Gonadotropin Secretion in Eugonadotropic Human Males and Postmenopausal Females Under Long Term Application of a Potent Analog of Gonadotropin-Releasing Hormone

Long-acting analogs are of special interest in long-term treatment with gonadotropin-releasing hormone (GnRH). However, inhibitory effects of agonist analogs on gonadotropin secretion or on reproductive processes have been observed in rats as well as in human males. Since these inhibitory effects seem to be dose-related, we checked the findings for d-Leu 6 -des-Gly 10 -GnRH-ethylamide within the dose range proposed by us for treatment. In six eugonadotropic human males, a significant decrease of luteinizing hormone and follicle-stimulating hormone responsiveness to a standard dose of GnRH and significant decrease of testosterone basal secretion were observed after 2 and 4weeks of subcutaneo…

Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis.

ObjectiveHomozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants (‘Pi*Z’ and ‘Pi*S’), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse.DesignWe analysed multicentric case–control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed.ResultsThe Pi*Z variant presented in 13.8% of p…

Odeion and imperial cult at Scythopolis - GABRIEL MAZOR AND ARFAN NAJJAR, with contributions by EDNA AMOS, RACHEL BAR-NATHAN, ARIEL BERMAN and DÉBORA SANDHAUS, BET SHE’AN I. NYSA-SCYTHOPOLIS. THE CAESAREUM AND THE ODEUM (IΑΑ Reports no. 33; Israel Antiquities Authority 2007). Pp. xxii + 293, many figs. ISBN 978-965-406-201-5.

The influence of penbutolol and placebo on blood sugar levels and insulin consumption in the glucose-controlled insulin infusion system ("artificial endocrine pancreas").

The aim of the study was to investigate the influence of 40 mg of the beta-blocker penbutolol (Betapressin TM; Hoechst Ltd., Frankfurt/Main) in comparison to placebo on the insulin consumption on the blood sugar profile in twelve insulin-dependent diabetes (IDDM) patients. The patients were treated with penbutolol and placebo for a period of three days, and then were examined with the help of the glucose-controlled insulin infusion system. The blood sugar profile and insulin consumption over a 24 hour period was not affected by either penbutolol or placebo, nor could any changes be measured in these parameters when measured after food intake. After a submaximal exercise load on the bicycle …

Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas

The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and brid…

Treatment of cryptorchidism with a potent analog of gonadotropin-releasing hormone.

Pernasal therapy of cryptorchidism with D-Leu6-des-Gly10-gonadotropin-releasing hormone ethylamide (D-Leu6-des-Gly10-GnRH-EA), a potent, long-acting GnRH analog, was attempted. Eleven prepubertal cryptorchid boys received between 25 microgram once daily and 25 to 50 microgram twice daily for 5 to 12 weeks. Complete testicular descent was achieved in 4 of the 11 boys. GnRH tests (1.5 microgram/kg intravenously), conducted in six boys before treatment, after 4 weeks of treatment, and in 2 boys 3 months after treatment, did not reveal changes in gonadotropin secretion indicative of precocious puberty or of decreased hypophyseal sensitivity to GnRH. Antibodies to the GnRH analog or to GnRH coul…

Gonadotropin and Testosterone Secretion in Normal Human Males After Stimulation With Gonadotropin-Releasing Hormone (Gnrh) or Potent Gnrh Analogs Using Different Modes of Application

Gonadotropin-releasing hormone (GnRH) and some potent long-acting GnRH analogs, applied by different routes of administration, were tested in six healthy human males. The effects on gonadotropin secretion were compared with the one after intravenous (i.v.) bolus injection of 25 microgram of GnRH. The net increase of luteinizing hormone (deltaLH) in serum produced by 25 microgram of GnRH i.v. was matched by subcutaneous (s.c.) injection of 100 microgram of GnRH, dissolved in 20% gelatin or without gelatin; 5 microgram of D-Ser (TBU)6-des-Gly10-GnRH-ethylamide i.v.; 5 microgram of D-Leu6-des-Gly10-GnRH-ethylamide i.v.; and 50 microgram of D-Trp6-des Gly10-GnRH-ethylamide given pernasally (p.n…