The extraneuronal compartments for the distribution of isoprenaline in the rat heart

The distribution of 3H-isoprenaline in the perfused rat heart was re-examined. After initial loading with 3H-isoprenaline hearts were washed out with amine-free solution; the efflux curves were subjected to the peeling technique, and half times for efflux and compartment sizes were determined. In contrast to earlier reports from his department (B?nisch et al. 1974;l B?nisch 1978), 3H-isoprenaline was found to distribute mainly into one extra-neuronal compartment, irrespective of whether COMT was intact or inhibited (by the presence of U-0521). It was also not influenced by pretreatment of the animals with reserpine. This type of distribution was influenced neither by the concentration of isoprenaline nor by the duration of the loading of the tissue with the amine. The one major extra-neuronal distribution compartment of 3H-isoprenaline has the characteristics of the "old" compartment III: it has a relatively short half time for the efflux of 3H-isoprenaline and it has a high activity of COMT. Moreover, corticosterone inhibits the inward and outward flux of 3H-isoprenaline into and from compartment III. The Ki for the inhibition by corticosterone of the efflux of 3H-isoprenaline (2 mumol/l) is very similar to the Ki for impairment of uptake2 (determined by B?nisch 1978). Apart from the major distribution compartment III, two minor distribution compartments were detected: On the one hand, experiments with hearts which had an intact COMT revealed that a minor distribution compartment IV (characterized by a long half time for efflux and by an absence of COMT activity) may exist, although its magnitude does not exceed one tenth of the former compartment IV. In addition, part of the quickly equilibrating (and rather small) compartment II was corticosterone-sensitive. When the results of Azevedo et al. (1983 are considered together with the present results, compartment III appears to represent the uptake of 3H-isoprenaline into myocardial cells, while it is likely that radioactivity accumulated in the smooth muscle of blood vessels may constitute the corticosterone-sensitive part of compartment II.     

Economic evaluation of treatments for respiratory disease

Considerable quantities of health service resources are being devoted to tackling the problems posed by respiratory diseases and this can be expected to continue as the prevalence of such diseases increases. This paper provides an assessment of the most efficient use of these healthcare resources by reviewing the literature on economic evaluation relating to interventions in the field of respiratory medicine. Currently, this literature largely comprises cost-minimisation studies of both management and educational interventions. Asthma educational interventions, whether targeted at adults or children, appear to be effective in improving patient self-management and adherence to medications, and appear to be associated with a lower overall use of healthcare resources. In terms of management interventions the overall picture is rather less clear although there is some support for the greater efficiency of patient administration of beta-adrenergic agonists by metered dose inhalers over therapist-administered up-draft nebulisation. Two features of respiratory disease make evaluation in this field somewhat unusual: there are alternative methods of delivering therapy to patients, which makes patient compliance an important issue, and since most respiratory diseases are chronic conditions the long-term effectiveness of interventions must be assessed. The scarcity of cost-effectiveness and cost-utility studies in this field may, in part, reflect the difficulties of measuring outcomes in respiratory disease.     

Transparent blocks—an aid in simulation

The use of standard cutouts made of pressed wood¹ and lead solder is advocated for treatment simulation of blocked fields. The advantages offered are the ability to see “through” the block and the capability of planning simple or complex blocking within the limits of existing lead block shapes.     

Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer

Purpose: To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy.

Materials and Methods: Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value ≥ 1 ng/ml; or 2. a PSA value that rose ≥ 0.5 ng/ml in ≤ 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as (iPSA) + 10(GS-6), and high risk was defined as %rLN+ ≥ 15%. Univariate and multivariate analyses were performed.

Results: A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome.

Conclusion: Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.     

Human sperm endothelial nitric oxide synthase expression: correlation with sperm motility

Objective: To characterize the pattern of endothelial nitric oxide synthase (eNOS) expression on human spermatozoa and to determine whether sperm eNOS expression correlates with sperm function.

Design: Prospective, observational study.

Setting: University infertility clinic.

Patient(s): Twelve nonazoospermic infertile men.

Intervention(s): Semen samples (n = 12) obtained from nonazoospermic infertile men were fractionated on discontinuous Percoll gradients. Endothelial nitric oxide synthase staining on spermatozoa was correlated with sperm motility in Percoll gradient–fractionated spermatozoa. Endothelial nitric oxide synthase protein was detected with the use of a previously characterized monoclonal antibody. Control slides were incubated with preabsorbed antibody or mouse immunoglobulin G.

