Comments on economic evaluation of chemotherapy.
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Antineoplastic Agents↗
Biomedical subjects
B E Christensen
Publications and source records attributed to B E Christensen.
CB/CC diffuse lymphoma: a distinct subtype of non-Hodgkin's lymphoma? A study of 1593 patients from a Danish population-based registry. Danish LYFO Study Group.
Between 1983 and 1993, 3165 cases of non-Hodgkin's lymphoma (NHL) were reported to the West Danish Lymphoma Registry (LYFO). Out of these, 148 (4.7%) were of the CB/CC diffuse subtype according to the Kiel classification. However, in the new European-American NHL consensus classification (REAL, 1994), CB/CC diffuse lymphoma was categorized as a provisional subtype only. In the LYFO material, death-probability curves show a significantly shorter survival in CB/CC diffuse than in CB/CC follicular. In order to detect further possible differences between CB/CC diffuse and other NHL subtypes, a number of clinical parameters at presentation were analyzed in a subset of five types of lymphoma. This subset included 148 cases of CB/CC diffuse, 435 cases of CB/CC follicular, 667 cases of CB diffuse, 202 cases of CC diffuse, and 131 cases of peripheral T-cell lymphoma. Using logistic regression analysis, significant differences could be demonstrated between CB/CC diffuse and the four other subtypes as regards sex ratio, age distribution, and sites of both nodal and extranodal involvement. These findings indicate that CB/CC diffuse has a distinct clinical phenotype and imply the existence of real biological differences between CB/CC diffuse and other subtypes of lymphoma.
Aged↗
[Primary cerebral non-Hodgkin's lymphomas and primary malignant brain tumors in a well-defined geographical area. Population-based data from the registry of non-Hodgkin's lymphoma in western Denmark, LYFO and the cancer registry, Kraeftens Bekaempelse].
In a Danish population-based non-Hodgkin's lymphoma (NHL) registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumours of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related primary central nervous system lymphomas (PCNSL) accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumours. Incidence of primary malignant brain tumours was stable, except for age ranges over 70 years. Histologically, 85% were high grade, centroblastic diffuse (60%) and immunoblastic lymphoma (13%) (Kiel classification). No T-cell lymphomas were detected. Treatment included surgical resection, whole brain irradiation (WBRT) and chemotherapy. Median survival for those receiving either WBRT or WBRT and chemotherapy was eight months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at one, two and five years. Cox-regression analysis identified only one factor having independent impact on survival in performance score > or = 2 (PCNSL p < 0.001, RR = 5.8).
Adult↗
Degradation of double-stranded xanthan by hydrogen peroxide in the presence of ferrous ions: comparison to acid hydrolysis.
Conformationally ordered, double-stranded xanthan, degraded in the presence of H2O2 and Fe2+ (at 20 degrees C) or in dilute acid (0.1 M HCl at 80 degrees C), produced xanthan variants with weight-average molecular weights (Mw) ranging from 2 x 10(6) to 5.4 x 10(4). In both cases the fraction of cleaved linkages in the glucan backbone (alpha), measured as reducing ends, increased to very high values (0.05 for Mw = 2-3 x 10(4)), demonstrating that a large number of linkages in the backbone could be cleaved without a correspondingly large reduction in Mw, in accordance with the double-stranded nature of xanthan. Extensive degradation (more than 10-fold reduction in Mw) in both cases released single-stranded, conformationally disordered oligomers; this release was accompanied by an increase in the rate of acid hydrolysis of the glucan backbone and a pronounced increase in the rate of release of glucose monomer. In contrast, there was no significant change in the rate of reducing end-group formation associated with the release of oligomers upon degradation with H2O2/Fe2+. Both types of degradation were accompanied by changes in the composition of the side chains. However, in contrast to acid hydrolysis, where the terminal beta-D-mannose is preferentially hydrolyzed, the reaction with H2O2/Fe2+ resulted in removal of both mannose and glucuronic acid at approximately equal rates. This observation can be explained by a preferential attack on the inner alpha-D-mannose, with concomitant removal of the entire side chain. Removal of side chains and the release of single-stranded oligomers by H2O2/Fe2+ strongly influenced the optical rotation and also broadened the chiroptically detected conformational transition, whereas no change in the transition temperature was observed.
Carbohydrate Conformation↗
Physicochemical studies on xylinan (acetan). I. Characterization by gel permeation chromatography on sepharose Cl-2B coupled with static light scattering and viscometry.
