Going beyond the clinic: confronting stigma and discrimination among men who have sex with men in Mysore through community-based participatory research

Community-based participatory research (CBPR) has gained considerable popularity in recent decades given its ability to address social inequities, improve health outcomes and enhance community participation and ownership with respect to various health-related interventions. This paper describes the engagements of a community of self-identified men who have sex with men, most of whom also identified as male sex workers, in a long-term iterative and systematic process of knowledge production, reflection, and action. The project took place in 2006 in Mysore, South India, under the larger umbrella of an HIV intervention formed by the University of Manitoba and the sex workers collective known as Ashodaya Samithi, funded by the Bill & Melinda Gates Foundation (Avahan). CBPR is revealed as uniquely suited for tackling stigma and discrimination as subjects of scientific inquiry and as key methodological obstacles. As the community cultivated their own analysis around stigma, the concept became a key rallying point for increasing equity with respect to access to health services for this community. CBPR proved highly effective in mobilizing community participation and increasing access to sexual health services, over the long-term, because it was supported by and was able to feed community insights into a much larger infrastructure that sought to mobilize sexual minorities. More broadly, by highlighting various positive effects arising from CBPR, we have sought to further emphasize the greater possibilities of public health practitioners working more democratically with disenfranchised and highly stigmatized communities.     

Serum Gastrin and Gastric Acidity

Summary: The relationship between serum levels of gastrin and intragastric acidity was studied using an immunoassay for gastrin which was specific for the biologically active C-terminal sequence of the gastrin molecules.
Eighty-three combined serum gastrin and intragastric pH estimations were performed on 43 subjects (4 normal, 13 patients with gastric ulceration and 26 patients with duodenal ulceration). The serum gastrin response to gastric acidification by betazole hydrochloride was studied in 9 patients with duodenal ulceration.
There was a highly significant (P <0.001) negative correlation (r=-0.37) of serum gastrin on basal intragastric pH, i.e. the patients with the higher gastrin levels had lower intragastric pH. Gastric acidification by betazole hydrochloride suppressed the hyper-gastrinaemia associated with duodenal ulceration.
The correlation between serum gastrin and intragastric pH suggests that gastrin is a factor in maintaining basal gastric acid secretion. Suppression of the hypergastri-naemia associated with duodenal ulceration by gastric acidification is consistent with the concept of an increased vagal tone in these patients.     

Lymphokine-activated killer cell functions in patients with leukemic B- lymphoproliferative diseases

Nine patients with leukemic B-lymphoproliferative diseases (B-LPD) were evaluated for development of in vitro recombinant interleukin-2 (rIL-2)- activated killer (LAK) cells. B-cell cultures were established from peripheral blood mononuclear cells (PBMNCs) containing 63% +/- 29% malignant cells. Short-term cultures were tested after 5-day activation with 500 U rIL-2/mL. Long-term cultures were maintained for 4 to 6 weeks by weekly addition of 500 U rIL-2 and autologous irradiated feeder cells. In the first week, the cells decreased considerably in the long-term cultures but thereafter cells proliferated (mainly T cells) on the average 300-fold (range 30- to 1,000-fold). In the short- term cultures, there was a 36% reduction of malignant B cells. In long- term cultures, B cells were reduced from 63% to 8%; three cultures still contained greater than 15% B cells. The CD16-positive cell percentage was comparable in both types of cultures and ranged from 2% to 17%. Effector cells lysing the natural killer (NK)-sensitive cell line K562 could be induced in all patients. Except in patients with chronic lymphocytic leukemia (CLL) and high malignant cell numbers, NK activity was already restored after 5 days. Optimal NK activity was obtained after 1.5 to 2.5 weeks. LAK cells killing NK-resistant lymphoma cell lines showed optimal activity after 2 to 3 weeks of culture. However, LAK cells killing greater than 10% of autologous malignant cells were obtained in only one third of the patients. The discrepancy between strong cytolytic activity against the NK-sensitive (K562) target cells obtained in all patients and the cytotoxic activity against NK-resistant cell lines contrasts with the poor development of LAK cells against autologous tumor cells. This discrepancy does not appear to be explained by soluble inhibitory factors released during the tumor cultures, as allogeneic LAK cells were not inhibited by supernatants from patients' cultures. Further investigations are warranted to reveal cell-mediated inhibition by tumor cells or suppressor cells.     

Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.     

Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening.

Thyroid peroxidase antibodies (TPOAb) in pregnancy are a marker for postpartum (PPTD) and long-term thyroid dysfunction, with variable sensitivity and specificity in PPTD prediction. To test its utility in prediction, we recruited 308 TPOAb-positive (147 developed PPTD (PPTD group) and 161 remained euthyroid [PPTE group]) and 102 TPOAb-negative women (none developed PPTD), in early pregnancy (median, 18; range, 9-19 weeks' gestation). TPOAb levels were higher in the PPTD group (median) (125.2 kIU/L; p < 0.001), and in its hypothyroid (162.4 kIU.; p < 0.0001), hyperthyroid (114.2 kIU/L; p < 0.007), and biphasic (105.1 kIU/L; p < 0.02) variants, compared to the PPTE group (66.7 kIU/L) The incidence of PPTD was significantly higher with TPOAb levels above 58.2 kIU/L (early pregnancy versus postpartum; relative risk, 1.37 [95% confidence interval [CI] 1.17-1.61] versus 0.78 [95% CI 0.5-1.2]) compared to levels below. The integrated postpartum TPOAb response was higher in the PPTD group (median) (159 kIU/L per week) and its variants (hypothyroid; 199 kIU/L per week; biphasic, 180 kIU/L per week; hyperthyroid, 120 kIU/L per week), compared to the PPTE group (86 kIU/L per week p < 0.004). Median early pregnancy TPOAb levels in the PPTD and PPTE groups correlated well with the postpartum antibody response (r = 0.58, p < 0.001). The sensitivity of TPOAb in PPTD prediction was 100% (early pregnancy and postpartum), specificity 62% (early pregnancy) versus 41% (postpartum) and positive predictive value 48% (early pregnancy and postpartum). The timing of TPOAb testing, the sensitive assay used and the absence of PPTD in TPOAb-negative subjects contributed to this high sensitivity. We recommend TPOAb in early pregnancy as a useful predictor of PPTD, particularly in populations where PPTD does not occur in TPOAb-negative women.     

Normal lactotroph sensitivity to graded low-dose dopamine infusions in pathological hyperprolactinemia

The question as to whether there is lactotroph resistance to dopamine (DA) in pathological hyperprolactinemia (PHP) is unresolved. Previous studies utilizing low-dose DA infusions to study lactotroph function have not considered the diurnal changes in prolactin (PRL) secretion that occur in normals but which are lost in PHP. As PRL levels show a fall in the hours after waking, studies performed during this time of day will falsely show a greater fall of PRL in normals than in PHP patients. The aim was to readdress the issue of lactotroph sensitivity using a study designed to minimize the problem arising from diurnal PRL changes. Eight normal subjects, 17 patients with PHP, and 6 hyperprolactinemic patients with nonfunctioning pituitary tumors (NFTs) were studied with three graded doses of DA - (0.01, 0.05, and 0.5 micrograms/kg X min) - by relating the changes induced by each dose to the maximal spontaneous fall in PRL that occurred during a 3-hour control saline study. The mean +/- SE maximal fall in PRL during control saline infusion to 46.0 +/- 4.1% of basal in normal subjects was significantly greater (p less than 0.001) than the fall in patients with PHP (88.0 +/- 1.0%) or NFTs (87.5 +/- 2.6%). The apparent fall in PRL was significantly greater in normals during the two lower infusion doses, but not at the highest dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression and function of Fas (APO-1/CD95) in patient myeloma cells and myeloma cell lines

