Search PubMed⌕ Search

Biomedical subjects

W Lang

Publications and source records attributed to W Lang.

At least 91 records · Page 5Linked to original sources

[Cerebral ischemia during carotid clamping: diagnosis and prevention].

A serious complication in carotid endarterectomy (CEA) is the occurrence or aggravation of neurological deficits caused by insufficient collateral cerebral blood flow during cross-clamping. At the moment, patients with failure of collateral circulation at this point cannot be identified preoperatively. Thus, intraoperative monitoring and methods to prevent clamping-related cerebral ischemia are required. To put this strategy into clinical practice there are several methods of monitoring cerebral function (e.g. surgery performed in awake patients, electroencephalography, somatosensory evoked potentials), changes of hemodynamic (e.g. carotid stump pressure, transcranial Doppler ultrasonography) or metabolic parameters (e.g. jugular bulb oximetry or transcranial oximetry). One technique that meets nearly all requirements of an ideal monitoring under general anesthesia is the use of somatosensory evoked potentials (SEPs). Registration of SEPs is simple to perform and indicates with a high sensitivity and specificity critical cerebral hypoperfusion during cross-clamping. Thus, SEPs monitoring indicates the necessity of shunt placement. As a result, the use of an indwelling shunt as the most effective method to prevent clamping ischemia can be limited to selected cases, avoiding the risks of shunting in patients with sufficient collateral flow. In addition, correct shunt function is immediately indicated by recovering potentials. Whether a combination of SEPs with transcranial Doppler measurements will be successful to provide additional information about cerebral embolisation should be determined.

Brain Ischemia↗

Isolation and identification of urinary metabolites of porfiromycin in dogs and humans.

Porfiromycin (PM), a bioreductive alkylating agent, is currently under development for the treatment of head and neck cancers as an adjunct to radiation therapy in phase III clinical trials. After i.v. administration of a single dose of PM to patients at 40 mg/m2, urinary metabolites were isolated by HPLC and identified by atmospheric pressure chemical ionization mass spectrometry. In dogs, [methyl-3H]PM was administered i.v. to three Beagle dogs at a single dose of 2 mg/kg. Urinary excretion of radioactivity and PM at different times was determined by liquid scintillation counting and by HPLC, respectively. An average of 48.0% of total radioactivity given to the dogs was cumulatively excreted in urine over a period of 7 days. Unchanged parent drug excreted in urine accounted for 10.8% of the administered dose over the same period of time. The results indicated that the majority of excreted dose in dog urine was in the form of metabolites. Three phase I and four phase II metabolites of PM were identified in human and dog urine. The phase I metabolites are 2-methylamino-7-aminomitosene, 1,2-cis and 1,2-trans-1-hydroxy-2-methylamino-7-aminomitosenes. The phase II metabolites are a pair of isomeric N-acetylcysteine S-conjugates and a pair of isomeric cysteine S-conjugates of mitosenes at the C-1 and C-10 positions. Most of the identified metabolites were confirmed by comparison with synthetic reference standards using HPLC and liquid chromatography/mass spectrometry (LC/MS). The identification of mercapturic acids and cysteine S-conjugates in urine indicates that the metabolism of PM may be through GSH conjugation.

Animals↗

Collagen patch coated with fibrin glue components. Treatment of suture hole bleedings in vascular reconstruction.

BACKGROUND: Bleeding from suture holes during vascular reconstruction, particularly when polytetrafluoroethylene (PTFE) prostheses are used, is still a problem which can lead to intraoperative delay and increased blood loss. The aim of this prospective, randomised, open, controlled multicentre study was to evaluate whether the use of a new local haemostyptic would reduce intraoperative blood loss and the time to haemostasis. METHODS: Thirty patients received a new haemostyptic (TachoComb H, Nycomed Pharma AG), whereas another 30 patients were treated with compresses. The vascular reconstructions were either anastomoses or patch angioplasties and were performed using PTFE vascular prostheses. RESULTS: The mean time to haemostasis of suture hole bleeding in the haemostyptic group (326.0 sec) was significantly shorter compared to the control group (514.3 sec) (p=0.006). The median intraoperative blood loss was 24.5 g in the treatment group and 57.3 g in the control group (p=0.045). CONCLUSIONS: It was shown that collagen patches coated with components of fibrin glue significantly reduce the time to haemostasis as well as blood loss at the operation site in patients undergoing vascular reconstruction with PTFE grafts.

