The "valve" of the ductus arteriosus--an enigma.

The urine/plasma creatinine ratio (U/P Cr), the urine sodium concentration (UNa), and the diuretic response to mannitol infusion in 23 patients were reviewed in an attempt to differentiate functional renal failure (FRF) from acute tubular necrosis (ATN). FRF was diagnosed if the plasma urea nitrogen (PUN) or serum creatinine stabilized within 72 hours. When renal failure persisted longer, patients had ATN. Subjects dying within 72 hours were excluded. Ten patients had ATN and five survived. The minimum duration of renal failure among survivors was 10 days. None responded to mannitol. Of 13 patients with FRF, 11 survived. Seven of 12 who received mannitol responded with a diuresis. The mean UNa in the patients with ATN was 51.4 mEq./1. ± 9.48 (SE). The mean U/P Cr was 11.2 ± 1.12. In patients with FRF, the mean UNa was 14.0 mEq./1. ± 4.2 and the mean U/P Cr was 42.5 ± 11.5. A significant overlap was present between the two groups. When UNa was factored by the U/P Cr, the resultant ratio was significantly different for the two groups of patients (P < 0.01), and this proved to be a useful clinical index with which to distinguish FRF from established ATN.     

The Effect on Serum Ionic Magnesium of Exchange Transfusion with Citrated as Opposed to Heparinized Blood

Serum Mg++ levels before, during, and after replacement transfusion were determined in 20 newborn infants. In 10 infants exchanged with acid-citrate-dextrose (ACD) blood, the level fell from 1.75 ± 0.16 mEq./l. to 0.99 ± 0.16 mEq./l. By contrast, levels in 10 infants exchanged with two types of heparinized blood were unchanged: the pre-exchange values were 1.59 ± 0.11, and the postexchange levels were 1.59 ± 0.08 mEq./l. Mean values for donor bloods were 0.42 ± 0.07 mEq./l. with ACD blood, and 1.45 ± 0.03 mEq./l. with heparinized blood. In vitro studies involving the addition of known amounts of citrate to standard Mg++ solutions demonstrated that the citrate caused a reduction of ionic magnesium. It is proposed that the fall in serum Mg++ when ACD blood is used for exchange transfusion is the combined result of Mg++ binding by the citrate, and the dilution effect of the relatively large proportion of anticoagulant to blood (1:3) used with the ACD mixture.     

Anionic salts and dietary 25-hydroxyvitamin D stimulate calcium availability in steers

The influence of feeds containing varying dietary cation–anion differences (DCADs) with and without supplements of 25-hydroxyvitamin D (25(OH)D) on urine pH and excretion of macro minerals was determined in fistulated crossbred steers (mean live weight 315 ± 45 kg). A basal forage diet comprising lucerne hay and wheat chaff was used, to which varying quantities of MgCl₂ or K₂CO₃ were added to achieve four levels of DCAD: −300, 50, 150 or 250 mEq/kg dry matter (DM). Steers were allocated to one of six treatments, one treatment for each diet and a further treatment for both the 50 and 150 mEq/kg DCAD diets, which were supplemented with 25(OH)D at a rate of 3 mg/steer per day. Urine pH from steers offered the diets comprising DCADs of 50, 150 and 250 mEq/kg ranging from 8.3 to 8.8. In treatments not containing 25(OH)D with DCADs of 50 to 250 mEq/kg, there were no significant differences in urine pH or Ca excretion. However, steers offered the diet with a DCAD of −300 mEq/kg DM produced urine with a significantly lower pH (6.5 to 7.5). Daily output of Ca in urine was also significantly higher from steers given this diet. Supplementation with 25(OH)D significantly increased urinary Ca excretion from steers offered diets of DCADs 50 and 150 mEq/kg DM. Estimates of daily urinary Ca excretion, calculated using the ratio of creatinine to Ca in ‘spot’ urine samples, were less variable than those based on total collection (residual mean square of 0.54 and 0.63, respectively).     

