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Treatment of acute hyponatremia: ensuring the excretion of a predictable amount of electrolyte-free water.

BACKGROUND: Hypertonic saline is the recommended therapy to shrink swollen brain cells in patients with acute hyponatremia accompanied by seizures. OBJECTIVES: In the absence of hypertonic saline, hypertonic mannitol will shrink the cell volume. Because mannitol is excreted rapidly, our aim was to ensure that it would be excreted with electrolyte-free water (EFW) and to evaluate the renal mechanisms responsible for EFW excretion. DESIGN: A randomized, prospective, placebo-controlled study in rats was carried out in a research laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The control group of rats (n = 6) was administered hypotonic saline, a loop diuretic, vasopressin, and glucose by the intraperitoneal route; in the experimental group (n = 6), glucose was replaced with mannitol. Plasma electrolytes were measured at 0 and 210 mins, and balances for water, sodium, and potassium were obtained from 0 to 90 mins and from 90 to 210 mins. MEASUREMENTS AND MAIN RESULTS: Virtually 100% of the administered mannitol was excreted within 210 mins, and half was excreted in the first 90 mins. The urine contained EFW only in the mannitol group because of a larger volume in the first 90 mins (EFW, 3.7 mL) and to a lower excretion of NaCl in the next 120 mins (EFW, 3.5 mL). CONCLUSIONS: The combined use of mannitol and a loop diuretic caused the excretion of a predictable volume of EFW because the urine was iso-osmotic to plasma and contained all the administered mannitol. The calculated decrease in intracellular fluid volume was equivalent when mannitol was retained or excreted.

Acute Disease↗

The biliary and urinary excretion of sodium tyropanoate and sodium ipodate in dogs: pharmacokinetics, influence of bile salts and choleretic effects with comparison to iopanoic acid.

The biliary and urinary excretion of sodium tyropanoate (Bilopaque) and sodium ipodate (Oragrafin) were studied in unanesthetized bile-fistula dogs using stepwise, increasing, intravenous infusions of the contrast materials. A constant intravenous infusion of sodium taurocholate was administered at the rate of either 0.5 or 2.0 mu moles per min per kg throughout each experiment. The biliary excretion of sodium tyropanoate or sodium ipodate was not effected by the rate of sodium taurocholate infusion. The maximum rate of biliary excretion of sodium ipodate was significantly greater than that of sodium tyropanoate with the low taurocholate infusion, but there was no significant difference between the two with the high taurocholate infusion. With the low taurocholate infusion the maximum biliary excretion rate of sodium tyropanoate (0.956 mu moles per min per kg) and sodium ipodate (1.472 mu moles per min per kg) were significantly greater than the maximum biliary excretion of iopanoic acid (Telepaque) (0.671 mu moles per min per kg). With the high taurocholate infusion the maximum biliary excretion rates of the three contrast agents were not statistically different. Both sodium tyropanoate and sodium ipodate produced an increase in canalicular bile flow (8-11 ml per millimole). These data suggest that in clinical cholecystography sodium tyropanoate and sodium ipodate are not excreted in bile more rapidly than iopanoic acid, except when the rate of biliary excretion of bile salts is low; that is, except in patients who are fasting or those who are on a fat-free diet.

Animals↗

Left ventricular mass assessed by electrocardiography and albumin excretion rate as a continuum in untreated essential hypertension.

OBJECTIVE: To study an association between albumin excretion rate and left ventricular mass (LVM) determined by electrocardiogram (ECG)-based criteria, and with respect to ambulatory blood pressure, in patients with newly diagnosed and never-treated essential hypertension. METHODS: We measured 24 h ambulatory blood pressure, albumin excretion rate and LVM in 74 patients with newly diagnosed (within the past year) and never-treated essential hypertension, who were admitted to the hypertension clinic (Ulleval University Hospital). Albumin excretion rate was evaluated by determination of the albumin:creatinine ratio in the first-voided morning urine sample. LVM was assessed by ECG using Cornell voltage-QRS duration product and Sokolow- Lyon criteria. RESULTS: Albumin excretion rate was significantly related to ambulatory blood pressure. There was a weak but significant negative correlation between the decrease in diastolic blood pressure during the night and the rate of excretion of albumin. The patients classified as dippers had a significantly lower albumin excretion rate compared with the non-dippers (1.36+/-0.83 compared with 1.68+/-0.87 mg/mmol; P = 0.03). LVM was found to be significantly related to ambulatory blood pressure. A weak relationship was observed between albumin excretion rate and LVM as evaluated by Cornell criterion (r = 0.23, P = 0.045). When only normoalbuminuric patients were included (i.e. four patients with microalbuminuria were excluded), the relationship was stronger (r = 0.36, P = 0.002). CONCLUSIONS: The present findings show a continuous relationship between albumin excretion rate, LVM and ambulatory blood pressure in newly diagnosed patients with essential hypertension, and suggest the occurrence of early effects on target organs (kidneys and heart). These associations were observed using easily applicable methods such as ECG monitoring and determination of the albumin:creatinine ratio in morning urine samples.

