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A Elias

Publications and source records attributed to A Elias.

At least 19 recordsLinked to original sources
PubMed1996

Diagnostic value of anti-RA33 antibody, antikeratin antibody, antiperinuclear factor and antinuclear antibody in early rheumatoid arthritis: comparison with rheumatoid factor.

The goal of this prospective longitudinal study was to determine the serological profile of early rheumatoid arthritis (RA), and to test whether antikeratin antibody (AKA), antiperinuclear factor (APF), anti-RA33 antibody and antinuclear antibodies (ANA) had an additional diagnostic value when prescribed after rheumatoid factor (RF)-detecting methods. Sixty-nine patients with early polyarthritis suggestive of RA, seen between 1991 and 1993, were included. Five autoantibodies (i.e. RF, AKA, APF, RA33, ANA) were looked for at regular intervals. After 24 months follow-up, patients were classified as having RA (n = 49), unclassified polyarthritis (UP; n = 15) or other rheumatic diseases. Among patients with early RA, the sensitivity of these markers was 40.8% for RF, 36.7% for AKA, 28.6% for APF and 28.6% for anti-RA33. Among RF-negative RA patients, 51.7% were positive for AKA, APF, anti-RA33 antibodies and/or ANA. Positivity of the three recent markers usually persisted throughout follow-up, whereas RF was lost by 58% of patients with early, RF-positive, treated RA. Using multivariate analysis, only latex, RF test and AKA or APF had an independent and statistically significant diagnostic value for early RA. Our data suggest that RF and AKA (or APF) should be concomitantly determined for diagnosis in patients with suspected early RA.

Adolescent↗
PubMed1995

Analysis of 4-hydroxycyclophosphamide in human blood.

Cyclophosphamide is a prodrug activated by cytochrome P450 isozymes in the liver. The product of hepatic activation of cyclophosphamide is 4-hydroxycyclophosphamide. Previously reported methods for determining 4-hydroxycyclophosphamide were either impractical or unreliable for monitoring infusion pharmacokinetics in conjunction with clinical trials. One procedure in which a fluorescent hydroxyquinoline derivative was prepared from 4-hydroxycyclophosphamide and analyzed by HPLC appeared to work at first, but gradually lost its selectivity due to degradation of the column by the strongly acidic mobile phase. An alternative procedure was developed using a weakly acidic eluent and postcolumn treatment with trifluoroacetic acid. This provided for protonation of the hydroxyquinoline, required for sensitive fluorescence detection, but spared the column. The resulting assay was sensitive, selective, reproducible, and accurate. The method was used to monitor 4-hydroxycyclophosphamide pharmacokinetics during and after 4 day infusions of 1.5 g/m2-day of cyclophosphamide given to three patients. It was also used to measure the time-dependent disappearance of acrolein and 4-hydroxycyclophosphamide added to human blood from healthy donors and that of metabolically derived 4-hydroxycyclophosphamide in the blood of a patient treated with cyclophosphamide. Slower decomposition was observed in the latter two cases than in the blood spiked with acrolein. Reliable data were obtained from > 1000 determinations using the same column without significant degradation of its stationary phase.

Chromatography, High Pressure Liquid↗
PubMed1995

High-dose ifosfamide, carboplatin, and etoposide pharmacokinetics: correlation of plasma drug levels with renal toxicity.

An autologous bone marrow transplant regimen of ifosfamide, carboplatin, and etoposide (ICE) has been developed as treatment for certain malignancies. At maximum tolerated doses renal insufficiency precludes dose escalation. The objective was to examine whether measurement of plasma drug levels early during treatment would provide warning of renal failure. Nine patients received a 96-h continuous infusion of ifosfamide 16,000 mg/m2, carboplatin 1600 mg/m2, and etoposide 1200 mg/m2. Pharmacokinetics, including drug levels and plasma concentration-time curves, of ifosfamide, ultrafiltrable platinum (uPt) and etoposide were analyzed and correlated with renal function. One of the nine patients developed anuric renal failure requiring hemodialysis. By 17 h from the start of infusion, this patient showed substantially higher drug levels of ifosfamide (200 vs mean 217 microM) and uPt (19 vs mean 10 microM) than those patients with preserved renal function. The 95% confidence intervals suggested that a 16-22 h ifosfamide level > 153 microM and an uPt level > microM predict the development of significant renal dysfunction. Although drug levels were substantially higher at 56 h, the serum creatinine did not yet reflect kidney injury. This study suggests that high plasma ifosfamide and uPt levels, analyzed early in the course of a 96-h infusion of high-dose ICE, provide warning of severe and potentially fatal renal injury. Since ICE has substantial activity in a number of malignancies, but significant renal morbidity, real-time pharmacokinetic-guided dosing may reduce treatment-related toxicity.

