Platelet aggregation and reversible platelet aggregates in type I-diabetes staged by retinal fluorescein angiography.

In 70 patients with juvenile-onset, insulin-dependent (type I) diabetes and 75 age- and sex-matched controls the reversible platelet aggregates expressed as platelet count ratio (PCR) and the ADP-induced platelet aggregation were studied. Retinal microangiopathy was staged by retinal fluorescein angiography. The mean PCR of the patients (0.82 +/- 0.02) was statistically significantly lower than that of the controls (0.97 +/- 0.01). However, in different stages of retinopathy no significantly different PCR could be observed. ADP-induced platelet aggregation (0.5 and 1.0 micromol/l) exhibited a higher reactivity of diabetic platelets, but with the exception of tangent alpha (see later), the differences were not statistically significant in comparison to the controls. After collagen-induced platelet aggregation (0.5 and 1 microgram/ml) the lag time in diabetics was significantly (p less than 0.001) lower than in the controls, whereas the other quantitative parameters exhibited higher platelet reactivity in general, though not statistically significant. No relationship between PCR and the in vitro induced aggregation was found. The degree of retinopathy had no significant influence on platelet aggregation. In general, the data demonstrate an increase in sensitivity of platelets in juvenile-onset diabetics, whereas no influence of stage of microangiopathy could be detected.

The behaviour of various platelet function tests during long-term prostacyclin infusion in patients with peripheral vascular disease.

In 20 patients with peripheral vascular disease treated with prostacyclin (5 ng/kg/min) we observed a significant activation of platelet function as measured by platelet proteins, ADP-induced aggregation platelet sensitivity and platelet count. Only the platelet survival was significantly prolonged by the treatment.

Bicyclo-prostaglandin E2 metabolite in congestive heart failure and relation to vasoconstrictor neurohumoral principles.

Vasodilator prostaglandins may play a role in maintaining circulatory homeostasis in patients with congestive heart failure (CHF). Plasma levels of bicyclo-prostaglandin E2 metabolite (PGEm), a chemically stabilized degradation product of the vasodilator prostaglandin E2, were determined in 45 patients with chronic CHF (New York Heart Association class II, III or IV). Mean circulating levels of bicyclo-PGEm were significantly elevated in patients with functional class III (72 +/- 8 pg/ml) or IV CHF (77 +/- 10 pg/ml) compared with control subjects (49 +/- 3 pg/ml) and patients with functional class II CHF (49 +/- 4 pg/ml). Bicyclo-PGEm concentrations correlated with plasma renin activity (r = 0.68, p less than 0.001) and plasma angiotensin II (r = 0.56, p less than 0.001) and plasma noradrenalin levels (r = 0.34, p less than 0.05). An inverse correlation was found between serum sodium concentrations and levels of bicyclo-PGEm (r = 0.46, p less than 0.01) as well as plasma renin activity (r = 0.66, p less than 0.001). Thus, prostaglandin E2 levels in plasma are increased in patients with severe CHF.

Platelet sensitivity to prostacyclin in smokers and non-smokers.

Platelet activating effect of cigarette smoking appears to be important in the development of atherosclerosis. We previously demonstrated a reduced sensitivity of platelets to exogenous prostacyclin (PGI2) in vitro from patients with proven atherosclerotic disease, indicating a possible role of altered platelet function in the development of atherosclerosis. We now hypothesize that cigarette smoking might be an important cause of altered platelet sensitivity to PGI2 observed in patients with atherosclerosis. To test this hypothesis, the response of platelets to exogenous PGI2 was tested in chronic smokers and non-smokers, prior to and after smoking two cigarettes (active smoking) and prior to and after exposure to a tobacco smoke-contaminated atmosphere (passive smoking). This study indicates that platelets of chronic smokers are less sensitive to exogenous PGI2 than platelets of non-smokers. In addition, active as well as passive smoking decreases platelet sensitivity to PGI2 in non-smokers, whereas chronic smokers exhibit no further decline. We conclude that decreased platelet sensitivity to PGI2 might be an important contributing factor to the altered platelet function observed in patients with atherosclerosis.

Cardial decompensation caused by hypertension and polyglobulia associated with multiple renal oncocytomas.

A 43 year old man was referred to the Internal Department for the examination of cardial decompensation, hypertension, polyglobulia and atrophy blanche of the lower legs. Clinical and supersonic examination revealed two tumors in the left kidney (diameter 8 and 3.5 cm) and some small tumors in the right kidney. Laboratory studies disclosed erythropoietin levels up to 170 mU/ml (standard 14-61 mU/ml) and a red blood cell count of up to 8 X 10(6)/ml. After recompensation, a radical left nephrectomy and the removal of three small tumors of the right kidney four weeks later was initiated. Postoperative erythropoietin levels and red blood cell count sank to the normal range leading to the reduction of antihypertensive therapy. The clinical course indicates a strong etiological connection between hypertension as well as polyglobulia with the multiple bilateral oncocytomas. Polycythemia also led to the atrophy blanche which had resulted from disturbances of microcirculation.

