Headache cessation by an educational intervention in grammar schools: a cluster randomized trial.

BACKGROUND AND PURPOSE: Headache is a common health problem in adolescents. There are a number of risk factors for headache in adolescents that are amenable to intervention. The aim of the study was to assess the effectiveness of a low-level headache prevention programme in the classroom setting to prevent these risk factors. METHODS: In all, 1674 students in 8th-10th grade at 12 grammar schools in greater Munich, Germany, were cluster randomized into intervention and control groups. A standardized 60-min prevention lesson focusing on preventable risk factors for headache (physical inactivity, coffee consumption, alcohol consumption and smoking) and providing instructions on stress management and neck and shoulder muscle relaxation exercises was given in a classroom setting. Seven months later, students were reassessed. The main outcome parameter was headache cessation. Logistic regression models with random effects for cluster and adjustment for baseline risk factors were calculated. RESULTS: Nine hundred students (intervention group N = 450, control group N = 450) with headache at baseline and complete data for headache and confounders were included in the analysis. Headache cessation was observed in 9.78% of the control group compared with 16.22% in the intervention group (number needed to treat = 16). Accounting for cluster effects and confounders, the probability of headache cessation in the intervention group was 1.77 (95% confidence interval = [1.08; 2.90]) higher than in the control group. The effect was most pronounced in adolescents with tension-type headache: odds ratio = 2.11 (95% confidence interval = [1.15; 3.80]). CONCLUSION: Our study demonstrates the effectiveness of a one-time, classroom-based headache prevention programme.

[Consistency and Reliability of MDK Expertise Examining the Encoding in the German DRG System]. / Einheitlichkeit der richtlinienkonformen Begutachtung durch den Medizinischen Dienst der Krankenversicherung bei der Prüfung der Kodierung im G-DRG-System.

INTRODUCTION: Hospital inpatient stays are reimbursed on the basis of German diagnosis-related groups (G-DRG). The G-DRG classification system is based on complex coding guidelines. The Medical Review Board of the Statutory Health Insurance Funds (MDK) examines the encoding by hospitals and delivers individual expertises on behalf of the German statutory health insurance companies in cases in which irregularities are suspected. A study was conducted on the inter-rater reliability of the MDK expertises regarding the scope of the assessment. METHODS: A representative sample of 212 MDK expertises was taken from a selected pool of 1 392 MDK expertises in May 2013. This representative sample underwent a double-examination by 2 independent MDK experts using a special software based on the 3MTM G-DRG Grouper 2013 of 3M Medica, Germany. The following items encoded by the hospitals were examined: DRG, principal diagnosis, secondary diagnoses, procedures and additional payments. It was analysed whether the results of MDK expertises were consistent, reliable and correct. RESULTS: 202 expertises were eligible for evaluation, containing a total of 254 questions regarding one or more of the 5 items encoded by hospitals. The double-examination by 2 independent MDK experts showed matching results in 187 questions (73.6%) meaning they had been examined consistently and correctly. 59 questions (23.2%) did not show matching results, nevertheless they had been examined correctly regarding the scope of the assessment. None of the principal diagnoses was significantly affected by inconsistent or wrong judgment. CONCLUSION: A representative sample of MDK expertises examining the DRG encoding by hospitals showed a very high percentage of correct examination by the MDK experts. Identical MDK expertises cannot be achieved in all cases due to the scope of the assessment. Further improvement and simplification of codes and coding guidelines are required to reduce the scope of assessment with regard to correct DRG encoding and its examination.

Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical trial.

