Corneal perforation after conductive keratoplasty with previous refractive surgery

A 56-year-old woman had conductive keratoplasty (CK) for residual hyperopia and astigmatism. Three years before the procedure, the patient had arcuate keratotomy, followed by laser in situ keratomileusis 2 years later for high astigmatism correction in both eyes. During CK, a corneal perforation occurred in the right eye; during the postoperative examination, an iris perforation and anterior subcapsule opacification were seen beneath the perforation site. The perforation was managed with a bandage contact lens and an antibiotic-steroid ointment; it had a negative Seidel sign by the third day. The surgery in the left eye was uneventful. Three months after the procedure, the uncorrected visual acuity was 20/32 and the best corrected visual acuity 20/20 in both eyes with a significant improvement in corneal topography. Care must be taken to prevent CK-treated spots from coinciding with areas in the corneal stroma that might have been altered by previous refractive procedures.     

Chevron v Echazabal: public health issues raised by the "threat-to-self" defense to adverse employment actions

In June of 2002, the US Supreme Court upheld a regulation that allows employers, under the Americans with Disabilities Act, to make disability-related employment decisions based on risks to an employee's own personal health or safety. Previous judicial decisions had allowed employers to make employment decisions based on the threat that a worker's medical condition posed to others but had not addressed the issue of risk posed to an employee's health by his or her own disability. The authors comment on the potential effects of the court's decision for occupational health practitioners charged with assessing the degree of risk and harm of a particular workplace environment and for public health efforts aimed at curbing workplace injury and sickness.     

Myocardial infarction among professional drivers

BACKGROUND: Professional drivers are at an increased risk of myocardial infarction but the underlying causes for this increased risk are uncertain. METHODS: We identified all first events of myocardial infarction among men age 45-70 years in Stockholm County for 1992 and 1993. We selected controls randomly from the population. Response rates of 72% and 71% resulted in 1067 cases and 1482 controls, respectively. We obtained exposure information from questionnaires. We calculated odds ratios (ORs), with and without adjustment for socioeconomic status, tobacco smoking, alcohol drinking, physical inactivity at leisure time, overweight status, diabetes and hypertension. RESULTS: The crude OR among bus drivers was 2.14 (95% confidence interval = 1.34-3.41), among taxi drivers 1.88 (1.19-2.98) and among truck drivers 1.66 (1.22-2.26). Adjustment for potential confounders gave lower ORs: 1.49 (0.90-2.45), 1.34 (0.82-2.19) and 1.10 (0.79-1.53), respectively. Additional adjustment for job strain lowered the ORs only slightly. An exposure-response pattern (by duration of work) was found for bus and taxi drivers. CONCLUSIONS: The high risk among bus and taxi drivers was partly explained by unfavorable life-style factors and social factors. The work environment may contribute to their increased risk. Among truck drivers, individual risk factors seemed to explain most of the elevated risk.     

Evaluation of the novel antiepileptic drug,AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys

AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 microg/kg/injection). When AWD 131-138 (10-100 microg/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 microg/kg i.v. AWD 131-138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low.     

Expression profiling to predict outcome in breast cancer: the influence of sample selection

Gene expression profiling of tumors using DNA microarrays is a promising method for predicting prognosis and treatment response in cancer patients. It was recently reported that expression profiles of sporadic breast cancers could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors. Having observed an overlap in those data between the genes that predict outcome and those that predict estrogen receptor-alpha status, we examined their predictive power in an independent data set. We conclude that it may be important to define prognostic expression profiles separately for estrogen receptor-alpha-positive and estrogen receptor-alpha-negative tumors.     

Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and dihalomethanes

A primary route of metabolism of dihalomethanes occurs via glutathione (GSH) transferase-catalyzed conjugation. Mammalian theta class GSH transferases and a group of bacterial dichloromethane dehalogenases are able to catalyze the hydrolytic dehalogenation of dihalomethanes via GSH conjugation and subsequent formation of HCHO. Dihalomethanes have been shown to induce revertants in Salmonella typhimurium TA 1535 expressing theta class GSH transferases. Two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and the bacterial dehalogenase DM11 were compared in the in vitro conjugation of CH(3)Cl and using in vitro assays (HCHO formation) and the S. typhimurium mutagenesis assay with the dihalomethanes CH(2)Cl(2), CH(2)Br(2), CH(2)BrCl, CH(2)ICl, CH(2)I(2), and CH(2)ClF. GSTs 5-5 and T1 had similar characteristics and exhibited first-order rather than Michaelis-Menten kinetics for HCHO formation over the range of dihalomethane concentrations tested. In contrast, the DM11 enzyme displayed typical hyperbolic Michaelis-Menten kinetics for all of the compounds tested. A similar pattern was observed for the conjugation of CH(3)Cl. The reversion tests with S. typhimurium expressing DM11 or GST 5-5 showed a concentration-dependent increase in revertants for most of the dihalomethanes, and DM11 produced revertants at dihalomethane concentrations lower than GST 5-5. Collectively, the results indicate that rates of conversion of dihalomethanes to HCHO are not correlated with mutagenicity and that GSH conjugates are genotoxic. The results are compared with the conjugation and genotoxicity of haloethanes in the preceding paper in this issue [Wheeler, J. B., Stourman, N. V., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1107-1117]. The halide order appears most important in the dihalomethane conjugation reactions catalyzed by GST 5-5 and less so in GST T1 and DM11, probably due to changes in the rate-limiting steps.     

Health-Related Quality of Life Measured with EQ-5D in Patients Treated for Depression in Primary Care

OBJECTIVE: The objective of the present study was to assess the impact of depression on patients' health-related quality of life (HRQL) with the EQ-5D instrument over 6 months while on antidepressant treatment. METHODS: A total of 447 patients were recruited at 56 primary care centers to this naturalistic longitudinal observational study. Patients older than 18 years with depressive symptoms, and who initiated an antidepressant therapy because of depression were included in the study. Data on patients' sociodemographics, daily activity, and quality of life (EQ-5D) were collected using questionnaires completed during outpatient general practitioner visits for a follow-up period of 6 months. RESULTS: The mean EQ-5D utility score at baseline was 0.47 (0.44-0.49). Milder cases of depression reported a health utility of 0.60, whereas moderately and severely depressed patients reported utility values of 0.46 and 0.27, respectively (P < 0.01). At end of follow up the average utility was 0.69 (0.67-0.72), corresponding to an increase of 0.23 over 6 months (P < 0.01). Regression analyses showed that, all else equal, patients who were on sick leave were associated with 10% lower utility. CONCLUSIONS: Depression has a substantial impact on HRQL. Our results indicate that treatments for depression are associated with significant improvement in EQ-5D index score over a course of 6 months. Self-reported patient valuations are important outcomes for cost-utility analysis of new treatments for depression and the present study provides important evidence for future economic evaluations.     

Electron beam tomography of interpulmonary saddle embolism: extent and vascular distribution.

PURPOSE: The purpose of this work was to assess morphology and secondary signs of interpulmonary emboli extending across the bifurcation of the main pulmonary artery (PA). METHOD: Retrospective evaluation of 780 electron beam tomographic studies of the chest yielded 17 cases of interpulmonary saddle embolism. Length, diameter, vascular distribution of the emboli, and secondary findings were prospectively assessed by two blinded reviewers. Follow-up studies were carried out in 12 of 17 patients (71%). RESULT: Mean total length of the emboli was 46.6 cm (range 20.9-81.5 cm). The mean diameter of the saddle embolus was significantly smaller at the level of the bifurcation than in the left or right PA (4.5, 7.7, and 7.4 mm, respectively; p < 0.01). Dilatation of the right heart was found in 10 of 17 cases (59%). At follow-up, the saddle state was no longer present in 8 of 12 patients (67%). CONCLUSION: Interpulmonary saddle emboli appear to be a transient form of acute pulmonary embolism, the site of predilection for rupture of the embolus being the level of the bifurcation. Their frequency may therefore be underestimated.