Management of aortic valve disease during aortic surgery.

BACKGROUND: Alternative management strategies for aortic valve disease and aortic operation include valve preservation and aortic repair (VPR), composite valve graft (CVG), or separate valve and aortic repair (SVR). We evaluated these approaches. METHODS: Of 250 ascending/arch operations, 151 patients had aortic valvular disease and dissection (n = 56, 37%) or aneurysms operated between November 1990 and January 1998. Sixty-seven patients underwent CVG insertion, 50 SVR, 13 VPR, and 21 only aortic repair alone (RA). Sixty (40%) patients also had aortic arch repairs and 53 (35%) coronary artery bypasses. RESULTS: The early 30-day survival and stroke rates were 99% (150 of 151) and 0% (0 of 151), respectively: CVG 100% (67 of 67), 0%; VPR 100% (13 of 13), 0%; SVR 98% (49 of 50), 0%; RA 100% (21 of 21), 0% (p = not significant [NS]). On late follow-up of all patients (5 to 92 months; 96% complete 1998), 3 CVG, 2 VPR, 6 SVR, and 0 RA patients died with respective 5-year Kaplan-Meier survival rates of 88.4%, 70%, 69%, and 100% (p = 0.07, log-rank test). The respective linear rates for stroke were 0%, 5.5% (n = 1), 0%, and 0%; for hemorrhage were 0%, 0%, 0%, and 0%; and for endocarditis were 2.2% (n = 3), 0%, 0%, and 0% (p = NS). There were 11 late deaths and no patient required reoperation or ruptured the ascending aorta or the aortic arch. CONCLUSIONS: With careful selection of the appropriate method excellent early and late results can be achieved.

Addition of a water-soluble alpha-tocopherol analogue to University of Wisconsin solution improves endothelial viability and decreases lung reperfusion injury.

BACKGROUND: Reperfusion injury following lung preservation has been associated with free radical formation and subsequent endothelial cell damage. Trolox is a water-soluble analogue of the free radical scavenger alpha-tocopherol. We hypothesized that addition of this form of vitamin E to University of Wisconsin (UW) solution would decrease reperfusion injury and improve lung function after cold ischemic preservation. MATERIALS AND METHODS: Bovine aortic endothelial cells were cultured and stored at 4 degrees C for 12, 24, and 48 h in UW or UW + Trolox (UWT). Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. An isolated rat perfused lung (IPL) model was used and lungs were flushed with the respective solutions with cold storage times of 6 and 12 h. Following storage, the lungs were reperfused with fresh blood and lung function was assessed by blood gas analysis, alveolar-arterial gradient, and compliance. RESULTS: There was no difference in endothelial cell viability between UW and UWT after 12 or 24 h; however, UWT had higher endothelial cell viability than UW with 48 h of cold ischemic storage. Using the IPL model, the pO2 was higher with UWT than UW after 6 and 12 h of cold ischemia. The alveolar-arterial oxygen difference was significantly lower for UWT versus UW at 6 h. UWT provided increased compliance at 6 and 12 h of ischemia. CONCLUSIONS: The addition of a water-soluble vitamin E analogue to UW solution resulted in increased endothelial cell viability after prolonged storage and improved whole lung preservation in the postreperfusion period as evidenced by higher oxygenation and increased compliance. These results are clinically relevant as the lung is extremely sensitive to reperfusion injury and UW solution is being increasingly used in lung transplantation and remains the predominant solution in abdominal organ transplantation.

Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection.

