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1.
Phys Rev Lett ; 129(18): 180504, 2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36374697

ABSTRACT

The ability to control microwave emission from a spin ensemble is a requirement of several quantum memory protocols. Here, we demonstrate such ability by using a resonator whose frequency can be rapidly tuned with a bias current. We store excitations in an ensemble of rare-earth ions and suppress on demand the echo emission ("echo silencing") by two methods: (1) detuning the resonator during the spin rephasing, and (2) subjecting spins to magnetic field gradients generated by the bias current itself. We also show that spin coherence is preserved during silencing.

2.
Anaesthesist ; 64(9): 683-8, 2015 Sep.
Article in German | MEDLINE | ID: mdl-26275386

ABSTRACT

Baroreceptor stimulators are novel implantable devices that activate the carotid baroreceptor reflex. This results in a decrease in activity of the sympathetic nervous system and inhibition of the renin-angiotensin-aldosterone system. In patients with drug-resistant hypertension, permanent electrical activation of the baroreceptor reflex results in blood pressure reduction and cardiac remodeling. For correct intraoperative electrode placement at the carotid bifurcation, the baroreceptor reflex needs to be activated several times. Many common anesthetic agents, such as inhalation anesthetics and propofol dampen or inhibit the baroreceptor reflex and complicate or even prevent successful placement. Therefore, a specific anesthesia and pharmacological management is necessary to ensure successful implantation of baroreceptor reflex stimulators.


Subject(s)
Electrodes, Implanted , Pressoreceptors , Prosthesis Implantation/methods , Anesthesia , Baroreflex , Electric Stimulation Therapy , Humans
3.
J Hist Neurosci ; 20(1): 16-25, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21253935

ABSTRACT

This article describes the life and work of the Dutch neurologist Joseph Prick (1909-1978) and his idea of an anthropological neurology. According to Prick, neurological symptoms should not only be explained from an underlying physico-chemical substrate but also be regarded as meaningful. We present an outline of the historical and philosophical context of his ideas with a focus on the theory of the human body by the French philosopher Maurice Merleau-Ponty (1908-1961) and the concept of anthropology-based medicine developed by Frederik Buytendijk (1887-1974). We give an overview of anthropological neurology as a clinical practice and finally we discuss the value of Prick's approach for clinical neurology today.


Subject(s)
Anthropology/history , Nervous System Diseases/history , Neurology/history , Neuropsychology/history , Anthropology/methods , History, 20th Century , Humans , Netherlands , Neurology/methods
4.
Thorac Cardiovasc Surg ; 57(4): 232-3, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19670119

ABSTRACT

Abnormalities of the vena cava system are usually asymptomatic and are found incidentally during pacemaker implantation or catherization. We report a case of dilative cardiomyopathy requiring cardiac resynchronization defibrillator therapy (CRT-D). During the operation, a persistent left superior vena cava with an absent right vena cava was discovered. During open chest surgery, we implanted a CRT-D with epicardial patches and pacing leads, which is a simple technique for safe and reliable biventricular defibrillator therapy in these patients.


Subject(s)
Cardiac Pacing, Artificial , Cardiomyopathy, Dilated/therapy , Electric Countershock , Incidental Findings , Vena Cava, Superior/abnormalities , Aged , Fluoroscopy , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation , Humans , Male , Mitral Valve/surgery , Radiography, Thoracic , Vena Cava, Superior/diagnostic imaging
5.
Clin Vaccine Immunol ; 15(5): 750-6, 2008 May.
Article in English | MEDLINE | ID: mdl-18353924

