A DOUBLE-BLIND,COMPARATIVE STUDY OF DOTHIEPIN AND CLOMIPRAMINE IN THE TREATMENT OF MAJOR DEPRESSIVE ILLNESS

Dothiepin, a well-established antidepressant, has been compared with clomipramine in a single-blind study which demonstrated that dothiepin was better tolerated but there was no difference in efficacy. The present study was performed to recent European guidelines on good clinical practice using a randomised, double-blind, parallel-group methodology. One hundred and one patients suffering from major depressive disorder as defined by DSM-III-R were randomised to receive either clomipramine (25-150 mg daily) or dothiepin (75-150 mg daily) for up to six weeks. The clomipramine group comprised 51 patients, the dothiepin group 50 patients. At baseline, both groups had a mean age of 41-43 years and gave similar mean scores on the Hamilton Depression Rating Scale (23.5 for clomipramine, 23.6 for dothiepin). At endpoint it was reduced in both groups but there were no significant differences between the groups (mean change from baseline for the clomipramine and dothiepin groups was -14.6 and -14.1 respectively). Thirty-one clomipramine patients and 41 dothiepin patients completed six weeks' treatment. Withdrawal from treatment (20 patients for clomipramine, nine for dothiepin) was significantly different (p=0.0105). When reasons for withdrawal were analysed, 13 clomipramine patients and two dothiepin patients withdrew because of adverse events, this difference being significant (p=0.002). Thus both treatments were effective in treating patients suffering from major depressive disorder, but patients receiving dothiepin suffered fewer adverse events and were more likely to complete their treatment.     

CLINICAL COURSE and RELAPSE RATE IN INTESTINAL BEHCET'S DISEASE

Behçet's disease is a multisystemic recurrent inflammatory disease. Gastrointestinal tract involvement in Behçet's disease has been identified throughout the alimentary tract and causes diverse symptoms. Various treatment have been utilized to induce or maintain remission. However, little is known about clinical course and prognosis in Behçet's disease with intestinal involvement. The aims of this study were to evaluate the clinical course and relapse rate in intestinal Behçet's disease and to investigate factors that may affect relapse.
Methods  Clinical course and characteristics, including demographic parameters, gastrointestinal symptoms as well as systemic manifestations, laboratory data, endoscopic findings, and treatment strategies for the induction of remission, of 97 patients (49 male, 48 female) with intestinal Behçet's disease were retrospectively reviewed. Cumulative relapse free rate and factors related with relapse were analysed by Kaplan–Meier method and log–rank test, respectively.
Results  The median duration of the relapse free period was 7 months (ranges from 1 to 171 months). One, two, and five year relapse free rates were 41.2, 29.7 and 10.2%, respectively. Sex, clinical subtype of Behçet's disease, symptom and laboratory data at onset, colonoscopic findings, such as distribution of lesions as well as number, size, depth, and shape of ulcer, and initial treatment (medical vs. surgical) did not affect relapse rate. However, large ulcers (> 20 mm) and young age at onset (< 37 years old) were factors significantly related with higher relapse rate ( P  < 0.05, log–rank test).
Conclusion  High relapse rate in intestinal Behçet's disease was identified. Age at onset and size of the ulcer are factors related with long-term prognosis of intestinal Behçet's disease.     

Successful allogeneic cryopreserved marrow transplantation

Cryopreservation has been used extensively in autologous marrow transplantation (BMT), but there has been limited use in allogeneic BMT. We describe here 6 cases of successful engraftment following allogeneic BMT with cryopreserved marrow. Patients suffered from Wiscott-Aldrich syndrome, osteopetrosis, aplastic anemia, and acute lymphocytic, acute non-lymphocytic, and chronic myelogenous leukemia, and ranged in age from 5 mos to 35 yrs. Marrow was collected using standard techniques. In one case T-cells were removed to prevent graft-vs-host disease. Marrow was frozen for a variety of reasons. Buffy coat cells were frozen at controlled rate in 10% DMSO, and stored in liquid nitrogen for 6 to 49 d. Engraftment (WBC greater than 1000/uL x 3 d) occurred from 13 to 37 d post BMT. In 4 of 4 cases in which data are available, donor origin of engraftment was documented, 1 with cytogenetics, 2 with red cell typing, and 4 with restriction fragment length polymorphisms. 3 patients are alive and well 21, 21, and 42 months post BMT. These results suggest frozen marrow can be successfully used for allogeneic BMT.     

