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Biomedical subjects

A D'Angelo

Publications and source records attributed to A D'Angelo.

At least 91 records · Page 5Linked to original sources
PubMed1999

Increased endothelial nitric oxide synthase mRNA level in Bartter's and Gitelman's syndrome. Relationship to vascular reactivity.

AIM: Patients with Bartter's syndrome and Gitelman's syndrome have reduced vascular reactivity, normo-hypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension. Since we found that both types of patients have increased urinary NO2-/NO3-, metabolites of NO, that correlated with their increased urinary cGMP, second messenger of NO, we examined the possible role of NO system in the pathophysiology of these syndromes. PATIENTS AND METHODS: We used a molecular biologic approach and studied ecNOS gene expression by PCR-amplification of cDNA obtained by RT-PCR of RNA extracted by patients and healthy controls monocytes. RESULTS: ecNOS is overexpressed in monocytes from patients with Bartter's and Gitelman's syndrome relative to controls: - 0.306 +/- 0.012 Densitometric Units (0.313 +/- 0.006, N = 3 for Bartter's patients; 0.302 +/- 0.009, N = 5 for Gitelman's patients) vs. 0.192 +/- 0.018, p < 0.0001. CONCLUSION: This overexperession presumably accounts for their increased NO production; thus it could be likely that elevated ecNOS and NO levels are a part of pathophysiological process(es) that leads to their characteristic reduced vascular responses. However, the relationship between the alterations in the NO signalling system observed in this study and the mutations in either Na+-K+-2Cl cotransporter or in a K+ channel ROMK or in Cl- channel ClCNKB in Bartter's syndrome and in Na+-Cl- cotranstransporter in Gitelman's syndrome, recently reported as their primary defects remains to be defined.

Adult↗
PubMed1998

High-performance liquid chromatographic method for measuring total plasma homocysteine levels.

We have modified a high-performance liquid chromatographic (HPLC) procedure based on SBD-F (ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate) pre-column derivatization to obtain an assay that is useful for routine clinical total plasma homocysteine (tHcy) analysis. The introduction of easily handled sodium borohydride instead of the traditional tri-n-butylphosphine in dimethylformamide as a reductant and a 14-min run-time using basic isocratic HPLC equipment are the more notable advantages. The addition of mercaptopropionylglycine as an internal standard contributed to improvements in the reproducibility of the assay, yielding within- and between-run precisions of 1.9 and 4% (C.V.), respectively. Reference values for fasting tHcy were 7.65+/-2.3 and 8.9+/-2.4 micromol/l, while post-methionine load gave tHcy levels of 19.9+/-5.5 and 26.8+/-5.5 micromol/l, for women and men, respectively (n=40).

Chromatography, High Pressure Liquid↗
PubMed1998

Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery.

BACKGROUND: Compression stockings are recommended for prophylaxis against venous thromboembolism in patients undergoing neurosurgery, but anticoagulant agents have not gained wide acceptance because of concern about intracranial bleeding. METHODS: In a multicenter, randomized, double-blind trial, we assessed the efficacy and safety of enoxaparin in conjunction with the use of compression stockings in the prevention of venous thromboembolism in patients undergoing elective neurosurgery. Enoxaparin (40 mg once daily) or placebo was given subcutaneously for not less than seven days beginning within 24 hours after the completion of surgery. The primary end point was symptomatic, objectively confirmed venous thromboembolism or deep-vein thrombosis assessed by bilateral venography, which was performed in all patients on day 8+/-1. Bleeding side effects were carefully assessed. RESULTS: Among the 307 patients assigned to treatment groups, 129 of the 154 patients receiving placebo (84 percent) and 130 of the 153 patients receiving enoxaparin (85 percent) had venographic studies adequate for analysis. An additional patient in the placebo group died before venography of autopsy-confirmed pulmonary embolism. In this analysis, 42 patients given placebo (32 percent) and 22 patients given enoxaparin (17 percent) had deep-vein thrombosis (relative risk in the enoxaparin group, 0.52; 95 percent confidence interval, 0.33 to 0.82; P=0.004). The rates of proximal deep-vein thrombosis were 13 percent in patients receiving placebo and 5 percent in patients receiving enoxaparin (relative risk in the enoxaparin group, 0.41; 95 percent confidence interval, 0.17 to 0.95; P=0.04). Two patients in the placebo group died of autopsy-confirmed pulmonary embolism on days 9 and 16. Major bleeding occurred in four patients receiving placebo (intracranial bleeding in all four) and four patients (intracranial bleeding in three) receiving enoxaparin (3 percent of each group). CONCLUSIONS: Enoxaparin combined with compression stockings is more effective than compression stockings alone for the prevention of venous thromboembolism after elective neurosurgery and does not cause excessive bleeding.

