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Biomedical subjects

A D'Angelo

Publications and source records attributed to A D'Angelo.

At least 127 records · Page 7Linked to original sources

Calciotropic hormones and nephrolithiasis.

In recurrent calcium stone formers interfering factors or changes in receptor sensitivity may alter the interrelationships among calcium-regulating hormones, and hormonal behavior often does not fit with the theoretical assumptions. The vitamin D system appears to have the most important metabolic and clinical effects. Abnormal up-regulation of the synthesis of calcitriol and the consequent parathyroid hormone (PTH) suppression can induce hypercalciuria. Consequently, the hypocalciuric effect of thiazide would be caused by an enhanced response to PTH and by a reduction in 1,25(OH)2-vit D. A negative role of vitamin D on the skeleton has been observed in the presence of a negative calcium balance. Moreover, vitamin D also plays a role in urine oxalate excretion. PTH seems not to be directly stimulated in hypercalciuria and recurrent calcium nephrolithiasis, and patients with hyperparathyroidism and recurrent calcium nephrolithiasis show a similar degree of bone demineralization, irrespective of the presence of absence of the so-called 'primary hyperparathyroidism.' Calcitonin plays a contributory role in the pathogenesis of recurrent calcium nephrolithiasis that seems to be strictly related to dietary calcium intake. A higher sensitivity of thyroid C cells, particularly in absorptive hypercalciuric patients, could be related to the pathogenesis of hypercalciuria and contribute to its persistence.

Calcitonin↗

Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy.

BACKGROUND: Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics. METHODS: In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] < or = 2.8) in 71% of the patients and high (> 2.8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories. FINDINGS: 43% of the patients were women. Nearly three-fifths of the patients were aged 60-79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7.6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10.5 per 100 patient-years in those aged 70 or over, 6.0 in those aged under 70 (relative risk 1.75, 95% Cl 1.29-2.39, p < 0.001). The rate was also higher when the indication was peripheral and/or cerebrovascular disease than venous thromboembolism plus other indications (12.5 vs 6.0 per 100 patient-years) (1.80, 1.2-2.7, p < 0.01), and during the first 90 days of treatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p < 0.001). A fifth of the bleeding events occurred at low anticoagulation intensity (INR < 2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.0-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR > 4.5, 7.91, 5.44-11.5, p < 0.0001). INTERPRETATION: We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.

Acenocoumarol↗

Prenatal ultrasound diagnosis of cerebral arteriovenous fistula.

BACKGROUND: We describe a case of arteriovenous fistula of the middle and posterior cerebral arteries detected in a fetus. CASE: Fetal echocardiography revealed a high-output cardiac failure. Color Doppler ultrasound demonstrated an arteriovenous fistula, localized at the middle and posterior cerebral arteries, which drained in a large venous aneurysm occupying the posterior fossa. The aneurysm caused cerebellar dislocation and temporal lobe hypoplasia. Necropsy after pregnancy termination confirmed the ultrasound findings. CONCLUSION: This case demonstrates that malformation of a fetal cerebral artery can lead to brain hypoplasia and thus to severe mental handicap. This possibility needs to be considered in patient counseling.

Abortion, Eugenic↗

Continuous and cyclical clodronate therapies and bone density in postmenopausal bone loss.

OBJECTIVE: To evaluate the effectiveness of different clodronate regimens in postmenopausal osteoporosis. METHODS: In groups of 20, 60 women were randomly assigned to one of three treatments: oral calcium, 1000 mg/day; oral calcium plus oral clodronate, 400 mg/day; oral calcium plus oral clodronate, 400 mg/day for 30 days, followed by a 60-day period of calcium supplement alone. This last regimen was repeated four times in the 12-month study period. RESULTS: Patients who received calcium alone showed a decline in spinal bone mass, both after 6 and 12 months (P < .03 and P < .005, respectively); femoral density in this group also decreased after 6 and 12 months (P < .002 and P < .05, respectively). On the other hand, both clodronate-treated groups had increased levels of lumbar bone mass compared with controls, both after 6 and 12 months of therapy. However, at the end of the study, patients treated with cyclical clodronate had higher spinal bone mass compared with those treated continuously (3.32 +/- 0.71 versus 0.43 +/- 0.89%, P < .02). After 6 months, femoral bone density was significantly higher both in subjects treated with clodronate, both cyclically and continuously (P < .01), compared with controls. Continuous clodronate treatment resulted in a clear fall in biochemical indices of bone resorption, together with a consequent decrease in osteocalcin at 6 (P < .02) and 12 months (P < .003) and a significant increase in parathyroid hormone after 12 months (P < .001) of therapy. CONCLUSION: One-year treatment with clodronate induces a gain in bone mass, especially in the spine. The continuous regimen does not result in any further benefit in lumbar bone density over the cyclical one, probably because of a greater suppression of bone turnover.

