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W D Travis

Publications and source records attributed to W D Travis.

At least 145 records · Page 8Linked to original sources

In vivo administration of interferon alpha and interleukin 2 induces proliferation of lymphoid cells in the organs of mice.

We have previously shown that interleukin 2 (IL-2) synergizes with interferon alpha (IFN-alpha) in mediating the regression of established pulmonary and hepatic metastases and the reduction of intradermal tumor in various murine tumor models. To understand the mechanism of synergy, we have examined lymphoid cell proliferation in various organs of mice in response to IL-2 and IFN-alpha administration. We have utilized a technique for labeling newly synthesized DNA in vivo with 5-[125I]iodo-2'-deoxyuridine to examine proliferation of endogenous cells in response to IL-2 and IL-2 plus IFN-alpha. A proliferation index was calculated by dividing cpm in the tissues treated with cytokines by cpm obtained in corresponding tissues of control mice. After 4 days of IL-2 administration, a significant uptake of 5-[125I]iodo-2'-deoxyuridine was observed in the lungs, liver, kidneys, and spleen (proliferation index of 13, 10.3, 3.6, and 3.2, respectively). IFN-alpha alone mediated very little incorporation of radiolabel but when administered in combination with IL-2 a reduction of IL-2-induced proliferation was seen on day 4. For example 19,272 +/- 4,556 cpm (mean +/- SE) were obtained in the liver of IL-2-treated mice, compared to 8,103 +/- 2,111 cpm in livers of IL-2 plus IFN-alpha-treated mice (P less than 0.05). Similar inhibition of IL-2-induced proliferation was observed in the lungs, kidneys, and spleen. In contrast, on days 7 or 8, higher uptake of radiolabel was obtained in IFN-alpha plus IL-2-treated lungs, liver, and kidneys, compared to organs of mice treated with IL-2 alone or IFN-alpha alone. A proliferation index of 30.5, 9.8, and 10 was obtained in the lungs, liver, and kidneys of IL-2- plus IFN-alpha-treated animals, compared to 9.6, 3.6, and 5.5 in the corresponding organs of IL-2-treated mice. The effects of IFN-alpha on IL-2-induced proliferation was dose dependent; very low dosages of IFN-alpha (1,000 units/dose) were able to cause the inhibition of proliferation at 3 days of therapy and increase at 7 days of therapy. Continued proliferation of cells was observed in most organs when IL-2 plus IFN-alpha was injected for 9 consecutive days. Pretreatment irradiation of mice at 500 rad largely eliminated the proliferative response to IL-2 as well as to IFN-alpha plus IL-2 at both 3 and 7 days. Histological studies of lungs receiving cytokine therapy for 3 and 7 days corroborated the results of the 5-[125I]iodo-2'-deoxyuridine incorporation assay. At day 3 a significant infiltration of lymphoid cells was seen in IL-2-treated lungs, whereas little or no lymphocytic infiltration was observed in IL-2- plus IFN-alpha-treated lungs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Manipulation of oxygen radical-scavenging capacity in mice alters host sensitivity to tumor necrosis factor toxicity but does not interfere with its antitumor efficacy.

The role of oxygen free radicals in the toxicity and antitumor effect of tumor necrosis factor was investigated in vivo. Treatment of non-tumor-bearing mice and mice bearing methylcholanthrene-induced sarcomas with bovine CuZn superoxide dismutase or recombinant human CuZn superoxide dismutase afforded significant protection to these mice from a subsequent challenge with recombinant human tumor necrosis factor (rhTNF). Pretreatment with superoxide dismutase increased survival rates, at 48 h after rhTNF injection, in non-tumor-bearing mice from 22 to 65% and in tumor-bearing mice from 25 to 79%. Protection from rhTNF toxicity was not associated with any reduction in the therapeutic efficacy of rhTNF against methylcholanthrene-induced sarcomas in either s.c. or visceral sites (e.g., cure rates in mice bearing s.c. tumors which were treated with rhTNF without or with superoxide dismutase pretreatment were 18 and 39%, respectively). Furthermore, the administration of L-buthionine-S,R-sulfoximine, an inhibitor of glutathione synthesis, to mice bearing s.c. tumors resulted in increased rhTNF toxicity but no improvement in therapeutic efficacy. Tumor necrosis factor toxicity is mediated by the release of oxygen free radicals, probably from activated neutrophils, but its antitumor effect in methylcholanthrene-induced sarcomas is not dependent on their generation.

Animals↗

Studies of effects of recombinant human tumor necrosis factor on autochthonous tumor and transplanted normal tissue in mice.

