PubMed Health⌕ Search

Biomedical subjects

M Holmberg

Publications and source records attributed to M Holmberg.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative trait loci affecting fertility and calving traits in Swedish dairy cattle.

Impaired fertility is the main reason for involuntary culling of dairy cows in Sweden. The objective of this study was to map quantitative trait loci (QTL) influencing fertility and calving traits in the Swedish dairy cattle population. The traits analyzed were number of inseminations, 56-d nonreturn rate, interval from calving to first insemination, fertility treatments, heat intensity score, stillbirth, and calving performance. A genome scan covering 20 bovine chromosomes was performed using 145 microsatellite markers. The mapping population consisted of 10 sires and their 417 sons in a granddaughter design. Nine of the sires were of the Swedish Red Breed, and one was a Swedish Holstein. Least squares regression was used to map loci affecting the analyzed traits, and permutation tests were used to set significance thresholds. Cofactors were used in the analyses of individual chromosomes to adjust for QTL found on other chromosomes. The use of cofactors increased both the number of QTL found and the significance level. In the initial analysis, we found 13 suggestive QTL that were mapped to chromosomes 6, 7, 9, 11, 13, 15, 20, and 29. When cofactors were included, 30 QTL were detected on chromosomes 1, 3, 4, 18, 19, 22, and 25, in addition to the 8 previously mentioned chromosomes. Some of the results from the cofactor analysis may be false positives and require further validation. In conclusion, we were able to map several QTL affecting fertility and calving traits in Swedish dairy cattle.

Animals↗
PubMed2005

Pharmacokinetics and tolerability of different doses of fentanyl following sublingual administration of a rapidly dissolving tablet to cancer patients: a new approach to treatment of incident pain.

AIMS: It is estimated that two-thirds of cancer patients will at some point during their illness experience breakthrough pain. In this study, the pharmacokinetics of a novel sublingual dosage form of fentanyl developed for breakthrough pain was evaluated. METHODS: Eleven Caucasian patients (seven male and 4 female, aged 34-75 years, median 60 years) with metastatic malignant disease were recruited initially, but three patients withdrew. Prior to the study all patients were on continuous nonfentanyl opiate medication. The study was a double-blind, cross-over trial, consisting of three 1-day treatment periods. A new rapidly dissolving preparation of fentanyl, was administered sublingually in single doses of 100, 200 and 400 microg, respectively, on three separate occasions. Plasma fentanyl concentrations were determined using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated by noncompartment analysis. Tolerability and the occurrence of adverse events were monitored throughout the study by patient questionnaire. RESULTS: The data from nine subjects who completed at least two periods were used in the analysis of variance. There were no significant differences between doses (100, 200 and 400 microg) for dose adjusted AUC (F = 0.42, P = 0.6660), dose adjusted C(max) (F = 0.08, P = 0.9206) and Tmax (F = 0.94, P = 0.4107). Thus, these parameters showed dose proportionality. The differences (400-100microg) in dose adjusted AUC from the three-period crossover analysis was -0.016 min.ng/ml (t = 0.71, P = 0.8718). Interindividual variability in systemic exposure to fentanyl was fairly small (25-40%), which may be related to a good in vivo biopharmaceutical performance of the sublingual tablet, and a relatively small fraction of the dose being swallowed. The first detectable plasma concentration of fentanyl was observed between 8 and 11 min after administration. t(max) increased from 39.7 +/- 17.4 to 48.7 +/- 26.3 and 56.7 +/- 24.6 min for the 100, 200 and 400 microg doses, respectively. Adverse events were few and did not increase with increasing dose. CONCLUSION: With this rapidly dissolving fentanyl formulation, the first detectable plasma concentration of fentanyl was observed at 8-11 min after administration. The pharmacokinetics of the drug showed dose proportionately. This formulation of fentanyl seemed to be well tolerated by the patients.

Administration, Sublingual↗
PubMed2004

Quantitative trait loci affecting health traits in Swedish dairy cattle.

