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Biomedical subjects

A Wagner

Publications and source records attributed to A Wagner.

At least 163 records · Page 9Linked to original sources
PubMed2000

Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancer. In families with BRCA1 or BRCA2 mutations, identification of mutation carriers is clinically relevant in view of the options for surveillance and prevention. METHODS: We assessed presymptomatic DNA testing and prophylactic surgery in 53 consecutive families presenting to the Rotterdam Family Cancer Clinic with a known BRCA1 or BRCA2 mutation. We identified predictors for DNA testing and prophylactic surgery with univariate and multivariate analysis. FINDINGS: 682 unaffected individuals with a 50% risk (275 women and 271 men) or with a 25% risk (136 women) for carrying a mutation were identified and offered a DNA test. Presymptomatic DNA testing was requested by 48% (198 of 411) of women and 22% (59 of 271) of men (odds ratio for difference between sexes 3.21 [95% CI 2.27-4.51]; p<0.001). In women, DNA testing was significantly more frequent at young age, in the presence of children, and at high pre-test genetic risk for a mutation. Of the unaffected women with an identified mutation who were eligible for prophylactic surgery, 51% (35 of 68) opted for bilateral mastectomy and 64% (29 of 45) for oophorectomy. Parenthood was a predictor for prophylactic mastectomy but not for prophylactic oophorectomy. Age was significantly associated with prophylactic oophorectomy, but not with prophylactic mastectomy, although there was a tendency towards mastectomy at younger ages. INTERPRETATION: In a clinical setting, we show a high demand for BRCA1 and BRCA2 testing by unaffected women at risk, and of prophylactic surgery by unaffected women with the mutation. Young women with children especially opt for DNA testing and prophylactic mastectomy.

Adult↗
PubMed2000

Decoupled evolution of coding region and mRNA expression patterns after gene duplication: implications for the neutralist-selectionist debate.

The neutralist perspective on molecular evolution maintains that the vast majority of mutations affecting gene function are neutral or deleterious. After a gene duplication where both genes are retained, it predicts that original and duplicate genes diverge at clock-like rates. This prediction is usually tested for coding sequences, but can also be applied to another important aspect of gene function, the genes' expression pattern. Moreover, if both sequence and expression pattern diverge at clock-like rates, a correlation between divergence in sequence and divergence in expression patterns is expected. Duplicate gene pairs with more highly diverged sequences should also show more highly diverged expression patterns. This prediction is tested for a large sample of duplicated genes in the yeast Saccharomyces cerevisiae, using both genome sequence and microarray expression data. Only a weak correlation is observed, suggesting that coding sequence and mRNA expression patterns of duplicate gene pairs evolve independently and at vastly different rates. Implications of this finding for the neutralist-selectionist debate are discussed.

Biological Evolution↗
PubMed2000

Rapid antiviral effect of inhaled zanamivir in the treatment of naturally occurring influenza in otherwise healthy adults.

The antiviral and clinical effects of inhaled zanamivir (10 mg twice daily for 5 days, started within the first or second day of a flulike illness) were evaluated in a randomized, placebo-controlled trial during the 1997-1998 influenza season in Canada. Pharyngeal secretions were collected with swabs every 12 h during 6 days, and symptoms were self-evaluated twice daily during 14 days. After only 12 h of treatment (1 dose), median virus titers decreased by 1.0 log10 TCID50/mL in the zanamivir group (n=17), compared with a 0. 42-log10 increase in the placebo group (n=10; P=.08). This was associated with a 4.5-day (47.4%) reduction in the median time to alleviation of all significant flu symptoms in the zanamivir recipients (P=.03 after adjusting for the initial virus titer and the time between onset of symptoms and treatment). Resistance to zanamivir was not detected in virus isolates by either phenotypic or genotypic assays.

Administration, Inhalation↗
PubMed2000

Correlation between raised body temperature and acute mountain sickness score at moderate altitude.