Cross-linkage of the Fas antigen induces programmed cell death in many normal and malignant lymphoid cells by a process known as apoptosis. In this study, we examined the sensitivity of myeloma cell lines and patient plasma cells to a cytolytic anti-Fas monoclonal antibody (MoAb). Eight of 10 myeloma cell lines were induced to undergo programmed cell death by anti-Fas MoAb as determined by DNA fragmentation and morphologic changes. Of the two myeloma cell lines that were resistant to anti-Fas treatment, one did not express the Fas antigen. Only the U266 cell line expressed Fas, but was not killed by the anti0Fas MoAb. To extend these studies, we have examined the expression and function of Fas in freshly isolated CD38hiCD45neg-int plasma cells from patients with multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and primary amyloidosis (AL). By three-color flow cytometry, we found Fas expression in CD38hiCD45neg-int plasma cells from all patient groups to be variable, as Fas was expressed in 15 of 28 MM, 3 of 6 MGUS, and 2 of 7 AL patients. In morphologic studies of apoptosis, Fas-positive myeloma cells in patient bone marrow mononuclear cell (MNC) cultures appeared to be resistant to anti-Fas-mediated apoptosis. By contrast, purified myeloma cells from the same patient were sensitive to anti-Fas treatment, suggesting the presence of a protective factor(s) in unseparated MNC cultures that may inhibit Fas-induced apoptosis of plasma cells. Of interest, serum from normal individuals and myeloma patients also protected myeloma cell lines from undergoing Fas-mediated apoptosis. These studies show that Fas expression in myeloma cell lines and CD38hiCD45neg-int patient plasma cells is variable and may reflect a variance in the maturation status of the various plasma cell populations. Moreover, Fas-mediated killing of patient cells and myeloma cell lines was also variable, which may be influenced, in part, by the presence of a soluble protective factor.     

Effects and mechanism of action of lithium chloride on gastric acid secretion in rats

Lithium chloride reduce the measured parameters of gastric secretion (gastric volume, hydrogen ion concentration, and gastric acid output) 2 h after intracerebroventricular, intravenous, or subcutaneous administration in pylorus-ligated rats, in a dose-dependent manner. Intracerebroventricular administration of lithium was approximately five times and 10 times more potent than intravenous and subcutaneous injection, respectively. Time-course study demonstrated that the action of lithium (400 micrograms) on gastric secretion reached a peak at 1 h after intracerebroventricular administration; however, the effects on volume and output were still significant after 8 h. Prior intracerebroventricular injection of indomethacin (400 micrograms) reversed the action of centrally administered lithium on gastric secretion. However, central administration of the opiate receptor blocker naltrexone (100 micrograms), as well as subcutaneous administration of indomethacin (5 mg/kg), failed to modify the effect of lithium on gastric acid secretion. Our data suggest that lithium appears to act centrally to modulate gastric acid secretion in rats through a mechanism involving the synthesis of prostaglandinlike material(s) in the brain. Furthermore, the effect of centrally administered lithium is independent of stimulation of opiate receptor(s) in the brain.     

Treatment with monocyte-derived partially purified GM-CSF but not G-CSF aborts the development of transplanted chloroleukemia in rats

We have previously demonstrated that cultured rat chloroleukemia cells, MIA C51, will terminally differentiate to macrophages when treated with rat lung-conditioned medium in vitro and in vivo. In the present study we fractionated rat monocyte-conditioned medium by ultrafiltration according to molecular size. The fraction with molecular weight (mol wt) 30 to 50 Kd containing partially purified granulocyte-macrophage colony-stimulating factor (GM-CSF) activity caused the differentiation of C51 cells to macrophages in vitro and in diffusion chambers in vivo. Treatment of young rats with this fraction aborted the development of chloroleukemia from transplanted C51 cells. In contrast, the fraction with mol wt 10 to 30 Kd containing virtually all the G-CSF activity exhibited no differentiation activity either in vitro or in vivo. It is concluded that in this rat myelogenous leukemia model partially purified GM-CSF but not G-CSF contains the effector molecule(s) causing terminal differentiation of C51 cells and tumor cell rejection.