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Biomedical subjects

R F Lodato

Publications and source records attributed to R F Lodato.

36 records · Page 2Linked to original sources
PubMed1990

Localized leukemic pulmonary infiltrates. Diagnosis by bronchoscopy and resolution with therapy.

Although commonly found at autopsy, leukemic infiltration of the lung is rarely recognized as a cause of respiratory symptoms or roentgenographic densities. Previously reported cases of patients who had symptomatic or roentgenographic acute leukemic lung diseases invariably presented with diffuse pulmonary infiltrates. We describe three patients with leukemic involvement of the lung who presented with cough, fever, and localized roentgenographic infiltrates suggestive of bacterial pneumonia. In each case, the diagnosis was made by transbronchial biopsy specimen and confirmed by complete response to chemotherapy. In common with the other reported cases, all of our patients had peripheral blast counts above 40 percent (greater than 6,000 blasts per ml3) at the time the pulmonary diagnosis was made. Leukemic invasion of the lung should be considered in patients with acute leukemia who develop lung infiltrates--whether diffuse or focal--in association with a high peripheral blast count.

Adult↗
PubMed1990

Immunohistochemical evaluation of c-erbB-2 oncogene expression in ductal carcinoma in situ and atypical ductal hyperplasia of the breast.

Cases of ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) of the breast were examined for expression of the protein product of the c-erbB-2 (neu, HER-2) oncogene using two different polyclonal antibodies via an avidin-biotin immunoperoxidase method on formalin- or Bouin'-fixed, paraffin-embedded tissue. Fifty-five percent (18/33) of DCIS and 10% (2/21) of ADH were positive. Significant c-erbB-2 expression in DCIS was generally divided on histologic grounds: ten of ten comedocarcinomas showed strong membrane staining, while only one of 14 small cell DCIS cases (micropapillary or cribiform patterns) showed immunostaining (which was weak and basilar in this single case). DCIS cases of mixed histology were strongly positive in areas of comedocarcinoma. In two of three cases of associated Paget's disease strong membrane staining was seen. The two c-erbB-2-positive ADH cases showed weak basilar staining akin to the small cell DCIS cases. Five cases of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) associated with DCIS or ADH were negative for c-erbB-2 expression. We conclude that comedocarcinoma in situ and Paget's disease frequently express the c-erbB-2 protein and are both histologically and biochemically distinct from ADH and small cell patterns of DCIS. We advocate precise subclassification of DCIS on histopathologic reports, particularly in view of reports that overexpression of the c-erbB-2 oncogene in infiltrating breast carcinomas may be associated with a poor prognosis.

Breast↗
PubMed1990

Oxygen toxicity.

The paradox of oxygen therapy is that it can be both life saving and life destroying. Considered as one of the most important drugs available to the clinician, its "dose," determined as the product of the oxygen concentration used and the duration of its use, must be titrated to avoid toxicity while still achieving adequate systemic oxygenation.

Free Radicals↗
PubMed1989

Decreased O2 consumption and cardiac output during normobaric hyperoxia in conscious dogs.

Recent reports indicate that under certain restricted conditions hyperoxia may decrease tissue O2 consumption. However, this effect has not been established for whole body O2 consumption in the intact healthy conscious state. The goal of the present study was to document the effect of hyperoxia on resting whole body O2 consumption and hemodynamics under these latter more general physiological conditions. The inspired gas was delivered by mask to six fasted resting conscious dogs and alternated hourly between air and O2-enriched air (hyperoxia) for 5 h, while hemodynamics and blood gas data were obtained every 20 min. Compared with air breathing, hyperoxia increased the mean arterial O2 tension from 95 to 475 Torr and decreased heart rate, cardiac output, pulmonary vascular resistance, and right and left ventricular work rates and thus, presumably, myocardial O2 consumption. Hyperoxia also increased systemic vascular resistance and right atrial pressure but did not change stroke volume or systemic arterial pressure. The increase in arterial O2 content during hyperoxia was counterbalanced by the decrease in cardiac output, so that O2 delivery was unchanged by hyperoxia. Surprisingly, hyperoxia decreased the arterial-to-mixed venous difference in O2 content; this decrease together with the decrease in cardiac output produced a decrease in resting whole body O2 consumption from 5.88 +/- 0.68 to 4.80 +/- 0.62 ml O2.min-1.kg-1 (P = 0.0002). It is concluded that under physiological conditions normobaric hyperoxia may decrease metabolic rate in addition to cardiac output, which may have important implications for the metabolic regulation of O2 utilization as well as for the medical and nonmedical uses of O2.