BACKGROUND: Aim of the study was assessment of efficacy and safety of transcutaneous stimulation of the auricular branch of the vagal nerve (t-VNS) in the treatment of chronic migraine. METHODS: A monocentric, randomized, controlled, double-blind study was conducted. After one month of baseline, chronic migraine patients were randomized to receive 25 Hz or 1 Hz stimulation of the sensory vagal area at the left ear by a handhold battery driven stimulator for 4 h/day during 3 months. Headache days per 28 days were compared between baseline and the last month of treatment and the number of days with acute medication was recorded The Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires were used to assess headache-related disability. RESULTS: Of 46 randomized patients, 40 finished the study (per protocol). In the per protocol analysis, patients in the 1 Hz group had a significantly larger reduction in headache days per 28 days than patients in the 25 Hz group (-7.0 ± 4.6 vs. -3.3 ± 5.4 days, p = 0.035). 29.4 % of the patients in the 1 Hz group had a ≥50 % reduction in headache days vs. 13.3 % in the 25 Hz group. HIT-6 and MIDAS scores were significantly improved in both groups, without group differences. There were no serious treatment-related adverse events. CONCLUSION: Treatment of chronic migraine by t-VNS at 1 Hz was safe and effective. The mean reduction of headache days after 12 weeks of treatment exceeded that reported for other nerve stimulating procedures.

An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice.

AIMS/HYPOTHESIS: Loss of circadian clocks from all tissues causes defective glucose homeostasis as well as loss of feeding and activity rhythms. Little is known about peripheral tissue clocks, so we tested the hypothesis that an intrinsic circadian clock of the pancreas is important for glucose homeostasis. METHODS: We monitored real-time bioluminescence of pancreas explants from circadian reporter mice and examined clock gene expression in beta cells by immunohistochemistry and in situ hybridisation. We generated mice selectively lacking the essential clock gene Bmal1 (also known as Arntl) in the pancreas and tested mutant mice and littermate controls for glucose and insulin tolerance, insulin production and behaviour. We examined islets isolated from mutants and littermate controls for glucose-stimulated insulin secretion and total insulin content. RESULTS: Pancreas explants exhibited robust circadian rhythms. Clock genes Bmal1 and Per1 were expressed in beta cells. Despite normal activity and feeding behaviour, mutant mice lacking clock function in the pancreas had severe glucose intolerance and defective insulin production; their isolated pancreatic islets had defective glucose-stimulated insulin secretion, but normal total insulin content. CONCLUSIONS/INTERPRETATION: The mouse pancreas has an autonomous clock function and beta cells are very likely to be one of the pancreatic cell types possessing an intrinsic clock. The Bmal1 circadian clock gene is required in the pancreas, probably in beta cells, for normal insulin secretion and glucose homeostasis. Our results provide evidence for a previously unrecognised molecular regulator of pancreatic glucose-sensing and/or insulin secretion.

Efficient haemodialysis despite complete central venous thrombosis.

Two cases with a fully functional haemodialysis access, in spite of complete thrombotic occlusion of the ipsilateral subclavian and/or brachiocephalic vein are reported. The coincidentally detected complete venous occlusions may indicate that occult venous stenosis or thrombosis is more frequent than generally assumed. In order to avoid deterioration of the haemodynamic situation interventions may be withheld unless clinical problems related to a diminished outflow occur.

Tubulin mRNAs of Trypanosoma brucei.

The tubulin genes of Trypanosoma brucei are located in a single, tightly packed cluster of ten tandemly arranged alternating alpha and beta-genes. No tubulin genes are detected outside the clustered array. Therefore, the cluster can be assumed to be the locus of tubulin gene expression. Single bands of alpha and beta-tubulin mRNAs are observed in cultured procyclic as well as in bloodstream trypanosomes. Both alpha and beta-tubulin mRNAs have distinct 5' termini, which carry a 35-nucleotide mini-exon sequence. The 3' termini of both mRNA populations are heterogeneous.

PET with 18fluorodeoxyglucose and hexamethylpropylene amine oxime SPECT in late whiplash syndrome.

