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Haiti, one of the world's five poorest nations, gets international attention because of the number of refugees who leave by boat in search of a better future. The 80,000 inhabitants of Ile de la Gonave are neglected, even in Haiti--there is no government medical post, and facilities in the health posts run by missions are minimal. Typhoid and cholera epidemics threaten the island. Médecins Sans Frontières plans to send staff and supplies and train local health workers.
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Immunisation has proved to be a generally safe and effective means of disease control, particularly where environmental approaches are impractical. Recent developments in vaccine production, aimed at selecting or synthesising in pure form the antigens needed to evoke a protective response, give hope of more effective and less toxic vaccines in future. Adequate trials of improved vaccines may, however, be difficult to carry out under modern conditions. Policies for the use of vaccines are sometimes controversial, particularly when there is concern about reactions, as with pertussis vaccine. Acceptance rates for measles and rubella vaccines in the UK have hitherto been disappointingly low and need to be increased if the aims of elimination of measles and congenital rubella are to be achieved. Cost-benefit analyses generally support the use of immunisation in disease control.
BACKGROUND: High-grade serous ovarian cancer (HGSOC) is commonly accompanied by malignant ascites, a clinically relevant tumor niche that promotes immune evasion, metastasis, and treatment resistance. Although natural killer (NK)-cell dysfunction has been described in ovarian cancer, the broader innate lymphoid landscape of ascites and the mechanisms linking ascites-derived signals to innate immune suppression remain insufficiently resolved. METHODS: We performed single-cell RNA sequencing of NK/innate lymphoid cells from ovarian cancer ascites to define cellular heterogeneity and differentiation states. Functional assays assessed NK-cell cytotoxicity, degranulation, and receptor expression following exposure to patient-derived ascites, with or without transforming growth factor-β (TGF-β) receptor inhibition. Proteomic profiling was used to characterize the soluble ascites milieu, and clinical associations were examined for innate lymphoid subsets. RESULTS: Single-cell analysis identified eight transcriptionally distinct NK/innate lymphoid states, including cytotoxic, precursor, early-like, tolerant/immunoregulatory, regulatory, proinflammatory, and innate lymphoid populations. Ovarian cancer ascites was characterized by depletion of cytotoxic and precursor NK-cell states together with enrichment of early-like, tolerant, regulatory, pro-inflammatory, and innate lymphoid cell (ILC) populations. Trajectory analysis indicated impaired maturation toward terminally differentiated cytotoxic NK cells. Notably, ascites contained an expanded population of programmed cell death protein 1 (PD-1)+ ILC2s, which were more abundant in patients with shorter progression-free survival. In functional assays, short-term exposure of healthy donor NK cells to ascites suppressed degranulation and tumor-cell killing, reduced expression of activating receptors including NKp30 and DNAM-1, increased inhibitory receptor expression, and shifted NK cells toward a CD56highCD16low phenotype. Proteomic profiling supported a soluble milieu consistent with type 2 immune skewing and NK-cell suppression. Importantly, TGF-β receptor inhibition partially restored NK-cell activation and function in the presence of ascites. CONCLUSIONS: HGSOC ascites establishes a type 2-skewed immunoregulatory niche that coordinately drives NK cell dysfunction and PD-1+ ILC2 accumulation. The findings identify TGF-β-linked suppression and ascites-associated immune regulators as candidate immunotherapeutic vulnerabilities for restoring antitumor immunity in ovarian cancer.
Four studies reported an increasing incidence of pyloric stenosis during the late 1970s from geographically diverse areas of the United Kingdom. It was suggested that the increased incidence might be related to changes in infant feeding practices. We used data from the Metropolitan Atlanta Congenital Defects Program, a population based birth defects registry, to examine the secular trends and descriptive epidemiology of pyloric stenosis in a North American city. For the period 1968 to 1982, the incidence of pyloric stenosis was 1.33 per 1000 live births; there was no evidence of an increasing trend for either race or sex specific rates of pyloric stenosis. The descriptive epidemiology of the pyloric stenosis cases showed higher rates for males, whites, and infants of higher birth weight. We found no increasing trend in pyloric stenosis incidence in Atlanta, despite well documented changes in US infant feeding practices (an increased prevalence of breast feeding) during the 1970s.
