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Biomedical subjects

T R Martin

Publications and source records attributed to T R Martin.

At least 145 records · Page 8Linked to original sources
PubMed1987

Life-threatening theophylline toxicity is not predictable by serum levels.

We questioned whether there was any way to predict which patients with high serum theophylline levels would develop life-threatening toxicity and thereby determine which patients might benefit from prophylactic therapeutic measures, such as hemoperfusion or hemodialysis. We reviewed the records of 54 consecutive patients seen over a five-year period in whom the serum theophylline level was 39 micrograms/ml or higher (range 39-78 micrograms/ml, mean theophylline level 49.5 +/- 9.6 micrograms/ml). Toxicity sought included cardiovascular--major arrhythmias (asystole, ventricular tachycardia, ventricular fibrillation) and minor arrhythmias, (central nervous system--major [seizures], minor [confusion, agitation]); and gastrointestinal (nausea, vomiting and diarrhea). In our sample of patients with extremely high theophylline levels, the incidence of life-threatening complications was low, and the subgroup of patients with high serum theophylline levels who developed life-threatening toxicity could not be easily identified. We conclude that major interventional procedures such as hemoperfusion or hemodialysis should not be used prophylactically in this population of patients of middle age to elderly men with high theophylline levels. We recommend a more conservative approach of using oral activated charcoal therapy in all patients with high serum theophylline levels, and reserving hemoperfusion or hemodialysis for those patients who develop seizures or major arrhythmias.

Aged↗
PubMed1987

The relationship between malnutrition and lung infections.

In summary, the association between malnutrition and infections, including respiratory infections, seems clear from consistent experience in developing nations. Young children are at the greatest risk, both of severe malnutrition and complicating infections. The cell-mediated immune system is the most affected by protein-calorie malnutrition, but antibody responses are also affected and complement levels are low. Infections with organisms handled by cell-mediated immunity would be the most predictable, but the immunoglobulin responses that are important for opsonization of invading microorganisms may also be impaired. The experience in developing nations has been extrapolated to patients in US hospitals, because hospitalized patients often have one or more abnormal nutritional parameters. However, severe malnutrition of the sort found in children in developing nations is uncommon in hospitalized patients, and the effects of malnutrition on host defenses in adults are likely to be less severe than in children. Whether the degrees of malnutrition that have been described in hospitalized patients produce clinically significant effects on antibacterial defenses in the lungs of adults remains uncertain. Despite the intuitive importance of nutritional support, and the repeated observation that nutritional parameters improve with nutritional support, a number of controlled trials have failed to show a clear improvement in patient outcome with aggressive nutritional therapy, including parenteral hyperalimentation. The results of these studies, together with the risks involved in parenteral alimentation have led some to suggest that "the emperor has no clothes," and that aggressive nutritional support is not worthwhile for most patients. The major problem in interpreting the data is the lack of clear clinical endpoints, and this may obscure potentially important responses to nutritional therapy. Nutritional status is only one of many interacting variables that may affect clinical outcome, particularly in patients in critical care units. Survival usually depends on many factors, particularly the status of major organ systems independent of nutrition, so that survival as an endpoint for nutritional studies is likely to be too insensitive. Prospective studies of the incidence and significance of infections, particularly pneumonia, in malnourished patients and the effects of nutritional therapy are lacking. At present, the prudent approach is to treat infections aggressively in malnourished patients, with antibiotics and drainage if necessary, and to provide nutritional supplementation in all patients via the gut as long as possible.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

High-altitude pulmonary edema. Characteristics of lung lavage fluid.

To evaluate the cellular and biochemical composition of bronchoalveolar fluid in high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage in three climbers with HAPE in a research facility at 4400 m on Mount McKinley. Three healthy climbers were used as controls. The HAPE fluids contained marked increases in high-molecular-weight proteins, erythrocytes, and leukocytes, most of which were alveolar macrophages. The HAPE fluids also contained detectable amounts of leukotriene B4 and other lipoxygenase products of arachidonic acid metabolism, complement fragments (C5a), inhibitors of neutrophil chemotaxis, and acid proteases but not hydroxyproline, a constituent of collagen. The data from this study indicate that HAPE involves a transient "large pore" leak in the pulmonary circulation. Despite the presence of two potent mediators of inflammation, leukotriene B4 and C5a, HAPE is not characterized by the intense neutrophil accumulation that is typical of other forms of acute lung injury.

