Increased serum lithium concentration secondary to treatment with tiaprofenic acid and fosinopril

OBJECTIVE: To describe a patient in whom the administration of tiaprofenic acid and fosinopril was associated with decreased lithium clearance, resulting in increased serum lithium concentrations. CASE SUMMARY: A woman treated with lithium for bipolar affective disorder was concurrently treated with tiaprofenic acid 200 mg tid for shoulder pain. Previously initiated treatment with fosinopril was maintained during this time. The urinary lithium clearance was decreased during this combination therapy, necessitating a reduction in the lithium dosage. DISCUSSION: Lithium is approximately 80% reabsorbed in the proximal tubule, and the addition of tiaprofenic acid may have resulted in enhanced tubular lithium reabsorption. The possible influence of concurrent fosinopril therapy may also have contributed to altered lithium pharmacokinetics in this case. CONCLUSIONS: Serum lithium concentrations should be monitored if patients taking lithium are treated with tiaprofenic acid.     

Amelioration by quinapril of myocardial infarction induced by coronary occlusion/reperfusion in a rabbit model of atherosclerosis: possible mechanisms

BACKGROUND: The increased severity of the myocardial injury produced by coronary occlusion-reperfusion in models of atherosclerosis is associated with an increase in leukocyte accumulation in the ischemic myocardium. Expression of P-selectin, an adhesion molecule involved in the interaction between leukocytes and endothelium, is increased in atherosclerotic vessels. Long-term angiotensin-converting enzyme (ACE) inhibition has been shown to reduce atherosclerotic vascular change in experimental models. METHODS AND RESULTS: We examined changes in the size of the infarct resulting from coronary occlusion/reperfusion in normally fed and cholesterol-fed rabbits that were chronically treated with quinapril. Infarct size was significantly larger in the cholesterol-fed versus normally fed rabbits. ACE activity in the ischemic and nonischemic myocardium was significantly reduced by quinapril. Chronic quinapril administration significantly ameliorated the increased myocardial injury in cholesterol-fed rabbits. Quinapril administration markedly increased the myocardial cGMP content and reduced the myeloperoxidase activity in the border region of the ischemic myocardium in cholesterol-fed rabbits. The enhanced expression of P-selectin in myocardial tissue of cholesterol-fed rabbits was also effectively reduced by quinapril treatment. The above effects of quinapril were eliminated by blockade of bradykinin B2 receptors or inhibition of nitric oxide synthesis. CONCLUSIONS: Chronic quinapril treatment ameliorated the severity of myocardial injury produced by coronary occlusion/reperfusion in cholesterol-fed rabbits, possibly because of reversal of the enhanced interaction between leukocytes and endothelium in the ischemic myocardium via a bradykinin-related pathway.     

Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate

The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. The alpha-ketoglutarate binds in the active site at the same position and orientation as isocitrate, with a difference between the two bound molecules of about 0.8 A. The Ca2+ metal is coordinated by alpha-ketoglutarate, three conserved aspartate residues, and a pair of water molecules. The largest motion in the active site relative to the isocitrate enzyme complex is observed for tyrosine 160, which originally forms a hydrogen bond to the labile carboxyl group of isocitrate and moves to form a new hydrogen bond to Asp 307 in the complex with alpha-ketoglutarate. This triggers a number of significant movements among several short loops and adjoining secondary structural elements in the enzyme, most of which participate in dimer stabilization and formation of the active-site cleft. These rearrangements are similar to the ligand-binding-induced movements observed in globins and insulin and serve as a model for an enzymatic mechanism which involves local shifts of secondary structural elements during turnover, rather than large-scale domain closures or loop transitions induced by substrate binding such as those observed in hexokinase or triosephosphate isomerase.     

Effect of quinapril on the albumin excretion rate in patients with mild to moderate essential hypertension. Multicenter Study Group

The rising number of emergency admissions and the increasing specialisation of medicine sometimes cause problems in the organisation of care for patients admitted as emergencies to medical beds. A multidisciplinary working group from general practice and the hospital sector identified five main areas in which problems occurred-communication, appropriateness of referral, finding beds, waiting by patients, and the organisation of clinical care. Guidelines and standards were suggested. We then carried out an audit of acute care in 42 hospitals with 400 or more acute beds. The most significant problems that emerged were the suboptimal involvement of consultants in acute care, the frequent lack of appropriateness of the admitting specialty to the patient's condition, and confusion about policies for admitting elderly patients.     

