[Severe and moderate haemophilia under prophylactic replacement treatment--maximal knee extensor and flexor torque of children and adolescents]. / Schwere und mittelschwere Hämophilie unter prophylaktischer Substitutionstherapie. Maximale Drehmomente der Knieextensoren und Knieflexoren bei Kindern und Jugendlichen.

UNLABELLED: Due to its influence on haemophilic arthropathy, the evaluation of knee extensor (K(Ext)) and flexor (K(Flex)) torques plays an important role in the preventive and rehabilitative context of haemophilia. Thus, the present study aimed at investigating maximal static torque (M(Max)) of K(Ext) and K(Flex). 14 boys with haemophilia (8 severe, 6 moderate; age: 11.7 ± 2.8 years; prophylactic treatment > 5 years) and 14 healthy carefully pair-matched controls (age: 11.5 ± 2.7 years) were separately measured for the left and right leg for M(Max). Furthermore, the ratio K(Flex)/K(Ext )was calculated and the joint situation assessed using the Haemophilia Joint Health Score. RESULTS: No significant group-effect was observed for M(Max) of the K(Ext) and K(Flex) as well as for the ratio K(Flex)/K(Ext) (p>0.05). Despite significant higher joint scores in haemophilic children compared to their healthy controls (p<0.01), patients merely showed minor joint impairments. CONCLUSION: Children and adolescents with severe and moderate haemophilia under prophylactic replacement treatment with a good joint status showed comparable maximal strength performance of relevant knee muscles compared to their healthy peers.

Prophylactic treatment of haemophilia patients with inhibitors: clinical experience with recombinant factor VIIa in European Haemophilia Centres.

Many patients with haemophilia develop inhibitors to factor VIII and require bypassing agents to provide haemostatic cover for limb- or life-threatening bleeding episodes. Due to the reduced risk of blood-borne pathogen transmission with recombinant products, on-demand recombinant factor VIIa (rFVIIa; NovoSeven is the treatment of choice for children with inhibitors. In haemophiliac patients without inhibitors, primary prophylaxis has been clinical practice for several years. This paper summarises 13 case histories of rFVIIa secondary prophylaxis for haemophilia patients with inhibitors. This was a retrospective survey of adult and paediatric severe haemophilia patients with inhibitors treated with rFVIIa from ten European Haemophilia Centres. There was a wide variation in administered rFVIIa dose, from 200-250 microg kg(-1) per week to 220 microg kg(-1) daily. In many cases, this was lower than the recommended on-demand dose of rFVIIa. In 12/13 cases, prophylaxis with rFVIIa considerably reduced the number of bleeding episodes compared with previous treatment. Eight/nine patients were satisfied or very satisfied with rFVIIa treatment, and in cases reporting subjective quality of life (QoL), all were improved, much improved, or significantly improved. In haemophilia patients with inhibitors, prophylaxis with rFVIIa is highly effective in reducing the number of bleeding episodes and results in good patient compliance and improved QoL. Randomised controlled trials are needed to confirm these findings. Results of a recently completed clinical trial on secondary prophylaxis with rFVIIa in frequently bleeding haemophilia patients with inhibitors are expected in late 2006.

Treatment of children with haemophilia in Europe: a survey of 20 centres in 16 countries.

A survey was made of the current status of treatment of haemophilic boys at 20 centres in 16 European countries and includes approximately 1500 of the estimated 6500 haemophiliacs in the participating countries. Many mild haemophiliacs are not seen, or seen infrequently, at haemophilia centres and this requires study. Nine of 18 centres provide continuous prophylaxis to 80-100% of their patients, five centres provide it to 55-80% and the remaining four centres to 15-40% of the boys. The median dose given was 6240 U kg-1 year-1 (range 3120-7800). Four centres administered only recombinant concentrates to children with severe haemophilia A, while seven centres administered recombinant concentrates to 75-90% and the remaining centres to less than 50% of the boys (two centres < 10%). When asked for the choice of concentrate for a newly diagnosed boy with severe haemophilia A, all but one centre preferred recombinant concentrate. Most boys below 6 years received concentrates via a peripheral vein but three centres preferred a central venous line for 80-100% of the boys. Thirteen of 18 centres applied home treatment to 84-100% of the boys and the remaining five centres to 57-77% of the boys.

