Prevalence and correlates of HIV infection among young injection drug users in San Francisco

OBJECTIVE: We assessed the prevalence of HIV infection and associated risk behaviors among street-recruited young injection drug users (IDUs) in San Francisco. METHODS: In a cross-sectional study, 304 young (age <30 years) IDUs with a history of injecting in the previous 30 days were interviewed and tested for antibodies to HIV. Analyses assessing independent associations with HIV infection were limited to males only, due to the low number of infections in women. RESULTS: The prevalence of HIV infection was 5.3% overall but was highly stratified by gender and sexual preference (15.6% among homosexual/bisexual men vs. heterosexual men) and recruitment neighborhood (18% in the Polk Street area). Of 16 HIV infections, 14 (88%) were in males. Factors independently associated with HIV infection in males included sexual preference (homosexual/bisexual vs. heterosexual: adjusted odds ratio [AOR], 7.5; 95% confidence interval [CI], 1.5-36.6), recruitment neighborhood (Polk Street neighborhood vs. other neighborhoods: AOR, 4.8; 95% CI, 1.4-16.7), and duration of residence in San Francisco (>or=1 year vs. <1 year: AOR, 11.8; 95% CI, 1.4-95.8). CONCLUSIONS: The prevalence of HIV infection was highest among male IDUs who have sex with men. The strong associations between HIV infection and sexual orientation and HIV infection and recruitment locale suggest that risk may be attributable largely to sexual risk. In addition to successful prevention efforts aimed at reducing needle-associated risk, current intervention models aimed at young IDUs should target high-risk neighborhoods and emphasize sexual risk reduction measures, in particular among men who have sex with men.     

CXCR4 and CCR5 expression on CD4+ T cells in vivo and HIV-1 antigen beta-chemokine production in vitro after treatment with HIV-1 immunogen (REMUNE)

BACKGROUND: The chemokine receptors CXCR4 and CCR5 have been identified as the major coreceptors for HIV-1 on CD4+ cells and macrophages. The natural ligands for these receptors are SDF-1 and the beta-chemokines (MIP-1alpha, MIP-1beta, RANTES), respectively, and are the products of a variety of immune cells, including CD8+ T lymphocytes. STUDY DESIGN/METHODS: We hypothesized that the ability to stimulate the natural ligands for these receptors using an immune based therapy might influence in vivo chemokine receptor expression. RESULTS: In vivo CXCR4 expression remained stable after treatment with an HIV-1 Immunogen (REMUNE), whereas CCR5 expression on CD4+ T cells decreased (p < .05). Furthermore, HIV-1 antigen-specific production of beta-chemokines in vitro was also augmented (P < .05). CONCLUSIONS: These preliminary results suggest that this HIV-1-specific immune-based therapy can stimulate antigen-specific beta-chemokine production in vitro and downregulate CCR5 receptor expression on CD4 cells in vivo.     

Eosinophil granule lysis in vitro induced by soluble antigen antibody complexes

A simple test system is described, for the demonstration of antigen—antibody reactions capable of causing eosinophil granule lysis in vitro. The antigen preparations used were extracts of the nematode Amplicaecum robertsi and body fluid of Ascaris suum. Antisera were obtained from rats infested with Amplicaecum. Eosinophils were obtained from the peritoneal cavity of normal rats. Centrifugation of the cells to form a cell button was an essential step in the procedure. Lysis of eosinophils occurred with antiserum obtained from the animals between the 12th and 32nd days of infestation with Amplicaecum, and was accompanied by vacuole formation in macrophages and mast cell disruption. The reaction was most pronounced during the 3rd week. Serum from adrenalectomized infested animals caused the most marked changes in eosinophils. Serum from cortisonetreated infested animals failed to cause eosinophil changes.

Attempts at purification of the antigen in Ascaris body fluid resulted in two fractions with marked activity in the test system. The same two fractions were found to form precipitin lines on agarose gel diffusion against rat antiserum.

It is postulated that antigen—antibody complexes soluble in low concentration were responsible for the changes observed in the eosinophils, macrophages and mast cells. One or more labile factors in the serum were found to be necessary for eosinophil granule lysis. The evidence, though incomplete, would favour the suggestion that both labile antibody and complement were necessary.

     

Observer variability in the histopathological reporting of abnormal rectal biopsy specimens.

AIMS--To study the consistency of reporting of abnormal rectal biopsy specimens, especially in the differentiation of inflammatory bowel disease from other causes of abnormality. METHODS--Sixty rectal biopsy specimens were identified from patients presenting with bloody diarrhoea. These were then circulated to the 11 consultant pathologists in the study who filled in a proforma with a list of 12 diagnostic categories and 22 features. RESULTS--Forty one of the 60 cases were examples of inflammatory bowel disease. In 33 of these cases nine or more pathologists had made the diagnosis. Further categorisation into ulcerative colitis and Crohn''s disease showed better recognition of ulcerative colitis. In the 19 cases of non-inflammatory bowel disease recognition of pseudomembranous colitis and solitary rectal ulcer syndrome was good, but the results were poorer in the case of infective colitis. CONCLUSION--The findings suggest that a group of consultant pathologists can differentiate between inflammatory bowel disease and other causes of an abnormal rectal biopsy specimen and can also recognise pseudomembranous colitis and solitary rectal ulcer syndrome satisfactorily.     