Adult↗
PubMed1998

Complications of internal jugular vein retrograde catheterization.

We report on the incidence of complications of 172 internal jugular vein retrograde catheterizations (IJVRCs) performed on 126 patients. Standard cannulation and X-ray control of the catheter tip placement were performed. Difficulties encountered during the manouvre were registered. Patients with a jugular catheter in place for more than one day had neck echography on catheter removal and one week later. Carotid artery puncture occurred in 20 (12%) cases and lymphatic vessel puncture in one. In 13 (8%) cases IJVRC failed due to difficulties in advancing the guide. X-ray films documented catheter misplacement in 39 (23%) cases: loop into the internal jugular vein in 11 (6%); paravertebral venous plexus cannulated in one; other extracranial jugular afferent cannulated in 4 (2%); catheter tip into the jugular lumen in 10 (6%); catheter tip beyond the jugular bulb in 13 (8%). First neck echography documented: one perivascular hematoma (absent one week later); 3 (4%) jugular vein thrombosis (2 asymptomatic and absent one week later; one symptomatic and still evident one week later). Positive neck echography was not associated with difficulties, length of catheterization, diameter of the catheter. IJVRC is a simple and safe procedure with a low incidence of serious complications.

Adult↗
PubMed1998

Antithrombin III (ATIII) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study.

BACKGROUND: ATIII is decreased in sepsis and/or shock and its baseline value correlates with mortality. The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit (ICU) in a double-blind, randomized, multicenter study. METHODS: 120 patients admitted to the ICU with an ATIII concentration < 70% were randomized to receive ATIII (total dose 24000 units) or placebo treatment for 5 days; 56 patients had septic shock. RESULTS: ATIII concentrations in the treated group remained constant throughout the treatment period (range 97-102%). The Kaplan-Meier analysis showed no difference in overall survival between the two groups: 50 and 46% for ATIII and placebo, respectively. Septic shock and hemodynamic support were unbalanced in the two groups at admission. Therefore the Cox analysis was carried out after adjusting for these two variables. Treatment with ATIII decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates analyzed, septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1% increase in the ATIII plasma concentration at baseline. CONCLUSIONS: The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only.

APACHE↗
PubMed1998

Effect of doxazosin in mild to moderate hypertensive patients with insulin-dependent diabetes mellitus.

Diabetic patients often develop hypertension, and the presence of both hypertension and diabetes doubles the risk of death from coronary heart disease (CHD). Moreover, the presence and importance of abnormalities such as high low-density lipoprotein (LDL) cholesterol and triglycerides levels as CHD risk factors in insulin-dependent diabetes mellitus type 1 have been downplayed, while increasing evidence suggests that the management of type 1 patients should include control of dyslipidemia and hyperglycemia and an effective antihypertensive treatment able also to reduce risk factors for coronary artery events. In this study we assessed the antihypertensive and metabolic effects of doxazosin in hypertensive patients with type 1 diabetes. We show that the drug normalizes blood pressure, and while no improvement in glucose control was observed, it reduced total cholesterol and increased HDL cholesterol as well as the HDL to total cholesterol ratio. The changes of the various parameters studied, including the calculated CHD risk score based on the Framingham equation, suggest that doxazosine can reduce the CHD risk for hypertensive type 1 patients.

Adolescent↗
PubMed1998

Budd-Chiari syndrome during nephrotic relapse in a patient with resistance to activated protein C clotting inhibitor.

It has long been known that patients with nephrotic syndrome have a hypercoagulable state, which explains the association between nephrotic syndrome, renal vein thrombosis, and thromboembolism. However, the Budd-Chiari syndrome has never been reported in nephrotic patients. This is the first report of such an association that, most likely, depended on a primary resistance to activated protein C.