Morning versus evening administration of nifedipine gastrointestinal therapeutic system in the management of essential hypertension.

The nifedipine gastrointestinal therapeutic system (GITS) is a recently developed controlled-release formulation for once-a-day dosing. We evaluated the influence of morning versus evening administration of the drug in a randomized double-blind cross-over study including 15 essential hypertensives. Five patients had to be excluded from blood pressure analysis because of noncompliance (three cases) or intolerable side effects (two cases). To assess the exact duration of the antihypertensive efficacy noninvasive automatic ambulatory blood pressure monitoring was performed. After a placebo period patients were given 30 mg nifedipine GITS either at 1000 or 2200 hours. Twenty-four-hours systolic and diastolic blood pressure profiles documented a sustained antihypertensive effect of both nifedipine regimens throughout the whole period without affecting the circadian rhythm. Statistical analysis revealed no significant difference between morning and evening administration. Two patients stopped their medication because of intolerable side effects (fatigue and muscle cramps, respectively). Two more cases suffered from mild reversible headache which provoked no discontinuation of the drug. In conclusion our results document a sustained antihypertensive efficacy of 30 mg nifedipine GITS in patients with moderate essential hypertension. Time of administration has no impact on day- and nighttime blood pressure control.

Pharmacokinetic profile of nifedipine GITS in hypertensive patients with chronic renal impairment.

25 hypertensive patients with normal or impaired renal function underwent pharmacokinetic and safety studies after single and multiple dose administration of nifedipine GITS (Gastro-Intestinal Therapeutic System) 60mg tablets. Complete pharmacokinetic data were obtained from 23 of these patients. Blood pressure and heart rate changes were compatible with the known properties of the drug. Impaired renal function did not affect the maximum plasma concentrations or bioavailability of nifedipine after single or multiple dose administration of nifedipine GITS, nor was there any evidence of excessive drug accumulation in the presence of renal impairment.

Antihypertensive effect of nifedipine-retard and acebutolol in patients with hypertension: a randomized double-blind study

A randomized double-blind, comparative study, with a new slow release preparation of nifedipine (nifedipine-retard), was undertaken in patients with mild, moderate and severe essential hypertensión WHO (stage I-II). After a two-week placebo period, patients were divided into three groups: 1) group I received nifedipine-retard 20 mg orally twice daily; 2) group II received acebutolol 200 mg orally twice daily; and 3) group III received nifedipine-retard 20 mg once daily plus acebutolol 200 mg orally once daily. All three dosage regimens were administered for six weeks. Nifedipine-retard (group I) reduced supine blood pressure from 162 ñ 4.2/105 ñ 1.4 mmHg (21.6 ñ 0.5/14.0 ñ 0.2 Pa) to 139 ñ 4.2/92 ñ 2.6 mmHg (18.5 ñ 0.5/12.3 ñ 0.3 kPa) and slighrly increased the heart rate. Acebutolol (group I) reduced supine blood pressure from 163 ñ 5.3/107 ñ 2.8 mmHg (21.7-0.7/14.2 ñ 0.4 kPa) to 144 ñ 5.0/93 ñ 3.7 mmHg (192 ñ 0.7/12.4 ñ 0.5 kPa) and decreased the heart rate. Nifedipine retard plus acebutolol (group III) reduced supine blood presure from 144 ñ 3.0/101 ñ 1.3 mmHg (19.2 ñ 0.4/13.4 ñ 012 kPa) to 123 ñ 3.4/84 ñ 2.8 mmHg (16.4 ñ 0.5/11.2 ñ 0.4 kPa) and did not significantly alter the heart the heart rate. There was a significant correlation (r = 0.65, p < 0.03) betwee baseline blood pressure and diastolic blood pressure after six weeks of therapy nifedipine-retard. There was a no significant trend between the age of patients and decrease of diastolic blood pressure, positive for nifedipine-retard, and negative for acebutolol. There was a low incidence of side effects with all dosage regimens..

