Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 55 records · Page 3Linked to original sources

PubMed2001

The safety and efficacy of MenoTreat, a new balloon device for thermal endometrial ablation.

BACKGROUND: An evaluation of the performance and safety of the prototype of a new device, MemoTreat (Atos Medical) for thermal endometrial balloon ablation in patients with menorrhagia. The evaluation was performed at four Swedish hospitals. METHODS: In total 51 consecutive, premenopausal patients, suffering from menorrhagia due to benign causes and not responding to conventional treatment, were treated between March 1997 and March 1998. The treatment entailed heated (85 degrees C) sterile saline circulated in a uterine balloon at a treatment pressure of 200 mmHg for 11 minutes. The procedure was performed mainly under general anesthesia and no pre-treatment endometrial thinning was performed. A validated pictorial assessment technique was used to evaluate changes in menstrual blood loss before and after treatment. Changes in quality of life and severity of dysmenorrhea were also evaluated. Data analysis was based on the 'intention to treat' method. RESULTS: The success rate in terms of a 50% reduction in menstrual bleeding was 84.3% at 6 months after treatment. Five patients became amenorrheic. The quality of life assessment showed substantial improvement and the severity of dysmenorrhea was markedly reduced. No intra-operative treatment complications occurred and the post-treatment morbidity was similar to that reported for other similar treatment methods. CONCLUSIONS: MenoTreat significantly reduced menstrual bleeding in menorrhagic patients, with a concomitant improvement in quality of life. The findings in this study resulted in a redesigned device with a thinner balloon catheter, improved cervical protection and treatment temperatures kept at a constant level.

Adult↗

PubMed2001

Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11.

Celiac disease (CD) is a common chronic inflammatory disorder of the small intestine with a multifactorial aetiology. HLA is a well-known risk factor, but other genetic factors also influence disease susceptibility. To identify the genes involved in this disorder, we performed a genome-wide scan on 106 well-defined Swedish and Norwegian families with at least two affected siblings. We investigated familial segregation of 398 microsatellite markers, and utilised non-parametric linkage analysis. The strongest linkage with disease was found to the HLA locus (6p) (P<0.000006). There were eight regions besides HLA with a point wise P value below 0.05. Among these eight regions were 11q and 5q, both of which have been suggested in several linkage studies of independent celiac disease families. We also performed a stratification analysis of families according to their HLA genotypes. This resulted in significant differences on chromosome 2q. These results indicate that 11q, 5q and possibly also 2q are true susceptibility regions in CD.

Adolescent↗

PubMed2001

The HCR gene on 6p21 is unlikely to be a psoriasis susceptibility gene.

The PSORS1 locus in the human major histocompatibility complex on 6p21 has been consistently associated with psoriasis in populations of diverse ethnicity. The HLA-C allele Cw*0602, located therein, has been found in up to 67% of psoriasis patients but is no longer considered a candidate gene in itself. The alpha-helix coiled-coil rod homolog gene (HCR, previously Pg8) is located 110 kb from the HLA-C gene, positioned between the CDSN and SC1 genes, within a region thought to harbor a psoriasis gene (PSORS1). We investigated the HCR gene for disease association by direct sequencing of nine polymerase chain reaction products amplified from a series of Swedish psoriasis patients and controls. We found that HCR is a very polymorphic gene with 25 polymorphisms in the open reading frame alone, of which 10 demonstrated disease association; however, the relationship between HCR polymorphisms and HLA-Cw*0602 indicates that HCR cannot truly be considered a likely candidate gene. We investigated Cw*0602 association while stratifying for HCR single nucleotide polymorphisms. We also investigated HCR single nucleotide polymorphism association with the disease while stratifying for the presence of Cw*0602. We found that whichever single nucleotide polymorphism that was stratified for, there was still a strongly significant Cw*0602 association with psoriasis; however, when we stratified for Cw*0602 presence, only one silent polymorphism showed significant association. In a recent similar study this polymorphism was actually found to be decreased in psoriasis individuals. Thus we conclude that HCR polymorphisms display association with psoriasis due to linkage disequilibrium with Cw*0602 and is, therefore, unlikely to be directly involved in the development of psoriasis.

