A human parthenogenetic chimaera.

In mice, parthenogenetic embryos die at the early postimplantation stage as a result of developmental requirements for paternally imprinted genes, particularly for formation of extraembryonic tissues. Chimaeric parthenogenetic<==>normal mice are viable, however, due to non-random differences in distribution of their two cell types. Species differences in imprinting patterns in embryo and extra-embryonic tissues mean that there are uncertainties in extrapolating these experimental studies to humans. Here, however, we demonstrate that parthenogenetic chimaerism can indeed result in viable human offspring, and suggest possible mechanisms of origin for this presumably rare event.

Postpartum aHUS secondary to a genetic abnormality in factor H acquired through liver transplantation.

We report here a young female who underwent a successful deceased donor liver transplant for hepatic vein thrombosis. Five years after transplantation she developed postpartum atypical hemolytic uremic syndrome (aHUS). She did not recover renal function. Mutation screening of complement genes in her DNA did not show any abnormality. Mutation screening of DNA available from the donor showed a nonsense CFH mutation leading to factor H deficiency. Genotyping of the patient showed that she was homozygous for an aHUS CD46 at-risk haplotype. In this individual, the development of aHUS has been facilitated by the combination of a trigger (pregnancy), an acquired rare genetic variant (CFH mutation) and a common susceptibility factor (CD46 haplotype).

Successful renal transplantation in factor H autoantibody associated HUS with CFHR1 and 3 deficiency and CFH variant G2850T.

Factor H (CFH) autoantibodies are associated with atypical hemolytic uremic syndrome (aHUS). Peritransplantation plasma exchange therapy and intensification of immunosuppression, with adjuvant use of anti-CD20 monoclonal antibodies has recently been advocated for cases of CFH-autoantibody associated aHUS. In this report, we describe successful deceased donor renal transplantation in a case of CFH-autoantibody associated aHUS with combined CFHR1 and 3 deficiency in addition to the CFH sequence variant, (cG2850T, pGln950His). CFH-autoantibodies were detected 2 weeks prior to transplantation. Disease recurrence was not observed using basiliximab, an IL2-receptor antagonist and high-dose corticosteroids with mycophenolate mofetil. Adjuvant therapies such as Rituximab nor intensification of plasma therapy were employed. Consequently, careful consideration needs to be given to the use of additional immunosuppression in certain cases of CFH-autoantibody associated aHUS. Serial measurement of CFH-autoantibodies is required in the immediate pre- and posttransplantation period to further clarify their role as a factor in the recurrence of aHUS posttransplantation. Furthermore, delineation of the functional significance of CFH-autoantibodies is warranted in individual cases.

The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts.

BACKGROUND: In both familial and sporadic atypical haemolytic-uraemic syndrome (aHUS), mutations have been reported in regulators of the alternative complement pathway including factor H (CFH), membrane cofactor protein (MCP), and the serine protease factor I (IF). A characteristic feature of both MCP and CFH associated HUS is reduced penetrance and variable inheritance; one possible explanation for this is that functional changes in complement proteins act as modifiers. OBJECTIVE: To examine single nucleotide polymorphisms in both CFH and MCP genes in two large cohorts of HUS patients (Newcastle and Paris). RESULTS: In both cohorts there was an association with HUS for both CFH and MCP alleles. CFH and MCP haplotypes were also significantly different in HUS patients compared with controls. CONCLUSIONS: This study suggests that there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical HUS.

Platelet-density analysis and intraplatelet granule content in young insulin-dependent diabetics.

This study was designed to assess the density characteristics of platelets from controls (N = 10) and three groups of diabetics (N = 32) exhibiting various degrees of glycemic control. With continuous gradients of Percoll, platelets from controls and diabetics (N = 8) with an HbA1 less than or equal to 9% formed a band extending from 1.0625 g/ml to 1.0925 g/ml with a mean platelet density of 1.0775 g/ml. In the two groups of diabetics with HbA1 greater than or equal to 10%, there was an increase in the proportion of low-density platelets recovered on the gradients and the mean platelet density was reduced to 1.0750 g/ml (HbA1 = 10-13%) and 1.070 g/ml (HbA1 greater than or equal to 14%). All three groups of diabetics had normal levels of intraplatelet ATP/ADP and beta-thromboglobulin. It is unlikely that in vivo degranulation of platelets after activation was responsible for the altered density profiles. We propose that abnormal platelet subpopulations with low density but normal intraplatelet granule content were responsible for the changed density profiles.

Reliability of a single beta-thromboglobulin measurement in a diabetic population: importance of PGE1 in anticoagulant mixture. Damad Study Group.

During the collection of samples for plasma beta-thromboglobulin (beta-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single beta-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE1. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p less than 0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artificially high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGE1 decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

Risk factors for Alzheimer's disease: a population-based, longitudinal study in Manitoba, Canada.

