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Biomedical subjects

C De Angelis

Publications and source records attributed to C De Angelis.

At least 73 records · Page 4Linked to original sources

Circulating endothelin-1 concentrations in patients with chronic hypoxia.

AIMS: To evaluate the behavior of plasma endothelin-1 in patients with chronic hypoxia. METHODS: Fifteen male patients (mean age 52.1 +/- 3.1 years) with mild chronic obstructive pulmonary disease (COPD) were studied. Twelve healthy men (mean age 48.3 +/- 5.4 years) served as controls. Both patients and controls underwent standard pulmonary function tests, echocardiographic evaluation, and arterial blood gas evaluation. Blood samples for endothelin-1 assay were taken from a previously incannulated antecubital vein after 60 minutes of rest in the supine position. Endothelin-1 was measured by radioimmunoassay after extraction from plasma. RESULTS: Patients with chronic hypoxia had lower PaO2 values (66.1 +/- 6.2 mmHg) than controls (83.8 +/- 2.7 mmHg) but PaCO2 values were similar (38.1 +/- 2.5 v 36.7 +/- 3.1 mmHg, respectively). Arterial pulmonary pressure, therefore, was higher in patients (18.1 +/- 3.7 mmHg) than in controls (10.4 +/- 2.7 mmHg) as were circulating endothelin-1 concentrations (1.22 +/- 0.36 v 0.57 +/- 0.1 pg/ml). Furthermore, plasma endothelin-1 concentrations were negatively correlated with PaO2 and directly correlated with pulmonary pressure levels. No significant correlations were found in controls. CONCLUSIONS: These results show a clear relation between chronic hypoxia and circulating endothelin-1 concentrations. Therefore, chronic hypoxia may be regarded as an important stimulus for endothelin-1 release and as one of the main contributors to increased vasoconstriction in the vascular pulmonary bed which often accompanies lung disease.

Chronic Disease↗

Acetyl-L-carnitine prevents age-dependent structural alterations in rat peripheral nerves and promotes regeneration following sciatic nerve injury in young and senescent rats.

Morphologic and morphometric alterations of the sciatic nerve from old Sprague-Dawley rats and of lesioned tibial nerve from young and senescent Sprague-Dawley rats were studied. The possible therapeutical effects of treatment with acetyl-L-carnitine (ALCAR) were also investigated, ALCAR being a compound shown to exert a beneficial pharmacological action on diabetic neuropathies. Nerve sections from animals sacrificed under anesthesia were stained with toluidine blue. In old rats, a 6-month treatment with ALCAR markedly reduced the percentage of myelinated fibers (MF) characterized by age-dependent morphologic alterations (4% in treated rats versus 11% in untreated ones), such as myelin balloons, infolded loops of myelin, myelin reduplication, and ovoids. In the lesioned animals, ALCAR-treatment (15-60 days for young rats and 6-9 months for senescent rats) produced a significant increase versus controls in the density of regenerating myelinated fibers (RMF) at 15 days (young rats) and at 30 days (senescent rats) after crush, as well as an increase in the axon diameter in both young and senescent rats at 60 days after nerve crush. The MF diameter (sheath + axons) was significantly larger in treated senescent rats than in controls at 100 days after nerve crush. In ALCAR-treated rats, both young and senescent, the density of degenerative elements was lower and the RMF ratio (RMF density/RMF density + density of degenerative elements) was higher than that in controls at all detection times.

Acetylcarnitine↗

Plasma endogenous digoxin-like substance levels are dependent on blood O2 in man.

1. Recently, we have demonstrated that hypoxic breathing is followed by an increase in plasma digoxin-like substance in normal men. 2. This study was undertaken in order to evaluate whether or not a low arterial O2 partial pressure is combined with an increase in plasma digoxin-like substance in chronic pathological conditions also. 3. Sixteen male patients (mean age 53.1 +/- 3.7 years) affected by chronic obstructive pulmonary disease of a mild stage were studied. They were further subdivided according to their arterial O2 partial pressure into 'mild hypoxic' (n = 8, mean age 52.5 +/- 2.7 years), with an arterial O2 partial pressure between 66 and 75 mmHg, and 'severe hypoxic' (n = 8, mean age 54.3 +/- 5.1 years), with an arterial O2 partial pressure < or = 65 mmHg, groups. Seven healthy men (mean age 48.5 +/- 4.8 years) voluntarily participated as the control group. 4. Plasma digoxin-like substance levels were significantly higher in 'severe hypoxic' patients (203.5 +/- 9.9 pg/ml) than in both 'mild hypoxic' patients (169.5 +/- 31.4 pg/ml, P < 0.02) and normal subjects (158.9 +/- 12.4 pg/ml, P < 0.0001) and were directly correlated with urinary Na+ excretion (severe hypoxic group, r = 0.756, P < 0.007; mild hypoxic group, r = 0.789, P < 0.02). Considering the two hypoxic groups together, plasma digoxin-like substance levels were negatively correlated with arterial O2 partial pressure (r = -0.740, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Erythrocyte Na-K-Cl cotransport activity in low renin essential hypertensive patients. A 23Na nuclear magnetic resonance study.

