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Biomedical subjects

S Carlone

Publications and source records attributed to S Carlone.

At least 37 records · Page 2Linked to original sources

Alveolar cell population in HIV infected patients.

Alveolar lymphocytosis, in the face of blood lymphopenia, is a common finding among patients with AIDS. We studied by bronchoalveolar lavage (BAL), the alveolar cell profile of 43 human immuno deficiency virus (HIV) seropositive patients divided into three groups involving the advanced stages of the disease: group A (n = 9; CDC III), ambulatory individuals without systemic or respiratory symptoms; group B (n = 15; CDC IV) patients admitted for evaluation of fever of unknown origin (FUO) without pulmonary involvement; group C (n = 19; CDC IV), patients admitted for evaluation of an acute pulmonary condition. Sex, age and risk factor were comparable among the groups. Alveolar lymphocytosis was found in no group A patients, in 2 out of 15 group B patients (both with P. carinii lung infection) and in all group C patients, where pulmonary involvement was due to opportunistic infection or to nonspecific interstitial pneumonitis. Our findings suggest that in patients with advanced HIV infection alveolar lymphocytosis may be an expression of a concomitant process within the lungs either clinically manifest or inapparent, or possibly related to HIV primary lung involvement.

Acquired Immunodeficiency Syndrome↗

The effect of oxygen on sodium excretion in hypoxemic patients with chronic obstructive lung disease.

In advanced chronic obstructive lung disease (COLD), sodium retention is common, associated with reduction in renal plasma flow (RPF) and stimulation of the renin-aldosterone (PRA-PA) system, two abnormalities due to or influenced by hypercapnia: the independent role of hypoxemia in perturbing sodium homeostasis is unknown. In five stable patients with COLD (FEV1 = 0.9 +/- 0.21, mean +/- SE) with mild edema, during two weeks of a low sodium diet (one week on room air: pH = 7.39 +/- 0.02; PaO2 = 55 +/- 4 mm Hg; PaCO2 = 49 +/- 4 mm Hg; and one week on O2: pH = 7.38 +/- 0.01; PaO2 = 72 +/- 6 mm Hg; PaCO2 = 52 +/- 4 mm Hg) we monitored sodium balance, systemic and renal hemodynamics, plasma sodium and potassium, PRA, PA, and atrial natriuretic hormone (ANH). During air breathing, patients uniformly showed a depression of RPF despite normal cardiac output; plasma hormone levels did not differ from controls but there was elevation (greater than 2 SD above the normal mean) of PRA in four patients, PA in two patients, and ANH in two of five patients. During O2 breathing, urinary sodium increased significantly from 67 +/- 7 to 102 +/- 10 mEq/24 h. Surprisingly, the patients experienced a small but significant weight gain (0.6 +/- 0.1 kg). None of the other variables was affected by O2 therapy. The following conclusions were reached: in advanced COLD, correction of hypoxemia results in sodium diuresis, indicating that hypoxemia (in the presence of hypercapnia) contributes to sodium retention. The mechanism for this beneficial effect of O2 will require further investigation.

Aldosterone↗

Incidence of acid-base and electrolyte disturbances in a general hospital: a study of 110 consecutive admissions.

To establish the overall frequency distribution and combination of acid-base and electrolyte disturbances as they occur in a general population requiring hospital care, we studied arterial blood gases and plasma electrolytes (sodium, potassium and chloride) in 110 consecutive patients (age = 68 +/- 8 SE; 64 M, 46 F) at the time of admission to a general medical ward. Disturbances were defined on the basis of the standard pH/pCO2 plot and the normal (mean +/- 2 SD) electrolyte range for our laboratory. Sixty-two patients (56%) showed a disturbance in acid base equilibrium: acidosis: respiratory 16, metabolic 6; alkalosis: respiratory 26, metabolic 10; in 4/62 the acid base disturbance was mixed. In 47 of the 62 patients, the acid base imbalance were associated with electrolyte derangements (low PNa+, 12; high PNa+, 1; low PK+, 10; high pK+, 7; increased anion gap, 17). Electrolyte disturbances with a normal acid base status were detected in only 2 patients. Of significance, in 7 of the 58 individuals considered to have a "pure" acid base disturbance on the basis of the pH/pCO2 plot (5 respiratory alkalosis; 1 respiratory acidosis; 1 metabolic alkalosis), a widened anion gap revealed that the acid-base change was mixed, i.e. there was a concomitant component of metabolic acidosis. Thus, the total number of mixed acid base equilibrium disorders were eleven. This study emphasizes the frequent incidence of acid base and electrolyte disorders, very often in combination, among unselected adult patients admitted to a general medical ward. In addition it reinforces that a high prevalence of hidden cases of mixed acid base disturbances can be recognized by concomitant analysis of acid base and electrolyte parameters, including anion gap calculation.

