No change in neuropsychological dysfunction or emotional processing during treatment of major depression with cognitive-behaviour therapy or schema therapy.

BACKGROUND: Impaired neuropsychological functioning is a feature of major depression. Previous studies have suggested that at least some aspects of neuropsychological functioning improve with successful treatment of major depression. The extent to which medications may affect the degree of normalization of these functions is unclear. The aim of the current study was to examine the course of neuropsychological functioning during treatment of major depression with cognitive-behaviour therapy (CBT) or schema therapy (ST). METHOD: A total of 69 out-patients with a primary diagnosis of major depression and 58 healthy controls completed mood ratings, neuropsychological measures, and measures of emotional processing at baseline and after 16 weeks. Participants were randomized after baseline assessment to a year-long course of CBT or ST. Patients reassessed at 16 weeks were medication-free throughout the study. RESULTS: Significant neuropsychological impairment was evident at baseline in depressed participants compared with healthy controls. After 16 weeks of psychotherapy, mean depression rating scores fell more than 50%. However, no neuropsychological measures showed convincing evidence of significant improvement and emotional processing did not change. CONCLUSIONS: Persisting impairment in neuropsychological functioning after the first 16 weeks of CBT or ST suggests a need to modify psychological treatments to include components targeting cognitive functioning.

A safety analysis of oral prednisone as a pretreatment for rituximab in rheumatoid arthritis.

The administration of 100 mg of methylprednisolone intravenously (IV) 1/2 h prior to rituximab decreases the incidence of acute infusion reactions (AIRs). However, this pretreatment adds considerable time and conveys potential risk. We performed an open-label prospective assessment of oral prednisone as a pretreatment to rituximab. This was a 26-week open-label trial of 40 mg of oral prednisone given 1/2 h prior to rituximab as a prophylaxis against AIRs in patients with rheumatoid arthritis (RA). The primary endpoint was AIRs in the first 24 h after their initial infusion. Secondary endpoints include AIRs during the 24 h following their second infusion and any adverse events experienced during the 26-week study; efficacy measures were also followed as secondary endpoints. Sixty-four subjects were screened, and 50 subjects qualified. Fourteen out of the 50 (28 %) subjects had AIRs within 24 h of their first infusion. There were four AIRs (8.3 %) within 24 h of their second infusion. One of day 0 AIRs required drug discontinuation (wheezing/bronchospasm). Forty out of 50 (80 %) subjects experienced an adverse event during the 26 weeks. There were three SAEs deemed not to be study-drug related. The DAS28 and HAQ-DI all improved significantly at weeks 8, 16, and 26 compared to baseline. Historical controls demonstrate that 27 % of RA subjects experience AIRs with their first rituximab infusion. Our data suggest a smaller dose of oral prednisone is an effective alternative to IV methylprednisolone as a pretreatment for rituximab in patients with RA.

Measures of temperament and character are differentially impacted on by depression severity.

BACKGROUND: Cloninger's Temperament and Character Inventory (TCI) is a widely used measure of personality. Two scales of the TCI, harm avoidance (HA) and self directedness (SD), have been shown to be influenced by depressed mood. We examined how the seven TCI scales and their subscales are correlated with depression severity before and after treatment. We also examined whether changes in personality measures could be attributed to changes in depression severity. METHODS: Two clinical samples of depressed out-patients were recruited for trials to examine predictors of treatment response to antidepressants (N=195) and psychotherapies (N=177). Assessment included the Montgomery-Asberg depression rating scales (MADRS), Hopkins Symptom Checklist (SCL-90) and TCI at baseline and after treatment. RESULTS: After treatment, in both samples, depression severity correlated significantly with HA and negatively with SD. Multiple regression analysis revealed that changes in SD and HA over treatment were related to improvement in depression. In the psychotherapy trial baseline MADRS scores correlated with low SD and high HA. LIMITATIONS: The trial results are applicable to mild-moderately depressed out-patients. CONCLUSIONS: Depression severity influences the total scales and most of the subscale measures of HA and SD. Some personality traits, as measured by the TCI, were not impacted upon by mood. Clinically mood should be taken into account when assessing personality measures of negative affect using the TCI.

Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial.

OBJECTIVE: Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia-induced ReA. METHODS: This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline. RESULTS: The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups. CONCLUSION: These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia-induced ReA.

Psoriasiform lesions induced by tumour necrosis factor antagonists: a skin-deep medical conundrum.

Rarely, tumour necrosis factor (TNF)alpha antagonist therapy has been associated with de novo psoriasiform eruptions. This is unusual in that these same drugs are used to treat psoriasis. Most of these cases involve the palms and soles, yet palmoplantar pustular psoriasis represents only 1.7% of all cases of psoriasis. Keratoderma blenorrhagicum is a psoriasiform rash that occurs primarily on the palms and soles of some patients with reactive arthritis. It is grossly and histologically indistinguishable from pustular psoriasis. Chlamydia trachomatis is a common aetiological agent for reactive arthritis, and in vitro studies have shown that chlamydial replication is inversely proportional to TNFalpha levels. Three patients taking TNFalpha antagonists are presented who developed such lesions and who were found to be positive for C trachomatis DNA in the affected skin. It is proposed that these psoriasiform lesions may not be psoriasis, but rather keratoderma blenorrhagicum.

The effect of a low-carbohydrate diet on bone turnover.

INTRODUCTION: Low-carbohydrate diets have become popular as weight loss techniques. These diets are high in protein, saturated fats, and omega-6 fatty acids. They also lead to a ketogenic state. These factors could lead to increased bone turnover. This study was designed to see whether a low-carbohydrate diet would lead to increased bone turnover in humans. METHODS: Thirty patients (15 study subjects and 15 controls) were recruited for this 3-month study. The 15 patients on the diet were instructed to consume less than 20 g of carbohydrates per day for the 1st month and then less than 40 g per day for months 2 and 3. Control subjects had no restrictions on their diet. The primary end point was urinary N-telopeptide (UNTx) at 3 months. Secondary end points included UNTx at 1 month, bone-specific alkaline phosphatase (BSAP) at 1 month, bone turnover ratio (BSAP/UNTx) at 1 month, and weight loss. RESULTS: The mean UNTx in the study subjects increased by 1.6 [95% confidence interval (CI) +/-22.8] compared with an increase of 1.9 (95% CI +/-17.6) in the controls at 3 months (p=0.86). The mean UNTx decreased by 2.2 (95% CI +/-27.2) and 3.1 (95% CI +/-17.6) at 1 month in the dieters and controls, respectively (p=0.36). The mean BSAP decreased by 0.53 (95% CI +/-2.96) in the dieters and increased by 0.34 (95% CI +/-2.92) in the controls at 1 month (p=0.27). The bone turnover ratio increased by 0.08 (95% CI +/-0.81) in the dieters and by 0.05 (95% CI +/- 0.27) in the controls at 1 month (p=0.78). The dieters lost 6.39 kg versus 1.05 kg for the controls at 3 months (p=0.0008). CONCLUSIONS: Although the patients on the low-carbohydrate diet did lose significantly more weight than the controls did, the diet did not increase bone turnover markers compared with controls at any time point. Further, there was no significant change in the bone turnover ratio compared with controls.

The relationship between performance on the standardised field sobriety tests, driving performance and the level of Delta9-tetrahydrocannabinol (THC) in blood.