The purpose of this study was to map quantitative trait loci (QTL) affecting health traits in Swedish dairy cattle. A genome scan covering 17 chromosomes was performed. Ten grandsire families were used in a granddaughter design. Nine of the families belonged to the Swedish Red and White breed, which is related to other Nordic Ayrshire breeds, and one family was of the Swedish Holstein breed. A total of 417 bulls were genotyped for 116 microsatellite markers distributed over 17 chromosomes. Daughter yield deviations for clinical mastitis, somatic cell count (SCC), and other diseases (OD) were included in the analysis. Least squares interval mapping using putative QTL as cofactors was applied both within and across grandsire families. Significance thresholds were set by permutation tests. In the across-family analysis, we detected 8 suggestive QTL and 3 QTL significant at the genome level. The QTL affecting clinical mastitis were found on 3 chromosomes (9, 11, and 25), 4 QTL for SCC were found (on chromosomes 5, 9, 11, and 23), and we detected 4 QTL for OD (on chromosomes 9, 11, 15, and 25). In addition, we found several QTL that segregated within single families but where the QTL effect was not significant in the across-family analysis. In conclusion, we were able to locate QTL for all 3 analyzed traits, and overlapping QTL for several traits were observed.

Animals↗
PubMed2003

Regional distribution of alpha(2C)-adrenoceptors in brain and spinal cord of control mice and transgenic mice overexpressing the alpha(2C)-subtype: an autoradiographic study with [(3)H]RX821002 and [(3)H]rauwolscine.

Behavioral studies on gene-manipulated mice have started to elucidate the neurobiological functions of the alpha(2C)-adrenoceptor (AR) subtype. In this study, we applied quantitative receptor autoradiography to investigate the potential anatomical correlates of the observed functional effects of altered alpha(2C)-AR expression. Labeling of brain and spinal cord sections with the subtype non-selective alpha(2)-AR radioligand [(3)H]RX821002 and the alpha(2C)-AR-preferring ligand [(3)H]rauwolscine revealed distinct binding-site distribution patterns. In control mice, [(3)H]rauwolscine binding was most abundant in the olfactory tubercle, accumbens and caudate putamen nuclei, and in the CA1 field of the hippocampus. A mouse strain with overexpression of alpha(2C)-AR regulated by a gene-specific promoter showed approximately two- to four-fold increased levels of [(3)H]rauwolscine binding in these regions. In addition, dramatic increases in [(3)H]rauwolscine binding were seen in the nerve layer of the olfactory bulb, the molecular layer of the cerebellum, and the ventricular system of alpha(2C)-AR-overexpressing mice, representing "ectopic" alpha(2C)-AR expression. Competition-binding experiments with several alpha(2)-AR ligands confirmed the alpha(2C)-AR identity of these sites. Our results provide quantitative evidence of the predominance of the alpha(2A)-AR subtype in most regions of the mouse CNS, but also disclose the wide distribution of alpha(2C)-AR in the normal mouse brain, although at relatively low density, except in the ventral and dorsal striatum and the hippocampal CA1 area. alpha(2C)-AR are thus present in brain regions involved in the processing of sensory information and in the control of motor and emotion-related activities such as the accumbens and caudate putamen nuclei, the olfactory tubercle, the lateral septum, the hippocampus, the amygdala, and the frontal and somatosensory cortices. The current results may help in specifying an anatomical framework for the functional roles of the alpha(2A)- and alpha(2C)-AR subtypes in the mouse CNS.

Adrenergic alpha-Antagonists↗
PubMed2003

Bartonella infection in sylvatic small mammals of central Sweden.

Sylvatic small mammals were captured in rural habitats near Uppsala, Sweden, to measure the prevalence of bartonella infections, characterize bacterial isolates and identify their host range, and increase our understanding of host-pathogen ecology. During 7 nights of trapping at 3 localities, 236 small mammals were captured (trap success 30%). Bartonella were isolated from bloods of Apodemus flavicollis (19 of 110 tested), Apodemus sylvaticus (6/25), Clethrionomys glareolus (9/60), Microtus agrestis (1/3), Mus musculus (1/18), and Sorex araneus (3/20). Nucleotide sequencing (a 338 bp fragment of the gltA gene) of 40 isolates yielded 6 unique genotypes. Five of the 6 genotypes were most similar to other known bartonella isolated from Old World small-mammal hosts. The most frequent genotype (83%) was isolated from A. flavicollis and M. musculus and was identical to Bartonella grahamii, a recently demonstrated human pathogen. These two hosts were most frequently captured in and around human structures and work places, thus providing conditions that could potentially lead to frequent human infections.