Acid-Base Imbalance↗

[Use of reconstituted basal membranes for the study of invasion of human tumor cells: current status and future prospects].

Tumor metastasis is the major cause of death of oncology patients. One of the characteristic properties acquired by the metastatic cell is the ability to cross basement membranes. These are compartments of extracellular matrix composed largely by collagen type IV, laminin and a heparan sulphate proteoglycan. Here we review the use of a reconstituted basement membrane (Matrigel) in the Boyden chamber assay (Chemoinvasion Assay) for the assessment of the invasiveness of tumor cells of human origin. The possibility of using this test for the rapid evaluation of human tumor specimens from operated patients is discussed.

Basement Membrane↗

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↗

Effect of vitamin A on chemotactic and chemoinvasive behaviour of an osteosarcoma cell line.

Vitamin A is known to be able to modulate cell growth and differentiation and to act as an inhibitor of the process of carcinogenesis in some experimental models. Here we have studied the effect of different concentrations of vitamin A on chemotactic and chemoinvasive behaviour of a metastatic osteosarcoma cell line. The cell proliferation was partially inhibited in the presence of 10(-5) M retinol after 4 days of incubation. Retinol effect on chemotactic and chemoinvasive activity of osteosarcoma cells seemed to be dose-dependent. The highest retinol concentration used (10(-5) M) had an inhibitory effect on migratory and invasive cell response. Lower retinol concentrations seemed to be able to enhance (10(-8) M) both chemotactic and chemoinvasive activity of osteosarcoma cells. Chemotaxis and chemoinvasion assays provide rapid and quantitative tools to study the "in vitro" behaviour of metastatic cells. Furthermore, they represent a mean to screen for drugs, hormones and other substances able to alter the metastatic phenotype.

Chemotaxis↗

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↗

Growth of cells from esophageal squamous cell carcinoma biopsies in a reconstituted basement membrane.

Cells from esophageal carcinoma biopsies were cultured on or inside a three-dimensional basement membrane matrix (matrigel). Their growth was compared to cells derived from control esophageal biopsies. Cells from both normal and neoplastic tissue attached poorly to tissue culture plastic. Matrigel coating improved adhesion and growth. When cells were grown inside a matrigel matrix, a striking difference was noticed between carcinoma cells and controls. Carcinoma cells grew invasively in the three-dimensional substrate and digested the matrix after a few weeks; control cells did not grow and only a few necrotic cells were visible with time. Matrigel provided a better growth substrate than plastic for esophageal derived cells and discriminated between carcinoma-derived and control cells when used as a three-dimensional growth substrate. Our studies suggest a possible use of matrigel for the selective growth of tumor cells derived directly from tissue biopsies.

Basement Membrane↗

High chemotactic motility and growth in hard agar of a variant of RSV-transformed fibroblasts are lost in late passages.