Adolescent↗

PubMed2001

Trends in the misuse of androgenic anabolic steroids among boys 16-17 years old in a primary health care area in Sweden.

OBJECTIVE: To evaluate the effects of an appearance programme in preventing the misuse of androgenic anabolic steroids among male adolescents in a primary health care area in Sweden. METHODS: Attitudes to steroid hormones among 16-17 years old male and female adolescents are discussed. A well-established anonymous multiple-choice questionnaire was answered by 921 adolescents and statistically analysed. RESULTS: The misuse of androgenic anabolic steroids tended to decrease after the intervention. CONCLUSIONS: The misuse of androgenic anabolic steroids did not increase, and even tended to decrease, after the intervention, indicating that drug-abuse among male adolescents can be decreased through discussions about appearance and attitudes. Repeat and prospective studies have to be done before this intervention programme can be generalised.

Adolescent↗

PubMed2001

The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of chemotherapy effects in some major tumour types--summary and conclusions.

This report by The Swedish Council on Technology Assessment in Health Care (SBU) reviews, classifies, and grades the scientific literature on cancer chemotherapy in some major tumour types, describes the practice of chemotherapy in Sweden, compares practice with scientific knowledge, and analyses the costs and cost-effectiveness of chemotherapy. The report is intended primarily for decision-makers at various levels, both practitioners and administrators. It is also of interest for the medical profession. The extensive body of scientific literature was reviewed according to strict criteria that reflected the scientific weight of the literature. Sixteen experts representing different disciplines (oncology, surgery, internal medicine, health economy and quality of life research) participated in the literature review. Each section was discussed within the project group and was reviewed by at least one, but usually two international researchers. Additional input was provided by national experts representing different scientific disciplines. For the final evaluation to be as close to the objective truth as possible, a concerted effort was made to guarantee objectivity and thorough assessment of current knowledge about the effects of chemotherapy on the selected cancers. The tumour types selected for this assessment include firstly those types where three investigations had shown an increased use of chemotherapy in Sweden during the latest decade. These were non-small cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary bladder cancer. Secondly, the two tumour types comprising the greatest number of patients treated with chemotherapy in Sweden, breast cancer and haematological malignancies, were included. Among the haematological malignancies, the most prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the large B-cell type and indolent NHL of follicular type were evaluated. These constitute about 75%, of all haematological malignancies. Thirdly, ovarian cancer was included since chemotherapy has been extensively used and since, at the time of the planning of this overview, a group of very expensive drugs, the taxanes, had preliminarily shown promising results. A wealth of scientific literature has been published on cancer therapy. The review presented in this report is limited to scientific studies judged to be important for evaluating chemotherapy efficacy. Assessments of the content and quality of these studies, and a critical summary of the results in all stages of the selected tumours, have never before been attempted in this way. However, similar comprehensive overviews of certain stages of the tumours have previously been made. These overviews were also critically evaluated. Totally 1,496 studies involving 558,743 patients were reviewed. The survey of practice of chemotherapy use involved all departments of surgery, urology, gynaecology, internal medicine including haematologic units, pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two health care regions in Sweden, covering 39% of the Swedish population. During the 4 weeks of the survey, all patients with the diagnoses concerned who received chemotherapy were registered. The study included 1,590 patients. The working group's general conclusions are summarised in the following points: The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. The use of chemotherapy is of utmost importance for the possibility of cure in certain tumour types. In other tumours, chemotherapy increases the possibility of cure when added to local and regional treatments, particularly surgery. In the instances of no possibility of cure, chemotherapy may to a variable extent improve both patient survival and well-being. In Sweden chemotherapy is largely used in accordance with that documented in the scientific literature. The extent of both over- and under-treatment seems to be limited but cannot be excluded at the individual patient level. The literature-based knowledge is scientifically of lower quality in the most chemotherapy sensitive tumours than in tumours showing more limited sensitivity. In the more sensitive tumours, positive effects on a symptomatic stage and survival were seen several decades ago. In those days, clinical treatment studies did not fulfil the current high quality requirements. Small life-prolonging effects of chemotherapy are sometimes very well documented in large, high quality scientific studies. Some of these s

