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Biomedical subjects

K Thomas

Publications and source records attributed to K Thomas.

At least 145 records · Page 8Linked to original sources

Determination of renin, angiotensin converting enzyme and angiotensin II levels in human placenta, chorion and amnion from women with pregnancy induced hypertension.

OBJECTIVE: Pregnancy induced hypertension has been shown to be associated with a normal or low activity of the maternal circulating renin-angiotensin system (RAS) but little is known of the local RAS in placenta and fetal membranes. The present study attempts to determine, at full term of human preeclamptic pregnancies, the activity of the chorioplacental renin-angiotensin system. PATIENTS AND MEASUREMENTS: We analysed the concentrations of active renin, prorenin, angiotensin converting enzyme (ACE) and angiotensin II in homogenates of human placenta and fetal membranes from preeclamptic patients at full term pregnancy. The values of renin, ACE and angiotensin II found in the patients with moderate preeclampsia (gestosis index 0-1) (n = 10) were compared with those of normal pregnant women (n = 8). RESULTS: Our experiments showed that in preeclamptic pregnancies, the chorion membrane contained the highest concentrations of active renin (2905 +/- 152 pg/g, mean +/- SD), prorenin (21,315 +/- 2849 pg/g) and ACE (1258 +/- 302 U/g) whereas the placenta had more angiotensin II than the chorion and amnion (741 +/- 45 vs 456 +/- 40 and 428 +/- 64 pg/g, respectively). In the placenta, as in the fetal membranes, no significant difference was found in the levels of active renin, ACE or angiotensin II between hypertensive patients and normal subjects but a slightly lower level of chorionic prorenin (P < 0.05) was observed in pregnancy induced hypertension. CONCLUSION: These findings indicate that in moderate preeclampsia (gestosis index 0-1), the activity of the renin-angiotensin system in term human placenta and fetal membranes remains essentially normal.

Amnion↗

How complete is a transurethral resection of the prostate?

OBJECTIVE: To determine the completeness of transurethral resection of the prostate (TURP). PATIENTS AND METHODS: The prostate volume of 432 patients was measured by transrectal ultrasonography (TRUS) before they underwent a TURP performed by one of three consultant urological surgeons. The prostate tissue collected at resection was weighed, multiplied by 1.2 to compensate for 'shrinkage', and the amount of tissue removed expressed as a percentage of the pre-operative prostate volume determined by TRUS (resection ratio). The patients were categorized into groups based on pre-operative prostate size. RESULTS: The mean weight of prostate tissue resected was 25.6 g. Resection ratios increased with prostate size, with the largest occurring in prostates of 71-110 g. The surgeon did not resect more than 50% of the gland volume in any group. CONCLUSION: This study counters the theory that a complete resection of the prostate is routinely achieved. The endoscopic appearances probably imply a complete resection of the adenoma but a considerable volume of the gland remains. This has important implications for the detection of prostate carcinoma at TURP and for the staging of the disease.

Endoscopy↗

Urethral caruncle: an unusual presentation of ovarian tumour.

Secondary female urethral cancer presenting as urethral caruncle is extremely rare. We report a primary ovarian adenocarcinoma in a 78-year-old female patient presented initially as a urethral caruncle. This case represents the first reported case in the world literature. The clinical features, investigations and pertinent literature are reviewed.

Adenocarcinoma↗

Down-regulation of angiotensin AT1 receptor by progesterone in human placenta.

Regulation of the angiotensin AT1 receptor in human placenta is poorly understood. In this study, we analyzed the time course of angiotensin AT1 receptor expression, internalization, and recycling by human trophoblast cells. We also studied the effects of estradiol, progesterone, and chloroquine on regulation of the angiotensin AT1 receptor in 48-h cell culture. The angiotensin II receptor expression increased with the time of incubation, reaching a level at 48 h of culture that was about 120% above the initial value. A large majority of angiotensin II receptors was of the AT1 subtype, as it was completely inhibited by losartan (1 mumol/L). The internalization of [125]angiotensin II binding and the angiotensin AT1 receptor recycling were also time dependent, with t1/2 values of 12 and 21 min, respectively. In human trophoblast cells exposed to progesterone (10 mumol/L) for 48 h, angiotensin AT1 receptor density was decreased by 49%, whereas estradiol (10 mumol/L) or chloroquine (100 mumol/L) treatment was ineffective. In the freshly isolated trophoblast cells initially treated with unlabeled angiotensin II (200 nmol/L) for 30 min, chloroquine was shown to decrease angiotensin AT1 receptor recycling by 73%, whereas estradiol and progesterone had no effect. These findings indicate that progesterone induces a down-regulation of the angiotensin AT1 receptor in human placenta and that the recycling of this receptor can be delayed by chloroquine.

Angiotensin I↗

Pictorial review: the radiological spectrum of vertically-acquired HIV infection.

Anonymous antenatal and newborn screening demonstrates a positive HIV seroprevalence of one in 400 in areas of inner city London. European Collaborative Study data show a vertical transmission rate of 15% and suggests that 23% of infected children will develop clinical manifestations of AIDS before reaching 1 year of age [1], meaning that recognition of the radiological findings in vertically-acquired HIV is important. 75 serial cases of vertically-acquired HIV (age range 6 weeks to 12 years, mean age 35 months) presenting to a national referral centre over 48 months were reviewed; the radiographic findings we describe constitute a core of typical abnormalities together with a selection of the rarer manifestations of vertically-acquired HIV.

AIDS-Related Complex↗

Pharmacological discrimination of GluR5 and GluR6 kainate receptor subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahyd roisdoquinoline-3 carboxylic-acid.

The pharmacological tools available for the discrimination of kainate receptor subtypes are limited. We examined the effects of (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydr oisoquinoline-3-carboxylic acid (LY293558) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) on inward currents associated with activation of non-N-methyl-D-asparate (NMDA) receptors in acutely isolated rat cerebellar Purkinje neurons, rat dorsal root ganglion neurons, and human embryonic kidney 293 cells transfected with human glutamate receptors (GluR) 5 and 6. LY293558 and NBQX inhibited kainate-induced currents in cerebellar Purkinje cells, DRG neurons, and human GluR5-transfected cells. In contrast, human embryonic kidney 293 cells expressing GluR6 receptors, although blocked by NBQX, were unaffected by LY293558 at concentrations of < / = 100 microM. The selective antagonism by LY293558 of GluR5 receptors should allow the determination of the functional role of GluR5 and GluR6 in more complex systems.

Animals↗

Evaluation of an ELISA for the diagnosis of brucellosis.

Brucela serology using ELISA and standard agglutination test was performed on 23 patients with prolonged fever where the test was requested, on 26 randomly chosen patients with prolonged fever where it was not requested and on 17 controls. ELISA was positive in 39.1, 26.9 and 0 per cent respectively in these groups. Brucellosis may often be unsuspected because of its varied clinical manifestations and may be a more important cause of fever than previously considered. Our data reaffirm that ELISA is superior to the standard agglutination test for the diagnosis of brucellosis.

Agglutination Tests↗

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↗