A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression.

BACKGROUND: Effectiveness of repetitive transcranial magnetic stimulation (rTMS) for major depression is unclear. The authors performed a randomized controlled trial comparing real and sham adjunctive rTMS with 4-month follow-up. METHOD: Fifty-nine patients with major depression were randomly assigned to a 10-day course of either real (n=29) or sham (n=30) rTMS of the left dorsolateral prefrontal cortex (DLPFC). Primary outcome measures were the 17-item Hamilton Depression Rating Scale (HAMD) and proportions of patients meeting criteria for response (50% reduction in HAMD) and remission (HAMD8) after treatment. Secondary outcomes included mood self-ratings on Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. Patients had 6-week and 4-month follow-ups. RESULTS: Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant groupxtime interaction (p=0.09) or group main effect (p=0.85); the mean difference in HAMD change scores was -0.3 (95% CI -3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06); 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2); the mean difference in HAMD change scores was 2.9 (95% CI -0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters. CONCLUSIONS: Adjunctive rTMS of the left DLPFC could not be shown to be more effective than sham rTMS for treating depression.

The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis.

OBJECTIVE: To investigate if repetitive transcranial magnetic stimulation (rTMS) was as effective as electroconvulsive therapy (ECT) in treating major depressive episodes and to perform a cost-effectiveness analysis. DESIGN: A single-blind pragmatic multicentre randomised controlled trial (RCT) with 6 months of follow-up to test equivalence of rTMS with ECT. SETTING: The South London and Maudsley NHS Trust and Pembury Hospital in the Invicta Mental Health Trust in Kent. PARTICIPANTS: Right-handed adult patients referred for ECT for treatment of a major depressive episode (DSM-IV) were assessed. During the 2.5-year trial period, 260 patients were referred for ECT, of whom 46 entered the trial. The main reason for not entering the trial was not consenting to ECT while being formally treated under the UK Mental Health Act 1983. INTERVENTIONS: Patients were randomised to receive a 15-day course of rTMS of the left dorsolateral prefrontal cortex (n = 24) or a course of ECT (n = 22). MAIN OUTCOME MEASURES: Patients were assessed before randomisation, at end of treatment and at the 6-month follow-up. Primary outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD) and proportion of remitters (defined as HRSD score

An observational case study of ozone and precursors inflow to South East England during an anticyclone.

Summertime photochemical air pollution episodes within the United Kingdom have been proposed via modelling studies to be strongly influenced by regional scale inflow of air from the continental European boundary layer. We present a vertically resolved case study using measurements made from the NERC/Met Office BAe 146 research aircraft on 18th August 2005 over the South East of England and the North Sea during a weak anticyclone centred over Northern Europe. The vertical distribution of ozone, CO, NO(x), peroxyacetyl nitrate (PAN) and a wide range of both nonmethane hydrocarbons (NMHC) and oxygenated volatile organic compounds (OVOCs) were determined between 500 ft (approximately 152 m) and 7000 ft (approximately 2134 m) over the East Anglia coastline and 50 km inland. In excess of 80 ppbV ozone was observed within inflowing boundary layer air over the North Sea coast in a broad N-S sloping feature around 60 km wide. The inflowing feature of European origin was also observed further inland within the boundary layer albeit with lower, more variable, ozone mixing ratios. The increased variability in ozone over land was a product of titration by fresh surface emissions of NO via rapid upward transport in thermals, a hypothesis supported by the observed vertical wind speed component. Fast boundary layer mixing over land was further illustrated by a uniform distribution in reactive alkenes. A comparison between aircraft and surface O(3) UK AUN (Automatic Urban Network) measurements showed good agreement with the inland site, Sibton, but marked differences with the coastal monitoring site at Weybourne, potentially due to gradients established by ocean deposition in stably stratified marine air.

Depression and the perpetuation of an incapacitated identity as an inhibitor of return to work.

