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Biomedical subjects

W D Travis

Publications and source records attributed to W D Travis.

At least 127 records · Page 7Linked to original sources
PubMed1992

Expression of surfactant associated protein-A and Clara cell 10 kilodalton mRNA in neoplastic and non-neoplastic human lung tissue as detected by in situ hybridization.

Two markers for the progenitor cells of peripheral airways and their tumors are the 10 kilodalton (kd) Clara cell protein and the major surfactant associated protein-A (SP-A). We used the RNA-RNA in situ hybridization technique to study expression of the genes encoding these proteins at the cellular level in 19 pairs of non-neoplastic and neoplastic tissues from resected human lungs. Our results show that in non-neoplastic lung tissue, the Clara 10 kd protein gene was expressed in nonciliated cells of both bronchial and bronchiolar epithelium, indicating that, in contrast to previous assumptions, cells with Clara cell-like differentiation in humans may not be restricted to bronchiolar cells. The incidence of Clara 10 kd protein gene expression, as detected in lung carcinomas (1 out of 19 cases positive) was less than expected based on previous ultrastructural reports. The SP-A gene was strongly expressed in normal alveolar type II cells in non-neoplastic lung and, at higher levels, in hyperplastic cells. In addition, SP-A mRNA expression was observed in scattered bronchial and bronchiolar epithelial cells in 40% of the airways examined. Five out of 17 lung tumors, all of which were adenocarcinomas, were positive for SP-A expression, albeit generally less intense than type II cells. This expression was seen in carcinomas with papillolepidic as well as solid and glandular growth patterns. Our findings provide new insights into the peripheral airway cell differentiation.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Mucinous (so-called colloid) carcinomas of lung.

We present 24 cases of primary mucinous (so-called colloid) carcinomas of the lung. The patients were between 33 and 81 yr old (median: 57 yr), including 15 men and nine women. The lesions were discovered incidentally on chest X-ray, where they presented in diverse forms. No predilection for a particular lobe or pulmonary segment was observed. The tumors varied from 0.5 to 10 cm in greatest diameter. Grossly, the tumors were poorly circumscribed, soft, tan-to-gray mucoid lesions. Microscopically, they showed intra-alveolar pools of mucin containing small clusters of atypical cells floating in the mucin, and foci of neoplastic columnar epithelium lining scattered alveoli. Seven cases showed areas of solid, well-differentiated malignant glands adjacent to pools of mucin. In two cases, lymph node metastases were found at surgery. Eleven (57%) of 19 patients were alive over a follow-up period ranging from 2 to 192 mo; one of them had metastases to bone and another had intrapulmonary recurrence. Eight patients died with/of their tumors, two of them with known metastases to bone and/or brain, and one with recurrence after 2 yr of initial diagnosis. No follow-up was obtained in five patients. Although the extent of clinical evaluation varied, no other primary neoplasms (i.e., breast, gastrointestinal tract, or other organs where primary mucinous carcinomas are known to occur) were observed. These tumors probably represent a variant of bronchioloalveolar carcinoma and share the prognosis of that neoplasm. However, because of their often bland cytologic features and paucity of malignant cells, they may be difficult to diagnose as neoplasms.

Adenocarcinoma, Mucinous↗
PubMed1991

An ultrastructural study of in vivo interactions between lymphocytes and endothelial cells in the pathogenesis of the vascular leak syndrome induced by interleukin-2.

Lymphokine-activated killer (LAK) cells play a major role in the induction of the vascular leak syndrome (VLS). To understand the mechanism of this syndrome, the authors examined light and electron microscopic alterations in the lung, liver, spleen, kidney, and heart of mice in which VLS was produced by the administration of interleukin-2 (IL-2) (seven injections of 600,000 IU each for a period of 4 days). The results of these studies disclosed that considerable damage had been done to the endothelial cells that consisted of cytoplasmic edema, vacuoles, and myelin figures; in addition, there were frequent sites of transendothelial passage of lymphoid cells, probably IL-2-activated cells, that penetrated through their cytoplasm by means of "temporary migration pores" and accumulated in the perivascular spaces. The results of this study indicate that a direct in vivo interaction between IL-2-activated cells (probably LAK cells) and endothelium results in cytotoxicity to endothelial cells.

