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Biomedical subjects

K Ghosh

Publications and source records attributed to K Ghosh.

At least 127 records · Page 7Linked to original sources

Obstetrical outcomes among women with extrapulmonary tuberculosis.

BACKGROUND: The prevalence of tuberculosis, especially extrapulmonary tuberculosis, is increasing worldwide. Because information on the outcome of pregnancy among women with extrapulmonary tuberculosis is limited, we studied the course of pregnancy and labor and the perinatal outcome in these women and their infants. METHODS: From 1983 to 1993, we followed 33 pregnant women who had extrapulmonary tuberculosis (12 with tuberculous lymphadenitis and 9 with intestinal, 7 with skeletal, 2 with renal, 2 with meningeal, and 1 with endometrial tuberculosis) through their deliveries. Of the 33, 29 received antituberculosis treatment during pregnancy. The antenatal complications, intrapartum events, and perinatal outcomes were compared with those among 132 healthy pregnant women without tuberculosis who were matched for age, parity, and socioeconomic status. RESULTS: Tuberculous lymphadenitis did not affect the course of pregnancy or labor or the perinatal outcome. However, as compared with the control women, the 21 women with tubercular involvement of other extrapulmonary sites had higher rates of antenatal hospitalization (24 percent vs. 2 percent, P< 0.001), infants with low Apgar scores (< or =6) soon after birth (19 percent vs. 3 percent, P=0.01), and low-birth-weight (<2500 g) infants (33 percent vs. 11 percent, P=0.01). CONCLUSIONS: Extrapulmonary tuberculosis that is confined to the lymph nodes has no effect on obstetrical outcomes, but tuberculosis at other extrapulmonary sites does adversely affect the outcome of pregnancy.

Adult↗

Design and models for estimating antagonist potency (pA2, Kd and IC50) following the detection of antagonism observed in the presence of intrinsic activity.

The antagonist activity of the metabotropic glutamate receptor ligand (2S,1'S,2'S)-2-methyl-2(carboxycyclopropyl)glycine (MCCG) was examined using the [35S]GTPgammaS binding and forskolin (FSK)-stimulated adenosine 3':5'-cyclic monophosphate (cAMP) assays with recombinant Chinese hamster ovary (CHO) cells expressing the G protein-coupled human subtype 2 metabotropic glutamate (hmGlu2) receptor. Whereas MCCG proved to be a partial agonist in the GTPgammaS binding assay, it not only antagonized the agonist effect of (IS,3R)-ACPD in the cAMP assay but further produced an anomalous increase of the cAMP level relative to baseline. The anomalous MCCG response was also observed following treatment of the cells with MCCG in the absence of added agonist. Determination of the glutamate concentration in the incubate at the start and end of the cAMP reaction revealed the existence of micromolar concentrations of cellularly released glutamate throughout the course of the assay, reaching levels which exceeded its reported affinity for the mGlu2 receptor. Considering MCCG's partial agonist effect in the GTPgammaS binding assay and its pseudo-inverse agonist effect in the cAMP assay, available methods of estimating its antagonist potency were inappropriate since the classical Schild method and the alternative model suggested by Waud both assume the antagonist to lack a concentration-response relationship. We derived an alternate design and models that permit estimation of the pA2 (pAx), Kd and IC50 for antagonists which produce a concentration related effect when applied by themselves. With their use, the data acquired in both assays support the designation of MCCG as a competitive antagonist of the hmGlu2 receptor and provide similar pA2 estimates between assays. In addition, the newly derived models and design permit the determination of antagonist potency for partial and inverse agonists so characterized in studies employing the Schild design.

Amino Acids, Dicarboxylic↗

See-and-treat in the management of high-grade squamous intraepithelial lesions of the cervix: a resource utilization analysis.

