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A Cases

Publications and source records attributed to A Cases.

At least 55 records · Page 3Linked to original sources
PubMed1997

In vivo evaluation of platelet activation by different cellulosic membranes.

This study was undertaken to evaluate platelet activation in vivo induced by different cellulosic membranes by measuring the expression of P-selectin on the platelet surface during hemodialysis in 9 uremic patients. Hollow fiber dialyzers of similar surface with different cellulosic membranes (Cuprophan, cellulose acetate, cellulose triacetate, and Hemophan) were evaluated and compared to a synthetic membrane (polysulfone). Blood samples were obtained before hemodialysis and from the efferent and afferent limbs 5 min after the beginning of dialysis. P-selectin exposure was evaluated by flow cytometry (FACScan) using a monoclonal antibody (RUU 2.17). The percentage of platelets expressing P-selectin before hemodialysis and the percentage from the arterial line during hemodialysis were similar. All membranes evaluated induced platelet activation (estimated as the increase in percentage of platelets expressing P-selectin in samples obtained from the venous line with respect to the arterial line). Cuprophan induced more platelet activation than any other membrane (p < 0.05). The activation induced by cellulose acetate and cellulose triacetate membranes was also higher than that observed with Hemophan (p < 0.05). Hemophan-induced platelet activation was similar to that of polysulfone. These results indicate that all cellulosic membranes induce platelet activation during hemodialysis although there are quantitative differences among them. While Cuprophan induced the highest degree of platelet activation, Hemophan was the only cellulosic membrane that showed a degree of platelet activation similar to the biocompatible membrane polysulfone.

Adult↗
PubMed1997

Hemodynamic and renal effects of cross-linked hemoglobin infusion.

It is well known that hemoglobin binds nitric oxide (NO) and produces a pronounced vasoconstriction in isolated arteries. However, it is debatable whether such an effect takes place in whole animals, because hemoglobin also catalyzes the formation of prostaglandins from arachidonic acid. Short-term studies were performed to evaluate the effects induced by intravenous infusion of cross-linked hemoglobin (XL-Hb) on blood pressure (BP) and renal, iliac, and mesenteric flows, and on renal function in six anesthetized dogs. A similar volume-matched expansion with 6% dextran was used as a control (n = 6). Glomerular filtration rate (GFR), urinary flow, and total and fractional sodium excretion were measured before and after XL-Hb or dextran infusion to evaluate possible renal function changes. XL-Hb administration resulted in a 29% elevation in BP and a significant decrease of blood flow (30-37%) to the three vascular beds. XL-Hb did not alter GFR or sodium excretion, despite the increase in BP. In contrast, the administration of dextran did not significantly alter BP but induced a significant increase (6-13%) of blood flow in the three vascular beds. These changes were accompanied by threefold increases in urinary flow and sodium excretion without alterations in GFR. The binding effect of XL-Hb on NO was studied in isolated renal arteries in organ chambers. These in vitro studies showed that XL-Hb blunted the endothelium-mediated vasodilator response to calcium ionophore A-23187 and to acetylcholine. Our results demonstrate that XL-Hb administration is followed by hypertension, vasoconstriction, and blunted natriuresis. All these effects are compatible with the scavenging effect on NO attributed to XL-Hb.

Acetylcholine↗
PubMed1996

Nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria.

A trial to study the efficacy, safety and tolerability of nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria (MA) was performed to compare the effects of both drugs in the prevention of the renal impairment. Twenty-eight valid patients [13 with nitrendipine (N) and 15 with enalapril (E) with NIDDM, hypertension (diastolic blood pressure between 90 to 114 mm Hg) and MA (urinary albumin between 30 to 300 mg/24 hr) were recruited in a double blind, randomized trial. Following a placebo run-in period of two to four weeks, all eligible patients were randomly allocated to either N or E treatment. Treatment lasted six months, with two different visits at three and six months in which blood pressure (BP), heart rate (HR), renal function and MA were measured. No statistically significant differences on BP and metabolic parameters were found between both treatment groups. The geometric mean of final glomerular filtration rate (GFR) in the N group was 34.5% higher than in the E group, while the reduction on MA was most important in the E group. Eleven patients reported adverse events (AEs) and there were four dropouts, three of them due to AEs. We conclude that both treatments are a good choice for treating diabetic hypertensive patients with early altered renal function, as they reduce BP without altering metabolic parameters, increase GFR and reduce MA with a low frequency of AEs.

Adult↗
PubMed1996

Polymorphisms of the human alpha 2A-adrenergic receptor gene in a Catalan population: description of a new polymorphism in the promoter region.

