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K Thomas

Publications and source records attributed to K Thomas.

At least 37 records · Page 2Linked to original sources

Serotyping of Streptococcus pneumoniae by agglutination assays: a cost-effective technique for developing countries.

There is a need for additional data on the distribution of pneumococcal serotypes in developing countries. We report the use of a coagglutination (COA) and a latex agglutination (LA) test for serotyping Streptococcus pneumoniae which were evaluated using 114 clinical isolates in Vellore, India. In tests to serotype 30 fresh isolates of pneumococci from meningitis (8 isolates), bacteraemia/septicaemia (21 isolates) and peritonitis (1 isolate) cases, there was complete concordance among the three methods. An additional 20 isolates (11 from cerebrospinal fluid and 9 from blood cultures) were serotyped using both LA and COA, with full agreement between the results. With a further 30 isolates, there was 93% concordance for the COA types with serotypes assigned by a WHO reference laboratory. The COA and LA serotyping results were equivalent in accuracy to those obtained using quellung serotyping. Both these agglutination tests are rapid, valid, and relatively cheap, and with appropriate validation by reference laboratories they could be more widely used in developing countries to obtain local and regional data on pneumococcal serotype distribution.

Agglutination Tests

Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning.

Organophosphorus (OP) poisoning is most frequently encountered among our community. Treatment of poisoning is primarily aimed at reversing the effects of the compound by administration of atropine. Oximes have been shown to be efficacious in case reports. The dose of this drug in these reports varies from 1 gm which is a very low dose and physiologically no dose, to doses upto 16 gm. This is also a very expensive imported drug which causes the nation considerable loss of foreign exchange. We report our experience with the use of two treatment regimens of Pralidoxime (P2AM) in the management of patients with OP poisoning in a prospective trial. Seventy-two adult patients presenting to a large university affiliated teaching institution with a history of consumption of OP compounds and requiring intensive care were entered into the trial. Patients were randomized using a block randomisation to receive either a single bolus dose of 1 gm P2AM at admission (Low dose group) followed by placebo infusion over the next 4 days or a single placebo bolus at admission followed by P2AM 12 gm as a continuous infusion over the next 4 days. Outcome measures analyzed were mortality, duration of ICU stay, need for ventilation and duration of ventilation, time to recovery of consciousness, development of intermediate syndrome and infections. A higher prevalence of intermediate syndrome (p = 0.08) was observed in the high dose group. Ventilatory requirement was also more in the high dose group (p = 0.09). Since this was an equivalence study designed to show that the low dose was as effective as the high dose, these results attain greater significance as the low dose group fared better than the high dose group, even though the pre-test hypothesis was in the reverse direction. Subgroup analysis of patients who received at least 1 gm of P2AM within 12 hours of ingestion of the OP poison with those who received P2AM after 12 hours, showed that there was a significant reduction of intermediate syndrome (p = 0.05) but no significant difference was noted in number ventilated. High dose P2AM infusion has no role in the routine management of patients with OP poisoning. These results also suggest that the time of administration of P2AM after the ingestion of the poison mabe a crucial factor which determines response to therapy. A prospective double blind placebo controlled trial is now justified in the light of the above findings.

Adult

Antitumor reactivity induced by liposomal MTP-PE in a liver metastasis model of colon cancer in the rat.

The antitumor effects of muramyl tripeptide phosphatidylethanolamine, incorporated within the lipophilic phase of liposomes (lipMTP-PE) were studied using a model of liver metastasis of colon cancer in the rat. Intravenous immunotherapy with lipMTP-PE, when started 2 days before the inoculation of tumor cells and given twice a week, significantly reduced subsequent tumor growth in the liver. The main effect of treatment appeared to be a substantial local increase in the number of tumoricidal macrophages and lymphocytes. Tumor cell lysis by isolated macrophages in vitro, however, appeared not to be elevated above the level triggered by tumor growth alone. Therefore, the observed therapeutic effect of lipMTP-PE probably results from a combination of (1) an increase in the number of cytotoxic macrophages at the onset of metastatic growth in the liver, thus increasing the probability of lethal contacts between tumoricidal effectors and tumor cells and (2) indirect effects of lipMTP-PE, via the induction of cytokine production by liver macrophages, leading to increased numbers and/or activity of cytotoxic lymphocytes and natural killer cells.