Animals↗
PubMed1991

Disseminated human malignant melanoma in congenitally immune-deficient (bg/nu/xid) mice.

Congenitally immune-deficient bg/nu/xid (BNX) mice are severely compromised in their ability to mount T-cell, B-cell, and lymphokine-activated killer (LAK) cell responses. Successful engraftment of BNX mice with human hematopoietic stem cells has been demonstrated recently. We have investigated the potential use of BNX mice for studies relating to the biology and immunotherapy of human malignant melanoma. The intravenous injection of fresh single-cell suspensions of human malignant melanomas into mice resulted in widely disseminated disease. Metastatic spread of human melanoma in BNX mice mimicked that observed in patients: eg, there were numerous tumor nodules identified in the subcutaneous tissues as well as in a variety of visceral organs, including spleen, kidneys, thyroid, adrenals, lungs, heart, and brain. BNX mouse lymph nodes were replaced consistently by human malignant melanoma cells. The presence of human tumor cells in these mice was confirmed by histologic analysis and microcytofluorometry analyses using human melanoma-specific monoclonal antibodies (MAbs). Moreover, human melanoma cells passaged in BNX mice remained lysable in vitro by specifically cytolytic, autologous human tumor-infiltrating lymphocytes (TILs). The capacity of fresh human malignant melanoma to disseminate widely in BNX mice may prove valuable not only for study of the biology of metastatic spread but also for studies of the immunotherapy of human melanoma using melanoma-specific MAbs and chemotherapeutic agents, as well as human TILs and LAK cells with or without retrovirus-mediated gene transfer modification.

Animals↗
PubMed1991

Hematologic manifestations of systemic mast cell disease: a prospective study of laboratory and morphologic features and their relation to prognosis.

PURPOSE: Systemic mast cell disease (SMCD) follows an indolent course in most patients, but a significant number of patients die of neoplastic hematologic disorders. Reviews of the literature and retrospective studies in a single institution have defined features that may be associated with a poor prognosis, but prospective studies have been lacking. Therefore, we prospectively analyzed the relationship between clinical, laboratory, and hematopathologic findings and clinical outcome in a series of 46 patients with mast cell disease. This analysis was employed to both define clinically useful prognostic variables and describe the histologic evolution of bone marrow mast cell infiltration and its relationship to hematologic neoplasia. PATIENTS AND METHODS: Forty-six adult patients were referred to the National Institutes of Health (NIH) with clinical and/or pathologic evidence of mast cell proliferation. All patients had bone marrow examinations, and 10 patients underwent serial bone marrow biopsies. The diagnosis of SMCD required pathologic documentation of bone marrow mast cell infiltrates. The patients were followed for up to 13 years at the NIH (up to 30 years after the initial pathologic diagnosis of mast cell disease). Statistical analysis defined the correlation between variables and the presence of diagnostic bone marrow lesions. The Kaplan-Meier method was used to construct survival curves, and the effects of various variables on the survival time were examined. RESULTS: Thirty-two of 46 patients (74%) had a bone marrow biopsy diagnostic for SMCD. The remaining 14 patients were considered to have cutaneous mast cell disease (CMCD). Univariate analysis showed that hepatosplenomegaly, alkaline phosphatase level, absolute lymphocyte count, and age at onset of symptoms were positively correlated with SMCD, whereas hemoglobin level was negatively associated with diagnostic bone marrow lesions. With multivariate analysis, only hemoglobin and absolute lymphocyte count remained as significant independent predictors of bone marrow findings. No CMCD patient died or had significant clinical deterioration in the 1- to 30-year period of follow-up (median = 8.5 years), whereas 10 of 32 SMCD patients (31%) died from 1 to 22 years after diagnosis (median = 2.5 years) (p less than 0.0001). Univariate analysis revealed the following variables as significantly increasing the risk of death in patients with SMCD: later onset of symptoms, absence of cutaneous mastocytosis, thrombocytopenia, elevated lactate dehydrogenase (LDH) level, anemia, bone marrow hypercellularity, qualitative peripheral blood smear abnormalities, elevated alkaline phosphatase level, and hepatosplenomegaly. Multivariate analysis showed that only the age at onset of symptoms and LDH levels were significant independent predictors of survival. Eight of the 10 SMCD patients who died had myeloproliferative or myelodysplastic syndromes or acute nonlymphocytic leukemia. CONCLUSION: Our prospective study has defined a number of important variables in patients with clinical evidence of mast cell proliferation that can predict both the presence of SMCD and the likelihood of fatal disease. Since recent evidence suggests that mast cells derive from a bone marrow hematopoietic progenitor, SMCD may represent a myeloproliferative condition with the propensity to evolve into a neoplastic granulocytic disorder in a significant minority of patients.

