Rickets: a roentgenographic scheme for diagnosis.
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Biomedical subjects
Publications and source records attributed to O Mehls.
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Haemofiltration was used in 12 children with terminal chronic renal failure. This method is an alternative for short-term treatment of renal failure by haemodialysis and can be combined with the single-needle-technique. It was also used in a 2 years old girl with acute renal failure. The main advantages of haemofiltration versus haemodialysis are a more rapid removal of fluid in the presence of stable blood pressure readings and a good tolerance by the patient. The primary indication for haemofiltration is hypervolaemia. The high water and salt losses during the procedure have to be exactly calculated and substituted. According to our current experience the volume needed for substitution of filtrate by fluid to be infused i.v. has to be in the range of 50% of body weight.
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Growth in length, weight gain and gain of body nitrogen were compared in rats with stable long-term uremia (U) resulting from subtotal two-stage nephrectomy with irradiation of residual parenchyma, in sham-operated pair-fed control rats (PFC) and in ad libitum fed control rats (LC). Growth in length and weight gain were considerably lower in U than in LC rats, reflecting mainly diminished intake of food in uremia. However, they were also significantly lower in U than in PFC despite identical intake of food, pointing to a specific adverse effect of uremia on growth. Whole body dry matter, whole body nitrogen and weight of a reference muscle (triceps surae) were significantly lower in U than in PFC animals, showing that dietary nitrogen and/or energy are less efficiently utilized for protein synthesis in U animals. Diminished net nitrogen retention was paralleled by increased urinary nitrogen loss (excretion of urea, alpha-amino nitrogen, protein, and creatinine). Within the precision of the method used, no significant difference of oxygen consumption between U and PFC animals could be demonstrated. The plasma amino acid pattern was deranged and the tyrosine/phenylalanine ratio was decreased despite no change in hepatic phenylalanine hydroxylase. The findings document increased nitrogen and/or energy cost of growth in rats with stable chronic uremia; this finding agrees with previous observations of disturbed protein metabolism and hypercatabolism in experimental uremia.
Ten years' experience of renal transplantation in 40 children (aged 5--18 years) is reviewed. Including 3 second transplantations 40 cadaver grafts and 3 living donor grafts were transplanted. Mean graft survival was found to be 19 months, the longest being 8 years. At the time of last examination 24 children were alive wtith a functioning graft (mean serum creatinine level 1.5 mg/dl). After graft failure 9 children were again on intermittent hemodialysis. 7 children had died mainly because of infections or cardiovascular complications. Cumulative survival rate of patients and cadaver grafts after 2 years was 84 and 53% respectively. Growth velocity was variable but improved in the majority of patients compared to the previous dialysis period. Full social rehabilitation could be achieved in every case. Main complications were acute rejections (irreversible in 7 of 67), chronic rejections (irreversible in 6 of 10), side effects of immunosuppressive drugs (infections; hematologic, metabolic, and bone disorders), hypertension (60%), recurrence of primary renal disease (in 5 of 9 patients with focal segmental glomerulosclerosis) and surgical complications (28%). Therapeutic guide-lines are given emphasizing the role of specialized children's centres and the cooperation between pediatric nephrologists, immunologists, urologists and psychologists including the time before, during and after transplantation.
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Lipid metabolism was studied in experimental uremia. Uremic (U) rats were compared with sham-operated, pair-fed (PF) controls and with ad-lib-fed (AL) controls. In U animals, fasting glucose concentrations were normal, immunoreactive serum insulin (IRI) levels were decreased, and immunoreactive glucagon levels were increased. A significant increase in the serum concentration of all lipid classes was observed: triglycerides were elevated 10-fold above the values in PF and AL controls; phospholipids, twofold; total cholesterol, threefold; and free cholesterol, sixfold. Cholesterol concentration was increased in beta- and pre-beta-lipoproteins and even more so in alpha- and pre-alpha-lipoproteins. There was an increase in the ratio of free cholesterol/total cholesterol. The fatty acid composition of serum lipoproteins was unchanged. Concomitantly, in liver tissue, there was no change in lipid content (triglyceride, cholesterol) and fatty acid composition. These findings argue against glucose- or insulin-mediated changes in hepatic de novo fatty acid synthesis, chain elongation, or poly-desaturation. In U animals, the HMG-CoA-reductase activity of liver microsomes was slightly, but not significantly, reduced as was tritiated water incorporation into cholesterol in isolated perfused liver preparations. In adipose tissue, there was a decrease in triglyceride content. The results provide evidence against insulin-mediated hepatic overproduction as a major cause of hyperlipoproteinemia in this model of experimental renal insufficiency and point to peripheral under-utilization of lipoproteins.
