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Biomedical subjects

H Michalsen

Publications and source records attributed to H Michalsen.

At least 37 records · Page 2Linked to original sources

Ceftazidime treatment of chronic Pseudomonas infection in patients with cystic fibrosis.

Twenty-one patients with cystic fibrosis (CF), aged 1-18 years, with chronic lower respiratory tract infection caused by Pseudomonas aeruginosa, received 38 treatment courses of ceftazidime of 10-14 days duration. A favorable clinical response was observed in 28 of the 38 treatment courses. The minimal inhibitory concentration values of ceftazidime for the Pseudomonas isolates were concentrated around 0.5-1.0 mg/l, although a wide range of sensitivities was found (less than 0.03-32 mg/l). P. aeruginosa was eliminated after five treatment courses, but recurred after 1 month in four of these patients. The organism was permanently eradicated in one patient until his death 8 months later. Ceftazidime was well tolerated. The doses used in this study (50 mg/kg body weight i.v. twice daily) should probably be increased in order to achieve better microbiological response.

Adolescent↗

Pulmonary function and oxygen uptake during exercise in 11-year-old patients with cystic fibrosis.

Ten patients with cystic fibrosis (CF), 5 girls and 5 boys, 11 years of age, underwent pulmonary function and bicycle exercise testing. The material includes all but 2 CF patients in this age group in southern and eastern Norway. The CF children had a moderately reduced pulmonary function, the girls more pronounced than the boys. The mean maximal oxygen uptake (max VO2) in the CF boys was 55 ml/kg/min (94% of age predicted value; range 79-105%), and the CF girls 42 ml/kg/min (79% of age predicted value; range 67-89%). The mean maximal peak heart rate was 195 beats/min. Only one CF girl showed apparent pulmonary limitation during exercise. Increased ventilatory equivalent for oxygen was found during both rest and exercise for the CF girls, but only during rest for the CF boys. Max VO2 was fairly well related to the habitudinal physical activity of the children (r = 0.79).

Child↗

Cystic fibrosis: protease activity in saliva evaluated with chromogenic substrates.

The protease activities in saliva from individuals with cystic fibrosis (CF) were studied using four different chromogenic substrates. In the CF-group a significantly decreased protease activity in the range 50-70% was found, compared to an age- and sex-matched control group, but with considerable overlap between the CF-patients and the control patients. The trypsin-like activity found in CF-patients without chronic colonisation with Pseudomonas aeruginosa was significantly decreased and without overlap compared to the control patients. The results indicate that determination of salivary protease activity using chromogenic substrates may give additional information in patients with suspected cystic fibrosis, and indicate the possibility of an additional diagnostic test.

Adolescent↗

Pharmacokinetic evaluation of cefsulodin in children with and without cystic fibrosis treated for infectious diseases.

The pharmacokinetic characteristics of cefsulodin have been studied in 7 patients suffering from cystic fibrosis (CF) and compared to the findings in 6 children without CF. They were given intravenous bolus doses (3 min) of 40 mg/kg. The antibiotic concentrations were assayed by high-pressure liquid chromatography. The serum concentrations were lower in the CF group as reflected by the mean total area under the serum concentration curves of 180 vs. 309 mg h/1, and the serum concentrations after 8 hours which were below the detection limit in the CF patients compared to 4.7 mg/l in the non-CF. The patients with cystic fibrosis had a not significantly lower total body clearance (5.8 vs. 7.0 1/h). The serum half-life was slightly shorter in patients with CF (1.2 vs. 1.4 hours). Consequently, given microbes of the same MIC's, patients with CF should receive higher doses than those recommended for patients without cystic fibrosis.

Adolescent↗

Pharmacokinetics of azlocillin in children with and without cystic fibrosis treated for infectious diseases.

