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Biomedical subjects

P Werner

Publications and source records attributed to P Werner.

At least 19 recordsLinked to original sources

Distal myasthenia gravis frequency and clinical course in a large prospective series.

OBJECTIVES: In Myasthenia gravis (MG) proximal limb, ocular and/or bulbar muscles are most commonly affected, whereas distal extremity muscles are typically spared. The aim of the current study was to assess the frequency of primarily distal MG in the Tyrol and to describe its clinical peculiarities. MATERIAL AND METHODS: Over the past 20 years 84 patients with MG have undergone follow-up at the Department of Neurology of Innsbruck University. Types of presentation, clinical course and treatment response were followed over a period of 20 years (1980-2000). RESULTS: Six of 84 MG patients showed a predominance of muscle weakness and fatigability in distal limb muscles (two at presentation, four over the later course of the illness). There was no difference between distal MG and MG with a more typical distribution of muscle weakness regarding age, gender and response to therapy. CONCLUSIONS: The case series indicates that predominantly distal presentations of otherwise typical MG are more frequent than generally assumed and should be considered in the differential diagnosis of diseases with distal limb weakness.

Adult↗

Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy.

BACKGROUND: White matter vacuolization of the spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B(12) deficiency suggests that abnormal metabolism of the B(12)-dependent transmethylation pathway may be important in the pathogenesis of AM. METHODS: The authors compared S-adenosyl-methionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs. 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV--infected reference population (NC). All patients had normal B(12), folate, and methylmalonic acid levels. RESULTS: There was a decrease in CSF SAM in the AM group compared with the HWM group (p < 0.0001) and the NC group (p < 0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p = 0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p = 0.006). CONCLUSIONS: AM is associated with an abnormality of the vitamin B(12)-dependent transmethylation pathway.

Adult↗

Vertex corrections near the stripe phase.

We calculate the vertex corrections within a model for fermion quasiparticles coupled with charge and spin fluctuations, which provide the relevant scattering mechanism near the stripe instability in high- T(c) cuprates. The logarithmic divergence of the vertex, which characterizes the spin-fermion model near the antiferromagnetic instability, is ruled out, due to the incommensuration of the charge and spin modulation within the stripe phase, as revealed by neutron scattering. This simplifies the skeleton structure of the problem. The vertex is negative in the relevant kinematical regime, effectively reducing the interaction strength. Our results apply to generic incommensurate instabilities of electronic origin.

Journal Article↗

The diagnosis of osteoporosis: attitudes and knowledge of Israeli physicians.

BACKGROUND AND AIMS: Osteoporosis is the most common human bone disease. Although proper diagnosis may minimize injury and disability, this depends to a great extent on the knowledge and attitudes of physicians. The aim of the present study was to assess physicians' attitudes, knowledge and practice regarding the diagnosis of osteoporosis. METHODS: A questionnaire was mailed to 1900 Israeli physicians addressing their knowledge and attitudes about osteoporosis and its diagnosis, and their perceptions regarding the cost-effectiveness of different diagnostic methods. RESULTS: Answers were received from 19% of the physicians. The majority of the respondents supported screening for osteoporosis, especially in high-risk women. Overall, the participants had good knowledge about the definition of osteoporosis and its risk factors, but poor knowledge about its prevalence. Female physicians had better knowledge and stronger attitudes than male physicians. Similarly, younger and less experienced physicians showed better knowledge. The majority of the participants reported being familiar with, and using all types of clinical methods. They also perceived these methods as highly cost-effective. CONCLUSIONS: Findings of the present study stress the need to extend the knowledge of physicians regarding diagnosis of osteoporosis and the research aimed at understanding their attitudes.

Adult↗

Women's willingness to pay out-of-pocket for drug treatment for osteoporosis before and after the enactment of regulations providing public funding: evidence from a natural experiment in Israel.

