Search PubMed⌕ Search

Biomedical subjects

K Hoppu

Publications and source records attributed to K Hoppu.

At least 37 records · Page 2Linked to original sources

Flunarizine of limited value in children with intractable epilepsy.

Fourteen ambulatory children and adolescents with intractable epilepsy were studied in an open phase II study to investigate the pharmacokinetics and pharmacodynamics of flunarizine as an add-on treatment. Flunarizine was given in increasing doses starting with 0.1-0.3 mg/kg/day until effect was observed or a steady-state plasma concentration of 50-60 ng/ml was reached. Treatment was continued for 3 months at steady state. Pharmacokinetics were determined during the immediate posttreatment period. Positive antiepileptic effect (> or = 50% reduction in seizure frequency) was observed in 4 of 14 patients (29%; 95% CI: 52-5). Independently of antiepileptic effect, 10 of 14 parents (71.4%; 95% CI: 95-48) observed positive cognitive effects. In all patients treatment was withdrawn due to either lack of effect or weight gain. Flunarizine was rapidly absorbed; mean time of peak concentration (Tmax) was 2.7 hours (range: 1-8). The mean terminal half-life was 23.2 days (range: 7-48), the total plasma clearance of flunarizine per fraction of the dose absorbed (CLp/F) was 0.28 ml/min/kg (range: 0.07-042), and the volume of distribution of flunarizine per fraction of the dose absorbed (Vd/F) was 187 L/kg (range: 99-348). We conclude that flunarizine (0.1-0.3 mg/kg/day) seems to be of limited antiepileptic value in children with intractable epilepsy. The pharmacokinetic profile of flunarizine complicates its clinical use.

Adolescent↗

Effect of age on the fulfilment of the IHS criteria for migraine in children at a headache clinic.

In a headache clinic, 247 children suffering from severe recurrent headaches were studied in relation to the IHS criteria for migraine. Of the 247, 163 had migrainous headache, with 100 (67.5%) of these having migraine in accordance with the IHS criteria. The remaining 53 (32.5%) had headache attacks fulfilling all but one of the IHS criteria. Coverage of the IHS criteria for migraine was 93%. Symptoms of unilateral headache, aggravation by physical activity, and nausea showed the greatest differences in frequency between those with migraine and those with probable migraine. All children with aura fulfilled criteria for migraine. Children with migraine with aura (11.8, 95% CI: 11.0-12.6 years) were older than those without aura (10.1, 9.4-10.8 years; p = 0.001). Children with pulsating headache were slightly older than children without pulsating headache. No differences in age were detected with other IHS criteria.

Adolescent↗

Neonatal Candida parapsilosis outbreak with a high case fatality rate.

A Candida parapsilosis outbreak of 58 cases in a neonatal intensive care unit lasted for 55 months. Patients infected by or colonized with C. parapsilosis were mainly very low birth weight infants (birth weight < 1500 g). Their mean birth weight was 817 g and their mean gestational age was 28 weeks. Statistical analysis including logistic regression confirmed that prematurity was the main risk factor. The analysis also suggested that C. parapsilosis infection (or colonization) was associated with a poor prognosis. In infants with gestational age < 29 weeks the risk for death in C. parapsilosis-infected patients was 16-fold greater than in those with no C. parapsilosis infection. The case fatality rate of C. parapsilosis patients was higher than that of the controls (9 of 23 vs. 1 of 40; P < 0.0001). The outbreak was most likely a result of cross-infection because C. parapsilosis could be isolated only from the patients and from the hands of four nurses immediately after they had cared for a colonized patient. Cessation of the outbreak was temporally associated with long term parenteral fluconazole (6 mg/kg/day) prophylaxis.

Antifungal Agents↗

Maternal drug treatment and human milk banking.

We studied prospectively during one year temporary drug use by mothers donating breast milk to assess the problem of drug treatment of donors. Sixty-four of the 284 mothers (22.5%) had to abstain from donating due to medication. The indication was infection in 50/56 treatments (89.3%). Antimicrobial agents were prescribed 44/52 times (84.6%). The channelling of milk from mothers in early phases of lactation to premature and newborn infants was identified as a special risk situation, if mothers on medication are not excluded. The limited number of such donors leads to use of milk unpooled or pooled to small volumes with increased risk for adverse effects to babies as a consequence. We recommend a wash-out period of 5 half-lives of the drug after the last ingested dose. For the majority of drugs in this study, with some important exceptions, a wash-out period of 1 day was sufficient.

Adult↗

Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life.

