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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 19 recordsLinked to original sources
PubMed1999

Motor system abnormalities in heterozygous relatives of a D90A homozygous CuZn-SOD ALS patient of finnish extraction.

Presently, 64 mutations in the gene encoding the enzyme CuZn-superoxide dismutase have been found in a small fraction of amyotrophic lateral sclerosis patients worldwide. All but one of these mutations show autosomal dominant inheritance. In Scandinavia, the D90A mutation is inherited as an autosomal recessive trait and patients have an easily recognizable characteristic phenotype with little variation among patients, even amongst different families. Importantly, all D90A heterozygous relatives of Scandinavian D90A homozygous patients have been reported as clinically unaffected. We have investigated a Canadian family of Finnish extraction in which the D90A homozygous proband developed ALS with the characteristic phenotype. Remarkably, two D90A heterozygous relatives show slight symptoms and signs of motor system involvement, suggesting that the final phenotype of an individual with a CuZn-superoxide dismutase mutation is shaped by the combination of the particular CuZn-SOD mutation, other polymorphic modifying genes elsewhere in the genome, stochastics and possible environmental factors.

Aged↗
PubMed1999

Differential effects of lipopolysaccharide and tumor necrosis factor on monocytic IkappaB kinase signalsome activation and IkappaB proteolysis.

The inflammatory mediators lipopolysaccharide (LPS) and tumor necrosis factor (TNF) are potent activators of NF-kappaB. This study compared the effect of these stimuli on endogenous IkappaB kinase (IKK) signalsome activation and IkappaB phosphorylation/proteolysis in human monocytic cells and investigated the role of the signalsome proteins IKK-alpha, IKK-beta, NF-kappaB-inducing kinase (NIK), IKK-gamma (NF-kappaB essential modulator), and IKK complex-associated protein. Kinase assays showed that TNF elicited a rapid but short-lived induction of IKK activity with a 3-fold greater effect on IKK-alpha than on IKK-beta, peaking at 5 min. In contrast, LPS predominantly stimulated IKK-beta activity, which slowly increased, peaking at 30 min. A second peak was observed at a later time point following LPS stimulation, which consisted of both IKK-alpha and -beta activity. The endogenous levels of the signalsome components were unaffected by stimulation. Furthermore, our studies showed association of the IKK-alpha/beta heterodimer with NIK, IkappaB-alpha and -epsilon in unstimulated cells. Exposure to LPS or TNF led to differential patterns of IkappaB-alpha and IkappaB-epsilon disappearance from and reassembly with the signalsome, whereas IKK-alpha, IKK-beta, and NIK remained complex-associated. NIK cannot phosphorylate IkappaB-alpha directly, but it appears to be a functionally important subunit, because mutated NIK inhibited stimulus-induced kappaB-dependent transcription more effectively than mutated IKK-alpha or -beta. Overexpression of IKK complex-associated protein inhibited stimulus-mediated transcription, whereas NF-kappaB essential modulator enhanced it. The understanding of LPS- and TNF-induced signaling may allow the development of specific strategies to treat sepsis-associated disease.

Enzyme Activation↗
PubMed1999

[Breaking of bad news. Practical advice to physicians for successful communication with patients].

BACKGROUND: In the more and more complex world of modern medicine, communication skills become increasingly important. Many physicians are however unaware of their difficulties in giving information in a clear and comprehensible way. This is especially true for breaking bad news. Keys for good communication consist in: careful preparation of the physical context of the interview; finding out how much the patient knows or suspects; giving the information in small amounts and a balanced way; responding to the patient's feelings and finally making a contract for the future.

Communication Barriers↗
PubMed1999

Guidelines for assessing outcomes of antihypertensive treatment.

Because of the changing nature of medical practice and the need to more accurately monitor and quantify the clinical benefits and cost-effectiveness of treatment, the Sixth Report of the Joint National Committee (JNC VI) recommends that the outcomes of antihypertensive therapy be classified as short, intermediate, and long term. Short-term outcomes are most relevant to the practitioner and include such measures as blood pressure control, laboratory changes, and quality of life. In contrast, long-term outcomes, typically measured in randomized clinical trials, are of particular interest to policy makers and guidelines writers, and focus on whether treatments affect survival and the incidence of major cardiovascular events. Intermediate-term outcomes, usually measurable within months of starting treatment, deal with such clinical surrogates as treatment-induced changes in left ventricular structure, arterial compliance, and renal function. No longer are the traditional short-term outcomes adequate to describe a new drug; hypertension specialists, formulary committees, healthcare economists, and even regulatory agencies now expect sponsors to plan studies that define a drug's full range of outcomes. This article briefly discusses some of the criteria for these outcome measures.

