Clonidine: adverse responses.
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Biomedical subjects
Publications and source records attributed to F Levy.
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OBJECTIVE: The aim of this paper is to review and integrate recent literature on aetiological factors that have been postulated for attention deficit hyperactivity disorder (ADHD). METHOD: Recent studies relating to perinatal brain damage, intra-uterine toxic effects, neurochemical, brain imaging and genetic studies are reviewed, and those considered most significant are discussed. Where possible, recent findings are integrated and directions of future research are suggested. Clinical implications are briefly discussed. RESULTS: Perinatal studies indicate that children with a birth weight under 750 g may be disadvantaged for attentional skills. Magnetic resonance imaging (MRI) and steady state visually evoked potential studies show differences in prefrontal, caudate and parietal areas in ADHD children, suggesting right hemispheric dysfunction. Functional MRI studies hold promise in further elucidating attentional systems in the central nervous system that are involved in ADHD. Genetic studies suggest genes related to dopaminergic systems may be important. CONCLUSIONS: Recent research on ADHD has made considerable advances, particularly in the areas of brain imaging and genetic studies. Genetic studies should provide further aetiological understandings of ADHD, leading to more targeted treatments.
BACKGROUND: Hemodynamic improvement after heart transplantation is expected to normalize the neuroendocrine balance, but circulating atrial natriuretic peptide (ANP) remains elevated. Endothelin stimulates ANP secretion and its concentration increases after heart transplantation, suggesting a role for this peptide in the cardiovascular adaptative response to heart transplantation. METHODS: To investigate whether endothelin may induce ANP increase in heart transplant recipients, we monitored daily ANP, endothelin, and related hormonal, biologic, and hemodynamic parameters before and during the first week after either heart transplantation (n = 15) or coronary artery bypass grafting (n = 10). RESULTS: Surgery induced a transient secretory peak of arginine vasopressin and endothelin in both groups at day 1. Bypass grafting did not modify normal ANP (11.8 +/- 2.1 pmol/L), endothelin (2.4 +/- 0.3 pmol/L), renin activity (0.11 +/- 0.04 pmol/L/sec), or aldosterone (492 +/- 122 pmol/L) values. Heart transplantation normalized the renin-aldosterone axis, but the early decrease observed for ANP (from 27.2 +/- 4.8 to 21.14 +/- 1.4 pmol/L) was only partial and transient. Endothelin further increased (from 4.4 +/- 0.8 to 9.14 +/- 1.8 pmol/L; p < 0.01) after transplantation. Positive correlations were observed between endothelin, isoproterenol dose, creatinine, right atrial pressure, and ANP, but multiple correlation analysis showed the important role of endothelin (r = 0.69, p < 0.001). Cyclic guanosine monophosphate correlated with ANP (r = 0.65, p < 0.001). CONCLUSIONS: Elevated endothelin, suggesting vascular dysfunction, likely contributes to the ANP increase observed early after heart transplantation. Furthermore, ANP, through a cardiac endothelium feedback, may act in the maintenance of circulatory homeostasis in heart transplant recipients.
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The effect of floor cleaning on bacteria, organic materials and particles in the patients' rooms was studied at Ullevål University Hospital, Oslo, Norway. Four cleaning methods were compared; dust-adhesive (dry), humified, wet mopping, and regular wet washing (RWW) without a mop. The following tests were taken from the floor before and after cleaning: bacterial counts (colony forming units = CFU) and ATP (presence of organic materials), and from the air: CFU/m3 air, and particle counts/m3 air. Humified mopping and dry mopping reduced the bacterial counts from the floor by 75% and 55% respectively (p = 0.005 and p = 0.014, using contact medium). The wet mopping had no statistically significant effect, while the wet washing even increased the CFU on the floor by 35-50% (p = 0.017 with contact medium, and p = 0.028 with petrifilm). The two wet methods were the most effective, however, in removing organic materials from the floor; 65% to 70% reduction (p = 0.051 and p =0.008). The CFU/m3 air was low both before (50-130 CFU/m3) and after (70-110 CFU/m3) cleaning. A slight increase in airborne particles was measured after dry mopping. Combined use of humified mopping and wet mopping is recommended, but is dependent on a well prepared and finished floor surface.
