Occupational exposure to hexachlorocyclohexane

Summary Sixty male workers in a lindane (y-hexachlorocyclohexane)-producing factory were examined with regard to health in comparison with an external control group of 20 clerks.Case history, physical examination, neurologic status, and ECG revealed no significant differences between groups. However, the following significant differences in clinical-chemical blood tests were ascertained: higher polymorphonuclear leukocyte count, lower lymphocyte count, higher reticulocyte count, lower prothrombin (Quick's) test, and lower blood concentrations of creatinine and uric acid. No significant differences were observed in total red and white blood cell as well as platelet counts, hemoglobin content, the other counts of differential blood picture, -GT, GOT, GPT, LDH, cholinesterase, triglycerides, cholesterol, and urea.In spite of a pronounced exposure to the -, -, and -isomers of hexachlorocyclohexane, no signs of severe impairment of health were observed; only small deviations in some laboratory tests were found having no pathologic significance. However, biological monitoring and health supervision of HCH-exposed workers should be carried out.     

Occupational exposure to hexachlorocyclohexane

Summary In a lindane (-hexachlorocyclohexane)-producing factory 54 male workers (mean age 40 years, mean duration of exposure 8 years) were studied with regard to their blood levels of testosterone, LH, and FSH. Twenty clerks of nearly the same age were examined for control purposes in the same way. Serum-LH concentrations of the exposed workers were significantly higher than in controls. Geometric mean values were 8.8 mIU/ml and 5.7 mIU/ml respectively. On the other hand, FSH levels were insignificantly higher. Concerning testosterone concentrations in serum, these were found to be slightly lower in the group of workers than in control persons but this difference could not be proved to be statistically significant.These results indicate certain perturbations in sex hormone regulation probably as a consequence of HCH-exposure. To judge the pathological significance of these alterations further investigation will be necessary.     

An intramural hematoma of the small intestine, during anticoagulant therapy: radiological course. Concerning one case]

The authors present a case of intramural hematoma of the small intestines during anticoagulant treatment. With reference to this case, they study the frequency, etiopathogenesis and anatomy of this hematoma and particularly look at the radiological manifestations. In this respect they distinguish three stages in the evolution. The first, when the straight X-ray of the abdomen and barium followthrough demonstrate an axial stenosis of the small intestines with dilation of the proximal loops; the second (between the 7th and 20th days) when the loop affected by the hematoma takes on a characteristic "palissade" or "spring" -like sausage appearance; finally the third (after the 3rd week), when only thickening of the haustrations persists with progressive return to normal. The radiological diagnosis is discussed, not only with intramural hematomas of the small intestines of other etiologies (traumatic, during pancreatitis, during disorders in hemostatis), but also with conditions giving rise to similar radiological pictures: malabsorption, inflammatory conditions, etc.     

Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins.

Human GH represents a family of proteins rather than a single hormone. The circulation contains a bewildering array of GH forms, including several monomeric variants, their homo- and heteropolymers, fragments, and complexes with at least two BPs. The net biological activity of this mixture is difficult to predict, as the various molecular forms interact as partial agonists and/or antagonists at the receptor level. The number of GH forms that can be counted in plasma exceeds 100. Table 5 attempts to illustrate what is known and provide estimates for circulating variants. It does not include GH-V and its variants, which have to be added in pregnancy. Of note, what is commonly understood as "plasma GH," i.e. free monomeric 22K, represents only 21% of total immunoreactivity in plasma. In view of this complicated picture, it should be no surprise that different assays of plasma GH yield different results (107, 108, 290). While immunoassays are relatively unaffected by the BPs (291), receptor assays are seriously affected by the high affinity BP (261). Immunoassays, particularly of the monoclonal variety, are vulnerable to differential recognition of molecular variants depending on the unique epitope specificity of the antibody used. Polyclonal assays are more robust in this regard because of "epitope averaging" among the wide spectrum of epitope specificities present in the antibody population. Future work should aim at developing antibodies that are specific for individual GH variants. Such molecular probes will be helpful not only in standardizing immunoassays, but also in delineating the biological role of the various GH forms. The physiological significance of the numerous GH forms (or of the BPs) is still largely unknown. Progress in this area has been hampered, on the one hand, by the unavailability of pure GH variants in quantities sufficient for biological studies, and, on the other, by a certain lack of interest stemming from suspicions about artifacts. The recent resurgence of interest in GH and in its receptor and BPs should also refocus attention on the various molecular forms. Thus far, this interest has been largely confined to monomeric 22K, which is certainly effective for its original intended purpose, namely growth promotion. Whether 22K is sufficient for optimal growth and development, or whether it can fulfill all the functions of the GH family is unknown. It can be argued that evolutionarily conserved GH variants probably have biological importance.(ABSTRACT TRUNCATED AT 400 WORDS)     