Acute Kidney Injury↗
PubMed1995

Weak immunogenicity of the preS2 sequence and lack of circumventing effect on the unresponsiveness to the hepatitis B virus vaccine.

The preS2 sequence is known to circumvent immunological unresponsiveness to the S protein and to induce a 'carrier' effect on the anti-S antibody production, in mice. In humans, an anti-S response was found in 100% and 97% of healthy subjects vaccinated with the S and S + preS2 preparations, respectively, whereas less than 50% of drinkers responded whatever the vaccine used. Anti-preS2 were found in 44% of healthy recipients of the S + preS2 vaccine, whereas there were no anti-preS2 responders in drinkers. Anti-preS2 remained undetectable in 32% of the blood donors hyperimmunized with the S + preS2 vaccine, whereas anti-S antibody boosted in all cases. In humans, in contrast to mice, immunogenicity of the preS2 sequence appears weak and the preS sequence does not circumvent the anti-S unresponsiveness.

Adult↗
PubMed1995

The collection and evaluation of peripheral blood progenitor cells sufficient for repetitive cycles of high-dose chemotherapy support.

BACKGROUND: The development of an optimized peripheral blood progenitor cell (PBPC) harvest protocol to provide support for repetitive chemotherapy cycles is described. STUDY DESIGN AND METHODS: PBPCs mobilized by cyclophosphamide plus granulocyte-colony-stimulating factor (G-CSF) were studied in 163 leukapheresis harvests from 26 lymphoma patients. Harvested cells were transfused with two chemotherapy cycles and with an autologous bone marrow transplant. Progenitor cell content was examined in the context of hematopoietic engraftment. RESULTS: Mobilization allowed the harvest of large numbers of PBPCs. Peak harvests tended to occur after the recovering white cell count exceeded 10 x 10(9) per L. CD34+ lymphomononuclear cell (MNC) and colony-forming units-granulocyte-macrophage (CFU-GM) counts correlated poorly, but both measures peaked within 24 hours of each other in 21 of 26 patients, which demonstrated PBPC mobilization. Engraftment of platelets (> 50 x 10(9)/L) and granulocytes (> 500 x 10(6)/L) was achieved in a median of 20.5 and 16 days, respectively. A minimum number of progenitors necessary to ensure engraftment could be derived. CONCLUSION: Cyclophosphamide and G-CSF allowed the harvest of sufficient PBPCs to support multiple rounds of chemotherapy. Harvest should commence when the recovery white cell count exceeds 10 x 10(9) per L. PBPC harvest CD34+MNC counts are as useful as CFU-GM results in the assessment of PBPC content, and they may allow harvest protocols to be tailored to individual patients.

Adult↗
PubMed1995

Prognostic factors for prolonged progression-free survival with high-dose chemotherapy with autologous stem-cell support for advanced breast cancer.

PURPOSE: With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS). METHODS: From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepa, and carboplatin with autotransplantation. Data encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS. RESULTS: The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (> or = 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066). CONCLUSION: We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach.

Adolescent↗
PubMed1994

Continuous-infusion cisplatin, 5-fluorouracil, and leucovorin for advanced non-small cell lung cancer.

BACKGROUND: Cisplatin, 5-fluorouracil, and leucovorin (PFL) have demonstrated synergistic activity in preclinical models. Continuous infusion of these agents maximizes the potential for synergistic interaction and forms the basis of the PFL regimen. METHODS: Sixty-one patients with advanced (Stages IIIB and IV) non-small cell lung cancer were entered into the study. Thirty-one were treated with cisplatin 25 mg/m2/day on days 1-5, 5-fluorouracil 800 mg/m2/day on days 2-6, and calcium leucovorin 500 mg/m2/day on days 1-6. Because of severe mucositis, the final 30 patients were treated with the same dosage of cisplatin but with the deletion on day 6 of leucovorin and 5-fluorouracil. Cycles were repeated every 28 days. Response was assessed after two cycles. Responding patients received an additional two cycles. Patients with Stage IIIB disease received radiation therapy to the mediastinum and sites of involved disease. RESULTS: PFL had an overall response rate of 41%. Median survival was 8.1 months, and median time to treatment failure was 4.2 months. Importantly, 68% (17 of 25) of responses were maximal after just two cycles of chemotherapy. Notable toxicities included mucositis (43% > or = Grade 3) and myelosuppression. Response, time to failure, or survival did not differ between the two schedules. Mucositis was less severe with 4-day PFL. CONCLUSIONS: PFL as given in this manner is an active regimen for the treatment of patients with advanced non-small cell lung cancer. The rapidity of response makes it a regimen for incorporation into protocols for Stage IIIA disease. A neoadjuvant study using PFL is underway.

