Baseline Excretion Research Articles

Kemp's Ridley Sea Turtle Waste Characterization Study: Precursor to a Recirculating Holding System Design

AbstractThe decreasing population of the endangered Kemp's ridley sea turtle (Lepidochelys kempi) has necessitated research into more cost effective captive nurseries. Captive nurseries are an attempt to increase the survival of the Kemp's ridley past the first year of life. Presently, Kemp's ridleys are reared in captivity at the Headstart rearing facility in Galveston, Texas. This facility consists of a labor intensive, flow‐through system. Alternatively, recirculating systems permit development of inshore facilities with decreased labor and operating costs. This paper presents baseline excretion data necessary for designing filtration units required for water quality maintenance in recirculating holding systems. The total ammonia nitrogen excretion rate based on a 24 hour isolation period (fed) was fairly constant at 0.19 mg N/g‐turtle‐day, while the BOD5 loading rate was highly variable, averaging nearly 0.50 mg O2/g‐turt1e‐day. In addition, comparisons of filtered versus nonfiltered samples suggest that a suspended solids removal mechanism prior to the filtration unit would dramatically decrease BOD5 and, thus, improve filter efficiency and increase its capacity.

Cardiorenal actions of endothelin, part II: Effects of cyclooxygenase inhibitors

The effects of cyclooxygenase inhibitors (meclofenamate and indomethacin) on endothelin-induced changes in renal function were evaluated in pentobarbital anesthetized female rats. Two groups (n=5/group) of rats were evaluated: one group received a continuous intravenous infusion of meclofenamate (0.03 mg kg −1 min −1) and the second group received a bolus injection of indomethacin (5 mg/kg). Following surgery, rats were allowed 60 min to stabilize and 3 × 20 min control clearances collected. Endothelin-1 (100 ηg kg −1 min −1) was then added into the infusate for 30 min. Neither meclofenamate nor indomethacin caused significant changes on endothelin-induced systemic vasoconstriction; blood pressure increased from 107 ± 3 to 136 ± 2 mmHg (p<0.01) with endothelin alone, from 103 ± 6 to 135 ± 6 mmHg (p<0.01) with endothelin plus meclofenamate, and from 105 ± 6 to 131 ± 10 mmHg (p<0.01) with endothelin plus indomethacin. Similarly, endothelin-induced decreases in glomerular filtration rate (GFR) were not affected by either meclofenamate or indomethacin; GFR decreased from 2.7 ± 0.2 to 0.8 ± 0.3 ml/min (p<0.01) with endothelin alone, from 2.3 ± 0.5 to 0.7 ± 0.4 ml/min (p<0.01) with endothelin plus meclofenamate, and from 2.6 ± 0.4 to 0.6 ± 0.4 ml/min (p<0.01) with endothelin plus indomethacin. Baseline excretion rates of sodium, potassium and urine volume were also not affected by the inhibitors of cyclooxygenase. These data demonstrate that, under the conditions of the current study, endothelin-induced changes in renal and cardiovascular function are not affected by inhibiting prostaglandin production.

Splanchnic and peripheral release of 3-methylhistidine in relation to its urinary excretion in human infection

The present investigation was undertaken in order to determine the release of 3-methylhistidine (3MH) from the splanchnic region and from the leg, and the contributions these make to the increase in urinary 3MH excretion in infection. Thirteen febrile patients with infection were investigated. After an overnight fast, hepatic vein, femoral vein, and radial artery catheterizations were performed. Splanchnic and leg blood flows were determined by dye dilution technique. Plasma 3MH was analyzed by a modified HPLC method. The release of 3MH from the leg was 0.064 ± 0.007 μmol/min (±SE) and from the splanchnic region 0.012 ± 0.013 μmol/min. These releases of 3MH constitute 27% ± 2% and 8% ± 6% of the individual urinary excretions, respectively. With increasing degree of catabolism, measured as individual 3MH increase above baseline excretion or as the 3MH to creatinine ratio (3MH:Cr), the relative contribution to urinary excretion from the leg was increased (individual increase, P = 0.08; 3MH:Cr, P < 0.01). Since this contribution was not decreased in the more catabolic patients, as would have been expected if the increase in urinary 3MH originated elsewhere, it is concluded that skeletal muscle is the source, and these results thus validate the use of urinary 3MH excretion as a marker of myofibrillar protein catabolism in infected patients.

