Biomedical subjects

E E Lower

Publications and source records attributed to E E Lower.

At least 37 records · Page 2Linked to original sources

PubMed1997

Predicting respiratory failure in sarcoidosis patients.

BACKGROUND AND AIM OF WORK: Although sarcoidosis is a multisystem disease, mortality from sarcoidosis is usually due to respiratory failure. In order to identify those patients at risk of death from respiratory failure from sarcoidosis, we analyzed a seven-year experience of patients seen at the University of Cincinnati Interstitial Lung Disease clinic. RESULTS: A total of 479 patients were seen during that time. Of these, 22 (4.6%) died. Thirteen patients died from respiratory failure, three died from cardiac disease, and two each from neurologic or hepatic disease. Two patients died from unrelated disease. Analysis of the patients who died from respiratory failure was compared to the other patients. All patients who died from respiratory failure had fibrotic changes demonstrated by chest roentgenogram. All patients who died had at least one vital capacity less than 2.5 liters, with the majority of patients who died of respiratory failure having a vital capacity of less than 1.5 liters. CONCLUSIONS: Patients who die from respiratory failure from their sarcoidosis have fibrosis demonstrated on chest roentgenogram and a reduced vital capacity, usually less than 1.5 liters.

Adult↗

PubMed1996

Plasma membrane phosphotyrosine, Her2-NEU, and epidermal growth factor receptor in human breast cancer. A comparative study.

Experimental therapeutic regimens for breast cancer include strategies to block the activity of specific oncogenes. Because oncogenesis is a multistep process, specific oncogenes may drive tumor production at one stage yet not function in another. Since the effectiveness of therapy targeted against oncogenes depends on their function in the tumor, correlation of oncogene function to specific stages of tumor development has therapeutic implications. Among the oncogenes known to be important in breast cancer production are two cell surface growth factor receptors, epidermal growth factor receptor (EGFR) and Her2-NEU (NEU). These proteins are receptor tyrosine kinases that autophosphorylate specific tyrosine residues on activation. The oncogenic potential of these receptors depends on this autophosphorylation. We examined 86 primary formalin-fixed, paraffin-embedded breast tumors for overexpression of EGFR and NEU and correlated our findings with the presence of cell surface phosphotyrosine as an indicator of tyrosine kinase activity at the plasma membrane. Our data indicate that only 34% of tumors that overexpress EGFR or NEU show plasma membrane phosphotyrosine, indicating that in the majority of these tumors, the overexpressed oncogene may not be active at this stage.

Breast Neoplasms↗

PubMed1995

Prolonged use of methotrexate for sarcoidosis.

BACKGROUND: To determine the safety and efficacy of methotrexate as a steroid-sparing agent in patients with symptomatic sarcoidosis, a nonrandomized interventional study of patients with chronic sarcoidosis treated with methotrexate for at least 2 years was performed. Efficacy was assessed for all patients after 2 years of treatment. Toxicity was assessed for all patients receiving therapy for the entire time (a total of 150 patient-years). METHODS: Patients were treated in a subspecialty ambulatory clinic at a university hospital. Patients with biopsy-confirmed sarcoidosis who had persistent symptoms and who were eager to avoid or reduce corticosteroid therapy were selected for study. A total of 50 patients completed at least 2 years of methotrexate therapy. Patients were treated with oral methotrexate once a week. Dosage was adjusted based on the patient's white blood cell count. Clinical response was measured in the affected organ, including the lung (measurement of vital capacity), skin (regression of skin lesions), and central nervous system (magnetic resonance imaging). Also noted was the initial and subsequent dosage of prednisone used as therapy for sarcoidosis. RESULTS: Improvement in vital capacity or other affected symptomatic organ was noted in 33 of 50 treated patients. Corticosteroids were discontinued in an additional six patients who remained stable with clinical or symptomatic improvement. The major toxic effects noted in 150 patient-years of therapy were hepatic (six patients), leukopenia requiring hospitalization (one patient), and cough (one patient). Forty-one liver biopsy procedures were performed in 33 patients. Of these, six demonstrated significant changes related to methotrexate that led to drug discontinuation. CONCLUSION: Methotrexate is a well-tolerated therapeutic agent with significant steroid sparing and efficacy for the treatment of chronic symptomatic sarcoidosis.

