Volume receptors in guinea pig labyrinth: relevance with respect to ADH and Na control.

We tested the hypothesis that changes in extracellular fluid volume are reflected by pressure changes within structures of the inner ear and that through neural pathways, a control mechanism exerts an influence on antidiuretic hormone (ADH) release and Na excretion. The study was performed on 35 guinea pigs. In protocol 1, 13 animals were studied before and after decompression of the inner ear by bilateral fluid withdrawal in an experimental setting of sustained isotonic expansion that kept the osmoreceptor partially activated and the intrathoracic volume receptors suppressed. A group of six sham-operated animals served as control. In protocol 2, nine animals were studied before and after a unilateral rise in their inner ear pressure during slightly hypertonic low-rate infusions that kept the osmoreceptor and thoracic volume receptors stimulated. A group of seven sham-operated guinea pigs served as controls. Decompression of the inner ear was attended by a rise in plasma ADH from 11.9 +/- 2.4 to 29.1 +/- 6.9 pg/ml, in urine osmolality (Uosmol) from 470 +/- 48 to 712 +/- 46 mosmol/kg (P less than 0.001), and a fall in urine flow rate (V) from 184 +/- 47 to 71 +/- 11 microliters/min (P less than 0.01), whereas plasma Na (PNa) and osmolality (Posmol) did not change. During inner ear hypertension, plasma ADH fell from 25.6 +/- 3.9 to 18.4 +/- 3.1, Uosmol from 829 +/- 58 to 627 +/- 43 (P less than 0.001), and V rose from 51 +/- 11 to 130 +/- 23 (P less than 0.001), whereas glomerular filtration rate, PNa, and Posmol did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Variaçöes eletrolíticas do cloro na saliva humana mista, soro e urina em pacientes com traumas faciais, submetidos à terapêutica cirúrgica / Electrolytic variations of chlorine in human mixed saliva, serum and urine in facial traumatized patients submitted to surgical therapy

O autor faz uma análise bioquímica das alteraçöes eletrolíticas do cloro, na saliva humana mista, soro e urina em pacientes traumatizados da face submetidos a terapêutica cirúrgica, obtendo resultados conclusivos destas alteraçöes em relaçäo ao grupo controle

Surface studies of calcium oxalate dihydrate single crystals during dissolution in the presence of stone-formers' urine.

Dissolution of calcium oxalate dihydrate (COD) single crystals was studied at different pH levels and in different dilutions of stone formers' (SF) urine. The Fourier descriptors of the contour were determined during dissolution of COD using a quantitative morphological technique. The surface ruggedness of COD single crystals was determined from fractal analysis. The results obtained were compared with COD single crystals behavior in different dilutions of normal urine previously reported. The shape parameters and surface geometry of the dissolving COD crystals were significantly different in normal and SF urine. The data suggest that the shape descriptors and fractal geometry is likely to be a potential factor in identifying the urine of stone formers.

Gastrocystoplasty: an alternative solution to the problem of urological reconstruction in the severely compromised patient.

An isolated segment of stomach was used for bladder augmentation in 10 patients or construction of a continent urinary reservoir in 3. Diagnosis in these 13 patients included cloacal exstrophy (5), myelodysplasia (4), posterior urethral valves (2), radiation cystitis (1) and neurogenic bladder secondary to a rectal pull-through procedure (1). Indications for the use of stomach in bladder reconstruction were decreased renal function and acidosis (6 patients), insufficient large and small bowel (6) and decreased mucus production (1). Postoperative followup averaged 13 months (range 6 to 23 months). All patients have stable upper tracts radiographically and stable or improved renal function. Of 13 patients 10 require intermittent clean catheterization to empty and 11 are completely continent. Nine patients have remained free of infection, while 4 had asymptomatic bacteriuria. Mucus production is reduced relative to other intestinal segments and 10 patients require no bladder irrigations. Postoperative urodynamic evaluation is similar to that of ileocystoplasty or colocystoplasty. Use of stomach has protected these patients from the development of new or worsened hyperchloremic acidosis. Serum chloride values have decreased and serum total carbon dioxide values have increased after bladder reconstruction, particularly in patients with impaired renal function. Stomach should be considered when lower urinary tract reconstruction is necessary in such compromised patients.