We retrospectively reviewed 290 cases in which an albumin-impregnated polyester prosthetic graft was used for surgical management of aortic bifurcation disease between November 1987 and December 1990. The purpose of this review was to determine the incidence and volume of blood transfusion and to evaluate the rate of patency and the incidence of infection achieved using this type of prosthesis. The indication for surgery was abdominal aortic aneurysm (AAA) in 218 cases (190 elective procedures and 28 emergency procedures) and occlusive disease of the aortic bifurcation (ODAB) in 72 cases. Mean follow-up was 25.5 +/- 13.4 months (range: 1 and 50 months). The incidence of blood transfusion for elective AAA and ODAB surgery was 30.2% and 32.3% intraoperatively, 21.3% and 12.9% postoperatively, and 40.4% and 42.6% overall. The mean number of red cell packs transfused for elective AAA and ODAB surgery was respectively 1 and 0.8 intraoperatively, 0.4 and 0.6 postoperatively, and 1.4 and 1 overall. No immediate or late graft infection prosthesis was observed in any patient in this series. Primary and secondary patency was 95.5% and 97.5% at 6 months with no graft thrombosis during further follow-up. The fact that use of an impregnated graft in management of aortic bifurcation disease was accompanied by a high incidence and volume of blood transfusion suggests that these grafts do not reduce perioperative blood loss. Use of an impregnated prosthesis had no effect on the rate of patency and the incidence infection.
OBJECTIVE: To investigate heritability and continuum versus categorical approaches to attention-deficit hyperactivity disorder (ADHD), using a large-scale twin sample. METHOD: A cohort of 1,938 families with twins and siblings aged 4 to 12 years, recruited from the Australian National Health and Medical Research Council Twin Registry, was assessed for ADHD using a DSM-III-R-based maternal rating scale. Probandwise concordance rates and correlations in monozygotic and dizygotic twins and siblings were calculated, and heritability was examined using the De Fries and Fulker regression technique. RESULTS: There was a narrow (additive) heritability of 0.75 to 0.91 which was robust across familial relationships (twin, sibling, and twin-sibling) and across definitions of ADHD as part of a continuum or as a disorder with various symptom cutoffs. There was no evidence for nonadditive genetic variation or for shared family environmental effects. CONCLUSIONS: These findings suggest that ADHD is best viewed as the extreme of a behavior that varies genetically throughout the entire population rather than as a disorder with discrete determinants. This has implications for the classification of ADHD and for the identification of genes for this behavior, as well as implications for diagnosis and treatment.
OBJECTIVE: To investigate the Continuous Performance Test in discriminating a group of 56 attention deficit hyperactivity disorder (ADHD) children from 56 school children individually matched for age, sex and social class. METHODOLOGY: The children all completed the Continuous Performance Task (CPT). The mothers and teachers completed a Conners Parent-Teacher Rating Scale for the clinic children. RESULTS: The ADHD sample was selected so that the average IQ was 99.8 to match the school sample. A non-parametric discriminant function showed that the subtests of the CPT that best discriminated ADHD were age-normalized errors of commission (NCPTC) and age-normalized mean reaction time (NMNRT). CONCLUSION: Optimal use of the CPT for discrimination of ADHD should include age normalization and mean reaction time to targets. Further evoked potential studies may show brief cortical events involved in reaction time over the course of the CPT, and the processes involved in behavioural control.
IgE isotype switching of human B cells requires physical interaction of T and B cells via surface molecules, and either IL-4 or IL-13 secreted by T cells. In this study we analyzed the role of IL-4 versus IL-13 in IgE production in atopy. We found that peripheral blood mononuclear cells (PBMC) from atopic individuals but not from nonatopic subjects secreted IgE without addition of IL-4 or IL-13, if T and B cells were simultaneously activated by anti-CD3 mAb and soluble CD40L, respectively. IgE production by atopic PBMC was dependent on endogenously secreted IL-4 and IL-13, since it could be blocked by a combination of anti-IL-4 plus anti-IL-13 antibodies. No differences in the B cell compartment of nonatopics and atopics were detectable, since PBMC from both donor populations secreted comparable amounts of IgE, if only the B cells were activated by soluble CD40L plus either exogenous IL-4 or IL-13. Further phenotypic analysis of T cells from atopics revealed that activated CD4+45RO- secreted IL-4 but no IL-13, whereas CD4+45RO+ memory T cells secreted low amounts of IL-4, but large amounts of IL-13. Accordingly, prolonged activation of native CD4+45RO- T cells in vitro induced expression of CD45RO, and strongly favored secretion of IL-13 rather than IL-4. Addition of exogenous IL-4 during activation further increased both IL-4 and IL-13 production to a similar degree. However, the potential of CD4 T cells from atopics to deliver contact-dependent activation signals to B cells and to induce IgE production (in the absence of soluble CD40L) increased with prolonged activation, and coincided with IL-13 rather than IL-4 production. Under similar conditions, CD8 effector cells secreted IL-13 but no IL-4, did not express CD40L, and could not help Ig(E) production by B cells. These results suggest that, in atopy, persistently stimulated CD4+45RO+memory/effector T cells provide contact-dependent activation signals to B cells, and that these cells may induce IgE switching largely via secretion of IL-13.