Adrenal Cortex Hormones↗

PubMed1995

Increased phosphotyrosine in breast cancer tissue is associated with a worse prognosis.

We have previously demonstrated that phosphotyrosine can be identified in breast cancer cells using an immunohistochemical stain. We have subsequently used this technique to characterize 106 women with breast cancer (46 with Stage 1 and 60 with Stage 2) who have been followed for at least four years by one oncologist. We analyzed all primary breast cancer tissue using immunohistochemical staining and the amount of phosphotyrosine (PT) was scored on a 0 to 3 range. The PT score of the primary tumor was unrelated to either breast cancer stage or estrogen and progesterone receptor analysis, as high PT scores were noted in both disease stages and all receptor categories. We did find that patients with either no or trace (1+) amounts of PT survived longer than those patients with higher amounts of PT. The patients with low PT had significantly lower chance of relapse (Chi Square = 15.8, p < 0.001) and a lower mortality (Chi Square = 13.1, p = 0.001). We conclude that immunohistochemical methods to determine the PT score may identify patients at higher risk for disease relapse independent of tumor stage or hormonal status.

Breast Neoplasms↗

PubMed1994

Paranoid psychosis due to neurosarcoidosis.

We present two patients with known sarcoidosis who developed neurosarcoidosis manifested by paranoid psychosis and clinical diabetes insipidus with hypernatremia. Both had gadolinium enhanced magnetic resonance imaging which demonstrated leptomeningeal and hypothalamic enhancement. Both had elevated protein and a lymphocytosis in their cerebrospinal fluid, which improved after corticosteroid therapy. The patients improved clinically with this therapy as well. We suggest that new onset psychosis in a sarcoid patient, particularly with symptoms of hypothalamic/pituitary involvement, should be evaluated for neurosarcoidosis with an MRI and CSF examination. If the results are consistent with neurosarcoidosis, the patient should be treated promptly with corticosteroids.

Adult↗

PubMed1993

Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in breast cancer specimens.

Using a synthetic peptide substrate, tyrosine protein kinase (TPK) activity was measured in 21 tumors from patients with histologically confirmed breast cancer and in five normal breast tissues from patients undergoing reduction mammoplasty. In 20 of 21 cancer specimens, tumor was available to assess phosphotyrosine (PT) immunohistochemically. Breast cancer specimens possessed significantly more TPK activity than normal breast tissues (Cancer = 43.9 +/- 3.1 pm/mg protein/min, [Mean +/- S.E.M.]; Normal = 3.4 +/- 0.9, p < 0.001). TPK activity was higher in the clinically more aggressive infiltrating ductal cancers compared to the less aggressive intraductal cancers (Infiltrating = 55.9 +/- 5.8; Intraductal = 17.2 +/- 3.4, p < 0.01). TPK activity in tumors with both infiltrating and intraductal histology was intermediate (34.0 +/- 7.2). Significant correlation existed between membrane TPK enzymatic activity and PT expression by immunohistochemistry. There was no relationship between estrogen or progesterone receptor status and TPK activity or PT; however, TPK activity from node negative breast cancer tissue was significantly less than from node positive specimens (p < 0.01). We conclude that breast cancer specimens possess elevated amounts of TPK which correlate with PT expression, and that increased tyrosine phosphorylation appears to correlate with the biologic aggressiveness of the malignant tumor.

Breast↗

PubMed1993

Thrombocytopenia in the intensive care unit.

