Decision analysis applied to selection of histamine H2-receptor antagonists for the formulary

The use of decision analysis in selecting a histamine H2-receptor antagonist for the formulary at a hospital in Spain is described. Cimetidine, ranitidine, and famotidine were identified as the possible alternatives. The evaluation criteria established were therapeutic efficacy, adverse effects, drug interactions, years of clinical use, dosage interval, cost, and dosage forms. The relative importance of the criteria was determined by assigning utility values to each. Probability values were assigned to estimate how well each drug met each criterion. By multiplying the utility and probability values for each criterion and summing the scores, a total score was calculated for each drug. The alternative with the highest total score was ranitidine. A sensitivity analysis showed that the results were stable over a plausible range of probability and utility values. Accordingly, ranitidine was selected for inclusion on the formulary. Decision analysis provided an effective method for selecting which histamine H2-receptor antagonist to include on the hospital's formulary.     

Effect of chronic intake of ethanol on the binding of vasoactive intestinal peptide to rat spleen lymphoid cells

1. The effect of chronic intake of ethanol on the binding of vasoactive intestinal peptide (VIP) to rat spleen lymphoid cells was investigated. 2. The intake chronic of ethanol elicited an increase in specific VIP binding. 3. This increase was due to an increase in binding capacity of both the high and the low affinity binding sites. 4. There was a decrease in the affinities of both classes of VIP binding sites.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisci plinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6–20 MeV electron beams. The median follow-up time for the entire group is 25 months (2–65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.     

Usefulness of antiendomysial antibodies as a serological marker in coeliac children

The new diagnostic criteria of coeliac disease (CD) give more importance to serological markers. Immunoglobulin A antiendomysial antibodies (IgA-EmA) were determined in 138 sera from 79 coeliac children and the antibody levels compared to IgG and IgA antigliadin antibodies (IgG-AGA, IgA-AGA) in the sera. The assessment was also carried out in 29 children with other gastrointestinal diseases, 29 with non-gastrointestinal diseases and 35 healthy children. The IgA-EmA had a 91.4% specificity and a 88.4% sensitivity for active CD. The corresponding figures were 89.8% and 64.4% for IgA-AGA and 73.7% and 86.2% for IgG-AGA, respectively. The results of IgA-EmA determinations were concordant with the intestinal biopsy findings in 90% of cases, versus 80% for IgA-AGA and 83% for IgG-AGA. In most of the discordant cases the biopsy showed only minor changes, making the classification difficult. All patients with positive IgA₂-EmA also had positive IgA₁ EmA antibodies. IgA-EmA are an excellent serological marker of CD activity in children and they are useful to decrease the number of intestinal biopsies which are needed to confirm the diagnosis in coeliac patients.     

Intraoperative radiotherapy of upper abdominal tumours

Thirty patients with malignant tumours in the upper abdomen underwent surgery and intraoperalive radiation (IORT), using electron beam, to: the surgical bed, residual or unresected tumour. The technical aspects and results of this treatment are described. Renal, adrenal, bile duct and gastrointestinal tumours were treated. along with several other lesions. The surgical procedure consisted in 10 cases simply of exposure of the tumour for IORT and in 20 the tumour was resected. The TORT dose ranged from 10 to: 20 Gv. In 13 patients, external beam radiation was also given to: residual tumour or to: areas of high risk for recurrence. Chemotherapy was given to: 10 patients. Tolerance to: the combined treatment was acceptable; with few complications related to: IORT.The median follow-up and survival time 23 months (range 4-more than 70 months). Local tumour control rate (or tumour stabilisation) is 90%. Distant metastases developed in 19 patients (63%). The actuarial survival rate for the group projected at 70 months (maximum follow-up) is 37%. IORT in useful in the management of tumours arising in the upper abdominal organs, for palliation surgery or when resectability of the tumour is in doubt. Indications for IORT include patients with uncommon tumours of the upper abdomen who are not be candidates for standardised cancer treatment.Presented at the European Congress of Radiology, Vienna, September 15–20,1991     

The glycine receptor: pharmacological studies and mathematical modeling of the allosteric interaction between the glycine- and strychnine-binding sites

The displacement by glycine of 3H-strychnine binding to rat spinal cord membranes cannot be explained by a simple competitive interaction. Indeed, protein-modifying reagents can completely abolish the inhibition of 3H-strychnine binding by glycine and other agonists, whereas the interaction of strychnine itself and other related compounds with the binding site is unimpaired. Moreover, glycine cannot inhibit completely saturable 3H-strychnine binding, the extent of its maximum inhibitory effect depending on the ionic composition of the medium. Hill coefficients less than 1 (whose magnitude also depends on the assay medium) were obtained from glycine displacement curves. These properties are consistent with a mathematical model of two different, but mutually interacting, binding sites for strychnine and glycine on the glycine receptor. The effect of ions and protein-modifying reagents might be explained in this model as modifications of the mechanisms that mediate the allosteric interaction, and/or the affinity of glycine for the receptor. The agonists beta-alanine and taurine and the new antagonists, THAZ, iso-THAZ, and 4,5-TAZA, also seem to interact with a site different from the strychnine-binding site, probably the glycine-binding site.     

3H]-flunitrazepam binding after morphine treatment and under abstinence syndrome.

Chronic morphine treatment produced increases in [3H]-flunitrazepam binding in some hippocampal areas of the rat brain. The differences in binding were statistically significant in some cases. Both morphine-dependent and morphine-deprived (abstinence syndrome) animals showed an identical response in binding, which confirms a real, although small, increase in benzodiazepine binding sites in the hippocampus after morphine treatment, that is not affected by a naloxone-induced abstinence syndrome under the conditions studied. These findings support the hypothesis of a morphine-induced up-regulation of benzodiazepine binding sites in the hippocampus. A possible different response in benzodiazepine binding sites 1 and 2 could explain the different findings reported in the literature. Our data suggest that the detected increase in benzodiazepine binding would be mainly due to type 2 binding sites, since the hippocampus has a higher density of this type of benzodiazepine binding sites.