Situating experiences of HIV-related stigma in Swaziland.

With the world's highest antenatal HIV prevalence rate (39.2%), Swaziland has also been described as among the most stigmatising. Yet, only recently was an anti-HIV stigma and discrimination (S&D) platform included in the government's National Multisectoral HIV and AIDS Policy. This study draws on a medical anthropological project in rural Swaziland to examine experiences of stigma among people living with HIV/AIDS (PLWH). Qualitative methods included a semi-structured questionnaire and interviews (n=40) to identify patterns of stigma across three domains: verbal, physical and social. Key informant interviews (n=5) were conducted with health personnel and support group leaders. Descriptive statistics were situated within a thematic analysis of open-ended content. Among the findings, participants reported extensive HIV-related rumouring (36.4%) and pejorative name-calling (37.5%). Nearly one in five (18.2%) could no longer partake of family meals. Homesteads, which are an organising principle of Swazi life, were often markedly stigmatising environments. In contrast to documented discrimination in health care settings, the health centre emerged as a space where PLWH could share information and support. Given the UNAIDS call for national partners to 'know your epidemic' by tracking the prevalence of HIV-related S&D, results from this study suggested that unless 'knowing your epidemic' includes the lived experiences of HIV stigma that blister into discernible patterns, effectiveness of national initiatives is likely to be limited. Multidisciplinary and locale-specific studies are especially well suited in examining the cultural dynamics of HIV stigma and in providing grounded data that deepen the impact of comprehensive HIV/AIDS policies and programming.

The etiology of community-acquired pneumonia at an urban public hospital: influence of human immunodeficiency virus infection and initial severity of illness.

In a prospective study, the etiology of community-acquired pneumonia (CAP) was investigated among consecutive patients admitted to an academic, urban public hospital in Seattle. The study population was uniquely young, was predominantly male, and had high rates of homelessness, cigarette smoking, alcoholism, injection drug use, and human immunodeficiency virus (HIV) infection. Leading causes of CAP among HIV-negative patients were aspiration, followed by Streptococcus pneumoniae, Legionella species, and Mycoplasma pneumoniae. Among HIV-positive patients, Pneumocystis carinii, Mycobacterium tuberculosis, S. pneumoniae, and M. pneumoniae were the most common etiologic agents. Severe CAP was associated with typical bacterial infections and aspiration pneumonia but not Legionella infection among HIV-negative patients and with Pseudomonas aeruginosa infections among HIV-positive patients. These findings emphasize the need to tailor empirical antibiotic therapy according to local patient populations and individual risk factors and highlight the importance of recognizing underlying HIV infection in patients who are hospitalized with CAP.

Practices of the pregnant self: compliance with and resistance to prenatal norms.

A major challenge of medical anthropology is to assess how biomedicine, as a vaguely-defined set of diverse texts, technologies, and practitioners, shapes the experience of self and body. Through narrative analyses of in-depth, semi-structured interviews with 158 pregnant women in southern California, this paper explores how the culture of biomedicine, encountered formally at prenatal care check-ups and informally through diverse media, influences pregnant women's perceptions of appropriate prenatal behavior. In the spirit of recent social scientific work that draws on and challenges Foucauldian insights to explore social relations in medicine, we posit a spectrum of compliance and resistance to biomedical norms upon which individual prenatal practices are assessed. We suggest that pregnancy is, above all, characterized by a split subjectivity in which women straddle the authoritative and the subjugated, the objective and the subjective, and the haptic as well as the optic, in telling and often strategic ways. In so doing, we identify the intersection between the disciplinary practices of biomedicine and the practices of pregnant women as a means of furnishing more fruitful insights into the oft-used term "power" and its roles in constituting social relations in medicine.

Lead loading of urban streets by motor vehicle wheel weights.