STUDY OBJECTIVE: To determine the prevalence of thrombocytopenia in an ICU and assess which factors were associated with thrombocytopenia. DESIGN: A review of the medical records of patients admitted during 3 separate months during 1 academic year. Patients must have survived at least 12 h in the ICU. SETTING: A medical ICU at a university hospital. PATIENTS: General medicine patients admitted to the ICU. INTERVENTIONS: All medical records were reviewed. During the ICU stay, daily medications, events, and platelet count were noted. All patients were followed up until death or hospital discharge. In 22 patients, including 18 who had thrombocytopenia, bone marrow aspirates were performed. MEASUREMENTS AND RESULTS: One hundred sixty-two admissions were evaluated. Thirty-eight (23 percent) had platelet counts less than 100,000/mm3 at least once, and 17 (10 percent) patients had platelet counts less than 50,000/mm3. Several factors were associated with thrombocytopenia; however, only sepsis, use of antineoplastic chemotherapy, elevated creatinine level, or elevated bilirubin value were independent risk factors for severe thrombocytopenia. In only one patient were the bone marrow findings different from those expected by the clinical presentation. Thrombocytopenia was associated with longer hospital stay (p < 0.001) and higher mortality (p < 0.001). CONCLUSION: Thrombocytopenia is a common occurrence in the ICU, usually due to the underlying disease, and is associated with an increased mortality.

Bone Marrow Examination↗

PubMed1992

c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma.

c-myc, c-erbB-2, and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas. The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues. Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors, while the level of expression in normal breast tissue was much less than that in breast cancer. Membrane staining of the c-erbB-2 protein was demonstrated in 29% (4 of 14) of noninvasive ductal carcinomas and in 45% (19 of 42) of invasive breast carcinomas. None of the 11 normal breast tissue samples was positive. The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue, 4.57 +/- 1.36% for noninvasive ductal carcinoma, and 12.76 +/- 2.18% for invasive breast cancer. In 42 invasive breast carcinomas, the expression of c-myc, c-erbB-2, and Ki-67 proliferation marker were compared with lymph node status, estrogen receptor status, progesterone receptor status, and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status. We concluded that they might be additional prognostic factors for breast carcinoma.

Breast↗

PubMed1992

Increased tyrosine protein kinase activity in hairy cell and monocytic leukemias.

Tyrosine protein kinases (TPK) help regulate cellular growth and differentiation. Several proto-oncogenes encode for protein products with associated tyrosine kinase activity. An assay for TPK activity was performed in cell extracts using a synthetic peptide substrate and [32P] adenosine triphosphate (ATP). TPK activity was elevated in K-562 cells, which possess an amplified c-abl oncogene, compared to normal blood mononuclear cells (K-562 = 9.37 +/- 1.72 [mean +/- standard deviation] pmol ATP/10(6) cells/min; normal = 1.14 +/- 0.46, p less than 0.01). TPK activity was measured in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL), myelomonocytic leukemia (MOL), acute myeloblastic leukemia (AML), and chronic lymphocytic leukemia (CLL). In patients with clinically active disease, elevated TPK activity was measured in mononuclear cells from five HCL patients (range 3.76-24.15) and from seven MOL patients. These elevated levels appeared to parallel disease activity, as low levels of TPK activity were measured in patients with inactive (treated) disease. Low levels of TPK were measured in mononuclear cells from active AML and CLL patients. Elevated TPK levels in patients with HCL and MOL may reflect the overexpression of a proto-oncogene or increased growth factor activity in immature or rapidly dividing leukemic cells. Serial TPK levels in HCL and MOL patients correlated with change in disease activity.