Laboratory-made samples of the polysaccharide xylinan (acetan) were fractionated on Sepharose Cl-2B using 0.1M NaCl as eluant. The weight average molar masses and intrinsic viscosities were estimated in the fractions by multiangle laser light scattering (off-line) and capillary viscometry, respectively. The Mark-Houwink-Sakurada plot was found to be indicative of semiflexible coils (a = 0.90). The angular dependence of scattered light was interpreted by fitting with theoretically calculated "Master Curves" in terms of a wormlike chain model. The ambiguity of the interpretation of scattering curves owing to the overlapping effects of chain stiffness and polydispersity is discussed in detail. The experimental data is found to be consistent with a persistence length of Lp = 100 nm. The main proportion consists of double-stranded chains (consistent with a robust double-helix), but single- and multistranded chains also are present. Our results suggest a fractionation according to the contour length rather than the molar mass.
Acetobacter↗
Dependence of the content of unsubstituted (cellulosic) regions in prehydrolysed xanthans on the rate of hydrolysis by Trichoderma reesei endoglucanase.
Removal of side chains from the bacterial polysaccharides xanthan and xylinan (acetan) results in the formation of unsubstituted cellulosic regions that are susceptible to hydrolysis by cellulases (beta-1,4-endoglucanases). In contrast to cellulose derivatives, low degrees of substitution (DS) may be obtained in xanthan without affecting the solubility in water, and longer unsubstituted regions are obtained for the same DS due to the regular distribution of side chains. By varying the fraction of cellobiosic residues carrying a side chain from 1.0 to 0.54, the viscosimetrically detected rate of hydrolysis by cellulase of conformationally disordered xanthan, increased by 4 orders of magnitude. An increase was also obtained by removing side chains from xylinan. An analysis of the kinetic data suggests that very long unsubstituted regions (more than 10 glucose residues) are required for maximum rate of hydrolysis by cellulase.
Carbohydrate Sequence↗
The bone-marrow infiltration pattern in B-cell chronic lymphocytic leukemia is not an important prognostic factor. Danish CLL Study Group.
In a multicentre study of 635 consecutive newly diagnosed patients with B-CLL, the histological bone marrow (BM) specimens were reviewed independently by each of 3 pathologists and found evaluable for BM infiltration pattern in 575 patients, 404 of whom had a CD5+, mainly FMC7-, faint surface-membrane immunoglobulin (SIg) fluorescence-intensity ppenotype. In these 404 patients the following BM infiltration patterns were found: mixed nodular-interstitial (30%), moderate interstitial (44%), heavy interstitial (20%) and diffuse packed (6%). In univariate survival analysis, significant differences were found according to BM pattern (p < 0.05), the presence of nodules being a favorable prognostic sign. In multivariate survival analysis in a model including age, clinical stage, BM pattern, BM lymphocytosis, WBC and sex, only age and stage but not BM pattern or BM lymphocytosis had independent prognostic significance. In stage A, progression-free survival was significantly longer in patients with nodular than in patients with non-nodular bone-marrow pattern. The overall survival of these patients, however, did not differ, possibly owing to the prompt and prolonged treatment given to most patients at the time of progression to stage B or C. We conclude that in CD5+, SIg(faint), mainly FMC7-B-CLL, bone-marrow histology may predict unstable disease in early clinical stage but is not important for treatment decisions, when these are based on clinical stage.
Age Factors↗
Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL).
It has previously been reported that the expression of the complement receptors CR1 (CD35) and CR2 (CD21) on malignant B cells in CLL is reduced compared with the expression on normal B cells, while deposition of complement C3 fragments, as a consequence of alternative pathway (AP) activation of complement, is observed on mononuclear cells from patients with B CLL. Following our demonstration that normal B cells are capable of activating the AP of complement in a CR2-dependent fashion, we have chosen to re-examine the complement-activating ability of B CLL cells in relation to their altered phenotype with respect to CR2 and the complement regulatory membrane proteins, CR1, decay accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46). Flow cytometry was used to measure expression of complement receptors and regulatory proteins on CD5+ B cells from CLL patients, as well as the deposition of C3 fragments occurring both in vivo and after in vitro AP activation. We have confirmed the reduced expression of CR1 and CR2 on CLL cells and have shown that AP activation in the presence of homologous, normal serum was reduced on B CLL cells compared with normal B cells. The degree of AP activation correlated directly with CR2 expression. In addition, we observed that CLL cells bear in vivo-deposited C3d,g, although at a significantly lower level than normal B cells.
Animals↗
Clinicopathological features, survival and prognostic factors of primary central nervous system lymphomas: trends in incidence of primary central nervous system lymphomas and primary malignant brain tumors in a well-defined geographical area. Population-based data from the Danish Lymphoma Registry, LYFO, and the Danish Cancer Registry.
It has been claimed that Primary Central Nervous System Lymphomas (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extranodal non-Hodgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate 11-year period from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had B-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WBRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at 1, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL: performances score > or = 2 (p < 0.001, RR = 5.8).
