Obesity Paradox in Caucasian Seniors: Results of the PolSenior Study.

OBJECTIVES: To investigate the influence of overweight and obesity on general performance and mortality in seniors. DESIGN: Cross-sectional multidisciplinary study on ageing of the Polish population. SETTING: Community-dwelling individuals aged 65 years or older, selected using three-stage stratified, proportional draw. PARTICIPANTS: 4944 Polish Caucasian seniors, aged 65 years or older recruited between October 2007 and October 2010. MEASUREMENTS: All study subjects underwent measurement of body mass index (BMI), waist circumference (WC), and arm circumference (AC). The physical and cognitive performance was evaluated using the Katz Activities of Daily Living (ADL) score and Mini-Mental State Examination (MMSE), respectively. Morbidity data were obtained from a medical questionnaire. Mortality data were obtained from the Population Register of Poland between October 2015 and October 2018. RESULTS: Increasing age was associated with a decreased prevalence of obesity (all p<0.001). Higher BMI, WC and AC values were associated with higher ADL and MMSE scores (all p<0.001). On multivariate analysis, all three body measurements in women remained independent predictors of the ADL score (BMI p=0.002, WC p=0.005, AC p<0.001) and MMSE score (p<0.001, p=0.003, p<0.001). In men, physical functioning was associated with AC (p=0.003), and cognitive status was associated with AC (p<0.001) and BMI (p=0.013). There was no association between general obesity, abdominal obesity, or AC with several aging-related adverse conditions. Kaplan-Meier survival curves showed that overweight and obesity were associated with the lowest mortality. On multivariate analysis, BMI and AC values remained independent predictors of mortality. In successfully aging individuals, neither BMI, WC, nor AC remained such predictors. CONCLUSIONS: Overweight and obesity in Caucasian seniors are not associated with deterioration of physical and cognitive function or with increased mortality.

The predictive value of achieved motor milestones assessed in 441 patients with infantile spinal muscular atrophy types II and III.

Proximal spinal muscular atrophy (SMA) is classified into three main subtypes (I-III), defined by age at onset and achieved motor milestones. As age at onset can be very early in SMA II and III (IIIa, onset < 3 years) and does not necessarily correlate with prognosis, the question arises whether the child can be correctly assigned to a specific SMA type at the time of presentation based on the assessment of motor function. Therefore we studied the motor milestones in 175 SMA type II and 266 SMA type III patients. In SMA II, 73% of the patients sat within the normal age range (up to 9 months), the remainder learned to do so at ages between 10 and 30 months. In SMA III, the walking milestone was passed with delay (given an upper normal limit of 18 months) in 10% of all and 16% of SMA IIIa patients (median age 13 months, range 9-53 months). There was a correlation between late sitting and walking in SMA III, since those who sat after 9 months were responsible for the majority of delayed walkers. The median age when becoming chairbound did not differ between early-onset SMA III patients who walked with delay and those who walked within the normal age range (10.2 versus 10.5 years). In conclusion, a significant proportion of patients with early-onset SMA classified as SMA II on the basis of achieved motor function turned out to be SMA III at later follow-up. It is important to reassess a child in the first 2-4 years, to determine whether walking can be achieved with or without aids, as children who start to walk late have a similar favourable outcome for ambulation compared to earlier walkers.

The effect of treatment with risperidone, olanzapine or phenothiazines on cognitive functions in patients with schizophrenia.

INTRODUCTION: Theaimofthestudywastocomparetheeffectsofrisperidone, olanzapine and phenothiazines on cognitive functions in schizophrenia during short-term (4 - 6 weeks) and long-term (3 - 4 months) treatment. METHOD: Seventy patients with schizophrenia were investigated: 30 treated with risperidone, 20 with olanzapine and 20 with phenothiazines, in standard doses. Psychometric measurements were made with the Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests included the Trail Making Test (TMT), the Stroop Test and the Wisconsin Card Sorting Test (WCST). RESULTS: PANSS negative symptoms decreased significantly after risperidone and olanzapine, did not change after short-term, and improved marginally after long-term, phenothiazine treatment. Risperidone treatment resulted in significant amelioration of performance on all neuropsychological tests after both short- and long-term treatment. Olanzapine gave benefit on five out of seven subtests, although in most instances this effect was noted only after long-term treatment. Olanzapine was inferior to risperidone in improving WCST performance. Treatment with phenothiazines brought about improvement on two subtests while the results on three showed significant deterioration. CONCLUSION: The results obtained suggest that novel antipsychotics show differential effect on cognition, with risperidone especially improving working memory; however, their effect on negative symptoms and cognitive functions is better than that of typical neuroleptics.