Contained neonatal urinoma: management and functional results.

Between 1970 and 1985, 10 male newborns with a contained urinoma were treated at our institution. An underlying congenital obstructive uropathic condition was discovered in every patient, the most common of which was posterior urethral valves. All 10 patients underwent surgical correction of the primary obstructive process. Direct drainage of the urinoma was required in 4 patients because of progressive clinical symptoms. Radiographic and renal functional parameters returned to normal at followup. Clinical presentation, evaluation, treatment and pathophysiology of this rare entity are discussed.

Loss of renomedullary interstitial cells in Brattleboro rats after vasopressin treatment.

Previous studies have shown a disappearance of interstitial cells from the renal medulla of rats with hereditary diabetes insipidus (Brattleboro) when the animals were treated with vasopressin in high doses. The present study was undertaken to elucidate the mechanisms behind this cell loss. The disappearance of interstitial cells from the renal medulla of Brattleboro rats was quantitatively determined by electron microscopic stereology after various types of treatment. A considerable decrease in the volume density of interstitial cells was induced by the administration of either 8-arginine vasopressin or 1-desamino-8-D-arginine vasopressin. This lesion of the interstitial cells was not prevented by the simultaneous administration of oxytocin. Even a 48-hour period of water deprivation also resulted in a slight decrease in the volume density of interstitial cells. The results indicate that the observed loss of renal medullary interstitial cells is not a direct effect of the hormone on the cells but probably secondary to the marked increase in the renal medullary solute (urea) concentration. The fact that animals with hardly any renomedullary interstitial cells concentrated their urine to a virtually normal level shows that these cells cannot play an important role in the concentrating mechanism. The interstitial cells recovered rapidly when the vasopressin treatment was discontinued, but it could not be determined whether this was due to local proliferation or to the immigration of cells from extrarenal tissue.

A influência do fosfato na eleminaçäo da carga ácida / The phosphate influence in acid excretion

Os ânions fosfato atuam como tampöes para ácidos no sangue e na urina. No presente trabalho, infusöes de fosfato ácido em ratos com hipercapnéia mostraram que a excreçäo urinária ácida estava aumentada. Isto foi causado pelo aumento do tampäo e do nível de urina. A possibilidade de adicionar fosfato para facilitar a excreçäo ácida é mencionada

Metabolism of [14C]2-aminobiphenyl in vivo by different species.

[14C] 2-Aminobiphenyl is predominantly metabolised in vivo to 3- and 5-hydroxy conjugated derivatives in all species. In some species, 2-aminobiphenyl is also excreted to a small extent as N-conjugated derivatives. Renal excretion accounts for about 30-40% of the administered dose during the first 24 hours. The 5-O-sulphate and 5-O-glucuronide of 2-amino-5-hydroxybiphenyl have been found as major metabolites with all species; 2-amino-3-hydroxybiphenyl-O-sulphate is also a significant metabolite. There were metabolic differences observed between species in this study. HPLC and TLC analytical techniques were used for separation and detection of [14C] 2-aminobiphenyl and its metabolites. Formation of different isomeric metabolites may be explained by electronic Hückel molecular orbital calculations and stereochemical factors.

Effect of intranasal histamine on nasal mucosal blood flow and the antidiuretic activity of desmopressin.

The effects of exogenous histamine on nasal mucosal blood flow and the systemic activity of intranasally administered desmopressin, a vasopressin analogue, were studied in normal volunteers. Ten subjects received either saline or histamine (1, 20, 100, and 500 micrograms) by intranasal spray. Maximal nasal mucosal blood flow response, determined by laser doppler velocimetry, demonstrated a significant (P less than 0.05) linear relationship to histamine dose. Eight additional subjects received each of the following intranasal treatments: 20 micrograms histamine followed by 10 micrograms desmopressin; normal saline followed by 10 micrograms desmopressin; 20 micrograms histamine followed by vehicle; or normal saline and vehicle. Nasal blood flow was determined before and after each treatment. Desmopressin activity was assessed by measuring urine osmolality, flow rate, electrolyte, and creatinine concentration for 24 h after each treatment. The effect of histamine and desmopressin was greater than desmopressin alone, with respect to nasal blood flow response (103 +/- 24 vs. 4 +/- 17%, mean +/- SEM, P less than 0.02), initial urine osmolality (520 +/- 123 vs. 333 +/- 75 mosM, P less than 0.03), urine electrolyte (potassium, 45 +/- 11 vs. 28 +/- 7 meq/liter; sodium, 68 +/- 21 vs. 36 +/- 8 meq/liter, P less than 0.03) and creatinine concentrations (95 +/- 23 vs. 60 +/- 13 mg/dl, P less than 0.03), and the duration of decrease in urine flow rate compared with saline and vehicle. These results suggest that the systemic activity of intranasal desmopressin is enhanced by increasing local nasal blood flow and are consistent with increased transnasal absorption of the peptide.