Renin-angiotensin-aldosterone system and vasopressin in cyclosporine-treated renal allograft recipients.

Eleven patients, who had undergone renal transplantation and who had hypertension, aged 19-56 years, were treated with cyclosporine and prednisolone. We measured plasma renin activity, aldosterone and vasopressin (RIAs) at the first, second and third week and again 9 to 12 months after transplantation. Plasma renin activity was in the low-normal range throughout (0.31 +/- 0.05, 0.30 +/- 0.03, 0.32 +/- 0.05 ng/ml/h on short- vs. 0.32 +/- 0.04 ng/ml/h on long-term), aldosterone showed a tendency to decrease (114 +/- 27, 72 +/- 18, 71 +/- 11 pg/ml on short- vs. 54 +/- 23 pg/ml on long-term), whereas vasopressin remained moderately increased during the observation period (10.5 +/- 0.8, 10.4 +/- 1.6, 8.9 +/- 0.6 pg/ml on short- vs. 9.6 +/- 1.0 pg/ml on long-term). We then investigated the reactivity of the renin-system in 5 of the patients by stimulating renin release by captopril. Increases in plasma renin activity were only moderate (0.35 +/- 0.03 vs. 0.66 +/- 0.21 ng/ml/h) and blood pressure dropped only slightly (148 +/- 2.0/98 +/- 1.2 vs. 141 +/- 4.6/95 +/- 4.2 mmHg). Levels of plasma aldosterone were significantly suppressed from a low baseline (46.4 +/- 13.5 vs. 25.3 +/- 6.1 pg/ml, p less than 0.05). The increase in vasopressin was unaffected by captopril (9.6 +/- 1.0 vs. 8.8 +/- 0.4 pg/ml). Our results suggest that in renal transplantation patients with good graft function, the activity of the renin system is unaffected by cyclosporine treatment on short- and on long-term. Vasopressin stimulation does not seem to depend on the renin system and might play a role as a vasoconstrictor in the face of a denervated kidney.

Increase in bicycloprostaglandin E2 metabolite in congestive heart failure in response to captopril.

Vasodilating prostaglandins may be increased in patients with chronic congestive heart failure (CHF) to balance out the effects of vasoconstricting forces. Significant increases in plasma levels of bicycloprostaglandin E2 metabolite (PGEm), a chemically stable degradation product of the vasodilating prostaglandin E2, were found in response to captopril (39.4 +/- 7.8 vs. 46.2 +/- 8.2 pg/ml; p less than 0.01). With chronic captopril treatment bicyclo-PGEm remained elevated for 12 h after the last dose after 1 and 2 months (75.5 +/- 5.5; p less than 0.05 and 72.1 +/- 6.3 pg/ml; p less than 0.05, respectively). Upon readministration of captopril during chronic captopril treatment the significant increase of bicyclo-PGEm in response to captopril was sustained, as were changes in plasma renin activity, angiotensin II, and blood pressure. Plasma catecholamines were unchanged with captopril or decreased slightly, vasopressin remained moderately increased throughout. Taken together, the results suggest that vasodilating prostaglandin E2 production might play a part in captopril's beneficial action in chronic congestive heart failure.

Prostacyclin synthesis in human lymphatics.

The ability of human lymphatics to generate prostacyclin in important amounts (4.5 +/- 2.1 pg/mg/min) is described. The prostacyclin produced, exhibits the same properties as reported for arterial and venous tissue. No age and sex difference could be observed. The role of prostacyclin in physiology of lymphatics, however, is unknown.

[Dose-dependent increase in prostacyclin synthesis from various vascular tissues by dipyridamole]. / Dosisabhängige Steigerung der Prostazyklinsynthese aus verschiedenen Gefässgeweben durch Dipyridamol.

Due to the more detailed knowledge of prostaglandin metabolism in the recent past increasing interest was focused onto dipyridamole acting as platelet active substance. It was the goal of this study to investigate whether dipyridamole is able to exert any effect on vascular PGI2-synthesis. It is demonstrated that dipyridamole has a dose-dependent (0.1-100 microM) increasing effect on PGI2-synthesis or 6-oxo-PGF1 alpha-levels, respectively (the stable metabolite of prostacyclin). At a dose range of more than 10 microM this increase reaches the level of significance. Assuming that PGI2 acts as a local hormone in the vascular system this effect on PGI2-synthesis stimulation might contribute to the knowledge of the in vivo action of the substance.