Humans↗

PubMed1992

Use of intermittent, intravenous cyclophosphamide for idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: To determine the safety and efficacy of intravenous cyclophosphamide for patients with idiopathic pulmonary fibrosis. DESIGN: Nonrandomized, open-labeled study of efficacy in symptomatic patients. SETTING: Patients were treated as outpatients in a referral clinic. PATIENTS: All patients had idiopathic pulmonary fibrosis with symptoms of dyspnea on exertion. Patients had either worsening disease or contraindication to corticosteroids. INTERVENTION: Thirty-three patients were treated with intravenous cyclophosphamide every two weeks. Initial dosage was 500 mg, and the dose was escalated provided the total white blood cell count remained > 3,000 cells per cubic millimeter. The maximum dose administered was 1,000 to 1,800 mg of cyclophosphamide. Corticosteroid therapy was tapered as tolerated by the patient. MEASUREMENTS AND RESULTS: Patients were treated for at least six months or until death. For the 33 patients, 18-month probability of survival was > 50 percent. For those patients surviving six months, there was a significant rise in the vital capacity (from 1.6 +/- .61 L [mean +/- SD] to 1.8 +/- .52 L, p < 0.01) which persisted for at least 18 months of treatment. This was associated with a significant fall in the average prednisone dosage from 32 +/- 13.0 mg/day to 4 +/- 10.4 mg/day (p < 0.01) by 12 months. Only one patient required hospitalization for possible drug-related toxic reaction. CONCLUSIONS: Intermittent, intravenous cyclophosphamide therapy was associated with improved pulmonary function and reduced corticosteroid dosage in patients with idiopathic pulmonary fibrosis who survived at least six months after institution of therapy.

Cyclophosphamide↗

PubMed1992

Pulmonary lymphangitic metastasis from breast cancer. Lymphocytic alveolitis is associated with favorable prognosis.

BACKGROUND: More than 20 percent of patients with breast cancer have pulmonary lymphangitic spread at death. Previous reports have indicated that some patients may respond to aggressive chemotherapy that includes corticosteroids. METHODS: Bronchoscopy with bronchoalveolar lavage (BAL) was used to assess pulmonary infiltrates in 14 patients with infiltrating ductal breast cancer. All patients had received prior cytotoxic or hormonal therapy. Following a diagnosis of pulmonary metastasis by BAL or biopsy specimen, all patients received prednisone and chemotherapy. RESULTS: BAL confirmed the diagnosis of metastatic tumor in 10 of 14 patients. The conditions of the remaining patients were diagnosed by one or more other bronchoscopy specimens. Patients were divided into two groups based on BAL lymphocyte percentage (10 percent is the upper limit of normal in our laboratory). Seven patients had > 10 percent lymphocytes (high lymphs: 26 +/- 11.6 percent [mean +/- SD]) compared with seven patients with normal lymphocyte percentage (low lymphs: 4 +/- 1.9 percent, p < 0.01). Six of seven patients with low lymphs died within three months of BAL compared with one in seven patients with high lymphs (p < 0.01). Within six months, all patients with low lymphs were dead whereas five of seven patients with high lymphs were alive, (p < 0.01). Comparing the two groups, there was no significant difference in percentage of BAL neutrophils, patient age, duration of disease prior to diagnosis, or arterial-alveolar oxygen gradient. CONCLUSION: In breast cancer patients with pulmonary lymphangitic metastasis, a lymphocytic alveolitis is associated with a better overall prognosis.

Adult↗

PubMed1991

Crackles in interstitial lung disease. Comparison of sarcoidosis and fibrosing alveolitis.

STUDY OBJECTIVE: Determine why crackles on chest auscultation are characteristic of most interstitial lung diseases, but may not be heard in sarcoidosis. DESIGN: All patients with sarcoidosis or cryptogenic fibrosing alveolitis seen during a four-week period were studied. In a second study to relate ausculatory findings to anatomy, patients with fibrotic changes on their chest roentgenogram were studied. SETTING: Patients were recruited from outpatient clinics. PATIENTS: In the first part, all patients seen over the course of one month were studied. In the second study, patients with pulmonary fibrosis seen on chest roentgenograms were studied. INTERVENTIONS: For the first study, two independent observers performed auscultation on five sites for crackles and reviewed four roentgenogram quadrants for changes. For the second study, patients underwent VC measurements, auscultation, and high resolution computer tomography scans. MEASUREMENTS AND RESULTS: For the first study, crackles were noted at greater than 2 sites in all 11 CFA patients, but only one of 17 SARC patients (p less than 0.001). Roentgenogram changes were seen in greater than 2 quadrants in nine of 11 CFA patients and eight of 17 SARC patients (p = ns). In the second study, the VC was similar in the two groups: SARC: 1.96 +/- .90 L (means +/- SD), 58 +/- 20.4 percent predicted; CFA: 1.81 +/- .33 L, 59 +/- 9.2 percent predicted). Only two of 14 SARC patients had crackles in greater than 1 area, while all 14 CFA patients had crackles at greater than 2 sites. The HRCT studies were read by a radiologist unaware of the diagnosis. The presence and degree (0 to 3 scale) of subpleural and peribronchial fibrosis were scored. Twelve SARC patients had peribronchial changes (mean score 1.9 +/- 1.08), while only eight had subpleural fibrosis (mean score .6 +/- .52). There was a significantly different pattern in the CFA patients, where eight had peribronchial fibrosis (mean score = .9 +/- .78, p less than 0.05) and all 14 had subpleural fibrosis (mean score = 1.6 +/- .73, p less than 0.01). CONCLUSIONS: We conclude that crackles are more frequent in fibrosing alveolitis than in sarcoidosis; this difference may be due to the distribution of parenchymal fibrosis.