Postglomerular capillary solute flux restricted by shape and charge in the dog.

The permselectivity characteristics of the postglomerular (PG) microcirculation in dog kidney were investigated employing 3H-labeled cationic (DEAE) and anionic sulfated dextrans (dextran-SO4) ranging from 19 to 29 A Stokes-Einstein Radius. With the use of the multiple-indicator dilution (MID) technique, a bolus injection was made into the left renal artery and timed serial samples were obtained from renal venous and urine outflows. The injection solution contained 125I-labeled albumin (plasma reference), [14C]inulin and/or creatinine (glomerular and interstitial references), and a test [3H]dextran probe. A control run was carried out with tracer, then charge interaction was analyzed by repeating the MID run with excess unlabeled compound or after protamine sulfate infusion. After loading, renal vein recovery and mean transit time (t) were unchanged relative to [14C]inulin for [3H]dextran-SO4. But excess DEAE resulted in reduced recovery and decreased t for [3H]DEAE. After protamine sulfate, the renal vein and urine recoveries of [3H]dextran-SO4 decreased and the renal vein t increased. These findings demonstrate saturable anionic binding sites in the PG microcirculation. Under conditions where charge interaction was eliminated, the ratio of renal vein t for 125I-albumin to cationic or anionic dextran was always less than its ratio to neutral dextran, implying a larger apparent volume of distribution. We concluded that PG capillaries also limit solute flux on the basis of shape.

Effect of left atrial to left femoral artery bypass and renin-angiotensin system blockade on renal blood flow and function during and after thoracic aortic occlusion.

Temporary thoracic aortic occlusion can result in renal insufficiency with or without adjuncts to avoid distal hypoperfusion. In a canine model of thoracic aortic occlusion, left atrial to left femoral bypass was compared with blockade of the renin-angiotensin system. Renin-angiotensin system blockade with the converting enzyme inhibitor, MK422, resulted in restoration of baseline renal blood flow and glomerular filtration 30 minutes after cross-clamp release. Left atrial to left femoral bypass resulted in significant reduction in both renal blood flow and glomerular filtration 30 minutes after cross-clamp release. Stimulation of the renin-angiotensin system plays a significant role in the altered renal hemodynamics and glomerular filtration rates after thoracic aortic occlusion.

Etoposide pharmacokinetics in patients with normal and abnormal organ function.

Precise guidelines for dose modification of etoposide in patients with hepatic dysfunction have not been determined. Etoposide pharmacokinetics were determined in 17 patients. Nine patients had bilirubin less than or equal to 1 mg/dL and eight had bilirubin ranging from 1.9 to 23 mg/dL. Twelve patients received etoposide 100 mg/m2 days 1, 3, and 5, in combination with cisplatin 70 mg/m2 or iproplatin 225 mg/m2 on day 1. Five patients received only one dose of etoposide. Etoposide was measured using a published high pressure liquid chromatography (HPLC) method which also quantitates picro etoposide and its hydroxy acid. Systemic clearance, Vdss and t1/2 beta averaged (+/- SD) 21.4 (+/- 7.4) mL/min/m2, 10.7 (+/- 4.1) L/m2, and 8.1 (+/- 2.8) hours in the nine patients with bilirubin less than or equal to 1 mg/dL, and 22.4 (+/- 9.6) mL/min/m2, 13.6 (+/- 11.3) L/m2, and 8.4 (+/- 3.9) hours in the eight patients with bilirubin 1.9 to 23.0 mg/dL. Stepwise multiple linear regression analysis of liver and renal function tests and other patient-specific variables identified creatinine clearance as the strongest predictor of etoposide systemic clearance (r2 = 40.8). Serum albumin was identified as the next strongest predictor, improving the r2 to 57.3%. Cumulative biliary excretion of unchanged etoposide and glucuronide or sulfate conjugates over 48 hours accounted for less than 3% of the dose in six patients studied. Toxicity occurred in patients with normal and abnormal bilirubin and was unrelated to etoposide clearance. Patients with total bilirubin 1.9 to 23 mg/dL, but creatinine clearance greater than 30 mL/min/m2 had etoposide clearance within the range for patients with normal liver function (16.8 to 35 mL/min/m2). Although these patients did not have reduced etoposide clearance, the major routes of etoposide non-renal elimination remain to be clearly defined. Additional patients should be evaluated to establish more precise guidelines for dosing etoposide in patients with abnormal liver function.

