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Biomedical subjects

C I Chen

Publications and source records attributed to C I Chen.

At least 19 recordsLinked to original sources
PubMed2006

Sequential, cycling maintenance therapy for post transplant multiple myeloma.

High-dose chemotherapy with autologous stem cell transplantation in patients with newly diagnosed multiple myeloma can prolong survival but is not curative. Maintenance therapy post transplant may prolong the disease-free interval and impact overall survival. We have conducted a phase II pilot study of 28 post transplant myeloma patients treated with a sequential, cycling maintenance regimen. The regimen was designed to include a variety of active myeloma agents chosen for ease of administration to enhance patient compliance and scheduled sequentially to minimize toxicity. The 12-month cycling schedule included dexamethasone (months 1-3); melphalan and prednisone (months 4, 5); cyclophosphamide and prednisone (months 6, 7); alpha-interferon (months 8-10); followed by a drug holiday (months 11, 12). The regimen was generally well tolerated with five patients developing reversible grade III-IV toxicity (diabetes-induced hyperglycemia in four, neutropenia in one). There was one toxic death on study due to non-neutropenic pneumonia and sepsis. Median event-free survival from transplant was 36.9 months (95% CI 23.6 - upper limit not yet reached) with median overall survival not yet reached at a median follow-up of 44 months. This concept of cycling, sequential maintenance with various agents, perhaps including newer biological, targeted agents, warrants further investigation in multiple myeloma.

Anti-Inflammatory Agents↗
PubMed2004

Treatment for Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia is a rare form of indolent lymphoma characterized by the production of a monoclonal immunoglobulin M protein, and complications such as hyperviscosity, cytopenias and peripheral neuropathy. Conventional treatment approaches are based on alkylators or nucleoside analogs, but in the absence of a clearly superior regimen, a broad array of alternative therapies exists. Choices range from biological agents to combination chemotherapy to stem-cell transplantation. A rational approach therefore must be based on careful patient assessment and individualization of therapy.

Antineoplastic Agents, Alkylating↗
PubMed2003

Intermediate dose thalidomide (200 mg daily) has comparable efficacy and less toxicity than higher doses in relapsed multiple myeloma.

Thalidomide at doses >200 mg has 100% grade 1-2 and 25% grade 3-4 toxicities requiring discontinuation. We report a retrospective study of relapsed myeloma patients treated with thalidomide 200 mg with no dose escalation. Thirty patients were identified; 43% of patients responded with paraprotein decline >75% -- 2 (6%), 50-75% -- 7 (23%), 25-50% -- 4 (14%) and 2 (6%) were stable. All five patients with 13q deletion responded. Only 54% reported grade 1-2 toxicities (none reporting > grade 2) with 5 (17%) discontinuing treatment due to toxicity. Thalidomide 200 mg daily with no dose escalation appears as effective and better tolerated than escalated doses for relapsed myeloma patients.

Adult↗
PubMed2002

'Relative' chemotherapy sensitivity: the impact of number of salvage regimens prior to autologous stem cell transplant for relapsed and refractory aggressive non-Hodgkin's lymphoma.

The purpose of the study was to assess the impact of number of salvage regimens needed to demonstrate chemotherapy sensitivity on relapse rates, survival, and toxicity following high-dose therapy and autologous bone marrow transplantation (ABMT) in relapsed or refractory non-Hodgkin's lymphoma. We retrospectively reviewed 136 patients with intermediate-grade lymphoma who underwent ABMT. All patients were treated with salvage therapy to maximum tumor reduction. Three quarters (102/136) of the patients received one salvage regimen, while 31 (23%) patients received two or more regimens. When compared to patients requiring >or= two regimens, patients requiring only one salvage regimen to demonstrate chemosensitivity were more likely to have a longer previous CR from initial therapy (CR >or=12 months in 47% vs 26%; P = 0.04) and to have attained CR with salvage (54% vs 16%; P = 0.001). Both median relapse-free survival (RFS) and overall survival (OS) have not yet been reached in patients receiving one salvage regimen (median follow-up 50.6 months). This is superior to the median RFS of 9.1 months (P = 0.004) and OS of 11.1 months in patients requiring >or=two regimens to demonstrate chemosensitivity (P = 0.002). Time to engraftment, toxic deaths and incidence of myelodysplasia were similar in the groups. The survival rate observed in patients requiring >or=two salvage regimens, although inferior to that of patients receiving a single salvage regimen, are still generally superior to results in the literature for patients treated with chemotherapy alone without ABMT. We conclude that high-dose therapy with ABMT is appropriate for lymphoma patients even when disease reduction requires repeated numbers of salvage regimens.

