PubMed Health⌕ Search

Biomedical subjects

M Holmberg

Publications and source records attributed to M Holmberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

Incidence, duration and survival of ventricular fibrillation in out-of-hospital cardiac arrest patients in sweden.

UNLABELLED: The chance of survival from ventricular fibrillation (VF) is up to ten times higher than those with other cardiac arrest rhythms. To calculate the effect of out-of-hospital resuscitation organisations on survival, it is necessary to know the percentage of cardiac arrest patients initially in VF and the relationship between delay time to defibrillation and survival. AIM: To study the incidence of VF at the time of cardiac arrest and on first ECG, the duration of VF and the relation between time to defibrillation and survival. METHOD: The Swedish Cardiac Arrest Registry has collected standardised reports on out-of-hospital cardiac arrests from ambulance organisations in Sweden, serving 60% of the Swedish population. RESULTS: In 14065 cases of out-of-hospital cardiac arrest collected between 1990 and 1995, resuscitation was attempted in 10966 cases. INCIDENCE: The first ECG showed VF in 43% of all patients. The incidence of VF at the time of cardiac arrest was estimated to be 60-70% in all patients and 80-85% in the cases with probable heart disease. DURATION: The estimated disappearance rate of VF was slow. Thirty minutes after collapse approximately 40% of the patients were in VF. SURVIVAL: Overall survival to 1 month was only 1.6% for patients with non-shockable rhythms and 9.5% for patients found in VF. With increasing time to defibrillation, the survival rate fell rapidly from approximately 50% with a minimal delay to 5% at 15 min. CONCLUSIONS: This study suggests a high initial incidence of VF among out-of-hospital cardiac arrest patients and a slow rate of transformation into a non-shockable rhythm. The survival rate with very short delay times to defibrillation was approximately 50%, but decreased rapidly as the delay increased.

Adolescent↗
PubMed2000

Evidence for a common Spinocerebellar ataxia type 7 (SCA7) founder mutation in Scandinavia.

Spinocerebellar ataxia type 7 (SCA7) is a neuro-degenerative disorder characterised by progressive cerebellar ataxia and macular degeneration. SCA7 is one of the least common genetically verified autosomal dominant cerebellar ataxias (ADCAs) in the world (4.5 to 11.6%), but in Sweden and Finland SCA7 is the most commonly identified form of ADCA. In an inventory of hereditary ataxias in Scandinavia (Sweden, Norway, Denmark and Finland) we identified 15 SCA7 families, eight in Sweden and seven in Finland, while no cases of SCA7 could be found in Norway or Denmark. We examined whether the relatively high frequency of SCA7 families in Sweden and Finland was the result of a common founder effect. Only two out of 15 families could be connected genealogically. However, an extensive haplotype analysis over a 10.2 cM region surrounding the SCA7 gene locus showed that all 15 families studied shared a common haplotype over at least 1.9 cM. This strongly suggests that all Scandinavian SCA7 families originate from a common founder pre-mutation.

Ataxin-7↗
PubMed2000

A comparison between patients suffering in-hospital and out-of-hospital cardiac arrest in terms of treatment and outcome.