Metabolic Studies,Aldosterone Secretion Rate,and Plasma Renin after Carbenoxolone Sodium

A formal metabolic study of carbenoxolone sodium (Biogastrone) 300 mg./day has been performed for 17 days on a woman with gastric ulcer who in a previous 21-day trial, on a 52-mEq sodium diet, showed weight gain, retention, and rise in plasma sodium and chloride concentrations, as well as hypokalaemia without change in potassium balance. In the present trial sodium intake was restricted to 26 mEq/day; while plasma electrolyte changes of lesser degree still occurred, there was no retention of water, sodium, or chloride. Aldosterone secretion in the control period was 202 μg./24 hours, and fell to 74 μg./24 hours after carbenoxolone, but plasma renin was unchanged.These results suggest that the mineralocorticoid effects of carbenoxolone (and presumably of liquorice and its other derivatives) are due to an intrinsic aldosterone-like action, and that, with sodium deprivation, aldosterone secretion is suppressed by a mechanism which is not renin-mediated—possibly hypokalaemia.     

A method for the estimation of 6-oxygenated metabolites of progesterone in urine

1. A method is described for the estimation of the 6-oxygenated metabolites of progesterone in urine. After hydrolysis the extract of urine is chromatographed on alumina to obtain a fraction containing mainly the 6-oxygenated metabolites. This fraction is oxidized to convert the metabolites into pregnane-3,6,20-triones, which are estimated as the dinitrophenylhydrazones. 2. The reliability criteria of the method are presented. Normal subjects excrete 0.1-0.6mg./day, and at the end of pregnancy values of 3.3-11.6mg./day are obtained.     

The Clinical Significance of Elevated Blood Lactate

Three patients with elevated blood lactate values are described. The first, despite moderate hyperlactatemia of 5.3 mEq./1. and severe acidosis with an arterial blood pH of 6.98, had no “excess lactate”. In a second patient, moderate acidosis with a pH of 7.27 and blood lactate of 7.5 mEq./1., of which 33% was excess lactate, was found to be secondary to tissue hypoxia on an ischemic basis and preceded the onset of clinical shock by four hours. A third patient, diabetic and under treatment with phenformin hydrochloride, presented with many features suggestive of pulmonary embolism, including marked pulmonary hypertension. A diagnosis of idiopathic lactic acidosis was established when the arterial blood pH was found to be 6.77 and a blood lactate value of 14.2 mEq./1., 60% as excess lactate, was discovered in the absence of a demonstrable cause of tissue hypoxia. Exploration of the pulmonary vascular bed showed no sign of mechanical blockage. The diagnostic, therapeutic and prognostic value of measuring blood lactic acid, and of quantitating the proportion circulating as “excess lactate”, is emphasized.     

Relationship Between Serum Lithium, Salivary Lithium, and Urinary Lithium in Patients on Lithium Therapy

Lithium carbonate is used in the treatment of both psychiatric and nonpsychiatric disorders. The aim of this study was to explore the relationship between serum lithium, salivary lithium, and urinary lithium. Blood, saliva, and urine samples were collected from 50 patients, and estimation of serum, salivary, and urine lithium was done using an atomic absorption spectrophotometer. Mean serum lithium was 0.75 ± 0.25 mEq/L, mean salivary lithium was 1.91 ± 0.80 mEq/L, and mean urine lithium was 7.16 ± 4.84 mEq/L. A significant direct correlation was found between serum lithium and salivary lithium (r = 0.695, p < 0.001). This correlation was higher in females (r = 0.770, p < 0.001) when compared to males (r = 0.665, p < 0.001). Even though a significant correlation was found between serum and salivary lithium levels, more studies are needed in this domain to establish salivary therapeutic monitoring as a feasible option for patients on lithium carbonate therapy.     