Alpha 2A-adrenergic receptor polymorphisms were investigated in 55 unrelated Caucasian Catalan individuals. Phenotypes were expressed by alpha 2-adrenoreceptor density and affinity determined by radioligand binding. In addition to the two previously described biallelic restriction fragment length polymorphisms (RFLP) (DraI and Bsu36I) [Hoehe et al 1988; Sun et al 1992], a transition was located in the promoter region of the human alpha 2A-adrenergic receptor using a non-radioisotopic single-strand conformational polymorphism (SSCP) analysis. DNA sequence analysis of this region showed that this transition produces the loss of a HhaI site. In our sample, the estimates of the frequency of this allele was 11% and those of DraI alleles were similar to those reported for other Caucasian populations but different from those observed in Afro-Americans. In addition, frequencies of the Bsu36I alleles in the Catalan population differed from those of Japanese and American White populations. A slight linkage disequilibrium between Bsu36I-DraI was found in our population. No association between phenotypes and RFLP genotypes was observed.

Alleles↗
PubMed1995

Reticulated platelets in uremic patients: effect of hemodialysis and continuous ambulatory peritoneal dialysis.

Platelet RNA content can be detected by flow cytometry using thiazole orange staining to identify platelets recently released into the circulation. We studied platelet RNA content and platelet function in uremic patients under different treatment regimens. Four groups were studied: (I) 15 end-stage renal disease (ESRD) patients (10M/5F) on maintenance hemodialysis (HD); (II) 11 ESRD patients (6M/5F) on continuous ambulatory peritoneal dialysis (CAPD); (III) 8 patients with chronic renal failure managed conservatively (5M/3F); and (IV) 34 controls (20M/14F). A double color labeling technique using a phycoerythrin-tagged antibody against glycoprotein Ib (CD42b) and RNA labeling by thiazole orange was performed and read by flow cytometry. Aggregation studies were made in platelet-rich plasma using ADP, epinephrine, collagen, arachidonic acid, and ristocetin. In group I, samples were also obtained after HD. Platelet counts did not differ among the groups. Aggregation studies showed a lower response to ADP and ristocetin in the HD patients, but not in the CAPD or in the chronic renal failure patients. The percentage of platelets with high RNA content in group I was significantly lower than in controls (3.72 +/- 1.72% vs. 9.05 +/- 3.53%, P < 0.01), but was also lower than in the remaining groups (I vs. II P < 0.01, and I vs. III P < 0.01). No differences were seen in platelet RNA content among groups II (8.67 +/- 2.73%), III (9.14 +/- 3.04%) and IV. In group I, the percentage of reticulated platelets decreased further after HD (2.14 +/- 1.09%, P < 0.01). Aggregation studies showed a significantly lower response to ADP and ristocetin in group I (P < 0.05), but not in groups II or III in comparison with controls. Aggregation response to ADP and ristocetin decreased after HD (P < 0.05). In conclusion, HD may decrease the percentage of RNA-rich platelets through elimination of the younger and more active platelets and worsen the thrombopathy present in uremic patients.

Adult↗
PubMed1995

Effect of antihypertensive treatment on the increased beta 2-adrenoceptor density in patients with essential hypertension.

The effect of different antihypertensive drugs on the increased surface beta 2-adrenoceptor density in essential hypertension was evaluated to elucidate whether the possible effect of the treatment on these receptors was secondary to blood pressure decreases or a specific effect of the drugs. Thirty-nine untreated essential hypertensive patients and 28 normotensive control subjects were studied in basal conditions. Hypertensive patients were randomly assigned to three treatment groups: bisoprolol (10 mg/day, n = 15), enalapril (20 mg/day, n = 12), and verapamil SR (240 mg/day, n = 12), and were studied before and after 1 month of treatment. Plasma catecholamines were determined by a radioenzymatic assay. Surface beta 2-adrenoceptors were measured in intact lymphocytes by radioligand binding assay using the hydrophilic ligand [3H]-CGP12177. beta 2-adrenoceptor density was increased in hypertensive patients (P < .01). After treatment, mean blood pressure decreased similarly in the three groups, while plasma catecholamines showed no significant changes in any group. beta 2-adrenoceptor number decreased only in bisoprolol-treated patients (P < .05). Mean blood pressure decreases correlated with beta 2-adrenoceptor decrements only in bisoprolol-treated patients (r = 0.65, P < .05). beta 2-adrenoceptor density correlated with plasma epinephrine levels in the control group (r = -0.50, P < .01), but not in hypertensive patients before treatment. This correlation was also observed in hypertensive patients treated with bisoprolol (r = -0.52, P < .05), but not in those treated with verapamil or enalapril. Our results suggest that bisoprolol treatment reduces the increased surface beta 2-adrenoceptor density and restores its regulation by epinephrine in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Uraemic medium causes endothelial cell dysfunction characterized by an alteration of the properties of its subendothelial matrix.

