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Biomedical subjects

A Besarab

Publications and source records attributed to A Besarab.

At least 19 recordsLinked to original sources
PubMed1992

The relationship between dialysis graft pressure and stenosis.

RATIONALE AND OBJECTIVES: Pressure measurements during dialysis have been used to screen for venous outlet stenosis, but the relationship between the degree of stenosis and pressure has not been defined. METHODS: To determine this relationship, failing or failed dialysis grafts (n = 34) were studied with angiography and pressure measurements from the segment of the graft near the arterial anastomosis. RESULTS: By linear regression, the relationship between the highest grade stenosis in or central to the graft and pressure was as follows: percent stenosis = 55 systolic graft pressure/systolic blood pressure+13 (r = 0.75). CONCLUSIONS: There is a positive correlation between the severity of stenosis and graft pressure, confirming the use of this measurement in screening for stenosis. It is hypothesized that this relationship is the result of progressive elimination of the normal pressure drop between the artery and arterial limb of the graft as the degree of stenosis increases.

Angiography↗
PubMed1992

Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration.

The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.

Adolescent↗
PubMed1991

Elevated plasma histamine in chronic uremia. Effects of ketotifen on pruritus.

A role for histamine in the pathogenesis of uremic pruritus was investigated in maintenance hemodialysis patients. Venous plasma histamine levels, as determined by radioenzymatic assay, were significantly higher (p less than 0.05) in hemodialysis patients with pruritus (368 +/- 103 pg/ml [mean +/- SEM], n = 6) than in those without pruritus (146 +/- 22 pg/ml, n = 5) and in normal controls (142 +/- 16, n = 5). Arteriovenous fistula histamine levels (202 +/- 52 pg/ml, n = 6) were significantly lower (p less than 0.05) than simultaneously drawn venous samples. Markedly elevated histamine-degrading enzyme (histaminase) activities were found in both hemodialysis patients with (2.95 +/- 0.18 pg histamine degraded/minute) and without (2.44 +/- 0.28) pruritus, but was undetectable in normal controls. Histaminase activities did not significantly differ in simultaneously drawn venous and fistula samples. With hemodialysis, histaminase activities fell significantly (p less than 0.01), whereas plasma histamine did not change. We further examined the effects of ketotifen, a putative mast cell stabilizer, on severe uremic pruritus. Five of five patients had significant (p less than 0.01) reductions in pruritus, as judged on a six-point pruritus index, after 8 weeks of drug (x = 2.3), as compared to conventional therapy (x = 5.9). Despite these improvements, no significant differences were noted in pre- versus post-drug plasma histamine levels, histaminase activities, or the histamine content per gram of skin biopsy specimen. These data support prior hypotheses that mast cell activation contributes to the pruritus of uremia.

Chronic Disease↗
PubMed1979

Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective.

Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.

Antineoplastic Agents↗
PubMed1979

Excretion and metabolism of catecholamines by the isolated perfused rat kidney.

The excretion and metabolism of labeled epinephrine and norepinephrine by the isolated, perfused rat kidney were studied. The excretion of both catecholamines significantly exceeded the amount filtered, thus providing direct evidence of net tubular secretion. Renal clearance of epinephrine was significantly greater than that of norepinephrine. Tubular secretion was a linear function of the concentration of unbound catecholamine in the medium with no demonstrable tubular maximum at the concentrations studied. The isolated kidney removed catecholamines from the medium by metabolism as well as excretion in the urine. O-Methylation was the major metabolic route and O-methylated metabolites were rapidly excreted and concentrated in urine. Preferential excretion and metabolism of epinephrine were confirmed in double-label experiments in which [14C]epinephrine and [3H]norepinephrine were perfused together. The ratio of 14C:3H in urine exceeded that in perfusion medium for total radioactivity as well as for catecholamines and O-methylated amines. The present study thus provides direct evidence for (a) net tubular secretion of epinephrine and norepinephrine with a direct relationship between secretion and medium concentration; (b) significant renal metabolism of both epinephrine and norepinephrine with O-methylation as the major metabolic route; and (c) preferential excretion and metabolism of epinephrine.

Animals↗
PubMed1978

A possible role for propranolol in the treatment of renal osteodystrophy.

The effect of propranolol upon parathyroid hormone (P.T.H) concentrations was investigated in patients undergoing chronic haemodialysis. 9 patients receiving propranolol for the treatment of hypertension or angina pectoris were compared with 25 similar patients not taking the drug. P.T.H. and alkaline phosphatase concentrations were lower in patients receiving propranolol and there was less radiological evidence of renal osteodystrophy in these patients. Prospective studies are needed to determine whether propranolol may be helpful as an adjunct to other therapy in reversing or preventing renal osteodystrophy.

