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A D'Angelo

Publications and source records attributed to A D'Angelo.

At least 19 recordsLinked to original sources
PubMed1992

Monoclonal antibody-based enzyme-linked immunosorbent assays (ELISA) for the measurement of vitamin K-dependent protein S: the effect of antibody immunoreactivity on plasma protein S antigen determinations.

Two monoclonal antibodies (Mabs) specifically directed to human protein S (PS) - named 5E9E9 and 3B10.25 - were produced and their properties compared to those of 2 previously characterized anti-PS-Mabs (HPS-2 and S10). 3B10.25, similar to S10, was directed to the calcium-free conformation of PS and had virtually identical affinity for free and C4b-binding protein (C4b-BP)-bound PS; 5E9E9 similar to HPS-2, had no calcium-dependency and was selectively directed to free PS. All Mabs were equally reactive to freshly purified and thrombin-cleaved PS. To evaluate the influence of C4b-BP bound PS on PS antigen determinations, ELISA systems employing the four Mabs individually as capture antibody (Ab) and peroxidase-conjugated polyclonal anti-PS IgG as detecting Ab were developed and compared to immunoelectrophoresis (EIA) and to an ELISA employing polyclonal anti-PS IgG as capture and detecting Ab, in the determination of PS in purified systems and in plasma. With all the ELISAs there was parallelism of dilution curves obtained with normal plasma and purified PS; however, supplementation of plasma with purified C4b-BP resulted in loss of parallelism when employing the Mabs directed to free PS as capture Ab. Influence of high C4b-BP on PS antigen determinations was confirmed in a series of plasma samples from patients with C4b-BP levels ranging from 70% to over 200%. Compared to the values obtained with the S10- or 3B10.25 - based ELISAs - which were similar despite a 10-fold difference in sample dilution - plasma PS was underestimated by the ELISAs employing 5E9E9 or HPS-2 while it was overestimated by EIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Venous thromboembolism in acute stroke. Prognostic importance of hypercoagulability.

To assess the incidence, risk factors, and clinical importance of deep vein thrombosis in acute stroke, we studied 70 consecutive patients who underwent hemostasis screening at the time of entry into the study and followed up these patients with serial venous Doppler examinations and the iodine 125-labeled fibrinogen uptake test. Mortality was significantly higher among the 20 patients who developed a deep vein thrombosis, and eight of them had necropsy evidence of pulmonary embolism. Severity of leg paresis and a shortened activated partial thromboplastin time were significantly associated with subsequent deep vein thrombosis with multivariate analysis. Significantly higher levels of fibrinopeptide A were found in patients with postmortem evidence of pulmonary embolism. Deep vein thrombosis is a frequent complication of acute stroke and may influence the prognosis by inducing pulmonary embolism. Our findings allow rapid identification of high-risk patients who may benefit maximally from prophylactic treatment of venous thromboembolism.

Adult↗
PubMed1992

Normal tissue plasminogen activator and plasminogen activator inhibitor activity in plasma from patients with type 1 diabetes mellitus.

The fibrinolytic system was investigated in 38 patients (21 males and 17 females) affected by type 1 diabetes mellitus (18 free from complications, 10 with retinopathy, and 10 with autonomic neuropathy) and in 8 healthy controls. Two separate fibrinolysis-stimulating tests were done: standardized venous occlusion and 1-desamino-8-D-arginine vasopressin infusion. Plasma tissue plasminogen activator antigen and activity and plasma plasminogen activator inhibitor activity were measured. All the patients were in good metabolic control (mean HbA1c 7.4%, range 6.1-8.0%). No significant differences were observed either between the diabetic patients and the control subjects, nor among the subgroups of diabetic patients. The fibrinolytic system is probably not involved in type 1 diabetes mellitus.

Deamino Arginine Vasopressin↗
PubMed1992

Hyperparathyroidism: cause or consequence of recurrent calcium nephrolithiasis?