Absorptiometry, Photon↗

Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry.

PURPOSE: To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies. PATIENTS AND METHODS: Three hundred sixty consecutive patients (118 males, 242 females, median age 39 years [range 2 to 78]) fulfilling the currently accepted criteria for diagnosis of lupus anticoagulant (LAC) (n = 326) and/or raised immunoglobulin G anticardiolipin antibodies (IgG ACA) (n = 185) were collected from 16 Italian institutions and prospectively observed for a median of 3.9 years (range 0.5 to 5). Main endpoints were the occurrence of arterial or venous thrombosis, the outcome of pregnancies, and any severe complications leading to hospitalization or death. RESULTS: Thirty-four patients developed a thrombotic complication, with a total incidence of 2.5% patient-years. Multivariate logistic regression analysis identified two independent risk factors for thrombotic events: a previous thrombosis (RR 4.9; 95% CI, 1.76 to 13.7; P < 0.005) and IgG ACA titer above 40 units (RR 3.66; 95% CI, 1.24 to 10.8; P < 0.01). A total of 28 pregnancies were observed in 25 women and 11 (39%) were abortive. Adverse pregnancy outcomes were significantly more frequent in women with a history of miscarriage or vascular occlusion (9/16, 56%) than in asymptomatic women (2/12, 17%) (P = 0.035). Four patients developed non-Hodgkin's lymphoma during the follow-up. Eighteen patients died. Vascular events and hematological malignancies represented the most frequent causes of death (n = 5 for each). CONCLUSIONS: The present study shows that: (a) previous thrombosis and ACA titer > 40 U are independent predictors of thrombosis; (b) history of miscarriage or vascular disease is significantly associated with adverse pregnancy outcome; (c) hematological malignancies can develop during follow-up in patients with antiphospholipid antibodies.

Adolescent↗

Increased urinary NO2-/NO3- and cyclic guanosine monophosphate levels in patients with Bartter's syndrome: relationship to vascular reactivity.

Nitric oxide (NO) is a potent endogenous vasodilator and plays a pivotal role in the control of vascular tone by the formation of cyclic guanosine monophosphate (GMP). Patients affected by Bartter's syndrome have lower than normal vascular reactivity with normohypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension, and it is possible that increased production of NO may be involved in maintaining this reduced vascular response and vasodilatation. We have examined this possibility by studying NO2-/NO3- and cyclic GMP urinary excretions to assess NO production in vivo in seven patients affected by Bartter's syndrome compared with seven healthy controls. A group of five patients with hypokalemia other than Bartter syndrome (pseudo-Bartters) was also included in the study to evaluate the effect of hypokalemia on NO production. NO2-/NO3- urinary excretion (0.45 +/- 0.14 v 0.25 +/- 0.04 micromol/micromol urinary creatinine [controls], P < 0.005, v 0.28 +/- 0.05 [pseudo-Bartters], P < 0.01) and cyclic GMP urinary excretion (0.057 +/- 0.028 v 0.022 +/- 0.01 micromol/micromol of urinary creatinine [controls], P < 0.009, v 0.024 +/- 0.004 [pseudo-Bartters], P < 0.02) were increased in patients with Bartter's syndrome in comparison with controls and pseudo-Bartters, and a linear correlation between these two parameters was also present (P < 0.001). We conclude that in Bartter's syndrome the increased NO2-/NO3- and cyclic GMP urinary excretions point to an increased NO synthesis, which could account for the reduced vascular response of the disease, therefore adding its role in determining the vascular hyporeactivity of Bartter's syndrome.

Adolescent↗

Fetal inguinoscrotal hernia: prenatal ultrasound diagnosis and pathogenetic evaluation.