This study examines women's willingness to pay (WTP) for drug treatment for osteoporosis before and after the enactment of regulations approving public funding for the drugs and for a hypothetical more effective but not funded drug. One hundred and nine postmenopausal women recruited sequentially from a large bone metabolism outpatient clinic in central Israel were asked by telephone interview to report their maximum WTP out-of-pocket for a drug that would reduce the risk of hip fracture by 50% in four hypothetical cases varying by the level of risk described. Additionally, after the regulations, responses were elicited also for a hypothetical more effective drug. Information regarding participants' sociodemographic and health characteristics, as well as their knowledge of osteoporosis, was also collected. Women would pay considerable sums of money (between 85% to 124% of the price of the drugs) for osteoporosis treatment and these sums increase significantly as the risk of suffering a hip fracture increases. After the enactment of the regulations, women were still willing to pay 54% to 100% of the price of the drugs out-of-pocket. Increased WTP after the regulations was associated with increased ability to pay and to lower levels of knowledge of the disease. After the enactment, participants' WTP for a more effective drug was no different from their WTP for a less effective drug. WTP measures show relative stability over time. The dissemination of information regarding policy or regulatory changes should be encouraged in order to ensure rational decision-making processes.

Aged↗

Sleeping metabolic rate in relation to body mass index and body composition.

OBJECTIVES: To determine whether patterns of sleeping metabolic rate (SMR) are altered in obesity. Specifically to determine the relationship between changes in SMR and body weight, body mass index (BMI, kg/m(2)), and fat-free mass (FFM); and to compare resting metabolic rate (RMR) with SMR during different periods of sleep. SUBJECTS: Eighteen healthy, pre-menopausal, obese (BMI >30, n=9) and non-obese (BMI <30, n=9), female subjects (six Caucasians and 12 African-Americans), with an average age of 36 y (range 22-45). MEASUREMENTS: Total energy expenditure (TEE or 24 h EE), metabolic rate (MR), SMR (minimum, average and maximum) and resting metabolic rate (RMR) or resting energy expenditure (REE) measured by human respiratory chamber, and external mechanical work measured by a force platform within the respiratory chamber. Physical activity index (PAL) was derived as TEE/REE. Body composition was determined by dual-energy X-ray absorptiometry (DXA). RESULTS: SMR decreased continuously during sleep and reached its lowest point just before the subject was awakened in the morning by the research staff. Although averages for RMR and SMR were similar, RMR was lower than SMR at the beginning of the sleeping period and higher than SMR in the morning hours. The rate of decrease in SMR was faster with increasing body weight (-0.829, P<0.0001), BMI (correlation factor -0.896, P<0.0001) and FFM (-0.798, P=0.001). The relationship between the slope of SMR decrease and BMI (y=-5 x 10(-6)x(2)+0.0002x-0.0028) is highly significant, with a P-value of <0.0001 and r(2) value of 0.9622. CONCLUSIONS: The rate of decline in metabolic rate during sleep is directly related to body weight, BMI and FFM. Average SMR tends to be lower than RMR in obese subjects and higher than RMR in non-obese subjects.

Absorptiometry, Photon↗

Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the oxidative inactivation of calcineurin.

Approximately 10% of all familial cases of amyotrophic lateral sclerosis (fALS) are linked to mutations in the SOD1 gene, which encodes the copper/zinc superoxide dismutase (CuZnSOD). Recently, wild-type CuZnSOD was shown to protect calcineurin, a calcium/calmodulin-regulated phosphoprotein phosphatase, from inactivation by reactive oxygen species. We asked whether the protective effect of CuZnSOD on calcineurin is affected by mutations associated with fALS. For this, we monitored calcineurin activity in the presence of mutant and wild-type SOD. We found that the degree of protection against inactivation of calcineurin by different SOD mutants correlates with the severity of the phenotype associated with the different mutations, suggesting a potential role for calcineurin-SOD1 interaction in the etiology of fALS.

Amyotrophic Lateral Sclerosis↗

COMT-dependent protection of dopaminergic neurons by methionine, dimethionine and S-adenosylmethionine (SAM) against L-dopa toxicity in vitro.

L-dopa may be toxic to dopamine neurons, possibly due to catechol-autoxidation. Catechols are O-methylated by catechol-O-methyltransferase (COMT) in a SAM consuming reaction, preventing the initiation of catechol autoxidation. We hypothesized that SAM or SAM-precursors ameliorate L-dopa neurotoxicity, in a COMT-dependent fashion. We tested this hypothesis in primary mesencephalic cultures by adding 200 microM L-dopa with 2 mM methionine or 1 mM dimethionine or 0.5 mM SAM with or without 0.2 microM of the COMT-inhibitor 2', 5'-dinitrocatechol (OR 486). L-dopa was found to be neurotoxic as the surviving neurons had fewer and shorter processes. Methionine, dimethionine and SAM all protected DA neurons against damaged induced by L-dopa. The COMT inhibitor dinitrocatechol (DNC) completely abolished the protective effect against L-dopa toxicity. We conclude that supplementation with methionine, dimethionine or SAM ameliorates L-dopa neurotoxicity to dopamine neurons, while inhibition of COMT may aggravate or unmask L-dopa neurotoxicity.

