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     

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.     

Personal and family risk factors for adolescent suicidal ideation and attempts.

Despite research indicating that suicidal ideation is strongly related to future suicide attempts, there is limited data on variables associated with continued suicidal ideation and behaviors in adolescents. The objective of this study is to investigate whether personal, cognitive and family risk factors can differentiate adolescent suicidal ideation and attempts. Twenty-four attempters, 50 ideators and 50 non-suicidal adolescents (aged 14 to 25 years) were asked during an interview to complete individual and psychosocial measures. Both suicidal groups reported greater personal vulnerability and perceived their family as less functional than did the non-suicidal group. However, no differences were found between both suicidal groups. The results suggest the presence of common factors in both adolescent suicidal ideators and attempters.     

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.     

Technology anxiety as a potential mediating factor in response to medical technology

Technology anxiety, defined as a fear of working with medical equipment, was measured via the use of the Technology Response Questionnaire. Nurses (N=414) working on nine types of nursing units at two hospitals participated in the study. Nurses working on psychiatric units were found to be most anxious about working with medical equipment, while nurses working on surgical and adult intensive care units were least anxious. A comparison of the nurses who were highest and lowest on technology anxiety indicated that those who were most anxious about technology were less positive toward computers, felt more stressed by their work, were lower on job satisfaction, less positive toward the physicians they worked with, lower on personality scales of autonomy and adaptability, were less likely to do care planning regularly or to use nursing diagnoses, and tended to be older than less anxious nurses.     

Cell kinetics of lamina propria fibroblasts in normal adult hamster bronchus.

Forty-nine 12-week-old male Syrian golden hamsters (Mesocricetus auratus), weighting 108 to 128 g, were injected i.p. with [3H]-thymidine (3HTdR 2 microCi/g body wt). Animals were divided into 7 weight-matched groups and were killed at 1 hour (day zero) and 1, 2, 3, 4, 7, and 14 days after thymidine injection. Lungs were fixed by vascular perfusion of 4% formalin/1% glutaraldehyde in 0.2 M cacodylate buffer at pH 7.4, cut at 2 microns, dipped in Kodak NTB3 or NTB2 nuclear emulsion, exposed for 2 weeks, developed and stained. In each airway cross-section, total epithelial and fibroblast counts and labeled cell count were estimated. A cell was considered labeled when 3 or more silver grains appeared on its nucleus. The background grain count was less than 1 grain per nucleus. Mean epithelial and fibroblast cell density in a 100 microns segment were respectively 14.8 +/- 0.1 and 6.6 +/- 0.1 cells (the second number is one standard error of the mean). One hour after labeling, their respective labeling indices (L.I.) were 0.13 +/- 0.02 and 1.24 +/- 0.1. On day 1, their L.I. doubled and then returned to the initial value. One hour after labeling, epithelial and fibroblast mean grain counts did not differ significantly. They were respectively 20.6 + 1, and 15.8 +/- 2. Because grain count intensity is closely related to DNA synthetic time, it seems plausible that epithelial and fibroblast synthetic times do not differ much. Cell turnover and cell cycle times were estimated from grain count dilution curves.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular and molecular effects of trimethyltin and triethyltin: Relevance to organotin neurotoxicity

Many of the neurotoxic aspects of organotin exposure have been described. Organotin exposure culminates in its accumulation in the CNS and PNS. The clinical picture is dominated by neurological disturbances; yet, the primary basis for their neurotoxicity is unknown. Trimethyltin (TMT) is primarily a CNS neurotoxin affecting neurons within the hippocampal pyramidal band and the fascia dentata. Triethyltin (TET) is a neurotoxin that produces a pathological picture dominated by brain and spinal cord edema. The first part of this review summarizes the current understanding of the interaction of TMT and TET with biologically active sites in the induction of neurotoxicity. In the second part, several hypotheses for the differential neurotoxic effects of these organotins and their shortcomings are discussed.