51Cr-Ethylenediaminetetraacetic Acid Absorption Test: Methodologic Aspects

The 51Cr-ethylenediaminetetraacetic acid (EDTA) absorption test was evaluated in 83 healthy, male volunteers. Base-line 24-h excretion after peroral administration ranged from 0.88% to 7.96%, with a higher median absorption than reported by most authors (2.45%). However, the reproducibility and stability of the method and the reproducibility of the results were satisfactory. Urinary excretion after intraduodenal instillation (n = 18) was comparable to that seen after peroral test dose administration, indicating a limited significance of gastric 51Cr-EDTA absorption under normal conditions. In 16 subjects a single intake of alcohol immediately before the test gave a modest and short-lasting increase in 51Cr-EDTA absorption. No correlation was seen to body mass index, creatinine clearance, urinary volume, or small-bowel transit time, possibly reducing the number of confounding factors in the evaluation of absorption data. A small but significant negative correlation was, however, found to body surface area and age.

Unimpaired excretion of an acute salt load in conscious hypoproteinaemic dogs.

1. The role of hypoproteinaemia in the sodium retention seen in conditions such as the nephrotic syndrome is incompletely known. 2. To define the influence of severe hypoproteinaemia on kidney function, we studied the effect of an intravenous infusion of an isotonic saline load (133 mmol of sodium), as 1 litre of Ringer lactate solution, on sodium excretion and renal haemodynamics in conscious dogs before and after reduction of plasma protein from 68 +/- 3 to 36 +/- 2 g/l by repeated plasmapheresis and a low protein diet. 3. During hypoproteinaemia, 2 days after a period of plasmapheresis, glomerular filtration rate and effective renal plasma flow were lower than in the control study. After the sodium load, both rose to values nearly identical with the pre-infusion levels found in normoproteinaemia, the filtration fraction remaining unchanged. This contrasted with the rise in filtration fraction after expansion in normoproteinaemia, where filtration fraction increased from 32 to 39% due to a rise in glomerular filtration rate. 4. After expansion, natriuresis rose to similar levels in normoproteinaemia (0.18 +/- 0.06 mmol/min) and hypoproteinaemia (0.20 +/- 0.06 mmol/min), and increments in fractional excretion of sodium, potassium and chloride were also similar. However, baseline excretion was higher in the hypoproteinaemic dogs due to their overhydrated condition in this period immediately after plasmapheresis. 5. The fractional excretion of lithium, an alleged marker of proximal tubular sodium reabsorption, rose to comparable levels. 6. Hence, both the increase in filtration and decrease in reabsorption of sodium after an isotonic saline load are not affected by severe reduction in plasma protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the hepatocyte microtubular system in the excretion of bile salts and biliary lipid: implications for intracellular vesicular transport.

