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Biomedical subjects

L D Hudson

Publications and source records attributed to L D Hudson.

At least 163 records · Page 9Linked to original sources
PubMed1980

Immunologic aspects of enzyme replacement therapy. An evaluation of the immune response to unentrapped, erythrocyte- and liposome-entrapped enzyme in C3H/HeJ Gush mice.

The ability of autologous erythrocytes and liposomes to provide nonimmunogenic vesicles which protect entrapped enzyme from immunologic surveillance and initiation of an immune response was assessed in C3H/HeJ Gush mice following repeated administration of these vesicles with and without entrapped enzyme. Erythrocyte-entrapped bovine beta-glucuronidase elicited no antibody response detectable by double diffusion, passive hemagglutination, complement-dependent lysis, or time-course experiments. Moreover, erythrocyte entrapment protected the enzyme from circulating antibody in mice previously sensitized with unentrapped enzyme. In contrast, repeated IV injection of negatively-charged liposomes loaded with enzyme induced both humoral and cellular responses. Low levels of antibody to the bovine enzyme were detectable by the double antibody technique; no antibodies to the liposome were detectable by complement lysis. In time-course experiments, significant decreases in tissue recoveries of liposome-entrapped beta-glucuronidase were observed in mice sensitized with enzyme-loaded liposomes compared to the recoveries in unsensitized mice, due in part to the rapid degradation of antigen-antibody complexes. A similarly decreased tissue recovery of liposome-entrapped enzyme was apparent in mice with circulating anti-beta-glucuronidase antibody, indicating the inability of liposomes to protect entrapped protein from immunologic surveillance. The cellular response to the liposome vesicle was characterized by the enhanced phagocytic activity of reticuloendothelial cells in the liver and spleen, and the activation of peritoneal macrophages. These results identify erythrocytes as nonimmunogenic carriers capable of protecting entrapped protein from immunologic surveillance and therefore suitable for enzyme replacement endeavors. However, the demonstration that both buffer- and enzyme-loaded liposomes induce an immune response mandates further investigation of these carriers prior to clinical trials of liposome-entrapped therapeutic agents.

Animals↗
PubMed1980

Enzyme therapy XIV. Comparison of methods for enzyme entrapment in human erythrocytes.

Seven methods of erythrocyte entrapment--six by hypotonic exchange loading and one by chlorpromazine-induced endocytosis--were evaluted for (1) efficiency of incorporation of beta-glucuronidase, inulin, and glucose; (2) presence of beta-glucuronidase on the erythrocyte surface, as detected by hemagglutination or complement-dependent lysis in the prsence of antibody to beta-glucuronidase; (3) in vitro leakage of entrapped markers; and (4) morphologic alterations by scanning electron microscopy. Dependent on the method of entrapment, the incorporation of markers ranged from 0.7% to 6.2% for beta-glucuronidase, 3.4% to 31% for inulin, and 1.2% to 12.2% for glucose. Maximal incorporation by hypotonic exchange loading occurred when the initial concentration of sodium chloride (150 mM) was reduced to 50 or 75 mM. However, beta-glucuronidase was detected on the erythrocyte surface by hemagglutination for these methods as well as a dialysis method of loading. Essentially no leakage of entrapped enzyme was detected (< 1%) for all methods, although up to 11% of entrapped glucose was released during a 3 hr incubation at 37 degrees C in buffered whole blood. Finally, entrapment methods requiring the greatest reduction in salt concentration resulted in the formation of echinocytes, whereas stomatocytes were observed after entrapment by methods requiring lesser salt dilutions. These results demonstrate the efficiency of entrapment and relative integrity of erythrocytes following various loadng procedures and suggest that in vitro assessment may provide a useful predictor of the imunogenicity and in vivo fate of erythrocyte-entrapped enzymes or other therapeutic agents.

Antigens, Surface↗
PubMed1979

Impaired alveolar macrophage chemotaxis in patients with acute smoke inhalation.

