Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.     

The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: The osteoporotic fractures in men (MrOS) study

Low 25‐hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case‐cohort design. “Abnormal” was defined as lowest quartile for VitD (<20 ng/mL), bioavailable testosterone (BioT, <163 ng/dL), and bioavailable estradiol (BioE, <11 pg/mL); and highest quartile for SHBG (>59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate‐adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6‐year median follow‐up was 1.2 (0.8–1.8) for low VitD alone; 1.3 (0.9–1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1–2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health. © 2012 American Society for Bone and Mineral Research.     

The impact of social networks and partnership status on treatment choice in men with localized prostate cancer

Study Type – Decision analysis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Very little is known about prostate cancer decision‐making. Hence, marital status is often assumed a proxy for the amount of social support. While marital status is often used as a proxy for social support, we found that the quality of support may impact treatment type more than the extent of the social matrix.

OBJECTIVES

• ? To determine whether martial status and social support impact treatment choice.
• ? The decision to pursue radical prostatectomy for prostate cancer is often influenced by factors outside the realm of tumour risk, such as a man's support system at home.

PATIENTS AND METHODS

• ? We performed a retrospective cohort study of 418 low‐income men who were diagnosed with non‐metastatic prostate cancer and underwent definitive treatment with either radical prostatectomy or radiotherapy.
• ? We performed univariate and multivariate mixed‐effects logistic regression analysis, with the dependent variable being treatment type.
• ? Confidence intervals (CIs) for the predicted probabilities and relative risks were derived using bias‐corrected bootstrapping with 1000 repetitions.

RESULTS

• ? Men with two or more members in their support system were more likely to be older, Hispanic, have less than a high school education, earn more than US $1500 monthly, have high‐risk disease and be in a significant relationship.
• ? In multivariate analysis, partnered men with fewer than two social support members (relative risk, RR, 1.23; 95% CI, 1.02–1.63) were more likely to undergo surgery, whereas men who were morbidly obese (RR, 0.46; 95% CI, 0.09–0.88), high school graduates (RR, 0.80; 95% CI, 0.64–0.99) or had high‐risk disease (RR, 0.58; 95% CI, 0.44–0.85) were less likely to undergo surgery than their respective referent groups.
• ? Partnered men with two or more social support members were no more likely to undergo surgery than unpartnered men who lacked any social support.

CONCLUSIONS

• ? In the present study cohort, married men with fewer than two members in their social network were more likely to have undergone surgery.
• ? Although marital status is often used as a proxy for social support, we find that the quality of support and partner may impact treatment type more than the extent of the social matrix.

     

Pelvic fractures in a pediatric level I trauma center

OBJECTIVES: Assess the characteristics associated with the risk of complications and mortality in children sustaining pelvic fractures. SETTING: Urban university pediatric Level I trauma center in a large metropolitan community. PATIENTS/PARTICIPANTS: Retrospective analysis of 57 consecutive children with 66 pelvic fractures seen between 1993 and 1999. INTERVENTION: Fifty-two patients were treated nonoperatively, and five patients required operative stabilization (four acetabular fractures and one partial sacroiliac joint disruption). MAIN OUTCOME MEASURE: Type and cause of pelvic fracture, type of management used, incidence of associated injuries, hemorrhage requiring transfusion, and mortality. RESULTS: Hemorrhage directly related to the pelvic fracture occurred in only one patient (2%), whereas 11 other patients required transfusions associated with other body-area injuries. Three patients with pelvic fractures died (5%), but deaths were due to other body-area injuries. CONCLUSIONS: Children with pediatric pelvic fractures require careful evaluation for other body-area injuries, as these are most likely to be related to hemorrhage or mortality.     

Successful use of sacral neuromodulation after failed bladder augmentation

Sacral neuromodulation has become a standard minimally invasive therapy for refractory urinary urge/frequency and urge incontinence. Prior to the widespread use of sacral neuromodulation, augmentation cystoplasty was a standard treatment for refractory overactive bladder (OAB). The use of sacral neuromodulation following bladder augmentation has not been previously reported in the literature. We report 2 cases of successful sacral neuromodulation in patients with OAB refractory to bladder augmentation.     

