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Cerebral aneurysm growth is influenced by hemodynamical factors, which are commonly estimated by means of a computational fluid dynamics (CFD) model of a small 3D patient-specific segment of the arterial tree. Since direct in vivo assessment of the boundary conditions for the 3D segment is often not possible, the flow pulses are generally computed with a patient-generic 1D model. The aim of this study is to evaluate the necessity of, and requirements for, full patient-specific modeling, i.e., both geometry and boundary conditions based on patient data. The flow waveforms obtained with several models from literature and a patient-specific geometry of the arterial tree are compared and analysed. By comparing patient-specific and patient-generic models, it is investigated whether different but all reasonable modeling assumptions result in substantial differences in flow distribution. The flow pulses obtained at the boundaries of the arterial segment of interest are significantly affected by the 1D geometry and boundary conditions associated with the different modeling assumptions. The geometry as well as the in- and outflow conditions of the 1D model should be patient-specific, as they significantly influence the flow pulses to be prescribed at the boundaries of the 3D arterial segment. [ABSTRACT FROM AUTHOR]

Background.Microvascular compressions of the cochlear nerve can lead to hearing loss. Due to the tonotopic organization of the cochlear nerve any focal compression of the cochlear nerve will result in a frequency specific hearing loss. Decompressing the cochlear nerve could result in a frequency specific hearing improvement, without improving overall hearing.Method.Thirty one patients underwent microvascular decompression operations of the vestibulocochlear nerve for vertigo or tinnitus. Preoperative audiograms were substracted from postoperative audiograms obtained 2 years after microvascular decompression. The frequencies of maximal hearing improvement postoperatively were determined.Findings.Of the 31 patients studied, 19 had improvements of 5?dB or more at one or more frequencies postoperatively, and 15 patients had improvements of 10?dB or more. Three patients had improvements of 25?dB or more postoperatively. The postoperative hearing improvement was frequency-specific and related to the anatomical location of the vascular contact on the auditory nerve. The improvement of hearing becomes diluted when the difference between pre- and postoperative hearing thresholds are averaged over all audiometric frequencies. We therefore present results for each frequency that was tested.Conclusions. Microvascular decompression of the cochlear nerve can improve hearing in selected patients. The improvement seems too small to justify decompressive surgery for the sole purpose of hearing improvement, but it could be considered if associated short vertigo spells, ipsilateral tinnitus, otalgia and cryptogenic hemifacial spasm are present. Decompression should be performed early, before BAEP changes become noticeable. 3D-MRI could become a valuable tool for selecting good surgical candidates. [ABSTRACT FROM AUTHOR]

STUDY DESIGN::Survey. OBJECTIVES::Insight in (1) the changes in participation in vocational and leisure activities and (2) satisfaction with the current participation level of people with spinal cord injuries (SCIs) after reintegration in society. DESIGN::Descriptive analysis of data from a questionnaire. SETTING::Rehabilitation centre with special department for patients with SCIs, Groningen, The Netherlands. SUBJECTS::A total of 57 patients with traumatic SCI living in the community, who were admitted to the rehabilitation centre two to 12 years before the current assessment. MAIN OUTCOME MEASURES::Changes in participation in activities; current life satisfaction; support and unmet needs. RESULTS::Participation expressed in terms of hours spent on vocational and leisure activities changed to a great extent after the SCI. This was mainly determined by a large reduction of hours spent on paid work. While 60%of the respondents successfully reintegrated in work, many changes took place in the type and extent of the job. Loss of work was partially compensated with domestic and leisure activities. Sports activities were reduced substantially. The change in participation level and compensation for the lost working hours was not significantly associated with the level of SCI-specific health problems and disabilities. As was found in other studies, most respondents were satisfied with their lives. Determinants of a negative life satisfaction several years following SCI were not easily indicated. Reduced quality of life was particularly related to an unsatisfactory work and leisure situation. CONCLUSIONS::Most people with SCI in this study group were able to resume work and were satisfied with their work and leisure situation.Spinal Cord (2005) 43, 241-248. doi:10.1038/sj.sc.3101683; Published online 9 November 2004 [ABSTRACT FROM AUTHOR]