Acetylmuramyl-Alanyl-Isoglutamine

A proven and highly cost-effective method of early detection of breast cancer for developing countries.

Carcinoma of the breast is the third most common cancer in Indian women. With rapid industrialization and effective control of communicable diseases, better diagnostic and treatment facilities, cancer is emerging as a major health problem. Since early detection is the only way to reduce morbidity and mortality from breast cancer, we undertook a pilot project to evaluate efficacy of using existing manpower and resources for screening women in the high risk group. Methodology pros and cons, results, and recommendations are presented. Our method can be adopted by any developing country interested in a screening programme for malignant disease.

Adult

Modulation of human immunodeficiency virus type 1 infection of human monocytes by IgA.

The effect of IgA from human immunodeficiency virus type 1 (HIV-1)-infected patients on infection of primary human blood monocytes with the monocyte-tropic strain HIV-1Bal was evaluated in vitro. Preincubation of HIV-1Bal with purified serum IgA from 6 of 14 patients but from none of 5 seronegative subjects caused a > 50% increase in reverse transcriptase activity. This increase was inhibited by preincubation of monocytes with nonimmune IgA, suggesting a role for Fc alpha receptors. Results were independent of CD4 T cell number and clinical stage. The IgA-mediated enhancement extended to more biologically relevant human mononuclear cells isolated from the intestinal lamina propria. The ability of serum IgA to enhance HIV-1 infection may be relevant to infection of both circulating monocytes and mucosal macrophages. These studies suggest the need to characterize the complex contribution of IgA and the mucosal immune system in promoting and preventing primary HIV-1 infection.

Acquired Immunodeficiency Syndrome

Diagnostic evaluation of the lupus band test in discoid and systemic lupus erythematosus.

BACKGROUND: The usefulness of the lupus band test (LBT) in the diagnosis of cutaneous lupus erythematosus remains controversial. The study was done to determine the sensitivity, specificity, and predictive value of the LBT in discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE). METHODS: During the study period, 32 patients with SLE and 28 patients with DLE were included. The final classification of cases was based on the American Rheumatism Association Criteria (ARA) for SLE, histopathology, and consensus of the clinical staff. Thirty controls, 15 each for DLE and SLE, were chosen from a group of patients, who had lesions clinically simulating DLE and SLE, but could be excluded by histopathology, laboratory tests, and follow-up. Histopathologic examinations and direct immunofluorescence (DIF) tests were done on lesional skin. RESULTS: In DLE, the sensitivity of the LE band test was 58% and the specificity 87%. The positive predictive value was 95% and negative predictive value was 32%. In SLE the sensitivity was 93% and specificity 87%. The positive predictive value was 64% and negative predictive value 98%. CONCLUSIONS: The high negative predictive value of LBT in SLE suggests that it is valuable in excluding diseases clinically similar to SLE.

Adolescent

Esters of L-dopa: structure-hydrolysis relationships and ability to induce circling behaviour in an experimental model of hemiparkinsonism.

A number of carboxylate esters of L-dopa, some of which are novel, were examined for their physicochemical and biological properties. A few esters of tyrosine and phenylalanine were included for comparison. The compounds displayed great differences in their lipophilicity and stability towards chemical and enzymatic (human plasma) hydrolysis. Within subseries, relationships exist between structural properties and rate constants of chemical or enzymatic hydrolysis. In an experimental model of hemiparkinsonism (circling behaviour in rats), some of the L-dopa esters (the isopropyl, sec-butyl and 2-(tetrahydropyranyl)methyl esters) showed an activity distinctly greater than that of L-dopa, although the difference was not statistically significant.

Animals

Angiotensin-II stimulates estradiol secretion from human placental explants through AT1 receptor activation.