Animals↗
PubMed2002

Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1.

Migraine is the most common type of chronic episodic headache. To find novel susceptibility genes for familial migraine with and without aura, a genomewide screen was performed in a large family from northern Sweden. Evidence of linkage was obtained on chromosome 6p12.2-p21.1, with a maximum two-point lod score of 5.41 for marker D6S452. The patients with migraine shared a common haplotype of 10 Mb between markers D6S1650 and D6S1960.

Adult↗
PubMed2002

The epidemiology of out-of-hospital 'sudden' cardiac arrest.

It is difficult to assemble data from an out-of-hospital cardiac arrest since there is often lack of objective information. The true incidence of sudden cardiac death out-of-hospital is not known since far from all of these patients are attended by emergency medical services. The incidence of out-of-hospital cardiac arrest increases with age and is more common among men. Among patients who die, the probability of having a fatal event outside hospital decreases with age; i. e. younger patients tend to more often die unexpectedly and outside hospital. Among the different initial arrhythmias, ventricular fibrillation is the most common among patients with cardiac aetiology. The true distribution of initial arrhythmias is not known since several minutes most often elapse between collapse and rhythm assessment. Most patients with out-of-hospital cardiac arrest have a cardiac aetiology. Out-of-hospital cardiac arrests most frequently occur in the patient's home, but the prognosis is shown to be better when they occur in a public place. Witnessed arrest, ventricular fibrillation as initial arrhythmia and cardiopulmonary resuscitation are important predictors for immediate survival. In the long-term perspective, cardiac arrest in connection with acute myocardial infarction, high left ventricular ejection fraction, moderate age, absence of other heart failure signs and no history of myocardial infarction promotes better prognosis. Still there is much to learn about time trends, the influence of patient characteristics, comorbidity and hospital treatment among patients with prehospital cardiac arrest.

Death, Sudden, Cardiac↗
PubMed2002

Characteristics and outcome among patients having out of hospital cardiac arrest at home compared with elsewhere.

OBJECTIVE: To describe the characteristics and outcome of patients who have a cardiac arrest at home compared with elsewhere out of hospital. PATIENTS: Subjects were patients included in the Swedish cardiac arrest registry between 1990 and 1999. The registry covers about 60% of all ambulance organisations in Sweden. METHODS: The study sample comprised patients reached by the ambulance crew and in whom resuscitation was attempted out of hospital. There was no age limit. Crew witnessed cases were excluded. The patients were divided into two groups: cardiac arrest at home and cardiac arrest elsewhere. RESULTS: Among a study population of 24 630 patients the event took place at home in 16 150 (65.5%). Those in whom the arrest took place at home differed from the remainder in that they were older, were more often women, less often had a witnessed cardiac arrest, were less often exposed to bystander cardiopulmonary resuscitation (CPR), were less often found in ventricular fibrillation, and had a longer interval between collapse and call for ambulance, arrival of ambulance, start of CPR, and first defibrillation. Of patients in whom the arrest took place at home, 11.3% were admitted to hospital alive, v 19.4% in the elsewhere group (p < 0.0001); corresponding figures for survival after one month were 1.7% v 6.2% (p < 0.0001). The adjusted odds ratio for survival after one month (at home v not at home; considering age, sex, initial arrhythmia, bystander CPR, aetiology, and whether the arrest was witnessed) was 0.40 (95% confidence interval 0.33 to 0.49; p < 0.0001). CONCLUSIONS: Sixty five per cent of out of hospital cardiac arrests in Sweden occur at home. The patients differed greatly from those with out of hospital cardiac arrests elsewhere, and fewer than 2% were alive after one month. Having an arrest at home was a strong independent predictor of adverse outcome. Further research is needed to identify the reasons for this.

Adolescent↗
PubMed2001

Linkage analysis suggests a region of importance for multiple sclerosis in 3p14-13.

