The macrophage-derived cytokine tumor necrosis factor alpha (TNF alpha) has been proposed as the major mediator of endotoxin-induced injury. To examine whether a single infusion of human recombinant TNF alpha (rTNF alpha) reproduces the pulmonary effects of endotoxemia, we infused rTNF alpha (0.01 mg/kg) over 30 min into six chronically instrumented awake sheep and assessed the ensuing changes in hemodynamics, lung lymph flow and protein concentration, and number of peripheral blood and lung lymph leukocytes. In addition, levels of thromboxane B2, 6-ketoprostaglandin F1 alpha, prostaglandin E2, and leukotriene B4 were measured in lung lymph. Pulmonary arterial pressure (Ppa) peaked within 15 min of the start of rTNF alpha infusion [base-line Ppa = 22.0 +/- 1.5 (SE) cmH2O; after 15 min of rTNF alpha infusion, Ppa = 54.2 +/- 5.4] and then fell toward base line. The pulmonary hypertension was accompanied by hypoxemia and peripheral blood and lung lymph leukopenia, both of which persisted throughout the 4 h of study. These changes were followed by an increase in protein-rich lung lymph flow (base-line lymph protein clearance = 1.8 +/- 0.4 cmH2O; 3 h after rTNF alpha infusion, clearance = 5.6 +/- 1.2), consistent with an increase in pulmonary microvascular permeability. Cardiac output and left atrial pressure did not change significantly throughout the experiment. Light-microscopic examination of lung tissue at autopsy revealed congestion, neutrophil sequestration, and patchy interstitial edema. We conclude that rTNF alpha induces a response in awake sheep remarkable similar to that of endotoxemia. Because endotoxin is a known stimulant of TNF alpha production, TNF alpha may mediate endotoxin-induced lung injury.
Tumor necrosis factor alpha (TNF alpha) is a monokine released in response to endotoxin and has been suggested as a primary mediator of endotoxic shock. We have recently demonstrated that infusion of recombinant human tumor necrosis factor alpha (rTNF alpha) into sheep elicits a physiologic response in the lung that closely resembles endotoxemia. The present study examines the morphologic changes that accompany these alterations in pulmonary physiology. Five anesthetized, open-chest sheep received 0.01 mg/kg of protein (2.24 x 10(7) U rTNF alpha/mg) intravenously over 30 min. Lung biopsy tissue for light and electron microscopy was obtained from random lobes 7.5, 15, 30, 60, 120, 180, and 240 min after beginning the infusion. Pulmonary (Ppa) and systemic arterial pressures, cardiac output, and peripheral blood leukocyte number and differential counts were monitored throughout the study. Three control animals were treated in a similar manner but received either saline (n = 1) or rTNF alpha denatured by boiling for 30 min (n = 2). rTNF alpha caused an early increase in Ppa and peripheral blood leukopenia. Light microscopy revealed a threefold increase in the number of granulocytes per 100 alveolar profiles by 30 min and a fivefold increase by 2 h. From 60 min, increased alveolar wall thickness, red cell congestion, and peribronchovascular edema were apparent; from 2 h, there was increased cellularity of the alveolar walls and mononuclear cell infiltration of perivascular connective tissue. Electron microscopy revealed damage to alveolar Type I and II pneumonocytes and progressive endothelial injury from 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Rationale: Zinc supplementation has been considered a safe prophylactic measure against COVID-19 infection, but the risks have not been well established.Patient concerns: We describe a 73-year-old patient who presented with bronchoscopy 10 days after zinc tablet aspiration. Diagnoses: Circumferential Chemical Airway Burn leading to Airway StenosisInterventions: Bronchoscopy with bronchodilation Outcomes: After the initial bronchoscopy, the patient was administered a course of steroids, but on repeat bronchoscopy, significant airway stenosis was encountered, and balloon dilationwas performed.Lessons: Zinc tablet aspiration is a previously unreported risk of zinc prophylaxis and requires prompt bronchoscopic evaluation for foreign body removal.
REDUCTION in environmental temperature is known to depress enzyme activity. Pancreatic enzyme activity is generally considered to be intimately associated with the development and perpetuation of the patho-physiologic changes of acute pancreatitis. In view of these observations, it would seen that hypothermia might have a place in the treatment of acute pancreatitis. duodenum (Fig. 1). The catheter was brought out through a stab wound in the abdominal wall to the level of the subcutaneous tissues and then routed back through the abdominal wall, via a second stab wound, and into the stomach. The tube was fixed in the stomach with a double purse-string suture. One week later, after complete recovery from the initial operation, the dog was anesthetized with pentobarbital and the tubing was exposed through a small incision. The tubing was divided and from it pancreatic secretions collected for six hour periods (Fig. 2). A plug was placed in the gastric end of the tubing during collections. When the collection was completed, continuity of the tubing was restored and pancreatic secretions were again routed into the stomach. During the collection periods the animal received a 500 cc. intravenous infusion of 5 per cent dextrose in saline. An initial six-hour collection of pancreatic secretion was made at normothermic levels, as determined by rectal temperatures 380-390 C. A six-hour collection was then made after reducing the body temperature (340-280 C.) by means of a cooling blanket and ice packs. During hypothermia an endotracheal tube and mechanical respirator were used to assist respirations. In some instances the collection under hypothermia was made immediately following the normothermic collection. In other animals the hypothermic collection was accomplished the following day. In some instances hypothermic collection preceded normothermic collection.At the termination of a hypothermic collection, the animal was warmed to 360 C.
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