Adult↗
PubMed2001

Radiation-associated pneumonitis following autologous stem cell transplantation: predictive factors, disease characteristics and treatment outcomes.

High-dose therapy followed by autologous stem cell transplantation (ASCT) prolongs survival in patients with multiple myeloma and is relatively safe with treatment-related mortality rates of only 1-5%. Interstitial pneumonitis (IP) is normally an infrequent complication of ASCT with a reported incidence of 0-16%. Between 1992 and 1998, 94 myeloma patients at our center underwent ASCT using a high-dose regimen of etoposide (60 mg/kg), melphalan (160 mg/m2) and fractionated TBI 12 Gy. An unusually high incidence of IP (29/94 (31%)) was noted. Mortality in the IP patients was high at 45%. Patients developing IP were more frequently anemic than those who did not have pulmonary complications (hemoglobin <100 g/l) prior to transplant (P = 0.03) but no other pre-transplant factors were predictive (ie age, gender, smoking history, CMV status, pulmonary function, creatinine, beta2-microglobulin or C-reactive protein, prior cumulative chemotherapy or chest irradiation). A significantly lower IP rate was noted in 32 contemporaneous myeloma control patients conditioned with BU-CY without TBI at our center (3/32 (9%); P=0.03) and in 32 lymphoma control patients conditioned with the same melphalan and etoposide regimen minus the TBI (2/32 (6%); P = 0.003). In contrast, when using the same TBI-containing regimen in 32 concurrently treated lymphoma patients, an increase in IP similar to that seen in our myeloma cohort (7/32 (22%); P = 0.3) was noted. This strongly suggests that TBI is the predominant factor contributing to lung toxicity. We conclude that radiation-associated pneumonitis cannot be easily predicted by pretransplant variables. Therefore surveillance, early recognition and prompt therapy are recommended.

Adult↗
PubMed2001

Autotransplants for histologically transformed follicular non-Hodgkin's lymphoma.

Histological transformation from a follicular non-Hodgkin's lymphoma (NHL) to a higher grade lymphoma carries a poor prognosis despite treatment with aggressive anthracycline-based chemotherapy. We retrospectively analysed 35 patients with histologically transformed NHL who underwent high-dose therapy and autotransplantation at our centre. Patients up to 65 years old were eligible for autotransplant at the time of transformation or with subsequent relapses, provided that chemosensitivity to a salvage regimen could be demonstrated. All patients received high-dose therapy [etoposide 60 mg/kg, melphalan 160 mg/m2 and fractionated total body irradiation (TBI) 12 Gy] followed by unpurged autologous bone marrow or blood stem cell rescue. Most patients (69%) had advanced stage disease (stages 3--4) at transformation and bone marrow involvement was common (49%). Twenty-six (74%) patients were in partial remission (PR) and nine (26%) in complete remission (CR) at the time of transplant. Median duration from transformation to transplant was 10.9 months (range, 5.2 months--4.6 years). At a median follow up of 52 months after autotransplant, 19 (54%) patients had died. Causes of death were progressive lymphoma in nine patients (26%), treatment-related mortality (TRM) in seven (20%) and myelodysplasia in three (8%). Only five patients in our cohort were > 60 years old, but all died as a result of treatment-related causes (mostly pulmonary infections). Five-year overall survival and progression-free survival from time of transplant were 37% and 36% respectively. Using multivariate analysis of factors including gender, age, stage, extranodal disease, disease bulk, B symptoms, number of prior therapies, relapse status and CR/PR status at transplant, only advanced age significantly predicted for survival from autotransplant (P = 0.002). Our survival data are comparable to previous reports of autotransplantation for transformed NHL and suggest a benefit over standard chemotherapy alone in selected patients. However, our high TRM cautions the use of aggressive therapy, including TBI, in patients over 60 years old.