Discrimination of human pathogenic subspecies of Francisella tularensis by using restriction fragment length polymorphism

We describe the use of two insertion sequence elements (ISFtu1 and ISFtu2) in Francisella tularensis to type strains by restriction fragment length polymorphism (RFLP). The RFLP profiles of 17 epidemiologically unrelated isolates were determined and compared. Our results showed that RFLP profiles can be used to assign F. tularensis strains into five main groups corresponding to strains of F. tularensis subsp. tularensis, F. tularensis strain ATCC 6223, strains of F. tularensis subsp. holarctica, strains of F. tularensis subsp. holarctica from Japan, and F. tularensis subsp. mediaasiatica. The results confirm the genetic identities of these subspecies and also support the suggestion that strains of F. tularensis subsp. holarctica from Japan should be considered members of a separate biovar. These findings should support future studies to determine the genetic differences between strains of F. tularensis at the whole-genome level.     

Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera: the Trimera system.

An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested.     

Light and Electron Microscopic Study of an Invasive Cribriform Carcinoma with Extensive Microcalcification Developing in a Breast with Silicone Augmentation

Although recent epidemiologic studies suggest that silicone augmentation of the breast is not associated with an increased risk of mammary carcinoma, cases of breast carcinoma arising in augmented breasts are being increasingly encountered as a large number of patients who had augmentation are getting older. A case of a 51-year-old woman with a 20-year history of breast augmentation who developed an invasive cribriform carcinoma associated with extensive microcalcification is presented. The patient had submammary silicone implants 20 years ago that were replaced, because of local complications, in subpectoral positions 10 years later. Dispersive X-ray microanalysis failed to demonstrate silicone in sections of the tumor and adjacent breast tissue. Appropriately fixed tumor tissue was available for electron microscopic examination. The tumor cells were rich in mitochondria, and their luminal surfaces were endowed with abundant microvilli, but the cell surfaces that came closest to the calcified microspheriols were devoid of microvilli and had cellular buddings between the microspheriols. It is suggested that the tumor cells might have been actively involved in the process of microcalcification.     

Correlation of lysosomal enzyme abnormalities in various forms of adult leukaemia

Lysosomal enzyme activities were studied in cells derived from the following types of leukaemia: chronic myeloid, acute myeloid, acute myelomonocytic, acute monocytic, non-T, non-B cell acute lymphoblastic, T-cell acute lymphoblastic, B-cell chronic lymphocytic and T-cell chronic lymphocytic. Activities of beta-hexosaminidase and alpha-mannosidase were significantly higher in cells from acute monocytic and acute myelomonocytic leukaemias, and somewhat higher in the other myeloid leukaemias, when compared with control granulocytes. Activities of beta-hexosaminidase, alpha-mannosidase, alpha-fucosidase, beta-glucuronidase and acid phosphatase were markedly lower in B cells of chronic lymphocytic leukaemia when compared with control or other leukaemic lymphoid cells. On isoelectric focusing abnormal patterns of beta-hexosaminidase, alpha-mannosidase and beta-glucuronidase activities were commonly found in myeloid and non-T, non-B cell leukaemias. All patients with acute myeloid leukaemia exhibited a relative decrease in the B form of beta-hexosaminidase activity. The results described show that studies on lysosomal enzymes may assist in the classification of different types of leukaemia.     

Comparison of Two Culture Methods for Detection of Tobramycin-Resistant Gram-Negative Organisms in the Sputum of Patients with Cystic Fibrosis

A culture method utilizing quantitative plating on antibiotic-containing media has been proposed as a technique for the detection of tobramycin-resistant organisms that is more sensitive than standard methods. Typical sputum culture methods quantitate the relative amounts of each distinct morphotype, followed by antibiotic susceptibility testing of a single colony of each morphotype. Sputum specimens from 240 cystic fibrosis patients were homogenized, serially diluted, and processed in parallel by the standard method (MacConkey agar and OF basal medium with agar, polymyxin, bacitracin, and lactose) and by plating on antibiotic-containing media (MacConkey agar with tobramycin added at 25 microg/ml [MAC-25] and 100 microg/ml [MAC-100]). MICs of tobramycin were determined for all Pseudomonas aeruginosa isolates by broth microdilution. Growth of P. aeruginosa on MAC-25 was considered to be equivalent to a tobramycin MIC of > or = 16 microg/ml, and growth on MAC-100 was considered to be equivalent to a tobramycin MIC of > or = 128 microg/ml. Analysis of method-specific detection rates showed that tobramycin-containing medium was more sensitive than the standard method for the detection of tobramycin-resistant P. aeruginosa, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans but was less sensitive for the detection of Burkholderia cepacia than the standard method. When MICs for P. aeruginosa that grew on tobramycin-containing medium were tested by broth microdilution, the MICs for 28 of 121 strains (23%) growing on MAC-25 and 22 of 56 strains (39%) growing on MAC-100 were MICs < 16 and < 128 microg/ml, respectively. Addition of a tobramycin-containing MacConkey plate to the routine media for sputum culture may provide additional, clinically relevant microbiologic data.