Electroencephalographic coherence and cortical acetylcholine during ketamine-induced unconsciousness. British Journal of Anaesthesia, 2015; 114(6): 979-89, DOI 10.1093/bja/aev095.

This article was published by mistake in the June issue of BJA due to an administrative error. It was supposed to go into this special issue on Memory and Awareness in Anaesthesia. The article can be accessed free of charge at the following link: http://bja.oxfordjournals.org/lookup/doi/10.1093/bja/aev095 The Publisher apologizes for the error.

Electroencephalographic coherence and cortical acetylcholine during ketamine-induced unconsciousness.

BACKGROUND: There is limited understanding of cortical neurochemistry and cortical connectivity during ketamine anaesthesia. We conducted a systematic study to investigate the effects of ketamine on cortical acetylcholine (ACh) and electroencephalographic coherence. METHODS: Male Sprague-Dawley rats (n=11) were implanted with electrodes to record electroencephalogram (EEG) from frontal, parietal, and occipital cortices, and with a microdialysis guide cannula for simultaneous measurement of ACh concentrations in prefrontal cortex before, during, and after ketamine anaesthesia. Coherence and power spectral density computed from the EEG, and ACh concentrations, were compared between conscious and unconscious states. Loss of righting reflex was used as a surrogate for unconsciousness. RESULTS: Ketamine-induced unconsciousness was associated with a global reduction of power (P=0.02) in higher gamma bandwidths (>65 Hz), a global reduction of coherence (P≤0.01) across a broad frequency range (0.5-250 Hz), and a significant increase in ACh concentrations (P=0.01) in the prefrontal cortex. Compared with the unconscious state, recovery of righting reflex was marked by a further increase in ACh concentrations (P=0.0007), global increases in power in theta (4-10 Hz; P=0.03) and low gamma frequencies (25-55 Hz; P=0.0001), and increase in power (P≤0.01) and coherence (P≤0.002) in higher gamma frequencies (65-250 Hz). Acetylcholine concentrations, coherence, and spectral properties returned to baseline levels after a prolonged recovery period. CONCLUSIONS: Ketamine-induced unconsciousness is characterized by suppression of high-frequency gamma activity and a breakdown of cortical coherence, despite increased cholinergic tone in the cortex.

The role played by depression associated with somatic symptomatology in accounting for the gender difference in the prevalence of depression.

PURPOSE: A variety of studies suggest the existence of a distinct phenotype of somatic depression, i.e., depression accompanied by significant somatic symptomatology. Previous research suggests that the gender difference in the prevalence of depression is primarily due to a difference in somatic depression. The aim of this study was to compare the gender difference in the prevalence of somatic depression and of depression not accompanied by significant somatic symptomatology (labelled "pure" depression) in two representative samples, the National Comorbidity Survey-Replication (NCS-R) and the Zurich Study. METHOD: The gender difference in lifetime somatic depression was compared to that of pure depression based on analyses weighted back to the general population in two representative samples. The NCS-R analyses involved a narrow definition of somatic depression with items from the DSM criteria for depression--appetite, sleep, and fatigue. The analysis of the Zurich study added headaches, body image issues, and breathing difficulties to the criteria and comparison to atypical depression. RESULTS: In both samples, the gender difference in depressive prevalence was due to a large difference in somatic depression with other phenotypes showing little or no gender difference. The gender differences were found to be due to the somatic symptoms rather than the number of symptoms and were much larger for somatic than for atypical depression. CONCLUSION: The gender difference in the prevalence of depression results from the higher prevalence among women of a specific phenotype, somatic depression.

Inter-observer reliability of forceful exertion analysis based on video-recordings.

