Biomedical subjects

W Lang

Publications and source records attributed to W Lang.

At least 37 records · Page 2Linked to original sources

PubMed2003

Association of parental history of stroke with clinical parameters in patients with ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Data regarding hereditary influences on stroke remain controversial. We investigated possible associations of a family history of stroke with clinical parameters in a large cohort of well-documented patients with ischemic cerebrovascular events, with special reference to sex-specific differences. METHODS: We analyzed the association between a maternal and/or paternal history of stroke and clinical parameters in 1564 patients with known maternal and paternal history of stroke and suffering from ischemic stroke or transient ischemic attack within the Vienna Stroke Registry. RESULTS: Patients with a maternal history of stroke were significantly more often female (54%) than those without (44%; P=0.003). Hypertension was more prevalent in female patients with than in those without a maternal history of stroke (87% versus 74%; P=0.001). These associations remained significant after multivariate adjustment (adjusted odds ratio, 1.9; 95% CI, 1.1 to 3.5; P=0.024). Of those female patients with an echocardiogram (n=225), those with a maternal history of stroke more often had left ventricular hypertrophy (48%) than those without (20%) (adjusted odds ratio, 3.6; 95% CI, 1.5 to 8.2; P=0.003). In contrast, hypertension was equally prevalent in male patients with or without a maternal history of stroke (75% versus 74%; P=0.754). We found no significant associations of clinical parameters with a paternal history of stroke. CONCLUSIONS: Our results indicate a sex-specific relationship between a maternal history of stroke and the prevalence of hypertension and left ventricular hypertrophy in female patients with ischemic cerebrovascular events.

Aged↗

PubMed2003

Preserved memory traces within diencephalic amnesia.

A male patient with bilateral thalamic lesions (medio-ventral nuclei) was investigated. Despite explicit memory impairments his lexical ability was normal. We recorded magnetic field changes (magnetoencephalography, MEG) during the performance of an animate/inanimate discrimination task in which some words where repeated after long delays. Normally, repeated items are classified significantly faster than their first presentations which is accomplished by an unconscious process called priming. The patient did not show any behavioural evidence of priming but the physiological data indicated preservation of this robust form of memory. Brain activation associated with repetitions was attenuated at early stages. The activity difference was posteriorly distributed which is consistent with previous reports about repetition priming. The present study indicated that the bilateral thalamic lesions of our patient disconnected the information processing stream between the primed information and the behavioural response.

Amnesia↗

PubMed2003

Indications of neutralising anti-idiotypic antibodies and selective proteolytic fragmentation in polyclonal anti-D IgG preparations.

Proteolytic fragmentation is the only suggested cause of potency losses during storage of liquid human polyclonal anti-D Ig. Besides the effect of fragmentation, we have investigated the potential contribution of neutralising anti-idiotypic antibodies (anti-Ids). Potency changes during storage and/or upon pH reduction in anti-D IgG batches with or without addition of plasminogen and urokinase were quantitatively analysed by the autoanalyser (AA) method or by a special procedure of flow cytometry (FC). Moreover, simultaneous changes of the molecular size distribution pattern have been determined by size exclusion chromatography. In contrast to the AA procedure, the particular FC methodology was found to be almost insensitive to proteolysis comprising up to 30% of total IgG. Data interpretation was based on the assumption that both assays cannot detect Ids with neutralised paratopes. In the absence of detectable neutralisation (functional absence of anti-Ids), it could be demonstrated that the anti-D IgG subpopulation is more sensitive to fragmentation by endogenous protease as compared to the unrelated bulk. However, both methods detected batch- and assay-dependently variable potency losses during storage. Moreover, the increase of potency induced by pH reduction correlated with the increase of monomeric IgG, essentially on the expense of dimers. This finding was interpreted to indirectly indicate the neutralising action of anti-Ids known to be the major driving force of dimer formation in polyclonal IgG. A more or less pronounced pH-dependent potency increase was also detectable in three arbitrarily selected batches of two other manufacturers. The data allows to assume that anti-Id-mediated neutralisation can significantly contribute to losses of anti-D potency. In addition, it turned out that anti-D plasma itself can be the source of anti-Ids.