UNLABELLED: In high altitude mountaineering, a rise in body temperature has long been associated with acute mountain sickness. No data exist on the situation at moderate altitudes in the Austrian Alps. The objective of this study was to investigate a potential relationship between an increase in body temperature and acute mountain sickness (AMS) and hypoxemia at moderate altitude. Body temperature and arterial oxygen saturation (SaO2) were measured in 40 alpinists at 1000 m altitude and after ascent to 3100 m altitude, and the AMS score was measured at 3100 m altitude. At 3100 m altitude, 3 alpinists with AMS (score 3) experienced a 0.87 +/- 0.12 degree C rise in body temperature and a 10.67 +/- 1.15% reduction in SaO2. In 8 moderately affected alpinists, temperature increased by 0.49 +/- 0.16 degree C and SaO2 was reduced by 6.75 +/- 1.75%. In 29 alpinists without signs of AMS, temperature did not change (difference 0.02 +/- 0.14 degree C) and SaO2 decreased by 4.59 +/- 0.82%. The difference between temperatures at the two altitudes correlated significantly with the SaO2 difference between the two altitudes (rs = 0.408, p < 0.01) and with the AMS scores (rs = 0.814, p < 0.01). CONCLUSION: Comparable with maximal forms of AMS at high altitude, our data provide reason to speculate that systemic inflammatory disease could also be causal in less severe forms of acute mountain sickness. Therefore, in cases of fever at moderate altitude, the differential diagnosis must include acute mountain sickness.

Acute Disease↗
PubMed2000

[Dilatation tracheotomy after Ciglia--its use in an internal-medicine intensive care unit].

BACKGROUND AND OBJECTIVE: Since the first description of percutaneous dilatation tracheostomy (DTT), it has become an alternative method of equal value to surgical tracheostomy. This study collected the experience with DTT in a medical intensive care unit (ICU), with special reference to early and late complications and their management, outcome, and changes in ventilation parameters and blood gases. PATIENTS AND METHODS: Between March 1994 and April 1998, 74 DTTs were performed on 71 patients (52 men, 19 women; mean age 61.8 [30-80]) years. The admission or main diagnoses were cardiovascular disease in 34 patients, pulmonary disease in 21, the remainder having had a variety of conditions. RESULTS: The procedure caused complications in 21 procedures (28%): 10 cases of stomal bleeding (13.5% of total number of procedures), 2 of intratracheal bleeding (2.7%), 2 of severe tracheal injury (2.7%) and mediastinal emphysema in 1 (1.3%). None required intervention because of these complications. 38 patients were discharged from hospital. Cause of death in the other 33 was unrelated to the DTT. One patient developed tracheomalacia as a late complication. Ventilatory parameters and blood gases 12 hours post-DTT were the same as before the procedure. CONCLUSIONS: Ciaglia's method of dilatation tracheostomy is a safe procedure also in the context of a medical ICU, if the indications are correct and the procedure performed by experienced personnel. Compared with surgical tracheostomy it significantly reduces the burden on the patient as well as requiring fewer personnel and less equipment.

Adult↗
PubMed2000

Determination of liposome size distribution by flow cytometry.

BACKGROUND: An essential parameter that describes the quality of liposome suspensions is the mean size, respectively the size distribution. Currently several analytical methods including laser light scattering techniques (LLST) are being employed. METHODS: Here we present an alternative technique using flow cytometry (FCM) to characterize uni- and polydisperse suspensions. As model liposomes preparations containing dipalmitoylphosphatidylcholine (DPPC) were used. A constant number of particles (1,500/s) in the fluid stream and a representative number of 10,000 particles of each sample was measured. Fluorescence-labeled latex beads were measured identically, and their side scatter signals were calibrated and correlated to the results obtained with liposome vesicles. RESULTS: Evaluation of the measurement and validation of the FCM results in comparison to LLST confirm the reliability of results obtained with our method. Latex beads in the range of 100-1000 nm were used for calibration to classify liposomes. Although measurement characteristics and calculation in both methods are basically different, very good agreement of the results was achieved. CONCLUSIONS: Demonstration of stability, reproducibility, and reliability of results make the employment of this method acceptable for an adequate routine analysis technique.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

[Telenavigation and expert consultation using a stereotaxic surgical videoserver].

The exponential increase of medical information creates a need for new methods in the visualization of medical imaging modalities for diagnosis and therapy. In this sense, visualization includes the display of medical image data and image-guided stereotaxic navigation as well as the advice of an expert. The Artma Virtual Patient System enables a remote expert to observe the surgical procedure via the Internet and interactively modify the interoperative visualization from the remote location. The expert in the remote location receives the planning data almost in real time over TCP/IP from a stereotaxic videoserver. In addition to live video streaming, stereotaxic navigation data are sent over the network as rigid body coordinates. The expert modifies the surgical simulation on the remote computer and the modified operating plan is sent back to the operating site. By teleconsulting, the composite images and overlapping graphics--instruments, target structures, landmarks, contour--can be seen in affiliated clinics with the possibility of interactive graphical assistance. With this image fusion technology the knowledge of a remote expert is included in virtual data structures and visualized by the overlay with live video data (augmented reality) in real time during surgery.