Serum and Urinary Folate in Liver Disease

During the active phase of viral hepatitis urinary folate loss was found to be 8·0 to 48·3 (mean 31·1) μg./day, compared with a normal urinary folate excretion of 0·1 to 18·0 (mean 9·5) μg./day. In cirrhosis and cardiac failure with congestive hepatomegaly the corresponding values were 25·8 to 55·0 (mean 35·7) μg./day and 2·5 to 61·6 (mean 26·9) μg./day, respectively. Urinary folate loss may be a significant factor in the aetiology of folate deficiency of chronic liver disease, particularly when dietary intake is poor.After prolonged dialysis in Visking casing urinary folate was almost totally dialysable, but an appreciable fraction of serum folate was not, even after 72 hours. The dialysable (free) folate fraction of serum and urine disappeared maximally during the first six hours'' dialysis, and was virtually cleared after 24 hours'' dialysis; clearance curves in normal individuals and in liver disease were comparable. The non-dialysable serum folate fraction was of similar magnitude in all subjects studied, in spite of marked variation in total folate, and probably represented protein-bound folate.     

Venous Stasis and Forearm Exercise During Venipuncture as Sources of Error in Plasma Electrolyte Determinations

A study was made of errors in plasma sodium, potassiu, chloride and calcium determinations caused by venous stasis and forearm exercise during venipuncture. Blood samples were taken from both arms of healthy young adults, one arm being used as a control. Analyses were performed in a routine hospital laboratory and the technicians were unaware of the identity of the samples. Laboratory precision was assessed at the same time.Venous stasis alone for two minutes caused no significant change, but the use of continuous slow forearm exercise for one minute caused mean elevations of 0.73 mEq./1. in potassium, and 0.4 mg. per 100 ml. in calcium, the maximum elevations being 1.1 mEq/1. and 1.3 mg. per 100 ml., respectively. A clinically unimportant but significant increase in sodium values of 1.40 mEq./1. was also observed. Chloride values were not affected. In addition there was a substantial error in calcium determinations in the laboratory, which emphasizes the need for repeated calcium determinations to avoid diagnostic error.The conclusion is reached that forearm exercise must be avoided during venipuncture.     

Biochemical effects of garlic protein on lipid metabolism in alcohol fed rats

Garlic protein is a very good hypolipidemic agent. In the present study the water soluble protein fraction of garlic was investigated for its effect on hyperlipidemia induced by alcohol (3.76 g/kg. body wt./day). The hypolipidemic action is mainly due to an increase in cholesterol degradation to bile acids and neutral sterols and mobilization of triacyl glycerols in treated rats. Garlic protein (500 mg./kg body wt./day) showed significant hypolipidemic action comparable with a standard dose of gugu-lipid (50 mg./kg. body wt./day).     

Differential effects of DOCA on renal and gastrointestinal handling of sodium and potassium in pigs

Young, male pigs eating standard pig chow, ad libitum, received approximately 170 mEq Na and 290 mEq K per day. Electrolyte intake, urinary and fecal electrolyte output, and plasma electrolyte levels were determined daily in 12 deoxycorticosterone acetate (DOCA)-treated pigs and in 6 control pigs. Daily Na and K balances (dietary intake - urinary + fecal output) were calculated. DOCA caused a reduction in urinary Na output from 1.53 mEq/kg/day to 0.57 mEq/kg/day during the first 48 hr following implantation. Escape from the renal sodium retaining effect of DOCA was complete within 3 days, with urinary Na output returning to pre-DOCA levels. Fecal Na output decreased from 0.65 mEq/kg/day during the preimplant period to 0.13 mEq/kg/day during the postimplant period. No escape from GI Na retention occurred by Day 15. Plasma Na rose to significantly higher levels by Day 15. Sodium balance was significantly elevated in DOCA-treated pigs for that first 48 hr postimplant. Urinary K output decreased from 3.50 mEq/kg/day to 1.74 mEq/kg/day during the first 2 days, but returned toward preimplant levels by Day 4. Fecal K output was increased for the first week, and thereafter returned to preimplant levels. Plasma K fell from 3.9 to 2.9 mEq/liter by Day 15. Potassium balance fell slightly in both experimental and control animals. No significant differences in potassium balance were present between the two groups. The control pigs showed no significant changes in plasma electrolyte concentration or in electrolyte balance. It is concluded that DOCA has differential effects on renal and gastrointestinal handling of electrolytes and that DOCA may induce an intracellular shift of potassium in pigs.     