The acute hemorrhagic necrosis of tumor nodules caused by the systemic administration of recombinant human tumor necrosis factor alpha (rhTNF-alpha) has been partially attributed to changes in tumor neovascularity. In this study, the effects of rhTNF-alpha were tested on primary autochthonous sarcomas induced in C57BL/6 mice by 3-methylcholanthrene, on spontaneous mammary tumors in C3H/HEN mammary tumor virus positive mice, and on the rejection of normal tissue transplants at different stages of maturity in C57BL/6 mice. Primary i.m. tumors induced by injection of 3-methylcholanthrene grew slowly over a 3-month period and became acutely necrotic after i.v. injection of rhTNF-alpha (2-6 micrograms). In addition, rhTNF-alpha caused a reduction in tumor area of 24% over 10 days compared to a 43% increase in tumor area in control mice receiving excipient (P2 less than 0.01). Histopathologically, tumors underwent central necrosis with a neutrophilic infiltration as was observed previously for serially transplanted tumors following rhTNF-alpha administration. Spontaneous, virally induced mammary tumors underwent a 11% regression on administration of rhTNF-alpha (4-6 micrograms) compared to a 24% growth in mice receiving excipient (P2 less than 0.05). Normal mice were grafted with syngeneic (C57BL/6) or partially allogeneic (C57BL/10 to C57BL/6) skin and were treated with a single dose of rhTNF-alpha (5-20 micrograms) i.v. at either 5, 10, or 15 days posttransplantation. rhTNF-alpha administration had no effect on the integrity of the skin grafts at any maturation point tested (syngeneic graft survival at 60 days: excipient, 35 of 36 versus 20 micrograms rhTNF-alpha, 35 of 36; allogeneic graft survival: excipient, 46 +/- 8 days versus 20 micrograms rhTNF-alpha, 48 +/- 10 days). In addition, rhTNF-alpha had no effect on the integrity of a syngeneic neonatal s.c. heart graft (graft survival at 60 days, excipient, 35 of 36 versus rhTNF-alpha, 30 of 33). Thus, although rhTNF-alpha administration led to marked necrosis and growth inhibition of vascularized tumor, no effect was observed on vascularized normal tissue transplants. To evaluate possible systemic effects of the tumor bearing state on the maturing neovascularity of normal tissue grafts, the three transplant models were studied in mice bearing a 9-day established MCA-106 s.c. sarcoma. After treatment with rhTNF-alpha (2-6 micrograms), acute necrosis and tumor size reduction was apparent in the s.c. tumors; however, no effect was seen in any of the normal tissue transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Oral squamous cell carcinoma arising in a patient with long-standing lichen planus. A case report.

The risk of malignant transformation of oral lichen planus remains a controversial point. Many previous reports have been discounted on the basis of inadequate information or lack of histologic confirmation of lichen planus. We report a well-documented case of long-standing cutaneous and oral lichen planus in which squamous cell carcinoma of the dorsal portion of the tongue occurred. There is an apparent difference in the sites of oral carcinomas in patients with lichen planus compared with the general population. This suggests that lichen planus increases the risk of oral cancer in affected sites.

Carcinoma, Squamous Cell↗

Premature alveolar bone loss in Erdheim-Chester disease.

Erdheim-Chester disease is a rare histiocytosis also known as lipoid granulomatosis. Oral findings have not been reported previously to our knowledge. This case report documents evidence of oral sequelae of Erdheim-Chester disease. A patient whose course was followed for 10 years at the National Institutes of Health had premature alveolar bone resorption. He underwent full-mouth extraction at age 29 years because of severe periodontitis. Histopathologic evidence of Erdheim-Chester disease was demonstrated in the periodontal soft tissues. In the ensuring years, accelerated resorption of the residual ridges precluded the use of conventional dentures. We recommend early preventive dental management for patients with Erdheim-Chester disease.

Adult↗

Pathologic findings associated with interleukin-2-based immunotherapy for cancer: a postmortem study of 19 patients.

The use of interleukin-2 (IL-2), either alone or in combination with lymphokine-activated killer cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women, with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma, who died after receiving IL-2-based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death unrelated to the presence of metastatic tumor was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: two patients with acute myocardial infarction, one with and one without significant coronary artery disease, two cases of unexplained lymphocytic myocarditis, and one case of fatal pulmonary capillary plugging following an infusion of lymphokine-activated killer cells. Thus, not unlike other forms of therapy for cancer, IL-2-based immunotherapy does not appear to be without significant toxicity.

Adult↗

Interpretation of head and neck biopsies in Wegener's granulomatosis. A pathologic study of 126 biopsies in 70 patients.

