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Biomedical subjects

E E Lower

Publications and source records attributed to E E Lower.

At least 19 recordsLinked to original sources
PubMed2005

Fungal infections as a complication of therapy for sarcoidosis.

BACKGROUND: Treatment of symptomatic sarcoidosis usually includes systemic immunosuppressive agents. These agents may render the patient more susceptible to opportunistic infections. In addition, the fungal infection may be difficult to distinguish from the underlying sarcoidosis. AIM: To examine the presentation and management of invasive fungal infections in sarcoidosis patients. DESIGN: Retrospective record review. METHODS: We reviewed the notes of all sarcoidosis patients (n = 753) seen at our clinic over an 18-month period. RESULTS: Seven patients (0.9%) with previously diagnosed sarcoidosis developed fungal infections: two each with Histoplasma capsulatum and Blastomyces dermatitidis and three others with Cryptococcus neoformans. No cases of invasive aspergillus or tuberculosis were identified. The diagnosis of fungal infection was made by bronchoscopy (four cases), open-lung biopsy (one case), bone-marrow aspirate (one case), and spinal fluid examination (one case). All patients were receiving corticosteroids at the time of worsening chest X-ray or clinical status. Four patients were also receiving methotrexate prior to infection. No patient with systemic fungal infection was receiving either infliximab or cyclophosphamide. All patients responded to anti-fungal therapy and a reduction in immunosuppression. DISCUSSION: Fungal infections occur rarely in treated patients with sarcoidosis. Deterioration of chest X-ray, especially a localized infiltrate, warrants investigation.

Antifungal Agents↗
PubMed2005

Infliximab in chronic ocular inflammation.

OBJECTIVE: Infliximab is a chimeric antibody which binds tumor necrosis factor (TNF). It is effective in several chronic inflammatory conditions, including sarcoidosis. METHODS: We report our experience with infliximab in chronic ocular inflammation as part of a retrospective review of all patients treated for chronic inflammatory ocular conditions seen over a 2-year period at our institution. RESULTS: 14 patients with various underlying ocular conditions were treated during the previous two years including patients with sarcoidosis (7), Crohn's disease (2), birdshot choroiditis (2), idiopathic disease (2), Volt-Koyanagi-Harada (1) and Behçet's disease (1). All patients had persistent inflammation despite systemic immunosuppressive agents and all but one patient experienced marked improvement in ocular inflammation with infliximab. One patient was non-compliant and non-evaluable; four patients, who had previously received etanercept with either no response (3 patients) or subsequent relapse (1 patient), responded to infliximab. CONCLUSION: Infliximab is an effective therapy in chronic inflammatory eye disease, especially when related to sarcoidosis.

Adult↗
PubMed2001

Infliximab for refractory sarcoidosis.

BACKGROUND AND AIM OF WORK: Tumor necrosis factor-alpha (TNF-alpha) appears to be an important cytokine in the inflammation of sarcoidosis. Infliximab is a chimeric monoclonal antibody which specifically inhibits TNF-alpha. We investigated the efficacy of infliximab for the therapy of chronic, resistant sarcoidosis. METHODS: Patients with persistent symptomatic sarcoidosis despite corticosteroids and immunosuppressive agents were selected for treatment with infliximab. Patients were treated initially and at 2, 4, and 12 weeks with 5 mg/kg of infliximab at each treatment. Index lesions, which had progressed despite corticosteroid therapy, were reevaluated at 16 weeks. RESULTS: Three patients were treated. In two patients, the index lesion was lupus pernio, which significantly improved with infliximab. The third patient had restrictive lung disease. At week 16, there was a 26% improvement in the vital capacity from pretreatment values. All patients tolerated the treatments well. CONCLUSIONS: Infliximab was associated with significant improvement in chronic sarcoidosis.

Antibodies, Monoclonal↗
PubMed2001

Combination therapy for sarcoidosis.

Combination therapy has proved useful in infectious, rheumatologic, and oncologic diseases. The role of combination therapy in sarcoidosis is less defined. A stepwise approach to therapy in sarcoidosis treatment includes multiple agents, such as topical and systemic corticosteroids. The introduction of cytotoxic agents has led to the combination of these drugs with lowered doses of corticosteroids. Recently, the combination of cytotoxic and immune modifiers has been used for some cases of refractory sarcoidosis. The rationale use of combination therapy may enhance efficacy with reduced toxicity.

