PubMed Health⌕ Search

Biomedical subjects

D Brunner

Publications and source records attributed to D Brunner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Segregation analysis reveals a major gene effect controlling systolic blood pressure and BMI in an Israeli population.

It has been suggested that genetic factors control blood pressure level at all ages. However, the evidence is limited because of the composite nature of blood pressure and the heterogeneity of the studied samples. The purpose of the present study is to test for genetic influences on systolic blood pressure (SBP) level in a community-based Israeli family study. Segregation analysis was performed on 622 adults from 208 pedigrees. Age, sex, and body mass index (BMI) were significant covariates of SBP. Segregation analysis rejected the environmental transmission model but not the mixed Mendelian transmission model. The best-fitting genetic model was the mixed codominant model, with a heritability of 0.32 and an allele frequency of 0.18 for high SBP level. We further tested whether SBP and BMI shared a common major gene effect. Using bivariate segregation analysis involving two traits and a single locus, we found evidence for a single-locus pleiotropic effect on SBP and BMI. The allele frequency of this major locus was 0.24. The residual genetic correlation resulting from additive polygenes and the environmental correlation between these two traits were not different from zero after taking into account the shared major gene effect. The proportion of phenotypic variation attributable to this major gene effect increased with age for SBP but decreased with age for BMI.

Adult↗
PubMed1998

Baseline characteristics of patients participating in the Bezafibrate Infarction Prevention (BIP) Study.

Low high density lipoprotein (HDL) cholesterol, elevated triglycerides, or a combination of both, carries an increased risk of coronary heart disease (CHD). The benefit of therapy that increases serum HDL cholesterol concentrations and lowers triglyceride concentrations on the reduced incidence of myocardial infarctions and mortality has not been unequivocally demonstrated in healthy persons or patients with CHD. The Bezafibrate Infarction Prevention (BIP) study randomized men and women, with CHD and with total serum cholesterol 180 - 250 mg. dl-1, low density lipoprotein (LDL) cholesterol < or = 180 mg. dl-1 (< or = 160 mg. dl-1 below age 50 years), HDL cholesterol < or = 45mg. dl-1 and triglycerides < or = 300 mg. dl-1, to bezafibrate retard (400 mg once daily) or placebo. In addition to its effect on the lipids, this drug significantly lower plasma fibrinogen. The demographic, clinical and biochemical characteristics and existing cardiovascular therapy at baseline of 3122 patients randomized onto the study are presented here. A comparison is made with other on-going or recently published secondary prevention studies of lipid modification in CHD patients.

Adult↗
PubMed1998

[The diabetic foot].

Problems of the diabetic foot are frequent. The magnitude of the clinical picture and morbidity mirrors the severity and complexity of the underlying pathobiology. The three pathogenetic mechanism involved are ischemia, neuropathy and infection. Seldom do these mechanisms work in isolation, rather most foot problems result from a complex interplay among all three. The clinical picture of the diabetic foot reaches from the neuropathic deformity with diminished or absent sensation of pain to limited gangrene or superficial ulcer. The polymicrobial infection leads to extensive tissue destruction (plantarphlegmone) with osteomyelitis. The patients often notes no pain and may become aware of the infection only through the presence of drainage or a foul odor. These infections are usually more extensive than would be predicted by clinical signs and symptoms. These lesions must be debrided and drained promptly and completely. This often requires amputations of one or more toes, combined with an incision along the entire course of the infected track on the plantar or dorsal aspect of the foot. Cultures should be taken from the depth of the wound. Initial treatment should be with broad-spectrum antibiotics, with subsequent adjustment based on culture results. The diabetic foot is a clinical problem that can be solved with a high degree of success when the approached by an interdisciplinary team (specialists in infectious and vascular disease, podiatry and diabetology). Arterial reconstruction should be designed to restore maximum perfusion to the foot. The most effective result can be obtained with infra-inguinal vein bypass with distal anastomosis to the most proximal artery with direct continuity to the ischemic territory. The single most important factor in the achievement of the reduction of amputation is the autologous vein bypass. The overall outcome in the diabetic patient in terms of graft patency and limb salvage is equal to that in the nondiabetic.

Diabetic Foot↗
PubMed1997

Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice.