Randomized controlled trial comparing the controlled rehabilitation with early ambulation and diet pathway versus the controlled rehabilitation with early ambulation and diet with preemptive epidural anesthesia/analgesia after laparotomy and intestinal resection

BACKGROUND: Multimodal postoperative care regimens accelerate recovery after abdominal surgery. The benefit of thoracic epidural (TE) analgesia over patient-controlled analgesia (PCA) remains unproven when used with a fast-track postoperative care plan. METHODS: Fifty-six patients undergoing major intestinal resection, and on a fast-track postoperative care plan, were randomized to preemptive TE or PCA. Patients were evaluated at standard time points for pain score, quality of life (Short Form-36), and complications. Oral analgesia was substituted for TE and PCA on the second postoperative day. Discharge criteria were identical for both groups. RESULTS: Six patients (20.6%) had a failed epidural. There was no difference in length of stay (5.8 versus 6.2 days, TE versus PCA, P = .55), total length of stay (including readmissions), pain scores, quality of life, complications, or hospital costs at any time point. CONCLUSION: TE offers no advantage over PCA for patients undergoing major intestinal resections who are on a fast-track postoperative care plan using PCA.     

蒙药如达溃疡散对大鼠乙酸性胃溃疡及其血清促胃液素的影响

目的:探讨如达溃疡散对大鼠乙酸性胃溃疡的作用及对其血清促胃液素(gastrin)含量的影响.方法:采用乙酸法复制胃溃疡模型,将大鼠随机分为对照组、如达溃疡散组、雷尼替丁组,观察如达溃疡散对大鼠胃溃疡的作用,并检测其对大鼠血清中促胃液素含量的影响.结果:与对照组相比,如达溃疡散能明显抑制溃疡的发生,抑制血清促胃液素含量.结论:如达溃疡散具有抗胃溃疡的作用,其作用机理可能是通过抑制促胃液素释放,进一步减少胃酸分泌来实现的.     

Significance of tumor spread in adenocarcinoma of the ampulla of Vater

Twenty-eight patients with ampullary carcinoma were treated between 1965 and 1988: 22 underwent pancreaticoduodenectomy with 1 operative death (5 percent), 1 had local excision, 3 had bypass, and 2 were not explored. Of the 21 patients who survived pancreaticoduodenectomy, 4 had tumor confined to the ampulla, 7 had tumor extending into the duodenum, and 10 had tumor invasion beyond the duodenum. Nine of these patients had positive lymph nodes and 12 had negative lymph nodes. The patient who had local excision was disease-free at last follow-up 104 months postoperatively. Each of the three bypassed patients died of tumor progression within 15 months. The estimated 5-year survival rate for resected patients was 60 percent and was independently related to lymph node metastases (p = 0.031) and to tumor size (p = 0.039). This experience suggests that long-term survival is possible in patients with lymph node metastases or invasive tumors extending beyond the duodenal wall and that curative pancreaticoduodenectomy can be performed with a low operative mortality; therefore, aggressive surgical resection is recommended for all patients with ampullary carcinoma.     

The selective retention of lutein, meso-zeaxanthin and zeaxanthin in the retina of chicks fed a xanthophyll-free diet

Lutein and zeaxanthin are pigmented oxygenated carotenoids, or xanthophylls, derived from plants and concentrated in the retina of primates and birds. We investigated the transport, distribution and depletion of lutein and zeaxanthin in the plasma and tissues of newly hatched chicks fed xanthophyll-free diets. One-day-old Leghorn chicks were randomly divided into two groups. A control group was fed a diet containing lutein and zeaxanthin (5.2 and 1.7 mg/kg diet, respectively) for 28 days. An experimental group was fed a diet containing no lutein and zeaxanthin for 28 days. Plasma and tissues were analyzed for lutein and zeaxanthin at 28 days (control) and on days 1, 14 and 28 (experimental). At hatching, lutein and zeaxanthin were the predominant carotenoids present in the blood and tissues. As indicated by their similar mass contents, there was complete transfer of these carotenoids from egg yolk to chick. Lutein and zeaxanthin concentrations in the plasma and tissues of chicks fed the xanthophyll-free diet decreased rapidly to almost zero (with a depletion time of seven days [t(1/2)]). In contrast, the retina retained its initial concentrations of lutein and zeaxanthin similar to the control group. meso-Zeaxanthin and cis-zeaxanthin were identified only in the retina. The retina concentrated zeaxanthin over lutein. Lutein and zeaxanthin were selectively retained in the retinas of chicks fed a xanthophyll-free diet. In contrast, the plasma and other tissues lost up to 90% of their original content of xanthophylls. These data emphasize the relative stability of lutein and zeaxanthin in the cone-rich retina where they are present as esters in oil droplets. The tissue depletion suggests the need for a regular dietary intake of lutein and zeaxanthin because of rapid depletion in the body. It is clear that these xanthophylls may have an essential role in the cone-rich retina of the chick as evidenced by their selective retention.