Novel brain reactive autoantibodies: prevalence in systemic lupus erythematosus and association with psychoses and seizures

Autoantibodies can cause neuropsychiatric manifestations in lupus patients by altering the physiological function of neuronal cells. In this study, we identified Brain Reactive Autoantibodies (BRAAs) against murine neuronal membrane proteins (M.W. 27.5 and 29.5 kD) and found them correlating with psychosis and/or seizures in lupus patients. They were specific to neuronal membrane tissues of mammalian origin and are significantly associated with psychosis and/or seizures (p<0.0001). These membrane proteins mass spectrometry profiles did not match to any published protein sequences. These BRAAs may play important roles in the pathophysiology of neuropsychiatric lupus.     

Surgical outcomes of combined phacoemulsification and glaucoma drainage implant surgery for Asian patients with refractory glaucoma with cataract

PURPOSE: To examine the safety and efficacy of combined phacoemulsification and glaucoma drainage implant surgery in providing reduction of intraocular pressure (IOP) and visual rehabilitation in eyes with refractory glaucoma and cataract. DESIGN: Interventional case series. METHODS: A retrospective chart review was performed on all subjects who underwent combined phacoemulsification with intraocular lens implantation and glaucoma drainage implant surgery by a single surgeon at the National University Hospital, Singapore. The implants used were the 185 mm2 Ahmed glaucoma valve and the 350 mm2 Baerveldt glaucoma implant. In terms of IOP, a complete success was defined as IOP of between 6 to 21 mm Hg without medication, qualified success as IOP between 6 to 21 mm Hg with one or more medication, and failure as a sustained IOP of >21 mm Hg or <6 mm Hg with or without one or more medication on two or more visits. RESULTS: A total of 32 combined phacoemulsification and glaucoma implant surgeries in 32 patients was performed. All patients were of Asian origin, and the mean age was 58 +/- 16 years (range, 20-78 years). The Baerveldt glaucoma implant and Ahmed glaucoma valve implant were inserted in 16 eyes each. With a mean follow-up of 13 +/- 5 months (range 6 to 22 months), IOP was reduced from a mean of 28.0 +/- 11.5 mm Hg to 15.2 +/- 6.0 mm Hg postoperatively (P <.0001), whereas the number of antiglaucoma medications decreased from a mean of 2.4 +/- 1.4 to.3 +/-.7 (P <.0001) at last follow-up. Overall, there were 24 eyes (75%) that were classified as complete successes, 4 eyes (12.5%) that were qualified successes, and 4 eyes that failed (12.5%). Twenty-three eyes (72%) had improvement of visual acuity, while only one eye had a loss of more than 1 line of Snellen acuity. There was no case that encountered an intraoperative complication, and postoperative complications occurred in 12 eyes (38%), the most common of which was hypotony (in six eyes, 19%). CONCLUSION: For subjects with refractory glaucoma and cataract, combined phacoemulsification and glaucoma drainage implant surgery provide good visual rehabilitation and control of IOP, with low incidence of complications.     

Identifying barriers to the adoption of evidence-based medicine practice in clinical clerks: a longitudinal focus group study

OBJECTIVE: To identify and explore common barriers to the adoption of evidence-based medicine (EBM) practice in the undergraduate setting. DESIGN: Nested longitudinal, focus group-based, qualitative study. Setting The University of Hong Kong Medical School, Hong Kong, China. PARTICIPANTS: A group of 39 Year 4 medical undergraduates who participated in an EBM intervention cluster randomised crossover trial. MAIN OUTCOME MEASURES: Students' attitudes, opinions and perceptions of barriers to EBM use. RESULTS: General attitudes towards EBM and the teaching intervention were positive. Four sets of barriers to greater EBM use were identified as follows. (1) Learning environment including prevailing norms for student learning involving examination-oriented, textbook learning, prior availability of clinical practice guidelines, lack of encouragement from teachers and economy of time by utilising teacher expertise. (2) Limitations of evidence consisting of poor point-of-care access to medical literature, difficulty in locating evidence and the perceived low relevance of overseas evidence to Chinese patients. (3) Lack of opportunity to practise EBM due to lack of continuity of care and anxieties about negative teacher attitudes towards EBM use at the point-of-care. (4) Time constraints such as competing study demands and long evidence search time. CONCLUSIONS: Significant barriers to the successful implementation of EBM learning in the clinical clerkship setting were identified. These can be specifically targeted to ameliorate any inhibition of clinical learning they may impose.     

