Occupational stress: a survey of management in general practice

OBJECTIVES: To identify approaches to and barriers associated with the management of patients with work-related stress by general practitioners (GPs). DESIGN: Cross-sectional postal survey using a self-administered questionnaire which included a case vignette of a patient with work-related stress and questions ascertaining perceived barriers to the effective general practice management of work-related stress. PARTICIPANTS AND SETTING: 450 Western Australian GPs on the mailing list of a GP journal. The survey was conducted between 22 March and 28 April 2000. MAIN OUTCOME MEASURES: Likelihood that GPs would (i) choose to open a workers compensation claim and (ii) provide time off work for the patient described in the vignette. RESULTS: Response rate was 50.1%. Eighty-five percent (95% CI, 79.6%-19.7%) of respondents advised the hypothetical patient to take time away from work; however, only 44.0% (95% CI, 37.2%-50.7%) chose to initiate a workers compensation claim. GPs with training or experience in occupational health were less likely to advise the patient to stay away from work (odds ratio [OR], 0.30; 95% CI, 0.12-0.73), but were just as likely to initiate a claim. GPs were reluctant to involve the employer in management decisions, because of concern about patient confidentiality and the potential to make matters worse for the patient. These, and the adversarial nature of the workers compensation system, were the strongest perceived barriers to effective management of the condition. CONCLUSIONS: Our findings indicate that general practitioners take a pragmatic and varied approach to the management of work-related stress. The perceived difficulties with contacting employers challenges the principles of injury management within a workers compensation system which is dependent on liaison between system stakeholders.     

Local injection of pertussis toxin attenuates morphine withdrawal excitation of rat supraoptic nucleus neurones

Morphine inhibits oxytocin neurones via G(i/o)-protein-linked mu-opioid receptors. Following chronic morphine administration oxytocin cells develop dependence, shown by withdrawal excitation after administration of the opioid antagonist, naloxone. Here, inactivation of G(i/o)-proteins by pre-treatment of morphine-dependent rats with pertussis toxin injected into the left supraoptic nucleus reduced withdrawal-induced Fos protein expression within the injected nucleus by 41+/-10% compared to the contralateral nucleus, indicating that functional G(i/o)-proteins are essential for the development and/or expression of morphine dependence by oxytocin cells in the supraoptic nucleus. In another group of rats, pertussis toxin did not alter the responses to either systemic cholecystokinin administration or systemic hypertonic saline administration, indicating that pertussis toxin does not prevent oxytocin cells from responding to stimuli that are not mediated by G(i/o)-proteins. Finally, pertussis toxin reduced acute morphine inhibition of systemic hypertonic saline-induced Fos protein expression in the supraoptic nucleus, confirming that pertussis toxin effectively inactivates G(i/o)-proteins in the supraoptic nucleus. Thus, the expression of morphine withdrawal excitation by supraoptic nucleus oxytocin cells requires the functional integrity of G(i/o)-proteins within the nucleus.     

Costs and quality of life of multiple sclerosis in the United Kingdom

This cost-of-illness analysis for the United Kingdom is part of a Europe-wide study on the costs of multiple sclerosis (MS). The objective was to analyze the costs and quality of life (utility) related to the level of disease severity. People with MS from a database administered by a UK charity (the MS Trust) were asked to participate in the survey by answering a postal questionnaire. In addition to details on the disease (type of disease, relapses, level of functional disability), the questionnaire asked for information on all resource consumption, medical, non-medical, work absence and informal care as well as utility. The response rate was 19%, and a total of 2048 people were included. The mean age of the cohort was 51 years, and 23% of people were ≥60 years of age. Disease severity was concentrated in people with moderately severe MS (Expanded Disability Status Scale [EDSS] score of 4 to 6.5), with 21, 60 and 19% of people reporting mild, moderate and severe disease, respectively. Costs and utility are highly correlated with disease severity. Mean annual costs for all people in the study increase from approximately £ 12.000 at an EDSS score <4 to almost £ 60.000 at an EDSS score ≥7. In particular, employment rates are reduced from 82% in early disease to 2% at an EDSS score of 8, while the costs of inpatient care, investments, informal care and productivity losses increase by more than tenfold between an EDSS score of 0-1 and a score ≥7. Utility decreases from 0.92 at an EDSS score of 0 to a state worse than death in the most severe state (–0.18 at an EDSS score of 9). Compared to the results in an earlier cost study in the United Kingdom using a comparable methodology, costs have substantially increased, by roughly 40%. Part of the increase is due to a higher use of disease-modifying drugs and, possibly linked with this, a higher use of ambulatory care and services. Another part of the increase is most likely due to an increased age in the current sample, with more patients on early retirement due to MS and more intense use of informal care. However, another reason may lie in the methodology, e.g. different unit costs or differences in the sample distribution, despite a similar mean EDSS score of 5.1.     

Pituitary hypoplasia in patients with a mutation in the growth hormone-releasing hormone receptor gene

