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J Muntwyler

Publications and source records attributed to J Muntwyler.

At least 19 recordsLinked to original sources
PubMed2006

Genetic diversity among horse populations with a special focus on the Franches-Montagnes breed.

Genetic characterization helps to assure breed integrity and to assign individuals to defined populations. The objective of this study was to characterize genetic diversity in six horse breeds and to analyse the population structure of the Franches-Montagnes breed, especially with regard to the degree of introgression with Warmblood. A total of 402 alleles from 50 microsatellite loci were used. The average number of alleles per locus was significantly lower in Thoroughbreds and Arabians. Average heterozygosities between breeds ranged from 0.61 to 0.72. The overall average of the coefficient of gene differentiation because of breed differences was 0.100, with a range of 0.036-0.263. No significant correlation was found between this parameter and the number of alleles per locus. An increase in the number of homozygous loci with increasing inbreeding could not be shown for the Franches-Montagnes horses. The proportion of shared alleles, combined with the neighbour-joining method, defined clusters for Icelandic Horse, Comtois, Arabians and Franches-Montagnes. A more disparate clustering could be seen for European Warmbloods and Thoroughbreds, presumably from frequent grading-up of Warmbloods with Thoroughbreds. Grading-up effects were also observed when Bayesian and Monte Carlo resampling approaches were used for individual assignment to a given population. Individual breed assignments to defined reference populations will be very difficult when introgression has occurred. The Bayesian approach within the Franches-Montagnes breed differentiated individuals with varied proportions of Warmblood.

Animals↗
PubMed2006

Analysis of pedigree and conformation data to explain genetic variability of the horse breed Franches-Montagnes.

Franches-Montagnes is the only native horse breed in Switzerland, therefore special efforts should be made for ensuring its survival. The objectives of this study were to characterize the structure of this population as well as genetic variability with pedigree data, conformation traits and molecular markers. Studies were focused to clarify if this population is composed of a heavy- and a light-type subpopulation. Extended pedigree records of 3-year-old stallions (n = 68) and mares (n = 108) were available. Evaluations of body conformation traits as well as pedigree data and molecular markers did not support the two-subpopulation hypothesis. The generation interval ranged from 7.8 to 9.3 years. The complete generation equivalent was high (>12). The number of effective ancestors varied between 18.9 and 20.1, whereof 50% of the genetic variability was attributed to seven of them. Genetic contribution of Warmblood horses ranged from 36% to 42% and that of Coldblood horses from 4% to 6%. The average inbreeding coefficient reached 6%. Inbreeding effective population size was 114.5 when the average increase of the inbreeding coefficient per year since 1910 was taken. Our results suggest that bottleneck situations occurred because of selection of a small number of sire lines. Promotion of planned matings between parents that are less related is recommended in order to avoid a reduction of the genetic diversity.

Animals↗
PubMed2005

[Molecular genetic studies of the "Einsiedler" horse population].

In this study it was investigated whether the "Einsiedler" warmblood horse, a historically old horse population from central Switzerland (Abbey of Einsiedeln), is distinguishable from micellaneous horse breeds, using molecular genetic techniques. The breeding history of Einsiedler horses is characterised by systematic line breeding through the dams. Therefore, two Einsiedler dam lines (N = 28), going back to the middle of the 19th century according to pedigree entries, were the focus of the survey. Random samples of diverse warmblood horse populations, but also samples from more distinct types of horse breeds, served as comparison populations (N = 52). Variation in the mitochondrial genome appeared to be only partially informative to demarcate the studied horses, as horses of distinct breeds may share identical mtDNA sequence fragments. Both dam lines revealed haplotypes commonly found in Iberian horse breeds. This is to take as an indication on the genetic origin of Einsiedler horses. Furthermore, the Klima dam line held a homologous mtDNA sequence fragment with E. ferus przewalskii. Therefore, this seems to be a phylogenetically old haplotype. The analysis of microsatellite loci revealed that horses from the two Einsiedler dam lines were in fact distinguishable from more distinct types of horses, but not from closely related European warmblood horse breeds and English thoroughbred.

Animals↗
PubMed2005

Bovine spinal muscular atrophy: AFG3L2 is not a positional candidate gene.