Auscultation↗

PubMed1991

An inhibitor of tumor necrosis factor found in pleural effusions.

Tumor necrosis factor (TNF) has significant biologic effects. Inhibitors of TNF have been isolated from urine and blood. We studied pleural fluid from 22 patients with benign or malignant effusions. Pleural macrophages from these effusions were capable of releasing TNF, especially when stimulated with lipopolysaccharide. The cell-free supernatant from some of these pleural effusions contained an inhibitor of TNF. Fluid from 12 malignant effusions contained an inhibitor of 17% +/- 15.4% (mean +/- SD) of 500 U/ml of TNF activity, whereas the mean inhibition in 10 benign effusions was 2% +/- 5.6% (p less than 0.05). Only one of 10 benign effusions had more than 10% inhibitory activity. This inhibitor was found to be heat sensitive and unaffected by dialysis, and the molecular weight of at least one of the inhibitors was 60 to 80,000 daltons. Enzyme digestion studies were consistent with a protein portion being the major determinant of activity. We conclude that some malignant effusions contain an inhibitor of TNF activity.

Cells, Cultured↗

PubMed1990

The use of low dose methotrexate in refractory sarcoidosis.

Symptomatic sarcoidosis is usually treated with glucocorticoids; however, glucocorticoids are associated with significant morbidity. Because low dose methotrexate has been successful in treating other inflammatory diseases, methotrexate was used in patients with persistent, symptomatic sarcoidosis. Fifteen patients with either progressive advancing disease or severe side effects with prednisone were treated with methotrexate for at least 6 months. In 13 of 14 evaluable cases there was symptomatic improvement. In 12 of 14 patients there was significant improvement in objective parameters, including a greater than 15% increase in the vital capacity (5 patients), improvement in chest roentgenogram (6 patients), or a greater than 50% reduction in skin lesions (4 patients) or liver function tests (2 patients). In five patients the disease relapsed as methotrexate was being withdrawn; all patients responded to reinstitution of the drug.

Adrenal Cortex Hormones↗

PubMed1990

The effect of corticosteroid or methotrexate therapy on lung lymphocytes and macrophages in sarcoidosis.

Methotrexate appears to be an effective alternative to corticosteroid therapy for some patients with sarcoidosis. The mechanism of action of methotrexate as an immunosuppressive is unknown. Patients with symptomatic pulmonary sarcoidosis underwent pulmonary function tests and bronchoscopy with bronchoalveolar lavage. Patients were treated with 10 mg methotrexate or prednisone weekly for at least 6 months and repeat studies were performed. A comparison was made between those patients receiving methotrexate (12 patients) and those receiving prednisone (12 patients). For both groups, there was a significant improvement in the vital capacity with therapy (Prednisone: Pre = 2.5 +/- 0.14 L (Mean +/- SEM); Post = 3.1 +/- 0.18 L, p less than 0.01; Methotrexate: Pre = 2.4 +/- 0.14 L; Post = 2.8 +/- 0.18 L, p less than 0.01). In addition, the percentage of lymphocytes in the lavage fell significantly for both the prednisone (Pre: 30 +/- 3.5%; Post: 16 +/- 2.7%, p less than 0.001) and methotrexate (Pre: 37 +/- 3.4%; Post: 13 +/- 2.9%, p less than 0.001) groups. Alveolar macrophages from the symptomatic sarcoid patients were found to be spontaneously releasing hydrogen peroxide and tumor necrosis factor. After treatment with either prednisone or methotrexate, alveolar macrophages retrieved by lavage spontaneously released less of either macrophage product. We found that effective doses of methotrexate for sarcoidosis led to significant changes in lymphocyte and macrophages retrieved by lavage.

