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Biomedical subjects

M Zelter

Publications and source records attributed to M Zelter.

17 recordsLinked to original sources

Alveolar liquid and protein clearance in anesthetized ventilated rats.

Alveolar and lung liquid clearances were studied over 1, 4, and 6 h in intact anesthetized ventilated rats by instillation of 5% albumin solution with 1.5 microCi of 125I-labeled albumin (3 ml/kg into 1 lung or 6 ml/kg into both lungs). Alveolar protein clearance as measured by residual 125I-albumin in the lung over 6 h was similar to the slow rates measured in other species. Alveolar liquid clearance was estimated by the concentration of albumin in the air spaces. After 1 h, this concentration was 7.8 +/- 0.7 g/dl, which was significantly greater than the initial protein concentration of 5.3 +/- 0.2 g/dl (P < 0.05). Amiloride (10(-3) M) inhibited 45% of the basal alveolar liquid clearance, and ouabain (10(-3) M), instilled and intravenously infused (0.004 mg), inhibited 30% of the clearance. beta-Adrenergic agonist instillation increased alveolar liquid clearance to the fastest 1-h rate (48 +/- 3% of instilled volume) that we observed in any intact species. The removal of the instilled fluid from the lung (expressed as lung liquid clearance; 0.96 +/- 0.3 ml/h) was twice as fast as the rate of alveolar and lung liquid clearance reported in the isolated or in situ rat lung models. The rate of alveolar and lung liquid clearance in these intact rats was significantly faster than those in prior studies in dogs and sheep and was similar to the rates in rabbits.

Adrenergic beta-Agonists

A prospective study on the treatment of retinoblastoma in 72 patients.

Seventy-two patients with retinoblastoma (RTB) (unilateral [47 patients] and bilateral [25 patients]) were studied for a period of 6 years. Treatment consisted of enucleation of those eyes that had severe involvement and was followed by radiation therapy and/or chemotherapy (systemic or intrathecal) according to clinical pathologic staging. All patients who underwent nonsurgical treatment received systemic chemotherapy. Intrathecal chemotherapy was administered when there was involvement of the central nervous system. Nonsurgical treatment consisted of radiation therapy and/or light coagulation, followed by enucleation if there was no response. The overall survival rates were 79% for unilateral disease (median follow-up time, 63 months) and 72% for bilateral disease (median follow-up time, 81 months). Vision was regained in 14 of 21 conserved eyes.

Antineoplastic Combined Chemotherapy Protocols

Effects of aerosolized artificial surfactant on repeated oleic acid injury in sheep.

We studied the effects of an artificial surfactant, Exosurf, administered as an aerosol on respiratory system compliance (Crs), total respiratory resistance (RT), and gas exchange (PO2) in anesthetized, paralyzed sheep with oleic acid (OA)-induced lung injury. Paired experiments with OA were performed in 10 sheep, 5 of which received Exosurf in the first experiment and aerosolized 0.9% NaCl in the second; in the other 5 sheep the order of Exosurf and NaCl was reversed. Paired experiments without OA were performed in 6 additional sheep that served as controls. In the first set of experiments, OA caused significant abnormalities, compared to control and baseline values (p less than 0.02), in Crs, RT, and PO2; there was no difference between animals that received Exosurf and those that received NaCl. Baseline values for PO2 and Crs during the second set of experiments with OA were lower than controls (p less than 0.002), indicating that the animals had not fully recovered from their initial injury. After OA, the animals that received NaCl (i.e., the ones that received Exosurf the first time) had higher PO2 and Crs values (p less than 0.01) than those that received NaCl first and Exosurf second. There was no difference in postmortem lung water content between the animals that received Exosurf or NaCl first, both of which were higher than control (p less than 0.01). Studies in 3 additional sheep showed peripheral deposition of aerosol. Thus, we failed to show an acutely beneficial effect of aerosolized Exosurf in OA-induced lung injury; Exosurf did, however, appear to provide protection against some of the consequences of repeated lung injury.

Aerosols

Treatment of retinoblastoma. Results obtained from a prospective study of 51 patients.

During 4 years, 51 patients with retinoblastoma were studied (unilateral 32, and bilateral 19). Treatment consisted of enucleation of those eyes which showed massive involvement followed by radiotherapy when there was optic nerve and/or orbit involvement. Systemic chemotherapy was administered to all patients who underwent nonsurgical treatment and when the histologic examination showed choroidal optic nerve head and/or optic nerve involvement or residual tumor after enucleation. When there was compromise of the central nervous system intrathecal chemotherapy was administered. Nonsurgical treatment consisted of radiotherapy and/or light coagulation. Survival was 90.6% for unilateral cases and 84.2% for the bilateral. The median follow-up was 31 months and 29 months, respectively. Of 19 conservated eyeballs, 16 preserve useful vision (63%).

Antineoplastic Agents

[Activity of almitrine bismesylate on pulmonary hemodynamics and on the liberation of prostanoids in the lymph nodes in sheep].

