Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial

Context  There is a paucity of effective, well-tolerated drugs available for migraine prophylaxis. Objective  To determine whether treatment with the angiotensin II receptor blocker candesartan is effective as a migraine-prophylactic drug. Design and Setting  Randomized, double-blind, placebo-controlled crossover study performed in a Norwegian neurological outpatient clinic from January 2001 to February 2002. Patients  Sixty patients aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly from newspaper advertisements. Interventions  A placebo run-in period of 4 weeks was followed by two 12-week treatment periods separated by 4 weeks of placebo washout. Thirty patients were randomly assigned to receive one 16-mg candesartan cilexetil tablet daily in the first treatment period followed by 1 placebo tablet daily in the second period. The remaining 30 received placebo followed by candesartan. Main Outcome Measures  The primary end point was number of days with headache; secondary end points included hours with headache, days with migraine, hours with migraine, headache severity index, level of disability, doses of triptans, doses of analgesics, acceptability of treatment, days of sick leave, and quality-of-life variables on the Short Form 36 questionnaire. Results  In a period of 12 weeks, the mean number of days with headache was 18.5 with placebo vs 13.6 with candesartan (P = .001) in the intention-to-treat analysis (n = 57). Some secondary end points also favored candesartan, including hours with headache (139 vs 95; P<.001), days with migraine (12.6 vs 9.0; P<.001), hours with migraine (92.2 vs 59.4; P<.001), headache severity index (293 vs 191; P<.001), level of disability (20.6 vs 14.1; P<.001) and days of sick leave (3.9 vs 1.4; P = .01), although there were no significant differences in health-related quality of life. The number of candesartan responders (reduction of 50% compared with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with migraine. Adverse events were similar in the 2 periods. Conclusion  In this study, the angiotensin II receptor blocker candesartan provided effective migraine prophylaxis, with a tolerability profile comparable with that of placebo.      

Parental perception of cold extremities and other accompanying symptoms in children with cerebral palsy.

Cold extremities have been noted in non-walking children with cerebral damage compared with healthy controls. Whether this is a general problem in children with cerebral palsy (CP) and associated with other symptoms is unknown. This study describes accompanying symptoms such as cold extremities, constipation, pain, sleeping disorders and impaired well-being in children with CP as well as treatment the children have undergone. Associations between cold extremities and other symptoms borne by the children were analysed and discussed. From information in postal surveys received from parents of children with CP, 107 children (60 boys and 47 girls) aged 5-13 years, mean 11 years 8 months (SD 2 years 11 months), were described and analysed. Besides neurological impairments, many children had cold extremities and pain, sleeping disorders, constipation, and impaired well-being. Most children had had one or more of these symptoms for over 1 year but the symptoms were largely untreated. Non-walkers generally had more symptoms than walkers. Although pain, constipation, and sleeping disorders may have different underlying causes in children with CP, these symptoms might also be mediated or aggravated by dysfunction in the autonomic nervous system. To improve the child's well-being, early recognition and treatment of accompanying symptoms is important.     

Antibodies to measles virus surface polypeptides in an immunized student population before and after booster vaccination

Serum specimens collected from 82 students before and after booster immunization with live measles virus (MV) vaccine were tested for MV surface protein-specific antibodies using a previously developed competitive enzyme immunoassay (E1A). The specificity of the assay in measuring antibodies against three sites on the haemagglutinin (H) and two on the fusion (F) protein was demonstrated. All subjects in this study were vaccinated, as one to two year-olds, three times with inactivated killed vaccine and later once or more with live vaccine. Fifty-three students were administered only live measles virus vaccine (M), whereas 29 were vaccinated with the MV combined with mumps and rubella (MMR). There was a clear tendency to a lower increase in antibody titres when MMR vaccine was used. This difference between the groups was most pronounced in antibodies against the site defined by a monoclonal antibody (mAb) 129. Antibodies to the site defined by the mAb 16AG5 on the F protein had no correlation with any of the other tests which suggests that subjects originally vaccinated with killed vaccine may have developed a distinct response to this site.     