Animals↗
PubMed1989

Cardiopulmonary interactions in the cardiac patient in the intensive care unit.

Critically ill cardiac patients often undergo mechanical ventilation. The interplay between pulmonary and cardiac mechanics is complicated and in many cases may result in impaired transfer of O2 from the atmosphere to the tissues. This article addresses the principles of pulmonary and peripheral gas exchange, as well as the mechanical effects of respiration on the circulation.

Cardiac Output↗
PubMed1988

Variability of resting respiratory drive and timing in healthy subjects.

Studies of breathing pattern have focused primarily on changes in the mean values of the breathing pattern components, whereas there has been minimal investigation of breath-to-breath variability, which should provide information on the constancy with which respiration is controlled. In this study we examined the variability of breathing pattern both on a breath-to-breath and day-to-day basis by calculating the coefficient of variation (i.e., the standard deviation expressed as a percentage of the mean). By examining breath-to-breath data, we found that the coefficients of variation of tidal volume (VT) and fractional inspiratory time (TI/TT, an index of timing) obtained with an inductive plethysmograph and spirometer were within 1% of each other. Examination of breath-to-breath variability in breathing pattern over a 15-min period in 65 subjects revealed large coefficients of variation, indicating the need to base calculations on a relatively large number of breaths. Less breath-to-breath variability was observed in respiratory frequency [f, 20.8 +/- 11.5% (SD)] and TI/TT (17.9 +/- 6.5%) than in VT (33 +/- 14.9%) and mean inspiratory flow (VT/TI, an index of drive; 31.6 +/- 12.6%; P less than 0.0001). Older subjects (60-81 yr) displayed greater breath-to-breath variability than young subjects (21-50 yr). Use of a mouthpiece did not affect the degree of variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Absence of neural modulation of hypoxic pulmonary vasoconstriction in conscious dogs.

Our objectives were 1) to quantify the magnitude of the hypoxic pulmonary vasoconstrictor (HPV) response in conscious dogs by utilizing pulmonary vascular pressure-cardiac index (P/Q) plots and 2) to assess the extent to which the autonomic nervous system (ANS) modulates the HPV response. Multipoint P/Q plots were constructed in conscious dogs during normoxia and during bilateral alveolar hypoxia by stepwise constriction of the thoracic inferior vena cava to reduce Q. With the ANS intact, the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) increased (P less than 0.01) approximately twofold during hypoxia over a broad range of Q. The absolute magnitude of the HPV response was related (P less than 0.01) to the level of Q. We hypothesized that if ANS activation reduces the magnitude of HPV in intact dogs, then we would expect the magnitude of HPV to be increased both after combined sympathetic alpha-(phentolamine) and beta-(propranolol) adrenergic block and after total autonomic ganglionic block (hexamethonium). A marked HPV response (P less than 0.01) was observed after both combined sympathetic block and ganglionic block over a broad range of Q during alveolar hypoxia. The magnitude of the HPV response with the ANS intact, however, was not significantly different from the magnitude of HPV after combined sympathetic block (P = 0.45) or after ganglionic block (P = 0.64) at any level of Q. Thus, during bilateral alveolar hypoxia, the ANS does not appear to attenuate the HPV response of intact conscious dogs.

Animals↗
PubMed1987

Does rib cage-abdominal paradox signify respiratory muscle fatigue?

Studies suggesting that abnormal motion of the rib cage (RC) and abdomen (Ab) may indicate respiratory muscle fatigue have not separated the influence of respiratory load from that of fatigue in its pathogenesis. We hypothesized that abnormalities on RC-Ab motion are primarily related to increased load rather than fatigue. We tested this hypothesis in subjects breathing against resistive loads while maintaining 30 and 60% of maximum mouth pressure (Pmmax). RC-Ab asynchrony and paradox and the degree of variation in compartmental contribution to tidal volume were measured by inductive plethysmography and quantitated by the Konno-Mead method of analysis. Comparing measurements of base line and 30 and 60% of Pmmax indicated that the degree of asynchrony, paradox, and variation in compartmental contribution were significantly related to the level of the load; significant abnormalities were observed at even 30% of Pmmax, a target pressure that can be sustained indefinitely. In another group of subjects, fatigue was induced by sustaining 60% of Pmmax to the limits of tolerance. Indexes of abnormal RC-Ab motion increased from base line during the 1st min of loaded breathing but displayed no progression from the beginning to the end of the fatigue run. Immediately on discontinuation of the load, the indexes returned to levels similar to base line despite persistence of the fatigue state. These results in healthy subjects breathing against severe resistances indicate that RC-Ab asynchrony and paradox and variation in compartmental contribution to tidal volume are predominantly due to increases in respiratory load rather than muscle fatigue.