The role of the hepatocyte microtubular system in the transport and excretion of bile salts and biliary lipid has not been defined. In this study the effects of microtubule inhibition on biliary excretion of micelle- and non-micelle-forming bile salts and associated lipid were examined in rats. Low-dose colchicine pretreatment had no effect on the baseline excretion of biliary bile salts and phospholipid in animals studied 1 hr after surgery (basal animals), but slightly retarded the excretion of tracer [14C]taurocholate relative to that of lumicolchicine-pretreated (control) rats. However, colchicine pretreatment resulted in a marked reduction in the excretion of 2 mumol/100 g doses of a series of four micelle-forming bile salts of differing hydrophilicity, but had no significant effect on the excretion of the non-micelle-forming bile salt, taurodehydrocholate. Continuous infusion of 0.2 mumol of taurocholate/(100 g.min) following 24 hr of biliary drainage (depleted/reinfused animals) resulted in physiologic bile flow with biliary excretion rates of bile salts, phospholipid, and cholesterol that were markedly inhibited (mean 33, 39, and 42%, respectively) by colchicine or vinblastine pretreatment. Excretion of tracer [14C]taurocholate also was markedly delayed by colchicine in these bile salt-depleted/reinfused animals. In contrast, colchicine did not inhibit bile salt excretion in response to reinfusion of taurodehydrocholate. Thus, under basal conditions, the microtubular system appears to play a minor role in hepatic transport and excretion of bile salts and biliary lipid. However, biliary excretion of micelle-forming bile salts and associated phospholipid and cholesterol becomes increasingly dependent on microtubular integrity as the transcellular flux and biliary excretion of bile salts increases, in both bile salt-depleted and basal animals. We postulate that cotransport of micelle-forming bile salts and lipids destined for biliary excretion, via an intracellular vesicular pathway, forms the basis for this microtubule dependence.

Enhanced gastrointestinal absorption of aluminumin in uremic rats

To investigate the possibility of enhanced gastrointestinal absorption of aluminum in uremia, we measured the urinary aluminum excretion of rats following an oral load of 11 mg aluminum. Rats, in which uremia had been established by the remnant kidney model, excreted 1.5 to 2.2-fold higher amounts of aluminum in their urine over a collection period of five days compared with their controls. Within this period of time up to 0.17 +/- 0.08% of the oral dose of aluminum was recovered in the urine of the uremic animals. Serum concentrations of aluminum were significantly elevated five hours after ingestion of aluminum, but this increase was similar in rats with normal or reduced renal function. Uremic rats excreted significantly less aluminum during the first 24 hours after i.v. administration of 15 micrograms aluminum if the data were corrected for the higher baseline excretion rates. The excretion rate showed a negative correlation with the serum creatinine. Selective parathyroidectomy had no effect on the pattern or amount of urinary aluminum excretion after an oral load in either uremic rats or in rats with normal renal function. We conclude that the gastrointestinal absorption of aluminum is increased in uremic rats, and that parathyroid hormone has no detectable effect on the magnitude of aluminum absorption, regardless of the renal function in this model.

Gallium nitrate inhibits accelerated bone turnover in patients with bone metastases.

Bone metastases are a major source of morbidity in patients with cancer. Previously, we found that gallium nitrate was a highly effective treatment for cancer-related hypercalcemia. Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We evaluated the clinical effects of gallium nitrate on biochemical parameters of increased bone turnover in 22 patients with bone metastases. Treatment with gallium nitrate for five to seven days caused a median reduction in 24-hour urinary calcium excretion of 66% relative to baseline measurements (P less than .01). Hydroxyproline (OHP) excretion was also significantly reduced (P less than .01). The greatest reduction in hydroxyprolinuria occurred in patients with high baseline excretion. Ionized serum calcium and serum phosphorous declined significantly after treatment (P less than .01 for each). Serum immunoreactive parathyroid hormone (PTH) increased significantly (P less than .01), as did serum levels of 1,25 (OH)2-vitamin D3 (P less than .05). Urinary phosphorous excretion and serum levels of 25-OH-vitamin D3 were not significantly changed. No major toxic reactions occurred as a result of this treatment. These results indicate that gallium nitrate significantly reduces biochemical parameters associated with accelerated bone turnover and that this agent may be useful for preventing pathologic conditions associated with bone metastases.