Adolescent↗
PubMed1991

Unusual aspects of allergic bronchopulmonary fungal disease: report of two cases due to Curvularia organisms associated with allergic fungal sinusitis.

We report two cases of allergic bronchopulmonary fungal disease (ABPFD) caused by Curvularia sp and associated with allergic fungal sinusitis (AFS). Curvularia lunata was cultured in one case and Curvularia senegalensis was cultured in the other. Based on these cases and a review of the literature, we discuss unusual clinical and pathologic features that can occur in ABPFD. Unusual clinical aspects of ABPFD include associated AFS, absence of asthma, progression to Churg-Strauss angiitis and granulomatosis, concomitant hypersensitivity pneumonitis, and underlying cystic fibrosis. Atypical pathologic features that may occur in ABPFD include follicular bronchiolitis, xanthomatous bronchiolitis, limited tissue invasion, fungus balls, and association with unusual fungi. Prominent follicular bronchiolitis and xanthomatous bronchiolitis were misleading histologic features in one of our cases and led to a delay in recognition of the diagnosis. Both patients presented primarily with AFS; ABPFD was detected subsequently. This suggests that a small subset of patients with AFS may be at risk for ABPFD. The goal of this review is to increase awareness of unusual clinical and pathologic manifestations of ABPFD. It is hoped that this will result in accurate diagnosis and proper therapy, especially for patients who present with atypical features. Unusual fungal species should be considered in patients who have clinical findings compatible with ABPFD but who do not demonstrate immunologic reactivity to Aspergillus sp, especially Aspergillus fumigatus. In addition, ABPFD should be considered in patients with AFS who develop new pulmonary lesions.

Adolescent↗
PubMed1991

Surgical pathology of the lung in Wegener's granulomatosis. Review of 87 open lung biopsies from 67 patients.