OBJECTIVE: To find a dose of fluconazole for very low birth weight infants during an outbreak of Candida parapsilosis. METHODS: Twelve premature infants (mean gestational age, 27.4 weeks; mean birth weight, 912 gm) receiving fluconazole prophylactically from the first day of life were enrolled in an open phase I-II pharmacokinetics, safety, and tolerance trial. Up to 5 doses of 6 mg/kg were administered intravenously every 72 hours during the first 2 weeks of life. Pharmacokinetic characteristics of fluconazole were determined after the first, third, and fifth doses. RESULTS: The mean peak and trough concentrations after the 3 doses were 5.5 and 2.6 micrograms/ml, 12.8 and 4.3 micrograms/ml, and 10.0 and 2.9 micrograms/ml (p = 0.0002 and p = 0.07), respectively. The mean fluconazole half-lives were 88.6 hours (n = 7), 67.5 hours (n = 9), and 55.2 hours (n = 4; p = 0.3). The mean total clearance corrected for weight (CL/kg) was 0.18 ml/min/kg (n = 7), 0.33 ml/min/kg (n = 7), and 0.52 ml/min/kg (n = 4; p = 0.02), and the mean volume of distribution 1.18 L/kg (n = 7), 1.84 L/kg (n = 7), and 2.25 L/kg (n = 4; p = 0.05). Weight-corrected clearance increased with postnatal age (r = 0.61; p = 0.007). CONCLUSIONS: With the used fluconazole dose (6 mg/kg every 3 days), the mean serum peak and trough concentrations increased during the first week but decreased during the second week. After the first week we suggest a dose of 6 mg/kg every 2 days, or even daily.

Candidiasis↗

Medical charcoal for a child's poisoning at home: availability and success of administration in Finland.

In a prospective study, 174 families were interviewed over the telephone to find out whether the treatment of their child's poisoning with medical charcoal was successfully completed. The majority (103; 59.2%) of the families had no charcoal at home. The mean delay in administration for those who had to obtain charcoal was 41.6 min; significantly longer than the 24.5 min taken for those who had charcoal at home (P < 0.001). The treatment succeeded in all but five of the 102 patients given charcoal at home. Thus for mild poisoning in young children, the administration of activated charcoal at home, under the guidance of a Poison Information Centre, could be a rapid and safe first-aid treatment. Presently the widespread unavailability of charcoal in the home in Finland causes an unnecessary delay in treatment that could be of clinical importance.

Accidents, Home↗

Inositol supplementation in premature infants with respiratory distress syndrome.

BACKGROUND: Inositol influences cellular function and organ maturation. Feeding premature infants inositol-rich breast milk increases their serum inositol concentrations. Whether inositol supplementation benefits infants receiving fluids for parenteral nutrition, which are inositol-free, is not known. METHODS: We carried out a placebo-controlled, randomized, double-blind trial to determine the effects of administering inositol (80 mg per kilogram of body weight per day) during the first five days of life to 221 infants with respiratory distress syndrome who were receiving parenteral nutrition (gestational age, 24 to 32 weeks; birth weight, less than 2000 g). All the infants were treated with mechanical ventilation and some with surfactant as well. The primary end point was survival at 28 days without bronchopulmonary dysplasia. RESULTS: The 114 patients given inositol had significantly lower mean requirements for inspiratory oxygen (P less than 0.01) and mean airway pressure (P less than 0.05) from the 12th through the 144th hour of life than did the 107 infants given placebo. Eighty-one infants given inositol and 51 given placebo survived without bronchopulmonary dysplasia (71 vs. 55 percent; P = 0.005). In the 65 infants given surfactant, however, inositol had no effect on the degree of respiratory failure. Thirteen infants given inositol and 21 given placebo had retinopathy of prematurity (13 vs. 26 percent; P = 0.022); none of the infants given inositol had stage 4 disease, whereas 7 of those given placebo did (0 vs. 9 percent; P = 0.012). Among the infants given placebo, those who had poor outcomes (death, bronchopulmonary dysplasia, or stage 4 retinopathy of prematurity) had lower serum inositol concentrations during days 2 through 7 than those who had good outcomes (P less than 0.01). CONCLUSIONS: The administration of inositol to premature infants with respiratory distress syndrome who are receiving parenteral nutrition during the first week of life is associated with increased survival without bronchopulmonary dysplasia and with a decreased incidence of retinopathy of prematurity.

Bronchopulmonary Dysplasia↗

Accidental astemizole overdose in young children.