BACKGROUND: Cyclosporine-based immunosuppressive regimens (INN: ciclosporin) in human lung transplantation continue to result in a high incidence of acute cellular rejection. We investigated the use of sirolimus, a macrolide with structural similarity to tacrolimus, as monotherapy and in combination with cyclosporine in a rodent lung transplant model. METHODS: Orthotopic left lung transplantation was performed in Lewis recipients from Brown-Norway donor rats with syngeneic Lewis-to-Lewis controls. Open biopsies were performed on postoperative day 7, and the severity of acute lung rejection was graded by a pathologist blinded to the protocol. RESULTS: All recipients survived despite the amount of acute rejection seen on examination of the biopsy tissue. Lewis-to-Lewis isografts demonstrated near normal pulmonary architecture. Allogeneic recipients receiving high-dose cyclosporine (25 mg/kg) monotherapy showed mild to moderate acute rejection with some perivascular focal interstitial infiltrates. Recipients receiving low-dose cyclosporine (5 mg/kg) monotherapy or low- or high-dose sirolimus (0.5 or 2.0 mg/kg, respectively) monotherapy demonstrated massive cellular infiltration leading to necrosis and infarction and could not be graded. However, the addition of low-dose sirolimus (0.5 mg/kg) to low-dose cyclosporine (5 mg/kg) demonstrated a significant potentiating immunosuppressive effect, and the addition of high-dose sirolimus (2.0 mg/kg) to low-dose cyclosporine (5.0 mg/kg) demonstrated an even greater effect, with rejection scores better than those obtained with high-dose cyclosporine monotherapy and similar to those obtained with isografts. CONCLUSIONS: This study demonstrates that low-dose sirolimus has a cyclosporine-sparing effect and that a higher dose of sirolimus in combination with cyclosporine strongly protects lung allografts from acute cellular rejection. These results suggest that sirolimus may be indicated as an adjunct to current cyclosporine-based immunosuppressive regimens in clinical lung transplantation.

Nitric oxide mediates hyperglycemia-induced defective migration in cultured endothelial cells.

PURPOSE: To examine the effects of elevated glucose on the migration and proliferation of vascular endothelial cells in an in vitro wound model and to investigate whether nitric oxide (NO) mediates the effects of elevated glucose. METHODS: Migration was investigated in monolayers of bovine aortic endothelial cells wounded by scraping and measuring the distance, the number of cells migrating, and the area covered by the migrating cells in the presence of various concentrations of glucose. The effects of NO were evaluated by adding to the cultures NG-monomethyl arginine (NMMA), an inhibitor of NO synthase, or S-nitrosylated penicillamine, which is a slow-release agent of NO. Proliferation was investigated in the presence of various concentrations of serum, glucose, or both. RESULTS: Elevated glucose levels (16.5 and 27.7 mmol/L) inhibited endothelial cell migration in a dose-dependent manner compared with cells cultured in the presence of 5.5 mmol/L glucose. Inhibition of migration was also observed when wounded mono-layers cultured in 5.5 mmol/L glucose were treated with S-nitrosylated penicillamine, which generates NO. Inhibition of NO synthase by NMMA prevented the inhibition of migration observed in media containing 27.7 mmol/L glucose. Elevated glucose levels did not affect cell proliferation except in the presence of 20% fetal bovine serum. CONCLUSIONS: An elevated glucose level inhibits endothelial cell migration in an in vitro wound model, and the inhibition appears to be mediated by increased levels of NO.

Use of a modified Delphi technique to guide coordination of cancer education in Texas medical schools.

Delphi technique is a method of structuring group communication and is useful in achieving consensus on goals, plans, or positions. The Delphi technique was used to determine a course of action to enhance cancer education at each of eight medical schools in Texas. Participants in this study were deans of medicine and a faculty member considered to be the lead cancer expert in the curriculum. A three-generation Delphi study was conducted with the deans using a telephone interview, a personal interview, and a conference of participants, including cancer experts. The Delphi technique was found to be an effective approach for increasing awareness of the statewide cancer plan, for involving all medical schools in achieving the goals of the plan, and for identifying means for enhancing cancer education at each medical school. A consensus was reached to develop a statewide standardized assessment of graduating medical students' knowledge about principles of cancer prevention and screening. The results could serve as a means of determining cancer education needs at each medical school.

Expectations of preschool children to protect themselves from cigarette smoke: results of a smoking prevention program for preschool children.

Because preschoolers and first graders show signs of readiness to try smoking and because they are already learning about smoking through their environment, smoking prevention at the preschool level is appropriate. The large numbers of children seen in primary care practices and day care facilities are indicative of the numbers that could be exposed to smoking prevention instruction through these settings. This study assessed the future expectations of children to protect themselves from sidestream smoke after participating in a preschool smoking prevention program offered in four primary care settings. Through this program, children and their parents read stories and complete activities concerning the human body and the health risks of smoking. Using a randomized posttest-only case control design, the authors found that children who were exposed to the curriculum were more than twice as likely as others to report the intention to act to protect themselves from adult sidestream smoke.