Adult↗
PubMed1998

Action of L-acetylcarnitine on different cerebral mitochondrial populations from cerebral cortex.

The maximum rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase) was evaluated in non-synaptic (free) and intra-synaptic mitochondria from rat brain cerebral cortex. Three types of mitochondria were isolated from rats subjected to i.p. treatment with L-acetylcarnitine at two different doses (30 and 60 mg.kg-1, 28 days, 5 days/week). In control (vehicle-treated) animals, enzyme activities are differently expressed in non-synaptic mitochondria respect to intra-synaptic "light" and "heavy" ones. In fact, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists, due to their location in vivo. Treatment with L-acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities, while increased cytochrome oxidase and alpha-ketoglutarate dehydrogenase activities only in intra-synaptic mitochondria. Therefore in vivo administration of L-acetylcarnitine mainly affects some specific enzyme activities, suggesting a specific molecular trigger mode of action and only of the intra-synaptic mitochondria, suggesting a specific subcellular trigger site of action.

Acetylcarnitine↗
PubMed1998

Efficacy and safety of three 7-day Helicobacter pylori eradication regimens containing ranitidine bismuth citrate.

BACKGROUND: This multicentre, randomized study was designed to assess the clinical efficacy, safety and tolerability of three novel 7-day triple therapies containing ranitidine bismuth citrate (RBC) and two antibiotics. METHODS: We studied patients with non-ulcer dyspepsia and gastritis who were randomly assigned to one of three treatment regimens given for 7 days in a b.d. dosing schedule: RBC 400 mg plus clarithromycin 250 mg and tinidazole 500 mg (RBCCT): RBC 400 mg plus clarithromycin 500 mg and amoxycillin 1 g (RBCCA); RBC 400 mg plus tinidazole 500 mg and amoxycillin 1 g (RBCTA). H. pylori status was determined by CLO-test, histology and 13C-urea breath test. A repeat breath test was performed at least 28 days after completion of therapy to assess eradication. RESULTS: One hundred and fifty-seven patients were eligible for intention-to-treat analysis (ITT) and 140 patients completed the study and returned for assessment of eradication. Intention-to-treat cure rates were 78% with RBCCT, 71% with RBCCA and 61% with RBCTA. An all-patients-treated analysis (APT), performed on evaluable patients, demonstrated eradication rates of 85% with RBCCT, 81% with RBCCA and 70% with RBCTA. No statistically significant difference was found between treatment groups. Twenty-four patients experienced side-effects, but in only seven cases was treatment discontinued due to adverse events. CONCLUSIONS: A 7-day course of RBC, clarithromycin and either tinidazole or amoxycillin provides a good rate of H. pylori eradication. Three novel RBC-based triple therapies proved to be safe and well tolerated, with discontinuations due to side-effects occurring in less than 5% of cases.

Adolescent↗
PubMed1998

In vivo and in vitro neurotoxic action of plasma ultrafiltrate from uraemic patients.

BACKGROUND: In order to investigate the aetiology of uraemic neuropathy, we evaluated the neurotoxic activity of plasma from uraemic patients. To this end we prepared a concentrate (1:1000) of 2-60 kDa MW compounds from paired filtration dialysis ultrafiltrate and evaluated its activity on peripheral nerve conduction in vivo and in vitro. METHODS: The in vivo neurotoxicity was tested on rat sciatic nerve by intraneural injection of the uraemic concentrate, followed, 1 to 6 days later, by electrophysiological assessment of motor response and maximum conduction velocity. In vitro experiments were performed on isolated frog sciatic nerve in the presence of uraemic concentrate, and the neurotoxicity was evaluated from the rate of the decrease in the amplitude of the evoked maximal action potential. RESULTS: In the in vivo experiments, the sciatic nerves injected with the uraemic concentrate showed a decrease in maximum conduction velocity and a progressive impairment in evoked motor response. In the in vitro experiments uraemic concentrate induced a dose-dependent neurotoxic effect. CONCLUSIONS: Our study demonstrates the presence in plasma of uraemic patients of a compound of 2-60 kDa MW with neurotoxic activity.

Action Potentials↗
PubMed1998

Molecular biology of diabetic glomerulosclerosis.