Primary hyperparathyroidism (PHP) might be characterized by either prevailing bone or renal stone patterns with different metabolic features. To explore the possibility of different hormonal patterns we studied 129 patients with PHP: 95 stone formers (SF) and 34 nonstone formers (NSF). Females prevailed over males in both groups. Severe and specific bone lesions were more evident in NSF than SF. Parathyroid gland histology displayed a prevalence of adenoma in NSF, whereas isolated hyperplasia prevailed in SF. SF had lower levels of serum Ca, urinary Ca, ALP and serum PTH than NSF. As expected serum 1,25-dihydroxyvitamin D [1,25(OH)2 D] levels were greater in both groups of patients than in controls but we found no difference between the two groups. 25-Hydroxyvitamin D was neither increased with respect to controls nor different between groups. We conclude that patients with PHP may represent well separated metabolic and clinical entities, but we cannot confirm that serum 1,25(OH)2D levels play a key role in discriminating the different clinical features. In addition, the findings of predominant parathyroid hyperplasia in SF and the clinical evidence of recurrent hyperparathyroidism only in these patients suggest the possibility that the endocrine disorder might be the consequence over time rather than the cause of nephrolithiasis.

Adult↗
PubMed1991

Determination of serum levels of complement component C4b-binding protein: influence of age and inflammation.

C4b-binding protein (C4b-BP) is a high molecular weight plasma protein which inhibits the activity of the classical complement pathway C3 convertase. In addition to multiple binding sites for C4b, C4b-BP possesses a single binding site for vitamin K-dependent protein S, an inhibitor of blood coagulation. As protein S bound to C4b-BP has no anticoagulant activity, C4b-BP participates in the regulation of both the complement and the coagulation pathways. We have produced and immunochemically characterized a series of murine monoclonal antibodies to human C4b-BP. A mixture of four monoclonal antibodies precipitating C4b-BP both in agarose gel and in solution was used to develop a highly reproducible radial immunodiffusion method for the measurement of C4b-BP in human serum. C4b-BP levels were measured in sera from 284 patients referred to our central laboratory. Samples from subjects with an increased erythrocyte sedimentation rate (ESR), a1-acid glycoprotein (a1-AGP) or C-reactive protein (CRP) had significantly higher C4b-BP levels (307 mg/l, 292-322 mg/l, geometric mean and 95% confidence limits of the mean) than those from subjects without elevation of the aforementioned established acute phase reactants (231 mg/l, 226-237 mg/l, P less than 0.00001). C4b-BP was significantly (P less than 0.001) correlated with ESR (r = 0.715), a1-AGP (r = 0.692) and CRP (r = 0.567). There was no gender-related difference in C4b-BP levels. In subjects with no increased acute phase reactants there was a significant correlation between C4b-BP levels and age (r = 0.387, P less than 0.001). High C4b-BP might contribute to the increased thrombotic risk associated with inflammation and aging.

Adult↗
PubMed1991

Diabetes mellitus and hypertension: a physiologic basis for a rational therapeutic approach.

The basic mechanisms that initiate and sustain hypertension in the diabetic population are poorly understood. Obesity, insulin, genetic factors, and abnormalities in calcium homeostasis may contribute, and could be related to an elevated Na+/H+ antiport activity. In the first study described in this investigation, hypertensive subjects with insulin-dependent diabetes mellitus (IDDM) who had an elevated Na+/Li+ countertransport activity were found to have a lower whole body glucose utilization, a lower insulin-stimulated forearm carbohydrate oxidation, larger ultrasound kidney volume, and increased left ventricular mass index when compared with hypertensive IDDM subjects with a normal Na+/Li+ countertransport activity or normotensive IDDM subjects. Thus an elevated Na+/Li+ countertransport activity appears to identify a subset of IDDM patients who are more susceptible to the development of the renal and cardiac complications associated with hypertension. This underlines the importance of choosing an appropriate antihypertensive therapy that will not produce a deterioration in glucose and lipid metabolism. In the second part of the report, results are presented for the treatment of hypertensive patients with non-insulin-dependent diabetes mellitus with doxazosin. The selective alpha 1-inhibitor produced a significant reduction in blood pressure, together with favorable changes in the serum lipid profile. As a result, the calculated risk of developing coronary heart disease was significantly reduced. Throughout the study no patients required a dose reduction or discontinuation of doxazosin because of side effects, and no clinically significant changes in laboratory tests were apparent. Thus doxazosin could be considered a useful antihypertensive agent in hypertensive patients with IDDM who are insulin-resistant and who have renal and cardiac abnormalities.