Aged↗

[Experimental infection of a novel nonenveloped DNA hepatitis virus in Rhesus monkey].

OBJECTIVE: To test the susceptibility of the Rhesus monkey to the TT virus and to establish its transmission route. METHODS: Rhesus monkeys were administered orally and intravenously with the inoculum that was prepared with feces collected from a patient at the incubation period. Passage study was done with monkey' s positive feces. The blood, bile and feces were tested with polymerase chain reaction (PCR), and the liver, the jejunum tissues with in situ hybridization. RESULTS: The viremia occurred 4-7 days after intravenous inoculation and 7-10 days after oral administration. The virus was also excreted in the feces in a few days after oral infection and simultaneously with viremia after intravenous inoculation. The virus was also detected in the bile during the viremic phase. There was a prolonged carrier state that the viremia and fecal virus excretion persisted for more than 6 months. No serum transaminase elevation was found during the infection. There were virus signals in hepatocytes in columnar epithelium and lamina propria cells of jejunum villi, but no significant pathology was demonstrated in both sites. CONCLUSIONS: The liver infection of Rhesus monkey was established hb either oral or parenteral virus Inoculation. The virus may be released from liver into blood and intestine vial the bile or just from the gut wall into feces, and hence it may be transmitted by both routes.

Animals↗

A phase II safety and efficacy study of amprenavir in combination with zidovudine and lamivudine in HIV-infected patients with limited antiretroviral experience. Amprenavir PROAB2002 Study Team.

OBJECTIVE: To determine the safety and efficacy of amprenavir (APV) in combination with lamivudine (3TC) and zidovudine (ZDV). DESIGN: Multicenter, randomized, partially blinded trial. SETTING: Nine study sites in the United States and Europe. PATIENTS: A group of 84 HIV-infected subjects with no prior 3TC or protease inhibitor therapy experience, CD4 cell count > or = 150 x 10(6) cells/l, and plasma HIV RNA > 10000 copies/ml. INTERVENTIONS: 3TC/ZDV with one of three doses of APV (900, 1050, or 1200 mg) versus 3TC/ZDV with 1050 mg placebo. All medications were dosed twice daily. The 1050 mg placebo and the APV 1050 mg dose were administered blinded. After 12 weeks, APV 1050 mg was substituted for 1050 mg placebo in the control group and the blind was maintained. MAIN OUTCOME MEASURES: Reduction in plasma HIV RNA from baseline; proportion of subjects with plasma HIV RNA < 400 copies/ml; and an increase in CD4 cell count from baseline. RESULTS: During the initial 12-week study period, APV/3TC/ZDV-treated subjects had greater viral suppression than the group receiving two nucleosides. By 48 weeks, 89% of subjects in the group taking the highest APV dose (1200 mg) had plasma HIV RNA < 400 copies/ml while 42% of the 900 mg group and 60% of the 3TC/ZDV group (1050 mg APV added at week 12) had plasma HIV RNA < 400 copies/ml using an as-treated analysis. By 60 weeks, 86% of subjects in the APV 1200 mg group had plasma HIV RNA < 400 copies/ml in the as-treated analysis, while 25% (900 mg), 43% (1050 mg), and 20% (1200 mg) of subjects had viral load <400 copies/ml in a strict intent-to-treat analysis owing to treatment discontinuations. Median CD4 cell count increases at week 60 were highest for the three treatment groups who received APV throughout the study, by intent-to-treat and as-treated analyses. The most common adverse events considered to be possibly drug related were nausea, rash, oral paresthesia, diarrhea, and fatigue. CONCLUSIONS: Treatment with APV, dosed at 1200 mg twice daily in combination with 3TC/ZDV, resulted in sustained viral suppression. This combination represents a potent alternative initial antiretroviral regimen for protease inhibitor-naive individuals.

