Airway hypocapnia increases microvascular leakage in the guinea pig trachea.

We have previously shown that airway hypocapnia induced bronchoconstriction in the guinea pig lung by releasing tachykinins. To examine whether airway hypocapnia could also cause an increase in airway microvascular leakage, a tracheal segment was isolated in vivo in anesthetized guinea pigs and unidirectionally ventilated (200 ml/min) for 1 h with fully conditioned air (0% CO2) or isocapnic gas (5% CO2). The lungs were ventilated through a distally placed tracheal cannula. Microvascular leakage was quantitated by the injection of Evans blue (EB) and its extraction from the tracheal segment. EB extravasation was increased in tracheae exposed to 0% CO2 (52.3 +/- 2.0 micrograms/g wet tissue) compared with tracheae exposed to 5% CO2 (26.4 +/- 2.9 micrograms/g; p less than 0.05) and to tracheae from spontaneously breathing guinea pigs (25.2 +/- 2.3 micrograms/g; p less than 0.05). Groups of animals in which trachea were unidirectionally ventilated with 0% CO2 were then pretreated with a range of drugs in an attempt to determine the mediators responsible for the microvascular leakage with 0% CO2. Capsaicin and morphine pretreatment did not significantly alter 0% CO2-induced EB extravasation, and phosphoramidon prevented rather than increased extravasation, suggesting that tachykinins did not play a role. The hypocapnia-induced increase in microvascular leakage was, however, prevented by indomethacin pretreatment and significantly attenuated by dazmegrel, a thromboxane synthetase inhibitor. We conclude that airway hypocapnia causes microvascular leakage in the guinea pig trachea and that this effect is mediated by prostaglandins and/or thromboxane.     

Trends and Predictors for Vagotomy When Performing Oversew of Acute Bleeding Duodenal Ulcer in the United States

Background In the era of Helicobacter pylori treatment, the role of vagotomy in bleeding duodenal ulcers is debatable. National outcomes were evaluated to determine the current surgical treatment and use of vagotomy for bleeding duodenal ulcers. Methods Data from the Nationwide Inpatient Sample (NIS) were used from years 1999 to 2003. Patients were selected using diagnostic codes for acute duodenal ulcer bleed and procedure codes for simple oversew of a bleeding ulcer and vagotomy. Data were analyzed using multiple linear and logistic regression. Results Between 1999 and 2003, 100,931 patients with an acute bleeding duodenal ulcer were identified. Over time, there was a decrease in the number of acute bleeding ulcers (p = 0.027) and a decrease in the number of vagotomies (p = 0.027). A high co-morbidity index [odds ratio (OR), 0.60, p = 0.017], operation in the Midwest (OR 0.50, p < 0.001) and operation in the West (OR 0.68, p = 0.034) were predictive of no vagotomy during surgery for a bleeding duodenal ulcer. Conclusions A vagotomy is not commonly performed during surgical treatment of an acute bleeding duodenal ulcer. This variation in practice was not fully explained by patient characteristics. We must seek new evidence to determine the safety of combined medical and surgical management of this clinical problem. Presented at DDW/SSAT May 20–24, Los Angeles, California.     

Rumination: One Construct, Many Features in Healthy Individuals, Depressed Individuals, and Individuals with Lupus

Rumination has been associated with depression and negative health effects. Yet measures of rumination appear to index multiple constructs that may be differentially related to clinical phenomena. To clarify this literature, we explored convergence and divergence among self-report measures of rumination in 349 undergraduates, 59 depressed adults, 81 healthy adults, and 15 never-depressed adults with Systemic Lupus Erythematosis (SLE). Results suggested there are separate constructs labeled rumination with different relationships to depression. Yet, aggregate measures index a central construct. Depressed individuals ruminated more, across measures, than individuals with SLE, who ruminated more than healthy individuals; this relationship was mediated by dysphoria. Thus, administering multiple rumination measures and attending to constructs assessed by rumination measures appears important in clinical studies.     

Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.     

Use of the Noninvasive Ankle Distractor With Talar Dome Osteochondral Graft Transplantation

Talar dome lesions greater than 1 cm in diameter are often treated with ankle joint mosaicplasty. The purpose of this article is to present the use of a noninvasive ankle distractor that can improve access to the talus when used with a malleolar osteotomy. The use of the distractor allows for graft insertion at a more appropriate angle in relationship to the talar cartilage, avoidance of invasive distractor usage, and potential use of a smaller osteotomy.     

Tau isoform expression in frontotemporal dementia without tau deposition

In many cases of sporadic frontotemporal dementia (FTD) and in FTD caused by tau mutations (FTDP-17) there is disruption of the normal splicing of tau leading to the aberrant expression of tau isoforms and neurodegeneration. This suggests a central role for tau in the pathogenesis of FTD. However, more than half the cases of sporadic FTD show no tau deposition. We question whether altered expression is also involved in the pathogenesis of tau-negative FTD. Real-time polymerase chain reaction was used to investigate tau isoform expression in tau-negative FTD and age-matched controls. There were no differences in total tau mRNA or 4R versus 3R isoform expression. Our study suggests that perturbed tau mRNA expression is unlikely to be involved in the pathogenesis of tau-negative FTD.