The objectives were to examine inter-observer reliability of job-level forceful exertion analyses and temporal agreement of detailed time study results. Three observers performed the analyses on 12 different jobs. Continuous duration, frequency and % time of lifting, pushing/pulling, power and pinch gripping exertions and estimated level of the exertions were obtained. Intraclass correlation coefficient and variance components were computed. Temporal agreement analyses of raw time study data were performed. The inter-observer reliability was good for most job-level exposure parameters (continuous duration, frequency and % time of forceful exertions), but only fair to moderate for the estimated level of forceful exertions. The finding that the between-observer variability was less than the between-exertion variability confirmed that the forceful exertion analysis method used in the present study can detect job exertion differences.Using three observers to perform detailed time studies on task activities and getting consensus of the majority can increase the between-observer agreement up to 97%. STATEMENT OF RELEVANCE: The results inform researchers that inter-observer reliability for job-level exposure measurement of forceful exertion analysis obtained from detailed time studies is generally good, but the observers' ability in the estimation of forceful exertion level can be poor. It also provides information on the temporal agreement of detailed forceful exertion analysis and guidelines on achieving better agreement for studies where accurate synchronisation of task activities and direct physiological/biomechanical measurements is crucial.

Multicenter study to assess potential hazards from exposure to lipid peroxidation products in soya bean oil from Trilucent breast implants.

In response to a Hazard Notice by the Medical Devices Agency of the UK in 2000 regarding the Trilucent breast implant (TBI), an expert panel was convened to implement a research program to determine whether genotoxic compounds were formed in the soybean oil filler (SOF) of TBIs and whether these could be released to produce local or systemic genotoxicity. The panel established a research program involving six laboratories. The program recruited 47 patients who had received TBIs (9 patients had received silicone implants previously). A reference group (REBI) of 34 patients who had exchanged either silicone (17 patients) implants (REBI-E) or patients (17) who were to receive primary implantation augmentation with silicone (REBI-PIA), and who were included as needed to increase either the pre- or post-explantation sample number. Of the 17 REBI-E patients, 5 had silicone implants and 12 had saline implants previously (prior to the last exchange). Investigation was undertaken before and after replacement surgery in the TBI patients and before and after replacement or augmentation surgery in the REBI patients. The pre- to post-operative sample interval was 8-12 weeks. Pre-operative samples were collected within 7 days prior to the operation. Information on a variety of demographic and behavioral features was collected. Biochemical and biological endpoints relating to genotoxic lipid peroxidation (LPO) products potentially formed in the SOF, and released locally or distributed systemically, were measured. The SOF of explanted TBIs was found to have substantial levels of LPO products, particularly malondialdehyde (MDA), and low levels of trans-4-hydroxy-2-nonenal (HNE) not found in unused implants. Mutagenicity of the SOF was related to the levels of MDA. Capsules that formed around TBIs were microscopically similar to those of reference implants, but MDA-DNA adducts were observed in capsular macrophages and fibroblasts of only TBI capsules. These cell types are not progenitors of breast carcinoma (BCa) and the location of the implants precludes LPO products reaching the mammary epithelial cells which are progenitors of BCa. Blood levels of LPO products were not increased in TBI patients compared to REBI patients and did not change with explantation. In TBI patients, white blood cells did not show evidence of increased levels of LPO-related aldehyde DNA adducts. In conclusion, based on a number of measured parameters, there was no evident effect that would contribute to breast or systemic cancer risk in the TBI patients, and the recommended treatment of TBI patients involving explantation was judged appropriate.

Immunological, morphological, and electrophysiological variation among retinal ganglion cells purified by panning.

Two different monoclonal antibodies to the Thy-1 antigen, T11D7 and 2G12, were used to purify and characterize retinal ganglion cells from postnatal rat retina. Although Thy-1 has been reported to be a specific marker for ganglion cells in retina, retinal cell suspensions contained several other types of Thy-1-positive cells as well. Nevertheless, a simple two-step "panning" procedure allowed isolation of ganglion cells to nearly 100% purity. We found that postnatal ganglion cells differed in antigenic, morphological, and intrinsic electrophysiological characteristics, and that these properties were correlated with one another. Minor variations of this panning protocol should allow rapid, high yield purification to homogeneity of many other neuronal and glial cell types.

Incident and recurrent back injuries among union carpenters.