Adult↗

Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women: a randomized trial.

CONTEXT: Enhancing participation in long-term exercise may translate into improved long-term weight loss in overweight adults. OBJECTIVES: To compare the effects of intermittent with traditional continuous exercise on weight loss, adherence, and fitness, and to examine the effect of combining intermittent exercise with that using home exercise equipment. DESIGN: Randomized trial from September 1996 through September 1998. SETTING AND PARTICIPANTS: A total of 148 sedentary, overweight (mean [SD] body mass index, 32.8 [4.0] kg/m2) women (mean [SD] age, 36.7 [5.6] years) in a university-based weight control program. INTERVENTIONS: Eighteen-month behavioral weight control program with 3 groups: long-bout exercise (LB), multiple short-bout exercise (SB), or multiple short-bout exercise with home exercise equipment (SBEQ) using a treadmill. MAIN OUTCOME MEASURES: Body weight, body composition, cardiorespiratory fitness, and exercise adherence. RESULTS: Of 148 subjects, 115 (78%) completed the 18-month program. At 18 months, mean (SD) weight loss was significantly greater in subjects in the SBEQ group compared with subjects in the SB group (-7.4 [7.8] kg vs -3.7 [6.6] kg; P<.05). Mean (SD) weight loss for subjects in the LB group (-5.8 [7.1] kg) was not significantly different than for subjects in the SB or SBEQ groups. Subjects in the SBEQ group maintained a higher level of exercise than subjects in both the SB and LB groups (P<.05) at 13 to 18 months of treatment. All groups showed an increase in cardiorespiratory fitness from baseline to 18 months, with no difference between groups. Mean (SD) weight loss at 18 months was significantly greater in individuals exercising more than 200 min/wk throughout the intervention (-13.1 [8.0] kg) compared with individuals exercising 150 to 200 min/wk (-8.5 [5.8] kg) or less than 150 min/wk (-3.5 [6.5] kg) (P<.05). CONCLUSIONS: Compared with the LB group, subjects in the SB group did not experience improved long-term weight loss, exercise participation, or cardiorespiratory fitness. Access to home exercise equipment facilitated the maintenance of SB, which may improve long-term weight loss. A dose-response relationship exists between amount of exercise and long-term weight loss in overweight adult women.

Adult↗

[Current therapy of cerebrovascular infarct].

In general, the acute treatment of ischemic stroke is intended to achieve three goals: a) reduce the volume of the infarct, b) prevent further embolism or thrombotic occlusion of vertebrobasilar or carotid arteries, and c) prevent or react quickly to complications. Methods to expedite clot lysis and restore circulation (thrombolysis) can limit the extent of brain injury and improve outcome. Further therapeutic aims are to optimize collateral perfusion in the penumbra--the area surrounding the core of the ischemic focus--and to reduce ischemia-related secondary injury mechanisms (neuroprotection). Patients at high risk of further embolism or those at risk of acute thrombotic occlusion of a major vessel may--under certain circumstances--be candidates for the application of high-dose heparin.

Acute Disease↗

Implicit memory within a word recognition task: an event-related potential study in human subjects.

First, we recorded brain potentials from 15 healthy young subjects during the performance of a word/non-word discrimination task. During continuous visual presentation, some of the meaningful words were repeated after 86-94 s. We found a significant decrease of response time associated with the classification of repeated words which is an index for priming, an unconscious brain process. However, event-related potentials (ERPs) did not differ significantly between first and second presentations. Second, we recorded brain potentials during a following recognition test. Some of the meaningful words which were presented only once during the semantic discrimination task were repeated and had to be discriminated from randomly interspersed new words. We compared ERPs produced by incorrectly classified repeated words (misses) with ERPs produced by correctly classified new words (correct rejections). We found early ERP differences between 250 and 400 ms and later differences starting at about 500 ms after the stimulus onset. The early effect occurred over parietal scalp locations and the later effect over frontal, parietal and occipital scalp locations. This is evidence for unconscious brain activity related to the processing of missed repeated words. We suggest that the later frontal effect we found is due to an enhanced effort of the retrieval of item representations during word recognition and that the earlier parietal effect reflects partial recognition.

