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Biomedical subjects

R M Senior

Publications and source records attributed to R M Senior.

At least 127 records · Page 7Linked to original sources

Clinical experience with theophylline. Relarionships between dosage, serum concentration, and toxicity.

Relationships between theophylline dosage, serum theophylline concentration, and theophylline toxicity were evaluated retrospectively in 47 hospitalized adults. The amount of theophylline administered daily varied more than sixfold, from 6 to 38 mg/kg. The serum theophylline concentrations, however, varied 24-fold from 2 to 49 mug/ml. The relationship between daily dosage and serum concentration was unpredictable in an individual patient. Fourteen patients (30%) had a toxic reaction to theophylline. Toxic symptoms, which were not always gastrointestinal, occurred commonly with serum concentrations over 25 mug/ml but were not noted with concentrations below 15 mug/ml. High serum theophylline concentrations and a toxic reaction developed just as often with the oral route as when the drug was given intravenously. In six patients, measurement of serum theophylline concentration disclosed subtherapeutic concentrations. Serum theophylline determination appears to be important clinically in guiding effective and safe usage of theophylline.

Administration, Oral↗

The elastase activity of alveolar macrophages: measurements using synthetic substrates and elastin.

Hamster, rat, guinea pig, and rabbit alveolar macrophage extracts were tested for elastase activity using elastin suspended in agar and two synthetic substrates, p-nitrophenyl N-tert-butyloxycarbonyl L-alaninate (NBA) and succinyl-L-alanyl-L-alanyl-L-alanine-p-nitroanilide (SLAPN). Activity against NBA was easily detectable, but there was no activity against SLAPN or against elastin-agar, although the assay procedures employing these substrates measured as little as 50 and 2 ng of pancreatic elastase, respectively. We concluded that unstimulated alveolar macrophages from these animals do not contain elastase, and that NBA activity is misleading as an indicator of elastolytic activity in crude alveolar macrophage extracts from these species.

Animals↗

Unilateral lung function. Comparison of the lateral position test with radionuclide ventilation-perfusion studies.

Twenty-seven patients underwent studies of unilateral lung function by the lateral-position test (LPT) and by computer-analyzed radionuclide imaging of ventilation and perfusion. The patients were divided into two groups, symmetric or asymmetric, on the basis of the physical examination of the chest and the chest radiograph. In patients with symmetry, the estimate of unilateral lung function by the LPT and isotopic estimates for unilateral lung volume, unilateral distribution of tidal volume, and unilateral perfusion, agreed within 2 percent, 4 percent, and 3 percent, respectively. In patients with asymmetry, the differences were 9 percent, 8 percent, and 13 percent. In settings of marked unilateral ventilation-perfusion imbalance, the LPT primarily reflected ventilation. Prediction of unilateral ventilatory function based upon the LPT and spirometric measurements agreed closely with unilateral ventilation determined isotopically by 133xenon, even in the presence of chronic obstructive lung disease. Our results confirm that the LPT provides valid information about unilateral lung function.

Adult↗

How to detect and treat arrhythmias in chronic lung disease.

Investigators suspect that arrhythmias are behind the high incidence of sudden death in patients with severe chronic bronchitis and emphysema. Continuous electrocardiographic monitoring may help boost survival statistics, since it has repeatedly shown its ability to detect irregularities that standard ECGs miss. So-called benign arrhythmias, such as atrial fibrillation, frequent ventricular premature contractions, and atrial flutter, are anything but harmless. In patients whose heart and lung function is already impaired by severe airway obstruction, these rhythm disorders can rapidly progress to a fatal cardiac arrest. Deciding how to treat the arrhythmia depends on the type of disturbance and the patient's clinical status. Direct-current shock or antiarrhythmic drugs can turn the tide in a desperately ill patient with acute respiratory failure. Correction of coexisting metabolic and ventilatory disorders often is crucial to successful therapy.

Aged↗

The left ventricle in emphysema and chronic bronchitis.

