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Biomedical subjects

R Bouchard

Publications and source records attributed to R Bouchard.

At least 19 recordsLinked to original sources

Interactions of PIN and PGP auxin transport mechanisms.

Polarized transport of the plant hormone auxin influences multiple growth processes in plants and is regulated by plasma-membrane-localized efflux and uptake carriers. The PGP (P-glycoprotein) ABC transporters (ATP-binding-cassette transporters), PIN (pin-formed) subfamily of major facilitator proteins and members of AUX/LAX families have been shown to independently transport auxin both in planta and in heterologous systems. However, PIN- and PGP-mediated transport in heterologous systems exhibits decreased substrate specificity and inhibitor-sensitivity compared with what is seen in plants and plant cells. To determine whether PIN-PGP interactions enhance transport specificity, we analysed interactions of the representative auxin-transporting PGPs with PIN1 and AUX1 in planta and in heterologous systems. Here, we provide evidence that PINs and PGPs interact and function both independently and co-ordinately to control polar auxin transport and impart transport specificity and directionality. These interactions take place in protein complexes stabilized by PGPs in detergent-resistant microdomains.

ATP-Binding Cassette Transporters↗

Characterizing neuropsychiatric symptoms in subjects referred to dementia clinics.

OBJECTIVE: To characterize the neuropsychiatric symptoms (NPS) of subjects classified as not cognitively impaired (NCI), cognitively impaired-not demented (CIND), and dementia. METHODS: A Canadian Cohort Study of Cognitive Impairment and Related Dementias (ACCORD) is a longitudinal investigation of individuals referred to eight Canadian dementia centers for evaluation of cognitive impairment and neurobehavioral symptoms. Of the inception cohort of 804 subjects for whom the informant-based Neuropsychiatric Inventory (NPI) was completed at study entry, 35 were classified as NCI, 193 as CIND, and 576 as dementia. The three diagnostic groups were compared on each of the 12 NPI items. Within each diagnostic group, comparisons were also made between symptomatic (NPS+; total score > 1) and asymptomatic (NPS-; total score = 0) subjects on measures of general cognitive status and functional disability. A subset of the NCI and CIND individuals were also compared on a comprehensive neuropsychological test battery. RESULTS: There was at least one NPI item reported in 60% of subjects with NCI, 74% with CIND, and 89% with dementia. The item scores for delusions, hallucinations, agitation, apathy, disinhibition, aberrant motor behavior, and problems with appetite were greater in dementia subjects than in NCI or CIND. There were no significant differences between subjects with NCI and CIND on any NPI item. For each diagnostic group, NPS+ subjects were more impaired on functional but not neuropsychological measures. CONCLUSIONS: Across all levels of cognition, neuropsychiatric symptoms (NPS) are an important feature in individuals referred to dementia clinics. The current data suggest that NPS may precede cognitive deficits in individuals classified as not cognitively impaired and cognitively impaired-not demented.

Aged↗

[Current perioperative antibiotic prophylaxis].

Perioperative antimicrobial prophylaxis (PAP) leads to a reduction in surgical site infections. The aim of PAP is adequate serum and tissue concentrations of the antimicrobial drug in the field of operation. The antibiotic must be effective against the expected pathogens during the operation, safe, and have the fewest possible side effects. The indication for PAP should take into account the risks of the operative procedure and especially the individual risk factors of the patient. Depending on pharmacokinetics, the antibiotic should be administered within 60 min before incision. After closure of the wound, further applications of the antibiotic drug have no influence on the infection rate of the wound but do increase the side effects (resistance, CDT colitis, allergy). Operation-specific recommendations according to guidelines of the Paul Ehrlich Society are given.

Adult↗

[Fungi in the mediastinum: rare, but relevant].