Analysis of creatine kinase activity in 504 patients with proximal spinal muscular atrophy types I-III from the point of view of progression and severity.

Mild to moderately elevated creatine kinase (CK) activity is a frequent biochemical finding in proximal spinal muscular atrophy (SMA). In a collaborative study on all types of childhood and juvenile onset SMA, we analysed the CK activity of 504 SMA patients (138 type I, 127 type II, 144 type IIIa, and 95 type IIIb patients). Under the assumption of a lognormal distribution of CK activity as the most appropriate statistical model, CK levels were transformed into logarithms and compared by standard deviation scores = CK-SDS (log). CK activity was statistically different between early and later onset SMA: in SMA I and II, about one-third of patients showed CK-SDS (log) >2 SD, the analysis of the means did not show significant differences. In SMA III, CK-SDS (log) was significantly higher (p < 0.01) than in the two other groups, which was most pronounced in SMA IIIb. More than 90% of SMA IIIb patients showed CK-SDS (log) values >2 vs. 57% in SMA IIIa. As similar values were obtained for a subgroup of 100 patients in whom the diagnosis of autosomal recessive SMA was confirmed by a deletion of the telomeric copy of the survival motor neuron gene, our results can be considered representative for SMA I-III. There was no correlation between CK level and disease duration. The fact that patients were ambulatory or chair-bound had no influence on CK activity in type III SMA. There was no sex influence in SMA I, II and IIIa. The observed higher male values in the group SMA IIIb are most likely the result of a lack of female patients with onset after puberty.

A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients.

We analyzed clinical data of 569 patients in two combined series with childhood and juvenile proximal SMA. This cohort included only patients who had achieved the ability to sit unaided (type II and III SMA). The survival rate among 240 type II patients (who sat but never walked) was 98.5% at 5 years and 68.5% at 25 years. SMA III (n = 329) (those who walked and had symptoms before age 30 years) was subdivided into those with an onset before and after age 3 years (type IIIa, n = 195; SMA IIIb, n = 134). In patients with SMA III, life expectancy is not significantly less than a normal population. The probabilities of being able to walk at 10 years after onset was 70.3%, and at 40 years, 22.0% in SMA IIa. For SMA IIIb, 96.7% were walking 10 years after onset and 58.7% at 40 years. The subdivision of type III SMA was justified by the probability of being ambulatory depending on age at onset; the prognosis differed for those with onset before or after age 3 years. The data provide a reliable basis of the natural history of proximal SMA and support a classification system that is based primarily on age at onset and the achievement of motor milestones.

[Clinical-genetic studies of infantile and juvenile proximal spinal muscular atrophy]. / Badania kliniczno-genetyczne dzieciecego i mlodzienczego ksobnego rdzeniowego zaniku miesni.

The present paper describes clinico-genetic characteristics of childhood and juvenile proximal spinal muscular atrophy (SMA). The investigation involved sporadic and familial cases out in 37 families. These cases showed typical or unusual course of SMA (e.g. the pedigrees suggesting an inheritance other than autosomal recessive, coexistence of SMA with other inherited diseases, unusual patterns in EMG and muscle biopsy). All cases mapped in genetical analysis to the chromosome 5q11.2-13.3 Spino-bulbar form of SMA was excluded in families in which only males were affected. The method of carriership identification is presented.

[Deletions within the gene of dystrophin in Duchenne and Becker muscular dystrophy]. / Wystepowanie delecji w obrebie genu dystrofiny w dystrofii miesniowej typu Duchenne'a i Backera.

DNA was isolated and analysed in 96 patients with Duchenne or Becker muscular dystrophy (DMD, BMD); 9 of them were affected with BMD. Delections were found in 60 Patients (62.5%) using six cDNA probes. In some cases the PCR technique was also applied. In patients with BMD all deletions but one were in frame and involved exons 45-54. On the contrary, most deletions in DMD were out of frame and varied in their location. In five families prenatal diagnosis was carried out.

Emery-Dreifuss muscular dystrophy: linkage to markers in distal Xq28.

