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Biomedical subjects

F Manfredi

Publications and source records attributed to F Manfredi.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ketoconazole administration in hypercortisolemic depression.

Ketoconazole, an antiglucocorticoid drug, was administered to 10 hypercortisolemic depressed patients for up to 6 weeks. Three patients dropped out because of side effects or intercurrent illness. The remaining seven had significant ketoconazole-associated decreases in serum cortisol levels and in depression ratings. Antiglucocorticoid agents may be useful probes for investigating the sequelae of hypercortisolemia in patients with major depression.

Adult↗
PubMed1992

The effect of oxygen with exercise on atrial natriuretic peptide in chronic obstructive lung disease.

A recent study on stable, hypoxemic, COLD patients in which ANP was stimulated by LBPP demonstrated that in these individuals elevation of ANP does not exert a "normal" suppressing effect on the PRA-PA axis. Accordingly, we exercised ten comparable COLD patients, another maneuver known to stimulate ANP and to elicit cardiorespiratory responses substantially different from those observed with LBPP. Patients were studied breathing room air and on 40 percent O2 to determine whether the level of oxygenation would modify ANP secretion. Basal levels of ANP on room air were markedly elevated above controls (269 +/- 65 SE vs 70 +/- 20 pg/ml, p less than 0.05); PRA (13.0 +/- 5.4 ng/ml/90 min) and PA (8.6 +/- 3.5 ng/100 ml) were elevated (greater than 2 SD over control levels of 8.1 +/- 1.3 and 2.6 +/- 0.7) in 6/10 and 2/10 patients, respectively. During exercise while breathing O2, only ANP increased; PRA and PA remained unchanged when breathing air and O2. Comprehensive statistical analyses failed to demonstrate a negative relationship between ANP and PRA or ANP and PA. We conclude that in patients with advanced COLD, ANP response to moderate exercise is significantly affected by correction of hypoxemia. This effect may be mediated through changes in airway resistance and consequently cardiac filling pressure.

Aldosterone↗
PubMed1992

Oxygen may lower the O2 cost of ventilation in chronic obstructive lung disease.

It is known that the O2 COV in COLD is high; O2 administration to these patients lowers airway resistance, a major determinant of the COV. Thus, O2 should lower the COV. We measured the COV in ten stable COLD patients and five normal control subjects breathing room air and 30 percent O2. Results indicate that the COV of our patients was elevated above that of control subjects, was related to disease severity, and was decreased with 30 percent O2. The COV of control subjects also was lowered by O2. At rest, O2 lowered VE, VEQ O2 and HR. During submaximal exercise O2 lowered VE, reduced VEQ O2 and extended total exercise time. An inverse correlation was noted between COV and maximal O2 uptake. Thus, in stable COLD, the COV is elevated in proportion to the degree of airway obstruction, inversely related to exercise capacity and lowered by O2 administration.

Air↗
PubMed1992

Antiglucocorticoid strategies in hypercortisolemic states.

Major depressive illness is frequently associated with cortisol hypersecretion. The pathophysiologic significance of this is unknown, although it is possible that hypercortisolemia exacerbates or perpetuates depressive symptoms. In both depression and Cushing's syndrome, certain depressive symptoms are correlated with cortisol levels and, in the latter condition, therapeutic lowering of cortisol levels is associated with remission of psychiatric symptomatology. We review the behavioral effects of anticortisolemic drug administration in Cushing's syndrome and major depression. Preliminary data from small-scale studies suggest that ratings of depressive symptoms in hypercortisolemic major depression may be lowered by such interventions. Such results, if confirmed in larger scale, double-blind studies, might help clarify the role of endocrinologic disturbance in psychiatric symptomatology and might lead to the development of a novel class of antidepressant agent for hypercortisolemic depressed patients.

Depressive Disorder↗
PubMed1991

Pharmacologic elevation of blood inorganic phosphate in hypoxemic patients with COPD.

