Histological Examination Of Lung Tissue Research Articles

A specific receptor antagonist for interleukin 1 prevents Escherichia coli ‐induced shock in rabbits

Despite antibiotic therapy, the septic shock syndrome continues to have a high mortality. Tumor necrosis factor (TNF) and interleukin 1 (IL 1), two polypeptide cytokines produced during sepsis, are thought to mediate the hypotension and tissue damage of shock. In the present studies, rabbits were infused with Escherichia coli organisms to produce shock. The IL 1 receptor antagonist (IL 1ra), which competes with IL 1 for occupancy of the IL 1 cell-surface receptors without agonist properties, was given 15 min before the bacterial infusion and during the subsequent 4 h. In saline-treated controls, hypotension was sustained for 4 h and death occurred for two of five rabbits; in rabbits treated with the IL 1ra, however, blood pressure was only transiently decreased, returned to pre-E. coli levels, and no deaths occurred. The associated leukopenia was also reduced by treatment with the antagonist (P less than 0.05). Histological examination of lung tissues showed reduced infiltrating neutrophils in the IL 1ra treatment group. Despite the attenuated responses in animals treated with the IL 1ra, circulating TNF and IL 1 levels were nearly identical in both groups. We conclude that specific blockade of IL 1 at the receptor level demonstrates an essential role for this cytokine in the pathogenesis of septic shock.

Primary pulmonary hypertension. Vascular structure, morphometry, and responsiveness to vasodilator agents.

The use of pharmacologic agents in the treatment of pulmonary hypertension has not proved to be uniformly successful or predictable. One possible reason for the vagaries in response is that the pulmonary vascular lesions are not consistent. We examined the relation between the structure of the pulmonary resistance vessels in unexplained (primary) pulmonary hypertension and the response to pulmonary vasodilators. Our study involved 19 patients with clinically unexplained pulmonary hypertension (mean pressure, 59 +/- 14 mm Hg). After characterizing them clinically and performing control hemodynamic measurements, we determined the acute effects of a series of vasodilator agents that have different mechanisms of action. In 16 patients, lung biopsy material was related to the hemodynamic studies; in nine patients, including six who had undergone open lung biopsy, the hemodynamic studies were related to the pathologic changes found at autopsy. Histologic specimens from all 19 patients were evaluated qualitatively and sorted into three subsets of hypertensive pulmonary arteriopathy: medial hypertrophy (with minimal intimal proliferation), arteriopathy with plexiform lesions (associated predominantly with concentric laminar intimal proliferation and fibrosis), and arteriopathy with microthrombotic lesions (associated predominantly with eccentric intimal proliferation and fibrosis). The 16 lung biopsies were also quantitated by morphometric techniques. Using a decrease in calculated pulmonary vascular resistance of more than 30% accompanied by a decrease in mean pulmonary arterial pressure of at least 10% to define vasodilation, only four patients were responders. The patients varied considerably in their responses to different vasodilator agents. Patients with similar clinical and hemodynamic profiles differed considerably with respect to the nature of their pulmonary vascular obstructive lesions and their responses to vasodilator agents. Qualitative histologic examination of lung tissue did not provide a basis for predicting how individual patients would respond to vasodilator agents. However, quantitative morphologic analysis of the initial open lung biopsy specimens did prove helpful in predicting acute responsiveness to vasodilator agents and the subsequent clinical course of these patients with unexplained (primary) pulmonary hypertension. An intimal area of more than 18% of the vascular cross-sectional area had an 85% predictive value for identifying the patients who did poorly during the first 36 months of follow-up.

Schistosoma mansoni: migration and attrition of challenge parasites in naive rats and rats protected with vaccine serum

The migration of isotopically labelled Schistosoma mansoni challenge cercariae was monitored, by means of squashed organ autoradiography, in naive Sprague-Dawley rats and rats protected with serum harvested from twice vaccinated donors. The majority of challenge larvae migrated from the skin to the lungs in both groups of rats, but a significantly increased number of larvae was retained in the lungs of serum recipients on day 8 post-challenge. An average of 25% of the challenge population succeeded in migrating to the livers of naive rats by day 14, compared to only 13% in passively protected animals; serum recipients were shown by perfusion on day 21 to be 73% immune. Histological examination of lung tissue harvested from naive rats challenged intravenously with lung-stage schistosomes revealed small foci composed of mononuclear cells that sometimes enclosed larvae; these worms are likely to be lost due to innate resistance. In the lungs of serum-protected rats, many challenge larvae were seen to be surrounded by extensive eosinophil-enriched inflammatory foci; parasite remnants were also observed within such reactions. Ultrastructural examination of worms recovered from the lungs of passively protected animals revealed muscle disruption and internal vacuolation, although the tegument remained intact. It is proposed that challenge attrition in serum-protected rats occurs essentially in the lungs and involves larval immobilization and subsequent death, perhaps mediated by cellular mechanisms.