The control of DNA integrity in mammalian cells is important to maintain the cell homeostasis and prevent neoplastic transformation. Control of cell division and cell death permits repair or elimination of damaged cells. Since asbestos fibers can produce DNA damage, chromosome alterations and apoptosis in several sorts of cells, including mesothelial cells, it was interesting to investigate cell cycle disturbances in rat pleural mesothelial cells (RPMC) treated with asbestos fibers. Cell cycle analyses were performed in RPMC exposed to crocidolite (10 and 20 microg/cm2) and chrysotile (5 and 10 microg/cm2) for different times (4 to 48 h). Both fiber types entailed a G2/M accumulation in agreement with a delay in the mitosis course. Chrysotile fibers produced a G0/G1 accumulation associated with a time-dependent p53 and p21 expression. Crocidolite exposure resulted in a delay in the G1/S transition paralleling a low rate of p53 expression. These results are in agreement with a DNA damaging potential of asbestos fibers since similar results were found following RPMC exposure to gamma rays. In asbestos-treated RPMC, a low rate of apoptosis was found suggesting that RPMC may follow a DNA repair pathway that could contribute to the formation of DNA lesions. In addition, the cell cycle disturbances at the G2/M checkpoint suggest that genetically altered cells have progressed through the cycle and support the already published findings on the ability of asbestos fibers to impair cell division.
Multiple chemical sensitivity (MCS) could be called a phenomenon rather than an illness. No single widely accepted test of physiological function can be shown to correlate with the symptoms presented by the patients. In addition to allergy and asthma, patient history can include various "illnesses", and the "diagnosis" is often made by the patient, usually alone or with the help of clinical ecologists. This paper reports the experiences from a department of occupational medicine. More than 80% of the patients were women and solvent exposure was the most common cause of chemical intolerance reported by the patients. Many patients also reported psychosocial stressors. The patients also showed mood disorders with irritability, anxiety, sleep disturbances and depression, often with thoughts centered around different organ symptoms. The symptomatology of MCS is still nonspecific and in no way diagnostic of a specific illness or a medically acceptable syndrome. It may indicate many other conditions, both organic disease and psychopathology.
A library of random 10 residue peptides fused to the N-terminus of a reporter protein was screened in the yeast Saccharomyces cerevisiae for sequences that can target the reporter for degradation by the N-end rule pathway, a ubiquitin (Ub)-dependent proteolytic system that recognizes potential substrates through binding to their destabilizing N-terminal residues. One of the N-terminal sequences identified by this screen was used in a second screen for mutants incapable of degrading the corresponding reporter fusion. A mutant thus identified had an abnormally low content of free Ub. This mutant was found to be allelic to a previously isolated mutant in a Ub-dependent proteolytic system distinct from the N-end rule pathway. We isolated the gene involved, termed UFD3, which encodes an 80 kDa protein containing tandem repeats of a motif that is present in many eukaryotic proteins and called the WD repeat. Both co-immunoprecipitation and two-hybrid assays demonstrated that Ufd3p is an in vivo ligand of Cdc48p, an essential ATPase required for the cell cycle progression and the fusion of endoplasmic reticulum membranes. Further, we showed that, similarly to Ufd3p, Cdc48p is also required for the Ub-dependent proteolysis of test substrates. The discovery of the Ufd3p--Cdc48p complex and the finding that this complex is a part of the Ub system open up a new direction for studies of the function of Ub in the cell cycle and membrane dynamics.