STUDY DESIGN:: Survey. OBJECTIVES:: To explore the process of reintegration in paid work following a traumatic spinal cord injury (SCI), including the role of early expectations of individual patients regarding return to work, indicators of success of job reintegration and a description of reintegration interventions and barriers. SETTING:: Dutch rehabilitation centre with special department for patients with spinal cord injuries. METHODS:: Descriptive analysis of data gathered by a mailed questionnaire, which was returned by 57 persons (response 83%) with traumatic SCI, aged 18-60 years, and data of earlier expectations reported by the individual patients during the rehabilitation admission following SCI from 1990 to 1998. RESULTS:: Of 49 respondents who were employed at the moment of the SCI, 45% expected to be able to resume work. These positive expectations were associated with a higher educational level. In 67%, return to work was successful. The chance to reintegrate successfully was better if the patient expected to resume work. Logistic regression analysis did not reveal other significant indicators. About one-third of the 49 respondents working preinjury followed vocational retraining, which was successful for most of them so far. In the majority of work situations modifications have been made, such as job adaptations and reduction of working hours. Several unmet needs regarding reintegration interventions were also reported. CONCLUSIONS:: Positive expectations regarding resumption of work after a SCI are an important indicator of successful reintegration in work. An active role of the rehabilitation team is recommended in drawing up a vocational reintegration plan to prepare the patient, the employer and professionals involved in the reintegration process.Spinal Cord (2004) 42, 177-184. doi:10.1038/sj.sc.3101581 Published online 3 February 2004 [ABSTRACT FROM AUTHOR]

A phase I dose-escalation study was performed to determine whether isolated hepatic perfusion (IHP) with melphalan (L-PAM) allows exposure of the liver to much higher drug concentrations than clinically achievable after systemic administration and leads to higher tumour concentrations of L-PAM. Twenty-four patients with colorectal cancer confined to the liver were treated with L-PAM dosages escalating from 0.5 to 4.0 mg kg[SUP-1]. During all IHP procedures, leakage of perfusate was monitored. Duration of IHP was aimed at 60 min, but was shortened in eight cases as a result of leakage from the isolated circuit. From these, three patients developed WHO grade 3-4 leukopenia and two patients died due to sepsis. A reversible elevation of liver enzymes and bilirubin was seen in the majority of patients. Only one patient was treated with 4.0 mg kg[SUP-1] L-PAM, who died 8 days after IHP as a result of multiple-organ failure. A statistically significant correlation was found between the dose of L-PAM, peak L-PAM concentrations in perfusate (R = 0.86, P ≤ 0.001), perfusate area under the concentration-time curve (AUC; R = 0.82,P < 0.001), tumour tissue concentrations of L-PAM (R = 0.83,P = 0.011) and patient survival (R = 0.52,P = 0.02). The peak L-PAM concentration and AUC of L-PAM in perfusate at dose level 3.0 mg kg[SUP-1](n = 5) were respectively 35- and 13-fold higher than in the systemic circulation, and respectively 30- and 5-fold higher than reported for high dose oral L-PAM (80-157 mg m[SUP-2]) and autologous bone marrow transplantation. Median survival after IHP (n = 21) was 19 months and the overall response rate was 29% (17 assessable patients; one complete and four partial remissions). Thus, the maximally tolerated dose of L-PAM delivered via IHP is approximately 3.0 mg kg[SUP-1], leading to high L-PAM concentrations at the target side. Because of the complexity of this treatment modality, IHP has at present no place in routine clinical practice. [ABSTRACT FROM AUTHOR]

