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Biomedical subjects

H I Pass

Publications and source records attributed to H I Pass.

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

Corticotropin-secreting carcinoid tumors of the thymus: diagnostic unreliability of thymic venous sampling.

Three patients with Cushing syndrome due to ectopic production of corticotropin underwent total thymectomy on the basis of elevated concentrations of corticotropin in selective samples from thymic veins but in the absence of a radiographically detectible thymic mass. In one patient, radiologic examination demonstrated hyperplasia of neuroendocrine cells staining positively for corticotropin throughout the thymus but no discrete mass. This patient had complete remission after total thymectomy. The other two patients had no evidence of an intrathymic source of corticotropin, and both had persistent Cushing syndrome. Elevated levels of corticotropin in thymic vein samples may reflect corticotropin production by pulmonary bronchial carcinoid tumors, mediastinal metastases, thymic carcinoids, or diffuse hyperplasia of intrathymic neuroendocrine elements. In the absence of a demonstrable intrathymic mass, corticotropin gradients in thymic veins do not reliably indicate a thymic source of corticotropin and should not necessarily be used as a basis for exploratory thoracotomy or blind thymectomy.

Adrenocorticotropic Hormone↗
PubMed1992

Role of tumor necrosis factor in oxygen toxicity.

mRNA from lungs of mice exposed to high-dose oxygen (greater than 95%) for 3 days demonstrated increased expression of the genes for tumor necrosis factor (TNF), interleukin-1, and interleukin-6 compared with mRNA from lungs of mice exposed to room air. Daily treatment of mice exposed to high-dose oxygen with an antibody to TNF improved survival compared with mice receiving a similar dose of control immunoglobulin G. Pretreatment of mice with repetitive sublethal intraperitoneal doses of recombinant human TNF for 3 days or a single intravenous dose followed by exposure to high-dose oxygen afforded a significant survival advantage compared with high-dose oxygen-exposed mice pretreated with vehicle or interleukin-1. The repetitive intraperitoneal TNF pretreatment reduced the development of interstitial pneumonitis, pulmonary edema, and lung weight gain associated with oxygen toxicity and enhanced expression of the gene for the free radical protective enzyme manganous superoxide dismutase in lung tissue, a gene that is augmented as mice are exposed to high-dose oxygen. Furthermore a single intravenous dose of TNF 24 h after oxygen exposure was still protective. The results suggest that the toxicity of oxygen therapy can be partially ameliorated by either treatment with anti-TNF antibody or pretreatment and early treatment with TNF. These findings are consistent with the hypothesis that oxygen exposure induces TNF, which causes part of the toxicity of high-dose oxygen, and that pretreatment or early treatment with TNF induces the gene for an enzyme that recently has been shown to be very effective in protecting mice from the toxicity of oxygen.

Animals↗
PubMed1992

Virilizing adrenal cortical neoplasm arising ectopically in the thorax.

We describe a 44-yr-old woman with a 12-yr history of clinical virilization and serum testosterone levels up to 28.1 nmol/L (normal range, 1-3.3 nmol/L) in whom repeated clinical evaluation and surgical procedures failed to reveal the source of androgen production. At the time the patient was referred to the Clinical Center of the NIH, an intrathoracic mass was seen on upper cuts of an abdominal computer-aided tomography scan, confirmed by computer-aided tomography scan and magnetic resonance imaging of the chest. A 6 x 5 x 3.5-cm mass, attached to the posterior pericardium, was removed by thoracotomy. Pathological examination revealed an adrenal cortical neoplasm of uncertain malignant potential that contained testosterone, 11-deoxycortisol, progesterone, and 17-hydroxyprogesterone. After the operation, the patient's serum testosterone levels decreased to the normal range. Ectopic adrenal cortical rests in the thorax and neoplasms arising from these rests are extremely rare, and we are not aware of a similar case previously reported. In women with virilization, radiological studies of the thorax as well as other reported sites of ectopic adrenal cortex should be performed if radiological studies of the abdomen and pelvis fail to locate the source of the neoplasm.

Adrenal Cortex Neoplasms↗
PubMed1992

Surgical strategy in the management of non-small cell ectopic adrenocorticotropic hormone syndrome.

