Brief dialectical behavior therapy (DBT-B) for suicidal behavior and non-suicidal self injury.

The purpose of this study is to evaluate the effectiveness of a shorter course of Dialectical Behavior Therapy (DBT) in enhancing treatment retention and reducing: urges to engage in non-suicidal self injury (NSSI), NSSI, suicide ideation, and subjective distress in borderline personality disorder (BPD). Twenty patients with BPD received a six-month course of Dialectical Behavior Therapy (DBT-B). DBT-B was delivered in the standard manner except for the shortened duration from one-year minimum to six months. All variables were measured at baseline, and at six months. Data were analyzed using paired t-tests. Treatment retention rate was 95%. Significant reductions were found in NSSI urges, NSSI, suicide ideation, subjective distress, depression, and hopelessness between baseline and six months. These results support the use of DBT-B in a six-month format when NSSI and suicidal behavior and ideation are the targeted behaviors. Target behaviors were reduced significantly and retention was extremely high in comparison to other interventions for this population. A large scale randomized controlled trial investigating its efficacy is warranted to determine if the results can be replicated and if improvement can be sustained.     

The effects of three nebulized osmotic agents in the dry larynx.

PURPOSE: This investigation examined the effects of nebulized hypertonic saline, isotonic saline (IS), and sterile (hypotonic) water on phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) following a surface laryngeal dehydration challenge. METHOD: In a double-blind, randomized experimental trial, 60 vocally healthy women (n = 15 per group) underwent a laryngeal desiccation challenge involving oral breathing for 15 min using medical-grade dry air (RH<1%). Three of the four groups then received nebulized isotonic saline (0.9% NaCl), hypertonic saline (7% NaCl), or sterile (hypotonic) water, respectively; the 4th group served as a nontreatment control. PTP and PPE were estimated for high-pitched productions at baseline, immediately postdesiccation, and at 5, 20, 35, and 50 min postnebulization. RESULTS: PTP increased significantly for all groups following the desiccation challenge. PTP values were, on average, 0.5 cm H(2)O greater immediately postdesiccation versus baseline. In contrast, PTP values did not change significantly following the administration of nebulized treatments, although a temporary trend toward a reduction in PTP was observed for the IS group. Unexpectedly, PPE ratings decreased significantly after the desiccation challenge. In general, PPE ratings were poorly correlated with PTP measures. CONCLUSION: A laryngeal desiccation challenge (i.e., temporary exposure to extremely low relative humidity while breathing transorally) significantly increased PTP. Although interesting trends emerged, none of the nebulized treatments significantly enhanced recovery from the negative effects of desiccation on PTP. In light of very low correlations between PTP and PPE, serious questions are raised regarding presumed associations between these measures.     

The peroxisome proliferator-activated receptor gamma coactivator-1 alpha gene (PGC-1alpha) is not associated with type 2 diabetes mellitus or body mass index among Hispanic and non Hispanic Whites from Colorado.

The objective of the study was to test for an association between type 2 diabetes mellitus (T2DM) and body mass index (BMI) and three single nucleotide polymorphisms (SNP)s in the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) gene. We were also interested in whether these associations differed by tertiles of diet, physical activity or presence of polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene among Hispanics and Non-Hispanic Whites (NHW) from Colorado. We studied 216 Hispanic pedigrees (1850 nuclear families) and 236 NHW pedigrees (1240 families) from the San Luis Valley and Denver. We genotyped the Gly482Ser, Thr528Thr and Thr612Met polymorphisms in the PGC-1alpha gene and the Pro12Ala polymorphism of the PPAR-gamma gene. Historical physical activity (average METS/week) as well as average dietary intake over the past year was assessed by self-report. Data were analyzed using the Family Based Association Test (FBAT) as well as generalized estimating equations (GEE). We did not find any significant association between three SNPs in the PGC-1alpha gene and T2DM in Hispanics or NHW; however, using FBAT, we found the common Thr612Thr allele of the PGC-1alpha gene to be associated with T2DM among Hispanic subjects carrying the rare Pro12Ala allele of the PPAR-gamma gene (p=.003). We found similar associations when we considered a haplotype containing that allele (p=.002). However, the results of the GEE analysis did not confirm these findings: odds ratio (OR)=1.68, 95% CI (0.5, 5.2) suggesting these results may due to chance. BMI also did not show any consistent associations with the PGC-1alpha gene. In conclusion, we did not find an association between the PGC-1alpha gene and T2DM or BMI and there were no consistent interactions with diet, physical activity or the Pro12Ala polymorphism of the PPAR-gamma gene.     

Rat Cytomegalovirus-Accelerated Transplant Vascular Sclerosis Is Reduced with Mutation of the Chemokine-Receptor R33

Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Deltar33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 x 10(5) pfu RCMV or RCMV-Deltar33 on postoperative day (POD) 1. Grafts from RCMV-Deltar33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Deltar33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Deltar33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-receptor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration.     

Comment on the 'pilot' GRACIA-2 randomized trial: reply

We thank Dr Villata et al. for their thought-provoking comments.Their concern about the suitableness to choose combined endpointsin clinical trials deserves some comment.     

Noninvasive measurement of systemic vascular resistance using Doppler echocardiography.

BACKGROUND: Systemic vascular resistance (SVR) is an integral therapeutic component of patients with heart failure and shock. We hypothesized that the ratio of the peak mitral regurgitant velocity (MRV) (m/s) to left ventricular outflow time-velocity integral (TVI(LVOT)) (cm) by Doppler would provide a noninvasive correlate of SVR. METHODS: SVR was correlated to MRV/TVI(LVOT) in 33 patients undergoing right heart catheterization. Receiver operating characteristic curves were generated to determine the best-balanced sensitivity and specificity to identify SVR > 14 Wood units (WU) and <10 WU. RESULTS: MRV/TVI(LVOT) correlated well with SVR (r = 0.842, 95% confidence interval 0.7-0.92, P <.001, Y = 0.459 + 49.397*X). By receiver operating characteristics, MRV/TVI(LVOT) > 0.27 had a 70% sensitivity and a 77% specificity to identify SVR > 14 WU. MRV/TVI(LVOT) < 0.2 had a 92% sensitivity and a 88% specificity to identify SVR < 10 WU. CONCLUSION: Doppler echocardiography provides a reliable noninvasive assessment of SVR.     

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.     

Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.     

Diabetes in female rats; changes in liver microsomal aminopyrine N-demethylase and UDP-glucuronyl transferase activities

Short or long term diabetes in female rats produced remarkable activation of aminopyrine N-demethylation, inhibition of oestrone and p-nitrophenol glucuronidation and no changes in morphine UDP-glucuronyltransferase activity in vitro. Km and Vmax for these reactions were determined. Insulin treatment partially antagonized diabetes activation of aminopyrine N-demethylation: it restored decreased UDP-glucuronyltransferase activities for oestrone and p-nitrophenol only in long term and short term diabetes, respectively. Insulin also markedly inhibited morphine glucuronidation. Triton X-100 also displayed a differential pattern of activation for the glucuronidation reactions in liver microsomes of diabetic rats. Results suggest that diabetes in female rats may increase the actual amount of enzyme protein for aminopyrine metabolism and to decrease that for oestrone and p-nitrophenol.