Prevention of surgical site infection by antibiotic spraying in the operative field during cardiac surgery

OBJECTIVE: Despite the many procedures introduced to prevent surgical site infection during cardiothoracic surgery, serious infections still occur. We attempted to reduce surgical site infection by spraying antibiotic solution in the operative field--a procedure since introduced at 4 other Japanese institutions. METHODS: In the latter half of 1990, we began spraying an antibiotic solution of cefazolin (1g) and gentamicin (40 mg)/40 ml of saline placed in a 50 ml syringe and dispensed through an 18 G needle bent at 60 to 80 degrees to clean the wound during surgery. RESULT: No deep surgical site infections or deaths due to infection have occurred among the 502 patients undergoing cardiothoracic surgery under cardiopulmonary bypass at our hospital. This method was used in over 2,100 cases of similar procedures at 4 other institutions. There were 3 deaths due to severe surgical site infection (0.11%). At one institution treating over 1,000 cases a year, the incidence of death due to surgical site infection decreased significantly after this method was introduced. CONCLUSION: These preliminary experiences show that spraying antibiotic solution in the operative field reduces the risk of surgical site infection in cardiothoracic surgery.     

Evaluating the drug-target relationship between thymidylate synthase expression and tumor response to 5-fluorouracil. Is it time to move forward?

Thymidylate synthase is a target of 5-fluoruracil, a pyrimidine analog used to treat gastrointestinal and other cancers. The 5-fluorouracil metabolite, fluoro-deoxyuridine monophosphate, forms a ternary complex with thymidylate synthase and 5,10-methylene tetrahydrofolate. The purpose of this study was to evaluate the time-honored connection between thymidylate synthase and 5-fluorouracil. From our literature search spanning reports from 1995 to 2007 published in journals having an impact factor greater than 2, we stratified the tumors within each article, according to low versus high thymidylate synthase expression. These groups were subdivided into responders, stable disease or disease progression. The relationship between thymidylate synthase expression and 5-fluorouracil response was analyzed for the overall group, as well as for subsets. Overall, the literature supported an approximately 2-fold inverse relationship between thymidylate synthase expression and response to 5-fluoruracil. We found no change in the trend for a relationship between thymidylate synthase and 5-fluorouracil when the literature was stratified by date of publication, impact factor of the journal in which the report was published, or substrate (mRNA versus protein) for measuring thymidylate synthase expression. Of note, there is no significant change in the trend when comparing 5-fluorouracil treatment alone or in combination with leucovorin. We found a decline of this trend when certain chemotherapeutics were used in combination with 5-fluorouracil. In sum, the connection between thymidylate synthase expression and patient response to 5-fluorouracil does not satisfy expectations for an effective drug-target relationship; and thus, studies of the thymidylate synthase tandem repeat status might only be clinically valuable in regards to patient toxicity. Thus, we question the reliability of thymidylate synthase expression as a clinical predictor of 5-fluorouracil response. Future research could perhaps be directed towards alternate targets and metabolites of 5-fluorouracil, in an effort to find a clinically relevant biomarker panel for response and to optimize fluoropyrimidine-based therapy.     

Monitoring of minimal residual disease in acute myeloid leukemia

Two highly sensitive methods, multiparameter flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR), are increasingly used to monitor minimal residual disease (MRD) and to guide risk-adapted management in acute myeloid leukemia (AML). An independent prognostic impact has been demonstrated for MRD levels obtained by both methods. MFC has been found particularly useful for assessment of early clearance of malignant cells and after consolidation therapy. At the latter checkpoint, MRD levels quantified by RQ-PCR in AML with fusion genes also have the strongest prognostic power. In addition, highly predictive initial expression levels have been identified by RQ-PCR. Both methods are capable of early detection of relapse. Through the use of all available markers including NPM1 mutations and FLT3 mutations in addition to fusion genes, RQ-PCR-based MRD assessment is possible in more than half of patients, whereas MFC is applicable to most AML cases. With a sensitivity of 10(-4) (PML-RARA) to 10(-7) (patient-specific primers, FLT3 and NPM1 mutations), RQ-PCR is more sensitive in most cases. Large clinical trials will determine the exact role and place of immunologic and RQ-PCR-based monitoring of MRD in the therapy of patients with AML.     

