Recently somatostatin analogues were successfully used to control insulin-induced hypoglycemia in patients with insulinoma. We observed a transient decrease in glucose levels and symptomatic hypoglycemia after administration of the long-acting somatostatin analogue octreotide (Sandostatin\s=r\) in two insulinoma patients. We studied the acute effects of octreotide (administered before breakfast) on blood glucose and glucoregulatory hormones in these patients. In one patient, we studied the effects of glucagon replacement and changing the time of breakfast (relative to octreotide administration) on octreotide-associated changes in blood glucose and glucoregulatory hormones. Compared with control levels, octreotide therapy reduced insulin levels. During hypoglycemia glucagon and growth hormone levels were suppressed, but cortisol levels appropriately increased. The increase in catecholamine levels was normal in one patient, but markedly attenuated in the other. A transient decrease in serum glucose after octreotide was absent after glucagon replacement, but present when breakfast was taken before administration of octreotide. We conclude that in patients with insulinoma, octreotide therapy may be associated with clinically important hypoglycemia, during which counterregulatory hormone secretion may be attenuated.Patients with insulin-secreting islet cell tumours are at risk for severe hypoglycemia. Surgical remo¬ val of the tumour is the treatment of choice. Medi¬ cal therapy is often required in the period preced¬ ing surgery and in patients with metastatic disease. Recently, long-acting somatostatin analogues were successfully used to control insulin-induced hypo¬ glycemia in patients with insulinoma (1-5).Important advantages of long-acting somatos¬ tatin analogues compared with native somatos¬ tatin are their prolonged half life, the possibility of subcutaneous administration, and the lack of a re¬ bound increase in insulin levels after discontinu¬ ing treatment. Furthermore, no clinically import¬ ant adverse effects during short-term therapy have been reported in insulinoma patients (1-5). We re¬ cently observed a transient aggravation of hypo¬ glycemia associated with treatment with the longacting somatostatin analogue octreotide (SMS 201-995, Sandostatin®) in a patient with malignant in¬ sulinoma (6). We here report the acute effects of oc¬ treotide on blood glucose and glucoregulatory hormones in this patient and in a second one in whom we observed a similar worsening of hypo¬ glycemia after administration of octreotide. Patients and MethodsPatient A, a 77-year-old woman, was admitted with a hy¬ poglycémie coma (blood sugar 2.0 mmol/1) at 05.00 h. After iv administration of glucose she regained con¬ sciousness. There was no history of liver disease, alcohol abuse, use of hypoglycémie drugs or prolonged (> 10 h) fasting. Results of diagnostic fasting, abdominal ultra¬ sound and computed tomography were compatible with a diagnosis of fasting hypoglycemia due to a pancreatic insulinoma.

Bringing the antimicrobial peptides, AMPs, in pharmaceutical business was a long process with many technical hurdles after their discovery more than 30 years ago. Structure, classification and mode of action of the AMPs as well as the selection of AMPs for clinical use are discussed. The preclinical and clinical trial results in phase 1 and phase 2 studies are discussed for 9 AMPS. These results are encouraging for the future of the AMPs as alternative antibiotics.

Renal digoxin clearance was compared in patients suffering from atrial fibrillation with well preserved cardiac function (n = 9; salt intake +/- 170 mmol daily) and patients with chronic congestive heart failure (n = 10; salt intake 50 mmol daily and maintenance treatment with diuretics). There was no difference between the groups concerning digoxin dosage, creatinine clearance, diuresis or sodium excretion in the urine. Digoxin clearance in chronic heart failure proved to be significantly lower than in atrial fibrillation (48 +/- 21 vs 71 +/- 36 ml X min-1, p less than 0.05), and Cdig/Ccreat was similarly reduced at 0.73 +/- 0.15 compared to 1.09 +/- 0.27 (p less than 0.005). Steady state serum digoxin concentration was significantly higher in patients with congestive heart failure (1.44 +/- 0.47 vs 0.87 +/- 0.33 micrograms X 1(-1), p less than 0.01). Chronic congestive heart failure is a state with reduced digoxin clearance by the kidney, which could lead to digoxin intoxication not explicable by overdose, reduced renal function or the effect of interacting drugs.

