Elevated levels of serum CD44 and E-cadherin predict an unfavourable outcome in myelodysplastic syndromes.
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Adult↗
Biomedical subjects
M Herold
Publications and source records attributed to M Herold.
Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO).
PURPOSE: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). PATIENTS AND METHODS: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. RESULTS: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. CONCLUSION: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.
Adult↗
Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).
PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.
Adult↗
Chronomics, neuroendocrine feedsidewards and the recording and consulting of nowcasts--forecasts of geomagnetics.
A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5-20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on antiphasic lighting regimens happened to start on the day after the second extremum of a moderate double magnetic storm gauged by the planetary geomagnetic Kp index (which at each extremum reached 6.3 international [arbitrary] units) and by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter on the first day of the sampling. Neuroendocrine chronomes (specifically circadian time structures) differed during magnetically affected and quiet days. The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude and tended to advance in acrophase, while the MESOR and amplitude of the hypothalamic circadian melatonin rhythm were higher during the days with the storm. The circadian parameters of circulating corticosterone were more labile during the days including the storm than during the last three quiet days. Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a mechanism underlying physiological and probably also pathological associations of the brain and heart with magnetic storms. Investigators in many fields can gain from at least recording calendar dates in any publication so that freely available information on geomagnetic, solar and other physical environmental activity can be looked up. In planning studies and before starting, one may gain from consulting forecasts and the highly reliable nowcasts, respectively.
Animals↗
Circadian and extracircadian exploration during daytime hours of circulating corticosterone and other endocrine chronomes.
During 7 consecutive days, blood and several tissues were collected during daytime working hours only, three times per day at 4-h intervals from inbred Wistar rats, which had been previously standardized for 1 month in two rooms on a regimen of 12 h of light (L) alternating with 12 h of darkness (LD12:12). In one room, lights were on from 09:00 to 21:00 and in the other room, lights were on from 21:00 to 09:00 (DL12:12; reversed lighting regimen). This setup provides a convenient design to study circadian and extracircadian variations over long (e.g., 7-day) spans. Prior checking of certain circadian rhythms in animals reared in the room on reversed lighting (DL) as compared with animals in the usual (LD) regimen provided evidence that the 180 degrees phase-shift had occurred. These measurements were limited to the circadian (and not extended to infradian) variation. As marker rhythm, the core temperature of a subsample of rats was measured every 4 h around the clock (by night as well as by day) before the start of the 7-day sampling. An antiphase of the circadian rhythm in core temperature was thus demonstrated between rats in the LD vs. DL rooms. A sex difference in core temperature was also found in each room. A reversed rhythm in animals kept in DL and an antiphase between rats kept in DL vs. LD was again shown for the circulating corticosterone rhythm documented in subsamples of 8 animals of each sex sampled around the clock during the first approximately 1.5 day of the 7-day sampling. The findings were in keeping with the proposition that sampling rats at three timepoints 4 h apart during daytime from two rooms on opposite lighting regimens allows the assessment of circadian changes, the daytime samples from animals kept on the reversed lighting regimen accounting for the samples that would have to be obtained by night from animals kept in the room with the usual lighting regimen. During the 7-day-long follow-up, circadian and extracircadian spectral components were mapped for serum corticosterone, taking into account the large day-to-day variability. A third check on the synchronization of the animals to their respective lighting regimen was a comparison (and a good agreement) between studies carried out earlier on the same variables and the circadian results obtained on core temperature and serum corticosterone in this study as a whole. The present study happened to start on the day of the second extremum of a moderate double magnetic storm. The study of any associations of corticosterone with the storm is beyond our scope herein, as are the results on circulating prolactin, characterized by a greater variability and a larger sex difference than corticosterone. Sex differences and extracircadian aspects of prolactin and endothelin determined in the same samples are reported elsewhere, as are results on melatonin. Prior studies on melatonin were confirmed insofar as a circadian profile is concerned by sampling on two antiphasic lighting regimens, as also reported elsewhere. Accordingly, a circadian map for the rat will eventually be extended by the result of this study and aligned with other maps with the qualification of the unassessed contribution in this study of a magnetic storm.