Angiotensin Receptor Antagonists↗
PubMed1999

Feasibility and efficacy of routine PCR screening of blood donations for hepatitis C virus, hepatitis B virus, and HIV-1 in a blood-bank setting.

BACKGROUND: Despite sensitive antibody-based blood-donor screening, a residual risk of transfusion-transmitted viral infections exists. Only direct monitoring by sensitive nucleic-acid tests would provide data accurately to measure the risk and to assess risk-reduction procedures. We investigated the feasibility and efficacy of routine screening of donors for hepatitis C virus (HCV), hepatitis B virus (HBV), and HIV-1 by PCR. METHODS: For PCR testing, individual donor plasma samples were pooled (96x100 microL) overnight by two automatic pipetting machines. Viruses were concentrated by centrifugation and nucleic acids were extracted. HCV PCR was done on the Cobas Amplicor system (Hoffmann-La Roche, Mannheim, Germany). HBV and HIV-1 sequences were amplified by single (non-nested) in-house PCRs and detected by agarose-gel electrophoresis. Detection limits were 1000-5000 genome equivalents/mL in the donor blood. FINDINGS: PCR testing was done in parallel to antibody screening with a maximum throughput of 3000 samples in 7-8 h. Positive samples were identified 1-2 days later. 111 of 373,423 donations (107 of 4500 pools) were PCR and antibody/antigen-confirmed positive. We found one HCV PCR-positive antibody-negative donation with normal alanine aminotransferase and one HCV PCR-positive donation with an elevated alanine aminotransferase (100 IU), which was negative in the AxSYM 2.0 and Matrix 1.0, but positive after control in the Abbott Prism test (Abbott GmbH, Wiesbaden, Germany). INTERPRETATION: PCR is a suitable and fast blood-donor screening procedure and contributes to a reduction in viral transmission by transfusion of blood components. In our selected donor population, the yield of detected contaminated donations from donors in the time window in which they are highly infectious but do not have any symptoms or detectable antigen and antibody concentrations (diagnostic window), confirms theoretical estimates.

Blood Banks↗
PubMed1999

[12 basic rules in drug therapy of tumor pain].

Successful pharmacologic treatment of cancer pain is founded upon careful assessment and measurement of pain before and during therapy. Strong opioids should be used timely in accordance to the WHO 3-step analgesic ladder. The oral route should always be favored. Frequent opioid side effects include constipation, temporary nausea and vomiting and are to be treated adequately. Slow release morphine preparations are to be administered every 12 hours. Adjustment of dose follows pain intensity. Immediate release morphine for breakthrough pain should be provided routinely to patients maintained on a 12-hourly regimen of slow release morphine. The appropriate rescue dose will be 1/6 of the total daily morphine dosis. In case of changement of route of administration the relative potency ratio of oral morphine to parenteral morphine is about 3:1. The coadministration of nonopioids is essential for the relief of cancer pain in many cases. Adjuvant drugs may provide pain relief in specific types of pain (e.g. neuropathic pain).

Analgesics↗
PubMed1999

Clinical predictors of hypoxaemia in Gambian children with acute lower respiratory tract infection: prospective cohort study.

OBJECTIVES: To determine clinical correlates and outcome of hypoxaemia in children admitted to hospital with an acute lower respiratory tract infection. DESIGN: Prospective cohort study. SETTING: Paediatric wards of the Royal Victoria Hospital and the hospital of the Medical Research Council's hospital in Banjul, the Gambia. SUBJECTS: 1072 of 42 848 children, aged 2 to 33 months, who were enrolled in a randomised trial of a Haemophilus influenzae type b vaccine in the western region of the Gambia, and who were admitted with an acute lower respiratory tract infection to two of three hospitals. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia, defined as an arterial oxygen saturation <90% recorded by pulse oximetry, and the relation between hypoxaemia and aetiological agents. RESULTS: 1072 children aged 2-33 months were enrolled. Sixty three (5.9%) had an arterial oxygen saturation <90%. A logistic regression model showed that cyanosis, a rapid respiratory rate, grunting, head nodding, an absence of a history of fever, and no spontaneous movement during examination were the best independent predictors of hypoxaemia. The presence of an inability to cry, head nodding, or a respiratory rate >/= 90 breaths/min formed the best predictors of hypoxaemia (sensitivity 70%, specificity 79%). Hypoxaemic children were five times more likely to die than non-hypoxaemic children. The presence of malaria parasitaemia had no effect on the prevalence of hypoxaemia or on its association with respiratory rate. CONCLUSION: In children with an acute lower respiratory tract infection, simple physical signs that require minimal expertise to recognise can be used to determine oxygen therapy and to aid in screening for referral. The association between hypoxaemia and death highlights the need for early recognition of the condition and the potential benefit of treatment.

