Robert C. Kelsch

Fragmentation and polymeric complexes of albumin in human urine

Analysis of urine proteins of some individuals with proteinuria by SDS-PAGE and silver staining revealed protein bands in urine which did not appear to be present in plasma. The bands migrated with apparent molecular weights of 260 000, 180 000, 110 000, 45 000, 40 000, 30 000, 24 000, 18 000 and 11 000. These bands were shown to be albumin polymer and fragments by using a polyclonal antibody to (a) immunoprecipitate radiolabelled urine proteins, and (b) identify bands blotted from SDS-PAGE gels onto nitrocellulose paper. The specificity of the polyclonal anti-albumin antibody was confirmed by using two mouse monoclonal antibodies raised against human albumin which, between them, recognized the same protein bands on nitrocellulose paper as did the polyclonal antibody. The results of these studies of albumin in human urine confirm that albumin exists as polymer and also show that albumin fragmentation occurs in urine. Fragmentation occurs by proteolysis of the albumin molecule both at sites within and outside disulfide loops. The predominant cleavage site appears to be approximately two-fifths of the distance from one end of the albumin molecule to produce disulfide-linked fragments of about 45 000 and 30 000 molecular weight.

Renal papillary necrosis in juvenile rheumatoid arthritis

Three patients who developed renal papillary necrosis while receiving long-term, high-dose aspirin therapy for juvenile rheumatoid arthritis are presented. It appears that aspirin alone or aspirin in combination with other drugs is the causative agent. The incidence and biologic significance of renal papillary necrosis are insufficient to alter the use of aspirin as the drug of choice in management of JRA. It is recommended that all children with JRA be encouraged to drink ample fluids and be followed with periodic urinalysis and blood pressure measurements. Those children who develop hematuria or hypertension should be evaluated by excretory urography.

Studies on dietary correction of metabolic abnormalities in hepatorenal glycogenosis.

Extract: This study reports the effects of frequent glucose feeding on the metabolic abnormalities observed in a patient with hepatorenal glycogenosis. Use of this diet resulted in correction of metabolic acidosis and hyperlacticacidemia. External calcium balance became positive secondary to a decrease in the loss of calcium in urine. Long-term use of the diet caused a reduction to normal values of triglyceride and cholesterol levels in serum. Continued use of the diet for nine months resulted in increased growth rate and increased calcification of bone. Evidence based on excretion of epinephrine and 17-hydroxy-corticosteroids in urine did not indicate that an increased excretion of these hormones occurred in response to hypoglycemia. Concentrations of growth hormone were low despite hypoglycemia; however, after nine months of treatment, the patient showed a rapid decline in the levels of blood sugar with an increase in the levels of growth hormone in blood.Speculation: Partially controlled hepatorenal glycogenosis is in some ways similar to juvenile diabetes mellitus since patients with this disease sustain intermittent starvation of the peripheral tissues for glucose. Study of the metabolic sequellae of peripheral glucose deprivation and repletion in some forms of glycogenosis may lead to a better understanding of the complications of juvenile diabetes mellitus.

Demonstration of Increased Catecholamine Excretion in the Nephrotic Syndrome.

Summary In 7 edematous nephrotic children, the mean excretion of norepinephrine was significantly greater than in these children during remission or in 7 control subjects. The increased excretion did not correlate with glomerular filtration rate or quantity of urine protein but correlated with magnitude of sodium retention. Steroid therapy caused a prompt decrease of excretion of catecholamines and their metabolites. These findings may relate to circulatory changes or to other unrecognized abnormalities.

The effect of pancuronium bromide on plasma norepinephrine and cortisol concentrations during thiamylal induction

Summary and ConclusionEffects of pancuronium on free norepinephrine and cortisol concentrations in plasma were investigated in eight elective surgical patients. A dose of 0.09 mg/kg of pancuronium was administered intravenously following thiamylal induction during nitrous oxide-oxygen inhalation and prior to intubation and surgical preparation. No hypoxic or hypercarbic episodes were demonstrated by arterial blood gas studies.No significant changes from the base line level were observed either in free norepinephrine levels or in plasma cortisol levels for ten minutes following the administration of pancuronium. Although pancuronium did not cause a rise in free norepinephrine concentration in plasma, it counteracted the hypotension usually observed following the intravenous administration of thiamylal. Heart rate and blood pressure, however, were not significantly increased.RésuméLes effets du Pancuronium sur la concentration de Norépinéphrine et de Cortisol dans le plasma, furent étudiés chez huit patients électifs. Après une induction au Thiamylal, précédant l’intubation endotrachéale et la préparation chirurgicale, une dose de 0.09 mg/kg de Pancuronium fut administrée sous Protoxyde-Oxygène. Aucun épisode hypoxique ou hypercarbique ne fut démontré par l’éude du sang artériel.Aucun changement significatif ne fut observé dans la concentration plasmatique de la Norépinéphrine ou du Cortisol pendant les dix minutes suivant l’administration du Pancuronium. Même si le Pancuronium ne provoque pas d’é1évation de la Nor-épinéphrine plasmatique libre, il annulle l’hypotension habituellement observée après administration intra-veineuse de Thiamylal. Le rythme cardiaque et la tension artérielle ne se sont pas élevés de façon significative.