Almitrine Bismesylate (0.25 mg X kg-1) was perfused for 10 minutes into the pulmonary artery of 4 sheep (40 kg) which were anaesthetized, paralysed and ventilated with 50% oxygen in air and prepared according to Staub et al (J. Surg. Res. 19:315, 1975). The preparation was followed for 2 hours baseline and for four hours after perfusion and comparisons made using analysis of variance. We noted a transitory phase marked by a peak of pulmonary vascular resistance (PVR) at 25 +/- 15 minutes due to a rise in mean pulmonary artery pressure PAP from 14 +/- 2 to 23 +/- 5 cm H2O. PO2 fell from 220 +/- 40 to 180 +/- 25 Torr. A stable haemodynamic state was attained after 90 minutes. PAP was slightly above control and PaO2 significantly elevated (230 +/- 30 Torr P less than 0.05). Left atrial pressure, PCO2, pH, and lung lymph flow did not change. The mild stable vasoconstriction associated to a rise in PaO2 at constant ventilation and high PaO2 does not suggest a straightforward role for chemoreceptors. It is compatible with redistribution of VA/Q ratios by local mediators. Lung lymph was assayed for prostanoids using radio immunological methods. A significant rise in 6 keto PGF1 alpha immunoreactivity was found posterior to the haemodynamic peak. HPLC is required to quantify further this rise.

6-Ketoprostaglandin F1 alpha

[Autohistoradiographic study of the pulmonary retention of almitrine bismesylate].

The histo-autoradiographic distribution of labelled Almitrine was quantitatively assessed on semi-fine cuts of rat lung. The experimental set-up consisted of an isolated heart-lung preparation, perfused for two hours with homologous blood containing 10 microCi per ml of H3 almitrine (990 mCi/mM) et 0.1 microCi per ml of C14 almitrine (9.9 mCi/MM). Sequential histological biopsies were made. There was an apparent heterogeneous radioactivity of the tissues overall with no observed increase in fixation with perfusion time (v.i.). Nevertheless the auto-radiograph enabled this conclusion to be rectified by revealing the cause of the heterogeneity, the embolisation of micro-aggregates of the labelled product. After correction was made for this factor the scattering of the fixed radioactivity in the samples was weak. The localisation of the labelled product showed a good stability for the fixed marker in the tissues, and identified the distribution of the tracers H3 and C14, a preferential fixation by alveolar macrophages, type-2 pneumocytes, Clara cells and adipocytes. A remarkable fixation was noted in the cardiac fibres of the pulmonary veins. Amongst the cells of the bronchi, the mucus cells were notably active for the fixation of Almitrine. There was no detectable fixation associated with the nervous tissues and the neuro-epithelial body was not labelled. A sequential analysis showed that only fixation in smooth muscle fibres rose significantly with perfusion time.

Almitrine

Effect of lung injuries on [14C]urea permeability-surface area product in dogs.

To determine whether [14C]urea permeability-surface area product (PS) is a reliable indicator of changes in permeability in various injuries and its relationship to indicator-dilution and gravimetric lung water contents, we studied six groups of anesthetized, paralyzed, and mechanically ventilated dogs (5 animals each). The groups consisted of control dogs, those injured by intravenous alloxan, oleic acid, or glass beads, and those exposed to acute hypoxia or increased left atrial pressure from volume loading (Pla). Interanimal variation of PS was large (3.0-15.0 ml/s), but successive hourly values in individual animals were stable for 2 h in experimental groups and for 4 h in controls. The PS increased after alloxan, elevated Pla, and 2 h of hypoxia; PS decreased after oleic acid and microemboli. The gravimetric lung water increased after alloxan, oleic acid, and microemboli, and indicator-dilution lung water increased only after alloxan. We conclude 1) that intersubject variability requires normalization to enable detection of significant deviation from base line, and 2) that decreased PS after oleic acid and microvascular injury occurred because vascular obstruction, which decreased surface area, masked probable coexisting increases in capillary permeability.

Alloxan

Measurement of pulsatile flows and variable volumes by bolus injection of indicator in a model of the pulmonary circulation.

The reliability and accuracy of the bolus injection-dye dilution technique were assessed for a physiological range of frequencies (13-49 min-1) and stroke volumes (60-160 ml) on a glass model where flows and volumes varied as a preset function of time (n = 320). We found that the technique overestimates flow by about 8% with a 95% confidence interval of +/- 10% for one measurement. Mean transit times are accurate within a +/- 7% confidence interval for one measurement. In a time-dependent flow and volume system this technique measures the mean volume as related to time with fluctuations up to +/- 30% around the mean. Results are independent of time and site of injection. The double injection-single sampling technique gives results that are equivalent to those obtained by single injection and sampling of dye.

Humans

Prevalence of group B streptococci in parturient mothers and their infants.