Uraemic patients suffer from haemorrhagic disorders and accelerated atherosclerosis. To evaluate the possible role of the vessel wall in these haemostatic alterations associated with uraemia, we investigated the effect of a uraemic milieu on human endothelial cell (EC) cultures and the reactivity of the extracellular matrices (ECM) generated by these cells towards platelets. EC cultures were exposed to a pool of sera (20% in the culture medium) obtained either from uraemic patients or from normal donors, and the following parameters were evaluated: (1) EC viability (trypan blue exclusion test); (2) von Willebrand factor (vWF) levels in supernatants and associated with ECM; (3) the reactivity of EC and EC-derived ECM towards platelets, measured 'ex vivo' under flow conditions (5 min, wall shear rate 800 s-1); and (4) ultrastructure of the ECM. The viability of EC cultured in the presence of uraemic sera was similar to controls. Platelet interaction with ECM generated by EC exposed to uraemic sera was significantly reduced (P < 0.05). This decrease was mainly related to a reduction in platelet adhesion (9.8 +/- 1.9% vs 16.7 +/- 1.8% in controls, P < 0.02). VWF levels in supernatants and associated with ECM were similar to controls. Ultrastructural analysis of the ECM generated by EC exposed to uraemic sera revealed a deficient matrix. An increased removal of EC was observed in experiments in which EC cultured in the presence of uraemic sera were perfused with citrated blood. These results indicate that a uraemic milieu induces quantitative and qualitative changes in the vascular subendothelium, characterized by a less intrincate network of fibrils, as well as a decreased attachment of EC and reduced thrombogenicity to the ECM. These changes may represent another mechanism which contributes to the haemostatic dysfunction observed in uraemic patients.

Blood Platelets↗
PubMed1995

Patients with multiple myeloma requiring long-term dialysis: presenting features, response to therapy, and outcome in a series of 20 cases.

From January 1982 to December 1993, 30 patients with multiple myeloma (MM) required haemodialysis (HD) at our institution. The subgroup of 20 patients who survived more than 2 months on HD is the subject of this study. Four patients were already on HD, due to previous nephropathy, when MM was diagnosed. 13 patients presented with acute renal failure and were on dialysis from the time of diagnosis. The remaining three cases developed renal failure later in the course of the disease. The objective response rate was 40% (8/20). Only two patients could discontinue HD (one had a late partial recovery and one received a kidney graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who survived < 1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup with a survival > 1 year mean hospitalization days was 9.6 (P < 0.001). The median survival was 20 months and six patients survived for > 3 years. In summary, patients with MM and severe renal failure who survive the first 2 months on dialysis have an objective response rate to chemotherapy of 40% and a median survival of almost 2 years, with 30% long-term survivors.

Acute Kidney Injury↗
PubMed1995

Reversible decrease of surface beta 2-adrenoceptor number and response in lymphocytes of patients with pheochromocytoma.

To study the effect of chronic exposure to elevated plasma catecholamines on surface beta 2-adrenoceptor density, we measured these receptors in the lymphocytes of 9 patients with pheochromocytoma as well as in 27 healthy control subjects. Binding experiments were performed on intact lymphocytes using the hydrophilic ligand [3H]-CGP12177. Lymphocyte beta 2-adrenergic response was also measured in three patients. beta 2-adrenoceptor density (p < 0.01), and isoproterenol-stimulated increase in cAMP were reduced in patients with pheochromocytoma. Both parameters normalized (p < 0.05) when patients were reevaluated 4 weeks after tumor removal, coinciding with normalization of plasma epinephrine (r = -0.95, p < 0.01) and to log of plasma norepinephrine (r = -0.58, p < 0.05) in patients. We conclude that chronic catecholamine excess induces a decrease of lymphocyte beta 2-adrenoceptor surface number and response that is reversible upon normalization of plasma catecholamine levels. This regulation is mainly dependent on plasma levels of the hormone epinephrine, but norepinephrine may also play a regulatory role at supraphysiological levels.

Adrenal Gland Neoplasms↗
PubMed1994

[Intravenous calcitriol in the treatment of the refractory secondary hyperparathyroidism of terminal chronic kidney failure].