Pulmonary clearance and toxicity of respirable gallium arsenide particulates intratracheally instilled into rats.

Gallium arsenide (GaAs) is an intermetallic compound that is recognized as a potential toxicological risk to workers occupationally exposed to its dust. Previous results have shown that rats intratracheally instilled with a fraction of GaAs particulates, characterized with a mean count diameter of 8.30 microns and a mean volume diameter of 12.67 microns, developed signs of systemic arsenic intoxication, pulmonary inflammation, and pneumocyte hyperplasia. The results of the present study confirm these findings and also show that a significantly smaller fraction of GaAs is a relatively more severe pneumotoxicant. Decreasing the particle mean count and mean volume diameter to 1.63 micron and 5.82 microns, respectively, increased the in vivo dissolution rate of GaAs, increased the severity of pulmonary lesions previously associated with GaAs exposure, and resulted in unique pathological sequelae in affected lung tissue. Pulmonary fibrosis, as indicated by analysis of lung 4-hydroxyproline content, was not considered statistically significant although histological examination of lung tissue revealed a mild fibrotic response. These results provide additional evidence that pulmonary exposure to respirable GaAs particulates is a potential health hazard in the semiconductor industry.

Immunization against fatal experimental Klebsiella pneumoniae pneumonia.

The ability of serospecific anti-capsular polysaccharide (CPS) antibody to prevent fatal Klebsiella pneumoniae pneumonia was evaluated in a rat lung model. Rats were immunized intramuscularly with 100 micrograms of purified serotype 2 CPS and challenged intrabronchially 14 days later with a serotype 2 strain of K. pneumoniae. Vaccination engendered high levels of serum anti-CPS antibody which afforded significant protection (P less than 0.01) against fatal pneumonia. Immunization promoted clearance of the challenge bacteria from the lungs and prevented bacteremia. Histological examination of lung tissue from infected control animals showed pronounced inflammatory cellular infiltrate in the alveolar spaces, intra- and peribronchial inflammation, and tissue necrosis. In contrast, pathological changes noted in lungs from immunized animals were restricted to infrequent intra- and peribronchial involvement.

A germ-free status does not protect from the lethal effects of acute lung damage caused by o,s,s,-trimethyl phosphorodithioate

To investigate whether a normal resident microbiological flora of conventional rats influences the lethality of chemical-induced lung damage, the pneumotoxin O,S,S-trimethyl phosphorodithioate (OSSMe, 75 or 100 mg/kg, s.c.) was administered to age-matched conventional and germ-free male F344 rats. Microbiological and serological examinations confirmed the germ-free state of the germ-free rats and showed that no specific lung pathogens were present in the conventional rats. As in conventional rats, clinical symptoms and death of OSSMe-treated germ-free rats resulted from respiratory failure. The germ-free rats were not more resistant, but rather more susceptible to OSSMe than conventional rats. Increases in lung weight and histological examination of lung tissue 3 days after dosing with OSSMe (75 mg/kg, s.c.) showed no differences between germ-free and conventional rats. Despite alterations in their nasopharyngeal flora, death in the conventional rats was probably not caused by bacterial superinfection. The higher susceptibility of germ-free rats to OSSMe can be partly attributed to pharmacokinetic differences, since plasma levels of OSSMe decreased more slowly in germ-free than in conventional rats. It is concluded that germ-free rats are not protected from the lethal consequences of acute chemical-induced lung damage.

Intravenous Bleomycin Does Not Alter the Toxic Effects of Hyperoxia in Rabbits

The purpose of this study was to test the hypothesis that bleomycin administration enhances the toxic effects of oxygen on the respiratory system. Twenty-one rabbits, with no evidence of respiratory disease, received intravenous injections of 45 units of bleomycin (Blenoxane), twice a week, for a total dose of 300 units. Fifteen rabbits received an equal volume of saline and served as controls. Treatment with bleomycin resulted in failure to thrive, weight loss, and 30% mortality from nonpulmonary causes, as indicated by the lack of respiratory distress or cyanosis, during or shortly after the injection period. The remainder of the animals were allowed to recover for 21 days following the last injection. At that time, no differences were found between the experimental and the control groups with respect to arterial blood gases, total lung capacity, compliance, and hydroxyproline content. Histologic examination of lung tissue revealed normal lung architecture. When exposed to 100% O2, bleomycin-treated rabbits developed arterial hypoxemia and died from respiratory failure at the same rate as the controls. It was concluded that pretreatment of healthy rabbits with 300 units of intravenous bleomycin did not result in the development of significant amounts of lung fibrosis or enhance the toxic effects of oxygen on the respiratory system.

