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Biomedical subjects

E Z Rabin

Publications and source records attributed to E Z Rabin.

At least 19 recordsLinked to original sources

Uptake of glucose during continuous arteriovenous hemofiltration.

OBJECTIVE: To quantify glucose balance related to continuous arteriovenous hemofiltration (CAVH) when a glucose-rich replacement fluid is used for the plasma ultrafiltrate removed. DESIGN: Prospective, nonintervention study. SETTING: Medical/surgical and cardiac surgical intensive care units of a university hospital. PATIENTS: Critically ill patients (n = 20) with acute oliguric renal failure undergoing CAVH. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Timed collections of CAVH effluent were analyzed and other observations were made. Serum creatinine and blood urea nitrogen concentrations decreased substantially during CAVH in each patient. The mean measured glucose concentration of the replacement fluid (Dianeal 1.5%) was 1.40 +/- 0.11 (SD) g/dL (77 +/- 6 mmol/L) and rate of infusion was 1.39 +/- 0.43 L/hr. Effluent volume was 1.51 +/- 0.49 L/hr and glucose was 0.47 +/- 0.10 g/dL (26 +/- 5 mmol/L). The glucose content of the replacement fluid infused was consistently and substantially greater than that value of the effluent removed during the same period. Thus, the average net glucose uptake in relation to the CAVH circuit was 11.9 +/- 3.1 g/hr (range 4.3 to 17.6). Serum glucose concentrations increased in each patient with initiation of CAVH (from 135 +/- 44 to 278 +/- 80 mg/dL [7.4 +/- 2.4 to 15.3 +/- 4.4 mmol/L]; p < .001). Negative fluid balance achieved during CAVH was approximately 100 mL/hr. CONCLUSIONS: CAVH using predilution with replacement fluid is effective in managing uremia and fluid overload in critically ill patients. The use of a glucose-rich replacement fluid is accompanied by the net uptake of large amounts of glucose, approaching 300 g/day on average in our patients and representing a major exogenous calorie source. This finding has important implications for the metabolic management of critically ill patients during CAVH and should be taken into account in prescribing their nutritional support.

Acute Kidney Injury↗

Once- vs. twice-daily nitrendipine in the treatment of mild to moderate hypertension, Canadian Nitrendipine Study Group.

Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Effectiveness and tolerability of once versus twice daily nitrendipine in the treatment of mild to moderate hypertension. The Canadian Nitrendipine Study Group.

Improved measurement of plasma concentrations of nitrendipine demonstrates a plasma half-life of 17 to 21 h allowing once daily dosing for antihypertensive treatment. To determine the effectiveness and tolerability of nitrendipine given once versus twice daily, 78 patients with mild to moderate essential hypertension were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 20 mg once daily (n = 39) or nitrendipine 10 mg bid (n = 39). Blood pressures measured at the end of the dosing interval were similar on 20 mg once daily and 10 mg bid. Adverse events considered to be drug related (flushing and headaches) occurred mostly at the beginning of active treatment and more frequently on the once daily dosing, resulting in a greater number of patients being withdrawn from the once daily treatment group. Thus, nitrendipine 20 mg once daily lowered blood pressure as effectively as 10 mg bid but was associated with a higher incidence of adverse events. These could be minimized by starting at nitrendipine 10 mg once daily and increasing to 20 mg once daily after two to four weeks.

Blood Pressure↗

Analytical problems encountered during high-performance liquid chromatographic separation and coulometric detection of bopindolol metabolites in human plasma.

Good clinical control of hypertension is achieved with low doses of the potent beta-blocker bopindolol. Pharmacokinetic evaluations therefore require an analytical technique of high sensitivity. Analysis of plasma by high-performance liquid chromatography (HPLC) using electrochemical detection provides this sensitivity. This article describes the development of an analytical procedure and presents a reversed-phase HPLC method with coulometric detection suitable for plasma analyses during pharmacokinetic investigations of bopindolol therapy.

Adrenergic beta-Antagonists↗

Can plasma catecholamine levels be a useful index of sympathetic nervous system activity?