Twenty four hour intermittent, ambulatory blood pressure monitoring.

Blood pressure and heart rate were measured every 30 minutes during the day and every hour during the night in 43 children (20 girls and 23 boys, aged 10 to 16) with a portable automated monitor. The apparatus was better accepted in girls than in boys, and the failure rate was lower during the day. The overall failure rate was 22%, which corresponds with comparable studies in adults. During the night blood pressure and heart rate fell by 10% and 14% of the daytime values, respectively. Mean (SD) blood pressure was significantly higher in boys than in girls (126/72 (17/8) v 109/64 (9/5) mm Hg) and measurements correlated positively with age, body weight, and height of the subjects. Heart rate was not significantly influenced by gender or age. A positive correlation between heart rate and blood pressure was found when expressed as standard normal deviations or hourly variations. In children intermittent monitoring of ambulatory blood pressure and heart rate is a suitable method for measuring individual diurnal patterns.

[Prospective evaluation of coagglutination and latex agglutination in the diagnosis of bacterial meningitis in childhood]. / Prospektive Evaluation von Coagglutination und Latex-Agglutination in der Diagnostik der bakteriellen Meningitiden im Kindesalter.

UNLABELLED: Two simple and low-priced kits to detect bacterial antigens in cerebrospinal fluid (CSF) specimens from patients with suspected meningitis have recently become available. Methods employed by these kits are staphylococcal coagglutination (COA) and latex agglutination (LA). The COA "Phadebact CSF-kit" (Pharmacia) detects Haemophilus influenzae type b (HIb), Neisseria meningitidis (NM) groups A, B, C, Y and W 135 and Streptococcus pneumoniae (SP), whereas the LA "Slidex Méningite-kit" (BioMérieux) includes HIb, NM A, NM C and SP. These two diagnostic tests were compared with the standard methods for analyzing CSF specimens from children with suspected meningitis. A total of 336 CSF specimens were tested. Forty-three were from children with bacterial meningitis due to HIb, NM or SP obtained before antimicrobial therapy. Thirty-four of them (79%) were correctly detected by COA, 23 (54%) by LA, and 42 (97%) by microscopic analysis of stained smears. There were 65 CSF samples of such meningitis cases obtained after initiation of antimicrobial therapy: COA detected 26 (40%), LA 17 (26%) and staining 26 (40%). With culture-positive CSF specimens from patients before therapy, the best sensitivities were obtained with LA for SP (100%) and COA for HIb (87%), whereas the results for NM antigen detection were only 43% with COA and 0% with LA (no reagent against NM B). Cross-reactions with other bacterial antigens were frequent with COA (26%) and rare with LA (2%), resulting in false-positive findings in 6 of the 66 positive tests with COA (9%) but in none of the 40 positive tests with LA (0%). One of the 48 specimens from aseptic meningitis cases was false-positive for HIb by COA, whereas all 172 normal specimens were negative with both methods. With 5 culture-negative CSF specimens from patients with unequivocal purulent meningitis COA detected bacterial antigen in 5 and LA in 2. CONCLUSIONS: The two kits evaluated cannot replace standard methods for analyzing CSF specimens, in view of insufficient sensitivity (mainly LA) or frequent cross-reactions and false-positive values (COA). However, due to their simplicity, rapidity, and possible identification of bacterial pathogens after initiation of antimicrobial therapy, these kits are recommended as an useful addition to standard methods.