A 2-year study of sertraline in the treatment of obsessive-compulsive disorder

The present study investigated the tolerability, safety profile, and anti-obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor, during long-term treatment of patients with obsessive-compulsive disorder (OCD). Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study comparing sertraline and placebo subsequently entered a 1-year open extension. Among the 51 patients who had been treated with sertraline during the double-blind phase, the mean total duration of sertraline treatment was 690 days. Only treatment responders who completed the 52-week double-blind treatment phase were permitted to enter the open extension. The higher rate (p < 0.02) of sertraline patients (51 out of 241) than of placebo patients (eight out of 84), who responded to treatment and entered the open-label phase is therefore consistent with the greater mean improvement observed in the sertraline group during double-blind treatment. Placebo responders differed from sertraline responders in that they were less impaired at baseline of the double-blind study [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4] and they exhibited less improvement during double-blind treatment (-6.1 versus -11.4). In the open-label phase all patients received sertraline at a starting dose of 50 mg once a day, titrated in 50 mg increments to a maximum dose of 200 mg according to clinical response. At end-point the mean Y-BOCS score for all patients decreased by a further 3.6 points. Patients previously treated with placebo showed greater improvement after being switched to sertraline than those who received continued sertraline treatment. Patients who completed the study and received 2 full years of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points using the Y-BOCS. Sertraline was well tolerated during both the double-blind phase and the open extension, and the incidence of adverse experiences was generally reduced during the second year of treatment. Three patients discontinued open treatment because of adverse experiences. Long-term sertraline treatment did not appear to be associated with the emergence, increased incidence, or increased severity of adverse experiences or clinically significant abnormalities in laboratory tests, vital signs, or the electrocardiogram. The study supports the long-term safety and tolerability of sertraline over a 2-year treatment course and the sustained efficacy of sertraline in patients with OCD.     

Diagnosis and therapy of hyperandrogenism

Diagnostic categories in hyperandrogenism include polycystic ovary syndrome (PCOS) and its variants, adrenal and ovarian steroidogenic enzyme deficiencies, adrenal and ovarian androgen secreting tumours and other endocrine disorders such as hyperprolactinaemia, Cushing syndrome and acromegaly. About 95% of hyperandrogenic women will have PCOS. Endometrial hyperplasia can be prevented in hyperandrogenic, anovulatory women by the oral contraceptive pill or progestins. Hirsutism is best treated by a combination of the oral contraceptive pill and an anti-androgen. The first line of therapy for ovulation induction is clomiphene citrate, with human menopausal gonadotrophins (hMG) or laparoscopic ovulation induction reserved for clomiphene failures. hMG together with gonadotrophin-releasing hormone agonist may decrease the risk of spontaneous abortion following ovulation induction in PCOS. Weight loss should be vigorously encouraged to ameliorate the metabolic consequences of PCOS.     

Chest radiographic data acquisition and quality assurance in multicenter studies

Dorsal fusion with the internal fixator has become the standard treatment of instabilities and deformities of the thoracolumbar spine. With our new device, the modular spine fixator (MSF), which has been specially designed for short-distance instrumentations, we have increasingly been treating unstable injuries of the thoracolumbar spine by one-level stabilization. Prerequisite is an accurate evaluation of the indication, including CT and MRI to assess the involvement of the intervertebral disc and the ligamental structures. The operative technique differs in some details from the procedure in more-multi-level instrumentations, especially concerning the application of the pedicle screws. The instrumentation is always combined with posterior allogenic bone grafting. Since the beginning of 1993 we also perform anterior autogenic transpedicular bone grafting. Between January 1991 and July 1995, 57 one-level stabilizations with the MSF were performed. Of the 57 patients operated on 39, 27 men and 12 women, with an average age of 41 years, have had a clinical and radiographic follow-up examination so far, on average, 27 months after the accident. Seventeen patients were completely free of pain and 17 patients (were only) sensitive to weather changes or had minor pain during great physical stress. Five patients had pain even during slight physical stress or at rest. The preoperatively measured Cobb angle was 15.1 degrees on average, after the operation 5.2 degrees, and at the time of the follow-up examination amounted to 8.1 degrees. The patients' range of motion was normal. Only five minor complications have been seen. No implant fatigue failure has been noted in this series. We derive from these results that, for correct indications, one-level stabilization can be performed successfully and should be firmly established in the operative treatment of unstable fractures of the thoracolumbar spine.     

