Biomedical subjects

M F McDermott

Publications and source records attributed to M F McDermott.

43 records · Page 3Linked to original sources

PubMed1997

Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians.

Vitamin D has important immunomodulatory properties and prevents development of diabetes mellitus in an animal model of insulin-dependent diabetes (IDDM). We have studied the vitamin D receptor locus as a candidate for genetic susceptibility to IDDM in Southern Indian families. We found evidence for an association of one particular vitamin D receptor allele with IDDM susceptibility in this community. Ninety-three South Indian families consisting of available parents and an affected offspring were genotyped for three vitamin D receptor polymorphisms using the restriction enzymes TaqI, ApaI and BsmI as well as an adjacent microsatellite located to 12q14 (D12S85). Transmission disequilibrium testing analysis was used to assess preferential transmission of polymorphic markers and haplotypes with IDDM. There was significant excess transmission of vitamin D receptor alleles containing the BsmI restriction site to affected offspring in these families (p = 0.016). No association was found between D12S85 and IDDM. This study suggests that a polymorphism within or close to the vitamin D receptor gene may modify susceptibility to IDDM in this ethnic group.

Adolescent↗

PubMed1996

No linkage or association of telomeric and centromeric T-cell receptor beta-chain markers with susceptibility to type 1 insulin-dependent diabetes in HLA-DR4 multiplex families.

The T-cell receptor beta locus (TCRB) on chromosome 7q35 was studied as a candidate region for genetic susceptibility to type 1 insulin-dependent diabetes (IDDM). A highly polymorphic microsatellite marker mapping to the TCRBV6.7 gene and a TCRB C-region RFLP were used to genotype the members of a total of 21 multiplex IDDM families from two different geographical areas. There was no evidence to support linkage to either of these markers with IDDM, and conventional two-point analysis excluded linkage to the telomeric end of the TCRB complex, in the region of the highly informative TCRBV6.7 marker. There was significant linkage of IDDM to the class II HLA-D locus with significant lod scores > 3.0 obtained for the HLA-DRB1 and HLA-DQB1 genes. Affected sib-pair (ASP) and transmission disequilibrium (TDT) association tests confirmed these findings.

Adolescent↗

PubMed1996

Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.

The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF c1 alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 "shared epitope" (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF c1 and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.

Arthritis, Rheumatoid↗

PubMed1993

Aminophylline in the treatment of acute asthma when beta 2-adrenergics and steroids are provided.

BACKGROUND: The purpose of this study was to test the contribution of aminophylline in improving peak expiratory flow rate (PEFR) during emergency department treatment of acute asthma when metaproterenol sulfate and steroid therapy are also provided. METHODS: In a prospective, randomized, double-blind, and placebo-controlled trial at a municipal hospital emergency department, 44 patients with acute asthma, aged 18 to 45 years, with theophylline levels below 28 mumol/L, who had failed to achieve a PEFR of 40% predicted after one nebulized metaproterenol treatment, were recruited. An aminophylline or placebo loading dose and maintenance infusion were administered. All patients received hourly nebulized metaproterenol and initial methylprednisolone sodium succinate. The PEFR was measured hourly for 5 hours. Two-factor repeated-measures analysis of variance of improvement in PEFR ([final-initial PEFR]/predicted PEFR) was assessed. RESULTS: There was no difference in improvement of PEFR at any hour between the treatment and placebo groups. After 5 hours, the difference in improvement ratio was 0.40 (aminophylline) vs 0.36 (placebo) (P = .30; n = 22 in each group). The treatment group suffered more tremor, nausea or vomiting, and palpitations (P < .05). CONCLUSION: In the emergency department setting, aminophylline contributes no significant improvement in PEFR when beta 2-agonists and corticosteroids are being provided, while causing more side effects.

Acute Disease↗

PubMed1993

Emergency department treatment of severe asthma. Metered-dose inhaler plus holding chamber is equivalent in effectiveness to nebulizer.