Antibodies, Anti-Idiotypic↗

PubMed2003

The effects of alteration of effector and side of movement on the contingent negative variation.

OBJECTIVE: The contingent negative variation (CNV) is a widespread electroencephalographic (EEG) potential that occurs during the interval between a warning stimulus and a subsequent imperative stimulus if a mental or motor response is required. The present study was designed to explore the impact of the previous trial on the CNV of the forthcoming trial, that is, how a previous movement affects brain activation preparing the next movement. Effects of alteration of finger (from index to middle, and vice versa) and hand (from left to right, and vice versa) were examined independently from each other. METHODS: CNV was recorded in 20 right-handed healthy subjects with electrodes placed at F7, F5, F3, F4, F6, F8, FC5, FC3, FC1, FC2, FC4, FC6, T7, C5, C3, C1, C2, C4, C6, T8, CP5, CP1, CP2, CP6, P7, P3, P4 and P8. In a visual/visual S1-choice paradigm, an earlier informative (S1) stimulus which instructed for side and finger of the following movement was followed 3 s later by an imperative (S2) stimulus providing the command to move. Subjects had to respond to each imperative stimulus with an appropriate button press made by brisk flexion movements with the index or middle finger of each hand. The CNV recorded in the interval between the informative and the imperative stimulus was analysed with respect to finger and hand of the present and the preceding movement. RESULTS/CONCLUSIONS: (1) A change of the side of movement is associated with a widespread increase of negativity contralateral to the currently prepared movement. (2) A change of finger is associated with a focal increase of negativity contralateral to the side of the current movement over temporoparietal and mid-parietal areas. (3) A change of finger results in a widespread increase of negativity over the left hemisphere.

Adult↗

PubMed2003

[Diabetic neuropathic osteoarthropathy (Charcot foot)].

Diabetic neuropathic osteo-arthropathy (DNOAP; Charcot's foot) is a dramatic complication of diabetic polyneuropathy. The diabetic foot is the most neglected long-term sequela of diabetes mellitus, and this is especially true for DNOAP. The increasing number of diabetics presenting in the foot ambulance with DNOAP demonstrates this general lack of knowledge and indicates that this complication is more frequent than hitherto assumed. In view of this dilemma, the pathogenesis, diagnosis and therapy of DNOAP are reviewed. Special emphasis is given to the differentiation between the neuropathic and neuroischemic foot as well as between acute DNOAP and bacterial infection. Therapy of DNOAP is predominantly conservative. The indication for surgery should be restricted to serious deformities of the foot, instability of joints, imminent skin perforation caused by fracture-induced dislocation of bones, and recurrent ulcers caused by prominent bones. Surgery comprises ulcer excision, ablation of bony prominences, as well as orthopedic surgery for the reconstruction of the foot skeleton.

Arthropathy, Neurogenic↗

PubMed2003

Improved conformation-dependent immunoassay: suitability for human prion detection with enhanced sensitivity.

The presence of pathogenic prion protein (PrP(Sc)) in lymphoid tissues of variant Creutzfeldt-Jakob disease (vCJD) patients raises questions as to whether prions may be present in bodily fluids as well. Currently, transgenic mice are highly sensitive in vivo tools for the study of prions in tissues or fluids containing high levels of normal prion protein (PrP(C)). We report here an in vitro assay with virtually equivalent sensitivity incorporating a capture antibody into a sandwich conformation-dependent immunoassay (CDI), resulting in 30- to 100-fold increased sensitivity compared with the original, direct CDI. Furthermore, spiking plasma with vCJD prions in different preparations demonstrated that sandwich CDI detects prions with different biophysical properties at high sensitivity, even without proteinase K pretreatment of samples. Thus, sandwich CDI represents a powerful tool to study prions in bodily fluids of CJD/vCJD patients, with a turnaround time of less than 24 h.