Bovine spinal muscular atrophy (BSMA) is a neurodegenerative disorder, which is widespread in Brown Swiss cattle. Main symptoms of the disease are muscular atrophy and recumbency. Affected calves die within few days or weeks. BSMA seems to be inherited as a recessive trait and the disease allele appears to have a common origin. In this study, a pedigree with 30 affected BSMA calves was used to genetically localize the BSMA locus. Linkage analysis was performed between microsatellite markers of seven chromosomes, where the homologous genes of human neurodegenerative disorders are located according to comparative mapping data, and the disease genotype. BSMA was mapped to chromosome 24 confirming the recently published localization (Medugorac et al. 2003). The candidate gene AFG3L2 was physically mapped to chromosome 24q24 using fluorescence in situ hybridization. Due to their different localizations AFG3L2 is not a positional candidate for BSMA. An informative marker localized on the telomeric side of the BSMA locus would be beneficial for marker-assisted selection as well as searching for the causative gene. However, finding a marker distal to BSMA locus is difficult because of its position at the end of the chromosome.

Adenosine Triphosphatases↗
PubMed2002

Consequences of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

Aside from causing hemolytic reactions the ABO blood group system does not have an impact on outcome after allogeneic bone marrow or peripheral blood stem cell transplantation (SCT). However, only a few studies have addressed the effect of ABO incompatibility on the incidence of GVHD, time to engraftment, relapse and survival. Therefore, we performed a retrospective two-center analysis of 562 consecutive patients receiving allogeneic SCT, including 361 ABO-identical, 98 minor, 86 major and 17 bidirectional ABO-incompatible SCT. In multivariate analysis adjusted for potential confounders survival was significantly associated with ABO incompatibility (P = 0.006). Compared to ABO-identical SCT, bidirectional ABO incompatibility increased the risk significantly (RR, 2.8; 95% CI, 1.5-5.1; P = 0.0009), whereas survival of patients with minor (RR, 1.2; 95% CI, 0.9-1.7; P = 0.27), or major ABO-incompatible SCT (RR, 1.3; 95% CI, 0.9-1.8; P= 0.18) was not significantly different. RBC engraftment was delayed in major ABO-incompatible SCT (RR, 0.66; 95% CI, 0.51-0.85; P = 0.001). The incidence of acute GVHD (grade I-IV) was higher in minor ABO-incompatible SCT as compared to ABO identity (RR, 2.8; 95% CI, 1.3-5.9, P = 0.009). This difference was limited to mild GVHD; in moderate-to-severe GVHD (grade II-IV) no significant difference was found among the groups (P = 0.53). The relapse rate was not influenced by ABO incompatibility (P = 0.78). In conclusion, these results suggest that ABO incompatibility represents a risk factor not only for post-transplant hemolysis, but also for survival and the rate of mild GVHD after allogeneic SCT.

ABO Blood-Group System↗
PubMed2002

One-year mortality among unselected outpatients with heart failure.

OBJECTIVE: To estimate 1-year mortality and prognostic factors in unselected outpatients with heart failure, and to compare the observed mortality with the estimates of the primary care physicians. METHODS AND RESULTS: Four hundred and eleven consecutive patients with heart failure New York Heart Association (NYHA) class II-IV (mean population age 75 years, 56% males) were enrolled in 71 primary care offices throughout Switzerland. During a mean follow-up period of 1.4 years, 68 patients had died. One-year total mortality was 12.6% compared to 4.3% in the underlying Swiss population (standardized mortality ratio 3.0). Among patients with heart failure NYHA II, III and IV, mortality was 7.1%, 15.0% and 28.0%, respectively. In multivariate Cox regression, statistically significant (P<0.05) predictors of mortality were NYHA class (NYHA III: risk ratio [RR]=1.6; NYHA IV: RR=2.2), recent hospital stay for heart disease (RR=2.3), creatinine>120 micromol.l(-1) (RR=1.8) systolic blood pressure<100 mmHg (RR=2.4), heart rate>100 min(-1) (RR=2.7), age (per 10 years, RR=1.6) and female gender (RR=0.49). Among patients with reduced left ventricular ejection fraction, 1-year mortality was 14.3%, and predictors were similar except that female gender was no longer associated with reduced mortality. Primary care physicians significantly overestimated 1-year mortality (estimated mortality 25.9% vs observed mortality 12.6%,P =0.001). CONCLUSIONS: Unselected outpatients with heart failure have a poor prognosis, particularly those with advanced heart failure and a recent hospital stay for heart disease. Primary care physicians are aware of the high mortality of this growing patient population.