STUDY OBJECTIVE: To compare the effectiveness of administration of albuterol by nebulizer or by a metered-dose inhaler having a holding chamber attachment (hereafter "inhaler") for treatment of acute asthma in an emergency department (ED). DESIGN: A randomized, double-blind, placebo-controlled intervention study conducted at two sites. SETTING: The EDs of a large municipal hospital and a university teaching hospital. PATIENTS: Thirty-five patients 10 to 45 years of age seeking treatment at an ED for acute asthma. INTERVENTIONS: Patients were randomly assigned to receive either albuterol by nebulizer plus placebo by inhaler (n = 20) or albuterol by inhaler plus placebo by nebulizer (n = 15). The dose was repeated every 30 min until the FEV1 was at least 80 percent of predicted, the patient became asymptomatic, or 6 doses had been given. MEASUREMENTS AND RESULTS: All references in this article to spirometric measurements of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) represent percentages of the predicted normal value. No significant (p > 0.58) differences occurred in baseline mean FEV1, FVC, or PEFR for the two groups. For both groups, significant improvement occurred in mean FEV1 at 30 min (p < 0.02) and at 60 min (p < 0.02), and in maximum mean FEV1 (p < 0.001). However, no significant (p > 0.6) differences occurred between groups in mean FEV1, FVC, or PEFR at 30 and 60 min, or in maximum improvement attained. The sample size was sufficiently large to detect a 12 percent difference in improvement with a power of 90 percent. Thirty-three of 35 patients were treated successfully with the study protocol, became asymptomatic, and were discharged home. One patient from each group required further treatment. CONCLUSIONS: There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for treatment of acute asthma. There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for the treatment of acute asthma when the dose was titrated to clinical response. When compared with nebulizer, the metered-dose inhaler with holding chamber delivers a full dose of albuterol more quickly and at no higher cost.

Administration, Inhalation↗

PubMedDate not supplied

Pancreatitis in fibrocalculous pancreatic diabetes mellitus is not associated with common mutations in the trypsinogen gene.

BACKGROUND: A distinct type of pancreatitis associated with diabetes, termed fibrocalculous pancreatic diabetes (FCPD), has been reported in tropical developing countries including Bangladesh. The molecular basis for autosomal dominant hereditary pancreatitis (HP) has recently been attributed to mutations in exons 2 and 3 of the trypsinogen gene. We have investigated the hypothesis that mutations in the aforementioned exons of this gene might also predispose to FCPD. METHODS: Seventy Bangladeshi and 50 South Indian unrelated FCPD patients and seven South Indian families with FCPD probands were studied. Pancreatic calcification was confirmed by abdominal X-ray, ultrasound and/or ERCP. Established mutations of exons 2 and 3 of the trypsinogen gene were studied in these subjects by PCR-RFLP analysis and DNA sequencing. RESULTS: The mutations found in hereditary pancreatitis were not observed in this collection of FCPD subjects, and complete DNA sequencing of exons 2 and 3 of the fourth cationic trypsinogen gene also excluded any new mutations. CONCLUSIONS: These results indicate that chronic pancreatitis of FCPD is unlikely to be caused by common mutations in the trypsinogen gene.

Adult↗

PubMedDate not supplied

Family association studies of markers on chromosome 2q and Type 1 diabetes in subjects from South India.

BACKGROUND: Several Type 1 diabetes susceptibility loci have been located to chromosome 2q12-21. However, results have not always been consistent and this may reflect study design and the population analysed. We have used a family-based design to look for an association between Type 1 diabetes and markers located to 2q12-21. METHODS: Ninety-one South Indian families consisting of subjects with Type 1 diabetes and their parents were genotyped for eight polymorphic markers localised to 2q12-21, which includes the interleukin-1 gene cluster. Radiation hybrid mapping was used to localise the map position of D2S308 and D2S363 on 2q12-21. The extended transmission disequilibrium test was used for statistical analysis. RESULTS: No associations were found between Type 1 diabetes and markers located in and around the interleukin-1 gene cluster or the interleukin-1 Type 1 receptor. In contrast, a suggestive association was found between Type 1 diabetes and two closely-linked markers telomeric of the interleukin-1 gene cluster (D2S308 and D2S363, separated by 3.3 cR) (p=0.004 and p=0.002, respectively). CONCLUSION: This preliminary study suggests that a locus close to D2S308 and D2S363 is involved in the aetiology of Type 1 diabetes in the South Indian population.

Adolescent↗