ABSTRACT

This study was performed to examine the adaptive immune response generated by three Mycobacterium bovis bacillus Calmette-Guérin (BCG) substrains to determine if the number of genomic regions of deletion played a significant role in determining the magnitude of the immune response or affected their ability to reduce the bacterial burden following low-dose aerosol challenge with a virulent M. tuberculosis strain. BCG Connaught, Pasteur, and Sweden were chosen as representative substrains, as they possessed many, intermediate, and few regions of deletion, respectively, as a result of changes in the genome in various regions. Mice were vaccinated subcutaneously and were then examined at 14, 21, and 42 days postvaccination. BCG was observed in the spleen, lung, and lymph nodes. BCG Connaught induced a greater pulmonary T-cell response than the other two substrains at day 14 postvaccination, although by 42 days postvaccination activated T-cell levels dropped to the levels observed in control mice for all three substrains. Among the three substrains, BCG Connaught induced significantly greater levels of interleukin-12 in bone marrow-derived macrophage cultures. Mice challenged at days 14, 21, and 42 postvaccination displayed an equal capacity to reduce the bacterial burden in the lungs and spleen. The data provide evidence that although the BCG substrains generated qualitatively and quantitatively different immune responses, they induced similar reductions in the bacterial burden against challenge with a virulent M. tuberculosis strain in the mouse model of tuberculosis. The data raise questions about the assessment of vaccine immune responses and the relationship to a vaccine's ability to reduce the bacterial burden.


Subject(s)
Antibodies, Bacterial/blood , BCG Vaccine/administration & dosage , Gene Deletion , Mycobacterium bovis/immunology , Animals , BCG Vaccine/immunology , Disease Models, Animal , Mice , Mice, Inbred C57BL , Mycobacterium bovis/genetics , Vaccination
6.
Eur J Anaesthesiol ; 25(2): 152-7, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17655810

ABSTRACT

BACKGROUND AND OBJECTIVE: It has been demonstrated that volatile anaesthetics have cardioprotective properties during open-heart procedures, especially when administered continuously. European Council Directive 93/42/EEC concerning medical devices bans the supplementary incorporation of anaesthetic vaporizers in the bypass circuit. Since the uptake of volatile anaesthetics via diffusion membrane oxygenators is severely reduced, it is hypothesized that clinically relevant concentrations of sevoflurane will remain in the patients' blood following saturation with a volatile agent before start of cardiopulmonary bypass. This study was designed to compare conventional and diffusion membrane oxygenators regarding their in vivo elimination of sevoflurane. METHODS: Twenty patients undergoing elective coronary bypass surgery were randomly allocated to two groups, either using a conventional polypropylene membrane oxygenator or a plasma-tight poly-(4-methyl-1-pentene) membrane oxygenator in a miniaturized extracorporeal circuit. Anaesthesia was maintained with sevoflurane, which was stopped at the start of cardiopulmonary bypass. During cardiopulmonary bypass, sevoflurane concentration was measured in blood and in the exhausted gas from the oxygenator. RESULTS: The elimination of sevoflurane, expressed as the relative blood concentration, was significantly increased in polypropylene membrane oxygenators compared to poly-(4-methyl-1-pentene) membrane oxygenators. This resulted in an approximately threefold higher sevoflurane blood concentration in the poly-(4-methyl-1-pentene) group over the course of cardiopulmonary bypass. CONCLUSIONS: With the incorporation of a poly-(4-methyl-1-pentene) oxygenator in a miniaturized bypass circuit, relevant concentrations of a previously applied volatile agent can be maintained even without further supply throughout cardiopulmonary bypass. This might be an alternative approach to cardioprotection when sevoflurane cannot be administered through cardiopulmonary bypass.


Subject(s)
Anesthetics, Inhalation/blood , Methyl Ethers/blood , Oxygenators, Membrane , Aged , Aged, 80 and over , Area Under Curve , Cardiopulmonary Bypass , Chromatography, Gas , Diffusion , Elective Surgical Procedures , Equipment Design , Extracorporeal Circulation/methods , Female , Humans , Male , Middle Aged , Polyenes , Polypropylenes , Sevoflurane
8.
Epilepsy Res ; 67(3): 143-51, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16288850

