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  • 1
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Indications of a genetic predisposition to nicotine dependence have been derived from numerous epidemiological data and from individual genetic studies suggesting the involvement of the dopaminergic D2 receptor. Previous association studies defined the TaqlA polymorphism as a risk factor for addiction, in particular for alcoholism and tobacco dependence. Results of investigations into this polymorphism in 110 severely addicted smokers and a control group of 60 population-matched German non-smokers did not support these findings. However, our results indicate an association between the DRD2-Fokl-1 allele and the onset and intensity of smoking.
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen, Denmark : Munksgaard International Publishers
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Low vitamin A levels have been found in a number of diseases in children. The aim of this study was to examine the vitamin A status in children with asthma and to correlate the changes with severity of disease. Serum levels of vitamin A, retinol-binding protein (RBP), and albumin were estimated in 35 asthmatic children (24 males) in the age group of 2–12 years (mean 5.89 years) and 29 controls (19 males). Both study and control groups were similar with respect to age, sex, and overall nutritional status. Twenty-four children in the study group (68.6%) had moderate to severe persistent asthma and eight children had mild persistent asthma. Only three patients suffered from mild intermittent asthma. Vitamin A levels in children with asthma (mean ± SD 22.14 ± 5.38 µg/dl) were found to be significantly lower than their controls (mean ± SD 27.54 ± 4.83 µg/dl) (p = 0.0001). Age, age of onset of asthma, and gender had no correlation with serum vitamin A levels. Low serum vitamin A levels (〈 20 µg/dl) were observed four times more commonly in the study group (28.6%) than controls (6.9%). Severity of asthma had a negative correlation with serum vitamin A levels (r = − 0.61, p = 0.0001). Children with severe persistent asthma had markedly low serum vitamin A levels (mean ± SD 13.42 ± 5.19 µg/dl) as compared with mild intermittent asthma (mean ± SD 24.61 ± 2.32 µg/dl). Therapeutic trials are needed to prove whether low vitamin A levels contribute to asthma severity and the clinical utility of vitamin A supplementation in asthmatic children.
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  • 3
    ISSN: 1072-8368
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Biochemical studies indicate that dimerization is required for the catalytic activity of herpesvirus proteases, whereas structural studies show a complete active site in each monomer, away from the dimer interface. Here we report kinetic, biophysical and crystallographic characterizations of ...
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  • 4
    ISSN: 1573-904X
    Keywords: temozolomide ; cancer ; population pharmacokinetics ; nonlinear mixed-effects models ; pharmacokinetics-toxicity relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate covariate effects on the pharmacokinetics of temozolomide in cancer patients, and to explore the dose-pharmacokinetics-toxicity relationship of temozolomide. Methods. Non-linear mixed-effects modeling approach was used to analyze the data from 445 patients enrolled in eleven Phase I and Phase II clinical trials. All patients in the phase I trials had advanced cancer. Patients in the phase II trials had anaplastic astrocytoma (AA), glioblastoma multiforme (GBM) or malignant melanoma (MM). A sparse sampling scheme was prospectively developed using Phase I data and was successfully implemented in Phase II trials. Population factors included age, gender, height (HT), weight (WT), body surface area (BSA), serum creatinine (Sr.Cr.), estimated creatinine clearance, serum chemistry data as indices of hepatic function and disease, smoking status, and selected concomitant medications. Descriptive statistics were used to summarize the toxicity and temozolomide dose and exposure relationship. Results. The pharmacokinetics of temozolomide follows a one-compartment model with first order absorption and elimination. Temozolomide clearance (CL) increased with BSA for both genders. The population mean clearance for GBM or AA patients was 11.2 L/hr for male with BSA equal to 2.0 m2, and 8.8 L/hr for female with BSA equal to 1.7 m2. The mean clearance for MM patients was slightly higher. The inter-subject variability in clearance was 15%, and the residual variability was 26%. Other factors investigated in this analysis had little effect on clearance. The overall incidence of neutropenia and thrombocytopenia were 5-8%. Temozolomide dose and AUC did not predict nadir neutrophil and platelet counts due to large variability in counts. Conclusions. The current dose regimen is administered according to BSA which is the most important factor influencing temozolomide clearance. No further dose adjustment is required.
