Alcohol increases tumor necrosis factor alpha and decreases nuclear factor-kappab to activate hepatic apoptosis in genetically obese mice

Both obesity and alcohol can cause oxidative stress, cytokine induction, and steatohepatitis. To determine the consequences of their combination, we compared the hepatic effects of moderate ethanol binges in lean and obese ob/ob mice. Mice received water or ethanol (2.5 g/kg) by gastric intubation daily for 4 days, and were killed 2 hours after the last administration. Some obese mice also received pentoxifylline, an inhibitor of tumor necrosis factor-alpha (TNF-alpha) production, before each ethanol administration. In lean mice, these moderate ethanol doses did not increase plasma TNF-alpha and hepatic caspase-3 activity, but triggered some apoptotic hepatocytes. Naive ob/ob mice had a few necrotic and apoptotic hepatocytes, but exhibited little oxidative stress, possibly because of adaptive increases in manganese superoxide dismutase, heat shock protein 70 (Hsp70), mitochondrial cytochrome c, and mitochondrial DNA. Alcohol administration to ob/ob mice did not increase oxidative stress despite increased CYP2E1, but increased plasma TNF-alpha, further increased Hsp70, and profoundly decreased p65 nuclear factor kappaB (NF-kappaB) protein and DNA-binding activity in nuclear extracts. Caspase-3 was activated, and more apoptotic hepatocytes were found in intoxicated obese mice than naive obese mice. In intoxicated obese mice, pentoxifylline fully prevented the increase in plasma TNF-alpha the decrease in nuclear NF-kappaB activity, and the increase in hepatic caspase-3, and it also decreased hepatic triglycerides. In conclusion, obese mice develop adaptations that may limit oxidative stress. Moderate ethanol intoxication does not increase oxidative stress in obese mice, but increases TNF-alpha and also decreases nuclear NF-kappaB activity, thus unleashing the apoptotic effects of TNF-alpha.     

Transgluteal approach for draining pelvic fluid collections in pediatric patients

PURPOSE: To evaluate a transgluteal approach for draining pelvic fluid collections in pediatric patients. MATERIALS AND METHODS: Institutional review board approval and informed consent for interventional procedures were obtained. From September 1995 to December 2002, 140 abdominopelvic fluid collections were drained at two institutions. Retrospective analysis of a prospectively gathered procedural database revealed that a transgluteal approach was used to drain 53 of these 140 collections (38%) in 51 patients (29 female, 22 male; mean age, 11.2 years; age range, 0.2-19 years). All patients received antibiotics before the procedure. A retrospective analysis was conducted of the patients' medical records and diagnostic imaging and interventional procedure findings, including the reason for referral; location, volume, and character of collections; method and equipment used for evacuation; duration of therapy; evidence of complications; results of microbiologic examination of specimens; and success rates. RESULTS: Transgluteal drainage was performed with computed tomographic (CT) guidance in 45 of the 53 collections (85%), with fluoroscopic guidance in three (6%), and with a combination of both modalities in five (9%). A drainage catheter was successfully placed in 49 collections; four small collections were aspirated without drain placement. Infected fluid was obtained from 41 collections, and serosanguineous fluid was obtained from 12 collections. The mean volume aspirated was 80 mL (2-600 mL). A positive culture was obtained at 28 of the 53 procedures. The mean duration of catheter placement was 4 days (range, 2-14 days). There were no major complications. CONCLUSION: The transgluteal approach to the drainage of abdominopelvic fluid collections with imaging guidance is safe and effective.     

The contribution of statistical parametric mapping in the assessment of precuneal and medial temporal lobe perfusion by 99mTc-HMPAO SPECT in mild Alzheimer's and Lewy body dementia

