Search PubMed⌕ Search

Biomedical subjects

W Lang

Publications and source records attributed to W Lang.

At least 109 records · Page 6Linked to original sources
PubMed1999

What predicts weight regain in a group of successful weight losers? .

This study identified predictors of weight gain versus continued maintenance among individuals already successful at long-term weight loss. Weight, behavior, and psychological information was collected on entry into the study and 1 year later. Thirty-five percent gained weight over the year of follow-up, and 59% maintained their weight losses. Risk factors for weight regain included more recent weight losses (less than 2 years vs. 2 years or more), larger weight losses (greater than 30% of maximum weight vs. less than 30%), and higher levels of depression, dietary disinhibition, and binge eating levels at entry into the registry. Over the year of follow-up, gainers reported greater decreases in energy expenditure and greater increases in percentage of calories from fat. Gainers also reported greater decreases in restraint and increases in hunger, dietary disinhibition, and binge eating. This study suggests that several years of successful weight maintenance increase the probability of future weight maintenance and that weight regain is due at least in part to failure to maintain behavior changes.

Adult↗
PubMed1999

Development of a parenteral formulation of an investigational anticancer drug, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone.

The objective of this study was to develop an injectable formulation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) suitable for intravenous infusion. The solubility of 3-AP in different solvents and pH conditions was determined. The developed formulation underwent stability assessment and compatibility testing with large volume parenteral (LVP) solutions. The aqueous solubility of 3-AP was found to be 0.1 mg/ml and could only be increased marginally by altering the pH or adding surfactants. To achieve the desired concentration (> 4 mg/ml), 3-AP was formulated at 5-10 mg/ml in a nonaqueous system consisting of 70% polyethylene glycol 300 and 30% ethanol. However, 3-AP readily precipitated from this formulation when diluted with LVP solutions. Dilution-induced drug precipitation was eliminated by acidifying the solution with citric acid. Ascorbic acid, 0.1%, was found to minimize oxidative degradation of 3-AP. Accelerated stability data indicated that the formulation is compatible with the packaging components and is chemically stable at 2-8 degrees C, and retained > 90% of 3-AP at 40 degrees C for 3 months. Simulated infusion studies showed that the citric acid formulation was compatible with LVP solutions. However, because of the potential of extraction of plasticizers from polyvinyl chloride (PVC) plastic containers, it is recommended that the formulation be diluted in glass containers prior to administration.

Antineoplastic Agents↗
PubMed1999

Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial.

BACKGROUND: The positive association between body weight and bone mineral density (BMD) is well documented; in contrast, the effect of changes in body weight on BMD is not well understood, particularly, in normal-weight populations. OBJECTIVE: We examined the effect of a lifestyle intervention aimed at lowering dietary fat intake and increasing physical activity to produce modest weight loss or prevent weight gain on BMD in a population of 236 healthy, premenopausal women aged 44-50 y. DESIGN: All women were participating in a clinical trial known as The Women's Healthy Lifestyle Project and were randomly assigned to intervention or control groups. Dual-energy X-ray absorptiometry of BMD at the lumbar spine and proximal femur were made before and after 18 mo of participation in the trial. RESULTS: The intervention group (n = 115) experienced a mean (+/-SD) weight loss of 3.2 +/- 4.7 kg over the 18 mo compared with a weight gain of 0.42 +/- 3.6 kg in the control group (n = 121) (P < 0.001). The annualized rate of hip BMD loss was 2-fold higher (P < 0.015) in the intervention group (0.81 +/- 1.3%) than in the control group (0.42 +/- 1.1%); a similar, although nonsignificant pattern was observed for the loss in spine BMD: 0.70 +/- 1.4% and 0.37 +/- 1.5% (P = 0.093) in the intervention and control groups, respectively. Large increases in physical activity attenuated spine BMD loss, but had no significant effect on BMD loss at the hip. CONCLUSIONS: The intervention group, who modified their lifestyle to lose weight, had a higher rate of BMD loss at the hip and lumbar spine than did the weight-stable control group. Recommendations for weight loss must be made with consideration that such an endorsement may result in BMD loss.