Humans↗
PubMed2000

[Hallervorden-Spatz disease: findings in the nigrostriatal system].

Hallervorden-Spatz disease (HSD), a rare extrapyramidal motor illness, is usually only confirmed after death. In vivo diagnosis has relied hitherto on the combination of typical magnetic resonance imaging (MRI) findings (the "eye of the tiger" sign) and heterogeneous clinical symptoms of movement disorder which have been regarded as almost pathognomonic. We report on the diagnostic contribution of 123J-beta-CIT single photon emission computed tomography (SPECT) and 123J-IBZM SPECT in akinetic-rigid Parkinson's syndrome occurring in a case of HSD. In contrast to Parkinson's disease and multisystem atrophies, the results of both tests were normal. This constellation of findings shows that the degeneration lies primarily outside the nigrostriatal system, supporting arguments for the nosologic distinction of HSD from other extrapyramidal illnesses.

Adolescent↗
PubMed2000

[Clinical and fine motor therapy assessment in Wilson disease].

At the time of diagnosis and after therapy, we examined 33 patients suffering from Wilson's disease. We applied a standardized diagnostic score system on the basis of clinical signs. Without observing any differences between pseudoparkinsonian and pseudosclerosis subtypes, patients with neurological symptoms significantly improved by 2.33 points. Patients with initially more severe symptoms showed the same improvement as less affected patients. Fine motor disturbances were evaluated using the V-scope system. Finger tapping and drawing a spiral were compared to values of a healthy control group (n = 52). Patients with neurological symptoms showed significantly decreased frequencies in both tests. The clinical score was related to frequencies in finger tapping but not in drawing a spiral. Therefore finger tapping can be used as an objective diagnostic tool to evaluate the severity of Wilson's disease, while spiral testing appears to be a sensitive screening tool.

Adult↗
PubMed2000

Angioma serpiginosum with extensive cutaneous involvement.

Angioma serpiginosum is a rare condition that involves both the proliferation and dilatation of superficial blood vessels in the skin. It classically begins in childhood, is more common in females, and is asymptomatic. Typical lesions appear on the extremities and are often asymmetric. We report a case of angioma serpiginosum involving extensive areas of the extremities and the trunk to emphasize that extensive cutaneous involvement must be included in the clinical spectrum of this condition.

Adult↗
PubMed2000

The North-East-South gradient of coronary heart disease mortality and case fatality rates in France is consistent with a similar gradient in risk factor clusters.

In France, the mortality and case fatality rates of coronary heart disease follow a decreasing North-East-South gradient. The aim of the study was to evaluate the contribution of major cardiovascular risk factors to this gradient. To this end, the results of the third population survey of the WHO-MONICA Project conducted in three French geographically contrasted regions (the Urban Community of Lille in the North, the district of Bas-Rhin in the East and the district of Haute-Garonne in the South) are presented. One thousand seven hundred seventy-eight men and 1730 women aged 35-64 years were randomly selected from the electoral rolls. Major coronary heart disease risk factors (hypertension, hypercholesterolemia, low high-density lipoprotein (HDL)-cholesterol, obesity, smoking, physical inactivity, diabetes) were studied. The results show that the distribution of major coronary heart disease risk factors is heterogeneous among geographical areas in France. However, the proportion of subjects with more than three risk factors is higher in the North than in the other regions and the number of subjects with no risk factor is higher in the South than in the other areas. This distribution of risk factors among regions supports the hypothesis that accumulation of coronary heart disease risk factors contributes to the decreasing North-East-South gradient of cardiovascular mortality rates in France.

Adult↗
PubMed2000

Robustness against mutations in genetic networks of yeast.

There are two principal mechanisms that are responsible for the ability of an organism's physiological and developmental processes to compensate for mutations. In the first, genes have overlapping functions, and loss-of-function mutations in one gene will have little phenotypic effect if there are one or more additional genes with similar functions. The second mechanism has its origin in interactions between genes with unrelated functions, and has been documented in metabolic and regulatory gene networks. Here I analyse, on a genome-wide scale, which of these mechanisms of robustness against mutations is more prevalent. I used functional genomics data from the yeast Saccharomyces cerevisiae to test hypotheses related to the following: if gene duplications are mostly responsible for robustness, then a correlation is expected between the similarity of two duplicated genes and the effect of mutations in one of these genes. My results demonstrate that interactions among unrelated genes are the major cause of robustness against mutations. This type of robustness is probably an evolved response of genetic networks to stabilizing selection.