BACKGROUND: Current knowledge of risk factors for Alzheimer's disease (AD) is limited. Data from a longitudinal, population-based study of dementia in Manitoba, Canada were used to investigate risk factors for AD. METHODS: Cognitively intact subjects completed a risk factor questionnaire assessing sociodemographic, genetic, environmental, medical and lifestyle exposures. Five years later, 36 subjects had developed AD and 658 remained cognitively intact. RESULTS: Older subjects or those who had fewer years of education were at greater risk of AD. After adjusting for age, education and sex, occupational exposure to fumigants/ defoliants was a significant risk factor for AD (relative risk [RR] = 4.35; 95% CI : 1.05--17.90). A history of migraines increased the risk of AD (RR = 3.49; 95% CI : 1.39--8.77); an even stronger effect was noted among women. Self-reported memory loss at baseline was associated with subsequent development of AD (RR = 5.15; 95% CI : 2.36--11.27). Vaccinations and occupational exposure to excessive noise reduced the risk of AD. CONCLUSIONS: Some well-known risk factors for AD were confirmed in this study and potential new risk factors were identified. The association of AD with a history of migraines and occupational exposure to defoliants/fumigants is of particular interest because these are biologically plausible risk factors.

The balance of exchange in instrumental support with network members outside the household.

The exchange of six types of instrumental support with individuals outside the household was examined using data from the 1990 Canadian General Social Survey. The balance of exchange within the network as a whole was considered in relation to age, gender, social class, availability of social relationships, and health status. The findings reveal the complexity of examining the provision and receipt of support simultaneously. Results are generally consistent with propositions under exchange theory regarding the association between age and reciprocity, depending on assumptions made about the nature of exchange. Implications for future research are discussed.

Lay explanations of chronic illness in later life.

This study explores lay explanations of chronic illness in later life. More specifically, perceived causes, treatment strategies, and perceived outcomes of arthritis and heart/circulatory problems from the perspective of older adults who have such problems are examined. Variations in these explanations according to selected sociodemographic and health status characteristics are explored. Among the arthritis sufferers, the most prevalent explanations were physical work/working conditions, age, and injury, whereas those with heart/circulatory problems most often explained the cause as due to tension/stress, physiology, or heredity. A variety of treatments were identified, including doing nothing, seeking or continuing medical treatment, altering lifestyle, and using folk remedies. Selected sociodemographic and health status characteristics appear important for understanding explanations about arthritis, although it is primarily health status indicators that emerge for heart/circulatory problems. Directions for future research are highlighted.

Cognitive impairment, disruptive behaviors, and home care utilization.

Disruptive behaviors by an elder with cognitive impairment, such as violence, abrupt mood swings, and overt inappropriate sexual behaviors have been known to create caregiver distress, but little is known about how these behaviors may influence the use of home care services by that elder or their informal caregiver. The purpose of this study is to explore the associations between type of cognitive impairment (cognitive impairment with no dementia, and dementia), selected disruptive behaviors, and the use of four home care services (homemaking/cleaning, personal care, in-home nursing, home-delivered meals). Secondary data analysis from the 1991-1992 Manitoba Study on Health and Aging data set was conducted, using a sample of 124 community-dwelling elders and their unpaid caregivers. Multivariate analysis revealed that disruptive behaviors were significantly associated with the use of two services: personal care and home-delivered meals. Being cognitively impaired with dementia was significant for only home-delivered meals. Overall functional status of the elder emerged as a consistent predictor.

Favorable long-term outcome after liver-kidney transplant for recurrent hemolytic uremic syndrome associated with a factor H mutation.

A male child initially presented with atypical hemolytic uremic syndrome (HUS) at the age of 4 months and progressed within weeks to end stage renal disease (ESRD). At the age of 2 years he received a live-related kidney transplant from his mother, which, despite initial good function, was lost to recurrent disease after 2 weeks. Complement factor H analysis showed low serum levels and the presence of two mutations on different alleles (c.2918G > A, Cys973Tyr and c.3590T > C, Val1197Ala). His survival on dialysis was at risk because of access failure and recurrent bacteremic episodes. Therefore, at the age of 5 years he received a combined liver-kidney transplant with pre-operative plasma exchange. Initial function of both grafts was excellent and this has been maintained for over 2 years. This report suggests that despite setbacks in previous experience, combined liver-kidney transplantation offers the prospect of a favorable long-term outcome for patients with HUS associated with complement factor H mutations.

Use of health services in later life: the influence of health beliefs.