AIM: To compare treatment and outcome amongst patients suffering in-hospital and out-of-hospital cardiac arrest in the same community. PATIENTS: All patients suffering in-hospital cardiac arrest in Sahlgrenska University Hospital covering half the catchment area of the community of Göteborg (500 000 inhabitants) and all patients suffering out-of-hospital cardiac arrest in the community of Göteborg. Criteria for inclusion were that resuscitation efforts should have been attempted. TIME OF SURVEY: From 1 November 1994 to 1 November 1997. METHODS: Data were recorded both prospectively and retrospectively. RESULTS: In total, 422 patients suffered in-hospital cardiac arrest and 778 patients suffered out-of-hospital cardiac arrest. Patients with in-hospital cardiac arrest included more women and were more frequently found in ventricular fibrillation. The median interval between collapse and defibrillation was 2 min in in-hospital cardiac arrest compared with 7 min in out-of-hospital cardiac arrest (< 0.001). The proportion of patients being discharged from hospital was 37.5% after in-hospital cardiac arrest, compared with 8.7% after out-of-hospital cardiac arrest (P < 0.001). Corresponding figures for patients found in ventricular fibrillation were 56.9 vs. 19.7% (P < 0.001) and for patients found in asystole 25.2 vs. 1.8% (P < 0.001). CONCLUSION: In a survey evaluating patients with in-hospital and out-of-hospital cardiac arrest in whom resuscitation efforts were attempted, we found that the former group had a survival rate more than four times higher than the latter. Possible strong contributing factors to this observation are: (i) shorter time interval to start of treatment, and (ii) a prepared selection for resuscitation efforts.

Adolescent↗
PubMed2000

Experiences from treatment of out-of-hospital cardiac arrest during 17 years in Göteborg.

AIMS: To describe changes in different factors at resuscitation and survival in a 17-year survey of patients suffering from out-of-hospital cardiac arrest. METHOD: The investigation was carried out in the community of Göteborg with 450 000 inhabitants during 1981-1997 on all patients suffering out-of-hospital cardiac arrest in whom resuscitation was attempted. RESULTS: The number of cases per year, the proportion of witnessed arrests and the proportion of arrests of cardiac aetiology remained similar over time. There was an increase in median age from 68 to 73 years (P<0.0001), in the proportion of females from 27% to 33% (P=0.035) and in the proportion of patients receiving bystander cardiopulmonary resuscitation from 14% to 28% (P<0.0001) with time. There was a shortening of the median interval from collapse until defibrillation from 9 min to 6 min (P<0.0001) over time but a decrease in the occurrence of ventricular fibrillation as the initially recorded arrhythmia from 39% to 32% (P=0.022). There was an increase in the proportion of patients having a bystander witnessed cardiac arrest of cardiac aetiology being hospitalized alive from 32% to 45% (P<0. 0001 for change over time). The proportion of patients discharged alive from hospital increased from 16% to 29% until 1993, but thereafter decreased to 13% in 1997 (P=0.002 for change over time). CONCLUSION: In a survey covering 17 years of resuscitation of out-of-hospital cardiac arrest patients we found that the occurrence of ventricular fibrillation as the initially recorded arrhythmia decreased. There was an increase in age, in the proportion of females and in the use of bystander cardiopulmonary resuscitation. The interval between collapse and defibrillation was shortened. Survival changed over time with an increase until 1993 but with a decrease thereafter.

Adolescent↗
PubMed2000

Distribution of ataxin-7 in normal human brain and retina.

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disease caused by the expansion of a CAG repeat encoding a polyglutamine tract in the protein ataxin-7. We developed antibodies directed against two different parts of the ataxin-7 protein and studied its distribution in brain and peripheral tissue from healthy subjects. Normal ataxin-7 was widely expressed in brain, retina and peripheral tissues, including striated muscle, testis and thyroid gland. In the brain, expression of ataxin-7 was not limited to areas in which neurones degenerate, and the level of expression was not related to the severity of neuronal loss. Immunoreactivity was low in some vulnerable populations of neurones, such as Purkinje cells. In neurones, ataxin-7 was found in the cell bodies and in processes. Nuclear labelling was also observed in some neurones, but was not related to the distribution of intranuclear inclusions observed in an SCA7 patient. In this patient, the proportion of neurones with nuclear labelling was higher, on average, in regions with neuronal loss. Double immunolabelling coupled with confocal microscopy showed that ataxin-7 colocalized with BiP, a marker of the endoplasmic reticulum, but not with markers of mitochondria or the trans-Golgi network.

Adult↗
PubMed2000

Sequence variation in the ftsZ gene of Bartonella henselae isolates and clinical samples.