OBJECTIVE: To use activity-based costing techniques to compare see-and-treat with conventional evaluation and treatment of women presenting with a screening Papanicolaou smear demonstrating high-grade squamous intraepithelial lesion (SIL). METHODS: A total of 4000 theoretical patients were assumed to be evaluated and treated following one of four management algorithms: conventional algorithm I, with colposcopy and directed biopsies, followed by cryotherapy or cold-knife conization; conventional algorithm II, substituting the loop electrosurgical excision procedure for cold-knife conization; conventional algorithm III, substituting the loop electrosurgical excision procedure for cold-knife conization and cryotherapy; or see-and-treat algorithm IV, using the loop electrosurgical excision procedure. Costs associated with patient management in each algorithm were calculated including those for the procedure, patient time, physician time, and disposable expenses, as well as costs to manage complications, treatment failures, and follow-up for 1 year. RESULTS: Algorithm I was the most expensive, costing $899,405 for 1000 patients with high-grade SIL. Substituting the loop electrosurgical excision procedure for cold-knife conization (algorithm II) decreased the cost by 32%, whereas substituting it for cryotherapy also (algorithm III) reduced the cost by only 25%. The most cost-effective management was the see-and-treat single visit of algorithm IV. This strategy cost $531,281, offering a 41% cost reduction compared with algorithm I. CONCLUSION: A see-and-treat approach to the management of women with high-grade SIL, although incorporating more procedures, offers significant cost savings over conventional management algorithms.

Algorithms↗

Successful non-invasive ventilatory support in a patient with regimen-related toxicity during allogeneic bone marrow transplantation.

A 13-year-old patient with transfusion-dependent beta thalassemia major developed acute regimen-related lung toxicity after the conditioning regimen but before allogeneic bone marrow transplantation. He was successfully managed on non-invasive ventilatory support. Advances in non-invasive ventilatory support may drastically improve the outlook of this subset of patients who otherwise have a grim prognosis.

Adolescent↗

Ultrastructural changes in peripheral blood neutrophils in a patient receiving ganciclovir for CMV pneumonitis following allogenic bone marrow transplantation.

A 13-year-old splenectomized, multitransfused beta-thalassemia major, male patient received an allogenic BMT from his HLA-compatible brother after suffering grade III regimen-related pulmonary toxicity. He developed features of CMV pneumonitis with positive pp65 CMV antigenemia involving 2.5% peripheral blood neutrophils from day +46. The patient received intravenous immunoglobulin and ganciclovir 5 mg/kg intravenously twice daily. His neutrophil count was maintained above 1 x 10(9)/l by G-CSF 5 microg/kg subcutaneously as and when required. From day 7 onwards following twice daily ganciclovir his peripheral blood smear started showing isolated cytoplasmic inclusions, 1-3 per neutrophil, 3-5 mu in diameter, involving 2-3% of the neutrophils and occasional monocytes. Transmission election microscopy of peripheral blood neutrophils showed type I and type II intranuclear inclusions. These inclusions disappeared within 48 h of stopping ganciclovir. Inclusions were not seen in three patients who were given prophylactic ganciclovir 5 mg/kg once daily for 5 days every week following allogenic BMT after the same conditioning regimen. These patients were also negative for CMV antigenemia. Development of type I and type II intranuclear inclusions in blood neutrophils in patients receiving ganciclovir therapy has not been reported previously, and the striking light microscopic changes provide simple morphological evidence of the toxic effect of this drug on blood neutrophils.

Adolescent↗

Carrier detection in haemophilia A families: comparison of conventional coagulation parameters with DNA polymorphism analysis - first report from India.

Linear discriminants that include data on factor VIII:C and von Willebrand factor antigen levels are well-established tools in estimating the probability of carriership in haemophilia A families. A comparison between the conventional coagulation data, i.e. the ratio of factor VIII:C and von Willebrand factor antigen, and the DNA analysis techniques was made in 98 confirmed carriers (39 obligatory, 69 detected by gene tracking analysis) and 71 normal age matched females who did not have any history of bleeding and were not taking any drug. The lowest misclassification rate, i.e. 7% among the carriers, was seen when a cut-off value of 0.7 was chosen. In the case of normals, all were outside this cut-off value. Thus, it was considered as a workable reference value for classifying the carriers in haemophilia A families in our laboratory. We conclude that the optimal service for haemophilia A carrier diagnosis must include above coagulation test probabilities as well as DNA marker studies. However, it is recommended that the smaller laboratories in developing countries can benefit immensely by only establishing factor VIII:C and von Willebrand factor antigen estimation.

