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Biomedical subjects

O Koskimies

Publications and source records attributed to O Koskimies.

At least 19 recordsLinked to original sources
PubMed1992

Characteristics at entry of children with severe primary vesicoureteral reflux recruited for a multicenter, international therapeutic trial comparing medical and surgical management. The International Reflux Study in Children.

A total of 532 children, 401 from Europe and 131 from the United States, was recruited into an international multicenter study comparing the results of medical and surgical treatment of children with international grade III or IV vesicoureteral reflux and urinary tract infection. Patient age was less than 11 years, glomerular filtration rate was greater than 70 ml. per minute per 1.73 m.2 and there was no obstruction, renal malformation, previous urinary tract surgery or neuropathic bladder. A total of 80 children had less than grade III vesicoureteral reflux on a second pre-entry cystourethrogram required by the European protocol, and they were followed separately as a sideline group. At entry the age distribution, history of urinary tract infection and proportion of children with grade IV vesicoureteral reflux were similar in Europe and the United States. Of the European and United States children 48% and 54% had renal scarring, and 17% and 14% had parenchymal thinning, respectively. In each group renal length and planimetric area were normal in two-thirds and 5% had small kidneys (<2 standard deviations from normal). Differences included sex distribution (24% boys in Europe and 11% in the United States group), the proportion of children in whom vesicoureteral reflux was previously known (18% Europe and 69% United States) and the proportion of children with bilateral reflux (77% Europe and 57% United States). Randomization and stratification for treatment were successful.

Child↗
PubMed1992

Infection pattern in children with vesicoureteral reflux randomly allocated to operation or long-term antibacterial prophylaxis. The International Reflux Study in Children.

A total of 306 children with grade III to IV vesicoureteral reflux (international classification) and a history of documented urinary tract infection was randomized into medical (155 patients) or surgical (151 patients) treatment arms in the European portion of the International Reflux Study in Children. Children treated medically were maintained on prophylactic antibacterials as long as the reflux persisted, while those treated surgically were covered prophylactically until followup studies at 6 months postoperatively demonstrated the reflux to be corrected. Standard definitions for bacteriuria were used, and the distinction was made clinically among acute pyelonephritis, cystitis and asymptomatic bacteriuria, supported in many instances by additional laboratory testing. Urine was cultured after 3 months and whenever suspicious symptoms occurred. Urinary tract infections developed during the first 5-year followup period in 59 patients (38%) in the medical group and in 59 (39%) in the surgical group but the incidence of pyelonephritis was higher in the medical group (21%) than in the surgical group (10%) (p < 0.01). Pyelonephritis often followed catheterization or cystoscopy but asymptomatic bacteriuria was uncommon after these procedures in either group. Recurrent infections were related to age, sex and treatment center. They were common in boys and girls entering under 1 year of age but were less common in girls and rare in boys entering after 1 year of age. Recurrences were lowest among the Finnish children and highest in the German and Belgian children.

Anti-Bacterial Agents↗
PubMed1991

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↗
PubMed1991

Renal growth and function 11-28 years after treatment of Wilms' tumour.

In order to obtain more information on the long-term effects of treatment of Wilms' tumour we investigated 30 subjects treated at the Children's Hospital between 1960 and 1976. All had been nephrectomized and in 4 the length of the remaining kidney was subnormal. In the other subjects kidney length was related to follow up time and age at follow up. Blood pressure was elevated in 5 subjects. Urinary albumin excretion deviated only slightly from normal. Tubular functions were well preserved in all subjects. In this small series we were unable to establish any relation between the abnormalities observed and the treatment given. Our results suggest that, despite wide interindividual variation those who survive Wilms' tumours seldom have long-term renal complications.

Albuminuria↗
PubMed1991

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↗
PubMed1991

Percutaneous needle biopsy preceding preoperative chemotherapy in the management of massive renal tumors in children.

While the National Wilms' Tumor Study (NWTS) Group in the United States puts an emphasis on accurate staging and histology before any therapy is given for Wilms' tumor, the International Society of Pediatric Oncology (SIOP) in Europe focuses on preoperative therapy and safer surgery. Our current approach combines the benefits of both policies in the management of massive renal tumors in children. In seven consecutive patients we first obtained a percutaneous posterior needle biopsy to obtain adequate tissue for histology, and proceeded with preoperative chemotherapy with vincristine and dactinomycin until tumor shrinkage was sufficient. Tumor removals were feasible and uneventful. At the time of operation, two tumors were found to be totally or almost totally necrotic. In the others, which still included viable tumor, the histology corresponded well to the needle biopsy findings. One case with unfavorable histology and one with rhabdoid sarcoma would have been missed and given suboptimal therapy without the primary needle biopsy. As possible biopsy-related complications, subcapsular intratumoral bleeding was recognized in two patients. We conclude that percutaneous posterior needle biopsy is safe and yields definite, detailed histology in massive renal tumors in children. Preoperative chemotherapy facilitates surgery in these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Risk of progressive kidney damage after acute leukemia.

In order to evaluate potential long-term renal sequelae of childhood leukemia, we studied 62 consecutive patients successfully treated for acute leukemia in 1971-83. At the time of this follow-up study they had been off therapy for 1-9 years and they were all in complete remission. Relative renal length was measured from X-ray films of intravenous pyelograms. Median relative renal length prior to the start of chemotherapy was +1.0 SD (range -1.5 to +4.0, n = 35), at discontinuation of therapy +0.5 SD (range -1.5 to +2.2, n = 22), and at follow-up -0.3 SD (range -3.9 to +2.6, n = 61). The mean calculated decrease in relative kidney size was 0.1 SD unit per year during the follow-up time. The median glomerular filtration rate was 110 ml/min/1.73 m2 (range 70 to 164). Six of 60 patients had glomerular filtration rates below 85 ml/min/1.73 m2. Three patients had some evidence of tubular dysfunction documented by increased excretion of urinary amino acids and/or beta-2-microglobulin or by reduced concentrating capacity. In spite of these abnormalities, we conclude that in most long-term survivors of childhood leukemia renal size and function are relatively well preserved. However, slightly reduced glomerular filtration rates in some patients indicated renal damage. A longer follow-up time is needed to find out whether the decrease in relative renal length is still continuing.