Adult↗

Event-related potential correlates of false recognitions of faces.

In a recognition memory experiment we recorded event-related brain potentials (ERPs) following the presentation of faces. We compared correctly classified repetitions of faces (hits) with new faces classified as repeated (false alarms). Stimulus-related averaging yielded significantly more negative ERPs to false alarms between 750 and 900 ms after onset of stimulus presentation. With response-related averaging we found significantly more negative ERPs to false alarms within the last 100 ms before movement onset. The differential activity was distributed over central and frontal regions and was still present in the period after the response. We interpret the phenomenon as an electrophysiological manifestation of false recognition as described by Schacter et al. (Schacter, D.L., Norman, K.A. and Koutstaal, W., The cognitive neuroscience of constructive memory, Annu. Rev. Psychol., 49 (1998) 289-318). False recognition could be the result of a preliminary decision based on illusionary familiarity and be associated with post-retrieval processing.

Evoked Potentials↗

Substrate specificity and stereoselectivity of rat brain microsomal anandamide amidohydrolase.

Anandamide amidohydrolase (AAH) catalyzes the hydrolysis of arachidonylethanolamide (anandamide), an endogenous cannabinoid receptor ligand. To delineate the structural requirements of AAH substrates, rat brain microsomal AAH hydrolysis of a series of anandamide congeners was studied using two reverse-phase high-performance liquid chromatography (RP-HPLC) assays developed in our laboratory. Arachidonamide (1) was found to be the best substrate with an apparent Km of 2.34 mM and a Vmax of 2.89 nmol/min/mg of protein. Although anandamide (2) has a similar Km value, its Vmax is approximately one-half that of arachidonamide. N, N-Bis(2-hydroxyethyl)arachidonamide (3) was not hydrolyzed, suggesting specificity for unsubstituted or mono-N-substituted arachidonamides. Analogues with a methyl group at the 1'-position of the ethanolamido headgroup were also found to have greater resistance to enzymatic turnover and therefore increased metabolic stability. The enzyme exhibited high stereoselectivity as the rate of hydrolysis of (R)-alpha-methanandamide (2.4%) (anandamide = 100%) was about 10-fold lower than that of its (S)-enantiomer (23%). In contrast, (R)-beta-methanandamide was 6-times more susceptible (121%) than the (S)-beta-enantiomer (21%). Interestingly, an inverse correlation was shown between AAH stereoselectivity and the brain cannabinoid receptor affinity as the enantiomers with high receptor affinity displayed low susceptibility to hydrolysis by AAH. Metabolic stability is also imparted to analogues with a short hydrocarbon headgroup as well as to those possessing 2-monomethyl or 2,2-dimethyl substituents. 2-Arachidonylglycerol and racemic 1-arachidonylglycerol were shown to be excellent AAH substrates. To identify AAH inhibitors, hydrolysis of anandamide was also studied in the presence of a select group of cannabimimetics. Of these, (-)-Delta8-THC and SR141716A, a biarylpyrazole CB1 antagonist, were found to inhibit enzymatic activity. These newly defined enzyme recognition parameters should provide a foundation for the rational development of stable, therapeutically useful anandamide analogues with high receptor affinity.

Amidohydrolases↗

Weight loss and leptin changes in individuals with type 2 diabetes.