The majority of patients with classic Wegener's granulomatosis present with symptoms of head and neck disease; accordingly, accurate interpretation of biopsy specimens from these sites is essential. This report details the histologic findings in 126 head and neck biopsy specimens from 70 patients (36 male and 34 female). Tissues were obtained from the following sites: 60 nasal, 27 paranasal sinuses, 17 laryngeal, five periorbital, five oral, four middle ear, three mastoid, two external ear, and three salivary gland. Vasculitis, necrosis, and granulomatous inflammation together were seen in only 16% of all head and neck biopsy specimens. Both vasculitis and granulomatous inflammation were seen in 21% and vasculitis and necrosis in 23% of the biopsy specimens reviewed. We discuss the problems in differential diagnosis, particularly the importance of excluding granulomatous infectious processes, which can imitate the histopathologic features of Wegener's granulomatosis. Based on this study, we propose criteria for the diagnosis of Wegener's granulomatosis based on biopsy specimens from the head and neck region.

Abscess↗

Atypical pathologic manifestations of Pneumocystis carinii pneumonia in the acquired immune deficiency syndrome. Review of 123 lung biopsies from 76 patients with emphasis on cysts, vascular invasion, vasculitis, and granulomas.

The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP.

Acquired Immunodeficiency Syndrome↗

A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation.

Based on a clinicopathologic study of 34 patients with biopsy-confirmed diffuse pulmonary hemorrhage (DPH), we present an approach to the differential diagnosis of DPH with attention to histologic features such as capillaritis and the importance of laboratory tests such as anticytoplasmic autoantibodies (ACPA). The following DPH syndromes were encountered: antibasement membrane antibody (ABMA) disease (four cases); idiopathic pulmonary hemorrhage (four cases); Wegener's granulomatosis (WG) (five cases); probable WG (six cases); systemic necrotizing vasculitis otherwise unclassified (three cases); systemic lupus erythematosus (two cases); rheumatoid arthritis (one case); seronegative juvenile rheumatoid arthritis (one case); IgA nephropathy (one case); idiopathic glomerulonephritis (two cases--one with and one without immune complexes); and unclassified pulmonary-renal syndromes (five cases). Capillaritis was found in lung biopsy samples from 30 of the 34 patients (88%) and included patients with every type of DPH syndrome. Serologic testing for ACPA was useful in the diagnosis of WG. Identification of ABMA in the serum, kidney, or lung was the defining feature for the diagnosis of ABMA-mediated disease. Subclassification of the cases could not be done solely on histologic grounds except for cases of WG that showed granulomatous inflammation, foci of necrosis, or vasculitis. Classification of the remaining cases required correlation with (a) clinical and laboratory data; (b) biopsy samples from other sites such as the kidney, nasal sinuses, or skin; and (c) results of immunofluorescence or electron microscopy of kidney or lung biopsy samples.

Adolescent↗

Thin-walled cavities, cysts, and pneumothorax in Pneumocystis carinii pneumonia: further observations with histopathologic correlation.

Thin-walled pulmonary cystic lesions were found in five immunocompromised patients, four with acquired immunodeficiency syndrome (AIDS). Four patients had Pneumocystis carinii pneumonia (PCP), and one had pulmonary lesions and disseminated P carinii infection. Two patients demonstrated P carinii within necrotizing, thin-walled, smaller intraparenchymal cavities lined by organisms, exudate, and chronic inflammation. Larger, typically apical and subpleural cysts, lined by fibrosis and/or alveolar parenchyma with little inflammation, were also found during acute episodes. The larger subpleural cysts can arise via rupture of intraparenchymal necrotizing cavities into the subpleural area. Pneumothorax in the four patients with AIDS could not be cured by close thoracostomy drainage; all required pleurodesis. The cysts persisted in cases that were followed up. All cysts were more obvious and numerous with computed tomography (CT), especially with 1.5-mm collimation. CT may be indicated in immunocompromised patients with unexplained pneumothorax or when tube thoracostomy has failed and surgery is being considered, as it can positively influence the operative approach.

Acquired Immunodeficiency Syndrome↗

von Hippel-Lindau disease: radiologic screening for visceral manifestations.

The visceral manifestations of von Hippel-Lindau (VHL) disease can cause significant morbidity and mortality. The authors prospectively screened 37 persons from a single kindred. Twenty-five subjects underwent abdominal ultrasound (US), contrast material-enhanced abdominal computed tomography (CT), and nonenhanced abdominal magnetic resonance (MR) imaging. Eight subjects younger than 16 years of age underwent abdominal US and MR imaging only. Scrotal US was employed in 25 male patients. Eleven subjects had renal cysts or tumors. Contrast-enhanced CT depicted renal abnormalities in 10 of these subjects, US in seven, and MR imaging in nine. Among 12 subjects with pancreatic cysts or tumors, CT showed pancreatic abnormalities in all 12, US in nine, and MR imaging in nine. Three subjects (mean age, 34.5 years) had renal tumors, and three had pancreatic masses. Scrotal US revealed epididymal cystadenomas in seven subjects; two of these tumors were surgically verified. A combination of contrast-enhanced CT and scrotal US in male patients appears to be the best way to screen for visceral manifestations of VHL disease.