The pharmacokinetic characteristics of azlocillin were compared in 7 children with cystic fibrosis (CF) and 6 children without this disease who were all treated for infectious diseases. Azlocillin was administered as intravenous bolus injections in doses of 200 mg/kg. The serum concentrations were somewhat lower in CF than in non-CF as reflected by total areas under the serum concentration curves of 594 and 677 mg h/1, and serum levels after 8 hrs of 10.7 mg/1 in non-CF vs. a concentration below the detection limit in CF. The CF children had a lower serum half-life (1.1 hrs) than the children without this disease (3.3 hrs). The difference is explained by higher total body clearance in CF (12.7 1/h) than the non-CF group (8.4 1/h). The dose interval should either be shorter, or the doses increased, when azlocillin is administered to patients with CF.

Adolescent↗

Generalized amyloidosis in cystic fibrosis.

A boy suffering from cystic fibrosis (CF) complicated by generalized amyloidosis is reported. His condition was fairly good during the first 10 years of life, but after this time he had repeated pulmonary infections caused by Staphylococcus aureus. From the age of 14, he developed increasing hepato- and splenomegaly and a liver biopsy revealed massive amyloidosis. At the age of 16 he died of respiratory and cardiac failure. Post-mortem examination revealed wide-spread amyloidosis in addition to pulmonary and pancreatic findings characteristic of CF.

Adolescent↗

Renal biopsies in cystic fibrosis.

Pharmacokinetic studies on antibiotics as well as other studies on renal function indicate renal malfunction in cystic fibrosis. Renal biopsies from two children, and post mortem examination from one child, with this disorder were normal by light microscopy and close to normal by immunofluorescence examination and transmission and scanning electron microscopy, even in cases with advanced disease and marked renal malfunction. Renal biopsy interpretation thus seems to be of little value in the evaluation of renal malfunction in this disorder, and this suggests that the functional abnormalities are caused by metabolic/biochemical defects.

Adolescent↗

Pharmacokinetic assessment of netilmicin in newborns and older children.

The pharmacokinetics of netilmicin were analyzed in 30 children, including 13 premature and seven gestationally mature newborns. Ten were children ranging in age from 3.5 months to 13 years. The newborns exhibited more variation in serum levels than the older children, and the premature babies more than those born at term. The serum half-life (t1/2), tended to show higher values in premature than in mature newborns, although this was not statistically significant. The newborns had a t1/2 of 5.9 hours, compared to 2.5 hours in the older children. There was no statistically significant difference in distribution volumes or coefficients between the two groups of newborns who had an insignificantly higher relative apparent beta-phase distribution volume coefficient of 0.420 l/kg, compared to 0.377 l/kg in the older children. All had distribution coefficient values within the same range. The total body clearance in absolute terms, and when referred to body surface of 1.73 m2, was significantly lower in the newborns than in the older children, but the clearance, when referred to body weight, was of the same order in the babies and older children. The age differences affect dosage. Dosage schedules based on pharmacokinetics are proposed for gestationally premature babies, mature newborns, and older children. Premature infants can receive 2.5 mg/kg body weight and gestationally mature newborns 3.0 mgkg, both every 12 hours; the monitoring of serum concentrations is mandatory. Children aged three months and older can receive 3.0 mg/kg every eight hours.

Adolescent↗

Pharmacokinetics of netilmicin in children with and without cystic fibrosis.

The pharmacokinetics of intravenous netilmicin was studied in cystic fibrosis (CF) and non-CF patients who were closely matched according to age. The serum concentrations showed a moderately higher variance within the CF group. The serum half-life in CF patients was 1.37 h compared with 2.29 h in the non-CF subjects (P less than 0.05). The apparent distribution coefficients were 0.306 and 0.356 liters/kg in the CF and non-CF groups, respectively. The mean body clearance was 6.6 liters/h per 1.73 m2 in the CF group compared with 5.3 liters/h per m2 in the non-CF controls, but the difference was not significant. The mean renal clearance in CF patients was 4.7 liters/h per 1.73 m2. From a pharmacokinetic point of view, the dosage of netilmicin required may be the same in CF as in non-CF patients.

Child↗

Azlocillin with and without an aminoglycoside against respiratory tract infections in children with cystic fibrosis.