Emery-Dreifuss muscular dystrophy (EMD) is characterised by (1) early contractures of the Achilles tendons, elbows, and postcervical muscles, (2) slowly progressive muscle wasting and weakness with a predominantly humeroperoneal distribution in the early stages, and (3) cardiomyopathy with conduction defects and risk of sudden death. Inheritance is usually X linked recessive but can be autosomal dominant. Family linkage studies have mapped X linked EMD to the distal long arm of the X chromosome but precise genetic localisation has been hampered by the rarity of this condition. We report three new families with X linked Emery-Dreifuss muscular dystrophy studied with DNA markers from Xq27-qter and three previously published families typed for additional markers. No recombination was observed with the red/green cone pigment locus, RGCP (lod score, Z = 2.46), the factor VIII coagulant gene locus, F8C (Z = 6.39), or with DXS115 (Z = 4.94). Two recombinants were observed which mapped EMD distal to DXS15 (DX13) and DXS52 (St14) respectively. Multipoint linkage analysis gave odds exceeding 200:1 for EMD being distal to these markers. A multipoint analysis incorporating published data gave the map cen-DXS304-9cM-DXS15-3cM-DXS52-2 cM-(RGCP,EMD)-3cM-F8C-2cM-DXS115 with odds of 120:1 in favour of a location for EMD between DXS52 and F8C as compared to the next best position distal to F8C.

Interrelationship between gene, its product and phenotype in Duchenne and Becker muscular dystrophy.

DNA analysis was carried out in 113 patients of 103 families. In 58 families (55%) deletions were found using different cDNA probes. The attempt of studying the correlation between mental retardation in patients and the exon deletions was made. Dystrophin was evaluated in 80 patients including 12 affected females. One girl had chromosomal translocation X;22 and was a true DMD case. An unusual pedigree typical of X-linked transmission with affected subjects showing clinical features of DMD but with normally expressed dystrophin is presented. Owing to DNA and dystrophin analysis the correct diagnosis in some doubtful cases of muscular dystrophies could be established and some unusual pedigrees detected.

[Examination of dynamic changes of certain biochemical parameters in blood of rats poisoned with sodium nitrite]. / Badanie dynamiki zmian niektórych parametrów biochemicznych we krwi szczurów zatruwanych azotynem sodu.

In Wistar rats poisoned by daily addition of sodium nitrite to drinking water (1 g/dm3), determination was made of the dynamics of changes in: blood methemoglobin and 2,3-diphosphoglyceric acid levels, contents of protein and non-protein thiol groups in erythrocytes, blood glucose-6-phosphate dehydrogenase and peroxide dismutase activities, as well as plasma vitamin E and hydroxyproline levels, Determinations were performed after 15, 30, 45, 60, 75 and 90 days of poisoning. There occurred a linear relationship between the drop in glucose-6-phosphatase dehydrogenase activity and in vitamin E level, on one hand, and the duration of poisoning with sodium nitrite. Moreover, a significant rise of 2,3-diphosphoglyceric acid level in erythrocytes and a decrease in the non-protein thiol groups took place. Rhe results indicated that the determinations--in blood--of: methemoglobin, glucose-6-phosphate dehydrogenase activity in erythrocytes, and vitamin E in plasma or serum, could be included among the diagnostic tests performed (at the laboratories attached to industrial plants or making part of the industrial health service) for evaluation of the health hazard in the nitro-compound industry or in other nitrite contaminated working places.

Population data on acute infantile and chronic childhood spinal muscular atrophy in Warsaw.

This study provides epidemiological data on acute infantile (ASMA) and chronic childhood spinal (CSMA) muscular atrophy in Warsaw for the period 1976-1985. All calculations are based on the assumption that ASMA and CSMA result from mutations at two different gene loci. The incidence of ASMA and CSMA was 1 in 19474 live births with a corresponding gene and carrier frequency of 714 x 10(-5) and 1 in 70, respectively. The prevalence of CSMA for the year 1985 was 1.26 x 10(-5). These figures are higher than in similar studies in other countries. This fact might be connected with the careful ascertainment in this study.

Segregation analysis of 1885 DMD families: significant departure from the expected proportion of sporadic cases.

The proportion of sporadic cases of Duchenne muscular dystrophy has been estimated by classical segregation analysis in a pooled sample of 1885 sibships from 7 different countries. A significant departure from the theoretical expectations based on mutation-selection equilibrium is observed (segregation frequency = 0.439 +/- 0.017; frequency of sporadic cases = 0.229 +/- 0.026, at the maximum likelihood). The occurrence of germinal mosaicism in some of the mothers of Duchenne cases may account for this peculiar finding, although a possible role of inequality of mutation rates in the two sexes cannot be ruled out.

[Effect of the combined action of sodium nitrite and fenitrothion on certain biochemical parameters in rat blood]. / Wplyw skojarzonego dzialania azotynu sodu i fenitrotionu na wybrane parametry biochemiczne we krwi szczurów.