To date, both in Spain and virtually all the other European Union (EU) countries, dependency has been seen to be a fundamentally private problem to be dealt with by the family concerned. In this way, whether through informal carers or contracted professionals, in the domestic environment or in care homes, it is the dependent person themselves and their families who currently bear the majority of the costs. In light of this, current concern lies in the social change that is coming on, mainly the accelerated aging process and the increased participation of middle-aged women in the labour market, which heighten the need for collective organisation of that which until now has been resolved within family circles. In this context, at the same time that the Government announces to issue a < > by the end of 2005, our paper briefly analyzes what we consider the four crucial issues in this area: the current scope of dependency problems and its possible future evolution, the characteristics of the current spanish long-term care system and its main problems; the role that health services should have in the dependency issue; and finally, the benefits and drawbacks of the main alternatives that the Administration could manage in case it intends to increase its involvement in this field.
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The distribution of the ratios of plasma high-density lipoprotein cholesterol (HDL-C) to total cholesterol (TC) and of HDL-C to low-density lipoprotein cholesterol (LDL-C) are presented for 6900 white and 495 black examinees greater than 4 years old. Measurements were obtained during the visit 2 survey of the Lipid Research Clinics (LRC) Program Prevalence Study, and correspond to a 15% random sample of 60,502 participants screened during the LRC visit 1 survey. Age-specific means, medians, and selected percentiles are given by sex and by gonadal hormone use in white women. Apparent in these cross-sectional data was a consistent age-related decline in the ratio of HDL-C to TC for white male participants, from a mean of 0.360 in the age group 5 to 9 to a mean of 0.211 in the age group 50 to 54. Thereafter the mean ratio increased slightly. In white women not using gonadal hormones the age-related decline in the ratio was only evident starting at the age group 35 to 39, from which it declines from 0.329 to 0.258 in the age group 55 to 59. White women using gonadal hormones showed very minor age-related changes in the HDL-C/TC ratio, varying around a mean of 0.300. The number of blacks examined was low and thus the racial comparisons must be interpreted with caution. For each gender, age-related trends were similar in black and white study participants. Black men, however, had a higher percentage of TC carried as HDL-C than white men in all age groups examined. Black women had a higher percentage of TC in HDL-C than white women only below age 20; in the adult age range no appreciable differences were seen. Pearson correlation coefficients between the lipid, lipoprotein, and lipoprotein ratios are presented. The ratio HDL-C/TC correlated highly with the ratio HDL-C/LDL-C (greater than 0.92 for all groups) and the former may be a more conveniently determined surrogate for the latter. Although not exhaustive regarding the information it conveys about a lipid pattern, the ratio HDL-C/TC has the advantage of summarizing complex associations into a single numerical approximation.
BACKGROUND: Antibodies to endothelial cells (aECs) and to cardiolipin (aCLs) are implicated in autoimmune diseases like systemic lupus erythematosus vasculitis. Beta2-Glycoprotein 1 (beta2GP1) is a cofactor for aCLs. The present study investigated the possible role of aECs, aCLs, and abeta2GP1 in borderline hypertension. METHODS AND RESULTS: Seventy-three men with borderline hypertension (BHT) and 73 age-matched normotensive (NT) men (diastolic blood pressure, 85 to 94 and <80 mm Hg, respectively) were recruited from a population screening program. Antibody levels were determined by ELISA. Presence of carotid atherosclerosis was determined by B-mode ultrasonography, and 29 individuals had atherosclerotic plaques. BHT men had significantly higher aEC and abeta2GP1 levels of IgG class than NT control subjects (P=0.029 and P=0.0001, respectively). aEC levels of IgM class were higher in BHT (P=0.012), but not abeta2GP1 levels. There was no correlation between aCL levels and BHT. Individuals with atherosclerotic plaques had significantly higher aEC levels of both IgG (P=0.042) and IgM subclasses (P=0.018) than those without plaques, but no difference was found in aCL and abeta2GP1 levels. Endothelin and aECs of IgM class were significantly associated. CONCLUSIONS: We demonstrate the first evidence of a significant elevation of aEC and abeta2GP1 levels in borderline hypertension. These findings provide a new link between hypertension and atherosclerosis and indicate that humoral immune reactions to the endothelium may play an important role in both conditions.