Influence of human model resolution on computed currents induced in organs by 60-Hz magnetic fields

The effects of human body model resolution on computed electric fields induced by 60 Hz uniform magnetic fields are investigated. A recently-developed scalar potential finite difference code for low-frequency electromagnetic computations is used to model induction in two anatomically realistic human body models. The first model consists of 204290 cubic voxels with 7.2-mm edges, while the second comprises 1639146 cubic voxels with 3.6-mm edges. Calculations on the lower-resolution model using, for example, the finite difference time domain or impedance methods, push the capabilities of workstations. The scalar method, in contrast, can handle the higher-resolution model using comparable resources. The results are given in terms of average and maximum electric field intensities and current density magnitudes in selected tissues and organs. Although the lower-resolution model provides generally acceptable results, there are important differences that make the added computational burden of the higher-resolution calculations worthwhile. In particular, the higher-resolution modelling generally predicts peak electric fields intensities and current density magnitudes that are slightly higher than those computed using the lower-resolution modelling. The differences can be quite large for small organs such as glands.     

Transient shallow anterior chamber induced by supraciliary fluid after vitreous surgery

PURPOSE: To report a patient with idiopathic retinal venous beading and recurrent preretinal hemorrhage. METHOD: Case report of a 17-year-old girl with bilateral retinal venous beading, greater in the left eye than in the right eye, and recurrent preretinal hemorrhage in the left eye. RESULTS: Complete blood cell count, platelet count, blood glucose level, and hemoglobin electrophoresis were normal. Fluorescein angiography showed normal retinal arterial and venous filling with no evidence of retinal capillary nonperfusion or neovascularization. CONCLUSION: Idiopathic retinal venous beading may be associated with recurrent preretinal hemorrhage, even in the absence of retinal ischemia or neovascularization.     

Obstruction of the renal pelvis due to an insoluble blood clot after epsilon-aminocaproic acid therapy: resolution with intraureteral streptokinase instillations

alpha-Melanocyte stimulating hormone (alpha-MSH) regulates skin and hair pigmentation by modulating the activity of MSH receptor (MC1R). We have identified Arg151Cys variant of human MC1R in genomic DNA isolated from a person with red hair and light skin of type I. The Arg151Cys variant of MC1R binds to radio-labelled analogue of alpha-MSH with identical affinity as wild type MC1R but can not be stimulated to produce cyclic AMP (cAMP). The mutation Arg151Cys renders human MC1R completely nonfunctional, which explains the red hair, light skin and poor tanning ability (skin type I). This is the first report ever describing a nonfunctional MC1R isolated from a human subject.     

Arsenic methylation patterns before and after changing from high to lower concentrations of arsenic in drinking water

Inorganic arsenic (In-As), an occupational and environmental human carcinogen, undergoes biomethylation to monomethylarsonate (MMA) and dimethylarsinate (DMA). It has been proposed that saturation of methylation capacity at high exposure levels may lead to a threshold for the carcinogenicity of In-As. The relative distribution of urinary In-As, MMA, and DMA is used as a measure of human methylation capacity. The most common pathway for elevated environmental exposure to In-As worldwide is through drinking water. We conducted a biomarker study in northern Chile of a population chronically exposed to water naturally contaminated with high arsenic content (600 micrograms/l). In this paper we present the results of a prospective follow-up of 73 exposed individuals, who were provided with water of lower arsenic content (45 micrograms/l) for 2 months. The proportions of In-As, MMA, and DMA in urine were compared before and after intervention, and the effect of other factors on the distribution of arsenic metabolites was also analyzed. The findings of this study indicate that the decrease in arsenic exposure was associated with a small decrease in the percent In-As in urine (from 17.8% to 14.6%) and in the MMA/DMA ratio (from 0.23 to 0.18). Other factors such as smoking, gender, age, years of residence, and ethnicity were associated mainly with changes in the MMA/DMA ratio, with smoking having the strongest effect. Nevertheless, the factors investigated accounted for only about 20% of the large interindividual variability observed. Genetic polymorphisms in As-methylating enzymes and other co-factors are likely to contribute to some of the unexplained variation. The changes observed in the percent In-As and in the MMA/DMA ratio do not support an exposure-based threshold for arsenic methylation in humans.     