Although the concept of impulsivity has proved useful in human and animal studies of addiction, violent aggression, and violent suicide, and has been recognized as an important component of human behavior, little research has been done to understand the underlying psychobiological mechanisms. We explore the concept of impulsivity and its relation with the neurotransmitter serotonin in the context of aggressive behavior and behavior associated with positive reinforcement using a knockout mouse that lacks one of the serotonin receptors, the 5-HT1B receptor. This knockout mouse shows more impulsive aggression, acquires cocaine self-administration faster, and drinks more alcohol than the corresponding wild-type control. We show that the impulsive characteristics of these mice are not due to change in cognitive functions: in a cognitive task involving a choice between a small immediate one and a larger more delayed reward, knockout mice showed intact choice and timing capabilities and good discrimination of reward amounts. Thus, this mouse may prove an animal model of addiction and motor impulsivity.

Animals↗
PubMed1997

Mnemonics for variability: remembering food delay.

Three experiments with White Carneaux pigeons (Columba livia) investigated memory and decision processes under fixed and variable reinforcement intervals. Response rate was measured during the unreinforced trials in the discrete-trial peak procedure in which reinforced trials were mixed with long unreinforced trials. Two decision models differing in assumptions about memory constraints are reviewed. In the complete-memory model (J. Gibbon, R.M. Church, S. Fairhurst, & A. Kacelnik, 1988), all interreinforcement intervals were remembered, whereas in the minimax model (D. Brunner, A. Kacelnik, & J. Gibbon, 1996), only estimates of the shortest and longest possible reinforcement times were remembered. Both models accommodated some features of response rate as a function of trial time, but only the second was compatible with the observed cessation of responding.

Animals↗
PubMed1997

Low total cholesterol is associated with high total mortality in patients with coronary heart disease. The Bezafibrate Infarction Prevention (BIP) Study Group.

The present non-intervention screening study was undertaken to explore the relationships between pre-existing low total cholesterol and all-cause mortality. Eleven thousand, five hundred and sixty-three patients with coronary heart disease who attended a screening visit but were not included in the Bezafibrate Infarction Prevention study were followed-up for a mean of 3.3 years after determination of baseline total cholesterol. Five hundred and ninety-five (5%) of this largely unselected population who had total cholesterol levels < or = 160 mg.dl-1 formed the study population. The remaining 10968 patients acted as controls. The relative risk of all-cause mortality among patients with low cholesterol compared to others was 1.49 (95% CI: 1.16-1.91). The relative risk of non-cardiac death was 2.27 times higher in the low cholesterol group than in the controls (95% CI: 1.49-3.45), whereas the risk of cardiac death was the same in both groups (relative risk 1.09; 95% CI: 0.76-1.56). The most frequent cause of non-cardiac death associated with low total cholesterol was cancer. These results in patients with coronary heart disease add weight to previous studies associating low total cholesterol with an increased risk of non-cardiac death. However, a longer follow-up of this cohort of patients is necessary in order to clarify this association.

Adult↗
PubMed1997

[Epidemiologic studies of the occurrence of bovine virus diarrhea/mucosal disease in 2892 cattle in 95 dairy farms].

Blood samples were collected from 2892 cows and heifers of various ages from 95 dairy farms in the Kanton of St. Gallen and were tested for antibodies against bovine virus diarrhea. The percentages of seropositive, seronegative and inconclusive cases were 83.7%, 13.0% and 3.3%, respectively. In all herds, at least one case was seropositive, and in 29% of the herds, all the animals tested were seropositive. On a herd basis, the seroprevalence ranged from 16.2% to 100% with a mean (+/- SD) of 85.8 +/- 17.6%. The seroprevalence in one to two-year-old heifers was not significantly different from that of the entire sample.

Animals↗
PubMed1996

Tel Aviv-Heidelberg three-generation offspring study: genetic determinants of plasma fibrinogen level.

Elevated plasma fibrinogen concentrations (fibrinogen) are an important independent risk factor of atherosclerotic disease. Using the kinetic method, we measured fibrinogen in 808 individuals, of which 757 were members of 204 pedigrees. Correlation analysis and two-way analysis of variance (ANOVA) showed a significant association of fibrinogen with age, body mass index (BMI), sex, smoking habits, sport activity, and other lifestyle factors. However, multivariate regression analysis of fibrinogen established an independent significant contribution of only the first three factors. Fibrinogen levels adjusted respectively were subjected to complex segregation analysis. Our aim was to identify the contribution of major gene effects and residual (within the genotype) family correlations on fibrinogen variation. Results of this study suggest codominant alleles at a major locus accounting for 39% of variation. There was also evidence of a significant residual parent/offspring correlation.

Age Factors↗
PubMed1996

Validation of family history of breast cancer and identification of the BRCA1 and other syndromes using a population-based cancer registry.