The aim of the current study was to conduct a qualitative investigation of attitudes to work among people diagnosed with clinical depression. It was of particular interest to understand the role played by illness in attitudes to recovery. The economic and social burden of adult depression on society is becoming increasingly apparent. It has been argued that recovery from mental illness of this kind is most appropriately understood in 'functional terms' (i.e. 'getting on with life beyond illness'). One important goal in this process is return to work. Accordingly, in-depth semi-structured interviews were conducted with 19 people formally diagnosed with clinical depression. These interviews were the analyzed using Interpretative Phenomenological Analysis: a method of investigation and analysis concerned with making sense of participant experiences and accounts of their ill-health. This process identified three master themes, only one of which is the focus of this paper. This theme pertains to the unwitting role that can be played by the health care system in reinforcing the 'sick role' and in so doing providing a continued justification for an 'off-work' identity. Consequently, this study provides an unusually penetrating insight into the way depression can, through institutional practices, become inextricably part of someone's identity, with important implications for functional recovery.

Multi-branching flows from one mother tube to many daughters or to a network.

Multiply branching fluid flows are modelled in two contexts. The first (type I) is for one-to-many branching. Computations are described for flow through a channel, with fully developed motion upstream, which branches abruptly into a number of subchannels downstream. The differences in pressure between the upstream end of the channel and the downstream ends of the subchannels are substantial. Comparisons with recent analytical predictions show fair agreement for Reynolds numbers in the low tens and above. The second context (type II) has successive generations of bifurcation in a network. Modelling, computations and analysis include the effects of many bifurcations.

Droplet impact on water layers: post-impact analysis and computations.

An inviscid model of droplet impact into a water layer is examined analytically for small times just after impact and computationally for order-one distortion times. Various layer depths are considered, as are surface-tension effects. Good correspondence is found between analysis, computation and experiments.

Treating first episode psychosis--the service users' perspective: a focus group evaluation.

UK national guidance has prioritized developing specialist services for first episode psychosis. Such services are in the early stages of development and a definitive treatment model has yet to be established. The aim of this study was to explore service users' experiences of a first episode intervention designed along evidence-based 'best practice' guidelines and to establish specific elements seen as effective to help inform future service planning and provision. Twelve users of a specialist first episode service participated in focus groups. These were then analyzed using Interpretative Phenomenological Analysis, a specialized form of content analysis. Key elements identified by the service users included the 'human' approach as a key to the recovery process, being involved in treatment decisions, flexibility of appointments, high nurse to patient ratio, reduction in psychotic symptoms, increased confidence and independence and the provision of daily structure. To our knowledge, this is the first systematic qualitative evaluation of users' experience of a specialist first episode treatment intervention. Our findings indicate that adherence to best practice guidelines was appreciated. Regular focus groups provide a continuous audit cycle incorporating service improvements in line with government recommendations, centrally informed by the service users' and caregivers' perspective.

Two high-speed, portable GC systems designed for the measurement of non-methane hydrocarbons and PAN: results from the Jungfraujoch High Altitude Observatory.

Near real-time measurements of light non-methane hydrocarbons (NMHCs) and peroxyacetyl nitrate (PAN) have been performed in the free troposphere using two fast gas chromatography (GC) instruments designed for use on aircraft. A GC-helium ionisation detector (HID) system measured 15 C(2)-C(5) hydrocarbons with 5 min time resolution and a dual channel GC-Electron Capture Detector (ECD) measured PAN with 90 s resolution. Both instruments had low parts per trillion by volume (pptV) detection limits and ran continuously at the remote Jungfraujoch (JFJ) research station in the Swiss Alps (46.55[degree]N, 7.98[degree]E), 3580 m above mean sea level (AMSL), during February/March 2003. Carbon monoxide, ozone, nitrogen oxide and nitrogen dioxide and all odd nitrogen species (NO(y)) were also measured continuously. Hydrocarbons and CO were strongly correlated in all air-masses whilst PAN exhibited both positive and negative correlations with respect to O(3), dependent on age and origin of the air-mass sampled. PAN was found to contribute [similar]20% to the NO(y) sampled on average. The experiment, as well as providing interesting datasets from this remote location, also demonstrated that when optimised, GC techniques have the potential to measure at a time resolution significantly greater than is traditionally considered, with high sensitivity and low uncertainty.

Nurses' attitudes toward do-not-resuscitate orders.