Adrenal Cortex Hormones↗
PubMed2001

Breast disease in sarcoidosis.

BACKGROUND: Breast disease in sarcoidosis can be classified as sarcoidosis patients with breast granulomas, sarcoidosis patients with breast cancer, and breast cancer patients displaying sarcoidosis-like breast reactions. METHODS: We reviewed the medical records of 629 women with sarcoidosis followed in the Interstitial Lung Disease Clinic at the University of Cincinnati for findings associated with breast disease. In addition, three women with breast cancer who had granulomas in proximity to their tumors were also examined. RESULTS: Abnormal breast examinations or mammograms were reported in 15 patients with sarcoidosis (2% of women with sarcoidosis). Breast biopsy revealed granulomas consistent with sarcoidosis in six. One of them developed breast cancer five years later. Breast cancer was identified in twelve further patients, therefore a total of thirteen patients with breast cancer were identified. Ten were diagnosed with breast cancer plus sarcoidosis: sarcoidosis preceded breast cancer in three, followed breast cancer in five, the two diseases appeared simultaneously in two. Three additional women with breast cancer were also evaluated and classified as patients with sarcoid-like reaction. Review of the mammographic and physical findings could not distinguish between sarcoidosis in the breast and breast cancer. CONCLUSION: Sarcoidosis patients develop breast cancer at the expected frequency. The breast cancer diagnosis may precede or follow that of sarcoidosis. There is no relationship between stage of sarcoidosis or treatment and the development of cancer. Because physical examination and mammography findings are unable to distinguish between sarcoidosis and malignancy, biopsy of all suspicious lesions in sarcoidosis is recommended.

Adrenal Cortex Hormones↗
PubMed2000

Bilateral synchronous breast cancer: mode of detection and comparison of histologic features between the 2 breasts.

BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%-2.6% of all patients with breast cancer), and most physicians do not accumulate a large personal experience of patients with this disease. We reviewed our experience with patients with bilateral synchronous breast cancer, focusing on the mode of detection and histologic features in the 2 breasts. METHODS: The charts of patients who were treated at this institution for bilateral synchronous breast cancer during the 15-year period of 1984 through 1999 were reviewed. Information regarding age, mode of detection, histopathologic features, treatment, and overall survival were analyzed. RESULTS: During the study period, 51 patients (all women) were treated at our institution for bilateral synchronous breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated for breast cancer during the same period of time. The first cancer was detected by palpation in 81% and by mammography in 14%. The corresponding figures for the contralateral cancer were 24% and 54%, respectively. The histologic type of cancer was identical in the 2 breasts in 29 patients (57%) and was different between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was 63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by mammography and is frequently of the same histologic type as the index cancer. A better awareness of the risk for this disease may help detect bilateral breast cancer earlier.

Adult↗
PubMed2000

Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial.

BACKGROUND AND AIM OF THE WORK: Methotrexate has been steroid sparing for some patients with chronic sarcoidosis. We wished to determine whether methotrexate can be steroid sparing in the first year of corticosteroid therapy in sarcoidosis. METHODS: Patients with new onset, symptomatic disease within four weeks of starting on prednisone were randomized to receive either methotrexate or placebo for the next year. They were seen monthly and prednisone dosage was tapered following a pre-determined schedule. RESULTS: Of 24 patients enrolled, only 15 received at least six months of therapy. Since methotrexate appears to take six months to be effective, only patients who completed six or more months of therapy were evaluated. The amount of prednisone per day decreased for both groups: methotrexate (First 6 months: Median 26 (Range 15-37) mg/day); Second 6 months 8 (1-22) mg/day, p < 0.01) and placebo (First 6 Months 28 (24-33) mg/day; Second 6 months 16 (11-22) mg/day, p < 0.02), with less prednisone used for the methotrexate patients versus placebo in the last six months (p < 0.01). There was also less weight gain for those patients receiving methotrexate. There was no difference in toxicity between methotrexate and placebo. The difference between methotrexate versus placebo was not seen when all patients (including the dropouts) were analyzed. CONCLUSIONS: Methotrexate can be a steroid sparing agent in acute sarcoidosis.