Abdomen↗
PubMed1987

Konno-Mead analysis of ribcage-abdominal motion during successful and unsuccessful trials of weaning from mechanical ventilation.

Respiratory muscle fatigue is considered a common cause of weaning failure but its detection is hampered by the lack of a satisfactory diagnostic test. Abdominal paradox has been proposed as a valuable clinical index of fatigue and thus its presence may lead to curtailment of weaning trials. However, sensitivity and specificity of this sign as a predictor of weaning outcome is unknown. We hypothesize that abnormal ribcage-abdominal (RC-Ab) motion is a common finding in the early stages of weaning and its presence does not inevitably imply an unsuccessful weaning outcome. We tested this hypothesis in patients undergoing a weaning trial: one group had a successful weaning outcome and were extubated (n = 10) and the other group failed the trial (n = 7). Normal RC-Ab motion was separately characterized in 17 healthy subjects. Employing a calibrated respiratory inductive plethysmograph, quantitative assessment of asynchrony and paradox was obtained by computing several indices from series of breaths at fixed time periods using the Konno-Mead method of analysis. During the weaning trial, both groups of patients displayed significant increases in asynchrony and Ab paradox compared to normal values. As a group, patients who failed the trial displayed significantly greater asynchrony and paradox of the RC and Ab than patients with a successful outcome. However, there was considerable overlap between the individual patients in the 2 study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1986

Neural antagonists modulate pulmonary vascular pressure-flow plots in conscious dogs.

Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed in conscious dogs during normoxia by graded constriction of the thoracic inferior vena cava to reduce Q. P/Q plots were generated with the autonomic nervous system (ANS) intact and following total autonomic ganglionic block, cholinergic block, and sympathetic alpha- and beta-adrenergic block alone and in combination. With the ANS intact, the relationship between the pulmonary vascular pressure gradient [pulmonary arterial pressure (PAP)--pulmonary capillary wedge pressure (PCWP)] and Q was linear with an extrapolated pressure intercept of 0 mmHg. Total autonomic ganglionic block increased PAP-PCWP over the entire range of Q studied (60-140 ml . min-1 . kg-1). Cholinergic block resulted in a small increase in PAP-PCWP at a Q of 60 ml . min-1 . kg-1, a small decrease in PAP-PCWP at a Q of 140 ml . min-1 . kg-1, but no change in PAP-PCWP over the midrange of Q. Sympathetic beta-adrenergic block increased, and sympathetic alpha-adrenergic block decreased PAP-PCWP over the entire range of Q studied. Combined sympathetic alpha- and beta-adrenergic block also increased PAP-PCWP at each level of Q. Thus the ANS, either directly or via circulating catecholamines, exerts an active regulatory influence on the pulmonary vascular P/Q relationship of intact conscious dogs during normoxia over a wide range of Q. Activation of sympathetic beta-adrenergic receptors results in pulmonary vasodilatation, whereas, alpha-receptor activation results in vasoconstriction. Surprisingly, based on the effects of total autonomic ganglionic block and combined sympathetic alpha- and beta-adrenergic block, the net effect of the ANS on PAP-PCWP/Q during normoxia appears to be pulmonary vasodilatation.

Adrenergic alpha-Antagonists↗
PubMed1986

The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation.

We prospectively examined the pattern of breathing in patients being weaned from mechanical ventilation: one group (n = 10) underwent a successful weaning trial and were extubated, whereas another group (n = 7) developed respiratory failure and required the reinstitution of mechanical ventilation. During the period of ventilator support, minute ventilation (VI), tidal volume (VT), and respiratory frequency (f) were similar in the 2 groups. After discontinuation of the ventilator, VI remained similar in the 2 groups, but VT was lower and f was higher in the patients who failed the trial compared with those who were successful, 194 +/- 23 and 398 +/- 56 ml (p less than 0.001), respectively, and 32.3 +/- 2.3 and 20.9 +/- 2.8 breaths/min (p less than 0.001), respectively. The failure group displayed a significant increase in PaCO2 (p less than 0.005) during spontaneous breathing, without a concomitant increase in the alveolar-arterial PO2 difference. Eighty-one percent of the variance in PaCO2 was accounted for by the pattern of rapid, shallow breathing. During weaning, resting respiratory drive (reflected by mean inspiratory flow, VT/TI) and fractional inspiratory time (TI/Ttot) were similar in the 2 groups. The patients in the failure group showed significant increases in VT/TI, 265 +/- 27 to 328 +/- 32 ml/s (p less than 0.01), and VI, 5.82 +/- 0.53 to 7.32 +/- 0.52 L/min (p less than 0.01), from the beginning to the end of the weaning trial; VT and f showed no further change.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMed1985