A complete renin-angiotensin system has been shown to be present in human placenta, but its physiological role is poorly known. To investigate the implication of this system in the regulation of steroid hormone secretion, we studied the effect of angiotensin-II on the release of estradiol and progesterone from human placental explants. Our experiments showed that angiotensin-II stimulated estradiol secretion from term placental explants in a dose- and time-dependent fashion, although progesterone release was unaffected. Estradiol release induced by angiotensin-II (0.2 mumol/L) was blocked by angiotensin AT1 receptor antagonist losartan in a dose-dependent manner, suggesting the involvement of the AT1 receptor subtype in the process. On the contrary, the angiotensin AT2 receptor antagonist PD123319 (1 mumol/L) or the angiotensin AT2 receptor agonist CGP42112A (1 mumol/L) had no effect. Analysis of the amount of steroid hormones in the placental tissues incubated for 12 h showed that angiotensin-II increased estradiol production by 34% compared with the unstimulated explants, whereas the total levels of the estrogen precursor androstenedione and testosterone were decreased by 30-45% in the presence of the peptide, suggesting a stimulatory effect on the aromatization step. This hypothesis was reinforced by the absence of effect of angiotensin-II on both estradiol and testosterone concentrations in the placental explants pretreated with the aromatase inhibitor 4-hydroxyandrostenedione (25 mumol/L). Progesterone synthesis was not affected by angiotensin-II. The present study indicates that angiotensin-II induces the secretion of estradiol from human placenta through the angiotensin AT1 receptor subtype activation, and this effect seems to be linked to the stimulation of local androgen aromatization.

Angiotensin II

Assessing the outcome of making it easier for patients to change general practitioner: practice characteristics associated with patient movements.

BACKGROUND: The government white paper, Promoting better health, suggested that primary health care services should be made more responsive to patient needs and that competition, brought about by the freer movement of patients between practices, could act as a mechanism for improving the quality of the services provided. Policy changes reflecting these aims were introduced with the 1990 contract for general practitioners. AIM: A study was carried out to estimate the volume of patient movement between practices not attributable to a patient's change of address or to a major change in the practice they had left, and to investigate which practice characteristics patients moved towards and which they moved away from when changing general practitioner. METHOD: Data on 2617 patient movements during June 1991 were collected from five family health services authorities. These patient movements were analysed in relation to data on practice characteristics obtained from family health services authority records. RESULTS: The estimated volume of movement of patients between practices was small (1.6% of the registered population per year). The majority of movements were between group practices; a quarter of the movements recorded were to single-handed general practitioners. However, the ratio of the number of movements from group practices to single-handed general practitioners compared with those from single-handed general practitioners to group practices was 1.37 (95% confidence interval 1.19 to 1.57). In choosing single-handed general practitioners these patients were willing to forgo access to a woman general practitioner, extended services and greater hours of general practitioner availability. Among the subset of movements between group practices, patients were more likely to gain access to a practice nurse, longer surgery hours and a woman general practitioner as a consequence of their move. CONCLUSION: The scale of patient movement observed did not indicate any substantial mechanism by which the new policy of encouraging consumerist behaviour on the part of primary care users could effect desired changes in primary care practice. Among the patient movements observed, the evidence suggests that when choosing a practice potential patients were not deterred by the fact that a practice was single-handed. The public's perception of the factors contributing to a high quality of service may conflict with the official characterization of good practice and high quality services in primary health care.

Adolescent

[Consumption coagulopathy during pregnancy: a case of afibrinogenemia during the second trimester].

We report a case of a membrane disruption at 19 weeks 3 days of gestation complicated by a consumption coagulopathy with clotting tests suggesting primary fibrinogenolysis rather than a disseminated intravascular coagulation usually seen in such cases. A review of the literature revealed 5 cases of coagulopathy during the second trimester of pregnancy among which only two were suspected to be associated with primary fibrinogenolysis. Management of this coagulopathy is discussed.

Abruptio Placentae

Incidence of intermediate syndrome in organophosphorous poisoning.

