Bronchiolitis obliterans with organizing pneumonia in AIDS.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
R A Harley
Publications and source records attributed to R A Harley.
Immunological function in post-traumatic splenosis.
A 28-year-old male medical student underwent splenectomy at 8 years of age due to traumatic rupture of the spleen sustained in a motor vehicle accident. Eighteen years later the patient had major abdominal surgery performed for an unrelated condition and, at the time of surgery, over 100 splenic nodules were found embedded throughout the patient's omentum, small bowel, and mesentery. An extensive study of immunological functions was carried out during the following 2 years. Through the course of this investigation, it was determined that the patient's peripheral blood smear lacked Howell-Jolly bodies and deformed or damaged erythrocytes, indicating that the splenotic tissue had the capacity to remove intranuclear inclusions from circulating red cells and to phagocytose old erythrocytes. The patient's levels of complement, serum immunoglobulins and the numbers of circulating T and B lymphocytes, helper T cells, and cytotoxic/suppressor T cells all were within the normal range. The response to Streptococcus pneumoniae polysaccharides was also normal, with increased levels of specific antibodies to all serotypes included in the vaccine 4 months after immunization. Finally, histological examination of his biopsied splenotic nodules revealed tissue that was indistinguishable from normal spleen.
Adult↗
The role of mast cells in the development of skin fibrosis in tight-skin mutant mice.
Chronic inflammatory conditions can evolve a fibrotic phenotype often associated with an increase in the number of mast cells (MC) near or within the granulation tissue. Despite the potential of MC to mediate fibrosis, it is unclear whether these cells play a central role in the pathogenesis of fibrosis or whether their presence is simply circumstantial. The tight-skin (Tsk) mouse develops an inherited fibrotic disease (sharing many similarities with the human disease scleroderma, systemic sclerosis) in which the lesions are associated with increased numbers and heightened granule release implicating MC in the pathogenesis of fibrosis. Despite their close association with the skin fibrosis of Tsk mice, the precise role of the MC in the pathogenesis of this inherited disease is unknown. Therefore, to assess directly whether MC are key elements in the pathogenesis of Tsk fibrosis, we generated MC deficient mice carrying the Tsk locus by utilizing selective interbreeding between Tsk and mutant mice deficient in mast cells (W, dominant white-spotting). We found that in the absence of MC, the early natural history of Tsk fibrosis was not altered. Furthermore, in older (5-7 months) Tsk mice, we found that the number of cutaneous MC was correlated with a more pronounced fibrosis. Therefore, we conclude that Tsk skin lesions are a pleiotropic manifestation of the Tsk gene in which MC are involved/recruited by an uncharacterized mechanism and that subsequent proliferation and activation of MC leads to augmentation of fibrosis.
Animals↗
Electron probe microanalysis of silicon and the role of the macrophage in proximal (capsule) and distant sites in augmentation mammaplasty patients.
Electron probe x-ray microanalysis was used to locate silicon (Si) within macrophages from 12 women who had previously undergone polymer prosthesis augmentation or reconstruction. Silicon was identified within macrophages and extracellularly in all fibrous breast capsules. In four women with arthritic joint pain and one woman with sclerodermatous skin lesions, silicon also was identified within macrophages residing in joint synovium and skin, respectively. It is suggested that the silicon-laden macrophages observed in the remote lesions may have accumulated silicon from other macrophages that had previously resided in the connective-tissue capsule around the silicone breast implants.
Adult↗
Talc slurry pleurodesis. Pleural fluid and histologic analysis.
Although talc slurry pleurodesis is effective for control of malignant pleural effusions and recurrent pneumothorax, the mechanisms of pleurodesis remain incompletely defined. We instilled 70 mg/kg of sterile asbestos-free talc slurry into the pleural space of New Zealand white rabbits and studied the inflammatory response at 1, 2, 3, 7, 15, 30, 60, 90, and 120 days by observing pleural fluid and histologic characteristics. Talc slurry caused mesothelial denudement and an exudative neurotrophilic pleural effusion that resolved after 48 h. A transient mononuclear vasculitis was seen within the lung at 1, 2, and 3 days after instillation. Pleural adhesions were minimal and did not increase in number over time. Talc was found outside of the pleural space in mediastinal lymph nodes (4 of 23 animals examined), kidney (1 of 6), and spleen (4 of 10). The predominant cause of pleurodesis with talc slurry instillation is an acute pleural injury similar to the tetracycline class agents.
Animals↗
A murine model of the eosinophilia-myalgia syndrome induced by 1,1'-ethylidenebis (L-tryptophan).
