The pharmacokinetics of high-dose epirubicin and of the cardioprotector ADR-529 given together with cyclophosphamide, 5-fluorouracil,and tamoxifen in metastatic breast-cancer patients

A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-m silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600–1000 mg/m²) together with different doses of epirubicin (E, 60–100 mg/m²), fixed-dose cyclophosphamide (C, 600 mg/m²), fixed-dose 5-fluorouracil (F, 600 mg/m²), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m². We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity.     

Is the IV obstructed or infiltrated? A simple clinical test

Objective. The objective of our study was to determine if clinical observation of pressure-flow relationships (PFR) can differentiate between partial external obstruction (obstruction) and infiltration as a cause of poor performance of gravity-fed infusions.Methods. A total of 24 patients with functional intravenous cannulae in situ had obstruction simulated by the application of a tourniquet proximal to the cannula. The change in flow (F) for a discrete change in pressure (P) was determined in each case by counting drop rates at two different elevations of the fluid reservoir level, 10 cm apart. The same process was repeated in 15 patients in whom the cannula was in an extra vascular location (infiltration). Three sizes of cannula—16-gauge, 18-gauge, and 20-gauge—were examined, with equal distribution of sizes in each group. The effect on flow rates of inflating a blood pressure (BP) cuff proximally on the cannulated limb was assessed. The ratio P/F is the total resistance of the infusion system, and by subtracting known values for resistance of infusion tubing and cannula, the venous or tissue resistance was calculated.Results. There was a statistically significant difference between the change in flow for obstructed compared with infiltrated cannulae for the same change in pressure for each cannula size. The mean venous resistance was 23 mm Hg/L/hr, while that of tissue was 280 mm Hg/L/hr, with no overlap between groups. There was no effect on flow rate with blood pressure cuff inflation in the infiltrated group whereas flow progressively fell in the obstructed group.Conclusions. Clinical observation of PFRs in poorly functioning gravity-fed IV infusions can assist in detecting infiltration as a cause. Inflation of a blood pressure cuff will further impair flow where the cannula is intravascular, but will have no effect in an extravascular location.     

Success in Surgical Intervention for Morbid Obesity: Is Weight Loss Enough?

Varieties of gastric surgery have increasingly been used in the management of morbid obesity. Generally, however, research and commentary in this area have related to surgical technique, with weight loss or morbidity being regarded as the most important dependent measures. In the context of the publication of several papers relating to the effects of surgery in the long-term, we believe that it is timely for surgeons to examine their criteria for success. In this paper, we argue that weight loss is inadequate as a primary criterion for success in this context, and that the value of the intervention should be measured against a multidimensional concept of success.     

The voluntary community health movement in India: A strengths,weaknesses, opportunities,and threats (SWOT) analysis

There has been a prolific growth of voluntary organizations in India since independence in 1947. One of the major areas of this growth has been in the field of community health. The purpose of this article is to historically trace the voluntary movement in community health in India, analyze the current status, and predict future trends of voluntary efforts. A review of the literature in the form of a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was the method of this study. Some of the key trends which emerged as the priority areas for progress and for strengthening voluntary organizations in the future were enhancing linkages between health and development; building upon collective force; greater utilization of participatory training; establishing egalitarian and effectual linkages for decision making at the international level; developing self-reliant community-based models; and the need for attaining holistic empowerment at individual, organizational, and community levels through duty consciousness as opposed to merely asking for rights.The authors would like to express gratitude to Voluntary Health Association of India for sharing the necessary documents and to Dr. Rick Petosa for valuable editorial comments.     

Body mass index and cardiovascular risk factors in pacific Island Polynesians and Europeans in New Zealand

Objectives. To examine relationships between body mass index (BMI) and cardiovascular risk factors in 279 Europeans and 231 Polynesian Pacific Islanders in New Zealand.

Methods. Participants were recruited from Seventh‐Day Adventist church meetings or camps, and were surveyed by self‐administered questionnaire. Blood pressure, weight and height were measured. Fasting blood samples were analysed for lipids, glucose and fructosamine.