Four genomic screens for linkage in multiple sclerosis (MS) have been reported. They confirmed the established role of the human leucocyte antigen (HLA) complex genes in MS and, in addition, suggested the importance of a few other chromosomal segments. Here we report evidence for the importance of 3p14-13 region identified by suggestive linkage in genomic screens from Canada and the United Kingdom. When studying 146 Nordic MS multiplex families, mostly affected sib-pairs, with eight microsatellite markers, spanning a 36-cM region, we observed a two-point non-parametric linkage (NPL) score of 2.39 (P = 0.007) by the GENEHUNTER package for marker D3S1285 and a multipoint NPL score of 1.20 in the same region. Association studies in Swedish MS patients revealed modest allelic associations of uncertain significance not supported by transmission analysis. Analysis of the trinucleotide repeat sequence of the SCA7 gene in Swedish index cases did not reveal expansions. We conclude that support was obtained for the location of a gene or genes with importance for MS susceptibility in 3p14-13 region.

Alleles↗
PubMed2001

Factors modifying the effect of bystander cardiopulmonary resuscitation on survival in out-of-hospital cardiac arrest patients in Sweden.

AIM: To describe possible factors modifying the effect of bystander cardiopulmonary resuscitation on survival among patients suffering an out-of-hospital cardiac arrest. PATIENTS: A national survey in Sweden among patients suffering out-of-hospital cardiac arrest and in whom resuscitative efforts were attempted. Sixty per cent of ambulance organizations were included. DESIGN: Prospective evaluation. Survival was defined as survival 1 month after cardiac arrest. RESULTS: In all, 14065 reports were included in the evaluation. Of these, resuscitation efforts were attempted in 10966 cases, of which 1089 were witnessed by ambulance crews. The report deals with the remaining 9877 patients, of whom bystander cardiopulmonary resuscitation was attempted in 36%. Survival to 1 month was 8.2% among patients who received bystander cardiopulmonary resuscitation vs 2.5% among patients who did not receive it (odds ratio 3.5, 95% confidence interval 2.9-4.3). The effect of bystander cardiopulmonary resuscitation on survival was related to: (1) the interval between collapse and the start of bystander cardiopulmonary resuscitation (effect more marked in patients who experienced a short delay); (2) the quality of bystander cardiopulmonary resuscitation (effect more marked if both chest compressions and ventilation were performed than if either of them was performed alone); (3) the category of bystander (effect more marked if bystander cardiopulmonary resuscitation was performed by a non-layperson); (4) interval between collapse and arrival of the ambulance (effect more marked if this interval was prolonged); (5) age (effect more marked in bystander cardiopulmonary resuscitation among the elderly); and (6) the location of the arrest (effect more marked if the arrest took place outside the home). CONCLUSION: The effect of bystander cardiopulmonary resuscitation on survival after an out-of-hospital cardiac arrest can be modified by various factors. Factors that were associated with the effect of bystander cardiopulmonary resuscitation were the interval between the collapse and the start of bystander cardiopulmonary resuscitation, the quality of bystander cardiopulmonary resuscitation, whether or not the bystander was a layperson, the interval between collapse and the arrival of the ambulance, age and the place of arrest.

Aged↗
PubMed2001

Serological and epidemiological analysis of the prevalence of Bartonella spp. antibodies in Swedish elite orienteers 1992-93.

The emergence of the popular, physically demanding and highly nature-interactive sport of orienteering was marked in Sweden by an elevated rate of sudden unexpected cardiac deaths in young competitors during the years 1979-92, with a common underlying cause or causes suspected. Subsequently, sera were collected during 1992-93 from the elite segment of orienteers holding a nationally ranked position, and a survey compiling various epidemiological data was performed. In this study, a total of 1136 sera were analyzed by indirect-fluorescent antibody assay for the presence of IgG antibodies against 3 Bartonella spp.: B. henselae, B. elizabethae and B. quintana. In total, 31% (355/1136) were seropositive for at least 1 species of Bartonella, with titers ranging up to 1/512; 350/1136 (31%) had antibodies against B. elizabethae, 34/1136 (3.0%) against B. henselae and 16/1136 (1.4%) against B. quintana. Males and females showed equal rates of 31% seropositisity to Bartonella spp. (males 241/766; females 114/370). In comparison, 322 time-matched sera from healthy blood donors had antibodies to Bartonella spp. in 6.8% of cases (p < 0.001). The observed high prevalence of Bartonella spp. antibodies found in Swedish elite orienteers may be indicative of a connection with risk factors for the development of myocarditis and sudden unexpected cardiac death.

