Dogma disputed: alternate-day steroid therapy in the nephrotic syndrome of childhood.
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Biomedical subjects
Publications and source records attributed to A Spitzer.
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Previous studies using 31P nuclear magnetic resonance (NMR) saturation transfer techniques to quantitate the energy metabolism of the kidney have often resulted in estimates of adenosine triphosphate (ATP) turnover which are much lower than those predicted from the renal oxygen consumption and reasonable values of the P/O ratio. We measured the ATP turnover in isolated perfused kidneys of rats, using 31P NMR saturation transfer and a new procedure for quantitation of the intracellular Pi concentration. The estimated turnover rates of ATP were higher than previously reported. The P/O ratios calculated on the basis of these rates of ATP turnover and rates of renal oxygen consumption reported in the literature were within the range of theoretically possible values. Thus, 31P NMR saturation transfer can be used to quantitate the ATP turnover in the isolated perfused rat kidney.
The concentration of intracellular sodium [Na+]i has been measured in the perfused rat kidney using 23Na nuclear magnetic resonance (NMR) in combination with the extracellular shift reagent Dy(PPPi)7-(2). The data show 100% visibility of Na+ in interstitial spaces. A measurement of the resonance intensities of intra- and extracellular 23Na ions along with a knowledge of the extracellular space as a fraction of the total kidney water space yielded an average [Na+]i of 27 +/- 2 mM for the kidney at 37 degrees C. After prolonged ischemia [Na+]i rose to approach that in the external medium. In the absence of 5% albumin in the perfusion medium, the linewidth of the 35Cl resonance of an adult kidney (45 Hz) was about twofold larger than that of the medium alone (25 Hz). In contrast, the linewidth of 35Cl resonance of an adult kidney perfused with an albumin-containing medium (82 Hz) was only about 27% of that from the medium alone (300 Hz). We interpret this effect to be due to compartmentation of albumin in the extracellular space such that the interstitial space is not freely accessible to albumin. However, for a developing, immature kidney from a growing animal, perfused with an albumin-containing medium, the linewidth of the 35Cl resonance (233 Hz) was only slightly less than that of the medium alone (300 Hz), indicating a much greater albumin permeability of the capillary walls. 19F NMR of a perfused adult kidney, loaded with the membrane-impermeant intracellular calcium indicator 5FBAPTA, yielded a value of 256 nM for [Ca2+]i. Induction of ischemia for 10 min caused the [Ca2+]i to rapidly rise to 660 nM, which could not be fully reversed by reperfusion, suggesting irreversible injury.
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The effect of age on compensatory hypertrophy and functional adaptation to loss of 75 percent of renal mass was studied in canine puppies. In one group of animals the surgery was done between 1-5 days after birth and in another group, at two months of age. All animals were studied six weeks later. Shamoperated littermates served as controls. The newborn puppies in the experimental group were able to grow and maintain homeostasis as well as their controls, whereas the older experimental animals grew poorly and had significantly higher levels of plasma creatinine than their sham-operated counterparts (p < .05). The increase in mass of the remaining kidney was twice as much in the newborn as in the older dogs. Functional adaptation, as expressed by GFR, was nearly complete in the young, but reached only about 45 percent of controls in the older age group (p<.005). The intrarenal blood flow distribution was similar for experimental and control animals in both groups studied. There were, however, marked differences in the pattern of single glomerular perfusion rates: whereas in the older dogs the increase was confined to the deeper nephrons, in the newborn an increase occurred in all zones of the kidney. These studies demonstrate that compensation for massive loss of renal tissue is complete when the injury is sustained in the immediate postnatal period but only partial when it occurs later on in life. A loss in the adaptive capacity of the superficial nephrons appears to account for this age-related difference.
On their surface, renal tubular cells present intercellular adhesion molecule-1 (ICAM-1) during acute renal allograft rejection. We propose that the extent of ICAM-1 expression by renal tubular cells can be estimated from urine immunocytology. To test this hypothesis, we obtained 52 samples of urine from 31 renal transplant recipients with either acute tubular necrosis, rejection or stable renal function. Cytocentrifuged aliquots of urinary sediment were incubated with monoclonal antibodies to ICAM-1 in an avidin-biotin-peroxidase technique. To corroborate our findings, biopsy specimens were obtained for conventional and immunohistology one hour following vascular anastomosis and during rejection episodes. The proportion of renal tubular cells that expressed ICAM-1 was low in patients with acute tubular necrosis (23.8 +/- 3.6%) and high in patients with rejection (53.1 +/- 4.4% [SEM]) (P < .001). In 11 patients who recovered from rejection, the proportion of ICAM-1-positive renal tubular cells decreased from 55.9 +/- 5.6% to 25.5 +/- 4.3% (P < .05). In two patients who initially had acute tubular necrosis and then rejected their transplants, the expression of ICAM-1 on renal tubular cells tended to increase (from 27.5 +/- 2.5% to 60.0 +/- 20.0%, P = .12). In eight patients with acute tubular necrosis who never rejected their transplants, ICAM-1 expression remained low (23.1 +/- 3.8%). Immunocytology correlated well with immunohistology and the clinical diagnosis. Our findings suggest that urine immunocytology may be useful in monitoring adhesion molecule expression by renal tubular cells.
The aim of our study was to investigate the relationship between cardiac autonomic neuropathy and dysfunction of myelinated and unmyelinated nerve fibres in the peripheral nerve. We measured nerve conduction velocities, warmth/cold perception thresholds at the foot dorsum, sympathetic skin response (SSR), and performed the quantitative sudomotor axon reflex test (QSART). Forty-three diabetic patients with distal-symmetric polyneuropathy were included. According to the results of heart rate variation, 20 patients had cardiac autonomic neuropathy (CAN+). Apart from motor nerve conduction velocities, all tests were more often abnormal in CAN+ patients. Warmth thresholds (afferent C-fibres) and reduced compound muscle action potentials (CMAPs) of the tibial and peroneal nerve, indicating axonal damage, were more often abnormal in CAN+. Cold threshold and sural nerve conduction velocity were indicators of involvement of myelinated small and large nerve fibres, but not of the cardiac autonomic system. Ninety-four percent (94%) of patients with absent SSR and 78% of patients with abnormal QSART had CAN+. SSR and QSART may be useful for assessment of autonomic neuropathy in diabetic patients with cardiac arrhythmia where direct measurement of heart rate variability is not possible. In the majority of our patients with CAN+, the vagal-cardiac and the sudomotor-sympathetic systems were involved simultaneously, although two entirely different systems were tested. This may reflect a C-fibre directed selectivity of the pathological process in autonomic diabetic neuropathy. In conclusion our results show that diabetics with and without cardiac autonomic neuropathy have a different profile of involvement of peripheral nerve fibres.