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     

rt-PA Lyse bei Patienten mit schwerer Lungenembolie und rechtskardialen Transitthromben Diagnostik und Verlaufskontrolle mit Hilfe der transösophagealen Echokardiographie

Zusammenfassung Bei Nachweis von rechtskardialen Thromben handelt es sich in den meisten F?llen um sogenannte ,,Transit-Thromben`` aus dem peripheren Venensystem, die nur kurz im rechten Herzen verweilen. Die Inzidenz von transthorakal echokardiographisch nachgewiesenen ,,Transit-Thromben`` bei Patienten mit Lungenembolie liegt bei etwa 3 – 4%. Unbehandelt ist die Letalit?tsrate dieser Patienten jedoch auf Grund der hohen Rate konsekutiver fulminanter Lungenembolien sehr hoch (30 – 40%). Bis vor einigen Jahren galt die operative Embolektomie als das Therapieverfahren der Wahl, das jedoch heute zunehmend durch die systemische, intraven?se Lysetherapie als Alternative ersetzt wird. Im Zeitraum von 1/94 bis 12/95 wurden in unserer Klinik 66 Patienten mit nachgewiesener Lungenembolie behandelt. Bei sieben dieser Patienten mit schwerer oder fulminanter Lungenembolie (10,6%; 5 M?nner, 55 – 74 Jahre alt) fanden sich rechtskardiale Thromben, die in allen F?llen mittels transthorakaler/ trans?sophagealer Echokardiographie (TEE) diagnostiziert wurden. In sechs F?llen sahen wir extrem mobile, wurmf?rmige Thromben im rechten Atrium, die zum Teil diastolisch tief in den rechten Ventrikel prolabierten. Bei einem Patienten waren die Thromben im rechten Ventrikel lokalisiert und fielen ventrikel-systolisch in den rechtsventrikul?ren Ausflu?trakt. In drei F?llen lie?en sich mittels TEE auch Thromben in der rechten Pulmonalarterie darstellen. Fünf Patienten wurden unmittelbar im Anschlu? an die TEE-Untersuchung ohne weitere angiographische Diagnostik mit einer systemischen, intraven?sen Lysetherapie mit 100 mg front-loaded rt-PA über 90 Minuten behandelt. Ein prim?r reanimationspflichtiger Patient erhielt als ,,Ultima Ratio`` 100 mg rt-PA als Bolus, eine weitere Patientin 50 mg rt-PA als Bolus gefolgt von 50 mg über 2 Stunden. Bei allen Patienten stabilisierte sich der h?modynamische Zustand innerhalb kürzester Zeit. In sechs F?llen konnte mittels TEE und einmal mittels transthorakaler Echokardiographie innerhalb von 15 Stunden die komplette Aufl?sung der rechtskardialen Thromben dokumentiert werden. Bei einem Patienten kam es zu einer intracerebralen Blutung und ein Patient verstarb nach 10 Tagen an den Folgen der protrahierten Reanimation mit hypoxischem Hirnschaden. Mittels TTE/TEE lassen sich rechtskardiale Transitthromben als koinzidenter Befund bei Patienten mit klinischen Hinweisen für eine fulminante Lungenembolie gut diagnostizieren sowie der Therapieerfolg verfolgen. In diesen F?llen ist die sofortige systemische Lysetherapie ohne weitere bildgebende Diagnostik durchzuführen, um einer weiteren Verschlechterung der klinischen Situation in Folge Transports und Umlagerung des Patienten mit der Gefahr des Abschwemmens des Transitthrombus vorzubeugen. Eingegangen: 15. Mai 1996 Akzeptiert: 23. Oktober 1996     

Presence of synaptonemal complex protein 1 transversal filament-like protein in human primary spermatocytes

The synaptonemal complex (SC) is involved in the pairing of chromosomes during meiosis. We found that antibodies raised against a protein component (P1) of the mouse synaptonemal complex, mouse SCP1, also identified the SC in human primary spermatocytes. Biopsies from 18 men presented with infertility were evaluated by light-field microscopy and grouped into five categories: normal spermatogenesis, Sertoli cell-only syndrome, meiotic disturbances, spermiogenic (i.e. differentiation) disturbances, and other combined disturbances. In all the normal subjects the SCP1 antibody distinctly stained the synaptonemal complexes of primary spermatocytes, whereas Sertoli cells, spermatogonia or spermatids were never stained. In three of the groups, which had germ cells but showed spermatogenic disturbances, the staining was similar to that seen in normal subjects. In sharp contrast to this, in sections from men with Sertoli cell-only syndrome no specific staining was seen. This study demonstrates that a SCP1-related protein is also conserved in the synaptonemal complex in meiotic cells from man. Further studies will reveal to what extent the absence or the non-functionality of SCP1 contributes to male infertility.      

A comparison of clinical and research DSM-III-R diagnoses of schizophrenia in a Finnish national birth cohort

As a prerequisite to the use of the Finnish National Hospital Discharge Register in psychiatric epidemiological research, we studied the diagnostic reliability of the register in terms of the psychiatric morbidity experienced by a national birth cohort. We investigated all entries to the register for a sample based upon the Northern Finland 1966 birth cohort at the age of 16 years (n=11017). Until the end of 1993 (age 27 years), a total of 563 subjects had a register diagnosis indicating a psychiatric illness, 37 of them being schizophrenia. When operational criteria (DSM-III-R) were applied to clinical information in the available original hospital records for cases of psychosis, personality disorder and substance abuse (n=249), 71 fulfilled criteria for schizophrenia, including all of the 37 cases in the register and an additional 34 (48% false-negatives), most frequently diagnosed in the register as schizophreniform or other psychosis. Despite the official use of DSM-III-R nomenclature, it appears that the clinical concept of schizophrenia in Finland, manifest within the register, remains very restrictive. The application of operational criteria is a necessary prerequisite for scientific research on schizophrenia.