Cystoenteric conversion and reduction cystoplasty for treatment of bladder dysfunction after pancreas transplantation

PURPOSE: Bladder drainage of pancreatic exocrine secretions during pancreas transplantation can lead to significant urological complications. Our experience with cystoenteric conversion (CEC) is reviewed with respect to safety and efficacy. Select patients underwent concurrent reduction cystoplasty. MATERIALS AND METHODS: A total of 255 pancreas transplantations were performed at the University of Washington between 1990 and 2001, of which 236 were bladder drained and 33 required enteric conversion of bladder drainage. An additional patient from an outside institution required conversion. These cases were reviewed retrospectively. Of the patients 21 with large capacity (greater than 500 ml) bladders underwent concurrent reduction cystoplasty. RESULTS: Mean age of the 20 male and 14 female patients was 44 years (range 33 to 60) and mean interval between transplantation and CEC was 4.3 years (0.6 to 9). The most frequent indication for CEC was recurrent urinary tract infections (15 of 34 cases, 44%). Mean followup after CEC was 2.5 years (range 0.3 to 6.5). Six complications requiring reoperation were seen in 5 of the 34 patients (15%), one of which led to death (3%). Normal pancreatic graft function persisted in 30 of the 34 cases (88%). After reduction cystoplasty mean bladder capacity in all 34 cases decreased from 900 to 465 ml intraoperatively (p <0.0001) and from 650 to 362 ml in 9 according to urodynamics (p <0.015). Of the patients 30 (88%) experienced resolution of symptoms, while 3 (9%) experienced improvement and 1 (3%) continued to have recurrent infections. CONCLUSIONS: Although we advocate maximal conservative treatment of the urological complications of pancreas transplantation, CEC offers safe and effective management of these complications, and can easily be combined with reduction cystoplasty in select cases to optimize postoperative voiding function.     

Enforced expression of the tumor suppressor p53 renders human leukemia cells (U937) more sensitive to 1-[beta-D-arabinofuranosyl]cytosine (ara-C)-induced apoptosis

The effects of enforced expression of p53 on the sensitivity of p53(-/-) human monocytic leukemia cells (U937) to apoptosis following exposure to the S-phase-specific antimetabolite 1-[beta-D-arabinofuranosyl]cytosine (ara-C) were examined. Cells were stably transfected with a plasmid containing a chimeric DNA construct encoding a temperature-sensitive p53 variant (135(ala-->val)), which transactivates at 32 degrees but is non-functional at 37 degrees. A significant reduction in the S-phase population was observed in ptsp53 mutants incubated at 32 degrees. Nevertheless, while vector controls did not exhibit differential sensitivity to ara-C at 32 degrees versus 37 degrees, temperature-sensitive p53 mutants displayed a significant increase in apoptosis at the permissive temperature. This was not accompanied by increased ara-CTP formation, DNA incorporation of [3H]ara-C, or altered expression of Bcl-2 or Bax. Enhanced sensitivity was associated with increased mitochondrial injury (e.g. cytochrome c release), caspase activation, and loss of clonogenic survival. Significantly, ptsp53 cells synchronized in S phase were markedly more sensitive to ara-C-mediated mitochondrial injury and apoptosis at 32 degrees, indicating that wild-type p53 specifically enhances the susceptibility of this subpopulation to ara-C lethality. Consistent with these results, transient transfection of human wild-type p53 cDNA rendered parental U937 cells more sensitive to ara-C-mediated cell death. Collectively, these findings indicate that p53 expression renders S-phase U937 cells more susceptible to ara-C-mediated mitochondrial dysfunction, cytochrome c release, apoptosis, and loss of clonogenic survival without enhancing ara-C metabolism. Such findings raise the possibility that loss of functional p53 activity allows leukemia cells to circumvent ara-C lethality.     

Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1

We report 4 cases of malignant peripheral nerve sheath tumors (MPNST) with neurofibromatosis type 1 (NF1). Mean age was 29.5. Two of them had a family history. Three of them were male. All of them had enlarging mass and pain in the background of neurofibromas. Locations were popliteal, thigh and forearm. The masses were greater than 5 cm in diameter in each case. In two cases the mass was showing continuity with a nerve. One patient had a nonossifying fibroma as well as a MPNST. Wide excision and radiotherapy were applied to three of the patients. One of them did not take any therapy after surgical resection. Two of the patients died of lung metastases after a mean period of 12.5 months. In a majority of NF1 patients MPNST emerges from a preexisting neurofibroma. The patients with NF1 are at greatest risk for developing sarcomas, so they should be followed closely.     

Promoting prevention: skill sets and attributes of health care providers who deliver behavioral interventions

Preventive therapies have been shown to reduce morbidity and mortality from cardiovascular disease. However, health care providers are not addressing prevention and not treating patients according to evidence-based guidelines. Reasons frequently cited for not delivering health promotion/disease prevention oriented care is lack of training or skills to provide counseling, and a lack of confidence in health care provider skills. This article outlines the skills and attributes considered essential for a health care provider to promote behavioral change and risk reduction. The skills and attributes of the health care provider, such as expertise and knowledge, skills for assessing readiness for behavior change, relationship building skills, and skill in considering the patient's attitudes and beliefs about the disease or treatment are discussed. Principles of communication to guide the patient-provider encounter, key behavioral change strategies, and use of technology are reviewed and resources available to support prevention goals are presented.