Adult↗

The effect of ramipril on albumin excretion in diabetes and hypertension: the role of increased lysosomal activity and decreased transforming growth factor-beta expression.

OBJECTIVES: Albumin excretion is modulated post-filtration by lysosomal processing that produces a spectrum of albumin-derived material in urine, much of which is not detected by conventional immunoassays. This study aimed to determine the efficacy of ramipril treatment (+ RAM) after 24 weeks on total albumin excretion (intact plus albumin-derived peptides) in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with (d) and without (c) diabetes. METHODS: Intact albumin excretion was analysed by radioimmunoassay and total albumin excretion was analysed by measuring radioactivity derived from circulating [ C]albumin. Renal lysosomal activity was determined by urinary [ H]dextran sulphate desulphation. Renal transforming growth factor-beta 1 (TGF-beta 1), TGF-beta inducible gene-h3 (beta ig-h3) and angiotensinogen mRNA production were analysed by real time reverse transcriptase-polymerase chain reaction. RESULTS: Hypertension (SHR-c and SHR-d) resulted in a significant increase in intact albumin excretion, which was significantly reduced by ramipril treatment (P < 0.05 for SHR-c + RAM and 0.001 for SHR-d + RAM compared to non-treated). This was accompanied by a significant decrease in blood pressure (P < 0.001 for SHR-c + RAM and SHR-d + RAM), renal beta ig-h3 mRNA production (P < 0.05 for SHR-c + RAM and SHR-d + RAM), and an increase in lysosomal activity. Diabetes (WKY-d and SHR-d) primarily caused a significant increase in total albumin excretion, predominantly in the form of albumin-derived fragments in the WKY-d group and intact albumin in the SHR-d group. Ramipril treatment reduced total albumin excretion in the WKY-d + RAM group (P < 0.001). CONCLUSIONS: Ramipril prevents increases in both intact albumin and total albumin excretion in hypertensive and diabetic states, respectively.

Albuminuria↗

Faecal bile acid and dietary residue excretion in cystic fibrosis: age group variations.

BACKGROUND: Earlier studies report the excessive faecal excretions of bile acids and dietary residues in cystic fibrosis (CF). However, few of these investigated large groups of patients using modern pancreatin preparations and little data exists reporting carbohydrate excretion. We therefore aimed to characterise the general levels of malabsorption within age groups of 132 patients attending a regional CF centre. METHODS: The faecal excretions of bile acids, fat, nitrogen and carbohydrate were measured. Most of these patients were treated with either (Creon) (n = 58) or Pancrease (n = 51) and prophylactic antibiotics. The patients were grouped in age ranges 0.5 to 5 years, 6 to 10 years, 11 to 15 years and >16 years. Carbohydrate excretion was determined in the 11 to 15 year group. RESULTS: Increased excretions with increment in age group were found which, for bile acids, was twice that of age matched controls. Modest relationships were found between the overall excretion of bile acids and fat, and between the excretion of bile acids and nitrogen. Primary bile acids were a feature of cystic fibrosis stools but the patterns of individual bile acid excretion revealed a trend towards a normal bile acid types with increment in age group. Faecal carbohydrate was significantly increased to levels which may significantly alter large bowel microflora. CONCLUSIONS: The data adds to the evidence that maldigestion initiates bile acid sequestration and consequently, the predominance of primary bile acids.

Adolescent↗

Excretion of urokallikrein in renal transplant patients. Relation to graft rejection, renal function, and blood pressure.