Absorption of Magnesium from Orally Administered Magnesium Sulfate in Man

The use of magnesium sulfate (Epsom salt) as a cathartic in patients with impaired renal function can lead to severe toxicity due to hypermagnesemia. Although toxicity is uncommon in healthy subjects, little is known concerning the extent of absorption of magnesium after a cathartic dose of magnesium sulfate. The bioavailability of magnesium following a large oral dose of magnesium sulfate in normal volunteers was examined in the present investigation. Baseline 24-hour urinary excretion rates of magnesium and creatinine were determined over 3 consecutive days in 6 healthy men. The oral administration of 13.9 g (56.5 mmoles) magnesium sulfate U.S.P., in 4 equal hourly increments, resulted in the urinary excretion (corrected for baseline excretion rate) of 4.0 +/- 2.9% (mean +/- SD) of the dose of magnesium during the first 24 hours and 6.9 +/- 7.0% of the dose during a 72-hour interval. Magnesium sulfate administration had no effect on the 24-hour urinary excretion rate of creatinine. The baseline excretion rate of magnesium was significantly correlated with that of creatinine (r = 0.875) and inorganic sulfate (r = 0.921). All of the subjects experienced mild or moderate diarrhea. Therefore, magnesium is absorbed to a limited and variable extent in healthy adults following a cathartic dose of magnesium sulfate.

Effects of the intravenous administration of magnesium sulfate on corrected serum calcium level and nephrogenous cyclic AMP excretion in normal human subjects.

The effect of intravenous magnesium sulfate infusion on corrected serum calcium level and parathyroid function assessed by determination of nephrogenous cAMP (NcAMP) excretion were studied in normal human subjects. Significant hypermagnesemia induced by the magnesium sulfate infusion for 120 minutes was accompanied by a gradual and progressive decrease in the corrected serum calcium level. NcAMP excretion fell rapidly, reaching a nadir between 60 and 120 minutes after the infusion began, and after that rose above the baseline excretion. Urinary calcium excretion gradually increased, reaching a peak between 120 and 180 minutes after the infusion began and then gradually decreased. Since magnesium was given as the sulfate, it is not clear whether these changes were attributable to magnesium or sulfate or both. As a control study, we performed intravenous sodium sulfate infusion. The sodium sulfate infusion caused slight hypocalcemia, slight hypercalciuria, and a significant increase in NcAMP excretion. These findings indicate that the hypocalcemia and the hypercalciuria caused by the magnesium sulfate infusion is mainly due to the effect of magnesium, and that the decrease in NcAMP excretion during the infusion is due to the effect of magnesium alone. We conclude that the hypocalcemia caused by the magnesium sulfate infusion is mainly due to the renal calcium loss, and that the inhibition of parathyroid function caused by hypermagnesemia may be only partially involved in the early phase of this hypocalcemia.

Low adrenal androgenic-anabolic steroids in women with rheumatoid arthritis (RA): Gas-liquid chromatographic studies of RA patients and matched normal control women indicating decreased 11-deoxy-17-ketosteroid excretion

Using GLC, multiple adrenal corticosteroid urinary metabolites, including androgenic-anabolic, glucocorticoid, pregnanediol, and pregnanetriol, were measured in eight ambulatory female RA patients and eight matched normal control subjects on baseline, ACTH-, and metyrapone-stimulation days under carefully monitored clinical research center protocol. Neither group had been treated previously with any steroid hormones. The 11-deoxy-17-KS metabolites, derived from adrenal androgenic-anabolic steroids, and comprising androsterone, etiocholanolone, and DHA, were significantly lower in RA patients on baseline (P less than .001), ACTH (P less than .005)-, and metyrapone (P less than .02)-stimulation days. To the contrary, the 11-oxy-17-KS metabolites, derived mainly from glucocorticoids, showed some lowered excretion at baseline (P less than .05), but none on ACTH- or metyrapone-stimulation. RA patients had lower tetrahydrocortisone (P less than .001) and tetrahydro-11-deoxycortisol (P less than .01) excretion at baseline, but not during ACTH- or metyrapone-stimulation, than control subjects. Pregnanetriol excretion was lower (P less than .005) in RA patients than control subjects only during ACTH-stimulation. No difference was found between groups in tetrahydrocortisol or pregnanediol excretion on any day studied. Under conditions of oral metyrapone administration (750 mg every four hours for seven doses) each control subject increased their DHA excretion, but no RA patient showed an increase over baseline excretion (P less than .02). Except for 11-deoxy-17-KS, no difference was found in the other metabolites studied during metyrapone stimulation, ie, pregnanediol, pregnanetriol, tetrahydro-11-deoxycortisol, and tetrahydrocortisol. The 24-hour oral metyrapone test provided a greater stimulus to total 11-deoxy-17-KS excretion than an eight-hour intravenous ACTH test in control and particularly RA (P less than .01) subjects even though the DHA excretion decreased in the RA groups. Our findings of lower adrenal androgenic-anabolic metabolite excretion in female RA patients than normal matched control subjects under various conditions and other supportive androgenic hormone and metabolite studies reviewed in the English reports suggest an abnormality of adrenal androgen synthesis or metabolism in RA, whether it be a primary predisposing or secondary factor in disease. The recognized female sex preponderance and age-specific patterns of occurrence of RA are consistent with adrenal androgenic function in adrenarche, adrenopause, and later changes in aging. Metabolite excretion patterns at baseline, ACTH-, and metyrapone- stimulation indicate the greatest relative