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  • 5
    ISSN: 1615-6706
    Keywords: Schlüsselwörter: Paraneoplastisches Syndrom ; Myelitis ; Funikuläre Spinalerkrankung ; Key Words: Paraneoplastic syndrome ; Myelitis ; Subacute combined degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract: Paraneoplastic syndroms of the central nervous system may precede the clinical presentation of a tumor by years. An early diagnosis may improve the prognosis of the underlying disease. We report clinical and imaging sings of a patient presenting with paraneoplastic polyneuropathy and myelitis, 18 months before the diagnosis of a small anaplastic breast carcinoma could be made. Spinal MRI showed primarily involvement of the dorsal columns, thought to be suggestive of a subacute combined degeneration due to vitamin B12 deficiency.
    Notes: Zusammenfassung: Paraneoplastische Erkrankungen des Zentralnervensystems sind seltene Frühsymptome einer Tumorerkrankung. Ihre Erkennung kann eine schnelle Behandlung der Grunderkrankung bewirken und ist zudem von großer differenzialdiagnostischer Bedeutung. Das diagnostische Verfahren zur Beurteilung einer medullären Schädigung ist heute die MRT. Wir berichten über den Fall einer Patientin mit paraneoplastischer sensorischer Neuropathie und Myelitis, die der klinischen Diagnose eines Mammakarzinoms um 18 Monate vorausging. Bemerkenswert war der bevorzugte Befall der Hinterstränge des Rückenmarks, der differenzialdiagnostisch an eine funikuläre Spinalerkrankung denken ließ.
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  • 6
    ISSN: 1460-9592
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Neostigmine given through the neuraxial route has been found to have analgesic properties. In this clinical trial, we evaluated for the first time the efficacy of a varying dose of caudal neostigmine for postoperative analgesia in children undergoing genitourinary surgery.Method: In this double blind prospective study, we studied 120 children ASA physical status I in age group of 2–8 years scheduled for surgical repair of hypospadias under general anaesthesia. Children were randomly allocated to one of the six groups (n = 20 each) and received either no caudal block (group C) or neostigmine (groups I-V) in doses of 10, 20, 30, 40 and 50 μg·kg−1 respectively at the end of the surgery. Postoperatively pain was assessed using an objective pain score for 24 h. Blood pressure, heart rate, SpO2, total amount of analgesic consumed and adverse effects, if any, were also recorded.Result: The duration of postoperative analgesia did not differ significantly between group C and I (P 〉 0.05). There was significant prolongation in the duration of analgesia in rest of the groups (group II-3.52 ± 1.37 h; group III-6.50 ± 1.93 h; group IV-10.45 ± 3.41 h; group V-13.70 ± 5.52 h) (P 〈 0.05). A dose dependent increase in the incidence of nausea and vomiting was also observed with highest incidence in group IV and V (group C-15%; group I-20%; group II and III-30%; group IV-45% and group V-60%) (P 〈 0.05). No significant alteration in vital signs and other adverse effects were noticed.Conclusion: Caudal neostigmine in the dose range of 20–50 μg·kg−1 provides dose dependent analgesia. However, dose exceeding 30 μg·kg−1 is associated with a higher incidence of nausea and vomiting.
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  • 7
    ISSN: 1460-9592
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Tracheal intubation in children can be achieved by deep inhalational anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium being widely used despite several side-effects. Studies have shown that oral intubation can be facilitated safely and effectively in children after induction of anaesthesia with propofol and alfentanil without a muscle relaxant. Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is 20–30 times more potent than alfentanil. This clinical study was designed to assess whether combination of propofol and remifentanil could be used without a muscle relaxant to facilitate tracheal intubation in children.Methods : Forty children (5–10 years) admitted for adenotonsillectomy were randomly allocated to one of two groups to receive remifentanil 2 μg·kg−1 (Gp I) or remifentanil 3 μg·kg−1 (Gp II) before the induction of anaesthesia with i.v. propofol 3 mg·kg−1. No neuromuscular blocking agent was administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Mean arterial pressure (MAP) and heart rate (HR) measured noninvasively before induction of anaesthesia to 5 min after intubation (seven time points).Results : Tracheal intubation was successful in all patients without requiring neuromuscular blocking agent. Intubating conditions were clinically acceptable in 10 of 20 patients (50%) in Gp I compared with 18 of 20 patients (90%) in Gp II (P 〈 0.05). MAP and HR decreased in both groups after induction of anaesthesia (P 〈 0.01). Both HR and MAP were significantly lower in Gp II compared with Gp I after tracheal intubation (P 〈 0.01). No patient in the present study developed bradycardia or hypotension.Conclusions : We conclude that remifentanil (3 μg·kg−1), administered before propofol (3 mg·kg−1) provides acceptable tracheal intubating conditions in children, and completely inhibited the increase in HR and MAP associated with intubation.
