Elevated serum triiodothyronine and intellectual and motor disability with paroxysmal dyskinesia caused by a monocarboxylate transporter 8 gene mutation

Monocarboxylate transporter 8 ( MCT8 or SLC16A2) is important for the neuronal uptake of triiodothyronine (T3) in its function as a specific and active transporter of thyroid hormones across the cell membrane, thus being essential for human brain development. We report on a German male with Allan–Herndon–Dudley syndrome presenting with severe intellectual and motor disability, paroxysmal dyskinesia combined with truncal muscular hypotonia, and peripheral muscular hypertonia at his current age of 9 years. Additionally, the patient has a lesion in the left putamen region revealed by magnetic resonance imaging and elevated serum T3 levels. The male appeared to have a hemizygous mutation (R271H) in the MCT8 gene that was sequenced directly from genomic DNA and occurred de novo in the maternal germline, as both his mother and his sister were not carriers of the mutation. Ruling out a common polymorphism, 50 normal individuals of the same ethnic background did not harbour the mutation. The identified MCT8 gene mutation (R271H) is very likely to be the genetic cause for neuronal hypothyroidism despite elevated serum T3 levels.     

Female executives are particularly prone to the sleep-disturbing effect of isolated high-strain jobs: a cross-sectional study in German-speaking executives

This study assessed the main, curvilinear, interactive and gender-dependent effects of job demands, job control and social support in the prediction of sleep quality. Participants were 348 male and 76 female executives and managers from Germany, Austria and Switzerland. A multiple regression controlling for age, occupational hierarchy and various health behaviors was computed. On the level of the main effects of the Job–Demand–Control–Support (JDCS) model, the results indicate a sleep-promoting effect of social support. A significant three-way interaction of job demands, job control and social support was observed. This interaction confirms the buffering effect of high job control and high social support on high job demands. Further, this three-way interaction of the JDCS dimensions is moderated by gender as indicated by a significant four-way interaction. The directions of the significant interactions suggest that female executives are especially prone to react with impaired sleep quality when exposed to isolated high-strain jobs. The study seems to imply that the JDCS model is a suitable framework for the prediction of sleep quality among executives and managers. The results suggest that the JDCS model might contribute to a better understanding of the higher prevalence of poor sleep amongst female executives. Further, the results imply that high job control and high social support might help executives to maintain good sleep quality despite experiencing high job demands.     

Response to sodium benzoate treatment in non-ketotic hyperglycinaemia

Therapy with benzoic acid in a case of classic neonatal non-ketotic hyperglycinaemia (NKH) was successful in stopping seizures but not in promoting mental development. Serum glycine levels were normalizable even by administering low doses of 53 mg sodium benzoate/kg body mass (BM) per day. Despite giving a higher dosage (240 mg/kg BM per day) normalization of glycine concentration in cerebrospinal fluid (CSF) was not achieved. However, seizures ceased. Restriction of protein intake (≤2 g/kg BM per day) seemed to be profitable. CSF glycine concentrations below 100 μmol/L may be sufficient to prevent seizures in older infants who have adapted to neuronal glycine exposure. No toxicity of sodium benzoate treatment was detected when administering doses of up to 470 mg/kg BM per day but side effects such as itching and hyperactivity were obvious.     

THE VALUE OF THE RATIO OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN FOR STAGING PURPOSES IN PREVIOUSLY UNTREATED PROSTATE CANCER

Purpose

We analyzed the use of the ratio of free-to-total prostate specific antigen (PSA), also termed percentage of the free PSA, for predicting tumor stage, volume and grade in patients with clinically localized prostate cancer.

Materials and Methods

A total of 515 consecutive patients underwent further prostate evaluation due to elevated PSA (greater than 4.0 ng./ml.) or abnormal digital rectal examination. Prostate cancer was diagnosed in 307 patients (59.6%), including 170 (55.4%) who underwent radical retropubic prostatectomy. Data on pathological stage, Gleason grade, and total and Gleason grade 4 cancer volume were available in all patients. In the remaining 208 men (40.4%) benign prostate hyperplasia was diagnosed. Total and free PSA was measured in preoperative serum.

Results

Total PSA was significantly higher (p <0.0001) in the 71 men with stage pT3 tumors than in the 91 with pT2 disease. Eight patients had stage pT4 tumors. Cancer volume correlated well with advancing pathological stage (p <0.0001) and total PSA (p <0.0001). The free-to-total PSA ratio was not significantly different (p = 0.93) in stages pT2 and pT3 tumors, and it did not correlate with total (p = 0.71) or pure Gleason grade 4 (p = 0.94) cancer volume. However, the ratio of free-to-total PSA tended to decrease (p = 0.07) in tumors of increasing Gleason grade.