The consumption of Delta9-tetrahydrocannabinol (THC) as cannabis has been shown to result in impaired and culpable driving. Testing drivers for the presence of THC in blood is problematic as THC and its metabolites may remain in the blood for several days following its consumption, even though the drug may no longer have an influence on driving performance. In the present study, the aim was to assess whether performance on the standardised field sobriety tests (SFSTs) provides a sensitive measure of impaired driving behaviour following the consumption of THC. In a repeated measures design, 40 participants consumed cigarettes that contained either 0% THC (placebo), 1.74% THC (low dose) or 2.93% THC (high dose). For each condition, after smoking a cigarette, participants performed the SFSTs on three occasions (5, 55 and 105 min after the smoking procedure had been completed) as well as a simulated driving test on two occasions (30 and 80 min after the smoking procedure had been completed). The results revealed that driving performance was not significantly impaired 30 min after the consumption of THC but was significantly impaired 80 min after the consumption of THC in both the low and high dose conditions. The percentage of participants whose driving performance was correctly classified as either impaired or not impaired based on the SFSTs ranged between 65.8 and 76.3%, across the two THC conditions. The results suggest that performance on the SFSTs provides a moderate predictor of driving impairment following the consumption of THC and as such, the SFSTs may provide an appropriate screening tool for authorities that wish to assess the driving capabilities of individuals suspected of being under the influence of a drug other than alcohol.

Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity.

AIMS/HYPOTHESIS: Beta cell inflammation and cytokine-induced toxicity are central to autoimmune diabetes development. Lipid mediators generated upon lipoxygenase (LO) activation can participate in inflammatory pathways. 12LO-deficient mice are resistant to streptozotocin-induced diabetes. This study sought to characterise the cellular processes involving 12LO-activation lipid inflammatory mediator production in cytokine-treated pancreatic beta cells. METHODS: Islets and beta cell lines were treated with a combination of IL-1beta, IFN-gamma and TNF-alpha, or the 12LO product 12(S)-hydroxyeicosatetraenoic acid (HETE). Insulin secretion was measured using an enzyme immunoassay, and cell viability was evaluated using an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay. 12LO activity was evaluated and 12LO protein levels were determined using immunoblotting with a selective leucocyte type 12LO antibody. Cellular localisation of 12LO was evaluated using immunocytochemistry. RESULTS: Basal expression of leucocyte type 12LO protein was found in human and mouse islets and in several rodent beta cell lines. In mouse beta-TC3 cells, and in human islets, cytokines induced release of 12-HETE within 30 min. Cytokine addition also induced a rapid translocation of 12LO protein from the cytosol to the nucleus of beta-TC3 cells as shown by subcellular fractionation and immunostaining. Cytokine-induced cell death and inhibition of insulin secretion were partially reversed by baicalein, a 12LO inhibitor. 12(S)-HETE inhibited beta-TC3 cell insulin release in a time- and concentration-dependent manner. Incubating beta-TC3 cells with 100 nmol/l of 12(S)-HETE resulted in a 57% reduction in basal insulin release (6 h), and a 17% increase in cell death (18 h) as compared with untreated cells. 12(S)-HETE activated the stress-activated protein kinase c-Jun N-terminal kinase and p38 within 15 min, as judged by increased kinase protein phosphorylation. CONCLUSIONS/INTERPRETATION: The data suggest that inflammatory cytokines rapidly activate 12LO and show for the first time that cytokines induce 12LO translocation. The effects of 12-HETE on insulin secretion, cytotoxicity and kinase activation were similar to the effects seen with cytokines. The results provide mechanistic information of cytokine-induced toxic effects on pancreatic beta cells and support the hypothesis that blocking 12LO activation could provide a new therapeutic way to protect pancreatic beta cells from autoimmune injury.

Infants in a neonatal intensive care unit: parental response.

