Administration Of Urea Research Articles

Effects of Urease Inhibition in Hyperammonemia: Clinical and Experimental Studies with Acetohydroxamic Acid

Summary Acetohydroxamic acid (AHA), an inhibitor of urease, was used in the treatment of coma and azotemia complicating hepatic failure on six occasions in 5 patients. Under the circumstances of the study, no consistent clinical effect was observed, but a significant reduction in blood am monia concentrations was produced. In dogs with Eck fistulas, AHA reduced fasting blood ammonia concentrations and prevented the hyperammonemia which otherwise occurred after intravenous administration of urea. In animals, the compound is rapidly absorbed from the gastrointestinal tract and excreted in the urine, and no toxic effects were observed. These preliminary data warrant further investigation of the compound as an adjunct to treatment in some instances of hepatic coma.

On the nature of the renal concentrating defect in malnutrition

The concentrating and diluting ability of the kidney was studied in adult patients with protein malnutrition before and after protein repletion. During malnutrition, values for maximal urine osmolality and solute-free water reabsorption (T cH 2O) were diminished. Renal diluting capacity, measured by minimal urine osmolality and free-water clearance (C H 2O ), was normal. The renal response to the administration of exogenous antidiuretic hormone (ADH) was adequate, as was the response to nicotine and hypertonic saline solution. During protein repletion there was an improvement in maximal urine osmolality and T cH 2O values. The improvement in concentrating ability occurred pari passu with an increase in urinary nitrogen excretion. The oral administration of urea to four malnourished patients resulted in changes in maximal urine osmolality and T cH 2O similar to those observed with protein repletion. A classification of renal concentrating defects is presented and the mechanism of the renal concentrating defect in malnutrition is discussed within the framework of this classification. The primary role of decreased urea concentration in the renal medulla as the cause of the concentrating defect in malnutrition is emphasized.

Hypertonic urea: Its effects on cortical and subcortical evoked potentials in cat

The effects of urea and concomitant cerebral dehydration on potentials evoked in the cerebral cortex, midbrain reticular formation, and cerebellar cortex by somatic stimulation were studied in the cat. Urea (1.5 g/kg i.v.) typically augmented the negative and late positive phases of triphasic positive-negative-positive evoked cerebral cortical responses recorded monopolarly. This change began about 15 min after urea administration. It paralleled the onset of cerebral shrinkage and was maximal after about 1 h. These evoked potential changes persisted for 5 to 7 h in most cases, but sometimes returned to control levels after about 2 h. Resumption of the original cortical volume was not essential for return to baseline amplitudes.

The effects of urea and hydrochlorothiazide on the renal functions of rat and domestic fowl.

1. Rats and domestic fowls were given by stomach tube water, urea and hydrochlorothiazide, alone or in combination, in the following amounts: water, 5 ml./100 g; urea, 4 ml. of 1.5% solution + 1 ml. water/100 g; hydrochlorothiazide, 4 ml. of 1.5% urea solution + 1 ml. containing 0.1 mg hydrochlorothiazide/100 g.2. The onset of water diuresis was faster in the fowl than in the rat. It was accompanied by a lower rate of excretion of osmotically active solutes in the former than in the latter. The rate of excretion of creatinine in rats was fourfold that in birds.3. After urea administration, the amount of urea excreted by the fowl was about one fifth that excreted by the rats. While urea produced in rats an osmotic diuresis, with enhanced excretion of osmotically active solutes, in birds it had little effect on either urine flow or solutes excretion.4. Administration of hydrochlorothiazide in rats produced a moderate antidiuresis accompanied by a marked increased excretion of Na and K; in birds, a small increase in the excretion of Na and K but no effect on the urine flow.5. The differences observed between rats and birds can be attributed to the poor development of filtration rate and the absence of a well developed counter-current system in the fowl.

The Osmotic Fragility of Human Red Cells Caused by Urea Administration During Hypothermia

The Osmotic Fragility of Human Red Cells Caused by Urea Administration During Hypothermia

The Osmotic Fragility of Human Red Cells Caused by Urea Administration During Hypothermia

The Osmotic Fragility of Human Red Cells Caused by Urea Administration During Hypothermia

Severe Chickenpox Encephalopathy

ENCEPHALOPATHY is a rare complication of chickenpox. Estimates of its incidence vary between 0.01% and 0.1%. Most cases are mild, the mortality is low, possibly of the order of 5% of those affected, and the prognosis for complete recovery in the remainder is good.1The present patient became so critically ill that little hope was held for her survival. Dramatic improvement followed the intravenous administration of urea, and she recovered completely after further treatment with hypothermia and dexamethasone. Report of Case A 6-year-old white girl developed the first lesions of chickenpox on Dec 13, 1964. Chickenpox was prevalent in the community at the time. For the first few days she was only slightly ill. At no time was aspirin or any other salicylate given. On December 16 she became excessively drowsy and was admitted to the Moses Cone Hospital. That evening she responded to painful stimuli only, and her

THE REBOUND PHENOMENON AND HYPERTONIC SOLUTIONS.