We have shown that in patients with COPD, myocardial efficiency during exercise is enhanced following acute elevations of plasma phosphate (Pi). A decrease in Hb-O2 affinity (increase in P50) was not responsible for the improvement. We postulated that the physiologic benefit was due to the acute reversal of a subclinical myocardial Pi depletion. To further test this hypothesis in a chronic state, we studied nine stable hypoxemic (PaO2 = 64 +/- 2 mm Hg [+/- SEM]) patients with COPD over five weeks: two weeks at normal plasma Pi; and three weeks at elevated plasma Pi, induced by etidronate disodium (Didronel; 750 mg orally daily). Administration of etidronate disodium increased (p less than 0.05) plasma level of Pi (4.4 +/- 0.2 to 5.8 +/- 0.1 mg/dl), RBC level of Pi (3.1 +/- 0.2 to 4.1 +/- 0.2 mg/dl), RBC level of 2,3-DPG (16.2 +/- 1.1 to 21.3 g+/- 1.3 mumol/g of Hb) and P50 (23.7 +/- 0.5 to 26.0 +/- 0.8 mm Hg). At the end of the treatment, the widening of the C(a-v)O2 with exercise (7.1 +/- 0.8 to 8.9 +/- 0.6 ml/dl) was less pronounced than under control conditions (6.9 +/- 0.4 to 10.1 +/- 0.6 ml/dl; p less than 0.02); concomitantly, the crossover point (COP; the PaO2 below which a rightward-shifted Hb-O2 curve causes the C(a-v)O2 to become narrower rather than wider) increased (37 +/- 2 to 49 +/- 1 mm Hg). Indicators of myocardial work efficiency were not affected by etidronate disodium at rest or during exercise. We postulate that during exercise the potential beneficial effect of the rightward shift of the Hb-O2 curve upon cardiac function was negated by the fall of PaO2 to or below the COP level, a situation which would limit increases in tissue O2 extraction.

2,3-Diphosphoglycerate↗
PubMed1990

Atrial natriuretic peptide and the renin-aldosterone axis during exercise in man.

Under non-exercise conditions, atrial natriuretic peptide (ANP) elevation suppresses plasma renin activity (PRA) and aldosterone (PA). A similar effect of ANP on PRA-PA during exercise has been suggested but not demonstrated. We measured ANP, PRA, PA, plasma potassium (K+), and changes in plasma volume (PV) and blood volume (BV) at rest and during incremental cycle ergometer exercise to exhaustion in ten healthy males. Plasma concentrations (mean +/- SE) of hormones and electrolytes increased (P less than 0.05) during exercise: ANP (68 +/- 14 to 207 +/- 48 pg.ml-1), PA (11.2 +/- 2.2 to 18.8 +/- 3.4 ng.dl-1), PRA (5.1 +/- 1.1 to 8.2 +/- 1.6 ng.ml-1.90 min-1), and K+ (4.2 +/- 0.1 to 5.5 +/- 0.1 mEq). PV and BV declined, reaching maximal deflections from baseline during the 100% stage (12.9 +/- 1.5 and 8.4 +/- 0.8% decreases, respectively). There were positive correlations between ANP and PRA (r = 0.58; P less than 0.01), ANP and PA (r = 0.56; P less than 0.01), and PRA and PA (r = 0.80; P less than 0.001). Increases in K+ did not correlate with increases in PA. The fall in PV correlated with elevations in PRA (r = -0.67; P less than 0.01) and PA (r = -0.58; P less than 0.01), and the fall in BV correlated with elevations in PRA (r = -0.62; P less than 0.01) and PA (r = -0.44; P less than 0.02). ANP production was related to exercise intensity (gauged by heart rate response; r = 0.58; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effect of positive and negative pressure breathing on sodium and water excretion.