Pulmonary infection is a leading cause of death in patients with smoke inhalation; however, few studies have evaluated the effects of inhaled smoke on the host defense mechanisms of the lung. In this study we investigated the effects of acute smoke inhalation on the random and chemotactic (stimulated unidirectional) migration of human pulmonary alveolar macrophages. Fiberoptic subsegmental pulmonary lavage was performed in 19 normal subjects (12 nonsmokers and 7 smokers) and 7 patients with smoke inhalation. After quantification of lavaged cell populations, random and chemotactic migration was measured using modified Boyden chambers. Zymosan-activated serum was used as a chemotactic stimulant. Mean +/- SE random migration was 6.2 +/- 0.8 cells per 20 microscopic fields in smoking control subjects, 5.7 +/- 0.7 in nonsmoking control subjects, and 5.2 +/- 0.7 in patients with smoke inhalation. These values are not significantly different. In contrast, the mean directed (chemotactic) migration of pulmonary alveolar macrophages was 26.5 +/- 1.9 in smoking control subjects, 22.7 +/- 3.0 in nonsmoking control subjects, and 11.4 +/- 1.4 in patients with smoke inhalation; the latter response was significantly different from that of the smoking (P less than 0.001) and nonsmoking (P less than 0.025) control subjects and the combined average of the 2 control groups (P less than 0.001. In vitro exposure of pulmonary alveolar macrophages to nontoxic doses of smoke produced similar impairment of chemotaxis. These findings may partially explain the enhanced susceptibility of patients with smoke inhalation to pulmonary infection.

Adult↗
PubMed1979

Acute lobar atelectasis: a prospective comparison of fiberoptic bronchoscopy and respiratory therapy.

To evaluate the usefulness of fiberoptic bronchoscopy for treatment of acute lobar atelectasis, 31 subjects were randomly allocated to fiberoptic bronchoscopy followed by respiratory therapy for 48 hours, or to respiratory therapy alone for the same period. No significant differences between groups with regard to restoration of volume loss were detected after the first treatment intervention, at 24 or at 48 hours (P greater than 0.20). Specifically, the mean percentage resolution of volume loss immediately after bronchoscopy (38 per cent) closely approximated that after the first respiratory therapy treatment in subjects who had not undergone bronchoscopy (37 per cent). An air bronchogram proved to be a predictor of delayed resolution for both groups. At 24 hours, 26 per cent of the air bronchograms demonstrated 83 per cent resolution (P less than 0.001). These results suggest that fiberoptic bronchoscopy does not add to respiratory therapy in the treatment of acute lobar atelectasis and that an air bronchogram predicts delayed resolution of collapse.

Adolescent↗
PubMed1979

The significance of wheezing in chronic airflow obstruction.

Eighty-three patients with chronic airflow obstruction were examined prospectively to determine the relationships among wheezing intensity, severity of obstruction, and response to inhaled isoproterenol. For each patient, expiratory wheezing scores were assigned during deep unforced breathing and during forced vital capacity efforts at spirometry. Unforced wheezing scores were independently correlated with severity of obstruction (r = 0.42) and bronchodilator response (r = 0.46), but these correlations did not permit consistent prediction of either variable for clinical purposes. The highest wheezing scores, however, were uniformly associated with moderate or severe obstruction. Twenty-nine of 48 patients with wheezing but only 3 of 35 patients without wheezing demonstrated 15% or greater improvement in one-second forced expiratory volume after bronchodilator inhalation (p less than 0.001). Wheezing during forced exhalation was not correlated with either degree of obstruction or bronchodilator response.

Aged↗
PubMed1979

Prolonged respiratory paralysis in wound botulism.

Two patients had wound botulism with longer duration of respiratory paralysis than previously described. Each sustained extensive trauma to soft tissues and grossly contaminated wounds when thrown from a vehicle in a rural area. Progressive muscular weakness and respiratory distress occurred 8 and 13 days after injury, in the presence of infected wounds and clinical and laboratory findings characteristic of botulism. Spontaneous vital capacity and inspiratory effort served as bedside indicators of ventilatory function throughout 11 weeks of ventilatory support in each case and paralleled other clinical assessments of progress and recovery. Wound botulism may result in neuromuscular paralysis for a prolonged period. These cases illustrate the primary role of scrupulous nursing and respiratory care throughout such a period of ventilatory insufficiency.

