Association of lipoprotein(a), prostaglandin I(2)--synthesis stimulating plasma factor, biological half-life of prostaglandin I(2)and high-density lipoproteins in HIV-1 infection of different stages.

Patients with human immunodeficiency virus show increased atheroembolism and premature arterial events (stroke, myocardial infarction), but no increased venous thromboembolism. This paper describes an association of elevated lipoprotein(a), a decreased prostaglandin I(2)(PGI(2)) synthesis stimulating plasma factor, diminished PGI(2)-stability in plasma and decreased high-density lipoprotein-cholesterol and apolipoprotein A. It is unclear to what extent these biochemical findings represent an acute phase reaction only or a disturbance in the prostaglandin system. Definitely, they are resulting in severe hemostatic imbalance decreasing local PGI(2)-availability with a dramatic reduction in the cytoprotective capacity favouring the onset of premature arterial events seen in some of the patients.

[Hyperthyroidism caused by a TSH producing pituitary adenoma]. / Hyperthyreose durch ein TSH-produzierendes Hypophysenadenom.

Elevated levels of free triiodothyronine (fT3) of 8.8 ng/dl (normal range 2.0 to 4.2) and free thyroxin (fT4) of 3.5 pg/ml (0.8 to 1.7) were found in the course of an examination of a 53-year old patient due to a planned hysterectomy. As thyrotropin (TSH) also was elevated with 5.8 mU/l (0.4 to 4.5), these findings corresponded to an inappropriate secretion of TSH (IST). Additional examinations revealed a blunted rise of TSH secretion after i.v. injection of 200 micrograms thyrotropin releasing hormone (TRH) as well as lacking suppression of TSH secretion after oral doses of 75 micrograms T3 during one week. alpha-TSH levels with 3.7 micrograms/l were elevated in comparison to a matched normal sample just as the molar ratio alpha-TSH/TSH with 6.95 and sex hormone-binding globulin (SHBG) with 175 nmol/l and showed an absence of inhibition in the T3 suppression test. These results were suggestive of neoplastic inappropriate secretion of TSH (nIST) due to a TSH-secreting pituitary adenoma. In concordance, the magnetic resonance imaging (MRI) showed a 1 cm tumor in the sella. The adenoma could also be visualized by 111In-octreotide and 123I-epidepride scintigraphies of the pituitary gland. After transsphenoidal resection, histological examination of the tumor resulted in the finding of a TSH-secreting adenoma. Postoperative TSH levels were not detectable, indicating the complete removal of the adenoma. Levels of fT3 and fT4 were slightly below normal with 1.9 pg/ml and 0.7 ng/dl, respectively. A control scintigraphy with 111In-octreotide following an equivocal MRI showed no uptake in the pituitary.

Severe short-term hypothyroidism is not associated with an increased incidence of myocardial ischemia as assessed by thallium-201 stress/rest myocardial scintigraphy.

Reversible silent myocardial ischemia associated with treatment of long-standing hypothyroidism has recently been reported using thallium-201 (201Tl) myocardial single photon emission tomography (SPET). The aim of the present study was to evaluate whether patients with short-term hypothyroidism (serum thyrotropin [TSH] levels above 30 mU/L) have an increased risk of silent myocardial ischemia. We studied 20 patients with differentiated thyroid carcinoma that had undergone thyroidectomy and ablative (131)I therapy. None of the patients had a known history of atherosclerotic cardiovascular disease. In the course of a planned follow-up examination, suppressive levothyroxine (LT4) therapy was discontinued 7 weeks prior to scintigraphy and replaced by triiodothyronine (T3) therapy for 4 weeks. No thyroid hormone medication was given during the 3 weeks preceding the diagnostic procedures. All patients were hypothyroid (TSH 87.2 +/- 30.8 mU/L, mean +/- SD) at the time of the examination. 20lTl-SPET was performed immediately after bicycle exercise stress test and again after a delay of 4 hours. In case of abnormal results, (n = 3) the examination was repeated after patients were euthyroid. Two patients showed effects of soft-tissue attenuation (breast attenuation in a female and diaphragmatic attenuation in a male subject). Myocardial ischemia was revealed in 1 patient but was seen in both hypothyroid and euthyroid examinations. The results of the present study show that short-term severe hypothyroidism as encountered in athyreotic patients after cessation of thyroxine medication for several weeks, is not associated with an impairment of myocardial perfusion.