BACKGROUND: Non-small cell ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of hypercortisolism that may require surgery for either curative resection or palliative adrenalectomy. METHODS: We report our surgical experience with 41 patients with ectopic ACTH syndrome and no evidence of small cell lung cancer at initial evaluation. RESULTS: All 41 patients had documented hypercortisolism secondary to ectopic production of ACTH. Based on imaging study results, we determined that 21 patients had localized/resectable disease; eight patients had metastatic disease, and 12 patients had occult disease at examination. Of the 21 patients with localized disease, 16 (76%) were cured of ectopic ACTH by surgery (15 bronchial carcinoid, one pheochromocytoma). Patients with bronchial carcinoid had the greatest probability for cure of ectopic ACTH syndrome, and patients with thoracic primary tumor were more likely to be cured than patients with abdominal primaries. Of the eight patients who had metastatic disease, none were cured of the disease; five patients underwent bilateral adrenalectomy, and three patients were given medical therapy. Only one patient was alive after 5 years. Of the 12 patients who had occult disease, four patients were eventually cured of the disease (three bronchial carcinoid, one thymic carcinoid); one patient died of disease (small cell lung cancer), and seven patients still have occult disease. Nine of 12 patients with occult disease underwent bilateral adrenalectomy for surgical management of hypercortisolism. CONCLUSIONS: This study suggests that the most common primary focus of ectopic ACTH production is within the thorax with 25 of 34 (74%) identifiable tumors originating within either the thymus or bronchus. Adrenalectomy offers excellent palliation of hypercortisolism secondary to either occult or metastatic disease. Patients who initially have localized disease usually have bronchial carcinoids and have a high probability of cure with surgical resection (81%).

ACTH Syndrome, Ectopic↗
PubMed1992

Spin trap salvage from endotoxemia: the role of cytokine down-regulation.

BACKGROUND: The spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) affords protection from the lethality of septic (lipopolysaccharide) shock. We hypothesized that PBN may work through down-regulation of the sepsis-induced cytokine cascade. METHODS: C3H/HEN mice received 30 mg/kg lipopolysaccharide 15 minutes after pretreatment with PBN or vehicle. Animals were monitored for differences in behavior, histopathologic studies, survival, and serum levels of tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) after lipopolysaccharide. Northern blot analyses of TNF, IFN-gamma, c-fos, and IL-6 transcripts were also performed. RESULTS: Seventy-two-hour survival was significantly higher in the PBN-treated (59/60) compared with the saline-treated animals (13/60; p2 less than 0.005), and the PBN group exhibited a blunted endotoxemic response. TNF levels were significantly lower in the PBN-treated animals at 1 to 6 hours, whereas IFN-gamma levels were depressed at 8 hours. PBN down-regulated TNF transcription at 30 minutes, with maximum lowering of all cytokine transcripts at 6 hours. PBN depressed c-fos transcription within 15 minutes of lipopolysaccharide injection. CONCLUSIONS: Spin trap protection from endotoxemia may be related to interruption of the cytokine network, with profound effects on transcription and protein elaboration. Such compounds may prove useful in not only sepsis but also other cytokine-free radical-related pathophysiologic alterations.

Animals↗
PubMed1991

Cellular glutathione and thiol measurements from surgically resected human lung tumor and normal lung tissue.

Cellular glutathione (GSH) levels were measured from 27 human lung tumor biopsies, enzymatically disaggregated, and compared with cells isolated from normal lung of the same patients. GSH levels from normal lung were similar among patients with a mean value of 11.20 +/- 0.58 (SEM) nmol GSH/mg protein (24 patients) with a range from 6.1 to 17.5 nmol GSH/mg protein. GSH levels varied considerably within and across histological tumor types with the following values: adenocarcinomas, 8.83 +/- 0.96 nmol/mg protein (8 patients); large cell carcinomas, 8.25 +/- 2.51 nmol/mg protein (3 patients); and squamous cell carcinomas, 23.25 +/- 5.99 nmol/mg protein (8 patients). The cyclic GSH reductase assay gave only average GSH values and could not distinguish possible GSH variation among subpopulations of cells isolated. Cell volume measurements and microscopic evaluation of cells isolated from both tumors and normal lung revealed heterogeneity with respect to cell types present. To determine the extent of thiol variation among tumor cell subpopulations, tumor cell suspensions were stained with the thiol-specific stain, monochlorobimane (MCB). The accuracy of MCB staining was tested by flow cytometric analysis of 12 in vitro human tumor cell lines and 3 rodent cell lines. A linear relationship was found between the bimane cellular fluorescence and the cyclic GSH reductase assay for cell lines having less than 80 nmol GSH/mg protein (R2 = 0.82). Above 80 nmol GSH/mg protein the rate of change of the bimane fluorescence intensity with respect to increasing GSH concentrations was much reduced. However, by labeling cells with MCB it was possible to distinguish between cell lines with low versus high GSH content. MCB staining of tumor samples revealed multiple populations of cells with respect to thiol levels. In particular, 2 of 8 squamous cell carcinomas had a proportion of cells with elevated fluorescence intensities (from 10 to 35% of the population) suggesting the presence of cells with greatly elevated thiol levels. These findings underscore the complexity of quantitating intracellular GSH levels from tumor biopsies. The combined use of MCB with flow cytometry and conventional GSH assays may help to delineate subpopulations of cells within tumors with different thiol levels.