Antineoplastic Agents↗

PubMed2001

A systematic overview of chemotherapy effects in urothelial bladder cancer.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for urothelial bladder cancer is based on 234 scientific reports including two meta-analyses, 75 randomised studies and 143 other prospective studies, and totally comprising 31,974 patients. The conclusions reached can be summarised into the following points: Intravesical chemotherapy administered in an adjuvant setting to transurethral resection (TUR-B) of superficial tumour reduces short-term (one to three years) recurrence rate by approximately 20%. After a median follow-up of eight years, 8%, fewer recurrences were seen after intravesical chemotherapy. Long-term maintenance instillation chemotherapy ( > 1 year) does not further increase the recurrence-free interval nor the long-term recurrence rate when compared with immediate postoperative short-term intravesical chemotherapy. The majority of studies on intravesical Bacillus Calmette-Guerin (BCG) vs intravesical chemotherapy show superior protection from tumour recurrence for BCG. Despite prolongation of the disease-free survival, adjuvant intravesical chemotherapy has, in the majority of studies, no apparent long-term impact on the evolution of superficial into muscle invasive bladder cancer. There are no data showing a survival benefit from adjuvant intravesical chemotherapy. Chemotherapy with cisplatin-based regimens induce objective tumour response in at least 50% of patients with metastatic disease. A prolonged disease-free and overall survival (median two to three months) is seen in patients treated with cisplatin-based polychemotherapy compared with patients treated with cisplatin alone or less intensive chemotherapy. With the exception of one randomised study, there are no conclusive data on possible survival benefit for patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy prior to cystectomy or radiotherapy. Although the results from use of adjuvant chemotherapy after surgery or curative radiotherapy obtained are promising, the small studies performed lack statistical power and, hence, there is insufficient data to make any conclusion regarding a possible survival benefit from adjuvant chemotherapy. A growing body of data indicate that bladder preservation can be achieved by multi-modality approach in selected patients and that survival in these is similar to that seen after radical cystectomy, but randomised trials are still lacking.

Administration, Intravesical↗

PubMed2001

The prevalence of the use of androgenic anabolic steroids by adolescents in a county of Sweden.

BACKGROUND: The prevalence of the use of androgenic anabolic steroids has been poorly studied in Europe. This study was undertaken to examine the prevalence of the misuse--the non-medical use--of androgenic anabolic steroids among adolescents in a county of Sweden. METHODS: The total population of 16 and 17 year old male and female adolescents in a county on the south-west coast of Sweden was studied. The investigation was done by an anonymous multiple-choice questionnaire. The questionnaire was completed by 5,827 pupils and statistically analysed. The participation rate was 95%. RESULTS: Among male adolescents 16 and 17 years old, 3.6% and 2.8% had misused androgenic anabolic steroids, respectively. These male adolescents had also misused alcohol, growth hormones and narcotic drugs more than the steroid hormone non-users. Among female adolescents there was no recorded misuse of these drugs (0.0%). CONCLUSIONS: The misuse of androgenic anabolic steroids is a reality in both small and large municipalities in Sweden. The prevalence figures are higher among 16 year old compared to 17 year old male adolescents. There is an association between this drug misuse and other substance misuse such as narcotic drugs. Female adolescents do not misuse steroid hormones. The findings indicate the need for preventive work among male adolescents in order to induce adolescents not to start misusing androgenic anabolic steroids.

Adolescent↗

PubMed2001

Mortality among male and female smokers in Sweden: a 33 year follow up.