The Na-K-Cl cotransport activity in red blood cells from essential hypertensive men with low (n = 8, mean age 42 +/- 4 years) or normal renin activity (n = 4, mean age 43 +/- 3 years), and in normotensive men with normal renin activity (n = 7, mean age 38 +/- 4 years) has been evaluated by means of a recently developed 23Na nuclear magnetic resonance (NMR) method. Sodium efflux was determined by relating the resonating frequency of the NMR signal from extracellular sodium to sodium concentration in the presence of the shift reagent Dy(PPP)2(7-). The maximum Na+ efflux driven by cotransport (Vmax) was measured in Na(+)-loaded erythrocytes in the presence of ouabain to block the Na-K-Cl pump activity. A significant difference (P < 0.05) was found in Vmax values of low renin patients (0.70 mmol/h/L cells, range 0.40 to 0.90 mmol/h/L cells) as compared with normotensive controls (0.39 +/- 0.08 mmol/h/L cells) and normal renin hypertensives (mean 0.49 +/- 0.04 mmol/h/L cells). In conclusion, this study showed an increased activity of the Na-K-Cl cotransport in red blood cells from low renin hypertensive men as compared with normal renin hypertensives and normotensives.

Adult↗

Chemotherapy waste reduction through shelf-life extension.

Minimization of total drug expenditures within the health care system, without affecting patient outcome has become a rational goal in today's economic, environment. The objective of this study was to observe the effect of extending the shelf-life for three chemotherapy medications, [doxorubicin, epirubicin and mitoxantrone] on wastage of these medications. Prior to and following the introduction of new, longer, shelf-lives for these three medications, prospective, non-randomized, unblinded four-month chemotherapy wastage audits for all chemotherapy medications were completed at 18 institutional sites within Ontario (six Ontario Cancer Treatment and Research Foundation clinics, ten Ontario hospitals and two preparation sites in a large cancer treatment centre). Data were provided by 18 sites in 1989 but from only 12 sites in 1990. Ten of the 12 sites extended their shelf-lives for each of doxorubicin, epirubicin and mitoxantrone, and on average, waste at these sites was reduced to less than 1% of the 1989 total for epirubicin, less than 15% for doxorubicin and 35% for mitoxantrone. Many sites eliminated waste entirely for these drugs. For sites which did not extend their shelf-lives, the waste remained unchanged. We conclude that appropriate extension of the shelf-life for chemotherapy medications can reduce waste, and is a relatively simple method of reducing expenditures without affecting health outcomes or adding additional complications to IV chemotherapy.

Analysis of Variance↗

Oxygen administration increases plasma digoxin-like substance and renal sodium excretion in chronic hypoxic patients.

Despite the absence of cardiac or renal pathologies, edema and mild hyponatremia may often occur in patients affected by chronic obstructive pulmonary disease (COPD). Therefore, it has been suggested that hypoxia may influence the release of different hormones regulating renal sodium handling. To evaluate the effect of hyperoxia and O2 removal on plasma digitalis-like substance (DLS) levels, 9 patients affected by COPD and 7 normal subjects were studied. After 1 h in supine position, O2 was administered for 3 h by a tight-fitting face-mask. Blood samples for plasma DLS were taken at time 0, 60, 180 min and then for 3 h after O2 removal. In normal subjects, plasma DLS did not vary after O2 administration (from basal values of 162.25 +/- 8.59 to 107.75 +/- 6.65 pg/ml at 180 min; NS), and O2 removal (143.7 +/- 16.87 pg/ml after 3 h from O2 removal; NS). On the contrary, in patients affected by COPD, plasma DLS levels increased during O2 administration (from basal values of 138.98 +/- 8.31 to 202.14 +/- 8.21 pg/ml at 180 min; p < 0.05), and returned to baseline levels (142.59 +/- 8.28 pg/ml) 3 h after O2 removal. In the same patients, DLS increase was accompanied by a rise in Na+ excretion (from 0.08 +/- 0.01 at time 0 to 0.16 +/- 0.02 mEq/min after 3 h of O2 administration; p < 0.05). In conclusion, our findings showed an oxygen-related increase in plasma DLS levels and in urinary Na+ excretion in patients affected by COPD. This phenomenon could promote Na+ urinary loss during prolonged O2 therapy in these patients and should be taken into account in their management.