Adult↗
PubMed2001

Selective termination of aneuploidy utilizing rapid fluorescence in situ hybridization detection techniques.

Twin pregnancy following assisted reproductive technology with a euploid fetus and a coexisting aneuploid co-twin constitutes a conflicting situation; therefore, it is important for the genetic constitution of each co-twin to be diagnosed accurately and promptly for parental genetic counseling and subsequent aggressive management. A 35-year-old woman, gravida 1, with a 2-year history of infertility, presented bilateral fallopian tubal obstruction at her infertility workups, for which she received in vitro fertilization; subsequently she conceived a twin pregnancy. She underwent genetic amniocentesis at 16 weeks' gestation, as indicated by an advanced maternal age. Presented with the diagnosis of twin pregnancy with discordancy for trisomy 21, a rapid fluorescence in situ hybridization (FISH) technique for aneuploidy mapping was applied for subsequent abdominal selective fetal reduction. The FISH technique facilitates the rapid analysis of uncultured amniocytes. Normal (disomic) and trisomic samples can be distinguished clearly and rapidly for subsequent selective fetocide. The FISH technique is an important tool in prenatal diagnosis and clinical applications.

Adult↗
PubMed2000

A comparison of elderly patients with aggressive histology lymphoma who were entered or not entered on to a randomized phase II trial.

The purpose of this study was to compare the baseline patient characteristics, treatments and outcomes of elderly patients with aggressive histology lymphoma who were entered or not entered onto a randomized phase II trial. We previously conducted a randomized phase II trial in patients > or = 65 years of age who had advanced stage intermediate grade lymphoma. A registry of all patients meeting the inclusion criteria for that trial was maintained. Many patients were not entered on to the randomized trial because of the presence of at least one exclusion criterion, or because of patient or physician choice. We have compared the baseline characteristics, treatment, and survival of the randomized and non-randomized patients. Results show that 68 consecutive patients met inclusion criteria for the randomized trial. Thirty-eight patients satisfied all eligibility criteria, consented, and were randomized; 30 patients (44%) were not entered. In comparison with randomized patients, non-randomized patients were older (mean 75.9 vs. 72.4 years; P=0.013), had a poorer performance status (P=0.0006), were less likely to be given treatment with curative intent (60% vs. 100%; P<0.001), and were less likely to complete 6 cycles of such treatment (27% vs. 89%; P<0.001). With a median follow-up of > 7 years, actuarial 5-year survival is superior in randomized patients (44.3% vs. 10%; P<0.00001). In conclusion, a substantial number of patients did not enter our randomized trial phase II trial and had different characteristics, received different therapy and had inferior outcomes in comparison with randomized patients. Randomized trials of therapy for elderly lymphoma patients may include special selection criteria and results may not be generalizable to a substantial proportion of other older patients.

Actuarial Analysis↗
PubMed1999

Natural mass infection by heterophyid metacercariae in aquacultured Japanese eel in Taiwan.

A natural mass infection of heterophyid metacercariae in aquacultured Japanese eel Anguilla japonica in Taiwan was observed. Of the 28,000 adult eels in 2 ponds, about 25,000 (90%) showed swollen, cloudy and white eyes. Although morbidity was about 90%, there was no mortality among the affected eels. Histopathological sections showed edema and hemorrhage of the eye. Numerous metacercariae were observed in the muscle tissues around the eyeball, the subcutaneous tissue and even in the cartilage. Of the 6 eels digested with artificial gastric juice, all were found to contain metacercariae in their muscle tissues. The average number of metacercariae recovered from the 6 eels was 1219, with a range of 50 to 3762. These metacercariae, when fed orally to immunodeficient (scid) mice, developed into adult worms which were identified as Procerovum cheni Hsu 1950. The naturally infected eels were transferred to a new pond without snails and their eye lesions were not apparent anymore after 2 wk. In a follow-up investigation, 19 of 20 apparently healthy eels in a nearby aquaculture farm were found to harbour metacercariae in their muscles. However, the number of the metacercariae ranged from 1 to 14, with an average of 4.21. This is the first report of heterophyid metacercariae causing mass morbidity in aquacultured eels.

