PubMed Health⌕ Search

Biomedical subjects

O H Oetliker

Publications and source records attributed to O H Oetliker.

At least 19 recordsLinked to original sources

Differential regulation of bradykinin receptor density, intracellular Ca2+, and prostanoid release in skin and foreskin fibroblasts. Effects of cell density and interleukin-1alpha.

1. Bradykinin (BK) receptors, cytosolic Ca2+, and prostanoids were studied in human skin and foreskin fibroblasts. 2. Bmax values of BK receptors were higher in foreskin than in skin fibroblasts, increasing with cell densities in both cell types. IL-1alpha-dependent receptor induction was blocked by cycloheximide. 3. BK-stimulated cytosolic Ca2+ elevation was higher in confluent than in non-confluent cultures and larger in foreskin than in skin fibroblasts. Responses were not enhanced after IL-1-alpha-induced up-regulation of BK receptors. 4. Intrinsic prostanoid production was higher in foreskin than in skin fibroblasts at comparable cell densities. In foreskin, but not in skin fibroblasts, BK stimulation increased the release of PGE2 10 fold and that of 6-oxo-PGF1alpha 6-7 fold. 5. Preincubation with IL-1alpha had a marked effect on prostanoid release in foreskin fibroblasts only. Subsequent BK stimulation increased the release of PGE2 and 6-oxo-PGF1alpha 7-10 fold in skin fibroblasts while this increase was only 30% in foreskin fibroblasts. Release of TXA2 reached values up to one third of the other prostanoids. The IL-1alpha induced rise in BK-stimulated PGE2 synthesis was fully abolished by specific inhibition of cyclo-oxygenase 2. 6. IL-1alpha sensitized BK-stimulated prostanoid synthesis and modulated prostanoid patterns differently in fibroblasts from skin and foreskin. The IL-1alpha effects on prostanoid release were not related to BK receptor numbers nor to the BK-stimulated Ca2+ signal but appear to be due to induction of prostanoid synthesizing enzymes. Foreskin fibroblasts seem to be unique and significantly different from fibroblasts of other skin locations in respect to their response to inflammation-associated kinins and cytokines.

6-Ketoprostaglandin F1 alpha↗

[Demonstration of mesangial IgA deposits in kidney biopsies of pediatric patients: comparison with the clinical picture].

Clinical and morphological findings were evaluated in 25 children with mesangial IgA deposits. 19 patients had recurrent macroscopic hematuria (n = 10), chronic proteinuria > 40 mg/(m2.h) (n = 5), recurrent hematuria with chronic proteinuria (n = 3), or chronic nephrotic syndrome (n = 1). The glomerular involvement was similar in six patients with history of Schönlein-Henoch purpura and in 13 patients without such history: normal or nearly normal glomeruli (n = 3), focal and segmental glomerulonephritis (n = 11) and diffuse proliferative glomerulonephritis (n = 5). End-stage renal disease developed in two patients with proteinuria > 40 mg/(m2.h) and more than 50% of their glomeruli are affected by crescents. The common histopathological features in patients with and without history of Schönlein-Henoch purpura suggest a common pathogenesis. The risk of poor outcome appears, related to the severity of proteinuria and to the presence of crescents, in more than 50% of glomeruli. Mesangial IgA deposits were also demonstrated in six children with steroid-responsive idiopathic nephrotic syndrome: light microscopic studies revealed normal or nearly normal glomeruli in five and focal segmental glomerular sclerosis in one patient. The microscopic findings were clearly different in the six patients with idiopathic nephrotic syndrome as compared with the patient with chronic nephrotic syndrome, who presented with severe glomerular lesions and extensive crescent formation. The results indicate that the presence of mesangial IgA deposits in the clinical setting of idiopathic childhood nephrotic syndrome is incidental and that such patients should still be considered as having idiopathic nephrotic syndrome in spite of their immunopathological features.

Adolescent↗

Histological features of glomerular immaturity in infants and small children with normal or altered tubular function.

In children with renal tubular disorders the existence of retarded histological features of glomerular maturation has been suggested by our group. However, no valuable information is available on the frequency of histopathologically immature glomeruli in the normal kidney. For this reason we established a simple, semiquantitative definition of postnatal glomerular development: immature glomeruli (with at least half of the circumference of capillary loops densely lined with cuboidal epithelial cells), intermediate glomeruli (circumference of capillary loops lined with at least five adjoining cuboidal cells), and mature glomeruli. This definition was applied in a set of 71 normal kidneys from ages birth to 5 years. The relative frequency of the mentioned stages of glomerular maturation was strongly age dependent. In comparing the patients data with the normal findings it was possible to separate patients with the finding of disproportionately high fractions of immature glomeruli, provided the right age at biopsy is chosen. It is therefore concluded that the previous suspicion of late glomerular maturation may be validated in at least in some bioptic specimens.