Yatrogenia psicológica

A fin de investigar los criterios que tienen los estudiantes de medicina de la Facultad de Ciencias Médicas de Cienfuegos, que reciben docencia en el hospial provincial clínico quirúrgico "Dr. Gustavo Aldereguía Lima" sobre la existencia de yatrogénia psicológica, se seleccionó una muestra aleatoria suficientemente representativa que ascendió a 127 estudiantes de tercero hasta quinto año de dicha carrera, luego de tabular los resultados, se calcularon los porcientos y se representaron mediante tablas y gráficos

Behavioral prescription writing in smoking cessation counseling: a new use for a familiar tool.

Tobacco use, a self-inflicted epidemic, causes more than 390,000 deaths in the United States each year. Smoking is a habit perpetuated by both physiologic and psychosocial mechanisms. Physician use of behavioral prescriptions is a practical, familiar, and efficient method for achieving smoking cessation. Physicians should ask patients if they want to quit smoking, take a smoking history, motivate patients to quit by personalizing risks, set a quit date, and then follow the behavioral prescription. Behavioral prescription involves writing prescriptions based on a plan that leads the patient through five successive weeks of behavioral modification, culminating in complete cessation of cigarette use. Physician time involved is minimal, since the approach requires only two meetings in person--one at an initial patient visit, and a second at a follow-up appointment.

An ecological approach to the prevention of injuries due to drinking and driving.

Among the many alcohol-related public health concerns, motor vehicle crashes account for nearly one-third of all deaths attributable to alcohol. Adolescents and young adults, particularly males, are important target populations for intervention efforts. Taking an ecological perspective of individuals within their social and physical environments, a diagnostic framework is employed in reviewing the literature on factors associated with drinking and driving injuries and on interventions to prevent injuries due to drinking and driving. Intervention planning is conceptualized according to a multilevel intervention framework, which consists of four phases: (1) health goals selection, (2) intervention planning, (3) intervention, and (4) evaluation. Possible intervention objectives, targets of the intervention actions, intervention approaches, and evaluation criteria are identified and discussed for three societal levels and four practice settings.

Chemical carcinogen-induced decreases in genomic 5-methyldeoxycytidine content of normal human bronchial epithelial cells.

The genomic content of DNA 5-methyldeoxycytidine (m5dC) was measured in dividing normal human bronchial epithelial cells treated with a broad range of chemical carcinogens. At noncytotoxic concentrations, all of the carcinogenic agents tested significantly reduced cellular DNA m5dC content whereas the weakly carcinogenic and noncarcinogenic agents, benzo[e]pyrene and phenanthrene (respectively), did not. These reductions varied from 8% to 31% depending on the agent and the donor cells. The reductions in genomic m5dC levels were concentration dependent for the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene. We speculate that carcinogen-induced perturbation of DNA m5dC patterns may lead to heritable changes in gene expression and contribute to the molecular alterations involved in the initiation and the subsequent steps of the carcinogenesis process.

Genomic 5-methylcytosine determination by 32P-postlabeling analysis.

A simple and sensitive method for the quantitation of 5-methyldeoxycytidine in DNA has been developed by the adaptation of the Randerath 32P-postlabeling technique. Nucleic acids were digested to 3'-monophosphate nucleotides, which were converted to 32P-labeled 3',5'-bisphosphate nucleotides, the 3'-phosphate was cleaved by the action of nuclease P1, and the resultant 5'-[32P]-monophosphate nucleotides were separated by two-dimensional thin-layer chromatography. Less than 1 microgram of DNA was required for the precise quantitation of 5-methyldeoxycytidine content to a detectable limit of 0.01% of the total cytidine residues methylated. The genomic 5-methyldeoxycytidine content may thus be quantitated in tissue samples, small or selective cell populations, senescing or terminally differentiating cells, or DNA from any source. We report here, for the first time, the genomic 5-methyldeoxycytidine content of normal human bronchial epithelial and normal human pulmonary mesothelial cells. The chromatographic separation of all of the normal and some of the rare monophosphate deoxyribonucleotides and ribonucleotides has been characterized. Thus, 5-bromodeoxyuridine and the RNA contamination of DNA or the DNA contamination of RNA can also be quantitated during the same analysis.