Blood Proteins↗

Renal sodium excretory function during acute oxygen administration.

To evaluate the effect of O2 administration and O2 removal on renal Na+ excretion, 12 hypoxemic eucapnic patients affected by chronic obstructive pulmonary disease (COPD) and 9 normal subjects were studied. After 1 h in the supine position, O2 was administered for 3 h by a tight-fitting face-mask. Urine and blood samples for renal Na+ excretion evaluation were taken at times 0, 60 and 180 min. After O2 removal both the blood and the urine samples were taken again for a further 3 h. In normal subjects, urinary Na+ excretion did not vary after both O2 administration and removal. On the contrary, in patients affected by COPD renal Na+ excretion significantly increased during O2 administration (from basal values of 0.08 +/- 0.01 to 0.17 +/- 0.02 mEq/min at 180 min, p < 0.05), and returned to baseline levels (0.13 +/- 0.03 mEq/min) after 3 h from O2 removal. The basal fractional excretion of filtered Na+ was significant lower in hypoxemic patients than in normal subjects (0.72 +/- 0.3% in patients with COPD vs. 0.95 +/- 0.7% in normal subjects, p < 0.05), while, at the end of O2 administration, it became higher in patients with COPD than in controls (1.62 +/- 0.4% in patients with COPD vs. 0.89 +/- 0.5 in control subjects, p < 0.001). In conclusion, our findings showed an oxygen-related increase of both the urinary Na+ excretion and the fractional excretion of filtered sodium in patients affected by COPD.

Carbon Dioxide↗

Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3.

A phase I/II study of intraperitoneal (ip) radioimmunotherapy was conducted in ovarian or breast cancer patients with symptomatic chemotherapy-resistant ascites using a novel anti-mucin monoclonal antibody (mAb) 2G3 labeled with 131I. Tracer doses of 2 mCi [131I]2G3 were given by ip injection to 11 patients, followed by increasing therapeutic doses up to 150 mCi (cumulative) in 9 patients. There was no serious toxicity. Temporary palliation of ascites was observed in 3 of 4 patients who received doses greater than 50 mCi. Total body elimination half-life of the radiolabeled antibody assessed by gamma scintigraphy ranged from 95 to 250 hr, longer than data previously reported in patients without ascites treated with ip administered radiolabeled antibodies. However, uptake of radiolabel by tumor nodules was small and variable (2 x 10(-4) - 2 x 10(-2) % ID/g), and preferential uptake by tumor compared to normal peritoneum was observed in only 2 of 5 patients in whom biopsies were obtained. These results suggest that the observed palliation of ascites is due to prolonged retention of radiolabeled antibody in the peritoneal cavity even in the absence of specific targeting.

Adult↗

Immiscible fluids permeability by T1 imaging.

Soil pollution by hydrocarbon compounds is an important part of the more general pollution problem. Some analogies with research problems encountered in studies of oil reservoirs in rocks suggested to us the opportunity to study the pollution dynamics by imaging the spatial distribution of the pollutant in a wet soil model by an NMR imaging technique. Some preliminary results using T1-weighted imaging are reported here.

Magnetic Resonance Spectroscopy↗

Age-dependent increase of rabbit aortic atherosclerosis. A morphometric approach.