Adult↗
PubMed1999

Bilateral subthalamic nucleus stimulation improves frontal cortex function in Parkinson's disease. An electrophysiological study of the contingent negative variation.

Parkinson's disease involves impaired activation of frontal cortical areas, including the supplementary motor area and prefrontal cortex, resulting from impaired thalamocortical output of the basal ganglia. Electrophysiologically, such impaired cortical activation may be seen as a reduced amplitude of the contingent negative variation (CNV), a slow negative potential shift reflecting cognitive processes associated with the preparation and/or anticipation of a response. Surgical interventions aimed at increasing basal ganglia-thalamic outflow to the cortex, such as electrical stimulation of the subthalamic nucleus with chronically implanted electrodes, have been shown to be effective in improving the clinical symptoms of Parkinson's disease. This study examined changes in cortical activity, as reflected in the CNV, associated with bilateral subthalamic nucleus stimulation in Parkinson's disease. The CNV was recorded from 10 patients with Parkinson's disease when on and off bilateral subthalamic nucleus stimulation, and was compared with the CNV of 10 healthy control subjects. Without subthalamic nucleus stimulation, Parkinson's disease patients showed reduced CNV amplitudes over the frontal and frontocentral regions compared with control subjects. With bilateral subthalamic nucleus stimulation, however, CNV amplitudes over the frontal and frontocentral regions were significantly increased. Results therefore suggest that impaired cortical functioning in Parkinson's disease, particularly within the frontal and premotor areas, is improved by subthalamic nucleus stimulation.

Adult↗
PubMed1999

Colonic primary large cell lymphoma with marginal zone growth pattern presenting as multiple polyps.

We report a rare case of primary gastrointestinal lymphoma, stage IE, in a 58-year-old white man who had multiple colonic polyps measuring up to 1 x 1.1 cm. The tumor originated in the marginal zone of the follicles infiltrating the interfollicular spaces. Follicular colonization was frequently seen. The mucosa was spared by the infiltrate. Morphologically, the neoplastic cells were monomorph, intermediate-sized blasts. Rare small to intermediate sized cells, some with centrocyte-like morphology, intermingled the blastic infiltrate. The neoplastic cells expressed CD20 and had a monotypic immunoglobulin of cytoplasmic IgM (kappa) on paraffin sections. Tumor cells stained negative for CD45RO, CD5, CD10, IgD, and CD23. Polymerase chain reaction revealed a clonal V-D-J rearrangement. Bcl-1 and bcl-2 rearrangement were not detected. We therefore suggest the diagnosis of primary large cell lymphoma with marginal zone growth pattern mimicking colonic adenomas.

Antigens, CD↗
PubMed1999

Inhibitory effects of trospium chloride on cytochrome P450 enzymes in human liver microsomes.

Trospium chloride, an atropine derivative used for the treatment of urge incontinence, was tested for inhibitory effects on human cytochrome P450 enzymes. Metabolic activities were determined in liver microsomes from two donors using the following selective substrates: dextromethorphan (CYP2D6), denitronifedipine (CYP3A4), caffeine (CYP1A2), chlorzoxazone (CYP2E1), S-(+)-mephenytoin (CYP2C19), S-(-)-warfarin (CYP2C9) and coumarin (CYP2A6). Incubations with each substrate were carried out without a possible inhibitor and in the presence of trospium chloride at varying concentrations (37-3000 microM) at 37 degrees in 0.1 M KH2PO4 buffer containing up to 3% DMSO. Metabolite concentrations were determined by high-performance liquid chromatography (HPLC) in all cases except CYP2A6 where direct fluorescence spectroscopy was used. First, trospium chloride IC50 values were determined for each substrate at respective K(M) concentrations. Trospium chloride did not show relevant inhibitory effects on the metabolism of most substrates (IC50 values considerably higher than 1 mM). The only clear inhibition was seen for the CYP2D6-dependent high-affinity O-demethylation of dextromethorphan, where IC50 values of 27 microM and 44 microM were observed. Therefore, additional dextromethorphan concentrations (0.4-2000 microM) were tested. Trospium chloride was a competitive inhibitor of the reaction with Ki values of 20 and 51 microM, respectively. Thus, trospium chloride has negligible inhibitory effects on CYP3A4, CYP1A2, CYP2E1, CYP2C19, CYP2C9 and CYP2A6 activity but is a reasonably potent inhibitor of CYP2D6 in vitro. Compared to therapeutic trospium chloride peak plasma concentrations below 50 nM, the 1000-times higher competitive inhibition constant Ki however suggests that inhibition of CYP2D6 by trospium chloride is without any clinical relevance.