Computational Biology↗
PubMed2000

Assessing individual outcomes during outpatient multidisciplinary chronic pain treatment by means of an augmented SF-36.

OBJECTIVE: To meet the growing demand for objective outcomes measurement during treatment of chronic pain, we developed an instrument to track outcomes of individual patients. METHOD: In a 2-phase study, existing and novel outcomes instruments were applied in an interdisciplinary pain management program. In the initial phase, 408 patients were administered the Short Form 36-item questionnaire and during phase 2, 437 patients (87 of whom were followed) were given an expanded (191-item) questionnaire. RESULTS: When applied to individual patients, the Short Form 26-item questionnaire lacked measurement reliability for assessment of treatment outcomes and sensitivity to upper extremity or facial pathology, and failed to separate limitations of work versus everyday activity. A novel group of scales derived from responses to 61 questions, including the Short Form 36-item questionnaire, proved sufficiently reliable for routine follow-up of individual chronic pain patients. CONCLUSIONS: This new Treatment Outcomes in Pain Survey allows assessment of individual patient outcomes, and aggregate or individual clinician performance, during interdisciplinary treatment of chronic pain.

Journal Article↗
PubMed2000

Neurologic complications of cerebral angiography. A retrospective study of complication rate and patient risk factors.

PURPOSE: To evaluate the neurologic complication rate and individual patient risk factors in cerebral angiographies using the digital subtraction angiography (DSA) technique and non-ionic contrast media in a department with many radiologists in training. MATERIAL AND METHODS: A retrospective study of 483 cerebral angiographic examinations in 454 patients was carried out. The following parameters were registered: sex and age of the patient, indication for the angiography, cerebral CT diagnosis, laboratory data, type of anesthesia, type of angiographic procedure, level of training of the angiographer, number of participating angiographers, type of catheters, number of vessels catheterized, number of exposures, use of compression series, total amount of contrast media, diagnosis of the angiogram, complications and duration of complications. RESULTS: The frequency of all neurologic complications was 2.3%, the frequency of persistent neurologic deficits was 0.4%. Non-neurologic complications were observed in 14.7% of the examinations. Of all the parameters studied, the only factor that significantly increased neurologic risk was a normal angiogram, a finding we are inclined to ascribe to chance. Performance of a compression series showed a trend towards increasing the neurologic risk. CONCLUSION: This study showed a complication rate of persistent neurologic deficits of 0.4% which is in accordance with other recent reports. A compression series should not be performed routinely, but only on special indication. This study confirms the low risk of cerebral angiography when performed in a neuroradiological department using the DSA technique and non-ionic contrast media.

Adolescent↗
PubMed2000

The role of population size, pleiotropy and fitness effects of mutations in the evolution of overlapping gene functions.

Sheltered from deleterious mutations, genes with overlapping or partially redundant functions may be important sources of novel gene functions. While most partially redundant genes originated in gene duplications, it is much less clear why genes with overlapping functions have been retained, in some cases for hundreds of millions of years. A case in point is the many partially redundant genes in vertebrates, the result of ancient gene duplications in primitive chordates. Their persistence and ubiquity become surprising when it is considered that duplicate and original genes often diversify very rapidly, especially if the action of natural selection is involved. Are overlapping gene functions perhaps maintained because of their protective role against otherwise deleterious mutations? There are two principal objections against this hypothesis, which are the main subject of this article. First, because overlapping gene functions are maintained in populations by a slow process of "second order" selection, population sizes need to be very high for this process to be effective. It is shown that even in small populations, pleiotropic mutations that affect more than one of a gene's functions simultaneously can slow the mutational decay of functional overlap after a gene duplication by orders of magnitude. Furthermore, brief and transient increases in population size may be sufficient to maintain functional overlap. The second objection regards the fact that most naturally occurring mutations may have much weaker fitness effects than the rather drastic "knock-out" mutations that lead to detection of partially redundant functions. Given weak fitness effects of most mutations, is selection for the buffering effect of functional overlap strong enough to compensate for the diversifying force exerted by mutations? It is shown that the extent of functional overlap maintained in a population is not only independent of the mutation rate, but also independent of the average fitness effects of mutation. These results are discussed with respect to experimental evidence on redundant genes in organismal development.

Animals↗