A study was carried out to evaluate burn nurses' attitudes toward do-not-resuscitate (DNR) orders. Questionnaires were submitted to 57 staff members, 52 of whom responded. Seventy-five percent of those responding ranged in age from 30 to 49 years. Seventy-one percent were registered nurses or licensed practical nurses. Sixty-five percent of the respondents had been in health care for more than 10 years; 25% had been in burn care for more than 10 years. Fifty percent were Protestants. Thirty-seven percent of the total described themselves as very religious. Ninety-four percent of respondents felt that DNR orders are sometimes appropriate. Eighty-eight percent felt that DNR decisions should not be made solely by the physician. Ninety-five percent felt that input from patients, family members, or both is essential. Having formal ethics committees make such decisions was opposed by 75% of the respondents. Fifty-six percent felt nurses should be involved in such decisions and 21% opposed such involvement. There was considerable uncertainty, disagreement, or both about whether a DNR order should include stopping all medical treatment, ventilators, intravenous fluids, gastric feedings, and medication. The study indicated statistically significant support for the view that DNR orders are appropriate in some cases. Which patients should be given DNR status and who should make the decision about writing DNR orders were more controversial questions.

Postburn psychologic adaptation of family members of patients with burns.

Although long-term followup studies have shown that the quality of family support is the most important factor influencing a patient's postburn adjustment, little has been published regarding the process of postburn adaptation of family members. This article describes a model of postburn adaptation that delineates the most common sequence of cognitive and emotional issues faced by autonomous, adult family members of burn survivors from the time of the patient's acute injury through completion of the patient's recovery and rehabilitation. In addition to focusing burn team attention on the needs of family members, this model includes descriptions of specific interventions burn staff can make with family members to resolve the issues faced and thus facilitate appropriate postburn adjustment.

Cutaneous and subcutaneous endometriosis. Surgical and hormonal therapy.

BACKGROUND: Cutaneous or subcutaneous endometriosis is a rare entity that should be suspected in any female presenting with cyclic pain emanating from a mass in the vicinity of an abdominal surgical scar or the umbilicus. OBJECTIVE: The purpose of this report is to examine the diagnostic procedures for endometriosis and to review the therapeutic value of surgical excision alone or in combination with hormonal treatment. METHODS: Endometriosis presenting cutaneously in an infraumbilical laparoscopy scar and endometriosis occurring subcutaneously in a cesarean section scar were both diagnosed via incisional biopsy. Both lesions were treated with hormonal therapy followed by surgical excision. RESULTS: Hormonal therapy with danazol or with leuprolide resulted in reduction of symptoms but was associated with amenorrhea in both cases and with dyspareunia in the second patient. Subsequent laparoscopy and surgical excision of the endometrioma were curative. CONCLUSION: Preoperative hormonal therapy, although sometimes associated with such side effects as amenorrhea, may be used in cases of large endometriotic masses to reduce the size of the surgical defect, but surgical excision remains the treatment of choice.

Sporotrichosis presenting as arthritis and subcutaneous nodules.

Arthritis is a rare manifestation of systemic sporotrichosis. A patient who had sporotrichal arthritis of both wrists and elbows is described. Predisposing factors included alcoholism, rose gardening, and antecedent trauma. The onset of the arthritis was insidious, and the diagnosis was made 2 1/2 years after his first symptoms were noted. Treatment with surgical debridement and a 23-week course of ketoconazole was unsuccessful. A review of the literature suggests that some combination of intravenous or intraarticular amphotericin B and potassium iodide, ketoconazole, or surgery is necessary for effective treatment.

Enhanced tumor imaging with pokeweed mitogen.

Traditional tumor imaging with biotracer techniques relies solely on the target specificity of the biomolecule. We hypothesize that specific imaging is possible by altering the rate of tissue clearance (both normal and aberrant) of any given radiotracer. Pokeweed mitogen (PWM) as a biomodulator, represents a class of molecules which regulate cellular differentiation and cell-cell interactions and, as part of these mechanisms alter tissue clearance rates (both normal and aberrant). Utilizing the B-16/C57BL/6 model, 7 days post-transplantation (which represents log phase growth of the tumor), 10 animals were imaged following an i.v. injection of 1-2 mCi 99mTc-PWM in order to visualize the tumors and determine the optimal imaging kinetics. A specific tumor image is achieved between 120 and 240 min post-injection. In addition, tumor imaging studies using a non-tumor-specific biomolecule were conducted by injecting 19 animals i.v. with 1-2 mCi of 99mTc-human serum albumin (HSA). Twelve of these animals were given 10 micrograms of PWM i.p. at various intervals prior to the 99mTc-HAS administration. Imaging and biodistribution studies were performed at various intervals up to 2 h post-99mTc-HSA injection. A 32-59% increase in the tumor-to-muscle ratio was observed in the PWM-treated animals relative to the non-treated controls. To further investigate the PWM-induced tissue clearance alteration hypothesis, tissue clearance studies using 99mTc-diethylenetriaminepentaacetic acid (DTPA) were conducted in non-tumor bearing ICR mice and the B-16/C57BL/6 tumor bearing animals. 99mTc-DTPA normal tissue clearance rates were significantly increased in the PWM treated animals relative to the non-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic and biochemical heterogeneity in patients with the rhizomelic form of chondrodysplasia punctata--a complementation study.