There's no doubt that chronic obstructive lung disease can have a disastrous impact on the heart's right ventricle--often producing hypertrophy or even failure--but its effects on the left ventricle are less clear. Some researchers speculate that disease of the right ventricle leads to disease of the left, while others consider the lung disease itself to be the more likely mechanism. Ordinarily, the left ventricle holds up well, even in far-advanced emphysema and chronic bronchitis. Recognizing the cases that do occur is important, however, since only minimal left ventricular failure can seriously compromise respiratory function. Treatment is the same as for left ventricular failure of any cause, but special precautions should be observed, particularly in prescribing diuretics. If frank pulmonary edema supervenes, mechanical ventilation and supplemental oxygen are necessary.

Aged↗

The induction of emphysema with elastase. II. Changes in connective tissue.

Both clinical and experimental evidence implicate proteolytic enzymes active against elastin in the pathogenesis of emphysema. Paradoxically, however, the elastin content of emphysematous human lungs at autopsy has been normal. When emphysema was produced in hamsters by a single intratracheal injection of 25 units of porcine pancreatic elastase, the elastin content of the lungs was reduced from 1.40 +/- 0.22 mg. in controls to 0.43 +/- 0.10 mg. 24 hours after injection, and histologic sections showed that many elastic fibers had disappeared. The elastin content of the lungs gradually increased, approaching normal values by 2 months after injection. The incorporation of 14C-proline into elastin was markedly elevated during the first 2 weeks after injection, decreasing nearly to normal by 2 months. The synthesis of collagen was also increased, indicated by an increase in the collagen content of the lung, an increase in the prolyl hydroxylase activity, and an increase in incorporation of labeled proline into collagen. During the period of active resynthesis of elastin, small clumps of microfibrils and elastic fibrils were visible by electron microscopy within grooves on the surface of septal connective tissue cells in the lungs. Many elastic fibers seen in histologic sections up to 4 months after injection were of abnormal configuration and disorganized.

Animals↗

Status asthmaticus.

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Administration, Oral↗

The Jewish Hospital of St. Louis therapeutic grand rounds number 10. Chemoprophylaxis of tuberculosis.

Isoniazid therapy has been proved an effective means of preventing overt clinical tuberculosis in persons with positive tuberculin skin tests, persons who are close contacts of active cases, and persons with inactive tuberculosis that were never treated. The administration of isoniazid in standard dosage for one year in these situations will help greatly to reduce tuberculosis as a community health problem in the future. Studies in recent years, however, point to hepatic dysfunction as a complication of isoniazid therapy in up to 10% of patients. In a few patients, liver disease as a complication of this therapy has been fatal. The likelihood of this complication increases with age. Accordingly, isoniazid chemoprophylaxis should be undertaken with the understanding that the patient has to be followed up closely, especially for evidence of liver disease during the course of therapy. This potentially serious side effect suggests that isoniazid chemoprophylaxis should be used primarily with patients in high risk groups.

Adult↗

Characteristics of sodium and potassium transport in the lung.

Freshly prepared lung slices were incubated in an oxygenated Krebs-Ringer bicarbonate medium for 90 min at 0.5 degrees C (chilling) followed by 60 min at 38 degrees C (rewarming). Fresh tissue cation contents (mean +/- SE) in mmol/kg dry wt were: sodium, 431 +/- 7; potassium, 416 +/- 10. After chilling, tissue sodium increased to 757 +/- 11 and potassium decreased to 113 +/- 6. Upon rewarming there was a net increase in tissue potassium of about 150 (mmol/kg dry wt) and a net decrease in tissue sodium of about 130. Tissue extrusion of sodium and reaccumulation of potassium observed at 37 degrees C were abolished when 1 mM ouabain, dinitrophenol, or iodoacetamide was added to the incubation medium. Similar results were obtained when the medium contained no potassium or when medium Na was replaced by choline. The data indicate the presence of active Na+-K+ transport in lung cells somewhat similar to that found in other mammalian tissue.

Animals↗

The effects of proteolytic enzymes on the tensile strength of human lung.

Human lung tissues were exposed to proteolytic enzymes to determine the effects on tensile strength and to clarify the relationship between tensile strength and the amounts of collagen and elastin in the tissue. Elastase and papain depleted the tissue of elastin but failed to alter tensile strength. Trypsin had no effect on tensile strength, or on collagen and elastin content. collagenase lowered tensile strength and reduced the amount of collagen in the tissue. The findings with collagenase were in agreement with measurements in control tissues that showed a direct relationship between tensile strength and collagen content. These results confirm collagen as the principal determinant of the tensile strength of human lung.

Aged↗