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  • 8
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objectives To assess endothelial function and vascular mechanical properties in normotensive pregnant women with high resistance in the uteroplacental circulation.Design Cross-sectional prospective study.Setting Doppler ultrasound laboratory at university department of obstetrics and gynaecology referral centre for high risk pregnancies.Participants Forty-two caucasian normotensive pregnant women: 23 with uncomplicated pregnancies and 19 with bilateral uterine artery notches.Methods Flow-mediated dilatation of the brachial artery was measured by ultrasonography at 25 gestational weeks. Concentrations of nitrite and nitrate in the plasma were established at 25 and 32 gestational weeks. The elastic properties of the common carotid artery, abdominal aorta and popliteal artery were measured with an ultrasonic echo-tracking system.Results Flow-mediated dilatation at two minutes after cuff deflation was significantly lower in the bilateral notch group compared with the control group, 8.3% and 13.7%, respectively (P= 0.0007). The ability to sustain vasodilatation was reduced in the bilateral notch group (P= 0.02). Lower values of nitrite and nitrate in the plasma were found at 32 gestational weeks in the bilateral notch group than in the control group (mean 24.76 μM/L (SD 5.6) and 30.93 μM/L (8.2), respectively; P= 0.008). Nitrite and nitrate levels tended to be lower in the bilateral notch group even at 25 gestational weeks (29.45 μM/L (8.3) and 35.73 μM/L (11.0) in the bilateral notch and control group, respectively; P= 0.09). There was no difference in aortic, carotid or popliteal elasticity between the two groups.Conclusions Healthy normotensive pregnant women with bilateral uterine artery notches show impaired endothelial function, but no differences in vascular mechanical properties.
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Addiction 99 (2004), S. 0 
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
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  • 10
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Rationale Asthmatic airway remodelling is characterized by myofibroblast hyperplasia and subbasement membrane collagen deposition. We hypothesized that cytokines and growth factors implicated in asthmatic airway remodelling are increased in bronchoalveolar lavage (BAL) fluid of asthmatics after segmental allergen challenge (SAC), and that these growth factors and cytokines increase α-smooth muscle actin (α-SMA) and collagen III synthesis by human lung fibroblasts (HLFs).Methods Transforming growth factor (TGF)-β1, TGF-β2, IL-4 and IL-13 levels were measured in BAL fluid from 10 asthmatics and 9 non-asthmatic controls at baseline and then 1 day, 1 week and 2 weeks after SAC. Confluent cultures of HLFs were stimulated by exogenous addition of TGF-β1, TGF-β2, IL-4 or IL-13 (concentration range 0.01–10 ng/mL) over 48 h. Collagen III was measured in culture supernates and α-SMA in cell lysates by Western blot.Results At baseline, there was no difference in BAL fluid concentrations of TGF-β1, IL-4 and IL-13 between asthmatics and controls; however, non-asthmatics had higher concentrations of total TGF-β2. In asthmatics, BAL fluid concentrations of all four factors increased significantly 1 day after SAC. TGF-β1, TGF-β2 and IL-13 concentrations returned to baseline by 1 week after SAC, but BAL fluid IL-4 concentration remained elevated for at least 2 weeks. TGF-β1, TGF-β2 and IL-4 significantly increased α-SMA in fibroblasts, but only IL-4 caused corresponding increases in collagen III synthesis. IL-13 had no direct effects on collagen III synthesis and α-SMA expression.Conclusions Because IL-4 caused a dose-dependent increase in α-SMA and collagen III synthesis, it may be an important cytokine mediating asthmatic airway remodelling. TGF-β1 and TGF-β2 may also play a role in airway remodelling by stimulating phenotypic change of fibroblasts to myofibroblasts. Additionally, collagen III synthesis appears to be independent of myofibroblast phenotype and is apparently regulated by different growth factors and cytokines.
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