Aged↗
PubMed2001

Post-prandial lipaemia and endothelial function among healthy men.

BACKGROUND: There is evidence that elevated post-prandial lipoproteins adversely affect progression and outcome of cardiovascular disease. Traditional risk factors are associated with impaired endothelium-mediated vasodilatation. However, studies regarding the relationship between post-prandial lipaemia and endothelial function are divergent. METHODS: Twelve healthy non-smokers were included in this study. Before and after intake of a lipid cocktail rich in dairy fat, we tested endothelial-dependent (acetylcholine 0.8-160 mg/min per 100 ml forearm tissue) and -independent (sodium nitroprussid 0.6 microgram/min) vascular function in the forearm vascular bed with plethysmography. Moreover, we tested the effect of 1-NMMA, a competitive inhibitor of the NO synthetase, on base-line flow. Extent of post-prandial lipaemia was assessed with the increases in triglycerides and retinyl-palmitate, a marker for intestinally derived lipoproteins. RESULTS: Baseline flow was higher after the test meal than during fasting (preprandial 6.5 +/- 0.5 ml/min* 100 ml tissue, post-prandial 8.0 +/- 0.5, p = 0.03), but similar after 1-NMMA (p = 0.85). Before and after intake of the test meal, there was no significant difference in acetylcholine-induced endothelium-dependent vasodilatation (repeated measurement ANOVA, p = 0.22). At the highest acetylcholine dose, forearm flow was very similar (fasting 18.4 +/- 1.9, post-prandial 17.9 +/- 1.9, p = 0.75). At maximum acetylcholine dose, there was a weak inverse but non-significant correlation between forearm flow and post-prandial triglyceridaemia (r = -0.38, p = 0.23) and intestinally derived lipoproteins (chylomicrons r = -0.29, p = 0.35, chylomicron remnants r = -0.15, p = 0.63). However, at the lowest acetylcholine dose there was a suggestion for a positive correlation between change in flow and post-prandial lipaemia (triglyceridaemia, r = 0.53, p = 0.07; chylomicrons, r = 0.41, p = 0.18 and remnants, r = 0.51, p = 0.09). Endothelium-independent vasodilatation in response to sodium nitroprusside did not significantly change (p = 0.23). CONCLUSION: Our results suggest that among healthy men post-prandial lipaemia is not associated with a notable impairment of endothelium-mediated vascular function in forearm resistance vessels.

Adult↗
PubMed2001

Graft-versus-host disease and survival after ABO-incompatible allogeneic bone marrow transplantation: a single-centre experience.

The effect of ABO-incompatibility on graft versus host disease (GVHD) and survival was evaluated in 173 consecutive patients receiving allogeneic bone marrow transplantation (BMT). Thirty-four percent of the patients developed GVHD and univariate analysis suggested a higher incidence of GVHD in minor ABO-incompatibility than in ABO-identity (14/30, 47% versus 37/112, 33%; P = 0.02). However, using logistic regression adjusted for potential confounders, the GVHD risk did not differ significantly. During a mean follow-up time of 59 months, the mortality was 37% and survival was significantly dependent on ABO-compatibility (P = 0.004). In particular, patients with bidirectional ABO-incompatibility had an excess mortality rate (RR, 7.6; 95% CI, 2.5-23.2; P = 0.0004). Taken together, these results suggest that ABO-incompatibility may represent a risk factor in allogeneic BMT.

ABO Blood-Group System↗
PubMed2000

[Medical treatment of heart failure: an analysis of actual treatment practices in outpatients in Switzerland. The Swiss "IMPROVEMENT of HF" Group].

