Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.     

Age-related changes in centripetal ciliary body movement relative to centripetal lens movement in monkeys

The goal was to determine the age-related changes in accommodative movements of the lens and ciliary body in rhesus monkeys. Varying levels of accommodation were stimulated via the Edinger-Westphal (E-W) nucleus in 26 rhesus monkeys, aged 6–27 years, and the refractive changes were measured by coincidence refractometry. Centripetal ciliary process (CP) and lens movements were measured by computerized image analysis of goniovideographic images. Ultrasound biomicroscopy (UBM) at 50 MHz was used to visualize and measure accommodative forward movements of the ciliary body in relation to age, accommodative amplitude, and centripetal CP and lens movements. At ～3 diopters of accommodation, the amount of centripetal lens movement required did not significantly change with age (p = 0.10; n = 18 monkeys); however, the amount of centripetal CP movement required significantly increased with age (p = 0.01; n = 18 monkeys), while the amount of forward ciliary body movement significantly decreased with age (p = 0.007; n = 11 monkeys). In the middle-aged animals (12–16.5 years), a greater amount of centripetal CP movement was required to induce a given level of lens movement and thereby a given level of accommodation (p = 0.01), compared to the young animals (6–10 yrs). Collectively, the data suggests that, with age, the accommodative system may be attempting to compensate for the loss of forward ciliary body movement by increasing the amount of centripetal CP movement. This, in turn, would allow enough zonular relaxation to achieve the magnitude of centripetal lens movement necessary for a given amplitude of accommodation.     

Prevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screening.

AIMS: Autoimmune diseases such as Addison's or coeliac disease can contribute to hypoglycaemia or malabsorption and are more common in Type 1 diabetes (T1DM). This brief report describes the prevalence of known and newly detected autoimmune disease in clinical islet transplant candidates with longstanding T1DM and severe hypoglycaemia and/or glycaemic lability who are routinely screened for coexisting autoimmune disease. METHODS: One hundred and twenty-four C-peptide negative T1DM subjects [77 (62%) female, mean age 44 +/- 9 years, diabetes duration 28 +/- 11 years, body mass index 24.9 +/- 3.5 kg/m(2)] with indications for clinical islet transplantation at the University of Alberta were screened for autoimmune disease by history and measurement of anti-transglutaminase antibodies (positive > 10 U/ml), 09.00 h cortisol (followed by adrenocorticotrophic hormone-stimulation if < 495 nmol/l) and thyroid-stimulating hormone to determine the prevalence of coeliac disease, Addison's disease and autoimmune thyroid disease, respectively. RESULTS: Forty per cent of subjects had one or more coexisting autoimmune disease. The prevalence of autoimmune disease was 35%, coeliac disease 8% and Addison's disease 1.6%. In 11 individuals (9%), one or more autoimmune disease were newly detected (seven coeliac disease and five thyroid disease). Seven of 10 cases of coeliac disease were newly detected. A gluten-free diet in individuals with newly diagnosed coeliac disease reduced gastrointestinal symptoms, but indications for clinical islet cell transplantation persisted. CONCLUSIONS: Coexisting autoimmune disease is common in candidates for clinical islet cell transplantation. Screening in this group identified a substantial number of previously unrecognized cases. Clinicians should consider the presence of autoimmune disease even in the absence of classical symptoms.     

Teaching ethics to paediatrics residents: the centrality of the therapeutic alliance