Aging has been indicated as one of the major risk factors for development of atherosclerotic lesions, although the role aging plays, lacks accurate evaluation. Our study was aimed at quantitatively defining such a role by using morphometric analysis. Aged (median age 3 years and 8 months) and young (4 months) white New Zealand rabbits received a hyperlipemic diet enriched with a low dose of cholesterol for 16 months. At regular intervals, levels of serum lipemic parameters were checked. A Quantimet 920 image analyzer was used on paraffin-embedded sections of the entire aortas to measure the volume density of the tunica intima, the volume density of atheroma, the ratio intima/media and the surface area of the tunica intima. Our results indicated for aged hyperlipemic rabbits a statistically significant increase in all morphometric parameters examined as compared to young hyperlipemic animals, and no statistically significant differences in serum cholesterol, triglycerides and phospholipids.

Aging↗

Effects of high altitude exposure on plasma and urinary digoxin-like immunoreactive substance.

Six young healthy subjects underwent a 20 day exposure to altitude, at 4930 m (16,174 ft), to evaluate possible plasma and urine digoxin-like immunoreactive substance (DLIS) changes accompanying the altered water and electrolyte balance induced by hypoxia. We studied DLIS, plasma renin activity (PRA), aldosterone, atrial natriuretic peptide (ANP), and arginine vasopressin (ADH) in serial blood and urine samples. An increase in DLIS in plasma (P less than .005) and urine (P less than .01) was found, while aldosterone was decreased (P less than .02). PRA, ADH, and ANP did not change significantly. A trend to a greater loss of sodium through urinary excretion, correlated with urinary DLIS values (r = 0.47, P less than .01), was observed. Data suggest a possible important role of DLIS in adaptive response of human organism to high altitude.

Adult↗

Histological study of alcoholic, nonalcoholic, and obstructive chronic pancreatitis.

Pancreatic tissue obtained from 26 patients with alcoholic chronic pancreatitis (ACP), nine patients with nonalcoholic idiopathic chronic pancreatitis (NAICP), and seven patients with obstructive chronic pancreatitis (OCP) was studied in an attempt to determine whether clinical or etiologic differences have a morphologic counterpart. Histologically it was easy to distinguish ACP from OCP occurring distal to an obstruction of the pancreatic duct. Nine patients with NAICP showed histological features similar to those found in ACP. Plugs and calcifications were found as frequently in NAICP as in ACP, suggesting that NAICP, whatever the etiology, is truly pancreatolithiasis, which leads to slowly progressive fibrosis and acinar atrophy in the obstructed pancreatic lobule. Nerve fibers were found to be more numerous in all disease categories. Inflammatory foci of lymphocytes associated with nerves were observed in 57 and 35% of cases with OCP and ACP, respectively, but only in one patient with NAICP. These findings may constitute a pathological basis for the existing clinical data showing that NAICP frequently runs a pain-free course.

Adult↗

Morphological and electrophysiological changes of peripheral nerve-muscle unit in the aged rat prevented by levocarnitine acetyl.

The effects of levocarnitine acetyl on structure and function of the sciatic nerve and neuromuscular junctions of the soleus and extensor digitorum longus muscles were studied in the aged rat. To that end, neuromuscular conduction velocity (NMCV) was measured in vivo and morphological and morphometric evaluations were performed. Treatment with levocarnitine acetyl, 150 mg/kg day for six months, restored NMCV values to the levels measured in the young rat; significantly reduced the number of degenerating elements; and increased the number of myelinated fibres having normal structural features. In the soleus and extensor digitorum longus muscles, levocarnitine acetyl increased the complexity of neuromuscular junctions. These experimental findings suggest a neurotrophic action of levocarnitine acetyl on the peripheral nervous system that might have therapeutical applications in age-related peripheral nerve changes.

Acetylcarnitine↗

Levocarnitine acetyl stimulates peripheral nerve regeneration and neuromuscular junction remodelling following sciatic nerve injury.