The eosinophilia-myalgia syndrome (EMS) is a recently described disease that has been associated with the ingestion of L-tryptophan containing trace amounts of several impurities. The first such contaminant to be identified and linked epidemiologically to the EMS epidemic was 1,1'-ethylidenebis(L-tryptophan) (EBT), but its role in the etiology and pathogenesis of the syndrome has been controversial. We report the development of inflammation and fibrosis affecting the dermis and subcutis, including the fascia and perimyseal tissues, after the daily intraperitoneal administration of EBT to female C57BL/6 mice. Such changes are accompanied by increased numbers of mast cells, many of which appear to be degranulating. Plasma levels of quinolinic acid, a metabolic product of L-tryptophan via the kynurenine pathway, are reduced initially, and then become elevated when inflammation and fibrosis are more pronounced. The nature and location of the inflammatory cell infiltrate and fibrosis, as well as the presence of mast cells and alterations of L-tryptophan metabolism, are consistent with findings reported in patients with EMS. This murine model suggests that EBT may have been one of the mediators of EMS and should facilitate studies of the pathogenesis of EMS.
Animals↗
Cardiomyopathy and myocarditis in children with ventricular ectopic rhythm.
OBJECTIVE: The objective of this study was to evaluate the histologic features of the myocardium in children with abnormal ventricular ectopic rhythm but a structurally normal heart. BACKGROUND: Abnormal ventricular ectopic rhythm in children with a structurally normal heart is an uncommon but serious condition. Previous studies in adults with these findings have shown that approximately 10% have "primary electrical disease" and that 40% to 100% of these have abnormal histologic findings. METHODS: Endomyocardial biopsy samples were obtained prospectively in 33 subjects presenting with ventricular ectopic rhythm but a structurally normal heart by physical examination and noninvasive studies. Biopsy specimens were evaluated for histologic changes consistent with dilated cardiomyopathy or myocarditis and these results were compared with noninvasive and invasive clinical findings. RESULTS: Of the 33 subjects, 16 (48%) had normal myocardial histologic features (Group A), 14 (42%) had changes similar to the histologic features seen with idiopathic dilated cardiomyopathy (Group B) and 3 (9%) had lymphocytic myocarditis (Group C). Presenting clinical symptoms, surface electrocardiograms (ECGs), exercise stress testing and electrophysiologic stimulation tests failed to predict the biopsy results. Twenty-four-hour ambulatory ECGs showed a statistical difference between sustained and nonsustained ventricular tachycardia in Group A versus Group B (p less than 0.007), with Group A having more sustained ventricular tachycardia. Left ventricular function measured by fractional shortening on echocardiography did not differ between groups, but left ventricular end-diastolic dimension was greater in the subjects with abnormal histologic findings (Group B) (p less than 0.03). CONCLUSIONS: These results provide evidence that approximately 50% of children with abnormal ventricular ectopic rhythm but a structurally normal heart may have subclinical cardiomyopathy or unsuspected myocarditis.
Biopsy↗
Pulmonary hypertension and human immunodeficiency virus infection. Two reports and a review of the literature.
Pulmonary hypertension may be primary (idiopathic) or secondary. While the etiologies for secondary pulmonary hypertension are diverse, infection with the human immunodeficiency virus (HIV) has not been included. To date there have been 16 reported cases of pulmonary hypertension in the HIV-infected population. Plexogenic arteriopathy was the most common pathologic finding. We report two HIV-infected patients who were concomitantly found to have pulmonary hypertension with plexogenic arteriopathy. One patient had lymphocytic interstitial pneumonitis, an entity not previously associated with pulmonary hypertension. We review the 16 previous cases of pulmonary hypertension and HIV infection and discuss this association.
Adult↗
Pulmonary reactions from illicit substance abuse.
The epidemic spread of illicit substance abuse in the United States and the adaptation of novel modes of drug delivery have increased the incidence of pulmonary complications of drug addiction. Chest manifestations of drug abuse relate not only to the particular substance used, but also to the route of administration, the presence of contaminating foreign material or microbiologic pathogens host response, and the practice of sharing drug paraphernalia. This article outlines the important lung disorders linked to drug addiction and discusses pathophysiologic mechanisms, diagnosis, and management.
Cannabis↗
Cocaine, pulmonary hemorrhage, and hemoptysis.
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Administration, Inhalation↗
Pleural effusions associated with ethchlorvynol lung injury result from visceral pleural leak.
Traditional thinking suggests that pleural fluid develops on the basis of systemic venous hypertension or a primary pleural process. Recent investigations, however, indicate that both acute lung injury and pulmonary venous hypertension can be important in the pathogenesis of pleural effusions. To evaluate the role of acute lung injury in the formation of pleural effusions, we developed a model of acute, reversible lung injury in NZW rabbits. Intravenous ethchlorvynol (ECV), known to produce permeability edema in humans, was used to produce permeability pulmonary edema in rabbits. The injury was examined over 14 days with bronchoalveolar lavage, pleural fluid analysis, and morphologic analysis. Ethchlorvynol injection (40 mg/kg) produced a PMN-predominant, exudative alveolitis (2 h), alveolar hemorrhage (6 to 10 h), and pleural effusions by 2 h (peak, 10 h). Pathologic findings included a patchy, subpleural, hemorrhagic PMN inflammatory response, which peaked by 24 h, and an acute PMN vasculitis of small arterioles and capillaries; these changes resolved in 5 to 7 days. No parietal pleural abnormalities were observed. We conclude that ECV induces an acute, reversible parenchymal lung injury resulting in a capillary leak and that fluid moves from the interstitium of the lung into the pleural space along a pressure gradient through a relatively permeable mesothelium. The data support the concept that diffuse or localized lung injury can result in pleural effusions.
