[Nephrology in general practice]. / Nephrologie in der Allgemeinpraxis.

Hints for the practitioner concerning the management of patients with renal disease are presented. Important facts relating to history, physical, laboratory and radiological findings are stressed and diagnostic assessment is briefly described. Although the general practitioner will refer such patients in most instances to a nephrologist, he should know what kind of further examinations and studies are necessary for correct diagnosis and adequate treatment. The present therapeutic possibilities have greatly improved, but one still disappointing aspect is the treatment of certain forms of glomerulonephritis. The cumulative survival rates in patients undergoing hemodialysis and renal transplantation are assessed and compared with the survival rates in patients suffering from myocardial infarct and carcinoma of the breast, colon and the lung. Essential preventive measures are avoidance of toxic substances like analgesics and consistent antihypertensive therapy even in patients with a renal ailment. The dosage of drugs which are mainly eliminated by the kidneys must be adapted to renal function (serum creatinine or clearance of endogenous creatinine).

[Pathogenesis of renal hypertension]. / Zur Pathogenese der renalen Hypertonie

Current pathogenetic concepts regarding renal hypertension are reviewed. Alterations of the renin-angiotensin-aldosterone system (RAA) on the one hand, and disturbances of NaCl and water metabolism on the other, represent the dominant factors in renal hypertension. The present view of the reactions within the RAA system and of its activators, inhibitors or antagonists is described schematically. The angiotensin II-antagonist 1-sar-8-ala-angiotensin II (Saralasin), when infused in a patient with angiotensinogenic hypertension, induces normalization of the blood pressure during the course of the infusion. The Saralasin infusion test may be of assistance in detecting cases with angiotensinogenic hypertension. The pressor(s) and the extracellular fluid volume appear to be the decisive pathogenetic factors in renal hypertension. As long as the functioning renal mass is sufficient to excrete water and salt normally or in excess, as is the case when the renal perfusion pressure in hypertension is elevated, the pressor is the dominating factor besides other, so far hypothetical mechanism such as the neurogenic. A critical reduction of the renal mass will enhance fluid and salt retention. Thus, an increase in extracellular fluid volume and blood volume will emerge as a major factor inducing hypertension. As a consequence of the volume gain and salt retention, renin secretion may slow down. The possibility is mentioned that the absence or ineffectiveness of renal depressor substances (prostaglandins) may be involved in renal hypertension. Finally, two hypotheses are presented which may explain the finding of LARAGH et al., who grouped their essential hypertensives into 'high, normal and low renin hypertensives'.

[Pathophysiology of renal hypertension (author's transl)]. / Pathophysiologie der renalen Hypertonie

The review discusses the pathophysiology of the renal mechanisms of blood-pressure control. The physiology of the renin-angiotensin system is described and the mineralo-corticoid function has also been considered. The implications of alterations of these systems in various nephropathies are briefly summarized (renal artery stenosis, infarction, Page's syndrome, acute glomerulonephritis, essential hypertension a.o.).

[Paget's deforming osteodysttophy]. / Die Osteodystrophia deformans Paget

The present clinical aspects of Paget's osteodystrophy are reviewed. The nosological definition, localiztion, natural course and signs are described and the recent description of "rheumatoid manifestations" in Paget's disease by FRANCK et al. is mentioned. The same authors revealed a positive correlation between the grade of extenstion of Paget's disease in the whole skeleton and the concentration values for alkaline phosphatase and uric acid in the serum. Among the complications of Paget's disease the orthopedic, neurological, haemodynamic, oncologic, hematological and dermatological are reviewed X-ray of the involved skeleton, which in most cases is diagnostic, may be supported by isotope scanning with 18F or 87mSr and bone biopsy for establishment of diagnosis. Current drug therapy is confined to diphosphonate and calcitonin. The antibiotic mithramycin, which is cytotoxic, reduces bone turnover and may improve the course in Paget's disease. However, toxic side effects on kidney, liver and hemopoiesis do not allow its further therapeutic use in this disease. A case is described which demonstrates that a spontaneous or traumatic fracture in the area of osteodystrophy exhibits almost the same potential for conso lidation as normal bone tissue following both conservative and osteosynthetic treatment of the fracture. In a further instance corrective osteotomy with osteosynthesis (plate) because of serious varisation and antecurvature of the femur due to Paget's disease were performed sucessfully without assisting drug therapy. A third patient displayed extensive osteodystrophy of the whole pelvic skeleton, which was discovered by X-ray as rehabilitation following CVA failed to progress due to severe bilateral reduction of hip joint function. In view of the age and general status of the patient and the absence of pain, no medication or surgical therapy was performed in this case.