In a search for methods for subtyping of Bartonella henselae in clinical samples, we amplified and sequenced a 701-bp region in the 3' end of the ftsZ gene in 15 B. henselae isolates derived from cats and humans in the United States and Europe. The ftsZ sequence variants that were discovered were designated variants Bh ftsZ 1, 2, and 3 and were compared with 16S rRNA genotypes I and II of the same isolates. There was no ftsZ gene variation in the strains of 16S rRNA type I, all of which were Bh ftsZ 1. The type II strains constituted two groups, with nucleotide sequence variation in the ftsZ gene resulting in amino acid substitutions at three positions, one of which was shared by the two groups. One 16S rRNA type II isolate had an ftsZ gene sequence identical to those of the type I strains. Variants Bh ftsZ 1 and 2 were detected in tissue specimens from seven Swedish patients with diagnoses such as chronic multifocal osteomyelitis, cardiomyopathy, and lymphadenopathy. Patients with similar clinical entities displayed either Bh ftsZ variant. The etiological role of B. henselae in these patients was supported by positive Bartonella antibody titers and/or amplification and sequencing of a part of the B. henselae gltA gene. B. henselae ftsZ gene sequence variation may be useful in providing knowledge about the epidemiology of various B. henselae strains in clinical samples, especially when isolation attempts have failed. This report also describes manifestations of atypical Bartonella infections in Sweden.

Adolescent↗
PubMed1999

The problem of out-of-hospital cardiac-arrest prevalence of sudden death in Europe today.

In Europe, 40% of all deaths of individuals who are 25-74 years of age are caused by cardiovascular disease. Cardiac disease is the underlying cause in two-thirds of out-of-hospital sudden deaths. The 28-day case fatality rate for the combined population of out-of-hospital coronary artery disease deaths and hospitalized acute myocardial infarction patients is approximately 50% in 29 of the regions included in the World Health Organization (WHO) Monitoring Trends and Determinants in Cardiovascular Disease registry. Of 14,065 patients included in the Swedish Cardiac Arrest Registry, resuscitation procedures were started in 10,966 patients. The remaining 3,099 were considered definitely dead; 70% were witnessed, cardiac arrests and 32.3% had been given bystander cardiopulmonary resuscitation (CPR). The incidence of ventricular tachycardia (VT)/ventricular fibrillation (VF) in all patients was 43%, in witnessed cases 54%, and in nonwitnessed cases, 31%. The initial incidence of VT/VF was calculated to be approximately 60% in the whole population and 80-85% in those with probable cardiac disease. Survival to 1 month was 5.0% in the total population, 9.5% for those with VT/VF on the first electrocardiogram compared with 1.6% for those not in VT/VF. Survival rate was also calculated in relation to delay time to first defibrillation. Survival was 50% when defibrillation was performed immediately and decreased gradually to 0% for those with a delay time of 20 minutes. The survival rate after bystander CPR was 2.6-fold higher than the rate for those where no treatment was given until the ambulance arrived.

Adult↗
PubMed1999

[Growing genes cause neurological diseases].

A growing number of hereditary neurodegenerative disorders have been found to be caused by expansion of trinucleotide repeats. A smaller number of diseases such as fragile X syndrome, myotonic dystrophy, and Friedreich's ataxia, have been found to be due to expansions in non-coding DNA. In a large group of diseases, the expansion consists of CAG repeats in the coding region of the gene, producing an expanded polyglutamine sequence in the protein. Nine diseases have so far been identified as belonging to this group: Huntington's disease, spinobulbar muscular atrophy (SBMA), dentatorubral pallidoluysian atrophy (DRPLA), autosomal dominant "pure" spastic paraplegia (ADPSP), and five forms of spinocerebellar ataxia (SCA 1,2,3,6 and 7). Except for SBMA, all of the CAG repeat disorders are characterised by autosomal dominant heredity and anticipation (i.e., earlier onset age and increasing severity in successive generations). The mutated protein causes disease via an as yet unidentified gain-of-function mechanism in specific subsets of neurones. Today, DNA analysis permits the diagnosis of a trinucleotide disease in individual cases.