Anguilla↗
PubMed1999

Birth after the injection of sperm and the cytoplasm of tripronucleate zygotes into metaphase II oocytes in patients with repeated implantation failure after assisted fertilization procedures.

OBJECTIVE: To assess the technique of injecting a single sperm and cytoplasm obtained from tripronucleate zygotes into metaphase II oocytes for the treatment of patients with repeated implantation failure after intracytoplasmic sperm injection or IVF. DESIGN: Clinical study. SETTING: Private infertility clinic. PATIENT(S): Patients with repeated implantation failure after intracytoplasmic sperm injection or IVF. INTERVENTION(S): The metaphase II oocytes of recipients were injected with their husbands' spermatozoa and cytoplasm aspirated from the tripronucleate zygotes of donors. MAIN OUTCOME MEASURE(S): Fertilization after cytoplasm and sperm injection, embryo development, and successful pregnancy. RESULT(S): In total, 62 metaphase II oocytes from nine recipients were injected. Of the 62 injected oocytes, 3 (5%) degenerated and 43 (69%) had two pronuclei 18 hours after injection. Thirty-nine oocytes with two pronuclei cleaved to the two-cell to six-cell stage after another 24 hours of culture. All cleaved embryos were transferred into the uteruses of recipients. Four clinical pregnancies occurred in four recipients. No abnormal chromosomes were observed after amniocentesis and karyotyping in all pregnancies. Five healthy infants were born. CONCLUSION(S): Injection of the cytoplasm of tripronucleate zygotes may enhance the clinical pregnancy rate in patients with repeated implantation failure after intracytoplasmic sperm injection or IVF.

Adult↗
PubMed1999

Early alteration of coronary hemodynamics in late restenosis after coronary angioplasty.

It is not known whether changes in coronary hemodynamics may antedate the development of restenosis after percutaneous coronary transluminal angioplasty (PTCA). The purpose of this study was to evaluate the early change in coronary microvascular function in patients with late restenosis after PTCA. Coronary hemodynamics were studied in series before, immediately after, 2 weeks and 3 months after successful PTCA in 12 male patients with a single lesion of the left anterior descending coronary artery. In each patient, great cardiac venous flow (GCVF) and oxygen content were measured both at baseline and during hyperemia induced by adenosine infusion. The sequential changes of coronary hemodynamics were compared between patients with and without restenosis at 3 months after PTCA. Basic characteristics did not differ between the patients with (n = 6) and those without restenosis (n = 6). Luminal diameter stenosis (in percentage) was also similar between the two groups both before (79.2 +/- 18.4% vs 83.0 +/- 9.6%, p = NS) and up to 2 weeks after PTCA (25.8 +/- 10.9% vs 28.5 +/- 7.9%, p = NS). In patients without restenosis, basal and hyperemic GCVF was unchanged up to 2 weeks after PTCA. There was a significant increase in CFR 3 months after PTCA. In patients with restenosis, basal GCVF was significantly increased and hyperemic GCVF was unchanged immediately after PTCA. However, 2 weeks after PTCA, basal GCVF was decreased while luminal diameter was still preserved. In comparison with those without restenosis, patients with restenosis had significantly lower CFR before (1.98 +/- 0.42 vs 2.69 +/- 0.46, p = 0.019), immediately after (1.47 +/- 0.27 vs 2.24 +/- 0.47, p = 0.006) and 3 months after PTCA (1.51 +/- 0.32 vs 3.40 +/- 0.54, p = 0.001). In patients without restenosis, the recovery of coronary microvascular function was delayed up to 3 months after PTCA. In patients with late restenosis, basal coronary microvascular tone was altered within 2 weeks after PTCA suggesting early deterioration of coronary microvascular function before the development of angiographic restenosis.

Aged↗
PubMed1998

A high-performance double-crystal monochromator soft X-ray beamline.