A major risk factor for breast cancer is family history of the disease in first-degree relatives. This study evaluates the validity of family history information on breast cancer in mothers and sisters of breast cancer probands from the cancer registry (CR) compared to personal interviews (PI) of 359 consecutive population-based cases of breast cancer. Breast cancer is seen in mothers of 14% of probands by CR compared to 12% by PI. Further, 13% of probands have a sister with breast cancer using CR compared to 12% by PI. Using PI as the standard, the sensitivity of the CR family history data in mothers is 92% and the specificity is 99%, while in sisters they are 88% and 99%, respectively. These estimates were calculated on cases where family history information is available in the CR. Sensitivity and specificity are recalculated, recording an "error" whenever family history information is not available, and they are 75% and 68%, respectively, for mothers and 72% and 70%, respectively, for sisters. Estimates of proband-mother and proband-sisters familial breast cancer from CR and PI are sufficiently similar to warrant the use of CR family history data in studies of genetic epidemiology. The family phenotype consistent with the BRCA1 syndrome was found in four (1.1%) probands, all below age 50 years, while for BRCA2 there were five (1.4%) probands, three below age 50 years and two 50 years or older. Site-specific familial breast cancer was found in 23 (6.4%) probands. Population-based multiple-case breast cancer families can rapidly be identified through CR. These families can make substantial contributions to the study of genetic and environmental etiology of the disease as well as benefit from preventive and therapeutic efforts. As new knowledge and tools in molecular genetics become available, there is an urgent need for large population-based registries of families at high risk for cancer.

Adult↗
PubMed1996

Fibrinogen is a predictor of mortality in coronary heart disease patients. The Bezafibrate Infarction Prevention (BIP) Study Group.

Results of epidemiological studies have indicated that fibrinogen is an important primary cardiovascular risk factor. The role of fibrinogen as a predictor of mortality in coronary heart disease (CHD) patients is unclear. We investigated the association between fibrinogen and mortality in a large cohort of CHD patients screened for participation in a secondary prevention clinical trial. Of the total investigated, 3092 men who were not included in the trial and for whom vital status was known were followed up for a mean period of 3.2 years. In 54.4% of the 111 men who died, mortality was attributed to CHD. Mean baseline plasma fibrinogen levels were 29.4 mg/dL higher in patients who died than in the survivors. All-cause and CHD mortality rates increased with increasing fibrinogen levels. This relationship was also demonstrated within categories of the primary variables predicting mortality in these patients. The contribution of fibrinogen to CHD and all-cause mortality was assessed by multivariate analysis adjusting for age, CHD severity, and comorbidity. Risk of CHD and all-cause mortality for patients in the highest fibrinogen tertile were 1.67 and 1.75, respectively, relative to patients in the lowest tertile, and an increase of about 1 SD of plasma fibrinogen level (75 mg/dL) was found to increase risk of CHD and all-cause mortality 29% and 31%, respectively. These results indicate clearly that fibrinogen level is associated with significantly increased mortality in CHD patients. Implementation of a standardized measuring method is required to allow assessment of risk in CHD patients on the basis of fibrinogen levels.

Aged↗
PubMed1996

[Small-caliber polyurethane arterial prosthesis: clinical and angiomorphological follow-up of 20 patients in a prospective study].

The five year patency rate for femoropopliteal vein bypass grafts is around 70% according to the literature. Patency rates for synthetic grafts (eg PTFE, Dacron) range between 43 and 57%. If a vein is not available there is a new polyurethane 6 mm artery substitute on the market, that has shown in vitro promising physical characteristics and good long term results after implantation in dogs. In a prospective, randomized trial the results of the new polyurethane graft (PUR) were compared with those of a Dacron graft of the same diameter. Included in the study were 20 patients with lower limb ischemia stage Fontaine II B, III and IV, 10 in each group. Patency rates, handling of the graft and complications were analysed. During the one year follow up 7 PUR grafts had to be changed due to recurrent bypass occlusion within the first 3 months. At the end of the year there were only one PUR-bypass but 8 Dacron grafts open. 5 PUR grafts were examined histologically and no morphological reason for the occlusion, especially no myointimal hyperplasia, was found. A special regard was brought to the arterial run-off in both groups. It was confirmed to be comparable with only slightly better data for the PUR group. The exact reasons for the astonishing bad results of the PUR graft for femoropopliteal above knee bypass cannot be explained in our study. Due to the unexpected high occlusion rate the study was stopped earlier then planned.

Aged↗
PubMed1995

Tel Aviv-Heidelberg three-generation offspring study: genetic determinants of apolipoprotein A1 and apolipoprotein B.