Animals↗

PubMed2002

Surgery of a splenic artery aneurysm during pregnancy.

We report a case of ligation of the splenic artery with splenectomy during pregnancy due to a splenic artery aneurysm. The risk of aneurysmal rupture is increased in multipara and during pregnancy. As a result of high maternal and fetal morbidity and mortality elective surgery should be performed.

Adult↗

PubMed2002

Entropy of vortex cores near the superconductor-insulator transition in an underdoped cuprate.

We present a study of Nernst effect in underdoped La(2-x)Sr(x)CuO4 in magnetic fields as high as 28 T. At high fields, a sizable Nernst signal was found to persist in the presence of a field-induced nonmetallic resistivity. By simultaneously measuring resistivity and the Nernst coefficient, we extract the entropy of vortex cores in the vicinity of this field-induced superconductor-insulator transition. Moreover, the temperature dependence of the thermoelectric Hall angle provides strong constraints on the possible origins of the finite Nernst signal above T(c), as recently discovered by Xu et al. [Nature (London) 406, 486 (2000)].

Journal Article↗

PubMed2002

The effects of alteration of effector and side of movement on movement-related cortical potentials.

The amplitude of the movement-related cortical potential (MRCP) preceding self-paced voluntary movements is larger if subjects alter between flexions of two fingers compared with repetitive movements of the same finger. However, earlier studies were confined to alternating movements between limbs only and therefore could not differentiate effects of between-limbs from within-limb alteration. The present study was designed to examine effects of alteration of finger (from index to middle, and vice versa) and hand (from left to right, and vice versa) independently from each other. MRCPs were recorded in 20 right-handed healthy young subjects with electrodes placed at Fp1, Fp2, F7, F3, F4, F8, T7, C5, C3, C1, C2, C4, C6, T8, P7, P3, P4, P8, O1 and O2. Subjects made self-paced flexion movements with the index or middle finger of each hand by pressing one out of 4 response buttons. In the alternating conditions, subjects pressed two buttons in a strictly alternating fashion. Every finger was combined with every other finger, arriving at a total of 6 alternating conditions. In the 4 regular conditions, subjects pressed a particular button repetitively across trials. The results show the following: (1) MRCPs over contralateral sensorimotor areas are higher if subjects change the side of movement than if the movements are done with the same hand repeatedly. (2) MRCPs over lateral parietal areas are higher for ipsilateral than contralateral movements in the regular conditions but also increase contralaterally after a change of the side of movement. (3) Any change of side or finger is associated with a widespread increase of negativity over the left hemisphere.

Adult↗

PubMed2002

[CT-angiography of the carotid artery: First results with a novel 16-slice-spiral-CT scanner].

PURPOSE: To evaluate a novel multislice CT system (16-slice-spiral-CT scanner) for the diagnosis of carotid artery stenosis. MATERIAL AND METHODS: Five patients with symptomatic atherosclerotic disease of the carotid arteries were examined with a 16- slice-spiral-CT scanner. Collimation was 16 x 0.75 mm, table speed 36 mm/s (pitch of 1.5), rotation time 0.5 s, tube current was 160 eff.mAs at 120 kV. 60 ml of contrast material were injected with a power injector followed by a saline flush. The start delay was measured with test bolus method (20 ml CM). Interactive multiplanar reformation (iMPR) and thin slab MIP as well as volume rendering were used for image evaluation and presentation. RESULTS: Scan time was 9 s for a range of 300 mm. This allowed imaging the whole length of the carotid artery (aortic arch to circle of Willis) in a true arterial phase. Pulsation artefacts did not impair the evaluation of the vessels at the level of the aortic arch. Overall image quality of both "source images" and 3D-reconstructions was excellent, due to a reduced voxel size of 0.03 mm (3). Image evaluation and postprocessing (iMPR, MIP) was done within 15 min. iMPR was highly accurate for demonstrating plaque morphology and determining the percentage of the stenosis. CONCLUSION: For the first time, true arterial phase images of the entire carotid artery with high spatial resolution could be acquired using a 16-slice-spiral-CT scanner. This method offers the potential to replace catheter angiography in the evaluation of carotid artery stenosis.