BACKGROUND: In advanced cases of secondary hyperparathyroidism (HPT) in terminal chronic renal failure, the oral treatment of calcitriol is not possible due to the development of hypercalcemia. It has been demonstrated that calcitriol directly inhibits the secretion of parathormone (PTH), independently of calcium. Therefore the intravenous administration of high and intermittent doses of calcitriol (ivVD) has been proposed as an alternative treatment for resistant HPT. METHODS: The response of PTHi to treatment over 6 months with ivVD was evaluated in 18 patients with moderate-severe HPT resistant to the classical schedules. RESULTS: An important decrease was observed in the PTHi values (basal: 698 +/- 277 pg/ml, end of treatment: 272 +/- 200; p < 0.05). Alkaline phosphatase values followed a parallel course (basal: 476 +/- 286 U/l, end of treatment: 301 +/- 276 U/l, p < 0.05). Fifty-five percent of the patients presented hypercalcemia at some time (Ca > or = 11.5 mg/dl) being controlled by a decrease in the doses of calcitriol or calcium in dialysis fluid. No response was observed in 3 patients (17%) with treatment being discontinued due to presentation of uncontrollable hypercalcemia. CONCLUSIONS: The administration of intravenous calcitriol at high and intermittent doses is effective in a considerable number of patients with hyperparathyroidism resistant to the classical oral schedules. Its use may avoid surgical parathyroidectomy in some cases.

Adult↗
PubMed1994

Platelet activation during hemodialysis measured through exposure of p-selectin: analysis by flow cytometric and ultrastructural techniques.

P-selectin is a platelet protein in alpha-granules that is expressed on their membranes after platelet activation. Using a specific monoclonal antibody (RUU-2.17), we have studied platelet activation during hemodialysis with a cuprophan membrane in eight patients with uremia. Blood samples were obtained before hemodialysis from venipuncture (sample I), at the beginning of the hemodialysis from the arterial (sample II) and venous lines (sample III), and after 2 hours of hemodialysis from the venous line (sample IV). Exposure of P-selectin on platelet surface was studied by flow cytometry, and morphologic and immunocytochemical studies were performed. No differences in P-selectin expression were observed by single-labeling flow cytometry in samples I, II, and IV. However, a significant increase in fluorescence occurred in sample III (percentage of positive platelets [%PP], 18.0% +/- 6.1%) with respect to sample I (%PP, 6.9% +/- 2.0%; p < 0.01). An apparently decreased fluorescence was seen in sample IV (%PP, 8.8% +/- 3.9%) with respect to sample III. Double-labeling flow cytometry showed statistically significant differences between sample I (%PP, 7.1% +/- 2.6%) and sample III (%PP, 19.4% +/- 9.4%; p < 0.01) and IV (%PP, 19.0% +/- 10.1%; p < 0.01), but not between samples III and IV. The ultrastructural study revealed an increasing number of platelet morphologic signs of activation throughout the period of hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Intracellular calcium mobilization and activation of the Na+/H+ exchanger in platelets.

The aim of the present study was to evaluate the regulatory relationship between the cytosolic free calcium concentration ([Ca2+]i and cytosolic pH (pHi). [Ca2+]i and pHi were measured using the fluorescent dyes fura-2 and BCECF [2',7'-bis-(carboxyethyl)-5,6-carboxyfluorescein] respectively. In a medium with 1 mmol/l extracellular calcium, thrombin (2.5 units/ml) induced an increment in [Ca2+]i of 638 +/- 31 nmol/l (n = 5) and an intracellular alkalinization of 0.14 +/- 0.01 pH units (n = 8). Both responses were dependent on the concentration of thrombin, displaying a sigmoidal dose-response pattern. The intracellular alkalinization was dependent upon extracellular Na+ and was amiloride-sensitive, indicating that it was mediated by activation of the Na+/H+ exchanger. When extracellular calcium was chelated with EGTA prior to the addition of thrombin, the intracellular alkalinization was not affected (0.15 +/- 0.02 at 2.5 units/ml thrombin, n = 8). Under these circumstances, the [Ca2+]i increment represents mobilization from internal stores, reaching 157 +/- 42 nmol/l at 2.5 units/ml thrombin. When platelets were preloaded with the intracellular calcium chelator MAPTAM (1,2-bis-5-methylaminophenoxylethane-NNN'-tetraacetoxymethyl acetate) to block the increase in [Ca2+]i induced by thrombin, no increment in pHi was observed. Moreover, MAPTAM-loaded calcium-depleted platelets had a basal pHi that was more acidic than in the presence of 1 mmol/l extracellular calcium (6.93 +/- 0.09 versus 7.14 +/- 0.01, n = 26, P < 0.001). Ionomycin induced an elevation of [Ca2+]i that was accompanied by a concomitant increase in pHi, which was Na(+)-dependent and amiloride-sensitive. [Ca2+]i and pHi increases induced by ionomycin were both dependent on the concentration of ionomycin. In conclusion, an increase in [Ca2+]i is necessary for the agonist-induced activation of the Na+/H+ exchanger in platelets. Non-agonist-induced increases in [Ca2+]i seems to prompt activation of the exchanger. In addition, Ca(2+)-depleted platelets have a more acidic basal pHi, indicating that the basal level of [Ca2+]i is also important for maintaining the basal pHi.