Adult↗
PubMed1994

Hepatitis C virus (HCV) viremia in human immunodeficiency virus-seronegative and -seropositive patients with indeterminate HCV recombinant immunoblot assay.

Positivity of recombinant immunoblot assay (RIBA) for detection of antibodies to hepatitis C virus (anti-HCV) is usually associated with HCV viremia. The significance of an indeterminate RIBA result, defined by reactivity to only one HCV antigen, is unclear. Whether anti-human immunodeficiency virus (HIV)-negative or -positive subjects with an indeterminate RIBA have HCV viremia detectable by polymerase chain reaction was investigated. An indeterminate RIBA was found in 48 (15%) of 318 anti-HIV-negative and 38 (23%) of 167 anti-HIV-positive subjects (P < .05). Clinical stage was IV-C-1 or IV-C-2 in 82% of those anti-HIV-positive. HCV viremia was found more frequently in anti-HIV-positive (89%) than in anti-HIV-negative subjects (50%) with an indeterminate RIBA (P < .05). These results suggest an impaired anti-HCV response associated with HIV infection.

Alanine Transaminase↗
PubMed1994

Recombinant human erythropoietin for the treatment of the anaemia associated with autologous bone marrow transplantation.

Patients with solid tumours undergoing high-dose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements. Ten patients received high-dose chemotherapy (days -7 to -3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct < or = 25% and platelets for counts < 20,000/microliters. Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 x 10(9)/l) and a haematocrit > or = 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO-treated patients. Quick return of red blood cells (17 v 33 d) (P = 0.0001), platelets (14 v 19 d) (P = 0.04), and neutrophils (13 v 25 d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide-based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide-based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements. RHuEPO proved to be a well-tolerated agent in enhancing reticulocytosis following high-dose chemotherapy. Further study to elucidate the activity of erythropoietin on both erythroid and non-erythroid growth and maturation appears warranted.

Adult↗
PubMed1994

Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression.

Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.

Adolescent↗
PubMed1994

Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study.

PURPOSE: Twenty-seven percent of responding metastatic breast cancer patients remain progression-free a median 29 months following one intensification course of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European investigators report high complete response (CR) rates with melphalan for breast cancer. This trial studied the feasibility of two tandem high-dose intensification therapies in an attempt to optimize disease response and duration. PATIENTS AND METHODS: Women with at least partial responses (PRs) to induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC recovery. The women were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Twenty women were assessable. Fourteen (70%) required admission for fever (10% infection) or mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute neutrophil count (ANC) less than 500/microL and platelet count less than 20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after starting melphalan and had a hospital stay of 25 days. After CTCb, median days of ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and 24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%), mucositis (45%), and infection (20%). Toxicities were reversible without mortality. CONCLUSION: With mobilized PBPCs and growth factors, double dose-intensive chemotherapy is feasible with acceptable toxicity. When compared with trials using marrow alone, these supportive adjuncts decrease sepsis and organ toxicity. The concepts of dose and dose-intensity may now be more effectively and safely studied in chemosensitive tumors, including breast cancer.

Adult↗
PubMed1994

Phase II study of topotecan in metastatic non-small-cell lung cancer.

PURPOSE: Topotecan is an inhibitor of topoisomerase I that has shown preclinical activity against non-small-cell lung cancer (NSCLC). This phase II study was designed to determine the clinical activity and toxicity spectrum of topotecan in untreated patients with metastatic NSCLC. PATIENTS AND METHODS: Twenty previously untreated patients received topotecan every 21 days at the dose of 2 mg/m2/d intravenously (IV) for 5 days for two cycles, at which point response was assessed. Patients with either clinical response or stable disease (SD) received additional cycles of the drug until toxicity developed or disease progression (PRG) occurred. RESULTS: This study was designed to enter 30 patients. However, because no clinical responses were seen in the first 20 patients entered onto the study, the early-stopping rule was invoked and patient accrual was halted. Eleven patients (55%) had SD on topotecan, and nine (45%) had PRG. Toxicity included neutropenia and rash. The median survival duration for all patients was 7.6 months. CONCLUSION: We observed no objective clinical responses despite producing high-grade neutropenia. Phase II trials of topotecan using different schedules or higher doses supported by growth factors may clarify the role of topotecan in the treatment of NSCLC. The combination of topotecan with cisplatin and topoisomerase II inhibitors such as etoposide should be explored. Finally, the median survival duration of 7.6 months for 20 patients treated with an agent that failed to produce any obvious clinical responses compares favorably to the survival obtained with combinations of existing agents. This supports the further study of novel compounds in this clinical setting.