7-Hydroxymethotrexate concentrations in serum and cerebrospinal fluid of children with acute lymphoblastic leukemia

Summary Concentrations of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) were determinded by HPLC in the serum and cerebrospinal fluid (CSF) of 29 children with acute lymphoblastic leukemia. CSF and serum samples were obtained at the end of 104 infusions of MTX given in a dose range of 0.5–8.0 g/m². Concentrations, distribution ratios in serum and CSF for MTX and 7-OH-MTX, and the metabolic index were analyzed with regard to the MTX dose, age and clinical state of the patients. A wide inter-patient (2- to 12-fold) but narrower (1,1- to 3,5-fold) intra-patient variability of the concentrations was observed. A dose-proportional increase in the metabolite concentration was found in serum. On the other hand, the elevation of the level of metabolite in CSF was less than porportional to the dose. The CSF/serum distribution data suggest the existence of a saturable carrier system for MTX and 7-OH-MTX between serum and CSF that has lower affinity for 7-OH-MTX. No correlation was found between concentrations of MTX and 7-OH-MTX in the serum of patients receiving the same dose of MTX. No significant difference was observed in the values for metabolic index between relapsed patients and those who were in continuous complete remission. A significant correlation was found between age and metabolic index: the younger the patient, the higher the metabolite concentration measured in serum.     

Regulation of cerebral blood flow in patients with autonomic dysfunction and severe postural hypotension

Background: Whether cerebral blood flow (CBF) autoregulation is maintained in autonomic dysfunction has been debated for a long time, and the rather sparse data available are equivocal. The relationship between CBF and mean arterial blood pressure (MABP) was therefore tested in eight patients with symptoms and signs of severe cardiovascular autonomic dysfunction. Patients and methods: Eight patients were included, three of whom had Parkinson's disease, three diabetes, one pure autonomic failure and the last one had multiple system atrophy. By the use of two techniques, the arteriovenous oxygen [(a‐v)O₂] method and xenon‐inhalation with single photon emission tomography, 15 measurements (range 10–20) and three to four CBF measurements, respectively, were obtained in each patient. Following CBF measurements during baseline, MABP was raised gradually using intravenous noradrenaline infusion, and then lowered by application of lower body negative pressure. From the (a‐v)O₂ samples the CBF response to changes in MABP was evaluated using a computer program fitting one or two regression lines through the plot. Results and conclusion: Preserved autoregulation was observed in three patients, while the remaining five patients showed a linear relationship between CBF and MABP. Comparison of the results of the tomographic CBF measurements to the (a‐v)O₂ data demonstrated that it is not possible to assess whether CBF is autoregulated or not with only three to four pairs of data.     

Long-term monitoring of arterial pO2 in burned patients

Summary. Five patients, who were treated in a special ward for bums were followed by continuous intra-arterial pO₂ monitoring for a total of 1612 h (range 13–604 h). The pao₂ catheter electrodes used were surface-heparinized, and inserted either in the radial or the femoral artery. Some electrodes were accidentally withdrawn. Recalibration was performed for two of the 10 electrodes used. These electrodes presented a changed sensitivity after heavy stretching of the sensor during the nursing. The sensitivity of one of these electrodes was altered downwards and the other one upwards. After recalibration the pao₂ electrodes presented accurate values for the rest of the monitoring period. Without compensation for drift, the pao₂ electrode readout was compared to the results of traditional blood-gas analysis, which served as a reference. The regression function found was y = -0·62+ 1·04x (r=0·93, SD=1·40, n=60). The blood flow velocity around some of the pao₂ electrodes was studied by the pulsed Doppler technique. There was no influence of the surface-heparinked pao₂ electrode on the femoral artery blood flow velocity as compared to the contralateral, non-catheterized femoral artery. The blood flow velocity proximal to a traditional radial artery catheter was compared to the flow velocity in the contralateral radial artery containing a surface-heparinized pao₂ electrode. The surface-heparinked electrode did not decrease the mean flow velocity in contrast with the traditional radial artery catheter, which had to be withdrawn after 8 days because of clotting. The surface-heparinized catheter electrode was still monitoring pao₂ accurately after 25 days in the artery, which was the longest period studied for a particular sensor.     

