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Biomedical subjects

C M Grum

Publications and source records attributed to C M Grum.

54 records · Page 3Linked to original sources
PubMed1989

Hypothermia or continuous ventilation decreases ischemia-reperfusion injury in an ex vivo rat lung model.

The susceptibility of lung tissue to ischemia-reperfusion injury has made distant procurement of heart-lung allografts difficult. The effects of hypothermia, ventilation without perfusion, and various reperfusion solutions (PSS/Ficoll or whole blood) on the development of ischemia-reperfusion lung injury were investigated. Use of an ex vivo rat lung model in which the above variables were individually varied permitted a direct approach for these studies. Normothermic ischemia for 1 hour caused significant damage, documented by increased iodine 125 bovine serum albumin (125I-BSA) in alveolar lavage fluid and lung parenchyma compared with nonischemic controls. Hypothermic (4 degrees C) ischemia for 4 hours in lungs reperfused with salt solution and for as many as 12 hours in lungs reperfused with whole blood caused no significant increase in 125I-BSA in alveolar lavage fluid and lung parenchyma compared with nonischemic controls. Lungs ventilated without perfusion showed no increase in 125I-BSA leakage compared with controls. The ex vivo rat lung model is excellent for studying ischemia-reperfusion injury. It is reproducible, allows for variance of reperfusion solutions, and permits change in temperature and ventilation easily.

Animals↗
PubMed1988

Xanthine oxidase inhibition attenuates ischemic-reperfusion lung injury.

Ischemic-reperfusion lung injury is a factor potentially limiting the usefulness of distant organ procurement for heart-lung transplantation. Toxic oxygen metabolites are considered a major etiologic factor in reperfusion injury. Although oxygen-free radicals may be generated by many mechanisms, we investigated the role of xanthine oxidase in this injury process by using lodoxamide, a xanthine oxidase inhibitor, to inhibit ischemic-reperfusion injury in an isolated rat lung model. Isolated rat lungs were perfused with physiologic salt solution (PSS) osmotically stabilized with Ficoll until circulating blood elements were nondetectable in the pulmonary venous effluent. Lungs were rendered ischemic by interrupting ventilation and perfusion for 2 hr at 37 degrees C. After the ischemic interval, the lungs were reperfused with whole blood and lung injury was determined by measuring the accumulation of 125I-bovine serum albumin in lung parenchyma and alveolar lavage fluid as well as by gravimetric measurements. Lung effluent was collected immediately pre- and postischemia for analysis of uric acid by high-pressure liquid chromatography. Lodoxamide (1 mM) caused significant attenuation of postischemic lung injury. Uric acid levels in the lung effluent confirmed inhibition of xanthine oxidase. Protection from injury was not complete, however, implying that additional mechanisms may contribute to ischemic-reperfusion injury in the lung.

Animals↗
PubMed1988

Conventional mechanical ventilation.

Mechanical ventilation has become a very common and well-accepted practice in modern intensive care units. The use of the mechanical ventilator has progressed from being a support system during surgery and for acutely ill patients to being used in both moderate and long-term life support in patients with inadequate ventilation. The sophistication of modern ventilators and the ability of trained respiratory therapists and nursing personnel have permitted this technology to explode. This is occurring at a time when there are still many controversies about the relative benefits and modes of action of conventional ventilation. As newer techniques are developed, it is mandatory that the application of these techniques be tempered with controlled clinical trials, documenting their effectiveness. The beneficial effects of new modalities must be documented as mechanical ventilation expands from use in the intensive care unit to use in standard medical wards and the patient's home. In these latter two settings, the vigilance of an intensive care unit is absent and the simplest method will be preferable. The requirement to demonstrate efficacy of new techniques with adequate studies is especially necessary now as the economics of health delivery have come under increasing scrutiny. Even more important than new technologies may be the efficacy of prolonged mechanical ventilation. A recent study by Spicher and White evaluated the outcome in 250 patients ventilated for 10 days or more at the Hershey Medical Center (Pennsylvania State University). The mortality, morbidity, and disability in patients in this study population requiring prolonged ventilation were extremely high. As these studies have pointed out, further evaluations of predictors of meaningful survival are necessary to avoid unnecessary human suffering and to best use limited resources.

Biopsy↗
PubMed1987

Pulmonary function in thyroid carcinoma metastatic to the lung.