Acute Disease↗
PubMed1999

Assessment of upper and lower motor neurons in Kennedy's disease: implications for corticomotoneuronal PSTH studies.

We used peristimulus time histograms (PSTHs) to estimate characteristics of the composite excitatory postsynaptic potentials (EPSPs) generated at the anterior horn cell by a descending cortical volley induced by subthreshold transcranial magnetic stimuli in 11 normal subjects, 9 patients with DNA-confirmed Kennedy's disease, and 10 patients with amyotrophic lateral sclerosis (ALS). In Kennedy's disease the mean of the estimated EPSP amplitude (3.5 +/- 1.6 mV), as well as the means of duration (4.1 +/- 1.3 ms) and onset latency (20.4 +/- 2.7 ms) of the primary peak of 35 different motor units were not significantly different from normal subjects, in whom corresponding values of 49 motor units measured 2.9 +/- 1.6 mV (EPSP amplitude), 3.5 +/- 1.4 ms (duration) and 19.3 +/- 2.8 ms (onset latency). In 48 motor units of patients with ALS the mean of the estimated EPSP amplitude, duration, and latency measured 2.7 +/- 1.8 mV, 7.8 +/- 5.7 ms, and 24.0 +/- 6.5 ms, respectively, differing significantly from normal subjects and patients with Kennedy's disease. The normal cortically induced EPSP in Kennedy's disease is very different from the range of EPSP abnormalities in ALS, indicating that lower motor neuron disease per se does not result in an abnormal cortically induced EPSP derived from PSTHs. The normal findings in Kennedy's disease support our previous suggestions that the EPSP abnormalities in ALS are supraspinal in origin.

Adult↗
PubMed1999

Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes.

We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality of this phenomenon and its relevance to autoimmunity, we studied the responses of CD8 T cells from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome: n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encephalitis: n = 1) against viral proteins derived from EBV and another common herpes virus, human cytomegalovirus (CMV). T cell responses against EBV and/or CMV epitopes were frequently observed within CD8 T cells derived from chronic inflammatory lesions, irrespective of their location (knee, eye, brain) and autoimmune features. In most cases, CD8 T cells derived from affected organs yielded stronger anti-viral T cell responses than CD8 T cells derived from patients' PBL, even in chronic inflammatory diseases devoid of autoimmune features or induced by defined bacterial agents. Taken together, these results suggest that the presence of virus-specific T cells within inflamed lesions of patients suffering from autoimmune diseases is a general phenomenon associated with chronic inflammation rather than the initiating cause of the autoimmune process. Since this phenomenon was sometimes associated with long-term T repertoire biases within inflamed lesions, the physiopathological significance of T cell clonal expansions found in a recurrent fashion within chronically inflamed autoimmune lesions should be interpreted with caution.

Adult↗
PubMed1999

[Focus debridement of chronic sequestered talus osteomyelitis by TCNC arthrodesis. A new technique with ring fixateur].

A technique utilizing the Ilizarov ring fixator to stabilize a tibio-calcaneo-naviculo-cuboideal arthrodesis following talus resection is introduced. The advantages of this method will be demonstrated with the help of a case history. The described method permits early weight bearing, while supplying stability and compression of the fusion, thereby avoiding further loss of bone stock, while reducing the risk of thromboembolic complications. The Ilizarov ring fixator construction allows for the combination of the fusion with the correction of a preexisting or ensueing leg length discrepancy.

Adolescent↗
PubMed1999

Spondylodiscitis caused by viridans streptococci: three cases and a review of the literature.