Acute Disease↗
Adoptive transfer of tsk skin fibrosis to +/+ recipients by tsk bone marrow and spleen cells.
The tight skin mouse (Tsk/+) is an autosomal dominant example of inherited fibrosis whose pathogenesis is unclear. Autoimmune phenomena have been described previously. This study demonstrates the adoptive transfer of skin fibrosis to lethally irradiated syngeneic +/+ recipients by the transplantation of both bone marrow and spleen cells. The recipient skin fibrosis was not associated with mast cell proliferation or degranulation as it is in the tsk/+ mouse, representing for the first time a dissociation between mast cells and fibrosis and introducing the potential for direct T cell-fibroblast interactions.
Animals↗
A fasciocutaneous transposition flap for coverage of defects of the lower extremity.
During a three-year period, eleven fasciocutaneous transposition flaps were used in ten patients to cover a defect in the lower extremity that was due to trauma or infection. The patients were subsequently evaluated with respect to survival of the flap, sensation in the flap, healing of the donor site, and postoperative morbidity. Two cases are presented for illustration. Coverage with a fasciocutaneous transposition flap proved to be safe and simple. This technique offers several advantages compared with reconstruction using microvascular free muscle transfer, and it may be preferable for many patients who have a defect distal to the knee.
Adolescent↗
Pathology of pleural infections.
The pleura is protected by several tissue boundaries of differing degrees of strength. Penetration of the pleural space by mediastinal infection occurs more easily than from the lung, which in turn occurs more easily than through the diaphragm or chest wall. Infectious organisms of all classes, including bacteria, viruses, fungi, and protozoa are capable of causing pleural infection. The basic tissue response in the pleura is similar to that seen in other tissues but is modified by the peculiar anatomy of the pleura, flat serosal surfaces in constant motion against each other. Most pleural infections are initiated in the lung. Some of the most spectacular pathologic lesions are caused by aspergillus where vasculoinvasive fungi cause infected infarcts that result in round visceral pleural lesions. These in turn result in "kissing lesions" of the parietal diaphragmatic surfaces which are of the same size and shape as the visceral pleural lesions, indicating attachment and splinting of the pleural surfaces in these loci. Studies in rabbit demonstrate rapid resolution of experimental empyema with a standardized series of pathologic responses. In uncomplicated empyema, the end result is an extremely thin, almost undetectable scar. Thick fibrotic pleural lesions suggest a complicated course with continuing infection.
Animals↗
Inhibition of fibrosis in TSK mice by blocking mast cell degranulation.
The Tsk mouse has a genetically transmitted connective tissue disease whose skin lesions resemble those of scleroderma. After treatment with disodium cromoglycate, a marked decrease in skin fibrosis was observed, raising the possibility that disodium cromoglycate may be a potential treatment for human scleroderma.
Animals↗
Thoracic surgical implications of the yellow nail syndrome.
Idiopathic lymphedema associated with yellow discoloration of the nail beds constitutes the yellow nail syndrome. Pleural effusions and chronic sinusitis are also frequently present. This report describes a case of yellow nail syndrome in a 65-year-old woman.
Aged↗
Vascular steal: the pathogenetic mechanism producing sirenomelia and associated defects of the viscera and soft tissues.
Dissection of the abdominal vasculature in 11 cases of sirenomelia has demonstrated a pattern of vascular abnormalities that explains the defects usually found in this condition. The common feature is the presence of a single large artery, arising from high in the abdominal cavity, which assumes the function of the umbilical arteries and diverts nutrients from the caudal end of the embryo distal to the level of its origin. The steal vessel derives from the vitelline artery complex, an early embryonic vascular network that supplies the yolk sac. Arteries below the level of this steal vessel are underdeveloped and tissues dependent upon them for nutrient supply fail to develop, are malformed, or arrest in some incomplete stage. In contrast to the prevailing view that sirenomelia arises by posterior fusion of the two developing lower limbs, these studies suggest that the single lower extremity in sirenomelia arises from failure of the lower limb bud field to be cleaved into two lateral masses by an intervening allantois.
Abnormalities, Multiple↗
Long fibre asbestos in a chrysotile textile worker.
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Asbestos↗