AIMS: To describe incident and recurrent work-related back injuries among union carpenters, describe the hazard function for each and associated risk factors, and explore predictors of subsequent musculoskeletal back injury based on different definitions of the initial injury. METHODS: This study identified a dynamic cohort of 18 768 carpenters who worked in the State of Washington 1989-2003, their hours worked each month, and their work-related back injuries and medical claims for treatment including ICD-9 codes. Using Poisson regression we calculated rates and rate ratios (RRs) of incident and recurrent injury adjusting for age, gender, union tenure and type of carpentry work. Predictors of subsequent musculoskeletal back injury were explored based on different definitions of the incident injury, as were time periods of greatest risk following return to work. RESULTS: Recurrent back injuries occurred at a rate 80% higher than initial injuries. Survival curves were significantly different for incident and recurrent injuries, but patterns of relative risk were similar. Individuals with greatest union tenure were at lowest risk, likely reflecting a healthy worker effect or lower physical exposures with seniority. Individuals with long periods of work disability with their first injury were at particularly high risk of subsequent musculoskeletal injury compared with those with no prior history (RR 2.3; 95% CI 2.0 to 2.7), as were individuals with degenerative diagnoses (RR 2.0; 95% CI 1.5 to 2.6). Risk for second injury peaked between 1000 and 1500 h after return to work and then gradually declined. CONCLUSIONS: Carpenters with long periods of work disability following back injury warrant accommodation and perhaps better rehabilitation efforts to avoid re-injury. Challenges to workplace accommodation and limited ability to clearly define readiness to return to work following injury demonstrate the need for primary prevention of back injuries through attention to engineering solutions among carpenters involved in strenuous work.

Gender difference in the prevalence of clinical depression: the role played by depression associated with somatic symptoms.

OBJECTIVE: This study tested the hypothesis that female subjects may exhibit a higher prevalence than male subjects of depression associated with somatic symptoms but not a higher prevalence of depression not associated with these other symptoms. METHOD: The author reanalyzed research interview data on major depression from the National Comorbidity Survey, dividing respondents into those who met overall criteria for major depression and exhibited fatigue and appetite and sleep disturbance ("somatic depression") and those who met overall criteria but did not exhibit these somatic criteria ("pure depression"). RESULTS: Female subjects exhibited a higher prevalence than male subjects of somatic depression but not a higher prevalence of pure depression. Somatic depression was associated with a high prevalence of anxiety disorder and, among female subjects, with body aches and onset of depression during early adolescence. CONCLUSIONS: The gender difference in depression may result from a difference in a specific subtype of anxious somatic depression.

Fluorometric studies on the blood-retinal barrier in experimental animals.

Fluorophotometry was used to evaluate the blood-ocular barrier in rats following streptozocin-induced diabetes, experimental systemic hypertension, sodium iodate treatment, diet-induced galactosemia, and aldose reductase inhibitors. After administration of intravenous (IV) fluorescein sodium, diabetes, hypertension, or sodium iodate treatment resulted in an increased vitreous accumulation of IV fluorescein. Accumulation of dextran-labeled fluorescein (3,000 and 19,000 molecular weight [mol wt]) was not increased in diabetic or sodium iodate-treated animals. However, 3,000-mol wt dextran-labeled dye accumulated in the vitreous of hypertensive rats. The disappearance of fluorescein injected into the vitreous was significantly delayed in diabetic and sodium iodate-treated rats, whereas this rate was normal in hypertension animals. Galactosemia did not alter vitreous fluorophotometric measurements. Pretreatment for systemic effects with aldose reductase inhibitors did not correct the vitreous fluorophotometric measurements of diabetic rats.

Reduction of cyclosporine dosage with ketoconazole in a patient with birdshot retinochoroidopathy.