ABSTRACT

OBJECTIVE: This retrospective study addresses the cost-effectiveness of add-on therapy with lamotrigine in clinical practice. METHODS: Two years' observational data of 165 patients were used. Seizure frequency, adverse effects and direct medical costs were recorded for the year before and the year after the start of lamotrigine add-on therapy. Therapy effectiveness was measured by: (1) reduction in seizure frequency and (2) retention time. The incremental cost-effectiveness ratio expressed the direct medical cost per patient treated effectively with lamotrigine. RESULTS: The cost of medication was 492 (95% CI: 399-583) higher after the start of lamotrigine therapy. The extra cost of lamotrigine therapy (622) was partly offset by a reduction of the cost of co-medication (-130; 95% CI: -210 to -50). Overall, the total medical cost was 453 higher in the first year of lamotrigine therapy than in the year before the start of lamotrigine. Lamotrigine was effective in 47% of all the patients, making the resultant incremental cost-effectiveness ratio 954 per year. DISCUSSION: Add-on therapy of lamotrigine for patients with uncontrolled epilepsy offers improved health outcomes. Lamotrigine therapy is associated with increased cost (453) and an annual incremental cost-effectiveness ratio of 954. These data, together with utility data published in the literature, support the notion that lamotrigine should be considered as an add-on therapy in for patients with refractory epilepsy.


Subject(s)
Anticonvulsants/economics , Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Epilepsy/economics , Triazines/economics , Triazines/therapeutic use , Adult , Anticonvulsants/adverse effects , Cost-Benefit Analysis , Costs and Cost Analysis , Drug Therapy, Combination , Female , Humans , Lamotrigine , Male , Middle Aged , Retrospective Studies , Triazines/adverse effects
9.
Eur J Anaesthesiol ; 22(9): 658-65, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16163911

ABSTRACT

BACKGROUND AND OBJECTIVE: Accurate assessment of preload responsiveness is an important goal of the clinician to avoid deleterious volume replacement associated with increased morbidity and mortality in mechanically ventilated patients. This study was designed to evaluate the accuracy of simultaneously assessed stroke volume variation and pulse pressure variation using an improved algorithm for pulse contour analysis (PiCCO plus, V 5.2.2), compared to the respiratory changes in transoesophageal echo-derived aortic blood velocity (deltaVpeak), intrathoracic blood volume index, central venous pressure and pulmonary capillary wedge pressure to predict the response of stroke volume index to volume replacement in normoventilated cardiac surgical patients. METHODS: We studied 20 patients undergoing elective coronary artery bypass grafting. After induction of anaesthesia, haemodynamic measurements were performed before and after volume replacement by infusion of 6% hydroxyethyl starch 200/0.5 (7 mL kg(-1) ) with a rate of 1 mL kg(-1) min(-1). RESULTS: Baseline stroke volume variation correlated significantly with changes in stroke volume index (deltaSVI) (r2 = 0.66; P < 0.05) as did baseline pulse pressure variation (r2 = 0.65; P < 0.05), whereas baseline values of deltaVpeak, intrathoracic blood volume index, central venous pressure and pulmonary artery wedge pressure showed no correlation to deltaSVI. Pulse contour analysis underestimated the volume-induced increase in cardiac index measured by transpulmonary thermodilution (P < 0.05). CONCLUSIONS: The results of our study suggest that stroke volume variation and its surrogate pulse pressure variation derived from pulse contour analysis using an improved algorithm can serve as indicators of fluid responsiveness in normoventilated cardiac surgical patients. Whenever changes in systemic vascular resistance are expected, the PiCCO plus system should be recalibrated.


Subject(s)
Blood Pressure/physiology , Coronary Artery Bypass , Plasma Substitutes/therapeutic use , Respiration, Artificial , Stroke Volume/physiology , Aged , Algorithms , Aorta/physiology , Blood Flow Velocity/physiology , Blood Volume/physiology , Cardiac Output/physiology , Central Venous Pressure/physiology , Echocardiography, Transesophageal , Female , Humans , Hydroxyethyl Starch Derivatives/administration & dosage , Hydroxyethyl Starch Derivatives/therapeutic use , Infusions, Intravenous , Male , Middle Aged , Plasma Substitutes/administration & dosage , Pulmonary Wedge Pressure/physiology , Respiration , Thermodilution
10.
Epilepsy Res ; 65(1-2): 93-100, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16023833