STUDY OBJECTIVE: It is still unclear if men and women are equally susceptible to the hazards of tobacco smoking. The objective of this study was to examine smoking related mortality among men and women. DESIGN: In 1963 a questionnaire concerning tobacco smoking habits was sent out to a random sample from the 1960 Swedish census population. Date and cause of death have been collected for the deceased in the cohort through 1996. SETTING: Sweden. PARTICIPANTS: The survey included a total of 27 841 men and 28 089 women, aged 18-69 years. The response rate was 93.1% among the men and 95.4% among the women. MAIN RESULTS: After adjustment for age and place of residence positive associations were found between cigarette smoking and mortality from ischaemic heart disease, aortic aneurysm, bronchitis and emphysema, cancer of the lung, upper aerodigestive sites, bladder, pancreas in both men and women, but not from cerebrovascular disease. When the effect of amount of the cigarette consumption was considered, female smokers displayed, for example, slightly higher relative death rates from ischaemic heart disease. However, no statistically significant gender differential in relative mortality rates was observed for any of the studied diseases. CONCLUSIONS: Women and men in this Swedish cohort seem equally susceptible to the hazards of smoking, when the gender differential in smoking characteristics is accounted for. Although the cohort under study is large, there were few female smokers in the high consuming categories and the relative risk estimates are therefore accompanied by wide confidence intervals in these categories.

Accidents↗

PubMed2001

Mechanisms of estrogen action.

Our appreciation of the physiological functions of estrogens and the mechanisms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen receptors had been inactivated and we thought that we were about to understand the role of estrogen receptors in physiology and pathology, it was found that there was not one but two distinct and functional estrogen receptors, now called ER alpha and ER beta. Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estrogens in the body than was previously thought. This decade also saw the description of a male patient who had no functional ER alpha and whose continued bone growth clearly revealed an important function of estrogen in men. The importance of estrogen in both males and females was also demonstrated in the laboratory in transgenic mice in which the aromatase gene was inactivated. Finally, crystal structures of the estrogen receptors with agonists and antagonists have revealed much about how ligand binding influences receptor conformation and how this conformation influences interaction of the receptor with coactivators or corepressors and hence determines cellular response to ligands.

Animals↗

PubMed2001

Biodistribution, blood half-life, and receptor binding of a somatostatin-dextran conjugate.

Derivatives of somatostatin (sms) are attracting increasing interest as part of the treatment of several cancer diseases expressing sms receptors (srs). Radiolabeled sms analogs can additionally be used for systemic radiotherapy and for diagnostic investigations. Glycosylated sms-14 (sms-dextran70) was characterized regarding in vitro srs binding, biodistribution, and blood half-life in mice. Rat brain cortex membranes (expressing srs 2) were used for the srs binding study. Tyr3-Octreotide was used as positive control. The binding data were analyzed by competition curve analysis. In the biodistribution study, the Bolton-Hunter reagent was used for the radioiodination of sms-dextran70. Organs and blood were collected at different time-points and the percentage of the injected dose per gram of tissue (%ID/g) was calculated. The conjugate was administered subcutaneously (sc). The sms-dextran70 showed high srs binding affinity (i.e., in the same nanomolar range as the reference ligand Tyr3-octreotide (IC50 approximately 2.5 nM). The blood half-life was approx 27 h after reaching maximum blood concentration 24 h postinjection. Because of the molecular weight of the conjugate (i.e., approx 75,000) being above the kidney threshold for dextran (i.e., 50,000), the digestion and excretion is assumed to be mainly through the hepatobiliary system. Increased uptake was seen in the adrenals, which are receptor-positive organs. Some accumulation was seen in the stomach, indicating certain deiodination of the conjugate label. The sms-dextran70 showed promising properties and its clinical relevance is currently being evaluated in clinical phase I-II studies.

Animals↗

PubMed2001

Allergic reactions at repeat femoral angiography with ioxaglate.

PURPOSE: To study the occurrence of allergy-like reactions at angiography, repeated several times, and, secondly, to evaluate the effect of prophylactic treatment in individuals who had earlier experienced such reactions. MATERIAL AND METHODS: One hundred and fifty-seven patients with hypercholesterolaemia, participating in the Probucol Quantitative Regression Swedish Trial (PQRST), underwent aortofemoral angiography with ioxaglate (Hexabrix) repeated annually for 3 years. Allergic reactions to the contrast medium were recorded. At the following angiographies, all patients who had earlier experienced such reactions were treated prophylactically with steroids and antihistamine. RESULTS: Allergic reactions were observed in 35 patients. Twelve reacted only year 0, 3 only year 1, 5 only year 2 and 6 only year 3. Eight patients had at least one reaction also when treated prophylactically. It was significantly (p<0.05) more common to react at year 0 but not at year 1 than to react at year 1 but not at year 0. At years 1, 2 and 3 the frequency of reactions was significantly greater in the group given prophylactic treatment than in the group without any earlier reaction at all: 8/20 versus 3/137, 4/23 versus 6/134, and 6/29 versus 6/128, respectively. CONCLUSION: Some individuals had an increased risk of an allergy-like reaction to the contrast agent. Prophylactic treatment reduced the risk of renewed reactions, but not to the same level as for those without earlier reaction. Nevertheless, individuals who have had earlier reactions can be investigated in the future, with prophylactic treatment.