Animals↗
Anti-CCP: history and its usefulness.
Antibodies directed to cyclic citrullinated peptides (anti-CCP) are highly specific for rheumatoid arthritis (RA) and can easily be detected in sera by using commercially available immunoassays. The second version of the anti-CCP test (anti-CCP2) demonstrated high specificity (89-98%) and good sensitivity (41-88%) for RA. Commercially available ELISA methods from three different companies are on the market. All three CCP2 assays show similar results as all CCP2 assays use the same antigen-coated plates. This study was an evaluation of a new automated method for the determination of anti-CCP2 in a routine laboratory setting. Five hundred and forty three serum samples were tested for anti-CCP2 within normal routine diagnostic using a commercially available ELISA and retested with a prelaunch version of a new and fully-automated method (EliA). The results were comparable. The new automated assay is easy to use and demonstrated a diagnostic sensitivity of 80% and specificity of 97%.
Antibody Specificity↗
Impairment of the NO/cGMP pathway in the fasting and postprandial state in type 1 diabetes mellitus.
The assessment of the postprandial state in diabetes mellitus has gained importance due to postprandial hyperglycemia being considered as an independent risk factor for cardiovascular disease. Hyperglycemia may contribute to vascular dysfunction through the alteration of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. The authors assessed the NO/cGMP pathway in the fasting and postprandial state in 20 type 1 diabetic patients (age: 34.1 +/- 2.6 years, body mass index (BMI): 24.1 +/- 1.3 kg/m (2), duration of diabetes: 16 +/- 2.2 years, HbA (1C): 8.3 +/- 0.4 %, [x +/- SEM], 10 without, 10 with late complications) and 20 matched control subjects (age: 39.7 +/- 1.9 years, BMI: 25.3 +/- 1.1 kg/m (2)). In the fasting state NO end product (nitrite/nitrate) levels did not differ between the diabetic and control group, cGMP levels were found to be significantly lower in the diabetic group (2.5 +/- 0.2 vs. 4.6 +/- 0.6 nmol/l, p = 0.01). A higher level of lipid peroxidation end products (TBARS) was found in diabetic subjects (6.7 +/- 0.4 vs. 5.0 +/- 0.3 micro mol/l, p = 0.004). The diabetic subgroup without late complications had significantly higher nitrite/nitrate levels compared to the patients with complications (57.8 +/- 6.6 vs. 30.4 +/- 4.3 micro mol/l, p = 0.006), their TBARS and cGMP levels were similar. The control subjects responded to the test meal with an increase in the cGMP levels (4.6 +/- 0.6 to 5.5 +/- 0.6 nmol/l, p = 0.02), while in the diabetic group no change was detected. Postprandial nitrite/nitrate levels decreased in both groups, they were significantly lower in the diabetic group. There was no difference between postprandial nitrite/nitrate, cGMP, or glucose levels in the diabetic subgroups. Postprandial glucose levels showed a significant negative correlation with cGMP levels in the diabetic group (r = - 0.50, p = 0.02). The results suggest that in subjects with type 1 diabetes mellitus NO might have an impaired ability to induce cGMP production in the fasting state prior to the development of late specific complications or microalbuminuria under hyperglycemic conditions. Postprandial hyperglycemia is suggested to interfere with endothelial NO action, as shown by the decreased nitrite/nitrate and unchanged cGMP plasma levels in the diabetic group. The impairment of the NO/cGMP pathway both in the fasting and postprandial state that was shown in patients without diabetic complications may be an early sign of hyperglycemia induced vascular damage in type 1 diabetes mellitus.
Adult↗
Quantitative assessment of periarticular osteopenia in patients with early rheumatoid arthritis: a preliminary report.