BACKGROUND: From several studies in Europe and the USA there is evidence that drug treatment of patients with congestive heart failure (CHF) could be improved. There are only sparse data on the treatment of this population in Switzerland. METHODS: In the context of a European Study (IMPROVEMENT of HF Study), in 1999, the treatment of 474 patients with symptomatic CHF was recorded by chart review with primary care physicians throughout Switzerland. The effect of potential predictors of drug treatment was tested using multivariate logistic regression. RESULTS: Mean age of the study population was 75 +/- 12 years. Overall, angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) were prescribed to 65% of the study population. Beta-blockers, loop diuretics/thiazides, spironolactone and digitalis were prescribed to 25%, 73%, 13% and 31% respectively. Compared with CHF patients < 65 years of age, the odds ratio of ACE-I/ARB prescription in patients aged 65-74, 75-84, and > or = 85 years was 0.80, 0.58 and 0.40 respectively (p < 0.001). The respective odds ratios for beta blocker treatment were 0.37, 0.21 and 0.06 (p < 0.001). In addition, NYHA classification, comorbid conditions such as renal failure and contraindications strongly predicted drug prescription. Gender and geographical area were not associated with drug selection. CONCLUSIONS: Overall drug prescription among CHF patients in Swiss primary care appears to be satisfactory. However, prescription of ACE-I/ARB and beta-blockers falls steeply with increasing age, independent of measured comorbid conditions and contraindications. Thus, improvement of treatment should focus on a more consistent use of these drugs in the segment of elderly CHF patients.

Adrenergic beta-Antagonists↗
PubMed2000

Diagnostic errors in three medical eras: a necropsy study.

BACKGROUND: Studies comparing the accuracy of clinical diagnosis in unselected patients who died in hospital in different medical eras have shown no decline of errors in the main diagnosis. We assessed changes in diagnostic accuracy over 20 years. METHODS: We analysed retrospectively diagnostic errors, with use of necropsy as the gold standard for diagnosis. We randomly selected 300 patients who died at a tertiary-care teaching hospital in Switzerland--100 in each of 1972, 1982, and 1992. We classified discrepancies between clinical diagnosis and necropsy findings as major and minor errors. FINDINGS: The overall necropsy rate at the hospital stayed at around 90% for the whole period. During the study, the frequency of major discrepancies declined significantly (1972, 30%; 1982, 18%; 1992, 14%; p=0.007). The rate of minor diagnostic errors increased significantly from 23% in 1972 to 46% in 1992 (p<0.001). The increase in overall diagnostic accuracy occurred mainly because of a significant improvement in specificity for cardiovascular diseases (1972, 85%; 1982, 82%; 1992, 97%; p=0.034) and non-significantly improved sensitivity (1972, 69%; 1982, 82%; 1992, 86%; p=0.061). Sensitivity also improved for infectious diseases (1972, 25%; 1982, 67%; 1992, 86%; p=0.036). Sensitivity and specificity for neoplastic diseases were high originally and did not change. The total number of diagnostic procedures per year increased from 191 in 1972 to 259 in 1992, mainly because of non-invasive techniques, such as ultrasonography, and endoscopies. INTERPRETATION: The frequency of major diagnostic errors in unselected patients who died in hospital was halved over 20 years, probably because of improved clinical skills and new diagnostic procedures.

Aged↗
PubMed2000

A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study.

CONTEXT: Although basic research provides plausible mechanisms for benefits of beta carotene supplementation on nonmelanoma skin cancer (NMSC) primarily consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), observational studies are inconsistent. Randomized trial data are limited to 1 trial of secondary prevention that showed no effect of beta carotene on the incidence of NMSC after 5 years. OBJECTIVE: To test whether supplementation with beta carotene reduces the risk for development of a first NMSC, including BCC and SCC. DESIGN: Randomized, double-blind, placebo-controlled trial with 12 years of beta carotene supplementation and follow-up. SETTING: Physicians' Health Study in the United States. PARTICIPANTS: Apparently healthy male physicians aged 40 to 84 years in 1982 (N = 22 071). INTERVENTION: Beta carotene, 50 mg, on alternate days. MAIN OUTCOME MEASURE: Relative risk (RR) and 95% confidence interval (CI) for a first NMSC, BCC, and SCC. RESULTS: After adjusting for age and randomized aspirin assignment, there was no effect of beta carotene on the incidence of a first NMSC (RR, 0.98; 95% CI, 0.92-1.05), BCC (RR, 0.99; 95% CI, 0.92-1.06), or SCC (RR, 0.97; 95% CI, 0.84-1.13). There was also no significant evidence of beneficial or harmful effects of beta carotene on NMSC by smoking status (current, past, or never). CONCLUSION: This large-scale, randomized, primary prevention trial among apparently healthy well-nourished men indicates that an average of 12 years of supplementation with beta carotene does not affect the development of a first NMSC, including BCC and SCC.

Adult↗
PubMed2000

Acute hemodynamic and neurohumoral effects of selective ET(A) receptor blockade in patients with congestive heart failure. ET 003 Investigators.