The relation between urinary kallikrein excretion ( Ukal ) and rejection, graft function, and blood pressure was studied in 45 renal transplant recipients. Ukal was assayed by means of an enzymatic (amidolytic) method, as well as with a specific radioimmunoassay. In a group of 10 patients studied longitudinally from the day of transplantation till day 35 +/- 3, an increase in urinary amidolytic activity without a concomitant increase in kallikrein antigen excretion was found to precede 11 out of 14 rejection episodes. This increased amidolytic activity generally persisted for several days. It was demonstrated by chromatography using an immunoadsorbent column of antiurokallikrein that the rejection-associated esterase, or esterases, differed from urokallikrein . In 35 outpatient recipients with stable graft function, Ukal excretion was decreased compared with that of healthy controls (42 +/- 7.5 vs. 107.5 +/- 7.3 micrograms/24 hr by radioimmunoassay and 0.70 +/- 0.08 vs. 1.10 +/- 0.07 U/24 hr, using the amidolytic method); for these patients a significant correlation between Ukal excretion and creatinine clearance was found (P less than 0.02). Both in transplant recipients and in controls there was a close correlation between the results of the two Ukal assays (P less than 0.001). No significant relation between Ukal excretion and blood pressure was found, either for patients or for controls. It is concluded that acute graft rejection is accompanied by an increased excretion of nonurokallikrein esterase(s). The lower Ukal excretion in patients with stable renal function seems to be related to their reduced renal function. No relation between Ukal excretion and blood pressure levels was found.

Adolescent↗

Phosphate Starvation Inducible Metabolism in Lycopersicon esculentum: I. Excretion of Acid Phosphatase by Tomato Plants and Suspension-Cultured Cells.

Both tomato (Lycopersicon esculentum cv VF 36) plants and suspension cultured cells show phosphate starvation inducible (psi) excretion of acid phosphatase (Apase). Apase excretion in vitro was proportional to the level of exogenous orthophosphate (Pi). Intracellular Apase activity remained the same in both Pi-starved and sufficient cells, while Apase excreted by the starved cells increased by as much as six times over unstressed control cells on a dry weight basis. At peak induction, 50% of total Apase was excreted. Ten day old tomato seedlings grown without Pi showed slight growth reduction versus unstressed control plants. The Pi-depleted roots showed psi enhancement of Apase activity. Severely starved seedlings (17 days) reached only one-third of the biomass of unstressed control plants but, because of a combination of psi Apase excretion by roots and a shift in biomass to this organ, they excreted 5.5 times the Apase activity of the unstressed control. Observed psi Apase excretion may be part of a phosphate starvation rescue system in plants. The utility of the visible indicator dye 5-bromo-4-chloro-3-indolyl-phosphate-p-toluidine as a phenotypic marker for plant Apase excretion is demonstrated.

Journal Article↗

Urinary pyridinoline and deoxypyridinoline excretion in children.

OBJECTIVE: There are few data on urinary markers of collagen breakdown in children. We have determined a normal range for urinary pyridinoline and deoxypyridinoline in children, assessed the variability in excretion in individual children and examined the effect of GH treatment on the excretion of these collagen cross-links. DESIGN: A cross-sectional study of a group of healthy children and sequential samples from children receiving GH treatment. PATIENTS: One hundred and nine healthy children aged 2-15 years, 8 healthy children aged 4-11 years and 4 children receiving GH treatment. MEASUREMENTS: Total pyridinoline and deoxypyridinoline excretion were measured by high performance liquid chromatography after initial acid hydrolysis and cellulose extraction steps. Serum parathyroid hormone was measured using a two-site immunoradiometric assay and urinary hydroxyproline by Ehrlich's reaction using a colorimetric assay. Pyridinoline and deoxypyridinoline excretion were expressed as a ratio against urine creatinine. RESULTS: High excretion of pyridinoline (Pyr) and deoxypyridinoline (DPyr) was seen at all ages with no apparent relation to age (mean Pyr/Cr 115 nmol/mmol and DPyr/Cr 31 nmol/mmol). No correlation was found with serum parathyroid hormone or urinary hydroxyproline excretion. Marked day to day variation was seen in individual children. A progressive rise in excretion was seen in children receiving GH treatment with no significant correlation to height velocity. CONCLUSIONS: There is a high excretion of the pyridinium cross-linking amino acids in children of all ages compared to adults. However, a high variability exists in single morning urine samples which will limit the usefulness of these markers in growing children.

Adolescent↗

Urinary excretion of metals during treatment with D-penicillamine and 2-mercaptopropionylglycine in normal and cystinuric dogs.