Congenital inguinal hernias, relatively common among infants, have rarely been reported in utero. In this brief report, the prenatal diagnosis of this condition based on movement of the intestinal content within the ileal loops is described. The differential diagnosis with other masses protruding from the abdominal wall (omphalocele) or the perineal region (sacrococcygeal teratoma, hydrocele) is discussed.

Adult↗

Intracellular calcium signalling and vascular reactivity in Bartter's syndrome.

We investigated patients affected by Bartter's syndrome in the attempt to localize the intracellular defect mediating the reduced intracellular Ca2+ mobilization that may be responsible for the decreased vascular reactivity characteristic of Bartter's syndrome. Using the formylmethionyl-leucyl-phenylalanine (fMLP) receptor system, which causes, intracellular calcium release, we investigated fMLP-stimulated intracellular inositol 1,4,5-trisphosphate (IP3) production as well as the number and affinity of fMLP receptors in neutrophils from Bartter's syndrome patients and healthy controls. Scatchard plot analysis of radioactive fMLP binding to neutrophils indicated that there were no differences in either cell receptor number and affinity for ligand between healthy controls (n = 5) and patients with Bartter's syndrome (n = 5): 6,151 +/- 1,431 vs. 7,112 +/- 2,566 receptors/cell; K(D): 0.446 +/- 0.14 vs. 0.454 +/- 0.09 pM of fMLP. 5- and 10-second fMLP-stimulated intracellular IP3 production was instead reduced in patients affected by Bartter's syndrome: 2.479 +/- 1.07 vs. 4.073 +/- 1.04 nmol/10(7) cells at 5 s (n = 8; p < 0.01); 1.673 +/- 0.741 vs. 3.766 +/- 1.348 nmol/10(7) cells at 10 s (n = 8; p < 0.005). The results of this study indicate that the anomaly of intracellular calcium mobilization in patients with Bartter's syndrome arises from a defect at the postreceptor level. The anomalous calcium signalling that takes place in Bartter's syndrome may provide a mechanism for the hyporesponsiveness to pressor stimuli characteristic of these patients.

Adult↗

Nifedipine can preserve renal function in patients undergoing aortic surgery with infrarenal crossclamping.

Sixteen patients diagnosed with an aneurysm of abdominal aorta or Leriche disease underwent elective aortic surgery involving crossclamping of infrarenal aorta (ICC). These patients were randomized into two equal groups and 8 patients were infused with nifedipine starting from the isolation of aorta until the end of surgery (group A) while another 8 patients were infused with low-dose dopamine (group B) over the same surgical course. Plasma endothelin (ET) was measured before the induction of anesthesia, at the beginning and at the end of the clamp period and at the end of the operation. Intraoperatively, creatinine clearance and urinary excretion of PGE2, 6-keto PGF1 alpha and TxB2 were also determined before, during and after aortic crossclamping. Preoperative GFR as well as preinduction cardiac index (CI) and pulmonary capillary wedge pressure (PCWP) of the two groups did not differ. During cross-clamping plasma ET rose significantly in both groups. However, after clamp removal, plasma ET decreased in group A while it remained elevated in group B. Urinary excretion of TxB2, PGE2 and 6-keto PGF1 alpha increased during clamp in both groups, but the ratio of PGE2 + 6-keto PGF1 alpha/TxB2 during and after clamp was significantly higher in group A than in B. Postclamp creatinine clearance decreased in group B, and increased in group A; postoperative value of GFR was unchanged in group A and decreased significantly in group B. In conclusion, infusion of nifedipine, in contrast to dopamine, prevented the decrease of GFR in patients undergoing aortic surgery. This effect could be mediated by a nifedipine modulation of ET vascular synthesis and/or a preferential renal synthesis of vasodilating prostanoids.

Aged↗

Evaluation of a new rapid quantitative D-dimer assay in patients with clinically suspected deep vein thrombosis.