Results. Age‐adjusted BMI was higher in Pacific Islanders than in Europeans: 32.8(0.3) versus 25.6(0.3); means(SE); p = 0.0001). In Europeans, BMI was positively associated with systolic and diastolic blood pressures, triglycerides, total cholesterol, LDL cholesterol and fasting blood glucose, and negatively associated with HDL cholesterol. In Pacific Islanders, BMI was associated only with systolic and diastolic blood pressures, and with HDL cholesterol. These associations were stronger in Europeans than in Pacific Islanders.

Conclusions. In this group of Pacific Islanders, the association between BMI and cardiovascular risk factors was weaker than in Europeans. This suggests that either BMI is a poor measure of adiposity in Pacific Islanders, or that adiposity may be less strongly linked to cardiovascular disease in Pacific Islanders.     

Canal geometry changes associated with axial compressive cervical spine fracture

STUDY DESIGN: A laboratory study using isolated ligamentous human cadaveric cervical spines to investigate canal occlusion during (transient) and after (steady-state) axial compressive fracture. OBJECTIVES: To determine whether differences exist between transient and postinjury canal occlusion under axial compressive loading, and to examine the effect of loading rate on canal occlusion. SUMMARY OF BACKGROUND DATA: Prior studies have shown no correlation between neurologic deficit and canal occlusion measurements made on radiographs and computed tomography scans. The authors hypothesized that postinjury radiographic assessment does not provide an appreciation for the transient occlusion that occurs during the traumatic fracture event, which may significantly affect the neurologic outcome. METHODS: Twelve human cervical spines were instrumented with a specially designed canal occlusion transducer, which dynamically monitored canal occlusion during axial compressive impact. Six specimens were subjected to a fast-loading rate (time to peak load, approximately 20 msec), and the other six were subjected to a slow-loading rate (time to peak load, approximately 250 msec). After impact, two different postinjury canal occlusion measurements were performed. RESULTS: Each of the six specimens subjected to the fast-loading rate incurred burst fractures, whereas the slow-loading rate produced six wedge-compression fractures. For the fast-rate group, the postinjury occlusion-measurements were significantly smaller than the transient occlusion. In contrast, transient occlusion was not found to be significantly different from postinjury occlusion in the slow-rate group. All of the comparisons between loading rate groups showed significant differences, with the fast-rate fractures producing larger amounts of canal occlusion in every category. CONCLUSIONS: The findings indicate that even if canal occlusion could be measured immediately after axial compressive trauma, the measurement would underestimate the maximal amount of transient canal occlusion. Therefore, postinjury measurement of canal occlusion may indicate a smaller degree of neurologic deficit than what might be expected if the transient occlusion could be measured.     

Cervical approach for large thyroid mass with substernal extension

The large thyroid mass with substernal extension often requires a combination of cervical and thoracic approach for its access and removal. We have developed a technique that uses a cervical incision and combines clear access to the mass with low morbidity. The principle features include complete sternocleidomastoid mobilization, early identification of the neurovascular pedicle through a lateral approach, and finger dissection to deliver the substernal component of the mass. This article also describes the elements of our technique in detail, from preoperative considerations through wound closure and discusses the debate concerning the ideal treatment of these challenging tumors.     

Prophylactic Amnioinfusion During Labour Complicated by Meconium

EDITORIAL COMMENT: This study of amnioinfusion during labour complicated by the known passage of meconium shows that the technique seems clinically worthwhile, even in a centre without facilities for electronic fetal heart monitoring or scalp blood pH and blood gas analysis. The series is small and more data from larger studies is required to test the conclusions reported by the authors.
Summary: A prospective study to see the safety and efficacy of transcervical amnioinfusion in labour complicated by meconium-stained amniotic fluid (MSAF) was carried out in a teaching hospital with limited resources. Fifty patients in labour with meconium-stained amniotic fluid and fulfilling the inclusion criteria (vertex presentation, gestational age of 36 weeks or more, no medical or obstetrical complications and normal fetal heart rate at time of inclusion) were taken for the study; 25 patients received amnioinfusion. The control group received only supportive therapy. Labour outcome was compared in the 2 groups. The incidence of Caesarean section was seen to be decreased but neonatal parameters showed no significant difference in the amnioinfusion group.