[Tasered: medical consequences of the use of electric stun guns]. / Getaserd.

The Electronic Control Device (ECD) will be used by the primary police force in the Netherlands. Hence medical personnel will be confronted with persons that have received ECD shocks more often. In light of these developments, it is important that care providers are aware of potential medical consequences resulting from the use of electric stun guns. The darts usually result in minor injury with small penetration wounds requiring minimal treatment. However, in vulnerable areas, such as the eyes, the darts can cause serious injury and specialist care is indicated. The electric shock causes muscle contractions, potentially resulting in traumatic falls, or fractures. Cardiac problems occur only in exceptional cases; risk factors include long duration of the power surge, short distance from the darts to the heart and underlying heart problems. In rare cases a pneumothorax may occur. Finally, often there are underlying medical problems requiring appropriate treatment such as drug intoxication, excited delirium or psychiatric disorders. Systematic recording of the medical problems caused by anECD is indicated.

[Medication-overuse headache]. / Hoofdpijn door overgebruik van pijnmedicatie.

- Medication-overuse headache is a highly prevalent disorder with a major impact on the quality of life.- Medication-overuse headache is defined as headache on ≥ 15 days per month with overuse of acute headache medication for ≥ 3 months. We talk about overuse in case of intake of simple analgesics on ≥ 15 days per month or triptans or combinations of analgesics on ≥ 10 days per month.- The underlying type of headache is usually migraine or tension-type headache.- One of the possible underlying mechanisms of medication-overuse headache is changed sensitivity as a consequence of central sensitisation.- The initial treatment is detoxification of the headache medication. The preferred detoxification method is outpatient, abrupt withdrawal of all acute-headache medication and caffeine-containing products. Essential for successful detoxification is education about the reasons for detoxification, the expected course and the subsequent treatment.

Cardiac monitoring of high-dose verapamil in cluster headache: An international Delphi study.

BACKGROUND: In many patients, high-dose verapamil (HDV) is the only effective prophylactic treatment for cluster headache. Although cardiac adverse events and EKG abnormalities are relatively common, evidence-based guidelines for screening and monitoring patients on HDV are lacking. GOAL AND METHODS: Using the Delphi approach, we interviewed 22 international clinical experts in cardiac rhythm disorders to formulate EKG guidelines for the pretreatment screening and monitoring of cluster headache patients using HDV. RESULTS: The panel agreed only on performing pretreatment EKG to screen for pre-existing cardiac arrhythmia. Pretreatment EKG was deemed not necessary by most panel members for patients who did not have cardiac adverse events during a previous period of cluster headache attacks treated with HDV. Half the panel advised Holter EKG for patients on verapamil ≥ 480 mg/day. The highest recommended daily doses varied between 240 and 960 mg. Contraindications for use of verapamil largely followed FDA guidelines. DISCUSSION: Experts in cardiac rhythm disorders agreed on pretreatment EKG monitoring, but no consensus was reached on EKG monitoring during HDV treatment and around dose adjustments.

Are atraumatic spinal needles as efficient as traumatic needles for lumbar puncture?

The most frequent complication of lumbar puncture is post lumbar puncture headache (PLPH). Recent studies confirmed that the use of atraumatic spinal needles significantly reduces the risk of PLPH. However, the majority of neurologists still use traumatic needles, possibly caused by misconceptions and beliefs about practical performance of atraumatic spinal needles. Therefore, we investigated the practical characteristics of atraumatic and traumatic spinal needles. An experimental setup with a fluid column was used with (1) a physiological NaCl 0.9 % solution and (2) a high protein content solution. Flow rates and duration of pressure measurements were measured using a traumatic needle and an atraumatic needle. The average flow rate differed less than 10 % between the two needle types with NaCl solution, and for the high protein solution the difference was even smaller. Time taken to perform accurate pressure measurements did not differ between the two needle types using NaCl 0.9 %, and was even slightly shorter for the atraumatic needle when using the high protein solution. Average flow rates and duration of pressure measurements are comparable between atraumatic spinal needles and traumatic needles. Therefore, these performance characteristics are no reason to favor traumatic needles over atraumatic needles.

