Effects of Exposure to Welding Fume on Lung Function: Results from the German WELDOX Study.

The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker's lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15% of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.

Feasibility of automated matching of supine and prone CT-colonography examinations.

Matching of prone and supine positions in CT colonography may improve accuracy of polyp detection. The purpose of this study was to investigate the feasibility of automatic prone-supine matching in CT-colonography using proven polyps as fixed points of reference. The method is based on similarities in the direction of centre-lines and allows for compression and extraction of the centre-lines in both positions. To illustrate the impact of the match error of the new method in practice, the visibility of the matched polyps in a primary three-dimensional unfolded cube setting was determined as well. The method was compared with a method that relies on the normalized distance along the centre-line (NDAC method). The median absolute match error was 14 mm (range 0-59 mm, average 20 mm) either proximal or distal from the actual polyp in prone position. In the observer study, 70% (26/37) of the polyps were directly visible in prone view. The overall difference in median absolute match error between both methods was small (2 mm), although half way along the centre-line there were polyps with substantial differences in match error (larger with NDAC). We concluded that automated prone-supine matching of CT-colonography studies is feasible and has a low match error. The difference with the NDAC method was small and not significant, although half way along the centre-line some differences were seen.

Colorectal cancer screening and surveillance with CT colonography: current controversies and obstacles.

Computed tomographic (CT) colonography has been advocated as an alternative colorectal screening method because studies in populations with a high prevalence of polyps have demonstrated that sensitivity for patients with large (> or =10 mm) polyps is generally high (approximately 90%). In three recent studies in low-prevalence populations, however, these values vary from 55% to 94%. Many questions have been raised as to the cause of this remarkable variability, which hampers the implementation of CT colonography in colorectal cancer screening and surveillance. We provide an overview of some potential causes and discuss the available, often indirect, evidence. In addition, several other obstacles that may influence implementation are discussed. Many differences between the study with high sensitivity (94%) and the two studies with low sensitivity (55% and 64%) exist: the primary method to review the data (two or three dimensional), bowel preparation (with or without oral contrast agents), study design (verification method and analysis of adenomas only), reader's experience, and scanning technique (single vs. multislice, thin vs. thick sections). Additional obstacles for implementation in prevention of colorectal cancer may be controversial results concerning patient acceptance, the large-scale use of ionizing radiation, difficulties in detecting flat adenomas, and extracolonic findings. Use of primary three-dimensional review methods, addition of oral contrast agents to bowel preparation, and endoscopic verification of false-positive results on CT colonography are speculated to have a positive influence on sensitivity. Future investigations should demonstrate the influence of these potential factors on sensitivity of CT colonography. Despite a growing body of evidence, it remains uncertain to what extent patient acceptance, radiation issues, flat lesions, and extracolonic findings will be a stumbling block to using CT colonography for colorectal cancer screening.

Applications of the polymerase chain reaction to diagnosis of ophthalmic disease.

The polymerase chain reaction (PCR) is a powerful molecular biologic technique for the analysis of very small amounts of DNA. This technique has found increasing use in the past 10 years for the detection of pathogenic organisms associated with many forms of ocular inflammatory and infectious disease. PCR has shown utility in the diagnosis of viral uveitis, infectious endophthalmitis, and parasitic eye disease. The strengths and weaknesses of this diagnostic technique are discussed. Additionally, uses of PCR in linking known pathogens to disease, and to discovering novel pathogens, are addressed.

A review of technical advances in virtual colonoscopy.

Early detection of polyps has proven to lead to a decrease in incidence of colon cancer. In the past few years, virtual colonoscopy has been developed as a patient-friendly screen-ing technique. The procedure comprises the following steps. First, the patient's colon is cleansed and transanally inflated with air. Subsequently, a 3D image volume is acquired of the abdomen by CT or MRI. Finally, the bowel surface is extracted and visualized, after which the physician virtually navigates through the colon and examines the surface for abnormalities. This paper describes the progress in research for virtual colonoscopy.

Validation of a diagnostic multiplex polymerase chain reaction assay for infectious posterior uveitis.