Fungal infections of the mediastinum are rare. There are five forms to be differentiated: (i) hematogenous fungal infection of the mediastinum after fungemia; (ii) postoperative fungal infection after cardiosurgical sternotomy; (iii) as special form of a descending necrotizing fasciitis; (iv) infection of the mediastinum per continuitatem; (v) fungal infection of the posterior mediastinum after esophageal perforation. In the surgical department, University of Schleswig-Holstein, Campus Lübeck, five patients with a fungal mediastinitis were treated during a period of 10 years. Three patients suffered from a descending mediastinitis, one patient from a fungal infection after pseudarthrosis of the sternum (postoperatively after cardiosurgery). The section results of one other patient with pulmonary aspergillosis showed a complete invasion of the mediastinum by Aspergillus fumigatus.

Fungi↗

[Fungal infections in patients with necrotizing pancreatitis: risk-factors, incidence, therapy].

Haemorraghic necrotizing pancreatitis may lead to a serious disease with multi-organ failure, which is to be treated with intensive care. Patients suffering from infected necrosis are usually operated (necrosectomy). By doing this, it is possible to get a microbiological analysis. The most common virulent species are Enterobacteriaceae. According to the literature, fungal infections appear in 15-30% of the cases. Since 1996, 73 patients were treated surgically in our department. A number of 50 patients (68,5%) developed a fungal infection during the course of the disease. The mortality rate was 62%.

Antifungal Agents↗

[Therapy on mycoses after simultaneous pancreas-kidney transplantation].

Patients suffering from type I diabetes mellitus have a descending expectancy of life, after developing diabetic nephropathy and undergoing haemodialysis. After 3 years of haemodialysis, approximately only 40% of the patients are still alive. The only remedy of this incurable metabolic disease is the simultaneous pancreas-kidney transplantation. After transplantation, fungal colonization and fungal infection is a serious threat for the patient's life. In this context, it is necessary to distinguish between colonization and invasive mycosis. In the case of unsuccessful antimycotic treatment, the removal of the transplanted organ, depending on the patient's condition, may be necessary to save the patient's life.

Antifungal Agents↗

[Complicated course of oesophageal perforations because of fungal infections].

Perforations of the oesophagus are characterized by a high mortality rate, varying between 7 and 49%. In the analyzed group of patients between the years 1986 and 2003, the mortality rate of 28% was caused by septic complications such as mediastinitis and pneumonia. Microbiological examinations of samples from different locations and various secretions, detected mycoses in 28% of the patients (n = 16). Compared with the total of mycoses, a higher mortality of 50% was calculated. The invasive Candida infection of the oesophagus itself can cause a perforation. In perforations of the oesophagus, simultaneous mycoses arise by fungi invading sterile compartments or by haematogenous and lymphogenous dissemination up to sepsis. Uncomplicated courses do not need antimycotic therapy. At the beginning of the treatment, a microbiological monitoring should be provided, particularly with regard to the intraoperative facts. In relation to the course and the risk factors of the patients, an antimycotic therapy is initiated. Surgical clearing and sufficient drainage of the collateral compartments such as pleural and mediastinal compartments is highly significant.

Antifungal Agents↗

[Therapy of intraabdominal fungal infections].

Candida albicans is the fourth most germ that can be identified on surgical intensive care unit (SICU). During the course of severe peritonitis recognition of Candida is crucial for physicians but interpretation of Candida-positive microbiologic samples is difficult. The indication for antimycotic therapy requires differentiation between harmless contamination or severe invasive mycosis associated with high mortality. Therefore, we propose a four-stage classification. Stage I is the initial contamination of the abdominal cavity by Candida spp. Stage IIa is characterized by persistence of fungi in patients without risk factors, IIb with risk factors respectively. Stage III means histological evidence of Candida invasion into the peritoneal layer. Stage IV is a generalized infection with fungemia/fungal sepsis. We recommend antimycotic therapy in stage IIb or higher.

Abdominal Cavity↗

[Severe case of Candida peritonitis in a patient on CAPD--a successful treatment].