The sensitivity and specificity for deep vein thrombosis (DVT) of a new rapid, quantitative and precise (total imprecision < 10%) D-dimer assay suitable for individual measurements (VIDAS D-DIMER, bio-Mérieux, France) were evaluated in a consecutive series of 103 in- and out-patients submitted to serial compression ultrasonography (C-US) for the clinical suspicion of DVT (n = 66) or of DVT recurrence (n = 37) and symptoms lasting from 1 to 15 days. DVT was found in 22 patients at baseline testing and no patient with an initially negative C-US developed vein incompressibility at follow up. The time elapsed from the onset of symptoms was negatively associated with D-dimer levels both in patients with and in those without DVT. In the entire series of patients, the sensitivity of a positive D-dimer test ( > or = 1.0 microgram/ml) for the presence of DVT was 96% (21/22 patients, 95% confidence interval 75-100%) with a specificity of 75% (64-84%), a negative predictive value of 98% (90-100%), a positive predictive value of 51% (35-67%), and an overall accuracy of 80% (70-87%). A normal D-dimer value (0.22 microgram/ml) was observed in one patient with DVT and symptoms lasting from 15 days. The approach of withholding C-US testing in patients with symptoms lasting from less than 11 days and D-dimer levels below the cut-off value was compared to serial C-US testing alone in a cost-effectiveness analysis subdividing the 66 patients with a first episode according to their clinical pretest probability of DVT. Thrombosis was detected in 6.7% of the patients in the low probability group (n = 15), 16.7% of the patients in the moderate probability group (n = 24), 51.9% of the patients in the high probability group (n = 27) and 8.1% of patients with suspected DVT recurrence. Calculated cost-savings for each DVT diagnosed ranged from 5% in the high pretest probability group to 55% in the low pretest probability group and to 77% in patients with suspected DVT recurrence. The safety of avoiding C-US testing in symptomatic patients with a negative D-dimer test should be evaluated in clinical management studies.

Adult↗

The effect of cigarette-smoking on cardiovascular risk factors: a study of monozygotic twins discordant for smoking.

The association of cigarette smoking with the development of occlusive vascular disease is firmly established. Unfavourable changes in a series of variables held independent risk factors for the development of vascular lesions (HDL-cholesterol, haematocrit, white blood cell count, fibrinogen and plasminogen activator inhibitor-1 (PAI-1)) are thought to be directly influenced by cigarette smoking. However, the role played by the genotype in the effect of smoking on the above parameters has not been investigated. To control the genotype, we studied the relationship between cigarette smoking and a series of cardiovascular risk factors in 27 monozygotic twin pairs (7 male and 20 female pairs, mean age +/- SD: 47.4 +/- 12.9 yrs) with a life-long discordance for smoking. Smoking twins had a life-long dose of smoking (Brickman index) of 287.3 +/- 241.5. Body mass index, blood pressure, haematocrit, haemoglobin and red blood cell counts, total cholesterol levels and the acute phase reactants alpha 1-acid glycoprotein and C-reactive protein were similar in smokers and non-smokers. Triglyceride was higher by 12.6% (9.5-35%, 95% confidence interval, p = 0.02) and HDL-cholesterol lower by 7.5% (0.2-15%, p = 0.04) in the smoking co-twins, who also had 8.4% (-0.2-17%, p = 0.06) higher white blood cell counts and 4.1% (1.2-7%, p < 0.01) larger mean platelet volume. There was no significant difference in clottable fibrinogen (by two methods) or in the activity of plasminogen activator inhibitor-1 between the two groups, nor was the within-pair difference in these parameters related to the smoking dose. Echo-doppler examination of the carotid arteries of 24 twin pairs showed mostly minor atherosclerotic lesions in 46% and 42% of the smoking and non-smoking co-twins. After adjustment for age, systolic blood pressure and platelet count and volume were the only variables significantly associated to the presence of vascular lesions. Cigarette smoking is associated with an atherogenic lipid profile and with changes in platelets and white cells potentially reflecting endothelial cell damage. When controlling the genotype, fibrinogen and PAI-1 activity levels did not seem directly influenced by cigarette smoking.

Adult↗

Potential failure of the International Normalized Ratio (INR) System in the monitoring of oral anticoagulation in patients with lupus anticoagulants.