ABSTRACT

OBJECTIVE: Evaluation of the effectiveness of lamotrigine in a population-based cohort of epilepsy patients. METHODS: Medical charts of 360 patients treated in 37 centres in The Netherlands were reviewed. Effectiveness of lamotrigine therapy was assessed during the first year of use, with patients serving as their own controls. Effectiveness was measured by reduction in seizure frequency and retention time. RESULTS: Effectiveness could only be assessed in 165 patients; assessment in remaining patients was not possible due to various reasons, such as insufficient medical chart information. Lamotrigine was effective in 40% of patients who had been prescribed lamotrigine because of insufficient seizure control (n=112), and 14% of these 112 patients became seizure free. Duration of epilepsy, baseline seizure frequency, valproate use, drug load and number of antiepileptic drugs (AED) used were related to effectiveness of lamotrigine. In this group, 36% continued lamotrigine (LTG) throughout the first year without experiencing a >50% seizure reduction. Lamotrigine was effective in 63% of patients who received the drug because of poor tolerability of other antiepileptic drugs (n=53). DISCUSSION: Lamotrigine is an effective drug in clinical practice. Use of retention time measures only may not correctly reflect the efficacy of antiepileptic drugs.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Triazines/therapeutic use , Adult , Drug Interactions , Epilepsy/classification , Epilepsy/epidemiology , Female , Humans , Lamotrigine , Logistic Models , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome , Valproic Acid/therapeutic use
11.
Pharmacoepidemiol Drug Saf ; 14(2): 107-12, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15386696

ABSTRACT

OBJECTIVE: Community pharmacists may function as intermediaries in the recruitment of a population-based cohort of patients using specific drugs. In this study, baseline characteristics and the retention rate of patients that gave informed consent, refused and did not answer were compared. METHODS: A total of 1819 patients using the new antiepileptic drug (AED) lamotrigine were asked to provide informed consent for a retrospective chart study via their individual pharmacist. Four possible reactions resulted from the consent question: active consent, active refusal, passive refusal and non-informed. Patient characteristics and lamotrigine retention rate of the different groups were compared. RESULTS: Pharmacists did not inform a total of 183 patients (10%). Of the remaining patients, a total of 968 (59%) gave consent; 101 (6%) actively refused and 567 (35%) did not respond. Age, burden of illness, psychotropic co-medication and continuation of lamotrigine therapy were related to active consent. Lamotrigine retention rate in patients that gave consent was higher than in other patients. CONCLUSIONS: Patient recruitment with community pharmacists as intermediaries for observational studies on the effects of (new) drugs is feasible, and allows access to a broad population of patients. The recruitment procedure, however, may lead to selection bias.


Subject(s)
Anticonvulsants/administration & dosage , Community Pharmacy Services , Informed Consent , Patient Selection , Pharmacists/statistics & numerical data , Triazines/administration & dosage , Adolescent , Adult , Age Factors , Aged , Anticonvulsants/therapeutic use , Cohort Studies , Epilepsy/drug therapy , Female , Health Status , Humans , Lamotrigine , Male , Middle Aged , Retrospective Studies , Socioeconomic Factors , Triazines/therapeutic use
12.
Eur J Clin Pharmacol ; 60(10): 751-8, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15619137

ABSTRACT

INTRODUCTION: Lamotrigine is one of the recently introduced antiepileptic drugs (AEDs) licensed in the Netherlands in 1995. The objective of this study was to examine the diffusion of lamotrigine into clinical practice. Three different aspects of this diffusion process were examined: incidence of use, patient characteristics and changes in prescription patterns in the first 5 years following its introduction. METHODS: A retrospective follow-up study has been conducted using drug prescription data from the database of the Dutch Drug Information Project (GIP database). Patients were included who started with lamotrigine, carbamazepine, phenytoin or valproate in the period between January 1996 and December 2000. Incidence of use was calculated for the four drugs. Multiple logistic regression analysis was used to determine differences in baseline characteristics. The Chi-square test was used to analyse changes in the usage patterns of lamotrigine. RESULTS: The study population consisted of a total of 29,718 patients who were prescribed carbamazepine, phenytoin, valproate or lamotrigine for the first time in the study period. Carbamazepine and valproate accounted for the majority of all new prescriptions; the incidence of lamotrigine use remained stable with 4.4 patients per 100,000 per year. Baseline characteristics of lamotrigine differed depending on the patient's age and gender (OR 3.7, 95% CI 3.3-4.2; OR 1.4, 95% CI 1.3-1.5) relative to the conventional AEDs. In a large majority of cases, lamotrigine was used as a second-line or third-line AED. Physicians prescribing lamotrigine were predominantly neurologists, in contrast to prescribers of conventional AEDs. The prevalence of psychotropic medication and migraine-abortive drugs was significantly lower in users of lamotrigine than in users of conventional AEDs. During follow-up, several significant trends were noticed in the prescribing of lamotrigine with regard to age groups, gender, antiepileptic history and off-label use. DISCUSSION: Lamotrigine is prescribed to a population different from that using conventional AEDs. The uptake of lamotrigine in clinical practice is slow, for reasons probably related to characteristics of the drug itself and the prescribers. During the observation period, lamotrigine diffused gradually towards more first-line use as an AED and more off-label use.