Context Previous research on ethical issues encountered by medical professionals in training and practice have presented the thematic content of the cases they encounter rather than the activities in which clinicians engage and in which they most often encounter ethical issues. We conducted a direct observation study of paediatrics residents and their preceptors seeing patients in an out‐patient general paediatrics clinic. Our objectives were to describe the everyday ethics‐related issues paediatrics residents encounter as they interact with patients. Our ultimate goal is to use this knowledge to enhance current efforts to teach ethics to paediatrics residents. Methods The study team directly observed paediatrics residents discussing patients with their faculty preceptors (19 half‐day sessions, 76 hours) in an out‐patient general paediatrics clinic located in an urban academic medical centre. Each interaction between resident and preceptor about a single patient was considered a case for further analysis. Results A total of 247 cases were recorded. Forty‐one of the cases were coded as having ethics‐related content. A constant comparative method of qualitative data analysis revealed that residents were most likely to encounter ethical issues when engaged in the following activities: (i) maintaining a therapeutic alliance with the caregiver (e.g. the parent); (ii) prioritising patient or family needs; (iii) adjusting to the power embodied by the role of doctors, and (iv) distinguishing suboptimal care from abuse or neglect. In addition, our findings indicate that it is through their efforts to maintain the therapeutic alliance with the caregivers of their patients that residents engage in and integrate three processes: developing their medical knowledge; adhering to professional norms, and balancing the power inherent in the doctor’s role with their responsibility to serve the patient’s interests. Conclusions Medical faculty tasked with teaching ethics to paediatrics residents can utilise the results of this project to better target and enhance their ethics education efforts directed at residents in the out‐patient setting. Future research could further examine and test these findings in other clinical settings (e.g. adult general medicine).     

Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain

The receptor mGluR5 is a metabotropic glutamate receptor with messenger RNA abundantly present throughout cortex, hippocampus, and caudate/putamen that is also coupled to phosphatidyl inositide hydrolysis and calcium mobilization. In this study, the distribution of mGluR5 was examined in rat brain by immunocytochemistry. The antibody utilized is highly specific and does not cross react with the most closely related other metabotropic glutamate receptor, as determined by Western blot analysis of nonneuronal cells transfected with metabotropic receptor coding sequences. The receptor mGluR5 is widely expressed with the highest density in olfactory bulb, caudate/putamen, lateral septum, cortex, and hippocampus, as confirmed with both immunocytochemistry and Western blot analysis. Electron microscopic studies in hippocampus and cortex indicate that the labeling is mostly on membranes of dendritic spines and shafts. Light and electron microscopic evidence indicates that some mGluR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a presynaptic receptor.     

The contribution of a non-invasive test to clinical care. The impact of echocardiography on diagnosis, management and patient anxiety

We prospectively studied the impact of echocardiography on a cardiologist's diagnosis and management plan and on patient anxiety for 300 consecutive referrals. There was an impact on diagnosis in 90% of patients. Most common was confirmation of diagnosis usually with the addition of information pertinent to management (81%); change of disease category or resolution of diagnostic doubt was uncommon (9%). The consultant cardiologist believed the heart to be normal in 48 patients who did not have any associated disease; none had any echocardiographic abnormality. The cardiologist reported increased diagnostic confidence in 74% of all patients but management changed in only 9%. One-third of all patients reported reduced anxiety when this was an important clinical issue but in less than half of them did the cardiologist consider that echocardiographic information was essential for reassurance. Anxiety was increased in 6%, and in 12% the anxiety response was inconsistent with the test result. The clinical contribution of the test report was most obvious for those patients (30%) in whom this data was required for (a) a decision concerning specific diagnostic or technical intervention (b) a change of management plan which implied obvious or likely health benefit (c) reassurance which was a clinically important issue. The magnitude of this contribution was related to the study indication. The value of echocardiography is obvious when assessing patients for invasive intervention or when proper treatment or adequate reassurance are impeded by diagnostic doubt. However, for many current indications, we need better definition of factors which predict a clinically useful result. In particular, when the aim is to rule-out disease, our results suggest that an expert cardiological opinion would often be more appropriate than an echocardiogram.     

Sensorineural hearing loss in patients with typical retinitis pigmentosa

We performed detailed audiologic testing in 45 patients with retinitis pigmentosa and 45 age- and sex-matched controls. Ten (22%) of the retinitis pigmentosa patients had a sensorineural hearing loss that varied from mild to severe. None of the control subjects had a hearing loss. Audiograms measured over a ten- to 30-year period were available for four patients with retinitis pigmentosa and each showed progressive hearing loss. The results indicate the important role of audiologic evaluation in treating patients with retinitis pigmentosa.