Interaction of ristocetin and bovine plasma with guinea pig megakaryocytes: a means to enrich megakaryocytes based on membrane rather than physical characteristics

We have investigated whether megakaryocytes can be aggregated by ristocetin and bovine plasma and whether such aggregation can be used as a step in the purification of megakaryocytes from marrow cell suspensions. Guinea pig marrow cell suspensions were first enriched for megakaryocytes by density equilibrium centrifugation in continuous Percoll density gradients. The megakaryocyte-enriched marrow was stirred in a platelet aggregometer to which ristocetin or bovine plasma was added. Megakaryocytes were aggregated by both ristocetin and bovine plasma with the proportion aggregated being related to the concentration of ristocetin or bovine plasma. Maximal aggregation (greater than 90% of megakaryocytes) was achieved with 2.0 mg/mL ristocetin or 5% bovine plasma and required five minutes. All maturation stages of morphologically recognizable megakaryocytes were aggregated. The megakaryocyte aggregates were separated from the marrow suspension by sedimentation at 1 g and the megakaryocytes disaggregated by dilution with media (ristocetin aggregated) or addition of dextran sulfate (bovine plasma aggregated). Megakaryocyte purity and recovery were higher with bovine plasma than with ristocetin. A mean of 92% of the megakaryocytes in the bovine plasma aggregated cell suspensions were recovered with megakaryocytes constituting an average of 76% of the final cell suspensions. The viability as well as the diameters and DNA content distribution of these megakaryocytes were similar to those of the starting population. We conclude that guinea pig megakaryocytes behave like platelets in that they can be aggregated with ristocetin or bovine plasma and that megakaryocyte aggregation induced by ristocetin or bovine plasma provides a means to enrich these cells based on membrane rather than physical characteristics. This approach yields purified megakaryocyte populations that are representative of those in unfractionated marrow.     

Comparison of two- and three-dimensional transvaginal ultrasound in the visualisation of intrauterine devices

The aims of the study were to evaluate whether three-dimensional transvaginal ultrasound (3D TV US) is superior to two-dimensional transvaginal ultrasound (2D TV US) at visualising intrauterine devices and determining their position. This prospective study included 52 participants with an intrauterine device fitted, who underwent 2D TV US and 3D TV US. 2D TV US and 3D-reconstructed coronal images were reviewed by two gynaecological radiologists to assess ease of visualisation and position of the intrauterine devices. Statistical analysis was performed using Wilcoxon signed-rank, McNemar and Chi-squared tests. The inter-observer agreement was measured using Cohen’s Kappa. Intrauterine device visualisation scores were significantly higher with 2D TV US compared with 3D TV US (Radiologist 1 p = <0.001, Radiologist 2 p = 0.007). A significant number of T-arms appeared to perforate into the adjacent myometrium on the 3D-reconstructed coronal image, but were normal on the 2D images (Radiologist 1 p = <0.001, Radiologist 2 p = 0.008). Radiologist 1 found 19 perforated T-arms on 3D TV US compared with four on 2D TV US. Radiologist 2 found 13 perforated T-arms on 3D TV US compared with five on 2D TV US. Both radiologists agreed on the positions of the intrauterine devices substantially with 3D TV US (Kappa = 0.69) and moderately with 2D TV US (Kappa = 0.55). The 3D TV US did not visualise an intrauterine device better than 2D TV US. The 3D-reconstructed coronal image of the uterus can reliably display cases of T-arm perforation into the adjacent myometrium, which could be missed on 2D TV US images. The 3D TV US should be used in addition to 2D TV US in all cases where an intrauterine device is under evaluation.