BACKGROUND: Many patients have cognitive abnormalities and psychological problems after whiplash injury to the cervical spine. To our knowledge, neuroradiologic imaging has not depicted brain damage that explains the symptoms. Parietotemporo-occipital perfusion deficits on hexamethylpropylene amine oxime (HMPAO) SPECT studies have been described among patients who have sustained whiplash injury. METHODS: We examined 13 patients with typical late whiplash syndrome (study group) using HMPAO SPECT, 18fluorodeoxyglucose (FDG) PET, and MRI of the brain and compared the findings with those for 16 control subjects who underwent FDG PET. RESULTS: In the study group, statistical parametric mapping revealed significantly decreased FDG uptake in the frontopolar and lateral temporal cortex and in the putamen. The frontopolar hypometabolism correlated significantly with scores of the Beck Depression Inventory. However, in individual cases, reliability in the depiction of hypometabolic areas was relatively low. No alterations were found in the parietotemporo-occipital area. In these areas, decreased uptake of HMPAO and FDG correlated with cortical mass. CONCLUSION: FDG PET did not allow reliable diagnosis of metabolic disturbances for individual patients. Therefore, we do not recommend FDG PET or HMPAO SPECT as a diagnostic tool in routine examinations of patients with late whiplash syndrome.

The use of transgenic Trypanosoma brucei to identify compounds inducing the differentiation of bloodstream forms to procyclic forms.

The expression of procyclins is the earliest known marker of differentiation of bloodstream forms of Trypanosoma brucei to procyclic forms. We have generated transgenic bloodstream and procyclic forms in which the coding region of one procyclin gene was replaced by E. coli beta-glucuronidase (GUS). GUS activity can be monitored in a simple one-step colour reaction in microtitre plates; this assay is potentially suitable for large-scale screening for compounds that influence differentiation. GUS was stage-specifically expressed in procyclic forms and its synthesis occurred in parallel with that of procyclin when bloodstream forms were triggered to differentiate by the addition of cis-aconitate. GUS could also be induced by brief treatment with the proteases trypsin, pronase or thermolysin, but not with pepsin or thrombin. Interestingly, a combination of one of the active proteases with cis-aconitate resulted in increased GUS activity relative to either trigger alone. In contrast to cis-aconitate, protease treatment resulted in considerable cell death. Experiments with the pleomorphic strain AnTat 1.1 showed that long slender bloodstream forms were rapidly killed by proteases, whereas stumpy forms were largely resistant. Stumpy forms treated with trypsin differentiated synchronously and expressed procyclin with faster kinetics than when they were triggered by cis-aconitate. As predicted by the GUS assay, differentiation was even more rapid when both inducers were used simultaneously, with all cells expressing maximal levels of procyclin within 3 h.

Theophylline and warfarin interaction studies with grepafloxacin.

Two phase I trials, each involving 16 healthy adult volunteers, were performed to investigate possible interactions between grepafloxacin and theophylline or warfarin. In the theophylline study, grepafloxacin 600 mg was administered once daily for 10 days to 12 volunteers who were receiving a maintenance dose of theophylline. This dose of theophylline was designed to produce mean serum theophylline concentrations of 7.5 mg/L; 4 volunteers received theophylline plus placebo. Pharmacokinetic parameters of theophylline were determined before grepafloxacin treatment and on day 10 of grepafloxacin or placebo administration. Peak theophylline concentrations and the area under the concentration-time curve increased significantly during grepafloxacin treatment, and apparent total clearance of theophylline was reduced by approximately 50%. No changes were observed in the placebo group and theophylline appeared to have no effect on the pharmacokinetics of grepafloxacin. In the warfarin study, grepafloxacin 600 mg was given once daily for 14 days to volunteers receiving a maintenance dose of warfarin. Warfarin was discontinued during the last 4 days of grepafloxacin administration. The pharmacodynamics of warfarin did not change after administration of grepafloxacin. Similarly, warfarin had no significant effect on the pharmacokinetics of grepafloxacin. We conclude that during treatment with grepafloxacin maintenance, doses of theophylline should be reduced by 50%, and we recommend that serum concentrations of theophylline be monitored during treatment with grepafloxacin. However, no dose adjustment is necessary for grepafloxacin when it is coadministered with theophylline, and dose adjustment does not seem to be required in concomitant treatment with grepafloxacin and warfarin.

Reaching in the dark: enhanced responses in posterior parietal cortex.

