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H R Keiser

Publications and source records attributed to H R Keiser.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Role of magnetic resonance in the study of benign and malignant pheochromocytomas. Quantitative analysis of the intensity of the resonance signal].

In order to assess the clinical role of Magnetic Resonance (MR) imaging in patients with benign or malignant pheochromocytomas, the MR signal intensity ratios of benign and malignant tumors were evaluated. Eighteen patients (9 men and 9 women, mean age: 37 +/- 8 years) with benign (n = 10) or malignant (n = 8) pheochromocytomas were studied. A total of 27 lesions (12 benign and 15 malignant) were analyzed. In all patients, histology confirmed the disease. MR studies were performed using a 1.5-T superconducting magnet system. Sequences were used to obtain T1-weighted (TR/TE 300/12 ms) and T2-weighted (TR/TE 2000/80 ms) images. On both T1- and T2-weighted MR images, the mean absolute signal intensity values of tumor lesions, of liver, muscle and fat tissues, and of image background were measured to obtain the corresponding signal intensity ratios for each lesion. Our results exhibited no statistically significant differences in both T1 and T2 MR signal intensity ratios between benign and malignant lesions. In conclusion, our results suggest that MR imaging cannot differentiate benign from malignant lesions in patients with pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1993

Iodine-131-metaiodobenzylguanidine scintigraphy in preoperative and postoperative evaluation of paragangliomas: comparison with CT and MRI.

Iodine-131-metaiodobenzylguanidine (MIBG) scintigraphy, transmission computed tomography and magnetic resonance imaging were used to evaluate 36 patients with clinically suspected functioning paragangliomas. The patients were divided into two groups. In Group 1 (n = 21), studied before surgery, patients mainly had benign adrenal disease. In Group 2 (n = 15), studied after surgery, patients frequently had malignant or extra-adrenal tumors. In Group 1, transmission computed tomography and magnetic resonance imaging were more sensitive (100% for both) than MIBG scintigraphy (82%), which, however, was the most specific (100%). In Group 2, MIBG scintigraphy and magnetic resonance imaging were more sensitive (83% for both) than transmission computed tomography (75%), but MIBG was again the most specific (100%). Thus, all three were complementary modalities for localizing paragangliomas both preoperatively and postoperatively. MIBG imaging is indicated for both groups but it is especially recommended for postsurgical patients with recurrence because the disease is often malignant or extra-adrenal.

3-Iodobenzylguanidine↗
PubMed1993

Determination of metanephrines in plasma by liquid chromatography with electrochemical detection.

Metanephrines are O-methylated metabolites of catecholamines. We report the use of liquid chromatography with electrochemical detection to determine plasma concentrations of normetanephrine (NMN) and metanephrine (MN). Plasma NMN and MN in 32 normal volunteers and inpatients were compared with concentrations in 23 patients with pheochromocytoma. Metanephrines were adsorbed from plasma onto a cation-exchange column and eluted with ammoniacal methanol. The dried residue was dissolved in mobile phase and injected onto a reversed-phase column. Recoveries of NMN and MN from 1 mL of plasma averaged 50-70%, and results varied linearly with quantity injected over a range of 0.13-55 pmol. The detection limit was 25 fmol for NMN and 50 fmol for MN. Intra-assay CVs were < 5%. In normal volunteers and inpatients, plasma concentrations of NMN ranged between 0.12 and 0.73 nmol/L (mean 0.38 nmol/L), and MN between 0.06 and 0.63 nmol/L (mean 0.19 nmol/L). Plasma NMN concentrations were increased in all 23 patients with pheochromocytoma (range 1-172 nmol/L), whereas MN concentrations (range 0.10-382 nmol/L) were increased in only 9 patients. The assay method is reliable and sensitive and offers an approach to examine the extraneuronal metabolism of catecholamines. The method may also be useful in the diagnosis of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1992

Neutral endopeptidase inhibition increases the urinary excretion and plasma levels of endothelin.