PURPOSE: To report the successful reduction of cyclosporine dosage with adjunctive ketoconazole in a patient with birdshot retinochoriodopathy. METHOD: Case report. RESULTS: A 55-year-old woman treated with cyclosporine for birdshot retinochoroidopathy had ketoconazole (200 mg/day) added to her medical regimen. Her cyclosporine dosage was reduced to 40 mg per day from 200 mg per day, an 80% reduction. No toxic effect was observed during 12 months of follow-up nor was there progression of the birdshot retinochoroidopathy. CONCLUSIONS: Cyclosporine dosage may be reduced considerably in patients with uveitis who use adjunctive ketoconazole. The regimen appears to be safe and efficacious.

Disciform keratitis: a case of herpes zoster sine herpete.

PURPOSE: To describe a case of disciform keratitis in a patient with acquired immunodeficiency syndrome (AIDS) in which varicella-zoster virus was the causative agent. METHOD: Case report, Polymerase chain reaction-based assays for varicella-zoster virus, cytomegalovirus, and herpes simplex virus were used to analyze an aqueous aspirate. RESULTS: We examined a 41-year-old man with AIDS but without a history of varicella-zoster virus dermatitis who had disciform corneal edema in his left eye. Varicella-zoster virus was detected by a polymerase chain reaction-based assay in the aqueous of the left eye; however, neither cytomegalovirus nor herpes simplex virus DNA were detected by polymerase chain reaction-based assays. The corneal edema slowly resolved while the patient was treated with famciclovir. CONCLUSION: Varicella-zoster virus may cause disciform keratitis without a preceding skin eruption.

Cytomegalovirus-associated acute retinal necrosis syndrome.

PURPOSE: To describe a case of acute retinal necrosis syndrome in which a polymerase chain reaction-based assay provided evidence for cytomegalovirus as the causative agent of the syndrome. METHODS: Polymerase chain reaction-based assays were used to analyze a vitreous aspirate from a 70-year-old man with acute retinal necrosis syndrome. The specimen was tested for cytomegalovirus, varicella-zoster virus, and herpes simplex virus type 1 and type 2. RESULTS: The polymerase chain reaction assay for cytomegalovirus was positive, and polymerase chain reaction assays for varicella-zoster virus and herpes simplex virus type 1 and type 2 were negative. CONCLUSION: Cytomegalovirus may be a causative agent of acute retinal necrosis syndrome.

Microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus infection.

PURPOSE: To describe a case of microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus (HIV) infection. METHODS: Case report. An epithelial corneal scraping from a woman with chronic bilateral keratoconjunctivitis was evaluated by Giemsa stain. RESULTS: Giemsa stain of an epithelial corneal scraping disclosed intracellular and extracellular spores characteristic of microsporidia. An HIV enzyme-linked immunosorbent assay (ELISA) test was negative. The signs and symptoms of the bilateral keratoconjunctivitis resolved after treatment with albendazole. CONCLUSION: Microsporidia may cause a chronic epithelial keratoconjunctivitis in the absence of HIV infection.

Cystoid macular edema associated with cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

PURPOSE: To describe the clinical and fluorescein angiographic appearance of cystoid macular edema associated with cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). METHODS: We retrospectively examined the clinical and photographic records of four patients with AIDS and cytomegalovirus retinitis who developed cystoid macular edema. RESULTS: Seven eyes of four patients with AIDS and cytomegalovirus retinitis experienced decreased vision associated with cystoid macular edema. Vitreous inflammation was mild in each patient. In all eyes, the retinitis involved zone 1, and in all but one eye, the cytomegalovirus retinitis was inactive. In one eye, the cystoid macular edema was worsened by formation of a dense juxtafoveal epiretinal membrane. CONCLUSIONS: Although infrequently recognized, cystoid macular edema can cause visual loss in patients with AIDS and cytomegalovirus retinitis. Fluorescein angiography should be considered in any patient with cytomegalovirus retinitis and unexplained visual loss.

Cigarette smoking, nicotine addiction, and relaxation.