Biopsy↗

Normal prostaglandinuria E2 in Gitelman's syndrome, the hypocalciuric variant of Bartter's syndrome.

In familial Bartter's syndrome, hyperprostaglandinuria is considered a constant feature and prostanoid synthetase inhibition often positively influences the disease course. The urinary calcium excretion distinguishes two clinically and biochemically different variants, namely, classic Bartter's syndrome (normocalciuric or hypercalciuric variant; urinary calcium to creatinine > or = 35.3 mg/mg 10(-3)) and Gitelman's syndrome (hypocalciuric variant; urinary calcium to creatinine < 35.3 mg/mg 10(-3)). In the hypocalciuric variant of Bartter's syndrome prostanoid synthetase inhibition is of little benefit. Since the production of prostanoids has not been extensively studied in Gitelman's syndrome, the urinary excretion of prostaglandin E2 was assessed by radioimmunoassay in 11 untreated patients with Gitelman's syndrome (aged 10 to 21 years; five females and six males) and in 11 healthy controls (aged 11 to 20 years; five females and six males). The urinary excretion of prostaglandin E2 was similar in both study groups. The study provides the rationale for the poor effect of prostanoid synthetase inhibition in the hypocalciuric variant of Bartter's syndrome. The assessment of urinary excretion of prostaglandin E2 does not represent a diagnostic sine qua non in the context of familial Bartter's syndrome.

Adolescent↗

Outcome of idiopathic childhood nephrotic syndrome. A 20 year experience.

112 patients with idiopathic childhood nephrotic syndrome have been referred from 1970 through 1989 at the Department of Pediatrics, University of Berne. One patient remitted spontaneously without medication. Ninety-eight patients responded to prednisone: 15 had a single bout of nephrosis, 47 developed a tendency towards relapses and 36 steroid dependence. In 28 patients with tendency towards relapses cure took place on either prednisone alone or prednisone plus cyclophosphamide. In 18 patients with steroid dependency cure took place on prednisone alone or prednisone plus cyclophosphamide. Thirteen patients failed to respond to steroids. The course of the disease was more benign in 68 patients with minimal change disease as compared with 14 patients with focal and segmental glomerular sclerosis. Immunofluorescence studies demonstrated mesangial IgM deposits in 14 out of 54 patients, but this finding was not a marker for poor steroid response or progression to renal failure. The course of the disease was especially unfavourable in patients with persisting nephrosis on completion of the initial course of steroid therapy. In conclusion it appears appropriate to define the disease in terms of steroid responsiveness as steroid resistant patients sometimes show normal glomeruli, steroid responsive sometimes have focal and segmental glomerular sclerosis or mesangial IgM deposits, and decisions depend more on the steroid responsiveness than on the histological features.

Adolescent↗

[Management of children and adolescents with kidney transplantation].

Successful renal transplantation is widely accepted as the treatment of choice for end-stage renal failure in infants, children and adolescents. The major issues currently requiring consideration when contemplating renal transplantation in the mentioned patients are: primary renal disease, psychosocial status, life-related versus cadaver donor allograft, optimal immunosuppressive regimen including cyclosporine, and maximization of growth and pubertal development. In transplanted adolescents, noncompliance is now a major problem, ranking only second to rejection as a cause of graft loss.

Adolescent↗

[Levamisole in children with frequently recurring idiopathic nephrotic syndrome].

10 children (8 boys and 2 girls) with frequently relapsing idiopathic nephrotic syndrome were treated with levamisole (5 mg/kg weekly). In 6 children with steroid dependent nephrotic syndrome a marked reduction in steroids by 62% to 75% was possible. Severe, transient neutropenia was observed in one patient. Levamisole failed to influence the disease course positively in 3 patients with relapses associated with intercurrent illness. It is concluded that levamisole may favourably influence steroid dependence in children with frequently relapsing idiopathic nephrotic syndrome.

Child, Preschool↗

[Hemolytic-uremic syndrome in children: a 19-year retrospective study].

Forty-two children (22 girls and 20 boys, ranging in age between 2 months and 13 years, median age 17 months) were admitted with acute hemolytic-uremic syndrome to the University Children's Hospital, Berne from 1973 to 1991. Seventeen patients developed hypertension and 30 renal failure. Three out of the 19 cases necessitating acute dialysis progressed to end stage renal failure. Four out of the 7 patients with signs of severe central nervous system involvement died. The initial clinical course was consistently more favourable in 35 patients with diarrheal prodrome. Increased protein excretion in association with high blood pressure was observed in 4 patients with initial favourable course who were examined one year after disease onset. This study indicates the generally favourable immediate prognosis of childhood hemolytic uremic syndrome and the possible persistence of high blood pressure and pathological proteinuria on follow-up.

Child↗

High proximal excretion of sodium during activation of beta 2-adrenoreceptors in humans.