Endothelial dysfunction, atherosclerosis and diabetes.

The prevalence of early and accelerated development of atherosclerosis associated with high morbidity and mortality is markedly increased among individuals with diabetes and hypertension. Although the link between diabetes and vascular disease is not fully understood, loss of the modulatory role of the endothelium could be implicated in the pathogenesis of diabetic vascular complications. Diabetes-associated pathophysiologic conditions in the endothelium are modifications of lipoproteins, formation of advanced glycation end-products and circulating lipoprotein immune complexes, alteration of the nitric oxide pathway, and elevated levels of homocysteine. The main goals in restoration of endothelial function are optimal glycemic control, lipid lowering, cessation of smoking, normalization of elevated blood pressure, improvement of the NO-status, antioxidants for scavenging free oxygen radicals, normalization of homocysteine levels, antagonizing the hyperinsulinaemia, and regulation of rheology, respectively haemostasis to physiological levels. There is abundant evidence that some pharmacological agents exert direct beneficial effects on endothelium, suggesting that at least part of their therapeutic action is associated with improvement in endothelial dysfunction. A number of new findings about endothelial dysfunction may have potential clinical relevance.

Evaluation of Cyfra 21-1 as a marker for lung cancer.

The sensitivity and specificity of Cyfra 21-1 as marker for lung cancer was evaluated in comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). Patients with histologically verified lung cancer and different groups without lung cancer were investigated. Sensitivity of Cyfra 21-1 (cut-off level 2.9 micrograms/l) was 40% for non-small cell lung cancer (NSCLC), 60% for rare histological types and 21% for small cell lung cancer (SCLC). In NSCLC sensitivity of Cyfra 21-1 was 35% for squamous cell carcinoma and 41% for adenomous carcinoma. The highest sensitivity for CEA was 45% in NSCLC, with 57% in the subtype of adenomous cell carcinoma; for SCC 30% was achieved in squamous cell carcinoma and for NSE 66% sensitivity was reached in SCLC. In our patients Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC.

Treatment of type I diabetic with subcutaneous insulin resistance by a totally implantable insulin infusion device ("Infusaid").

A 22-yr-old diabetic female is described who developed insulin resistance due to subcutaneous (and intramuscular) "malabsorption" of insulin resulting in recurrent ketoacidosis and sepsis. Intravenous insulin sensitivity was maintained. Diverse attempts to prevent metabolic decompensation by "external" methods failed. The insulin resistance was treated successfully by a totally implantable insulin infusion device ("INFUSAID") with no episodes of ketoacidosis in the 6 months following implantation. With this constant rate insulin infusion pump, and no supplementation of insulin dose by other means, the plasma glucose control is excellent and serum lipid and glycosylated haemoglobin (HbA1) levels have returned to normal.

Guar and its effects on metabolic control in type II diabetic subjects.

The effect of guar mini-tablets (5 g t.i.d.) on carbohydrate and lipid metabolism of outpatients with overt diabetes mellitus with glycosuria (is greater than 5 g/24 h) was determined in an open-controlled, randomized, multicenter, crossover study. A 4-wk pretreatment period was followed by a 6-wk treatment period. The treatment period consisted of a 2-wk guar period (treatment period II), which was followed by the wash-out period. The other half of the patients received treatment in the reverse order. Out of 93 patient records, 79 (41 sulfonylurea [SU] and 38 insulin-treated) were suitable for statistical analysis. No relevant weight-reducing effect of guar could be found in both 2-wk treatment periods. At the end of treatment period II, the lowering of the 1-h postprandial values of blood glucose (SU 12%, insulin 10%), cholesterol (SU and insulin 25%) was significant after 2-wk of guar treatment compared with the wash-out period. No clinically relevant changes in the safety laboratory parameters were observed during guar treatment. Side effects were observed in 40 of the 93 patients included in the trial. Treatment had to be discontinued in 11% of the patients due to gastrointestinal side effects. On the basis of our results,guar treatment in combination with sulfonylurea and insulin can be recommended for the improvement of carbohydrate and lipid metabolism.