Blockade of presynaptic α-receptors and of amine uptake in the rat brain by the antidepressant mianserine

Summary Mianserine (Org GB 94, Tolvon^®) is 1, 2, 3, 4, 10, 14b-hexahydro-2-methyl-dibenzo [c, f] pyrazino [1, 3-a] azepine hydrochloride, a new antidepressant drug. Its effect on noradrenaline release and its capacity to inhibit amine uptake were investigated. Mianserine increased the release of ³H-noradrenaline from field-stimulated cortical slices previously labelled with the tritiated transmitter. The assumption that this effect is due primarily to the blockade of the presynaptic noradrenergic -receptors is supported by the fact that mianserine failed to augment ³H-noradrenaline release further after blockade of the presynaptic -receptors by phentolamine. In the reciprocal experiment, phentolamine failed to augment ³H-noradrenaline release after exposure of the slices to mianserine. The hypothesis is further reinforced by the fact that mianserine antagonized the reduction of ³H-noradrenaline release by clonidine in the same manner as the -blocking drugs phentolamine and phenoxybenzamine. Mianserine inhibited noradrenaline uptake in vitro and in vivo (in the rat heart and midbrain-diencephalon synaptosomes from pretreated rats.) Only a marginal inhibition of serotonin uptake was observed.It therefore appears that mianserine increases the concentration of noradrenaline in the synaptic cleft by blocking the presynaptic -receptors and inhibiting uptake. Whether or not this increase has functional consequences at postsynaptic noradrenergic receptor sites is unknown. It is possible, however, that postsynaptic receptor blockade counteracts the increase in available noradrenaline.A part of these results was presented at the 16th Spring Meeting of the German Pharmacological Society, Mainz, March 4–7, 1975     

Vergleich der Jahresdaten zweier Schlaganfallstationen in neurologischen Kliniken an Akutkrankenhäusern

The Stroke Unit concept of the German Neurological Society differs from its precedents in Scandinavia or the United Kingdom. Hallmarks of the German concept are very early onset of diagnosis and treatment, continuous surveillance of vital functions by bedside monitors and specialized care by a multiprofessional team. This comparison of two Stroke Units in Minden and Munich-Harlaching, working according to the new German concept, shows broad similarities in admission intervals, diagnostic procedures, treatment modalities and short term prognosis, with an exceedingly low in-hospital mortality of 3.4-5.6% and a high proportion of patients (64-69%) leaving the hospital with Barthel scores above 70. Ongoing studies will show how this kind of Stroke Unit treatment compares to general wards.     

Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results.

BACKGROUND AND PURPOSE: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. MATERIALS AND METHODS: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. RESULTS: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. CONCLUSIONS AND OUTLOOK: Further investigations at all levels of the translational research chain exploring the mechanisms of EGFR inhibition in the context of radiotherapy are needed to fully exploit the potential of such combinations and to develop predictive tests that direct their use.     

The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML).

The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is based upon weighted data on bone marrow (BM) blast percentage, cytopenia, and cytogenetics, separating patients into four prognostic groups. We analyzed the value of the IPSS in 142 children with de novo MDS and 166 children with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in MDS and JMML were analyzed separately. Among the criteria considered by the IPSS score, only BM blasts <5% and platelets >100 x 10(9)/l were significantly associated with a superior survival in MDS. In JMML, better survival was associated with platelets >40 x 10(9)/l, but not with any other IPSS factors including cytogenetics. In conclusion, the IPSS is of limited value in both pediatric MDS and JMML. The results reflect the differences between myelodysplastic and myeloproliferative diseases in children and adults.