We report the pulmonary pathologic features in 87 open lung biopsies from 67 patients with Wegener's granulomatosis (WG) who were treated at a single institution from 1968 to 1990. At the time of open lung biopsy, 48 patients (72%) had classical WG with renal involvement; 19 (28%) had limited WG without renal involvement. The pathologic features were divided into major and minor manifestations. In the 82 specimens demonstrating no infectious organism, the three major pathologic manifestations of classical WG observed were also useful diagnostic criteria and included: (a) parenchymal necrosis, (b) vasculitis, and (c) granulomatous inflammation accompanied by an inflammatory infiltrate composed of a mixture of neutrophils, lymphocytes, plasma cells, histiocytes, and eosinophils. Parenchymal necrosis was found in 84% of biopsy specimens either as neutrophilic microabscesses (65% of specimens) or as large (67%) or small (69%) areas of geographic necrosis. Areas of geographic necrosis were usually surrounded by palisading histiocytes and giant cells. Additional granulomatous lesions consisted of microabscesses surrounded by giant cells (69%), poorly formed granulomas (59%), and scattered giant cells (79%). Sarcoid-like granulomas were uncommon (4%), and in only one specimen (1%) appeared within an inflammatory lesion of WG. Vascular changes were identified in 94% of biopsy specimens. Vascular inflammation was classified as chronic (37% arterial, 64% venous), acute (37% arterial, 29% venous), non-necrotizing granulomatous (22% arterial, 9% venous), and necrotizing granulomatous (22% arterial, 10% venous). Fibrinoid necrosis was relatively uncommon (11% arterial, 6% venous). Cicatricial changes were found in arteries in 41% of biopsy specimens and in veins in 16%. Capillaritis was present in 31% of specimens. Minor pathologic lesions were commonly observed in biopsy specimens associated with classical WG lesions, but they were usually inconspicuous and not useful diagnostic criteria. These included interstitial fibrosis (26%), alveolar hemorrhage (49%), tissue eosinophils (100%), organizing intraluminal fibrosis (70%), endogenous lipoid pneumonia (59%), lymphoid aggregates (37%), and a variety of bronchial/bronchiolar lesions including acute and chronic bronchiolitis (51% and 64%), follicular bronchiolitis (28%), and bronchiolitis obliterans (31%). These minor lesions were often found at the periphery of typical nodules of WG. However, in 15 specimens (18%) a minor pathologic feature represented the dominant or major finding: pulmonary fibrosis (six specimens, 7%), diffuse pulmonary hemorrhage (six specimens, 7%), lipoid pneumonia (one specimen, 1%), acute bronchopneumonia (one specimen, 1%), and chronic bronchiolitis, bronchiolitic obliterans with organizing pneumonia (BOOP), and bronchocentric granulomatosis (one specimen, 1%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases.

Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.

Adrenocorticotropic Hormone↗
PubMed1991

Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism.

Between 1982 and 1989, 145 patients underwent operations for persistent or recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at outside institutions for HPT. Patients with locally recurrent HPT secondary to adenoma had a longer disease-free interval than patients with locally recurrent carcinoma. At the time of evaluation at the National Institutes of Health (NIH) for recurrent or persistent HPT, each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma. Locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients. These 15 patients underwent 18 reoperations at NIH for excision of locally recurrent parathyroid tumors. Following the final reoperation (two patients had more than one procedure), each patient had normal serum levels of calcium. In addition each patient remains biochemically cured (based on normal serum calcium level), with a median follow-up interval of 21 months. Local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent HPT and can be indistinguishable from parathyroid carcinoma. Findings suggestive of carcinoma include shorter disease-free interval, higher serum levels of calcium and parathyroid hormone, and histologic appearance. Whether the locally recurrent parathyroid neoplasm is benign or malignant, aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity.

Adenoma↗
PubMed1991

The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases.