Is urinary flow rate a major regulator of prostaglandin E excretion in man?

Urinary PGE₂ excretion is enhanced in several polyuric states in man suggesting that PGE₂ synthesis could be a mediator of diuresis. To explore the alternate hypothesis that polyuria is the cause of the increased PGE₂ excretion, we increased urine flow rate by intravenous administration of dextrose and water with different magnesium, calcium and potassium solutions in four normal males. Urinary PGE excretion rose in parallel with urine volume (r = 0.65 p < 0.01) independently of the electrolyte solution. To determine the effects of chronic alterations in water balance in 5 female subjects, we sequentially regulated oral water intake to induce 1, 2, 4 and 8 liters of urine volume/day. During low (40 mEq) sodium diets, PGE increased from 540 ± 50 to 4880 ± 1240 ng/d with increasing urinary volume (r = 0.81, p < 7.01). Similarly, for 200 mEq sodium intake PGE paralleled urinary volume (from 630 ± 100 to 4740 ± 800 ng/d, r = 0.61, p <0.01). In vitro sample dilution studies demonstrated no interference from method blank, and the addition of thin layer chromatography prior to Sephadex chromatography failed to alter assay measurements. We conclude that extreme increases in urinary flow rate may directly enhance PGE excretion in man.     

Sulphadimidine Acetylation Test for Classification of Patients as Slow or Rapid Inactivators of Isoniazid

Sulphadimidine acetylation studies were undertaken in 103 patients, 52 of whom had been classified as slow and 51 as rapid inactivators of isoniazid by a standard microbiological assay method. Each patient received sulphadimidine by mouth in a dose of 44 mg./kg. body weight, and free and total sulphadimidine were estimated in blood and urine collected at six hours. The findings suggest that patients may be classified as slow inactivators of isoniazid if the proportion of acetylated sulphadimidine (total minus free) is (a) less than 25% in blood or (b) less than 70% in urine. The sulphadimidine test is easy to perform and the result is available the same day; urine specimens for the test can be stored at room temperature for over a week without any loss of drug.     

Nitrogen Balance in Patients with Chronic Renal Failure on Diets Containing Varying Quantities of Protein

Twenty-four nitrogen balances have been performed in 16 patients with chronic renal failure, with a protein intake of 0·23 to 1·0 g./kg./day. The results show that most patients with chronic renal failure require about 0·5 g./kg./day (35 g. for a 70-kg. man) to remain in nitrogen balance. The proportion of high-quality protein in the diets varied from 40 to 98% and the calorie intake from 23·6 to 59·0 calories/kg./day (1,330 to 3,310 calories/day). Within these ranges the proportion of high-quality protein and the calorie content did not have a detectable effect on the nitrogen balance.It is concluded that when other forms of treatment for renal failure are available, reduced protein diets should be used for only short periods, and that the protein intake should be 0·5 g./kg./day to maintain the patient in nitrogen balance.     