T H E T E R M S secondary in cerebrospinal-fluid pressure or rebound phenomenon after administrationof hypertonic solutions should be defined as a significant increase in tension of cerebrospinal fluid following the period of maximum reduction of cerebro-spinal-fluid pressure and caused by mechanisms related directly to the use of the hypertonic solution. In 1920, 1 year after Weed and McKibben 32 introduced hypertonic solutions for reduction of cerebrospinal-fluid pressure, Ebaugh and Stevenson 9 reported a terminal rise in intracranial pressure after oral administration of ~00 cc. of 19 per cent Ringer's solution to a patient. Prior to the clinical introduction of hypertonic solution of urea, TM a number of papers had appeared in the literature reporting a secondary in cerebrospinal-fluid pressure or rebound phenomenon following administration of hypertonic solutions of sodium chloride and glucose. 3-5,14,23,25 Factors reported to cause increased cerebrospinal-fluid pressure include irritation of the meninges as the result of the presence of the needle, 13 meningitis, 14 pleocytosis ascribable to a solution in the manometer made from compressed tablets of sodium chloride dissolved in distilled water} ~ and administration of barbiturate anesthetics. 5,~ Since 1954 we have carried out studies on cerebrospinal-fluid pressure with prolonged periods of control prior to the injection of hypertonic solutions. ~5 Our experience with hypertonic urea includes 1500 patients and several hundred experiments in rhesus monkeys and dogs. After administration of urea a rebound of pressure to levels above maximum levels of cerebrospinal-fluid pressure, during

Intravascular Hemolysis Following Urea Administration During Hypothermia

Intravascular Hemolysis Following Urea Administration During Hypothermia

Role of a functional load in activation of cells during regeneration of the mouse kidney

The effect of increased function, caused by urea loading and nephrectomy, on regeneration of the partially resected kidney was studied. After partial resection of one kidney, the other being intact, administration of urea did not affect mitotic activity. If, in addition, the opposite kidney was removed beforehand or at the same time, mitotic activity and the dimensions of the cells increased in the partially resected kidney to a greater degree that when an intact kidney was present.

Enhancement of renal concentrating ability in the dog by urea and related compounds.

Experiments were performed on vasopressin-infused dogs to test the effect on renal concentrating ability of acute administration of urea and seven other organic nonelectrolytes. In each experiment a control assessment of concentrating ability was obtained during administration of mannitol. This was followed by administration of a test compound in an amount designed to maintain the previous rate of solute excretion. When compared to control values, urine osmolality was significantly higher during administration of urea, methylurea, acetamide, 1,2-propanediol and 1,3-dimethylurea, but not during administration of thiourea, glycerol, or hexamethylenetetramine. Others have suggested that the enhancement of concentrating ability by urea is related to the unique ability of urea to diffuse through the collecting-duct membranes. In the present study, there appeared to be no simple correspondence between the degree to which urine osmolality increased and the physical properties generally recognized to affect membrane permeation: oil:water partition coefficient, molecular size, or specific chemical groups.

Subdural Hematoma Following Administration of Urea for Diagnosis of Hypertension

THE INTRAVENOUS ADMINISTRATION of hypertonic urea solution has been advocated by Stamey in the diagnosis of unilateral renal disease by differential renal function studies. Its purpose is to promote maximal relative reabsorption of water in the ischmic kidney, and it also serves as an osmotic diuretic to assure satisfactory flow rates for the procedure. However, an additional effect of the infusion of urea solution is the decrease in cellular volume. When this occurs in the brain, intracranial hemorrhage may be precipitated. Report of a Case A 54-year-old male with known hypertension of many years duration, suffered a cerebrovascular accident in 1954 with resultant right hemiparesis. His hypertension was unsatisfactorily controlled by medical therapy. Physical examination revealed a blood pressure of 230/120 mm. Hg and a right hemiparesis marked by muscle atrophy and spasticity of the extremities on that side. A positive Babinski sign was noted on the right side. The

A technic for kidney scanning.

