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Biomedical subjects

W Huber

Publications and source records attributed to W Huber.

At least 19 recordsLinked to original sources
PubMed2002

[Achilles tendon and sports].

Because of the rising popularity of recreational sports activities achillodynia is an often associated symptom with running, soccer and athletics. Therefore radiologist are frequently asked to image this tendon. The origin of the damage of the Achilles tendon is explained by numerous hypothesis, mainly a decreased perfusion and a mechanical irritation that lead to degeneration of the tendon. High-resolution technics such as sonography and magnetic resonance imaging show alterations in the structure of the tendon which can be graduated and classified. Manifestations like tendinosis, achillobursitis, rupture and Haglunds disease can summarized as the tendon overuse syndrome. A rupture of a tendon is mostly the result of a degeneration of the collagen fibers. The task of the radiologist is to acquire the intrinsic factors for a potential rupture.

Achilles Tendon↗
PubMed2002

[Apophyseal damage in adolescent athlete].

The increasing demands on the adolescent athlete in high performance sports puts high biomechanical stress on the growing structures of the active and passive locomotor system. The "growing factor" itself increases stretching forces on tendon insertions, which are often overloaded when a physical demanding sport is performed additionally. The apophysis is an ossification nucleus near the tendon insertion, which appears before the growing age resumes and these apophysis finally fuses with the adjacent bone. The tensile forces from vigorous sports activity leads to a chronic or acute avulsion of the ossifying tendon insertion. The radiological appearance of this apophyseal damage with ossification and osteolytic processes is sometimes difficult with respect to differential diagnoses. Apophyseal impairment is associated with pain, tenderness to palpation and decreased muscle function. If it is not diagnosed and treated properly it can lead to end of career in many adolescent athletes.

Adolescent↗
PubMed2002

Fulminate intracardiac thrombosis associated with Budd-Chiari-syndrome and inferior vena cava thrombosis.

The most common cause of edema of the legs and dyspnea is congestive heart failure. Further differential diagnosis such as renal or hepatic failure have to be considered. We report the case of a previous healthy 65-year-old woman who developed dyspnea and massive edema of the legs followed by acute hepatic and renal failure. Imaging studies showed a thrombosis of the inferior vena cava (IVC) caused by a tumor between the right kidney and the IVC. Histological examination revealed a leiomyosarcoma of the IVC. Hepatic failure due to venous outflow obstruction (Budd-Chiari syndrome, BCS) was diagnosed. Coagulation profile showed a complex disorder due to acute hepatic failure. Factor V Leiden and prothrombin gene mutation G20210A could be excluded. The thrombosis extended from the femoral veins up to the right atrium. After 11 days of anticoagulation with heparin platelet counts decreased by more than 50%. Suspecting a heparin-induced thrombocytopenia the patient was placed on recombinant hirudin (lepirudin) for anticoagulation. Hepatic venogram showed a thrombosis of the hepatic vein orifices but not of the hepatic veins. The tumor and the thrombi were removed surgically. When the cardiopulmonary bypass was terminated new intracardiac thrombi occurred. Despite immediate surgical intervention the patient finally died due to right ventricular failure caused by the fulminate intracardiac thrombosis. In conclusion, thrombosis of the IVC may mimic congestive heart failure and may cause BCS. Neoplasms and coagulation disorders may cause thrombosis of the IVC.

Aged↗
PubMed2002

Recurrent pseudomembranous colitis as a cause of recurrent severe sepsis.

Clostridium difficile (C. difficile) colitis accounts for nearly 15-20 % of antibiotic-associated diarrhea. Manifestations include asymptomatic carriage, self-limited diarrhea, and pseudomembranous colitis, which is sometimes life-threatening. Despite effective therapy with metronidazole and vancomycin relapse rates are 15-33 %. Although colitis is seen in critically ill patients treated with combinations of broad-spectrum antibiotics, reports describing severe sepsis as a result of C. difficile infection are limited. We describe the case of recurrent severe sepsis due to recurrent local intestinal C. difficile infection as the only identifiable etiology. The mechanism of severe sepsis may be a derangement of the gastrointestinal barrier function. This could result in absorption of microbes or endotoxin or activation of inflammatory cascades in the submucosa of the intestine or liver. In general, for successful treatment of C. difficile infections other than anticlostridial antibiotics should be discontinued. However, in the present case bacterial translocation from the intestine is an attractive explanation for severe sepsis and therefore additional antibiotics had been administered.

Enterocolitis, Pseudomembranous↗
PubMed2002

Oxidative stress and TGFbeta in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.

Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to TGFbeta production, NO degradation, endothelial dysfunction, hypertension and post-transplant nephropathy. Carvedilol, alpha1-beta-blocker with strong antioxidant activity, may interfere with this chain of events. Therefore, we measured monocyte ecNOS, TGFbeta and heme oxygenase-1 (HO-1) mRNA level and plasma nitrite/nitrate, 3-nitrotyrosine, an estimate of peroxynitrite, and total plasma antioxidant power in kidney-transplanted patients with post-transplant hypertension, before and after treatment with carvedilol, 25 - 50 mg o.d. orally for 4 months (n = 15). The dihydropyridine calcium channel blocker nifedipine (n = 10) was used as comparator antihypertensive drug. Blood pressure fell to a similar extent with both drugs. Carvedilol increased plasma antioxidant power and HO-1 mRNA and reduced 3-nitrotyrosine and TGFbeta mRNA levels, while the same was not observed with nifedipine. Monocyte ec NOS mRNA levels and plasma nitrite/nitrate were higher in the patients than in a normotensive healthy control group and were unaffected by either treatment. In conclusion, carvedilol reduces the oxidative stress and corrects the altered cellular signaling mediated by oxidative stress in CsA-induced post-transplant hypertension. Therefore, it may prevent long-term complications, such as endothelial dysfunction, fibrogenesis and post-transplant nephropathy by decreasing NO degradation and production of TGFbeta, a key fibrogenic cytokine, and by activating HO-1 production.

Adrenergic beta-Antagonists↗
PubMed2001

Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis.

To evaluate the prognostic significance of cytogenetic findings in clear cell renal cell carcinoma (RCC), cytogenetic results of 118 primary RCCs were evaluated in relation to classical indicators of prognosis and overall survival. Losses in 3p (98.3%) were most prevalent and included 32 (27.6%) monosomies of chromosome 3 and 84 (72.4%) structural aberrations involving 3p, of which 36 were unbalanced translocations, der(3)t(3;5)(p11-p22;q13-q31), resulting in duplication of 5q sequences. Patients with gain of 5q31-qter resulting from either polysomies or structural rearrangements of 5q, the most frequent of which was der(3)t(3;5), had a significantly better outcome than those without this aberration (P = 0.001). There was no association between gain of 5q or der(3)t(3;5) and any of the well-known variables for prognosis, including low versus high clinical stage and grade of malignancy. Among additional chromosomal aberrations, loss of chromosome 9/9p was associated with distant metastasis at diagnosis (P = 0.006). The data indicate that gain of 5q identifies a clinically favorable cytogenetic variant of clear cell RCC and demonstrate the impact of specific chromosome aberrations as additional prognostic indicators in clear cell RCC.

Adenocarcinoma, Clear Cell↗
PubMed2001

Reduced incidence of radiocontrast-induced nephropathy in ICU patients under theophylline prophylaxis: a prospective comparison to series of patients at similar risk.

OBJECTIVE: To investigate whether the adenosine-antagonist theophylline reduces the incidence of contrast-induced nephropathy (CIN). DESIGN AND SETTING: Prospective, comparison to series of patients at similar risk of CIN in a university hospital medical ICU. PATIENTS: 78 ICU patients with at least one risk factor for CIN undergoing 150 consecutive contrast examinations. INTERVENTIONS: Administration of 200 mg theophylline/70 kg BW intravenously 30 min before that of 100 ml or more low-osmolarity contrast medium (CM). MEASUREMENTS AND RESULTS: Concentrations of serum creatinine and blood urea nitrogen (BUN), urine volume, fluid balance, and the incidence of CIN [increase in creatinine > or =20.5 mg/dl (= 44.2 micromol/l) within 48 h] were monitored for 48 h. Despite the large number of risk factors (6.8 per patient) including a high dose of CM (169.4 ml), impaired renal function (51%), diabetes (38%), aminoglycosides (61%), vancomycin (53%), catecholamines (52%), creatinine concentrations were not increased 24 h (1.40+/-0.92 mg/dl) or 48 h (1.38+/-0.88 mg/dl) after CM [1.47+/-1.0 mg/dl (= 130+/-88 micromol/l)] vs. baseline. The fluid balance was not different before (+3 ml/h) and after CM (-9 ml/h). The urine volume slightly increased after CM and theophylline (184 ml/h vs. 164 ml/h). Only three patients (2%) developed CIN. The incidence was significantly lower than that of 14% (78/565) in the control series with patients at comparable risk of CIN (p < 0.0001). CONCLUSIONS: Using a theophylline prophylaxis the incidence of CIN in patients with increased risk of CIN is as low as 2%.

Adenosine↗
PubMed2001

Life-threatening gastrointestinal bleeding due to a jejunal lesion of Henoch-Schönlein purpura.

