Plasma glutathione peroxidase deficiency and platelet insensitivity to nitric oxide in children with familial stroke.
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In a previous report by Freedman et al (J Clin Invest. 1996;97:979-987), plasma from 2 brothers with stroke or transient ischemic attack inactivated the antiplatelet effects of nitric oxide (NO), and this effect was found to be a consequence of a deficiency of plasma glutathione peroxidase (GSH-Px). In this study, we attempted to define the generalizability of this deficiency by studying NO-mediated antiplatelet effects in 7 families with familial childhood stroke. Seven families with familial childhood stroke that consecutively presented to a large referral center were included in the study. We monitored ADP-induced aggregation of normal gel-filtered platelets (GFP) in platelet-poor plasma (PPP) from normal individuals and from patients in the presence or absence of an NO donor (S-nitroso-glutathione). Surface P-selectin expression of normal GFP in patients' PPP was analyzed by flow cytometry after incubation with a P-selectin-specific monoclonal antibody in the presence or absence of the NO donor. We also measured GSH-Px activity in plasmas from family members and normal controls using standard methods. In 6 of 7 families, NO failed to inhibit platelet P-selectin expression and platelet aggregation in PPP from the affected family members and some of their relatives. Of 4 families studied, 3 probands and their corresponding affected parent had 50% decrease in plasma GSH-Px activity. In some patients with childhood stroke, impaired metabolism of reactive oxygen species as a result of reduced GSH-Px activity results in NO insufficiency that affects normal platelet inhibitory mechanisms and predisposes to arterial thrombosis. (+info)
Linkage of a marker in intron D of the estrogen synthase locus to rheumatoid arthritis.
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OBJECTIVE: To test for the presence of linkage of the estrogen synthase (CYP19) locus to rheumatoid arthritis (RA) in affected sibling pair (ASP) families. METHODS: Two data sets of RA ASPs (225 ASPs and 107 ASPs) were genotyped for a polymorphic tetranucleotide marker at the CYP19 locus using fluorescence-based semiautomated genotyping technology. Evidence of linkage was assessed by estimating allele sharing (identical by descent) in affected sibling pairs. The effect of this locus was also examined in patient subgroups stratified by sex and by age at disease onset. RESULTS: An increase in allele sharing at the CYP19 locus was observed in the first data set of 225 ASPs (logarithm of odds [LOD] 0.8; P = 0.04). There was also an increase in allele sharing in a second data set, but this did not reach statistical significance (LOD 0.34; P = 0.1). The highest increase in allele sharing was seen in patients with an age at disease onset that was >50 years (LOD 1.1; P = 0.02). CONCLUSION: An increase in allele sharing at the CYP19 locus has been demonstrated in 2 large samples of RA ASPs. The evidence for linkage was strongest in patients with an age at onset that was >50 years, which suggests that this locus may be a susceptibility locus for developing RA later in life. These data provide preliminary evidence that CYP19 may have a role in RA susceptibility. (+info)
Increased number of interleukin-10-producing cells in systemic lupus erythematosus patients and their first-degree relatives and spouses in Icelandic multicase families.
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OBJECTIVE: To evaluate the production of interleukin-10 (IL-10) as well as levels of IgG and antinuclear antibodies (ANA) in systemic lupus erythematosus (SLE) patients and their first-degree relatives and spouses in Icelandic SLE multicase families. METHODS: IL-10 production was studied by enzyme-linked immunospot assay of freshly isolated peripheral blood mononuclear cells. Total IgG and ANA were also investigated. Subjects consisted of 23 SLE patients and 47 of their first-degree relatives in 9 Icelandic multicase families. Subjects were ethnically matched by a group of healthy controls. A separate study investigated 12 SLE patients (also from SLE multicase families) and their spouses and a matched group of healthy controls. A predefined protocol was used to obtain both clinical and laboratory data, including information about SLE and other autoimmune disorders. RESULTS: The SLE patients had a significantly higher number of IL-10-producing cells compared with both first-degree relatives and healthy controls (P = 0.0005 and P < 0.0001, respectively). First-degree relatives also had a significantly higher number of IL-10-producing cells compared with healthy controls (P = 0.01). This was also true for the spouses of SLE patients, who had a higher number of IL-10-producing cells compared with matched healthy controls (P = 0.02). CONCLUSION: SLE patients and their first-degree relatives, as well as a limited number of healthy spouses of SLE patients, had increased numbers of spontaneous IL-10-producing cells. These data support the hypothesis that IL-10 production may be genetically determined, and may predispose one toward development of SLE. This has previously been suggested by studies of SLE patients and their relatives in another ethnic population, using another method for measuring IL-10 production. Although these data are based on a small number of observations, they suggest that not only genetic but also environmental factors may be of importance in determining IL-10 production, since the spouses of SLE patients also had an increased number of IL-10-producing cells. (+info)
Risk factors for psychological stress among international business travellers.
