Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy--and inhibits progression to status epilepticus (SE). Seizures after traumatic brain injury (TBI) may contribute to pathophysiology. Thus, we hypothesized that endogenous adenosine, acting via A1 receptors, mediates antiepileptic benefit after experimental TBI. We subjected A1-receptor knockout (ko) mice, heterozygotes, and wild-type (wt) littermates (n=115) to controlled cortical impact (CCI). We used four outcome protocols in male mice: (1) observation for seizures, SE, and mortality in the initial 2 h, (2) assessment of seizure score (electroencephalogram (EEG)) in the initial 2 h, (3) assessment of mortality at 24 h across injury levels, and (4) serial assessment of arterial blood pressure, heart rate, blood gases, and hematocrit. Lastly, to assess the influence of gender on this observation, we observed female mice for seizures, SE, and mortality in the initial 2 h. Seizure activity was noted in 83% of male ko mice in the initial 2 h, but was seen in no heterozygotes and only 33% of wt (P<0.05). Seizures in wt were brief (1 to 2 secs). In contrast, SE involving lethal sustained (>1 h) tonic clonic activity was uniquely seen in ko mice after CCI (50% incidence in males), (P<0.05). Seizure score was twofold higher in ko mice after CCI versus either heterozygote or wt (P<0.05). An injury-intensity dose-response for 24 h mortality was seen in ko mice (P<0.05). Physiologic parameters were similar between genotypes. Seizures were seen in 100% of female ko mice after CCI versus 14% of heterozygotes and 25% wt (P<0.05) and SE was restricted to the ko mice (83% incidence). Our data suggest a critical endogenous anticonvulsant action of adenosine at A1 receptors early after experimental TBI.
Ischemic colitis is a commonly misunderstood clinical condition. Although the colon is the most common region of ischemia in the gastrointestinal tract, many surgeons have difficulty with diagnosis and treatment of ischemic colitis. The process can occur from either occlusive vascular disease or nonocclusive disease, and can be gangrenous or nongangrenous. Differentiating gangrenous from nongangrenous disease can be a difficult clinical challenge as both sets of patients generally present with abdominal pain and bloody diarrhea. Although the majority of patients have transient ischemia with nongangrenous colitis that can be successfully managed nonoperatively, prompt recognition and surgical intervention is critical in patients with gangrenous colitis. In this article, the diagnosis and treatment of ischemic colitis is reviewed with emphasis on a systematic, evidence-based approach to management.
Recent studies have shown that the maximum transverse diameter of an abdominal aortic aneurysm (AAA) and expansion rate are not entirely reliable indicators of rupture potential. We hypothesize that aneurysm morphology and wall thickness are more predictive of rupture risk and can be the deciding factors in the clinical management of the disease. A non-invasive, imagebased evaluation of AAA shape was implemented on a retrospective study of 10 ruptured and 66 unruptured aneurysms. Three-dimensional models were generated from segmented, contrastenhanced computed tomography images. Geometric indices and regional variations in wall thickness were estimated based on novel segmentation algorithms. A model was created using a J48 decision tree algorithm and its performance was assessed using ten-fold cross validation. Feature selection was performed using the χ 2 -test. The model correctly classified 65 datasets and had an average prediction accuracy of 86.6% (κ = 0.37). The highest ranked features were sac length, sac height, volume, surface area, maximum diameter, bulge height, and intra-luminal thrombus volume. Given that individual AAAs have complex shapes with local changes in surface curvature and wall thickness, the assessment of AAA rupture risk should be based on the accurate quantification of aneurysmal sac shape and size.
Drug use poses significant challenges to medical management of HIV infection. While most research has focused on the influence of intoxication on unintentional adherence to HIV treatment, drug use may also lead to intentional non-adherence, particularly when individuals believe that mixing medications with drugs is harmful. This study examined whether interactive toxicity beliefs predict non-adherence to antiretroviral therapy (ART) over a prospective period of adherence monitoring. Men and women living with HIV who screened positive for drug use and were being treated with ART (N=530) completed computerized self-interviews, three prospective unannounced pill counts to measure ART adherence, provided urine specimens for drug screening, and HIV viral load results from medical records. Results showed that 189 (35%) participants indicated that they intentionally miss their ART when they are using drugs. These participants also reported common beliefs regarding the perceived hazards of mixing HIV medications with alcohol and other drugs. Multivariable models that controlled for demographic and health characteristics, as well as frequency of alcohol use, showed that intentional non-adherence predicted poorer ART adherence over the prospective month and also predicted poorer treatment outcomes as indexed by unsuppressed HIV viral load. These findings extend previous research to show that interactive toxicity beliefs and intentional non-adherence play a significant role in medication non-adherence for a substantial number of people living with HIV and should be actively addressed in HIV clinical care.
Health disparities in access to antiretroviral therapy (ART) as well as the demands of long-term medication adherence have meant the full benefits of HIV treatment are often not realized. In particular, food insecurity has emerged as a robust predictor of ART non-adherence. However, research is limited in determining whether food insecurity uniquely impedes HIV treatment or if food insecurity is merely a marker for poverty that interferes more broadly with treatment. This study examined indicators of poverty at multiple levels in a sample of 364 men and 157 women living with HIV recruited through an offering of a free holiday food basket. Results showed that 61% (N = 321) of participants had experienced at least one indicator of food insecurity in the previous month. Multivariate analyses showed that food insecurity was closely tied to lack of transportation. In addition, food insecurity was associated with lacking access to ART and poor ART adherence after adjusting for neighbourhood poverty, living in an area without a supermarket (food desert), education, stable housing, and reliable transportation. Results therefore affirm previous research that has suggested food insecurity is uniquely associated with poor ART adherence and calls for structural interventions that address basic survival needs among people living with HIV, especially food security.
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