Blood Flow Velocity↗

PubMed2002

Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection.

A multicenter, open-label study was performed to evaluate the safety, anti-hepatitis B virus (anti-HBV) activity, and pharmacokinetics of emtricitabine therapy administered once daily for 8 weeks to patients infected with HBV. Clinical and virologic evaluations were completed at the baseline; at 7, 14, 28, 42, and 56 days during treatment; and at 24, 48, and 28 days posttreatment. Forty-nine patients were enrolled in five dose cohorts (doses of 25, 50, 100, 200, and 300 mg, all of which were administered once daily [q.d.]). Peak plasma emtricitabine concentrations occurred within 1.5 h following dosing. Plasma emtricitabine concentrations (maximum concentrations of drug in plasma and areas under the concentration-time curves) increased nearly dose proportionally over the 25- to 300-mg dose range, with relatively small intersubject variabilities. The plasma half-life of emtricitabine ranged from 6 to 9 h. HBV DNA levels were measured by the Digene HBV Hybrid Capture II assay. Viral suppression (reduction in log(10) serum HBV DNA levels) occurred in all dose cohorts. All doses demonstrated potent and rapid antiviral activities, with a trend toward a greater suppression with daily doses of 100 mg or greater. At 2 months, the median change in the serum HBV DNA level from the baseline level ranged from -1.7 log(10) for the 25-mg dose administered q.d. to -3.3 log(10) for the 300 mg dose administered q.d. Emtricitabine was well tolerated over the 2-month dosing period. These results support further clinical development of emtricitabine for the treatment of chronic hepatitis B infection.

Adolescent↗

PubMed2001

Current strategies of secondary prevention after a cerebrovascular event: the Vienna stroke registry.

BACKGROUND AND PURPOSE: Oral anticoagulation (OAC) and antiplatelet drugs are effective in the secondary prevention of ischemic cerebrovascular events. Only few data exist about the factors influencing the choice of a specific therapy for secondary prevention in patients with a recent stroke or transient ischemic attack (TIA). METHODS: Within a cross-sectional study, nested in a cohort we identified 931 patients with a recent ischemic stroke or TIA who were discharged with OAC or with one of the antiplatelet medications aspirin, clopidogrel, or the combination of aspirin and extended-release dipyridamole. By means of multivariate logistic regression analysis, we determined the influence of several clinical variables on the decision between OAC and overall antiplatelet therapy as well as on the decision between different antiplatelet therapies. RESULTS: A cardioembolic etiology of the index event and atrial fibrillation were independently associated with the use of OAC. Age was inversely associated with the use of OAC. Different estimations of contraindications to OAC were the main reason for the considerable variability among the participating centers. The most important factor promoting the use of clopidogrel was therapy with aspirin before the index event. Patients with large- or small-vessel disease received clopidogrel more often than those with an event of undetermined etiology. We found an extremely high interhospital variability for the use of the combination of aspirin with extended-release dipyridamole. CONCLUSIONS: Current recommendations are applied in clinical practice, but great variability between different centers remains. More clearly defined guidelines for indications for, as well as contraindications against, a specific therapy are necessary.

Administration, Oral↗

PubMed2001

Does bed rest after cervical or lumbar puncture prevent headache? A systematic review and meta-analysis.