In an attempt to explain the self-report of smokers that cigarette smoking is relaxing, shock endurance was used to measure the amount of anxiety experienced in a stressful situation by nonsmokers, smokers who were allowed to smoke cigarettes containing either low levels or moderately high levels of nicotine, and smokers who were not allowed to smoke a cigarette. Smokers who were deprived of cigarettes and those who smoked cigarettes containing low levels of nicotine behaved more anxiously than nonsmokers and than smokers who smoked cigarettes containing moderately high levels of nicotine, but the high-nicotine smokers behaved no less anxiously than nonsmokers. These results supported the hypothesis that the calming effect attributed to smoking a cigarette is due to the action of nicotine in ending withdrawal symptoms in addicted smokers rather than to a sedative property of cigarette smoking.

Role of diagnostic tests in esophageal evaluation.

In the evaluation of esophageal disease, the appropriate question must be asked before the correct tests can be selected. Reflux can be demonstrated by radiologic methods, pH testing or radioisotopic techniques. Esophageal mucosal damage is best evaluated by x-ray, endoscopy or biopsy. Chest pain is demonstrated by acid infusion or by manometry. Two algorithms are presented for the evaluation of chest pain and reflux symptoms.

Washington State's late night retail worker crime protection regulation. Relationships with employer practices.

Washington's late night retail worker crime protection regulation, enforced by the state Occupational Safety and Health Administration (OSHA) program, was intended to prevent injuries by deterring violent crimes. We investigated whether the regulation was associated with businesses' violence prevention activities. We surveyed 1,516 employers at high risk of robbery, including gas stations, groceries, hotels, restaurants, and taverns, in 1995 to determine whether they had violence prevention training programs for their employees (a requirement of the standard). Awareness of the regulation was low (4.4%). Employers covered by the regulation were more likely to have programs (Odds Ratio [OR] = 1.4), as were those aware of a regulation (OR = 3.4). State OSHA plan contact (an inspection or consultation) was also associated with having a program (OR = 1.9). Despite low awareness of the standard, results suggested that regulatory efforts to protect high-risk employees were associated with employers' robbery and crime prevention activities.

A life-long prospective study on the role of psychosocial factors in neck-shoulder and low-back pain.

The predictive value of psychosocial factors in the development of neck--shoulder and low-back symptoms was investigated in a life-long follow-up study of 154 subjects. Measurements taken in adolescence, such as intelligence, alexithymia (low verbal productivity in projective personality tests), social confidence, hobbies, and the socioeconomic status of the family, showed no consistent associations with neck--shoulder or low-back symptoms in adulthood. Of the variables recorded in adulthood, weak mental resources for promoting health (poor sense of coherence) were consistently associated with neck--shoulder pain, whereas low fundamental education predicted low-back symptoms. The results suggest that psychosocial factors in childhood have a minor role as direct predictors of later symptoms.

Role of physical load factors in carpal tunnel syndrome.

Epidemiologic and experimental studies were reviewed to assess the role of postural factors, high handgrip and pinch forces, repetitive hand and wrist movements, external pressure, and vibration in the occurrence of carpal tunnel syndrome (CTS). Forceful repetitive work, vibration, and extreme wrist postures have been associated with CTS in several epidemiologic studies. Experimental studies have shown that certain forearm, wrist, and finger postures, even moderate hand loads and external pressure on the palm, can increase carpal tunnel pressure (CTP) at least temporarily to levels at which nerve viability is threatened. It is concluded that while more research is needed, there is sufficient information to suggest that reducing the duration, frequency or intensity of exposure to forceful repetitive work, extreme wrist postures and vibration is likely to result in a reduction of the incidence or severity of CTS in working populations.

Mortality among workers in a die-casting and electroplating plant.

A proportional mortality and case-referent analysis of 238 deaths among hourly employees in an automobile hardware manufacturing plant was conducted. The major operations of the plant were zinc die casting and electroplating. Chemical exposure included die-casting emissions and mists from chrome and nickel plating. The chief proportional mortality finding was a significant excess of lung cancer among both white men and women. A case-referent analysis indicated a possible association between lung cancer and work in certain departments. The findings support the hypothesis of a work-related carcinogenic risk. Follow-up recommendations have been made.