Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder

A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.     

Neuropsychological profiles of FMR-1 premutation and full-mutation carrier females

The present French-German investigation of fragile-X syndrome (fra-X) was undertaken to disentangle genetic from environmental effects on cognitive performance as assessed with the following measures: Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wisconsin Card Sorting Test, Trail-Making Test, Tower of Hanai, Verbal Fluency Test, Stroop Test, short-term and consolidation memory, and the d2 task. Groups with different genotypes (n = 11 mothers with a full mutation in the FMR-1 gene of fra-X children; n = 65 mothers with a premutation in the FMR-1 gene of fra-X children; n = 18 siblings of these mothers with normal CGG repeats) and with different psychosocial stressors from fra-X families (n = 14 siblings with a premutation but without affected children of their own) were examined. A group of mothers of non-fra-X autistic children (n = 39) formed an external control group. Previous findings were replicated concerning cognitive performance of FMR-1 full-mutation carrier mothers, who were characterized by lower overall IQ and poorer performance than the group of mothers with the FMR-1 premutation in verbal and performance subtests of the WAIS-R, tests of executive-frontal lobe functioning, and tests of sustained attention. Carriers of the FMR-1 premutation, whether they were mothers of affected children or not,performed in a similar way on all neuropsychological tasks to the intrafamilial control group without CGG amplification. On the basis of these results, it is concluded that there is no neuropsychological evidence of reduced cognitive performance of FMR-1 premutation carriers compared with performance of two control groups with normal CGG repeats. Furthermore, the psychosocial burden of raising fra-X children does not exert an environmental effect on neuropsychological test performance.     

Thrombolysis of cerebral clot embolism in rat: effect of treatment delay

Rats submitted to focal cerebral ischemia by middle cerebral artery clot embolism were treated with recombinant tissue plasminogen activator (rt-PA) at increasing delays (1.5, 3 and 4.5 h) after the onset of ischemia. Treatment efficacy was evaluated by NMR imaging of the apparent diffusion coefficient of water (ADC). In untreated animals the size of the ADC-detectable lesion gradually increased after clot embolism, expanding over 8 h to 174 +/- 17% of the volume visible at 30 min. Thrombolysis initiated 1.5 h after embolism did not reverse the ischemic lesion but reduced its growth to 113 +/- 19% (p < 0.05). Lesion size increased to 135 +/- 14% after 3 h (NS) and to 214 +/- 35% after 4.5 h delay (NS). Thrombolysis with rt-PA attenuates infarct expansion but does not reverse ischemic injury.     

Bilateral and simultaneous quadriceps tendon rupture in secondary hyperparathyroidism. A case report

A case of bilateral simultaneous rupture of the quadriceps tendon without significant trauma is presented. Generally there is an association with chronic metabolic disorders, such as chronic renal failure and secondary hyperparathyreoidism, as well as hormonal diseases. The ruptures appeared in a 34-year-old man with chronic renal failure and severe secondary hyperparathyreoidism. Etiology, diagnostic procedures and treatment in comparison with the international literature are described. We discuss the value of ultrasound screening as a diagnostical and follow-up tool.     

Quality of life following transplantation. The impact ofa new immunosuppressive substance

The improvement of quality of life is one of the major goals in the treatment of patients after renal transplantation. While immunosuppressive therapy is present in almost all of these patients, little is known about the effects of newer immunosuppressive agents. We therefore investigated the impact of tacrolimus on life quality. From November 1997 to January 1998, a questionnaire was handed out which focussed on physical and mental problems as well as sexual capacity and the attitudes towards graft, donor and transplant related side effects. 50 kidney graft recipients treated with tacrolimus were matched to 50 patients with a cyclosporine-based immunosuppression (= controls). Values are given as mean +/- standard deviation. Tacrolimus treated patients had a mean creatinine of 1.8 +/- 0.8 mg/dl, as compared to 1.6 +/- 0.7 mg/dl in controls. The overall status of health was assessed to be good in 82% of the tacrolimus group (controls: 80%). 38% were working full-time (controls: 20%). Only 14% of patients described their physical condition as poor (16% in controls). Sexual function was good in 66% (controls: 74%) and poor in 10% (controls: 12%). Mental function was assessed to be good in 92% (controls: 82%). The majority of patients felt comfortable with their physical, sexual and mental capabilities. This was independent from the immunosuppressive regimen.     