BACKGROUND: Headache after cervical or lumbar puncture has long been attributed to early mobilization; however, there is little evidence for this. We performed a systematic literature review and meta-analysis of randomized controlled trials to assess whether longer bed rest is better than immediate mobilization or short bed rest in preventing headache. METHODS: We searched EMBASE (1988 to March 2001), MEDLINE (1966 to May 2001), Pascal Biomed (1996 to February 2001), Current Contents (1997 to September 1999), PsycINFO (1966 to May 2001), the Cochrane Controlled Trial Register (last search May 15, 2001), textbooks and references of the papers selected. Studies were eligible if patients underwent cervical or lumbar puncture for any reason and were randomly assigned to either a long or a short period of bed rest. Data were abstracted independently by 2 investigators to a predefined form. RESULTS: We found 16 randomized controlled trials involving 1083 patients assigned to immediate mobilization or a short period of bed rest (up to 8 hours) and 1128 patients assigned to a longer period of bed rest (0.5 to 24 hours). Puncture was performed for anesthesia (5 trials), myelography (6 trials) and diagnostic reasons (5 trials). None of the trials showed that longer bed rest was superior to immediate mobilization or short bed rest for preventing headache after puncture. When pooling the results of the trials in the myelography group and the diagnostic group, the relative risks of headache after puncture were 0.93 (95% confidence interval [CI] 0.81-1.08) and 0.97 (95% CI 0.79-1.19) respectively. We did not pool the results from the trials in the anesthesia group because of clinical heterogeneity, but shorter bed rest appeared to be superior. INTERPRETATION: There was no evidence that longer bed rest after cervical or lumbar puncture was better than immediate mobilization or short bed rest in reducing the incidence of headache.

Bed Rest↗

PubMed2001

Pharmaceutical development and manufacturing of a parenteral formulation of a novel antitumor agent, VNP40101M.

The objective of this study was to develop and manufacture a stable parenteral formulation for Phase I clinical trials of VNP40101M (1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(2-methylamino)carbonyl] hydrazine), a novel antitumor agent. The solubility and stability of the drug was determined. Solubility studies suggested that VNP40101M exhibited poor aqueous solubility but showed appreciable solubility in nonaqueous solvents. The aqueous solubility of the drug could not be increased by adjusting the pH. At a pH above 7, base-catalyzed decomposition of VNP40101M occurred. The low octanol-water partition coefficient of 0.75 suggested poor solubility in lipophilic solvents. Based on these preformulation observations, a parenteral formulation containing 10 mg/mL of VNP40101M was prepared in a solvent system consisting of 30% ethyl alcohol and 70% polyethylene glycol-300 (PEG-300). To minimize base-catalyzed hydrolytic degradation, citric acid at 0.6% concentration was included to acidify the formulation. Rubber closures, filter membranes, and liquid transfer tubing were selected on the basis of compatibility studies and absence of loss of drug due to adsorption of these components. The formulation was subjected to accelerated stability studies and dilution studies with large volume parenteral (LVP) solutions, normal saline, and 5% dextrose injection (D5W). The results of the dilution study indicated that the formulation could be diluted in these solutions up to 2 mg/mL for 8 hours without drug precipitation and degradation. Accelerated stability studies suggested that the product should be kept at 2 degrees C to 8 degrees C for long-term storage. The developed formulation was successfully scaled up and manufactured for use in clinical trials.

Adsorption↗

PubMed2001

Novel role for JNK as a stress-activated Bcl2 kinase.