Urinary excretion of metals during treatment with 2-mercaptopropionylglycine (2-MPG) was studied in 11 normal and 20 cystinuric male dogs. The results were compared with those obtained during D-penicillamine treatment. Twenty-four-h urine and morning samples of urine were taken for determination of 13 metals before and during treatment. After single intravenous and oral D-penicillamine treatment of the normal dogs, significant increases were found in the 24-h urinary excretion of Ca, Cu and Zn. Oral intake of D-penicillamine increased the excretion of Co, Cr, Fe and Mg as well. No effect on renal metal excretion was observed after single intravenous and up to 2 months of daily oral treatment with 2-MPG. In 14 cystinuric dogs no effect was found after single intravenous and oral administrations of 2-MPG. However, after oral treatment of six cystinuric dogs with 2-MPG for 2-4 months, significantly increased excretions of Ca and Mg were found. Fourteen of the cystinuric dogs were also investigated after 2-6 years of continuous 2-MPG treatment, and after this period no significant elevation in the urinary excretion of metals was found. The present study shows that in contrast to D-penicillamine, 2-MPG does not increase the urinary excretion of metals to any appreciable extent. Observed increases in the excretion of Ca and Mg seemed to be a temporary effect only.

Administration, Oral↗

Effect of dietary intake on urinary oxalate excretion in calcium renal stone formers.

OBJECTIVE: To investigate the influence of dietary intake on urinary oxalate excretion in calcium renal-stone formers. PATIENTS AND METHODS: Dietary intake was monitored by using the dietary-record method in 60 idiopathic stone formers. The patients collected their urine for 24 h at home and their urinary oxalate excretion rate was determined. The relationship between the daily intake of various nutrients and urinary oxalate excretion was examined by both monovariate and multivariate analyses. RESULTS: By monovariate analysis, the intake of carbohydrate, total protein and fat were significantly correlated with urinary oxalate excretion, but the intake of calcium and body surface area were not. In addition, the intake of total protein was highly correlated with that of fat. By multivariate analysis, the intake of carbohydrate and fat were significantly related to urinary oxalate excretion, and the intake of calcium was inversely correlated with urinary oxalate excretion, but the intake of total protein showed no significant correlation. CONCLUSION: The intake of carbohydrate and fat was positively and the intake of calcium was inversely correlated with urinary oxalate excretion in stone formers and, taken together, these findings suggested that fat plays an important role in urinary oxalate excretion and that protein has a minimal effect.

Body Surface Area↗

Urinary growth hormone excretion during puberty in type 1 (insulin-dependent) diabetes mellitus.

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.

Acetylglucosaminidase↗

Indomethacin but not metoprolol reduces exercise-induced albumin excretion rate in type 1 diabetic patients with microalbuminuria.

The effects of a single oral dose of indomethacin (1 mg kg-1) metoprolol (1.5 mg kg-1) and placebo on exercise-induced albumin excretion rate (AER) were compared in a randomized, crossover design in 14 normotensive, young Type 1 diabetes patients, nine of them with microalbuminuria (AER > 15 micrograms min-1) and five without microalbuminuria at rest. The albumin excretion rate, blood pressure, heart rate, blood glucose, and plasma concentrations of indomethacin and metoprolol were determined before and after 30 min submaximal physical exercise. In microalbuminuric patients the rise in albumin excretion rate after exercise on indomethacin (7 micrograms min-1) was lower than after placebo (29 micrograms min-1, p < 0.001) whereas the rise in albumin excretion rate with metoprolol during exercise (18 micrograms min-1) did not differ from placebo (p = 0.48), in spite of the expected less marked increase in blood pressure. In normoalbuminuric patients no significant increase in albumin excretion rate was noted by exercise in any of the treatment periods. A tendency to a linear correlation (r = -0.54, p = 0.07) was seen between the plasma concentration of indomethacin and the inhibition of exercise-induced increase in albumin excretion rate. No correlations were observed between exercise-induced changes in albumin excretion rate and systolic blood pressure, heart rate or blood glucose. In conclusion, acute indomethacin treatment, presumably through inhibition of renal prostaglandin synthesis, reduces the exercise-induced rise in albumin excretion rate in Type 1 diabetic patients with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Circadian variation of urinary albumin excretion in pregnancy.