OBJECTIVE: To compare the psychosocial functioning of the parents (mother and father) of infants admitted to a neonatal intensive care unit (NICU) with the parents of infants born at term and not admitted to the NICU. DESIGN: Random sample of NICU parents and term non-NICU parents were assessed across a variety of psychiatric and psychosocial measures shortly after the birth of their infant. SETTING: Christchurch Women's Hospital, New Zealand. Labour ward and level III NICU. PARTICIPANTS: A total of 447 parents (242 mothers; 205 fathers) with an infant admitted to a regional NICU during a 12 month period; 189 parents (100 mothers; 89 fathers) with infants born at term and not requiring NICU admission. MAIN OUTCOME MEASURES: Depression and anxiety symptoms, psychosocial functioning. RESULTS: Overall, levels of anxiety and depression were low in both parent groups. Compared with control parents, a higher percentage of NICU parents had clinically relevant anxiety and were more likely to have had a previous NICU admission and be in a lower family income bracket. Infant prematurity was associated with higher levels of symptomatology in both NICU mothers and fathers. CONCLUSIONS: Specific interventions are not needed for most parents who have an infant admitted to the NICU as they appear to adapt relatively successfully. Infant prematurity impacts negatively on the father as well as the mother. Consequently these parents may benefit from increased clinical attention.

An evaluation of the sensitivity of the Standardised Field Sobriety Tests (SFSTs) to detect impairment due to marijuana intoxication.

The Standardised Field Sobriety Tests (SFST) were developed to test for alcohol intoxication but are currently being used by the State Police of Victoria (Australia) to test for driving impairment associated with drugs other than alcohol. The aim of the present study was to assess whether the SFSTs provide a sensitive measure of impairment following the consumption of a drug other than alcohol: delta-9-tetrahydrocannabinol (THC or cannabis). In a repeated-measures design, 40 participants consumed cigarettes that contained either 0% THC (placebo), 1.74% THC (low dose) or 2.93% THC (high dose). For each condition, after smoking a cigarette, participants performed the SFSTs on three occasions: 5 min (Time 1), 55 min (Time 2) and 105 min (Time 3) after the smoking procedure had been completed. The results revealed that there was a positive relationship between the dose of THC administered and the number of participants classified as impaired based on the SFSTs. Results also revealed that the percentage of participants classified as impaired decreased from Time 1 to Time 3 and that the addition of a new sign, head movements or jerks (HMJ), increased the percentage of participants classified as impaired in both the low and high THC conditions. These findings suggest that impaired performance on the SFSTs is positively related to the dose of THC administered and that the inclusion of HMJ as a scored sign in the SFSTs improves their predictive validity when testing for THC intoxication.

Inflammation blockade improves pancreatic islet function.

Pancreatic islet transplantation can replace insulin-secreting beta cells in patients with diabetes mellitus. However, current methodology for isolating islets from a pancreas only retrieves a portion of the total islets. Within these limited number of islets, nearly 50% of beta cells lose biological function before transplantation. Protecting and improving beta-cell viability and function was the goal of this study. Previously we observed that an anti-inflammatory compound, lisofylline (LSF), protects beta cells from cytotoxicity during diabetes development. In this study, we demonstrated that human islets treated in vitro with LSF retained beta-cell glucose responsiveness and insulin secretion in the presence of multiple proinflammatory cytokines. In addition, LSF treatment in vitro enhanced basal insulin production in beta cells, suggesting that LSF can directly improve beta-cell function. LSF reduced beta-cell apoptosis induced by proinflammatory cytokines by 50%. Importantly, 30% fewer LSF-treated islets were sufficient to achieve insulin independence in a murine islet transplantation model. These results demonstrate the ability of LSF-like compounds to protect and enhance beta-cell function, suggesting the potential of using LSF or its analogs in islet transplantation.

Impact of donor immune cells in pancreatic islet transplantation.

