Biomedical subjects

Judith Abrams

Publications and source records attributed to Judith Abrams.

23 records · Page 2Linked to original sources

PubMed2003

Decreased exhaled nitric oxide in sickle cell disease: relationship with chronic lung involvement.

A deficiency in airway nitric oxide (NO) could contribute to pulmonary vaso-occlusion in sickle cell disease (SCD). We measured the fractional expired concentration of NO (FE(NO)) by chemiluminescence during a slow vital capacity maneuver against a positive pressure of 16 cm H(2)O at an expiratory flow rate of 50 mL/sec in 44 stable ambulatory adults with SCD and 30 healthy controls. A history of acute chest syndrome was present in 29 patients, and 22 complained of dyspnea. Mean +/- SD FE(NO) was significantly reduced in the SCD group compared with controls (14.8 +/- 8.4 vs. 24.9 +/- 13.5 ppb, P < 0.001). SCD patients with dyspnea had lower FE(NO) than those without dyspnea (10.1 +/- 5.7 vs. 19.6 +/- 8 ppb, P < 0.001) and those with a history of ACS had lower values than those no episodes of ACS (13.0 +/- 8.3 vs. 18.4 +/- 7.6 ppb, P < 0.05). There was a weak correlation between FE(NO) and percent-predicted DLCO (r = 0.4, P = 0.02) among the SCD patients. We conclude that exhaled NO is reduced in adults with SCD, and this may play a role in the pathogenesis of acute chest syndrome and chronic sickle cell lung disease.

Adult↗

PubMed2002

Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease.

We partitioned exhaled nitric oxide (NO) into alveolar concentration (CA) and conducting airway flux (JNO(air,max)) in scleroderma (SSc) lung disease and hypothesized that CA would be elevated. Twenty patients with SSc, 15 with interstitial lung disease (SSc-ILD) alone, and 5 with pulmonary hypertension (SSc-PH) were compared with 20 control subjects. CA and JNO(air,max) were derived from the slope and y intercept, respectively, of the NO output versus expiratory flow rate ((V).exh) relationship obtained by measuring exhaled NO (FE(NO)) at multiple (V).exh values of 50-200 ml/second. There were no significant differences in FE(NO) at any (V).exh between the SSc group and control subjects. JNO(air,max) was reduced (0.6 +/- 0.1 versus 1.2 +/- 0.2 nl of NO per second; p = 0.01), whereas CA was increased (4.7 +/- 0.5 versus 1.8 +/- 0.2 ppb; p < 0.001) in the SSc group compared with control subjects. No differences were noted between SSc-ILD and SSc-PH. There was a negative correlation between CA and DL(CO) among the patients with SSc (R = -0.66, p = 0.002). We conclude that CA is increased whereas JNO(air,max) is decreased in SSc-ILD and SSc-PH. A reduced diffusing capacity of NO from the alveolar space into the blood could explain the observed increase in CA.

Female↗

PubMed2002

Ethnic differences in survival among women with ovarian carcinoma.

BACKGROUND: Ovarian carcinoma is the leading cause of death among all female reproductive malignancies. There are substantial differences in age-adjusted incidence rates and survival rates between Caucasian women and African-American women. The objective of this study was to examine ethnic differences in survival after ovarian carcinoma in a population-based sample of women. METHODS: Thirteen thousand eighty-three patients (12285 Caucasian women and 798 African-American women) who were diagnosed with primary ovarian carcinoma from the population-based Surveillance, Epidemiology, and End Results (SEER) Program were used for analysis. Odds ratios were used to estimate the association between prognostic variables and ethnicity. Chi-square tests were used to determine the statistical significance of these associations (using two-sided P values). Univariable and multivariable Cox proportional hazards models were used to assess survival differences. RESULTS: African-American women were significantly younger at the time of diagnosis, were more likely to be single, and were less likely to undergo site specific surgery compared with Caucasian women. In addition, the crude median survival for African-American women was nearly 1 year less than for Caucasian women (22 months vs. 32 months, respectively; P < 0.0001). African-American women were at a 30% increased risk of death from any cause when adjusting for all other prognostic variables that differed between the two ethnic groups. CONCLUSIONS: African-American women who are diagnosed with ovarian carcinoma are at a significant increased risk of death from any cause compared with Caucasian women who are diagnosed with ovarian carcinoma.