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The increase in plasma concentration of atrial natriuretic factor in heart transplant patients has not been fully elucidated. Besides an eventual pressure or volume overload leading to passive atrial distension, the atrial tension developed during atrial systole, or atrial ejection force, which may be increased by the transplantation procedure, is an important determinant of atrial natriuretic factor release. We therefore determined the plasma concentration of atrial natriuretic factor and the maximal atrial ejection force in 15 heart transplant patients and 8 controls, matched for age and body mass. Atrial ejection force, as defined as the force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, was obtained using combined two-dimensional imaging and doppler echocardiography. Serum creatinin concentrations, heart rate [91.9 (SD 13.2) vs 71.8 (SD 10.9) beats.min-1], mean arterial blood pressure [103.9 (SD 9.8) vs 87.4 (SD 5.8) mmHg, 13.85 (SD 1.31) vs 11.65 (SD 0.77) kPa], left ventricular posterior wall thickness and interventricular septum thickness were higher in heart transplant patients compared to controls. Plasma concentration of atrial natriuretic factor was also elevated in heart transplant patients [63.9 (SD 18.1) vs 34.0 (SD 3.2) pg.ml-1; P < 0.001]. In contrast, although the left atrial area was greater in heart transplant patients [28.2 (SD 4.8) vs 15.8 (SD 2.5) cm2; P < 0.001], mitral area, transmitral Doppler A-wave maximal velocity and atrial ejection force were similar in transplant and in control patients [7.7 (SD 3.5) vs 8.9 (SD 2.8) kdyn, 77 (SD 35) vs 89 (SD 28)mN]. No significant correlation was observed between concentration of atrial natriuretic factor and atrial ejection force, either in heart transplant patients or in controls. Thus, the elevated plasma concentration of atrial natriuretic factor observed in these heart transplant patients was multifactorial in origin, and was considered to depend upon an hypersecretion rather than upon a decreased clearance rate. Moreover, it is suggested that the atrial ejection force was unlikely to have participated in this enhanced release of atrial natriuretic factor.
The effect of methylphenidate preceded by a moderate dose of haloperidol on reaction times over the duration of a continuous performance test (CPT), was investigated in ten male children, with a DSM-III diagnosis of attention deficit disorder with hyperactivity disorder (ADDH). Using a within-subject double-blind design, the effects of methylphenidate preceded by haloperidol on reaction time during the first and second blocks of CPT test were compared. Methylphenidate maintained a significantly improved reaction time in the second block of the CPT test. When methylphenidate, preceded by placebo, was preceded by haloperidol this effect was not observed, suggesting opposing effects on attentional systems by methylphenidate versus haloperidol. The study is the first to examine the "blocking" effect of haloperidol over the course of a CPT. The results suggest that dopamine systems are involved in the maintenance of the CPT response, and support an "incentive motivation" theory of sustained attention.
AIM: To compare the peroperative blood loss and the postoperative systemic inflammatory reaction in patients receiving either a Vasculour II Albumin pre-impregnated prosthesis (VA group, n = 32) or a preclotted Vasculour II prosthesis (V group, n = 33) for elective surgery of the abdominal aorta. SETTING: University Hospital. DESIGN: Prospective, randomised study. METHODS: Peroperative blood loss was measured over two different periods: Phase I from the beginning of the operation to the completion of the proximal anastomosis, when blood loss cannot be related to the model of prosthesis implanted and phase II after the completion of the proximal anastomosis to the end of the operation. Postoperative blood loss was evaluated by the determination of the retroperitoneal drainage volume over a period of 2 days immediately following the operation. The presence of periprosthetic fluid was measured with echography at days 4, 9, 30 and 60. The postoperative systemic inflammatory reaction was evaluated by measuring the sedimentation rate and the C reactive protein levels daily from day 1 to day 9, and at days 14, 21, 28, 45, and 60, and by measuring the body temperature daily from day 1 to day 9. RESULTS: No significant differences of peroperative blood loss were observed. The same proportion of patients (35%) in both groups received homologous transfusion. The mean number of units of homologous blood transfused per patient was respectively 0.77 and 0.91 for the VA and the V group. The retroperitoneal drainage volume and the percentage of patients with periprosthetic fluid did not differ significantly. No significant differences in systemic postoperative inflammatory reaction were observed. CONCLUSION: There were no benefits in using albumin-impregnated prosthesis as opposed to preclotted prosthesis in terms of peroperative and postoperative blood loss, or by looking at the incidence of homologous blood transfusion. However, the glutaraldehyde cross-linked albumin did not induce any systemic inflammatory reaction.
Hierarchical sampling from populations, incipient and recognized varieties within Phacelia dubia and P. maculata has revealed high levels of intraspecific polymorphism in chloroplast DNA. Much of the variation is partitioned between populations as evidenced by population-specific variants at fixation in all three populations of P. dubia var. interior and in both populations of P. maculata. Nine of 16 populations were polymorphic for cpDNA haplotypes. A total of 16 haplotypes was found in a sample of 106 individuals; the most common occurred in eight of the 16 populations and in 31 per cent of the individuals in the entire sample. A phylogenetic analysis revealed four basic plastome types. The two major groups of plastomes were separated by four independent base-pair mutations which suggests an ancient split in the evolution of plastid genomes. Representatives from each major plastome division were found in each of five populations spanning two allopatric varieties of P. dubia. The geographical distribution of haplotypes and lack of evidence for recent admixture argue against migration as a source of the polymorphism. It is more likely that the current taxonomic varieties are descendants of a polymorphic common ancestor.