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Biomedical subjects

W D Travis

Publications and source records attributed to W D Travis.

At least 163 records · Page 9Linked to original sources
PubMed1990

Major salivary gland function in primary Sjögren's syndrome and its relationship to clinical features.

Unstimulated and stimulated salivary secretions of both the parotid and submandibular/sublingual glands were studied in 64 patients with primary Sjögren's syndrome to define further salivary changes in this disorder. The stimulated flows of the submandibular/sublingual glands were below normal in 56 of 64 patients, while stimulated parotid flows were decreased in only 35. Compositional changes of the submandibular saliva paralleled changes of parotid saliva, and these data suggest that ductal electrolyte resorption is altered in the glands of patients. Finally, stimulated parotid flow rates correlated inversely with focus scores of the minor salivary gland biopsies.

Adult↗
PubMed1989

Molecular basis of the liver and lung disease associated with the alpha 1-antitrypsin deficiency allele Mmalton.

Alpha 1-Antitrypsin (alpha 1AT) deficiency is characterized by reduced serum levels of alpha 1AT and a risk for the development of emphysema and liver disease. However, whereas there is an increased risk for emphysema associated with at least 10 alpha 1AT deficiency and null alleles, the hepatic disease is observed only in a subset of these alleles, suggesting that it is not the reduced serum levels of alpha 1AT per se which cause the liver disease. The present study characterizes the alpha 1AT deficiency allele Mmalton, an allele that like the common Z deficiency mutation (Glu342----Lys) is associated with both alpha 1AT deficiency and hepatic disease. Capitalizing on the identification of the homozygous inheritance of the rare Mmalton alpha 1AT deficiency allele, it was demonstrated that although caused by a very different mutation, the Mmalton allele shares with the Z allele the association of liver disease with the same type of abnormalities of alpha 1AT biosynthesis. Cloning of the Mmalton gene and sequence analysis demonstrated that it differs from the normal alpha 1AT M2 allele by deletion of the entire codon (TTC) for residue Phe52. Liver biopsy of the Mmalton homozygote revealed inflammation, mild fibrosis, and intrahepatocyte accumulation of alpha 1AT. Evaluation of de novo alpha 1AT biosynthesis in alpha 1AT-synthesizing cells of this individual demonstrated normal levels of alpha 1AT mRNA transcripts but abnormal intracellular accumulation of newly synthesized alpha 1AT at the level of the rough endoplasmic reticulum with consequent reduced alpha 1AT secretion. Finally, retroviral gene transfer of a normal alpha 1AT cDNA and an alpha 1AT cDNA with the Mmalton Phe52 deletion into murine cells demonstrated that the Mmalton cells reproduced the abnormal accumulation of newly synthesized alpha 1AT, thus directly demonstrating that the deletion mutation is responsible for the intracellular accumulation of the newly synthesized alpha 1AT. Thus, not only is the liver disease associated with alpha 1AT deficiency restricted to a subset of alpha 1AT deficiency alleles, it appears to be restricted to those alleles associated with intracellular accumulation of newly synthesized alpha 1AT, suggesting that it is the abnormal intrahepatocyte alpha 1AT accumulation which incites the liver injury.

Alleles↗
PubMed1989

Decrease in interleukin 2-induced vascular leakage in the lungs of mice by administration of recombinant interleukin 1 alpha in vivo.

The administration of interleukin 2 (IL-2) to mice and humans is limited by the induction of a dose-dependent increase in vascular permeability causing a vascular leak syndrome (VLS). We have investigated the impact of the injection of recombinant interleukin 1 alpha (IL-1 alpha) on the VLS induced by IL-2 by measuring the extravasation of 125I-albumin into tissues and by assessing wet and dry lung weights. IL-1 alpha alone did not induce any significant extravasation of radiolabeled albumin. IL-2 alone, however, caused a significant increase in the extravasation compared to control lungs. IL-1 alpha injection along with IL-2 significantly reduced the IL-2-induced extravasation of radiolabeled albumin [9,886 +/- 533 (SEM) cpm were observed in IL-2 and IL-1 alpha-treated lungs compared to 14,172 +/- 2,628 cpm in lungs treated with IL-2 alone (P less than 0.02)]. IFN-alpha in combination with IL-2 produced more severe vascular leakage than caused by IL-2 alone. IL-1 alpha also significantly decreased (P less than 0.05) the vascular permeability induced by the combination of IFN-alpha and IL-2. We observed 44,811 +/- 13,131 cpm in IFN-alpha- and IL-2-treated lungs compared to 18,350 +/- 2,622 cpm in IFN-alpha-, IL-2-, and IL-1 alpha-treated lungs. The IL-2- and IFN-alpha-induced increase in lung water weight was also reduced significantly by the addition of IL-1 alpha. The decrease in vascular leakage was dependent on the dose and timing of IL-1 alpha administered. When recombinant IL-1 alpha was given as a single i.p. injection, 24 h before the injection of IL-2 (or Hanks' balanced salt solution) or IL-2 and IFN-alpha no abrogation of the VLS was observed. Although IL-1 alpha decreased VLS significantly in mice treated with IFN-alpha and IL-2 the survival of mice was not improved by the simultaneous administration of IL-1 alpha. Histologically, treatment with IFN-alpha and IL-2 produced marked perivascular and intraalveolar edema which was completely eliminated by the addition of IL-1 alpha. However, some perivascular edema in IL-1 alpha-treated mice remained which was equivalent to that caused by IL-2 alone. Treatment of MCA-106 induced pulmonary metastases was enhanced by the administration of IFN-alpha and IL-2 together.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Altered macrophage activity and tumor necrosis factor: tumor necrosis and host cachexia.