The pathway for removal of the circulating potent vasoconstrictor peptide, endothelin (ET), is unclear. To determine the contribution of neutral endopeptidase (NEP) to ET metabolism, urinary excretion (UETV) and plasma levels of ET (P(ET)) were measured after infusion of the NEP inhibitor (NEP-I), SQ 29,072 (30 mg/kg [n = 10] and 60 mg/kg [n = 6]), in anesthetized Munich Wistar rats. Both doses significantly increased UETV at 30, 60, and 90 minutes; the maximal effect was obtained 30 minutes after infusion, and the response was longer in rats pretreated with the higher dose of the inhibitor. P(ET) increased 36% and 55% (P less than or equal to .05) at 30 and 120 minutes after injection of the larger dose of SQ 29,072. We also studied the effect of NEP-I on the excretion of exogenous ET after the infusion of 125I-ET (1 microCi) in rats pretreated with either NEP-I or vehicle. In rats treated with the lower dose of the inhibitor, urinary radioactivity increased 2.1- and 1.5-fold (P less than or equal to .05 v control) after 30 and 60 minutes, respectively. After the higher dose of NEP-I, urinary radioactivity increased 2.7- and 1.7-fold (P less than or equal to .05). The distribution of the urinary radioactivity as defined by high-performance liquid chromatography (HPLC) showed that intact labeled ET accounts for only 6% to 9% of the total counts recovered in urine from control rats, while the remainder was either free iodine or other products of hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Pharmacokinetics of ANF and urodilatin during cANF receptor blockade and neutral endopeptidase inhibition.

Urodilatin is a new member of the family of natriuretic peptides. It is of renal origin. Previous reports indicate that urodilatin is natriuretic in lower doses than atrial natriuretic factor (ANF)-(99-126) and that it might be more effective than ANF in the treatment of cardiovascular edema. The present study was designed to compare the pharmacokinetics of the hydrolysis and clearance of 125I-labeled urodilatin and 125I-ANF. In control rats, the volume of distribution (Vss), metabolic clearance rate (MCR), and distribution half-life (distribution t1/2) of urodilatin in plasma were not significantly different from those of ANF. Infusion of clearance (c)ANF-(4-23), a specific ligand for receptors that clear ANF in excess amounts (i.e., a bolus injection of 100 micrograms/kg followed by a continuous infusion of 10 micrograms.kg-1 x min-1), increased the amount of intact peptide in the plasma to the same extent for both urodilatin and ANF. In addition, cANF-(4-23) decreased the Vss and the MCR and increased the distribution t1/2 of both peptides to about the same degree. Prior treatment of rats with SQ-28,603, a specific neutral endopeptidase (NEP; EN 3.4.24.11) inhibitor, was without significant effect on the metabolic clearance of urodilatin, whereas it decreased the clearance of ANF by 65%. Furthermore, an infusion of SQ-28,603 suppressed the appearance of the hydrolytic products of ANF in blood but not of urodilatin. Moreover, the inhibitor increased the total amount of ANF recovered in the kidneys to five times the control values, whereas it did not alter the renal uptake of urodilatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1992

Renal and systemic effects of urodilatin in rats with high-output heart failure.

Urodilatin is a recently discovered natriuretic peptide [ANP-(95-126)] of renal origin, with a primary structure similar to ANP-(99-126). However, urodilatin is not biologically inactivated by renal endopeptidase, and it is a more potent natriuretic agent than ANP-(99-126). The present study was carried out to investigate the renal and systemic effects of urodilatin in rats before and after the induction of congestive heart failure (CHF) by creation of an aortocaval fistula (ACF). Administration of urodilatin in incremental doses (0.75-12 micrograms.kg-1.h-1) to Inactin-anesthetized sham-operated control rats resulted in dose-dependent increases in urine flow, glomerular filtration rate (GFR), excretion of guanosine 3',5'-cyclic monophosphate (cGMP), sodium, and potassium, and a significant decrease in mean arterial blood pressure. In rats with ACF the baseline values for GFR and sodium excretion were significantly lower than in control rats. Urodilatin infusion in rats with ACF led to significant increases in urine flow and sodium excretion, but the absolute levels of diuresis and natriuresis were significantly lower in rats with CHF than in normal rats. When urodilatin was infused into rats with ACF pretreated with neutral endopeptidase inhibitor (NEP-I; SQ-28,063 at a dose of 40 mg/kg iv), the absolute urine flow and sodium excretion were not different from that obtained in control rats. Thus the attenuated natriuretic and diuretic response to ANP-(99-126) in heart failure was not observed with urodilatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Role of neutral endopeptidase in the metabolism of endothelin.