Prepayment was superior to postpayment cash incentives in a randomized postal survey among physicians

OBJECTIVE: Improving response rates, particularly among physicians, is important to minimize nonresponder bias and increase the effective sample size in epidemiologic research. We conducted a randomized trial to examine the impact of prepayment vs. postpayment incentives on response rates. STUDY DESIGN AND SETTING: Self-completion postal questionnaires were mailed to 949 physicians who were respondents to an earlier survey and representative of the general physician population in Hong Kong. These physicians were randomly allocated to receive a HK dollar 20 cash prepayment incentive that accompanied the survey (n=474) or a postpayment reward of the same amount on receipt of the completed questionnaire (n=475). RESULTS: The final prepayment response rate was 82.9%, compared with 72.5% in the postpayment arm (P < .001). Of the eight alternative incentive and follow-up strategies evaluated, three lie on the efficiency frontier (i.e., not dominated), including postpayment with three mailings at HK dollar 42.7, prepayment with three mailings at HK dollar 66.5 and prepayment with three mailings and telephone follow-up at HK dollar 112.1 per responder recruited (US dollar 1=HK dollar 7.8). CONCLUSION: The findings demonstrate that prepayment cash incentives are superior to postpayment of the equivalent amount in improving response rates among a representative sample of Hong Kong physicians. Further research should concentrate on confirming the generalizability of these findings in other health care occupation groups and settings.     

Repeated laparoscopic ovarian diathermy is effective in women with anovulatory infertility due to polycystic ovary syndrome

OBJECTIVE: To assess the effectiveness of a second laparoscopic ovarian diathermy (LOD) in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective study. SETTING: Tertiary infertility clinic. PATIENT(S): Twenty anovulatory infertile women with PCOS who underwent LOD 1-6 years previously. Twelve subjects had previously responded positively to the first LOD, but the anovulatory status recurred (Group I), whereas eight subjects had not responded at all (Group II). INTERVENTION(S): Laparoscopic ovarian diathermy. MAIN OUTCOME MEASURE(S): Rates of ovulation, pregnancy and resumption of menstrual regularity, and biochemical changes. RESULT(S): An overall ovulation rate of 12 out of 20 women (60%) and a pregnancy rate of 10 out of 19 (53%) were achieved after the second LOD. In women (n = 12) who previously responded positively to the first LOD (LOD-sensitive), the ovulation and pregnancy rates were 10 out of 12 (83%) and 8 out of 12 women (67%), respectively, which were significantly (P<.05) higher than 2 out of 8 (25%) and 2 out of 7 (29%) of the previous nonresponders (LOD-resistant). Statistically significant hormonal changes including reduction of luteinizing hormone (LH), testosterone (T), and free androgen index (FAI) after the repeat LOD were only observed in the LOD-sensitive group. CONCLUSION(S): Repeat LOD is highly effective in women who previously responded to the first procedure.     

Uncoupling of proliferative potential and gain of effector function by CD8(+) T cells responding to self-antigens

Professional antigen-presenting cells (APCs) are capable of transporting self-antigens from peripheral tissues to secondary lymphoid organs where they are presented to potentially autoreactive CD8(+) T cells. In the absence of an inflammatory response, this results in immune tolerance. The presence of activated, antigen-specific CD4(+) T cells converts this tolerogenic encounter into an immunogenic one by promoting extensive proliferation of CD8(+) T cells and their development into effectors. Surprisingly, activation of APCs with an agonistic antibody specific for CD40 could not substitute for CD4(+) help in this task. Anti-CD40 induced recruitment of dendritic cells expressing high levels of B7 costimulatory molecules into the lymph nodes, which in turn, greatly enhanced activation and expansion of CD8(+) T cells. However, these activated CD8(+) cells did not demonstrate effector function. We conclude that proliferative potential and gain of effector function are separable events in the differentiation program of CD8(+) T cells.     

Chondroinduction of mouse mesenchymal stem cells in three-dimensional highly porous matrix scaffolds

Porous polyvinyl formal (PVF) resin and poly(lactide-caprolactone) [P(LA/CL)] sponges were examined as three-dimensional matrices for chondroinduction of cultured bone marrow mesenchymal stem cells (MSCs). Approximately 5 x 10(5) mouse MSCs were seeded in porous PVF resin or P(LA/CL) sponges and were cultured for up to 1 month in serum-free high-glucose Dulbecco's modified Eagle's medium containing 10 ng/mL transforming growth factor-beta3 and 100 nM dexamethasone for chondroinduction. After the 1-month culture period, the PVF resin and P(LA/CL) sponges contained approximately twice the amount of glycosaminoglycans compared with the control pellet. Safranin-O staining of PVF and P(LA/CL) after 1 month of culture revealed a cartilage-like extracellular matrix containing glycosaminoglycans and collagen. When implanted into nude mice, PVF and P(LA/CL) seeded with MSCs were found to be both biocompatible and chondroinductive. These highly porous scaffolds can maintain a large number of cells in a three-dimensional structure. Both are potentially promising for the chondroinduction of bone marrow MSCs for research and clinical applications.