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Biomedical subjects

R J Fallat

Publications and source records attributed to R J Fallat.

At least 37 records · Page 2Linked to original sources
PubMed1977

Alpha-1-antitrypsin. Plasma survival studies in the rat of the normal and homozygote deficient forms.

Alpha-1-antitrypsin from normal individuals (Pi type MM) from those with an inherited deficiency of circulatory protein (Pi type ZZ) were labelled with 125I and plasma clearance rates measured in rats either prior to, or following treatment with neuraminidase to remove terminal sialic acid residues. In addition, these proteins and the derivatives were tested for their ability to bind to an hepatic binding protein obtained from rabbit liver membranes that has been shown to be responsible for the clearance of serum asialoglycoproteins. Finally, the two native forms of alpha-1-antitrypsin were treated with galactose oxidase followed by reduction with tritiated potassium borohydride and then analyzed for tritium incorporation in the neutral sugar fraction. The results indicate: (a) clearance from plasma for both forms of alpha-1-antitrypsin is dramatically enhanced upon the loss of terminal sialic acid residues to the liver membrane protein; (b) Z protein does not exhibit terminal galactosyl residues; (c) the low level of Z protein in plasma cannot be accounted for by a faster rate of clearance relative to M protein. The relevance of these findings to the alpha-1-antitrypsin deficiency state are discussed.

Animals↗
PubMed1976

Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome.

In 45 consecutive patients referred for severe hypoxemia (Pao2 less than 100 mm Hg on positive end-expiratory pressure of 5 cm H2O and fraction of inspired O2 of 1.0), physiologic studies of gas exchange were correlated with pathologic features from 36 open lung biopsies and 15 autopsies. Three distinct groups were defined. Group 1 included 11 patients with the most severe hypoxia (Pao2, 47 +/- 12 mm Hg), minimal Pao2 response to a 10 cm H2O increase in positive end-expiratory pressure (+2.0 +/- 4.0 mm Hg), and a fixed shunt at all fractions of inspired O2. Pathologic study showed edema, exudation, and hemorrhage to the point of consolidation. In group 2 were 13 patients who had less severe hypoxia (Pao2, 60 +/- 17 mm Hg) and a moderate Pao2 response to a 10 cm H2O increase in positive end-expiratory pressure (+15 +/- 8 mm Hg), but whose maximal response was slowly achieved (30 min to several hours). Pathologic examination showed extensive fibrosis. The 21 patients in group 3 had the least hypoxia (66 +/- 15 mm Hg), and had a rapid and marked improvement in Pao2 with a 10 cm H2O increase in positive end-expiratory pressure (+68 +/- 59 mm Hg). Pathologic features were similar to but less severe than those in group 1. Venous admixture increased with decreasing inspired concentrations of O2, indicating diffusion or ventilation-perfusion abnormalities in groups 2 and 3. Prognosis was best for group 3, with 10 of 21 long-term survivors. Two of 11 group 1 patients survived, but only after prolonged periods of extracorporeal membrane oxygenation. Despite biopsy evidence of extensive fibrosis, 3 of 13 in group 2 survived with moderate to good pulmonary function, including 1 survivor who had had extracorporeal membrane oxygenation. Such combined physiologic and pathologic studies are useful (1) for optimal respiratory care, (2) for prognosis, (3) for development of indications for extracorporeal membrane oxygenation, and (4) for better understanding of the pathophysiology of adult respiratory distress syndrome.

Air Sacs↗
PubMed1976

Pulmonary pathology in acute respiratory insufficiency: lung biopsy as a diagnostic tool.