A new simple approach to study the effect of changes in urine flow and/or urine pH on renal clearance and its applications.

After entering the renal tubular lumen either through glomerular filtration or tubular secretion, drug molecules are considered to be removed from there by two competing processes: tubular fluid flow for urinary excretion and tubular reabsorption into blood circulation. The relative overall magnitude of the "force" or "efficiency" of these two processes will determine the fraction of drug molecules to be either excreted or reabsorbed, and hence their renal clearance (CLr). Urine flow rate (Q) is assumed to be proportional to the mean flow rate of tubular fluid at reabsorption sites (mainly in distal tubules), and used as an index to indirectly estimate the relative reabsorption "force" or "efficiency" (this may also be called apparent intrinsic reabsorption clearance). With the above assumptions, a plot of 1/CLr vs. 1/Q should yield a straight line under apparent first-order conditions. This has been confirmed for urea, theophylline, ethanol, chloramphenicol, amobarbital, riboflavin and fluoride based on human and dog (riboflavin only) data reported in the literature. Assuming that tubular reabsorption occurs only through the diffusion of unionized molecules, a plot of 1/CLr vs. fn/Q should also yield a straight line for weak acids and weak bases under linear conditions; the fn is the mean fraction of drug present in the unionized form at reabsorption sites whose mean pH is approximated or reflected by the urinary pH. The above straight line plot has been confirmed with human data for phenobarbital as well as human and rat data for salicylic acid. The effect of urine pH on biological half-life of pseudoephedrine in humans has also been successfully characterized.(ABSTRACT TRUNCATED AT 250 WORDS)

Modifiers of calcium oxalate crystallization found in urine. II. Studies on their mode of action in an artificial urine.

The relative potencies of various modifiers of the crystallization of calcium oxalate (CaOx) were determined under "whole urine equivalent" conditions using a batch crystallizer. The system was used to measure changes in the degree of agglomeration of CaOx crystals produced spontaneously at a level of supersaturation within the range found in the urines of recurrent CaOx stone-formers. The modifiers tested included RNA, heparin, chondroitin-4-sulphate, pyrophosphate (at pH 5, 6 and 7), Tamm-Horsfall mucoprotein and a greater than 10,000 dalton fraction of macromolecules obtained from pooled normal urine by dialysis. The effects of these urinary constituents were also measured on the zeta potential produced at the surface of CaOx crystals. In the case of pyrophosphate, there was a clear correlation between the degree of inhibition of agglomeration and the zeta potential observed on the crystal surface indicating that, for this ion, repulsive electrostatic forces dominate the tendency for CaOx crystals to agglomerate. For the other modifiers tested, the tendency to agglomerate appeared to be dependent on the balance between the positive viscous binding ("sticky") forces and the negative electrostatic forces produced by these macromolecules on the CaOx crystal surface.

The role of the sympathetic nervous system in the regulation of ultradian rhythms in urine excretions.

The effects of alpha and beta adrenoreceptors blockade and surgical kidney denervation on ultradian rhythmicity in urine excretion were investigated in four dogs. Pharmacological treatments and surgical denervation of the kidneys suppressed the ultradian rhythmicity in urine flow but did not completely eliminate the ultradian rhythms in urinary osmolality and in electrolyte concentrations. These findings suggest that the autonomic nervous system plays a major role in the regulation of the ultradian rhythms in water excretion in dogs. The partial persistence of ultradian rhythms in urine osmolality and electrolyte concentrations after autonomic denervation supports the assertion that the ultradian rhythms in solute concentrations are regulated by different mechanisms to those of water excretion, suggesting the possible involvement of a multioscillatory system.