Positive and negative pressure breathing purportedly alter renal sodium and water excretion by modifying hemodynamics and/or hormonal regulators of sodium and water homeostasis. To test this hypothesis we monitored hemodynamic and hormonal responses in seven normal men to (1) continuous positive pressure breathing (19 +/- 1 mm Hg for 30 minutes) after water loading (urine volume = 15 +/- 1 ml/min); and (2) continuous negative pressure breathing (11 +/- 1 mm Hg for 30 minutes) after maintenance water ingestion (urine volume = 4 +/- 1 ml/min), in random order. Each study was repeated on a control day without pressure breathing. Results were as follows (mean +/- SE, p less than 0.05): (1) continuous positive pressure breathing decreased urinary sodium from 0.28 +/- 0.07 to 0.17 +/- 0.04 mEq/min, increased atrial natriuretic peptide from 34.2 +/- 4.9 to 48.5 +/- 6.9 pg/ml, and had no effect on osmolar and free water clearances, cardiac output, plasma renin activity, or plasma aldosterone and plasma arginine vasopressin levels; and (2) continuous negative pressure breathing increased free water clearance from 0.6 +/- 0.7 to 4.5 +/- 1.2 ml/min, urine volume from 4.0 +/- 0.8 to 8.9 +/- 1.3 ml/min, and cardiac output from 5.1 +/- 0.4 to 7.0 +/- 0.6 L/min in a proportional manner (r = 0.40, p less than 0.01) and had no effect on osmolar clearance, urinary volumes of sodium and potassium, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Atrial natriuretic peptide, renin and aldosterone in obstructive lung disease and heart failure.

Elevations of atrial natriuretic peptide (ANP) in congestive heart failure (CHF) and chronic obstructive lung disease (COLD) are presumably due to atrial hypertension, while secondary hyperaldosteronism in these patients is thought to result from diminished renal perfusion. The responsiveness of the ANP and renin (PRA)-aldosterone (PA) systems to acute increases in right atrial pressure has not been studied in these patients, but in normals a reciprocal relationship between ANP with PRA and PA has been shown. The authors monitored venous pressure (VP, reflective of right atrial pressure), ANP, PRA and PA in 15 stable COLD patients, seven stable CHF patients and three normal controls at baseline and after elevation of VP by antishock trousers. Inflation of the trousers resulted in increased VP and ANP (p less than 0.05): control ANP, 84 +/- 17 to 108 +/- 23 pg/ml; COLD ANP, 176 +/- 5 to 200 +/- 7; and CHF ANP, 388 +/- 20 to 499 +/- 37. PRA and PA were not suppressed by increasing ANP levels and the delta ANP/delta VP ratio was similar among groups. No intergroup differences in resting PRA and PA were noted, but PRA was higher (p = 0.007) and PA tended to be higher (p = 0.08) in a sub-group of six edematous patients, as compared with non-edematous patients and controls. These findings: (1) confirm previously reported ANP differences between COLD and CHF; (2) indicate that the ANP system remains responsive to physiologic manipulations in COLD and CHF; and (3) demonstrate that ANP and the PRA-PA axis are not reciprocally related in either group.

Aged↗
PubMed1985

Effect of hypoxemia on sodium and water excretion in chronic obstructive lung disease.

To determine the role of hypoxemia in the pathogenesis of impaired sodium and water excretion in advanced chronic obstructive lung disease, 11 clinically stable, hypercapneic patients requiring long-term supplemental oxygen were studied. The renal, hormonal, and cardiovascular responses to sodium and water loading were determined during five-and-a-half-hour studies on a control day (arterial oxygen tension = 80 +/- 6 mm Hg) and on an experimental day under hypoxic conditions (arterial oxygen tension = 39 +/- 2 mm Hg). Hypoxemia produced a significant decrease in urinary sodium excretion but did not affect urinary water excretion. Hypoxemia also resulted in concomitant declines in mean blood pressure, glomerular filtration rate, and filtered sodium load. Renal plasma flow and filtration fraction were unchanged whereas cardiac index rose. On the control day, plasma renin activity and norepinephrine levels were elevated whereas aldosterone and arginine vasopressin levels were normal; none of these four hormones was affected by hypoxemia. Renal tubular function did not appear to be altered by hypoxemia as there was no significant change in fractional reabsorption of sodium. The concurrent decreases in glomerular filtration rate, filtered sodium load, and mean blood pressure at constant renal plasma flow suggest that the reduction in urinary sodium excretion was due to an effect of hypoxemia on glomerular function, possibly related to impaired renovascular autoregulation.