Benzilates↗
PubMed1999

Physiological HEPES buffer proposed as a calibrator for pH measurement in human blood.

N-(2-hydroxyethyl)-piperazine-N'-2-ethanesulfonic acid, known as HEPES buffer, with pK in the physiological range was studied for use as an alternative to conventional phosphate buffer for the calibration of pH in modern clinical analyzers. In different series of aqueous equimolar HEPES buffer, pH was measured at 37 degrees C with a capillary glass electrode standardized previously using phosphate, and variations due to changes in total HEPES buffer concentration (0.025 to 0.320 mol/l), and NaCl (0 to 0.250 mol/l) were monitored. For 0.05 equimolar HEPES buffer without NaCl, the pH of 7.362+/-0.003 (n = 15) obtained coincided well with the reference pH (7.364) from the National Institute of Standards and Technology (NIST). In particular, in the preferred 0.05 equimolar HEPES buffer/0.110 mol/l NaCl, which is isotonic to human plasma (0.160 mol/l), and termed physiological HEPES buffer (PHB), the pH of 7.346+/-0.003 (n = 84) can be related to the calculated corresponding reference pH from NIST without liquid junction (7.374), and is also compatible with the pH measured in normal arterial blood, pH = 7.403+/-0.003 (n = 20). Hence, in the two-point calibration of clinical analyzers, PHB, which is defined operationally with respect to the glass electrode and to phosphate buffer, may be useful as a calibrator in the range of buffer adjustment control to meet the correct values for pH when measuring in blood. Whereas Na-HEPES salt is hygroscopic and does not meet the declared purity grade (> 99%), pure HEPES acid is non-hygroscopic and conforms to the manufacturer's purity grade (> or = 99%). Therefore, for easy preparation of PHB, HEPES acid is the preferred starting material.

Blood Chemical Analysis↗
PubMed1999

Contrast enhanced MRA of peripheral arteries with the automatic "floating table".

Magnetic resonance angiography (MRA) is increasingly used as a non-invasive alternative to digital subtraction angiography (DSA). Besides plain time-of-flight (TOF) and phase contrast (PC) MRA a new MRA technique using positive contrast agent has been introduced recently. A fast 3D gradient-echo sequence is applied to reach a significant reduction of measurement time for acquisition of the MRA within the first pass of the contrast agent, thereby avoiding venous overlap. A significant progress was yielded by MR systems allowing manual table movement for examination of the pelvis and the lower limbs in one examination with a single contrast agent bolus. However, in this case it is necessary to have a coworker in the examination room moving the table manually. In this paper we report a prototype system which allows automatic table movement ("floating table"). Using this novel system we examined a patient with an aneurysm of the abdominal aorta and peripheral arterial occlusive disease (PAOD). Diagnostic results of contrast enhanced MRA and DSA were equivalent. In summary, the automatic floating table system introduced in this paper allows comfortable non-invasive examination of pelvic and lower limb arteries. The value of this technique in comparison to DSA has to be determined in future studies.

Arterial Occlusive Diseases↗
PubMed1999

Gd-BOPTA: "the MRA contrast agent of choice"?