OBJECTIVE: To validate a multiplex polymerase chain reaction (PCR) assay capable of simultaneously screening vitreous biopsy specimens for a panel of common pathogens in posterior uveitis. METHODS: A multiplex PCR assay using novel primer sets for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was developed. The sensitivity of the assay was determined for purified pathogen DNA. Twenty-one vitreous specimens from patients with posterior uveitis were tested by both multiplex and monoplex PCR. RESULTS: Fewer than 10 genomes of VZV and fewer than 100 genomes of HSV, CMV, and T gondii could be detected using the new primer sets. When used in multiplex, the assay lost less than 1 log of sensitivity. Monoplex PCR detected pathogen DNA in 18 of 21 patient samples; multiplex PCR detected pathogen DNA in 15 of the 18 samples positive by monoplex PCR. None of 10 negative control samples were positive for pathogen DNA. CONCLUSIONS: Multiplex PCR has adequate sensitivity to simultaneously screen a substantial differential diagnosis for posterior uveitis in a single reaction, without loss of specificity. This assay may reduce the time and cost involved in PCR-based molecular diagnostics of infectious pathogens. CLINICAL RELEVANCE: Mutiplex PCR may allow rapid diagnosis of infectious posterior uveitis.

Preservation of light signaling to the suprachiasmatic nucleus in vitamin A-deficient mice.

To investigate the role of retinal-based pigments (opsins) in circadian photoreception in mice, animals mutated in plasma retinol binding protein were placed on a vitamin A-free diet and tested for photic induction of gene expression in the suprachiasmatic nucleus. After 10 months on the vitamin A-free diet, the majority of mice contained no detectable retinal in their eyes. These mice demonstrated fully intact photic signaling to the suprachiasmatic nucleus as measured by acute mPer mRNA induction in the suprachiasmatic nucleus in response to bright or dim light. The data suggest that a non-opsin pigment is the primary circadian photoreceptor in the mouse.

Frontiers of polymerase chain reaction diagnostics for uveitis.

The polymerase chain reaction (PCR) is a powerful molecular biologic technique for the detection of pathogen DNA. Recent technical advances in the technique have broadened its scope considerably. Emerging applications of PCR in pathogen strain typing, rapid screening of differential diagnoses, and pathogen discovery are discussed.

Herpes simplex virus type 2 as a cause of acute retinal necrosis syndrome in young patients.

PURPOSE: To determine the causative virus in acute retinal necrosis (ARN) syndrome in a series of patients by calculation of modified Witmer coefficients. DESIGN: Noncomparative case series. PARTICIPANTS: Ten patients with ARN syndrome from four medical centers. METHODS: Aqueous samples, vitreous samples, or both were collected prospectively during surgery from patients with a clinical diagnosis of ARN syndrome. Serologic measures of intraocular and serum antibodies to potentially causative viruses were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Modified Witmer coefficients (immunoglobulin G and immunoglobulin A) for herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV), as well as adenovirus type 2, were calculated from aqueous or vitreous samples, or both. RESULTS: Intraocular antibody measurements were strongly suggestive of a single diagnosis in 9 of 10 patients tested. Modified Witmer coefficients demonstrated intraocular antibody production to HSV in five patients and antibodies to VZV in four patients, and the measurement was inconclusive in one patient. No patients were positive for adenovirus or CMV. Strain-specific antibody titers demonstrated that all HSV-positive patients were reactive only to HSV-2. Herpes simplex virus type 2 was found predominantly in younger patients with ARN syndrome (mean age, 21.2 +/- 10 years; range, 17-39 years), whereas VZV was more commonly seen in older patients (mean age, 40.8 +/- 12.2 years; range, 29-58 years; P = 0.033). Immunoglobulin A testing confirmed immunoglobulin G testing in all patients examined. CONCLUSIONS: Although VZV is thought to be the most common cause of ARN syndrome, HSV-2 is an important cause of ARN syndrome, particularly in younger patients. Because infection with HSV-2 has important medical ramifications, these results suggest that determination of a causal agent should be considered in some cases of ARN syndrome.

Non-visual ocular photoreception.

At least six light-regulated phenomena are preserved in the eyes of retinally degenerate mice, including the entrainment of circadian rhythms, the gating of ocular immune response, and pupillary reactivity. Some of these phenomena have also been observed in blind human patients. These findings have prompted the search for a non-visual ocular phototransduction mechanism. Molecular genetic studies have identified several candidate genes for these effects. These include genes encoding novel ocular opsins, such as melanopsin, as well as potential flavin-based photopigments. Data linking these potential photoreceptors to these phenomena are discussed, and the clinical implications of these findings are explored.

Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice.