A new radioisotopic technique was developed for accurately evaluating the secretory function of the kidney. It is based on the principle that acute obstruction of the ureters causes intrapelvic pressure to rise to a point where filtration will cease while tubular secretion continues. Thus, by temporarily depriving the kidney of its excretory function it is possible to map its secretory function. I/sup 131/-labeled sodium iodohippurate (Hippuran) was selected since it is secreted by the tubules and has a clearance identical with p- aminohippurate (PAH). The initial experiments were conducted on dogs, in which the kidneys were exposed through an anterior approach and both ureters catheterized. A high urine volume was established by intravenous administration of urea. following which both ureters were blocked. In 5 to 10 min, intrapelvic pressure had risen to 90 to 100 mm Hg and filtration ceased. Then approximates 50 mc Radiohippuran was given intravenously. The kidneys were scanned by hand with a small surgical scintillation detector. An excellent count was thus obtained over the kidneys while the urine in the pelvis was practically free of radioactivity. Renal blood flow was determined in both kidneys prior to ureteral obstruction by PAH clearances. When the ureters were thenmore » obstructed and Radiohippuran given intravenously, a close parallelism between PAH clearances and radioactivity was found. When small branches of the main renal artery were clamped. the ischemic area could be clearly delineated, due to lowered radioactivity. With improvement in technique it should be theoretically possible to detect nonfunctioning areas down to 0.5 cm in size. Successful application of this method in several patients is also described. (H.H.D.)« less

The Effect of Urea and Invert Sugar (Urevert) on Cerebral Damage Occurring After Cardiac Arrest

SUMMARY AND CONCLUSIONS Two groups of 15 dogs each were subjected to five minutes of ventricular fibrillation. Ventricular fibrillation stops all circulation. The brain was, therefore, subjected to a measured period of complete anoxia. The circulation was restored on the second after five minutes. This was done by hand pumping of the heart and by mechanical insufflation of the lungs with oxygen. The coordinated heart beat was restored. One test-group of dogs was given a solution of urea and invert sugar in water intravenously as soon as the period of anoxia was terminated. Otherwise the management of each group of dogs was the same. The conclusion is that intravenous administration of urea, invert sugar and water did not protect the dog after measured periods of cerebral anoxia. The mortality in the treated group was higher than in the untreated group. According to these experiments urea does not have the same beneficial effect as does hypothermia and it is not a replacement for hypothermia after resuscitation of the heart. The effect of hypothermia was published. It was determined in two groups of ten dogs each. The dogs in each series were given either promethazine or chlorpromazine in addition to morphine or meperidine to prevent shivering. There were no recovery dogs in the control group. There were three recoveries in the group under hypothermia and the survival period before death was longer in this group. The results in these two series of dogs, cooled and not cooled, are not the same as in the control series reported in this paper. The conclusion is that promethazine and chlorpromazine contributed to death in each series of dogs. The increased death rate seems to be significantly greater when these drugs were used.

Urea in intracranial surgery. A new method.

HE neurosurgeon is often confronted with the difficult problem of increased intracranial pressure. During intracranial operations this tension may be so high that it may cause disruption of the cerebral cortex on opening the dura mater, often in spite of a ventricular puncture. Cerebrospinal fluid drainage by the lumbar route is contraindicated when intracranial pressure is high. Experience with the administration of urea to 700 patients (Table 1) and to more than 150 animals under various experimcntal conditions has proved that this is a valuable agent for reduction of brain volume, cerebrospinal fluid pressure and intraocular pressure. The main purpose of this paper is to give a detailed description of the method that has proved most effective. 2 siderable shrinkage of brain. Larger doses are unnecessary because of excessive reduction of brain volume. On the other hand, when dealing with space-occupying masses within the cranial cavity with shift of the ventricular system, marked brain swelling caused by severe head injury, or raised eerebrospinal fluid pressure caused by a ruptured intracranial aneurysm, 1.5 gin. urea per kg. of body weight is the dose recommended during surgery. Urea is given as the sole solution through a #16 or #18 needle, except in children, when blood is administered through another needle simultaneously with urea, or in adults who require transfusion. Other solutions may be administered at the same time whenever necessary, preferably at a very slow rate. Administration of urea is begun at the start of the craniotomy incision DOSAGE AND METHOD Sterile lyophilized urea is dissolved in 10 per cent invert sugar in water 4 to make a 30 per cent weight-volume solution (90 gin. urea plus ~10 cc. of 10 per cent invert sugar in water yields ~70 cc. of 30 per cent ureaS). A dose of 1 gm. urea per kg. of body weight is used routinely in adults and children when it is desirable to gain good visualization without the trauma that may be caused by retraction of the brain, as in pituitary operations or in cases of intracranial aneurysms. There is no need for lumbar drainage of cerebrospinal fluid in these cases since this amount of urea is adequate to cause con

Further observations on metabolic alterations in the hypothermic rat.