OBJECTIVE: To identify variables associated with leptin change in subjects with type 2 diabetes after 3 weeks and 20 weeks of weight loss. RESEARCH METHODS AND PROCEDURES: Subjects with type 2 diabetes treated with diet or sulfonylureas (n = 54) were enrolled in a 20-week behavioral weight control program. Sulfonylureas were stopped > or =2 weeks before study entry. Seven subjects who restarted sulfonylureas after week 3 had their data analyzed separately after this point. RESULTS: Leptin, fasting plasma glucose, and insulin levels were measured at baseline and at 3, 10, and 20 weeks. After 3 weeks, subjects lost 2.7+/-2.0 kg (p<0.001), and had significant decreases in leptin (5.2+/-7.0 ng/mL, p<0.001), fasting plasma glucose (1.8+/-1.8 mmol/L, p<0.001), and insulin (23+/-60 pmol/L, p<0.03). Between week 3 and week 20, subjects lost an additional 6.3+/-4.4 kg (p<0.001), but had no further changes in leptin. The primary determinants of leptin change at all time-points were weight loss and initial leptin level. Changes in insulin were not related to changes in leptin after controlling for the effects of weight loss. At week 20, more recent weight loss (week 10 to week 20) was as strong a predictor of overall change in leptin as overall weight loss (baseline to 20 week). Subjects who restarted sulfonylureas had an increase in both leptin levels (+1.9+/-9.0 ng/mL, p<0.05) and insulin levels (+23+/-65 pmol/L, p<0.05), despite significant overall weight loss (-7.4+/-4.0 kg, p<0.01). Initial changes in leptin (0 weeks to 3 weeks) did not affect subsequent ability to lose weight. DISCUSSION: Both short- and long-term changes in weight had an effect on leptin changes in individuals with type 2 diabetes. Although physiological insulin changes did not independently influence changes in leptin concentration with weight loss, increases in insulin levels with sulfonylurea therapy were associated with increases in leptin levels despite weight loss.

Adult↗

Neuroimage of voluntary movement: topography of the Bereitschaftspotential, a 64-channel DC current source density study.

The Bereitschaftspotential (BP) was recorded at 56 scalp positions when 17 healthy subjects performed brisk extensions of the right index finger. Aim of the study was to contribute to our understanding of the physiology underlying the BP and, in particular, to specify the situation at BP onset. For this purpose, the spatial pattern of the BP was analyzed in short time intervals (35 and/or 70 ms) starting 2.51 s before movement onset. For each time segment a spherical model of the BP was calculated by using spline interpolation. Then the spatial distribution of the electric potential at the scalp surface was transformed into a spatial distribution of current source densities (CSD map). Onset times of the BP and onset times of initial CSD-activity ranged between 2.23 and 1.81 s before movement onset. We selected a time window between 1.6 and 1.5 s before movement onset in order to analyze the spatial CSD pattern in each subject. In 10 subjects there was a significant current sink in the scalp area located over medial-wall motor areas (pre-SMA, SMA proper and anterior cingulate cortex: electrode positions C1, C2, FCz, Cz) in the absence of a significant current sink over the primary motor cortex (MI: electrode positions C3, CP3, and CP5). In three subjects significant current sinks were present at both sites and in another three subjects a current sink only over the lateral motor cortex was observed. In one subject no significant current sinks were measured. It is concluded that there is a large group of subjects (13/17) in whom BP at onset is associated with a current sink over medial-wall motor areas. At a later time interval (0.6 to 0.5 s before movement onset), significant current sinks were found in 13 subjects in medial and in 10 subjects in lateral recordings. These data were considered to be consistent with the hypothesis that, at least in a majority of subjects, medial-wall motor areas are activated earlier than lateral motor areas when organizing the initiation of a simple self-paced movement. Surface-recordings of the EEG do not allow further specification of cortical areas, which contribute to the current sinks. But in context with the current literature of the electrophysiology of nonhuman primates and of brain imaging in humans it is suggested that SMA and anterior cingulate cortex contribute to the current sink, the fronto-central midline, and that the primary motor cortex (MI) contributes to the current sink in the scalp area, which is located above MI and closely posterior to it.

Adult↗

Mental representations of movements. Brain potentials associated with imagination of eye movements.