Anticipation, Genetic↗
PubMed1999

Missense and nonsense mutations in codon 659 of MLH1 cause aberrant splicing of messenger RNA in HNPCC kindreds.

Germline mutations that give rise to premature termination codons in mRNAs have frequently been associated with aberrant processing of the nascent transcripts. This can take the form either of nonsense-mediated mRNA decay or of aberrant splicing of the pre-mRNA. In a family affected by hereditary nonpolyposis colorectal cancer, a two-nucleotide deletion in codon 659, which introduces a frameshift and a new stop codon in exon 17 of the DNA mismatch repair gene MLH1, has been reported to lead to skipping of the exon. We now report that this phenomenon occurs also when there are missense or nonsense mutations in this codon. Our results thus suggest that in aberrant splicing the nature of the mutation may be less important than its position within the exon. These findings are of importance to mutation interpretation, as they imply that aberrant splicing could be associated even with silent mutations that do not lead to amino acid substitutions. Genes Chromosomes Cancer 26:372-375, 1999.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Adrenergic alpha2C-receptors reside in rat striatal GABAergic projection neurons: comparison of radioligand binding and immunohistochemistry.

We have investigated the distribution of alpha2c-adrenergic receptors in the rat striatum and characterized the striatal neuron types expressing these receptors. Sequential double-labelled immunocytochemistry was performed with a polyclonal antibody against rat alpha2c-adrenoceptors and antibodies against GABA, Calbindin-D28k, parvalbumin and calretinin. The subregional distribution of alpha2c-adrenoceptor binding sites in the striatum was also quantitatively investigated using selective radioligands. Almost all lightly stained striatal GABAergic neurons, with the morphological characteristics of medium-sized spiny projection neurons (94% of GABAergic cells counted), contained alpha2c-adrenoceptor-immunoreactive structures. Intensely labelled GABAergic inteneurons (6%) were devoid of alpha2c-adrenoceptor immunoreactivity. The co-localization of calbindin- and alpha2c-adrenoceptor immunoreactivity in the majority of the cells confirmed the presence of alpha2c-adrenoceptors in the population of medium-sized spiny neurons. Furthermore, the alpha2c-adrenoceptor/calbindin double-labelling disclosed the existence of three neuronal subsets in the matrix compartment of the striatum: a large proportion (83%) of double-labelled neurons, a population of neurons (8%) that exhibited only alpha2c-adrenoceptor immunoreactivity without calbindin immunoreactivity, and a population of neurons (9%) immunoreactive for calbindin, but lacking alpha2c-adrenoceptors. In addition, alpha2c-adrenoceptor immunolabelled neurons were observed in calbindin-free striatal patches. Parvalbumin- and calretinin-positive neurons never displayed alpha2c-adrenoceptor immunoreactivity, confirming that striatal GABAergic interneurons are devoid of alpha2c-adrenoceptors. The present findings indicate that alpha2c-adrenoceptors are localized in GABAergic medium-sized spiny projection neurons but not in interneurons of the rat striatum, and that they may modulate both the direct and indirect pathways of the basal ganglia, as well as participate in the regulation of mesencephalic dopaminergic neurons.

Adrenergic alpha-Antagonists↗
PubMed1999

Evaluation of human seroreactivity to Bartonella species in Sweden.