Further observations on metabolic alterations in fasted rats cooled under ice to rectal temperatures approximating 15 °C are reported. In the hypothermic rats, metabolism of injected lactic acid does not appear to be impaired. There is however: increased concentration of inorganic phosphorus in blood but not in liver; increased concentration of glutathione in liver but not in blood; increased plasma chloride concentration; decreased red cell potassium concentration; increased red cell water content; decreased plasma water content. Hypothermia, under these conditions, did not alter concentrations of liver acid-extractable glycogen, red cell sodium, plasma sodium, plasma potassium, nor serum calcium. Administration of urea in saline prior to cooling elevated plasma sodium and potassium concentrations in hypothermic rats. These observations are discussed in relation to previously reported effects of hypothermia on carbohydrate metabolite levels.

The mechanism of insulin's toxic effect on a frog's heart

The author suggests that the negative effect of toxic doses of insulin on cardiac activity is possibly caused by depression of the activity of the tissue sulfhydryl groups. To obtain experimental verification of this suggestion, the author studied the action of urea on the work of the isolated frog's heart under conditions of insulin intoxication. Following the arrest of the cardiac activity caused by toxic doses of insulin, urea administration helped restore the contractile myocardial function and the ECG indices. Such an effect is evidently due to the fact that urea, which has the ability to loosen the protein molecule and liberate the tissue sulfhydryl groups, brings about the restoration of disturbed processes in the cardiac muscle.

METABOLIC EFFECTS OF UREA ADMINISTRATION ON ACUTE HYPOTHERMIA IN RATS

Acute hypothermia (15 °C rectal temperature) has been induced in fasted rats with and without prior intraperitoneal administration of urea. In the hypothermic animal, not given urea, blood glucose and pH were significantly decreased; blood lactic acid, inorganic phosphorus, and packed cell volume were significantly increased; no alterations occurred in blood levels of pyruvic acid, total acid-soluble phosphorus, urea, nor amino nitrogen. Prior administration of urea prevented significant alterations of blood glucose and lactic acid in the cooled animal. In the non-cooled animal, urea treatment resulted in elevated blood glucose levels. These effects are discussed in relation to the beneficial action of urea in permitting successful resuscitation and survival in a normal condition of rats cooled to rectal temperatures of 0–3 °C.

Hypersmolarity (hypernatremia) and azotemia induced by the administration of urea.

Urea has proved to be a useful agent in lowering intracranial pressure and brain bulk.1,2This agent has generally been administered intravenously in a 30% solution. Urea has been administered orally in repeated daily doses for several weeks and, in a few instances, for several months.3 In the case to be described, urea was administered by gastric tube in amounts of 150 to 400 ml. of 30% solution for eight days. The osmotic diuresis which occurred appears to have been responsible for the hyperosmolarity and azotemia which developed. Report of a Case A 70-year-old woman, left-handed, began to have convulsive seizures in 1948. One year later she underwent a laparotomy for exploration of the common bile duct. She developed a vascular collapse during the procedure and remained in coma for two days following the operation. When she recovered, she had total amaurosis of the left eye. In retrospect

METABOLIC EFFECTS OF UREA ADMINISTRATION ON ACUTE HYPOTHERMIA IN RATS

Acute hypothermia (15 °C rectal temperature) has been induced in fasted rats with and without prior intraperitoneal administration of urea. In the hypothermic animal, not given urea, blood glucose and pH were significantly decreased; blood lactic acid, inorganic phosphorus, and packed cell volume were significantly increased; no alterations occurred in blood levels of pyruvic acid, total acid-soluble phosphorus, urea, nor amino nitrogen. Prior administration of urea prevented significant alterations of blood glucose and lactic acid in the cooled animal. In the non-cooled animal, urea treatment resulted in elevated blood glucose levels. These effects are discussed in relation to the beneficial action of urea in permitting successful resuscitation and survival in a normal condition of rats cooled to rectal temperatures of 0–3 °C.