Experiments on the growth of Penaeus vannamei Boone

Growth rates of Penaeus vannamei Boone were estimated from field and laboratory experiments using both marked and unmarked shrimp. Field results with unmarked shrimp indicated growth rates of between 0.05 mm increase in carapace length per day (mm c.l./day) and 0.17 mm c.l./day, although rates of up to 0.31 mm c.l./day were also recorded. Moult intervals ranged from5.5 to 34 days with a mean of 12.5 days. Moult increment ranged from 0.2 mm c.l./moult to 1.4 mm c.l./moult with an overall mean of 0.7 mm/moult. Growth was negatively correlated with size over all size ranges, with a marked decrease in growth rate occurring at about 28 mm c.l. Shrimp marked with Floy streamer tags generally grew more slowly than unmarked shrimp, but this was exaggerated by the stress of regular handling in some experiments. The relevance of these findings is discussed in relation to the existing commercial fishery.     

Maternal dehydration: impact on ovine amniotic fluid volume and composition

Maternal dehydration consistent with mild water deprivation or moderate exercise results in maternal and fetal plasma hyperosmolality and increased plasma arginine vasopressin (AVP). Previous studies have demonstrated a reduction in fetal urine and lung fluid production in response to maternal dehydration or exogenous fetal AVP. As fetal urine and perhaps lung liquid combine to produce amniotic fluid, maternal dehydration may affect the amniotic fluid volume and/or composition. In the present study, six chronically-prepared pregnant ewes with singleton fetuses (128 +/- 1 day) were water deprived for 54 h to determine the effect on amniotic fluid. Maternal plasma osmolality (306.5 +/- 0.9 to 315.6 +/- 1.9 mOsm/kg) and AVP (1.9 +/- 0.2 to 22.2 +/- 3.2 pg/ml) significantly increased during dehydration. Similarly, fetal plasma osmolality (300.0 +/- 0.9 to 312.7 +/- 1.7 mOsm/kg) and AVP (1.4 +/- 0.1 to 10.4 +/- 2.4 pg/ml) increased in parallel to maternal values. Amniotic fluid osmolality (276.8 +/- 5.7 to 311.6 +/- 6.5 mOsm/kg) and sodium (139.8 +/- 4.8 to 154.0 +/- 5.4 mEq/l) and potassium (9.1 +/- 1.3 to 13.9 +/- 2.4 mEq/l) concentrations increased while a significant (35%) reduction in amniotic fluid volume occurred (871 +/- 106 to 520 +/- 107 ml). These results indicate that maternal dehydration may have marked effects on maternal-fetal-amniotic fluid dynamics, possibly contributing to the development of oligohydramnios.     

Plasma atrial natriuretic peptide in conscious rats with reduced renal mass

The effect of salt intake and reduction of renal mass (RRM) on plasma immunoreactive atrial natriuretic peptide (iANP) levels in conscious rats was studied. Rats were divided into RRM and sham-operated groups, and then further subdivided into groups infused with 1 or 6 mEq of sodium per day. Plasma urea nitrogen increased in the groups with RRM. Plasma sodium, sodium balance, and heart rate did not differ between the sham and RRM groups. Rats with RRM maintained on 1 mEq of sodium per day did not have an elevation of water intake, arterial pressure, or plasma iANP. Rats with RRM maintained on 6 mEq of sodium per day had significantly (P less than 0.05) elevated water intake, arterial pressure, and plasma iANP. Arterial pressure and plasma iANP were correlated (r = 0.800) for rats with RRM on either 1 or 6 mEq of sodium per day. Increased plasma iANP in the RRM group on 6 mEq per day was not caused by either RRM or high sodium alone; it was an effect of RRM plus high salt intake. The increase in plasma iANP in the RRM group may be caused by the increase in arterial pressure, possibly due to an increase in extracellular fluid volume. ANP may not be responsible for the sustained increase in fractional sodium excretion observed in RRM.     

Effects of saline infusion and acute metabolic acidosis and alkalosis on water and electrolyte transport in the human colon.