Multipoint pulmonary vascular pressure-cardiac output plots in conscious dogs.

To characterize quantitatively the relationships among pulmonary vascular pressures (P) and cardiac output (Q) in conscious dogs, multipoint plots of pulmonary arterial (PAP), pulmonary capillary wedge (PCWP), PAP - PCWP, and left atrial (LAP) pressure versus Q were generated by graded constriction of the thoracic inferior vena cava (IVC) to vary Q. Slopes and extrapolated pressure intercepts from linear regression fits to the P/Q plots were determined for three inspired oxygen tensions: normoxia, hyperoxia, and hypoxia. During normoxia (arterial Po2 87 +/- 1 Torr), the extrapolated pressure intercepts for PAP, PCWP, and PAP - PCWP were virtually 0 mmHg, and for LAP, substantially negative (-5.5 +/- 1.1 mmHg; P less than 0.01). Hyperoxia (Po2 365 +/- 28 Torr) had no effect on any of the P/Q plots. In contrast, hypoxia (Po2 51 +/- 1 Torr) significantly increased the intercepts (P less than 0.01) as well as the slopes (P less than 0.05) of PAP and PAP - PCWP versus Q, but produced only minor changes in PCWP and LAP versus Q. These hypoxia-induced changes in intercepts, perhaps related to changes in critical closing pressures, demonstrate the limitations of pulmonary vascular resistance calculations (quotient of pressure gradient and Q) in quantifying changes in pulmonary vasomotor tone. In this way, the IVC constriction technique provides a more complete description of P/Q relationships than that permitted by simple calculations of pulmonary vascular resistance. We conclude that this technique can be utilized to investigate the effects of other physiological and pharmacological interventions on pulmonary vasomotor tone in conscious dogs.

Animals↗
PubMed1984

Mutant cell lines resistant to azetidine-2-carboxylic acid: alterations in the synthesis of proline from glutamic acid.

Two mutant Chinese hamster lung fibroblast lines have been isolated that are resistant to the toxic proline analog L-azetidine-2-carboxylic acid. The line designated AZCA-1 has 30-fold elevated activity of pyrroline-5-carboxylate synthase and a large increase in the rate of proline production and release compared to controls. Pyrroline-5-carboxylate synthase activity is not elevated in the resistant line designated AZCA-4, but the enzyme is less sensitive to inhibition by ornithine and proline than control enzyme. Intracellular proline is elevated in AZCA-4 cells, with no change in the rate of release of proline synthesized from glutamate. Resistance to azetidine carboxylic acid in both mutant lines is attributed to the expanded intracellular proline pool that results from alterations in pyrroline-5-carboxylate synthase. These results indicate that intracellular proline levels are determined at least in part by the regulated activity of pyrroline-5-carboxylate synthase.

Animals↗
PubMed1981

Regulation of proline biosynthesis: the inhibition of pyrroline-5-carboxylate synthase activity by ornithine.

Mammalian cells have the capacity for proline biosynthesis from ornithine or glutamic acid. Using a radioisotopic assay, we have studied the regulation by ornithine of delta 1-pyrroline-5-carboxylate synthase, the enzyme that catalyzes the first step of proline biosynthesis from glutamic acid. In homogenates from Chinese hamster ovary cells, ornithine was found to be a potent inhibitor of pyrroline-5-carboxylate synthase activity(50% inhibition at 0.37 mM). The effect was reversible and did not occur with amino acids other than ornithine. Preliminary findings suggest that the inhibition does not result from altered requirements for the cofactors NADPH and ATP. Significant inhibition was observed in four different Chinese hamster cell lines. Ornithine was also shown to inhibit the conversion of 3H-glutamic acid to 3H-proline in intact human skin fibroblasts. Cells from patients with a rare ocular disease, gyrate atrophy of the choroid and retina, were used for these studies since they lack interfering ornithine aminotransferase activity. We conclude that ornithine may be a physiologic regulator of the rate of proline formation from glutamic acid. This information allows us to construct an hypothetical model for the overall regulation of proline biosynthesis and also to suggest a pathophysiologic mechanism for the disease gyrate atrophy.

