plasma HDL cholesterol with age may help to explain why the coronary heart disease mortality rate in Japan is low compared with that in other developed countries.

Adolescent↗
PubMed1997

A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells.

Mammalian cells proteolytically release (shed) the extracellular domains of many cell-surface proteins. Modification of the cell surface in this way can alter the cell's responsiveness to its environment and release potent soluble regulatory factors. The release of soluble tumour-necrosis factor-alpha (TNF-alpha) from its membrane-bound precursor is one of the most intensively studied shedding events because this inflammatory cytokine is so physiologically important. The inhibition of TNF-alpha release (and many other shedding phenomena) by hydroxamic acid-based inhibitors indicates that one or more metalloproteinases is involved. We have now purified and cloned a metalloproteinase that specifically cleaves precursor TNF-alpha. Inactivation of the gene in mouse cells caused a marked decrease in soluble TNF-alpha production. This enzyme (called the TNF-alpha-converting enzyme, or TACE) is a new member of the family of mammalian adamalysins (or ADAMs), for which no physiological catalytic function has previously been identified. Our results should facilitate the development of therapeutically useful inhibitors of TNF-alpha release, and they indicate that an important function of adamalysins may be to shed cell-surface proteins.

ADAM Proteins↗
PubMed1997

Structure-function studies of interleukin 15 using site-specific mutagenesis, polyethylene glycol conjugation, and homology modeling.

Interleukin (IL)-15 is a multifunctional cytokine that shares many biological activities with IL-2. This functional overlap, as well as receptor binding subunits shared by IL-15 and IL-2, suggests tertiary structural similarities between these two cytokines. In this study, recombinant human IL-15 was PEGylated via lysine-specific conjugation chemistry in order to extend the circulation half-life of this cytokine. Although PEGylation did extend the beta-elimination circulation half-life of IL-15 by greater than 50-fold, the biological activity of polyethylene glycol (PEG)-IL-15 was significantly altered. Specifically, PEG-IL-15 lost its ability to stimulate the proliferation of CTLL but took on the properties of a specific IL-15 antagonist in vitro. In comparing sequence alignments and molecular models for IL-2 and IL-15, it was noted that lysine residues resided in regions of IL-15 that may have selectively disrupted receptor subunit binding. We hypothesized that PEGylation of IL-15 interferes with beta but not alpha receptor subunit binding, resulting in the IL-15 antagonist activity observed in vitro. The validity of this hypothesis was tested by engineering site-specific mutants of human IL-15 as suggested by the IL-15 model (IL-15D8S and IL-15Q108S block beta and gamma receptor subunit binding, respectively). As with PEG-IL-15, these mutants were unable to stimulate CTLL proliferation but were able to specifically inhibit the proliferation of CTLL in response to unmodified IL-15. These results supported our model of IL-15 and confirmed that interference of beta receptor subunit binding by adjacent PEGylation could be responsible for the altered biological activity observed for PEG-IL-15.

Amino Acid Sequence↗
PubMed1997

Effect of transforming growth factor alpha and interleukin 8 on somatostatin release from canine fundic D cells.

BACKGROUND & AIMS: Helicobacter pylori infection in patients who have peptic ulcer disease is associated with altered regulation of gastric secretion, hypergastrinemia, and diminished somatostatin expression in gastric mucosa. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 are the predominant cytokines produced in the gastric mucosa of patients with H. pylori infection. The aim of this study was to examine whether IL-8 and TNF-alpha could regulate somatostatin release from isolated canine gastric D cells. METHODS: Canine gastric D cells were isolated from fundic mucosa and enriched by centrifugal elutriation. Secretagogue-stimulated somatostatin release was measured by radioimmunoassay. RESULTS: TNF-alpha dose dependently increased somatostatin release after 2 hours of treatment. The stimulatory effect of TNF-alpha was additive to that of epinephrine but was unaffected by a maximal concentration of cholecystokinin. IL-8 did not alter basal or secretagogue (cholecystokinin, epinephrine)-mediated somatostatin release. The stimulatory effect of TNF-alpha (10 ng/mL) was potentiated by the addition of IL-8 (1 nmol/L), inhibited by octreotide and staurosporine, but unaffected by indomethacin. Pretreatment of D cells with TNF-alpha (10 ng/mL) for 24 hours abolished the subsequent stimulatory effect of this cytokine and secretagogues on somatostatin release. CONCLUSIONS: TNF-alpha was shown to regulate somatostatin release from cultured D cells in a divergent manner.

Animals↗
PubMed1997

Slime production, adherence and hydrophobicity in coagulase-negative staphylococci causing peritonitis in peritoneal dialysis.

Attachment of coagulase-negative staphylococci to plastic surfaces by means of hydrophobic interaction and slime production may be important in producing catheter associated infections. In continuous ambulatory peritoneal dialysis (CAPD), the relationship between these properties and disease is unclear and the effect of dialysate fluid is not considered. For a collection of coagulase-negative staphylococci from CAPD patients, slime production and adherence were measured by colorimetric methods and hydrophobicity was determined by autoaggregation in ammonium sulphate solution. Comparison of 73 nasal isolates with 69 isolates from peritonitis showed no significant differences with respect to three properties, with the exception of a greater adherence of peritoneal isolates in dialysate because of a greater proportion of staphylococcal species other than Staphylococcus epidermidis. Fewer strains showed adherence in dialysate (12/142 8.5%) than in broth (94/142 66%) but the proportion of strains producing slime was similar. The milieu of the bacteria rather than the organisms themselves may be of greater importance in the establishment of infection.

Bacterial Adhesion↗