Both the kidney and colon secrete bicarbonate and transport water and electrolytes. The respective contributions of these two organs to acid-base and electrolyte balance in normal man has thus been studied in eight healthy male volunteers who underwent simultaneous renal clearance studies, and colonic perfusion with a 0.9% saline or 7.2% mannitol solution, during metabolic alkalosis and acidosis, extracellular volume expansion, and control conditions. There was no influence of these acid-base conditions on electrolyte transport in the colon. In the urine, preferential loss of chloride over sodium averaged 81, 143 (P less than 0.001), and 141 (P less than 0.05) muequiv./min, during control, metabolic acidosis, and extracellular volume expansion conditions, respectively. During alkalosis more sodium than chloride was lost (146 muequiv./min) (P less than 0.001). Colonic pH averaged 7.41 during saline and 6.75 (P less than 0.005) during mannitol perfusion. Titratable acid was not produced in the colon during saline perfusion, and averaged 18 muequiv./min during mannitol perfusion. Urinary titratable acid increased from 19 to 25 muequiv./min (P less than 0.01) during volume expansion. With saline perfusion, bicarbonate secretion rate in the colon rose from 249 muequiv./min during control conditions to 289 muequiv./min during metabolic alkalosis (P less than 0.05). More bicarbonate was excreted in the urine during alkalosis when mannitol was introduced in the colon (243 muequiv./min) than when saline was perfused (152 muequiv./min) (P less than 0.05). This study indicates that the response of the human colon is trivial compared with that of the kidney during acute changes in acid-base balance.     

Hypercalcemia in glucocorticoid withdrawal

We found severe hypercalcemia in the course of hydrocortisone withdrawal in a patient who had undergone unilateral adrenalectomy to resect a cortisol-hypersecreting adenoma. Serum calcium gradually but progressively increased after unilateral adrenalectomy. Severe hypercalcemia developed on the 77th postoperative day (the 15th day after discontinuing hydrocortisone replacement). The serum concentration of calcium, PTH, 25(OH)D, and 1,25(OH)2D were 8.0 mEq/l, less than 100 pg/ml, 10.1 ng/ml and 29.6 pg/ml, respectively. This hypercalcemia was accompanied by marked urinary hydroxyproline excretion and less calcium excretion in the urine than the prevailing level of serum calcium. Serum concentrations of 25(OH)D, 1,25(OH)2D and PTH were not elevated during the severe hypercalcemia. We concluded that the hypercalcemia in this patient was due in part to enhanced bone resorption and increased renal tubular reabsorption of calcium as a result of glucocorticoid withdrawal, but not to the elevation of serum PTH or serum 25(OH)D and serum 1,25(OH)2D.     

Combined effect of ascorbic acid and selenium supplementation on alcohol-induced oxidative stress in guinea pigs

Oxidative stress is a key step in the pathogenesis of ethanol associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen reactive species or by decreasing the level of endogenous antioxidants. In this present study, four groups of male guinea pigs (Cavia porcellus) were maintained for 45 days as follows: Control group (1 mg ascorbic acid (AA)/100 g body wt./day); Ethanol group (1 mg AA/100 g body wt./day+900 mg ethanol/100 g body wt./day); Selenium+AA group (25 mg AA+0.05 mg sodium selenite/100 g body wt./day); Ethanol+Se+AA group (25 mg AA+0.05 mg sodium selenite/100 g body wt.+900 mg ethanol/100 g body wt./day). Malondialehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD) were significantly increased, while the activities of scavenging enzymes superoxide dismutase (SOD) and catalase were reduced in the alcohol administered groups. Co-administration of Se+AA along with alcohol increased the activities of scavenging enzymes and reduced the lipid peroxidation products level in hepatic tissues of guinea pigs. Activities of glutathione peroxidase (GPX) and glutathione reductase (GR) were enhanced in co-administered group. gamma-Glutamyl transpeptidase (GGT), a marker enzyme of alcohol induced toxicity, was also reduced, as was the glutathione content. This study suggests that the combined effect of Se+AA, provides protection against alcohol-induced oxidative stress as evidenced from the decreased levels of lipid peroxidation products and enhanced activities of scavenging enzymes.