AIM: To assess the role of 99mTc-hexamethylpropyleneamine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) imaging of the precuneus and medial temporal lobe in the individual patient with mild Alzheimer's disease and dementia with Lewy bodies (DLB) using statistical parametric mapping and visual image interpretation. METHODS: Thirty-four patients with mild late-onset Alzheimer's disease, 20 patients with early-onset Alzheimer's disease, 15 patients with DLB and 31 healthy controls were studied. All patients fulfilled appropriate clinical criteria; the DLB patients also had evidence of dopaminergic presynaptic terminal loss on 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane imaging. 99mTc-HMPAO SPECT brain scans were acquired on a multidetector gamma camera and images were assessed separately by visual interpretation and with SPM99. RESULTS: Statistical parametric maps were significantly more accurate than visual image interpretation in all disease categories. In patients with mild late-onset Alzheimer's disease, statistical parametric mapping demonstrated significant hypoperfusion to the precuneus in 59% and to the medial temporal lobe in 53%. Seventy-six per cent of these patients had a defect in either location. No controls had precuneal or medial temporal lobe hypoperfusion (specificity, 100%). Statistical parametric mapping also demonstrated 73% of patients with DLB to have precuneal abnormalities, but only 6% had medial temporal lobe involvement. CONCLUSION: These findings illustrate the capability of statistical parametric mapping to demonstrate reliable abnormalities in the majority, but not all, patients with either mild Alzheimer's disease or DLB. Precuneal hypoperfusion is not specific to Alzheimer's disease and is equally likely to be found in DLB. In this study, medial temporal hypoperfusion was significantly more common in Alzheimer's disease than in DLB. Statistical parametric maps appear to be considerably more reliable than simple visual interpretation of 99mTc-HMPAO images for these regions.     

Antioxidant restriction and oxidative stress in short-duration exhaustive exercise

PURPOSE: To determine the effect of dietary antioxidant restriction on oxidative stress, antioxidant defenses, and exercise performance in athletes. Oxidative stress has been shown to increase during exercise. To alleviate oxidative stress, a high intake of antioxidant rich foods or supplements may be required in trained athletes. METHODS: Plasma oxidative stress and antioxidant defenses were examined in 17 trained athletes who underwent two separate exercise tests. Before the initial exercise test participants followed their habitual (high) antioxidant (H-AO) diets. Then they followed a 2-wk restricted-antioxidant (R-AO) diet before the second exercise test. Blood was taken at rest, after submaximal and high-intensity exhaustive exercise, and after 1 h of recovery. RESULTS: The R-AO diet induced a threefold reduction in antioxidant intake when compared with habitual-antioxidant (H-AO) diets. F(2)-isoprostane concentration (marker of oxidative stress) was significantly higher after submaximal exercise (38%), exhaustion (45%), and 1 h of recovery (31%) when following the R-AO diet compared with the H-AO diet. Rate of perceived exertion was increased on the R-AO diet whilst exercise time to exhaustion was not affected. Total antioxidant capacity and circulating antioxidant concentrations, although not significantly different, tended to be lower when following the R-AO diet. CONCLUSION: Athletes regularly participating in up to 40 min of acute high-intensity exercise may require higher intakes of exogenous antioxidants to defend against increased oxidative stress during exercise, which can be met through an adequate intake of high-antioxidant foods. Thus, there seems no valid reason to recommend antioxidant supplements to athletes participating in acute high-intensity exercise events up to 40 min in duration, except in those known to be consuming a low-antioxidant diet for prolonged periods.     

Variation of salivary immunoglobulins in exercising and sedentary populations

PURPOSE: This study examined the nature of the variability in salivary immunoglobulin and albumin concentrations within an individual, between individuals, and between populations with differing levels of habitual physical activity. METHODS: Fourteen elite swimmers, and 21 active and 18 sedentary individuals provided 12 saliva samples over a 30-d period. Group classifications were based on interviews, anthropometric measurements, and physical activity records. Symptoms of illness and physical activity data were recorded daily. Salivary IgA, IgG, and IgM were measured by ELISA, and albumin concentrations were measured by nephelometry. Variability was assessed using ANOVA procedures. RESULTS: Elite swimmers, compared with active and sedentary individuals, had higher concentrations of salivary IgA (geometric mean=65 vs 32 and 40 mg.L, P=0.002) and greater variability in salivary IgA concentrations as individuals (P=0.007) and as a group (P=0.03). Salivary IgG variability in swimmers was also twofold greater than the other two groups (P=0.008). Salivary IgM and albumin variability were not significantly different between groups, but individual variability differed for swimmers and active individuals. The intraclass correlations for salivary IgA and IgG (but not for IgM or albumin) were 50% lower for swimmers than the other two groups (ICC for IgA: 20% swimmers vs 54% active and 46% sedentary individuals; ICC for IgG: 36 vs 59 and 57%). CONCLUSION: The variability and fluctuation of salivary immunoglobulin concentrations were consistently greater in the elite swimmers, but multiple samples from individual swimmers were less correlated compared with participants with lower physical activity levels. These findings have implications for monitoring mucosal immune status within individuals and when comparing salivary immunoglobulin concentrations between groups with differing levels of physical fitness and activity.     