Endothelin is a potent vasoconstrictor produced by endothelial cells. Although endothelin has been studied extensively, little is known about its metabolism in vivo. Neutral endopeptidase EC.3.4.24.11 is reported to degrade endothelin in vitro. Therefore, we studied the effect of neutral endopeptidase inhibition by SQ29,072 on plasma levels and urinary excretion of endogenous and exogenous endothelin. Injection of 30 or 60 mg/kg SQ29,072 into anesthetized rats increased the urinary excretion of endothelin nearly 14-fold. The response was maximal during the first 30 minutes of collection and lasted for 90 minutes. The larger dose of inhibitor caused a 37-43% increase (p less than or equal to 0.05) in the plasma concentration of endothelin. Only 0.20 +/- 0.04% of the total radioactivity injected as 125I-endothelin (1 microCi; 1,308 pg) into normal rats was recovered in the urine within 30 minutes. Urinary radioactivity increased to 0.54-0.63% (p less than or equal to 0.05) of the total infused in rats pretreated with SQ29,072. Chromatographic analysis of radioactivity in the urine revealed that intact endothelin accounted for only 6-9% of the total counts in control rats but 50-56% in rats pretreated with the inhibitor. We also studied the effects of another inhibitor of neutral endopeptidase, SQ28,063, on the distribution of radioactivity in the urine, kidney, and lung of rats injected with 125I-endothelin. SQ28,063 increased urinary excretion of labeled endothelin and increased total radioactivity accumulated in the lung and kidney from 157 and 105 pg to 234 and 157 pg, respectively. Intact endothelin accounted for 90% or more of the accumulated counts in both tissues. These results indicate that 1) little circulating endothelin is cleared into the urine, 2) endothelin in the urine is likely of renal origin, and 3) neutral endopeptidase EC.3.4.24.11 plays a major role in the inactivation of endothelin.

Amino Acids↗
PubMed1992

Interaction of prostaglandins with adenosine diphosphate induced increase in cytosolic free calcium in human platelets.

The interaction of prostaglandins with changes in cytosolic Ca2+ concentration ([Ca2+]) and aggregation of human platelets induced by adenosine diphosphate (ADP) were investigated. Cytosolic [Ca2+] was measured with the fluorescent dye Quin2. Addition of ADP (0.25-2.5 mumol l-1) to platelet suspensions produced a dose dependent increase in cytosolic [Ca2+] from a basal level of 51 +/- 1 nmol l-1 to maximum levels exceeding 1 mumol l-1 and induced platelet aggregation. Chelation of extracellular calcium with 100 mumol l-1 EGTA markedly reduced the increase in cytosolic [Ca2+] induced by 0.25 mumol l-1 ADP, while pretreatment with the calcium entry blocker verapamil was without effect. Stimulation of cyclic AMP with prostaglandins (PGD2, PGE1, PGE2, PGI2, but not PGF2 alpha) and forskolin, or incubation with dibutyryl-cAMP, inhibited the rise in cytosolic [Ca2+] and platelet aggregation following ADP. We conclude that prostaglandins inhibit the increase in cytosolic [Ca2+] and aggregation of human platelets induced by ADP, probably by stimulation of cyclic AMP generation, thereby opposing the mechanism by which ADP increases cytosolic [Ca2+] and subsequently induces platelet aggregation.

Adenosine Diphosphate↗
PubMed1991

Simultaneous measurement of plasma and brain extracellular fluid concentrations of catechols after yohimbine administration in rats.

The present study examined whether systemic injection of the alpha 2 adrenoceptor blocker, yohimbine, affects concentrations of norepinephrine (NE) and its metabolites in extracellular fluid in the brain and in blood. Microdialysis probes were inserted into the posterior hypothalamus, medulla, and caudate/putamen in rats. Microdialysate and arterial blood were sampled after intravenous administration of yohimbine. In the hypothalamus yohimbine produced significant increases in extracellular fluid concentrations of NE, its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), and methoxyhydroxyphenylglycol (MHPG), a major neuronal and extraneuronal metabolite of NE. The increases in these levels were small or absent in the caudate/putamen, where dopamine is the primary catecholamine transmitter. During systemic infusion of tracer amounts of [3H]NE, little if any radioactive NE or DHPG appeared in the microdialysate, whereas substantial levels of [3H]MHPG were present and increased as plasma [3H]MHPG levels rose. The results support the view that alpha 2 adrenoceptor blockade in the brain increases hypothalamic and medullary release, reuptake, and metabolism of NE. The findings cannot be explained by disruption of the blood-brain barrier for catecholamines by insertion of the microdialysis probes. Enhanced sympathetic outflow and peripheral release of NE when alpha 2 adrenoceptors are blocked appears to be attended by enhanced central NE release, presumably as a result of presynaptic alpha 2 adrenoceptor blockade at noradrenergic terminals in the brain. This is consistent with the hypothesis that central noradrenergic NE release is regulated by presynaptic alpha 2 adrenoceptors.

