In 79 South Indian nuclear pedigrees ascertained via probands with NIDDM and both parents living, parental diabetic status was established through previously diagnosed NIDDM (n = 97) or oral glucose tolerance testing (n = 61). There was no significant difference between diabetes prevalence in mothers and fathers (60 vs 53 (76% vs 67%), respectively, p = 0.22). 'Age at diabetes diagnosis' survival curves did differ according to parental gender (p = 0.02) but this may reflect gender differences in health provision rather than pathophysiology. No maternal excess effects of the magnitude evident in previous studies were detected, suggesting either ethnic differences or overestimation of the maternal effect when reported histories of parental diabetes have been used. The tRNA(Leu(UUR) gene region was studied for diabetes-associated variation given the role of mutations in this gene in some pedigrees displaying maternal transmission of NIDDM. None of 142 unrelated South Indian NIDDM subjects displayed the MELAS mutation at nt3243. However, sequencing identified two variants of potential importance: (a) at nt3290 in the tRNA(Leu(UUR) gene, seen in 7/142 diabetic and 1/85 control subjects (p = 0.11), (b) at nt3316 in the ND1 gene (4/142 vs 1/85 subjects, respectively (p = 0.51)). Further studies are needed to determine the relevance of these variants to the development of NIDDM.

Adult↗

PubMed1996

Auxiliary liver transplantation: regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure--a multicenter European study.

Auxiliary liver transplantation (LT) is a special procedure of LT which could be proposed to patients with fulminant hepatic failure (FHF) and has for aim that complete regeneration of the native liver (NL) left in place will allow the graft recipient to resume normal liver function after allograft withdrawal. We report 30 cases of auxiliary LT performed for FHF in 12 European centers. Twenty-five of 30 patients were younger than 50 years. The cause of FHF was hepatitis A virus (HAV) in 4 patients, hepatitis B virus (HBV) in 7, paracetamol overdose in 5, ecstasy in 2, hepatotoxic drugs in 4, autoimmune hepatitis in 2, liver lesions of preeclampsia in 1 and unknown in 5. A postoperative, both clinical and histological follow-up of more than 3 weeks was obtained in 22 patients, enabling us to look for indicators predictive of NL regeneration and outcome. Histological changes observed in the NL included complete regeneration in 68%, incomplete regeneration with obvious fibrous sequelae in 14% and severe liver fibrosis or cirrhosis in 18%, of the 22 patients studied. The percentage and distribution of necrosis observed in tissue samples of the NL at the time of transplantation was not related to the final outcome. Complete NL regeneration was observed in 15 patients, out of whom 14 were younger than 40 years. Patients with complete regeneration were mainly affected by FHF due to HAV, HBV, or paracetamol overdose. After a follow-up of 18/11 (mean/median) months (range, 3 to 67 months), 19 of the 30 patients (63%) survived and 13 of them (68%), i.e., 43% of the 30 patients, had resumed normal NL function, with interrupted immunosuppression, the ultimate goal of emergency auxiliary LT. We conclude that, in patients with FHF, auxiliary LT is a procedure feasible in a number of centers and is associated with a complete regeneration capability of the NL in a majority of survivors, especially in those younger than 40 years. Confirmation of these encouraging preliminary results by large-scale prospective studies is required.

Adolescent↗

PubMed1996

Cyclist road deaths in London 1985-1992: drivers, vehicles, manoeuvres and injuries.

We used coroners' records to investigate the fatal accidents of cyclists recorded on death certificates in London during 1985-1992. There were 124 deaths: 68 cyclists were injured in London and 56 injured in the "home counties" around London and died in London hospitals. The cyclists' ages were from 8-88, and 70% were male; the drivers were aged 17-74, and 96% were male. Of the 108 vehicles involved, 53 were cars (including one parked) and 40 heavy goods vehicles (HGVs) (including 14 large lorries and 18 articulated lorries), 5 light goods vehicles, 5 buses and coaches and 5 motorcycles. Fatal accidents occurred with a wide range of manoeuvres; of vehicles turning left (driving is on the left in the U.K.), 14 out of 15 were HGVs. Accidents were most often on 2 lane roads and one half were near a road junction. Law violations were recorded in half the accidents; alcohol intoxication contributed only rarely. While injuries to the head were the commonest reported direct cause of death, Inner London deaths were frequently due to multiple injuries. The study confirms the serious danger to cyclists (particularly women) in Inner London from large and articulated lorries, causing death from multiple injuries.

Accidents, Traffic↗

PubMed1996

Determinants of informal caregivers' satisfaction with services for dying cancer patients.