Isolation and determination of quaternary ammonium compounds by means of amberlite XAD-columns and thin layer chromatography

The potentials of XAD-columns for the isolation of quaternary ammonium compounds from aqueous media have been investigated. When adequate amounts of counter ions (perchlorate, chloride, phosphate, nitrate) were added to the aqueous sample, to the column pretreatment fluid and to the aqueous washing fluid, most quaternary compounds investigated were retained on the column and could be recovered by elution with methanol. This approach proved also suitable for urine. Quantitation of quaternaries isolated in this way from urine samples could be performed on silicagel thin layer plates through visualization with iodine, followed by densitometric evaluation. For decamethonium detection limits were 0.1 g/ml. Recoveries at the 1 g/ml level were between 80–90% with variation coefficients of less than 10%.Presented at the European Meeting of The International Association of Forensic Toxicologists, July 4–7, 1978, Utrecht, The Netherlands     

Ionic currents of cultured olfactory receptor neurons from antennae of male Manduca sexta.

Whole-cell and single-channel voltage-clamp techniques were used to identify and characterize the ionic currents of insect olfactory receptor neurons (ORNs) in vitro. The cells were isolated from the antennae of male Manduca sexta pupae at stages 3-5 of adult development and maintained in primary cell culture. After 2-3 weeks in vitro, the presumptive ORNs had resting potentials of -62 +/- 12 mV (n = 18) and expressed at least 1 type of Na+ channel and at least 3 types of K+ channels. Na+ currents, recorded in the whole-cell mode, were reversibly blocked by 0.1 microM tetrodotoxin. The predominant type of K+ channel observed was a voltage-activated K+ channel (gamma = 30 pS) with characteristics similar to those of the delayed rectifier. The activity of the 30-pS K+ channel could be inhibited by the application of nucleotides to the cytoplasmic face of inside-out patches of membrane. The nucleotides had relative potencies as follows: ATP greater than cGMP greater than cAMP, with an inhibition constant for ATP of Ki = 0.18 mM. Raising the intracellular Ca2+ concentration from 0.1 to 5 microM induced the opening of a Ca2(+)-activated K+ channel (gamma = 66 pS at 0 mV) that had a low voltage sensitivity. A third, transient type of K+ channel (gamma = 12-18 pS) could be activated by depolarizing voltage steps from very negative resting potentials. Properties of this channel were similar to those of the "A-channel." These results support the conclusion that M. sexta ORNs differentiate in vitro and provide the basis for studying primary mechanisms of olfactory transduction.     

Methyl group metabolism gene polymorphisms and susceptibility to prostatic carcinoma

BACKGROUND: Alterations of DNA methylation are very frequent in prostatic carcinoma. A possible cause underlying altered DNA methylation could be an insufficient level of S-adenosylmethionine as a consequence of nutritional imbalances or of weaker alleles of genes for its synthesis, i.e., encoding methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and beta-cystathione synthetase (CBS). Therefore, homozygosity or heterozygosity for such weaker alleles may underlie susceptibility to prostatic carcinoma. METHODS: The distribution of the two most frequent MTHFR, MS, and CBS alleles was determined in 132 prostatic carcinoma patients and 150 population controls by restriction fragment length polymorphism-(RFLP) PCR. RESULTS: In the controls, a Hardy-Weinberg equilibrium was observed for each allele pair. No significant differences were observed with respect to age or gender. No significant differences for single genes or combinations were found between prostatic carcinoma patients and controls, although the MTHFR Val allele was slightly overrepresented among the tumor patients. Neither did the allele distribution significantly differ among the prostatic carcinoma patients stratified according to age, clinical stage, or presence of metastases. However, the MTHFR Val allele tended to be associated with higher tumor grade. CONCLUSIONS: In general, the data do not support the hypothesis that weaker alleles in methyl group metabolism genes constitute a major factor in the high prevalence of DNA methylation alterations found in prostatic carcinoma. However, a potential association with the MTHFR genotype deserves further study.     