Acute Disease↗
PubMed1988

Dominant and recessive polycystic kidney disease in children: evaluation of clinical features and laboratory data.

The clinical features and laboratory data of 93 children with polycystic kidney disease were analysed. Family studies showed that the disease was dominant (DPKD) in 17 and recessive (RPKD) in 32 of them. Of the remaining 44 sporadic patients, 1 was classified by histological and/or imaging findings as having DPKD, 41 as having RPKD and 2 could not be classified. The symptoms tended to be more severe in RPKD than in DPKD, but there was much overlap. Death in early life was common in RPKD (55/73) and more rare in DPKD (4/18). If a child with DPKD had disease manifest during the neonatal period, then siblings were usually affected in the neonatal period. Survival to adulthood was seen in both diseases. In the patients who survived the neonatal period, hypertension was more common in RPKD (11/18) than in DPKD (4/14). Symptoms of portal hypertension were present in 2 patients with RPKD and none with DPKD. None of the laboratory investigations discriminated between the two entities. Glomerular filtration rate was diminished more often in RPKD (9/11) than in DPKD (2/8). Some difference was seen in the maximal urine concentrating ability; it was always reduced, often markedly, in RPKD but usually either normal or only moderately disturbed in DPKD. Studies on hepatic function and hepato-cellular damage were usually normal, but bacterial cholangitis was noted in some children with RPKD. The differential diagnosis between DPKD and RPKD needs to be based on the family history, family studies, radiological and/or histological features.

Adolescent↗
PubMed1988

Dominant and recessive polycystic kidney disease in children: classification by intravenous pyelography, ultrasound, and computed tomography.

Both dominant and recessive polycystic kidney disease appear in childhood. We have analyzed findings of intravenous pyelography, ultrasound and computed tomography in genetically classified cases of dominant (13 children) and recessive polycystic kidney disease (5 children) and thus defined criteria by which sporadic cases of childhood polycystic kidney disease can be classified to dominant or recessive polycystic kidney disease.

Child↗
PubMed1988

Trimethoprim in the treatment of acute urinary tract infections in children.

In the first study to assess the effect of trimethoprim in the treatment of acute urinary tract infections in children, we compared it with sulphisoxazole. Eighteen girls, mean age 5.3 years, were treated with trimethoprim 6 mg/kg/day. Seventeen girls, mean age 5.0 years, treated with sulphisoxazole 150-200 mg/kg/day for 10 days served as controls. All infections were cured. Three patients in each group had reinfections during the 6 months of follow-up. In each group, one of the reinfections occurred within 2 weeks after the end of the treatment. One patient developed a rash from sulphisoxazole and so required drug change. No other adverse effects were observed. We conclude that trimethoprim is as effective as sulphisoxazole in the treatment of simple acute urinary tract infections of children and recommend it, in the dosage used, as an alternative first-choice drug, especially for patients who have had side effects from sulphonamides or nitrofurantoin.

Acute Disease↗
PubMed1987

Food and guar decrease absorption of trimethoprim.

Absorption of trimethoprim suspension 3 mg/kg has been studied in 12 healthy adult volunteers when given alone, with food or with food and guar, using a randomised Latin-squares study design. Serum and urine trimethoprim concentrations were followed for 24 h. The mean peak serum concentration was higher when fasting subjects were treated (mean: 2.35, 1.84 and 1.97 micrograms/ml for the fasting, food and food + guar groups, respectively; ANOVA p less than 0.001 for the difference between fasting and non-fasting values). The times of the peak serum concentrations did not differ. Food ingestion decreased the area under the curve by 22.2%, as did food + guar. For maximal efficacy trimethoprim should be administered between meals.

Absorption↗
PubMed1987

Trimethoprim pharmacokinetics in children with renal insufficiency.

We studied the pharmacokinetics of trimethoprim in 14 children (two neonates) with renal insufficiency. They were 1 week to 16.4 years old and had glomerular filtration rates (GFR) between 10.8 to 72.3 ml/min/1.73 m2. The half-life (t1/2) of trimethoprim was inversely related to the GFR. The relation followed a power curve (correlation of t1/2 with GFR: r = -0.86; P less than 0.001). The slower elimination rate was mainly the result of lowered renal clearance of trimethoprim. The volume of distribution (Varea) was, in most patients, in the upper normal range for children. In some of the patients, chiefly infants with severe renal insufficiency, the Varea was larger than normal. In some individuals the pharmacokinetics of trimethoprim deviated from that to be expected from the GRF. We recommend reduced daily doses of trimethoprim if the GFR is less than 30 ml/min/1.73 m2. The reduction should be proportional to the reduction in GFR and primarily take the form of a prolonged dose interval.

Absorption↗
PubMed1986

C-reactive protein--an indicator of generalized bacterial infection in children with nephrotic syndrome.

The usefulness of C-reactive protein for detecting bacterial infections in children with nephrotic syndrome was studied in 12 children who had a total of 29 episodes of infection. Four episodes were septic, with CRP values of 127-270 mg/l and 25 superficial or focal with all CRP values below 47 mg/l; 13 were below 10 mg/l. CRP thus discriminated the invasive bacterial diseases from other infections. It was not affected by the nephrotic syndrome activity.

Bacterial Infections↗