Antihypertensive Agents↗
PubMed1991

Longitudinal study on osteodystrophy in primary biliary cirrhosis (PBC) and a pilot study on calcitonin treatment.

The aims of this study were to evaluate bone metabolism in primary biliary cirrhosis (PBC) and the effect of ADFR (activate, depress, free, repeat) therapy with vitamin D, calcium and calcitonin in preventing bone resorption. Sixty-nine female subjects entered the study: 38 PBC (AMA + ve) patients, 11 AMA-negative chronic liver disease patients and 20 age-matched healthy controls. Bone metabolism was evaluated by biochemical parameters and dual-photon absorptiometry of the lumbar spine at time 0, 6 and 18 months. Both PBC and chronic liver disease (CLD) patients showed low levels of serum 25-hydroxyvitamin D, osteocalcin and bone mineral content expressed as AAD (average area density) compared to healthy controls. Serum parathyroid hormone in PBC patients was at the lower limit of the normal range and was significantly lower than patients with chronic liver disease. At a 6-month interval, AAD significantly decreased in PBC patients (p less than 0.005). At the 6-month period PBC patients were allocated into two groups according to a cut-off AAD of 0.800 g/cm2: group A (no treatment, AAD greater than 0.800, n = 11), group B (treatment, AAD less than 0.800, n = 13). The latter group received a 4-week course with oral calcium carbonate (1500 mg daily) + oral 1,25-dihydroxyvitamin D (0.5 micrograms twice a day for 5 days) + carbocalcitonin (40 U MRC) i.m. thrice a week. The treatment was repeated with the same protocol at 2-month intervals for 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Infantile hereditary neuropathy with hypomyelination: report of two siblings with different expressivity.

We report the cases of two siblings both affected by inherited sensory-motor neuropathy of a demyelinative nature but with markedly different severity and pathological findings. The clinical, neurophysiological and morphological features in these two cases were consistent with the diagnosis of Hereditary Motor Sensory Neuropathy type 3 (HMSN 3), according to the classification of Dyck, with different expressivity. These results raise the still unsettled question of the phenotypic variants in inherited neuropathies. In fact the most severely affected of our cases had clinical and neurophysiological findings identical to those reported in cases of Congenital Hypomyelination Neuropathy (CHN), but the morphological picture in the sural nerve was inconsistent with this diagnosis. The criteria for the diagnosis and the reported cases of CHN have been reviewed.

Biopsy, Needle↗
PubMed1991

A comparison of nizatidine and ranitidine in the maintenance treatment of duodenal ulcer. A randomized, double blind, multicentre, 2-year study.

UNLABELLED: One hundred and eight patients with an endoscopically documented healed duodenal ulcer (DU) participated to a multicentre, randomized, double-blind, long-term study. The study was planned with the aim to compare the efficacy of nizatidine 150 mg with ranitidine 150 mg in preventing relapse during the 2 years following the DU healing. Fifty four patients were assigned to each treatment. Endoscopic examinations were scheduled at 6, 12 and 24 months. Clinical evaluations were performed every two months. Routine laboratory tests were investigated at the beginning of the study and at each of the scheduled endoscopies. STATISTICS: chi-squared test with Yate's correction, Student's t test for unpaired data, Wilcoxon Rank Sum test and Logrank test. Twenty five patients dropped-out: 15 in the nizatidine and 10 in the ranitidine group. The cumulative relapse rate was 18% for nizatidine and 21% for ranitidine treatment (p:ns). Both drugs resulted safe, as only minor side effects were registered. IN CONCLUSION: nizatidine is as effective and safe as ranitidine in the long-term (2 year) treatment of DU.