Subject(s)
Anticonvulsants/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Triazines/therapeutic use , Adolescent , Adult , Aged , Child , Female , Humans , Incidence , Lamotrigine , Logistic Models , Male , Medicine , Middle Aged , Netherlands/epidemiology , Pharmacoepidemiology , Practice Patterns, Physicians'/trends , Prevalence , Retrospective Studies , Specialization
13.
J Clin Pharm Ther ; 29(2): 131-8, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15068401

ABSTRACT

OBJECTIVE: Follow-up data on the long-term effectiveness (efficacy and tolerability) of lamotrigine are limited. A useful though crude measure for effectiveness in daily clinical practice is the treatment retention rate determined from drug dispensing data. This study describes the baseline characteristics, the usage patterns and the retention rate of this antiepileptic drug (AED) in a population-based cohort of lamotrigine users in the Netherlands during the first 5 years after its registration in 1995. Data from this cohort are compared with those from the initial randomized clinical trials (RCTs) in patients with refractory epilepsy. METHODS: This retrospective cohort study used dispensing data from community pharmacies. Baseline characteristics and usage patterns were evaluated for first time users of lamotrigine in this study. Usage patterns were characterized as continued, add-on or discontinued use during the patient observation time window. Cox regression analysis was used to explore possible relationships between baseline characteristics and specific usage patterns defined. The baseline characteristics and discontinuation rates in this cohort study were compared with RCT data reported in medical literature. RESULTS: A total of 3598 lamotrigine users were identified. The mean age of the population was 39 years and 54% were female. On average, patients used two other AEDs at the start of lamotrigine therapy and approximately 6% of the patients had no history of prior AED use. The discontinuation rate was 25% after 1 year, and approximately 32% at the end of the 5-year study. Addition of another drug or discontinuation was seen in more than half of the population 3 years after the start of therapy. Concurrent use of valproic acid was associated with a better retention rate. Absence of AED history, use of antidepressants, or use of migraine abortive drugs resulted in an increased likelihood of discontinuing lamotrigine. The population from RCTs differed from the study cohort with respect to age, concurrent use of AEDs and length of follow-up. CONCLUSION: Data from RCTs cannot easily be extrapolated to daily clinical practice. In this large, observational study, lamotrigine therapy failed in a considerable number of patients, although the mean retention rate was better than previously reported by others. Population-based linkage of health care records can be used to further clarify the effectiveness of lamotrigine.


Subject(s)
Anticonvulsants/administration & dosage , Drug Utilization , Epilepsy/drug therapy , Randomized Controlled Trials as Topic/statistics & numerical data , Self Administration/statistics & numerical data , Treatment Refusal/statistics & numerical data , Triazines/administration & dosage , Adolescent , Adult , Aged , Child , Child, Preschool , Cohort Studies , Databases, Factual , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Lamotrigine , Male , Middle Aged , Netherlands/epidemiology , Pharmaceutical Services/statistics & numerical data , Proportional Hazards Models , Research Design , Retrospective Studies
14.
J Neurol ; 251(12): 1429-42, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15645341