Abnormally increased endothelin-1 in plasma during the night in obstructive sleep apnea: relation to blood pressure and severity of disease

BACKGROUND: The mechanisms involved in development and maintenance of hypertension in obstructive sleep apnea (OSA) are not clarified. We hypothesize that patients with OSA have an abnormal nocturnal level of some vasoactive hormones during the night. METHODS: We studied 32 patients with OSA and 19 healthy control subjects during The night-time with serial determinations of endothelin-1 (ENDO-1), angiotensin II (Ang II), renin (PRC), aldosterone (ALDO) in plasma, and blood pressure (BP), and oxygen saturation. RESULTS: Patients with OSA had a higher plasma level of ENDO than healthy controls and the mean nocturnal level of ENDO correlated significantly to the apnea-hypopnea index (AHI) as a measure of the severity of OSA. This correlation remained statistically significant after analysis in a general linear model with correction for confounders. Patients with OSA also had a significantly higher BP than healthy controls and the ambulatory BP correlated positively to the AHI in patients with OSA. No significant differences were measured in Ang II, PRC, and ALDO between the two groups. The correlation between AHI and ENDO supports OSA as a stimulus of endothelin release or increased endothelin levels contributing to the severity of OSA. CONCLUSIONS: Endothelin seems to be a pathogenic factor in generating hypertension in OSA.     

'We're just sick people, nothing else': ... factors contributing to elderly stroke patients' satisfaction with rehabilitation

Objective: To identify factors contributing to elderly stroke patients' satisfaction with rehabilitation following stroke.Design: Qualitative study using semi-structured interviews.Setting: Interviews conducted in two phases, once in a stroke rehabilitation unit and once after hospital discharge.Subjects: Twelve elderly stroke patients (seven women and five men, aged 60-87 years).Results: One main category: 'To be treated with respect and dignity' was identified as a core factor contributing to patients' satisfaction with the rehabilitation services. This main factor was divided into five subcategories: (1) Being treated with humanity, (2) Being acknowledged as individuals, (3) Having their autonomy respected, (4) Having confidence and trust in professionals, (5) Dialogue and exchange of information. The statements covered a continuum from satisfaction via indifference to dissatisfaction. Expressions of satisfaction emerged mainly as general statements while expressions of dissatisfaction described situations in greater detail. Satisfaction was merely connected to daily care experiences and fulfilment of basic needs. Trust in providers and being dignified seemed more closely associated with satisfaction than being involved in treatment decisions. The findings demonstrate how the quality of patient-professional interaction influences patients' satisfaction with stroke rehabilitation.Conclusion: To be treated with respect and dignity seems to be a core element influencing vulnerable elderly stroke patients' satisfaction with rehabilitation. A merely functional definition of the success of rehabilitation should be expanded into an approach encompassing patients' perceptions and personal preferences. The meaning of dignity for elderly stroke patients in the rehabilitation setting should be further clarified and given practical substance.     

Pressure-pain threshold algometric measurement in patients with greater trochanteric pain after total hip arthroplasty

BACKGROUND: The evaluation of tenderness associated with greater trochanteric pain (GTP) syndrome is amenable to bias and depends on the examiner's experience. In this study, we tested whether the use of an electronic pressure algometer enhanced the reliability of this evaluation. PATIENTS AND METHODS: Pressure-pain threshold (PPT) was measured with an electronic algometer in 18 patients who developed GTP after total hip arthroplasty and in matched controls. Both groups were evaluated with visual analog scale. RESULTS: The PPT measurements showed large interindividual variability across patients. The correspondence of the PPT measurements in asymptomatic patients was good. We found good validity for the algometer used. The PPT ratio of 0.8 (affected vs. unaffected side) can be used as a cut-off ratio. The PPT measurements at the greater trochanter (local pain) were significantly lower than at the ilio-tibial band (radiated pain). There was no correlation between PPT measurements and visual analog scales. Despite the acceptable sensitivity and specificity of pressure algometer, because of low positive predictive value and large interindividual variability, pressure algometer has a limited value as a screening test. CONCLUSIONS: The examination of tenderness associated with GTP is facilitated by the used algometer. It is the intraindividual body-side PPT differences that yield the most sensitive measurement for the assessment of deep pain. A cut-off value of 0.8 can be used for diagnostic purposes. Interindividual differences might be considerable and could mask pathologic diagnostic findings.     

Fluoreszenzzystoskopie

Many studies confirm the clinical interest of photodynamic diagnostics (PDD) in non-muscle invasive bladder cancer management. PDD or fluorescence cystoscopy is not only of great value in occult urothelial cancer detection, but may have a positive impact on disease-free survival and prognosis. Yet, its specificity is found to be highly variable between studies mainly in relation to different disease profiles. New imaging techniques aimed at enhancing visualization to assess the bladder wall are under development.