This study examined the influence of health beliefs on the use of various health services by elderly individuals, employing Andersen-Newman's framework of predisposing, enabling, and need factors. Data are from a random sample of 743 individuals aged 60 and over living in Winnipeg, Canada. Need factors emerge as the strongest correlates of physician visits, hospitalization, and overall service use. The degree of medical skepticism appears to exert some influence on utilization, particularly in regard to physician visits. A stronger belief in the value of health maintenance activities is associated with the use of a greater number of services overall, suggesting that preventive health beliefs may promote use of the health care system. Generally health locus of control appears to be unrelated to health service utilization. Implications for further research are discussed.

Small inclusions in the cytoplasm of leukocytes in LE cell tests.

Small homogeneous basophilic and eosinophilic particles varying in size from 0.7 to 3.0 micra were seen in cytoplasm of monocytes and polymorphonuclear cells of leukocytes in LE cell tests. The aim of this investigation was to determine their frequency and diagnostic significance. Inclusions were found in one-third of LE cell tests on patients with rheumatic diseases and were not observed in normals. In 19.1% of 161 patients with SLE, they were present before LE cells were found. Sixty-eight% of patients who had particles had SLE, 8% had rheumatoid arthritis with LE cells, and 3% had nonrheumatic diseases.

Community-dwelling older adults' attributions about falls.

OBJECTIVE: To examine the extent to which 162 older adults attributed the cause of their fall to their own limitations and to their surroundings, and the relationship of these attributions with selected sociodemographic, health-related, locus of control, and fall-related characteristics. DESIGN: A stratified (by age > or = 65, gender, and area of residence) random sample; needs assessment survey on products and services to enhance independent living among older adults; included section on falls. SETTING: Community-dwelling individuals in both urban and rural settings. PARTICIPANTS: Potential respondents were drawn from the Manitoba Health database. Overall refusal rate was 22%. Final number of 1,406 participants were interviewed; 162 of these participants reported a fall. MAIN MEASURES: Outcome measures were: (1) the extent to which the fall was attributed to "own limitations" (internal attribution), and (2) the extent to which the fall was attributed to "surroundings" (external attribution). RESULTS: There is diversity in the extent to which individuals attribute falls to internal and external causes. Stepwise regression analyses indicated those reporting poorer self-rated health (p < .001); having dexterity difficulties (p < .01); and living in an apartment (p < .05) were more likely to attribute the fall to their own limitations. Those reporting better self-rated health (p < .01); and falling outdoors (p < .01) were more likely to attribute the fall to the surroundings. CONCLUSIONS: Fall attributions need to be more fully examined in the context of self-rated health and fall prevention programs.

Gender differences in disability, assistance, and subjective well-being in later life.

This study focused on gender differences in functional disability among older adults, their reliance on personal assistance and technical aids, and relationships among the use of these sources of assistance, functional disability, and subjective feelings of well-being. The analyses employ data from interviews conducted with 1,406 community-dwelling elders living in Manitoba, Canada. The results reveal (a) greater disability and somewhat greater use of personal assistance among women, and (b) differences between men and women in relationships between both personal and technical resources and subjective feelings of well-being across levels of functional disability.

Self-care in health and in illness.

This paper focuses on self-care, both expectations and actual behaviours, as health behaviour and as illness behaviour among a random sample of elderly individuals living in the community in a Canadian city (n = 743). The conceptualization of both health and illness behaviour follows Mechanic's (1,2) definition of illness behaviour as selective, interpretive, and evaluative. The data reveal a gap between intentions and behaviours, with elderly individuals de-emphasizing the importance of self-care and overemphasizing the importance of professional contact in their intentions compared with their behaviours. Further, self-care as health and as illness behaviour are uncorrelated with one another. Virtually all individuals engage in some health maintenance behaviours. Approximately two-thirds engage in self-care or do nothing as an initial response to common ailments. While different correlates emerge for each, health beliefs are significantly related, irrespective of whether it is health or illness behaviour.

Fried syndrome is a distinct X linked mental retardation syndrome mapping to Xp22.

In 1972, Fried described a large Scottish family affected by X linked mental retardation (XLMR), hydrocephalus, and mild facial dysmorphism. The phenotype has considerable similarity to the MASA syndrome, which results from mutations of the L1CAM gene in Xq28, and this family has since been assumed to be an example of this condition. We have reinvestigated the family for linkage to X chromosome markers, and obtained additional clinical information on surviving affected subjects. The phenotype in these patients has evolved into a distinctive syndrome, with severe mental retardation (MR), spastic diplegia, ventricular dilatation, and calcification of the basal ganglia. Linkage to Xq28 markers has been excluded, suggesting that Fried syndrome is not allelic with MASA syndrome. Two point and multipoint linkage analysis indicates that the gene for this condition lies within the interval KAL-DXS989 in Xp22. We propose the designation Fried syndrome to emphasise the disorder's distinctive phenotype.