Aged↗
PubMed1985

Renal and hormonal responses to acute hypoxia in normal individuals.

We studied, in normal volunteers, the effects of 1 hour of hypoxia on the concentration of angiotensin-converting enzyme and bradykinins, along with previously measured parameters of renal and endocrine function. Ten men, 18 to 42 years of age, undergoing water diuresis, breathed a low-oxygen mixture (five breathed 10.5% O2 and five 12% O2); all breathed 21% O2 on a control day. Measurements included mean blood pressure and heart rate every 2 to 3 minutes; plasma levels of renin activity, aldosterone, arginine vasopressin, norepinephrine, and bradykinin, and angiotensin-converting enzyme activity, before and at the end of gas breathing; and urine volume (UV), creatinine, Na+, and bradykinin concentration. Arterial blood gases and effective renal plasma flow were determined at the end of gas breathing only. Mean values +/- SEM for arterial blood gases with low O2 were pH 7.39 +/- 0.02, PO2 46 +/- 2 torr, PCO2 39 +/- 2 torr (12% O2) and 7.48 +/- 0.01, 35 +/- 1 torr, 33 +/- 1 torr (10.5% O2). Responses were otherwise identical in both groups, and data were combined for analysis. With hypoxia, heart rate and effective renal plasma flow increased significantly, P less than 0.005; no changes occurred in Uv, urine Na+ concentration, glomerular filtration rate, plasma or urine bradykinin concentration, serum angiotensin-converting enzyme activity, plasma renin activity, plasma aldosterone concentration, plasma arginine vasopressin concentration, or plasma norepinephrine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

In vitro elevation of red blood cell 2,3-diphosphoglycerate with fructose, phosphate, and methylene blue.

2,3-Diphosphoglycerate (2,3-DPG) is an important regulator of hemoglobin oxygen affinity and thus can theoretically affect tissue oxygenation. Marked stimulation of DPG with substances that would likely be well tolerated by humans has not been reported previously. In order to achieve such stimulation, we investigated (n = 102) the effect of various combinations of fructose (2.8-11.1 mM) and sodium phosphate (1.0-130.0 mM) on 2,3-DPG production by perfusing fresh human blood in dialysis tubing, 37 degrees C, pH 7.15-7.70, with the appropriate solutions and with compressed air or 100% O2 for up to 6 hours. The DPG increased significantly with fructose/phosphate incubations for 6 hours. At pH greater than 7.35 the average increase was 25%; at pH less than 7.35, 12%; PO4 greater than 6 mM + pH greater than 7.35 yielded the highest changes, 28%. Methylene blue 2.5-7.5 microM + PO4 greater than 2.5 mM + pH greater than 7.35 yielded similar results. Glucose + PO4 showed no effect on DPG. Results were comparable at all fructose levels either with compressed air or 100% O2. Significant elevations in 2,3-DPG were also noted at 4 hours but were of lesser magnitude. In conclusion, significant elevations in 2,3-DPG can be achieved by incubating whole blood with fructose/phosphate solutions or with methylene blue and phosphate for 4-6 hours. It should be possible to adapt these solutions for human use to raise 2,3-DPG. The potential physiologic value of rightward shifts in hemoglobin oxygen affinity can then be tested under appropriate conditions.