Gd-BOPTA is a new positive MR contrast agent for intravenous application. In comparison to other gadolinium-chelates it has a nearly two-fold increased relaxivity due to weak protein binding with plasmatic macromolecules. In the papers published yet it has been evaluated to be useful for liver imaging. The purpose of this study was to evaluate, whether Gd-BOPTA is suited as an "magnetic resonance angiography (MRA) contrast agent". We examined four patients (aortic dissection, carotid artery stenosis, portal vein stenosis, exclusion of subclavian artery stenosis) with Gd-BOPTA with a dosage of 0.05 mmol/kg body weight. Furthermore, peripheral MRA of the pelvis and lower extremities was acquired in two healthy volunteers comparing 0.1 mmol Gd-DTPA/kg with 0.1 mmol Gd-BOPTA/kg. There was a delay of one week between the Gd-DTPA and the Gd-BOPTA examinations. In another volunteer Gd-BOPTA was reduced to 0.05 mmol/kg. The patient examinations revealed sufficient quality comparable with Gd-DTPA examinations despite of reduced dosage. In the volunteers Gd-BOPTA proved to be superior especially in the delineation of small pedal arteries which is important for surgical planning. These preliminary results demonstrate the potential of Gd-BOPTA to become a useful contrast agent for MRA. Its efficacy for this purpose has to be evaluated in future prospective studies.

Aortic Valve Stenosis↗
PubMed1999

[Ischemic stroke: new therapeutic possibilities].

Recent randomized placebo-controlled studies have introduced new concepts in the therapy of acute ischemic stroke, such as thrombolysis either with intraarterial or intravenous administration, lowering of the level of fibrinogen or administration of aspirin. High dosis of heparin may be useful only in certain groups of patients. Stroke units proved to be effective in the acute care of stroke patients. Further advances are achieved by the introduction of new anti-platelet drugs in secondary stroke prevention and by precise definitions of the criteria for carotid surgery.

Anticoagulants↗
PubMed1998

[Heparin-induced thrombocytopenia type II. Intra- and postoperative lepirudin treatment in acute ischemia of the extremities].

HISTORY AND ADMISSION FINDINGS: A 60-year-old woman was admitted because of acute ischemia of the right leg. The patient had been immobilized during diagnostic procedures for a thoracic paraspinal space-occupying lesion and over 5 days had received unfractionated sodium heparin by subcutaneous injection. The pedal pulses were no longer palpable. INVESTIGATIONS, DIAGNOSIS AND TREATMENT: The thrombocyte count had fallen from 207,000/microliter to 45,000/microliter. Angiography revealed occlusion of the common femoral artery. Heparin-induced platelet aggregation (HIPA) test demonstrated type II heparin-induced thrombocytopenia. Thrombectomy was performed and intraoperatively an i.v. bolus of the recombinant hirudin, lepirudin (Refludan), was given (0.2 mg/kg body weight), continual lepirudin infusion being continued postoperatively. Normal blood flow was re-established in the limb and the pedal pulse was palpable. There were no complications. CONCLUSION: Recombinant hirudin is the only alternative licensed in Germany to heparin and seem to be suitable also for the intraoperative bolus administration in heparin-induced thromboembolic vascular occlusions.

Angiography, Digital Subtraction↗
PubMed1998

Determination of anandamide amidase activity using ultraviolet-active amine derivatives and reverse-phase high-performance liquid chromatography.

Anandamide amidase catalyzes the hydrolysis of anandamide (AEA) to arachidonic acid (AA) and ethanolamine (EA). Recently, we published a method for determining anandamide amidase activity based on the measurement of arachidonic acid with direct UV detection at 204 nm. However, this method cannot be used to determine the hydrolysis of non-UV-active AEA analogs. It also cannot be used to study AEA amidase inhibitors that contain the arachidonic acid tail, and which are also enzyme substrates. Here we report a novel, more general method for measuring amidase activity by o-phthaldialdehyde (OPA) precolumn derivatization and reverse-phase high-performance liquid chromatography (HPLC). The hydrolysis product, ethanolamine, after separation from protein was derivatized with OPA to form a UV-active isoindole derivative which was then detected at 230 nm. The detection limit for derivatized ethanolamine was 1.0 pmol and retention times were typically less than 8 min. Our new method can detect non-UV-active analogs through derivatization of the amine product. It can thus be used after careful selection of the HPLC conditions in competition experiments between AEA and AEA analogs possessing different head groups. The most effective competitive inhibitor tested was (R)-N-(1-methyl-2-hydroxyethyl)arachidonylamide (AM356), which is resistant to enzymatic hydrolysis and yet inhibits AEA hydrolysis in a competition experiment by 43%. Moreover, this method offers several advantages over existing methodologies using radioisotopes or solvent extraction procedures. Our work to date has shown that small structural changes in the AEA molecule can result in significant variation in both affinity and turnover rate for each analog with respect to AEA amidase.