Among the species that compose the expanding genus Bartonella, thus far only B. henselae and B. quintana have reportedly been isolated from humans in Europe. To evaluate the prevalence of Bartonella infection in Sweden, we conducted a retrospective serological examination of 126 human serum samples. These samples were analyzed for antibodies to B. henselae, B. quintana, and B. elizabethae. Serum samples from 100 blood donors, who spanned the ages of 20 to 60 and had no apparent clinical signs of illness, were also studied as a control group. An immunoglobulin G indirect fluorescence antibody assay revealed 4 and 8.3% Bartonella positivity rates for the blood donor and patient group, respectively, when a cutoff titer of >/=64 was chosen. Among the blood donors, four were seropositive to B. elizabethae; one of these also had concordant positive titer to B. henselae. In the patient group, 14 serum samples were positive against Bartonella spp. These serum specimens represented nine patients. In three of these seropositive patients, paired serum samples displayed a fourfold increase in antibody titer to at least one of the three antigens. These three patients are discussed. In this report we also present a case study of a 60-year-old Swedish male with fatal myocarditis. Postmortem serological analysis revealed a high titer against B. elizabethae. PCR and nucleotide sequencing of the myocardial tissue from this patient, and of liver tissue from one of the other three patients, showed sequences similar to B. quintana. The age, geographical origin, animal contacts, and serological response pattern to the different Bartonella antigens differed among the four patients. This study substantiates the presence of Bartonella spp. in Sweden, documents the seroreactivity to three Bartonella antigens in Swedish patients, and reports the first two cases of B. quintana-like infections in Sweden.

Adolescent↗
PubMed1998

Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated with classic phenylketonuira and mild phenylketonuria. Mutations in brief no. 143. Online.

PKU is one of the commonest genetic disease in man, affecting 1/10,000 individuals. It presents a wide phenotypical spectrum, from classic PKU to moderate Hyperpheylalaninemia depending on the residual enzymatic activity. Two novel mutations 1163/1164delTG and P362T in exon 11 have been detected during the mutational screening of the PAH gene in 84 families. 1163/1164delTC can be confused with V388M if the mutational screening is performed with BsaAI restriction enzyme, this mutation in heterozigosis presents a moderate phenotype. P362T mutation in heterozigosis with V388M shows a classical PKU phenotype. We report here two new mutations in exon 11 of the PAH gene (GenBank U49897), V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57 PKU and 36 HPA patients belonging to 84 unrelated families detected under a neonatal screening program performed in Catalonia.

DNA Mutational Analysis↗
PubMed1998

Survival after cardiac arrest outside hospital in Sweden. Swedish Cardiac Arrest Registry.

The voluntary Swedish Cardiac Arrest Registry has collected and analyzed 14,065 standardised reports on cardiac arrests up until May 1995. The reports have been collected from approximately half of Sweden's ambulance districts, which cover 60% of the population. Resuscitation was attempted in 10,966 cases. The median age was 70 years. In 70.0% the arrest was witnessed, and in 43.3% the first recorded rhythm was VT/VF. Bystander-CPR was initiated in 32.3% of the cases. Most cardiac arrests took place at home (65.8%) and 67.1% were judged to be of cardiac origin. In 1692 cases (15.4%), the patient was admitted alive in hospital and 544 patients (5.0%) were alive after 1 month. Survival to 1 month in the subgroup which presented with VT/VF was 9.5%. We found no significant difference between survival in large cities and smaller communities. The survivors were analysed in relation to time to defibrillation and we found a strong correlation between a short time and increased survival.

Aged↗
PubMed1998

Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7).

Spinocerebellar ataxia 7 (SCA7) is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene. We have analyzed the SCA7 mutation in 19 families and one isolated case of various geographical origins, presenting with autosomal dominant cerebellar ataxia with progressive macular dystrophy. The SCA7 CAG repeat was expanded in 77 patients and in 11 at-risk individuals, with alleles containing from 37 to 130 repeats, demonstrating that SCA7 is genetically homogeneous. Repeats on normal alleles contained from 7 to 35 CAGs. There was a strong negative correlation (r = -0.84) between the age at onset and the size of the CAG repeat expansion in SCA7 patients. Larger expansions were associated with earlier onset, a more severe and rapid clinical course, and a higher frequency of decreased vision, ophthalmoplegia, extensor plantar response and scoliosis. The frequency of other clinical signs such as dysphagia and sphincter disturbances increased with disease duration. The mutation was highly unstable during transmission, with a mean increase of 10 +/- 16 CAG repeats, which was significantly greater in paternal (15 +/- 20) than in maternal (5 +/- 5) transmissions. This correlated well with the marked anticipation (19 +/- 13 years) observed in the families. Gonadal mosaicism, observed in the sperm of a patient, was particularly important, with expanded alleles ranging from 42 to >155 CAG repeats. The degree of instability during transmission, resulting mostly in expansions, is greater than in the seven other neurodegenerative disorders caused by polyglutamine expansions.