STUDY DESIGN:: Descriptive analysis of data gathered in an information system. OBJECTIVES:: To explore the predictions of professionals and patients regarding functional outcome after spinal cord injury related to the final results after inpatient rehabilitation, in order to make prognostics of rehabilitation outcome more successful and enlarge the role of the patient in selecting realistic rehabilitation goals. METHODS:: Data from 55 patients with spinal cord injury admitted to the rehabilitation centre. Expectations of the rehabilitation team and the patients regarding future independence in performing six daily activities were compared to the functional results at discharge. The results of patients with different level and extent of lesion were analyzed. RESULTS:: In 52% of all performed skills, independence was achieved at discharge. Professionals and patients made similar predictions. If they both expected independence after rehabilitation, 90% of the skills were performed independently at discharge. If they both did not expect independence only 3% of the functional results were positive. Of all combined predictions 64% was correct. Correct predictions were most often found regarding self-care skills of patients with paraplegia and regarding mobility of patients with complete lesions. Prediction of self-care outcome of patients with tetraplegia is far more complicated. There was a considerable variation in predictions of mobility potential, especially regarding patients with incomplete lesions. If the team and patients agreed upon expected independence in mobility skills of these patients, the final results were mostly positive. CONCLUSIONS:: Prediction of functional outcome after spinal cord injury was most successful if the expectations of the team and patients were combined. Prognosis of self-care outcome of patients with paraplegia and mobility potential of patients with complete spinal cord lesions was usually clear at admission. However, selection of... [ABSTRACT FROM AUTHOR]

Purpose: Glutathione (GSH) plays an important role in the resistance of tumors to cytostatics. Therefore, depletion of GSH by the GSH synthesis inhibitor buthionine sulfoximine (BSO) has been proposed to enhance the efficacy of certain anticancer agents. We studied the effect of BSO in rats bearing intrahepatically implanted tumors of the CC531 colorectal cancer cell line on the antitumor activity of melphalan (L-PAM). Since these liver tumors tend to derive most of their blood supply from the hepatic artery, we evaluated whether delivery of BSO into the hepatic artery would more selectively decrease GSH levels in the implanted tumor tissue as compared with normal liver and extrahepatic tissues.Methods: Tumor-bearing rats were treated with a 24-h continuous infusion of 0.375 mmol/ kg BSO via the jugular vein, immediately followed by a bolus L-PAM (15 micromol/kg; 4.5 mg/kg) infusion via the hepatic artery. Laparotomy was performed on day 14 and 28 after treatment for measurement of the liver tumors. For the evaluation of locoregional administration of BSO, a 24-h continuous infusion of 0.375 mmol/kg BSO was delivered into either the hepatic artery, the portal vein, or the jugular vein in freely moving rats and GSH levels in the tumor, liver, kidney, lung, heart, bone marrow, and blood were measured.Results: BSO infusion via the jugular vein increased the antitumor efficacy of L-PAM injected into the hepatic artery 2-fold as determined at 14 days after treatment. Although infusion of BSO via the hepatic artery depleted GSH more severely in the tumor as compared with jugular vein or portal vein administration, the additional effect was only slight (10%). No difference was observed in any other tissue.Conclusion: GSH depletion increased the cytostatic efficacy of L-PAM 2-fold in vivo as determined at 14 days after treatment. Hepatic artery infusion of BSO translated into a statistically significant, but probably not therapeutically relevant, increase in tumor GSH depletion as compared with the other routes of BSO administration. [ABSTRACT FROM AUTHOR]