Adenocarcinoma↗
PubMed1991

Recurrent or metastatic disease in select patients with adrenocortical carcinoma. Aggressive resection vs chemotherapy.

In a retrospective, nonrandomized comparison of patients with first recurrence of adrenocortical cancer, 18 patients were treated with chemotherapy (primarily mitotane) and 15 patients were treated with surgical resection plus similar chemotherapy. Surgical resection of recurrent adrenocortical cancer was often extensive, with morbidity in 20% of patients and no mortality. Mitotane therapy was ineffective at controlling tumor growth. Median survival from the time of diagnosis for all patients was only 23 months and no patient was cured. Disease-free interval greater than 12 months was associated with prolonged survival, but it only occurred in six patients (18%), with a similar frequency in both treatment groups. Surgical resection of recurrent disease was associated with prolonged survival from the time of first recurrence. The potential benefit of this resection was evident in the 5 patients (33%) who were able to live greater than 5 years from the time of first recurrence with improvement in symptoms and signs of hypercortisolism. Although no patient with recurrent adrenal cancer could be cured, resection of recurrent disease was associated with a slight prolongation of survival and good palliation of Cushing's syndrome.

Adolescent↗
PubMed1991

Reoperative pulmonary resection in patients with metastatic soft tissue sarcoma.

Resection of pulmonary metastases from soft tissue sarcoma has been shown to be associated with a 3-year survival of 25% to 30%. The role of multiple resections for recurrent pulmonary metastases, however, has not been clearly defined. Since 1976, 43 patients have had two or more thoracic explorations for the purpose of resecting pulmonary metastases from adult soft tissue sarcoma at our institution. In 89 reexplorations, through either median sternotomy or lateral thoracotomy, the operative mortality was 0%, and 31 of the 43 patients (72%) could be rendered free of disease at the second thoracotomy. Median survival from the second thoracotomy for the patients with resectable disease was 25 months, whereas median survival of patients who had unresectable disease was 10 months. A disease-free interval between the first and second thoracotomies of greater than 18 months was associated with prolonged survival from the second thoracotomy. Owing to lack of other therapies with proven salvage efficacy and in the absence of randomized trials, repeated thoracotomies to render patients free of disease from pulmonary soft-tissue sarcoma metastases appear justified considering the potential survival benefit and low attendant risk.

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

A report of familial carotid body tumors and multiple extra-adrenal pheochromocytomas.

A case of familial carotid body tumors and multiple extra-adrenal pheochromocytomas is reported. The carotid body tumors, resected previously, were bilateral and associated with 4 intra-abdominal extra-adrenal pheochromocytomas. Magnetic resonance imaging was far superior to computerized tomography and 131iodine-metaiodobenzylguanidine in visualizing the intra-abdominal lesions, and may soon become the imaging technique of choice in the evaluation of patients with suspected pheochromocytoma.

3-Iodobenzylguanidine↗
PubMed1991

A light-diffusing device for intraoperative photodynamic therapy in the peritoneal or pleural cavity.

Light delivery to anatomic areas involved by tumor is critical for effective photodynamic therapy. The authors provide a detailed overview of a light-diffusing device which they have used for intraoperative illumination of the peritoneal and pleural cavities in patients with tumors involving the surfaces of these cavities. Their device represents an inexpensive modification of widely available endotracheal tubes. It has been used to deliver intraoperative photodynamic therapy in over 50 patients without episodes of device failure. When combined with a lipid-based, light-diffusing medium and on-line power/energy density monitoring, it allows homogeneous illumination of these complex surfaces.

Combined Modality Therapy↗
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

Intravenous vs intraperitoneal sensitizer: implications for intraperitoneal photodynamic therapy.