Acceleration of growth of uremic children after administration of vitamin D has been demonstrated by various authors. This has been attributed to healing of skeletal lesions. Clinical observations suggest that vitamin D has also an effect on food intake perhaps associated with improvement of vitality. This could be confirmed in an experimental study in which uremic rats (subtotal nephrectomy) with and without vitamin D supplementation were compared with sham-operated pair-fed control rats with and without vitamin D supplementation. In uremic animals supplemented with vitamin D, weight gain and growth were significantly greater than in uremic animals on the control diet. Both with and without vitamin D supplements, weight gain and growth rate were greater in sham-operated pair-fed control than in the corresponding uremic animals. Histological abnormalities in the growth zone of uremic rats were markedly reduced by vitamin D. Since food intake was greater in vitamin D-treated uremic animals than in nonvitamin D-treated uremic animals, the increase in growth rate under vitamin D cannot be attributed exclusively to the skeletal effects of vitamin D. This study demonstrates important extraskeletal actions of vitamin D which may be associated with or causally related to the improvement of growth.
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Protein-restricted diets are widely used in the dietary management of uremia. These diets are undoubtedly effective in ameliorating many aspects of the uremic syndrome. However, there is no consensus as to whether diets providing less than 0.6 g/kg per day of protein are nutritionally adequate and capable of preventing the wasting syndrome. Wasting is common in the adult patient with renal insufficiency as is growth failure in the uremic child. There is some evidence that wasted patients do less well on hemodialysis and are more prone to infection. Experimental studies in uremic animals point ot diminihsed efficiency of utilization of protein, increased gluconeogenesis from animo acids, and increased catabolism of protein in the fasting state; in addition, the metabolism of a number of individual amino acids is altered in uremia. In view of these multiple abnormalities, it would seem unwise to routinely provide less than the Recommended Daily Allowances of protein. More recent developments, i.e., supplementation of essential amino acids and perhaps alpha keto acids, may provide useful alternatives. One important aspect of dietary management, i.e. prevention of hyperlipidemia, has attracted surprisingly little attention so far. Therapy with protein restricted diets in nondialyzed uremic patients has to compete with other modalities of treatment currently available, i.e., hemodialysis and transplantation, in providing optimal medical rehabilitaiton of the patient.
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Haematuria in children is either of glomerular or nonglomerular origin. In the latter case intravenous urography should always be performed. A renal biopsy is indicated if unexplained haematuria persists for at least one year or if an unfavorable prognosis is indicated by the appearance of hypertension, significant proteinuria or persistently low levels of serum complement (C3). The importance of screening the families of haematuric patients is emphasized. More than half of our cases with persistent or intermittent haematuria undergoing renal biopsy showed no or only minimal glomerular changes. In other children with a similar clinical picture more severe histological lesions were detected. In any case the kidney tissue obtained by biopsy should be examined by immunofluorescence and by electron microscopy. One of the most frequent causes for persistent or intermittent haematuria during childhood is Berger's disease (IgA/IgG nephropathy).
In a cross-sectional study X-rays of the forefoot and the pelvis of 101 adult dialysis patients were taken. Vascular calcifications (forefoot) were observed in 20 patients. The incidence was higher in patients who had been started on dialysis several years ago. However, in a longitudinal prospective study de novo appearance of vascular calcificaitons was observed only in 1 out of 50 dialysed patients, although hyperparathyreoidism and moderate hyperphosphatemia persisted. Vascular calcifications were seen only once in 138 uremic children (56 uremic children without dialysis; 82 uremic children on maintenance hemodialysis). However at autopsy visceral calcifications of the lung were found in three (out of 11) children who did not have vascular calcificaitons on X-rays.
Stable long-term chronic renal failure in the growing Sprague Dawley rat causes marked bone disease with impaired mineralization (i.e. rickets) and evidence of increased parathyroid hormone activity. Although significant bone disease is present, the rate of longitudinal growth is not diminished in preterminal renal failure. However, it is significantly diminished in terminal renal failure, when uremic rats are compared with sham-operated control rats at identical levels of food intake. At identical levels of food intake, weight gain is also diminished in rats with terminal uremia as compared with sham-operated control rats, suggesting increased calorie cost for growth.
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Longitudinal growth; bone and growth zone histology; growth cartilage and bone mineralization (tetracycline technique); bone Ca content (neutron activation analysis); bone radiology; serum and urine chemistry; urinary cAMP and serum 25-OH-vitamin D3 were studied in a long-term model of experimental uremia in the rat. Uremia was induced by two-stage subtotal nephrectomy with irradiation of the remaining parenchyma. Ccr in the experimental group was 113 +/- 5.8 micron1/min X 100 g (19.8% of controls) and serum creatinine 1.67 +/- 0.04 mg% (5.1 X control value). Uremic animals were pair-fed with sham-operated controls. In the proximal tibia delayed transformation of cartilage into primary spongiosa with appearance of chondro-osteoid and delayed transformation of primary spongiosa into secondary spongiosa was observed (rickets). Increased amounts of osteoid were present although 25-OH-vitamin D3-levels were high. There were only modest signs of secondary hyperparathyroidism (osteoclast counts; urinary cAMP). In spite of the presence of bone disease, longitudinal growth was not reduced in uremic animals as compared with pair-fed sham-operated animals, but was significantly reduced as compared with ad lib fed control animals. In contrast, weight gain was significantly diminished in uremic animals as compared with pair-fed sham-operated control animals. It is concluded that diminished intake of food is the major determinant of growth retardation in preterminal experimental renal failure.
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