Sensitizing ability of derivatives of picryl chloride after exposure of mice on the skin and in the lung.

In the present study the immunizing efficacy of antigen or hapten administered by the respiratory route and the resulting inflammatory reactions in the lungs after challenge were studied. We compared the induction of delayed hypersensitivity (DH) and the IgG, IgM, IgA, and IgE antibody formation after immunization with three different trinitrobenzene derivatives by the epicutaneous, the intradermal, and the intraperitoneal routes with the intranasal route. Mice sensitized with picryl chloride (PiCl) epicutaneously or intradermally, or with picryl sulfonic acid (PSA) epicutaneously showed strong DH responses. Moderate DH responses were obtained after sensitization with PSA intradermally and with trinitrophenylated human serum albumin (TNP-HSA) intraperitoneally. Intranasal administration of PSA and TNP-HSA also resulted in moderate DH responses. Strong IgG responses were seen in mice sensitized with PiCl and PSA epicutaneously, intradermally, and also intranasally. Administration of TNP-HSA epicutaneously, intradermally, and intraperitoneally also gave high IgG responses, while intranasal administration only induced moderate ones. Considerable IgM responses were seen only in mice sensitized epicutaneously with PSA. Antibody responses of the IgA isotype were only seen after epicutaneous sensitization with PiCl or PSA and intradermally with PiCl. Histological examination of lung tissue from mice sensitized with PiCl epicutaneously or with PSA intranasally and challenged with PSA intranasally revealed some inflammatory cells around bronchioli, capillaries and in the interstitial tissue. Differentiation of mucous cells in the epithelium covering inflammatory cells was also seen, and a slight increase in mast cell numbers around vessels. However, after sensitization with PiCl epicutaneously, TNP-HSA intranasally, and challenge with 2% TNP-HSA intranasally, a weaker inflammation was seen. In conclusion, intranasal administration of PSA or epicutaneous administration of PSA and PiCl gave strong DH and IgG responses. These sensitization regimes also resulted in pronounced inflammatory reactions in the lungs.

Adiaspiromycosis in Tasmanian wombats?

The finding of small spherules in the lungs of two species of wombats from Tasmania is described. An histological examination of lung tissue caused adiaspiromycosis to be suspected and the etiological agent was thought to Chrysosporium parvum.

Observations on outbreaks of respiratory disease in calves associated with parainfluenza type 3 virus and respiratory syncytial virus infection

In four outbreaks of indoor calf pneumonia, dyspnoea was a prominent clinical finding. At necropsy it was associated with pneumonia involving the cranial lobes of the lung and severe pulmonary emphysema. Histological examination of lung tissue revealed bronchiolitis and alveolitis with alveolar epithelial cell hyperplasia and multinucleate syncytium formation. Intraalveolar haemorrhage, intra-alveolar oedema and hyaline membrane formation were also noted. In all cases parainfluenza type 3 (PI3) virus was isolated from the lungs. In each of the four outbreaks there was evidence of PI3 virus and respiratory syncitial virus (RSV) infection.

Mechanism of oxygen detoxification in neonatal rat lung tissue.

Abstract— Pulmonary macrophages obtained from neonatal rats contain approximately four times the activity of cyanide resistant superoxide dismutase and catalase compared with the cells from adult animals. The activity is highest immediately after birth and diminishes with age until the minimum level is reached at approximately 3 weeks of age. Superimposed upon this change in basal activity is the capability of neonatal cells to synthesize additional cyanide resistant superoxide dismutase and catalase when either the animals or isolated pulmonary macrophages are exposed to 95–100% oxygen. The inductive effect begins at 2–3 days after birth, peaks at 10 days, and disappears at approximately 15 days after birth. In contrast to adult rats, neonatal rats are extremely resistant to the toxic effects of oxygen. If, however, the oxygen mediated increase in both enzymes is prevented or the maximum effective pulmonary macrophage number is diminished in test animals, these animals become vulnerable to toxic effects of oxygen exposure, observed by gross and histologic examination of lung tissue, in a manner similar to adult animals. These data indicate that both cyanide‐resistant superoxide dismutase and catalase may be part of the endogenous defense mechanisms which provide neonatal rats with an exceptional resistance to oxygen toxicity.

