Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder.

BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.     

In situ hybridization of prostate-specific antigen mRNA in human prostate.

Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.     

Intra-operative parathyroid hormone assay for simplified localization of parathyroid adenomas.

Lack of success in parathyroid surgery is usually due to failure to identify the abnormal parathyroid gland correctly at operation. The surgeon may be helped by rapid parathyroid hormone (PTH) assay in peripheral blood after removal of a suspected adenoma, and by frozen section histology, but these are not true localization techniques. We have adapted a non-isotopic immunoassay for rapid measurement of PTH in samples from the upper, middle and lower thyroid veins taken at operation, before exploration begins. Fifteen patients with primary hyperparathyroidism were operated on. In 10 the parathyroid adenoma was located easily, and was associated with high local venous PTH levels. In four patients the abnormal parathyroid was not immediately apparent but the assay indicated its location, which was confirmed after further exploration. In one patient there was no difference in PTH levels in the six venous samples. An ectopic adenomatous gland was successfully identified behind the thymus. The operation was successful in all patients as shown by a fall in the plasma calcium to the normal range. We conclude that intra-operative selective venous sampling and rapid PTH assay facilitates operative localization of parathyroid adenomas.     

Mosquito (Diptera: Culicidae) dispersal: implications for the epidemiology of Japanese and Murray Valley encephalitis viruses in Australia

One hypothesis to explain the southern extension of Japanese encephalitis (JE) virus from Papua New Guinea into the Torres Strait islands in 1995 and to mainland Australia in 1998 is the dispersal of infected mosquitoes, particularly Culex annulirostris Skuse from which JE virus has been isolated repeatedly. To investigate whether this species disperses in this manner, mosquitoes were identified from 368 aerial kite trap collections operated at 50-310 m (altitude) at inland New South Wales between November 1979 to December 1984. Forty samples (9 during daylight and 31 at night) contained mosquitoes, of which 221 could be identified as Culex australicus Dobrotworsky & Drummond (58.8%), Culex annulirostris (21.3%), Anopheles annulipes Walker s.l. (10.4%), Aedes theobaldi (Taylor) (7.2%), Aedes rubrithorax (Macquart) (1.4%), and Aedes sagax (Skuse) (< 0.9%). During the night, mosquitoes were found in 22.6% of the collections at a mean density (+/- SD) of 91.3 +/- 151.7/10(6) m3 of air sampled. During the day, only 3.8% were positive at a mean density 125.3 +/- 152.1. When examined in relation to possible flying time and wind speed, mean +/- SD dispersal distances by day and night were 23.9 +/- 15.3 km and 152.4 +/- 116.3 km, respectively. These data provide circumstantial evidence that aerial carriage southward approximately 200 km from Papua New Guinea to Cape York peninsula is feasible, but that southern dispersal of Murray Valley encephalitis virus infected mosquitoes from tropical to temperate Australia is unlikely.     

Adolescent drug and alcohol usage: a comparison of urban and suburban pediatric practices.

Few pediatric practice-based drug and alcohol surveys have been conducted with adolescent patients. This study reports on similarities and differences in adolescent drug and alcohol use between urban (95% black) pediatric practices and a suburban (89% white) pediatric practice. While there were greater similarities between patient substance use and reported problems than differences, a number of significant differences emerged. White suburban youth were heavier users of tobacco products, alcohol, and inhalants, and experienced more difficulties with blackouts, family conflict, school absence, suicidal ideation, and loss of peer relationships. Other racial/ethnic and practice site differences are discussed. This study highlights characteristics of youth drug abuse in the private pediatric practice setting and implications for the pediatrician in caring for adolescents.