Animals↗

Correlates of family caregivers' knowledge about Alzheimer's disease.

OBJECTIVE: The aim of the present study was to assess family caregivers' level of knowledge about Alzheimer's disease and its correlates. DESIGN, SETTING AND PARTICIPANTS: Two hundred and twenty informal caregivers of an elderly person suffering from Alzheimer's disease were recruited from four large memory clinics across the country and interviewed by trained research assistants. MEASURES: Knowledge of the disease was assessed using a questionnaire including 17 items examining general knowledge, symptoms, treatment and services. Independent variables included caregivers' socio-demographic characteristics, patients' clinical characteristics and characteristics of the caregiving situation. RESULTS: Overall, low levels of knowledge were found, especially in items related to the prevalence, causes and symptoms of the disease. Low education and being a spouse were the most important vulnerability factors associated with poor knowledge. CONCLUSIONS: Further research on the correlates of caregivers' knowledge about AD should be promoted in order to allow better decision-making processes and better matching of the needs of caregivers and intervention programs.

Aged↗

Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage.

Glutamate excitotoxicity, recently demonstrated in an animal model of multiple sclerosis (MS), is evoked by altered glutamate homeostasis. In the present study, we investigated the major regulating factors in glutamate excitotoxicity by immunohistochemistry in MS and control white matter with markers for glutamate production (glutaminase), glutamate transport (GLAST, GLT-1 and EAAT-1), glutamate metabolism (glutamate dehydrogenase [GDH] and glutamine synthetase [GS]), axonal damage (SMI 32) and CNS cell types. Active MS lesions showed high-level glutaminase expression in macrophages and microglia in close proximity to dystrophic axons. Correlation between glutaminase expression and axonal damage was confirmed experimentally in animals. White matter from other inflammatory neurologic diseases displayed glutaminase reactivity, whereas normals and noninflammatory conditions showed none. All three glutamate transporters were expressed robustly, mainly on oligodendrocytes, in normal, control and MS white matter, except for GLT-1, which showed low-level expression around active MS lesions. GS and GDH were present in oligodendrocytes in normal and non-MS white matter but were absent from both active and chronic silent MS lesions, suggesting lasting metabolic impediments. Thus, imbalanced glutamate homeostasis contributes to axonal and oligodendroglial pathology in MS. Manipulation of this imbalance may have therapeutic import.

Adult↗

[Interference between a dual-chamber pacemaker and argon electrocautery device during hepatectomy].

We report an unusual electromagnetic interference induced by an argon electrocautery device during a left hepatectomy on a dual chamber pacemaker, implanted for sinus node dysfunction in 87-year-old patient. Argon electrocautery induced inhibition of atrial stimulation and occurrence of irregular ventricular triggered activity. Normal pacemaker function resumed after electrocautery interruption. This case illustrates the need to focus on cardiac rhythm when a new electrical device is used in a pacemaker patient.

Aged↗

cDNA cloning and physical mapping of porcine 3 beta-hydroxysteroid dehydrogenase/Delta 5-Delta 4 isomerase.

The 3 beta-hydroxysteroid dehydrogenase/Delta 5-Delta 4-isomerase (3 beta-HSD) enzymes are essential for the biosynthesis of steroid hormones. The 3 beta-HSD gene family has been reported to encode for different isoenzymes which function either as dehydrogenase/isomerase or as reductase. The 3 beta-HSD enzymes are involved in the formation of the pheromone androstenone (5 alpha-androst-16-ene-3-one) which contributes to the unpleasant odour present in the meat of uncastrated boars. An reverse-transcription-polymerase chain reaction (RT-PCR) probe from porcine testicular tissue of a 3 beta-HSD enzyme was used to screen a porcine adipose tissue cDNA library. Both strands of the positive clones were sequenced and the putative coding sequence of 1122 nucleotides encodes 374 amino acids. Comparison of the putative open reading frame with the bovine and the human type I homologues revealed 85.6 and 79.3% identity, respectively. Fluorescence in situ hybridization (FISH) was performed with a labelled PAC clone containing the gene of interest. The 3 beta-HSD gene was mapped to the porcine chromosome 4q16-4q21 which is in accordance with the comparative gene map.