Uncoupling of the parathyroid hormone receptor-adenylate cyclase system of canine kidney during dietary phosphorus deprivation.

The mechanisms involved in the renal resistance to the phosphaturic action of PTH during dietary phosphorus deprivation remain ill defined. Previous studies in dogs from our laboratory demonstrated that baseline excretion of cAMP and the increment after administration of parathyroid extract were markedly reduced during dietary phosphorus deprivation. The present studies examine the initial events in the actions of PTH, namely receptor binding and adenylate cyclase activation, in renal cortical membranes from normal and phosphorus-deprived animals. Mongrel dogs were fed a diet deficient in phosphorus for 4-6 weeks. Plasma phosphorus fell from 4.2 +/- 0.4 to 1.4 +/- 0.3 mg/dl. In renal cortical membranes from these animals, basal adenylate cyclase activity was not different from that in control normal animals. However, PTH-stimulated enzyme activity was markedly reduced (5785 +/- 303 pmol cAMP/mg protein X 30 min in controls vs. 2612 +/- 406 pmol cAMP/mg protein X 30 min; P less than 0.01). Kact (PTH concentration for half-maximal enzyme activation) was unchanged. PTH receptor binding assessed with [Nle8,Nle18,Tyr34]bovine PTH-(1-34) NH2 was not different in the two groups. The decreased PTH-stimulated adenylate cyclase activity was not corrected by GTP. Activation of adenylate cyclase by NaF was reduced in membranes from the phosphorus-deprived animals, whereas enzyme activation by guanylylimidodiphosphate was similar in both groups. Enzyme activity in the presence of Mn++ was not different from the control value. These data indicate that during dietary phosphorus deprivation there is uncoupling of the PTH receptor-adenylate system of canine kidney. This abnormality may play a role in the renal resistance to PTH during dietary phosphorus deprivation.

Absorption of sulfate from orally administered magnesium sulfate in man.

The purpose of this investigation was to determine the suitability of orally administered magnesium sulfate as a source of inorganic sulfate for counteracting the systemic depletion of sulfate caused by large doses of acetaminophen and certain other drugs that are metabolized to sulfate conjugates. Oral administration of 13.9 g magnesium sulfate U.S.P., in 4 equal hourly increments, to seven healthy men resulted in the urinary excretion (corrected for baseline excretion rate) of an amount of inorganic sulfate equivalent to 30.2 +/- 17.2 percent (mean +/- SD) of the dose during the first 24 hours. Excretion during the subsequent 48 hours was negligible. Six of the subjects experienced loose stools or diarrhea. Compared to sodium sulfate, magnesium sulfate appears to be absorbed less completely and more erratically, and to produce more adverse effects.

Renal function abnormalities induced by marathon running.

