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Biomedical subjects

A D'Angelo

Publications and source records attributed to A D'Angelo.

At least 163 records · Page 9Linked to original sources
PubMed1994

Hypercoagulability and high lipoprotein(a) levels in patients with central retinal vein occlusion.

A series of coagulation parameters and lipoprotein(a) (Lp(a)) were explored in plasma from 40 patients with central retinal vein occlusion (CRVO, non-ischemic type n = 12; ischemic type n = 28) free of local and systemic predisposing factors, 1 to 12 months after the acute event. Forty age- and sex-matched patients with cataract served as controls. Prothrombin fragment 1.2 (F1.2), D-dimer, FVII:C--but not FVII:Ag--were higher and fibrinogen was lower in CRVO patients than in controls. Patients with non-ischemic CRVO had higher F1.2 and FVII:C and lower heparin cofactor II than patients with ischemic CRVO. Lp(a) levels greater than 300 mg/l were observed in 12 patients with CRVO and in 4 controls (30% vs 10%, p < 0.025). Patients with high Lp(a)--consistently associated with the S2 phenotype--had higher FVII:C, FVII:C/Ag ratio, and fibrinogen than the remaining CRVO patients. Plasma F1.2 and D-dimer correlated fairly in controls (r = 0.41) and patients with normal Lp(a) levels (r = 0.55), but they did not in the group of patients with high Lp(a) (r = 0.19), where the latter parameter was negatively related to D-dimer (r = -0.55). There was no dependence of the abnormalities observed on the time elapsed from vein occlusion. The findings of activated FVII and high F1.2, D-dimer, and Lp(a) are not uncommon in patients with CRVO. Increased thrombin formation with fibrin deposition and impaired fibrinolysis may play a role in the pathophysiology of CRVO and require specific treatment.

Adult↗
PubMed1993

Comparison of functional assays for protein S: European collaborative study of patients with congenital and acquired deficiency.

Four functional assays for protein S were evaluated by 4 different laboratories, each center using its own method. The aim of this study was to compare these different assays and to establish a relationship with results of immunological assays of total and free protein S antigen and C4bBP. The same plasma samples were distributed to each center and tested in blind. In 47 normal subjects, there was no significant difference between the 4 functional assays, with mean values ranging from 93 to 100%. These values were in good agreement with those of free and total protein S antigen. In 34 patients with a quantitative congenital deficiency of protein S the mean values of protein S activity were decreased with the 4 assays, ranging from 25 to 40%. Free protein S antigen was reduced to a similar extent, whereas total antigen was either normal or decreased. The correlation of protein S activity with free protein S antigen was satisfactory for 3 methods, with coefficients of correlation varying from 0.84 to 0.92 whereas it was only 0.70 in one lab. When total protein S antigen was reduced, protein S activity was decreased in all the patients with the 4 assays. In contrast when total protein S antigen was normal an important overlap of protein S activity between normals and patients was observed in one lab with 12 patients misclassified. In 8 patients with a functional defect, results of protein S activity differed substantially according to the assay used and about half of these patients were misclassified.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Possible link between vitamin D and hyperoxaluria in patients with renal stone disease.

1. Vitamin D seems to play an essential role in the pathogenesis of idiopathic hypercalciuria at least in part via intestinal hyperabsorption of calcium. Hyperabsorption of calcium, in turn, might enhance the intestinal uptake of free oxalate, thus leading to hyperoxaluria. To verify this hypothesis we studied 75 calcium-stone-formers subdivided as follows: group 1 (15 patients) with isolated hyperoxaluria; group 2 (25 patients) with hyperoxaluria and hypercalciuria; group 3 (22 patients) with isolated hypercalciuria; group 4 (12 patients) with no metabolic abnormalities. 2. As expected, urinary calcium excretion differed in the various groups (P < 0.001), being highest in groups 2 and 3; urinary oxalate excretion, by definition highest in groups 1 and 2, was even more pronounced in group 2 than in group 1 (P < 0.05). Although in the normal range, the serum 1,25-dihydroxyvitamin D concentration was higher (P < 0.001) in the two hypercalciuric groups (2 and 3), showing peak levels in group 2. 3. When the data from the 75 stone-formers were pooled, there was a positive correlation between the serum concentration of 1,25-dihydroxyvitamin D and urinary calcium excretion (P < 0.001) and urinary oxalate excretion (P < 0.003), the latter relationship also being present when only the two hypercalciuric groups (groups 2 and 3) were considered together (P < 0.05). 4. Our data seem to confirm a relevant role for the vitamin D system in the pathogenesis of calcium nephrolithiasis due to increased intestinal calcium absorption, but also because this in turn induces a greater intestinal absorption of oxalate, thus leading to the occurrence or exacerbation of hyperoxaluria.

Adult↗
PubMed1993

Abnormal urate transport in erythrocytes of patients with idiopathic calcium nephrolithiasis: a possible link with hyperuricosuria.

1. The demonstration of an inheritable anomaly of erythrocyte oxalate transport in 'primary' calcium nephrolithiasis suggested that this disease might be a generalized metabolic disorder characterized by a defect in cellular anion transport. 2. To determine whether this anomaly is restricted to oxalate alone, we studied erythrocyte transmembrane urate self-exchange in calcium-oxalate renal stone formers in whom urinary excretion of uric acid is frequently increased. 3. Abnormal urate self-exchange was found in 30% of the patients. The urate self-exchange rate constant was correlated with 24 h urinary excretion of uric acid; the erythrocyte anomaly was also associated with the frequency of hyperuricosuria and a more intense disease activity. Transmembrane urate self-exchange was inhibited by stilbene and heparan sulphate. Morphazinamide administration did not reduce urinary urate excretion in patients with abnormal urate erythrocyte self-exchange. 4. These findings suggest that hyperuricosuria during calcium-oxalate renal stone disease might be due to a cellular defect in urate transport, and further support the hypothesis that idiopathic nephrolithiasis is a metabolic disorder characterized by a defect in cellular anion transport.

Biological Transport↗
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↗