The human platelet alphaIIb gene is not closely linked to its integrin partner beta3.
(25/2515)
alphaIIbb3 integrin is a heterodimeric receptor facilitating platelet aggregation. Both genes are on chromosome 17q21.32. Intergenic distance between them has been reported to be 125 to 260 kilobasepairs (kb) by pulsed-field gel electrophoresis (PFGE) genomic analysis, suggesting that they may be regulated coordinately during megakaryopoiesis. In contrast, other studies suggest these genes are greater than 2.0 megabasepairs (mb) apart. Because of the potential biological implications of having these two megakaryocytic-specific genes contiguous, we attempted to resolve this discrepancy. Taking advantage of large kindreds with mutations in either alphaIIb or beta3, we have developed a genetic linkage map between the thyroid receptor hormone-1 gene (THRA1) and beta3 as follows: cen-THRA1-BRCA1-D17S579/alphaIIb-beta3-qte r, with a distance of 1.3 centiMorgans (cM) between alphaIIb and beta3 and the two genes being oriented in the same direction. PFGE genomic and YAC clone analysis showed that the beta3 gene is distal and >/=365 kb upstream of alphaIIb. Additional restriction mapping shows alphaIIb is linked to the erythrocyte band 3 (EPB3) gene, and beta3 to the homeobox HOX2b gene. Analysis of alphaIIb(+)-BAC and P1 clones confirm that the EPB3 gene is approximately 110 kb downstream of the alphaIIb gene. Sequencing the region surrounding the human alphaIIb locus showed the Granulin gene approximately 18 kb downstream to alphaIIb, and the KIAA0553 gene approximately 5.7 kb upstream. This organization is conserved in the murine sequence. These studies show that alphaIIb and beta3 are not closely linked, with alphaIIb flanked by nonmegakaryocytic genes, and imply that they are unlikely to share common regulatory domains during megakaryopoiesis. (+info)
Treatment-resistant schizophrenia and staff rejection.
(26/2515)
This study examined the relationship between characteristics of patients suffering from treatment-refractory schizophrenia and staff rejection and criticism. Subjects were 30 inpatients with treatment-resistant schizophrenia and the 29 staff members treating them. Measures included assessment of the patients' symptoms and aggression risk profile using the Positive and Negative Syndrome Scale (PANSS) and assessment of staff attitudes toward these patients using the Patient Rejection Scale (PRS). Nursing staff completed the Nurses' Observation Scale for Inpatient Evaluation (NOSIE). PRS ratings did not correlate with patients' demographic and treatment characteristics. Significant correlations existed, however, between increased staff rejection and higher scores for PANSS cognitive factor and NOSIE manifest psychosis factor. Negative symptoms, although preponderant in the patient sample, were not significant predictors of staff rejection on the PRS. Older nursing staff tended to view patients as more irritable and manifestly psychotic. These findings suggest that disorganized behavior and impaired cognition dysfunction areas are more likely to be associated with high levels of rejection among staff working with treatment-resistant schizophrenia patients. Incorporation of the relatively new concepts of cognitive dysfunction and treatment resistance in staff training programs and multidisciplinary team reviews may greatly benefit schizophrenia patients and the staff treating them. (+info)
Circadian variation of symptomatic paroxysmal atrial fibrillation. Data from almost 10 000 episodes.
(27/2515)
AIMS: To determine the circadian rhythm of paroxysmal atrial fibrillation in a very large outpatient population. METHODS AND RESULTS: We reviewed all emergency telephone calls received in Shahal (a medical service covering 44 000 subscribers), from 1987 to 1997. Patients were included if new-onset atrial fibrillation was recorded. During this study period, 9989 episodes of paroxysmal atrial fibrillation were recorded. The time of onset was not uniformly distributed throughout the 24 h period. Instead, the distribution of arrhythmic episodes showed a double peak, with a significant increase in the number of episodes in the morning and a second rise in the evening (P<0.001). A non-uniform weekly distribution of events was also noted, with substantially fewer episodes on Saturdays (P<0.001). Finally, more arrhythmias occurred during the last months of each year (P<0.001). CONCLUSIONS: The onset of paroxysmal atrial fibrillation does not occur randomly. The large patient population in the present study suggests that the circadian rhythm of paroxysmal atrial fibrillation is similar to that described for other cardiovascular diseases, with clustering of events in the morning and (to a lesser degree) late in the evening. Weekly and yearly circadian patterns are also prominent. (+info)
Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.
(28/2515)
Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits. (+info)
Epidemiological characteristics of spotted fever in Israel over 26 years.