Adult↗
PubMed1984

Hormonal abnormalities affecting sodium and water balance in acute respiratory failure due to chronic obstructive lung disease.

The pathogenesis of edema and hyponatremia associated with chronic obstructive lung disease (COLD) is poorly understood. In ten edematous COLD patients with acute respiratory failure (ARF), we monitored plasma renin activity (PRA), aldosterone (PA), and antidiuretic hormone (arginine vasopressin, AVP) for six days. Six patients receiving supplemental oxygen and antibiotics had near normal PRA, PA, and AVP, and diuresed Na+ and H2O and lost weight; only one patient was hyponatremic (PNa+ less than 130 mEq/L). On the same therapy, nonresponders (n = 4), with persistently elevated PRA, PA, and AVP, demonstrated no loss of Na+, H2O, or weight; three patients were hyponatremic. The PRA and PA correlated inversely with sodium loss; AVP correlated inversely with free water clearance. These studies suggest that in patients with COLD, edema, and ARF (1) lack of sodium diuresis may be contributed to by secondary hyperaldosteronism; and (2) hyponatremia can be explained by inappropriately elevated plasma AVP.

Arginine Vasopressin↗
PubMed1984

Effect of decreased O2 affinity of hemoglobin on work performance during exercise in healthy humans.

A reduction in O2 affinity of hemoglobin should increase tissue oxygenation or maintain tissue oxygenation and at the same time spare cardiac work. Large, sustained reductions in O2 affinity of hemoglobin are induced best by primary (non-Bohr effect) stimulation of red blood cell 2,3-diphosphoglycerate (DPG) caused by a dual, cumulative effect on O2 affinity for hemoglobin, direct, from DPG itself, and indirect, from DPG-induced red blood cell acidosis. In an attempt to induce significant, sustained reductions in O2 affinity of hemoglobin by primary DPG stimulation, six normal humans were given a diphosphonate (etidronate disodium [Didronel] 20 mg/kg/day p.o.) followed by infusion of 10% fructose (0.5 L/hr for 3 hours) with added phosphate (0.28 mmol/kg/hr) and, subsequently, fructose-phosphate by itself. Participants underwent exercise testing (bicycle ergometer) and cardiopulmonary parameters were measured before and after administration of Didronel plus fructose-phosphate infusion, as well as before and after fructose-phosphate infusion alone. The sum of DPG and adenosine triphosphate as well as the P50 increased significantly after infusion of fructose-phosphate with and without prior administration of Didronel. DPG-ATP correlated closely with P50. When P50 was elevated, the cardiac index at high work load was lower than when P50 was normal (with comparable O2 consumption); changes in P50 correlated inversely with changes in cardiac index. Thus, with reduced O2 affinity of hemoglobin, participants could perform at comparable work loads and utilize the same amount of O2 with less cardiac work. Future studies should include adapting these findings to states of O2 deficit.

2,3-Diphosphoglycerate↗
PubMed1983

Plasma aminoacid levels across the brain in patients with respiratory failure.

Animal studies and theoretical considerations have suggested that in hypercapnic respiratory failure there is interconversion of glutamic acid to glutamine within the brain, perhaps as part of a local buffering mechanism to minimize hypercapnia-induced cerebral acidosis. Detection of transcerebral arteriovenous differences, positive for glutamic acid and negative for glutamine, would lend support to this hypothesis. We measured arterial and internal jugular venous levels of twenty-three aminoacids in four patients with hypercapnic respiratory failure and in four suitable controls. In patients, arterial as well as venous glutamine levels were elevated proportionally, and there was no demonstrable A-V difference across the brain; arterial and venous glutamic acid levels were the same as controls. All other aminoacid levels, arterial and venous, were normal. These findings confirm the previous observations that in hypercapnic respiratory failure glutamine metabolism is altered, but provide no support for the proposed glutamic acid-glutamine interconversions within the brain.