Adult↗
PubMed1979

Invasive aspergillosis presenting as pericarditis and cardiac tamponade.

A 38-year-old leukemic patient developed pericarditis and cardiac tamponade due to Aspergillus niger one month after undergoing bone marrow transplantation. She failed to improve even though amphotericin B and rifampin therapy had been initiated before infection was evident. Her unique case illustrates both the unusual presentations of invasive aspergillosis and the difficulty of diagnosing and treating this increasingly common disease.

Adult↗
PubMed1979

Hyperhaptoglobinemia and carcinoma of the gallbladder.

Cancer of the gallbladder is an uncommon malignancy which is seldom diagnosed early and often denotes a poor prognosis. Two reported cases describe the association of hyperhaptoglobinemia (greater than 700 mg./dl.) and advanced carcinoma of the gallbladder. When a patient presents with liver involvement from metastatic adenocarcinoma of suspected gastrointestinal origin and a markedly elevated serum haptoglobin (greater than 700 mg./dl.), it is suggested that a high index of suspicion be held for carcinoma of the gallbladder.

Adenocarcinoma↗
PubMed1978

Clinical evaluation of new office spirometer.

The accuracy of a simple, pneumatic, direct-recording spirometer suitable for office use was evaluated by comparing spirometry on a water-sealed, 13.5-liter, water-filled spirometer for 120 patients. Good correlation between the two spirometers was seen through a wide range of values for forced vital capacity, forced expiratory volume in one second, and forced expiratory flow during 25% to 75% of forced vital capacity, with coefficients of correlation being .988, .988, and .948, respectively. All correlations were significant. The pneumatic spirometer is accurate, simple to operate, and suitable for spirometry in the office and clinic.

Humans↗
PubMed1978

Lung injury following a 50-metre fall into water.

The pulmonary complications of a 50-metre fall to the water (a form of suicide attempt producing 87% mortality) were studied in 15 survivors. Presenting findings included crackles, haemoptysis, and hypotension. The alveolar-arterial oxygen difference was greater than 150 mmHg (20 kPa) in nine subjects on admission. Ventilatory failure developed in 10 of the patients, including all of those with massive haemoptysis. Radiographic findings included pneumothorax and diffuse pulmonary opacities adjacent to the area of impact. Pneumothorax developed within 12 hours of admission in 10 of 15 subjects but was associated with rib fractures in only four subjects. The clinical course of the condition is consistent with the hypothesis that the traumatic pulmonary tears produced interstitial emphysema, with subsequent development of pneumomediastinum, subcutaneous emphysema, and pneumothorax. Pneumothorax is a common complication of severe lung contusion even in the absence of penetrating pleural injury.

Adult↗
PubMed1978

Disseminated Nocardia caviae with positive blood cultures.

Disseminated Nocardia caviae infection with multiple positive blood cultures occurred in a bone marrow transplant recipient. Positive blood cultures are unusual in disseminated Nocardia infections and N caviea is an unusual species of Nocardia to cause infections in man, although its virulence in laboratory animals is similar to N asteroides. Multiple positive blood cultures in this case suggest a continuous or recurrent bacteremia rather than a transient bacteremia as previously has been thought to occur in disseminated Nocardia infections. The marked immunosuppressed state of the patient and an indwelling venous line could also have accounted for the recurrent bacteremia.

Adult↗
PubMed1977

Immunological evaluation of repeated administration of erythrocyte-entrapped protein to C3H/HeJ mice.

The immunogenicity of heterologous protein entrapped in autologous erythrocytes was evaluated in a mouse system. Multiple intravenous administrations of an erythrocyte-entrapped bovine beta-glucuronidase preparation resulted in little, if any, immunological response to the entrapped protein or erythrocyte carrier. Erythrocyte entrapment also protected protein from circulating antibody elicited by prior subcutaneous sensitization with unentrapped enzyme in adjuvant. Thus erythrocyte entrapment may protect potentially immunogenic agents from immunological surveillance.

Animals↗