Nine patients with cystic fibrosis have been treated with azlocillin alone and later with azlocillin combined with an aminoglycoside (gentamicin or tobramycin) for 50 treatment courses. In the initial series when azlocillin was employed alone, a gradual increase in MIC during successive courses was observed in Pseudomonas aeruginosa. When the beta-lactam antibiotic was combined with an aminoglycoside, the MIC was either maintained or reduced. Objective criteria like peak expiratory flow, erythrocyte sedimentation rate, fever, body weight or bacterial cultures could not clearly identify the combination therapy as better clinically than azlocillin monotherapy. However, the patients subjective and our clinical impression is that the combination therapy was better. The clinical course and the lack of increased resistance on combination therapy make a combination of azlocillin and an aminoglycoside preferable to the beta-lactam alone.

Aminoglycosides↗

Azlocillin in respiratory tract infections with Pseudomonas aeruginosa in children with cystic fibrosis.

In 5 children with cystic fibrosis, 13 courses of lower respiratory infections due to Pseudomonas aeruginosa were treated with azlocillin, 100--200 mg/kg body weight intravenously every 8 h for 10--15 days. The clinical course during azlocillin treatment was more favourable than had been the case previously in the same patients when treated with combinations of carbenicillin and aminoglycosides. No side effects ascribable to azlocillin were observed, although one allergic reaction occurred, but this was probably elicited by another allergen. Upon repeated courses of treatment, the minimum inhibitory concentration of the infecting organisms increased steadily against both azlocillin and carbenicillin. It is concluded that azlocillin represents an important alternative in the treatment of lower respiratory tract infections due to P. aeruginosa in patients with cystic fibrosis.

Adolescent↗

Netilmicin in the treatment of neonates with moderate and severe infections.

Thirty neonates and infants have been treated for verified or suspected infections with a combination of netilmicin and ampicillin intravenously for 7 days. The infecting organisms were isolated in 18 patients, of whom 2 had osteomyelitis and 2 had pneumonia. In 3 cases of pneumonia and 9 cases of suspected septicaemia bacteriological cultures were negative. None of the children died, and in all but the 2 cases of osteomyelitis, therapy led to complete resolution of the signs of infection and recovery without sequelae. No adverse reactions to antibiotic therapy were recorded. Upon follow-up examinations at the age of 3 months there has been no sign of auditory impairment as assessed by Brain Stem Evoked Response. Netilmicin is thus tolerated well in neonates and infants, and when guided by serum concentrations considered to be a safe and reliable aminoglycoside.

Drug Evaluation↗

Adynamia episodica hereditaria. Treatment with salbutamol.

Three sibs with adynamia episodica hereditaria are described. Treatment with salbutamol inhalation had a beneficial effect on the duration of their adynamic attacks. Continuous peroral treatment with salbutamol has been tried in these patients resulting in the almost complete prevention of attacks. No serious adverse effects have been recorded. Peroral treatment with salbutamol is recommended as the treatment of choice in young patients with adynamia episodica hereditaria and in patients with frequent attacks of adynamia.

Administration, Oral↗

Pharmacokinetics of azlocillin in children with cystic fibrosis.

6-E1(R)-2-(oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen) was given in doses of 100 and 200 mg/kg body weight to children with cystic fibrosis. After intravenous bolus infections, the serum half-life was 0.82 +/- 0.12 h after the lower dose and 0.98 +/- 0.18 h after the higher dose. This was consequent to a dose limited elimination kinetics due to limitation in both renal and non-renal processes of elimination. Upon doubling of the dose from 100 to 200 mg/kg, the total body clearance dropped from 13.93 to 5.10 1/h. Evaluation of data presented in other publications indicate that a dose limited elimination kinetics is the normal situation for azlocillin. Besides, the serum concentrations of patients with cystic fibrosis were considerably lower than seen in the healthy state. The reason is faster elimination by the renal route in cystic fibrosis.

Adolescent↗