[Interaction of sulfinpyrazone (Anturan) and glibenclamide (Euglucon) in type II diabetic patients]. / Interaktionsstudie mit Sulfinpyrazon (Anturan) und Glibenclamid (Euglucon) bei Typ-II-Diabetikern.

In a randomised double blind study on 19 with glibenclamide well controlled diabetics of type II the possible interaction between sulfinpyrazone (Anturan) and glibenclamide was studied with the help of the artificial endocrine pancreas. The trial substance in a dose of 800 mg/die or placebo were used over a period of 70 days. During the trial period and at the end of it there were no significant differences in the sulfinpyrazone group as compared to the placebo group concerning the metabolic control of the diabetic condition. It is therefore justified to assume that there exists no interaction between sulfinpyrazone and glibenclamide in this regard. The dosage of sulfinpyrazone used in this trial was well tolerated by all patients and no side effects were observed.

Lipid-lowering effect of the new drugs eniclobrate and beclobrate in patients with hyperlipidemia type II a and type II b.

First clinical results are presented for two newly developed drugs. Both are diphenylmethane derivatives named ethyl-(+/-)-2-([alpha-(p-chlorophenyl)-p-tolyl]-oxy)-2-methylbutyrate (beclobrate, B) and (+/-)-2-(4-[(4-chlorophenyl)methyl]phenoxy)-2-methyl-butanacid-3-pyridinylmethylester (eniclobrate, E). These drugs were given in a doubleblind crossover trial with placebo periods before, in between and afterwards to 6 patients with type IIb and 13 patients with type IIa hyperlipidemia. Beclobrate was given in a dosage of 100 mg twice daily and eniclobrate in a dosage of 130 mg twice daily. Besides effectively reducing LDL-cholesterol in type IIa there was a remarkable increase in HDL-cholesterol in both types of hyperlipidemia especially for beclobrate.

[Regression of florid proliferative diabetic retinopathy through achievement of normoglycaemic over five months by means of a portable insulin-dosage apparatus (author's transl)]. / Rüchbildung einer floriden proliferativen diabetischen Retinopathie durch 5 Monate lang dauernde Normoglykämie mittels eines tragbaren Insulindosiergeräts.

A portable insulin-infusion device (Siemens-Erlangen) was used by 24-year-old juvenile onset-type diabetic woman for a period of 5 months in order to achieve normoglycaemic conditions. The patient suffered from rapidly deteriorating florid proliferative retinopathy and was practically blind. Kidney function was serioudly impaired and severe neuropathy also existed. Insulin was infused through a polyethylene catheter inserted through the subclavian vein into a central vein. A continuous basal rate which was varied from day to night was infused with additional supplementary rectangular profiles of insulin at meals. Blood glucose was self-monitored with strip test apparatus in order to adjust insulin dosage to diet. HbA1 decreased from 16% during the pre-therapy phase to 8% (= normal range) at the end of the last phase. MBG decreased from 238 during the pre-therapy phase (6 24 hr profiles at 5 to 7 time points) to 97 during the latter phase (daily profiles from day 103 to day 150). After 3 weeks of this treatment the retinal bleeding had disappeared. During further treatment regression of the massive vascular proliferation was observed with fluorescein angiography, and perfusion of the retina improved. Vision also improved, so that the patient has now been able to resume her work as a bank employee. Albuminuria decreased and the neuropathic symptoms also disappeared. The originally planned hypophysectomy was, therefore, considered to be unnecessary.