ABSTRACT

The corticospinal tract develops over a rather long period of time, during which malformations involving this main central motor pathway may occur. In rodents, the spinal outgrowth of the corticospinal tract occurs entirely postnatally, but in primates largely prenatally. In mice, an increasing number of genes have been found to play a role during the development of the pyramidal tract. In experimentally studied mammals, initially a much larger part of the cerebral cortex sends axons to the spinal cord, and the site of termination of corticospinal fibers in the spinal grey matter is much more extensive than in adult animals. Selective elimination of the transient corticospinal projections yields the mature projections functionally appropriate for the pyramidal tract. Direct corticomotoneuronal projections arise as the latest components of the corticospinal system. The subsequent myelination of the pyramidal tract is a slow process, taking place over a considerable period of time. Available data suggest that in man the pyramidal tract develops in a similar way. Several variations in the funicular trajectory of the human pyramidal tract have been described in otherwise normally developed cases, the most obvious being those with uncrossed pyramidal tracts. A survey of the neuropathological and clinical literature, illustrated with autopsy cases, reveals that the pyramidal tract may be involved in a large number of developmental disorders. Most of these malformations form part of a broad spectrum, ranging from disorders of patterning, neurogenesis and neuronal migration of the cerebral cortex to hypoxic-ischemic injury of the white matter. In some cases, pyramidal tract malformations may be due to abnormal axon guidance mechanisms. The molecular nature of such disorders is only beginning to be revealed.


Subject(s)
Pyramidal Tracts/abnormalities , Pyramidal Tracts/embryology , Animals , Congenital Abnormalities/embryology , Embryonic Development , Humans , Macaca mulatta/embryology
15.
Eur J Neurol ; 10(4): 343-51, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12823484

ABSTRACT

After a short survey of the early history of neurology and psychiatry in the Netherlands, the development of the specialty of neurology is discussed. During the 20th century the training of neurologists and the certification of specialists evolved from an informal master-fellow organization towards a strongly reglemented and legally based procedure. A nationwide Specialist Registration Commission supervises the quality of the training of specialists. Registered neurologists in the Netherlands are subject to a re-certification programme that controls the requirements to be fulfilled by the specialists such as their active involvement in patient care (for at least 16 h a week), attendance of the annual postgraduate courses in neurology (5-year cycle) and regular participation in international congresses of neurology. The undergraduate training in neurology, the neurology clerkship and the postgraduate training in neurosciences are described. Measures taken in order to maintain the balance between the supply of and the demand for neurological care in the near future are reported.


Subject(s)
Neurology/economics , Neurology/education , Teaching , Certification/economics , Certification/standards , Certification/trends , Education, Medical/economics , Education, Medical/history , Education, Medical/organization & administration , Forecasting , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Needs Assessment/economics , Needs Assessment/standards , Needs Assessment/trends , Netherlands , Neurology/history , Neurology/trends , Psychiatry/history , Teaching/economics , Teaching/history
16.
CNS Drugs ; 17(6): 405-21, 2003.
Article in English | MEDLINE | ID: mdl-12697000

ABSTRACT

In recent years, several new antiepileptic drugs (AEDs) have been licensed: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. These drugs have proven efficacy as add-on therapy in patients with difficult-to-treat partial epilepsy, as 20-50% of patients treated in add-on trials experienced a seizure reduction of >or=50%. Relatively few trials have been conducted to evaluate these drugs as monotherapy for patients with newly diagnosed epilepsy. In the monotherapy trials that have been conducted, the newer drugs were often as efficacious as conventional drugs, and their tolerability was often better. However, the methodology of these trials can be criticised. Because of the relative lack of robust data for the newer agents, the conventional drugs have thus far maintained their status as first-line monotherapy. However, when first-line monotherapy fails, an alternative drug has to be chosen from the available conventional and newer drugs. This article aims to give detailed background information on the newer AEDs in order to enable physicians to make a rational choice from the available drugs for individual patients. Data are provided for the different newer AEDs on mechanisms of action; efficacy in refractory partial epilepsy, newly diagnosed epilepsy in adults and generalised seizure types; adverse effects; pharmacokinetics; and use in special patient categories.