THE EFFECT OF PANCURONIUM BROMIDE ON PLASMA NOR-EPINEPHRINE CONCENTRATIONS DURING KETAMINE INDUCTION

SummaryKetamine 2.0 mg/kg alone with nitrous oxide-oxygen inhalation caused a rise in blood pressure, pulse rate and frée nor-epinephrine levels in plasma in twelve elective surgical patients. Contrary to expectations, the combination of ketamine with pancuronium during nitrous oxide-oxygen inhalation caused no rise in nor-epinephrine in plasma and reduced the rise in arterial blood pressure and pulse rate. No intubation, surgical preparation, or positional changes were allowed. No hypoxia or hypercarbia was demonstrated by the blood gas studies. The mechanism of this blocking effect of pancuronium on ketamine-induced nor-epinephrine rise await clarification by further laboratory and clinical experiments. The combination of ketamine with pancuronium, can therefore be safely employed in patients in whom marked circulatory changes should be avoided.RésuméLa Ketamine à la dose de 2.0 mgm/kg, employée seule avec le protoxyde d’azote-oxygène en inhalation, produisit une élévation de la pression sanguine, de la fréquence cardiaque et des niveaux plasmatiques de nor-épinéphrine libre chez douze malades soumis à une chirurgie élective. Contrairement aux prévisions, l’association de Ketamine avec le Pancuronium durant 1’inhalation de protoxyde d’azote-oxygène n’amena aucune élévation de nor-épinéphrine libre dans le plasma et diminua l’élévation de la tension artérielle et de la fréquence cardiaque. L’intubation, la préparation chirurgicale et les changements de posture étaient interdits. L’étude des gaz sanguins ne démontra aucune hypoxie ni hypercarbie. Le mécanisme de cet effet de blocage du Pancuronium sur l’élévation de nor-épinéphrine suscitée par la Ketamine doit attendre, pour trouver son explication, de plus amples essais en laboratoire et en clinique. L’association de la Ketamine avec le Pancuronium peut done être utilisée avec sécurité chez les malades où l’on doit éviter des changements circulatoires marqués.

1630 THE NATURAL HISTORY OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE IN CHILDREN

Polycystic kidney disease in children has often been called “infantile” on the basis of age alone; we sought to identify children <18 years of age with autosomal dominant polycystic kidney disease (APKD) documented by family workup. Twenty-four children were diagnosed by ultrasound as having APKD; 33 were suspicious for APKD (SAPKD) when unilateral, inhomogeneous or <5 cysts were seen. The 24 children with APKD were 9.3±6.4 yr. of age (x ± 1 S.D.) with followup of 7.5±6.5 yr. (range 0-29 yr.). Sixty-two percent of APKD children had symptoms at presentation (abdominal pain, headaches, gross hematuria), 25% had hypertension (HTN), 20% had hernias, 12% had boney abnormalities. Forty-two percent had progression during followup (increased cysts, increased HTN, or decreased renal function). Twenty-one percent reached end-stage renal disease (ESRD) in 14.6±10.7 yr. (range 3-29 yr.). Four children had APKD diagnosed <1 year of age with followup 6.6±5.8 yr. Two reached ESRD: one at age 3, another at age 15 yr. The other two are stable at 1.5 and 5 yr. post-diagnosis. Thirty-three children with SAPKD (x age 12.7±3.4) had followup of 5.6±3.7 yr. Twenty percent had symptoms compatible with APKD, 77% progressed, 0% reached ESRD.Conclusions: There is wide variation in the onset and progression of APKD in childhood. Children with SAPKD may have prolonged stability but warrant meticulous followup. APKD in childhood is associated with other abnormalities.

Plasma norepinephrine concentration before and after albumin infusion in nephrotic children

A reduction of effective plasma volume secondary to a decrease in the quantity of circulating protein is postulated to initiate edema formation in the nephrotic syndrome, however reduction of plasma volume has not been consistently demonstrated during active disease. Acute and chronic reduction of plasma volume is associated with an increased excretion of norepinephrine, presumably secondary to increased sympathetic activity. We therefore studied certain aspects of norepinephrine metabolism in thirteen children with the active nephrotic syndrome. All children were on a l½–2 mEq/kg/day sodium intake and no diuretic therapy. Plasma norepinephrine concentration was measured on two consecutive mornings and again four hours later each day. Albumin (6–18 grams) was infused 3 hours prior to the second blood sample on the second day. All samples were obtained from the antecubital vein after the subject had remained at 30 degrees tilt for 20 minutes. Eight of the thirteen children had increased plasma norepinephrine concentrations in the early morning (> 0.5 ng./ml). The plasma norepinephrine concentration measured following albumin infusion was significantly reduced whereas that obtained on the control day was not. Urinary excretion of conjugated norepinephrine declined significantly within 48 hours after the initiation of prednisone treatment in these subjects. These data suggest the presence of increased sympathetic activity during the active phase of the nephrotic syndrome which can be altered by the infusion of albumin or the administration of prednisone.