Measuring pulmonary function in infancy

In recent years there has been a growing interest in the measurement of pulmonary function in infants for both clinical and research purposes. Such measurements remain limited by the complexity of the equipment as well as by the technical and physiological challenges of testing infants and neonates. Despite these problems, assessment of respiratory function in early life provides exciting information about the post-natal growth and development of lungs in health and disease. The aim of this paper is to discuss the physiological, technical and ethical problems surrounding these procedures, as well as reviewing the current methods of testing pulmonary function in the very young. Consideration is given to the developments needed if infant pulmonary function tests are to realise fully, their potential as research and clinical tools.     

Serial blood lactate levels as a predictor of mortality in children after cardiopulmonary bypass surgery.

OBJECTIVE: To assess the role of serial lactate levels in determining outcome after cardiopulmonary bypass surgery in children. DESIGN: Analysis of retrospectively collected data. SETTING: Cardiac intensive care unit of a tertiary care children's hospital. PATIENTS: Patients were 129 children who underwent surgery for congenital cardiac defects. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients were categorized for disease severity using the Risk Adjustment for Congenital Heart Surgery method. Blood lactate levels were obtained at admission to the cardiac intensive care unit and then serially until they were <2 mmol/L. Lactime, time during which the lactate remains >2 mmol/L, was noted for each patient. The primary outcome measured was mortality. Secondary outcomes measured were ventilator days and hospital days. Six patients died, and of these five were neonates. Nonsurvivors had higher initial postoperative lactate concentration (p = .01), peak postoperative lactate concentration (p = .003), and lactime (p = .05). In binomial logistic regression analysis, lactime was the strongest predictor of mortality (p = .03). The positive predictive value for all age groups was highest for lactime >48 hrs, with a positive predictive value of 60%, and among the neonates it was 75%. Initial lactate level >6 mmol/L had a positive predictive value of only 6%, and the peak lactate level >6 mmol/L had a positive predictive value of only 15%. Lactime also had a significant association with ventilator days and hospital days among the survivors (p = .001). CONCLUSIONS: Lactime was a useful predictor of mortality in children undergoing repair or palliation of congenital cardiac defects under cardiopulmonary bypass. Initial and peak lactate levels had a poor positive predictive value for mortality. Lactime also was associated with the number of ventilator days and hospital days in those who survived.     

Comparison of physicians' and cancer prone women's attitudes about breast/ovarian prophylactic surgery. Results from two national surveys

Prophylactic surgery is a major issue for breast/ovarian cancer prone women. Bio-clinical data to help in the decision-making are not sufficient. In this context of uncertainty, physicians' and women's attitudes to prophylactic surgery is information of great value. The physicians' attitudes were assessed by a randomised national sample of practitioners involved in breast and ovarian cancer management. The patients' attitudes were appraised with a pre-consultation self-administered questionnaire presented during a one-year period to all women in five cancer genetic clinics chosen, for their representative geographical locations and their activity level. Consent to prophylactic surgery is higher among physicians than among patients (p < 0.0001). Acceptability of mastectomy is lower than that of oophorectomy in both patients and physicians (p < 0.0001 in both groups). In addition, age at which the intervention is proposed to be performed is a key determinant for both mastectomy and oophorectomy acceptability, in both physicians and patients (p < 0.001 for each comparison). Particularly, the age of 40 years seems to be a critical threshold for the acceptability of prophylactic oophorectomy. In contrast, respondents' age at the time of the survey has no significant effect on the acceptability rate. The higher acceptability rate of prophylactic oophorectomy compared to that of mastectomy observed in the physicians' survey is paradoxical because a more substantial medical impact on life expectancy was expected from the latter. Our results indicate that assumed reduced mortality is not the main criterion steering acceptability. It was anticipated that prophylactic mastectomy should be rarely performed in France.     