Subject(s)
Anticonvulsants/therapeutic use , Drug Evaluation , Epilepsy/drug therapy , Animals , Anticonvulsants/adverse effects , Anticonvulsants/pharmacokinetics , Clinical Trials as Topic , Drugs, Investigational , Humans , Patient Selection , Treatment Outcome
17.
Int J Tuberc Lung Dis ; 5(11): 1028-35, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11716339

ABSTRACT

SETTING: The British Thoracic Society and the American Thoracic Society advise 12 months treatment for tuberculous meningitis, with at least isoniazid (H), rifampicin (R) and pyrazinamide (Z). OBJECTIVE: To establish whether a 6-month treatment regimen for tuberculous meningitis is equally as effective as longer treatment. METHOD: Medline search for papers published between 1978 and 1999. INCLUSION CRITERIA: study populations of patients with tuberculous meningitis in whom the diagnosis was confirmed with clinical, cerebrospinal fluid and epidemiological findings; a treatment regimen with at least HRZ and at least 12 months of follow-up after the completion of treatment. OUTCOME MEASURE: the number of relapses. RESULTS: There were four 6-month treatment regimens (G6) and seven longer treatment regimens (G>6); 160/197 (81%) patients completed the 6-month treatment regimens, while 577/675 (85%) completed the longer-term regimens. The clinical stage of patients in the G6 group was poorer than in the G>6 group. Relapse occurred in two out of 131 (1.5%) G6 and in 0 out of 591 G>6 patients. CONCLUSION: Although no studies have compared 6-month treatment regimens with longer treatment, it can be concluded on the basis of this literature review that 6-month treatment is sufficient for tuberculous meningitis with fully susceptible mycobacteria.


Subject(s)
Antitubercular Agents/administration & dosage , Tuberculosis, Meningeal/drug therapy , Adult , Child , Drug Administration Schedule , Drug Therapy, Combination , Humans , Isoniazid/administration & dosage , Pyrazinamide/administration & dosage , Recurrence , Rifampin/administration & dosage , Tuberculosis, Meningeal/complications
18.
Mol Cell Biochem ; 223(1-2): 15-25, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11681717

ABSTRACT

Glucose uptake, glut 4 translocation and activation of protein kinase B were measured in Langendorff perfused hearts from (i) Wistar control, (ii) lean, neonatal Streptozotocin induced (Stz) and (iii) Zucker (fa/fa) obese diabetic rats of 10-12 weeks old. Hearts were subjected to stimulation with insulin, isoproterenol (beta-adrenergic agonist) or a combination of insulin and isoproterenol, during the perfusion protocol. Basal myocardial glucose uptake was impaired in both diabetic models, but could be stimulated significantly by insulin. In the Zucker rats, the time-course of insulin action was delayed. Insulin and beta-stimulation of glucose uptake were not additive. Evaluation of sarcolemmal membranes from these hearts showed that the affinity of glut 4 was significantly lower in the Zucker but not in the Stz hearts while a reduced affinity found with a combination of insulin and beta-stimulation in control hearts, was absent in both diabetic models. Total membrane lysates were analyzed for glut 4 expression while an intracellular component was generated to quantify translocation on stimulation as well as activity of protein kinase B (PKB). At this age, the neonatal Streptozotocin induced diabetic animals presented with more faulty regulation concerning adrenergic stimulated effects on elements of this signal transduction pathway while the Zucker fa/fa animals showed larger deviations in insulin stimulated effects. The overall response of the Zucker myocardium was poorer than that of the Stz group. No significant modulation of beta-adrenergic signaling on insulin stimulated glucose uptake was found. The PI-3-kinase inhibitor wortmannin, could abolish glucose uptake as well as PKB activation elicited by both insulin and isoproterenol.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Glucose/metabolism , Insulin/pharmacology , Isoproterenol/pharmacology , Monosaccharide Transport Proteins/metabolism , Muscle Proteins , Myocardium/metabolism , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins/metabolism , Adrenergic beta-Agonists/pharmacology , Animals , Diabetes Mellitus/metabolism , Diabetes Mellitus, Experimental , Enzyme Activation , Glucose Transporter Type 4 , Heart/drug effects , In Vitro Techniques , Insulin/blood , Monosaccharide Transport Proteins/genetics , Obesity , Protein Transport/physiology , Proto-Oncogene Proteins c-akt , Rats , Rats, Wistar , Rats, Zucker
19.
Plant Physiol ; 127(1): 78-89, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11553736

ABSTRACT

The interaction between the tropical legume Sesbania rostrata and the bacterium Azorhizobium caulinodans results in the formation of nodules on both stem and roots. Stem nodulation was used as a model system to isolate early markers by differential display. One of them, Srchi24 is a novel early nodulin whose transcript level increased already 4 h after inoculation. This enhancement depended on Nod factor-producing bacteria. Srchi24 transcript levels were induced also by exogenous cytokinins. In situ hybridization and immunolocalization experiments showed that Srchi24 transcripts and proteins were present in the outermost cortical cell layers of the developing nodules. Sequence analyses revealed that Srchi24 is similar to class III chitinases, but lacks an important catalytic glutamate residue. A fusion between a maltose-binding protein and Srchi24 had no detectable hydrolytic activity. A function in nodulation is proposed for the Srchi24 protein.


