Prenatal diagnosis in Pelizaeus-Merzbacher disease using RFLP analysis

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with severe psycho-motor retardation and neurological symptoms due to an inborn abnormality of proteolipid protein (PLP), the major protein component of myelin. A tight linkage between the gene of PLP and PMD locus has been suggested. We have carried out a series of RFLP studies using a cDNA probe for PLP and an anonymous DNA-fragment DXYS12 in a large Finnish family with at least three affected individuals. DNA analysis on chorionic villus specimens allowed us to exclude the disease in a male fetus of a possible carrier mother and, likewise, to demonstrate carrier status in a female fetus in another at-risk pregnancy.     

Vascular clips in anastomoses of femoropopliteal arterial reconstruction

The vascular anastomoses are usually made with sutures. Some mainly experimental studies have been published about a new method of doing the vascular anastomoses with metal clips. We studied the suitability of vascular closure staple (VCS) clip applier system for making the anastomoses in femoropopliteal and femorotibial arterial reconstruction. During an 11-month period, VCS clips were used in 17 out of 27 patients who were operated due to severe claudication or incipient gangrena of the foot. Altogether 26 anastomoses were made with VCS clips using either great saphenous vein or PTFE graft. The making of anastomosis was easy and reliable. No postoperative bleeding was noticed. All anastomoses were patent 4–6 weeks postoperatively studied by palpation and measured by ankle brachial pressure index (mean 0.96). In Duplex Doppler examination all studied patients had well patent anastomoses on an average 11 months after the operation. With VCS clip applier system, it is possible to do anastomoses in arteriosclerotic arteries like in femoropopliteal reconstructions. This method helps making reliable anastomoses more easily.     

Comparison of self-rated health in older people of St. Petersburg,Russia, and Tampere,Finland: how sensitive is SRH to cross-cultural factors?

The aim of this study was to examine if there are differences in self-rated health (SRH) between older people in St. Petersburg, Russia, and Tampere, Finland. Two SRH measures were examined: a global measure without any frame of reference, and an age-comparative SRH with an explicitly elicited reference of age peers. The Tampere data, consisting of 737 60–89-year-old respondents, came from the Tampere Longitudinal Study on Ageing (TamELSA) in 1989. The St. Petersburg data, consisting of 1,168 people aged 60–89 years, came from the Planning of Medical and Social Services within Elder Care in St. Petersburg project (IPSE) in 2000. In both cities the data were collected by same structured questionnaire. Self-rated health, both global and comparative, was better in Tampere than in St. Petersburg when symptoms, chronic diseases and functional ability were adjusted for. Also, the association of chronic diseases with global SRH was different in St. Petersburg and Tampere. In addition to the real differences in the prevalence and seriousness of health problems, the differences in SRH may be caused by different ways of evaluating health. Our conclusion is that self-rated health is sensitive to cultural and social factors. Direct comparisons between different countries should be made with caution, and the differences in language use must be taken into account when interpreting the results.     

Long‐Term Physical Exercise and Atrial Natriuretic Peptide in Obese Zucker Rats

Abstract: Endurance training increases natriuretic peptide synthesis in the hypertrophied myocardium of spontaneously hypertensive rats. We examined the effects of 22‐week‐long treadmill exercise on plasma and tissue atrial natriuretic peptide in Zucker rats, a model of genetic obesity and moderate hypertension without clear cardiac hypertrophy. The blood pressures of the animals were measured by the tail‐cuff method, and plasma and tissue samples for the peptide determinations were taken at the end of the study. The training increased heart weight to body weight ratio, while atrial natriuretic peptide contents in the right and left atrium, ventricular tissue, and plasma did not change. The exercise prevented the elevation of blood pressure, which was observed in non‐exercised obese Zucker rats, and also reduced blood pressure in the lean rats. In conclusion, these results suggest that in the absence of preceding myocardial hypertrophy, the long‐term exercise‐induced workload is not deleterious to the heart in experimental obesity, since no changes in plasma and tissue atrial natriuretic peptide were detected.     

Pregnancy Outcome After Previous Stillbirth Resulting from Causes Other Than Maternal Conditions and Fetal Abnormalities

Background: An adequate fetomaternal circulatory system may be compromised by a variety of disturbances leading to stillbirth. The purpose of this study was to assess subsequent pregnancy outcome in women with a history of stillbirth as a result of causes other than maternal conditions and fetal abnormalities. Methods: Ninety‐two deliveries after stillbirth were identified among 11,910 deliveries of parous women recorded in the birth registry at Kuopio, Finland. Using logistic regression, pregnancy outcome measures were compared with those of a parous healthy obstetric population (n= 11,818). Results: Women with a history of stillbirth as a result of causes other than maternal conditions and fetal abnormalities were older than their unaffected controls (32.4 yr vs 30.3 yr). Stillbirth in an earlier pregnancy was associated with a significantly higher (p < 0.001) frequency of placental abruption in subsequent pregnancy (5.4% vs 0.7%). A history of stillbirth was predictive of preterm delivery (OR = 2.25) and low‐birthweight infants (OR = 2.70). No recurrence was reported. Conclusions: Pregnancy with a history of stillbirth as a result of causes other than maternal conditions and fetal abnormalities is a moderate risk state, with prematurity and low‐birthweight rates somewhat higher than those in the general population. The overall probability of a favorable outcome is good. These findings may be useful in counseling pregnant women with a history of stillbirth.     