Three cases of spondylodiscitis caused by viridans streptococci were observed within the course of 1 month. Although streptococci have been reported as the third most frequent cause of spondylodiscitis after staphylococci and gram-negative bacteria, alpha-haemolytic streptococci are rarely seen. The three patients presented with symptoms of low back pain; they felt well and did not have a fever or chills. Laboratory examinations revealed inflammation. Further examinations such as scintigraphy, computed tomography or magnetic resonance imaging were done. Bacteriological diagnosis was established by blood cultures in two cases and by needle biopsy of the disco-vertebral space in one. In one patient endocarditis was also documented. Because the prevalence of endocarditis was found to be higher in our cases of spondylodiscitis due to Streptococcus viridans than for other bacteria, the exclusion of this diagnosis must be pursued aggressively. These observations lead us to question if the spectrum of bacteria causing spondylodiscitis is undergoing a change. an aetiological agent could be isolated in 1168 patients (85.4%): in 48% a staphylococcus, in 28% a gram-negative bacterium and in only 10% a streptococcus. There were two cases of viridans streptococci (0.2%). These two cases together with other single case reports [14-22] account for 15 cases of spondylodiscitis due to alpha-haemolytic streptococci. Differentiation of the organisms to the species level was accomplished in six cases: S. mitis (3), S. sanguis (2) and S. anginosus (1). Although a multitude of organisms, bacterial as well as fungal, causing spondylodiscitis has been reported in recent years, almost all were single cases [23-42]. The unusual observation of three cases of spondylodiscitis due to alpha-haemolytic streptococci within 1 month prompted us to review the clinical and laboratory findings and to compare these cases with those caused by Staphylococcus aureus.

Adult↗
PubMed1999

Efficacy and tolerability of tasosartan, a novel angiotensin II receptor blocker: results from a 10-week, double-blind, placebo-controlled, dose-titration study. Tasosartan Investigators Group.

BACKGROUND: Angiotensin II receptor antagonists are selective blockers of the renin-angiotensin system and represent an alternative to angiotensin-converting enzyme inhibitors in the treatment of hypertension. Tasosartan is a newly developed nonpeptide AT1 receptor blocker. METHODS AND RESULTS: In this double-blind, randomized, dose-titration, multicenter trial, tasosartan and placebo were compared in patients with stage I and stage II hypertension. A prequalification washout period (antihypertensive medications withdrawn) and a 2-week qualification period (patients received single-blind placebo) preceded a 10-week, double-blind treatment period. The patients received either 50 mg tasosartan (n = 132) or placebo (n = 130) once per day and were evaluated once per week. The dose of tasosartan was increased at 3-week intervals to 100 mg and then to 200 mg if the mean sitting diastolic blood pressure (SiDBP) exceeded 90 mm Hg. Compared with placebo, tasosartan produced significantly (P <.05) greater reductions in both SiDBP (-9.4 +/- 0.7 vs -2.0 +/- 0.7 mm Hg) and sitting systolic blood pressure (SBP) (-12.2 +/- 1.2 vs +0.4 +/- 1.2 mm Hg). The rate of response (SiDBP </=90 mm Hg or a decrease from baseline of >/=10 mm Hg) was significantly (P <.05) greater in the tasosartan group than in the placebo group (55% vs 19%). The mean 24-hour blood pressure reduction with tasosartan was -12.6 +/- 0. 9/-8.1 +/- 0.6, significantly greater (P <.05) than the reduction with placebo (+0.6 +/- 0.9/+0.5 +/- 0.6 mm Hg). The trough-to-peak ratio (determined from the ambulatory data) was 0.66 for DBP and 0. 72 for SBP for the tasosartan treatment group, demonstrating 24-hour efficacy with once-a-day administration. The safety profile of tasosartan was similar to placebo. CONCLUSIONS: These results demonstrate that tasosartan at 50 to 200 mg given once a day over a titration period of 10 weeks was effective and safe in the treatment of essential hypertension.

Adult↗
PubMed1999

Documentation of severe pain, opioid doses, and opioid-related side effects in outpatients with cancer: a retrospective study.

Pain severity, prescribed opioids including "rescue" medication for breakthrough pain, bowel movements, and laxative prescription were evaluated in 54 cancer patients treated in an outpatient department devoted to hematology and oncology during 1996. Median number of visits per patient was 5.5 (range 1-48), and median duration of patient care during opioid therapy was 44.5 days (range 1-363). Pain severity and opioid dose were not documented, or documented in less than 25% of visits, in 62.9% and 48.2%, respectively. Rescue doses for breakthrough pain, laxative prescription and bowel movements were never mentioned in 70.4%, 68.5%, and 87% respectively, of all patient charts. Only 3 of 12 physicians documented pain severity in more than 15% of visits, and opioid dose was recorded in more than 30% of all visits only by four physicians. Rescue doses for breakthrough pain, laxative prescription, and bowel movements were never or only scarcely documented by all physicians. Pain measurement using a visual analog scale was recorded by one physician. Our data show inadequate documentation of important aspects of cancer pain in a large outpatient department of hematology and oncology. These deficiencies may have a major negative impact on the quality of cancer pain treatment.

Adult↗