The effects of acute beta 2-type adrenoreceptor activation with intravenous albuterol on plasma and urinary sodium, potassium, calcium, magnesium, phosphate and lithium were investigated in 9 volunteers during acute hydration. When compared with the control infusion with inactive vehicle, beta 2-type adrenoreceptor activation decreased plasma and urinary potassium and phosphate and increased the excretion of calcium and magnesium. In addition, activation of the beta 2 adrenoreceptors did not influence creatinine clearance and plasma level and the net fractional excretion of sodium but increased the fractional clearance of exogenous lithium which measures the fraction of filtered sodium delivered by the proximal tubule. The results indicate that activation of beta 2-type adrenoreceptors decreases the proximal reabsorption of sodium.

Adult↗

[Glomerulonephritis with transient C3 hypoclompimentemia and endotheliomesangial glomerulonephritis in childhood. A long-term experience].

62 children (20 girls and 42 boys, ranging in age between 3 and 15 years), presenting with acute hypocomplementemic glomerulonephritis or morphologically confirmed endotheliomesangial glomerulonephritis, were admitted to the University Children's Hospital, Berne from 1970 to 1991. The annual incidence of cases of acute hypocomplementemic glomerulonephritis was stable during the study period. The site of the antecedent infection was the throat in 26 patients, upper respiratory tract in 15, the skin in 9, and unknown in 10. The latent period ranged from 0.5 to 3.5 weeks. 41 patients developed hypertension and 17 renal failure. Hypertensive complications were observed in 6 patients and remitted completely in 5 cases. A nephrotic syndrome (edema, proteinuria of 40 mg/[m2.h], albuminemia < 25 g/l) was observed in 11 patients. Microscopic hematuria persisted in many patients for one year or more. Proteinuria remitted in all but one patient, who was found to have Alport syndrome. This study shows the stable frequency of hypocomplementemic glomerulonephritis since 1970, its good prognosis, and the importance of the measurement of C3-complementemia in children presenting with acute glomerulonephritis.

Adolescent↗

Cough and converting enzyme inhibitors.

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3-7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.

Adolescent↗

Specific and non specific stimulation of prostaglandin release by human skin fibroblasts in culture.--Are changes of membrane fluidity involved?

In order to study a bidirectional relationship between changes of membrane fluidity and prostaglandin synthesis, the arachidonic acid cascade was stimulated in cultured human skin fibroblasts by unspecific stimuli (hypotonicity, low calcium concentrations) and by the specific stimulus, bradykinin. Fluorescence anisotropy of trimethylammoniumdiphenylhexatriene was used to measure membrane fluidity in cell monolayers. Hypotonicity or low calcium concentrations induce membrane fluidisation and prostaglandin synthesis. However, after specific stimulation of prostaglandins with bradykinin (at normocalcic and isotonic conditions) a rigidification of plasma membranes was observed in living cells. Fluidisation of membranes and bradykinin activate phospholipase A2 and induce prostaglandin synthesis. Although in cell membrane preparations increased phospholipase A2 activity leads to fluidisation, in our model a membrane fluidisation was not observed after stimulation of phospholipase with bradykinin. This suggests that in living cells a fluidizing effect of lysolecithin resulting from phospholipase A2 activation may be rapidly counteracted by its removal. A decrease of phosphatidylcholin content and consequently a rigidification of the membrane may ensue. Thus, the cell culture model using two different ways of stimulating phospholipase activity, helps to define the directional relationship between changes of membrane fluidity and activation of phospholipase and the arachidonic acid cascade in living human cells.

Bradykinin↗

Acyclovir-induced renal failure: course and risk factors.

Of 19 children treated with high-dose intravenous acyclovir, 7, all of whom had encephalitis, also had a restricted fluid intake. Of these, 3 experienced non-oliguric renal insufficiency (plasma creatinine up to 176, 250 and 351 mumol/l, respectively) which resolved within 1 week of discontinuing acyclovir. Renal function was stable in the remaining 4 patients in this group and in the 12 children treated with acyclovir but without fluid restriction. We suggest the decreased renal function resulted from intratubular acyclovir crystalluria.

Acute Kidney Injury↗

Epoetin alfa in anaemic children or adolescents on regular dialysis.

Eighteen patients aged 5-18 years on regular dialysis had a packed cell volume (PCV) less than 0.27. On treatment with epoetin alfa (EA) PCV increased by 0.05 or more in all patients. Iron supplementation was necessary in 13 patients with a ferritinaemia less than 300 micrograms/l before study. During treatment, plasma potassium increased significantly and more vigorous antihypertensive measures were required in 8 patients, 5 of them being already on antihypertensive drugs before EA. Iliofemoral thrombosis occurred in 1 patient 10 days after renal transplant. The data indicate that EA ameliorates the anaemia of chronic renal disease. The main concerns arising during treatment with EA are hyperkalaemia, arterial hypertension and possibly thrombosis.

Adolescent↗