Pulmonary testing was carried out in 12 of 35 consecutive cases of differentiated thyroid carcinoma metastatic to the lung, which were identified in a retrospective analysis covering the 22-yr period from 1962-1984. In 7 of the 12 patients, pulmonary function tests showed abnormalities. Impaired pulmonary function was associated with a poor prognosis. Four of the twelve patients died; each had impaired pulmonary function and their ages (12-65 yr) were similar to those still living (13-65 yr). Specific types of functional abnormalities were not associated with pulmonary metastases, and underlying pulmonary disease contributed to the findings in some patients. Four patterns were defined on chest radiographs: macronodular, micronodular, miliary, and normal, but these patterns did not correlate with outcome. Scintiscan patterns varied from normal to diffuse concentration of 131I. Generally, following therapy with radioiodine, fewer abnormalities on chest x-ray and less uptake of 131I in the lungs was noted. However, therapy with radioiodine did not improve pulmonary function. Pulmonary function testing appears to be a better predictor of outcome in patients with thyroid carcinoma metastatic to lung than chest x-ray appearance or scintigraphic scanning.

Adolescent↗
PubMed1987

Purine efflux after cardiac ischemia: relevance to allopurinol cardioprotection.

Allopurinol is thought to protect hearts against damage due to hypoxia or ischemia by inhibiting xanthine oxidase and oxygen radical generation. We subjected isolated rabbit hearts, equilibrated by perfusion at 37 degrees C, to 1 h of global ischemia at 27 or 37 degrees C with or without brief pretreatment with 100 microM allopurinol. The total absence of xanthine or uric acid in the coronary effluent following ischemia, the presence of hypoxanthine (25 +/- 4 microM peak concentration), and the failure of allopurinol to alter purine washout profiles or postischemic cardiac function suggest that rabbit myocardium lacks xanthine oxidase or dehydrogenase. Data obtained with a similar rat heart preparation showed appreciable formation of xanthine (12 +/- 2 microM peak) and uric acid (10 +/- 3 microM). Allopurinol pretreatment inhibited xanthine and uric acid formation and significantly improved key indicators of postischemic left ventricular function. We conclude that there is species dependency in the myocardial activity of xanthine oxidase or dehydrogenase, that when present it can be inhibited by acute allopurinol pretreatment, and that xanthine oxidase activity and its ability to generate oxygen radicals are not universal contributors to cardiac ischemic damage.

Allopurinol↗
PubMed1987

Plasma hypoxanthine and exercise.

During exercise, ATP is converted to ADP and AMP to supply energy for muscular contraction. It is then regenerated via various pathways of intermediary metabolism. However, with high levels of exercise, net ATP degradation in muscle occurs. In exercise and other clinical situations, adenine nucleotide degradation leads to an accumulation of degradative purine products including hypoxanthine. In an effort to monitor events of energy metabolism, we examined plasma hypoxanthine levels at various exercise intensities. Peak plasma hypoxanthine levels after maximal exercise (18.9 +/- 2.6 microM, mean +/- SEM) were significantly greater than resting levels (1.1 +/- 0.1 microM; p less than 0.001). Hypoxanthine levels after steady state exercise at 52, 76, and 97% of ventilatory threshold did not exceed resting levels. However, plasma hypoxanthine rose significantly after exercise at 124% of ventilatory threshold (6.3 +/- 1.0 microM; p less than 0.01) and at 152% of ventilatory threshold (17.0 +/- 3.6 microM; p less than 0.001). Exercise at subventilatory threshold intensity (74% of ventilatory threshold) for a prolonged time period, such that total work equaled that performed at 152% of ventilatory threshold, did not elevate hypoxanthine levels (0.46 +/- 0.1 microM) above resting values. We conclude that elevation of plasma hypoxanthine levels occur during exercise at intensities that exceed the ventilatory threshold and indicate that net adenine nucleotide degradation has occurred.

Adenosine Triphosphate↗
PubMed1987

Nocturnal increase of urinary uric acid:creatinine ratio. A biochemical correlate of sleep-associated hypoxemia.