The daily light-dark (LD) cycle exerts a powerful influence on the temporal organization of behavior and physiology. Much of this influence is preserved in behaviorally blind retinally degenerate mice; the photoreceptors underlying this nonvisual phototransduction are unknown. The mammalian eye contains at least two classes of photoactive pigments, the vitamin A-based opsins and the vitamin B(2)-based cryptochromes. To genetically define the roles of these pigments in light modulation of behavior, we generated rd/rd;mCry1(-)/mCry1(-);mCry2(-)/mCry2(-) mutant mice lacking rods and most cones as well as both cryptochrome proteins. The response of the mutant mouse to photic input was analyzed at both behavioral and molecular levels. Behaviorally, mice lacking either classical photoreceptors or cryptochromes exhibited strongly rhythmic locomotor responses to 10 and 100 lux daily LD 12 h/12-h cycles; however, triple mutant mice carrying both cryptochrome and retinal degenerate mutations were nearly arrhythmic under both LD cycles and in constant darkness. At the molecular level, the light induction of c-fos transcription in the suprachiasmatic nucleus was markedly reduced in the triple mutant mouse compared with either rd/rd or cryptochrome mutant mice. These data indicate that classical opsins and cryptochromes serve functionally redundant roles in the transduction of light information to behavioral modulation and suggest a pleomorphic role for cryptochromes in both photoreception and central clock mechanism.

Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel.

PURPOSE: To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders. PARTICIPANTS: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care. EVIDENCE: Published clinical study results. Recommendations were rated according to the quality and strength of available evidence. PROCESS: The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although corticosteroids represent one of the mainstays in the management of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects.

Circadian rhythms: eyes of the clock.

The daily light-dark cycle synchronizes the internal circadian clock with the outside world. Blind organisms maintain this light-induced entrainment, suggesting the existence of a non-visual phototransduction pathway. The photoreceptor is unknown, but several intriguing candidates have recently come to light.

Neural network computer program to determine photorefractive keratectomy nomograms.

PURPOSE: To evaluate a commercially available neural network program for calculation of photorefractive keratectomy treatment nomograms. SETTING: University referral refractive surgery clinic. METHODS: PRK/LASIK Brain, a commercial neural network computer program, was trained using the demographics, preoperative clinical data, surgical parameters, and 1 year postoperative clinical data of 44 patients treated with a Summit Technology excimer laser using a 5.0 mm optical zone. The neural-network derived nomogram was compared with the standard treatment nomogram for each patient. The relative contribution of age, sex, keratometry, and intraocular pressure (IOP) to the predicted nomograms was also assessed. RESULTS: Nomograms produced by the neural network were qualitatively similar to the standard nomogram. The sequence of data entry during training affected the network's predictions. Entry ordered by outcome (as opposed to entry by chronological order) yielded a nomogram that was more consistent with the standard nomogram. However, both outcome- and chronologically ordered network-derived nomograms diverged from the standard nomogram in individual patients, including a subset for whom use of the standard nomogram yielded desired refractive results (within 0.25 diopter of emmetropia). Further analysis of the neural-network-derived nomograms revealed marked sensitivity to sex, age, keratometry readings, and IOP. CONCLUSIONS: Neural networks offer a potential means of individualizing treatment nomograms, to account for patient demographics, preoperative examination, surgeon style, and equipment bias. However, a data set of 44 patients was not sufficient to train the PRK/LASIK Brain network to accurately predict treatment parameters in individual cases in the training set. A larger training set or a different learning algorithm may be required to improve the neural network's performance.

A novel circadianly expressed Drosophila melanogaster gene dependent on the period gene for its rhythmic expression.

The Drosophila melanogaster period (per) gene is required for expression of endogenous circadian rhythms of locomotion and eclosion. per mRNA is expressed with a circadian rhythm that is dependent on Per protein; this feedback loop has been proposed to be essential to the central circadian pacemaker. This model would suggest the Per protein also controls the circadian expression of other genetic loci to generate circadian behavior and physiology. In this paper we describe Dreg-5, a gene whose mRNA is expressed in fly heads with a circadian rhythm nearly identical to that of the per gene. Dreg-5 mRNA continues to cycle in phase with that of per mRNA in conditions of total darkness and also when the daily feeding time is altered. Like per mRNA, Dreg-5 mRNA is not expressed rhythmically in per null mutant flies. Dreg-5 encodes a novel 298 residue protein and Dreg-5 protein isoforms also oscillate in abundance with a circadian rhythm. The phase of Dreg-5 protein oscillation, however, is different from that of Per protein expression, suggesting that Dreg-5 and per have common translational but different post-translational control mechanisms. These results demonstrate that the per gene is capable of modulating the rhythmic expression of other genes; this activity may form the basis of the output of circadian rhythmicity in Drosophila.

Partners in time. Circadian rhythms.

The timeless gene is a second essential component of the circadian clock in Drosophila; its product interacts physically with the only other known clock component, the period gene product. Together they control the daily cycle of expression of their own and other loci.