Consideration of the likely benefit from implementation of prostate image-guided radiotherapy using current margin sizes: a radiobiological analysis.

OBJECTIVE: To estimate the benefit of introduction of image-guided radiotherapy (IGRT) to prostate radiotherapy practice with current clinical target volume-planning target volume (PTV) margins of 5-10 mm. METHODS: Systematic error data collected from 50 patients were used together with a random error of σ=3.0 mm to model non-IGRT treatment. IGRT was modelled with residual errors of Σ=σ=1.5 mm. Population tumour control probability (TCP(pop)) was calculated for two three-dimensional conformal radiotherapy techniques: two-phase and concomitant boost. Treatment volumes and dose prescriptions were ostensibly the same. The relative field sizes of the treatment techniques, distribution of systematic errors and correlations between movement axes were examined. RESULTS: The differences in TCP(pop) between the IGRT and non-IGRT regimes were 0.3% for the two-phase and 1.5% for the concomitant boost techniques. A 2-phase plan, in each phase of which the 95% isodose conformed to its respective PTV, required fields that were 3.5 mm larger than those required for the concomitant boost plan. Despite the larger field sizes, the TCP (without IGRT) in the two-phase plan was only 1.7% higher than the TCP in the concomitant boost plan. The deviation of craniocaudal systematic errors (p=0.02) from a normal distribution, and the correlation of translations in the craniocaudal and anteroposterior directions (p<0.0001) were statistically significant. CONCLUSIONS: The expected population benefit of IGRT for the modelled situation was too small to be detected by a clinical trial of reasonable size, although there was a significant benefit to individual patients. For IGRT to have an observable population benefit, the trial would need to use smaller margins than those used in this study. Concomitant treatment techniques permit smaller fields and tighter conformality than two phases planned separately.

A treatment for tardive dyskinesia and some other extrapyramidal symptoms.

The effects of the administration of acetazolamide and thiamine (A + T) on the symptoms of tardive dyskinesia (TD) and parkinsonism of 8 elderly and 25 younger chronic hospitalized mental patients were examined in a placebo-controlled, double-blind, counterbalanced two-period cross-over study with initial baselines and intervening washout periods. All patients were maintained on their prestudy psychoactive and anti-Parkinson medications, without alteration, throughout the study. The elderly group received 1.5 g acetazolamide and thiamine per day in three divided doses for 3 weeks. The younger group received 1.5 g thiamine and 2.0 g acetazolamide per day in divided doses for 2 months. Both groups showed a significant decrease in scores on the Abnormal Involuntary Movement Scale (TD) and the Simpson-Angus Neurological Rating Scale (parkinsonism) while on A + T. The A + T effects were unrelated to age, gender, diagnosis, or maintenance medications.

Hypometabolism in olfactory cortical projection areas of male patients with schizophrenia: an initial positron emission tomography study.

Several studies have reported olfactory deficits in schizophrenic patients. This study examines local cerebral metabolic rate within two cortical areas in eight normal men and eight schizophrenic men. A significantly greater degree of hypometabolism was observed in the schizophrenic men in the cortical area of the nondominant hemisphere that receives direct uncrossed olfactory projections.

The Kallmann's syndrome variant (KSV) model of the schizophrenias.

The KSV model of the schizophrenias proposes that up to 70% of schizophrenics have a pathogenic allele, or abnormal expression, of the KALIG-1 gene which is located at Xp22.3. This gene encodes a nerve-cell adhesion molecule (N-CAM) like protein, and is deleted in 66% of patients with Kallmann's syndrome, anosmia with secondary hypogonadism. Although superficially distinct, the schizophrenias and Kallmann's syndrome show numerous parallel trait defects which occur with a similar sex distribution. These defects are usually more profound in Kallmann's syndrome. Occasionally, Kallmann's patients exhibit additional defects, such as ichthyosis, which are due to the further deletion or translocation of adjacent genes. Since schizophrenics exhibit virtually all known trait defects in Kallmann's except these, it suggests that the aberrant genes are defective, but not deleted in schizophrenia. It also appears that compensatory mechanisms, involving serine proteases, are active in schizophrenia, which largely preserve fertility, but at the expense of an increased vulnerability to develop a psychosis by an episodic disruption of the blood-CSF barrier. Consequently, schizophrenia is rare in Kallmann's patients, while most schizophrenics are capable of reproduction.

An electrophysiological study on the effects of tryptophan and cortisol on schizophrenic and other mentally ill patient groups and on normal subjects.

Direct current potentials measured on the scalp suprajacent to the midline prefrontal cortex appear to monitor the metabolic activity, via CO2 production, of this portion of the cerebrum. Changes in the frontal potential 90 min after oral administration of 2.0 g L-tryptophan and of 50 mg cortisol were studied in groups of subjects defined by age, sex, psychiatric diagnosis, and medication. Twelve normal males, 10 nonschizophrenic male psychiatric inpatients, and 6 normal females showed a significant decrease in their frontal voltages, most marked in the females, after tryptophan loading. A nonsignificant voltage increase was produced by subsequent administration of cortisol. Tryptophan-loading had an opposite, voltage-increasing effect, on the 30 schizophrenic subjects tested. This abnormal response was greatest in the male and postmenopausal schizophrenic subjects. Besides this sex effect, the abnormality increased with age up to a point, and was decreased by antipsychotic medication and cortisol. An explanation in terms of an abnormality in the relative hydroxylation of indoles in schizophrenic subjects is proposed.

Environmental noise level as a factor in the treatment of hospitalized schizophrenics.

Two groups of physically healthy schizophrenic patients comprised of fifteen withdrawn and fifteen actives per group with comparable sex and age distribution were selected for this study. Both groups were placed first in a quiet environment in which the noise level was kept between 40-60 decibels, for three hours each morning for six weeks' duration. Therapeutic and psychological and clinical parameters were used to examine the effects of this particular environment. At the end of six weeks, they were switched to a noisy environment with the noise level averaging 80-90 decibels. Noisy environment increased the withdrawn groups' motor and verbal performance, improved perceptual organization, improved sleep pattern and hallucinations. As a result, overall improvement caused medication decrease. For the active group, in a noisy environment, performance decreased, conceptual disorganization, anxiety and restlessness heightened, resulting in an increase of 40% in their medication. The withdrawn group in the quiet environment showed considerable regression with heightened autism, seclusiveness, more conceptual disorganization and disturbed sleep patterns with increased hallucinations. The active group in the quiet environment showed improved performance, decreased anxiety, more conceptual organization, less hallucinations, better sleep patterns; motor and verbal productivity increased.