Benzodiazepines: abuse and new use.

Both abuse and new uses for benzodiazepines are reviewed. The pharmacology of benzodiazepines is summarized and statistics regarding their general use are given. The question of benzodiazepine abuse is reviewed in some detail and the question of rebound, recurrence of symptoms and physiological withdrawal is differentiated. Benzodiazepines are regarded as a very safe class of drugs and the abuse potential is felt to be negligible provided that they are prescribed for appropriate conditions and monitored carefully. The dangers of alternatives to benzodiazepines such as alcohol or barbiturates is emphasized. New uses for benzodiazepines are reviewed including the use of benzodiazepines in panic disorder, as well as an adjunct in the therapy of mania and some psychotic states. Rational prescribing of benzodiazepines is encouraged and the attitude that these are dangerous and addictive drugs is discouraged and put into perspective.     

Complications of endoscopic examinations of the upper segments of the gastrointestinal tract

A ten-year experience with 106610 diagnostic esophagogastroduodenoscopies provided evidence of a 0.03% rate of relevant complications and 2.38% mortality. Out of 39 patients with endoscopy-related complications 5 were operated on: 4 had esophageal perforations, 1 had hemorrhage following biopsy of the ulcer. Out of 7384 therapeutic and operative endoscopies none were associated with lethal outcome. Surgery was avoided either. Complications developed in 45 patients (0.036%): in 44 patients hemorrhages occurred after electroexcision of the polyps.     

Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus

In this report, we examine the functional significance of the molecular microheterogeneity of alpha-fetoprotein (AFP). In doing so, we have taken the direct approach of purifying the naturally occurring isomeric forms of fetal-derived AFP using a preparative anion exchange column linked to an automated fast protein liquid chromatography (FPLC) system followed by parallel testing of each isolated molecular variant for in vitro immunoregulatory activity. The data obtained demonstrate the presence of seven distinct variants of AFP as defined by their retention volumes on FPLC elution profiles, by their pIs on analytical IEF gels, and by Western blot analysis. Molecular mass determination by SDS-PAGE showed each isomer to be equivalent in size to 69,000-dalton native unfractionated AFP molecules. All the immunosuppressive activity of AFP was localized to a single variant representing only 6% of the total composition of native AFP. The immunoregulating isomer termed AFP-1 was the least acidic of the seven isolated variants with a pI of 5.1 and displayed a sialic acid content of 1 mol/mol of protein. The inhibitory activity of AFP-1 could be readily measured on T cell-dependent antibody synthesis, Con A-induced stimulation of Lyt-1+23- thymocyte DNA synthesis, and lymphokine-activated NK cell activity. All other isomers were without effect in these test systems. The immunosuppressive AFP-1 isomer also displayed the strongest growth-promoting influence on cultured bone marrow lymphocytes. There was no correlation between functional activity and degree of expression of sialic acid residues on the AFP molecules. These findings demonstrate that the immunoregulating function of AFP is confined to a distinct and relatively small subpopulation of native AFP molecules and should therefore contribute to the resolution of outstanding questions regarding the structure/function relationship of this onco-fetal glycoprotein.     

Calcium absorption following small bowel resection in man. Evidence for an adaptive response

Seventeen patients who had undergone extensive small bowel resection were studied for calcium absorption (FACa) and plasma vitamin D metabolites. FACa was measured by a double radio-tracer technique and expressed as percentage of total oral dose. FACa was decreased compared with controls (34%, range: 3-46 v 65%, range: 57-73, P less than 0.01). A positive correlation (r = 0.49, P = 0.05) was found between FACa and the remaining length of small bowel (SBL). As wide variations in both SBL and duration after surgery were observed among the seventeen investigated patients, we were led to individualize less heterogeneous subgroups of patients. Better correlations were found when the patients were divided into two subgroups according to whether the time interval between the resection and the investigation was shorter (r = 0.75, n = 11, P less than 0.02) or longer (r = 0.89, n = 6, P = 0.05) than 2 years. In thirteen patients who had a SBL shorter than 100 cm, a positive correlation was observed between FACa and the time interval after surgery (months): r = 0.65, P less than 0.05. Plasma 1,25 (OH)2D was markedly reduced in the whole group (31 pmol l-1, range: 8-108) compared with controls (103 pmol-1, range: 59-134, P less than 0.01). The present study shows that in extensively small bowel resected patients, calcium absorption is reduced, the alteration being dependent both on the length of the remnant small bowel and on the time after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

The late results after axillo-femoral bypass grafts in patients with leg ischaemia

The late results--up to six years--after axillo-femoral bypass reconstruction are reported for 85 patients with leg ischaemia who were regarded as poor-risk patients for aortic bypass surgery, or who had aortic graft infection. Velour-Dacron grafts and expanded polytetrafluoroethylene (PTFE, Gore-Tex)--grafts have been used. The cumulative patency rate (life table) six years after graft implantation was 64% (PTFE-grafts) and 58% (Velour-Dacron grafts). The corresponding cumulative limb salvage rate six years after graft implantation was 88% when PTFE grafts were used and 77% when Velour-Dacron grafts were used. Our results demonstrate that axillo-femoral reconstruction is a useful procedure with a good patency rate 6 years after implantation. This procedure should be considered when dealing with poor risk patients with severe leg ischaemia.     

Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur

A retrospective multi-institutional study of 227 patients with osteosarcoma of the distal end of the femur was done to compare rates of local recurrence, metastasis, and survival. Three cohorts of patients who had had either a limb-sparing procedure, an above-the-knee amputation, or disarticulation of the hip were compared. The results revealed prevalences of eight of seventy-three, nine of 115, and zero of thirty-nine as to local recurrence; forty-three of seventy-three, sixty-five of 115, and twenty-one of thirty-nine as to metastasis; and thirty-three of seventy-three, forty-eight of 115, and eighteen of thirty-nine as to death. Of the seventeen patients who had a local recurrence, sixteen died. In the limb-salvage group, eighteen patients required amputation, because of local recurrence in eight and other local complications in ten. The Kaplan-Meier estimates of the percentage of patients who survived and the percentage of patients without recurrent disease showed no difference among the three surgical groups (Mantel-Cox test statistic: p = 0.8) after a median length of follow-up of five and one-half years. Various covariant adjusted estimates yielded similar results. For the entire group of patients, the rate of continuously disease-free survival was 42 per cent, and the over-all rate of survival was 55 per cent at five years. It appears that, compared with above-the-knee amputation or disarticulation of the hip, the use of a limb-salvage procedure for osteosarcoma of the distal end of the femur did not shorten the disease-free interval or compromise long-term survival.