To assess renal function changes induced by marathon racing in asymptomatic runners, we studied them before, six hours after, and one week after warm and cold weather marathons (26.2 miles [42 km]). Standard serum electrolytes, creatine phosphokinase (CPK), urinalysis, urinary myoglobin, and renal function tests (para-aminohippurate [PAH], inulin, and true creatinine clearances) were performed. After rehydration to their prerace weight, the subjects showed no postrace change in serum electrolytes. The CPK rose postrace and was two to three times higher in the warm weather runners than in the cold weather runners. All postrace urinalyses were grossly abnormal. Urinary myoglobins were positive postrace in warm weather runners and negative in cold weather runners. Warm weather runners showed a 50% decline in inulin clearance postrace but maintained PAH clearance. At one week, inulin clearance returned to baseline but fractional excretion of creatinine was below unity. In contrast, cold weather runners showed no change in inulin and PAH clearances postrace or at one week, but fractional excretion or creatinine postrace was less than unity returning to baseline at one week. We conclude that renal function abnormalities occur in marathon runners and that the severity of the abnormality is temperature-dependent.

Effect of Parathyroid Extract on Renal Cyclic AMP Excretion in Patients with Normocalciuric Nephrolithiasis

It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others.

Studies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids.

Urinary excretion of albumin, free light chains of immunoglobulins and beta-2-microglobulin was measured after injection of certain amino acids and derivatives. Substances with a positively charged group located terminally in the molecule (ornithine, lysine, arginine, and the almost not metabolized epsilon-amino-caproic acid, and Cyclocaprone) proved to inhibit instantaneously the tubular protein reabsorption. Lysine is the most effective molecule tested. We hypothesize that the initial event in the normal tubular protein reabsorption is a binding between a free positive amino- or guanidino-group in the protein molecule and a negative site on the tubular cell surface. In an attempt to achieve complete inhibition of tubular protein reabsorption, large doses of lysine were injected intravenously. The maximal protein clearance rose from the exceedingly low baseline excretion to values probably representing near complete inhibition of protein reabsorption. The minimal value of albumin concentration in the glomerular filtrate was calculated to 2.6 mg/l.

Dissociation of zinc excretion from other cations in man.

Abstract Zinc excretion was compared with sodium, potassium, calcium, and magnesium during clearance studies in 38 normal men. Base-line zinc excretion (per unit inulin clearance) averaged 44.2 ± 4.1 nEq. per 100 ml., and correlated modestly (r = 0.39) with plasma zinc concentrations. During isotonic saline loading, zinc excretion increased 28 per cent (P decreased 15 per cent while sodium, calcium, and magnesium excretion increased an additional 102, 61, and 33 per cent, respectively. After intravenous furosemide or ethacrynic acid, zinc excretion increased, but rapidly reverted to control values. In contrast, large increases in sodium, calcium, and magnesium excretion were maintained for 2 hours. Urine zinc concentrations decreased, while concentrations of sodium, calcium, and magnesium increased after diuretics. Although these studies do not elucidate the intrarenal mechanisms controlling zinc excretion, they do suggest that the renal handling of zinc differs markedly from other divalent cations.

Urinary excretion of 3′,5′-AMP in syndromes considered refractory to parathyroid hormone