Adolescent↗
PubMed2001

Subacute bartonella infection in Swedish orienteers succumbing to sudden unexpected cardiac death or having malignant arrhythmias.

During the period 1979-92, an increasing number of sudden unexpected cardiac deaths (SUCD) occurred in young, Swedish, male elite orienteers. Myocarditis was the most common diagnosis in the 16 victims, and in 4 cases was also associated with fatty infiltration mimicking arrhythmogenic right ventricular cardiomyopathy (ARVC). Tissues from autopsies of 5 orienteers were tested for Bartonella by PCR targeting the gltA (citrate-synthase) gene. The products were then sequenced. Antibodies to B. henselae, B. quintana and B. elizabethae were measured by indirect fluorescence antibody assay. Bartonella spp. DNA was detected in the hearts of 4 deceased orienteers, and in the lung of a fifth deceased case. The sequences were close to B. quintana in 2 cases and identical to B. henselae in 3. Four of these 5 cases, as well as 2 additional cases of elite orienteers with ARVC, indicated antibodies to Bartonella. It is suggested that Bartonella-induced silent subacute myocarditis, eventually leading to electric instability, caused the increased SUCD rate among the Swedish orienteers. It is further suggested that Bartonella infection may be a major pathogenetic factor in the development of ARVC-like disease. Although the mode of transmission is unknown, both zoonotic/vector-borne and parenteral person-to-person transmission may be involved.

Adult↗
PubMed2001

The identification and validation of common disease genes: relevance to the drug development process.

The understanding of the genetic factors contributing to the development of common diseases has presented a great challenge. Recent accomplishments in the field of genetics have now transformed this vision into a reachable goal. The increased knowledge will have great impact on our fundamental understanding of biological processes, as well as how we diagnose and treat common disease. Many obstacles still remain, and a careful choice of strategy will be critical to achieve these goals. One key point will be the validation of generated candidates in an optimized study set-up.

Drug Design↗
PubMed2000

[Improved survival after in-hospital cardiac arrest].

Internationally, survival among patients suffering in-hospital cardiac arrest is relatively low and unchanged at about 15%. Our experience at Sahlgrenska Hospital in Göteborg indicates a higher rate. We found survival to be related to the type of arrhythmia initially encountered, the highest rate having been observed among patients in ventricular fibrillation. We also found survival among patients suffering cardiac arrest to be higher in monitored as opposed to non-monitored wards. Whether the improved survival rate observed at Sahlgrenska as compared with international observations among patients suffering cardiac arrest is due to improvements in the organization or to patient selection is not clear. In order to achieve a higher survival rate after in-hospital cardiac arrest an efficient organization in which health care providers are given regular training and feed back is most likely of the utmost importance.

Cardiopulmonary Resuscitation↗
PubMed2000

Effect of bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients in Sweden.

BACKGROUND: Information from the Swedish Cardiac Arrest Registry was used to investigate: (a) The proportion of patients suffering an out-of-hospital cardiac arrest who were given bystander cardiopulmonary resuscitation (B-CPR). (b) Where and by whom B-CPR was given. (c) The effect of B-CPR on survival. METHOD: a prospective, observational study of cardiac arrests reported to the Swedish Cardiac Arrest Registry. Analyses were based on standardised reports of out-of-hospital cardiac arrests from ambulance organisations in Sweden, serving 60% of the Swedish population. From 1983 to 1995 approximately 15-20% of the population had been trained in CPR. RESULTS: Of 9877 patients, collected between January 1990 and May 1995, B-CPR was attempted in 36%. In 56% of these cases, the bystanders were lay persons and in 25% they were medical personnel. Most of the arrests took place at home (69%) and only 23% of these patients were given B-CPR in contrast to cardiac arrest in other places where 53% were given CPR. Survival to 1 month was significantly higher in all cases that received B-CPR (8.2 vs. 2.5%). The odds ratio for survival to 1 month with B-CPR was in a logistic regression analysis 2.5 (95% CI 1.9-3.1). CONCLUSIONS: In Sweden, the willingness and ability to perform B-CPR appears to be relatively widespread. More than half of B-CPR was performed by laypersons. B-CPR resulted in a two to threefold increase in survival.

Cardiopulmonary Resuscitation↗