Perceptions of parents seeking an experimental herpes simplex vaccine for their adolescent and preadolescent daughters

Perceptions of parents willing to enroll their daughters in genital herpes vaccine trials were examined by questionnaire. Respondents were knowledgeable about genital herpes and endorsed personal and societal protection as important reasons to vaccinate. A belief among some that the vaccine might promote sexual activity did not prevent them from seeking protection for their daughters.     

Aldose reductase and the development of renal disease in diabetic dogs

Effects of 5 years administration of an aldose reductase inhibitor (Sorbinil) on renal structure and albumin excretion were evaluated in diabetic dogs. Glycemia, estimated by frequent measurements of HbA1, glycated plasma proteins and glucosuria, was kept comparable between the placebo- and Sorbinil-treated diabetic groups. Kidney structure was evaluated using morphometric techniques by light and electron microscopy, and excretion of immunoreactive albumin was measured yearly. Placebo-treated diabetic dogs developed nephromegaly, glomerular enlargement, increased mesangial volume, and basement membrane thickening during the 5 years of study, and by the fifth year, excreted greater than normal quantities of albumin. Sorbinil treatment prevented sorbitol accumulation in erythrocytes and tended to have a similar effect in renal cortex, but had no beneficial effect on renal structure or albuminuria. Experimental galactosemia, another model of polyol over-production, failed to produce nephromegaly, glomerular enlargement, or mesangial expansion in dogs even after 5 years of galactose-feeding. The results suggest that polyol over-production and/or accumulation per se are not sufficient to account for the nephromegaly, glomerular enlargement, or increased mesangial volume observed in diabetic dogs.     

Ernährungsstatus krebskranker Kinder während Chemotherapie

Background and method

Parents and physicians often fear that children with malignant diseases will develop signs of malnutrition during intensive chemotherapy. We therefore determined the height, weight, body mass index, fat-free mass (bioelectrical impedance) and serum protein concentrations (albumin, prealbumin) in 18 children with acute leukaemia and 27 with malignant solid tumours weekly during the first month then monthly from diagnosis to the end of intensive chemotherapy for a mean time of 104 days (up to 357 days).

Discussion

Children with acute leukaemia showed an increase in weight (+5%) and body mass index (+0.90 SDS), and a decrease in fat-free mass (?6%). Therefore fat mass increased. These changes are induced by steroid therapy. In children with solid malignant tumors, weight (?8%) and body mass index (?1.04 SDS) decreased (however not significantly), and fat-free mass (?2%) remained stable. Therefore fat mass decreased. Only in patients with acute leukaemia did the body mass index increase significantly from diagnosis to the end of intensive chemotherapy (p=0.025). In addition, chemotherapy induced growth retardation (?0.2 SDS). Albumin and prealbumin were not useful parameters for the assessment of nutritional status. Our study disproved the assumption that malnutrition develops during chemotherapy. These findings provide a factual basis to the advice given to parents of children with cancer and will help reduce the fear of chemotherapy.     

Psychological well-being in adults transplanted in childhood

Few studies have explored the long-term psychological effects on young adults of childhood transplants. The aim of the present work was to examine psychological adaptation related to self-concept, self-esteem and subjective well-being in young adults who had undergone solid organ transplantation in childhood. Twenty-four adults transplanted in childhood participated in the study (13 of them received kidney transplants, five heart transplants and six liver transplants). Participants were of both sexes, aged 18-22, and were selected from three public hospitals in Madrid. The results reveal no differences in psychological adaptation according to the transplant type (kidney, heart, or liver), and a significant difference in negative affect between women and men (women present more negative affect than men). Hierarchical regression analysis, after controlling for possible confounding effects of demographic and clinical variables, showed the predictive power of self-esteem to explain positive affect (60% of the total variance). Furthermore, physical self-concept, health status and time on waiting list explain 71% of the negative affect variance. Our data suggest the importance of self-esteem for the positive affect, and the power of clinical variables for the negative affect in young adults transplanted in childhood.