Pharmacokinetics and antipsychotic effect of remoxipride in chronic schizophrenic patients

Single dose pharmacokinetics and the antipsychotic effect of 4 weeks treatment with three fixed dose levels of remoxipride (a selective D(2) receptor antagonist) were studied in chronic, stable schizophrenic inpatients. After a placebo washout of 1 month, 15 patients entered the study. Of these, 11 patients received a single 50 mg oral dose of remoxipride for pharmacokinetic evaluations. All 15 patients were randomly assigned to treatment with oral remoxipride either 25 mg t.i.d., 50 mg t.i.d. or 100 mg t.i.d. for 4 weeks. Blood samples for remoxipride and prolactin assays were taken at 0, 0.33, 0.5, 0.66, 1.0, 1.5, 2, 3, 4, 8, 12, 24, 28, 32 and 48 h after drug intake. The pharmacokinetic characteristics were similar to those previously found in normal healthy volunteers: the mean peak plasma concentration of remoxipride after 50 mg was 3.3 μmol/l, the mean time to reach this was 2.1 h; the mean area under the plasma concentration/time curve was 27.8 μmol/1.h.1( -1) and the mean elimination half-life of remoxipride was 5.5 h. A significant increase in prolactin levels was detected 2 h after administration of remoxipride but they had reverted to normal 8 h after drug intake in all but one patient. Antipsychotic effects were estimated using the brief psychiatric rating scale (BPRS) and the Krawiecka rating scale (KRS) at admission, baseline (end of the 4 week placebo washout period) and after 7, 14 and 28 days treatment. Following an increase in mean psychosis ratings for both positive and negative symptoms during the placebo washout period, these decreased during active treatment and at the end of the study were similar to the scores on admission. Thus the possible efficacy of remoxipride in chronic patients with negative symptoms should be further explored in placebo controlled studies. Remoxipride was well tolerated. Sleep disorders occurred in three patients, extrapyramidal symptoms were not aggravated and no clinically significant effects were observed on the cardiovascular system, in clinical chemistry or haematology.     

Epidemiological characteristics of uveitis in Switzerland

Since January 1990, data from uveitis patients have been systematically stored in a computer data bank. During the period from January 1990 to March 1993, 435 new patients (185 female and 250 male, mean age 43 years; range 6–92) were seen at the Uveitis Clinic of the Hopital Jules Gonin. These 435 patients (630 eyes) were subdivided into anterior uveitis (268 patients — 62%), intermediate uveitis (47 patients — 11%), posterior uveitis (89 patients — 20%) and panuveitis (31 patients — 7%). The incidence of uveitis for the referral area considered was calculated to be 17 per 100,000 inhabitants per year. A specifie diagnosis was found in 312 cases (72%). The most frequently diagnosed entities were HLA-B27-associated acute anterior uveitis (67 cases — 15.4%), uveitis associated with acute herpes zoster ophthalmicus (40 cases — 9.2%), toxoplasmosis (39 cases — 9%), typical pars planitis (29 cases — 6.7%), sarcoidosis (29 cases — 6.7%), Fuchs' heterochromic cyclitis (27 cases — 6.2%), herpetic anterior uveitis (21 cases — 4.8%) and acute retinal necrosis (11 cases — 2.5%). Incidence and distribution of most disease entities correspond to those of other European series.     

Characterization of the epitope recognized by a mAb that reacts differentially with murine suppressor T cells

Although reliable antibodies are available that distinguishhuman suppressor T (T_s) cells from CTL and other T cells, feware available for murine T_s cells. We have developed a mAb (984D4.6.5)that, in the presence of complement, depletes alloantigen-specificT_s cells but not CTL. This antibody recognizes activated TT_scells but not their precursors. In these studies, flow cytometricanalysis demonstrates that 984D4.6.5 reacts with several T_scell hybridomas, cloned T_h cell lines and WEHI-3 (a myelomonocytictumor cell line). Reactivity was not detected with BW5147, T_hcell hybridomas, cloned T_h cells, CTL lines and hybridomas,B cell lines, thymocytes, splenocytes, bone marrow cells nora variety of tumor cells. Among 984D4.6.5 positive lines, expressionis heterogeneous and the number of cells expressing high levelsof the epitope is increased when the hybridomas are maintainedat a relatively high cell density. Neuriminidase and pronasedeplete the epitope recognized by mAb 984D4.6.5. Protein synthesisand glycosylation inhibitors also reduce expression of thisepitope. These observations suggest that the epitope recognizedby 984D4.6.5 is a carbohydrate linked to a polypeptide. Thisantibody was tested by ELISA for binding to a large panel ofcarbohydrates and glycollpids coupled to BSA. The only one thatbound 984D4.6.5 was LS tetrasaccharide c (NeuNAc2-6Galpß1-4GIcNAcß1-3GaIß1-4Glc),an O-linked carbohydrate. Comparative analysis shows that boththe sequence and the linkage of these sugars are essential tothe reactivity with the 984D4.6.5 antibody. This epitope isexpressed by a glycoprotein of-200 kDa, as shown by Westernblots. The identity of this glycoprotein remains to be determined,but indirect evidence suggests that it is not CD45.     

