Prospective One Year Follow Up of HIV Infected Women Screened for Cervical Cancer Using Visual Inspection with Acetic Acid,Cytology and Human Papillomavirus Testing in Johannesburg South Africa

Background

Cervical cancer is the most common cancer in Sub-Saharan Africa. There are little of HIV-infected women one-year after screening using visual inspection with acetic acid (VIA), HPV or cytology in sub-Saharan Africa.

Methods

HIV-infected women in Johannesburg South Africa were screened one year later by Pap smear, VIA and human papillomavirus (HPV) testing. Women qualified for the 12 month follow-up visit if they had a negative or cervical intra-epithelial neoplasia (CIN) 1 results at the baseline visit. Modified Poisson regression was used to analyse associations between patient baseline characteristics and progression.

Results

A total of 688 of 1,202 enrolled at baseline study who were CIN-2+ negative and qualified for a 12 month follow-up visit. Progression to CIN-2+ was higher in women with positive VIA results (12.6%; 24/191) than those VIA-negative (4.4%; 19/432). HPV-positive women at baseline were more likely to progress to CIN-2+ (12.3%; 36/293) than those HPV-negative (2.1%; 7/329). Cytology-positive women at baseline were more likely to progress to CIN-2+ (9.6%; 37/384) than cytology-negative women (2.5%; 6/237). Approximately 10% (10.4%; 39/376) of women with CIN 1 at baseline progressed to CIN 2+. Women who were VIA or HPV positive at baseline were more likely to progress aIRR 1.85, CI 95% (1.46 to 2.36), aIRR 1.41 CI 95% (1.14 to 1.75) respectively.

Conclusion

Progression to CIN-2+ in HIV-infected women is significant when measured by baseline positive VIA, HPV or Pap and yearly screening by any method should be considered in this population if possible.     

In vitro production of cytokines is influenced by sulfatide and its precursor galactosylceramide.

Effects of sulfatide and its precursor galactosylceramide (gal-cer) on the kinetics of production of cytokines were studied. In human mononuclear leucocytes, gal-cer but not sulfatide induced significantly increased amounts of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF) mRNA. In phytohemagglutinin-stimulated cultures, gal-cer increased the levels of IL-1beta and IL-6 mRNA and secreted IL-1beta and IL-6, while sulfatide decreased the amounts of IL-6 mRNA and secreted IL-6. Gal-cer also increased TNF secretion. In lipopolysaccharide-stimulated cells, sulfatide but not gal-cer decreased the secretion of IL-1beta and IL-10, a potent suppressor of production of many cytokines. Thus, sulfatide and gal-cer affect cytokine production differently, most likely at the level of gene expression. This may have implications in diseases where inflammatory cytokines play a pathogenic role.     

Associations of Fat Distribution and Obesity with Hypertension in a Bi‐ethnic Population: The ARIC Study

Objective: To examine associations of hypertension with obesity and fat distribution among African American and white men and women. Research Methods and Procedures: The analysis sample included 15,063 African American and white men and women between the ages of 45 and 64 years who were participants in the 1987 through 1989 examination of the Atherosclerosis Risk in Communities Study (ARIC). Odds ratios and adjusted prevalences of hypertension were calculated across sexspecific quintiles of body mass index (BMI), waist‐to‐hip ratio (WHR), waist circumference, and waist‐to‐height ratio (waist/height) and adjusted for age, research center, smoking, education, physical activity, alcohol consumption, hormone replacement therapy, and menopausal status. Results: The prevalence of hypertension was higher among African Americans than whites. In the lowest quintile of BMI, 41% of African American women and 43% of African American men had hypertension compared with 14% of white women and 19% of white men. Elevated BMI, WHR, waist circumference, and waist/height were associated with increased odds of hypertension in African American and white men and women. In women, but not in men, there were significant interactions between ethnicity and the anthropometric variables studied here. The direction of the interaction indicated larger odds ratios for hypertension with increasing levels of anthropometric indices in white compared with African American women. Discussion: Obesity and abdominal fat preponderance were associated with increased prevalence of hypertension in African American and white men and women. Associations were similar among African American and white men, but obesity and fat patterning were less strongly associated with hypertension in African American than in white women.     