Adult↗

PubMed2002

Active immunotherapy of metastatic melanoma with allogeneic melanoma lysates and interferon alpha.

PURPOSE: A therapeutic lyophilized melanoma vaccine consisting of two mechanically disrupted allogeneic melanoma cell lines and the immunological adjuvant Detox-PC (Melacine) has demonstrated encouraging activity in metastatic malignant melanoma, often in regimens containing pretreatment with low-dose cyclophosphamide. In addition, IFN-alpha2b (INTRON A; Schering-Plough Corporation, Kenilworth, NJ) has shown efficacy in melanoma refractory to Melacine. In this Phase II trial, the combination of cyclophosphamide, Melacine, and IFNalpha was tested in metastatic malignant melanoma. EXPERIMENTAL DESIGN: Eligibility criteria included measurable disease, no prior systemic therapy for a minimum of 4 weeks, and adequate marrow, renal, and hepatic function. Cyclophosphamide was administered once at a dose of 300 mg/m(2) i.v. on day -3 before the first dose of Melacine. Melacine was administered at a dose of 2 x 10(7) tumor cell equivalents per dose admixed with 0.25 ml of Detox-PC s.c. once a week on weeks 1-4 and week 6. Melacine maintenance was then given monthly from the 8th week, until progression or intolerable toxicity. IFN was started in the evening after the fourth dose of Melacine at a dose of 5,000,000 units/m(2) 3 times a week, and continued until progression. RESULTS: Forty-seven patients were enrolled, of whom 39 completed the full course and were considered evaluable. The toxicity of the regimen was minimal and consisted mainly of pain at injection sites and granulomas caused by Detox-PC, and constitutional symptoms attributable to IFN. In 39 evaluable patients, the overall objective response rate was 10.2%, but 64% of patients had stabilization of their disease for at least 16 weeks. The median time to disease progression in evaluable patients was 8 months [95% confidence interval (CI), 6-13 months]. Median survival time for all of the 47 patients enrolled was 12.5 months (95% CI, 8-15 months) with a median time to disease progression of 4 months (95% CI, 3-7 months). CONCLUSION: Despite a low objective response rate, this combination holds great promise because of its tolerability and the high proportion of prolonged durations of remission or disease stabilization that it elicited.

Adult↗

PubMedDate not supplied

Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein.

Prostate cancer frequently metastasizes to the bone, and the treatment outcome for metastatic prostate cancer has been disappointing so far. Dietary genistein, derived primarily from soy product, has been proposed to be partly responsible for the low rate of prostate cancer in Asians. Our previous studies have shown that genistein elicits pleiotropic effects on prostate cancer cells, but there are no studies documenting comprehensive gene expression profiles and antitumor effects of dietary genistein on human prostate cancer grown in human bone environment. In this study, we investigated the effects of genistein on PC3 prostate cancer cells and experimental PC3 bone tumors created by injecting PC3 cells into human bone fragments previously implanted in severe combined immunodeficient (SCID) mice (SCID human model). We found that genistein significantly inhibited PC3 bone tumor growth using both prevention and intervention strategies. By using microarray and real-time polymerase chain reaction technology, we found that genistein regulated the expression of multiple genes involved in the control of cell growth, apoptosis, and metastasis both in vitro and in vivo. For example, the expression of various metalloproteinases (MMPs) in PC3 bone tumors was inhibited by genistein treatment, whereas osteoprotegerin was upregulated. MMP immunostaining and transfection experiments also demonstrated that MMP-9 expression was inhibited in PC3 cells in vitro and PC3 bone tumors in vivo after genistein treatment. These results, particularly the in vivo results, demonstrate that dietary genistein may inhibit prostate cancer bone metastasis by regulating metastasis-related genes. Genistein may thus be a promising agent for the prevention and/or treatment of prostate cancer.

Animals↗