Adult↗

PubMed2001

[Research contributions of Eskil Kylin].

Eskil Kylin (1889-1975), a Swedish physician, started his career in medical research by studying arterial hypertension. In his thesis in 1920 (5) the significance of small-vessel pressure is especially discussed. Kylin also made important observations with regard to the influence on blood pressure from autonomous nervous system, and calcium metabolism. In 1923 he described a syndrome characterized by hypertension, hyperglycemia, obesity, and hyperuricemia (6), today well-known as the metabolic syndrome (15). In the thirties Kylin turned his interest to endocrinology, especially to implantation and injection of pituitary extracts from the calf. In a summarizing report 1943 (10) he describes treatment of some 200 patients with a remarkable success in 75% of the cases. In fifty cases with anorexia nervosa more than 80% were helped; half of them recovering menstruation within one year. Kylin summarized his studies in extensive monographs published in German on arterial hypertension (8), blood proteins (1), and treatment with pituitary extracts (10). During the post-war era with a general neglect of medical literature written in German, Kylin's articles were mostly forgotten. In 1926 Kylin was appointed head of the medical department of Jönköping's hospital. Successively, the hot-tempered Kylin got into conflict with the hospital board, with colleagues, and also with some of his patients. These conflicts gave in 1943 rise to intervention from the supervising authority, Medicinalstyrelsen. After a protracted judicial process, Kylin was forced to resign. The court proceedings, with a massive coverage from the press, provide interesting insight into the situation of Swedish medical directors in a time when they had official governmental letters of appointment and therefore hard to dismiss.

Endocrinology↗

PubMed2000

Alternative methods providing enhanced sensitivity and selectivity in capillary electroseparation experiments.

The study of alternative and novel techniques for altering selectivity and enhancing sensitivity as well as injection and detection protocols are important in the ongoing development of capillary electroseparation protocols. Some recent research from our laboratory in these fields is presented and discussed in this review. To improve sensitivity an off-line sample enrichment technique utilising solvent evaporation in a levitated drop or an on-line solid-phase extraction protocol was used. The selectivity was tuned by the use of protein gels or molecularly imprinted polymer mediated capillary electrochromatography. Furthermore, a picolitre droplet injection method is described as well as a detection protocol based on laser-induced fluorescence imaging.

Electrophoresis, Capillary↗

PubMed2000

Airborne cell analysis.

A miniaturized analysis system for the study of living cells and biochemical reactions in microdroplets was developed. The technique utilizes an in-house-developed piezoelectric flow-through droplet dispenser for precise reagent supply and an ultrasonic levitator for contactless sample handling. A few-cell study was performed with living primary adipocytes. Droplets (500 nL) containing 3-15 individual cells were acoustically levitated. The addition of beta-adrenergic agonists into the levitated droplet using the droplet dispenser stimulated adipocyte lipolysis, leading to free fatty acid release and a consequent pH decrease of the surrounding buffer. The addition of insulin antagonized lipolysis and hence also the decrease in pH. The changes in pH, i.e., the cell response in the droplet, were followed using a pH-dependent fluorophore continuously monitored by fluorescence imaging detection. An image analysis computer program was employed to calculate the droplet intensities. To counteract droplet evaporation, found to affect the fluorescence intensities, a separate dispenser was used to continually add water, thus keeping the droplet volume constant.

Adipocytes↗

PubMed2000

Estrogen receptor transcription and transactivation: Basic aspects of estrogen action.