Amino Acids↗
PubMed1982

Plasma levels of false neurotransmitters across the brain in portal-systemic encephalopathy.

Arterial and internal jugular venous levels of false neurotransmitters (FNTs: octopamine, OCT, and phenylethanolamine, PEA), aromatic and branched-chain amino acids, glutamine, ammonia, and pH were measured in patients with portal-systemic encephalopathy (PSE) and in appropriate controls to define the role of these parameters in the pathogenesis of hepatic coma. The typical plasma patterns reported in the literature were observed: hyperammonaemia (59 +/- 8 mumol/l v. controls 30 +/- 4, P less than 0.005), elevated OCT (19 +/- 3 nmol/l v. 6 +/- 1, P less than 0.001) and PEA (64 +/- 8 nmol/l v. 27 +/-3, P less than 0.001), high ratio of aromatic to branched-chain amino acids (0.92 +/- 0.12 v. 0.32 +/- 0.04, P less than 0.005), and variable glutamine levels 216-734 mumol/l). No consistent net flux into or out of the brain could be demonstrated for any of these substances. The degree of encephalopathy correlated with the level of respiratory alkalosis (r=0.325, P less than 0.05) which, in turn, correlated with the degree of elevation of plasma OCT (r=0.439, P less than 0.05) and PEA (r=0.489, P less than 0.05) as well as with the excess of glutamine efflux from the brain (r=0.927, P less than 0.05). These findings support current views that hyperammonaemia, plasma amino acid imbalance, and elevated production of FNTs are interrelated disturbances which contribute to the pathogenesis of PSE. In addition, the data suggest that alkalosis accentuates the altered metabolism of these substances within the brain.

2-Hydroxyphenethylamine↗
PubMed1982

Acute effects of hypoxia on renal and endocrine function in normal humans.

The effects of hypoxia upon renal and endocrine function are unclear. Normal water-loaded subjects were exposed to hypoxia for 1 h (inspired PO2 = 74 Torr) in a decompression chamber (5,100 m, n = 8) or by breathing 10.5% oxygen at ambient pressure (n = 4). In four of eight subjects exposed to hypobaric hypoxia: urine flows (V) decreased (mean = 56%), urine osmolality increased (340%), plasma arginine vasopressin (AVP) increased (2,700%), plasma cortisol increased (256%), and mean blood pressure (BP) decreased (18%). V correlated inversely with AVP (r = 0.71, P less than 0.01) while AVP increases correlated with falls in mean BP (r = 0.72, P less than 0.05). Similar results were observed in the subjects exposed to normobaric hypoxia. Plasma aldosterone fell in the four subjects who maintained V on exposure to hypobaric hypoxia, but plasma renin activity did not change. In both groups prolactin levels were variable and solute and creatinine excretion were unchanged. No changes were observed in controls or in subjects exposed to hypobaria alone. Acute hypoxic exposure may produce significant hypotension with consequent increased AVP secretion resulting in diminished V.

Adolescent↗
PubMed1982

Computed tomography vs standard radiology in the evaluation of mediastinal adenopathy.

The value of computed tomography (CT) compared with standard radiology (SR) in the evaluation of mediastinal nodes has not been clearly defined. We compared SR and CT findings with the surgical-pathologic observations in a prospective study of 51 mediastinal nodes in 59 patients, 41 with bronchogenic carcinoma and 18 with benign lung lesions. CT was characterized by a low overall accuracy (true positivity plus true negativity = 60 percent) due to the false positivity (6 percent) and, to a much greater extent, the false negativity (51 percent). The pattern was the same in the malignant and in the benign group. In all instances CT findings were statistically the same as SR findings. We conclude that mediastinal CT provides no advantage over SR. Thus, SR alone is sufficient to select the surgical procedure of choice for evaluating mediastinal nodes, and no radiologic modality should replace surgical exploration in staging mediastinal nodal pathology.

Carcinoma, Bronchogenic↗