Eighty pregnant women and their newborn infants were studied for the presence of group B Beta hemolytic streptococci (G.B.S.). G.B.S. were recovered from endocervical cultures in 5 (6.5%) women and 2 (2.5%) had positive throat cultures. Six (7.5%) infants had umbilical and external ear cultures positive for G.B.S. Four infants presented with clinical signs of respiratory distress. All infected infants were treated with penicillin and gentamycin. One case developed fulminant sepsis and died in spite of early diagnosis and treatment. This study shows a high incidence of G.B.S. infection and sepsis with a high mortality rate.

Female

Splanchnic blood flow, O2 consumption, removal of lactate, and output of glucose in highlanders.

An impairment of gluconeogenesis has been proposed to explain the low arterial blood glucose of highlanders. Therefore, we studied splanchnic blood flow, splanchnic uptake of oxygen and lactate, and output of glucose in nine normal and six anemic highlanders at an altitude of 3,750 m. Splanchnic blood flow, arteriovenous difference for oxygen, and oxygen consumption were comparable at rest in both groups and in lowlanders from the literature, whereas splanchnic output of glucose, and uptake of lactate were approximately twice those in lowlanders. After 10 min of mild exercise in 12 subjects (7 normals, 5 anemic), no significant changes in splanchnic hemodynamics and metabolism were found. During 29% oxygen breathing in 8 subjects (5 normals, 3 anemics), arterial lactate, splanchnic uptake of lactate and output of glucose fell to normal sea-level values. We concluded that splanchnic hemodynamics are similar in adapted highlanders and in lowlanders, and that there is no evidence of an impaired gluconeogenesis at the altitude of the present study.

Adaptation, Physiological

Pressure-flow-volume relationships in pulmonary circulation of normal highlanders.

Pulmonary vascular pressures and blood flow were measured with and without unilateral pulmonary arterial occlusion (UPAO) at rest and during exercise in 10 normal highlanders at La Paz, Bolivia (altitude, 3,750 m). In 6 other highlanders at rest and during exercise, pulmonary pressures, flow, and blood volume were measured during air breathing (PIO2 congruent to 100 Torr) and 29-30% oxygen (PIO2 congruent to 150 Torr). During air breathing, pulmonary vascular resistance was elevated at rest and did not change with exercise. Pulmonary arterial pressure rose less at rest with UPAO than during exercise without UPAO, and pulmonary vascular resistance was less in the former. Raising PaO2 to normal sea-level values had no effects on the pulmonary circulation at rest but prevented to a large extent the rise in pulmonary arterial pressure during exercise. Hence pulmonary vascular resistance during exercise was lower with oxygen than without. Thus, hypoxic vasoconstriction contributed to the pulmonary hypertension during exercise in normal highlanders. Circumstantial evidence suggests that this is related to the profound mixed venous hypoxemia caused by exercise in a hypoxic environment.

Adolescent

[Pulmonary blood volume. Definition, measurement, normal values].

We propose a simplification of the double-injection method whereby left atrial catheterization is made unnecessary by use of injection of indicator in the pulmonary wedge position instead of into the left atrium. Normal values of PBV range between 204 +/- 51 ml. m-2 and 326 +/- 51 ml. M-2. Such a large scatter is due in all likelihood partly to techniques themselves, partly to the small number of studied subjects, which precludes standardization of normal values according to age, sex and body build. Determination of PBV may help in assessing the overall distensibility of the pulmonary vascular bed, but is of no avail to assess separately the distensibility of arteries, microcirculation, and veins whose respective volumes cannot be measured in vivo for lack of undisputable methods. Morphometric and physiological observations suggest that the measurement of PBV is no avail to estimate changes in caliber of pulmonary arterioles caused by vasoactive stimuli.

Blood Volume

[Validation of a new method for measurement of pulmonary blood volume (author's transl)].

The pulmonary blood volume (Q) can be measured by dye injection in the pulmonary artery (PA) and in the left atrium (LA) and by sampling in the brachial artery (double injection - single sampling method). We propose to replace the injection in the LA, for which a left heart catheterization is needed, by a pulmonary wedge injection (PW). No significant difference was found between the first and the second method in twenty-four measurements in six anesthetized and artificially ventilated dogs kept in steady hemodynamic state : QPW (1) equals 0.009 + 1.106 QLA (r equals 0.935). The results are independent of the capillary injection site. In man, the indirect validation was made by unilateral occlusion of a main pulmonary artery, allowing blood volume measurement of the occluded lung by two methods, one of them independent of the "capillary" injection. The results of both methods are comparable and highly correlated (r equals 0.86). The range of the values of pulmonary blood volume in sixteen normal supine subjects, at rest, was similar to that of other authors, whichever the technique they used (394 plus or minus 114 ml, 268 plus or minus 59 ml m-2). The reproducibility of the results was comparable. In five subjects, pulmonary blood volume did not change during a moderate muscular excerise in the supine position (57 watts). The pulmonary wedge injection in man can replace the LA injection of the double injection - single sampling method, without loss of precision nor effect on reproducibility.

Animals