Main Outcome Measure(s): Localization of eNOS on human spermatozoa and correlation between the pattern of sperm eNOS expression and sperm motility.

Result(s): Morphologically normal spermatozoa exhibited postacrosomal and equatorial eNOS immunostaining. However, abnormally shaped spermatozoa often exhibited aberrant staining (in the midpiece and/or head region). A significant negative correlation was observed between the percentage of sperm with aberrant eNOS immunostaining and the percentage of motile sperm (r = −.46).

Conclusion(s): The specific localization of eNOS to human spermatozoa suggests that nitric oxide may be involved in normal sperm physiology. However, aberrant patterns of sperm eNOS expression are associated with decreased sperm motility, possibly through the generation of excessive cytotoxic oxidants.     

Field and model investigations of external gamma dose rates along the Cumbrian coast, NW England.

A survey of the contribution to external dose from gamma rays originating from intertidal sediments in the vicinity of the British Nuclear Group Sellafield site showed that the major anthropogenic contributions were due to (137)Cs and (60)Co. At some sites, traces of other anthropogenic radionuclides were detected, namely (106)Ru, (125)Sb, and (154)Eu. The proportions of fine grained material (<63 microm) were used to improve model predictions of dose contribution due to external exposure to gamma rays, using the CUMBRIA77/DOSE77 model. Model dose predictions were compared to those directly measured in the field. Using the new proportions of fine grained material (1-17.5%) in conjunction with field gamma-ray spectra, model predictions were improved considerably for most sites. Exceptions were at Drigg Barn Scar and Whitehaven Coal Sands sites, which had their own unique characteristics. The highest (60)Co activity concentrations in this study were detected at Drigg Barn Scar. These relatively high activity concentrations of (60)Co were due to the presence of (60)Co in mussels and barnacles, hence upsetting the fine sediment relationships used in previous dose calculations. Whitehaven Coal Sands was unusual in that it contained higher levels of radionuclides than would be expected in sandy sediment. The mineralogy of these sediments was the controlling factor on (137)Cs binding, rather than the proportion of fine grained material. By adjusting the effective fine grained sediment proportions for calculations involving (60)Co and (137)Cs at Drigg Barn Scar and Whitehaven Coal Sands respectively, the CUMBRIA77/DOSE77 model predictions could be improved upon significantly for these sites. This work highlights the influence of particle size and sediment composition on external dose rate calculations, as well as the potential for external dose contributions from biota.     

Tobacco and Alcohol Use as an Explanation for the Association Between Externalizing Behavior and Illicit Drug Use Among Delinquent Adolescents

The prevalence and persistence of adolescent substance use and abuse is a national health issue, and substance use among adolescents is frequently comorbid with other psychiatric disorders. Most studies in this area utilize samples of middle or high school students or from inpatient settings. Less is known about substance use and psychiatric comorbidity among delinquent adolescents. The present study examined data from two cohorts of juvenile offenders collected over a 2-year period (n = 245, n = 299). Participants reported frequency of cigarette, alcohol, marijuana, and other substance use. Participants' parents completed a measure of behavior problems. Path analyses suggested that parental reports of externalizing problems were significantly related to self-reported substance use while parental reports of internalizing problems were not. Results also suggested that smoking and alcohol use act as mediators between externalizing problems and marijuana and other drug use. Although there were some mean differences by gender, the pattern of relationships amongst the variables did not differ by gender. Implications of the findings and future directions are discussed.     

Pharmacological Treatment of Mood Disturbances, Aggression, and Self-Injury in Persons with Pervasive Developmental Disorders

Aggression, self-injury, and mood disturbances in persons with autistic disorders, while not uncommon, do not constitute core features of autism. Moreover, these problems can occur for a variety of reasons, which need to be assessed in order to plan appropriate and frequently combined (behavioral-pharmacological) treatments. Drugs acting primarily in the dopaminergic, serotonergic, adrenergic, opioidergic, and glutamatergic systems all have been explored in the treatment of aggression and self-injury. While no single drug or class of medication has yet emerged as consistently effective, a number of drugs appear promising. Advances in the assessment of aggressive behaviors, the identification of predictors of drug response, and additional controlled clinical drug trials specifically aimed at these target behaviors are essential in improving the approach to these problematic behaviors in the context of autistic disorder.