Cloning efficiency in hard agar (0.6%) and high chemotactic migration toward fibroblast conditioned medium have been shown to characterize metastatic tumor cells. We studied growth in 0.6% agar and chemotaxis of two lines of Rous Sarcoma virus-transformed Balb/c3T3 cells, B77/3T3 (low metastatic) and AA12 (high metastatic), and compared them to their non-transformed counterpart, in order to verify whether these properties were maintained during several subcultivations. Cells were cryopreserved at early passages and thawed for experiments. Both assays were performed on freshly thawed cells (4-6 weeks in culture) and on cells which had been cultured 15-20 weeks after thawing. B77/3T3, which are tumorigenic but low metastatic and which have a very low cloning efficiency in hard agar (0.1-1%), showed a chemotactic response to Balb/c3T3 conditioned medium about two-fold higher than control Balb/c3T3. This response did not change with time in culture. AA12 cells, a genetic unstable variant of B77/3T3 selected for its growth in hard agar (0.6%), had a high cloning efficiency in hard agar and showed a high chemotactic motility (three-fold the controls). High growth in 0.6% agar and high chemotaxis of AA12 were lost in late passages, where cells behaved as the controls. It seems that besides the already reported variation in anchorage-independent growth, genetically unstable tumor cells can also have important variations in chemotactic motility during subcultivations.

Agar↗

Effects of fenoterol on oxygen transport in patients with chronic airflow obstruction.

A rise in cardiac output and a fall in arterial oxygen tension are well known side effects of bronchodilator drugs, particularly beta-adrenergic agonists. In recent years, fenoterol (Berotec), an effective beta-adrenergic agonist, has been used at increasing rates in asthmatic subjects, as well as in patients with chronic obstructive pulmonary disease (COPD). The effects of fenoterol on systemic hemodynamics or arterial oxygenation (or both) in patients with COPD have not been investigated; in these individuals, who often have increased sympathetic tone and hypoxemia even at rest, cardiovascular stimulation and a fall in arterial oxygen tension would be particularly undesirable side effects. In 14 patients with COPD (seven without a reversible component of airflow obstruction [group 1]; and seven with a reversible component of airflow obstruction [group 2]), we studied all of the important parameters of oxygen transport before and 60 minutes after administration of fenoterol. Studies were performed at rest and after exercise. At baseline, group 1 showed a faster heart rate, a lower cardiac output, a lower arterial oxygen flow, a wider arteriovenous oxygen content difference (C[a-v]O2), and a higher fraction of oxygen extracted by the tissues from a given arterial oxygen flow. In both groups, all measured parameters, including cardiac output and arterial oxygen pressure (PaO2) remained statistically unchanged one hour after administration of fenoterol; with exercise, the heart rate, blood pressure, minute ventilation, oxygen consumption, C(a-v)O2, and the percentage of oxygen extracted from arterial oxygen flow, as well as cardiac output and PaO2, increased in all instances; the exercise responses were not affected by the drug. These results suggest that at the time of its maximal effect on the airways (60 minutes), fenoterol has no untoward effect on the oxygen transport system, at rest or during exercise, in patients with COPD with or without a reversible component.

Aged↗

Characterization of the effects induced on DNA in mouse and hamster cells by lithocholic acid.

Lithocholic acid (LCA) is a promoting agent in colon carcinogenesis. In this work we have tried to characterize the DNA alteration induced by LCA in cells grown in vitro and in nuclei. Confirming previous findings, a clear increase in elution rate was observed at both alkaline and neutral pH. The extent of the increase was very similar at the two pHs. However, an increased elution rate could be observed only when lysing the nuclei at high ionic strength and low detergent concentration (2 M NaCl + 0.2% N-lauroylsarcosine sodium salt). No effect could be observed when the nuclei were lysed with a high detergent concentration (2% sodium dodecyl sulfate). In addition, a slight effect could be observed using a method for the evaluation of DNA unwinding in alkali. After termination of the incubation with LCA, the DNA alteration observed with DNA elution disappeared very rapidly both in intact cells and nuclei, even when the incubation buffer was totally unsuitable for the repair of the type of DNA damage induced by typical genotoxic agents. The effect of LCA on DNA was apparently not mediated through an inhibition of topoisomerase II. Only the intact chromatin of nuclei was responsive, not the quasinaked DNA of nuclei lysed at high ionic strength. We advance the hypothesis that the increased alkaline and neutral elution rate observed with LCA could be independent of DNA fragmentation and related to changes in chromatin structure.