The hemodynamic responses of the sympathetic nervous system to the Valsalva maneuver were related to changes in circulating levels of catecholamines, aldosterone and plasma renin activity. Fourteen healthy normotensives (aged 27 +/- 8 years) took part. A catheter was inserted in the forearm then the subject was rested quietly (supine) for 30 mins. The Valsalva maneuver was performed (duration 40 s, intrathoracic pressure 40 mmHg) with continuous recording of supine heart rate. Blood was sampled before the maneuver (basal state) and at the bradycardic post maneuver phase for measurement of plasma noradrenaline, adrenaline, renin activity and aldosterone. In six subjects the procedure was repeated for durations of 10, 20, 30 and 40 s with a 30-min rest between each maneuver. Plasma catecholamines increased consistently (P less than 0.001) from pre- to post bradycardic phases of the maneuver. No changes in plasma renin activity or aldosterone were observed. The maximum tachycardia observed during each maneuver and the increments in catecholamine concentrations were each linearly related to the duration of straining but there was no overall correlation between the tachycardia and catecholamine concentrations. In conclusion under controlled conditions, plasma catecholamine concentrations can be useful indices of the stimulation of the sympathetic nervous system; the Valsalva maneuver does not appear to affect significantly the peripheral renin-angiotensin system; and the heart rate response to the Valsalva maneuver does not appear to be mediated solely by the sympathetic nervous system.

Adult↗

The renal handling of human urinary ribonuclease by rat kidneys.

The purpose of the study was to find out how poly(C)-avid human urinary ribonuclease is handled by the kidney. Purified human urinary ribonuclease (molecular weight 33 000) was radiolabelled with 125I. The enzyme was injected intravenously into dogs and monkeys with and without kidneys. The disappearance rate from the animals without kidneys was markedly prolonged. In the dog and monkey with kidneys, the radiolabelled enzyme which was infused was recovered in the urine unchanged. No large molecular weight fragments were found. When 125I-labelled ribonuclease was infused into rats the material recovered in the urine was primarily identical with the material infused. A very small fraction of the material recovered was found to contain some fragments which had chromatographic characteristics of monoiodotyrosine and diiodotyrosine. Two other fragments were detected but could not be identified. Autoradiographic studies of the rat kidneys also showed some reabsorption of the radiolabelled ribonuclease, particularly in the proximal tubules. With electron microscopy the radiolabelled material could be seen in the lysosomes. These observations corroborate findings discovered for other low molecular enzyme such as lysozyme (molecular weight 14 000) and suggest that the human ribonuclease is mainly excreted by the kidneys unchanged and that a minor amount may be reabsorbed by the proximal tubules and metabolized in the lysosomes.

Animals↗

Ribonuclease inhibition of erythropoiesis in anemia of uremia.

The anemia of chronic renal failure was studied by assessing the effect of uremic serum on proliferation of human marrow erythroid stem cells into colonies in vitro. Of 50 sera tested, 46 inhibited "CFU-E" colony formation by a mean of 72%, and 42 inhibited "BFU-E" colonies by a mean of 53.5%, compared to normal sera. Analysis of the uremic sera revealed a striking increase of ribonuclease activity in every patient. Mean activity in the study group was 17,346 U/ml serum (range 6,700-36,250) compared to control mean of 1,047 +/- 247 U/ml. Purified ribonuclease added to marrow cultures in concentrations simulating uremic serum produced a dose-dependent decrease in CFU-E colonies suggesting that the substance has a role in the production of anemia of renal failure.

Adult↗

A highly sensitive method for identification of amino termini of proteins: application to multiple forms of poly(C)-avid ribonuclease and 17 beta-hydroxysteroid dehydrogenase.

A radiochemical method for the determination of the amino terminus on very small amounts (0.5-5 nmol) of protein is described. The high sensitivity of the method is achieved by using undiluted 1-fluoro-2,4-dinitro-[3,5-3H]benzene [( 3H]Dnp-F) as the labelling reagent under conditions in which a maximum amount of radioactive label is incorporated. Chemical homogeneity is achieved by reacting with excess unlabelled Dnp-F. High recovery is obtained by adding Dnp-albumin as carrier protein. A mixture of Dnp 14C-labelled amino acids is added prior to hydrolysis and identification of the amino terminus is made on the basis of the 3H/14C ratios of the separated Dnp-amino acids. The method was tested on insulin, pancreatic ribonuclease, and lysozyme which gave high 3H/14C ratios only in the expected amino-terminal amino acids. Application to multiple forms of poly(C)-avid ribonuclease gave only amino-terminal lysine. Two of four putative isozymes of 17 beta-hydroxysteroid dehydrogenase had serine as the amino terminus while the other two had aspartic acid or asparagine.