The yohimbine-induced anticonflict effect in the rat,part I. Involvement of noradrenergic,serotonergic and endozepinergic(?) mechanisms

Summary The ₂-adrenoceptor antagonist yohimbine has in several previous studies been found to produce anticonflict effects comparable to those produced by the benzodiazepines (BDZ) in rat punished conflict models. In this and a following paper we have tried to elucidate the neurochemical mechanisms underlying these effects in a modified Vogel's drinking conflict test. Since yohimbine previously has been demonstrated to interfere both with noradrenaline (NA) and serotonin (5-HT) neurochemistry, and, in addition, shows affinity for the BDZ binding site, we have focused on the putative involvement of these neuronal systems in the yohimbine-induced anticonflict effect. The ₂-adrenoceptor agonist clonidine (10 g/kg, i.p.) completely antagonized the anticonflict effect of yohimbine (4.0 mg/kg, i.p.), whereas the ₁-adrenoceptor agonist ST 587 (1.0 mg/kg, i.p.) had no effect. The anticonflict effect of yohimbine was totally abolished also following lesioning of NA neurons with 6-hydroxy-dopamine. A high dose of the mixed ₁ and ₂ adrenoceptor antagonist propranolol (8.0 mg/kg, i.p.) caused a partial blockade of the yohimbine-induced effect in intact animals, whereas the selective ₁-adrenoceptor antagonist metoprolol (4.0 mg/kg, i.p.) had no significant effect and the ₁-adrenoceptor antagonist prazosin instead potentiated the anticonflict action. The anticonflict effect of yohimbine was dose-dependently antagonized also by the 5-HT precursor L-5-hydroxytryptophan (25–100 mg/ kg, i.p.). The BDZ receptor antagonist flumazenil (10 mg/kg, p.O.), as well as Ro 15-4513 (1.0 mg/kg, p.o.), a partial inverse agonist at BDZ receptors, partly, but significantly, counteracted the yohimbine-induced anticonflict effect, whereas low doses of both the chloride channel blocker picrotoxin and the GABA_A antagonist bicuculline only tended to counteract the yohimbine effect. Taken together, the results in the present behavioral paper indicate that the anticonflict effect of yohimbine involves both increased NA and decreased 5-HT activity, and that direct or indirect activation of BDZ receptors may also be involved. Neurochemical findings related to these behavioral results are presented in a following paper.     

Treatment of Vitamin B12 Deficiency after Gastric Surgery for Severe Obesity

Background: Vitamin B₁₂ deficiency after gastric surgery for obesity is due to a failure of separation of vitamin B₁₂ from protein foodstuffs and to a failure of absorption of crystalline vitamin B₁₂ in the presence of intrinsic factor. The purpose of this study was to determine which of four oral doses of crystalline vitamin B₁₂ was most effective in treating vitamin B₁₂ deficiency in 102 patients. Methods and Results: At time of entry into the study, the patients had a serum vitamin B₁₂ < 100 pmol L ⁻¹, were 29.9 ± 21.7 months post-op, were 37 ± 8 years old and had a body mass index of 30 ± 6 kg m⁻². Eight (8%) had had a vertical banded gastroplasty and 94 (92%) a gastric bypass. For the first 3 months all patients received 350 μg per day of crystalline vitamin B₁₂ and all increased their serum vitamin B₁₂ levels to over 100 pmol L⁻¹. The patients were then assigned to receive for a further 3 month period one of four oral doses of crystalline vitamin B₁₂-100 μg, 250 μg, 350 μg and 600 μg. Serum vitamin B₁₂ levels were greater than 150 pmol L⁻¹ after 6 months in 83.3% of patients who received 100 μg; 92.3% of patients who received 250 μg; 94.7% after 350 μg and 95.2% after 600 μg (p%0.525). Conclusion: At least 350 μg per day is the appropriate oral dose of crystalline vitamin B₁₂ after gastric surgery for obesity to correct low serum vitamin B₁₂ levels in 95% of patients.     

Systematic Differences in Validity of Self-Reported Mammography Behavior: A Problem for Intergroup Comparisons?

Background. Prior studies of recall accuracy for screening mammogram behavior have examined relatively homogeneous groups. Data are limited on possible systematic group differences, so we evaluated women's recall accuracy in two separate care systems in one city.Methods. Women 50 to 70 years old with and without screening mammograms 10 to 14 months prior were identified from fiscal, clinic, and radiology records at a military care system (MCS) and a county-funded system (CFS) for indigents. Mammogram status was verified through radiology records. Women were excluded if mammograms were diagnostic, done for other than annual screening, or had abnormal results. Interview ers blinded to mammogram status surveyed randomly selected eligible women.Results. For 62 screened/31 unscreened MCS women and 78 screened/61 unscreened CFS women, specificity was similar, at 65 and 62%, respectively. In contrast, sensitivity varied significantly: 95% versus 79% (P = 0.011). Primary ethonocultural groups were Euro-American (MCS—60%) and Mexican American (CFS—85%). Although not different in specificity of recall (67% versus 61%), these major subgroups significantly differed in sensitivity (97% versus 80%, P = 0.017), proportion of true negatives due to never having a mammogram (35% versus 57%, P = 0.003), and proportion with ≥high school education (78% versus 19%, P < 0.00001).Conclusion. Systematic differences in recall validity may exist and compromise the accuracy of intergroup comparisons.     

Laparoscopy and Peripancreatic Neoplasia

Since its inception laparoscopy has been a valuable tool for diagnosis, and more recently it has become widely accepted as a medium for surgical intervention. In this light, the addition of minimally invasive techniques to the management of peripancreatic cancer has gained notable attention. Although most practitioners agree that there is some role for minimally invasive therapy, opinions vary as to the extent and significance these applications carry to the overall management of peripancreatic malignancies.