Recognition and management of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an inflammatory systemic disease that causes organ damage by the deposition of autoantibodies and complement activating immune complexes or by vascular occlusion due to procoagulant states associated with antiphospholipid antibodies. The vast majority of cases occur in women of childbearing age. SLE is diagnosed on the basis of its clinical manifestations and the demonstration of characteristic immunological phenomena, especially anti-nuclear antibodies. The prognosis in SLE has shown a distinct improvement over recent decades, the 5-year survival rate now approaching or exceeding 90%. The 15-year survival rate of 63 to 79%, on the other hand, underscores the need for further advances in diagnosis and treatment of the disease. Management of the disease includes regular monitoring of disease activity, avoidance of predisposing factors and close supervision of therapy. Drug therapy is guided by the activity and severity of the leading organ manifestations and ranges from nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents. Corticosteroids remain irreplaceable for the control of acute flares. Antimalarials and azathioprine are important long term drugs for treating mild or moderate disease activity. Intravenous pulse cyclophosphamide is safer than other regimens and at least as effective as oral cyclophosphamide for severe lupus nephritis. It is also effective in the treatment of central nervous disease and of other organ-threatening manifestations. Recently, an intensified protocol which included cyclophosphamide induced long term treatment-free remission in 60% of patients. The toxicity of cyclophosphamide is considerable, but can be ameliorated by various measures. The value of several new immunosuppressants and other compounds remains to be determined.     

Gallstone prevalence in relation to smoking, alcohol, coffee consumption, and nutrition. The Ulm Gallstone Study

BACKGROUND: Besides considering well-known risk factors for the development of gallbladder stones, such as age, sex, fecundity, and hereditary predisposition, efforts at prevention have focused increasingly on other factors, such as nicotine, alcohol, and caffeine consumption, as well as general nutrition, which may be modified. METHODS: A total of 1116 blood donors were examined between April 1994 and February 1995 in the central blood bank of the German Red Cross in Ulm, Germany. Each subject received a questionnaire and underwent to an upper abdominal ultrasound examination. RESULTS: Gallbladder stone disease (current cholecystolithiasis and history of cholecystectomy) was detailed in 5.8% of the men and 6.3% of the women. Neither regularity nor number of daily meals correlated with the frequency of gallstone disease. Vegetarians (n = 48), as a group, were not found to have gallstones. In relation to the consumption of alcohol, tobacco, or caffeine higher prevalence of cholecystolithiasis was found only in heavy drinkers of coffee (P = 0.051; odds ratio (OR), 1.083; 95% confidence interval (CI), 0.999, 1.174). CONCLUSION: Results of the present study do not show a definite relationship between nutritional factors and the consumption of alcohol, tobacco, or caffeine and an increased prevalence of gallbladder stone disease.     

Saturation of ecosystems with toxic metals in Sudbury basin, Ontario, Canada

Mining and resource recovery activities have not been kind to ecosystems in the Sudbury basin, Ontario. The combination of logging, smelting, fires and erosion resulted in an unusual anthropogenic ecosystem of denuded barren land with lifeless lakes, or a micro-desert. Since the 1970s, however, the concerted efforts made to reduce the emissions and rehabilitate parts of the degraded ecosystem have resulted in improvements in water quality, and recoveries in phytoplankton, zooplankton, zoobenthos and fish communities but have had little impact on toxic metal concentrations in many lakes. We show that most of the catchments in the Sudbury basin have become saturated with Cu and Ni, and some with Zn and Pb. It is estimated that mobilization of metals stored in soils and glacial overburden by surface runoff, groundwater drainage and wind re-working of tailings can sustain the high concentrations of Cu and Ni in many lakes for well over 1000 years. Strategies to immobilize the pollutant metals in the watershed rather than further emission controls may be required for dealing with high levels of toxic metals in surface waters of the saturated ecosystems.     

Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC

We investigated the effect of successive administrations of SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride), a novel cognitive enhancer with high affinity and selectivity for the sigma1 receptor subtype, on the cortical cholinergic dysfunction-induced impairment of the spatial learning performance in the Morris water maze (MWM) task in rats. The impairment of the spatial learning performance was produced by the ibotenic acid-induced lesion of the basal forebrain (BF) area in rats. Escape latencies to find the platform during the training trials of the MWM task were significantly prolonged in the BF-lesioned rats compared with the sham-operated rats. Daily treatment with SA4503 (0.1-0.5 mg/kg, P.O./day) for 13 days ameliorated this learning deficit. In the probe trial, BF-lesioned rats reduced the number of times each rat crossed the former platform location during the training trials (goal area) in comparison with sham-operated rats. Successive administrations of SA4503 (0.25 mg/kg, P.O./day) also significantly increased the BF lesion-induced reduction of the number of times each rat crossed the goal area. These results suggest that the successive administrations of SA4503 attenuate the impairment of the spatial learning performance in rats with cortical cholinergic dysfunction, and that SA4503 is useful as a therapeutic drug for Alzheimer's disease.     

