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B Christian

Publications and source records attributed to B Christian.

At least 19 recordsLinked to original sources
PubMed2005

Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2), and prednisone 40 mg/m(2) for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m(2) was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle. RESULTS: Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination. CONCLUSION: Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.

Aged↗
PubMed2005

Fludarabine plus cyclophosphamide in Waldenström's macroglobulinemia: results in 49 patients.

Fludarabine (FDR) therapy gives a response rate of about 30% in previously treated patients with Waldenström's macroglobulinemia (WM). The combination of FDR and cyclophosphamide (Cy) has been shown to be effective in chronic lymphoproliferative disorders. We administered the combination of FDR (30 mg/m2 i.v. D1-D3) and Cy (300 mg/m2 i.v. D1-D3) to 49 patients. Median age was 64 years. The median hemoglobin, albumin, beta 2 microglobulin and immunoglobulin M (IgM) levels were 9.9 g/100 ml, 39.6 g/l, 3 mg/l and 24.7 g/l, respectively. In all, 14 patients (29%) had not previously been treated. FDR/Cy was administered every 4 weeks for a median of four cycles. In all, 38 patients (77.6%) had partial responses, nine had stable disease and two had progressive disease. After a median of follow-up of 25 months, six patients relapsed and two patients developed large-cell lymphoma. The median time to treatment failure was 27 months. The main toxicity was hematological. In all, 12 patients died, four from progression, one from large-cell lymphoma, three from infection and four from a second malignancy. Two factors negatively influenced overall and event-free survival, age >65 years and IgM <40 g/l. The FDR/Cy combination, therefore, gives a high response rate in WM, even in previously treated patients with factors of poor prognosis.

Aged↗
PubMed2003

Prediction of pathology and survival by FDG PET in gliomas.

OBJECTIVES: Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-D-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy. METHODS: All PET scans prior to 1997 were acquired on an ECAT 951/31 scanner in 2D. Scans since 1997 were obtained on a Siemens HR+ scanner in 3D mode. The majority of FDG PET scans were co-registered with the magnetic resonance imaging (MRI) scans to aid in diagnosis and therapy. Based on independent visual inspection, two board certified nuclear medicine physicians graded the highest activity level of the tumor using the metabolic grading: 0 = no uptake; 1 = uptake less or equal to normal white matter; 2 = uptake greater than normal white matter and less than gray matter; 3 = uptake equal to or greater than gray mater. The measure of association of lambda (lambda) was used to measure the strength of predictive ability of FDG PET for pathological grading of the gliomas. The Cox proportional hazards regression model was used to assess the significance of grade of uptake on survival. RESULTS: A total of 331 patients were analyzed of which 137 had a PET scan prior to histological diagnosis and therapeutic intervention (mean age = 46.5 years; M:F = 1.7:1). Eighty six percent (143/166) of the patients with low uptake (metabolic scores 0,1) had low-grade gliomas (grade I,II) and 14% (23/166) high-grade gliomas (grade III,IV) on histologic examination. Ninety four percent (154/165) of the patients with high uptake (metabolic scores 2,3) on PET had high-grade gliomas and 7% (11/165) had low-grade gliomas on histologic examination. The grade of uptake had increasing significance on survival as the level increased from 'low' to 'high' (P = 0.0009). Ninety four percent (156/166) of the patients with low uptake survived for > 1 year (median survival of 28 months) and 19% survived for > 5 years. Only 29% (48/165) of patients with high uptake survived for > 1 year, (median survival of 11 months) and none survived for > 5 years. Irrespective of when the scan showed a high uptake of FDG, before or after intervention, the prognosis following that scan was poor. CONCLUSIONS: Our observations confirm the utility of FDG PET as a prognostic tool for the histological grading and survival in patients with gliomas and appears to more than complement pathological grading.

Adolescent↗
PubMed2001

Tumor necrosis factor alpha release is a major biological event associated with rituximab treatment.