OBJECTIVES: To investigate the hemodynamic effects of the selective endothelin (ET)A receptor antagonist LU135252 in patients with congestive heart failure (CHF). BACKGROUND: Nonselective ET(A/B( receptor antagonists improve hemodynamics in patients with CHF. Since ET(B( receptors mediate the release of nitric oxide and the clearance of ET-1, selective ET(A) antagonists are of special interest. METHODS: The hemodynamic effects of a single oral dose of the selective ET(A) receptor antagonist LU135252 (1, 10, 30, 100 or 300 mg) were investigated in a multicenter study involving 95 patients with CHF (New York Heart Association II-III) with an ejection fraction < or = 35%. RESULTS: Baseline ET-1 positively correlated with pulmonary vascular resistance, pulmonary capillary wedge pressure (PCWP), and mean pulmonary artery pressure (MPAP, r = 0.37-0.50, p < 0.0004) but were inversely related to cardiac index (CI; r = -0.36, p = 0.0004). LU135252 dose dependently increased CI and decreased mean arterial pressure and systemic vascular resistance (p < 0.03-0.0002), while heart rate remained constant or decreased slightly. Pulmonary capillary wedge pressure, MPAP, pulmonary vascular resistance and right atrial pressure also decreased significantly (p < 0.035- < 0.0001). Two hours after LU135252, plasma ET-1 did not significantly increase after 1 mg but did so by 23% (p = 0.003), 29% (p = 0.0018), 56% (p < 0.0001) and 101% (p < 0.0001) after 10, 30, 100 and 300 mg, respectively, while plasma catecholamines remained constant. CONCLUSIONS: In patients with CHF, a single oral dose of the selective ET(A) receptor antagonist LU135252 improves hemodynamics in a dose-dependent manner without activation of other neurohumoral systems and is well tolerated over a wide dose range.

Catecholamines↗
PubMed2000

Management of heart failure in Switzerland.

Similar to other countries, heart failure is a major cause of morbidity and mortality in Switzerland. Among heart failure patients admitted to a Swiss university hospital in 1998, admission therapy included: ACE inhibitors/AT-II blockers in approximately two-thirds; diuretics in approximately 70%; and beta-blockers in approximately one-third. Easy access to diagnostic tests and limited results of surveys suggest that quality of care of heart failure patients is satisfactory in Switzerland. However, results from ongoing studies are required to assess more reliably the quality of diagnosis and therapy of this high-risk population in Switzerland.

Heart Failure↗
PubMed2000

[Epidemiology of heart failure].

During the past decades incidence and prevalence of heart failure has markedly increased. This contrasts with most other cardiovascular diseases, which have declined. Among people aged 80 years and over prevalence may be as high as several percent of the population. According to the high prevalence of the disease, the high frequency of outpatient consultations, but in particular because of a high rate of hospitalizations with long average duration, costs for the health care system are very high. Patients with heart failure suffer from a reduction in quality of life exceeding that of most other chronic diseases, and mortality after diagnosis of heart failure remains high.

Adult↗
PubMed1999

[Lipid-lowering therapy in patients with coronary disease: proportion of patients requiring treatment according to recommendations of the Swiss Society of Cardiology].

BACKGROUND: Recent studies have confirmed that treatment with lipid-lowering drugs decreases cardiovascular morbidity and mortality in primary as well as secondary prevention of cardiovascular diseases. In 1999, new Swiss recommendations for treatment with lipid-lowering drugs have been published. We therefore performed a study to estimate the proportion of patients with coronary artery disease requiring lipid-lowering drugs. METHODS: We included 637 patients with coronary heart disease who were referred for coronary angiography during 1991-1993. We calculated the proportion of patients requiring lipid-lowering drugs according to the new Swiss guidelines, and compared them with European and US guidelines. RESULTS: According to the 1999 Swiss recommendations, 79% of the study population would have qualified for lipid-lowering treatment (males 80%, females 78%; patients aged up to 69 years 80%, patients aged 70 years and over 73%). Agreement with both the Recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention, and the ACC/AHA Guidelines for Management of Patients with Acute Myocardial Infarction, was 96% (Kappa 0.79 and 0.83 respectively). CONCLUSION: A large proportion of patients with coronary artery disease qualifies for treatment with lipid-lowering drugs. The new Swiss recommendations closely agree with European and US guidelines.

Aged↗