Adolescent↗
[Is ventricular lymphoma an infectious disease?].
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Helicobacter Infections↗
Testicular lymphoma: a population-based study of incidence, clinicopathological correlations and prognosis. The Danish Lymphoma Study Group, LYFO.
In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens (orchiectomy and/or radiotherapy) was 63.6% (P < 0.05). Median relapse-free survival was 28 and 14 months, respectively. Overall 5-year survival for all cases was 17%. Adverse prognostic factors at the univariate level were stage IV, constitutional symptoms, serum lactic dehydrogenase elevation and performance score (WHO 3-4). It is suggested that the treatment of stage IE/IIE TL should include early CCT and CNS prophylaxis.
Adolescent↗
Incidence, clinicopathological features and outcome of primary central nervous system lymphomas. Population-based data from a Danish lymphoma registry. Danish Lymphoma Study Group, LYFO.
BACKGROUND: Primary Central Nervous System lymphomas (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extranodal non-Hodgkin's lymphomas (NHL), seems to occur with increasing frequency in immunologically-normal as well as immunocompromised individuals. In an attempt to characterize the clinicopathological features, incidence rate and outcome of PCNSL, we here report our experience in a large unselected group of patients from a well-defined region. PATIENTS AND METHODS: In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million, all new cases of NHL were registered during the 10-year period from 1st January 1983 to 31st December 1992. The number of malignant brain tumors reported to the Danish Cancer Registry from the region covered by LYFO, during the 7-year period from 1st January 1983 to 31st December 1989, is compared to the number of PCNSL. RESULTS: During the 10-year period 2687 new cases of NHL were registered. Of these, 1004 (37%) were extranodal and 42 were non-AIDS-related PCNSL, accounting for 4.2% of extranodal NHL and 1.6% of all NHL, respectively. The incidence rate for PCNSL during the ten-year period (age range: 21-85 yrs, median: 62 yrs, M/F ratio: 0.9) was 15.6 cases per million population. Eighteen and 24 cases were diagnosed during the first and the second 5-year period, respectively (p > 0.05). During the 7-year period 1866 primary malignant brain tumors were registered in the region covered by the LYFO study group. In the same period 30 cases of PCNSL were detected. Thus, PCNSL accounted for 1.6% of all primary malignant brain tumors diagnosed in Western Denmark. Histologically, 83% were high-grade. Using the Kiel classification centroblastic diffuse (62%) and immunoblastic lymphoma (12%) were the most common subtypes. Thirty-seven patients had B-cell lymphoma; no T-cell lymphomas were detected. Forty-one cases were diagnosed pre mortem. Treatment included surgical resection (23 patients), whole brain irradiation (WBRT) (37 patients) and chemotherapy (22 patients). Median survival for those receiving either WBRT or WBRT and chemotherapy was 7.5 months and 12 months, respectively (p > 0.05). Survival was 43.9%, 31.7% and 7.3% at 1, 2 and 5 years.
Adult↗
[Non-Hodgkin lymphoma in the elderly].
Within a seven year period, 1597 newly diagnosed cases of non-Hodgkins lymphoma (NHL) were included in a Danish population-based NHL-register. Of these, 602 (38%) were aged 70 or older (age range 70-94, median: 76.8) and represented the population defined as "elderly" patients in the present study. Their average annual incidence rate was 35.7/10(5), as compared to 6.6/10(5) for patients aged < 70 (overall annual incidence: 9.5/105). Localised cases (stage I and II) and extranodal manifestations were more frequent among elderly patients. The most common sites of extranodal involvement were stomach (21% of all extranodal cases) and bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p < 0.01) in elderly patients as compared to their younger counterparts (< 70 years), who on the other hand had a lower occurrence of diffuse centroblastic cases (p < 0.01). Overall seven year survival for the elderly patient population was 35% (median: 1.7 years), and for patients aged < 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66% respectively, p < 0.0001). The following poor prognostic factors for elderly patients were identified by multivariate analysis: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were respectively 2.4, 2.2, 1.9 and 1.6.
Age Factors↗
Temperature-induced conformational transition in xanthans with partially hydrolyzed side chains.