Tumor necrosis factor (TNF) may be a mediator of cancer cachexia. This study evaluates the activity of macrophages from non-tumor-bearing (NTB) and tumor-bearing (TB) rats by measuring TNF production in response to endotoxin (LPS), both in vitro and in vivo, and correlates macrophage activity with tumor burden and parameters of host cachexia. Isolated macrophages from rats with small tumors, normal food intake, and weight gain secreted more TNF in response to 10 micrograms/ml LPS than macrophages from control NTB rats and behaved similar to activated macrophages from rats previously treated with thioglycollate. Heightened macrophage activity (increased production of TNF in response to LPS) in TB rats increased further as tumor burden increased (r = 0.889, P less than 0.001). Tumor resection reversed the heightened macrophage activity as LPS-induced levels of TNF secreted by macrophages from resected TB rats were not different from those of sham-operated NTB control rats. TB rats had serum levels of TNF activity following an iv bolus of 10 mg/kg LPS greater than those of NTB rats (P less than 0.05). In addition, peak serum TNF activity levels following iv LPS increased directly as tumor burden increased (r = 0.91, P less than 0.001). Supernatants from tissue cultures of the tumor (MCA sarcoma) failed to have any detectable TNF activity. However, large tumors in vivo had increased amounts of necrosis (78 +/- 8%), increased numbers of infiltrating macrophages, and increased levels of TNF (480 +/- 68 U/ml) compared to small tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Kaposi's sarcoma of the parotid gland in acquired immunodeficiency syndrome.

A patient with acquired immunodeficiency syndrome complained of a dry mouth and bilateral swelling of the parotid glands. Kaposi's sarcoma (KS) was found within the tissue of the parotid gland. Although KS is a common manifestation of acquired immunodeficiency syndrome, the presence of KS in the salivary glands is very rare. The human immunodeficiency virus I (HIV-I) genome was not identified in parotid glandular cells or in KS cells in this case, although the virus was detected in infiltrating lymphocytes and in tissue macrophages.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Clinically occult Leydig cell tumor presenting with gynecomastia.

An occult Leydig cell tumor is described in a patient who presented with gynecomastia. Diagnosis was established by means of testicular ultrasonography and selective testicular venous sampling. The pathophysiology and management of this rare disease entity are discussed.

Adult↗
PubMed1989

Primary signet ring cell adenocarcinoma of the bladder.

Primary signet ring cell adenocarcinoma of the bladder accounts for less than 1 per cent of all primary bladder neoplasms. This tumor is insidious because of its subepithelial infiltrative nature, which makes diagnosis possible only late in the course of the disease. Survival is poor; greater than 50 per cent of the patients are dead within a year after diagnosis. Exenterative procedures offer the only hope of palliation; irradiation and chemotherapy have not been effective. We add 5 cases of primary signet ring cell adenocarcinoma of the bladder and 1 case of high grade transitional cell carcinoma of the bladder with signet ring cell foci to the 14 cases reported in the literature. Pathological correlation supports the origin of this neoplasm from totipotential transitional epithelium.

Adenocarcinoma, Mucinous↗
PubMed1989

Hematopathology of the bone marrow in pediatric cutaneous mastocytosis. A study of 17 patients.