In order to assess the relative importance of visual input to area 7 reach-related neuronal activity, a monkey was trained to reach to visual targets displayed on a video-monitor, both with and without visual feedback. Visual feedback was removed by having the monkey reach in darkness to a previously illuminated target. Of 19 reach-related cells recorded in area 7 both in the light and the dark, ten showed an enhancement of discharge in the dark. These included area 7b cells sensitive to screen contact and area 7a cells active during reach. Dark enhancement of active somatic responsiveness may partially compensate for the loss of visual guidance.

Manipulation reach and visual reach neurons in the inferior parietal lobule of the rhesus monkey.

The characteristics of inferior parietal lobule (IPL) 'reach cell' responses were studied in the fixating monkey in order to obtain a clue to the function of this area in manipulative behavior. Two subclasses of reach neurons, one showing visual receptive field sensitivity, the other lacking such responsiveness are proposed as correlates of two types of reach behavior, one that takes place with, the other without visual guidance, respectively. Neuronal firing increment and/or firing decrement responses, stimulus-bound to reach behavior were obtained from either type of cell. These were presented as equivalent modes of signal encoding, on the basis of the transformability of neuronal firing increment to firing decrement response as a result of preconditioning stimulation of the oral pulvinar nucleus. Many of the responses obtained were bimodal and some were biphasic, i.e. consisting of incremental and decremental firing phases. As each such component was independently modifiable, they were regarded different signal entities. The multicomponental nature of the visual reach neuronal response was manifested when the reaching movement was into the receptive field of the neuron. Responses consisted then of an initial component, presumably visual, prefixed to a response component stimulus-bound to the reach-invoking stimuli. The early component occupied the same position as the visual response of the cell obtained with visual receptive field stimulation alone. Moreover, the early component could be negated by preconditioning stimulation of the LP and/or pulvinar targets, and then the residual response simulated the response of a non-visual reach neuron.(ABSTRACT TRUNCATED AT 250 WORDS)

A pharmacological analysis of autonomic pathways mediating myocardial disturbances originating in a lateral hypothalamic area of the cat.

A study was made of the mechanisms mediating autonomic changes resulting from stimulation of a site in the lateral hypothalamic area (LHA). This site, when stimulated, induced angina-like ECG disturbances similar to those observed in some cases of brain traumas. These ECG changes were often associated with other autonomic changes, such as pressor response, tachycardia (in some cases bradycardia), nictitating membrane (NM) contraction and pupillary dilatation. Most symptoms were sympathetic: they were largely abolished by spinal cord section between C1 and C2, but were not affected by vagotomy, except that bradycardia was converted to tachycardia. Adrenal catecholamines were not involved since adrenal vein ligation was without effect. Hexamethonium (5-10 mg/kg) prevented pressor response and tachycardia in most cats but only partly protected against ECG changes and NM contractions. Atropine methyl nitrate (0.2 mg/kg) abolished the remaining ECG abnormalities and NM tension. The beta-receptor antagonists, propranolol and practolol (50 micrograms/kg) completely prevented the ECG changes induced either by isoprenaline or LHA stimulation. It is concluded that the symptoms induced by LHA stimulation result from noradrenaline release in the target organs.

A motor-driven miniature multiple microelectrode manipulator for recording from the cortical neuropile of the awake monkey in operant behavior paradigms.

An improved version of the Blum and Feldman multiple microelectrode manipulator is described. The main innovation is a design based on miniaturization and light weight (75 g), which allows head mounting with minimal disturbance to the animal in awake monkey operant behavior studies. The major features of the previously described model are preserved: simultaneous independent manipulation of four microelectrodes, in order to record from at least four single units, that may be crosscorrelated. With the new design better adjustment of intermicroelectrode distances for studies of interneural distances of 300 microns to 7 mm, and an easier automatic, computer-controlled monitoring of distances transversed into the brain are possible.

Characterization of the [3H]-desipramine binding site of the bovine adrenomedullary plasma membrane.