Amino Acid Sequence↗

Nursing staff members' intentions to use physical restraints with older people: testing the theory of reasoned action.

AIM OF THE STUDY: To examine nursing staff members' attitudes, subjective norms, moral obligations and intentions to use physical restraints, using the Theory of Reasoned Action (TRA). RATIONALE: During the last two decades an extensive body of research has examined nurses' attitudes as one of the main factors affecting the decision to use or not to use physical restraints with older persons. However, no studies have examined empirically the antecedents to nurses' intentions to use physical restraints within a theoretically based framework. METHOD: A correlational design was used with 303 nursing staff members from an 800-bed elder care hospital in central Israel. Participants completed a questionnaire including questions based on the TRA as well as socio-demographic and professional characteristics. RESULTS: Regression analyses found attitudes, subjective norms and moral considerations to be significantly associated to intention to use physical restraints with older people. The TRA explained 48% of the variance in nurses' intentions. CONCLUSIONS: The TRA proved to be a useful framework for examining nurses' intentions to use physical restraints. Nurses' attitudes, beliefs and expectations of significant others should be examined before implementing educational programmes regarding the use of physical restraints.

Adult↗

[Humboldt as mediator: Schleiden and Mohl contra Liebig].

Justus Liebig's book Die organische Chemic in ihrer Anwendung auf Agricultur und Physiologie aroused strong opposition from scientists who felt that they were being attacked. A polarization arose particularly between Hugo von Mohl (1805-1872) and Matthias Jacob Schleiden (1805-1881) on one side, and Justus von Liebig (1803-1873) and his followers on the other side. The debate did not have the character of a purely scientific controversy, however, because social aspects also played a role. Alexander von Humboldt (1769-1859), who held the esteem of both parties, was able to intervene successfully to mediate this conflict. His task appeared at first difficult, but it turned out that both groups had a common enemy, the representatives and followers of the 'Romantic philosophy of nature'. Humboldt, who self-deprecatingly called himself a 'fossil', was forced to recognize that many of his friends and acquaintances, who stood nearer to, or even belonged among the founders of Naturphilosophie, for example, Friedrich Wilhelm Joseph von Schelling (1775-1854) and Johann Bernhard Wilbrand (1779-1846), were also under attack. Although he had earlier been inspired by the concerns and ideas of Schelling's Naturphilosophie, he now distanced himself from them in order to mediate between modern, experimental scientists.

Biological Science Disciplines↗

Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro.

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of Alzheimer's disease, although the underlying mechanisms are unknown. Glutamate excitotoxicity has been implicated in Alzheimer's disease, Parkinson's disease, and others. We examined the effects of aspirin, acetaminophen, and ibuprofen on cultured primary rat embryonic neurons from mesencephalon, the area primarily affected in Parkinson's disease. We evaluated whether these drugs protect dopaminergic neurons against excitotoxicity. All three NSAIDs significantly attenuated the decrease in dopamine uptake caused by glutamate, indicating preservation of neuronal integrity. One hundred micro-moles ibuprofen protected both dopaminergic neurons and neurons overall against glutamate toxicity. In addition, ibuprofen alone increased the relative number of dopaminergic neurons by 47%. Thus, NSAIDs protected neurons against glutamate excitotoxicity in vitro, and deserve further consideration as neuroprotective agents in Parkinson's disease.

Acetaminophen↗

AIDS myelopathy is not associated with elevated HIV viral load in cerebrospinal fluid.

The pathogenesis of AIDS-associated myelopathy is unknown. Elevated HIV-1 viral load in CSF has been associated with cognitive impairment. The authors investigated if a similar association exists in patients with myelopathy. The authors evaluated levels of HIV-1 RNA in the CSF of 16 individuals with AIDS myelopathy and in 16 nonmyelopathic HIV-infected control subjects. There was no correlation between levels of HIV-1 RNA and the presence or severity of myelopathy.

Acquired Immunodeficiency Syndrome↗