The clinical records and autopsy data of 75 patients dying with AIDS were reviewed to determine the frequency of individual diseases diagnosed premortem and postmortem, the significance of pulmonary processes found in the lungs at autopsy, and the clinical and pathologic causes of death. Cytomegalovirus (CMV) infection was identified histologically either premortem or postmortem in 81% of patients. The lungs and adrenal glands were infected most commonly. Only one-half of CMV infections were recognized premortem. Pneumocystis pneumonia and Kaposi sarcoma occurred in 68% and 59% of patients, respectively, but were not unsuspected premortem in any patient. Visceral involvement with Kaposi sarcoma, however, was frequently recognized only at autopsy. While disseminated M. avium-intracellulare infection was common (31% of patients), histologically documented pulmonary disease was uncommon (3% of patients). Cryptococcal infection, diagnosed in 10 patients, was confined to the central nervous system in only 1 patient. Toxoplasma, in contrast, infected the brain of only 6 patients. All 75 patients had one or more disease processes identified in their lungs or pleurae at autopsy. These processes included opportunistic infections in 76% of patients, neoplasms in 37% (Kaposi sarcoma in 36% and lymphoma in 3%), and other processes in 60%. The most prevalent pathogen, CMV was found in pulmonary tissue from 44 patients and caused significant disease in 21 patients. Five patients died due to CMV pneumonia. Pneumocystis carinii was found at autopsy in 24 patients. In spite of treatment, pneumocystis pneumonia was fatal in 11 patients. One patient died with concomitant CMV and pneumocystis pneumonia. Kaposi sarcoma, identified in the lungs of 23 patients, led to death in 5 patients via upper airway obstruction, hemorrhage, or parenchymal destruction. Other fatal pulmonary processes included bacterial pneumonia in 9 patients, idiopathic diffuse alveolar damage in 5, cryptococcosis in 2, and pulmonary hemorrhage in 1. Specific clinical criteria were used to determine the cause of death due to organ system failure. Fifty-one percent of patients died due to respiratory failure; 16% from neurologic disease; 17% from hypotension that was not caused by respiratory, neurologic, or cardiac disease; and 3% from cardiac dysfunction. Thirteen percent of deaths did not meet the clinical criteria defining these 4 categories. This clinical assessment was combined with autopsy data to identify specific diseases as causes of death.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Bronchoalveolar lavage analysis in Wegener's granulomatosis. A method to study disease pathogenesis.

A prospective analysis of bronchoalveolar lavage (BAL) in 13 patients with Wegener's granulomatosis (WG), 20 disease control subjects with idiopathic pulmonary fibrosis (IPF), and 24 normal control subjects was conducted to (1) evaluate the quality of the alveolar inflammatory response associated with active WG; (2) determine whether antineutrophil cytoplasmic antibody (ANCA) is present in alveolar fluid and produced in the lungs of patients with WG; and (3) determine whether inhaled particles or infectious agents may play an etiologic role in WG. BAL in untreated active WG had a marked increase in neutrophils (mean = 42% of total WBC count), and usually in eosinophils (mean = 4%) compared with that in normal control subjects (1.6% neutrophils, 0% eosinophils), and untreated WG in remission (5.9% neutrophils, 0% eosinophils). Disease control subjects with IPF, a process known to be associated with neutrophilic alveolitis, had an increased population of neutrophils (15.4%) and eosinophils (2.7%) in BAL. Leukocyte remnants, as well as intact leukocytes, could be identified within BAL macrophages in the patients with WG and IPF, and rarely in the normal control subjects. Normal subjects and control patients with IPF were all negative for ANCA in serum, whereas ANCA was found in serum and BAL in all patients with active WG who had generalized disease. Protein analysis of BAL revealed a disproportionate increase in the IgG to albumin ration compared with serum values (IgG index) in patients with active untreated disease. The increase in the IgG index suggests that IgG with ANCA reactivity is produced by pulmonary lymphoid tissue. An infectious agent in BAL was not identified by any of the techniques applied in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Cellular and molecular basis of the asbestos-related diseases.