Earlier studies showed that parathyroid hormone increases the urinary excretion of cyclic 3′,5′-AMP in normal subjects; patients with pseudohypoparathyroidism showed little or no response. In the current investigation this response to parathyroid hormone was examined in several apparently unrelated syndromes previously characterized as resistant to the hormone in tests for phosphaturia. The disorders studied included the basal cell nevus syndrome (BCN), Gardner's syndrome (GS), vitamin D-resistant osteomalacia (DRO), and the syndrome of basal ganglia calcification (BGC). Urine was collected on two successive mornings and 180 USP units of purified bovine parathyroid hormone were infused between 9 and 9:15 a.m. on day 2. During the control day (Day 1) normal volunteers showed average excretion of 3′,5′-AMP of 3.90 nmoles/mg. creatinine (range 2.4–5.4). Baseline excretion for patients averaged 2.90 (BCN), 5.19 (GS), 5.30 (DRO), and 5.27 (BGC) nmoles of 3′,5′-AMP/mg. creatinine. Base-line excretion rates for patients with GS, DRO, and BGC were significantly greater than normal. This finding possibly reflects secondary hyperparathyroidism in DRO but remains unexplained in GS and BGC. Infusion of hormone into normal subjects caused an increase to 23.7 nmoles of 3′,5′-AMP/mg. creatinine (range 13–42). The responses to the hormone for the patient groups were 32 (BCN), 48 (GS), 56.1 (DRO), and 47.4 (BGC) nmoles of 3′,5′-AMP/mg. creatinine. These results were within the limits of normal. There were wide fluctuations in phosphate excretion from day-to-day as well as hour-to-hour in all groups. These variations obscured the phosphaturic response in the normal subjects and in patients with Gardner's syndrome, vitamin D-resistant osteomalacia and the family with calcification of the basal ganglia. The basal cell nevus syndrome showed a significant phosphaturic response to the hormone. These results confirm previous conclusions that the phosphaturic response is not sufficiently reliable to categorize a syndrome as refractory to PTH. On the other hand, the rate of excretion of 3′,5′-AMP shows less variation and the response provides more valid discrimination between normal subjects and those refractory to the hormone. Thus, the current studies show that several syndromes previously described as resistant to parathyroid hormone indeed respond normally.

Renal regulation of acid-base balance in malnourished man

Renal excretion of acid in adult patients with moderate to severe protein malnutrition was studied before and after protein repletion. In malnourished patients steady-state blood pH and bicarbonate concentration values were found to be within normal limits, but total renal acid excretion during the malnourished state averaged only 16.4 mEq in twenty-four hours (2.6 mEq of titratable acid and 13.8 mEq of ammonium). Following a standard dose of ammonium chloride there was a striking decrease in blood pH and plasma bicarbonate concentrations. Total renal acid excretion rose only to 44.2 mEq per twenty-four hours (6.7 mEq of titratable acid and 37.5 mEq of ammonium) on the fifth day of ammonium chloride administration. After two to three months of protein repletion the total acid excretion increased over twofold (8.6 mEq of titratable acid and 27.3 of ammonium). On the fifth day of ammonium chloride administration titratable acid excretion increased to 27.3 mEq per twenty-four hours, ammonium excretion to 61.9 mEq per twenty-four hours. The decreased excretion of titratable acid during malnutrition was associated with a reduced rate of urinary phosphate excretion. Infusion of phosphate during the malnourished state resulted in a marked increase in titratable acid production. The baseline excretion of ammonium was much higher in the protein-repleted state. In addition greater increases in ammonium excretion were observed after protein repletion, following ammonium chloride administration, despite the presence of a lesser degree of metabolic acidosis than in the malnourished state. These studies thus provide evidence for a decreased renal excretion of acid in patients with protein malnutrition, due largely to a decreased generation of titratable acid which in turn is related to a decreased urinary excretion of phosphate in malnourished patients. The impaired adaptation in ammonia production in the malnourished state may relate to decreased ammonia production due to either decreased substrate delivery or decreased renal gluconeogenesis.

Excretion of 4-Pyridoxic Acid during Deoxypyridoxine and Pyridoxine Administration to Mongoloid and Non-Mongoloid Subjects

The excretion of 4-pyridoxic acid (4PA) was studied in mongoloid subjects and controls of similar age and weight living in the same cottages and eating the same diet. The base-line excretion of 4PA was similar in the two groups. On the first day of deoxypyridoxine (DP) administration, a fourfold increase in 4PA excretion occurred in both groups; but on continued DP administration, 4PA excretion increased significantly less in mongoloid subjects compared with controls. On pyridoxine and DP administration loading, a significantly greater excretion of 4PA occurred in mongoloids compared with controls. The above data suggest that mongoloid subjects have a smaller dissociable pool of vitamin B6 and that the enzymes of vitamin B6 catabolism have greater activity in mongoloid subjects than in controls.