Adult↗
PubMed1986

Association of low birth weight with passive smoke exposure in pregnancy.

In a prospective study of 3,891 antenatal patients at Yale-New Haven Hospital between 1980 and 1982, one fourth (23.6%) had not smoked cigarettes during pregnancy but had been exposed to sidestream smoke for at least two hours per day. Among the nonsmokers, passive smoke exposure was significantly related to delivering a low birth weight (less than 2,500 g) newborn. This relation only occurred in term (greater than or equal to 37 weeks) deliveries. Compared with unexposed women, the relative risk of low birth weight after adjustment for confounding factors was 2.17 (95% confidence interval (CI) = 1.05-4.50). Those exposed to passive smoke delivered infants 24 g lighter on average. There was no additive effect of passive smoking on smokers themselves. Repeating the analysis on all women with term deliveries, therefore, resulted in a slightly diminished risk of low birth weight due to passive smoking of 1.52 (95% CI = 0.90-2.56). The risk of low birth weight at term due to direct cigarette smoking was 3.54 (95% CI = 1.62-7.71). Gestational age was unrelated to passive smoking, which appears to exert its effect primarily through growth retardation in term newborns.

Adult↗
PubMed1986

Evaluation of physical health effects due to volcanic hazards: the use of experimental systems to estimate the pulmonary toxicity of volcanic ash.

Shortly after Mount St. Helens erupted in 1980, a number of laboratories began to investigate the effects of volcanic ash in a variety of experimental systems in attempts to predict effects that might occult in the lungs of humans exposed to volcanic ash. The published results are remarkably consistent, despite the use of non-uniform ash samples and variability in the experimental approaches used. The data indicate that volcanic ash, even in high concentrations, causes little toxicity to lung cells in vitro and in vivo, as compared with effects of free crystalline silica, which is known to be highly fibrogenic. Volcanic ash does not appear to be entirely inert, however, possibly because of low concentrations of free crystalline silica in the ash. The published experimental studies suggest that inhaled volcanic ash is not likely to be harmful to the lungs of healthy humans, but the potential effects of volcanic ash in patients with pre-existing lung diseases are more difficult to ascertain from these studies.

Air Pollutants↗
PubMed1986

Arachidonic acid metabolism in lung phagocytes.

Arachidonic acid metabolism in the lung leads to the formation of a variety of biologically active products, including one of the major mediator substances of asthma, SRS-A. Although a number of cell types in the lung release arachidonic acid products, the alveolar macrophage occupies a prominent role because of the high arachidonic acid content of its membrane and its potent secretory capacity. An improved understanding of the factors that regulate arachidonic acid metabolism and improved methods to modify it may lead to better treatments for disease processes within the lung.

Arachidonic Acid↗
PubMed1985

The effects of chronic bronchitis and chronic air-flow obstruction on lung cell populations recovered by bronchoalveolar lavage.

Bronchoalveolar lavage is used to evaluate parenchymal inflammation in patients with diffuse lung disease. Normal values for lavage cell counts and proteins are derived primarily from young subjects who are free from lung disease; however, older patients who undergo bronchoalveolar lavage often have used cigarettes for long periods of time and have developed variable degrees of chronic bronchitis and/or chronic air-flow obstruction. Therefore, we evaluated the effects of cigarette use, chronic bronchitis, and chronic air-flow obstruction on lavage cell populations by performing bronchoalveolar lavage in 48 male patients who were undergoing diagnostic fiberoptic bronchoscopy. Sixteen patients (33%) had elevated percentages of neutrophils (greater than or equal to 10%) in lavage fluid. Fourteen of these (87.5%) had chronic cough and/or phlegm production, but only 9 (64.3%) met criteria for definite chronic bronchitis. Patients with moderate or severe air-flow obstruction, defined spirometrically, had significantly greater percentages of lavage neutrophils and lower percentages of macrophages than did patients with mild or no air-flow obstruction. The first lavage aliquot contained the greatest proportion of neutrophils and the smallest proportion of macrophages. The percentage of neutrophils declined and the percentage of macrophages increased in sequential aliquots. The data indicate that patients with chronic cough and/or phlegm production and chronic air-flow obstruction may have increased proportions of neutrophils in bronchoalveolar lavage fluid in the absence of diffuse parenchymal lung disease or infections. These variables must be taken into account when interpreting lavage cellular analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1984