Aortic root pathology in Marfan syndrome increases the risk of migraine with aura.

AIM: To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor. METHODS: In a multicentre study 123 MFS patients (n = 52 with AR, n = 71 without AR), 82 age- and sex-matched controls and 51 patients with AR but without MFS, were interviewed using a semi-structured headache questionnaire. A multinomial logistic regression model was used to investigate risk factors for migraine with and without aura, adjusting for age and gender. RESULTS: Lifetime migraine prevalence was increased in female MFS patients (51%) compared to healthy female controls (29%), p = 0.017. In males lifetime migraine prevalence among MFS patients was only numerically increased. Lifetime prevalence of migraine with aura was increased among MFS patients compared to healthy controls both in males (19% vs. 3%, p = 0.048) and females (30% vs. 14%, p = 0.049). A history of AR, independently from MFS, gender and age, increased the lifetime prevalence of migraine with aura (OR 3.1 [1.2-8.0]). In all but one patient migraine started before the AR. CONCLUSIONS: The lifetime prevalence of migraine with aura, but not migraine without aura, is increased in patients with MFS. This association is driven by a history of AR. The replacement procedure itself is unlikely to be causally associated with migraine as in nearly all subjects, migraine started before the procedure. However this study adds to the evidence that underlying vessel wall pathology may be involved in migraine with aura.

Space headache: a new secondary headache.

Headache is a common, but rarely voiced, complaint during space flights, usually attributed to space motion sickness (SMS). We used a specifically designed questionnaire based on the criteria of the International Classification of Headache Disorders, 2nd edn (ICHD-II). Of the 16 male and one female astronauts who participated in the survey, 12 (71%) reported having experienced at least one headache episode while in space, whereas they had not suffered from headache when on earth. There were in total 21 space headache episodes, of moderate to severe intensity in 71%. In two astronauts (12%) the headache and associated symptoms would match the ICHD-II criteria for migraine and in three (18%) astronauts for tension-type headache; in 12 (70%) astronauts the headache was non-specific. The vast majority of headache episodes (76%) were not associated with symptoms of SMS. We conclude that space flights may trigger headaches without other SMS symptoms in otherwise 'super-healthy' male subjects. We propose to classify space headache as a separate entity among the secondary headaches attributed to disorders of homeostasis.

[Migraine and cardiovascular risk]. / Migraine en cardiovasculair risico.

New epidemiological studies suggest a relationship between migraine (especially migraine with aura) and cardiovascular disease. However, the absolute risk of cardiovascular disease for migraine patients is still low even though the relative risk is 2-4-fold higher. Further research will have to show whether migraine is an independent risk factor for cardiovascular disease and whether prophylactic treatment of migraine attacks will lower this increased risk for cardiovascular disease.

Paraneoplastic cerebellar degeneration preceding the diagnosis of Hodgkin's lymphoma.

Paraneoplastic cerebellar degeneration (PCD) can present as a severe and (sub)acute cerebellar syndrome. PCD can accompany different kinds of neoplasms including small cell lung cancer, adenocarcinoma of the breast and ovary, and Hodgkin's lymphoma. A 34-year-old patient is described with acute dysarthria, gait ataxia and diplopia. Despite extensive laboratory and radiological evaluations in this patient with rapidly deteriorating cerebellar syndrome, the diagnosis of a paraneoplastic syndrome was only made after several months, when an anti-Tr antibody was detected in his serum. The search for Hodgkin's disease as concomitant disorder was then started and resulted in stage II B disease. The patient was successively treated with six courses of etoposide, bleomycin, vinblastine and dexamethasone and radiotherapy, which resulted in a complete remission of the Hodgkin's disease. After starting therapy the cerebellar degeneration stabilised. The pathogenesis of neuronal damage in central nervous system paraneoplastic disorders such as the one we describe is not completely understood. Antitumour therapy is assumed to be the important cornerstone in stabilising the neurological condition. Improvement of the cerebellar syndrome in anti-Tr autoantibody paraneoplastic disease is a rare achievement. Early recognition of the concomitant disorders (anti-Tr autoantibody disease and Hodgkin's lymphoma) is of crucial importance.

