Prophylactic amifostine prevents a pathologic vascular response in a murine model of expander-based breast reconstruction.

BACKGROUND: Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when radiotherapy is implemented. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing amifostine in a murine model of expander-based breast reconstruction. METHODS: 30 rats were divided into three groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander. After a 45 day recovery period, all groups underwent vascular perfusion and micro-CT analysis. RESULTS: Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control (p = 0.021) and the AMF/XRT (p = 0.027). There was no difference between Control and AMF/XRT (p = 0.862). VVF was significantly higher in XRT than either Control (p = 0.043) and AMF/XRT (p = 0.040), however no difference was seen between Control and AMF/XRT (p = 0.980). VSp of XRT was smaller when compared to both Control and AMF/XRT specimens (p = 0.05 and p = 0.048, respectively), and no difference was seen between Control and AMF/XRT (p = 0.339). CONCLUSIONS: Amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine protects soft tissue in our model from a radiotherapy-induced pathologic vascular response.

Lamivudine in hepatitis B-associated membranous nephropathy.

BACKGROUND: Although lamivudine is effective for treatment of chronic hepatitis B (HBV) infection, its potential therapeutic impact on HBV-related membranous nephropathy (MN) in adults has not been characterized. METHODS: We treated 10 HBsAg-positive patients with biopsy-proven MN, elevated serum alanine aminotransferase (ALT), and HBV-DNAemia (group 1), and compared their clinical course with 12 patients diagnosed to have HBV infection, elevated serum ALT, and MN in the pre-lamivudine era (group 2). RESULTS: Baseline demographic and clinical parameters were not different between the 2 groups. In group 1, lamivudine treatment was associated with significant reduction in proteinuria, increase in serum albumin, normalization of ALT levels, and disappearance of circulating HBV-DNA during the first year. Four (40%) and 6 (60%) patients went into complete remission (proteinuria <0.3 g/d) at 6 and 12 months, respectively. In group 2, significant proteinuria persisted during the first year. One (8.3%) and 3 (25%) patients went into remission. Cumulative 3-year renal survival [using end-stage renal disease (ESRD) as primary end point] was 100% in group 1 and 58% in group 2 (P= 0.024, log rank test). Blood pressure control reached the target of below 130/85 mm Hg in both groups. Lamivudine was well tolerated and not associated with any adverse events. Hepatic decompensation or malignancy was not observed during follow-up in both groups. CONCLUSION: HBV-related MN leads to ESRD in a significant proportion of patients before the advent of antiviral therapy. Lamivudine treatment improves renal outcome in HBV carriers with MN and evidence of liver disease.

Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.

BACKGROUND: Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients. METHODS: We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding. RESULTS: We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001). CONCLUSIONS: Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.

Screening for colorectal cancer in Chinese: comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy.

BACKGROUND AND AIMS: Fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), and colonoscopy are the most commonly recommended screening tests for colorectal cancer. The aim of this study was to compare the accuracy and safety of these 3 screening procedures in a general population of ethnic Chinese. METHODS: Asymptomatic adults older than 50 years were recruited from the general public through health exhibitions. All enrolled subjects were offered FOBT and full colonoscopy under sedation. Advanced colonic lesions (defined as adenoma > or = 10 mm, villous adenoma, adenoma with moderate or severe dysplasia, or invasive cancer) were recorded. Lesions at the distal 40 cm in the left colon and rectum were taken as findings of FS. RESULTS: A total of 505 subjects (56% women; mean age +/- SD, 56.5 +/- 5.4 years) were enrolled, and 476 (94.3%) had a complete colonoscopy. Advanced colonic neoplasms were documented in 63 subjects (12.5%), of which 45 had lesions in the distal colon and 26 in the proximal colon. Among the 385 subjects with a normal distal colon, 14 (3.6%) had advanced lesions in the proximal colon that would be missed by FS alone. The sensitivity and specificity of FOBT for advanced colonic lesions were 14.3% and 79.2% and the sensitivity and specificity of FS were 77.8% and 83.9%, respectively. Combining FOBT with FS would not significantly improve the results of FS alone. Among these 505 subjects who underwent colonoscopy and 148 who underwent polypectomy, there was no perforation and only one occurrence of postpolypectomy bleeding recorded. CONCLUSIONS: Colonoscopy is a safe and accurate method for the screening of colorectal neoplasms in Chinese subjects.

Bone cancer risk estimates.

Due to confusion between endosteal (bone surface) dose and average skeletal dose, ICRP 60 has substantially overestimated the risk of radiogenic bone cancer. This confusion apparently stems from an incorrect reading of the BEIR IV report, which does not clearly draw this distinction. It should also be noted that what appear to be summary numerical risk estimates for bone sarcoma induction in BEIR IV and BEIR V refer only to average skeletal dose as calculated for 224Ra.

The growing conceptus of the domestic cat.

The feline conceptus is similar to larger mammals rather than to rodents in the amounts of fetal fluids and the contribution of the fetus to the total volume of the conceptus. When growth rates of several mammals are compared as Gompertzian functions, the feline fetus is more similar to that of the guinea pig or beagle than that of the mouse, rat, man, sheep or cow. The feline Gompertzian growth starts at about the 6th day of gestation. The weight of the fetus, +/- 10%, as a function of gestational age starting on day 28 is: Weight in grams = 2.6477 X 10(-10) exp (see article) when t = gestational age of 28 days or more. The feline weight to crown-rump relationship can most easily be expressed as a power function where: Crown-rump length in cm = 2.69 (weight in grams) 0.3508; with an error term of +/- 5%. The relationship of three variables gestational age, fetal weight, and fetal crown-rump length can also be expressed mathematically: Gestational age in days = 15.335 + 3.9805 (crown-rump length in cm) -0.0675 (weight in grams) Equations for crown-rump length or weight were calculated, but the inaccuracy of these expressions is too great to allow practical use.