INTRODUCTION: In patients with low-grade non-Hodgkin's lymphoma, rituximab (MabThera) produces infusion-related toxicity, including fever, rigors, and chills in greater than 50% of those treated. The majority of these reactions are grade 1 or 2. MATERIALS AND METHODS: In the GELA study LNH98-5, a total of 400 elderly patients with previously untreated diffuse large B-cell lymphoma were randomized to treatment with CHOP or with rituximab plus CHOP (R-CHOP). In a detailed investigation of biological events which may be associated with adverse reactions specific to rituximab infusion, a subgroup of 55 patients (26 in the CHOP group and 29 in the R-CHOP group) were selected for measurement of several biological parameters at baseline and at 1, 4 and 8 h (H1, H4 and H8, respectively) after commencing therapy. For 27 patients, measurements included cytokine and complement levels. RESULTS: Baseline demographic and disease characteristics were similar for patients in both treatment groups. Compared with the CHOP treatment group, patients in the R-CHOP group had significantly higher post-treatment changes in neutrophil, lymphocyte, and monocyte counts, LDH levels, C3a levels, and TNF-alpha levels. In the R-CHOP group, neutrophil levels increased at H4 (P<0.05), lymphocyte levels decreased at H1 (P<0.05), H4 (P<0.001) and H8 (P<0.05), monocytes levels decreased at H1 (P<0.01), LDH levels increased at H4 (P<0.05) and H8 (P<0.01), and C3a decreased at H1 (P<0.01). The most statistically significant changes were observed for TNF-alpha levels: Mean values of TNF-alpha increased more than 250% at H1 and H4 and were still increased by 170% at H8 (P<0.001 at all timepoints). Since only six of the 55 evaluated patients had severe adverse events, it was not possible to correlate severe toxicity with these biological variations. CONCLUSION: This analysis demonstrates that rituximab infusion was rapidly followed by activation of complement, B-lymphocyte cytolysis, and TNF-alpha release.

Aged↗
PubMed2000

9:-9:15. 3D Data Acquisition for Whole Body Images on the ECAT HR+

Purpose: Evaluation of 3D clinical whole-body FDG PET imaging using recent improvements in data correction and reconstruction methods.Methods: Phantom studies following the NEMA NU 2-2000 draft were performed to evaluate count loss and accuracy of attenuation and scatter correction algorithms. Phantom results were used to estimate 3D vs. 2D efficiency. For patient studies, an established 2D imaging protocol (9 min emission, 3 min transmission acquisition per bed position, commencing 60 min after injection of 15 mCi FDG) was used. This was followed by a 3D acquisition of the same duration, commencing approximately 110 min later, so that 3D acquisition was performed with approximately 50% lower patient activity than 2D. Images were compared in terms of anatomic structural definition and visible artifacts.The count loss study showed that in a dose range of 10-15 mCi, 3D produced an approximately two-fold increase in effective NEC compared to 2D. The phantom imaging study showed slightly improved target to background ratios for both hot and the cold "lesions" when using 3D imaging. In 5 patients studied so far, comparison of 2D and 3D studies demonstrated no systematic differences in image quality between the two methods.Conclusion: 3D whole-body imaging with improved image reconstruction may permit a two-fold reduction in emission acquisition time or injected dose, without decrease in image quality compared to standard 2D imaging techniques.

Journal Article↗
PubMed2000

[Large crusted ulceration of the scalp: first manifestation of cryptococcosis in an AIDS patient].

BACKGROUND: Cryptococcosis is an infection caused by the yeast-like fungus Cryptococcus neoformans. It primarily occurs in immunocompromised hosts. Crytptococcosis is usually a systemic disease and may be serious if the lungs or the central nervous system are involved. CASE REPORT: We describe a case of cutaneous cryptococcosis without systemic involvement occurring as the first manifestation of AIDS. The skin lesion in our patient consisted of a large crusted ulceration on the scalp. Fluconazole was successful. DISCUSSION: This case is a new observation of primary cutaneous cryptococcosis in a patient with AIDS. Clinical appearance may be misleading; skin lesions may be the primary sign in immunocompromised patients. Rapid treatment and secondary prophylaxis are required.

AIDS-Related Opportunistic Infections↗
PubMed1998

The anti-MUC1 monoclonal antibody BCP8 can be used to isolate and identify putative major histocompatibility complex class I associated amino acid sequences.

MHC class I molecules were isolated from the MUC1-positive human breast adenocarcinoma cell line MCF-7 by immunoaffinity using the panreactive anti-class I monoclonal antibodies (MAb) W6/32. Acid-eluted peptides from the class I molecules were separated twice by high-performance liquid chromatography and tested for reactivity with the MAb BCP8, which reacts with the minimal MUC1 core peptide sequence PDTRPA. A peak with strong and specific BCP8 reactivity was found in fractions eluting at 16.5-17.5 min. The protocol used for the MUC1+ pancreatic adenocarcinoma cell line CAPAN-1 (HLA.A2) was to perform sequential affinity purifications of class I molecules using MAb W6/32, followed by affinity purification of HLA.A2 molecules by the HLA.A2.1-specific MAb, MA2.1, and high-performance liquid chromatography fractionation of the acid-eluted material. A single peak with MAb BCP8 reactivity was noted at 18-19 min. The protocol for the MUC1+ breast adenocarcinoma cell line SKBr-3 (HLA.A11,B40), which used A11- and B40-specific MAbs, also resulted in the detection of BCP8-specific peaks at approximately 18-19 min. A preliminary mass spectral analysis of BCP8 affinity-purified class I associated material surprisingly revealed the presence of two 3-mer MUC1 amino acid sequences and one 6-mer sequence. A synthetic 9-mer MUC1 peptide, TSAPDTRPA, containing the isolated fragments was found to cause strong class I up-regulation in T2 cells as well as to serve as an epitope for CTL generated in a primary in vitro immune response. These studies suggest that MUC1-derived peptides are processed and presented in the context of MHC class I molecules on the surface of tumor cells and support the use of MAb BCP8 to further define MHC class I associated MUC1 motifs.