The conformational properties of xanthans with partially hydrolyzed side chains were investigated by optical rotation, CD, and differential scanning calorimetry (DSC). All variants displayed the well-known temperature-driven, cooperative order-disorder transition, and both optical rotation and DSC showed that the transition temperature was essentially independent of the content of terminal beta-mannose. It was found that up to 80% of the changes in the specific optical rotation accompanying the transition reflects conformational changes linked to the terminal beta-mannose in the side chains. Modification of the side chains also affected the CD when xanthan was in the ordered state, but in this case the data suggest that the glucuronic acid is the major component determining the magnitude of the CD signal. DSC measurements showed that the transition enthalpy (delta Hcal) increased linearly with the fraction of beta-mannose, again indicating that a significant part (up to 80%) of delta Hcal reflects conformational changes in the side chains. The conformational transition of the xanthan variants generally showed a higher degree of cooperativity (sharper transition) than unmodified, pyruvated xanthan. Calculation of the cooperativity parameter sigma by means of the Zimm-Bragg theory (OR data) or from the ratio between delta Hcal and the van't Hoff enthalpy (delta HvH) using DSC data showed a correlation between sigma and the content of beta-mannose, but the two methods gave different results when the content of beta-mannose approached 100%. The ionic strength dependence of the transition temperature, expressed as d (log I)/d(T-1m), was nearly identical for intact xanthan and a sample containing only 6% of the terminal beta-mannose. Application of the Manning polyelectrolyte theory does not readily account for the observed delta Hcal values, neither does it provide new information on the nature of the ordered and disordered conformations in xanthan.
Calorimetry, Differential Scanning↗
Acute mucocutaneous toxicity following high-dose hydroxyurea.
Three patients with advanced acute myeloid leukemia were treated with oral high-dose hydroxyurea at a dose of 10 g daily for 8-10 days. Severe acute stomatitis developed in all three patients. In addition, two of the patients developed a peculiar acute cutaneous type of toxicity associated with soreness, violet erythema, and edema of the palms and foot soles followed by intense universal hyperpigmentation of the skin. Apparently, the pronounced acute mucocutaneous toxicity was caused by the sustained high daily dose of hydroxyurea, indicating that myelosuppression may not be the dose-limiting toxicity of this drug.
Acute Disease↗
Incidence, presenting features and prognosis of low-grade B-cell non-Hodgkin's lymphomas. Population-based data from a Danish lymphoma registry.
During the period January 1983 to January 1988 1597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Western Danish population-based NHL registry. Of these, 31% (N = 496) were low-grade NHL (LG-NHL) consisting of (Kiel): 9% lymphocytic (LY), 27% lymphoplasmacytic/-cytoid (IC), 53% follicular centroblastic/-centrocytic (CB/CCf) and 11% unclassifiable low-grade. LG-NHL (age range: 26-94 yrs, median: 64 yrs; M/F ratio: 0.8) had an age-standardised incidence rate (IR) of 2.7/10(5)/yr. Age-specific IR's showed an age-related exponential rise in all subtypes except for CB/CCf. Compared with the intermediate (IG)- and high-grade (HG) group, LG-NHL had more female cases (M/F ratio: 0.79 vs. 1.2; p = 0.0002), a higher frequency of stage III-IV disease (66% vs. 53%; p < 0.00005) and of bone marrow involvement (39% vs. 19%; p < 0.00005). A later revision of all IC cases (N = 132) distinguished 79 non-polymorphic (ICnp) from 25 polymorphic (ICp) cases; 28 cases were differently classified. In 34 LG-NHL patients histologic transformation was verified: CB/CCf to CB diffuse (22 pts) and LY to immunoblastic or CB type (6 pts). The 7-yr survival for LG-NHL was 63% (IG: 48%, HG: 38%; p < 0.00005). A Cox-regression analysis identified the following adverse prognostic factors for survival in LG-NHL: age > 50 with a relative risk (RR) of 3.2, hepatic involvement (RR = 2.1), elevated s-LDH (RR = 1.9), B-symptoms (RR = 1.8) and IC histology (ICnp+ICp) (RR = 1.7).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia.
The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.
Adult↗
Non-Hodgkin's lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group.
Within a 7-year period 1,597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Danish population-based NHL registry. Of these, 602 (38%) were aged 70 years or older (age range 70-94, median: 76.8). They represent the population defined as 'elderly' patients in the present study. The average annual incidence rate for this elderly patient population was 35.7/10(5), as compared with 6.6/10(5) for patients aged less than 70 (overall annual incidence: 9.5/10(5)). Localised cases (stage I and II) and extranodal manifestations were found more frequently among elderly patients. The most common sites of extranodal involvement were the stomach (21% of all extranodal cases) and the bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p less than 0.01) in elderly patients as compared to their younger counterparts (less than 70 years), who in contrast had a lower occurrence of diffuse centroblastic cases (p less than 0.01). Overall 7-year survival for the elderly patient population was 35% (median 1.7 years), and for patients aged less than 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66%, respectively, p less than 0.0001). Elderly patients with poor prognosis were characterised by the following features identified in a Cox-regression model: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were in the order 2.4, 2.2, 1.9 and 1.6.
Aged↗