Interleukin (IL)-3-induced Bcl2 phosphorylation at Ser(70) may be required for its full and potent antiapoptotic activity. However, in the absence of IL-3, increased expression of Bcl2 can also prolong cell survival. To determine how Bcl2 may be functionally phosphorylated following IL-3 withdrawal, a stress-activated Bcl2 kinase (SAK) was sought. Results indicate that anisomycin, a potent activator of the stress kinase JNK/SAPK, can induce Bcl2 phosphorylation at Ser(70) and that JNK1 can be latently activated following IL-3 withdrawal to mediate Bcl2 phosphorylation. JNK1 directly phosphorylates Bcl2 in vitro, co-localizes with Bcl2, and collaborates with Bcl-2 to mediate prolonged cell survival in the absence of IL-3 or following various stress applications. Dominant-negative (DN)-JNK1 can block both anisomycin and latent IL-3 withdrawal-induced Bcl2 phosphorylation (>90%) and potently enhances cell death. Furthermore, low dose okadaic acid (OA), a potent protein phosphatase 1 and 2A inhibitor, can activate the mitogen-activated protein kinases JNK1 and ERK1/2, but not p38 kinase, to induce Bcl2 phosphorylation and prolong cell survival in factor-deprived cells. Since PD98059, a specific MEK inhibitor, can only partially inhibit OA-induced Bcl2 phosphorylation but completely blocks OA-induced Bcl2 phosphorylation in cells expressing DN-JNK1, this supports the conclusion that OA may stimulate Bcl2 phosphorylation via a mechanism involving both JNK1 and ERK1/2. Collectively, these findings indicate a novel role for JNK1 as a SAK and may explain, at least in part, how functional phosphorylation of Bc12 can occur in the absence of growth factor.

Animals↗

PubMed2001

A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.

This study evaluated dual protease inhibitor (PI) regimens containing amprenavir (APV) in PI-naive, HIV-1-infected patients over 48 weeks. Patients were randomized to 800-mg APV combined with 800-mg indinavir (IDV), 750-mg nelfinavir (NFV), or 800-mg saquinavir-soft gel capsule (SGV-SGC), all three times daily without nucleoside reverse transcriptase inhibitors, or APV given alone for 3 weeks and then with 150-mg lamivudine (3TC) and 300-mg zidovudine (ZDV), twice daily. Dual PI therapy demonstrated substantial antiviral activity and was generally safe and well tolerated. Eight patients had virologic failure; 5 were receiving dual PI therapy and 3 were in the APV/3TC/ZDV arm. The protease I50V mutation characteristic of APV resistance was not observed, although other key PI mutations were selected in 4 patients failing therapy, 2 of whom had PI resistance at baseline.

Adult↗

PubMed2001

Pseudoexfoliation syndrome and aneurysms of the abdominal aorta.

We assessed the association between pseudoexfoliation syndrome, a common age-related fibrillopathy of unknown cause, and vascular diseases, especially aneurysms of the abdominal aorta. In a prospective single-blind study we ophthalmoscopically examined 55 patients with aneurysms of the abdominal aorta and 41 controls with carotic-artery occlusion. 24 of 55 patients with aortic aneurysm showed signs of manifest (17 of 55 patients) or early-stage (seven of 55) pseudoexfoliation syndrome. Eight of 41 control patients showed manifest (seven of 41 patients) and early (one of 41) ocular pseudoexfoliation (p=0.016). These findings, including histopathological examinations, suggest an association between aneurysms of the abdominal aorta and pseudoexfoliation syndrome.

Aged↗

PubMed2001

Left temporal and temporoparietal brain activity depends on depth of word encoding: a magnetoencephalographic study in healthy young subjects.

Using a 143-channel whole-head magnetoencephalograph (MEG) we recorded the temporal changes of brain activity from 26 healthy young subjects (14 females) related to shallow perceptual and deep semantic word encoding. During subsequent recognition tests, the subjects had to recognize the previously encoded words which were interspersed with new words. The resulting mean memory performances across all subjects clearly mirrored the different levels of encoding. The grand averaged event-related fields (ERFs) associated with perceptual and semantic word encoding differed significantly between 200 and 550 ms after stimulus onset mainly over left superior temporal and left superior parietal sensors. Semantic encoding elicited higher brain activity than perceptual encoding. Source localization procedures revealed that neural populations of the left temporal and temporoparietal brain areas showed different activity strengths across the whole group of subjects depending on depth of word encoding. We suggest that the higher brain activity associated with deep encoding as compared to shallow encoding was due to the involvement of more neural systems during the processing of visually presented words. Deep encoding required more energy than shallow encoding but for all that led to a better memory performance.

Adult↗