Association of insulin pump therapy with raised serum amyloid A in type I diabetes mellitus.

Serum concentrations of serum amyloid A protein, the high-density-lipoprotein-associated tissue amyloid A precursor, were determined in 29 diabetic patients receiving insulin by subcutaneous injection and in 50 receiving subcutaneous infusion pump therapy. Insulin delivered by continuous subcutaneous pumps stimulated serum amyloid A production to levels nearly six times those in normal subjects, nearly twice as much as insulin given by subcutaneous injection. 85% of patients with serum amyloid A levels greater than or equal to 10(4) ng/ml were being treated with insulin pump therapy. The relation between insulin aggregation and amyloid A in diabetes was evaluated in 1 patient; treatment with syringe-aggregated insulin resulted in a nearly 300% increase in serum amyloid A levels. The use of high-potency non-aggregating insulins in the pump treatment of type I diabetic patients may be necessary for optimum therapy.

Adolescent↗
PubMed1984

Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung.

Leukotriene B4 (LTB4) is a lipoxygenase product of arachidonic acid that has potent chemotactic activity for blood leukocytes. To assess the potential role of LTB4 in lung inflammatory responses, we investigated the production of LTB4 by human alveolar macrophages and determined its chemotactic activity for lung and blood phagocytes in vitro and in vivo. Human alveolar macrophages were stimulated with the calcium ionophore A23187 (10 micrograms/ml), and lipoxygenase products in the supernatants were isolated by high-performance liquid chromatography. Leukotriene B4 was the predominant arachidonate lipoxygenase product from the alveolar macrophages of 2 nonsmokers (17.3 +/- 2.7 ng/10(6) cells) and 3 of 4 smokers (23.4 +/- 14.8 ng/10(6) cells). Alveolar macrophages produced more LTB4 than did similarly treated peripheral blood neutrophils. Stimulated alveolar macrophages also produced 5-hydroxyeicosatetraenoic acid (HETE) and 2 isomers of LTB4: 5-(S),12-(R)-6-trans-LTB4 and 5-(S),12-(S)-6-trans-LTB4. Leukotriene B4 showed little chemotactic activity for alveolar macrophages in vitro and was a more potent chemoattractant for peripheral blood neutrophils than for monocytes (p less than 0.05). When instilled into the airways of anesthetized rats, LTB4 was less potent as an attractant for neutrophils and mononuclear cells than either zymosan-activated serum or bacterial-derived chemotactic factors. Leukotriene B4 production by alveolar macrophages may provide a mechanism by which phagocytes are recruited to the human lung during inflammatory processes.

Adult↗
PubMed1984

The comparative toxicity of volcanic ash and quartz. Effects on cells derived from the human lung.

To evaluate the effects of volcanic ash and free crystalline silica on cells derived from the air space of the human lung, we compared the effects of these minerals on human alveolar macrophages and A549 cells, which are derived from human type II pneumocytes. The quartz was markedly cytotoxic to alveolar macrophages and A549 cells and stimulated the release of neutrophil chemotactic activity from alveolar macrophages. By contrast, volcanic ash was much less toxic to human alveolar macrophages and A549 cells and did not stimulate the release of neutrophil chemotactic activity from alveolar macrophages. The results with A549 cells were similar to findings with isolated type II pneumocytes recovered from rat lungs. Secretory IgA, IgG, and albumin, which are normally present in the air spaces of the lung, reduced the cytotoxicity of quartz in a dose-dependent manner. These results suggest that in the human lung quartz, but not volcanic ash, may cause direct damage to cells in the alveolar spaces and lead to the recruitment of phagocytes from the bloodstream to the lung.