Patients with antiphospholipid antibody syndrome (APS) experience a higher rate of recurrence of thrombosis than the general population of patients with thrombotic disease. Based on a retrospective analysis, it has been suggested that patients with APS should be kept on prolonged anticoagulation aiming at international normalised ratio (INR) values > 3.0. To evaluate whether the requirement for more intense anticoagulation depends on the variable sensitivity of thromboplastin reagents to the influence of aPLA, we monitored oral anticoagulant treatment in 10 patients with persistent lupus anticoagulants (LA) and venous thromboembolic disease using two thromboplastin reagents: Pro-IL-Complex (Instrumentation Laboratory, combined) and Recombiplastin (Ortho, recombinant). Acenocoumarol dosage was always assigned based on INR values obtained with the combined thromboplastin using diluted (1:20) test plasma, aiming at an INR interval of 2.0 to 3.0. Single INR determinations with both reagents were obtained throughout the study period for 110 aPLA-free patients on stable oral anticoagulation. Using the manufacturer's instrument-certified international sensitivity index (ISI) values, INR obtained with the recombinant reagent were significantly higher than those obtained with the combined reagent in LA-positive patients, but they were lower in LA-negative patients. After correction for local ISI calibration in LA-negative patients, INR values of 3.1 and 4.6 with Recombiplastin corresponded, respectively, to INR values of 2.0 and 3.0 with Pro-IL-Complex. These results indicate the thromboplastin-dependency of INR values in patients with LA, thereby questioning the validity of the INR system for the monitoring of oral anticoagulant treatment in these patients.

Administration, Oral↗

[7-year-follow up (1987-1994) of a population with asymptomatic persistent microhematuria and normal renal function].

A group od 129 patients with persistent asymptomatic microhematuria was studied for 7 years (1987-1994). At the beginning of the study, 31 patients showed mild proteinuria (less than 1 g/day) and in the rest of 98 patients, 21 showed microalbuminuria. At the end of the study none of the patients developed renal failure, urological disease, hypertension. Six patients out of 31 with mild proteinuria (less than 1 g/day), developed an increase of proteinuria over 2 and 3/day and underwent a renal biopsy while 2 out of 21 patients with altered microalbuminuria completely recovered after the follow-up period. The rest of 77 patients at the end of the study still showed isolated microhematuria. The results of this study support the hypothesis that in a population with age range between 16 and 28 years, the presence of persistent microhematuria, also associated with mild proteinuria, even for a long time, does not seem to lead to changes of renal function or to urological diseases.

Adolescent↗

Central retinal vein and branch artery occlusion associated with inherited plasminogen deficiency and high lipoprotein(a) levels: a case report.

We describe a case of central retinal vein and branch artery occlusion associated with inherited type I plasminogen deficiency (68%) and permanent elevation of Lp(a) (460 mg/l, S2 phenotype) in a 45 year old white woman with no associated local or systemic risk factors. Pedigree analysis revealed inheritance of plasminogen deficiency from the deceased father and of high Lp(a) levels from the mother. Both the patient's sons had plasminogen deficiency, but they had normal Lp(a) levels. In a series of 40 consecutive patients with central retinal vein occlusion we previously reported the observation of high Lp(a) levels--consistently associated with the S2 phenotype--in 30% of the patients as compared to a 10% incidence in controls. This case emphasizes the importance of screening patients with occlusion of the retinal vessels and no associated risk factors for coagulation abnormalities predisposing to thrombosis.

Female↗

Unusual bleeding manifestations in a case of primary amyloidosis with factor X deficiency but elevations of in vivo markers of thrombin formation and activity.

We describe a case of primary amyloidosis (AL) with severe factor X (FX) deficiency in an amateur cyclist presenting with muscular pain at rest and ecchymoses in his legs. No circulating inhibitor of FX was found by mixing studies and there was no deficiency of other vitamin K-dependent coagulation factors and inhibitors or of alpha 2-antiplasmin. Thrombin-time and reptilase time were abnormally prolonged and were not corrected by mixing with normal plasma. Administration of plasma or prothrombin complex concentrate (PCC) were unsuccessful in controlling bleeding: the apparent half-life of transfused FX was 6 minutes. Resting resulted in cessation of muscular pain and bleeding. Renal and cardiac deterioration led the patient to death 3 years after presentation. No further bleeding manifestations did occur during this period. FX levels remained consistently below 3%, but prothrombin fragment 1.2 and thrombin-antithrombin complex--measured at distance from PCC administration and prior to deterioration of renal and cardiac function--were markedly elevated. At autopsy, disseminated amyloidosis was found with sparing of the skeletal muscles and of the skin. This is the first report of increased in vivo prothrombin activation and activity in AL-associated FX deficiency.

Amyloidosis↗