Amidohydrolases↗
PubMed1998

Solubility of NH3 and apparent pK of NH4+ in human plasma, isotonic salt solutions and water at 37 degrees C.

The solubility of ammonia, alphaNH3 (mM/mmHg), was determined at 37 degrees C and low ammonia partial pressure (0.02-1 mmHg) in pure water (n =24) as 46.70+/-0.40; aqueous isotonic salt solutions (n = 7) as 46.8+/-0.81; and human plasma (n = 5) as 42.0+/-0.66. The last figure increases to 45.3+/-0.63 if expressed in molal units (mmol/kg plasma water x mmHg) instead of molarity with respect to the water content of the plasma (mean from four healthy and fasting donors: 0.908+0.005 kg H2O/kg plasma; mean density at 37 degrees C: 1.020+/-0.002 kg/l). In pure water, the solubility value is the mean of three different methods: (a) extrapolation of the salting-out effect of ammonia in aqueous NaOH to zero concentration; (b) slope of Henry-Dalton's law and (c) directly measured in pure water and 0.001 M aqueous NaOH. Based on the Henderson-Hasselbalch equation for the system NH4/NH3 in isotonic salt solutions and human plasma, both constants, apparent pK and solubility, can be derived from total ammonia concentration and pH at equilibrium with defined ammonia gas phase, if additionally the concentration of NH4 or NH3 is known. This was verified, in the first case, by determining the concentration of NH4+ by the experimental conditions, and in the second, by two measurements of total ammonia concentration at two different pH values. Total ammonia concentration was measured by a specific enzymatic standard test and pH with the glass electrode. The mean apparent pK was 8.968+/-0.013 in isotonic salt solutions (n = 7), and in human plasma (n = 10) it was 9.014+/-0.033.

Ammonia↗
PubMed1998

Early cortical activation indicates preparation for retrieval of memory for faces: an event-related potential study.

Event-related brain potentials (ERPs) were used to investigate the time course of memory processes following the presentation of faces. Following a phase in which subjects were asked to memorize faces presented on a computer screen (study phase) they had to distinguish the previously presented faces from others new to the experiment (test phase). We found that in a time period from 250 to 350 ms after onset of stimulus presentation ERPs show higher negativity for both repeated and novel faces in the test phase compared to the study phase. This situation dependent effect is most pronounced in occipito-temporal regions. We conclude that memory retrieval for faces is a sequential process. The early part of this process constitutes preparation for the retrieval of stored information, and a later part of the process comprises the discrimination between repeated and novel faces.

Adult↗
PubMed1998

The mode of movement selection. Movement-related cortical potentials prior to freely selected and repetitive movements.

In two previous studies, the readiness potential (RP) has been reported to be influenced by the mode of movement selection. Freely selected movements were found to have a higher RP amplitude than fixed repetitive movements. This was attributed to the higher demands on planning for the performance of freely selected movements. However, movements in the free mode are distinct from movements in the fixed mode in more than one respect. For example, they are also associated with a higher degree of alteration of the side and/or the finger of movement execution and hence serial "novelty" across blocks of trials. The aim of our study was to establish whether the greater novelty of movements in the free mode could also contribute to the enhanced RP amplitude of movements in the free mode of movement selection by comparing free versus fixed movements performed in long and short sequences that differ in terms of serial novelty. The RP was recorded in 31 healthy young subjects with electrodes placed over Fz, C3, Cz, C4 and Pz. Two types of movement were studied: randomly chosen button presses with right or left index or middle finger (free mode), and repetitive pressing of a predetermined button (fixed mode). We found that: (1) in confirmation of previous studies, the amplitude of the RP was higher for freely selected than free movements; (2) the effect of the mode of movement selection was present over central electrodes but was most pronounced for parietal electrode Pz, with movements in the free mode showing the earliest and greatest increase in negativity at this site; (3) this parietally enhanced negativity in free compared with the fixed mode was absent after the subjects had performed a block of long movement sequences, suggesting that serial novelty of movements also contributed to the effect of mode on the RP amplitude; (4) both the latency and the magnitude of the lateralized readiness potential (LRP) were altered by the mode of movement selection. Movements in the free mode showed an earlier onset of the LRP, which had a higher peak than the LRP prior to movements in the fixed mode. This effect was mainly due to an increased amplitude of the RP over the electrode contralateral to the side of movement prior to freely selected movements. These findings are discussed in relation to previous RP and positron emission tomography studies.