Is automatic disinfection between each endoscopy mandatory? Société Royale Belge de Gastro-entérologie

PURPOSE: The effects of chronic chloroquine administration on serum proteins and free amino acids of rabbits and the accompanying ultrastructural changes in the retina were investigated. METHODS: Thirty pigmented rabbits were injected intramuscularly with chloroquine diphosphate (14 mg/Kg bw). Fifteen rabbits served as control. Blood samples drawn after 1, 2, 3, 4, 5, 6 and 12 months were assayed for serum proteins by Bio-analytic kits and horizontal electrophoretic technique. Free amino acids were determined by Beckman analyzer. Central retinal tissue was fixed in 4% glutaraldehyde, embedded in araldite CY212 and sectioned for ultrastructural examination. RESULTS: Histopathologic changes were apparent within three months, initially affecting the pigment epithelium and photoreceptors and later involving the remaining neuroretinal layers. Hypoproteinemia gradually developed mainly due to a sharp drop in albumin and alpha 1 and 2 globulin fractions, inspite of an increase in beta and gamma globulin fractions. The concentration of non-essential amino acids varied considerably from a depletion of taurine, aspartine, glutamine, tryptophan and arginine to an increase of serine, alanine, GABA and ornithine. The most outstanding effect was the disappearance of tyrosine and its return to normal value at the end of the experiment. CONCLUSION: The disturbances in protein pattern and free amino acid levels are an indication of chloroquine toxicity and may be implicated in the retinopathy.     

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism

Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs. CYP2C9 activity in vivo is inducible by rifampicin. Evidence suggests that CYP2C9 substrates may also be induced variably by carbamazepine, ethanol and phenobarbitone. Apart from the mutual competitive inhibition which may occur between alternate substrates, numerous other drugs have been shown to inhibit CYP2C9 activity in vivo and/or in vitro. Clinically significant inhibition may occur with coadministration of amiodarone, fluconazole, phenylbutazone, sulphinpyrazone, sulphaphenazole and certain other sulphonamides. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino acid residues 144 (Arg144Cys) and 359 (Ile359Leu) of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, although the frequency of this allele is relatively low. Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. Individualisation of dose is essential for those CYP2C9 substrates with a narrow therapeutic index.     

Quality assurance of psychiatric consultations in somatic hospitals

Research has shown great variety in the clinical practice of consultation-liaison psychiatry in and between different countries. This paper presents the Norwegian experiences from a European collaborative study of quality management in consultation-liaison psychiatry. We describe a dynamic model for total quality management based on regular registration of some clinical data and the subsequent feed-back on changes of these. We discuss our experiences with this model and obstacles met in everyday work. Finally we point to different ways of implementing this method on a broader base in consultation-liaison psychiatry.     

Investigation of ultrasonic wave scattering by a randomly rough solid-solid interface

An imperfect interface between two dissimilar materials is modeled by a random interface profile. A theoretical study of the interaction of ultrasonic waves with the rough solid-solid interface is presented. The reflection and transmission coefficients for longitudinal and shear coherent waves are calculated as a function of the angle of incidence within the framework of a second order perturbation theory. The effects of the statistical interface parameters, as well as the interface spectral density on the scattered fields, are investigated. These results are used to determine the roughness-induced attenuation of the coherent fields as a function of the above parameters. In addition, the relation between the incoherent part of the scattering cross-section, and interface roughness is examined.     

A nonlinear spatially variant object-dependent system model forprediction of partial volume effects and scatter in PET

Accurate quantitation of small lesions with positron emission tomography (PET) requires correction for the partial volume effect. Traditional methods that use Gaussian models of the PET system were found to be insufficient. A new approach that models the non-Gaussian object-dependent scatter was developed. The model consists of eight simple functions with a total of 24 parameters. Images of line and disk sources in circular and elliptical cylinders, and an anthropomorphic chest phantom were used to determine the parameter values. Empirical rules to determine these parameter values for various objects based on those for a reference object, a 21.5-cm circular cylinder, were also proposed. For seven spheroids and a 3.4-cm cylinder, pixel values predicted by the model were compared with the measured values. The model-to-measurement-ratio was 1.03±0.07 near the center of the spheroids and 0.99±0.03 near the center of the 3.4-cm cylinder. In comparison, the standard single Gaussian model had corresponding ratios of 1.27±0.09 and 1.24±0.03, respectively, and the corresponding ratios for a double Gaussian model were 1.13±0.09 and 1.05±0.01. Scatter fraction (28.5%) for a line source in the 21.5-cm cylinder was correctly estimated by our model. Because of scatter. The authors found that errors in the measurement of activity in spheroids with diameters from 0.6 to 3.4 cm were more significant than previously appreciated