Adolescent↗

Pulmonary fibrosis associated with tocainide: report of a case with literature review.

A report is presented of an 85-yr-old woman who developed severe pulmonary fibrosis while receiving tocainide for treatment of ventricular arrhythmias. Severe bilateral interstitial fibrosis was documented in this patient by open lung biopsy and at autopsy. Review of the literature revealed other cases with an association between the use of tocainide and the development of pulmonary complications such as pulmonary fibrosis and interstitial pneumonitis, and suggested that clinical improvement occurs when the correct diagnosis is made early and tocainide therapy is stopped immediately. Because tocainide is currently being widely used for the treatment of ventricular arrhythmias, the pulmonary status of patients receiving tocainide should be monitored closely. Hopefully, awareness of this potential complication of tocainide therapy will minimize the number of cases of serious pulmonary toxicity.

Aged↗

Papillary cystadenoma of the epididymis. A report of three cases with lectin histochemistry.

Papillary cystadenoma of the epididymis is an uncommon benign tumor associated with von Hippel-Lindau disease. Since metastatic renal cell carcinoma may be histologically similar to papillary cystadenoma, and both are associated with von Hippel-Lindau disease, differentiation between these two entities may be difficult. We performed lectin histochemistry studies on three papillary cystadenomas and compared the results with the staining observed in epididymal ducts, epididymal efferent ductules, and three renal cell carcinomas. Common positive staining was observed following incubation with soybean agglutinin in epididymal ducts and two of the three papillary cystadenomas, while the three renal cell carcinomas did not stain. When epididymal tumors histologically consistent with papillary cystadenoma fail to react with soybean agglutinin, thorough clinical evaluation for an occult renal cell carcinoma should be performed.

Adult↗

Mucinous cystadenoma of the lung. A report of two cases with immunohistochemical and ultrastructural analysis.

We describe two patients who presented with solitary pulmonary masses that consisted of unilocular cysts lined by columnar mucinous epithelium. The cysts contained copious mucus. The epithelial lining of the cysts showed foci of stratification and papillary infolding. Histologically identical lesions have previously been termed unusual mucous cysts or mucinous cystadenomas. We believe that these tumors are true neoplasms differentiating toward the respiratory epithelial mucous cell. They should be distinguished from a variety of pulmonary neoplasms including bronchoalveolar carcinoma, bronchial mucous gland adenoma, mucoepidermoid carcinoma, and metastatic adenocarcinoma.

Cystadenoma↗

Respiratory cryptosporidiosis in a patient with malignant lymphoma. Report of a case and review of the literature.

Respiratory cryptosporidiosis is a rare complication of intestinal infection by cryptosporidia, with only six cases reported (to our knowledge) since its first description in 1983. We report the first case of respiratory cryptosporidiosis recognized at the National Institutes of Health, Bethesda, Md. An antemortem diagnosis was made based on recognition of acid-fast cryptosporidia in an induced sputum specimen obtained from a 64-year-old woman with malignant lymphoma and an associated profound immunodeficiency. Autopsy confirmed the presence of cryptosporidia along the apical aspect of the respiratory epithelium lining the trachea, bronchi, and bronchioles. Cryptosporidia were also identified in the duodenum and gallbladder. Immunohistochemical staining of the paraffin-embedded autopsy lung sections using a monoclonal antibody verified the diagnosis of cryptosporidiosis. Review of our case and the literature suggests that respiratory cryptosporidiosis is characterized by a chronic tracheitis, bronchitis, and bronchiolitis but generally does not cause severe pulmonary dysfunction.

Animals↗

Adenomatoid tumor of the adrenal gland with ultrastructural and immunohistochemical demonstration of a mesothelial origin.

We describe an adenomatoid tumor arising in the left adrenal gland of a patient who underwent bilateral adrenalectomy for the ectopic adrenocorticotropic hormone syndrome. The mesothelial origin of the tumor was confirmed by electron microscopy and positive immunohistochemical staining for keratin. The tumor had a prominent cystic component raising the question whether adrenal cysts are derived from mesothelial inclusions. It is proposed that consideration be given to adding a new category of "mesothelial cysts" to the classification of adrenal gland cysts.

Adrenal Gland Neoplasms↗

Mandibular osteomyelitis in a patient with sickle cell anemia: report of case.

A case is presented in which mandibular osteomyelitis and mental nerve paresthesia developed in a patient with sickle cell anemia. This infection appeared to precipitate a sickle cell crisis. The mechanisms for these patients' propensity to infection and the diagnosis and management of sickle cell osteomyelitis of the jaws are discussed.

Adult↗