Adolescent↗
PubMed1998

Expanded CAG repeats in Swedish spinocerebellar ataxia type 7 (SCA7) patients: effect of CAG repeat length on the clinical manifestation.

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disorder characterized by degeneration of the cerebellum, brainstem and retina. The gene responsible for SCA7, located on chromosome 3p, recently was cloned and shown to contain a CAG repeat in the coding region of the gene, that is expanded in SCA7 patients of French origin. We examined the SCA7 repeat region in four Swedish SCA7 families as well as in 57 healthy controls. All Swedish SCA7 patients exhibited expanded CAG repeats with a strong negative correlation between repeat size and age of onset. The repeat length in SCA7 patients ranged from 40 to >200 repeats. The largest expansion was observed in a juvenile case with an age of onset of 3 months, and represents the longest polyglutamine stretch ever reported. In patients with 59 repeats or more, visual impairment was the most common initial symptom observed, while ataxia predominates in patients with <59 repeats. Two of the Swedish SCA7 families analysed in this study were shown to be related genealogically. The other two SCA7 families could not be traced back to a common ancestor. All four families shared the same allele on the disease chromosome at a locus closely linked to SCA7, suggesting the possibility of a founder effect in the Swedish population.

Adolescent↗
PubMed1998

Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions.

Autosomal dominant cerebellar ataxia with progressive macular degeneration is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein. Neuronal intranuclear inclusions were detected in the brain of an early onset SCA7 case with the 1C2 antibody directed against an expanded polyglutamine domain. Nuclear inclusions were most frequent in the inferior olivary complex, a site of severe neuronal loss in SCA7. They were also observed in other brain regions, including the cerebral cortex, not considered to be affected in the disease. Using confocal microscopy we showed that some inclusions were ubiquitinated, but to varying degrees, ranging from <1% in the cerebral cortex to 60% in the inferior olive. In addition, we also observed cytoplasmic staining using the 1C2 antibody, particularly in the supramarginal gyrus, the hippocampus, the thalamus, the lateral geniculate body and the pontine nuclei. These data confirm that the presence of intranuclear inclusions in neurons is a common characteristic of disorders caused by CAG/polyglutamine expansions, but unlike what has been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were not restricted to the sites of severe neuronal loss.

Ataxin-7↗
PubMed1997

Surface Force Studies of Langmuir-Blodgett Cellulose Films

The interactions between cellulose surfaces, between chitosan-coated surfaces, and between one cellulose surface and one chitosan-coated surface have been studied using the interferometric surface force apparatus (SFA). The cellulose surfaces were prepared by depositing trimethylsilyl cellulose on hydrophobized mica using the Langmuir-Blodgett technique. The surfaces were desilylated in a humid HCl atmosphere to obtain regenerated cellulose. ESCA measurements and wetting studies demonstrated that the desilylation process was effective. Scanning force microscopy studies showed the cellulose surfaces to be smooth with a root-mean-square roughness of 0.16 nm. Surface force and ellipsometry measurements illustrate that the cellulose film swells considerably in humid air and in water, suggesting that it is mostly amorphous. The interaction between two cellulose surfaces is dominated by a steric repulsion caused by a few dangling tails. On separation an attractive force was present both between two cellulose surfaces and between one cellulose surface and one chitosan surface. The long-range interaction between cellulose and chitosan was shown to be attractive.

Journal Article↗