Sleep-associated hypoxemia may result in tissue hypoxia and increased production and excretion of adenosine triphosphate (ATP) degradation intermediates and uric acid. Urinary uric acid:creatinine(UA:Cr) ratio is a convenient method for estimating uric uric acid excretion. We measured the overnight changes in urinary UA:Cr ratio in 17 patients with documented sleep-associated hypoxemia, 13 control patients who remained normoxemic during polysomnography, and 14 normal volunteers. The urinary UA:Cr ratio increased overnight in patients with sleep-associated hypoxemia (+31.2 +/- 10.9%), whereas it decreased in the control patients with negative sleep studies (-13.6 +/- 4.6%; p less than or equal to 0.01) and in the normal volunteers (-23.2 +/- 5.8%). Repeat polysomnography revealed interval resolution of sleep-associated hypoxemia in 2 patients and significant improvement in a third. In every case, this clinical improvement was accompanied by a decrease in the overnight change in UA:Cr ratio. We report that urinary UA:Cr ratio increased overnight in a nonhomogeneous group of patients with sleep-associated hypoxemia.

Adult↗
PubMed1986

Absence of xanthine oxidase or xanthine dehydrogenase in the rabbit myocardium.

We directly measured the activity of the enzymes xanthine oxidase and xanthine dehydrogenase in rabbit and rat hearts, using a sensitive radiochemical assay. Neither xanthine oxidase activity nor xanthine dehydrogenase activity was detected in the rabbit heart. In the rat heart, xanthine oxidase activity was 9.1 +/- 0.5 mIU per gram wet weight and xanthine dehydrogenase activity was 53.0 +/- 1.9 mIU per gram wet weight. These results argue against the involvement of the xanthine oxidase/xanthine dehydrogenase system as a mechanism of tissue injury in the rabbit heart, and suggest that the ability of allopurinol to protect the rabbit heart against hypoxic or ischemic damage must be due to a mechanism other than inhibition of these enzymes.

Animals↗
PubMed1986

Oxidant activity in expired breath of patients with adult respiratory distress syndrome.

Hydrogen peroxide levels were measured in the breath condensate of 43 patients receiving mechanical ventilation. In 16 patients the mean breath condensate peroxide level was 1.68 +/- 0.35 mumol/l on the day they met diagnostic criteria for adult respiratory distress syndrome (ARDS). The peak breath condensate peroxide level in the 27 patients in whom ARDS did not develop was significantly lower (0.34 +/- 0.08 mumol/l). Plasma lysozyme, a measure of in-vivo neutrophil turnover, was significantly higher in ARDS than in non-ARDS patients (9.2 +/- 2.2 U/ml v 3.4 +/- 1.1 U/ml). These findings support the hypothesis that neutrophil activation and oxidant production are involved in the pathogenesis of ARDS.

Breath Tests↗
PubMed1986

C3a and adult respiratory distress syndrome after massive transfusion.

We compared the degree of complement activation in 15 patients receiving massive blood transfusions and 21 patients with the septic syndrome and examined its association with other risk factors for adult respiratory distress syndrome (ARDS). Patients with massive transfusion (n = 8) as their only risk factor for ARDS had lower C3a levels (250 +/- 80 ng/ml) and a lower incidence of ARDS (0%) than patients with massive transfusion plus other risk factors (n = 7; C3a, 600 +/- 120 ng/ml; ARDS, 55%) or patients with the septic syndrome (n = 21; C3a, 540 +/- 80 ng/ml; ARDS, 19%). In our patients, the degree of complement activation appeared to reflect the presence of complicating clinical conditions.

Complement Activation↗
PubMed1986

Respiratory dysfunction in patients with common variable hypogammaglobulinemia.

Patients with common variable hypogammaglobulinemia (CVH) are susceptible to recurrent respiratory infections. We studied the prevalence and severity of respiratory dysfunction in 32 patients with CVH by measuring routine pulmonary function tests (PFT) and interpreting chest radiographs using a quantitative score system. Pulmonary symptoms were determined by patient interview and standard questionnaire. The mean age of 29 living patients was 28 +/- 2.2 yr; there were 22 males and 10 females. The mean age at diagnosis was 17.3 +/- 2.4 yr. Sinopulmonary symptoms were present in all 32 patients and included chronic sinusitis, otitis, bronchitis, recurrent pneumonia, and bronchiectasis. Complete PFT in 25 patients revealed restrictive, obstructive, and normal patterns in 10, 6, and 9 patients, respectively. Nine patients had dyspnea on exertion. Recent chest radiographs in 32 patients showed evidence of recurrent pulmonary infection, including air trapping, linear markings, and pleural abnormalities. Panlobular emphysema, documented in one case at autopsy, was suggested in 5 other patients by the presence of lower lobe bullous lesions and marked lower lobe hyperlucency on chest radiographs. The forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) had remained stable in 19 adults (18 receiving adequate immunoglobulin replacement therapy) for 6.9 +/- 0.7 yr. The expected increase of the FEV1 and FVC with growth was normal in 6 of 8 children (all 8 receiving adequate therapy). Chest radiograph scores deteriorated only slightly from 20.3 +/- 0.6 to 18.4 +/- 0.8 (25 = normal) during the 6.9 +/- 0.7 yr in 30 patients (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Transbronchial biopsy during mechanical ventilation.