(29/2515)
During the summer of 1997, 2 confirmed and several suspected fatal cases of spotted fever (SF) occurred in previously healthy young adults in Israel. This unusual cluster of events stimulated the current study. The incidence of SF in Israel from 1971-98 was analyzed. Incidence increased until 1980, declined until 1994, and increased slightly from 1994-97. Incidence was higher during the summer, among children aged 0-9 years, and in rural settlements in central Israel. From 1971-1997, 31 deaths were reported, mostly in the elderly. The deaths that occurred in 1997 are a reminder that, despite the fact that morbidity due to SF is described mainly in children, SF can have a rapidly fatal outcome in healthy young adults. Thus, even during periods of low incidence, careful monitoring and high awareness for prompt diagnosis and treatment are needed. (+info)
Deaths within 90 days from starting renal replacement therapy in the ERA-EDTA Registry between 1990 and 1992.
(30/2515)
BACKGROUND: Patients who die within 90 days of commencing renal replacement therapy (RRT) may be recorded by some centres and not others, and hence data on mortality and survival may not be comparable. However, it is essential to compare like with like when analysing differences between modalities, centres and registries. It was decided, therefore, to look at the incidence of deaths within 90 days in the ERA-EDTA Registry, and to try to define the characteristics of this group of patients. METHODS: Between 1 January 1990 and 31 December 1992, 78 534 new patients started RRT in 28 countries affiliated to the ERA-EDTA Registry. Their mean age was 54 years and 31% were over 65 years old. Eighty-two per cent of the patients received haemodialysis (HD), 16% peritoneal dialysis (PD) and 2% had preemptive transplantation as first mode of treatment. RESULTS: From January 1990 to March 1993 the overall incidence of deaths was 19% and 4% of all patients died within 90 days from the start of RRT. Among those dying within 90 days 59% were over 65 years compared to 53% over 65 years in those dying beyond this time (P<0.0001). The modality of RRT did not influence the distribution of deaths before and after 90 days. Vascular causes and malignancy were more common in those dying after 90 days, while there were more cardiac and social causes among the early deaths. Mortality from social causes was twice as common in the elderly, who had a significantly higher chance of dying from social causes within 90 days compared to those aged under 65 years. The overall incidence of deaths within 90 days was 3.9% but there was a wide variation between countries, from 1.8% to 11.4%. Finally, patient survival at 2 years was markedly influenced in different age groups when deaths within 90 days were taken into account. CONCLUSIONS: The incidence of deaths within 90 days from the start of RRT was 3.9%, with a marked variation between countries ranging from 1.8% to 11.4%, which probably reflects mainly differences in reporting these deaths, although variable selection criteria for RRT may contribute. Deaths within 90 days were significantly more frequent in elderly patients with more early deaths resulting from cardiac and social causes, while vascular causes of death and malignancy were more common in those dying after 90 days. Patient survival analyses should take into account deaths within 90 days from the start of RRT, particularly when comparing results between modalities, countries and registries. (+info)
Primary hyperoxaluria type I: a model for multiple mutations in a monogenic disease within a distinct ethnic group.
(31/2515)
Primary hyperoxaluria type 1 is an autosomal recessive inherited metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of phenotypes ranging from renal failure in infancy to mere renal stones in late adulthood. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine:glyoxylate aminotransferase, are responsible for the disease. Seven mutations were detected in eight families in Israel. Four of these mutations are novel and three occur in children living in single-clan villages. The mutations are scattered along various exons (1, 4, 5, 7, 9, 10), and on different alleles comprising at least five different haplotypes. All but one of the mutations are in a homozygous pattern, reflecting the high rate of consanguinity in our patient population. Two affected brothers are homozygous for two different mutations expressed on the same allele. The patients comprise a distinct ethnic group (Israeli Arabs) residing in a confined geographic area. These results, which are supported by previous data, suggest for the first time that the phenomenon of multiple mutations in a relatively closed isolate is common and almost exclusive to the Israeli-Arab population. Potential mechanisms including selective advantage to heterozygotes, digenic inheritance, and the recent emergence of multiple mutations are discussed. (+info)
Dirofilaria repens infection in a dog in Israel.
(32/2515)
Only one case of canine infection with Dirofilaria repens has been reported in Israel to date; this occurred in 1934. This publication, 65 years later, represents the second case of D. repens infection in a dog in Israel. This dog was infected locally since it was born in Israel and was never taken abroad, suggesting that the life cycle of the filaria was completed in Israel. Since dogs, cats, and foxes serve as a reservoir for the filaria and these are abundant in Israel, and mosquitoes of the genera Culex and Aedes (both of which occur in Israel and the Middle East) are vectors, the conditions for establishment of the filaria in Israel exist, and warrant regional epidemiologic investigation. (+info)