Oral health in Europe with changing socioeconomic structures as seen by the epidemiologist

During the 20th century in Europe remarkable results were obtained in health and social care systems which positively influenced general and oral health. Among others this was favoured by the WHO-initiated multinational movement "Health for all by the year 2000". Political changes in Eastern Europe levelled the way for constructive collaboration also in the field of health promotion. In contrast to this, economic deprivation in all European countries limits the financing of continually increasing costs of dental care. Oral health improved during the last decades, although differences in the health level between socioeconomic classes increased. In Eastern Europe the transformation process towards a new dental care system is quite difficult and is still going on. The establishment of new health-structures depends on socioeconomic resources and has so far attained different levels in various countries. The epidemiological situation also varies greatly. In general, caries prevalence is higher than in Western Europe.     

Redistribution of ribosomal DNA after blocking of transcription induced by actinomycin D

In recent years there has been increased interest in the role of exercise in the alleviation of patellofemoral pain syndrome. Contradictions which result in a lack of a consensus amongst clinicians and researchers as to the most beneficial type of exercise are reviewed. The popularly held belief that there are imbalances between some components of the quadriceps femoris is also reviewed and conflicting evidence that quadriceps contractions can be enhanced by altering hip and knee positions is found. Some traditional exercises, previously considered essential to any regime for this common condition, were not found to be as beneficial as previously thought. Consequently, some of these exercises should be less prominent in a rehabilitation programme for patellofemoral pain syndrome.     

Sensitization to morphine induced by viral-mediated gene transfer

Repeated administration of morphine sensitizes animals to the stimulant and rewarding properties of the drug. It also selectively increases expression of GluR1 (an AMPA glutamate receptor subunit) in the ventral tegmental area, a midbrain region implicated in morphine action. By viral-mediated gene transfer, a causal relation is shown between these behavioral and biochemical adaptations: Morphine's stimulant and rewarding properties are intensified after microinjections of a viral vector expressing GluR1 into the ventral tegmental area. These results confirm the importance of AMPA receptors in morphine action and demonstrate specific locomotor and motivational adaptations resulting from altered expression of a single localized gene product.     

Relationship between suicide and myocardial infarction with regard to changing physical environmental conditions

The treatment of clinically resistant cytomegalovirus retinitis in AIDS patients requires a combination of foscarnet and ganciclovir, but the poor clinical condition of some patients may weigh against this intravenous regimen. We treated three patients with high-dose intravitreal foscarnet (2400 micrograms/0.1 ml; 25 injections; mean follow-up 14.6 weeks) combined with intravenous ganciclovir (5 mg/kg twice daily), and obtained complete control of the retinitis in a mean time of 3.4 weeks with no ocular or systemic side effects and no other eye/organ cytomegalovirus dissemination. This combined therapy seems useful for clinically resistant cytomegalovirus retinitis in AIDS patients.     

Reversible parkinsonism induced by prolonged treatment with valproate

We describe two patients who developed levodopa-responsive parkinsonism without dementia at least 4 years after beginning chronic valproate (VPA) treatment for seizures. Parkinsonism disappeared in less than 3 months after VPA substitution with carbamazepine.     

Incubation temperatures affect adherence to plastic of Candida albicans by changing the cellular surface hydrophobicity

The influence of cellular surface hydrophobicity on the adherence capacity to plastic of Candida albicans was investigated at two culture temperatures (37 and 22 degrees C). The majority of the 42 strains studied were hydrophobic at 22 degrees C and hydrophilic at 36 degrees C. The hydrophobic cells showed a consistent adherence capacity which was absent from the hydrophilic strains. The culture temperatures affect adherence to plastic of C. albicans by changing the cellular surface hydrophobicity.     

Intrinsic resistance to T cell infection with HIV type 1 induced by CD28 costimulation

When HIV-infected leukocytes are activated by the CD28 costimulatory receptor, HIV-1 is rapidly cleared from cultures, suggesting that costimulation can render T cells resistant to HIV-1 infection. In this study we tested the hypothesis that enhanced secretion of cytokines or chemokines could account for CD28-induced antiviral effects. In an acute infection system, resistance to infection with macrophage-tropic strains of HIV-1 was shown to be comprised of both soluble and cell-associated components. Induction of HIV-1 resistance was specific for CD28 costimulation, in that a variety of other accessory receptors, such as CD2, CD4, CD5, and MHC class I, failed to confer the antiviral resistance. The soluble component was secreted by both CD4 and CD8 T cells, was not unique to CD28 costimulation, and could be neutralized by removal of C-C chemokines (RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1alpha and -1beta) from the culture supernatants of costimulated CD4 T cells. In contrast, CD28 stimulation of CD4 cells resulted in the specific induction of a pronounced intrinsic resistance to HIV-1 infection by macrophage tropic isolates of HIV-1.