Adult↗
PubMed1990

L-asparaginase treatment reduces the anticoagulant potential of the protein C system without affecting vitamin K-dependent carboxylation.

The changes in plasma levels of the vitamin K-dependent natural anticoagulants protein C (PC) and protein S (PS) and procoagulant factors II, IX and X were evaluated in 8 adult patients during treatment with L-asparaginase (L-ase i.v. 120,000 U/m2 over 10 days). PC anticoagulant activity and factor IX, X and II coagulant activity decreased proportionally to their half-lives to a nadir of 50-60% of pretreatment values after 2-5 L-ase infusions, suggesting that inhibition of protein synthesis rather than consumption is the main mechanism responsible for the observed changes. Free PS antigen levels declined at a rate similar to total PS antigen, reaching a nadir of 56% of pretreatment values after 3 L-ase infusions; however due to C4b-binding protein levels higher than total PS levels (p less than 0.05), they were constantly lower than the corresponding total PS antigen levels (0.05 less than p less than 0.001). This implicates that total PS antigen levels cannot be taken as an indicator of PS activity. No differences between the antigenic levels and the anticoagulant activities of PC and free PS could be observed suggesting that L-ase does not affect the mechanisms of vitamin K-dependent carboxylation of Gla-residues. The faster rate of decline of PC and PS activities relative to that of factor II may be responsible for the onset of an hypercoagulable state during the early phase of L-ase treatment.

Adult↗
PubMed1990

Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis?

1. Since prostaglandin E2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stoneformers on urinary Ca2+ and prostaglandin E2, as well as on plasma bicyclo-prostaglandin E2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca2+ (P less than 0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P less than 0.001), plasma bicyclo-prostaglandin E2 (P less than 0.001) and 1,25-dihydroxyvitamin D (P less than 0.01), and an increase in plasma parathyroid hormone (P less than 0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P less than 0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P less than 0.005) and after (P less than 0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P less than 0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P less than 0.05). 4. It is suggested that a block of prostaglandin E2 synthesis plays a role in the effect of hydrochlorothiazide on Ca2+ metabolism, most probably through an inhibition of 1 alpha-hydroxylase activity.

Adult↗
PubMed1990

Effect of clot-detection methods and reagents on activated partial thromboplastin time (APTT). Implications in heparin monitoring by APTT.

Two automatic coagulometers, ACL 810 (Instrumentation Laboratory), a laser-nephelometric centrifugal analyzer, and KoaguLab 40 A (Ortho Diagnostics), an optical automatic coagulometer, were compared with the manual tilt-tube method for the performance of activated partial thromboplastin time (APTT). Seven commercial APTT reagents were used for duplicate determinations in 30 normal controls, 26 patients with liver disease, and 33 patients on full-dose heparin treatment. Clotting times were longer with the manual method than with ACL 810 and, to a lesser extent, with KoaguLab 40 A. Average imprecision of duplicate determinations (coefficient of variation [CV]) was less with ACL 810 (less than 1.5%) than with KoaguLab 40 A (2.9%) and the manual method (2.4%). Differences in slope of the regression curves of clotting times obtained with the coagulometers over the tilt-tube method were observed with all the reagents tested (P less than 0.01). Transformation of clotting times of controls, patients with liver disease, and patients on heparin therapy to APTT ratios did not eliminate the bias resulting from the different reagents (P less than 0.001) and clot-detection methods (P less than 0.001); in controls, significant (P less than 0.001) reagent-method interaction was also observed. The in vitro heparin sensitivity differed with the APTT reagents evaluated and was influenced by the clot-detection method used. Transformation of APTT ratios of anticoagulated patients to apparent plasma heparin levels--as derived from in vitro dose-response curves--effectively eliminated the bias resulting from the different clot-detection methods but had no effect on the bias resulting from the different APTT reagents. In vitro heparin activity curves thus have little, if any, relevance for the ex vivo monitoring of heparin treatment.