Lower intestinal modification of ureteral urine in hydrated house sparrows.

The ureters of birds empty into the posterior portion of the lower intestine, thereby providing the possibility for modification of ureteral urine by this latter organ. We have used in vivo perfusion to measure the transport of Na+, K+, and water across the lower intestine (colon and coprodaeum) of anesthetized house sparrows (Passer domesticus). Na+ was reabsorbed from (Vmax = approximately 22 mu eq . cm-2 . h-1, Km = approximately 69 meq/l) and K+ was secreted (at variable rates) into all saline perfusion fluids. The osmotic permeability of the intestinal epithelium was 0.39 microliter . cm-2 . h-1 . mosM-1 in the mucosal-to-serosal direction and 0.43 microliter . cm-2 . h-1 . mosM-1 in the serosal-to-mucosal direction. At isosmotic perfusion, Na+-linked water transport occurred at a rate of 1.7 microliter/mu eq Na+. In hydrated house sparrows the composition of ureteral urine (osmolarity = 351 mosM, Na+ = 86.5 meq/l, K+ = 60.5 meq/l) was significantly modified by transport in the lower intestine (voided fluid osmolarity = 344 mosM, Na+ = 60 meq/l, K+ = 90 meq/l). Interspecific comparisons of lower intestinal resorptive surface area and transport parameters at the level of the tissue, organ, and whole animal reveal no consistent pattern of adaptation related to habitat.

Self-selected vs. controlled diet as a baseline for human studies: effects of nutrient intakes on blood pressure and on constituents of blood and urine.

This study demonstrates that a three-week stabilization period, in which all subjects eat an identical diet, produced a more uniform but different baseline of metabolic parameters than the subject's self-selected or "habitual" diets. Subjects required more food energy to maintain initial body weights during the stabilization period than when they ate their reported self-selected diets; average intakes of almost all nutrients were higher from the stabilization than from the self-selected diet. The switch to the stabilization diet produced small but significant reductions in blood pressure, in some serum enzymes, urine volume, and sodium; and statistically significant increases in serum LDL cholesterol, potassium, aldosterone, protein, albumin, phosphorus, BUN, and in urine potassium. The findings indicate that results must be interpreted with caution from studies in which the baseline for measuring metabolic variables is established by feeding subjects a standardized diet that differed markedly from their regular, self-selected diets.

Measurement of glomerular filtration rate: single injection plasma clearance method without urine collection.

Glomerular filtration rate (GFR) can be calculated from the plasma clearance of any of several radiopharmaceuticals that are excreted by glomerular filtration. Simplified methods have been proposed that require only one or two plasma samples in lieu of a more complete clearance curve. We examined the error introduced by this simplification. Forty patients were studied using a dual-isotope technique employing [99mTc]DTPA and [169Yb]DTPA, obtaining eight plasma samples for each clearance curve at intervals from 10 to 240 min after injection. Data were fit to several empirical or semiempirical formulae and also to a two-compartment computer model that permitted GFR estimation from only one or two data points. The computer model gave good fit, but so did several simpler methods. The error that results from replacing the complete clearance curve by a single 3-hr sample was about 8 ml/min (residual s.d.). By using two samples (at 1 and 3 hr), the error could be reduced to 4 ml/min. Recommended one- and two-sample methods are presented.

Kidney stones. Medical management and newer options for stone 'removal'.

Patients with recurrent kidney stone disease or stone formers at increased risk of recurrence deserve a thorough metabolic workup. This should be based on a careful history and include urinalysis, serum chemistry studies, and analysis of 24-hour urine collections. Measures to prevent recurrent stone formation are aimed at correcting the metabolic imbalances detected in the workup. A variety of drugs are available that target one or more of the metabolic abnormalities that may be involved. For "surgically active" renal and ureteral stone disease, newer techniques make surgery unnecessary in most cases. Extracorporeal shock wave lithotripsy is becoming the preferred technique for disintegration of upper urinary tract stones. Percutaneous ultrasonic lithotripsy and electrohydraulic disintegration also are widely used. For lower urinary tract stones, the ureteroscope permits either extraction under visualization or ultrasonic disintegration.