Photodynamic therapy (PDT) is a potential treatment for peritoneal carcinomatosis. However, little data is available regarding the relative distribution of sensitizer to tumor and intra-abdominal organs, optimal route of sensitizer administration, and maximal tolerated light dose. Tumor and normal tissue sensitizer levels were measured by tissue extraction 3, 24, 48 and 72 h after 10 mg/kg of Photofrin II was given intraperitoneally (IP) or intravenously (IV) in a mouse peritoneal tumor model, and the maximal tolerated PDT light dose determined. Equivalent tumor sensitizer levels were obtained regardless of the route of sensitizer administration. Route of administration, however, did affect the kinetics of tumor sensitizer elimination, with the half-time for elimination (T1/2) 113.6 h for IP drug and 60.6 h for IV drug. Route of administration also affected sensitizer levels in several intra-abdominal organs, resulting in somewhat higher tumor to liver and kidney levels at 24 and 72 h after IP sensitizer administration. Despite these tissue distribution differences, route of sensitizer administration did not significantly affect PDT toxicity or mortality when mice were treated with 630 nm light. The maximum tolerated light dose was 1.04 J/cm2. These parameters will prove helpful in designing large scale animal trials assessing the efficacy and safety of intra-abdominal PDT.

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

Photodynamic therapy of oncogene-transformed cells.

Photodynamic therapy with dihematoporphyrin ether sensitizes malignant cells to damage by 630 nm light. The in vitro, in vivo photodynamic therapy sensitivity of a cell line transformed by the Kirsten ras oncogene (45342) was studied to establish a new photodynamic therapy model. With the colony formation assay, neither light alone nor dihematoporphyrin ether alone affected 45342 survival. Energy-dependent photodynamic therapy effects were seen in vitro in dihematoporphyrin ether-incubated and light-exposed cells (90% cytotoxicity = 950 joules/m2; 99% cytotoxicity = 1575 joules/m2; p2 less than 0.05). Subcutaneous allografts of 45342 were established in nu/nu mice, and ideal route (intravenous or intraperitoneal) of dihematoporphyrin ether delivery, dihematoporphyrin ether tissue kinetics, and in vivo photodynamic therapy effects were examined. Intravenous administration not only gave higher levels of the sensitizer in various tissues, but also was associated with less variation than the intraperitoneal route. Selective dihematoporphyrin ether retention was documented in the tumors at 24 hours after injection compared with other tissues, and photodynamic therapy with 0.3 W/cm2 to a total dose of 150 joules/cm2 led to progressive coagulative tumor necrosis and tumor regression. These studies confirm that transformed, malignant cells are sensitive to photodynamic therapy, and this model may prove in future studies to increase efficacy to photodynamic therapy (i.e., with dihematoporphyrin ether delivery by monoclonal antibodies).

Animals↗
PubMed1991

Chemotherapy amplifies production of tumor necrosis factor.

Several chemotherapeutic agents exert cytotoxicity through the generation of reactive oxygen species (ROS), and our laboratory has shown that ROS increase tumor necrosis factor (TNF) production. Therefore, we hypothesized that cis-dichlorodiammine platinum (CDDP), mitomycin-C, and doxorubicin hydrochloride (Adriamycin), by the release of ROS, would increase macrophage TNF production. Murine macrophages were incubated for 20 hours with varying doses of the chemotherapeutic drugs and 2.5 micrograms/ml endotoxin. Both CDDP and mitomycin-C increased TNF production compared to nondrug-exposed cells. Peak TNF values occurred at 10 micrograms/ml CDDP and 62.5 micrograms/ml mitomycin-C with 377 +/- 38 and 427 +/- 54 units/ml TNF produced, respectively. These increases were significant (p2 less than 0.05) compared to the nonchemotherapy; but endotoxin-exposed macrophages (CDDP 11 +/- 3 units/ml; mitomycin-C 10 +/- 3 units/ml). Only CDDP-increased production of TNF from non-endotoxin-primed macrophages (0 microgram/ml CDDP - 0 +/- 0 unit/ml TNF; 50 micrograms/ml CDDP - 13 +/- 5 units/ml TNF; p2 less than 0.038). 5-Fluorouracil, a non-ROS-generating chemotherapeutic, and Adriamycin failed to amplify TNF production. By Northern blot analysis, CDDP induced transcription of the TNF gene in non-endotoxin-primed macrophages as early as 3 hours after exposure to 50 micrograms/ml CDDP, and this preceded the increase in TNF protein in kinetic studies. Because CDDP, mitomycin-C, and Adriamycin all produce ROS, the mechanism for this selective chemotherapy-induced cytokine amplification remains unclear. This finding may explain both indirect toxic and tumoricidal properties of CDDP and mitomycin-C.

Animals↗