The contribution of major gene and multifactorial effects on variation of plasma apolipoproteins A1 and B has been tested in a large sample of population-based Israeli pedigrees. Our most parsimonious and best fitting model for both apolipoproteins is consistent with Mendelian transmissibility, with significant contribution of major genes (with 2 alleles recessive and dominant within each locus) and polygenes, but neglects effects of common sib environment as well as related intergeneration differences in polygenic effects. Total genetic effects explain 71 and 58% of phenotypic variance of APO-A1 and APO-B levels. The major genes account for about 44 and 32% of the variance in APO-A1 and APO-B, respectively, and the frequency of the recessive alleles determining the high level of apolipoproteins under the study in the Israeli population is in the vicinity of 40% at each locus.

Apolipoprotein A-I↗
PubMed1995

Asymptomatic hyperglycemia in coronary heart disease: frequency and associated lipid and lipoprotein levels in the bezafibrate infarction prevention (BIP) register. The BIP Study Group.

BACKGROUND: The lipid profile of patients with type-II diabetes is characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and increased levels of lipoprotein (a), all of which may affect the prognosis in patients with atherosclerotic cardiovascular disease. This study aimed to assess the prevalence of asymptomatic hyperglycemia and the associated lipid profile in a large group of patients with documented coronary heart disease. METHODS: From February 1990 to October 1992, 14,326 patients aged 45-74 years with documented coronary heart disease (a history of myocardial infarction or angina pectoris) were screened for inclusion in a secondary prevention study using bezafibrate retard. All screened patients underwent a medical examination and a blood test after fasting for 14 h. Asymptomatic hyperglycemia was defined as a fasting blood glucose level of 140 mg/dl or above in patients with no previous history of diabetes mellitus. RESULTS: The prevalence of asymptomatic hyperglycemia was 4%, with no differences between the sexes or age groups. Total cholesterol and triglyceride levels were significantly higher and the high-density lipoprotein cholesterol level significantly lower in asymptomatic hyperglycemic than in normoglycemic patients. After multiple adjustments, the relative risk of death was 1.75 and 1.71 in patients with diabetes or asymptomatic hyperglycemia compared with those with no glycemic disorders. CONCLUSION: Asymptomatic hyperglycemia was detected in 4% of patients with ischemic heart disease. The lipid profile in these 4% resembles that of patients with confirmed diabetes, and their morbidity and mortality may therefore be higher than that of normoglycemic patients. Repeated assessment of glucose levels in patients with coronary heart disease is mandatory.

Aged↗
PubMed1994

The ETS domain protein pointed-P2 is a target of MAP kinase in the sevenless signal transduction pathway.

The fate of the R7 photoreceptor cell in the developing eye of Drosophila is controlled by the Sevenless (Sev) receptor tyrosine kinase. Sev activates a highly conserved signal transduction cascade involving the proteins Ras1 and Raf and the Rolled/mitogen-activated protein (Rl/MAP) kinase. Here we show that the ETS domain protein encoded by the P2 transcript of the pointed (pnt) gene is a nuclear target of this signalling cascade which acts downstream of Rl/MAP kinase. The PntP2 protein is phosphorylated by Rl/MAP kinase in vitro at a single site and this site is required for its function in vivo. Furthermore, we present genetic and biochemical data suggesting that MAP kinase controls neural development through phosphorylation of two antagonizing transcription factors of the ETS family, Yan and PntP2.

Animals↗
PubMed1994

The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway.

Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the sevenless (Sev) RTK is required for development of the R7 photoreceptor cell. Components of the signal transduction pathway activated by Sev in the R7 precursor include proteins encoded by the gap1, drk, Sos, ras1 and raf loci. In this report we present evidence that a Drosophila MAP kinase, ERK-A, is encoded by the rolled locus and is required downstream of raf in the Sev signal transduction pathway.

Animals↗
PubMed1994

A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways.

In the Drosophila eye, activation of the sevenless (sev) receptor tyrosine kinase is required for the specification of the R7 photoreceptor cell fate. In a genetic screen for mutations that result in the activation of the sev signaling pathway in the absence of the inducing signal, we identified a gain-of-function mutation in rolled (rlSevenmaker [rlSem]), which encodes a homolog of mitogen-activated protein (MAP) kinase. In addition to the sev pathway, this mutation activates the pathways controlled by torso and the epidermal growth factor receptor homology. The rlSem mutation results in the substitution of a single conserved amino acid in the kinase domain. Activation of MAP kinase by the rlSem mutation is both necessary and sufficient to activate multiple signaling pathways controlled by receptor tyrosine kinases.

Alleles↗