Adult↗
PubMed1983

Comparative effects of inhaled volcanic ash and quartz in rats.

To investigate the relative toxicities of inhaled volcanic ash and quartz, we exposed matched groups of rats to either respirable volcanic ash (100 mg/m3), quartz (100 mg/m3), or clean air only for 6 h daily for 10 days. Thereafter, we examined animals sequentially for as long as 9 months, and measured changes in lung histopathologic aspects, air-space cells and lipids, and lung density. Neutron activation studies demonstrated that 3.3% of the inhaled daily dose of volcanic ash was detectable in the lung parenchyma. Volcanic ash was less toxic to the lung than quartz. Immediately after exposure, the lungs of animals treated with volcanic ash had ultrastructural evidence of damage to type I pneumocytes and early alveolar edema formation. By contrast, quartz-treated animals had an intense acute injury, with intraalveolar accumulation of lipid, protein, macrophages, and granulocytes. Six months after exposure, animals treated with volcanic ash had moderate interstitial thickening and fibrosis, whereas the quartz-treated animals had severe pulmonary fibrosis. Quartz, but not volcanic ash, caused a marked increase in lavage granulocytes, protein, and phospholipids. Lung density increased in quartz-exposed, but not in volcanic-ash-exposed animals. These data indicate that volcanic ash is less harmful to the lung parenchyma than is quartz. Persons exposed to volcanic ash for short periods are at much less risk of subsequent lung damage than are those who are exposed to similar amounts of quartz in the workplace.

Absorptiometry, Photon↗
PubMed1983

The effects of severe protein-calorie malnutrition on antibacterial defense mechanisms in the rat lung.

Protein-calorie malnutrition (PCM) impairs systemic immunity in humans and animals, but its effects on regional defense mechanisms in the lung are not clear. Therefore, we investigated lung phagocytic antibacterial defenses in vivo and in vitro in an animal model of PCM. Matched groups of weanling rats consumed Isocaloric diets containing either 0.8% (PCM) or 24% protein (Control, C). A third group of animals was fed the C diet in restricted amounts to match the daily caloric intake of the PCM animals (pair-fed control, PF). After 4 wk on the diet, PCM animals were hypoproteinemic, hypoalbuminemic, and anemic and had depressed systemic cell-mediated immunity. In vivo, the lung clearance rate of Listeria monocytogenes was markedly delayed in PCM animals (% bacterial recovery at 9 days, mean +/- SE:PCM = 120 +/- 25.1; PF = 5.2 +/- 3.0; C = 0.6 +/- 0.6; p less than 0.001 for PCM versus C). Only 36% of the PCM animals survived for 9 days after Listeria exposure, whereas more than 94% of the C and PF animals survived (p less than 0.01). Recruitment of macrophages to the lungs of PCM animals after Listeria aerosolization was markedly impaired compared with that in the PF and C animals (p less than 0.001). By contrast, lung clearance rates of 2 pyogenic organisms, Staphylococcus aureus 502a and Pseudomonas aeruginosa 177, were similar in all groups. In vitro, alveolar macrophage chemotaxis toward zymosan-activated serum, and microbicidal activity against Staphylococcus epidermidis were also similar in all groups of animals. Our findings indicate that in the rat, PCM impairs the pulmonary clearance of L. monocytogenes, and that this defect is associated with impaired macrophage recruitment to the lung after Listeria inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Adult respiratory distress syndrome following thrombolytic therapy for pulmonary embolism.

Pulmonary edema is rare in patients with pulmonary embolism and to our knowledge has not been described in association with thrombolytic therapy. We describe a patient with massive pulmonary embolism in whom the adult respiratory distress syndrome (ARDS) developed shortly after a course of streptokinase therapy. The possible association between streptokinase therapy or pulmonary embolism and ARDS should be recognized as streptokinase gains wider clinical use.

Female↗