The case of a 56-year-old patient with Henoch-Schönlein purpura (HSP) and fulminant gastrointestinal bleeding is reported. The patient was admitted to hospital because of palpable purpura on both legs, painful joints and diffuse abdominal pain. Suspected HSP was histologically proven and treated with prednisolone. Despite recovery, acute gastrointestinal bleeding, with melena and a drop in hemoglobin concentration from 11.2 to 4.2 g/dl, occurred 30 days after medication was started. Immediate endoscopic examination of the upper gastrointestinal tract showed no signs of bleeding whereas colonoscopy showed fresh blood and blood clots in the terminal ileum and the colon. Since the bleeding source could not be detected endoscopically, mesenteric angiography was performed, demonstrating active bleeding from a jejunal artery. Thereafter the bleeding source was located by intraoperative peroral enteroscopy and treated by resection of a short segment of jejunum.

Gastrointestinal Hemorrhage↗
PubMed2001

Identifying splits with clear separation: a new class discovery method for gene expression data.

We present a new class discovery method for microarray gene expression data. Based on a collection of gene expression profiles from different tissue samples, the method searches for binary class distinctions in the set of samples that show clear separation in the expression levels of specific subsets of genes. Several mutually independent class distinctions may be found, which is difficult to obtain from most commonly used clustering algorithms. Each class distinction can be biologically interpreted in terms of its supporting genes. The mathematical characterization of the favored class distinctions is based on statistical concepts. By analyzing three data sets from cancer gene expression studies, we demonstrate that our method is able to detect biologically relevant structures, for example cancer subtypes, in an unsupervised fashion.

Algorithms↗
PubMed2001

Repetitive transcranial magnetic stimulation effects on language function depend on the stimulation parameters.

In previous studies it has been shown that picture-naming latencies can be facilitated with both suprathreshold single and repetitive transcranial magnetic stimulation (TMS/rTMS) over Wernicke's area. The aim of this study was to investigate whether low-frequency rTMS (1 Hz) or high-frequency rTMS (20 Hz) at subthreshold intensities is also capable of influencing picture naming. In 16 healthy right-hand male subjects, trains of 1 Hz or 20 Hz were applied over either Wernicke's area, Broca's area, or the primary visual cortex. The subjects had to name 20 black-and-white line drawings, which were shown immediately after rTMS and again 2 minutes later. Naming latency could be facilitated only immediately after Wernicke's area stimulation at a frequency of 20 Hz and at an intensity of 55% of the maximal stimulator output, which was more than the motor threshold. All other stimulation procedures failed to influence naming latencies. These results indicate that language functions can be facilitated in healthy subjects only by high-frequency rTMS with intensities at or above the motor threshold.

Adult↗
PubMed2001

Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN-[gamma] blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/microL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN-[gamma] plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN-[gamma] production.

Adolescent↗
PubMed2001

[Tendon overuse syndrome: imaging diagnosis].

Injuries of muscles and tendons occur commonly during various sporting activities and in most cases the athletes feel such an accident to be sudden and unavoidable. The rupture of a tendon, however, has to be considered in many cases as the final stage of a long-standing progressive degeneration of collagen fibers. This process can be described as "tendon overuse syndrome (TOS)". Diagnostic imaging modalities, especially sonography and MRI, are suitable to detect and analyse the different stages of this syndrome and the degree of morphological abnormalities. The first stage is painful functional derangement, followed by tendovaginitis, peritendinitis, or bursitis. The third stage is tendinosis resulting from biomechanical or ischaemic injury of tendon fibers which may eventually be followed by partial or complete rupture. Regional or individual specifications of these four stages may occur at anatomically predisposing sites, so-called critical zones, or during periods of specific proneness, the vulnerable phases.

Athletic Injuries↗
PubMed2000

Residual HIV-RNA levels persist for up to 2.5 years in peripheral blood mononuclear cells of patients on potent antiretroviral therapy.

The long-term response of 10 asymptomatic, antiretroviral therapy-naive HIV-1-infected patients to potent combination antiretroviral therapy was characterized by monitoring levels of HIV-1 RNA in plasma, peripheral blood mononuclear cells (PBMC), and lymphoid tissue using highly sensitive HIV-1 RNA assays. Although plasma viral loads were continuously suppressed to levels below 50 HIV-1 RNA copies/ml for up to 2.5 years (60-128 weeks), HIV-1 RNA was still detectable at very low levels (1 to 49 HIV-1 RNA copies/ml) in 25% of the samples. In corresponding PBMC specimens, residual HIV-RNA was detectable in as much as 91% of samples tested (1 to 420 HIV-1 RNA copies/microg total RNA). Similarly, HIV-1 RNA levels in lymphoid tissue also remained detectable at a high frequency (86%). A highly significant correlation was demonstrated between therapy-induced change in PBMC HIV-1 RNA levels and change in plasma HIV-1 RNA levels (r2 = 0.69; p = 0.003). These findings support the concept that measurement of HIV-1 RNA in the easily accessible PBMC compartment is relevant for evaluating the potency of current and future antiretroviral therapies.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening.