Gangliosides in serum immune complexes from tumor-bearing patients

Immune complexes in the serum of tumor-bearing patients were adsorbed from whole blood or plasma on a protein A-Sepharose column. The adsorbed material was eluted, precipitated and analyzed for gangliosides. All precipitates obtained from eight patients at different treatment occasions contained gangliosides at concentrations varying from 0.1 to 12.2 nmol sialic acid/mg protein. The compositions of gangliosides were similar among the patients, regardless of the type of cancer, and quite different from that of normal serum. Most (75-85% of total sialic acid) belonged to the gangliotetraose series, of which 26-33% was GM1, 26-34% GD1a, 8-17% GD1b, and 5-13% GT1b. However, the dominant ganglioside in normal serum, GM3, was present in only trace amounts, which ruled out a nonspecific adsorption of serum ganglioside by protein A-Sepharose. Similar results were obtained for whole blood and plasma treatments, and these results suggest a specific interaction between gangliosides of the gangliotetraose series and serum immunoglobulins, either by the gangliosides acting as antigens and forming immune complexes or by their binding to already formed complexes.     

The effect of ascorbate on embryonic chick sternal chondrocytes cultured in agarose

Primary cultures of embryonic chick sternal chondrocytes were embedded in a three-dimensional matrix of 1% solid agarose which was overlaid with nutrient media. The chondrocytes divided and formed nests of spherically shaped cells which were surrounded by an extensive extracellular matrix containing high molecular weight proteoglycans. Using light and electron microscopy, condensation of proteoglycan was observed pericellularly, often forming septa between cells of a nest, and as part of the outer boundary of the cell nest. No cross-striated collagen fibers were observed in the extracellular matrix although proteoglycan appeared to decorate a network of fine strands. Upon the addition of ascorbate to the nutrient media high molecular weight proteoglycans were synthesized, but there was a marked decrease in the synthesis of proteoglycans after a 10 day exposure to ascorbate. Morphologically, the decrease in proteoglycan synthesis was manifested in the discontinuous arrangement of the pericellular matrix as well as the diffuse form of the cell-nest boundary. Both of these structures were clearly defined in control cultures and were enriched in proteoglycan as demonstrated by ruthenium red staining. This study demonstrates that embryonic chondrocytes remain differentiated when cultured in solid agarose for a period of up to 15 days. They continue to synthesize their tissue specific macromolecules and are phenotypically stable when exposed to ascorbate for extended periods of time.     

Basic fibroblast growth factor and epidermal growth factor downmodulate the growth of hematopoietic cells in long-term stromal cultures

The bone marrow microenvironment consists of stromal cells and extracellular matrix components which act in concert to regulate the growth and differentiation of hematopoietic stem cells. There is little understanding of the mechanisms which modulate the regulatory role of stromal cells. This study examined the hypothesis that mesenchymal growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) modulate stromal cell activities and thereby influence the course of hematopoiesis. Both bFGF and EGF were potent mitogens for marrow stroma. However, both factors proved to be inhibitory to hematopoiesis in primary log-term marrow cultures. Inhibition was also observed when hematopoietic cells and bFGF or EGF were added to subconfluent irradiated stromal layers, demonstrating that the decline of hematopoiesis was not due to overgrowth of the stromal layer. Loss of hematopoietic support in bFGF and EGF was dose-dependent. Removal of bFGF and EGF permitted stromal layers to regain their normal capacity to support hematopoiesis. In stroma-free long-term cultures, neither factor affected CFU-GM expansion. Basic FGF slightly enhanced granulocyte-macrophage colony forming unit (CFU-GM) cloning efficiency in short-term agarose culture. Basic FGF did not reduce the levels of interleukin-6 (IL-6), GM-CSF, or G-CSF released by steady state or IL-1-stimulated stroma. Similarly, the constitutive levels of steel factor (SF) mRNA and protein were not affected by bFGF. Basic FGF did not alter the level of TGF-β1 in stromal cultures. We conclude that bFGF and EGF can act as indirect negative modulators of hematopoietic growth in stromal cultures. The actual mediators of regulation, whether bound or soluble, remain to be identified. © 1995 Wiley-Liss, Inc.