This study documents that lead weights, which are used to balance motor vehicle wheels, are lost and deposited in urban streets, that they accumulate along the outer curb, and that they are rapidly abraded and ground into tiny pieces by vehicle traffic. The lead is so soft that half the lead deposited in the street is no longer visible after little more than 1 week. This lead loading of urban streets by motor vehicle wheel weights is continuous, significant, and widespread, and is potentially a major source of human lead exposure because the lead is concentrated along the outer curb where pedestrians are likely to step. Lead deposition at one intersection in Albuquerque, New Mexico, ranged from 50 to 70 kg/km/year (almost 11 g/ft(2)/year along the outer curb), a mass loading rate that, if accumulated for a year, would exceed federal lead hazard guidelines more than 10,000 times. Lead loading of major Albuquerque thoroughfares is estimated to be 3,730 kg/year. Wheel weight lead may be dispersed as fugitive dust, flushed periodically by storm water into nearby waterways and aquatic ecosystems, or may adhere to the shoes of pedestrians or the feet of pets, where it can be tracked into the home. I propose that lead from wheel weights contributes to the lead burden of urban populations.

A randomized controlled trial of filgrastim for the treatment of hospitalized patients with multilobar pneumonia.

This study assessed the safety and efficacy of filgrastim (r-metHuG-CSF [recombinant human methionine granulocyte colony-stimulating factor]), when combined with intravenous (IV) antibiotics, in the treatment of hospitalized adult patients with multilobar community-acquired pneumonia (CAP). Four hundred eighty patients were randomized to receive placebo (n=243) or filgrastim 300 microg/day (n=237), in addition to standard therapy. Treatment with study drug was continued for 10 days, until the peak white blood cell (WBC) count reached 75x109/L, until discharge from the hospital, until death, or until IV antibiotics were discontinued. Study-related observations continued through day 29. Filgrastim increased WBC counts (baseline median, 13.3x109/L; median peak, 43. 8x109/L). The 2 treatment groups were not statistically different with respect to the study end points; however, there was a trend toward reduction of mortality in patients with pneumococcal bacteremia. Although further studies will be required to validate this observation, filgrastim was safe and well tolerated when administered to patients with multilobar CAP.

Modulation of neutrophil-mediated activity against the pseudohyphal form of Candida albicans by granulocyte colony-stimulating factor (G-CSF) administered in vivo.

Renewed interest in neutrophil transfusions has emerged with the development and clinical use of granulocyte colony-stimulating factor (G-CSF). G-CSF not only increases neutrophil (polymorphonuclear leukocyte, PMNL) production but also modulates various physiological properties of PMNL. The effects of G-CSF on PMNL-mediated fungicidal activity were evaluated by administration of G-CSF (300 micrograms/day subcutaneously) to 5 healthy volunteers for 6 days. G-CSF significantly enhanced PMNL-mediated damage of Candida albicans pseudohyphae by 33% (P=.007) on day 2 and by 44% (P=.04) on day 6 at a 10:1 effector:target ratio. In contrast, the ability of PMNL to induce damage of hyphae from either Fusarium solani or Aspergillus fumigatus did not significantly change during the study period. These data demonstrate that G-CSF administered in vivo modulates PMNL-mediated fungicidal activity against the pseudohyphal form of C. albicans, thereby suggesting potential utility of G-CSF as a biologic response-modifying therapy in some opportunistic fungal infections.

Comparison of interferon-gamma, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor for priming leukocyte-mediated hyphal damage of opportunistic fungal pathogens.

Proinflammatory cytokines have been proposed as adjunctive therapeutic agents to enhance the host immune response during infections caused by opportunistic fungi. The study compared the differential in vitro priming effects of interferon-gamma (IFN-gamma), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on hyphal damage of opportunistic fungi mediated by isolated neutrophils (polymorphonuclear leukocytes, PMNL) and buffy coat cells (polymorphonuclear leukocytes/peripheral blood mononuclear cells, PMNL/PBMC) from healthy donors. IFN-gamma (1000 U/mL) effectively primed both PMNL and PMNL/PBMC for enhanced hyphal damage of Aspergillus fumigatus, Fusarium solani, and Candida albicans. G-CSF (100 ng/mL) increased hyphal damage mediated by both PMNL and PMNL/PBMC against F. solani, and GM-CSF (100 ng/mL) augmented the antifungal activity of PMNL/PBMC against hyphal forms of both F. solani and C. albicans. IFN-gamma may be superior to G-CSF or GM-CSF for enhancing the microbicidal activity of PMNL and PMNL/PBMC against opportunistic fungi.

Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance the antimicrobial functions of mature neutrophils. G-CSF differs from GM-CSF in its specificity of action on developing and mature neutrophils, its effects on neutrophil kinetics, and its toxicity profile. The toxicity profile of recombinant (r) GM-CSF is consistent with priming of macrophages for increased formation and release of inflammatory cytokines, whereas rG-CSF induces production of antiinflammatory factors, such as interleukin-1 receptor antagonist and soluble tumor necrosis factor receptors, and is protective against endotoxin- and sepsis-induced organ injury. The low toxicity of rG-CSF, results of animal models of infection, and extensive experience with neutropenic subjects have promoted clinical studies in nonneutropenic subjects, which indicate that rG-CSF may be beneficial as adjunctive therapy for treatment of serious bacterial and opportunistic fungal infections in nonneutropenic patients, including those with alterations in neutrophil function.

Teaching compassion and respect. Attending physicians' responses to problematic behaviors.

OBJECTIVE: To describe how and why attending physicians respond to learner behaviors that indicate negative attitudes toward patients. SETTING: Inpatient general internal medicine service of a university-affiliated public hospital. PARTICIPANTS: Four ward teams, each including an attending physician, a senior medicine resident, two interns, and up to three medical students. DESIGN: Teams were studied using participant observation of rounds (160 hours); in-depth semistructured interviews (n = 23); a structured task involving thinking aloud (n = 4, attending physicians); and patient chart review. Codes, themes, and hypotheses were identified from transcripts and field notes, and iteratively tested by blinded within-case and cross-case comparisons. MAIN RESULTS: Attending physicians identified three categories of potentially problematic behaviors: showing disrespect for patients, cutting corners, and outright hostility or rudeness. Attending physicians were rarely observed to respond to these problematic behaviors. When they did, they favored passive nonverbal gestures such as rigid posture, failing to smile, or remaining silent. Verbal responses included three techniques that avoided blaming learners: humor, referring to learners' self-interest, and medicalizing interpersonal issues. Attending physicians did not explicitly discuss attitudes, refer to moral or professional norms, "lay down the law," or call attention to their modeling, and rarely gave behavior-specific feedback. Reasons for not responding included lack of opportunity to observe interactions, sympathy for learner stress, and the unpleasantness, perceived ineffectiveness, and lack of professional reward for giving negative feedback. CONCLUSIONS: Because of uncertainty about appropriateness and effectiveness, attending physicians were reluctant to respond to perceived disrespect, uncaring, or hostility toward patients by members of their medical team. They tended to avoid, rationalize, or medicalize these behaviors, and to respond in ways that avoided moral language, did not address underlying attitudes, and left room for face-saving reinterpretations. Although these oblique techniques are sympathetically motivated, learners in stressful clinical environments may misinterpret, undervalue, or entirely fail to notice such subtle feedback.

A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group.

Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia. To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients. Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events. Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected. Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation). Filgrastim administration was safe and well tolerated in these patients. Additional trials are needed to establish the value of this approach to treatment of infectious diseases.

Complement factor H or a related protein is a marker for transitional cell cancer of the bladder.

The BTAstat and BTA TRAK tests are new immunoassays that detect and measure an antigen in the urine of individuals diagnosed with bladder cancer. As described in this report, the monoclonal antibodies used in these kits were developed by immunizing mice with partially purified protein preparations derived from the urine of patients with bladder cancer. The antigen that is recognized by the monoclonal antibodies was purified from the urine of bladder cancer patients by immunoaffinity chromatography and identified as being either complement factor H (FH) or a closely related protein (CFHrp) by partial amino acid sequence analysis. Like serum FH, the urine antigen was demonstrated to have a complement factor C3b binding site and to accelerate the degradation of C3b in the presence of complement factor I. The culture supernatants from several human bladder, cervical, and renal cancer cell lines contained antigen as determined by immunoassay, and antigen affinity-purified from HeLaS3 culture media was shown to have FH activity. Moreover, the cell lines were shown to make products of the expected sizes by reverse transcription-PCR using FH-specific primers. In contrast, normal human epithelial keratinocytes, a myeloid leukemia cell line, and the colon cancer line LS174T were negative for production of a FH-like protein (CFHrp). We propose that the expression of proteins with FH-like activities may confer a selective growth advantage to cancer cells in vivo by decreasing complement activity, thus aiding their escape from lysis by immune surveillance. Identification of these proteins as cancer products also suggests avenues of chemotherapy or immunotherapy of some cancers.