[2 cases of acute sickle cell crisis in subjects with sickle cell trait following high altitude exposure]. / Zwei Fälle akuter Sichelzellkrisen bei Sichelzell-Heterozygoten nach Höhenexposition.

We present two patients with sickle cell trait (HbAS) who developed acute sickle cell crisis after passive exposure to high altitude on the Jungfraujoch (3454 meters, 11,333 ft). Both suffered splenic infarction and the first patient also presented with acute renal failure. Splenic infarction is known to be a complication of altitude exposure in carriers of the trait, whereas acute renal failure due to altitude exposure alone has as far as we know never been described in the literature. These forms of high altitude complications are totally unusual in Switzerland.

[Accidental hypothermia in man]. / Akzidentele Hypothermie beim Menschen.

Accidental hypothermia, in contrast to medical hibernation, corresponds to a sudden, unforeseen lowering of the body temperature below 35 degrees C. This may occur endogenously in association with various diseases. On the other hand, it may be due to the exogenous influences of very low environmental temperatures. An impressive observation of accidental hypothermia is described and the pathophysiological findings in accidental hypothermia are reviewed.

Stabilization of Octastatin, a somatostatin analogue. Preparation of freeze-dried products for parenteral injection.

Octastatin (RC-160, vapreotide INN) is a somatostatin analogue being developed for use in oncological, enterologic and neuroendocrine applications. The pharmaceutical form is a freeze-dried preparation for parenteral injection use. Three dosage forms containing 0.5, 1.5 and 15 mg of vapreotide base have been investigated. Various freeze-drying conditions, stabilizing agents, membranes for sterile filtration and heating procedures have been examined. The formulation with glutamic acid-sodium glutamate buffer as a stabilizing agent, the type of membrane for filtration and the freeze-drying procedure have been found appropriate for subsequent industrial production. No evident degradation was observed either after manufacturing, or after a three-week accelerated stability study at 50 degrees C and 70% relative humidity.

Stabilization of Octastatin, a somatostatin analogue: comparative accelerated stability studies of two formulations for freeze-dried products.

Octastatin (vapreotide INN) is a somatostatin analogue being developed in gastro-enterologic, neuroendocrine and oncologic applications. The pharmaceutical form is a freeze-dried preparation for parental injection use. This study was intended to evaluate the stability of the freeze-dried products and to determine the optimally stable formulation. Two types of stabilizing agents (lactose and glutamic acid/sodium glutamate buffer) and three dosage forms (0.5, 1.5, 15 mg of vapreotide base) were investigated. The peptide content and chemical stability of cakes stored at 50 degrees C and 70% relative humidity were determined by HPLC and the regression analysis parameters calculated. Results indicate that the formulation with glutamate buffer is appropriate for long term storage.

The effect of saralasin (1sar-8-ala-angiotensin II) on blood pressure in patients with Cushing's syndrome.

To investigate the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome two patients with hypercorticism were infused with 20 mg saralasin (1-sar-8-ala-angiotensin II) over a period of 30 minutes under constant blood pressue control. In addition, one patient with primary aldosteronism, an established form of mineralocorticoid hypertension, served as control. Neither in the two patients with Cushing's syndrome nor in the patient with primary aldosteronism could a blood pressure lowering effect of saralasin be observed. In the two patients with hypercoritcism both renin activity and plasma aldosterone increased during saralasin infusion. The patient with primary aldosteronism only showed a weak increase in plasma aldosterone concentration.