L-Ala-substituted rat galanin analogs distinguish between hypothalamic and jejunal galanin receptor subtypes

In order to explore which amino acids or which blocks of amino acids in the 29 amino acid neuropeptide galanin are important for recognition of the endogenous ligand by galanin receptor subtypes present in the jejunum and in the hypothalamus, respectively, we have carried out L-Ala substitutions of individual amino acids or of blocks of amino acids in the rat galanin sequence and examined the binding of the obtained analogs to the rat hypothalamic and jejunal galanin receptor subtypes. This study reveals that the galanin sequence YLLGPH^9–14 is essential for recognition of galanin by both the rat hypothalamic and jejunal galanin receptor subtypes. Substitution of the N-terminal amino acids, GWTL^1–4, leads to total loss of affinity of galanin for both hypothalamic and jejunal galanin receptors. The α-helical C-terminal amino acid (25–29) part of galanin has no greater influence on the affinity of galanin to the hypothalamic galanin receptor subtype. L-Ala substitution of the C-terminal amino acids of galanin KHGLT^25–29 shows, however, that this C-terminal motif is essential for the recognition by the jejunal galanin receptor subtype, whereas amino acids in the middle portion of galanin NSAG^5–8 are of importance for binding to the hypothalamic but not to the jejunal receptor. [Ala^5–8] Galanin thus has a more than 100-fold higher affinity to jejunal receptor than to the hypothalamic receptor, while [Ala^25–29] galanin has a more than 100-fold higher affinity for the hypothalamic than for jejunal galanin receptor subtypes. pH dependence of the galanin binding to these receptor subtypes is also different. © Munksgaard 1997.     

Clodronate in the palliative therapy of bone-metastasized prostatic carcinoma]

Activity and side-effects of clodronate (Ostac), an inhibitor of osteoclastic bone resorption, were recorded in an open prospective uncontrolled study on 35 patients with metastatic prostatic cancer. All patients had progressive symptomatic bone metastases despite prior hormone therapy. Clodronate was initially administered i.v. for 8 days with 300 mg/day. This was followed by a daily oral administration of 1600 mg. The analgesic effect was evaluated by using a visual analogue scale and by recording the daily consumption of analgesic drugs. Karnofsky index and routine blood examinations, including PSA, were assessed. Repeated bone scans and radiological evaluations were performed. An improvement in pain was observed in 71% of the patients. The mean duration of improvement was 4 weeks. Average survival time was 12 weeks. There were no side-effects after i.v. administration. Slight gastrointestinal discomfort was observed in 3 patients after oral administration. No effect was observed on the extent or biology of the metastases. Clodronate is an effective drug for palliative treatment of symptomatic bone metastases of prostatic carcinoma. It causes fewer and less pronounced side effects than other palliative drug therapies.     

Hodgkin's disease of the prostate: a detailed case report

Malignant lymphoma of the prostate is an unusual entity, and nonHodgkin's lymphoma constitutes most reported cases. We report a well documented case of Hodgkin's lymphoma, initially involving the gastrointestinal tract and spleen, which recurred in the prostate following initial remission with chemotherapy. Treatment with external beam radiotherapy resulted in a rapid complete response that has been sustained for 18 months.     

Appendizitissonographie durch chirurgen — Erfahrungssache? Eine prospektive studie

A number of studies have shown that ultrasound has an advantage over physical examination in the diagnosis of acute appendicitis. Most of these studies were conducted by experts in the field of ultrasonography. In this study the influence of experience on the results of the sonography of actue appendicitis were evaluated. All 203 patients admitted to our unit between December 1990 and December 1992 were examined physically and sonographically by a team of surgeons consisting of one experienced sonographer and six inexperienced surgical trainees. Laparotomy was performed in 136 patients (46%). Appendicitis was demonstrated histologically in 119 cases (39.4%). Initial clinical findings were positive in 87 (28.8%). Sonography was positive in 119 patients (39.4%). The 163 patients not operated on demonstrated other pathology on ultrasound in 60 cases (19.9%). The rate of negative laparotomies amounted to 7.2% in our study. Sensitivity and specificity for the sonographic diagnosis were 92% and 95%, respectively. They were only 81% and 80% for physical examination. Overall accuracy was 92% for sonography. Sensitivity and specificity for the inexperienced surgeons were 87% and 93%, respectively, while the experienced surgeon reached values of 97% and 98%, respectively. The results of both groups are comparable with values in the literature, suggesting that ultrasound evaluation of appendicitis is not a diagnostic tool limited to a few experienced sonographers.