Adolescent↗
PubMed1978

Mechanisms of hypercalcemia in malignancy.

Various hormones have been implicated in the genesis of hypercalcemia in patients with malignancy. Ectopic secretion of PTH by tumor has been documented in only a few patients; rather, elevated levels of circulating iPTH have been presumed to reflect tumor production of hormone in most patients. Small fragments of PTH, as well as polypeptides larger than native PTH, have been described; their biological roles are unclear. The pattern of immunoreactivity, however, has been used to differentiate patients with ectopic hyperparathyroidism from patients with concomitant primary hyperparathyroidism. Vitamin D-like sterols produced by breast cancer seldom reach plasma levels necessary for physiological effects. Members of the prostaglandin family have been proposed to induce hypercalcemia through osteoclast activation or alteration of the immune system and also to affect the frequency of bone metastases. At present, no direct evidence is available to prove a direct role for these effects and prostaglandins are most useful as possible indicators of disease activity.

Bone Neoplasms↗
PubMed1978

Symptomatic hypocalcemia following combined calcitonin and mithramycin therapy for hypercalcemia due to malignancy.

Three patients with malignant disease received the usual recommended doses of mithramycin and calcitonin, either concurrently or concomitantly, because of severe life-threatening hypercalcemia. All three patients developed severe, symptomatic hypocalcemia. The mechanisms for this phenomenon are discussed. A possible synergism between calcitonin and mithramycin may prove to be hazardous in such patients and this possibility must be kept in mind when these agents are being considered as a combination treatment for hypercalcemia.

Calcitonin↗
PubMed1977

Effect of catecholamines on tubular function in the isolated perfused rat kidney.

Addition of norepinephrine or epinephrine to the isolated rat kidney perfused at constant pressure resulted in an increase in sodium reabsorption and the excretion of a dilute urine with an increase in free water clearance. Vasopressin reversed the fall in urinary osmolarity but not the diminution in sodium excretion. The urinary changes produced by catecholamines were blocked by propranolol but not by phenoxybenzamine, suggesting that they were mediated, at least in part, by beta receptors. Similar though less pronounced changes in sodium excretion and urinary osmolarity were produced by isoproterenol and phenylephrine, while the combination of these drugs induced marked dilution of the urine. The results suggest that circulating catecholamines or adrenergic nerves innervating the kidney directly influence renal tubular function and might, therefore, participate in the regulation of sodium and water excretion by the kidneys.

Animals↗
PubMed1976

Reversible renal failure following bilateral renal artery occlusive disease. Clinical features, pathology, and the role of surgical revascularization.

Three patients with severe hypertension and rapidly progressive oliguric renal failure who required dialysis were found by aortography to have bilateral renal artery occlusion or stenosis. Each had peripheral arteriosclerosis or an abdominal bruit. Following renal artery reconstructive surgery, all three patients recovered nearly normal renal function in 3 to 12 weeks, though mild hypertension persisted in two patients. The common findings of a normal-sized kidney with collateral blood flow and nearly normal histological features were predictive of recovery of renal function. Prolonged postoperative oliguria in two patients may have been due to increased preglomerular vascular resistance mediated by the renin-angiotensin system.

Acute Kidney Injury↗
PubMed1976

Multiple pumps for sodium reabsorption by the perfused kidney.

Several distinct transport mechanisms responsible for sodium reabsorption by the rat kidney can be identified by studying the function of isolated perfused kidneys. Approximately one-half of the fractional sodium reabsorption by the isolated perfused rat kidney appears to depend on Na-K-adenosine triphosphatase (AT-Pase) and is inhibited by ouabain. About 10 to 20% is associated with the reabsorption of bicarbonate and is blocked by acetazolamide. This fraction of transported sodium is unaffected by ouabain and therefore does not involve Na-K-ATPase. Neither furosemide nor ethacrynic acid produce further inhibition of sodium reabsorption in a kidney already exposed to ouabain and acetazolamide. Most of the residual transport of sodium is inhibited by cooling the perfused kidney, suggesting that it is powered by metabolic rather than physical sources of energy.

Acetazolamide↗
PubMed1975

Bicarbonate and sodium reabsorption by the isolated perfused kidney.