17-Hydroxysteroid Dehydrogenases↗

The isolation, purification, and properties of a ribonuclease (Mr 18 000) from human uremic serum, and its relation to the human urinary ribonuclease (Mr 33 000). II. Properties of the enzymes.

A low molecular weight ribonuclease (Mr 18 000) isolated and purified from human uremic serum was found to have similar properties to the high molecular weight ribonuclease (Mr 33 000) isolated from human urine. A detailed comparative study of both enzymes was undertaken to investigate the relationship between them. It is suggested that poly(C)-avid human ribonucleases have similar amino acid compositions but variable carbohydrate contents and that variations in the sugar content are responsible for variations in the molecular weight.

Amino Acids↗

Ribonuclease activity in renal failure. Evidence for toxicity.

Ribonuclease isolated from human urine is a glucoprotein of molecular weight 33,000. The purified enzyme inhibits: (1) the stimulation of 3H-thymidine uptake into lymphocytes by phytohemagglutinin, pokeweed, and concanavalin A; (2) the growth of pancreatic fibroblastoid cells in in vitro cell culture, and (3) the growth of colonies in bone marrow cell cultures. Ribonuclease levels in the uremic patient vary from 9,500 to 35,000 U/ml (normal 1,041 +/- 247). Serum ribonuclease levels are unaffected by dialytic procedures. It is suggested that the ribonuclease glycoprotein may represent a large number of nondialyzable high molecular weight uremic 'toxins'.

Acute Kidney Injury↗

Malignant hypertension.

Malignant or accelerated hypertension is a life-threatening disease whose complications may be prevented by rapid reduction of the blood pressure. Diazoxide is presently regarded as the preferred therapeutic agent, but drugs such as trimethaphan, sodium nitroprusside, phenoxybenzamine and hydralazine may be useful in particular situations. Treatment is best carried out in an intensive care unit, where appropriate monitoring and study of the patient can be done. Since the introduction of antihypertensive agents the life expectancy of these patients, even those with renal insufficiency, has increased.

Antihypertensive Agents↗

Ribonuclease activity in human serum, cerebrospinal fluid, and urine.

Poly(C)-avid ribonucleases of molecular weight 33 000 are present in the serum, cerebrospinal fluid and urine of humans. Purified human urinary ribonuclease was used to produce a monospecific antibody in rabbits. The antibody was capable of: (i) inhibiting the enzyme activities in the serum, CSF, and urine; (ii) reacting with antigens in the serum and CSF. The antigens in the serum, CSF and urine were found to be immunologically identical. Immunoelectrophoresis data suggested that the urinary and CSF RNAase are chemically identical. Succesful renal transplantation reduced elevated serum RNAase to normal levels. The data suggest that the most likely source of both urinary and CSF ribonuclease activity is the blood stream.

Humans↗

Ribonuclease activity in renal failure: evidence for toxicity.

The normal level of serum or plasma poly C-avid ribonuclease activity is 1047 +/- 247 U/mL. Serum levels increase proportionately with elevations in serum creatinine, reaching levels of 9,500-35,000 in patients undergoing dialysis. The levels can be normalised by successful renal transplantation but not by dialysis. Purified human urinary ribonuclease, a glycoprotein enzyme similar to the serum ribonuclease, was capable of: 1) inhibiting the incorporation of 3H-thymidine into mitogen-stimulated lymphocytes; 2) inhibiting the proliferation and growth of bone marrow red cell colonies; and 3) adversely affecting the growth and viability of precursor fat cells.

Cell Division↗

Ribonuclease activity of human cerebrospinal fluid.

The ribonuclease activity of cerebrospinal fluid of 219 patients was studied. The normal level was 269 +/- 95 units/ml. Consistent elevations above 550 units/ml were found in: 1. Chronic cerebrovascular disease; 2. Spinal cord compression; 3. Tumors. The molecular weights of the ribonucleases in the cerebrospinal fluid are approximately 33,000; 21,000 and 15,000; the major species is the one with m.w. 33,000. Although the increase in the CSF ribonuclease activity is not disease specific, the measurement has provided corroborative help in cases when the CSF protein is normal. The increase in CSF RNAase is not due to red or white blood cells and the immunologic data suggest that the CSF enzyme activity is derived from the blood stream. Further studies are necessary to rule out a nerve cell origin of the CSF ribonuclease activity.

Cerebrospinal Fluid↗