The genetic relationship between 10 patients with clinical manifestations of rhizomelic chondrodysplasia punctata (RCDP) was studied by complementation analysis after somatic cell fusion. Biochemically, 9 out of the 10 patients were characterized by a partial deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase (DHAP-AT) and an impairment of plasmalogen biosynthesis, phytanate catabolism and the maturation of peroxisomal 3-oxoacyl-CoA thiolase; 3-oxoacyl-CoA thiolase was strongly reduced in the peroxisomes of these patients. Fusion of fibroblasts from these 9 patients with Zellweger fibroblasts resulted in complementation as indicated by the restoration of DHAP-AT activity, plasmalogen biosynthesis, and punctate fluorescence after staining with a monoclonal antibody to peroxisomal thiolase. No complementation was observed after fusion of different combinations of the 9 RCDP cell lines, suggesting that they belong to a single complementation group. The tenth patient was characterized biochemically by a deficiency of DHAP-AT and an impairment of plasmalogen biosynthesis. However, maturation and localization of peroxisomal thiolase were normal. Fusion of fibroblasts from this patient with fibroblasts from the other 9 patients resulted in complementation as indicated by the restoration of plasmalogen biosynthesis. We conclude that mutations in at least two different genes can lead to the clinical phenotype of RCDP.

An outbreak of lindane-resistant scabies treated successfully with permethrin 5% cream.

An outbreak of scabies in 12 persons, after contact with a hospitalized patient with lindane-resistant Norwegian scabies, is described. Resistance to treatment was documented in 7 of 10 patients treated with lindane. Of these, one responded to crotamiton 10% cream, and the remaining six were cured by a single treatment with permethrin 5% cream.

Vasoconstriction and neural excitation in response to transient hypoxia in the rat hippocampal slice.

The vascular and neural responses to transient hypoxia in the rat hippocampal slice were studied. Neural hyperexcitability produced by tissue hypoxia was associated with localized decreases in the diameter of precapillary arterioles. Vasoconstriction occurred periodically along the length of vessels observed. The mean percent decrease in vessel diameter in these narrowed regions was 10.25%. Population spikes recorded in the cell body layer of the dentate gyrus showed a mean increase in amplitude of 71.3%. The mean latency to peak response was similar for both the vessels and neurons. The results suggest mechanisms by which autoregulatory influences on microvessel caliber may be counteracted in conditions of hypoxia and hypotension in the whole animal.

[Diagnosis of Zellweger's cerebrohepatorenal syndrome]. / Diagnostiek van het cerebro-hepato-renale syndroom van Zellweger.

The cerebro-hepato-renal syndrome of Zellweger is an autosomal recessive inborn error of metabolism. Clinically the disease is characterised by craniofacial malformations, a lack of muscle tone, disturbances in liver function, renal cysts and mental retardation. The disease is characterised biochemically by the absence of peroxisomes (microbodies) in liver and kidney and variable abnormalities in mitochondria. This results in elevated concentrations of pipecolic acid and of tri(di)hydroxycoprostanoic acid in urine, CSF and/or duodenal fluid, an elevation of the concentration of very long chain (greater than C22) fatty acids in plasma and fibroblasts and a deficiency of plasmalogens in tissues, erythrocytes and fibroblasts. Moreover, we recently found that in Zellweger patients the activity of dihydroxyacetone phosphate acyltransferase is deficient in tissues, fibroblasts and cultured amniotic fluid cells and that the incorporation of a radioactive precursor of plasmalogens into phospholipids is impaired in fibroblasts and amniocytes. These recent findings allow specific prenatal and postnatal diagnosis of this disease.