THE EFFECT OF PARENTERAL FAT EMULSIONS (PFE) ON TISSUE FATTY ACID COMPOSITION, THE MAJOR URINARY METABOLITES OF E PROSTAGLANDINS (PGEM) AND LUNG HISTOLOGY

The essential fatty acids (EFA) are incorporated into biological membranes and serve as prostaglandin (PCS) precursors. Plasma, RBC and tissues were analyzed in 2 neonates receiving total parenteral nutrition (TPN) for the first 11 weeks and in 3 controls fed breast milk (1) or formula (2). TPN included intralipid (IL-50% of which is linoleic acid) 1-4 gms/kg/24 hrs. Analysis of phospholipids, cholesterol esters, free fatty acids and triglycerides by TLC and GLC revealed that: (1) plasma, RBC and tissues from infants receiving IL contained higher levels of linoleic acid compared with controls (p< 0.001); (2) the higher polyenoic acid derivatives of linoleic acid, Δ-8,11,14 eicosatrienoic and arachidonic acids were lower in infants receiving IL (p<0.001); (3) the sum of the FA belonging to the linoleic acid series were similar in both groups. PGEM levels were lower in infants receiving iL (p<0.01) as compared with controls. Histological examination of lung tissues from both infants receiving IL revealed numerous globules of sudanophilic material in septal capillaries and in the cytoplasm of septal macrophages. Plasma lipid content was not elevated. Both infants required assisted ventilation. Further study is needed to evaluate the effects of PFE on biomembranes, PCS biosynthesis, lung capillary RBC investment and gas exchange.

Transbronchial Lung Biopsy Using Fiberoptic Bronchoscope

Transbronchial lung biopsy through the fiberoptic bronchoscope was done in 15 patients, and adequate pulmonary tissue was obtained in 14 (93.3%). A pathologic diagnosis was made in nine patients (64.3%), and through direct histologic examination of lung tissue in two patients certain disease entities were excluded, thus significantly influencing treatment. There was no significant hemorrhage and only one small pneumothorax occurred.

Transbronchial Forceps Lung Biopsy through the Fiberoptic Bronchoscope: Diagnosis of Diffuse Pulmonary Disease

Transbronchial forceps biopsy through the fiberoptic bronchoscope was performed in 37 patients. Tissue was technically inadequate for examination in two cases. A pathologic diagnosis was obtained in 26 (72 percent) and in five additional critically ill patients, direct histologic examination of lung tissue allowed exclusion of certain entities, thus significantly influencing therapy. Overall, the procedure was of value in 31 of 35 patients (90 percent). There was no significant hemorrhage and there was one 15 percent pneumothorax. The safety and high diagnostic yield of this technique in the diagnosis of diffuse lung disease is proved.

Diagnostic Open Lung Biopsy in the Critically Ill Child

Forty-six open biopsies in 40 acutely ill children with rapidly decreasing pulmonary reserve were performed at the University of Minnesota Hospitals between January 1, 1970, and January 1, 1972. Tissue obtained was adequate in all patients and no serious complications ensued. Information obtained resulted in the change in treatment in 30 patients. This procedure is recommended over closed biopsy when the magnitude of the patient's illness and degree of pulmonary function do not allow acceptance of the risks known to occur with a closed biopsy technique and when histologic examination of lung tissue is required.

Platelet aggregation and increased pulmonary vascular resistance in cats induced by DAS and ADP.

In cats the intravenous injection of a substance enriched from stored serum (DAS=depressor active substance) led to an extreme increase in pulmonary vascular resistance (PVR) and at the same time to a marked decrease in platelet count. The maximum increase in PVR was significantly related to the platelet count. The histologic examination of lung tissue—taken at the time of maximum increase in PVR—revealed an extensive microembolism of the terminal pulmonary vessels by platelet aggregates. DAS proved more active than adenosine diphosphate (ADP) from which it can be distinguished by its solubility in organic solvents and by a typical tachyphylactic response.

Eosinophilic Granuloma of the Lungs: Roentgenologic and Pathologic Features

Five patients with diffuse pulmonary disease thought to be tuberculosis, but proved on lung biopsy to be eosinophilic granuloma were admitted to the Municipal Tuberculosis Sanitarium in the last two years. The x-ray findings were those of a fine peribronchiolar lattice-work-like pattern of infiltration which, in later stages, became a mixture of fine nodular infiltrates and small cystic areas, leading eventually to the diagnosis of honeycomb lung. Predominant findings on microscopic examination of the lung tissue were the presence of granulomata consisting of histiocytic cells with a large number of eosinophils, histiocytic aggregates in the alveolar septa and bronchial walls and marked fibrosis of the lung with resulting bronchiolectasis. There was hyperplasia of the smooth muscle and epithelial elements. In our experience, confirmation of the diagnosis of eosinophilic granuloma hinges on the histologic examination of lung tissue taken for biopsy.