OBJECTIVE: The hypothesis was tested that circadian variations in urinary albumin excretion of pregnant women in the third trimester of normal pregnancy are different from nonpregnant individuals. DESIGN: Circadian variability in urinary albumin excretion was studied both in pregnant women and in nonpregnant controls either during normal daily activities or in contrast during continuous bedrest with standardised fluid and food intake to study endogenously generated rhythm. SETTING: Outpatient department and metabolic ward of a university hospital. MAIN OUTCOME MEASURES: Urinary albumin excretion during fixed time periods over the day and the night. RESULTS: Both ambulant pregnant and nonpregnant women have circadian rhythm in urinary albumin excretion but pregnant women have, firstly, a higher 24 h urinary albumin excretion, secondly, smaller relative day-night differences than nonpregnant controls and thirdly, in the metabolic ward some pregnant women demonstrate absence of rhythm. CONCLUSIONS: The higher albumin excretion during pregnancy in 24 h urine collections can largely be explained by a higher excretion during the night, compared with that of nonpregnant women. The day-night difference in urinary albumin excretion of ambulant pregnant women is exogenously determined.

Adult↗

The effect of high rates of vasopressin administration on renal potassium and sodium excretion during potassium loading in the sheep.

1 The influence of potassium loading on the renal excretion of sodium, potassium and solute during high rate vasopressin administration has been investigated in sheep. 2 Adrenalectomized sheep were infused with 0.43 M KCl at 2 ml/min for 2-2.5 hours. Coincident with the rise in plasma potassium concentration, the urinary excretion of sodium, potassium, solute and water was increased as was the reabsorption of solute-free water. The rates of urinary excretion of sodium and potassium, osmolal clearance (COsm) and solute-free water reabsorption (TcH2O) for the first 50 min of potassium infusion were each found to be linearly related to the plasma potassium concentration. 3 After 50 min an infusion of vasopressin at 1 or 4 mu/min was superimposed on the potassium infusion for a period of 30 minutes. The administration of vasopressin was consistently associated with further augmentation of potassium excretion and clearance, of osmolal clearance and of solute-free water reabsorption to values above those anticipated from the pre-vasopressin regression lines for these parameters. Urinary sodium showed a coincident depression in the rate of excretion and clearance during the same period. 4 Thirty to fifty minutes after the cessation of vasopressin infusion the potassium and sodium excretions had returnied to values which approximated the pre-vasopressin relations between plasma potassium and the urinary excretions of these ions. 5 Both rates of vasopressin infusion were equally effective in increasing the potassium clearance. Any differences in clearance between the two rates of vasopressin administration were not statistically significant. 6 The large increments in potassium excretion (averaging greater than 40%) were interpreted as indicating that, when vasopressin is present at high concentrations, the distal tubule is one site of action of the hormone in the nephron of sheep.

Animals↗

Enhancement of urinary prostaglandin excretion by chlorazanil in rats. Effects of indomethacin.

In conscious unloaded Sprague-Dawley female rats chlorazanil (10 mg/kg orally) markedly increased urinary prostaglandin E2-excretion from 51 +/- 9 to 813 +/- 112 ng/kg/6 hrs. Urinary flow rate increased from 12.8 +/- 0.6 to 42.0 +/- 1.4 ml/kg/6 hrs and urinary sodium excretion from 0.96 +/- 0.12 to 3.86 +/- 0.33 mmol/kg/6 hrs Urinary potassium excretion was unchanged. Indomethacin pretreatment (5 mg/kg orally) greatly induced the effect of chlorazanil on urinary prostaglandin E2-excretion. In addition indomethacin modified the excretory effects of chlorazanil, thus the enhancement of urinary flow rate was attenuated, the potassium excretion decreased, while sodium excretion tended to be potentiated. In non-pretreated condition chlorazanil variably affected urinary kallikrein excretion (TAMe-esterase activity) from 108 +/- 6 to 92 +/- 33 mEU/kg/6 hrs. After indomethacin pretreatment chlorazanil invariably reduced urine enzyme excretion from 111 +/- 6 to 32 +/- 4 mEU/kg/6 hrs.

Animals↗

Effect of various antidotes on biliary excretion of arsenic in isolated perfused livers of guinea pigs after acute experimental poisoning with As2O3.