[Prostacyclin (PGI2) activity in the rectal mucosa of patients with ulcerative colitis (author's transl)]. / Prostacyclin-(PGI2-)Aktivität in der Rektumschleimhaut bei Colitis ulcerosa.

PGI2 synthesis was investigated in rectal mucosa of 8 patients with active ulcerative colitis, 4 in remission and 16 controls. Determinations were carried out using Moncada's bioassay. The results demonstrated enhanced PGI2 synthesis in rectal mucosa in active ulcerative colitis. Further clinical studies should clarify whether or not selective inhibiton of PGI2 synthetase might be a useful therapeutic approach in ulcerative colitis.

[Influence of the venous wall--platelet interaction by dihydroergotamine (author's transl)]. / Beeinflussung der Venenwand-Thrombozyten-interaktion durch Dihydroergotamin.

The incubation of rabbit venous rings (vena cava) is followed by the synthesis and release of prostacyclin (prostaglandin I2, PGI2), as measured by the inhibition of ADP-induced platelet aggregation. The incubation of the venous rings in dihydroergotamine leads to a stimulation of PGI2 synthesis and/or release. This effect of dihydroergotamine, apart from the vasoactive properties of this compound, might prove advantageous as a prophylactic measure in venous thrombosis.

[Monoclonal gammopathy and platelet function (author's transl)]. / Monoklonale Gammopathie und Thrombozytenfunktion.

This study of 20 patients with monoclonal gammopathy (17 patients with multiple myeloma and 3 patients with Waldenström's syndrome) showed a decreased platlet aggregation induced by ADP and collagen, a reduced platlet retention and a prolonged bleeding time in 25% of the cases in comparison with 30 age- and sex-matched healthy controls. Using Wu and Hoak's technique as increased number of reversible platelet aggregates was observed. There was no relationship between the parameters of primary haemostasis and protein analysis. A disturbed mechanism of primary haemostasis is the main factor responsible for the bleeding diathesis in patients with monoclonal gammopathy.

[Influence of cimetidine, pentagastrin and somatostatin on prostacyclin synthesis of gastric mucosa in vitro]. / Einfluss von Cimetidin, Pentagastrin und Somatostatin auf die Prostazyklinsynthese der Magenschleimhaut in vitro.

In the presence of cimetidine, pentagastrin and somatostatin prostacyclin formation does not differ significantly from the value obtained with the buffer control, whereas cimetidine alone is able to inhibit ADP-induced platelet aggregation in vitro to a small degree. It is concluded that the in vivo action of the drugs if not primarily mediated by prostacyclin.

[Left ventricular function in young type I diabetic patients. A Doppler echocardiography study]. / Die Linksventrikelfunktion bei jungen Typ I-Diabetikern. Eine Doppler-echokardiographische Studie.

Systolic and diastolic left ventricular function was assessed by M-mode and pulsed Doppler echocardiography in 10 young type I diabetic patients without late complications and maximal diabetes duration of 5 years and in 10 healthy persons. Fractional shortening, a measure of systolic ventricular function, was significantly lower in diabetics than in controls (33.9 +/- 2.9 vs. 37.9 +/- 4.9; p less than 0.05). Fractional shortening decreased significantly with advancing diabetes duration (R = -0.819; p less than 0.01). Indexes of diastolic ventricular function (isovolumetric relaxation period and transmitral flow velocity pattern) were not significantly different in the two groups, but 3 patients had 1 parameter (3x isovolumetric relaxation period) and another patient had 2 parameters (isovolumetric relaxation period and early diastolic peak velocity E-E') outside the normal range. Follow-up studies should define the clinical significance of these alterations of systolic and diastolic left ventricular function.

[Prostaglandin I2 (PG I2; prostacyclin) synthesis by human gastric mucosa (author's transl)]. / Prostaglandin-I2-(PG-I2-; Prostacyclin-)Synthese in der menschlichen Magenschleimhaut.

The human gastric mucosa generates prostacyclin (22 +/- 6 ng PG I2/g). There is no age or sex difference in PG I2 formation by normal gastric mucosa. The properties of the substance are the same as reported in other tissues.

[Platelet retention and hypothyroidism: an investigation in patients with thyroid carcinoma treated by total thyroidectomy (author's transl)]. / Thrombozytenretention und Hypothyreose. Untersuchung an total thyreoidektomierten Schilddrüsenkarzinompatienten.