Blood Platelets↗
PubMed1993

Minimal-change glomerulopathy and carcinoma. Report of two cases and review of the literature.

We describe 2 patients with minimal-change glomerulopathy (MCG) associated with an undifferentiated carcinoma of unknown origin and urothelial carcinoma. Oliguric acute renal failure and histopathological changes consistent with acute tubular necrosis were also observed. Fourteen other cases of MCG complicating solid tumors reported in the literature are reviewed. MCG should be included in the nephropathies which cause nephrotic syndrome in adult patients with carcinoma.

Acute Kidney Injury↗
PubMed1993

Platelet activation on hemodialysis: influence of dialysis membranes.

During hemodialysis, platelets are activated and release alpha-granule-specific proteins. GMP-140 is a glycoprotein stored in the alpha-granules of platelets, which is selectively expressed on the plasma membrane of activated platelets. Using a specific monoclonal antibody against this protein (CD 62), we have evaluated the influence of different dialysis membranes on hemodialysis-induced platelet activation in vivo by flow cytometry in nine patients with end-stage renal disease on maintenance hemodialysis. Five membranes were evaluated: Cuprophane, cellulose acetate, polymethylmethacrylate, polysulphone and polyacrylonitrile (AN-69). Blood samples were obtained before hemodialysis and from the inlet and outlet lines five minutes after the beginning of hemodialysis. A significant increase in the GMP-140 expression was observed in samples obtained from the outlet line compared with samples obtained from the inlet line for all membranes evaluated, but the extent of this increase depended on the type of membrane used: Cuprophane 13.95 +/- 3.94%, cellulose acetate 7.4 +/- 4.52%, polymethylmethacrylate 6.93 +/- 4.6%, polysulphone 3.83 +/- 2%, and AN-69 2.14 +/- 2.19% (mean +/- SD). Cuprophane induced the highest degree of platelet activation (P < 0.05). Cellulose acetate and polymethylmethacrylate induced more platelet activation than polysulphone or AN-69 (P < 0.05). These data demonstrate that all hemodialysis membranes induce platelet activation but to a variable extent, cuprophane being the most activating membrane, cellulose acetate and polymethylmethacrylate showing an intermediate potential of activation, while the more biocompatible membranes, polysulphone and AN-69, inducing the lowest degree of platelet activation.

Adult↗
PubMed1993

Abnormal cytoskeletal assembly in platelets from uremic patients.

The mechanisms involved in the hemostatic abnormality of uremic patients remain obscure. We have explored the response of normal and uremic platelets to surface activation at the ultrastructural level and analyzed changes in the composition of proteins associated with normal and uremic platelet cytoskeletons after stimulation with thrombin (0.01 and 0.1 U/ml). Cytoskeletons were obtained by extraction with Triton X-100, processed by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and the presence of cytoskeletal proteins analyzed by densitometry. Under static conditions, uremic platelets spread with difficulty on formvar-coated grids. The percentage of platelets that spread fully on this polymer surface was statistically reduced compared with that of control platelets (11 +/- 1.4 vs. 21 +/- 1.6; P < 0.05). An impairment of cytoskeletal organization was observed in resting uremic platelets but abnormalities were more evident after thrombin activation. The incorporation of actin into the cytoskeletons of thrombin-stimulated uremic platelets was significantly reduced with respect to controls (6 +/- 3% vs. 29 +/- 5%; P < 0.01 after 0.01 U/ml and 28 +/- 9% vs. 59 +/- 10%; P < 0.05 after 0.1 U/ml). Decreased associations of actin-binding protein (P < 0.01), alpha-actinin (P < 0.05), and tropomyosin (P < 0.05) with the cytoskeletons of uremic platelets were also noted. No difference was observed for the incorporation of myosin into the cytoskeletons of activated uremic platelets. These results suggest functional and biochemical alterations of the platelet cytoskeleton in uremia, which may contribute to the impairment of platelet function observed in uremic patients.

Adult↗