Adult↗
PubMed1998

Language-related hemispheric asymmetry in healthy subjects and patients with temporal lobe epilepsy as studied by event-related brain potentials and intracarotid amobarbital test.

There are current attempts to replace the WADA test for pre-surgical evaluation of hemispheric language capabilities by one of the methods of functional brain imaging. Recent PET and fMRI studies using verbal cognitive tasks like verb generation, semantic monitoring or semantic ('deep') encoding of words showed asymmetries of activation in the fronto-lateral cortex. In a previous ERP study subjects were required to indicate whether pronounceable non-words and abstract geometric figures were presented for the first time ('new item') or whether they had been shown before ('old item'). Group analyses of this study showed significant material-specific hemispheric asymmetries with ERPs being more negative-going in recordings of the posterior part of the left hemisphere with verbal material (CP5/6) but more negative-going in recordings of the right hemisphere with the spatial material (P7/8). The aim of the present study was to test statistically ERP lateralization effects in individual healthy subjects as well as WADA-tested patients suffering from seizures of the mesio-temporal lobe (MTL). In all subjects ERP lateralization with verbal material was tested in the electrode pair CP5/6, and ERP lateralization with figures in the electrode pair P7/8. Statistical analyses of single trials showed that in 20 out of 24 subjects ERPs with verbal material started to be more negative-going in CP5 as compared to CP6 in the period between 100 and 200 ms after stimulus onset or the subsequent time epoch (200-300 ms). In one subject not CP5/6 but the closely adjacent electrode pair P7/P8 showed this verbal material-related hemispheric effect. In patients language dominance as indicated by ERPs was not always consistent with the data of the WADA test. In one patient with left MTL seizures ERPs with verbal material and figures were found to be significantly lateralized to the right hemisphere although the WADA test assigned this patient to have a language-dominant left hemisphere.

Adult↗
PubMed1998

Event-related potentials in patients with temporal lobe epilepsy reveal topography specific lateralization in relation to the side of the epileptic focus.

Event-related potentials (ERPs) were recorded during a continuous recognition memory paradigm in patients with left-sided (LTLE; n = 8) or right-sided temporal lobe epilepsy (RTLE; n = 6), and in healthy control subjects (n = 24). Control subjects and both patient groups exhibited consistent OLD/NEW ERP-differences from 200-600 ms after stimulus onset. ERPs did not differ significantly between LTLE and RTLE patients, with respect to OLD/NEW distinction or the type of presented material (verbal vs. non-verbal). However, ERP topography showed significant differences between LTLE and RTLE patients: in lateral fronto-temporal recordings, patients showed larger negativities contralateral to the seizure focus, whereas we found larger negativities ipsilateral to the seizure focus in parietal recordings. Differences between the groups were significant from 300 to 600 ms post-stimulus. As a consequence, the amplitude gradient from fronto-temporal to parietal recordings was higher on the right side in LTLE patients and on the left side in RTLE patients. Again, differences between LTLE and RTLE patients were highly significant. We assume that ERPs reflect disturbances of a cortico-cortical network dependent on the side of the seizure focus in temporal lobe epilepsy. Furthermore, scalp-recorded ERPs might be a useful tool in the prediction of the side of the seizure focus in patients with temporal lobe epilepsy.

Adult↗