Photostimulator allowing independent control of rods and the three cone types

This report describes a second-generation photostimulator with four primary lights that allows independent control of the stimulation of the four receptor types in the human eye. The new design uses LEDs (with light levels controlled by eight drivers that include voltage-to-frequency converters that provide 1-micros pulses at frequencies up to 250 kHz), with four center channels being combined by use of a fiber optic assembly, and likewise for four surround channels. Four fiber optic bundles are merged into a single bundle whose output is fed into a spatial homogenizer terminated by a diffuser. An interference filter is sandwiched between each LED and the fiber optic bundle. Two camera lenses collimate light from the diffusers, one for center and one for surround. The center-surround field configuration is formed by a photometric cube with a mirrored ellipse on the hypotenuse. A field lens places images of the diffusers in the plane of an artificial pupil. The fields are highly uniform. Following alignment and calibration, the center and surround fields are indistinguishable. An observer calibration procedure, designed to compensate for prereceptoral filtering, is shown by calculation to correct also for normal observer receptoral spectral sensitivity variation. With the instrument calibrated for the individual observer, a peripherally fixated 200-ms 40% contrast rod center field pulse, highly conspicuous under dark adaptation, is invisible following light adaptation.     

Pharmacokinetics of etoricoxib in patients with renal impairment

The effect of renal insufficiency on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, was examined in 23 patients with varying degrees of renal impairment (12 moderate [creatinine clearance between 30 and 50 mL/min/1.73 m2], 5 severe [creatinine clearance below 30 mL/min/1.73 m2], and 6 with end-stage renal disease requiring hemodialysis) following administration of single 120-mg oral doses of etoricoxib. Even the most severe renal impairment was found to have little effect on etoricoxib pharmacokinetics. The low recovery of etoricoxib in dialysate (less than 6% of the dose) supports that hemodialysis also has little effect on etoricoxib pharmacokinetics, and binding of etoricoxib to plasma proteins was generally unaffected by renal disease. Single doses of etoricoxib were generally well tolerated by patients with renal impairment. Based on pharmacokinetic considerations, dosing adjustments are not necessary for patients with any degree of renal impairment. However, because patients with advanced renal disease (creatinine clearance below 30 mL/min/1.73 m2) are likely to be very sensitive to any further compromise of renal function, and there is no long-term clinical experience in these patients, the use of etoricoxib is not recommended in patients with advanced renal disease.     

Molecular biology of upper gastrointestinal malignancies

While cancers of the upper gastrointestinal tract are related by location, they have distinct clinical and molecular characteristics. This review will focus on the molecular biology of esophageal adenocarcinoma (EAC) of which alterations in p53, overexpression of cyclin D1, loss of p16, and aneuploidy have been best characterized. Key similarities and differences, when compared to esophageal squamous cell carcinoma (ESCC), gastric adenocarcinoma (GC), and adenocarcinoma of the gastric cardia (AGC), will also be highlighted. Currently, malignancies of the upper gastrointestinal tract are often diagnosed at an advanced stage and are generally associated with a poor patient prognosis. With an improved understanding of the molecular biology of these tumors, there is hope that new targets for diagnosis, chemoprevention, and therapy will be developed.     

Obsessive-compulsive severity spectrum in the community: prevalence,comorbidity, and course

OBJECTIVES: To describe lifetime prevalence rates, course and comorbidity of obsessive-compulsive disorder (OCD), obsessive-compulsive syndromes (OCS) and OC-symptoms (OC-sx) up to age 41. METHODS: In the Zurich community cohort study 591 subjects were selected after screening at the age of 19 and studied prospectively by 6 interviews from 20 to 40; they represent 1599 subjects of the normal population. The diagnoses of OCD met DSM-IV criteria.Course was assessed by graphic illustrations and prospective data. RESULTS: The lifetime prevalence rate was 3.5 % for OCD (males 1.7%, females 5.4 %) and 8.7 % for OCS (males 9.9%, females 7.5 %). The onset of OC-sx was 18 years (median); and in 70% before age 20. OCD was treated in one third of cases, OCS in 6.1%. The course of symptoms was chronic in 60%,but OCD and OCS showed in most cases considerable improvements over time. OCD reduced quality of life mostly in the subject's psychological wellbeing and at work but to a considerable extent also in other social roles. Comorbidity was prominent with bipolar disorder, panic disorder and social phobia and also significant with bulimia, binge eating, generalized anxiety disorder and suicide attempts; there was no association with substance abuse/dependence. CONCLUSION: OCD and OCD are manifestations of a wide spectrum of severity with high prevalence and strong clinical validity. The long-term course is better than generally assumed.     

Is bipolar I disorder heterogeneous?

Abstract.Objectives: The question whether bipolar I disorder should be subdivided into a preponderantly manic group (M) with no depression or only mild depression (Md) and a nuclear manic-depressive group (MD) has been rarely studied although the problem was raised more than 50 years ago. This paper seeks to elucidate this question by contributing further data.Methods: 406 patients with mood disorders hospitalised at some time during the period 1959–1963 were followed-up every five years until 1985; mortality data were collected up to 1997. Data on episodes, outcome, suicides and attempted suicides, alcohol and substance abuse/dependence and long-term medication, as well as on personality (melancholic and manic type) were collected. Major mood disorders were subclassified according to their hospitalisation for depression (D) and/or mania (M).Results: 30 manic patients (M/Md), 130 bipolar I (MD), 60 bipolar II patients (Dm) and 186 major depressive patients (D) were compared. The manic group differed from the bipolar I group in several variables: better school achievement, milder course of the illness (fewer recurrences), significantly less suicidality and a trend to less chronicity and more recovery. Manic patients required less long-term medication than bipolars and they differed in personality types from bipolars, the personality of manic patients being more often of the manic rather than the melancholic type, they were also more aggressive than bipolars. The family history data showed that the overall morbidity risk of first degree relatives of manic patients was significantly lower than that of bipolar patients.Conclusions: In accord with several other studies our data point to the existence of a more manic (M/Md) group of bipolar subjects. The diagnosis predicts a better course, lower suicidality and fewer and different treatment needs than does nuclear bipolar I (MD) disorder. The M/Md groups, as clinically interesting subgroups of the mood spectrum, should become a target of further research.     

Persistent organic pollutants in air and vegetation from the Canadian Rocky Mountains

The exchange of chlorinated organic pollutants between air and vegetation in cold, mountain environments was investigated through the extraction of coniferous vegetation and high-volume air samples collected from the Canadian Rocky Mountains during the summers of 1999 and 2000. Concentrations of several compounds in vegetation increased as temperatures decreased, whereas atmospheric concentrations were not related to temperature. Daily cycling of these compounds between air and vegetation as a result of diurnal temperature changes was not observed. Compared with concentrations in vegetation from the Canadian Rocky Mountains, plant samples from the western valley in British Columbia (Canada) showed higher pollutant levels. Chemical partitioning between vegetation and air was not correlated with temperature, indicating that air contamination is governed by long-range transport and not by local revolatilization events. Based on these observations, we show that both deposition at higher altitudes and long-range atmospheric transport influence chemical accumulation in vegetation from the Canadian Rocky Mountains.