A high-performance double-crystal-monochromator soft X-ray (DCMSX) beamline has been constructed at the Synchrotron Radiation Research Center (SRRC). This beamline delivers monochromatic photon beams with energies from 1 to 9 keV and a resolving power (E/DeltaE) of up to 7000. This beamline provides users with an opportunity to study many important materials, such as high-T(c) superconductors, magnetic materials, catalysts, super-alloy compounds etc. Excellent EXAFS and NEXFS spectra have been routinely obtained from this beamline. Several interesting research projects are currently being conducted at this beamline. All the results show that this beamline has been constructed to meet its design goals.

Journal Article↗
PubMed1998

Studies of multimerin in patients with von Willebrand disease and platelet von Willebrand factor deficiency.

In normal platelet alpha-granules von Willebrand factor (VWF) is stored with multimerin and factor V in an eccentric electron-lucent zone. Because the platelet stores of VWF are deficient in 'platelet low' type 1 and type 3 von Willebrand disease (VWD), we investigated their electron-lucent zone proteins. The patients with VWD had partial to complete deficiencies of plasma and platelet VWF but normal alpha-granular multimerin and factor V, and normal alpha-granular fibrinogen, thrombospondin-1, fibronectin, osteonectin and P-selectin. In type 3 VWD platelets, alpha-granular electron-lucent zones lacking VWF-associated tubules were identified and multimerin was found in its normal alpha-granular location. These findings indicate that the formation of the electron-lucent zone and the sorting of multimerin to this region occur independent of VWE The isolated abnormalities in VWF suggests a VWF gene mutation is the cause of 'platelet low' type 1 VWD.

Blood Platelets↗
PubMed1997

Thermophilic biodegradation of BTEX by two consortia of anaerobic bacteria.

Two thermophilic anaerobic bacterial consortia (ALK-1 and LLNL-1), capable of degrading the aromatic fuel hydrocarbons, benzene, toluene, ethylbenzene, and the xylenes (BTEX compounds), were developed at 60 degrees C from the produced water of ARCO'S Kuparuk oil field at Alaska and the subsurface water at the Lawrence Livermore National Laboratory gasoline-spill site, respectively. Both consortia were found to grow at 45-75 degrees C on BTEX compounds as their sole carbon and energy sources with 50 degrees C being the optimal temperature. With 3.5 mg total BTEX added to sealed 50-ml serum bottles, which contained 30 ml mineral salts medium and the consortium, benzene, toluene, ethylbenze, m-xylene, and an unresolved mixture of o- and p-xylenes were biodegraded by 22%, 38%, 42%, 40%, and 38%, respectively, by ALK-1 after 14 days of incubation at 50 degrees C. Somewhat lower, but significant, percentages of the BTEX compounds also were biodegraded at 60 degrees C and 70 degrees C. The extent of biodegradation of these BTEX compounds by LLNL-1 at each of these three temperatures was slightly less than that achieved by ALK-1. Use of [ring-14C]toluene in the BTEX mixture incubated at 50 degrees C verified that 41% and 31% of the biodegraded toluene was metabolized within 14 days to water-soluble products by ALK-1 and LLNL-1, respectively. A small fraction of it was mineralized to 14CO2. The use of [U-14C]benzene revealed that 2.6%-4.3% of the biodegraded benzene was metabolized at 50 degrees C to water-soluble products by the two consortia; however, no mineralization of the degraded [U-14C]benzene to 14CO2 was observed. The biodegradation of BTEX at all three temperatures by both consortia was tightly coupled to sulfate reduction as well as H2S generation. None was observed when sulfate was omitted from the serum bottles. This suggests that sulfate-reducing bacteria are most likely responsible for the observed thermophilic biodegradation of BTEX in both consortial cultures.

Bacteria, Anaerobic↗
PubMed1997

New stenosis on proximal coronary segment after directional atherectomy. Two case reports.

Two patients with new coronary stenotic lesions subsequently developed proximal to the sites accepting directional coronary atherectomy (DCA) are reported. One lesion developed at the left main coronary artery and the other at the proximal segment of the left anterior descending artery. The mechanisms of the development of such new stenotic lesions after DCA were studied and procedure-related mechanical trauma over the proximal segment of the primary lesion may be the possible mechanism for such complication.

Aged↗