Sixteen bone marrow aspirates and 15 trephine core biopsies from 17 children with cutaneous mastocytosis, of which 15 exhibited urticaria pigmentosa and 2 exhibited diffuse cutaneous mastocytosis, were evaluated for the presence of bone marrow-associated pathologic conditions. Eight bone marrow aspirates from 8 children and 23 trephine core bone marrow biopsies from 16 children who had had evaluation for hematologic abnormalities not associated with cutaneous mastocytosis served as a control population. Eosinophilia was a prominent finding in bone marrows of 9 of 17 patients who had cutaneous mastocytosis. Increased mast cell numbers in bone marrow aspirates were observed in 5 children with cutaneous mastocytosis (5 of 16) and in 2 of the control children (2 of 8). Examination of the trephine core bone marrow biopsies obtained from patients with cutaneous mastocytosis demonstrated focal perivascular and paratrabecular aggregates consisting of mast cells, eosinophils, and early myeloid cells in 10 of 15 individuals. Similar lesions were observed in trephine core bone marrow biopsies of 3 of 16 control patients. The focal mast cell lesions characteristic of adult systemic mastocytosis were not observed. The authors conclude that cutaneous mastocytosis in the pediatric age group is rarely associated with definitive bone marrow findings suggestive of systemic mast cell disease and that this observation is consistent with previous reports that cutaneous mastocytosis in the majority of pediatric cases resolves by adulthood.

Bone Marrow↗
PubMed1989

Multifocal verruciform xanthoma of the upper aerodigestive tract in a child with a systemic lipid storage disease.

We report the clinical, light-microscopic, and ultrastructural features of a case of multifocal verruciform xanthoma in the upper aerodigestive tract of a child with a systemic lipid disorder. Lipid storage cells were found in liver, bone marrow, and as a component of verruciform xanthomas. To our knowledge this represents the first case of verruciform xanthoma reported in (a) a child, (b) as a multifocal lesion in the upper aerodigestive tract, (c) associated with a systemic lipid disorder, and (d) with ultrastructural evidence of lipid accumulation within endothelial cells. Although this patient presented with lesions involving the tongue and larnyx, subsequently lesions were found in the bone marrow and liver. Two months later more lesions were discovered on the epiglottis, posteior tongue, right glottis, and in grossly normal peritonsillar mucosa. Six months later a new oral lesion developed. Based upon these observations, we speculate that the pathogenesis of verruciform xanthoma involves accumulation of excess lipid in subepithelial sites which is scavenged by macrophages. Lipid-laden macrophages release epithelial growth factors that lead to epithelial hyperplasia. Depending on the degree of epithelial hyperplasia, the gross appearance of verruciform xanthomas may be flat, sessile, papillary, or verrucous.

Child, Preschool↗
PubMed1989

Primary adrenal causes of Cushing's syndrome. Diagnosis and surgical management.

Cushing's syndrome is rare with only 20% of patients having a primary adrenal cause of hypercortisolism. We have developed a strategy to evaluate patients with suspected Cushing's syndrome and to localize the pathologic condition responsible for the hypercortisolism. This report reviews the last 11 consecutive patients who had a primary adrenal cause of hypercortisolism. Each patient had elevated 24-hour urine free cortisol and 17-hydroxycorticosteroid excretion consistent with hypercortisolism. All but one patient had undetectable plasma ACTH levels. No patient suppressed urinary steroid levels with high-dose dexamethasone and only one patient increased plasma ACTH or cortisol levels with oCRH, findings that were consistent with a pituitary-independent form of hypercortisolism. No patient had a pituitary tumor detected by computed tomography or magnetic resonance imaging, and eight patients had adrenal tumors accurately imaged. MRI of the adrenal glands correctly diagnosed adenoma in 5 of 6 patients with adenomas, carcinoma in 1 patient, and ACTH-producing pheochromocytoma in 1 patient. One tumor classified as carcinoma by MRI appeared on pathologic examination to be an adenoma. Three patients underwent petrosal sinus sampling for measurement of ACTH before and after oCRH administration, and each had petrosal sinus ACTH levels equal to peripheral levels, consistent with a primary adrenal cause of hypercortisolism. Two of these patients had typical bilateral pigmented micronodular adrenocortical disease and the third patient had macronodular adrenocortical hyperplasia. Each of the 11 patients was cured of hypercortisolism by unilateral or bilateral adrenalectomy and no patient has developed recurrent disease during the 7 to 29 month follow-up period. New modalities including the ovine CRH test, MRI, and petrosal sinus sampling have improved the evaluation of certain patients with Cushing's syndrome.