Random screening provided no suitable lead structures in a search for novel inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach had to be developed. Relying on the detailed 3D structural information of the targeted ATP binding site, our approach combines as key techniques (1) an in silico screening for potential low molecular weight inhibitors, (2) a biased high throughput DNA gyrase screen, (3) validation of the screening hits by biophysical methods, and (4) a 3D guided optimization process. When the in silico screening was performed, the initial data set containing 350 000 compounds could be reduced to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay provided 150 hits clustered in 14 classes. Seven classes could be validated as true, novel DNA gyrase inhibitors that act by binding to the ATP binding site located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino-pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D guided optimization provided highly potent DNA gyrase inhibitors, e. g., the 3,4-disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than novobiocin (3).

Anti-Infective Agents↗
PubMed2000

Hemispheric lateralization at different levels of human auditory word processing: a functional magnetic resonance imaging study.

We used functional magnetic resonance imaging to disentangle the functional anatomy of brain systems involved in the processing of auditory word form and meaning. Three monitoring tasks on auditory stimuli, aimed at phonetic, lexical and semantic processing, were used. We found no lateralization of temporal lobe activations, when word processing was contrasted versus the complex phonetic task. Bilateral middle temporal activations (Brodmann Area [BA] 21) were attributed to processing of word-form. Areas specific to semantic processing were restricted to the left hemisphere: the posterior middle frontal (BA 9) and posterior parietal (BA 7/40) cortex, as well as an inferior temporal area (BA 20/21). Our data suggest, that left hemispheric dominance for auditory word comprehension occurred at the level of semantic processing.

Acoustic Stimulation↗
PubMed2000

Sequence diversity of the merozoite surface protein 1 of Plasmodium falciparum in clinical isolates from the Kilombero District, Tanzania.

Merozoite surface protein 1 of Plasmodium falciparum (PfMSP-1) is regarded as a key candidate antigen for malaria vaccine development. It exhibits significant antigenic polymorphism and has been divided into 17 building blocks based on the analysis of sequence diversity. Differences in the antigenic composition of PfMSP-1 in local P. falciparum populations may result in differences in the efficacy of vaccines, which contain sequences of particular allelic variant(s) of PfMSP-1. To contribute to the required knowledge of genetic diversity of malaria parasites in geographically diverse regions, we have used the polymerase chain reaction (PCR) to analyze the sequence diversity of blocks 1-4 of PfMSP-1 in disease isolates from the Kilombero District in Tanzania. In the semi-conserved block 1, in which dimorphic amino acid variances have been described at three positions, we found three of the five previously described combinations of these three pairs of amino acids. In addition one combination was found, which has not been reported before in parasite isolates from different locations worldwide. Of the two sequence variants, which were dominating, one (S44-Q47-V52) corresponded to the 83.1 sequence incorporated into the SPf66 malaria peptide vaccine, while the other one (G44-H47-I52) differed from the previous in all three dimorphic amino acids. The partial protection observed in a phase III SPf66 trial conducted in the Kilombero District in children aged 1-5, thus does not seem to be associated with a clear dominance of favourable variants of block 1 of PfMSP-1 in this area. All three different principle types of block 2, the major polymorphic region of PfMSP-1, were found in the Tanzanian isolates. Most of the sequences contained K1-type tripeptide repeats, but clones with MAD20-type repeats or no repetitive sequence (RO33-type block 2) were also present. K1- and MAD20-type tripeptide repeat motifs were never mixed within one parasite clone. In one sequence a hexapeptide repeat was found at the end of block 2, which has not been reported before. Dimorphism in 13 of the 17 previously described variable positions of the semi-conserved block 3 and three of four recombination types of block 4 (K/K, M/K and M/M) were found among the Tanzanian isolates. Apart from previously described dimorphic amino acid positions, polymorphism was rare in the non-repeated building blocks. Selection and spreading of parasite variants, which contain amino acid exchanges at other than the dimorphic positions thus, is not a common event. Parasite isolates frequently harboured more than one PfMSP-1 allele. Three of the four heterogeneous isolates analysed contained two different general types of sequences. One isolate contained at least four distinct clones, demonstrating the high endemicity of malaria in the Kilombero District, which is a well-established site for malaria vaccine field trials.

Amino Acid Sequence↗