Platelet retention was investigated using a standardized technique with a glass pearl column in 18 patients with malignant thyroid disease treated by thyroidectomy before and after high-dose radioiodine treatment (80 or 150 mCi). As compared with the normal controls platelet retention was significantly lower in 13 hypothyroid patients in whom thyroidectomy had been undertaken at least 6 months previously and hormone substitution therapy had been interrupted 3 weeks before the period of investigation. The remaining 5 patients, studied about 18 days following thyroidectomy, were euthyroid and displayed platelet retention values within the lower limits of the normal range except for one patient with markedly reduced values. Thyroid substitution therapy with synthetic preparations induced recovery of platelet retention in both groups examined over a 4 week period, the increase being highly significant in the group of hypothyroid patients. A transient increase in platelet retention was observed 24 hours after a therapeutic dose of radioiodine, and initial values being regained after a further 24-hour period. This phenomenon was found in both, the euthyroid and hypothyroid group, however, it was more pronounced in the latter patients. Our results indicate a dependence of platelet retention on thyroid hormone concentration. The observed transient increase after radioiodine may be due to a radiation effect.

[Sipple syndrome (bilateral phaeochromocytoma medullary C-cell carcinoma of the thyroid gland) with exceptionally prolonged clinical course]. / Sipple-Syndrom (bilaterale Phäochromozytome und medulläres C-Zell-Karzinom der Schilddrüse) mit besonders protrahiertem Verlauf.

The sporadic occurrence of the Sipple syndrome with bilateral phaeochromocytoma and medullary thyroid carcinoma is a well-known pathological entity. The present report refers to a patient with medullary thyroid carcinoma, initially misdiagnosed as Hurthle-cell adenoma after partial resection of the thyroid gland. 5 and 8 years later the patient underwent bilateral adrenalectomy for phaeochromocytoma. 4 years after the second phaeochromocytoma a palpable thyroid nodule developed, thyroidectomy was performed and the tumour diagnosed as a medullary thyroid carcinoma. This diagnosis was confirmed by reexamination of the histological specimens obtained during the first surgical intervention. We were prompted to report the current case history, because of the protracted course of the medullary thyroid carcinoma in this patient and to point out the value of the determination of pentagastrin stimulated calcitonin values in patients with medullary thyroid carcinoma for diagnosis, postoperative follow-up and in family screening studies.

[Platelet sensitivity to prostacyclin (PGI2) in patients with juvenile-onset diabetes mellitus (author's transl)]. / Plättchensensitivität für Prostacyclin (PGI2) bei Patienten mit juvenilem Diabetes mellitus.

Platelet function (ADP-induced platelet aggregation) in 20 patients with juvenile-onset diabetes mellitus was not different from that of age- and sex-matched controls. Platelet sensitivity to exogenous PGI2 was not diminished in diabetic patients. No sex differences were detected. There was no correlation between concomitant blood glucose levels and platelet sensitivity to PGI2.

[Technic of radioactive labeling of autologous human thrombocytes using 111-indium-oxine and 111-indium-oxine-sulfate and their clinical use]. / Technik der radioaktiven Markierung autologer menschlicher Thrombozyten mit 111-Indium-Oxin und 111-Indium-Oxin-Sulfat und deren klinische Anwendung.

Using 111indium oxine and 111indium oxine sulphate as platelet labels, maximal labelling efficiency can be achieved already after 3 minutes at an incubation temperature of 37 degrees C. Mean labelling efficiency values of about 90% are reached at a platelet count of greater than 10(9) platelets/ml, but the labelling efficiency is satisfactory also at a rather low platelet count of about 10(6) platelets/ml (71% on average). Platelet labelling with these tracers allows the calculation of platelet half-life in vivo, and gamma-camera imaging of platelet aggregates in thrombosis and renal transplant rejection as well. In the present study, the platelet half-life is significantly shortened in patients with coronary heart disease (n = 15), peripheral vascular disease (n = 13) and primary hyperlipoproteinaemia (n = 32) in comparison with 106 controls. No age dependence of platelet half-life was found in the different groups of patients whereas in the control group, a significant negative correlation between age and platelet half-life was observed.

[Angiologic, neurologic and orthopedic findings in vibration exposed chain saw operators]. / Angiologische, neurologische und orthopädische Befunde bei vibrationsexponierten Kettensägenarbeitern.

The present study was designed to evaluate and correlate angiological, neurological and orthopaedic findings in lumberjacks, professionally exposed to vibration by chain-saws with a frequency of 40 to 120 Herz. Raynaud's phenomenon was diagnosed in 16 of 33 subjects. The nerve conduction velocity was delayed in 13 of 32 lumberjacks, the sulcus nervus ulnaris syndrome was diagnosed in 41%, the vibration threshold was abnormal in 10/32 cases. Orthopaedic examination and X-ray studies revealed spondylotic (59%) and spondyloarthritic (65%) alterations of the cervical spine; cysts in bones of the distal upper extremities were observed in 75% of cases. Frequency and severity of angiological, neurological, and orthopaedic pathological findings correlated with the total chain-saw operating time. However, there was no correlation between the presence of digital vascular hyperreactivity and the sulcus nervus ulnaris syndrome or changes in nerve conduction velocity.