Subject(s)
Chitinases/chemistry , Fabaceae/microbiology , Membrane Proteins , Plant Proteins/genetics , Amino Acid Sequence , Azorhizobium caulinodans/physiology , Cytokinins/pharmacology , DNA, Bacterial , DNA, Complementary , Gene Expression Regulation, Plant , Glutamic Acid/metabolism , Hydrolysis , In Situ Hybridization , Lipopolysaccharides/metabolism , Molecular Sequence Data , Plant Proteins/chemistry , Plant Proteins/metabolism , Plant Roots/metabolism , Plant Roots/microbiology , Plant Stems/metabolism , Plant Stems/microbiology , Sequence Homology, Amino Acid , Symbiosis/genetics
20.
Radiother Oncol ; 59(2): 127-37, 2001 May.
Article in English | MEDLINE | ID: mdl-11325440

ABSTRACT

BACKGROUND AND PURPOSE: First, the aim was to determine the survival and quality of life after reirradiation of relapsing primary malignant brain tumours. The second aim was to assess the influence of a set of potentially prognostic factors on survival. MATERIALS AND METHODS: Forty-two patients received reirradiation for recurring primary brain tumours. The interval between the two consecutive treatments was at least 1 year. External beam irradiation for the initial and recurrent tumour was usually delivered with two opposing lateral fields or two wedged fields in orthogonal directions. The median physical doses of the first and second radiation course were 50 and 46 Gy, respectively. The median cumulative biological equivalent doses (BED) were 200.4 (alpha/beta = 2 Gy) and 115.2 Gy (alpha/beta = 10 Gy). During follow-up, corticosteroid medication and the WHO-performance were registered at regular intervals. The radiological response was assessed by reviewing all available CT- and MRI-films. Potentially prognostic factors with respect to survival were evaluated by both univariate and multivariate analyses. RESULTS: A clinical response (i.e. clinical improvement) was seen in 24% of the patients. Of the evaluable patients, nearly one-third showed a complete (8%) or partial (22%) radiological response. The median overall survival (OS) and progression-free survival (PFS) after retreatment were 10.9 and 8.6 months, respectively. By multivariate analysis, four independent prognostic factors for survival were identified: (1), the WHO-score before retreatment (P = 0.002); (2), the length of the interval between treatments (P = 0.008); (3), the tumour histology; and (4), the response to initial treatment (P values, 0.04). The median survival times for patients with WHO-scores of 0-1 and > or = 2 were 14.0 and 7.4 months, respectively. Patients with oligodendrogliomas had a median OS of 27.5 months, whereas patients with astrocytomas had a median OS of 6.9 months after retreatment. Long-term complications of retreatment were seen in three patients, all of whom had a cumulative BED(2) of > 204 Gy (with alpha/beta = 2 Gy). The quality of life after retreatment, however, was well preserved in the majority of patients. They remained ambulant and capable of self-care until the time of progression which occurred after 8.6 months (median PFS). CONCLUSIONS: After an initial treatment with radiation up to tolerance levels of normal brain tissue, reirradiation of recurring primary brain tumours seems feasible. During the time until clinical progression, patients remained independent with a reasonable quality of life.


Subject(s)
Brain Neoplasms/radiotherapy , Cranial Irradiation , Neoplasm Recurrence, Local/radiotherapy , Adrenal Cortex Hormones/therapeutic use , Adult , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Female , Humans , Male , Multivariate Analysis , Neoplasm Recurrence, Local/mortality , Prognosis , Proportional Hazards Models , Quality of Life , Radiotherapy Dosage , Survival Analysis , Treatment Outcome
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