Blood Coagulation Tests↗
PubMed1990

Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo.

To evaluate the occurrence of hypercoagulability during treatment with L-asparaginase (L-ase), thrombin-antithrombin complex (TAT) and D-dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. L-ase alone (20,000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to L-ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second L-ase infusion. Increased levels of TAT (P less than 0.05) and D-dimer (P less than 0.01) were observed prior to L-ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with L-ase alone, further elevation of TAT (P less than 0.05) and persistence of increased D-dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of D-dimer levels occurred during L-ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by L-ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to L-ase treatment remains to be determined.

Antithrombin III↗
PubMed1990

Prognostic significance of fibrinopeptide A in survivors of cerebral infarction.

We measured levels of fibrinopeptide A, beta-thromboglobulin, and fibrinogen in the plasma of 27 patients 2 months after their first stroke. Concentrations of fibrinopeptide A, a sensitive index of in vivo hypercoagulability, were significantly higher in the 18 ischemic stroke patients than in 40 age- and sex-matched controls and in the six patients who experienced recurrence within 5 years than in the 12 who remained asymptomatic. On the contrary, fibrinopeptide A levels had no prognostic significance among the nine patients with hemorrhagic stroke. Concentrations of beta-thromboglobulin, an index of platelet activation, were higher in the 27 stroke patients than in the 40 controls, but this index was not associated with stroke recurrence. Fibrinogen levels were not significantly higher in stroke patients than in controls. In a multivariate regression analysis of hemostatic and clinical variables, only fibrinopeptide A levels of greater than 4 ng/ml were significantly related to cerebral infarction. Our results support the role of hypercoagulability in the recurrence of ischemic stroke and may allow identification of subjects at high risk for it. If confirmed in more patients, our results could provide a rationale for clinical trials of anticoagulant therapy in such patients.

Cerebral Infarction↗
PubMed1990

Familial protein S deficiency presenting as deep vein thrombosis occurring during pregnancy.

Subjects with congenital deficiency of protein S, a natural anticoagulant which serves as a co-factor for the antithrombotic activity of activated protein C, are at risk of thrombosis. We describe a family in which deep vein thrombosis-occurring during pregnancy in three members with abnormally low protein S activity - was the only manifestation of congenital heterozygous protein S deficiency. Early diagnosis and active treatment of protein S deficiency should be pursued in any woman with a family history of thrombosis, who is planning pregnancy.

Adult↗
PubMed1990

Comparison of 150 mg nizatidine BID or 300 mg at bedtime, and 150 mg ranitidine BID in the treatment of gastric ulcer--an 8-week randomized, double-blind multicentre study.

One hundred and one active gastric ulcer patients concluded an 8-week, randomized, double-blind multicentre study, planned with the aim to compare the effectiveness of a new H2 blocker, nizatidine, with ranitidine. Thirty-three patients received 300 mg nizatidine at bedtime, 34,150 mg nizatidine b.i.d. and 34,150 mg ranitidine b.i.d. The three groups were well matched for the common clinical parameters. After 4 weeks, healing rates were 51.5% (confidence intervals 95%: 34.1-68.9%), 61.8% (41.2-82.4%), 76.5% (51-102%), respectively. At this check point ranitidine showed a significantly better outcome than did 300 mg nizatidine at bedtime (p less than 0.05). After 8 weeks, healing rates were 81.8% (54.1-109.5%), 88.2% (58.7-117.7%) and 88.2% (58.7-117.7%); these differences were not statistically significant. Age, sex, ulcer symptoms, alcohol and cigarette consumption, concomitant treatments, ulcer size and site and length of ulcer history were all found not to influence ulcer healing. Pain relief and antacid consumption were comparable in the three treatment groups. No clinically significant unwanted effects were recorded throughout the study. Nizatidine can, in our opinion, be successfully used in the treatment of active gastric ulcer.

Adult↗