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Biomedical subjects

D E Griffith

Publications and source records attributed to D E Griffith.

64 records · Page 4Linked to original sources

Asthmatic bronchitis.

Asthmatic bronchitis is a term that encompasses a large number of patients who generally smoke cigarettes and demonstrates chronic mucous hypersecretion and airway hyperreactivity. These patients are frequently labelled simply as asthmatic. In this setting, however, "asthma" is a nonspecific term applied to patients with a variety of symptoms. On the basis of history, bronchodilator response, and response to bronchoprovocating agents, it is frequently difficult to differentiate between groups of chronic bronchitics and asthmatics. Subjects with chronic bronchitis clearly demonstrate bronchial hyperreactivity to bronchoprovocating agents. This response does not appear to be due to an abnormality in bronchial smooth muscle. Chronic bronchitics may also respond to a variety of bronchodilating agents, again demonstrating the presence of bronchial hyperreactivity. Potential mechanisms for the observed bronchial hyperreactivity include reduced airway caliber, reduced resistance to airway narrowing, and airway inflammation. Airway inflammation may be the common link between airflow obstruction and airway hyperreactivity frequently seen in these patients. The finding of airway hyperreactivity in chronic bronchitis has implications far beyond simple therapeutic considerations and may lead to a better understanding of bronchial hyperreactivity under any circumstance.

Asthma↗

Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII.

Alveolar fibrin deposition commonly occurs in the lungs of patients with the adult respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) from patients with ARDS, control patients with interstitial lung disease (ILD), congestive heart failure, or exposure to hyperoxia, and normal healthy subjects was studied to determine whether local alterations in procoagulant activity favor alveolar fibrin deposition in the lungs in ARDS. Procoagulant activity capable of shortening the recalcification time of plasma deficient in either factor VII or factor VIII was observed in unconcentrated BAL of all patients, but was significantly greater in BAL from patients with ARDS when compared with that of control subjects (p less than 0.001). Unconcentrated BAL from patients with ARDS shortened the recalcification time of plasma deficient in factor X, but no functional thrombin was detectable. BAL procoagulant from patients with ARDS was inhibited by concanavalin A, an inhibitor of tissue factor. The hydrolysis of purified human factor X by BAL from the ARDS and other patient groups was determined by measuring the amidolytic activity of generated factor Xa on its N-benzoyl-L-isoleucyl-L-glutamyl-glycyl-L-arginine-p-nitroanilide substrate. The procoagulant activity of BAL was associated with the development of amidolytic activity, indicating activation of factor X. BAL from patients with ARDS contained more factor X activating activity than did BAL from control groups (p less than 0.001). This activity was calcium dependent and was maximal at 1 mM ionized calcium. The BAL factor X activating activity was most active at neutral pH and was sedimented by ultracentrifugation at 100,000 x g.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of common therapeutic concentrations of oxygen on lung clearance of 99mTc DTPA and bronchoalveolar lavage albumin concentration.

We studied the effects of oxygen concentrations (21 to 50%) considered clinically "safe" on clearance of inhaled technetium-labeled diethylene triamine pentaacetate (99mTc DTPA) and the concentration of albumin in bronchoalveolar lavage (BAL) fluid of normal subjects. We also measured several markers of cell injury and inflammation in the BAL fluid including total and differential cell counts, lactate dehydrogenase, alkaline phosphatase, extracellular potassium, and several eicosanoids. Subjects inhaled oxygen (50, 40, 30, or 21%) for a mean of 45 h; there were no symptoms or bronchoscopic signs of oxygen toxicity. The concentration of albumin in BAL fluid was increased compared with baseline measurements in a dose-dependent manner in subjects exposed to 30% oxygen and above. Clearance of 99mTc DTPA was increased only in subjects who inhaled 50% oxygen. There were no significant changes in BAL fluid volume or total and differential cell counts after oxygen exposure. A trend towards an increased percentage of polymorphonuclear leukocytes was noted in the 50% oxygen group. We found no evidence of cell injury or inflammation in the BAL fluid. Supplemental humidity did not appear to influence the findings in the 50% oxygen group. Thus, oxygen in concentrations considered clinically "safe" increases clearance of 99mTc DTPA and BAL albumin concentration in normal subjects after a relatively short time of exposure.

Adult↗

Drug intolerance to high-dose clarithromycin among elderly patients.

We treated 13 elderly patients with chronic mycobacterial lung disease with clarithromycin using 1000 mg b.i.d. as monotherapy. Patients had a mean age of 70 years, and 12 of 13 had creatinine clearances of 31-71 ml/min. Adverse events were seen in 100% of patients, with the most common being bitter taste (92%), nausea (92%), vomiting (54%) and central nervous system symptoms (54%). Elevated liver enzymes developed in five (38%) of 13 patients at weeks 1-6 of therapy. Mean serum levels of clarithromycin plus its 14-OH metabolite were 12.9 +/- 3.6 micrograms/ml (SD). There were 11 patients (85%) who discontinued the high dose within 3 months because of side effects. Serum drug levels of clarithromycin plus its 14-OH metabolite consistently exceeded 12 micrograms/ml in six of six patients who discontinued drug (10 of 10 values) compared with neither of two patients who tolerated the high dose (0 of 6 values). A dose reduction to 500 mg b.i.d. was well tolerated (nine of 10 patients). Future trials with clarithromycin in this population should use lower doses with attention to body mass and renal function to minimize side effects.

Aged↗

Clearance of proteins from the air spaces following cardiogenic edema in sheep.

Studies on the clearance of instilled fluid and protein into the lungs of sheep show that fluid initially clears rapidly from the lungs resulting in an increase in an increase in air space protein concentrations. This is followed by a slower monoexponential clearance of proteins during the next few days. To determine whether the clearance of edema fluid follows the same time course as instilled fluid, alveolar edema was induced in 11 sheep by inflating a balloon in the left atrium for 2 h to increase left atrial pressure 35-40 cm H2O. Protein concentrations in the epithelial lining fluid (ELF) were monitored by performing single-cycle lavages immediately after deflation of the left atrial balloon, and again 3, 21, 48, and 96 h later. During the first 3 h of recovery, 44% of the fluid cleared and ELF protein concentrations rose from 7 +/- 2 to 19 +/- 6 mg/mL in the 7 sheep that recovered well. The ELF protein concentration in these sheep remained elevated for 48 h and then cleared at rates similar to that seen following instillation of proteins. We conclude that insights about mechanisms of clearance of edema fluid obtained from studies of clearance of instilled fluid are valid in cardiogenic edema, but the time course of the clearance differs between the two models.

Animals↗

Juvenile hysteria and primary shock: report of case.

Hysterical aberrations may occur from circumstances other than fear and anxiety in a dental office. Irreversible shock from hysteria is well documented. It is important that causative factors of hysterical experiences be properly and promptly identified, and adequate measures be taken to allay these factors so that permanent adverse effects of the hysteria are aborted.

Child↗