Estrogen signaling has turned out to be much more complex and exciting than previously thought; the paradigm shift in our understanding of estrogen action came in 1996, when the presence of a new estrogen receptor (ER), ERbeta, was reported. An intricate interplay between the classical ERalpha and the novel ERbeta is of paramount importance for the final biological effect of estrogen in different target cells.

Animals↗

PubMed2000

Estrogen receptors alpha and beta in the rodent mammary gland.

An obligatory role for estrogen in growth, development, and functions of the mammary gland is well established, but the roles of the two estrogen receptors remain unclear. With the use of specific antibodies, it was found that both estrogen receptors, ERalpha and ERbeta, are expressed in the rat mammary gland but the presence and cellular distribution of the two receptors are distinct. In prepubertal rats, ERalpha was detected in 40% of the epithelial cell nuclei. This decreased to 30% at puberty and continued to decrease throughout pregnancy to a low of 5% at day 14. During lactation there was a large induction of ERalpha with up to 70% of the nuclei positive at day 21. Approximately 60-70% of epithelial cells expressed ERbeta at all stages of breast development. Cells coexpressing ERalpha and ERbeta were rare during pregnancy, a proliferative phase, but they represented up to 60% of the epithelial cells during lactation, a postproliferative phase. Western blot analysis and sucrose gradient centrifugation confirmed this pattern of expression. During pregnancy, the proliferating cell nuclear antigen was not expressed in ERalpha-positive cells but was observed in 3-7% of ERbeta-containing cells. Because more than 90% of ERbeta-bearing cells do not proliferate, and 55-70% of the dividing cells have neither ERalpha nor ERbeta, it is clear that the presence of these receptors in epithelial cells is not a prerequisite for estrogen-mediated proliferation.

Animals↗

PubMed2000

On-column conductive coating for thermolabile columns used in capillary zone electrophoresis sheathless electrospray ionisation mass spectrometry.

A simple and very mild approach for the application of a conductive layer for sheathless electrospray has been developed. A modified 'fairy dust' method is employed in which 2 microm gold particles are applied by a thin layer of silicone on shaped tips. This novel approach comprises fabrications at room temperature, under atmospheric pressure, and involves no etching, extensive cleaning or otherwise harsh conditions. With this approach, sheathless electrospray emitters have been fabricated from fused silica capillaries with chemically pre-modified inner walls and from heat-sensitive polypropylene hollow fibres. Long term stability for more than two weeks of continuous spraying has been achieved. Capillary zone electrophoresis/time-of-flight mass spectrometry demonstrates attomole sensitivity and no detectable band broadening. A comparison with a chromium-gold coated emitter in terms of chemical noise is made with continuous infusion experiments, showing no significant increase in background from the polymer involved.

Animals↗

PubMed2000

PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families.

Carbohydrate-deficient glycoprotein syndrome type IA (CDG IA) is an autosomal recessive disease characterized clinically by severe involvement of the central and peripheral nervous system, and biochemically by complex defects in carbohydrate residues in a number of serum glycoproteins. CDG IA is caused by mutations in the PMM2 gene located in chromosome region 16p13. In this study, 61 CDG type IA patients (122 chromosomes) were screened for mutations in the PMM2 gene using a combination of SSCP and sequence analysis. More than 95% of the mutations could be detected. All of them were missense mutations. Mutations 422G>A and 357C>A were strikingly more common in the material and comprised 58% of mutations detected. Of the 20 mutations found, 10 were not reported previously. Seven mutations, e.g. 26G>A (five alleles) and 548T>C (seven alleles), were found only in Scandinavian families. The most common genotype was 357C>A/422G>A (36%). Three patients were homozygous, 357C>A/357C>A (two cases), and 548T>C/548T>C (one case). No patients homozygous for the most common mutation 422G>A were detected. The different mutations were clustered e.g., in that most were located in exon 5 (five) and exon 8 (six), while no mutation was detected in exon 2. When the frequencies of each mutation were included, exon 5 comprised 61% (65 chromosomes) of the mutations; in Scandinavian patients the frequency of these mutations was 72%. Thus, analysis of exon five in these patients enables both reliable and time-saving first screening in prenatal diagnostic cases. This could be followed by a second step of additional strategies for the detection of other mutations.

Alleles↗