Antibodies, Monoclonal↗
PubMed1998

A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).

The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients >/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.

Age Factors↗
PubMed1998

Subsurface crypts and interstitial cells in the ovary of the seal (Phoca vitulina vitulina): light and electron microscopic findings.

This morphological study on the ovary of the seal focuses on two structures of special interest: the subsurface crypts and the interstitial cells. Ovaries from 110 seals (from 1,5 months to 12 years) were used. Most of the seals of our study originated from German North Coast, a few from Island. The ovaries were examined by light microscopic as well as by transmission and scanning electron microscopic techniques. The seal's ovary conforms to the basic structure of the ovary of other mammalian species. However, the surface epithelium cell layer lowers itself into an epithelium lined - broadly branching system of subsurface crypts. The size and extent of these crypts and the proliferation of the epithelium appear to be mainly related to the reproductive activity. The ultrastructure of crypt epithelium cells indicates a remarkable metabolic activity. In juvenile ovaries cell buds proliferate from the crypt epithelium and grow as plug-like strands into the cortical stroma. These cells show ultrastructural changes during their proliferation and appear to transform into steroid producing interstitial cells. In the adult seal the interstitial cells are completely differentiated established and, according to their origin, can be divided into epithelial and fibroblastic interstitial cells. It is suggested that a major function of the crypts is the formation of the ovarian blastema with particular reference to ovarian interstitial cells. The intensive proliferation of interstitial cells is in agreement with the extraordinary high level of 350 pmol estrogen/l blood serum.

Animals↗
PubMed1998

Palmitate oxidation by the mitochondria from volume-overloaded rat hearts.

In this work, an attempt was made to identify the reasons of impaired long-chain fatty acid utilization that was previously described in volume-overloaded rat hearts. The most significant data are the following: (1) The slowing down of long-chain fatty acid oxidation in severely hypertrophied hearts cannot be related to a feedback inhibition of carnitine palmitoyltransferase I from an excessive stimulation of glucose oxidation since, because of decreased tissue levels of L-carnitine, glucose oxidation also declines in volume-overloaded hearts. (2) While, in control hearts, the estimated intracellular concentrations of free carnitine are in the range of the respective Km of mitochondrial CPT I, a kinetic limitation of this enzyme could occur in hypertrophied hearts due to a 40% decrease in free carnitine. (3) The impaired palmitate oxidation persists upon the isolation of the mitochondria from these hearts even in presence of saturating concentrations of L-carnitine. In contrast, the rates of the conversion of both palmitoyl-CoA and palmitoylcarnitine into acetyl-CoA are unchanged. (4) The kinetic analyses of palmitoyl-CoA synthase and carnitine palmitoyltransferase I reactions do not reveal any differences between the two mitochondrial populations studied. On the other hand, the conversion of palmitate into palmitoylcarnitine proves to be substrate inhibited already at physiological concentrations of exogenous palmitate. The data presented in this work demonstrate that, during the development of severe cardiac hypertrophy, a fragilization of the mitochondrial outer membrane may occur. The functional integrity of this membrane seems to be further deteriorated by increasing concentrations of free fatty acids which gives rise to an impaired cooperation between palmitoyl-CoA synthase and carnitine palmitoyltransferase I. In intact myocardium, the utilization of the in situ generated palmitoyl-CoA can be further slowed down by decreased intracellular concentrations of free carnitine.

Adenosine Triphosphate↗
PubMed1998

Functional MRI statistical software packages: a comparative analysis.

Currently, there are many choices of software packages for the analysis of fMRI data, each offering many options. Since no one package can meet the needs of all fMRI laboratories, it is helpful to know what each package offers. Several software programs were evaluated for comparison of their documentation, ease of learning and use, referencing, data input steps required, types of statistical methods offered, and output choices. The functionality of each package was detailed and discussed. AFNI 2.01, SPM96, Stimulate 5.0, MEDIMAX 2.01, and FIT were tested. FIASCO, Yale, and MEDx 2.0 were described but not tested. A description of each package is provided.