Heat-shock proteins protect cells from damage but are also often the target of immune responses in inflammation and may therefore both induce and perpetuate the chronic inflammation characterizing atherosclerosis. Hypertension is a well-established risk factor for atherosclerosis, and recently, borderline hypertension also has been related to atherosclerosis. The present study investigated the possible role of heat-shock proteins in borderline hypertension and their relation to atherosclerosis by investigating antibody titers against the 65-kD heat-shock protein (HSP65). Sixty-six men with borderline hypertension and 67 age-matched normotensive men (diastolic pressure, 85 to 94 and < 80 mm Hg, respectively) were recruited from a population screening program. Titers of antibodies to HSP65 were determined by enzyme-linked immunosorbent assay. The presence of carotid atherosclerosis was determined by B-mode ultrasonography. Twenty-seven individuals had atherosclerotic plaques: 48 were smokers (more than one to two cigarettes per day). Borderline hypertensive men had higher anti-HSP65 reactivity than normotensive control subjects (P = .034). Smokers with atherosclerosis had low levels of antibodies to HSP65 compared with nonsmokers with atherosclerosis (P = .002). Furthermore, when high-risk individuals (borderline hypertension plus plaque, n = 15) were compared with matched low-risk individuals (normotensive with no plaque, n = 15), the high-risk men had significantly enhanced antibody titers to HSP65 (P = .041). In conclusion, we demonstrate that serum antibody titers to HSP65 are enhanced in individuals with borderline hypertension, which may indicate an ongoing immune reaction in the artery wall.
The phylogenetically conserved nature of heat shock proteins (Hsp) has led to the proposition that they may provide a link between infection and the inflammatory component to vascular disease. Hypertension is associated with atherosclerosis. Here, we measured circulating heat shock protein and heat shock protein antibody levels in association with borderline hypertension. Seventy-two men with borderline hypertension patients and 75 normotensive control subjects (diastolic blood pressure 85 to 94 and <80 mm Hg, respectively) were selected from a population-screening program. The levels of Hsp60; Hsp70; and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibodies were determined with enzyme immunoassay. The presence of carotid atherosclerosis and the intima-media thickness values were determined with ultrasonography. A major novel observation in this report was the detection of circulating Hsp60, which was present at a significantly enhanced level in patients with borderline hypertension. Furthermore, serum Hsp60 was associated with intima-media thicknesses (P<0.01). Anti-Hsp65 antibody levels were higher in borderline hypertension (P<0.001), whereas Hsp70 and anti-Hsp70 antibody levels did not differ. In contrast to anti-Hsp65 antibody, anti-Hsp60 antibody levels were lower in borderline hypertension (P<0.03), although the difference was quantitatively small. None of the parameters evaluated were associated with atherosclerosis, metabolic factors, or smoking. We identified elevated Hsp60 levels in patients with borderline hypertension and an association between early atherosclerosis and Hsp60 levels. The physiological role of Hsp60 release has yet to be defined, but given the proinflammatory properties, these proteins could be involved in the induction/progression of both hypertension and atherosclerosis, as well as being markers for early cardiovascular disease.
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Clinical practice in health maintenance organizations (HMOs) currently has many of the features that will become increasingly common in the managed-care environment in which mental health treatment will be provided in the 1990s. HMO policies calling for cost containment, attention to outcomes, practice audits, and treatment guidelines create distinctive demands on clinicians regarding their focus of attention, clinical stance, and professional role. The author identifies six crucial skills that can help clinicians meet these demands effectively: population-oriented practice management, population-oriented program development, ability to apply an adult developmental model, command of a broad repertoire of methodologies, ethical analysis, and advocacy. He uses brief case examples to illustrate how these skills may be used in managed-care settings.
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Numerous problem areas were encountered in the evaluation of a voluntary second surgical opinion program. Some problems could be handled only on a conceptual level, while others require for their solution the integration of existing with new data sets. (1) Reliance on program participants to provide medical data was sensitivity tested and found to have minimal impact. (2) Program impact on hospital bed reduction was considered in the context of the total market and political environment in the region, and the anticipated duration of the program. A reasonable judgment was that almost the entire fixed component in the per diem cost of anticipated patient days foregone could be written off as part of the cost savings of the program. (3) As hospital reporting systems identify only average per diem costs, a methodology was developed to separate surgical from nonsurgical case costs. (4) Quality of care evaluation will incorporate a substratum of cases for which there exists a control group within the program user population. Outcome measures obtainable through survey interviews were identified.
Seasonal migration to national amenity areas is a major form of cyclical migration in the United States. This article examines conditions under which seasonal movement serves as a substitute for, or precursor to, permanent migration among winter visitors to recreational vehicle (RV) parks in the Phoenix, Arizona area. Ties to the home community, ties to the seasonal residence, demographic characteristics, and commitment to a mobile lifestyle are specified as determinants of expectations of moving to Phoenix on a permanent basis. The model is tested using survey data for a sample of 1,001 winter visitors in Phoenix RV parks. Results of a discriminant analysis indicate that place ties and position in the life cycle condition expectations of permanently migrating to a seasonal residence.