The association between bereaved informal caregivers' satisfaction with services delivered by district nurses, general practitioners and hospital doctors, and various service and non-service variables was examined to assess whether satisfaction is a reflection of service characteristics, non-service related factors, or attributable to both. Secondary analysis was undertaken on a sub-sample from the "Regional Study of Care for the Dying" (RSCD) in which bereaved relatives or friends of a random sample of deaths in 1990 in 20 health districts across England were interviewed some ten months after the death. 1858 relatives or close friends/neighbours of people who died from cancer were included in this analysis. Using multiple logistic regression, larger odds ratio were found in association with service than non-service variables. For example, high satisfaction with district nurses was strongly associated with visiting the patient very frequently (OR = 10.8, 95% CI = 4.5 - 25.9), while the GP visiting 20 times or more (OR = 5.5, 95% CI = 3.6 - 8.5), and informing the informal caregiver of the diagnosis (OR = 3.3, 95% CI = 2.3 - 4.7) were associated with high satisfaction with GPs. However, some non-service variables were significantly associated with satisfaction. For instance, having no bereavement-related psychological problems was positively associated with high satisfaction with district nurses (OR = 2.3, 95% CI = 1.6 - 3.4) and GPs (OR = 2.0, 95% CI = 1.4 - 2.8), while the informal caregiver perceiving caring as rewarding as opposed to a burden was positively associated with high satisfaction with district nurses (OR = 3.7, 95% CI = 1.8 - 7.5) and negatively associated with high satisfaction with hospital doctors (OR = 0.46, 95% CI = 0.24 - 0.86). The findings indicate that, in post-bereavement surveys evaluating services delivered to dying cancer patients, informal caregivers' satisfaction is mainly determined by service characteristics. However, attributes of both patients and informal caregivers also play an important role.

Adult↗

PubMed1996

Is community-led maternity care a feasible option for women assessed at low risk and those with complicated pregnancies? Results of a population based study in south Camden, London.

OBJECTIVE: to assess the feasibility of obstetric offering community-led maternity care to most women, both those assessed to be at low obstetric risk and those with complicated pregnancies at 'booking'. Community-led care is defined as appropriate care by community midwives and general practitioners during pregnancy, birth and the puerperium, with routine hospital care kept to a minimum. DESIGN: observational study. SETTING: South Camden, London, UK: University College Obstetric Hospital and community. PARTICIPANTS: 453 women, resident in South Camden, including those 'booked' for home births, who were 'booked' for maternity care at University College Hospital between October 1993 and April 1994. MEASUREMENTS AND FINDINGS: this paper assesses the extent to which community midwives and general practitioners were able to give local women community-led care and describes the amount of care provided to women by their 'named' community midwives and team. Most local women were eligible for community-led care and 85% planned to have it. The majority of care was given by the community midwives, but the amount of hospital input varied. Women who remained at low obstetric risk generally had their antenatal care in the community, only attending hospital for two or three routine assessments and occasional extra referrals. Women attending hospital more frequently usually had a complicated pregnancy. Care given by a woman's 'named' midwives was generally provided antenatally, but care from familiar midwives was less common in labour and postnatally. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: community-led maternity care can be provided to the majority of women, even those with a complicated pregnancy, as long as specialist opinion and facilities are accessible and women are referred as necessary. Although the majority of women had access to local antenatal care from staff they got to know, the 'named' community midwives and teams found it difficult to provide comprehensive care, particularly to the women who developed complications, so priorities need to be established. Further research is needed to compare alternative models of care and their costs.

Community Health Nursing↗

PubMed1996

Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families.

Non-insulin dependent diabetes mellitus (NIDDM) affects more than 100 million people worldwide and is associated with severe metabolic defects, including peripheral insulin resistance, elevated hepatic glucose production, and inappropriate insulin secretion. Family studies point to a major genetic component, but specific susceptibility genes have not yet been identified-except for rare early-onset forms with monogenic or mitochondrial inheritance. We have screened over 4,000 individuals from a population isolate in western Finland, identified 26 families (comprising 217 individuals) enriched for NIDDM and performed a genome-wide scan using non-parametric linkage analysis. We found no significant evidence for linkage when the families were analysed together, but strong evidence for linkage when families were classified according to mean insulin levels in affecteds (in oral glucose tolerance tests). Specifically, families with the lowest insulin levels showed linkage (P = 2 x 10(-6)) to chromosome 12 near D12S1349. Interestingly, this region contains the gene causing the rare, dominant, early-onset form of diabetes MODY3. Unlike MODY3 families, the Finnish families with low insulin have an age-of-onset typical for NIDDM (mean = 58 years). We infer the existence of a gene NIDDM2 causing NIDDM associated with low insulin secretion, and suggest that NIDDM2 and MODY3 may represent different alleles of the same gene.

Adult↗

PubMed1996

Evidence that a locus for familial psoriasis maps to chromosome 4q.

Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.

Chromosome Mapping↗

PubMed1996

Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F.

Recurring outbreaks of acute hepatitis have been a significant cause of morbidity and mortality among Peruvian military personnel stationed in the Amazon Basin region of Peru. The role of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection was investigated as the possible cause of acute hepatitis among 88 military patients stationed at four different jungle outposts during 1992-1993. Analysis of serum markers indicated that 95% (84/88) had evidence of acute HBV infection; 64% (54/84) were also infected with HDV. Genetic analysis of PCR-amplified HDV and HBV fragments showed exclusively HDV genotype III and HBV genotype F. Furthermore, HDV RNA sequences were similar among patients from the same outpost but different from those at other jungle locations. The data suggested focal sources of HDV infection in the jungle environment of the outposts and, further, confirmed the unique association of HDV genotype III with severe cases of human disease in northern South America.

Acute Disease↗