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     

Percentile regression analysis of correlated antibody responses

Antibody responses following vaccination usually are analysed by comparing geometric mean concentrations across levels of relevant covariates and by comparing the proportions of vaccinees responding. In the regression setting, the analyses are done on log-transformed concentrations, estimating geometric mean responses conditional on a vector of covariates. More detailed analyses examining the relationship of covariates to different parts of the response distribution may be performed through the application of asymmetric least squares estimation of regression percentiles. We present a method for accounting for correlation in percentile regression analyses of longitudinal antibody response data. We illustrate the procedures with measles antibody response data from Haitian children who participated in a randomized trial of high titre vaccines. The strongest dose and strain effects were seen in the low end of the antibody concentration distributions.     

Dislocation of the second through fifth carpometacarpal joints

We report a case of dislocation of the second through fifth carpometacarpal joints and review the mechanism of injury and radiographic findings in such injuries.     

Preliminary Evaluation of Sexual Problems in Combat Veterans with PTSD

This study evaluated the potential relationship between posttraumatic stress disorder (PTSD) and sexual problems. The Golombok Rust Inventory of Sexual Satisfaction was mailed to combat veterans currently in treatment at an outpatient PTSD clinic. Completed questionnaires were received from 90 patients. Results indicated that over 80% of subjects were experiencing clinically relevant sexual difficulties. Impotence and premature ejaculation were the most frequently reported problems that have corresponding psychological diagnoses. The rates of sexual problems for this sample of veterans with PTSD was similar to those reported in other studies and exceeded rates of similar problems found in samples from community samples. These data suggest mat PTSD may be a risk factor for sexual problems.     

Predictors of Repeat Emergency Department Visits by Elders

Objective: To determine which characteristics of older patients who use a hospital ED are associated with repeat visits during the 90 days following the index visit.
Methods: The study was conducted in the ED of a 400-bed university-affiliated acute care community hospital in Montreal. Patients aged ≥75 years who visited the ED between 08:00 and and 16:00 on a convenience sample of days over an 8-week period (July and August 1994) were assessed using a questionnaire, physical and cognitive status instruments, and a functional problem checklist. The hospital's administrative database was used to identify repeat visits during the 90 days following the ED visit. The representativeness of the sample was assessed by analyses of ED visits made by 4,466 persons aged ≥65 years during a 12-month period (September 1993 to August 1994) using the hospital's administrative database.
Results: 256 patients aged ≥75 years visited the ED during the study period and 167 were assessed. Of these, 54 (32%) were admitted to the hospital. Among the 113 patients released from the ED, 27 (24%) made repeat visits during the next 90 days. In univariate analyses, repeat visits were significantly associated with the number of functional problems, cognitive impairment, and previous ED visits. In multiple logistic regression, male gender, living alone, and number of functional problems were independent predictors of repeat visits. In the administrative data analyses, nighttime arrival to the ED for the index visit was significantly associated with repeat visits.
Conclusions: Self-reported risk factors can help to identify a group of elders likely to make repeated ED visits; the development of a screening instrument incorporating questions on these problems and implementation of appropriate interventions might improve these patients' quality of life and reduce the demand for further ED care in this age group.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Substance Misuse Among Women Attending Family Planning Clinics in a Rural Area in Britain: prevalence and associated problems

Objectives: Little research has been carried out focusing on women who misuse substances, although existing evidence suggests that they represent a distinctive group. The aims of the current study are to determine prevalence of tobacco, alcohol and other drug use in women attending family planning services in a rural area and to investigate preferred sources of help-seeking. Methods: A prospective study using a self-completed questionnaire assessing use of tobacco, alcohol, other drugs, associated problems and sources of help-seeking. The sample included women attending family planning clinics in a rural area of southern England. Results: Fifty-three percent were current smokers,thirty-five percent misused alcohol and fourteen and a half percent had used other drugs in the last year. Those using each of the substances were significantly more likely to be 21 years or under. Not all those using substances indicated problems and sources of help varied with the presence of problems. Conclusions: Women attending family planing clinics are a self-selected group with a high level of substance use compared to the general population. This suggests that they may have a lifestyle incorporating more risky behaviours, including unsafe sexual behaviour. Once problems have occurred due to substance use, help needs to be more accessible.     

Rational approaches to the neurobiologic study of youth at risk for bipolar disorder and suicide

Objectives:  The aims of this paper are to provide an overview of neuroimaging findings specific to bipolar disorder and suicide, and to consider rational approaches to the design of future in vivo studies in youth at risk.
Methods:  Neuroimaging and related neurobiological literature pertaining to bipolar disorder and suicide in adult and pediatric samples was reviewed in a non-quantitative manner.
Results:  Specific structural and functional brain findings in bipolar disorder are described, where possible in the context of relevant current neurobiological theories of etiology. Diagnostic and prognostic implications are discussed.
Conclusions:  The simultaneous use of complementary neurobiological approaches may be a powerful way of identifying and validating factors reliably associated with bipolar disorder and suicide. A profile of neurobiological markers with which to screen for bipolar disorder and suicide risk may provide for earlier and more accurate diagnosis, perhaps even in the pre- or subsyndromal stages in high-risk youth.