Job ending among youth and adults with severe mental illness

This study examined job leaving over a 36-month period among 326 persons (74 youth and 252 adults) with severe mental illness who were participating in an urban vocational rehabilitation program. Data from 627 job endings indicated that younger clients displayed job-ending patterns that were different in some aspects from such patterns for nondisabled youth (such as displaying a lower average job tenure) yet similar to job-ending patterns for nonhandicapped youth in other ways (such as displaying a high frequency of job changing). Youth and their adult counterparts with mental illness displayed similar tenure on agency-sponsored placements but significantly different tenure on independent jobs. While adults held their independent jobs for an average of seven months, youth averaged only three months at competitive employment. Youth also were significantly more likely than adults to be fired from both placements and independent jobs. These findings and others are discussed in terms of their implications for development of public policy and service delivery models for providing on-going job support to youth and adults with severe psychiatric disabilities.     

Inhibin and age in men

OBJECTIVE: Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years. DESIGN: Single fasting blood samples were obtained between 0800 and 0900 h. PATIENTS: Working men in a large industrial company between the ages of 19 and 60 years participated in the study. MEASUREMENTS: FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively. RESULTS: The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years. CONCLUSION: The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.


     

Effects of food deprivation on cocaine base smoking in rhesus monkeys

Studies have shown that both food deprivation and response cost have important influences on the magnitude of self-administration of a wide variety of psychoactive drugs. In an attempt to extend these findings to the smoked route of drug self-administration, the effects of food allotment and fixed-ratio (FR) value were evaluated in four male rhesus monkeys trained to smoke cocaine base. In the first phase of the experiment, monkeys were trained to self-administer smoked cocaine base under a chained progressive-ratio (PR), fixed-ratio (FR) schedule during daily experimental sessions. Monkeys were required to make 20 lever-press responses and then five inhalations on a smoking spout to obtain the first smoke delivery. The lever ratio then increased to 60, 140, 300, 620, 1260, 2540, and 4940 for each successive smoke delivery. The initial lever ratio value was reset to 20 at the beginning of each daily session. The body weights of three monkeys were determined under free-feeding conditions. Monkeys were then restricted to 100 g food and, when body weights had stabilized, the daily food allotment was increased to 150 g, approximately 210 g, or greater than 400 g (satiation). As the daily food allotment and body weight increased, the mean number of smoke deliveries decreased in two of three monkeys. In the second phase of the experiment, three monkeys were maintained under either food-satiated or food-restricted conditions. Body weights were maintained at approximately 90% of their free-feeding weights under food-restricted conditions. The cost of the drug (lever FR value) was constant within each experimental session, but was increased after 3 consecutive days of stable responding. Fixed-ratio values were increased from 128 to 256, 512, 1024, and 2048. Monkeys were required to complete the lever FR value and then to make five inhalations on the smoking spout to gain access to 1.0 mg/kg per delivery cocaine base. The mean number of smoke deliveries increased at FR 256, 512, and 1024 when monkeys were food-restricted as opposed to food-satiated. Correspondingly, the mean number of responses increased under food-restricted conditions. Responding continued to increase over a wider range of FR values, and the peak number of responses was higher under food-restricted, as opposed to food-satiated conditions. These results, using the smoking route of administration, are consistent with the hypothesis that food deprivation increases the self-administration of reinforcing drugs.     

Executive cognitive deficits in primary dystonia.

Primary dystonia is a disorder of movement for which no consistent pathophysiology has been identified; in the absence of evidence to the contrary, it is assumed to be cognitively benign. We have studied a clinically heterogeneous group of 14 patients with primary dystonia on a battery of neuropsychological tests. Despite well-preserved speed of information processing, language, spatial, memory and general intellectual skills relative to normal controls, we have identified a constellation of attentional-executive cognitive deficits on the Cambridge Neuropsychological Test Automated Battery (CANTAB). Specifically, patients demonstrated significant difficulties negotiating the extra-dimensional set-shifting phase of the IED task. The implications of these findings for the pathophysiology of primary dystonia are discussed. This is, to the best of our knowledge, the first report of a significant cognitive deficit in patients with primary dystonia.     

Patients with schizophrenia previously stabilized on conventional depot antipsychotics experience significant clinical improvements following treatment with long-acting risperidone.

BACKGROUND: Conventional depot antipsychotics can provide constant pharmacologic treatment, eliminating partial compliance and reducing relapse risk. Atypical antipsychotics, have improved clinical profiles but require daily dosing, compromising their overall effectiveness. As oral risperidone provides safety and efficacy benefits over oral haloperidol, improvements may be realized by replacing conventional with atypical agents in long-acting therapy. This report examines 50-weeks of long-acting risperidone therapy in patients previously stabilized with conventional depot antipsychotics. METHODS: A multi-center, open-label study enrolled 725 patients with schizophrenia or schizoaffective disorder, judged clinically stable and maintained on stable antipsychotic doses for > or =4 weeks. Assignment by clinician judgment to receive 25-75 mg of long-acting risperidone every 2 weeks for 50 weeks followed, with performance of standard safety and efficacy assessments. Data are presented on patients receiving conventional depot antipsychotic monotherapy at study entry. RESULTS: In the 188 (25.9%) patients receiving conventional depot antipsychotic monotherapy at entry, mild-to-moderate mean (+/-S.D.) Positive and Negative Syndrome Scale (PANSS)-total scores improved significantly after receiving long-acting risperidone (64.2 +/- 18.9 to 58.2 +/- 20.3; P < 0.001). Clinical improvement of > or =20%, 40%, or 60% reduction in PANSS-total score, occurred in 52%, 34%, and 16% of patients, respectively. ESRS subjective ratings and objective physician ratings (Parkinsonism) decreased significantly (P < 0.001). CONCLUSION: Stable patients with mild, residual symptomatology treated with conventional depot antipsychotics experienced significant improvement in psychiatric and movement disorder symptomatology following 1-year of treatment with long-acting risperidone.     

Decreased relative efficacy of the ketogenic diet for children with surgically approachable epilepsy.

PURPOSE: In children with intractable, surgically approachable epilepsy, the ketogenic diet is often perceived as less efficacious than surgery. METHODS: A retrospective chart review was performed of 554 children started on the ketogenic diet since 1994. Forty-five children were identified as surgical candidates, with at least 2 focal routine EEGs, ictal video-EEG, and corresponding focal neuroimaging findings, of whom 24 eventually had resective surgery and were followed subsequently. A comparison cohort group was also created of 45 children matched for age and seizure frequency that received the diet but were not surgical candidates (multifocal or generalized seizures). RESULTS: Of the 24 children who received both dietary and surgical therapies, there was a higher likelihood after 6 months of both >90% seizure reduction (71% versus 17%) and seizure freedom (63% versus 0%) following surgery, both p < 0.0001. Similarly, the 45 cohort children who were not surgical candidates were more likely to be seizure-free (29% versus 13%, p = 0.041) and remained on the diet for shorter duration (10 months versus 18 months, p = 0.035) compared to the surgical group. CONCLUSION: Children with surgically approachable epilepsy do respond to the diet, but are more likely to be seizure-free following surgery.