Autoimmune-mediated cytotoxicity may cause pancreatic islet transplant failure, leading to recurrent diabetes. Protection of islet grafts depends on immunosuppressive control, which may also prevent autoimmune recurrence of diabetes. In this study, we compared the survival of syngeneic islet transplants using different strains of donor mice. We observed extended functional survival in the islet grafts from donors lacking the genetic background and potential of autoimmunity. Without immunosuppression, the islet grafts of NOR and immune-deficient NOD. Scid donors functioned up to 3 weeks in syngeneic islet transplants compared to 3-day survivals with the grafts from NOD donors. T-cell proliferation and activation markers, CD44 and CD69, were upregulated in NOD donors, suggesting that T-cell activation had occurred prior to pancreas procurement. Systemic delivery of a recombinant adenoassociated viral vector (AAV) encoding the viral (vIL-10) IL-10 gene (AAV vIL-10) in NOD recipients protected syngeneic islets from autoimmune destruction. Alternatively, pretreatment of NOD donor mice with AAV vIL-10 prolonged islet graft survival in untreated NOD recipients. Both studies indicate the effectiveness of vIL-10 gene therapy in autoimmune regulation. These results suggest that a donor factor may exist in autoimmune-prone donors. Therefore, autoimmune recurrence of diabetes may result from donor immune cells transferred during islet transplantation. The AAV vIL-10 gene therapy suppressed previously activated donor T cells and protected the grafted islets from autoimmune-mediated destruction.

Assessment of human pancreatic islets after long distance transportation.

Pancreatic islet transplantation can replace functional insulin-secreting beta cells for patients with type 1 diabetes. More than 300 patients who have received islet transplantation have returned to a euglycemic condition without using insulin. Therefore, islet transplantation has gained public attention and interest. Unfortunately, shortages in organ donations, suboptional antirejection regimens, and difficulties in islet isolation limit clinical utilization of this therapy. Recently, successful islet transplantation has been reported using a centralized islet isolation facility. The advantage of this experience is that it avoids the high costs in building an isolation facility and maintaining an experienced technical team. However, a private airplane carrier was required for transporting islets back to the transplantation site in a remote hospital. The cost of this specialized transportation was still too high to be considered as a routine procedure. In this study, we report our experience using commercial carriers to deliver isolated human islets from an established isolation facility to a remote medical center.

Chronic MDMA (ecstasy) use, cognition and mood.

RATIONALE: It has been suggested that 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) causes damage to the serotonergic system, and that this damage results in cognitive and mood impairments. OBJECTIVES: To examine the effect of chronic MDMA usage on a wide battery of cognitive tests and psychological abilities and processes. METHODS: In the present study, the performance of 17 participants with a history of MDMA use was compared to the performance of 15 control subjects on a battery of neuropsychological tests. This battery included tests for depression, immediate word recall, delayed recall, attention and working memory. RESULTS: Results indicated that the MDMA group had significantly higher scores for depression than the control group, and displayed poorer delayed recall and verbal learning than controls after accounting statistically for the effects of cannabis and depression. CONCLUSIONS: These results suggest that MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks.

Assessing inhibitory control: a revised approach to the stop signal task.

The stop signal task (stop task) is designed to assess inhibitory control and is a frequently used research tool in clinical disorders such as ADHD and schizophrenia. Previous methods of setting stop signal delay and of assessing inhibitory control are problematic. The current study reports two modifications that improve the task as a measure of inhibitory control. The first modification was to set stop signal delays proportional to go mean reaction time (go MRT) to better account for inter-subject variability in go MRT. Twenty-eight normal children were tested, and all standard, stop task dependent measures were obtained when delays were set by this method. The second modification was to calculate a novel dependent measure called the area of inhibition (AOI) which provides a more complete measure of inhibitory control than the slope of the relative finishing time z-scores (ZRFT-slope). Implications for the assessment of inhibitory control in clinical populations are discussed.

Soft tissue disease.

In the assessment of patients with soft tissue complaints, it is important to consider infectious etiologies in the differential diagnosis, especially in immunocompromised hosts. The exact categorization of some bacterial infections of the soft tissues may be difficult. The structures potentially involved include the skin, subcutaneous tissue, fascia, and skeletal muscle. Classification is usually based upon the anatomic structure involved, the infecting organism, and the clinical picture. The categorization is complicated by the fact that some infections may involve several soft tissue components and multiple bacterial species. In this review, we will cover cutaneous and subcutaneous tissue infections, fasciitis, septic bursitis, tendonitis, and pyomyositis.