OBJECTIVE: Current research in motor imagery is focused on similarities between actual and imagined movements on a central and a peripheral level of the nervous system. The present study measured slow cortical potentials (DC-potentials) during execution and internal simulation of memorized saccadic eye movements. METHODS: In 19 healthy righthanded subjects DC-potentials were recorded from 28 electrodes during execution and during imagination of a sequence of memorized eye movements during a visual imagery condition. RESULTS: Both oculomotor conditions showed a similar global level and similar topography of performance related DC-potentials, both strongly differed from the visual imagery condition and were lateralized to the left hemisphere. CONCLUSION: This study therefore supports the hypothesis that cortical brain structures responsible for execution and imagination of memorized saccadic eye movements are similar. The observed left hemispheric lateralization is in contrast to a previous study using bimanual movements. This discrepancy is discussed in relation to recent observations in apractic patients with parietal lesions.

Adult↗

Early occipito-parietal activity in a word recognition task: an EEG and MEG study.

OBJECTIVE: We investigated early brain activity (under 200 ms after the stimulus onset) related to the encoding and the retrieval of verbal information. METHODS: First, we compared ERPs produced by words which were encoded to ERPs produced by words from following test phases (correctly identified repetitions and correctly classified new words) in two different experiments. Experiment 1 consisted of an intentional learning paradigm and experiment 2 consisted of an incidental learning paradigm. In addition, we conducted a control experiment (experiment 3), which was a continuous recognition task with two different repetition intervals. Secondly, we conducted a magnetoencephalographic (MEG) study to further investigate early brain activity (experiment 4). The same intentional learning paradigm as in experiment 1 was used. RESULTS: We found that ERPs elicited by correctly classified test words (repeated words and new words) of both experiment 1 and experiment 2 were significantly more negative going than the ERPs elicited by the study words. This effect was apparent between 100 ms and 200 ms after the stimulus onset and was distributed over occipital and parietal scalp locations. In the control task (experiment 3), these early potential differences were missing (for both repetition intervals). Early event-related fields (ERFs) were also found to depend on the situation of the study phase and the test phase. This activity difference peaked at 120 ms after the stimulus onset. The distributions of the difference magnetic fields were occipito-parietal and thus consistent with the findings of experiment 1 (EEG-experiment). CONCLUSION: Whether the effect we defined in the present study is due to an increase of activity during the test situation or due to a decrease of activity during the study situation remains unclear. However, it might reflect attentional processes within a word recognition task depending on whether a word is encoded or an effort of word retrieval has to be made.

Adult↗

Extraanatomic bypass in the treatment of prosthetic vascular graft infection manifesting in the groin.

BACKGROUND: Infection of an alloplastic vascular graft is a serious complication and often involves the groin. We propose a therapeutic concept using extraanatomic bypass to avoid the septic groin in case of an infected alloplastic vascular reconstruction. PATIENTS AND METHODS: The course of 25 patients (18 men, 7 women, mean age 61 years) with a grade III inguinal infection following placement of an aortic or femoro-distal synthetic graft made of Dacron or PTFE was analysed. The treatment consisted of excision of the infected graft material and extraanatomic reconstruction with ringed PTFE grafts in all patients. Mean follow-up after the extraanatomic procedure was 21 months (1-91 months). RESULTS: Direct surgical exploration definitely secured graft infection in almost three-quarters of the cases. The most common organism isolated was Staphylococcus aureus (13/22 = 59%). At the time of infection 60% of the patients had critical limb ischemia necessitating vascular reconstruction simultaneously with total or partial excision of the infected graft. Complications of the extraanatomic bypass occurred in 7 cases (overall morbidity 28%). Postoperatively, one patient required major amputation. Hospital mortality was 8%. Primary patency and secondary patency rates of extraanatomic grafts amounted to 78.0% (+/- 10.0 SD) and 84.1% (+/- 8.7 SD) respectively after two years. Limb salvage rated 78.4% (+/- 11.6 SD) after 2 years, the 2-year-survival rate was 73.8% (+/- 9.3 SD). CONCLUSIONS: According to the favourable long-term limb salvage and survival rates, we support simultaneous vascular reconstruction by extraanatomic bypass and explanation of the infected graft material in case of grade III inguinal infection of alloplastic vascular reconstructions.

Aged↗