Adolescent↗
PubMed1989

Cushing syndrome due to primary pigmented nodular adrenocortical disease: findings at CT and MR imaging.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in infants, children, and young adults. It is characterized by non-adrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple, pigmented nodules of hyperplastic adrenocortical cells. With a single exception, adrenal glands have been described as normal with computed tomography (CT) in all previous series. Eight patients had Cushing syndrome due to surgically proved PPNAD. Four of the eight patients had stigmas of Carney complex (lentigines, calcified Sertoli cell tumors of the testes, and cardiac and soft-tissue myxomas). CT and/or magnetic resonance (MR) imaging demonstrated unilateral or bilateral nodularity in five of six patients examined. Macronodules (greater than 10 mm) were seen in the two oldest patients. As the clinical presentation of Cushing syndrome in this group of patients may be atypical (severe osteoporosis or short stature), the detection of multiple, small adrenocortical nodules with CT or MR imaging supports, or may even suggest, the diagnosis of PPNAD.

Adolescent↗
PubMed1989

Solid and hematologic malignancies in 60 patients with systemic mast cell disease.

Although the association of malignancies and systemic mast cell disease (SMCD) is well established, the nature of this relationship is poorly understood. The observation of 19 malignancies in 17 of 60 patients with SMCD raised several questions regarding the chronological relationship of onset of SMCD and the malignancies, whether these patients are at increased risk for developing malignancy, and whether the distribution of solid vs hematologic malignancies indicates a relationship between SMCD and a particular tumor. The following malignancies were observed: eight solid tumors, seven acute nonlymphocytic leukemias, three malignant lymphomas, and one refractory anemia with excess blasts in transformation. The majority (13/17) of patients were found to have malignancies before, or within 12 months of, SMCD diagnosis. Statistical analysis suggested that patients with SMCD are not at increased risk for malignancies subsequent to the diagnosis of SMCD. The varied types of solid malignancies observed indicated a random distribution, in contrast to the hematologic malignancies that appeared to primarily affect the myeloid cells.

Adenocarcinoma↗
PubMed1989

Primary pigmented nodular adrenocortical disease. A light and electron microscopic study of eight cases.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing's syndrome, which is adrenocorticotropic hormone-independent and involves both adrenal glands. The characteristic pathological features include multiple pigmented cortical nodules and atrophy of the internodular cortex. The adrenal size ranges from small to normal or slightly enlarged. Review of the gross, light microscopic, and ultrastructural features of eight cases seen at the National Institutes of Health revealed several very unusual findings. We observed the following in our patients: macronodules up to 3.0 cm; microscopic foci of necrosis; mitoses; cortical hyperplasia rather than internodular atrophy; focal confluence of nodules giving a diffuse pattern of cortical involvement, and a focal trabecular growth pattern. The nodules were composed primarily of eosinophilic, lipid-poor cells similar to those of the zona reticularis. However, lipid-rich cells similar to those of the zona fasciculata were also demonstrated in the nodules by both light and electron microscopy. This suggests that the adrenal cortical nodules of PPNAD may be derived from not only the zona reticularis, but also the zona fasciculata.

Adolescent↗
PubMed1989

IgA rheumatoid factor and IgA containing immune complexes in primary Sjögren's syndrome.

IgA rheumatoid factor (RF) and immune complexes containing IgA-IgG, C3-IgA, and C3-IgG from sera of patients with primary Sjögren's syndrome and controls were quantified by ELISA. Salivary tissue obtained from patients at the same time as serum was scored to simultaneously reflect lymphoplasmocytic infiltrate and fibrosis. Patients had significantly increased amounts of IgA RF and all complexes when compared to controls (p less than 0.0005). IgA-IgG complexes, thought to be IgG-IgA RF complexes, were inversely correlated to tissue pathology (p less than 0.001) and peripheral white blood cell counts. Additionally, IgA RF was inversely correlated to stimulated parotid flow. This suggests immune complex formation precedes tissue destruction or is associated with less destructive pathology in primary Sjögren's syndrome.

Adult↗
PubMed1988

Nonspecific interstitial pneumonitis without evidence of Pneumocystis carinii in asymptomatic patients infected with human immunodeficiency virus (HIV).