Current perspectives in hypertrophic cardiomyopathy with the focus on patients in the Finnish population: a review

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, with the prevalence of about 1/500. During the last two decades, the knowledge of the etiology, pathogenesis, risk stratification and prevention of sudden death in HCM has substantially advanced. Most often, HCM is familial and caused by mutations in sarcomere genes, inherited in an autosomal dominant manner. In Finland, genetic background of HCM is unique, with a few founder mutations in cardiac sarcomere genes accounting for a considerable proportion of the disease. Pathogenic mechanisms induced by disease-causing mutations are still poorly understood, although alterations in intracellular calcium handling and inefficient generation of contractile force in myocytes are considered key features in triggering the hypertrophic response. Clinical features of the disease are highly variable from no symptoms to the spectrum of exertional dyspnea, angina, palpitations, syncope and sudden death. In the current patient care, implantable cardioverter defibrillators (ICDs) are successfully used to prevent sudden cardiac death in high risk subjects. Targeted genetic testing is recommended to confirm the diagnosis in patients with HCM and to identify family members with the disease. Future research is needed to elucidate key cellular mechanisms leading to HCM, which may allow specific prevention and treatment of the disease.

• Key messages

• Hypertrophic cardiomyopathy, most often caused by defects in sarcomere genes, is the most common inherited heart disease, and a common cause of sudden cardiac death (SCD) in athletes and young subjects.

• Cardiac imaging, ECG and genetic testing are pivotal in the diagnosis of the disease in patients and first-degree relatives.

• Implantable cardioverter defibrillators in patients with high risk for SCD and tailored pharmacotherapy are efficient tools in patient care, but so far, exact mechanisms leading to cardiac hypertrophy in HCM are only partially understood, and there is no curative treatment for the disease.

     

Enzymic degradation of a beta-lactam antibiotic,ampicillin, in the gut: a novel treatment modality

Antibiotics can cause severe alterations in the gut microflora and promote diarrhoea and overgrowth of pathogenic bacteria. The present study investigated the potency of targeted recombinant beta-lactamase (TRBL) to degrade a beta-lactam antibiotic in the jejunum of fistula-operated beagles. We used different peroral doses of purified beta-lactamase (PenP) of Bacillus licheniformis in enteric-coated pellets together with intravenous ampicillin. Serum and jejunal samples were collected for ampicillin and beta-lactamase analysis. A dose-response effect of TRBL on ampicillin concentrations in the jejunal samples could be observed. The highest doses applied decreased the jejunal ampicillin concentrations to undetectable levels. In the serum samples, the ampicillin concentrations were not affected by the beta-lactamase dose used. Our results indicate that it may be possible to evolve a targeted treatment to degrade beta-lactam antibiotics intestinally and, thus, decrease antibiotic-induced adverse effects on the gut microflora.     

Geographical variation in the incidence of acute myocardial infarction in eastern Finland--a Bayesian perspective

BACKGROUND: Large geographical variation in the incidence and mortality of cardiovascular disease (CHD) has been repeatedly reported in Finland with persistent difference between east and west. We undertook this study to estimate the geographical distribution of Acute Myocardial Infarction (AMI) incidence in the high-risk province of North Karelia and in the province of Kuopio. METHODS: Data on men aged 25-64 years with first event of acute myocardial infarction (AMI) were obtained from the FINMONICA AMI register, which recorded detailed information of AMI events during the period 1983 to 1992. The geographical pattern of AMI incidence was studied in two five-year periods 1983 to 1987 and 1988 to 1992 separately in 10 km x 10 km grid cells employing the Geographical Information System (GIS) and a Bayesian hierarchical approach. RESULTS: In both periods Bayesian modeling revealed a geographical pattern of AMI incidence and high risk (probability that incidence exceeds the observed mean incidence) in the remote rural areas. CONCLUSIONS: Detection of high-risk areas in both provinces showed that underlying environmental and/or genetic risk factors of AMI are not evenly distributed within the province but enriched in certain geographical non-administratively defined locations in eastern Finland.