Poststroke hand swelling and oedema: prevalence and relationship with impairment and disability.

OBJECTIVE: To examine the prevalence of swelling and oedema of the hand in stroke patients and relationships with impairments and disability. DESIGN: Cross-sectional. SETTING: Stroke unit at Rehabilitation Centre De Hoogstraat, The Netherlands. SUBJECTS: Eighty-eight adult stroke patients who were admitted for clinical rehabilitation during one year (2000). MEASUREMENTS AND METHODS: Assessment took place two weeks after admission to the rehabilitation centre. Degree of swelling was measured with a hand volumeter and oedema was defined as a volumeter score deviating more than two standard deviations from the expected score derived from population data. Further assessment included tonus (Modified Ashworth Score), sensibility, tactile inattention, carefulness, and motor function (Utrecht Arm/Hand Test). Arm disability was measured with Frenchay Arm Test and Nine-hole Peg Test. RESULTS: Some degree of hand swelling was present in 72.7% and oedema in 33.0% of our patients. Swelling and oedema were significantly more often seen in patients with hypertonic fingers and impaired sensibility. Patients with hand oedema had significantly worse Frenchay Arm Test and Nine-hole Peg Test scores. CONCLUSIONS: Swelling and oedema of the hand are common among stroke patients in clinical rehabilitation.

Assessment of oedema in stroke patients: comparison of visual inspection by therapists and volumetric assessment.

PURPOSE: To examine the agreement of assessment of hand oedema in stroke patients by clinical judgement and by use of a hand volumeter. METHOD: A total of 88 rehabilitation patients with stroke received both assessments. Experienced physical therapists classified oedema as 'none', 'minor' or 'severe'. Swelling was independently measured with a hand volumeter. Population data were used to adjust volumeter reading differences for handedness and side of paresis, and to define a cut-off point for oedema of 2 SD of the population distribution. RESULTS: Based on volumetric assessment, 33% of patients had oedema. Physical therapists classified 50% of patients as having minor or severe oedema. Results of both methods were clearly related, but agreement between the assessments was not more than 'fair' (67% agreement; Kappa 0.34). The level of agreement was not substantially affected by the cut-off point used for the volumeter score, the time between both assessments or by the side of paresis. CONCLUSION: Agreement between clinical and volumetric assessment of hand oedema in stroke patients is less than desirable. Volumetric assessment of oedema is recommended for research purposes.

Platelet-derived microparticles stimulate coronary artery smooth muscle cell mitogenesis by a PDGF-independent mechanism.

This study investigates the role of platelet-derived microparticles for vascular smooth muscle cell (SMC) proliferation. Microparticles concentration dependently stimulated p42/p44 MAP kinase phosphorylation, c-fos induction, DNA synthesis, and proliferation of cultured bovine coronary artery SMC. The maximum mitogenic effects of microparticles were significantly higher than those of platelet-derived growth factor (PDGF)-BB. Microparticle-induced SMC mitogenesis was heat sensitive, whereas the effects of PDGF were not. In addition, neutralizing anti-PDGF antibodies prevented PDGF-induced DNA synthesis but did not inhibit the effects of microparticles. In contrast to PDGF, which potently stimulated SMC migration, microparticles had only minor migratory activity. These results demonstrate a novel mechanism of SMC mitogenesis by platelet-derived microparticles that is probably independent of PDGF.

Synthesis of cyclic dipeptide templates, their incorporation into peptides and studies on their conformational and biological properties.