Risco Cardiometabólico em Crianças e Adolescentes: O Paradoxo entre Índice de Massa Corporal e Aptidão Cardiorrespiratória

BackgroundCardiometabolic risk has been shown to be inversely associated with cardiorespiratory fitness (CRF) and positively associated with body mass index (BMI).ObjectiveOur objective was to analyze the association of cardiometabolic risk factors with combined BMI and CRF in schoolchildren from a city in southern Brazil.MethodsCross-sectional study with a sample of 1252 schoolchildren aged seven to 17 years. Total cholesterol (TC), HDL-c, LDL-c, triglycerides (TG), systolic (SBP) and diastolic blood pressure (DBP) were evaluated. CRF and BMI were grouped into one variable and the schoolchildren were classified as eutrophic/fit, eutrophic/unfit, overweight-obese/fit, and overweight-obese/unfit. Crude and adjusted analyzes were performed using Poisson Regression and an alpha of 0.05 was adopted.ResultsOverweight-obese and fit schoolchildren showed a prevalence ratio (PR) of 1.50 (1.04 – 2.16) for altered TG, 3.05 (2.05 – 4.54) for elevated SBP, and 2.70 (1.87 – 3.88) for elevated DBP. Overweight-obese and unfit schoolchildren showed a PR for high TC of 1.24 (1.11 – 1.39) and 1.51(1.11 – 2.04) for low HDL levels. In addition, they had a risk of 2.07 (1.60 – 2.69) for altered TG, 3.36 (2.31 – 4.60) for elevated SBP and 2.42 (1.76 – 3.32) for altered DBP.ConclusionBMI played a central role in the association with risk and CRF was shown to attenuate the association between risk factors and obesity. Overweight-obese children and adolescents had a higher cardiometabolic risk, but the effect size was larger among the unfit.     

Software-Automated Implant Detection for Intraoperative 3D Imaging—First Clinical Evaluation on 214 Data Sets

Previous studies have demonstrated a frequent occurrence of screw/K-wire malpositioning during surgical fracture treatment under 2D fluoroscopy and a correspondingly high revision rate as a result of using intraoperative 3D imaging. In order to facilitate and accelerate the diagnosis of implant malpositioning in 3D data sets, this study investigates two versions of an implant detection software for mobile 3D C-arms in terms of their detection performance based on comparison with manual evaluation. The 3D data sets of patients who had received surgical fracture treatment at five anatomical regions were extracted from the research database. First, manual evaluation of the data sets was performed, and the number of implanted implants was assessed. For 25 data sets, the time required by four investigators to adjust each implant was monitored. Subsequently, the evaluation was performed using both software versions based on the following detection parameters: true-positive-rate, false-negative-rate, false-detection-rate and positive predictive value. Furthermore, the causes of false positive and false negative detected implants depending on the anatomical region were investigated. Two hundred fourteen data sets with overall 1767 implants were included. The detection parameters were significantly improved (p<.001) from version 1 to version 2 of the implant detection software. Automatic evaluation required an average of 4.1±0.4 s while manual evaluation was completed in 136.15±72.9 s (p<.001), with a statistically significant difference between experienced and inexperienced users (p=.005). In summary, version 2 of the implant detection software achieved significantly better results. The time saved by using the software could contribute to optimizing the intraoperative workflow.