Animals↗
PubMed1991

Increased plasma levels and blunted effects of brain natriuretic peptide in rats with congestive heart failure.

The hemodynamic and renal effects of brain natriuretic peptide (BNP) were studied in conscious rats with experimental congestive heart failure (CHF) produced by an aortocaval fistula. The peptide had potent hypotensive, diuretic, and natriuretic effects in control rats, all of which were abolished in CHF. Plasma levels of BNP increased time-dependently during the development of CHF, and were more than four-fold higher in sodium retaining rats than in control rats. The data suggest that BNP secretion from the atria is increased in CHF, and that resistance to BNP, in addition to the relative resistance to atrial natriuretic factor, may contribute to sodium retention in CHF.

Animals↗
PubMed1991

Endogenous dopa and dopamine responses to dietary salt loading in salt-sensitive rats.

We measured daily urinary excretion rates of dopamine and dopa during dietary salt loading and natriuretic responses to exogenous dopamine in Dahl salt-sensitive (DS), Dahl salt-resistant (DR) and Sprague-Dawley rats. Excretion rates of dopa increased approximately sixfold during salt loading in all rat strains. Maximal urinary dopa responses were attained within 1 day of salt loading. Daily excretion rates of dopamine also increased about five- to sixfold in DS and DR rats and about twofold in Sprague-Dawley rats, with maximal dopamine responses attained by day 5. Dopamine infusion (3 micrograms/kg per min) increased urinary sodium excretion by 406 +/- 132 % (mean +/- s.e.m.) in Sprague-Dawley rats but only 267 +/- 131% and 147 +/- 80% in DS and DR rats (P less than 0.05 for Sprague-Dawley versus Dahl rats). The results demonstrate that salt loading markedly and rapidly increases dopa excretion in rats. Considering values for dopamine excretion in other rat strains, the results suggest that Dahl rats have increased formation of dopamine for a given amount of dopa delivery to the kidney and that this abnormality is unrelated to salt-sensitive hypertension in DS rats. The results also provide in vivo support for the view that the responsiveness of renal dopamine receptors mediating natriuresis is related to production of endogenous dopamine in the kidney.

Animals↗
PubMed1991

Glucagon and clonidine testing in the diagnosis of pheochromocytoma.

We assessed the sensitivity and specificity of glucagon stimulation and clonidine suppression tests in the diagnosis of pheochromocytoma in 113 hypertensive patients, 39 with and 74 without the tumor. In the glucagon stimulation test, blood was sampled 2 minutes after intravenous injection of 0.28 mumol (1 mg) glucagon, and in the clonidine suppression test, blood was sampled 3 hours after administration of oral clonidine, 1.30 mumol (0.3 mg)/70 kg body wt. Baseline levels of catechols in antecubital venous blood were abnormal, with norepinephrine greater than 7.10 nmol/l (1,200 pg/m), epinephrine greater than 1.51 nmol/l (276 pg/ml), norepinephrine/dihydroxyphenylglycol (DHPG) ratio greater than 1.09, or dopa greater than 35.53 nmol/l (7,000 pg/ml), in 30 of 39 patients with pheochromocytoma (sensitivity 77%) and 1 of 74 patients without pheochromocytoma (specificity 99%). Results of the glucagon test were abnormal (norepinephrine greater than 11.83 nmol/l [2,000 pg/ml] or more than threefold increase from baseline) in 25 of 31 patients with pheochromocytoma (sensitivity 81%) and 0 of 72 patients without pheochromocytoma (specificity 100%). Results of the clonidine test were abnormal (after clonidine norepinephrine greater than 2.96 nmol/l [500 pg/ml] or less than 50% decrease from baseline) in 29 of 30 patients with pheochromocytoma (sensitivity 97%) and in 7 of 30 patients without pheochromocytoma (specificity 67%). Very high baseline levels of catechols therefore indicated the presence of pheochromocytoma, but there were several false-negative results when normal levels were obtained. The glucagon test alone was highly specific but not sensitive, and the clonidine test was highly sensitive but less specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1991

Differences in response between SHRSP and WKY vascular smooth muscle cells to inhibition of cell proliferation by sodium nitroprusside.

