Effect of poly rI:rC treatment upon the metabolism of [14C]-paracetamol in the BALB/cJ mouse

The effect of the immunomodulator, poly rI:rC, upon the in vivo metabolism of [14C]-paracetamol has been investigated in male BALB/cJ mice. In both poly rI:rC treated and control groups of mice the major part of the dose was excreted in the 0-24 hr urine and the major urinary metabolites were the glucuronic acid and sulphate conjugates. The urinary excretion of these two conjugates and of free paracetamol was not significantly altered following poly rI:rC treatment. Following enzymic hydrolysis of glucuronides and sulphates, the 3-cysteine, 3-mercapturate, 3-thiomethyl and 3-methylsulphoxide metabolites of paracetamol were all identified in the 0-24 hr urine together with very small amounts of 3-methoxy paracetamol. Although poly rI:rC treatment reduced the proportional urinary excretion of each of the thio adducts the individual differences were not significant. However, total thio adduct excretion, an indirect estimate of the metabolic activation of paracetamol, was significantly lower following poly rI:rC treatment. This depression in the urinary excretion of thio adducts following poly rI:rC treatment is discussed in relation to possible implications for paracetamol toxicity.     

Phase II trial of PALA in combination with 5-fluorouracil in advanced pancreatic cancer

Summary Phosphonacetyl-l-aspartate (PALA), an inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m² on day 1, followed 24 h later by 2,600 mg/m² 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.Supported in part by grant CA 06927 from the National Cancer Institute     

A brief survey of chemical defense, crew rest, and heat stress/physical training issues related to Operation Desert Storm.

A brief questionnaire was administered to 148 soldiers, over two-thirds of whom were aviators, at the conclusion of Desert Storm. Questions were asked about chemical defense, work/rest schedules, an aspect of pharmacological support, and heat stress/physical training during Operations Desert Shield and Desert Storm. Follow-up face-to-face interviews also were conducted with some respondents. Some of the most noteworthy findings concerned (1) training issues and side effects related to pyridostigmine bromide, (2) problems with chemical defense clothing, (3) suggestions for improving crew rest, and (4) facts about the ways in which heat-related difficulties were minimized.     

Functional anatomy and biomechanics of the meniscus

The meniscus is no longer considered the evolutionary remnant in the knee joint.Rather, it is now well established as an important structure that is integral to the complex biomechanics and proper functioning of the knee. The medial and lateral menisci form two crescent-shaped wedges of fibrocartilage between the femoral condyles and tibial plateaus.The knee joint biomechanics are based on a complex interaction of these intra-articular structures. The functions ascribed to the menisci include load transmission, shock absorption, stability, proprioception, joint lubrication, and joint nutrition. Load transmission generally is accepted as one of its primary functions. The menisci transmit a portion of the axial forces across the knee joint by converting this load into “hoop stresses.” This is accomplished by their unique shape, composition, and anatomic attachments. The menisci are relatively mobile structures and their motion during knee flexion also is determined by their shape and soft tissue attachments/constraints. Preservation of the meniscal functions is essential, and the authors review the basic anatomic and biomechanical concepts necessary to understand techniques for repair and restoration of these functions.     

The impact of hospital structure and restructuring on the nursing workforce.

OBJECTIVE: Health systems throughout much of the world have been subject to 'reform' in recent years as countries have attempted to contain the rapidly rising costs of health care. Changes to hospital structures (restructuring) have been an important part of these reforms. A significant impact of current approaches to restructuring is the loss of, or changes to, nursing management roles and functions. SETTING: Australian hospitals PRIMARY ARGUMENT: Little evaluation has been undertaken to determine the impact of hospital structure and organisational restructuring on the nursing workforce. CONCLUSIONS: There is some indication that nurses have experienced a loss of key management positions, which may impact on their capacity to ensure that adequate and safe care is provided at the ward level.     

Relaxation Therapy and Compliance in the Treatment of Adolescent Headache

SYNOPSIS
Few controlled studies have examined the effectiveness of relaxation therapy for the treatment of adolescent headaches. In this study, ten chronic headache sufferers (migraine or muscle contraction), ranging in age from 12 to 17 years (M = 13.5 SD = 1.3), were sequentially assigned to either a relaxation therapy or waiting-list control group. Following treatment, subjects in the treatment group demonstrated significantly lower Headache Index scores than subjects in the control group (U = 0, p £ .004). Group differences in Headache Free Days, Peak Headache Rating, and Medication Index scores were not significant; differences in Medication Index scores approached significance at U = 3, p £ .03. Objective compliance to treatment data indicated subjects overreported their actual practice time, on average, by 70%. Results and implications for future research are discussed.