STUDY OBJECTIVE: To assess how often Pneumocystis carinii organisms, P. carinii pneumonia, or other pulmonary pathologic processes were present in persons infected with human immunodeficiency virus (HIV) without pulmonary symptoms or previous history of P. carinii, and with a normal chest roentgenogram. DESIGN: Serial, prospective assessment of eligible HIV-seropositive patients over 21 months. PATIENTS: Twenty-four HIV-seropositive patients with either a nonpulmonary manifestation of the acquired immunodeficiency syndrome (AIDS) (n = 12) or an absolute CD4 lymphocyte count of 0.200 X 10(9) cells/L or less (n = 12), no pulmonary symptoms, a normal chest roentgenogram, no history of P. carinii pneumonia, and no history of treatment with antipneumocystis prophylaxis. INTERVENTIONS: Pulmonary assessment with arterial blood gases, pulmonary function tests, gallium-67 citrate scans, and bronchoscopy with bronchoalveolar lavage and transbronchial biopsies. MEASUREMENTS AND MAIN RESULTS: Mean alveolar-arterial gradient was 11.1 mm Hg +/- 8.5 and mean diffusion capacity was 73.0% +/- 20.0% of predicted. None of the 24 patients showed P. carinii or other pathogens on stains of bronchoalveolar lavage fluid. No patient had histologic evidence of P. carinii pneumonia. Transbronchial biopsy specimens showed chronic, nonspecific interstitial pneumonitis (11 of 23) and no pathologic abnormality (12 of 23). Six patients have developed P. carinii pneumonia during 2 to 18 months of follow-up. CONCLUSIONS: HIV-infected patients without pulmonary symptoms did not have detectable Pneumocystis organisms in bronchoalveolar lavage fluid or transbronchial biopsy specimens; but 11 of 23 had evidence of chronic, nonspecific interstitial pneumonitis. Pneumocystis organisms in a pulmonary specimen from a symptomatic patient probably indicate the cause of the pulmonary dysfunction even if only a few are detected.

Adult↗
PubMed1988

Significance of systemic mast cell disease with associated hematologic disorders.

A clinical and hematopathologic review of 66 patients with systemic mast cell disease (SMCD) was undertaken to investigate the frequency and the clinical significance of associated hematologic disorders. Twenty-two patients were found to have a second hematologic disorder, 19 of which involved the myeloid cells (ten dysmyelopoietic syndromes, five myeloproliferative disorders, three acute nonlymphocytic leukemias, and one chronic neutropenia), and three of which involved the lymphoid cells (three malignant lymphomas). A chromosome analysis of the bone marrow revealed abnormalities characteristic of neoplastic myeloid disorders in four patients. Five-year survival for patients with hematologic disorders was 28% compared with 61% for other SMCD patients (P = 0.004). Patients with hematologic disorders differed significantly from other SMCD patients in that they were about 7 years older (P = 0.039), and they presented more commonly with anemia (P less than 0.001) and constitutional symptoms (P = 0.007). These patients also had less frequent skin symptoms (P = 0.003) and urticaria pigmentosa (P = 0.018). By definition, patients with hematologic disorders had a greater percent of hematopoiesis (P less than 0.001) and decreased fat cells (P = 0.011) on bone marrow biopsies. A multivariate model demonstrated that the following independent variables were associated with the presence of hematologic disorders: low hemoglobin (P = 0.001), the absence of hepatomegaly (P = 0.016), high leukocyte count (P = 0.021), and the presence of pathologic fractures (P = 0.051). The frequent coexistence of SMCD with dysplastic and neoplastic disorders of myeloid cells is consistent with the concept that SMCD itself is a disorder of myeloid cells and that the mast cell may be myeloid in origin.

Adult↗
PubMed1988

Pulmonary nodules resembling bronchioloalveolar carcinoma in adolescent cancer patients.

Pulmonary nodules morphologically indistinguishable from bronchioloalveolar carcinoma (BAC) were found in two adolescent cancer patients postchemotherapy. A solitary nodule was noted at thoracotomy for a single computerized tomography (CT) scan lesion in a 16-yr-old male, 6 yr after diagnosis of Ewing's sarcoma. A similar nodule was found in a 19-yr-old male coincident with resection of multiple lung metastases of a testicular germ cell tumor. Both lesions were discrete nodular masses (1 cm and 0.5 cm) consisting of atypical epithelial cells with a papillary and lepidic growth pattern and surrounded by histologically normal appearing lung. Immunohistochemistry of both cases was positive for laminoorganel (LO) antigen, which is found in normal type II pneumocytes, and one nodule showed carcinoembryonic antigen (CEA) staining. Quantitative DNA analysis in one case indicated aneuploidy. Thus the morphology, immunohistochemistry, and DNA content of these lesions suggest that they may represent early lung cancers despite the highly unusual clinical context. The extreme rarity of BAC in this age group makes this report significant in light of heightening concern about second malignancies in pediatric cancer patients and reports of chemically induced pulmonary adenomas in mice. It also underscores the importance of basing therapeutic decisions on a histologic diagnosis of lung nodules in cancer patients rather than assuming the presence of metastatic disease.

Adenocarcinoma, Bronchiolo-Alveolar↗