A cost-minimisation analysis of inpatient versus day surgery for gynaecological laparoscopy

The aim of this study was to investigate whether medium-term hospital resource use differed between ambulatory and inpatient laparoscopy surgery for benign gynaecological conditions. Patient-based costing data were collected through a randomised controlled trial involving 26 inpatients and 40 day-surgery patients. The perspective was that of the hospital gynaecological ward. Day surgery was significantly cheaper per patient than was inpatient surgery, mainly due to shorter operation times and lower hotel costs. Remedial surgery had a higher total cost than did evaluative surgery, but patient age, referral source and diagnosis, and surgeon seniority had no significant impact. Based on previous findings that ambulatory and inpatient surgery result in equivalent clinical outcomes, day surgery for benign gynaecological laparoscopy is cheaper and thus should be preferred to inpatient surgery.     

Fetal mitochondrial heart and skeletal muscle damage in Erythrocebus patas monkeys exposed in utero to 3'-azido-3'-deoxythymidine

3'-azido-3'-deoxythymidine (AZT) is given to pregnant women positive for the human immunodeficiency virus type 1 (HIV-1) to reduce maternal-fetal viral transmission. To explore fetal mitochondrial consequences of this exposure, pregnant Erythrocebus patas monkeys were given daily doses of 1.5 mg (21% of the human daily dose) and 6.0 mg (86% of the human daily dose) of AZT/kg body weight (bw), for the second half of gestation. At term, electron microscopy of fetal cardiac and skeletal muscle showed abnormal and disrupted sarcomeres with myofibrillar loss. Some abnormally shaped mitochondria with disrupted cristae were observed in skeletal muscle myocytes. Oxidative phosphorylation (OXPHOS) enzyme assays showed dose-dependent alterations. At the human-equivalent dose of AZT (6 mg of AZT/kg bw), there was an approximately 85% decrease in the specific activity of NADH dehydrogenase (complex I) and three- to sixfold increases in specific activities of succinate dehydrogenase (complex II) and cytochrome-c oxidase (complex IV). Furthermore, a dose-dependent depletion of mitochondrial DNA levels was observed in both tissues. The data demonstrate that transplacental AZT exposure causes cardiac and skeletal muscle mitochondrial myopathy in the patas monkey fetus.     

Ability of Doxorubicin-Loaded Nanoparticles to Overcome Multidrug Resistance of Tumor Cells After Their Capture by Macrophages

Purpose. Investigation of the ability of doxorubicin-loaded nanoparticles (NP/Dox) to overcome multidrug resistance (MDR) when they have first been taken up by macrophages. Methods. The growth inhibition of P388 sensitive (P388) and resistant (P388/ADR) tumor cells was evaluated in a coculture system consisting of wells with two compartments. The tumor cells were seeded into the lower compartment, the macrophages were introduced into the upper part in which the drug preparations were also added. Results. Doxorubicin exerted lower cytotoxicity on tumor cells in coculture compared with direct contact. In P388/ADR, NP/Dox cytotoxicity was far higher than that of free doxorubicin (Dox). Three different formulations of cyclosporin A (either free (CyA), loaded to nanoparticles (NP/CyA) or in a combined formulation with doxorubicin (NP/Dox-CyA)), were added to modulate doxorubicin efficacy. The addition of cyclosporin A to Dox increased drug cytotoxicity. Both CyA added to NP/Dox and NP/Dox-CyA were able to bypass drug resistance. Conclusions. Despite the barrier role of macrophages, NP/Dox remained far more cytotoxic than Dox against P388/ADR. Both NP/ Dox + CyA and NP/Dox-CyA allowed to overcome MDR, but the last one should present greater advantagein vivo by confining both drugs in the same compartment, hence reducing the adverse effects.     

The nutritional needs of rabbits

Rabbits are strict herbivores who require a high-fibre, abrasive diet for optimum digestive function. Diet plays a key role in preventing or lessening in severity several common health problems, as well as providing environmental enrichment, and therefore feeding rabbits correctly and understanding their nutritional needs is vital for veterinary nurses.