Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis

In recent years it has become clear that multiple sclerosis (MS) patients benefit from physical exercise as performed in aerobic training but little is known about the effect on functional domains and physiological factors mediating these effects. We studied immunological, endocrine and neurotrophic factors as well as coordinative function and quality of life during an 8-week aerobic bicycle training in a waitlist control design. In the immune-endocrine study (1) 28 patients were included, the coordinative extension study (2) included 39 patients. Training was performed at 60% VO(2)max after determining individual exertion levels through step-by-step ergometry. Metabolic (lactate), endocrine (cortisol, adrendocortico-releasing hormone, epinephrine, norepinephrine), immune (IL-6, soluble IL-6 receptor), and neurotrophic (brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF)) parameters were compared from a prestudy and a poststudy endurance test at 60% VO(2)max for 30 min. In study (1), lowered lactate levels despite higher workload levels indicated a training effect. Disease-specific quality of life (as measured by the Hamburg Quality of Life Questionnaire for Multiple Sclerosis, HAQUAMS) significantly increased in the training group. No significant training effects were seen for endocrine and immune parameters or neurotrophins. In study (2), two out of three coordinative parameters of the lower extremities were significantly improved. In summary, low-level aerobic training in MS improves not only quality of life but also coordinative function and physical fitness.     

Emergence of restless legs syndrome during subthalamic stimulation for Parkinson disease

The authors systematically studied the emergence of restless legs syndrome (RLS) after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Postoperatively, 11 of 195 patients with STN DBS reported new problematic symptoms of RLS. The mean reduction in antiparkinsonian medication was 74%. The mean RLS score at diagnosis was 15 (+/-5.9) of a possible 24 points and after symptomatic drug therapy 4.3 (+/-3.1) points. Reduction of antiparkinsonian medication during STN DBS may unmask symptoms of RLS and complicate therapy of both RLS and PD.     

CTA der A. carotis mit unterschiedlichen CT-Geräten

Noninvasive modalities like CTA are increasingly replacing selective angiography in the evaluation of carotid artery stenosis. Dedicated scan protocols and contrast injection techniques are mandatory for the morphological assessment of carotid artery stenosis. These protocols need to be adapted to different scanner types. The delineation of plaque components and the residual lumen is improved with high resolution scan protocols and dedicated reconstruction algorithms. The exact delineation of in-stent stenosis remains limited. Standardization of postprocessing is crucial in order to attain reproducible results. Multislice spiral CT allows reliable grading of carotid artery stenosis. Relevant venous opacification and pulsation artifacts have to be expected with 4-slice scanners, the short scan time of the latest CT scanners minimize these problems.     

Genetic polymorphism of cytochrome P450 2C19 in healthy Malaysian subjects

AIMS: Impaired S-mephenytoin 4'-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population. METHODS: Study subjects were 142 healthy, unrelated Malaysians aged 18-29 years. Baseline omeprazole and 2-h postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for CYP2C19 phenotype determination. Identification of CYP2C19 genotypes was performed with the use of polymerase chain reaction. RESULTS: Phenotyping of CYP2C19 revealed that the prevalence of poor metabolizers (PMs) in the Malaysian population was 14.1%, whereas prevalence of PMs in genotyping was 12.6%. The PM genotypic prevalence rate was 5.6% in Malays, 19.1% in Chinese and 10.0% in Indian subjects. There were significant differences in PM genotypic prevalence rates among the three primary ethnic groups (P < or = 0.05). CONCLUSIONS: Phenotyping and genotyping revealed significant differences in the prevalence rates among the three ethnic groups in Malaysia, with Chinese recording highest prevalence.     

High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1)

This study aimed to characterize possible relationships between polymorphisms in the drug transporter genes organic anion transporting polypeptide-C (OATP-C, SLCO1B1), OATP-B (SLCO2B1), multidrug resistance-associated protein 2 (MRP2, ABCC2) and multidrug resistance transporter (MDR1, ABCB1) and the pharmacokinetics of pravastatin. We studied 41 healthy Caucasian volunteers who had previously participated in pharmacokinetic studies with pravastatin. Six volunteers had a very high pravastatin AUC value and were defined as outliers according to statistical criteria. The OATP-C gene was sequenced completely in all subjects, and they were also genotyped for selected single nucleotide polymorphisms (SNP) in the OATP-B, MDR1 and MRP2 genes. Of the six outliers, five were heterozygous for the OATP-C 521T>C (Val174Ala) SNP (allele frequency 42%) and three were heterozygous for a new SNP in the promoter region of OATP-C (-11187G>A, allele frequency 25%). Among the remaining 35 subjects, two were homozygous and six were heterozygous carriers of the 521T>C SNP (allele frequency 14%, P = 0.0384 versus outliers) and three were heterozygous carriers of the -11187G>A SNP (allele frequency 4%, P = 0.0380 versus outliers). In subjects with the -11187GA or 521TC genotype, the mean pravastatin AUC0-12 was 98% (P = 0.0061) or 106% (P = 0.0034) higher, respectively, compared to subjects with the reference genotype. These results were substantiated by haplotype analysis. In heterozygous carriers of *15B (containing the 388A>G and 521T>C variants), the mean pravastatin AUC0-12 was 93% (P = 0.024) higher compared to non-carriers and, in heterozygous carriers of *17 (containing the -11187G>A, 388A>G and 521T>C variants), it was 130% (P = 0.0053) higher compared to non-carriers. No significant associations were found between OATP-B, MRP2 or MDR1 polymorphisms and the pharmacokinetics of pravastatin. These results suggest that haplotypes are more informative in predicting the OATP-C phenotype than single SNPs.     