6 cases of accidental astemizole poisoning in children have been reported to the Finnish Poison Information Center. The children were aged 1 year 7 months to 3 years 4 months and had taken doses of 2.5 to 16.7 mg/kg, at least twelve times that recommended. In 2 children the overdose was verified by measurement of drug concentrations. Despite measures to prevent drug absorption prolonged QTc-interval, a sign of cardiac toxicity, was found in all 5 children on whom an electrocardiogram was available for analysis, and severe ventricular arrhythmias developed in 1. Young children with accidental astemizole overdose should be carefully monitored in hospital. Similar precautions may be justified in cases of overdose with other selective H1-histamine receptor antagonists.

Accidents, Home↗

Pharmacokinetically determined cyclosporine dosage in young children.

To account for the individual variability in cyclosporine pharmacokinetics and the non-existence of dosing recommendations in young children, we studied the pharmacokinetics of cyclosporine before renal transplantation in ten children aged 1.1-2.5 years, to determine the appropriate individual dose. Our aim was to reach a steady-state cyclosporine blood level of 200-300 micrograms/l, 8 h after a dose in the first days after renal transplantation. Cyclosporine was given as a single oral dose (10 mg/kg) or as a 4-h i.v. infusion (3 mg/kg), and the blood concentration was determined for 24 h by a specific monoclonal radioimmunoassay. The mean terminal cyclosporine half-life (t1/2) was 9.3 h (range 2.8-20.4), blood clearance 10.8 ml/min per kilogram (range 6.8-22.7) and volume of distribution 2.8 l/kg (range 1.4-4.7). The bioavailability of oral cyclosporine was low; the mean amount absorbed was 21.8% of the administered dose (range 11-35). The mean calculated dose needed to attain the intended predose blood cyclosporine level of 200-300 micrograms/l at steady-state was 5 mg/kg per day for i.v. and 21 mg/kg per day for oral administration. In view of the short t1/2, we used three doses/day. The validity of the predicted doses is shown by the mean cyclosporine doses used during the first 10 days after transplantation, which were 93.5% of the calculated oral and 96.6% of the calculated i.v. doses. The observed mean cyclosporine concentration during the same period was 196 micrograms/l.

Cyclosporins↗

Evidence for pre-hepatic metabolism of oral cyclosporine in children.

1. The pharmacokinetics of cyclosporine were investigated before renal transplantation in 20 children aged 1.1 to 16.8 years. Cyclosporine was given as a single oral dose (10 mg kg-1) or as a 4 h i.v. infusion (3 mg kg-1). 2. The blood drug concentration was measured by both specific and nonspecific monoclonal radioimmunoassays. 3. The mean oral availability of cyclosporine was 20.6% (range 10.8-34.1%). 4. The mean ratio of AUCs measured by nonspecific and specific r.i.a. was 1.96 (range 1.4-2.7) after oral administration and 1.43 (range 1.1-2.0) after i.v. administration. The mean difference between the ratios was 38.5% (P = 0.0001). The ratio of AUCnonspecific to AUCspecific was inversely related to blood drug clearance (r = 0.57; P = 0.009). 5. The findings are suggestive of presystemic, pre-hepatic metabolism of cyclosporine which could contribute to the low, and highly variable bioavailability of this drug.

Administration, Oral↗

Surfactant proteins in the diagnosis of fetal lung maturity. II. The 35 kd protein and phospholipids in complicated pregnancy.

The major surfactant protein with a molecular weight of 35 kd and also saturated phosphatidylcholine and phosphatidylglycerol were analyzed in specimens of amniotic fluid; 68 were from cases of maternal diabetes, 41 from preeclampsia or maternal hypertension, 26 from premature rupture of the fetal membranes, and 45 from normal pregnancies. The relationship between the individual surfactant components was studied after covariance adjustment for the length of gestation. In severe early-onset preeclampsia, the 35 kd surfactant protein/saturated phosphatidylcholine ratio was significantly higher than in the other pregnancies. In diabetic pregnancies (classes B to D without preeclampsia), the phosphatidylglycerol/saturated phosphatidylcholine ratio was lower than in the other pregnancies. Isolated surfactant complex showed similar abnormalities. In severe early-onset preeclampsia and insulin-dependent diabetes without vascular disease, the phosphatidylglycerol/saturated phosphatidylcholine ratio correlated negatively with fetal growth. In four samples of amniotic fluids from cases of severe early-onset preeclampsia, the 35 kd protein falsely predicted lung maturity. All had abnormally high 35 kd protein/saturated phosphatidylcholine ratios (greater than 2 SD of controls). According to the present results, the 35 kd protein may give a false mature test result in severe preeclampsia.

Amniotic Fluid↗