The aim of the study was explaining of the combined action of low doses of sodium nitrite and fenitrothion on certain biochemical parameters in rat blood. The experiment was carried out on male adult Wistar rats. The animals were divided into 4 experimental groups: group I receiving 10 mg/kg of sodium nitrite, group II--2.5 mg/kg of fenitrothion (Owadofos), group III received a mixture of both these doses, group IV served as control. The preparations were given intragastrically through a tube for 90 days. After that time 2,3-diphosphoglyceric acid, vitamin E, SH groups in protein and non-protein compounds in erythrocytes, methaemoglobin and basic haematological parameters, as well as the activity of glucose-6-phosphate dehydrogenase, superoxide dismutase and choline esterase were determined. Sodium nitrite decreased the activity of glucose-6-phosphate dehydrogenase and vitamin E, with an increase of the activity of superoxide dismutase and protein SH groups and methaemoglobin level. fenitrothion caused similar changes as sodium nitrite and decreased the activity of choline esterase and the level of 2,3-diphosphoglyceric acid. No synergistic action of these compounds was noted. The level of non-protein SH groups was decreased. It seems that determination of the level of non-protein sulphohydryl groups may be one of the indicators of poisoning with sodium nitrite combined with phenitrotione.

Atypical form of X-linked proximal pseudohypertrophic muscular dystrophy.

A series of 95 families, consisting of 317 patients with severe and mild X-linked proximal pseudohypertrophic muscular dystrophy (MD), was analysed by the use of two different and rigid clinical criteria based on the age when the patient became chairbound. Using these criteria the families from Erfurt and Warsaw could be clearly separated into classical Duchenne (DMD) and classical Becker (BMD) type patients. A third group of patients was found with atypical clinical course, who could not be identified as neither Duchenne nor Becker cases. Statistically highly significant differences were found between the groups of classical DMD and atypical MD cases on the one hand and between the groups of atypical MD and classical BMD cases on the other, especially with respect to age when chairbound and age at death. The comparisons of progression of the disease, life expectancy and of fertility between the three groups of X-linked MD show that classical DMD and atypical MD may be considered as separate types of severe X-linked proximal pseudohypertrophic MD. On the basis of these findings the authors offer conclusions for the general practice of neurology, paediatrics and genetic counseling.

Emery-Dreifuss muscular dystrophy: localisation to Xq27.3----qter confirmed by linkage to the factor VIII gene.

Two families with Emery-Dreifuss muscular dystrophy (EMD) have been studied with DNA markers mapping to Xq27.3----qter. No recombination was observed in 11 phase known meioses informative for the factor VIII gene (F8C) and eight phase known meioses informative for DXS15 (DX13), giving maximum lod scores of 3.50 and 2.50 respectively at a recombination fraction of zero. DXS52 (St14) showed one recombinant in 12 phase known meioses giving a maximum lod score of 2.62 at a recombination fraction of 0.07. These results map EMD to the distal end of the long arm of the X chromosome and are an important step in the development of tests for carrier detection and prenatal diagnosis.

Localization of the gene for X-linked spinal muscular atrophy.

We used probes for DNA polymorphisms on the X chromosome to study genetic linkage in seven families with X-linked adult-onset spinal muscular atrophy. We found significant linkage to the marker DXYS1 on the proximal X chromosome long arm and loose linkage or nonlinkage to markers elsewhere. Our analysis localizes the gene defect for this form of anterior horn cell disease.

Chronic proximal spinal muscular atrophy of childhood and adolescence: problems of classification and genetic counselling.

Results obtained from a study of 354 cases of chronic proximal spinal muscular atrophy of childhood and adolescence suggest that the condition is not as homogeneous as it was previously thought. A tentative classification based on our results is proposed. Estimates of genetic risks are provided, taking into account the sex and age at clinical onset. In our opinion these factors are more reliable than the data hitherto available because they are based on a considerably larger series.

Chronic proximal spinal muscular atrophy of childhood and adolescence: sex influence.

Segregation analysis was performed on 354 cases of chronic proximal spinal muscular atrophy of childhood and adolescence (CPSMA) in the total series and in a number of subgroups formed according to the age at onset and sex. The analysis provided evidence of sex influence in the series studied, particularly in a subgroup of the milder form of the disease with onset between the 37th month and 18th year of life. In the latter subgroup, females were affected much less frequently. This was particularly striking after age at onset of 8 years, and only exceptionally were females affected after the age of 13 years. These facts point to incomplete penetrance of the gene.