This study investigated the diastereoselective synthesis of three dipeptide templates 1, 2 and 3, which may be regarded as conformationally restricted analogs of H-Gly-Xaa-OH, in which Xaa constitutes an aromatic amino acid. Bond formation between alpha-C of Gly and the aromatic moiety was achieved by proton-catalyzed intramolecular electrophilic aromatic substitution. The absolute configuration of the dipeptide templates was determined by single-crystal X-ray crystallography or by nuclear Overhauser enhancement measurements. A protective group strategy was elaborated to allow their incorporation into peptide sequences by liquid phase as well as by solid-phase peptide synthesis. The templates were used to generate an enkephalin analog 15, a modified peptidic neurokinin antagonist 20 and two dermorphin derivatives (24 and 33). Molecular dynamic simulations with 15 and 20 revealed the preference for a turn-like motif for 15. The biological activity, as investigated by respective receptor binding and functional assays, was strongly diminished with all four derivatives, indicating that their receptor-relevant molecular geometries lie outside the examined conformational space.

Synthesis of a new dipeptide template, its X-ray structure, and modeling studies on its conformational features.

The diastereoselective synthesis is reported of a dipeptide template which is closely related to H-Gly-Trp-OH. Intramolecular bond formation between alpha-C of Gly and ring position 2 of the Trp unit has been achieved by a Pictet-Spengler-type electrophilic aromatic substitution. The absolute configuration of the N-Moc protected dipeptide template 9.2H2O was determined by single-crystal X-ray crystallography and found to be (2S,5S). The cis orientation of the amino and carboxy termini prompted us to investigate the potential of 9 as a beta-turn mimic. MD calculations on the model pseudopeptide Ac-Ala-Gly-Trp-Ala-NHMe 11 suggest that an unusually tight turn should be favoured rather than a beta-turn. The proper protective situation as a pre-requisite for the incorporation of the template into a peptide has been established, and comments about its chemical properties are given.

Postnatal development of pyramidal dendritic and axonal bundles in the visual cortex of the rat.

We studied the development and spatial organization of vertically arranged pyramidal dendritic and axonal bundles in the visual cortex of the rat by using extracellular biocytin injections into frontal brain slice preparations. Vertical bundles of intracortical axons could be clearly observed at time of birth with a initial center-to-center distance of 18 microns +/- 3.1 microns. At the same time a clustering of pyramidal cell apical dendrites was completely absent. Dendritic bundles were demonstrated for the first time at postnatal day 5 when the supragranular layer 2/3 begins to differentiate. In the following weeks both axonal as well as dendritic bundles grew continuously and completely in parallel with regard to their center-to-center distances, diameters and number of elements up to their adult values at around postnatal day 90. At adulthood both types of bundles showed a center-to-center distance of 50.1 microns +/- 20.1 microns (axons) and 52.6 microns +/- 18.1 microns (dendrites), respectively. Our results demonstrate that axonal and dendritic bundles originating from the same neurons in the visual cortex of the rat correspond very well with regard to their size and distances. Developing neurons migrating along radial glia fibers group their axons together in fascicles before the lamination of the cortex is completely matured. After all layers have been developed, the apical dendrites of pyramidal cells with aggregated axons also group in clusters. The following development of axonal and dendritic bundles is presumably concerned with the volume increase of the maturating neocortex. Evidence for activity dependent plasticity after eye opening could not be found.

Cyclopeptide analogs for characterization of the neuropeptide Y Y2-receptor.

A discontinuous 17-amino acid peptide analog of neuropeptide Y (NPY), NPY 1-4-Ahx-25-36 containing 6-aminohexanoic acid instead of the residues 5 to 24, was found to bind preferentially to Y2 subtypes of NPY receptors. In order to further characterize the binding site, three different types of cyclic analogs were synthesized. Firstly lactamisation between residues 2 and 30 led to the most selective Y2-agonist, secondly lactamisation between the N-terminus and residue 31 reduced binding significantly. Thirdly, any cyclization including the C-terminus led to an inactive compound. Circular dichroism revealed different conformations for the three analogs with reduced alpha-helical content in comparison to the linear ana-log. The different conformation of the peptides has been confirmed by molecular dynamics simulations. A model for peptide-receptor interaction is suggested.