Asbestosis is an inflammatory and fibrotic process of the alveolar structures mediated, at least in part, by cytokines released by "activated" alveolar macrophages. The process of phagocytosis and "activation" of alveolar macrophages is poorly understood. Are all macrophages activated or only subpopulations? Which cytokines are up-regulated? How does the local milieu modulate profibrotic and antifibrotic mediators? Is protein release accompanied by up-regulation of gene transcription? Is there an ordered sequence of cytokine activity? What roles do neutrophils and lymphocytes play? How can disease progression best be quantified absent further exposure? Answers to these questions are important to direct rational strategies at interdicting the fibrotic process. The question of cancer and asbestos is more vexing. The processes of inflammation, fibrosis, and carcinogenesis appear to be closely intertwined. For example, proto-oncogenes such as c-sis (PDGF B-chain) are up-regulated in activated alveolar macrophages from fibrotic lungs; these and possibly others may play an important role in asbestos carcinogenesis. Second, asbestos can transfect DNA into cells. Furthermore, DNA can adhere to asbestos fibers, and these fibers are capable of direct transmigration into cells. The questions of the mechanisms of cigarette smoke cocarcinogenicity and latency remain. Lastly, if the bronchial epithelium is highly metaplastic throughout from cigarette smoking, what triggers a single (or several) nidus of cells to transform into carcinoma? Malignant mesothelioma poses the most challenging questions because of association with brief asbestos exposure by history. Mesothelial cells are susceptible to minute environmental manipulations, and changes occur after exposure to all fiber types. Yet epidemiologic studies point toward long amphiboles as having greater mesothelioma risk. To test this hypothesis, experimental data must be generated differentiating tumorigenesis risk from short, chrysotile fibers that can migrate to the parietal pleura from the associations of long amphiboles persisting in lung tissue. Despite the future decreasing numbers of clinical cases of asbestos-related disease, solving the important mechanistic questions remaining will contribute significantly to our understanding of fibrosis and cancer.

Animals↗
PubMed1991

Detection of ACTH-producing bronchial carcinoid tumors: MR imaging vs CT.

Adrenocorticotrophic hormone (ACTH)-producing bronchial carcinoid tumors tend to occur in the middle third of the lung adjacent to pulmonary vessels. Because they cause signs and symptoms when quite small (by virtue of their ACTH production), they may not be detected by CT. MR imaging was performed in 10 consecutive patients with surgically proved ACTH-producing bronchial carcinoid tumors in order to test the ability of MR to clarify equivocal or indeterminate findings on CT examinations. All bronchial carcinoid tumors had high signal intensity on T2-weighted and short-inversion-time inversion-recovery images, facilitating their distinction from pulmonary vasculature. In eight patients, the CT and MR images were equivalent in the detection of bronchial carcinoid tumors. In two patients, MR showed tumors in the middle third of the lung that were equivocal on CT. MR imaging may distinguish small bronchial carcinoid tumors from adjacent pulmonary vessels in the central third of the lung at a time when the CT study is nondiagnostic or equivocal.

Adrenocorticotropic Hormone↗
PubMed1991

Undifferentiated (embryonal) sarcoma of the liver. Clinical and pathologic study of 16 cases with emphasis on immunohistochemical features.

Undifferentiated (embryonal) sarcoma of the liver is a primitive mesenchymal neoplasm with predilection for individuals in the first 2 decades of life. In this study (10 boys, 6 girls), children in the age range of 6-10 years were most commonly affected (63%). Clinical features most frequently noted on presentation were abdominal pain or a palpable mass. In two cases there was cardiac involvement caused by invasion of the inferior vena cava with extension into the right atrium and ventricle; both children died of progressive dyspnea from tumor embolization to the lungs. One patient was a member of a kindred with the cancer family syndrome (Li-Fraumeni syndrome). There were 13 tumor-related deaths (86% mortality); on child was alive with recurrent tumor in the upper abdomen. Complete surgical resection was attempted in 10 of 15 children who underwent exploratory laparotomy; 2 were alive and well 1 and 5 years later, whereas 1 patient had a recurrence in the upper abdomen 3 years after diagnosis. Ultrastructural study (five cases) and immunohistochemistry (11 cases) supported a mesenchymal origin for the tumor, but failed to identify any diagnostic immunophenotype or specific line of differentiation. Coexpression of vimentin and cytokeratin was seen in three cases. Prompt detection of this aggressive tumor with complete surgical resection is the key to a successful outcome, but this is very difficult to achieve. Recent experience suggests that aggressive adjuvant chemotherapy may improve survival in some cases.