Dose-dependent effects of intravenously administered lorazepam on haemodynamic fluctuations were studied by means of spectral analysis, in order to elucidate sympathetic and parasympathetic components in cardiovascular control during situations of rest and mental stress after benzodiazepine administration. In a double-blind randomized cross-over study, nine male volunteers participated in two sessions: a placebo and lorazepam session. During these sessions, the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.06, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). During the placebo session the subjects received five placebo injections. For five of the nine subjects the lorazepam session was their first session. Heat rate (HR), blood pressure (BP) and respiration were recorded continuously. Power spectra were calculated per 2.5-min periods for HR, systolic (SBP) and diastolic BP (DBP). Spectral density was assessed for three frequency bands: low (LFB: 0.02-0.06 Hz), mid (MFB: 0.07-0.14 Hz) and high (HFB: 0.15-0.40 Hz). During the consecutive periods of rest, lorazepam induced a dose-dependent decrease in HR, and a dose-dependent increase in LFB, MFB and HFB power of HR, but lorazepam had no effect on BP. The effects were significant after 0.44 mg lorazepam for HR and HFB power, and after 0.94 mg lorazepam for the HR fluctuations in the LFB and MFB. Lorazepam did not influence the cardiovascular responses to the CWT. Our data underline that benzodiazepines can exert a specific influence on parasympathetic activity: lorazepam induced dose-dependent increases in cardiac vagal tone, resulting in decreased HR and increased HR variability, but only during periods of rest. The increase in vagal tone observed after low doses of lorazepam was not related to diminished sympathetic activity, altered respiration, or increased sedation. [ABSTRACT FROM AUTHOR]

Within the Center for Bio-Pharmaceutical Sciences research on toxicology has its main object in toxification and detoxification of xenobiotics. The pharmacokinetics of sulfation, glucuronidation and other conjugation reactions is studied. Conjugation may prevent tissue damage that is caused by covalent binding of reactive intermediates. Systems for testing the toxicity of such intermediates are being developed, and a similar screening programme is pursued for elucidating the involvement of reactive intermediates in carcinogenesis. [ABSTRACT FROM AUTHOR]

In the rat d-tubocurarine is taken up by the liver and excreted in bile. A fraction of the drug is taken up very rapidly by lysosomes. This lysosomal localization of the drug was demonstrated by purification of Triton WR 1339 loaded lysosomes ('tritosomes') on a sucrose density gradient by flotation; H-labeled d-tubocurarine was accumulated in the same fractions as acid phosphatase activity. Lysosome-bound d-tubocurarine is not available for biliary excretion and remains in the lysosomes even when the cytosolic concentration decreases to very low levels. The biliary excretion rate was linearly related to the amount of d-tubocurarine present in the cytosol. Lysosomal uptake of d-tubocurarine was decreased or prevented by the basic drug quinacrine in vivo. The lysosomal storage of d-tubocurarine is discussed in relation to its relevance for the clinical use of this and related drugs. [ABSTRACT FROM AUTHOR]

Motor processes partly determine reaction time (RT) in both choice reaction time and in binary classification tasks. These latter tasks are popular in cognitive psychology because the experimenter believes that he has kept the motor component simple and constant and therefore can attribute changes in RT to perceptual or cognitive processes. In this paper we used the P3 component of the event-related potential (ERP) as a time marker indicating the duration of perceptual and cognitive processes. The latency of this component is believed to reflect stimulus evaluation time independent of response selection and organization time. Two types of tasks were used: a choice-reaction time task and a binary classification task. Signal similarity and S-R compatibility additively affected RT, but only signal similarity affected P3 latency. The number of items in the positive set and response type affected both P3 latency and RT. Relative response frequency changed the bias in the cognitive evaluation of the stimulus, reflected in the latency of the P3 component, and affected RT only if the subjects preset their motor system (indexed by the late CNV). A model was presented which proposes that motor processes may partially overlap with the perceptual and cognitive evaluation of the stimulus. Both ERPs and RT are necessary tools in the study of the relative timing of these processes. [ABSTRACT FROM AUTHOR]

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A very simple and rapid technique for inserting a catheter in the portal vein and the hepatic vein in the anesthesized rat in vivo is described. The pointed, saline-containing PE tubing is frozen in liquid nitrogen, whereupon it is used as a 'needle' to insert the catheter into the blood vessel. Multiple blood samples can be obtained from the portal and the hepatic vein at the same time, so that in situ extraction of drugs by the liver can be measured in vivo, since hepatic blood flow is uninterrupted. [ABSTRACT FROM AUTHOR]