Bartonella (Rochalimaea) quintana bacteremia in inner-city patients with chronic alcoholism.

BACKGROUND: Bartonella (Rochalimaea) quintana is a fastidious gram-negative bacterium known to cause trench fever, cutaneous bacillary angiomatosis, and endocarditis. Between January and June 1993 in Seattle, we isolated B. quintana from 34 blood cultures obtained from 10 patients not known to be infected with the human immunodeficiency virus (HIV). METHODS: After identifying the isolates as B. quintana by direct immunofluorescence and DNA-hybridization studies, we determined strain hybridization with studies of restriction-fragment-length polymorphisms (RFLPs) of the intergenic spacer (noncoding) region of ribosomal DNA amplified by the polymerase chain reaction (PCR). To characterize the epidemiologic and clinical features of bartonella infections in these patients, we performed a retrospective case-control study using as controls 20 patients with blood cultures obtained at approximately the same time as those obtained from the index patients. RESULTS: B. quintana isolates from the 10 patients were indistinguishable by PCR-RFLP typing. All 10 patients had chronic alcoholism, and 8 were homeless (P = 0.001 for both comparisons with controls). The six patients who underwent HIV testing were seronegative. At the time of their initial presentation, seven patients had temperatures of at least 38.5 degrees C. Six patients had three or more blood cultures that were positive for B. quintana, and in four of these patients B. quintana was isolated from blood cultures obtained 10 or more days apart. Subacute endocarditis developed in two patients and required surgical removal of the infected aortic valve in one of them. Nine patients recovered; one died of sepsis from Streptococcus pneumoniae infection. CONCLUSIONS: B. quintana is a cause of fever, bacteremia, and endocarditis in HIV-seronegative, homeless, inner-city patients with chronic alcoholism.

Respiratory syncytial virus infections on an adult medical ward.

Eleven cases of respiratory syncytial virus (RSV) infection occurred in acutely ill hospitalized adults over a 7-week period. Nosocomial illness was suspected in two patients. Because RSV can cause serious infections in immunocompromised adults with the potential for nosocomial spread, the following recommendations are indicated: (1) during the winter months, early recognition and diagnosis of RSV infections both in hospital staff and in patients should be encouraged; (2) infected hospital personnel should avoid patient contact when possible; (3) during outbreaks, careful attention must be paid to hand washing and gloving; and (4) a high level of vigilance for RSV infection should be maintained on units with immunocompromised patients. Increased awareness of the potential risks of RSV infection is needed on adult medical units.

Leukocyte adhesion proteins: their role in neutrophil function.

In conclusion, the leukocyte proteins of the CD11/18 complex are highly conserved members of the integrin family in mammalian species. They play a key role in phagocytic and adherence mediated activities of neutrophils and appear to be centrally involved in adhesion to endothelial cells as well as transendothelial migration. Their importance in these processes has been documented by the occurrence of the disease now called leukocyte adhesion deficiency and the functional effects of a variety of monoclonal antibodies directed at different epitopes on the heterodimeric glycoprotein chains. These antibodies, as well as those directed at endothelial cell ligands for leukocyte adhesion proteins or peptides which mimic the functional epitopes, offer opportunities to manipulate or modify the inflammatory response in vivo where neutrophil accumulation or action can be harmful. They can also be employed to dissect out the role of PMNs in various repair processes such as wound healing. While bone marrow transplantation can ameliorate the deleterious consequences of severe LAD, continued elucidation of the multiple molecular mechanisms responsible for this disease will pave the way for its future genetic correction.