Adolescent↗
PubMed1991

Primary bilateral adrenocortical causes of Cushing's syndrome.

Nontumorous primary adrenal causes of Cushing's syndrome are exceedingly rare. Herein we review our results with seven patients in whom there is biochemical evidence of a primary (adrenocorticotropin independent) bilateral adrenal cause of endogenous hypercortisolism. Each patient had low plasma adrenocorticotropin levels. All patients had elevated 24-hour urinary free cortisol levels and 17-hydroxycorticosteroids that were not suppressed by high-dose dexamethasone. Plasma levels of adrenocorticotropin and cortisol were not elevated by ovine corticotropin-releasing factor. No patient had a gradient between petrosal and peripheral adrenocorticotropin levels. No pituitary tumors were detected by magnetic resonance imaging or computed tomography. Five of six patients who underwent iodocholesterol scanning showed bilateral adrenal activity. Computed tomographic and magnetic resonance imaging of the abdomen demonstrated bilateral small adrenal glands in three patients, an adrenal mass in one patient with Carney's complex, and massively enlarged glands in three patients. Each patient underwent bilateral adrenalectomy and was given glucocorticoid and mineralocorticoid replacement. Pathologic examination of four of these bilateral adrenal specimens revealed primary pigmented micronodular adrenocortical disease, with adrenal gland weights between 2.5 and 13.4 gm (mean 5.2 gm). However, the remaining three patients had primary adrenocorticotropin-independent bilateral macronodular adrenocortical disease with adrenal gland weights between 32 and 81 gm (mean 52 gm). Although each of the patients with primary pigmented micronodular adrenocortical disease was cured by bilateral adrenalectomy through a posterior approach, two of the three patients required an anterior approach. We conclude that Cushing's syndrome can arise through two distinct forms of primary bilateral adrenal cortical disease. Computed tomography is important in evaluation of these patients because the size of the adrenal glands influences the surgical approach.

Adolescent↗
PubMed1990

Endothelins, peptides with potent vasoactive properties, are produced by human macrophages.

Endothelins are peptides, originally isolated from endothelial cells, with potent vasoactive and mitogenic properties. In this study, we demonstrate that human macrophages synthesize and secrete endothelins. Cultured human macrophages were found by immunocytochemistry to stain positively for endothelin 1 and endothelin 3. Their capability to produce and release these peptides was confirmed by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassays, specific for endothelin 1 and 3, respectively. Immunoreactive peptides were identified both in cellular extracts and in macrophage-conditioned medium. The secretion of endothelin 1, but not of endothelin 3, from macrophages could be stimulated 6-10-fold by lipopolysaccharide or phorbol myristate acetate (PMA). Northern blot analysis of total macrophage RNA using an endothelin 1 cDNA probe revealed induction of endothelin mRNA in PMA-treated macrophages. Furthermore, immunoreactive endothelin 1 and 3 were found in U937 cells, a human promonocytic line, and in freshly isolated human monocytes. In contrast, no immunoreactive endothelin was detected in cell extracts from human neutrophils and lymphocytes. The expression of endothelins in tissue macrophages was demonstrated in paraffin sections of human lung using immunohistochemistry. In conclusion, the finding that human macrophages produce endothelins suggests an important role for these peptides in the microenvironment of tissue macrophages. Macrophage-derived endothelins may have an essential function in blood vessel physiology, and aberrant production may contribute to vessel pathology.

Cells, Cultured↗
PubMed1990

Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer.

The hearts of eight patients aged 22 to 67 years (mean, 41 years) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in two patients, sepsis in four patients, acute myocardial infarction in one patient, and myocarditis in one patient. Transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in five patients: the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one. Although treatment-related deaths associated with high-dose IL-2 therapy are uncommon (1.5% in 652 consecutive patients), the potential for significant myocardial ischemia or myocarditis exists, and careful monitoring for arrhythmias or myocardial failure is warranted.

Adult↗