Animals↗

Effect of inorganic phosphate in hypoxemic chronic obstructive lung disease patients during exercise.

We have shown that normal subjects exercise more efficiently with increased plasma phosphate, presumably due to decreased hemoglobin-oxygen affinity and thus enhanced tissue O2 extraction. We subjected nine stable hypoxemic COLD patients to exercise at 0 (control), 24 (experimental) and 48 hrs (recovery) after phosphate infusion. Baseline variables were identical for each time period. Exercise responses at 0 and 48 hours were also indistinguishable. Exercise response at 24 hrs differed from those at 0 and 48 hours as follows: widening of A-V O2 content difference was more pronounced (28 +/- 6 vs 15 +/- 6 ml/L, p less than 0.03) and the increment in tissue O2 extraction was larger (14 +/- 3 vs 8 +/- 3 percent, p less than 0.03). P50 and related variables did not change during the course of the study. Thus, like normal subjects, hypoxemic patients stimulated with phosphate administration can exercise perhaps more efficiently; but, in contrast to normal subjects, this effect cannot be attributed to changes in hemoglobin-oxygen affinity. These data suggest that phosphate administration may be beneficial in hypoxemic states where adequate tissue oxygenation cannot be achieved by other more conventional methods. The mechanism of this effect remains to be elucidated.

Female↗

Tolerance to inhaled Duovent. A long-term study.

Fenoterol with ipratropium bromide (Duovent) is a recently used combination between an anticholinergic and a beta-adrenergic drug useful in obtaining a more effective bronchodilatation and/or reducing the single drug doses. It has been suggested that, as in the case of beta-agonists, its clinical efficacy may be limited by the development of tolerance. We studied the effects of inhaled Duovent in 15 asthmatic patients for 3 months, using a rigidly controlled protocol. Appropriate serial physiological measurements were made at regular intervals during the 90-day study. In all instances the day-one bronchodilator response was significant, prompt and sustained: at 1, 4, 8 and 12 weeks the response was statistically the same as on day 1. It is concluded that, when the important variables are properly controlled, no evidence of tolerance to long-term therapy with Duovent is demonstrable.

Adult↗

Tolerance to inhaled fenoterol.

Fenoterol ( Berotec ; Th 1165a , Boehringer- Ingelheim , Spa., Firenze , Italy) is an effective, widely used bronchodilator. It has been suggested by some investigators that, as in the case of other beta-adrenergic agonists, its clinical usefulness may be limited by the development of tolerance; others have found no tolerance. These conflicting results appear to be related to differences in study designs. We studied for 3 months the effects of inhaled fenoterol in 15 asthmatics, using a rigidly controlled protocol. Appropriate serial physiologic measurements were made at regular intervals during the 90-day study. In all instances the day 1 bronchodilator response was significant, prompt, and sustained: at 1,3,4,8 and 12 wk the response was statistically the same as on day 1. It is concluded that, when the important variables are properly controlled, no evidence of tolerance to long-term therapy with fenoterol is demonstrable.

Adult↗

Carboxyhemoglobin and oxygen affinity of human blood.

We determined normal human blood p50 at various pH values (range 7.0 to 7.6) as a function of the proportion of carboxyhemoglobin (COHb) in total hemoglobin, from 0 to 23%. The d(log p50)/d[COHb] coefficient is 0.00848, independent of pH and 2,3-diphosphoglycerate. The derived equation allows the calculation of p50 as a function of COHb with an approximation of +/- 0.54 mmHg (about 72 Pa), and can be combined with other calculations (Clin Chem 27:1856-1861, 1981; Clin Chem 29:110-114, 1983) to predict p50 under any condition of pH within the range 7.0-7.6, ratio of [2,3-diphosphoglycerate] to [total hemoglobin] (range 0.3-2.5), pCO2 (range 20-90 mmHg), temperature (range 19-43 degrees C), and COHb (range 0-23%).

2,3-Diphosphoglycerate↗

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↗