Aged↗
PubMed1994

High-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy: analysis by age.

The analysis was undertaken to determine if the time to progression and survival for women with breast cancer treated with high-dose chemotherapy after a conventional-dose induction therapy differs significantly for women younger and older than 40 years of age. All patients treated in phase II or III protocols of high-dose chemotherapy for breast cancer are included in this analysis. Women were treated on one of six protocols: four sequential phase II protocols for metastatic breast cancer involving cyclophosphamide at a dose of 6000 mg/m2, thiotepa at 500 mg/m2, and carboplatin at 800 mg/m2 (CTCb) chemotherapy; one phase II study of CTCb chemotherapy for stage III or inflammatory breast cancer; and a Cancer and Leukemia Group B phase III study of cyclophosphamide, carmustine, and cisplatin for women with more than 10 involved lymph nodes after primary therapy. Eligibility criteria for the patients with metastatic disease included histologically documented breast cancer, at least a partial response to conventional dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m2, and physiologic age of 18-55 years. Patients with inadequate renal, hepatic, pulmonary, and cardiac function or tumor involvement of marrow or central nervous system were excluded. Of 99 registered patients, three (3%) died of toxicity. There were no toxic deaths in protocols for stage II and III disease, and to date none of these patients have relapsed. Thus, there are no differences by age for these studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of long term oral anticoagulants upon prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-Dimer levels in patients affected by proximal deep vein thrombosis.

We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 +/- 17 years, mean +/- SD) were sampled at the beginning of the OAC treatment (day 1), which was started 1 to 6 days after diagnosis confirmation and full heparinization, and then 8, 35 and 92 days after. The results were compared to those obtained in a blood donor population (39 +/- 10 years) and to an age-matched healthy population (63 +/- 19 years). The mean INR determined on days 8, 35 and 92 were almost identical (2.8 +/- 0.7, 2.9 +/- 0.9 and 2.8 +/- 0.6 respectively). In contrast, highly significant variations of the three markers were recorded during the observation period. Eight days after the beginning of OAC, increased levels of TAT complexes were associated with subnormal levels of F1 + 2 suggesting persistence of a hypercoagulable state. On the further sampling times, TAT complexes were in the normal range while F1 + 2 were far below the normal range. Between day 1 and day 92, the levels of D-Dimer continuously decreased reflecting a long-term fibrinolytic process. This study clearly indicates that high INR are not systematically associated with very low F1 + 2 levels, particularly in the acute phase of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Chronic non-B, non-C hepatitis among blood donors assessed with HCV third generation tests and polymerase chain reaction.

Forty five blood donors with increased serum aminotransferases levels had liver histologic assessment and were tested for antibodies to hepatitis C virus (anti-HCV) with second and third generation ELISAs and RIBAs, and for HCV RNA with polymerase chain reaction (PCR) in serum and liver tissue. Twenty-nine of these 45 donors (65%) had steatosis without chronic hepatitis. Sixteen (35%) had chronic hepatitis. Twelve had evidence of HCV infection. Four had no evidence of HCV infection demonstrable by ELISA, RIBA or PCR. These four patients had no known cause of chronic hepatitis and no risk factor for parenterally acquired viral infection was found in them. This observation supports the hypothesis that a non-B, non-C virus might be implicated in chronic hepatitis. However, this hypothesis remains to be demonstrated.

Blood Donors↗
PubMed1993

High-dose chemotherapy with autologous stem cell support for breast cancer: a review of the Dana-Farber Cancer Institute/Beth Israel Hospital experience.

The overall median survival of women with advanced or high-risk primary breast cancer has not changed with conventional chemotherapy. Regimens employing high-dose chemotherapy with autologous stem cell support (ABMT) have been developed with the hope of optimizing tumor response and increasing survival. Early phase I studies in women with advanced refractory disease achieved high response rates of short duration. Second generation studies combined an induction phase followed by one high-dose intensification at time of maximum tumor response. The Dana-Farber Cancer Institute/Beth Israel Hospitals have developed the high-dose intensification regimen of cyclophosphamide, thiotepa, and carboplatin (CTCb) for use in women with metastatic and high-risk stage IIIB/inflammatory breast cancer. To date, approximately 19% of women with metastatic disease remain progression free using this approach, with median length of follow-up approaching 40 months. Although the median duration of follow-up for the stage IIIB women is much shorter (approximately 12 months), greater than 90% of these women are thus far disease free. With the advent of hematologic support, such as blood stem cells and colony-stimulating factors, the morbidity, mortality, and costs associated with this treatment have been substantially reduced, allowing for two or more cycles of high-dose intensification to be employed, to exploit the potential of dose-intensity to optimize response.

Adenocarcinoma↗