The specific (i.e. nisoxetine-sensitive) binding of [3H]desipramine was studied in membranes prepared from bovine adrenal medullae. (1) [3H]desipramine bound reversibly and with high affinity (KD = 2.8 nmol/l) to a single class of non-interacting binding sites (Hill coefficient = 0.96); the maximal number of binding sites (Bmax) was 2.1 pmol/mg protein. (2) Binding of [3H]desipramine was dependent on [Na+] and [Cl-]. Increasing the concentrations of these ions increased binding. (3) Substrates and inhibitors of the neuronal noradrenaline transport system (uptake1) inhibited binding of [3H]desipramine with a rank order of potency typical for an interaction with the uptake1 carrier. The characteristics of [3H]desipramine binding remained essentially unchanged after solubilization of adrenomedullary membranes with the non-ionic detergent digitonin. The results indicate that the plasma membrane of bovine adreno-medullary cells is endowed with the neuronal uptake1 transporter.

A head holder and stereotaxic device for the rattlesnake.

We describe an apparatus for immobilization of the rattlesnake head for brain experimentation. Its design also allows its use as a stereotaxic instrument for electrophysiological studies employing microelectrodes. Attachment of the head is at the two orbital ridges and the hard palate. The bregma provides a zero reference for the frontal, lateral, and depth coordinates.

Stereotaxic head restraint for chronic and semi-chronic marmoset and macaque monkeys.

A device allowing head holding and stereotaxic manipulations in both small-sized Marmoset and in relatively large Macaca monkeys is described. Its design permits free access to most targets in the visual system and optimizes presentation of visual stimuli in awake-chronic and anaesthetized semi-chronic preparations. Extra-aural attachments to temporal bone are implanted stereotaxically, under anaesthesia, on both sides of the skull. This provides means for stereotaxic head-holding which minimizes discomfort to the animal. Maintenance of stereotaxic precision over long periods of time, possibility of realignment and use of one device for various monkey species are special features of the method.

Biochemical characterization and purification of the neuronal sodium-dependent noradrenaline transporter.

The protein properties of the neuronal sodium-dependent noradrenaline (NA) transporter of PC12 (rat pheochromocytoma) cells and of bovine adreno-medullary cells were studied by means of binding of 3H-desipramine (3H-DMI). 3H-DMI binding was decreased by proteases, phospholipase A2, by disulfide reducing agents and by the sulfhydryl-group alkylating agent N-ethylmaleimide. The NA transporter was partially purified by anion exchange and affinity chromatography. Tritiated desmethylxylamine (3H-DMX) bound irreversibly and in a DMI-sensitive manner to two PC12 membrane proteins (32kd and 53kd) which may represent components of the NA transporter.

The importance of panographic and dental evaluation for lesions of the antrum.

A large dentigerous cyst which displaced the antrum and partly eroded its bony walls was interpreted as a malignant neoplasm in routine sinus films. The true nature of the process was readily apparent in a panographic view which showed an unerupted third molar lying horizontally above the apices of the first and second molars. This case is an excellent demonstration of the important role of panographic views in the differential diagnosis of maxillary sinus lesions.

The use of clinical information systems to control cost as well as to improve care.

Clinical resources represent the major items of expense in hospital care. These resources are under the primary control of physicians. For a number of reasons it is difficult to manage these resources in the sense of ensuring their prudent use under all circumstances. Relevant clinical information brought to bear at the time and place of the decisions which allocate these resources can encourage prudent use directly (through reduction in waste) and indirectly (through improving the quality of care).

Survival of pig embryos flushed from the reproductive tract immediately or two hours after slaughter of donors.

Four- to eight-cell embryos were collected from genital tracts of slaughtered gilts. Prepuberal donors were synchronized and superovulated by PMSG and hCG, inseminated and eventually slaughtered approximately 78 h after the expected time of ovulation. Genital tracts were flushed either immediately after slaughter (group A) or after 2 h storage at either 37 degrees C (group B) or 20 degrees C). Best results were achieved in group A, followed by group B and, by a wide margin, group C. Differences in viability of embryos became more evident with longer culture times.