Continuous ambulatory peritoneal dialysis (CAPD) is a widespread method of treatment used in approximately 10% of all patients suffering from terminal renal insufficiency. The main problem of this procedure is the increased risk of peritoneal infection. The incidence of such a peritonitis is quoted at one episode per 13-18.4 months of treatment. Candida peritonitis is a particularly severe form of CAPD peritonitis. This is a nosocomial infection with a high lethality rate of about 60%. The incidence of Candida peritonitis in CAPD patients amounts to approximately 5% of all intraabdominal infections and is on the increase. The authors describe a severe case of Candida peritonitis in a patient on CAPD. The therapeutic concept of this severe illness is illustrated.

Adult↗

[Evaluation of tibial torsion--comparison of clinical methods and computed tomography].

PURPOSE: To determine variability between clinical goniometric methods and computed tomography (CT) in measuring posttraumatic malrotation of the tibia. MATERIALS AND METHODS: In a prospective study, absolute tibial torsion of both legs after unilateral fracture of the tibia as well as the difference between both legs (intra-individual torsional difference) was postoperatively determined with two goniometric and two CT methods in 40 patients (female : male = 16 : 24, mean age = 46 +/- 34 years). RESULTS: The mean difference between goniometric and CT methods in determining intra-individual torsional difference was not significant. Nevertheless, variance of values was higher in goniometric measurement (up to +/- 11 degree), with the measurements of torsional difference showing two times greater standard deviation in interobserver variability of goniometric methods as compared to CT. CONCLUSION: Goniometric methods do not significantly differ from the CT methods for determination of intraindividual torsional difference. The higher variance of interobserver values limits accuracy of goniometric methods. Therefore, goniometric determination of tibial torsion can only be considered an estimate but not a precise measurement.

Adolescent↗

[Anticoagulation in the treatment of sepsis. Correction of microcirculation: a new approach manipulating endothelial cell function].

The correction of coagulation disorders is only one aspect in the treatment of severe sepsis. The metabolic changes caused by sepsis are complex. They include the interactions of hundreds of plasma proteins. The system works in balanced patterns of agonists and antagonists, not allowing a preference for single substances. The endothelial cell plays a key role in multiple defence functions in sepsis. Thus, future research in sepsis has to focus on the manipulation of endothelial cell function.

Animals↗

Assessment of suspected dementia.

At the Second Canadian Consensus Conference on Dementia (CCCD) (February, 1998), a group of neurologists, geriatricians, and psychiatrists met to consider guidelines for evaluation of dementia in Canada. This review paper formed a background paper for their discussion of dementia diagnosis. These experts from across the country concluded that diagnosis of suspected dementia cases continued to rest on skilled clinical assessment. Mental status exam, preferably in some quantifiable form, has become an essential part of the assessment. Selected laboratory tests are advisable in all cases (CBC, TSH, electrolytes, calcium, and glucose), but the CCCD continued to advise that CT scanning was mandatory only in selected cases where clinical findings pointed to another possibility besides Alzheimer's disease. The growing list of other diagnostic measures with potential usefulness in diagnosis of Alzheimer's disease or dementia in general was reviewed, but the evidence was judged as insufficient to support routine use of these tests by physicians. As new treatments for Alzheimer's disease become available, neurologists face new diagnostic challenges--differentiating Mild Cognitive Impairment, Frontotemporal dementias and Mixed dementias, and Lewy Body Dementia. Guidelines to aid in differential diagnosis are presented.

Aged↗

The diagnosis of "mixed" dementia in the Consortium for the Investigation of Vascular Impairment of Cognition (CIVIC).