The value and risk of transbronchial biopsy (TBB) was assessed in 15 cases requiring mechanical ventilation for progressive pulmonary infiltrates. TBB was diagnostic in five patients, and in two additional cases a diagnosis was made from the accompanying bronchial secretions. TBB results significantly altered the therapeutic management in seven cases. The alveolar-arterial gradient P(A-a)O2, widened by a mean of 110 mm Hg in nine patients; however, this change was transient and clinically insignificant. Three instances of reversible hypercapnia (mean of 15 mm Hg) occurred. Complications included self-limited bleeding in three cases and one tension pneumothorax. No fatalities were attributable to TBB. In these hemodynamically stable patients requiring mechanical ventilation for diffuse lung disease, TBB was performed safely and provided important data.

Adult↗
PubMed1985

Evidence for adenosine triphosphate degradation in critically-ill patients.

Alterations of cellular energy metabolism may provide important markers during the clinical course of critically ill patients. To determine whether adenosine triphosphate (ATP) degradation occurs in critically ill patients, we measured levels of adenosine, inosine, hypoxanthine, and xanthine in 18 patients and seven control subjects. The mean concentration of hypoxanthine (3.8 microM) in the critically ill patients was elevated (p less than 0.01) compared to that of our control population (0.1 microM). A subgroup of seven critically ill patients had levels of hypoxanthine, xanthine, or inosine higher than those of any member of the control group. This subgroup was characterized by a lower systolic blood pressure, an increased requirement for vasopressors, and a markedly decreased survival rate when compared to the other critically ill patients. Arterial and mixed venous blood gas values were not helpful in predicting survival and did not correlate with levels of ATP degradation products. In two patients who showed subsequent clinical improvement, the initially elevated levels of hypoxanthine and xanthine returned to normal. This study indicates that critically ill patients have elevated levels of ATP degradation products. These increased levels may indicate cellular hypoxia.

Adenosine↗
PubMed1984

Adequacy of tissue oxygenation in intact dog intestine.

Changes in O2 consumption, O2 extraction, and intramural pH, resulting from a decreasing O2 delivery, were studied in the intact dog intestine. The O2 delivery was decreased by ischemia, hypoxia, and combined hypoxia-ischemia. A noninvasive approach for determining intramural pH based on the principle of tonometry was used. There was a strong correlation between the changes in intramural pH and intestinal O2 consumption as O2 delivery was decreased. Intramural pH and O2 consumption were initially maintained in the face of decreasing O2 delivery, but after a critical point they decreased. This critical point was 60.3 +/- 1.6% of base-line O2 delivery in the ischemic group and 51.3 +/- 2.7% of base line in the hypoxic-ischemic group. Despite a decrease to 36.0 +/- 5.6% of base-line O2 delivery, the intramural pH and O2 consumption did not decrease in the hypoxic group. O2 extraction increased with decreasing O2 delivery but did not plateau, indicating no diffusion limitation. The data suggest that blood flow is the major factor limiting intestinal O2 consumption. It is concluded that the noninvasive measure of intramural pH is a good marker of the adequacy of tissue oxygenation in canine intestine.

Animals↗
PubMed1977

The prune belly anomaly: heterogeneity and superficial X-linkage mimicry.

The genetic, clinical, and necropsy findings of 2 brothers with the prune belly anomaly are presented and the literature reviewed. The combined data emphasise the clinical and genetic heterogeneity of the disorder and show that in at least some instances a heritable component may be the primary insult. The most likely heritable explanation involves a two-step autosomal dominant mutation with sex-limited expression that partially mimics X-linkage.

Abdominal Muscles↗