BACKGROUND AND PURPOSE: Several anatomic abnormalities of the pituitary gland have been described as occurring in association with congenital growth hormone deficiency, including hypoplasia of the adenohypophysis, truncation of the pituitary stalk, and ectopia of the neurohypophysis. Their pathogenesis, however, is obscure. Normal pituitary development is dependent on the sequential expression of a series of ontogenetic factors. Growth hormone-releasing hormone (GHRH) is known to stimulate somatotroph proliferation, and a dwarf mouse model with a mutant GHRH receptor, the "little mouse," has a small anterior pituitary due to hypoplasia of the somatotrophs. We recently described the human homolog of the little mouse (dwarfism of Sindh), caused by a homozygous nonsense mutation in the GHRH receptor gene in a Pakistani kindred. We investigated MR imaging characteristics to gain information regarding the potential role of GHRH in human pituitary organogenesis. METHODS: MR images of the head were obtained of four affected male patients (age range, 22-29 years). Maximal anterior pituitary dimensions were determined from sagittal and coronal images, and pituitary volumes were estimated from cubic and ellipsoid formulae. The measurements were compared with normative values matched for age and sex. RESULTS: The adenohypophysis was small in each of the four patients. The maximal height for the anterior pituitary was 3 mm in three patients and 2 mm in one (mean +/- SD, 2.75 +/- 0.5 mm), which is significantly (P < .001) less than the expected height of 5.6 +/- 1.0 mm for men in this age group. Estimates of anterior pituitary volume in the patients ranged from 75 to 124 mm3 (104 +/- 21 mm3), which corresponds to 35% to 52% of the normal mean volume corrected for small head size (P < .005). No other cranial abnormalities were identified. CONCLUSION: We describe significant hypoplasia of the adenohypophysis occurring in four dwarfs with a nonsense mutation in the GHRH receptor. In addition to isolated growth hormone deficiency and severe dwarfism, affected patients have anterior pituitary hypoplasia, presumably due to somatotroph maldevelopment. Resistance to GHRH explains the hypoplasia of the adenohypophysis--a feature that contributes to growth hormone deficiency in this syndrome. This is one of the few instances in which the molecular basis of pituitary dysmorphogenesis has been identified.     

Overexpression of the insulin-like growth factor I receptor and activation of the AKT pathway in hyperplastic endometrium.

PURPOSE: Although there is considerable information on the molecular aberrations associated with endometrial cancer, very little is known of the changes in gene expression associated with endometrial hyperplasia. EXPERIMENTAL DESIGN: To address this, we have compared the level of expression of estrogen-regulated genes and components of the insulin-like growth factor I (IGF-I) signaling pathway in endometrial biopsies from subjects with normal endometrium, complex atypical endometrial hyperplasia, and endometrial adenocarcinoma (type I). RESULTS: There was a significant increase in the expression of the IGF-I receptor (IGF-IR) in biopsies from hyperplastic endometrium and endometrial carcinoma compared with the proliferative endometrium. The receptor was also activated, as judged by increased tyrosine phosphorylation. In addition, in endometrial hyperplasia and carcinoma, the downstream components of the IGF-IR pathway are activated, as reflected in increased Akt phosphorylation. Loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression in endometrial hyperplasia did not correlate with increased activation of IGF-IR. However, the simultaneous loss of PTEN expression and increased IGF-IR activation in hyperplasia was associated with an increased incidence of endometrial carcinoma. CONCLUSIONS: These results suggest that up-regulation of IGF-IR and loss of PTEN may be independent events that give rise to complementary activation of the IGF-I pathway and increase the probability of the development of cancer. These studies suggest that increased expression of IGF-IR may be an important contributor to the risk of endometrial hyperplasia and cancer.     

Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis.

PURPOSE: Current serum testing for the detection of prostate cancer (PCa) lacks specificity. On diagnosis, the optimal therapeutic pathway is not clear and tools for adequate risk assessment of localized PCa progression are not available. This leads to a significant number of men having unnecessary diagnostic biopsies and surgery. A search for novel tumor markers identified macrophage inhibitory cytokine 1 (MIC-1) as a potentially useful marker. Follow-up studies revealed MIC-1 overexpression in local and metastatic PCa whereas peritumoral interstitial staining for MIC-1 identified lower-grade tumors destined for recurrence. Consequently, we sought to assess serum MIC-1 measurement as a diagnostic tool. EXPERIMENTAL DESIGN: Using immunoassay determination of serum MIC-1 concentration in 1,000 men, 538 of whom had PCa, we defined the relationship of MIC-1 to disease variables. A diagnostic algorithm (MIC-PSA score) based on serum levels of MIC-1, total serum prostate-specific antigen, and percentage of free prostate-specific antigen was developed. RESULTS: Serum MIC-1 was found to be an independent predictor of the presence of PCa and tumors with a Gleason sum > or =7. We validated the MIC-PSA score in a separate population and showed an improved specificity for diagnostic blood testing for PCa over percentage of free prostate-specific antigen, potentially reducing unnecessary biopsies by 27%. CONCLUSIONS: Serum MIC-1 is an independent marker of the presence of PCa and tumors with a Gleason sum of > or =7. The use of serum MIC-1 significantly increases diagnostic specificity and may be a future tool in the management of PCa.     

Premorbid IQ in patients with functional psychosis and their first-degree relatives

Numerous studies have found deficits in premorbid IQ in schizophrenic patients, but it is not clear whether this deficit is shared by (a) patients with other functional psychoses, and (b) relatives of these patients. Ninety-one schizophrenic patients, 66 affective psychotic patients (29 schizoaffective and 37 manic or depressed), and 50 normal control subjects were administered the National Adult Reading Test (NART) which provides an estimate of premorbid IQ. The NART was also completed by 85 first-degree relatives of schizophrenic patients and by 65 first-degree relatives of affective psychotic patients. After adjustments were made for sex, social class, ethnicity and years of education, schizophrenic patients had significantly lower premorbid IQ than their relatives, the affective psychotic patients and controls. Manic and depressed patients had significantly lower NART scores than their first-degree relatives, but schizoaffective patients did not, and neither group differed significantly from controls. There was no significant difference in premorbid IQ between patients who had experienced obstetric complications (OC+) and those who had not (OC-). Both OC+ and OC- schizophrenic patients differed significantly from their relatives, but the disparity was greatest between OC+ patients and their relatives. Relatives of OC+ schizophrenic patients had significantly higher IQ than relatives of OC- schizophrenic patients.