Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient.

BACKGROUND: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation. METHODS: We evaluated mRNA expressions of alpha(V)beta3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of alpha(V)beta3 was present in the donor before transplantation, alpha(V)beta3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. RESULTS: The ICH Group showed significant increased mRNA expression of alpha(V)beta3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). CONCLUSIONS: Our report demonstrates the presence of systemic activation of alpha(V)beta3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient.     

Composite aortic root replacement in acute type A dissection: time to rethink the indications?

OBJECTIVE: The indications for aortic root replacement in acute type A dissection are unclear. We reviewed the immediate and long-term outcome of consecutive patients in a series in which a low-threshold policy of composite aortic root replacement had evolved. METHODS: From a prospectively compiled aortic surgery database, we identified 162 patients who had either supracoronary interposition grafting, Group A (n=89), or composite root replacement, Group B (n=73) for acute type A dissection. Patients receiving total arch replacements were excluded. Operative and clinical details were analyzed and patient survival was compared to an age and gender matched census cohort. Need for reoperation on the proximal or distal aorta was also noted. Follow-up totaled 795.5 patient-years. RESULTS: Hospital mortality rates were identical in both groups (12.3%: 11 deaths in group A; 9 in group B). Chronic pulmonary disease, diabetes, malperfusion, hemodynamic compromise and aortic root dilatation were independent risk factors for hospital death. Actuarial survival estimates at 1, 5 and 10 years were 79% (71-88%), 64% (53-75%), and 55% (41-68%) for group A, and 79% (70-86%), 73% (62-83%), and 65% (52-78%) for group B (P=0.48). Age and operative patency of the ascending false lumen were independent risk factors for death after hospital discharge. Proximal aortic reoperation was required for four patients in group A and none in group B (P=0.085). CONCLUSION: A strategy of replacement rather than repair of the dissected aortic root for specific indications in type A dissection yielded high survival and low proximal reoperation rates. These results support an aggressive policy of composite root replacement in acute type A dissection.     

Genotype/phenotype of familial pancreatic cancer.

It is estimated that 5% to 10% of pancreatic cancer cases are attributable to hereditary factors. We believe that the number of cases that are genetic in etiology are even greater, however, based not on a classic autosomal dominant pattern of inheritance but rather when one takes into account low-penetrant inherited susceptibility factors. There is also a growing recognition that the development of pancreatic cancer in pancreatic cancer-prone families is dependent not only on genetic variables but on nongenetic factors. The aim of this article is to review the challenges in identifying pancreatic cancer-prone families and how environmental factors interact with genetic factors in these families.     

Laparoscopic-assisted bowel surgery

The use of laparoscopic surgical techniques is now being applied to a variety of operations traditionally performed in an open fashion. Twenty patients underwent laparoscopic-guided large and small bowel surgery at our institution from March 1991 to April 1992. The indications for surgery included polyps, obstruction, bleeding, and perforation, and pathologic diagnoses included benign polyps, lipomas, inflammatory bowel disease, perforation of a jejunal diverticulum, colonic arteriovenous malformations, and adenocarcinoma. Mobilization of the colon, ligation of the mesentery, and closure of the mesenteric defect were performed using the laparoscopic equipment. One trocar site was enlarged to 3 cm to deliver the bowel through the abdominal wall. All anastomoses were hand-sewn. Postoperative hospitalization ranged from 2 to 31 days (median, five days). No mortality was noted, and morbidity was 20 percent. We conclude that laparoscopic-guided bowel surgery is technically feasible and should translate into shorter hospitalization and less patient discomfort.     