Forty-two patients underwent open-lung biopsy during the early phase of acute respiratory insufficiency. Correlation between the gross appearance of the lung at operation and the microscopic findings was good. Although only fair correlation was found between lung and tracheal cultures, the findings of two positive cultures in the lung only was of utmost importance. Biopsying multiple areas from the same operation showed identical pathology in 86 per cent of cases. The mortality rate of open-lung biopsy was zero; the morbidity rate was 4 per cent. The over-all survival rate of acute respiratory insufficiency (ARI) due to trauma was 39 per cent; that of pneumonia, 11 per cent. In 17 (33 percent) patients specific diagnoses and/or specific therapies were employed as a direct result of the biopsy or the thoracotomy. The incidence and prognostic implications of fibrosis and microthromboembolism are presented and discussed. Open-lung biopsy has been extremely safe and valuable in characterizing and managing ARI.

Acute Disease↗
PubMed1975

Complications associated with membrane lung support by venoarterial perfusion.

A series of patients supported with long-term venoarterial perfusion is presented. Gas exchange was achieved with a membrane oxygenator at flows usually in excess of 50% of the patient's baseline cardiac output. Perfusions were maintained for 7 to 12 days. Two major complications were encountered: thromboembolic myocardial infarction and liquefaction necrosis of the lung. Possible etiologies and suggestions for prevention are discussed.

Adolescent↗
PubMed1975

Effects of extracorporeal membrane oxygenation (ECMO) on pulmonary hemodynamics, gas exchange and prognose.

Hemodynamic and gas exchange studies on acute respiratory failure patients treated by extracorporeal membrane oxygenation led to the following conclusions: pulmonary circulation can be influenced to a large extent Lamy, et al. Effects of extracorporeal membrane oxygenation on pulmonary hemodynamics by changes in bypass cannulation mode and bypass flow rate. An increase in pulmonary flow is followed by an increase in mean pulmonary artery pressure, a drop in total pulmonary vascular resistance, and an increase in shunt fraction. Forced opening of previously shut down vascular area (possibly due to hypoxic vasoconstriction) is a potential explantation for these physiological changes. Increase in bypass flow rate leads to increase in total systemic flow (pulmonary and oxygenator), but does not change total CO2 production and possibly total O2 consumption. Mixed cannulation mode (venoarterial and venovenous) guarantees adequate oxygenation of all the organs. Oxygenation of the heart can be jeopardized by venoarterial bypass, although the use of an aortic root cannula may decrease this major risk. Extracorporeal membrane oxygenation reversed the disease process in some of the patients treated. The best criteria of reversibility seem to be an improvement in arterial PO2 decrease in shunt fraction across the lung, and decrease in total pulmonary vascular resistance. The most striking change of these parameters has been observed after 2 to 3 days on bypass.

Adolescent↗
PubMed1975

Pathophysiology of adult respiratory distress syndrome.

We have studied 45 patients with adult respiratory distress syndrome (ARDS). Pathological studies were performed on 30 open lung biopsies and 15 autopsies. Concomitantly the physiologic characteristics of the hypoxemia in response to different inspired oxygen fraction (FIO2) and Positive End Expiratory Pressure (PEEP) were determined. These studies allowed categorization of ARDS into 3 groups. Group I had the most severe hypoxemia and a severe fixed shunt at all PEEP and FIO2. Pathologically, there was extensive acute edema, hemorrhage, and exudation to the point of consolidation. Group II had less severe hypoxemia which improved moderately but slowly in response to PEEP and shunt increased with decrease in FIO2 indicating diffusion disturbances or severe ventilation-perfusion abnormalities. Pathology showed severe fribrosis. Group III had least hypoxia which rapidly and markedly improved with PEEP. Shunt also increased with decrease in FIO2. Pathology showed acute changes similar to but less severe than group I. Prognosis was best for group III with 10 of 21 long term survivors (one after ECMO or extracorporeal membrane exygenation). In group I only 2 of 11 survived after prolonged periods of ECMO. In group II, 3 of 13 survived (one required ECMO) with satisfactory pulmonary function despite biopsy evidence of severe fibrosis during the acute illness. These pathological and physiologic studies are useful to better understand ARDS, to optimize respiratory care and for prognosis.

Adolescent↗