ABO Blood-Group System↗

Gas gangrene in a patient with severe haemophilia A.

The haemophilia patient tends to live a more protected life than his normal counterpart, this is particularly so in underdeveloped and developing countries where due to poor health infrastructure, financial constraints and nonavailability of factor concentrates, patients quickly learn that they need to live a protected life. Under such circumstances, gas gangrene seems to be a very unusual infection for this group of patients. We report here a 25-year-old male with severe haemophilia who developed gas gangrene due to inadequate medical management following a road traffic accident. Subsequently, his affected limb was salvaged by conservative therapy. A literature search failed to reveal any reports of similar patients in the English literature.

Accidents, Traffic↗

Vector potential of Phlebotomus duboscqi and P. papatasi: a comparison of feeding behaviour, reproductive capacity and experimental infection with Leishmania major.

Phlebotomus duboscqi and P. papatasi are the incriminated vectors of Leishmania major, the causative agent of zoonotic cutaneous leishmaniasis (ZCL) in various parts of the world. Factors contributing to the vector potential of these two species were investigated in the laboratory. It was found that 90.1% of the P. duboscqi females tested completed feeding in 1 h and they could complete up to eight gonotrophic cycles in their maximum adult life-span in the laboratory of almost 2 months. In contrast, only 70.3% of the female P. papatasi took bloodmeals within 1 h and they could only complete a maximum of four gonotrophic cycles in the maximum adult life-span of just 1 month. Biting habit (proportion feeding/day of the gonotrophic cycle), survival (proportion surviving first oviposition), gonotrophic discordance (proportion refeeding on blood before first oviposition) and experimental infection (proportion of flies offered a bloodmeal containing L. major which became infected) were all higher for P. duboscqi (0.18, 0.91, 0.50 and 0.65, respectively) than for P. papatasi (0.14, 0.71, 0.12 and 0.56, respectively). It therefore seems likely that P. duboscqi is a much more effective vector of L. major than P. papatasi in several endemic foci of ZCL.

Animals↗

Functional and fibrinogen receptor studies in platelets in pre-eclamptic toxaemia of pregnancy.

It is believed that platelets play a key role in the production of pre-eclamptic toxaemia and toxaemia of pregnancy. Toxaemia of pregnancy is described as a condition of chronic DIC where there is thrombocytopenia as well as raised fibrin degradation products. Since fibrinogen receptors are involved in the final stage of the platelet aggregation reaction, we wanted to investigate the platelet receptors for fibrinogen in normal and abnormal pregnancy. Thirty-six normal pregnant women (12 in their 2nd trimester, 24 in their 3rd trimester), 24 pregnant pre-eclamptic toxaemia cases and 16 non-pregnant controls were included in the present study. All patients with pre-eclamptic toxaemia had oedema, proteinuria and hypertension. Flow cytometric study of platelets was undertaken utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated (final concentration 0.02 M) platelets. The intensity of platelet fluorescence was classified into three groups and expressed in arbitrary units. The results indicate that there are a higher number of stimulated platelets expressing fibrinogen receptors in the circulation of patients with pre-eclampsia. Thus, it is possible to hypothesize that platelets showing increased fibrinogen receptors aggregate and form microthrombi in smaller vessels in women with pre-eclamptic toxaemia.

Journal Article↗

Antibody-dependent reductions in mouse hookworm burden after vaccination with Ancylostoma caninum secreted protein 1.