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OBJECTIVES: This study investigated sources of self reported psychological stress among international business travellers at the World Bank, following up on a previous study showing that travellers submitted more insurance claims for psychological disorders. Hypotheses were that work, personal, family, and health concerns, as well as time zone travel, contribute to travel stress. METHODS: A travel survey was developed from focus groups and consisted of questions about these potential sources of travel stress. Surveys were sent to a random sample of staff, stratified by number of travel missions, age range, and sex. Canonical correlation analyses estimated the association between key survey items on sources of stress and two measures of travel stress. RESULTS: 498 staff completed the survey. More than a third reported high to very high travel stress. Correlations between predictors and travel stress showed that social and emotional concerns (such as impact of travel on family and sense of isolation) contributed the most to such stress, followed by health concerns, and workload upon return from travel. Surprisingly, time zone travel did not contribute to the self reported stress of these travellers. There were few modifiers of stress, although respondents suggested that a day of rest after travel and reduced workloads would help. CONCLUSIONS: The current study confirms clinical impressions about several correlates of travel stress. Similar research with travellers in other organisations could help to determine whether the findings from this study are valid and what measures can be taken to reduce the psychological health risks to travellers. (+info)
Familial clustering of Helicobacter pylori infection: population based study.
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OBJECTIVES: To assess the rate of intrafamilial transmission of Helicobacter pylori infection in the general population and the role of a family's social background. DESIGN: Population survey. SETTING: Campogalliano, a town in northern Italy with about 5000 residents. PARTICIPANTS: 3289 residents, accounting for 416 families. MAIN OUTCOME MEASURES: Prevalence of H pylori infection assessed by presence of IgG antibodies to H pylori. RESULTS: The overall prevalence of H pylori infection was 58%. Children belonging to families with both parents infected had a significantly higher prevalence of H pylori infection (44%) than children from families with only one (30%) or no parents (21%) infected (P<0.001). Multivariate analyses confirmed that children with both parents positive had double the risk of being infected by H pylori than those from families in which both parents were negative. Family social status was independently related to infection in children, with those from blue collar or farming families showing an increased risk of infection compared with children of white collars workers (odds ratio 2.02, 95% confidence interval 1.16 to 3.49). CONCLUSIONS: H pylori infection clusters within families belonging to the same population. Social status may also be a risk factor. This suggests either a person to person transmission or a common source of exposure for H pylori infection. (+info)
Familial sarcoidosis in Finland and Hokkaido, Japan--a comparative study.
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Two or more cases of sarcoidosis in one family is not unusual. To compare the frequencies of familial sarcoidosis in Finland and Hokkaido, Japan, and to analyse the type of associations reported, we collected data on all patients visiting hospitals for sarcoidosis in 1984 in Finland (1378 patients) and Hokkaido (208 patients), including information about familial sarcoidosis. We also analysed the familial cases seen among 571 sarcoidosis patients diagnosed at the Mjolbolsta hospital in Finland from 1955 to 1987 and among 686 Japanese patients seen in Sapporo from 1964 to 1988. In 1984, 50 sarcoidosis patients visiting Finnish hospitals and nine sarcoidosis patients in Hokkaido reported as familial cases. Of the sarcoidosis patients seen in Finland at the Mjolbolsta hospital in 1955-1987, 27 had a family member with the same disease, while this number was 20 in the Sapporo hospital in 1964-1988. Those surveys give a prevalence of familial sarcoidosis in Finland of 3.6-4.7% and in Hokkaido of 2.9-4.3%. Among familial cases, the dominating relationships were sister-brother and mother-child relationships. (+info)
Doctors as patients: postal survey examining consultants and general practitioners adherence to guidelines.
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OBJECTIVES: To examine the adherence by senior NHS medical staff to the BMA guidelines on the ethical responsibilities of doctors towards themselves and their families. DESIGN: Postal semistructured questionnaire. SETTING: Four randomly selected NHS trusts and three local medical committees in South Thames region. SUBJECTS: Consultants and principals in general practice. MAIN OUTCOME MEASURES: Personal use of health services. RESULTS: The response rate was 64% (724) for general practitioners and 72% (427) for consultants after three mailings. Most (1106, 96%) respondents were registered with a general practitioner, although little use was made of their services. 159 (26%) general practitioners were registered with a general practitioner in their own practice and 80 (11%) admitted to looking after members of their family. 73 (24%) consultants would never see their general practitioner before obtaining consultant advice. Most consultants and general practitioners admitted to prescribing for themselves and their family. Responses to vignettes for different health problems indicated a general reluctance to take time off, but there were differences between consultants and general practitioners and by sex. Views on improvements needed included the possibility of a "doctor's doctor," access to out of area secondary care, an occupational health service for general practitioners, and regular health check ups. CONCLUSION: The guidelines are largely not being followed, perhaps because of the difficulties of obtaining access to general practitioners outside working hours. The occupational health service should be expanded and a general practitioner service for NHS staff piloted. (+info)
The health of grandparents raising grandchildren: results of a national study.
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OBJECTIVES: This study sought to compare the functional and self-rated health of grandparents raising grandchildren with that of noncaregiving grandparents. METHODS: A secondary analysis of data from the 1992 to 1994 National Survey of Families and Households was conducted. Bivariate and logistic analyses compared 173 custodial and 3304 noncustodial grandparents in terms of functional health limitations, self-rated health, and satisfaction with health. RESULTS: Custodial grandparents were significantly more likely to have limitations in 4 of the 5 activities of daily living (ADLs) examined, with more than half reporting some limitation in 1 of the 5 ADLs. A logistic regression analysis indicated that caregiving grandparents had 50% higher odds of having an ADL limitation. Caregivers were significantly more likely to report lower satisfaction with health, and a statistical trend indicated that the caregivers had lower self-rated health. CONCLUSIONS: Further research is needed to determine whether the differences observed reflect artifacts or actual differences in functional abilities and other health measures. The need for policies that support rather than penalize grandparents raising grandchildren is stressed. (+info)