Seventy two patients admitted to the Intensive Care Unit following ingestion of organophosphorus compounds were studied prospectively with two different doses of pralidoxime (PAM). One group received 1 gm immediately after admission and no further PAM and the other group received infusion of PAM, 1 gm 8 hourly for four days (total 12 gms). The incidence of type II paralysis or intermediate syndrome was 47%. We observed a higher incidence in the 4 days of infusion of PAM group (61%) (20 patients) as compared to the single Bolus dose group (39%) (13 patients). Relative risk 1.48 (confidence interval = 0.9-2.4).

Adult

Down regulation of the angiotensin II receptor subtype AT2 in human myometrium during pregnancy.

Samples of human myometrium have been collected during pregnancy and from non-pregnant women. Binding studies revealed the presence of a 50-fold higher density of angiotensin II AT2 receptor in the non-pregnant state than during gestation. Low levels of the AT1 receptor subtype (approx. 20 fmol/mg protein) were detected in both pregnant and non-pregnant myometrium. Outside pregnancy, the AT2 receptor accounted for greater than 95% of all angiotensin receptors, whereas during pregnancy the value dropped to about 40%. The down regulation of the human myometrial AT2 receptor during pregnancy may be related to the high hormonal content of the environment induced by gestation. The mechanism by which the AT2 receptor is regulated appears to be different to that of the AT1 receptor.

1-Sarcosine-8-Isoleucine Angiotensin II

Angiotensin II induces human placental lactogen and pregnancy-specific beta 1-glycoprotein secretion via an angiotensin AT1 receptor.

The purpose of this work was to determine which subtype of angiotensin II receptors was involved in angiotensin II-induced human placental lactogen (hPL) and pregnancy-specific beta 1-glycoprotein (SP1) secretion from human placenta. The experiments were performed using placental explants and isolated trophoblast cells. They were pretreated with Dup753 (antagonist of angiotensin AT1 receptor), PD123319 (antagonist of AT2 subtype) or with CGP42112A (agonist of angiotensin AT2 receptor) before the addition of angiotensin II. The octapeptide angiotensin II significantly increased the hPL and SP1 release from both placental explants and isolated trophoblast cells. The angiotensin AT1 receptor antagonist Dup753 inhibited the angiotensin II-stimulated hPL and SP1 secretion in a dose-dependent manner but the AT2 specific ligands PD123319 and CGP42112A had no effect. This study indicates that the angiotensin AT1 receptor is the main mediator of angiotensin II in the stimulation of hPL and SP1 secretion from human placenta.

Angiotensin II

60 Hertz magnetic field exposure assessment for an investigation of leukemia in telephone lineworkers.

The purpose of this paper is to present the assessment of magnetic field exposure conducted as a part of a nested case-control investigation of leukemia mortality in telephone lineworkers. For the purposes of exposure classification, telephone company jobs were initially divided into two classes: those with potential for working in an electric environment, referred to as linework jobs, and those not working in an electric environment, referred to as nonlinework jobs. Linework jobs were further divided into the following four categories: outside plant technicians (OPT), installation/maintenance/repair (IMR) technicians, central office technicians (COT), and cable splicing technicians (CST). These job groupings were based on similarity of work tasks and exposure environments. Emdex data-logging dosimeters were used to measure personal exposures to ELF magnetic fields for 204 telephone company workers. Three general classes of exposure indices were calculated for each exposure record: measures of central tendency, measures of peak or maximum exposure, and measures of exposure variability. CSTs had the highest full-shift mean and median exposure, 4.3 and 3.2 mG, respectively. CSTs also ranked the highest, with average peak, average 95th percentile, and average time above background equal to 99.2 mG, 11.1 mG, and 156 min, respectively. In addition, the results suggest the OPT and IMR technicians have exposures similar to nonlineworkers. Exposure classifications, therefore, which misclassify all lineworkers into one "telephone lineworker" job grouping are not appropriate and future studies should concentrate on cable splicing technicians.

Case-Control Studies