The role of bicarbonate reabsorption and of transtubular chloride gradients in the bulk reabsorption of sodium and water by renal tubules can be tested in the isolated perfused kidney by perfusing with a medium from which bicarbonate has been omitted. Perfusion of the isolated rat kidney with an artificial medium in which bicarbonate is replaced by chloride results in a fall in fractional reabsorption of sodium from 97 to 84%. Stepwise restoration of bicarbonate concentration in the perfusion medium to 25 meq/liter is associated with a parallel recovery of sodium reabsorption to control levels. Inhibition of bicarbonate reabsorption with acetazolamide produces a slightly smaller reduction in sodium reabsorption (97-89%), an effect not seen in the absence of bicarbonate. Acetazolamide greatly increases phosphate excretion and free water clearance in a way consistent with suppression of proximal tubular reabsorption. By contrast, simple omission of bicarbonate from the perfusing medium does not alter phosphaturia or free water clearance. Reabsorption of bicarbonate appears to account for a fraction of sodium reabsorption roughly equivalent to the proportion of sodium associated stoichiometrically with bicarbonate in the glomerule filtrate. The data do not support the hypothesis that the development of a transtubular chloride gradient is critically important for the reabsorption of a large fraction of the glomerular filtrate.

Acetazolamide↗
PubMed1975

Potassium transport by the isolated perfused kidney.

Rat kidneys perfused outside of the body with an artificial medium are able to increase their fractional excretion of potassium in response to a rising concentration of potassium in the medium but never show net secretion of potassium. By contrast, isolated perfused kidneys from chronically potassium-loaded rats regularly secrete potassium in excess of the amount filtered. Ouabain completely blocks the secretion of potassium by these isolated kidneys, suggesting that Na-K-ATPase mediates potassium secretion by potassium-adapted rats. Neither sodium deprivation, pretreatment with deoxycorticosterone, nor pretreatment with methylprednisolone prepared the kidney to secrete potassium, despite stimulation of Na-K-ATPase activity in cortex or outer medulla. Potassium loading was the only maneuver tested that increased the activity of Na-Katpase in the inner medulla (white papilla) and also produced potassium secretion by the isolated kidney. Surgical ablation of the papilla abolished the net secretion of potassium normally seen in perfused kidneys of potassium-adapted rats, thus underlining the importance of the papilla in the process of potassium adaptation.

Adaptation, Physiological↗
PubMedDate not supplied

Sensitivity of in vivo X-ray fluorescence determination of skeletal lead stores.

Eighteen patients with known past occupational lead exposure underwent parenteral diagnostic chelation with ethylenediaminetetraacetic acid and x-ray fluorescent determination of in vivo skeletal lead stores at the distal styloid process of the ulna and at the temporal base bone using a cobalt 57 source and measuring lead Ka x-rays. X-ray fluorescent lead measurements in both locations correlated with results of diagnostic chelation. Using a post-chelation urinary excretion of greater than 600 micrograms lead/24 h as the definition of "high-" lead stores, sensitivity of x-ray fluorescence at the wrist and temple was 56% and 39%, respectively.

Bone and Bones↗
PubMedDate not supplied

Venous access pressures and the detection of intra-access stenosis.

Venous pressure measured by the dialyzer is an unreliable measure of intra-access venous pressure. During dialysis and zero extracorporeal blood flow, intra-access venous limb pressure (VPd) was measured directly 401 times in 133 subjects using a high flow "in-line" three-way stopcock adjacent to the venous return needle. Subjects with systolic VPd/systolic blood pressure (BP) > or = 0.4, inadequate blood flow, or edema in the access extremity were referred for angiography. Percent diameter lumen reduction by a stenosis (%D) > 50% was considered hemodynamically significant. The authors did 138 angiograms. It was found that VPd/BP increased with %D in both ePTFE bridge grafts and native fistulae. Measurements of venous limb VP/BP taken at the time of dialysis and at the time of angiography did not differ (n = 55). On 80 occasions, accesses had significant stenoses. The overall sensitivity of VPd/BP in ePTFE bridge grafts was 91% and specificity 91%. False negative results occurred in seven of 24 native and eight of 114 ePTFE graft studies; 14 of 15 patients had arm swelling caused by central stenosis. Recirculation > 15% was more sensitive (71%) in detecting stenosis in native accesses than was intra-access pressure. It was concluded that VPd/BP > 0.4 is a useful, sensitive, and specific criteria for detecting synthetic bridge graft accesses at risk for thrombosis.

Angiography↗