Adult↗
PubMed1999

The effect of estrogen usage on the subsequent hormone receptor status of primary breast cancer.

In order to determine if prior use of exogenous estrogens was related to the estrogen receptor (ER) content of primary breast cancers, a retrospective analysis was performed from 536 patients with invasive breast cancer. The patient's age, menopausal status, oral contraceptive or estrogen replacement therapy usage, and the ER and progesterone receptor (PR) content of the breast cancer were recorded for all patients. Hormone usage in premenopausal and postmenopausal patients was compared to ER and PR levels in primary breast cancers using non-parametric testing. Complete information was available from 508 (193 premenopausal and 315 postmenopausal) patients. Breast cancers were ER positive in 72% of postmenopausal patients and 57% of premenopausal patients. The majority of patients received 'Some' form of hormone therapy (111 of 193 premenopausal patients and 233 of 315 postmenopausal patients). Significantly more estrogen receptors were detected in tumors from patients receiving 'some' estrogen therapy compared to 'never' users. Postmenopausal patients 'never receiving estrogen therapy had a lower rate of ER positive tumors (62%) compared to 'some' users (75%, chi2 = 4.99, p < 0.05). The same relationship was seen for PR ('never' users 44% positive, 'some' users 58% positive, chi2 = 5.19, p < 0.05). We conclude that postmenopausal patients who received 'some' estrogen therapy are more likely to have breast cancers that are estrogen receptor and progesterone receptor positive.

Adult↗
PubMed1999

The risk of premature menopause induced by chemotherapy for early breast cancer.

The objectives of this retrospective case series were to determine the prevalence and timing of menstrual abnormalities in early-stage breast cancer patients undergoing adjuvant methotrexate or anthracycline-based chemotherapy and to more fully assess the possible mechanism of the amenorrhea reported after chemotherapy. One hundred forty-two premenopausal patients undergoing adjuvant chemotherapy were analyzed for patient age, breast cancer stage, type of chemotherapy, and menstrual abnormalities before, during, and after chemotherapy completion. A 24-month minimum follow-up after chemotherapy completion was available for all patients. One hundred nine of 142 patients were evaluable. Sixty-nine patients (46 node negative, 23 node positive) received methotrexate-based chemotherapy, 33 patients (3 node negative, 30 node positive) received anthracycline-based chemotherapy, and 7 patients received both treatments (all node positive). Amenorrhea occurred in about a third of patients during chemotherapy (methotrexate groups 31%, anthracycline group 33%), and a higher proportion were amenorrheic 1 year after chemotherapy was completed (methotrexate group 45%, anthracycline group 46%). Abnormalities were more likely to occur in older premenopausal patients (Chi square = 6.18, p < 0.05), although 28% of patients under age 35 developed persistent abnormal menses. In some amenorrheic patients, follicle-stimulating hormone (FSH) levels were decreased within 6 months of chemotherapy (24.4 IU). The levels tended to be higher after chemotherapy (59.1 IU), suggesting ovarian failure. Menstrual abnormalities and menopause will frequently occur in premenopausal early-stage breast cancer patients, with 30% of all patients amenorrheic 1 year after chemotherapy.

Adult↗
PubMed1999

Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis.

BACKGROUND AND AIM: A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-alpha in lung tissue of patients with idiopathic pulmonary fibrosis compared to control lung tissue. METHODS: Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale. RESULTS: Eleven patients with IPF were compared to seven control subjects. TGF-alpha immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF-R, one of the receptors for TGF-alpha, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. CONCLUSIONS: TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells.

Adult↗
PubMed1997

Diagnosis and management of neurological sarcoidosis.