Algorithms↗
PubMed1997

Metabolic alterations in muscle of thermally injured rabbits, measured by positron emission tomography.

The hypermetabolic inflammatory state that occurs after major trauma has been extensively studied at the whole body level, however, there is only limited information on metabolic changes in individual tissues. In this study, the effect of thermal injury on metabolic function of uninjured hind limb muscle of rabbits was measured noninvasively by positron emission tomography (PET). Rabbits were subjected to full thickness burn on 25% of their body surface area. Two to three weeks after injury, PET and arterial blood sampling was performed during inhalation of 15O2, C15O2 and 11CO and after injection of 18FDG. The tissue and blood data were analyzed by standard kinetic models for blood flow, oxygen extraction fraction (OEF), oxygen utilization and glucose metabolism. A total of seven injured and five sham animals were studied. Total body oxygen consumption was measured by indirect calorimetry and plasma concentrations of glucose, insulin and IGF-1 were measured with standard assays. Compared to sham rabbits, blood flow to muscle of injured animals was unchanged. However, OEF, oxygen utilization and glucose metabolism were significantly reduced (p<0.01) in uninjured muscle of burned rabbits. These data demonstrate that thermal injury is associated with alterations in muscle metabolism, which are not related to change in blood flow.

Animals↗
PubMed1996

Separation of enantiomers of drugs by capillary electrophoresis. III. Beta-cyclodextrin as chiral solvating agent.

Enantiomer separation by capillary zone electrophoresis was studied for a set of 34 chiral drugs. Keeping the concentration of beta-cyclodextrin as a chiral solvating agent as constant as possible led to the separation of seven enantiomeric pairs. Carvedilol, Tetryzoline, Tropicamide and Zopiclone gave a baseline separation, Chlorphenamine, Ketamine, and Orciprenaline a partial separation. Statistical analysis revealed that the best separation factors were observed for a medium degree of interaction with the cyclodextrin. A theory explaining this effect provides a helpful guideline for further optimization.

Azabicyclo Compounds↗
PubMed1995

Sequential induction chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone in adult acute lymphoblastic leukemia.

Sequential chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone doses was administered to 57 adult patients with acute lymphoblastic leukemia (ALL). Complete remission (CR) was achieved in 51 (89%, 95% confidence intervals, [CI] 78-96%). Among patients achieving CR, 62% were in CR after one sequence of chemotherapy, 23% after two sequences, and 5% after three sequences. Six patients (11%) had resistant disease. All patients experienced profound myelosuppression. Median time to recovery of neutrophils > 0.5 x 10(9)/1 was 22 days (range: 5-89 days), and of platelets > 100 x 10(9)/1 21 days (range: 0-45 days). Nonhematologic WHO grade 3 or more side effects consisted predominantly of hyperbilirubinemia (7%), mucositis (5%), nausea and vomiting (2%), and cutaneous toxicity (1%). Severe infectious complications occurred in only 14% of cases. One patient (2%, 95% CI 0-9%) died of therapy-related toxicity while in early CR. We concluded that sequential use of prednisone seemed at least as effective as continuous administration at the expense of a few adverse side effects.

Adolescent↗
PubMed1993

Self-efficacy, coping, and well-being among nursing students sexually abused in childhood.

Preparing nursing students to work with sexually abused children has received little attention by pediatric nurse educators. These students often are themselves survivors of such abuse. The population of undergraduate nursing students attending a major university was invited to participate in a mailed survey to test hypotheses concerning differences in self-efficacy, coping, and well-being between subjects who were sexually abused in childhood and those who were not. A total of 87 students (79 women and 8 men) responded by returning the completed survey. Forty-seven percent of the women (n = 37) and 38% of the men (n = 3) in the sample reported having had one or more unwanted sexual experiences in childhood. Significant correlations were found between self-efficacy and confrontive coping (r = .58), emotive coping (r = .49), and palliative coping (r = -.46); between well-being and emotive coping (r = -.24); and between well-being and palliative coping (r = -.25). One-way analysis of variance (ANOVA) techniques were used to analyze differences in self-efficacy, coping (confrontive, emotive, and palliative), and well-being between the two groups (abused = 40 and not abused = 47). A significant difference in emotive coping was found. These findings suggest that nurse educators and administrators need to be sensitive to pediatric nurses' childhood sexual experiences. Such nurses must be knowledgeable and emotionally equipped to support the child and family through the process of recovery. It is important for them to be aware of how their own coping strategies and well-being affect the care they provide vulnerable children.

Adaptation, Psychological↗