Conclusions

The ratio of free-to-total PSA does not help in the preoperative prediction of final tumor stage and volume. However, disease grading may alter the free-to-total PSA ratio.     

PROTON MAGNETIC RESONANCE SPECTROSCOPY IN DEMENTIA OF ALZHEIMER TYPE

Reduced N-acetyl aspartate (NAA) and increased myo-inositol (MI) levels have been reported in patients with dementia of Alzheimer type (DAT) in comparison with controls. We wished to assess the validity of these findings and to evaluate possible correlations of metabolite proportions with cognitive dysfunction in DAT. Twelve patients with DAT and 10 healthy age-matched controls were included. The severity of dementia was assessed using different scales including the Mini-Mental State Examination. MRS was performed with a conventional 1.5 Tesla scanner in a single voxel in the centrum semi-ovale (TE=30 ms or TE=136 ms TR=1500 ms). The evaluation of MRS results was limited by low interrater, intermeasurement (different echo times) and test–retest reliabilities, by a high interindividual variance and by the failure to measure absolute metabolite concentrations. These problems in mind, it was remarkable that previously reported reductions of NAA levels in patients with DAT could be reproduced in the present sample. The proportion of NAA was diminished in demented subjects in comparison with controls (37% vs 44.90%; short TE). A non-significant trend towards minor reductions of creatine, choline and MI proportions in these subjects might indicate that proportions of other metabolites necessarily increase when NAA is reduced. Cognitive dysfunction of demented subjects was significantly correlated with reductions of NAA, but not with increases of MI. Due to the present technical and methodological problems and to the non-specificity of findings, proton MRS cannot be applied to support the diagnosis of DAT in a clinical setting. © 1997 by John Wiley & Sons, Ltd.     

NUCLEAR p53 OVEREXPRESSION IS AN INDEPENDENT PROGNOSTIC PARAMETER IN NODE-NEGATIVE NON-SMALL CELL LUNG CARCINOMA

The prognosis of operated patients with non-small cell lung cancer (NSCLC) is poor despite thorough pre-operative staging. An improved preselection is needed of patients likely to profit from surgery. This study was undertaken to evaluate the prognostic significance of nuclear p53 overexpression in a cohort of 247 surgically treated patients with NSCLC. It showed that the prevalence of immunohistochemically detectable p53 overexpression varied between different tumour types. p53 overexpression was equally frequent in large cell carcinoma (53 per cent) and in squamous cell carcinoma (54 per cent), but significantly less frequent in adenocarcinoma (34 per cent; P =0·009). p53 overexpression was particularly rare in bronchioloalveolar carcinoma (positivity in 1 of 17 cases). These variations may reflect aetiological differences between the histological subtypes. p53 overexpression was also associated with high tumour grade ( P =0·0157) and the presence of lymph node metastasis ( P =0·0259), but not with advanced tumour stage. Survival analysis showed no difference in clinical outcome between p53-positive and p53-negative tumours within 101 node-positive tumours. In contrast, survival time was significantly better in p53-negative tumours than in p53-positive tumours within the group of 113 node-negative tumours ( P =0·032). Stepwise regression analysis showed that p53 overexpression is an independent prognostic factor in node-negative NSCLC.     

Neonatal rat cartilage has the capacity for tissue regeneration

One of the most relevant issues in future medicine is tissue regeneration. Transplantation medicine alone cannot solve the problem of incurable conditions of vital organs. One approach to this might be the replication of the spontaneous regeneration that is found in embryonic/neonatal tissue. In this study, a tissue model for basic investigation of regeneration mechanisms in vivo was established. We demonstrated by histology and immunohistochemical staining for types I and II collagen that neonatal rat cartilage unlike adult cartilage has the capacity for rapid scarfree regeneration after full-thickness incision. The underlying mechanism was identified in the preserved proliferative capacity of neonatal chondrocytes. This in vivo model should prove useful in further studies of the role of cellular (e.g., GA cell cycle regulators) and extracellular (e.g., cytokines) factors in tissue regeneration and wound healing.     

'Healthy Living is Fun' A creative way of health education

‘Healthy living is fun’ is a health education programmefor pupils aged 8–10 years. It consists of a curriculumcovering seven health topics, and was developed by a team ofa physician and teachers. The programme follows an integrated,cognitive concept of health education. By a creative approachthe pupils learn to appreciate their body and, consequently,to avoid risk factors. A prospective evaluation study is beingcarried out in cooperation with the German Institute for HighBlood Pressure Research, Heidelberg, Federal Republic of Germany.