Circumscribed low grade astrocytomas in the dominant opercular and insular region: A pilot study

Summary Intraoperative mapping techniques allow a reliable identification or exclusion of eloquent brain areas and are well tolerated by the patients. In dominant opercular tumours radical surgery can only be achieved without lasting deficits with intraoperative histological examination of the resection line and mapping. If an early post-operative MRI shows residual opercular tumour in non-eloquent areas re-operation is recommended.In large dominant insular or opercular-insular tumours only biopsy is recommended, because only an incomplete removal can be accomplished, because the trial of radical removal carries a high risk of postoperative deficits due to possible vascular damage of the lenticulo-striate arteries or internal capsule. Because subtotal removal of low grade gliomas does not increase the progression free interval, we would not recommend surgery in these cases, as they carry a significant risk of a further deficit.     

Structural vertebral changes in the horizontal plane in idiopathic scoliosis and the long-term corrective effect of spine instrumentation

Summary The rotation and structural changes of the apex vertebra in the horizontal plane as well as of the thoracic cage deformity were quantified by measurements on computed tomography (CT) scans from patients with right convex thoracic idiopathic scoliosis (IS). The CT scans were obtained from 12 patients with moderate scoliosis (mean Cobb angle 25.8°, r 13°–30°) and from 33 with severe scoliosis (mean Cobb angle 46.2°, r 35°–71°). In addition, CT scans of thoracic vertebrae from 15 patients without scoliosis were used as reference material. Ten of the scoliotic cases had had Cotrel-Dubousset instrumentation (CDI) and posterior fusion and had entered a longitudinal study on the effect of operative correction on the re-modelling of the apical vertebra. An increasingly asymmetrical vertebral body, transverse process angle, pedicle width and canal width were found in the groups with scoliosis as compared with the reference material. Vertebral rotation and rib hump index were significantly larger in patients with early and advanced scoliosis than in normal subjects. The modelling angle of the vertebral body, the transverse process angle index and the vertebral rotation in relation to the middle axis of the thoracic cage were significantly greater in patients with severe than with moderate scoliosis. The results of this longitudinal study suggest that the structural changes of the apical vertebra regress 2 years or more after CD instrumentation.     

Tamoxifen and kallikrein in therapy of oligoasthenozoospermia: results of a randomized study

Because of the good results achieved with tamoxifen in the treatment of oligozoospermia and with kallikrein in the treatment of asthenozoospermia, a randomized study of the combined treatment of oligoasthenozoospermia suggested itself. 67 patients with idiopathic normogonadotropic oligoasthenozoospermia were treated with 30 mg tamoxifen/day (n = 33) or with 30 mg tamoxifen/day and additionally 600 IU kallikrein/day (n = 34). It was shown that, apart from a significant increase in sperm density in both groups, the combination therapy also resulted in an overall significant increase (p less than 0.02) in sperm motility. Sperm morphology and the swell test remained unaffected. After 3 months of therapy, 4 pregnancies occurred in each group. In ejaculates with a sperm density of less than 10 million/ml not even one sperm parameter was significantly affected in any of the groups, while with an initial value of more than 10 million/ml the increase in motility was more significant (p less than 0.008) in the group with additional kallikrein therapy (n = 18). In the monotherapy group, no significant therapeutic effect on sperm motility was seen even in patients with a sperm density of more than 10 million. The combination of tamoxifen and kallikrein therefore seems to constitute an improvement of the systemic therapy of male subfertility in patients with moderately severe oligoasthenozoospermia.     

Occupational diseases of the musculoskeletal system of the SUVA (Swiss Accident Insurance Institute)

First there is given a definition of occupation related diseases of the musculoskeletal system as a subject to the Swiss federal law of social insurance. As a relation to age and sex, the incidence, the following time of work incapacity and the financial consequences of disability are reported within a period from 1970 to 1983. Although the results are highly specific to Swiss legislation, the international comparison might be of interest.     

Incidence of femoral and tibial shaft fractures. Epidemiology 1950-1983 in Malm?, Sweden

We studied 362 fractures of the femur that had occurred during the years 1950-57 and 1973-83, and 849 fractures of the tibia that occurred during the the years 1950-55 and 1980-83. There was an increase in age-specific incidence over aged 60 years. The risk of low-energy femoral shaft fractures also had increased in elderly women. Both fracture types shifted their age- and sex-specific incidence in the direction of a fragility pattern. There was no increase in the incidence of tibial shaft fractures. Fracture type, site, and degree of displacement of the tibial fractures remained unchanged during the 30 years, i.e, they were predominantly distal, longitudinal fractures with moderate displacement.     

The use of measures of influence in epidemiology

In epidemiological studies the units of observation often consist of political entities such as countries, each of which has its own specific inner structure. When a multiple regression is performed it is therefore of particular interest to analyse not only the overall behaviour of the dataset, but in addition, to investigate how each individual country contributes to, and deviates from, this overall behaviour. By means of the example 'relation between infant mortality and structural data of countries' several ways are discussed of how each individual country can influence the regression model. Firstly the potential influence which each country might exhibit due to the explanatory variables alone is analysed. Then the actual influence of each country is analysed by taking the explanatory variables and the target variable into account simultaneously. This is done by means of statistical measures not generally familiar to epidemiologists, which have been developed in recent years (leverage values, Cook's distances). These measures also point to deviations of countries from the model, and suggest directions in which to search for explanation. Finally the influence of the 'size' of the countries is investigated.     