Eight Days of Cyclosporine Overdose: A Case Report

A 25–year-old woman was admitted to the hospital because of rising trough cyclosporine concentrations thought to be due to self-administration of 4 times the normal dosage of the drug for 8 days. Her symptoms included colicky central abdominal pains and urinary retention; her serum creatinine concentrations were elevated. Whole blood cyclosporine and metabolite concentrations were measured by high-performance liquid chromatography and monoclonal radioimmunoassays. The highest reported trough cyclosporine concentration was 5877 ng/ml, and AM1 (M17) concentration was 3425 ng/ml. A cyclosporine half-life of 91 hours was calculated. Nine days after the agent was discontinued the patient's serum creatinine concentration had returned to normal and her symptoms resolved. Due to the availability of three sizes of cyclosporine capsules, and the need for frequent dosage changes, continued vigilance is necessary to ensure that patients understand their drug regimen.     

Is colonoscopic screening appropriate in asymptomatic patients with family history of colon cancer?

Colonoscopy has been advocated by some investigators as the most appropriate means of screening asymptomatic patients with a positive family history of colorectal cancer. However, results of such screening have been widely disparate. The purpose of this study was to evaluate the yield of colonoscopy in a cohort of completely asymptomatic individuals with one or two first-degree relatives with a history of colorectal cancer and to compare this yield with that of colonoscopy in a group of patients with apparent anal bleeding. Patients with possible genetic disorders, such as familial polyposis, were excluded. A total of 160 asymptomatic patients and a comparison group of 137 patients with nonacute anorectal bleeding underwent colonoscopy. Colonoscopy was completed in 143 of the 160 study patients (89 percent) and in all of the comparison patients and did not result in any complications. Twenty-two adenomas were found in 17 study patients (10.6 percent); 16 of the 22 adenomas were less than 1 cm in size. In the comparison group, eight adenomas were identified (5.8 percent of patients). No cancers were identified. The difference in polyp frequency between groups was not significant. The relatively low yield of colorectal neoplasms discovered at colonoscopy in this study may in part be due to the small sample size or to the strict criteria used to define these asymptomatic patients but does not lend strong support to the notion that colonoscopy is an appropriate first step in screening the asymptomatic patient with one or two first-degree relatives with colon cancer.     

Prevalence of mental illness and its impact on the use of home care and nursing homes: a population-based study of older adults in Manitoba.

OBJECTIVES: To determine the prevalence of mental illness in older adults and its effect on home care and personal care home (PCH) use. METHODS: Using nonidentifying administrative records (fiscal years 1997-1998 to 2001-2002) from the Population Health Research Data Repository housed at the Manitoba Centre for Health Policy, we determined the 5-year period prevalence for individuals aged 55 years and over (119 539 men and 145 752 women) for 3 mental illness categories: cumulative mental disorders (those having a diagnosis of depression, anxiety disorder, personality disorder, schizophrenia, and [or] substance abuse), any mental illness, and dementia. We calculated age-specific and age-adjusted rates of home care and PCH use and the prevalence of mental illness in PCH residents. RESULTS: From the group aged 55 to 59 years to the group aged 90 years or older, the prevalence of mental illness increased with the population's age. The prevalence of any mental illness rose from 32.4% to 45.0% in men and from 42.6% to 51.9% in women, and dementia prevalence rose from 2.0% to 33.6% in men and from 1.3% to 40.3% in women. The age-adjusted annual rates of open home care cases per 1000 population aged 55 and older varied by mental illness grouping (no mental disorder, 57 for men and 91 for women; cumulative mental disorders, 162 for men and 191 for women; dementia, 300 for men and 338 for women). The age-adjusted rates of PCH use per 1000 population aged 75 years and older also varied by mental illness grouping (no mental disorder, 53 for men and 78 for women; cumulative mental disorders, 305 for men and 373 for women; dementia, 542 for men and 669 for women). Among patients admitted to (or resident in) a PCH in 2002-2003, 74.6% (87.1%) had a mental illness, and 46.0% (69.0%) had dementia. CONCLUSIONS: Mental illness affects the use of home care and nursing homes profoundly. Individuals with dementia used home care at 3 times the rate of those having no mental illness diagnosis, and they used PCHs at 8 times the rate.