Adult↗

PubMed1990

The effect of cancer and chemotherapy on monocyte function.

Defective monocyte function has been described in human malignancies. This report assessed adherence and the production of hydrogen peroxide by peripheral blood monocytes in breast and lung cancer patients receiving cyclic chemotherapy. Monocyte adherence was similar in cancer patients and normal controls, and adherence was unchanged with chemotherapy. Release of hydrogen peroxide by adherent monocytes was measured before and after chemotherapy in 15 breast and 7 lung cancer patients and compared to cells from 15 normal controls. Monocytes from untreated breast cancer patients released significantly less hydrogen peroxide than controls (Breast = 75 +/- 17.7 nmol/10(6) monocytes; Controls = 150 +/- 19.2, p less than 0.05). Hydrogen peroxide release by monocytes decreased two weeks after chemotherapy in breast and lung cancer patients (Breast Post = 67 +/- 18.3; Lung Pre = 168 +/- 45.9; Post = 77 +/- 16.0, p less than 0.01). This effect was reversible as hydrogen peroxide release prior to the fourth chemotherapy cycle was greater than pre-chemotherapy levels. These findings suggest that chemotherapy causes a reversible impairment of monocyte function.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis.

Tumor necrosis factor (TNF) is a monokine released by macrophages and is important in the inflammatory response. We compared the spontaneous release of TNF by alveolar macrophages (AMs) from patients with symptomatic pulmonary sarcoidosis, some of whom were receiving corticosteroid therapy, with AMs from control smokers. TNF was released from AMs of sarcoidosis patients at significantly higher levels than was released by control AM subjects (sarcoids, 15 U/ml [0 to 1140 U (median [range]]); controls, all less than 5 U/ml, p less than 0.01). By using a specific polyclonal antibody, the detected TNF was found to be TNF-alpha. Among the sarcoidosis patients, the amount of TNF released was significantly lower for those patients given treatment with corticosteroids (5 U/ml [0 to 15 U/ml]) compared with untreated persons (50 U/ml [0 to 1140 U/ml], p less than 0.05). In vitro studies demonstrated that incubation of peripheral blood monocytes or AMs with dexamethasone for 42 hours suppressed subsequent release of TNF. We conclude that AMs from sarcoidosis patients often spontaneously release TNF and this release is suppressed by prolonged corticosteroid therapy.

Adrenal Cortex Hormones↗

PubMed1989

Isolation of functionally active pleural macrophages.

Pleural fluid provides an easily accessible source of tissue macrophages (MACS). We established a method for retrieval and isolation of these cells. Thirty thoracenteses were performed on patients with the clinical diagnosis of congestive heart failure or malignancy. Within 4 hr of thoracentesis, the specimen was placed on a Ficoll-Hypaque gradient, centrifuged, and the mononuclear cells were isolated. Assessment for total cell count, cell viability, and percentage of cells which were MACS as determined by nonspecific esterase staining was recorded. Pleural MACS were separated by glass adherence. In 24 cases, sufficient cells were available to measure the release of hydrogen peroxide spontaneously and with phorbol myristate acetate (PMA) stimulation. Nine of 24 specimens had spontaneous hydrogen peroxide release. In all cases, stimulation of pleural MACS resulted in a significant increase in the amount of hydrogen peroxide released. We report a simple method for retrieving viable and functionally active pleural macrophages.

Cell Count↗