Vaccination of mice with either third-stage Ancylostoma caninum infective hookworm larvae (L3) or alum-precipitated recombinant Ancylostoma secreted protein 1 from A. caninum (Ac-ASP-1) results in protection against hookworm challenge infections. Vaccine protection is manifested by reductions in lung hookworm burdens at 48 h postchallenge. Mice actively immunized 4 times with Ac-ASP-1 also exhibited reductions in hookworm burden in the muscles. Hookworm burden reductions from Ac-ASP-1 immunization were associated with elevations in all immunoglobulin subclasses, with the greatest rise observed in host IgG1 and IgG2b. The addition of a fourth immunization resulted in even higher levels of IgG and IgE. In contrast, L3-vaccinated mice exhibited marked elevations in IgG1 and IgM, including anti-Ac-ASP-1 IgM antibody. Passive immunization with pooled sera from recombinant Ac-ASP-1-vaccinated mice also resulted in lung hookworm burden reductions. It is hypothesized that recombinant Ac-ASP-1 vaccinations elicit antibody that interferes with parasite larval migration.

Ancylostoma↗

Population ecology of Phlebotomus argentipes (Diptera: Psychodidae) in West Bengal, India.

The population abundance of Phlebotomus argentipes Annandale & Brunetti was studied between January 1986 and December 1987 at 2 sites in West Bengal, India, in relation to 8 ecological parameters (air temperature, rainfall, windspeed, relative humidity, soil moisture, soil temperature, soil pH, and soil organic carbon). Sand flies were present throughout the year with minimum abundance in winter months and maximum during monsoon and postmonsoon months. Correlation analysis examined pairwise relationships among the 8 ecological parameters and P. argentipes abundance. Multiple linear regression of sand fly abundance on the 8 parameters showed that average soil temperature and soil moisture, both recorded 1 mo earlier, were associated positively with sand fly abundance. These findings have important implications for Indian kala-azar disease control and prevention. Effective vector management programs are needed most when weather conditions favor increased sand fly abundance, given that greater sand fly abundance increases the likelihood of host-vector contact and the transmission of Leishmania.

Animals↗

Experimental approaches to the development of a recombinant hookworm vaccine.

Hookworm infection is a major parasitic cause of morbidity in the developing nations of the tropics. Development of a genetically engineered vaccine would be a useful tool in the control of this infection in highly endemic areas. Recombinant polypeptides belonging to the Ancylostoma secreted protein (ASP)-1 family have shown promise for reducing hookworm burdens after larval challenge infections in mice. Typically, these polypeptides are expressed in Escherichia coli and administered as an alum precipitate. Vaccine protection is antibody dependent. It is anticipated that a cocktail of different recombinant hookworm antigens may be required in order to effectively prevent heavy hookworm infections and disease. The progress of this work has been hampered by the absence of both a convenient laboratory animal with which to study hookworm infections resembling human infection, as well as the lack of easy availability of native hookworm antigens. In addition, useful human serologic correlates of antihookworm immunity are still poorly defined.

Ancylostoma↗

Dominance of immunoglobulin G2c in the antiphosphorylcholine response of rats infected with Trichinella spiralis.