If vascular risk factors are risk for Alzheimer's disease (AD), and if "pure" vascular dementia (VaD) is less common than has been thought, what do we make of the diagnosis of mixed dementia? We report characteristics of those with mixed dementia in a prospective, seven center, clinic-based Canadian study. Of 1,008 patients, 372 were diagnosed with AD, 149 with vascular cognitive impairment (VCI) including 76 with mixed AD/VaD, and 82 with other types of dementia. The mean age of patients with mixed AD/VaD was 78.0 +/- 7.6 years; 49% were female. These proportions differed significantly between dementia diagnosis subgroup (p < 0.001) showing a trend which is evident in all comparisons--AD/VaD patients fall in between AD and VaD. Vascular risk factors were present significantly more often in mixed AD/VaD than in AD (p < 0.001). More mixed AD/VaD (20%) than AD patients (4%) had focal signs, compared with 38% of those with vascular dementia and 12% with other types of dementia. Between the initial clinical diagnosis and the final diagnosis (which utilized neuroimaging and neuropsychological data) AD/VaD was the least stable diagnosis. Neuroimaging of ischemic lesions was the most common reason for reassignment from AD to the mixed AD/VaD diagnosis (17 cases). These data suggest that an operational definition of mixed AD/VaD can be proposed on presentation and clinical/radiographic findings, but indifferent to vascular risk factors. The concept of mixed dementia should be extended to include vascular dementia in combination with dementias, other than Alzheimer's disease.

Aged↗

A triple-crystal diffractometer for high-energy synchrotron radiation at the HASYLAB high-field wiggler beamline BW5.

The triple-crystal diffractometer installed at HASYLAB beamline BW5 with a high-field wiggler of critical energy 27 keV for DORIS III, operated at 4.5 GeV electron energy, is described. Samples can be mounted in large cryostats or furnaces normally used in neutron scattering experiments. The instrument has been successfully applied to measure structure factors S(Q) in liquids and amorphous materials, to collect full data sets of highly accurate structure factors for charge-density work, to measure the spin component of the ground-state magnetization in transition-metal and rare-earth compounds, to study the diffuse scattering from stacking faults and dislocation loops in Si single crystals, and for the investigation of various aspects of structural phase transitions: critical scattering in SrTiO3, oxygen order and stripe order in high-To materials. A crossed-beam technique allows for local studies of texture, internal strain and phase changes in the bulk of materials.

Journal Article↗

Slow gating charge immobilization in the human potassium channel Kv1.5 and its prevention by 4-aminopyridine.

1. The relationship between ionic current inactivation and immobilization of 'off'-gating charge in human Kv1.5 channels expressed in human embryonic kidney (HEK293) cells was studied using 4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA-Cl). 2. The charge transferred during short (< 10 ms) depolarizations (Q(on)) was conserved on repolarization (Q(off)) although peak off-gating current (off-Ig) was reduced and the time course prolonged (tau decay increased from 0.4 to > 1.2 ms). For +80 mV pulses longer than 50 ms, Q(off) at 20 ms was less than Q(on) (Q(off)/Q(on) ratio was 0.26 +/- 0.06 at 450 ms). We attribute this to a relative 'immobilization' of gating charge during long depolarizations. 3. 4-AP (0.1-1 mM) prevented slowing of off-Ig, allowing saturation of peak off-Ig. 4-AP also completely prevented immobilization of off-Ig after long depolarizations. In 1 mM 4-AP, off-Ig waveforms decayed rapidly and the charge ratio Q(off)/Q(on) remained at 1.0. 4. In addition to its effects on Ig, 1 mM 4-AP prevented the slow inactivation of ionic current seen during strong depolarizations. An initial block was caused by 4-AP or 1 mM intracellular TEA internally applied. However, only 4-AP prevented the slower, later development of C-type inactivation. 5. We suggest that slow current inactivation is accompanied by a gating charge immobilization in Kv1.5. 4-AP potently inhibits the changes in Q(off)/Q(on0, off-Ig, and ionic currents that underlie slow inactivation. Some actions of 4-AP appear independent of its properties as a blocker of open K+ channels, and are not mimicked by internal TEA.

4-Aminopyridine↗

Alzheimer's disease: preliminary study of spatial distribution at birth place.

Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by a progressive loss of memory and the alteration of cognitive functions. At least three chromosomal segments have been associated with early-onset AD in genetic linkage studies. These results argue for a certain degree of heterogeneity in the genetic origin of some forms of AD, although environmental risk factors cannot be ruled out in late-onset AD. In this preliminary study, we analyzed the geographical distribution of the birth places of a sample of 235 AD cases born in a defined region of Quebec (Canada), between 1895 and 1935. We wished to test the hypothesis that risk factors acting at, or around birth place and time play a role in the etiology of AD. The field of study was divided into rural and urban areas. A reference population of live births was used to compute a measure of odds ratio (OR). The OR results showed a statistically significant excess of AD cases in the rural area as compared to the reference population. When stratified for sex, the OR results showed a global excess of female AD cases in both the rural and the urban areas. For men, only the urban area presented a statistically significant deficit. We also analyzed the structures of the genealogical kinships of the rural and urban sub-groups. Although AD cases from the rural sub-group were more closely related to each other than those from the urban one, removal of the kin pairs from the OR analysis seemed to have little effect on the rural/urban distribution of cases. Therefore, the OR results would not appear to be due primarily to a difference in the kinship structures of the two sub-groups. This could mean that some risk factors for AD afflict women more strongly than men, the effect being different depending on the urban or rural origin. However, potential biases such as a higher rate of report for women, differential migration between birth places or a differential mortality ratio between sexes could produce spurious results in the direction of what we have observed in this preliminary study.

Aged↗

Closed- and open-state binding of 4-aminopyridine to the cloned human potassium channel Kv1.5.

The effect of 4-aminopyridine (4-AP) on membrane and gating currents of Kv1.5 channels was studied in a human cell line. The rank order of block was cell-attached > whole cell >> outside-out macropatches, which suggested that 4-AP blocked channels from the cytosolic face. Stimulation after exposure to 4-AP during rest resulted in a "supernormal" current immediately after the onset of depolarization, followed by open channel block during maintained depolarization. 4-AP remained trapped in closed channels, and unblock after drug washout required depolarization. At higher concentrations, 4-AP induced channel block by binding to closing or nonconducting channels. This effect could be reduced by hyperpolarization and higher pulsing rates. Block of Kv1.5 channels under steady-state conditions was correlated with a dose-dependent reduction in gating charge movement. The normalized voltage dependence of gating was shifted to more negative potentials by 4-AP. A model incorporating both open and closed channel binding of 4-AP reproduced data, including the "supernormal" current, by shifting the Po - V curve slightly to the left. The results show that 4-AP can both enhance and block Kv1.5 current and suggest that 4-AP can bind with different affinities to more than one site on Kv1.5 channels.

4-Aminopyridine↗

Ethical issues involved in establishing a registry for familial Alzheimer's disease.

In January 1992, the IMAGE Project extended the establishment of its registry of familial Alzheimer cases to all areas of the province of Quebec, for collection of epidemiological and clinical data, as well as biological samples. The aim is to study genetic transmission patterns of Alzheimer's disease (AD) and to provide a sampling framework for further etiologic and risk factor studies. The IMAGE registry already includes data of a population-based study in the Saguenay-Lac-St-Jean area; the project to collect data on familial AD (FAD) cases across the province of Quebec is known as the ALGENE Initiative. The registry is thus a collection of "AD families" for both familial and sporadic cases. The establishment of the registry involves several steps in the field work: recruitment and selection of families; collection of information on family medical history; selection of informative families and genetic testing for AD/FAD by linkage analysis. As AD is not homogeneous in its etiology and since we do not know if, in the event that genetics is involved in AD whether or not penetrance of the gene(s) is high, we must be aware of the "genetic horizons" of AD in collecting and conserving data on families of cases, and in the genetic testing for AD/FAD by linkage analysis. Families who choose genetic testing must be aware of the implications of our undertaking, assured of the confidentiality of the test and, at the same time, they must understand its limitations. The experimental nature of our research project raises ethical dilemmas. This article examines these initial considerations of the field work involved in developing a registry pertaining to genetic testing for AD/FAD by linkage analysis and offers some preliminary observations on the experience of the first year of this project.

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