The effects of levocarnitine acetyl were investigated on both peripheral nerve regeneration and neuromuscular remodelling in male Sprague-Dawley rats, three months of age, following crush of their left sciatic nerve. Levocarnitine acetyl, 150 mg/kg/day in drinking water, was given from one week before to 5, 15, 20, and 60 days after nerve crush. The sciatic nerve was examined morphologically at all given times and morphometrically at 15, 20, and 60 days after the lesion. Morphology, at 5, 15, and 60 days, and morphometry, at 60 days after the nerve crush, were also performed on the neuromuscular junction in the soleus and extensor digitorum longus muscles. Five days after nerve crush, complete axonal degeneration was observed in both control and treated rats. At 15 and 20 days, recovery from injury in treated animals was better than in controls, as shown by a significantly higher increase in the number of regenerating axons. At the same times, denervated endplates were present in both groups. At 60 days, axonal regeneration restored the number of axons to normal values in all injured animals, while their size maturation was greater in treated rats than in controls. A markedly lower number of degenerating elements was found in treated animals. In the neuromuscular junctions of the soleus and extensor digitorum longus muscles, nerve terminal branch points were reduced in the lesioned rats in comparison with uninjured ones. However, morphometric analysis revealed a greater endplate complexity in treated animals in which, at 60 days after nerve crush, nerve terminal branching and sprouting index values were significantly higher than in controls. It is concluded that levocarnitine acetyl exerts a beneficial effect on nerve regeneration processes and synaptic remodelling in crush-induced neuropathies.

Acetylcarnitine↗

[Effects of acute and protracted hypoxia on plasma levels of atrial natriuretic factor].

Acute hypoxia stimulates the release of atrial natriuretic factor (ANF) from isolated rat and rabbit hearts. Increased ANF plasma levels have been found in rats exposed to chronic hypoxia and recently some studies have been conducted on men, with discordant results. The aim of the present study was to verify changes in ANF plasma levels during acute and prolonged hypoxia in young healthy men. We studied 22 subjects (aged 20-28 years, mean 22.7 years) during a simulated exposure to altitude (5000 m) in a hypobaric chamber for 3 hours (A), and 6 subjects (aged 24-51 years, mean 36.5 years) during the scientific expedition to mount Poumori (Nepal 4930 m altitude) with an exposure at maximum altitude for 20 days (B). ANF was measured by the radioimmunoassay method. Results (pg/ml): (A) baseline: 29.4 +/- 18.6; 120 min: 32.0 +/- 17.4 (NS); 180 min: 35.4 +/- 17.1 (p less than 0.05). (B) baseline: 39.6 +/- 13.3; third day: 38.2 +/- 14.1; fifth day: 31.3 +/- 11; seventh day: 29.1 +/- 13.5; tenth day: 32.2 +/- 20.8; fifteenth day: 37.9 +/- 20.2; twentieth day: 34.6 +/- 23.7 (all differences were not significant). In (B) we observed a higher dispersion of values perhaps due to individual variability. The different behaviour of ANF plasma levels in acute and chronic conditions might be due to the adaptive modification of different physiological parameters as loss of plasma volume, natriuresis and attenuation of tissue hypoxia by enhanced erythropoiesis, observed more evidently during prolonged exposure.

Acute Disease↗

Does mild autonomic neuropathy affect atrial natriuretic factor regulation in diabetic hypertensive patients?

The effect of postural changes on plasma atrial natriuretic factor (ANF) levels was investigated in 16 diabetic hypertensives (eight with and eight without mild autonomic neuropathy) and in 10 hypertensives. The presence of renal damage or secondary hypertension was excluded. All diabetic patients were in good metabolic control. In upright position, the mean levels of plasma ANF were of 23.1 +/- 7.6 pg/mL in neuropathic diabetic hypertensives, 24.2 +/- 8.3 pg/mL in diabetic hypertensives, and 21.6 +/- 6.7 in essential hypertensives. Percentage decrease observed after the assumption of supine position was 47 +/- 18, 50 +/- 10, and 46 +/- 13, respectively. No significant difference was found between hypertensives and diabetic hypertensives, even in the presence of mild autonomic neuropathy. Plasma ANF response to postural changes was similar in all groups.

Adult↗

Inpatient narcotic infusions for patients with cancer pain.

Morphine and hydromorphone infusions of 6 or more (average 25.75) days in duration were used with increasing frequency (up to 7%) by our oncology inpatients. Eighty-six percent of the 135 inpatients we reviewed realized good pain control with dose rates up to 700 morphine-equivalent (ME) mg/h. Local toxicity occurred on only 10 occasions. Systemic side effects secondary to the infusion were reported 75 times and were generally readily reversed. Myoclonus was seen in 11% of our patients at dose rates as low as 60-90 ME mg/h. Adjuvant therapies were not used as frequently as might be warranted. We believe that narcotic infusions, particularly subcutaneous ones, are safe and effective. Further prospective trials are needed to clarify how they should be combined with other therapies to control cancer pain that is poorly responsive to narcotics, and to better understand the etiology and management of serious side effects.

Adult↗