Animals↗
PubMed1980

Pyrroline-5-carboxylate synthase activity in mammalian cells.

Although glutamic acid is known to be a precursor for proline biosynthesis, the enzymatic conversion of glutamic acid to pyrroline-5-carboxylic acid, the immediate precursor of proline, has not been demonstrated in cell-free systems. By providing appropriate concentrations of ATP and NADPH and blocking further metabolism of pyrroline-5-carboxylic acid, we have developed a method for measuring the formation of pyrroline-5-carboxylic acid from glutamic acid in homogenates of mammalian cells. We have designated this activity pyrroline-5-carboxylate synthase. To confirm that our assay is a valid measure of the initial step in proline biosynthesis from glutamic acid, we have compared two mutant lines of Chinese hamster ovary cell. Proline prototrophic cells, which can synthesize proline from glutamic acid, have easily measurable pyrroline-5-carboxylate synthase activity (5.97 nmol of pyrroline-5-carboxylic acid per hr per mg of homogenate protein). In contrast, proline auxotrophic cells, which are unable to synthesize proline from glutamic acid, have no detectable pyrroline-5-carboxylate synthase activity.

Adenosine Triphosphate↗
PubMedDate not supplied

Protective effect of NG-monomethyl-L-arginine against hypotension inducted by combined tumour necrosis factor-alpha and whole body hyperthermia in rats.

We studied: (a) the adverse effects of tumour necrosis factor-alpha (TNF) given during whole body hyperthermia (WBH) on mean arterial pressure (MAP) and gut mucosa in anaesthetized rats; (b) the potential protective effect of NG-monomethyl-L-arginine (L-NMA), an inhibitor of nitric oxide synthase; and (c) the influence of L-NMA on the antitumour effect of the trimodality therapy, WBH + TNF + Carboplatin (CBDCA). In normothermic rats, TNF alone (10(5) or 10(6) U/kg) did not cause hypotension, but increased MAP (p < 0.05). L-NMA alone (5, 10 and 20 mg/kg) increased MAP moderately and dose-dependently (p < 0.05). WBH (41.5 degrees C for 2 h) increased MAP markedly (from 103 +/- 4 to 161 +/- 4 mm Hg). This increase in MAP was sustained throughout the hyperthermia, but was followed by a transient relative hypotension (MAP = 80 +/- mm Hg) on cessation of WBH and an eventual return to near baseline at 30 min post-WBH (MAP = 94 +/- 5 mm Hg). WBH + TNF (10(5) or 10(6) U/kg) initially increased MAP similarly to WBH alone. During the second hour of WBH, however, MAP decreased towards pre-treatment levels, and cessation of WBH was followed by sustained hypotension. This late hypotensive state was associated with a mortality during the early (first 2 h) post-WBH period of 17 and 100% at TNF dose of 10(5) and 10(6) U/kg TNF, respectively. L-NMA given to rats receiving WBH + TNF (10(6) U/kg) maintained MAP at levels similar to WBH alone during WBH treatment. L-NMA prevented the post-WBH hypotension, and extended the survival beyond the early (first 2 h) post-WBH period. No rat, however, receiving high dose TNF (10(6) U/kg) survived more than 12 h even with L-NMA (totally 40 mg/kg). WBH + TNF (10(5) and 10(6) U/kg) also produced marked histopathological injury to the gut mucosa at 2 h post-treatment. L-NMA substantially protected the gut from this injury. In rats bearing a transplantable fibrosarcoma, L-NMA did not decrease the antitumour effect consisting of WBH + TNF (10(5) U/kg) + CBDCA, while it decreased (p < 0.05) the general toxicity (weight loss, diarrhea and foot oedema) of this combination. We conclude that L-NMA may prevent or ameliorate the early toxicity but not the late lethal effects of WBH + high dose TNF (10(6) U/kg). Additionally, L-NMA reduces some of the toxicity of WBH + TNF (10(5) U/kg) + CBDCA without decreasing the antitumour effect of this trimodality therapy. Inhibitors of nitric oxide synthase such as L-NMA may provide a novel approach to overcoming the toxicity of TNF in combination with WBH.

Animals↗