In this mini-review the role of parathyroid hormone-related peptide (PTHrP) in physiology and pathophysiology is discussed. Evolving from an unknown humoral factor in the HHM (Hypercalcemia of malignancy) syndrome its role as a "masterregulator" in the PTH family following identification is reviewed. PTHrP has more paracrine and autocrine functions in virtually all tissues than classical endocrine functions and is essential in embryonic, fetal and post-natal life. The physiological functions are near endless. The development of PTH/PTHrP receptor antagonist and agonists has been difficult and disappointing. Its role as a possible cytokine itself and as a regulatory thermogenesis factor in brown adipose tissue in cancer cachexia is discussed. PTHrP assays must be improved for PTHrP to be a reliable biomarker in oncology and to resolve the function of local proteolytic PTHrP fragments which are largely a mystery until now.

Selective Androgen Receptor Modulators (SARMs) were discovered in the late 1990's.They may have an application in treatments of various diseases, including muscle wasting, cancer cachexia, breast cancer, osteoporosis, andropause and sarcopenia. In this minireview the development, pharmacodynamics, and the phase 1 and 2 trial results of the SARMs are discussed with a special emphasis on the illicit use of the SARMs.

In this mini-review herd immunity is discussed by reviewing some recent vaccination campaigns for HPV, MEN-C, MEN-W and Ebola. It is concluded that vaccination coverage is rapidly declining due to societal factors, financial and logistical hurdles. Herd immunity depends now on unpredictable herd effects, Secondary declining transmission dynamics and carriage figures favour strong herd effects. Different target populations in the MEN-W vaccination programs of the UK and the Netherlands don't improve public confidence in an anti-vaxxers climate. Herd immunity is not a realistic target anymore and is dependent on herd effects varying with vaccination coverage percentages and this should be explained to the public in a clear way.

Transdermally delivered nitroglycerin (TTS-NTG) through a rate-controlling membrane yields stable blood levels for 24 h. We studied the effect of TTS-NTG (25 mg per 10 cm2) on exercise induced angina in 10 patients with stable angina pectoris, all in NYHA class III, who were not under treatment with other cardiac drugs. In a pre-study exercise test, all patients had angina pectoris and more than one mm ST depression. The study was placebo controlled and double blind with a randomized cross-over. Exercise tests were carried out on a treadmill according to the Bruce-protocol, 12 to 16 h after administration of TTS-NTG or of an identical placebo. After a 48 h wash-out period, the procedure was repeated after application of a plaster with the alternative content. A significant improvement was seen on TTS nitroglycerin compared with placebo in the total duration of exercise (7.2 +/- 3.6 min (mean +/- SD) vs 6.2 +/- 3.8 min; P less than 0.002). In 7 patients, the time to onset of angina was extended by TTS nitroglycerin. Maximal ST depression (lead V4 and V6) was significantly lower on TTS nitroglycerin (1.85 +/- 1 mm) compared with placebo (2.2 +/- 1 mm; P less than 0.05). It is concluded that 12 to 16 h after administration, transdermally delivered nitroglycerin improves exercise capacity and reduces maximal ST depression in patients with stable angina.

Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (\g=D\nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 \m=+-\4.68 nmol/100 ml glomerular filtrate vs 29.52 \m=+-\25.62 nmol/100 ml glomerular filtrate; P < 0.005). In the group of patients with primary hyperparathyroidism \g=D\ nephrogenous cAMP was 13.41 \m=+-\7.54 nmol/100 ml glomerular filtrate (P < 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 \m=+-\10.74 nmol/100 ml glomerular filtrate (P < 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 \m=+-\0.10 vs 0.22 \ m=+-\0.09 mmol/l and 0.09 \ m=+-\ vs 0.22 \ m=+-\ 0.09 mmol/l; P <0.025 and P <0.005, respectively). It is concluded that in hypercalcaemic patients with a solid tumour a humoral factor is present which inhibits the interaction of exogenous PTH and its renal receptors. In a subset of normocalcaemic patients with a squamous cell cancer the same circulating factor might be present.