Cataract surgery with implantation of toric silicone lenses for severe astigmatism after keratoplasty

BACKGROUND: The treatment of high astigmatism after keratoplasty is often not possible with glasses or refractive corneal surgery, particularly in patients with anisometropia and contact lens incompatibility. METHODS: In 3 patients with cataract and high astigmatism after penetrating keratoplasty, phacoemulsification was performed via a 4 mm sclerocorneal tunnel incision. A toric silicone lens with Z-haptic was implanted in the bag (Type MS 6116 TU, Dr. Schmidt). All patients had high anisometropia and contact lens incompatibility. The follow-up was ten weeks, uncorrected and corrected visual acuity, corneal and total astigmatism were evaluated. RESULTS: A 68-year-old female presented with corneal astigmatism of 10 dpt. Keratoplasty was performed two years earlier. After implantation of a toric lens (+ 22.5 + 11.0 dpt.) uncorrected visual acuity increased from 1/50 to 20/40, corrected visual acuity increased from 20/30 to 20/25. A 78-year-old male presented with irregular corneal astigmatism of 6.5 dpt. Keratoplasty was performed 25 years previously. Due to high myopia (corneal radii 5.3/5.9 mm), implantation of a toric lens (- 3.0 + 7.0 dpt.) in the bag was combined with implantation of a spheric lens (- 6.0 dpt., Type MS 614, Dr. Schmidt) in the sulcus. Uncorrected visual acuity increased from light perception to 1/20, corrected visual acuity increased to 1/10. An 84-year-old female presented with irregular corneal astigmatism of 8.6 dpt. Keratoplasty was performed two years earlier. After implantation of a toric lens (+ 16.0 + 11.0 dpt.) uncorrected visual acuity increased to 20/50, corrected visual acuity increased from 20/100 to 20/25. During the follow-up all implanted lenses were well-centered and no significant IOL rotation was observed. CONCLUSION: Implantation of foldable toric silicone lenses during cataract surgery may improve considerably the uncorrected visual acuity by reducing the total astigmatism in patients with high astigmatism after keratoplasty. Preoperatively, a reliable keratometry is important.     

Impact of the case payment reimbursement method on the utilization and costs of laparoscopic cholecystectomy

The purpose of this study was to examine the relationship between adoption of case payment for laparoscopic cholecystectomy (LC) and the growth rate of LC, outcomes of patients undergoing LC, and total healthcare expenditures on cholecystectomy.We used the claims data from Bureau of National Health Insurance (BNHI) to identify patients who underwent LC and open cholecystectomy (OC). Data were available from January 1996 to October 1997 and from January 1998 to October 1999, enabling use to compare data from before and after the introduction of the new case payment system.Results showed that the volume and the proportion of LCs increased after adoption of the new payment method. We did not find a sharp increase in the cholecystectomy rate during the study period. In terms of outcomes, the admission rate for emergencies decreased; the surgery mortality rate decreased, but the readmission rate increased. The average cost and length of hospital stay for LC subjects decreased; however, the total cost of cholecystectomy increased.The impact on LC of the introduction of a case payment method failed to reduce total health expenditures for cholecystectomy.     

Can we disentangle life course processes of accumulation, critical period and social mobility? An analysis of disadvantaged socio-economic positions and myocardial infarction in the Stockholm Heart Epidemiology Program

The accumulation hypothesis would propose that the longer the duration of exposure to disadvantaged socio-economic position, the greater the risk of myocardial infarction. However there may be a danger of confounding between accumulation and possibly more complex combinations of critical periods of exposure and social mobility. The objective of this paper is to investigate the possibility of distinguishing between these alternatives. We used a population based case-control study (Stockholm Heart Epidemiology Programme) of all incident first events of myocardial infarction among men and women, living in the Stockholm region 1992-94. The analyses were restricted to men 53-70 years, 511 cases and 716 controls. From a full occupational history each subject was categorized as manual worker or non-manual at three stages of the life course, childhood (from parent's occupation), at the ages 25-29 and 51-55, resulting in 8 possible socio-economic trajectories. We found a graded response to the accumulation of disadvantaged socio-economic positions over the life course. However, we also found evidence for effects of critical periods and of social mobility. A conceptual analysis showed that there are, for theoretical reasons, only a limited number of trajectories available, too small to form distinct empirical categories of each hypothesis. The empirical task of disentangling the life course hypotheses of critical period, social mobility and accumulation is therefore comparable to the problem of separating age, period, and cohort effects. Accordingly, the interpretation must depend on prior knowledge of more specific causal mechanisms.