BACKGROUND: Neurological involvement is a significant cause of morbidity and mortality in patients with sarcoidosis. Detection and management of neurosarcoidosis remains problematic. Our interest in immunosuppressive agents for chronic sarcoidosis has given us experience with various agents for the treatment of sarcoidosis, including cyclophosphamide and methotrexate. METHODS: We analyzed all patients with sarcoidosis seen in our clinic during a 10-year period. Evaluation for neurological disease included routine physical examination. Magnetic resonance imaging, cerebral spinal fluid analysis, and neural tissue biopsy were performed where clinically indicated. Patients were treated with corticosteroids, methotrexate, or cyclophosphamide. RESULTS: Neurological disease was identified in 71 of 554 patients with sarcoidosis. Seventh (facial) cranial nerve paralysis was the most common manifestation identified in 39 patients. This included 24 patients with facial nerve palsy as the only manifestation of neurological sarcoidosis in whom complete recovery was seen in all but 1 patient. Forty-eight patients with disease other than facial nerve palsy received corticosteroids or other therapies. Corticosteroids benefited only 14 patients (29%). Methotrexate successfully treated 17 (61%) of 28 patients and cyclophosphamide controlled disease in 9 (90%) of 10 assessable patients. Methotrexate and cyclophosphamide were each associated with a higher response rate than corticosteroids alone (chi 2, 14.6; P < .001). CONCLUSIONS: Neurological symptoms can be significant manifestations of sarcoidosis. Facial nerve paralysis is a common, but usually self-limited form of disease. Other manifestations are usually chronic and agents other than corticosteroids appear to have increased efficacy with lower morbidity.

Central Nervous System Diseases↗
PubMed1997

Quantitation of vascular endothelial growth factor mRNA levels in human breast tumors and metastatic lymph nodes.

In situ hybridization analysis provides a means to qualitatively study the heterogeneity of primary tumors and metastases based on the types of genes transcribed. In this study, we have tested some parameters for quantitative analysis of in situ hybridizations with paraffin-embedded human breast tumors and measured mRNA levels for the angiogenic protein, vascular endothelial growth factor (VEGF). VEGF mRNAs were highly tumor specific, with the highest levels near necrotic regions within the tissues (0.1 to 2.7 dpm/mm2). Normal cells within the tissue sections did not have detectable levels of VEGF mRNA. For comparison, tumor levels of c-myc (4 to 46 dpm/mm2) and glyceraldehyde-3-phosphate dehydrogenase mRNAs (48 to 214 dpm/mm2) were measured. The mRNAs for both of these genes were more broadly expressed across the tissue sections. The hybridization pattern for VEGF mRNAs was consistent with hypoxia-induced VEGF mRNA steady-state levels and supports the hypothesis that oxidative stress regulates VEGF expression in breast tumors.

Biomarkers, Tumor↗
PubMed1997

Steroid-sparing alternative treatments for sarcoidosis.

Alternatives to corticosteroids for the treatment of sarcoidosis are reviewed. These include cytotoxic agents such as methotrexate, azathioprine, and cyclophosphamide. In addition, agents such as hydroxychloroquine and cyclosporine are reviewed. The efficacy, toxicity, and timing of these drugs in the management of sarcoidosis is discussed.

Antimalarials↗
PubMed1997

Sleep apnea in sarcoidosis.

BACKGROUND AND AIM OF WORK: Sleep apnea is reported to occur in 2-4% of the general population. Patients with sarcoidosis are at increased risk for sleep apnea, possibly due to factors such as steroid use, neurosarcoid, or upper airway obstruction. METHODS: In order to determine the prevalence and risk factors for sleep apnea in sarcoidosis patients, we studied 83 consecutive patients with sarcoidosis seen over a six-week time period. Patients were screened using the Epworth Sleepiness Scale questionnaire and the age, sex, race, weight, and medications were recorded. The presence of previously diagnosed sleep apnea, neurosarcoid, lupus pernio, and sinus disease were also noted. A control group of 91 patients seen in general pulmonary clinics were similarly screened. Patients with a positive sleep questionnaire were referred for sleep studies. RESULTS: A total of 14 sarcoid patients (17%) were found to have sleep apnea, which was significantly higher than our control group with 3/91 (3%, p < 0.001). The presence of lupus pernio was significantly more frequent in the sleep apnea group. Although 5/51 (10%) female sarcoid patients had sleep apnea, overall it was more frequent in male sarcoid patients. CONCLUSIONS: Sleep apnea was frequent in sarcoid patients and was associated with lupus pernio.

Adult↗