The effects of sodium nitroprusside on the proliferation of cultured vascular smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were examined. Sodium-nitroprusside (SNP, 1mM) inhibited DNA synthesis by SMC from SHRSP and WKY by 90% and 95%, respectively. SNP also decreased cell proliferation. However, SNP was inactive when SMC were pretreated 6 and 12 hrs before growth stimulation by FCS. On the other hand, the inhibitory action of SNP decreased with time (posttreatment) in SHRSP SMC (42% inhibition at 12 hr post addition). However, in WKY SMC, the decrease of inhibitory action was very slight and SNP still inhibited 73% of DNA synthesis at 12 hr post treatment. SNP inhibited RNA synthesis for 3-6 hr and 6-9 hr after FCS stimulation, however no difference was noted between SHRSP and WKY. Protein synthesis was inhibited more strongly by SNP (9-12 hr after FCS stimulation) in WKY SMC than SHRSP SMC. It is probable that the specific protein(S) whose synthesis is inhibited by SNP is/are responsible for the differences in cell proliferation rate between SHRSP and WKY SMC.

Animals↗
PubMed1991

Presence of immunoreactive endothelin in synovial fluid: analysis of 22 cases.

The endothelins are a family of recently defined active peptides with a wide range of activities, including the activation of the synthesis of prostaglandins. The concentration of endothelin in inflammatory and noninflammatory synovial fluids (SF) was measured by a sensitive radioimmunoassay. Endothelin-like immunoreactivity was detectable in all SF samples and the mean concentration of endothelin was 2.6 +/- 0.3 pg/ml, more than twice that in normal human plasma. The mean level of endothelin in SF in rheumatoid arthritis was 2.5 +/- 0.4 pg/ml (n = 11), and was not statistically different from either osteoarthritis, 3.0 +/- 0.5 pg/ml (n = 7), or acute inflammatory arthritis, 2.0 +/- 0.4 pg/ml (n = 4). Our data do not support the hypothesis that endothelin plays an important role in the pathogenesis of inflammatory arthritis.

Aged↗
PubMed1990

Opposite effects of endothelin-1 and Big-endothelin-(1-39) on renal function in rats.

Bolus injections of Big-endothelin-(1-39) (Big-ET; 0.1-3.0 nmol/kg) induced a dose-dependent diuretic and natriuretic response in conscious Sprague-Dawley rats. Endothelin-1-(1-21) (ET-1; 1 nmol/kg) induced an opposite effect with almost complete renal shut down. Renal blood flow did not change with Big-ET but was reduced by half with ET-1. Although the maximal pressor responses of the two peptides were comparable the renal resistance did not change with Big-ET but increased 4-fold with ET-1. These data suggest that Big-ET may have a different mechanism of action than ET-1.

Anesthesia↗
PubMed1990

Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features.

The clinical and pathologic features of 120 adrenal and extraadrenal paragangliomas were studied in an attempt to identify features which might predict malignant behavior. Clinical follow-up was obtained in 98 cases (82%); 64 tumors were clinically benign, and 34 were malignant as evidenced by regional or distant metastases and/or extensive local invasion. Thirty-two of the 34 malignant tumors (94%) were functionally active. Features noted more frequently in malignant tumors included male predominance (74%; P2 [two-sided P value] = .002), extraadrenal location (52%; P2 less than .0001), greater tumor weight (mean 383 g versus 73 g for nonmalignant tumors), confluent tumor necrosis, and the presence of vascular invasion and/or extensive local invasion. Intracytoplasmic hyaline globules were seen in 59% and 32% of benign and malignant tumors, respectively (P2 = .001). Logistic regression analysis of 16 nonhistologic and histologic parameters showed four of them to be most predictive of malignancy--extraadrenal location, coarse nodularity of the primary tumor, confluent tumor necrosis, and absence of hyaline globules. Most malignant paragangliomas had two or three of these features (71%), while 89% of benign tumors had only one (or none; P less than .0001). According to the statistical model developed, there was better than a 95% probability that more than 70% of tumors could be classified correctly on the basis of the four factors indicated. Although limitations still exist, results of this study provide some basis for evaluating malignant potential of these tumors.

Adolescent↗