Diabetic nephropathy is one of the leading causes of renal failure in Western countries, where diabetic patients account for nearly half of all patients on haemodialysis. Progressive expansion of the mesangial matrix, and thickening of the glomerular and tubular basement membranes without signs of major cell proliferation are hallmarks of human and experimental diabetic nephropathy. These lesions eventually lead to glomerular fibrosis, a central pathological feature in many human acute and chronic kidney diseases, which progressively destroys the renal filtration unit, and may finally cause renal failure. Indeed, structure function relationship studies have shown that mesangial matrix expansion is strongly related to the clinical manifestation of diabetic nephropathy.

Diabetic Nephropathies↗
PubMed1998

Relationship between homocysteine and thrombotic disease.

Hyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin deficiency (folate, B12 and B6) or a genetic defect. Epidemiologic evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls. Eight of these studies demonstrated positive association with odds ratios that ranged from two to 13. This association was enhanced by including a methionine loading test. There is some evidence which suggests that hyperhomocysteinemia and activated protein C resistance have synergistic effect on the onset of thrombotic disease. Recent studies with animal models for mild hyperhomocysteinemia provided encouraging results in the understanding of the mechanism that underlies this relationship between mild elevations of plasma homocysteine and vascular disease. These animal models pointed to the possibility that the effect of elevated homocysteine is multifactorial, affecting both the vascular wall structure and the blood coagulation system.

Animals↗
PubMed1998

Reduced susceptibility to oxidation of low-density lipoprotein in patients with overproduction of nitric oxide (Bartter's and Gitelman's syndrome).

BACKGROUND: The oxidation of low-density lipoprotein (LDL) might play an important role in the development of atherosclerosis. OBJECTIVE: To establish whether greater than normal production of nitric oxide (NO) in vivo protects LDL from oxidation. PATIENTS AND METHODS: We studied nine subjects affected by Bartter's and Gitelman's syndrome (both characterized by greater than normal production of NO), and 10 subjects matched for age, sex and lipid levels as controls. LDL particles were isolated from plasma by density gradient ultracentrifugation. Susceptibility of LDL to oxidation was evaluated after incubation with copper sulfate solution, by measuring the formation of conjugated dienes, the thiobarbituric acid-reactive substances, and the volatile peroxidation products of n-3 (propanal) and n-6 (pentanal and hexanal) polyunsaturated fatty acids. Phospholipid fatty acid composition of LDL was determined by gas chromatography. LDL alpha-tocopherol concentrations were measured. RESULTS: Patients with Bartter's and Gitelman's syndrome had LDL particles smaller and/or denser than those of controls [Rf = 0.38 +/- 0.03 versus 0.42 +/- 0.02 (mean +/- SD), P < 0.01], which hence were assumed to be more oxidizable. The phospholipid fatty acid composition of LDL and the alpha-tocopherol concentrations did not significantly differ between patients and controls. The duration of the lag phase, which is the time preceding formation of conjugated dienes, did not differ between groups, but the lag phase times were related to urinary excretion of nitrite/nitrate from patients (r = 0.66, P < 0.05). Moreover, patient LDL had produced less thiobarbituric acid-reactive substances after 5 h (P < 0.04), and less pentanal and hexanal after 5 and 6 h (P < 0.04 and P < 0.02, respectively) than had that of controls. CONCLUSIONS: Greater than normal production of NO in vivo is associated with lower than normal susceptibility of LDL to oxidation in vitro, suggesting that NO plays a protective role in the development of atherosclerosis.

Adult↗
PubMed1998

Constitutive endothelial nitric oxide synthase (ecNOS) gene expression in human monocytes.

This study evaluates using a polymerase chain reaction (PCR)-based molecular biological approach to study the gene expression of the constitutive endothelial isoform of nitric oxide synthase (ecNOS) in human monocytes. When PCR was carried out with specific primers for ecNOS, 302 bp product was amplified, which sequence analysis determined as having 100% identity to the reported human ecNOS isoform gene sequence. The data presented here demonstrate a reliable technique for assessing ecNOS mRNA levels in circulating human monocytes. This then permits use of this easily available cell to monitor ecNOS levels and provides a means to investigate mechanisms involved in controlling NO synthase levels as well as NO synthesis.

Gene Expression↗