Plasma nitrate plus nitrite changes during continuous intravenous infusion interleukin 2.

Nitric oxide (NO), a biologically active mediator generated in many cell types by the enzyme NO synthase, may play an important role in cardiovascular toxicity that is frequently observed in cancer patients during intravenous (i.v.) interleukin 2 (IL-2) therapy. The induction of NO synthase and the production of NO seem to be involved in the pathogenesis of the vascular leakage syndrome, as well as in the regulation of myocardial contractility. In the present study, we evaluated the pattern of plasmatic NO changes during multiple cycles of continuous i.v. infusion (CIVI) of IL-2 in ten advanced cancer patients (five males, five females, median age 59 years, range 33-67 years; eight affected by renal cell cancer and two affected by malignant melanoma). The patients received IL-2 at 18 MIU m-2 day-1 (14 cycles) or 9 MIU m-2 day-1 (seven cycles) for 96 h, repeated every 3 weeks. Interferon alpha (IFN alpha) was also administered subcutaneously (s.c) during the 3 week interval between IL-2 cycles. For each cycle, plasma samples were collected before treatment (t0), 24 h (t1), 48 h (t2), 72 h (t3) and 96 h (t4) after the start of IL-2 infusion, and 24 h after the end of the cycle. NO concentration was determined spectrophotometrically by measuring the accumulation of both nitrite and nitrate (after reduction to nitrite). The following observations may be drawn from data analysis: (1) plasma nitrate + nitrite significantly raised during treatment (P = 0.0226 for t0 vs t3), but statistical significance was retained only when cycles administered with IL-2 18 MIU m-2 day-1 are considered (P = 0.0329 for t0 vs t3; P = 0.0354 for t0 vs t2 vs t4) (dose-dependent pattern); (2) during subsequent cycles a significant trend toward a progressive increase of plasma nitrate + nitrite levels, with increasing cumulative dose of IL-2, was observed (linear regression coefficient r = 0.62, P = 0.0141 for t0; r = 0.80, P = 0.0003 for t1; r = 0.62, P = 0.013 for t2; r = 0.69, P = 0.045 for t3); (3) plasma nitrate + nitrite levels peaked earlier in subsequent cycles than in the first cycle; (4) all patients experienced hypotension. The mean of the systolic blood pressure values was significantly lower at the time of plasma nitrate + nitrite peak than at t0 (P = 0.0004); (5) the two cases of grade III hypotension occurred in patients with the higher mean and peak plasma nitrate + nitrite values. We conclude that determination of plasma nitrate + nitrite levels during CIVI IL-2 can usefully estimate, in a dose-dependent pattern, the degree of peripheral vascular relaxation and capillary leakage associated with cytokine action, clinically manifested as hypotension. However, isolated cardiac toxicity that continues to represent a relevant problem during IL-2 therapy, does not appear to correlate with plasma nitrate + nitrite levels; therefore, further studies are required to understand adequately the mechanisms underlying IL-2-induced cardiac toxicity.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Infradian biorhythms of enzymuria in man?

The temporal courses of dipeptidyl peptidase IV gamma-glutamyltransferase and alanine aminopeptidase were followed over 70 days in the morning urine of 15 healthy persons. Subsequent to basic statistical analysis a two-step procedure was performed, including spectral analysis and the fit of a cosine function by non-linear regression. The excretion of the 3 enzymes followed an infradian biorhythm with a mean period length of 10.04 for dipeptidyl peptidase IV, 13.34 for gamma-glutamyltransferase and 10.17 for alanine aminopeptidase. In addition to the basic rhythmic process described by the fitted cosine functions, in most of the enzyme patterns steap peaks of very high excretory activity appeared which was verified in repeated measurements. These infradian biorhythms with changes in the range of 100% and more, as well as their interindividual variations, have to be considered in assessing the excretion of enzymes.     

Splicing of the mitochondrial group-II intron rl1: conserved intron-exon interactions diminish splicing efficiency

The mitochondrial intron rI1 is a self-splicing group-II intron of algal mitochondria that can be transferred into chloroplasts from the green alga Chlamydomonas reinhardtii for in vivo investigations (Herdenberger et al. 1994). Thus, rI1 is a suitable system to compare in vitro and in vivo RNA processing. Interestingly, rI1 shows correct RNA splicing, although typical cis-acting exon-sequences (IBS2, δ) of group-II introns are lacking. In order to examine the effect of these exon-intron interactions on splicing, we introduced the endogenous mitochondrial IBS2 sequence in order to produce optimal IBS2-EBS2 base pairing. In addition, the first nucleotide of the 3′exon (δ′) was substituted to create an optimal δ-δ′ interaction. Neither of the two mutations, nor a combination of both, had any effect on the precision of the splice-site selection. Unexpectedly, introduction of IBS2 led to a reduction in the efficiency of the second splicing step in vitro but not in vivo. These findings lead us to conclude that trans-acting factors are present in vivo to optimize splicing efficiency. The possibility is discussed that these factors may, for example, stabilize tertiary intron structures that are a prerequisite for correct RNA processing. Furthermore, our data indicate that similar trans-acting factors promote correct intron splicing in chloroplasts and mitochondria. Received: 18 October / 4 December 1997