The antibody response to the L1 stage of Trichinella spiralis has been described as biphasic. Worms resident in the intestine during the first week of infection stimulate an antibody response against a subset of larval proteins. L1 larvae in the muscle at the end stage of infection stimulate a second antibody response against tyvelose-bearing glycoproteins. Antityvelose antibodies protect rats against challenge infection with larvae. The aim of this study was to characterize the rat B-cell response against larval antigens during the intestinal phase of T. spiralis infection and to test the antiparasitic effects of such antibodies. Strain PVG rats were infected orally with 500 larvae. Antibodies specific for phosphorylcholine-bearing proteins of L1 larvae first appeared in serum 9 days postinfection. Absorption experiments showed that the majority of antilarval antibodies produced in rats 16 days after infection with T. spiralis were specific for phosphorylcholine-bearing proteins. A fraction of these antibodies bound to free phosphorylcholine. Immunoglobulin G2c (IgG2c) producing cells in the mesenteric lymph node dominated this early antibody response. IgG2c is associated with T-independent immune responses in the rat; however, a comparison of athymic rats with euthymic controls suggested that only a small fraction of the phosphorylcholine-related antibody response against T. spiralis was T independent. Phosphorylcholine is a common epitope in antigens of bacteria and nematode parasites and has been shown to be a target of protective immunity in certain bacteria. A monoclonal IgG2c antibody was prepared from infected rats and shown to be specific for phosphorylcholine. Monoclonal phosphorylcholine-specific IgG2c failed to protect rats against intestinal infection with T. spiralis. Therefore, our findings do not support a role for phosphorylcholine-bearing antigens in immune defense against T. spiralis; however, the potency of the immune response induced suggests an immunomodulatory role for the lymphocytes involved.

Animals↗

Role of the membrane anchoring and cytoplasmic domains in intracellular transport and localization of viral glycoproteins.

The role of the transmembrane and the cytoplasmic regions of viral glycoproteins namely, the envelope glycoprotein gD of herpes simplex virus and the integral membrane glycoprotein E3-11.6 K of the nonenveloped adenovirus that are localized in the nuclear envelope has been studied. Chimeras of the cell surface glycoprotein G of vesicular stomatitis virus containing the transmembrane and (or) the cytoplasmic-tail domains of either herpes simplex virus gD or adenovirus E3-11.6 K protein were examined for their intracellular transport and localization. The results show that hybrids containing the membrane anchoring and (or) the cytoplasmic tail domains of either herpes simplex virus gD or adenovirus E3-11.6 K glycoprotein were localized in the nuclear envelope as well as in the endoplasmic reticulum and the Golgi complex. These results suggest that the membrane anchoring and the cytoplasmic domains of herpes simplex virus glycoproteins gD, as well as the adenovirus integral membrane protein E3-11.6 K, were necessary for localization in the nuclear envelope and could influence retention in the endoplasmic reticulum and the Golgi complex.

Adenovirus E3 Proteins↗

A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide.

OBJECTIVE: To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive medications. DESIGN: A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial. PARTICIPANTS: A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated. INTERVENTION: After completing a washout of ocular hypotensive medications, patients were randomized to receive either the dorzolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide three times daily. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each study visit. RESULTS: Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol. At morning peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the combination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences was also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group (7% vs. 1%, P = 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, and tearing eye. CONCLUSIONS: After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide-timolol combination was greater than that of either of its components administered as monotherapy. The combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its individual components.

Adrenergic beta-Antagonists↗

Variable clinical severity of Hb E beta-thalassemia among Indians.

OBJECTIVE: The aim of this preliminary report was to look at the effect of genetic variations in the alpha, beta and gamma globin genes in 7 cases of hemoglobin E/beta-thalassemia with diverse clinical expression of the disease. METHODS: beta-thalassemia mutations were characterized by PCR and dot blot hybridization. G gamma gene polymorphism (Xmnl) was determined by PCR followed by restriction enzyme digestion and polyacrylamide gel electrophoresis. alpha genotyping was done by Southern blot hybridization. RESULTS: Six cases had a severe beta+ mutation [IVS 1 nt 5 (G-->C)] and one case had a beta zero mutation [F/S 41/42 (-CTTT)]. Hence, the beta-thalassemia mutation does not seem to contribute towards the clinical diversity. alpha-genotyping showed a single alpha-gene deletion of the rightward type in three of the five milder cases. The -158 G gamma (C-->T) substitution was present at least in heterozygous state (+/-) in all the milder cases. CONCLUSIONS: Deletional alpha thalassemia and presence of the -158 G gamma (C->T) substitution are the two factors which appear to be more important in decreasing the severity of the disease rather than the nature of the beta thalassemia mutation.

Adolescent↗