The effect of the dithiols British Anti-Kewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA) and a new metal binding agent 2,3-bis-(acetylthio)- propanesulfonamide (BAPSA) on the biliary excretion of arsenic in perfused livers of guinea pigs after acute experimental poisoning with As2O3 was investigated. Guinea pigs received As2O3, 10.0 mg/kg subcutaneously at 9 a.m. as a single injection. One hour after the injection the livers were perfused (2.5 ml x min.-1 x g-1 liver) with Krebs-Henseleit buffer and glucose for 80 min. After 40 min. of saline perfusion (control) 0.1 or 0.7 mmol/l BAL, DMSA, DMPS, or BAPSA were added to the perfusate and arsenic elimination in the bile and effluent perfusate was measured. The biliary excretion of arsenic in control livers between 40 and 80 min. was 0.7% of the total arsenic liver content before perfusion (= arsenic liver content after perfusion + portion excreted in the bile+perfusate). After antidote addition (0.1 mmol/l) the excretion was 0.2% for livers perfused with BAL, 6.8% for DMSA, 10.6% for DMPS, and 11.1% for BAPSA, respectively. After 0.7 mmol/l antidote the excretion of arsenic was 0.1% in livers perfused with BAL, 9.6% for DMSA, 12.3% for DMPS, and 13.3% for BAPSA, respectively. Except BAL, all compounds and most effectively BAPSA increased biliary excretion of arsenic. This indicates that excretion of arsenic which normally is mainly renal is shifted towards faecal excretion by the dithiols.

Animals↗

The effect of various therapeutic trials on the prophyrin excretion in a case of congenital erythropoietic prophyria.

A patient with a biochemically "new" type of congenital erythropoietic porphyria has been studied under various therapeutic trials. Splenectomy had no demonstrable effect on porphyrin excretion or clinical picture. Vitamin E caused a moderate fall in porphyrin excretion, however, there was no significant improvement in light tolerance and tendency to hemolysis. Beta-carotene reduced skin photosensitivity appreciably, while total porphyrin excretion remained unchanged and the tendency to develop hemolytic anemia showed only slight improvement. Red cell transfusion caused a rapid, dramatic fall in prophyrin excretion (in 4-5 days) and a transient increase in light tolerance, while the distribution of the different porphyrins excreted remained unchanged. These observations indicate that all or nearly the abnormal porphyrins excreted are of erythropoietic origin, and that the overwhelming part of the porphyrins originate from an abnormal population of shortlived red cells. Findings on fluorescence microscopy of blood and bone marrow support this view. Meticulous protection against light of the shorter wavelengths caused a similar rise in hemoglobin level as produced by red cell transfusion, however, in this instance the total excretion of porphyrins did not fall. It is suggested that the inhibitory effect of transfusion on erythropoiesis (and thereby porphyrin excretion) might be due partly to a depression of erythropoietin formation, partly to the presence of an erythropoiesis inhibiting factor (chalone) in the transfused red cells.

Blood Transfusion↗

Clinical significance of urinary C-peptide excretion in children with insulin-dependent diabetes mellitus.

In order to evaluate the accuracy of urinary C-peptide determination and the clinical significance of C-peptiduria for the early course of insulin-dependent diabetes (IDDM), the rate of urinary excretion of C-peptide was determined in 32 children and adolescents with IDDM and correlated with serum C-peptide concentration, urinary excretion of albumin and beta 2-microgloublin and with the glomerular filtration rate (GFR) measured in terms of the clearance of 99mTc-DTPA. The age of the subjects ranged from 9.1 to 17.1 years (mean 13.1) and the duration of diabetes from 0.3 to 11.9 years (mean 4.6). There was a good correlation between postprandial serum C-peptide concentration and the 24-hour urinary C-peptide excretion rate (r = 0.81; p less than 0.001). GFR and urinary albumin excretion were slightly elevated in the diabetic patients as compared with non-diabetic subjects (p less than 0.05 and p less than 0.001, respectively), but C-peptide excretion was unrelated to the degree of hyperfiltration or albuminuria, neither was there any correlation between the excretion rate of beta 2-microglobulin and C-peptide. Glycaemic control was poorer in the diabetic children who had only trace amounts of C-peptide in their urine (less than 0.05 nmol/m2/24 h) than in those with minimal (0.05-1.0 nmol/m2) or moderate 24-hour urinary C-peptide excretion (greater than 1.0 nmol/m2). It is concluded that urinary C-peptide excretion serves very well to reflect residual beta-cell function and is unrelated to the slight renal hyperfunction and albuminuria often seen in diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