Rehabilitation after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind comparison of programs administered over 2 different time intervals

BACKGROUND: There are adverse effects associated with immobilization of the knee after anterior cruciate ligament reconstruction, yet very little is known about how much activity will promote adequate rehabilitation without permanently elongating the graft, producing graft failure, or creating damage to articular cartilage. HYPOTHESIS: Rehabilitation with either an accelerated or nonaccelerated program produces no difference in anterior-posterior knee laxity, clinical assessment, patient satisfaction, functional performance, and the synovial fluid biomarkers of articular cartilage metabolism. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Twenty-five patients who tore their anterior cruciate ligament were enrolled and underwent anterior cruciate ligament reconstruction. Patients were randomized to accelerated rehabilitation or nonaccelerated rehabilitation. At the time of surgery and 3, 6, 12, and 24 months later, measurements of anterior-posterior knee laxity, clinical assessment, patient satisfaction, functional performance, and cartilage metabolism were completed. RESULTS: At the 2-year follow-up, there was no difference in the increase of anterior knee laxity relative to the baseline values that were obtained immediately after surgery between the 2 groups (2.2-mm vs 1.8-mm increase relative to the normal knee). The groups were similar in terms of clinical assessment, patient satisfaction, activity level, function, and response of the bio-markers. After 1 year of healing, synthesis of collagen and turnover of aggrecan remained elevated in both groups. CONCLUSION: Anterior cruciate ligament reconstruction with a bone-patellar tendon-bone graft followed by either accelerated or nonaccelerated rehabilitation produces the same increase of anterior knee laxity. Both programs had the same effect in terms of clinical assessment, patient satisfaction, functional performance, and the biomarkers of articular cartilage metabolism. There is concern that the cartilage biomarkers remained elevated for an extended period.     

Controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) for multi-slice imaging.

In all current parallel imaging techniques, aliasing artifacts resulting from an undersampled acquisition are removed by means of a specialized image reconstruction algorithm. In this study a new approach termed "controlled aliasing in parallel imaging results in higher acceleration" (CAIPIRINHA) is presented. This technique modifies the appearance of aliasing artifacts during the acquisition to improve the subsequent parallel image reconstruction procedure. This new parallel multi-slice technique is more efficient compared to other multi-slice parallel imaging concepts that use only a pure postprocessing approach. In this new approach, multiple slices of arbitrary thickness and distance are excited simultaneously with the use of multi-band radiofrequency (RF) pulses similar to Hadamard pulses. These data are then undersampled, yielding superimposed slices that appear shifted with respect to each other. The shift of the aliased slices is controlled by modulating the phase of the individual slices in the multi-band excitation pulse from echo to echo. We show that the reconstruction quality of the aliased slices is better using this shift. This may potentially allow one to use higher acceleration factors than are used in techniques without this excitation scheme. Additionally, slices that have essentially the same coil sensitivity profiles can be separated with this technique.     

An abnormal cervicovaginal cytology smear in uterine carcinosarcoma is an adverse prognostic sign: analysis of 25 cases

Carcinosarcoma of the uterus has been poorly characterized on cervicovaginal (Pap) smears, and we examine whether they effectively screen for carcinosarcoma and whether an abnormal Pap smear result has any clinical importance. Twenty-five patients with histologically confirmed carcinosarcoma had a conventional Pap smear shortly before diagnosis. Eleven smears (44%) originally were read as abnormal (malignant or atypical), and 4 additional cases were read as abnormal on retrospective review (15/25 [60%]). All malignant elements were epithelial, and 2 cases (8%) had atypical spindle cells, but no diagnostic sarcoma. Cervical involvement was the only histologic parameter correlating with an abnormal Pap smear result (P = .04). Univariate analysis found stage III or IV disease was an adverse prognostic sign compared with stage I or II disease (mean survival, 8 vs 36 months, respectively; P = .001), and multivariate analysis indicated that an abnormal Pap smear result correlated with worse survival (P = .023). The conventional Pap smear is insensitive (60%) for detecting carcinosarcoma, but when the result is abnormal, the Pap is an important stage-independent adverse prognosticator.