Lack of germ-line mutations of CDK4, p16(INK4A), and p15(INK4B) in families with glioma

Gliomas are tumors of the central nervous system that may be inherited in some patients. The gene(s) responsible for the clustering of gliomas in families have not yet been identified. Molecular studies of sporadic high-grade gliomas have revealed mutations or deletions of the genes encoding the protein kinase inhibitors p16(INK4A) and p15(INK4B) in a large proportion of tumors. Moreover, those tumors without deletions frequently display gene amplification and/or over-expression of mRNA encoding the protein kinase cdk4. We hypothesized that germ-line mutations in the p16(INK4A), p15(INK4B), or CDK4 genes might contribute to some cases of familial gliomas. To address this issue, we analyzed 36 kindreds with a predisposition to glial tumors. Genomic DNA from index members of these families was screened by PCR-single-strand conformational polymorphism analysis. We did not detect any functional mutations in the p16(INK4A), p15(INK4B), or CDK4 genes, although two individuals did have a previously described A140T polymorphism in p16(INK4A). Thus, despite the association between the sporadic forms of high-grade glioma and abnormalities of p16(INK4A), p15(INK4B), or CDK4, we found no evidence that germ-line mutations in the coding region of these three genes predispose to inherited glial tumors.     

Use of small and large bowel in renal transplantation

The continued success of renal transplantation has provided a higher quality of life for properly selected patients with ESRD. It is also a much more cost-effective and efficient treatment of ESRD compared with chronic dialysis. Innovative urologic reconstructive surgery using enteric segments for both continent and incontinent urinary diversions has permitted this therapeutic modality to be offered to the recipient with lower urinary tract disease not previously amenable to renal transplantation. These same reconstructive techniques using ileal segments have also permitted preservation of renal allografts with previously nonreconstructable renal pelvic or ureteral disease.     

Microbial resistance: what is to be done? Information from the panel of experts

This document represents the recommendations of a panel of Spanish experts on antibiotic use and resistance. In a Task Force, under the auspices of the Spanish Ministry of Health and Consumer Affairs that took place in 1994 in Madrid, the members were gravely concerned about the national increase in antibiotic resistance. They analysed the development, evolution and spread of antibiotic resistance among community-acquired human bacterial pathogens in Spain, its relation with antibiotic consumption, and they proposed future surveillance strategies for monitoring the patterns of antibiotic use and consumption. Success will require a collective action among the producers (pharmaceutical industry), prescribers (doctors, veterinarians), dispensers (pharmacists), and consumers (patients). Two similar documents have been recently published by the American Society of Microbiology and the World Health Organization showing the global concern about this topic.     

Mapping the prion protein using recombinant antibodies

The fundamental event in prion disease is thought to be the posttranslational conversion of the cellular prion protein (PrPC) into a pathogenic isoform (PrPSc). The occurrence of PrPC on the cell surface and PrPSc in amyloid plaques in situ or in aggregates following purification complicates the study of the molecular events that underlie the disease process. Monoclonal antibodies are highly sensitive probes of protein conformation which can be used under these conditions. Here, we report the rescue of a diverse panel of 19 PrP-specific recombinant monoclonal antibodies from phage display libraries prepared from PrP deficient (Prnp0/0) mice immunized with infectious prions either in the form of rods or PrP 27-30 dispersed into liposomes. The antibodies recognize a number of distinct linear and discontinuous epitopes that are presented to a varying degree on different PrP preparations. The epitope reactivity of the recombinant PrP(90-231) molecule was almost indistinguishable from that of PrPC on the cell surface, validating the importance of detailed structural studies on the recombinant molecule. Only one epitope region at the C terminus of PrP was well presented on both PrPC and PrPSc, while epitopes associated with most of the antibodies in the panel were present on PrPC but absent from PrPSc.     

Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF

We employed a morphological assay of outer segment collapse to determine if growth factors or other supplements directly affect dissociated rod photoreceptors in vitro. The morphological changes in outer segments were correlated with the light responsiveness of rods. Time-lapse video microscopy was used to observe the collapse of rod outer segments from isolated single cells and small clumps of cells. A consistent pattern of outer segment collapse into the inner segment was observed, yielding a convenient assay of the effects of neurotrophic factors on photoreceptor functional maintenance. The functional state of rods, defined as light-responsiveness, was measured with suction electrode recordings and matched with the various stages of outer segment collapse. Ciliary neurotrophic factor (CNTF) and glial cell-line-derived neurotrophic factor (GDNF) at a high concentration, yielded statistically significant improvements in rat outer segment survival times. Basic fibroblast growth factor (bFGF), which rescues photoreceptors in several rodent models of retinal degeneration, produced a significant increase in survival time in the presence of the cofactor heparin. In 4 out of 10 cases using human tisue, bFGF also yielded a significant increase in survival times. When brain-derived neurotrophic factor (BDNF) was applied to rat rods, outer segment survival times did not change. Outer segments collapsed more quickly when either pigment epithelial cell derived factor (PEDF) or sugar N-acetyl D-galactosamine (NAD-gal) were present. Our results show that rod photoreceptors can respond to bFGF, GDNF and CNTF in vitro and provide evidence for a direct effect of these neurotrophic factors on rods. The rapid collapse of isolated photoreceptors in this model provides a convenient means for testing various neurotrophic agents and the induced cellular responses.