BACKGROUND: Involvement of the metacarpophalangeal (MP) joints is one of the major problems in patients with rheumatoid arthritis (RA). Although several data about the cumulative influence of steroid intake on bone are available, the course of demineralisation in RA has not been described by quantitative methods until now. PATIENTS AND METHODS: Computed tomography (CT) sections of 96 MP joints in 12 RA patients and of 32 MP joints in four age-matched healthy controls were investigated. Patients were classified according to Steinbrocker. Densitometric evaluation of subchondral bone density was performed by CT osteoabsorptiometry (CT-OAM). Quantitative CT-OAM was used to evaluate mineralisation of the articular surfaces in MP joints. RESULTS: In the distal articular surface of MP joints, the number of density maxima was reduced from 3 to 2.1+/-0.3, 1.9+/-0.5 and 1.3+/-0.3 in RA patients with early, mild to moderate, and severe disease, respectively. Means of calcium concentrations were 633.4+/-35. 3 mg Ca2+/mL, 518.9+/-56.2 mg Ca2+/mL, 497.7+/-23.8 mg Ca2+/mL and 455.1+/-28.6 mg Ca2+/mL for controls and RA patients with early, mild to moderate, and severe RA, respectively. Mineralisation of the distal articular surface was significantly reduced in all groups of RA patients [probability (p) = 0.005]. Regarding the number of density maxima, no differences were detected in the proximal articular surface of normal and RA fingers. However, mineralisation of the proximal articular surface was significantly reduced in all groups of RA patients (p = 0.004). Means of calcium concentrations of the proximal articular surface were 494.1+/-48.5 mg Ca2+/mL, 413.0+/-16.2 mg Ca2+/mL, 406.0+/-51.4 mg Ca2+/mL, 390,4+/-41.1 mg Ca2+/mL for controls and RA patients with early, mild to moderate, and severe RA, respectively. CONCLUSION: Patients with early and untreated RA show loss of mineralisation and altered morphology of the MP joints of the hand, even before corticosteroid therapy. CT-OAM provides evidence for an early alteration of functional anatomy in MP joints.
Adult↗
Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group.
BACKGROUND: Aviscumine is an Escherichia coli-derived recombinant type II ribosome-inactivating protein with potent antitumor activity in vitro and in vivo. It is the recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the intravenous (i.v.) administration of aviscumine in cancer patients. Translational research included the evaluation of pharmacokinetics and monitoring of plasma cytokine and anti-aviscumine antibody induction after administration of the drug. PATIENTS AND METHODS: Aviscumine was given twice weekly as a 1 h central i.v. infusion in patients with advanced, refractory progressive, solid malignant tumors who had not been previously exposed to natural mistletoe preparations. They had histologically or cytologically verified disease, were > or =18 years old, had an Eastern Cooperative Oncology Group performance status < or =2 and adequate bone marrow, liver and renal function. DLT was defined as any non-hematological grade 3-4 toxicity (National Cancer Institute Common Toxicity Criteria version 2.0), neutrophil count <500/microl for > or =7 days, febrile neutropenia or thrombocytopenia grade 4. The MTD was defined as the dose at which >20% of patients experienced DLT during the first treatment cycle. The Continual Reassessment Method was used to determine the number of patients required per dose level. RESULTS: Forty-one fully eligible patients (19 male, 22 female) with a median age of 56 years (range 37-74) were enrolled. Colorectal, ovarian, renal cell and breast cancer were the most common tumor types. Dose levels of aviscumine ranged from 10 to 6400 ng/kg. The median number of cycles was two (range one to eight). Common clinical toxicities in cycle 1 were fatigue, fever, nausea, vomiting and allergic reactions. Fatigue grade 3 was dose limiting in one of six patients at 4000 ng/kg and reversible grade 3 liver toxicity (elevation in alkaline phosphatase, transaminases and/or gamma-glutamyltransferase) occurred in one of 10 patients at 4800 ng/kg and in two of five patients at 6400 ng/kg. The best response (RECIST criteria) was stable disease in 11 patients, lasting for two to eight cycles. The pharmacokinetic evaluation revealed a short alpha half-life of 13 min and linear kinetics on dose levels > or =1600 ng/kg. Aviscumine stimulated the immune system with a release of cytokines such as interleukin (IL)-1beta, IL-6 and interferon-gamma, and induced immunoglobulin (Ig) G- and/or IgM-anti-aviscumine antibodies of uncertain clinical relevance. CONCLUSIONS: The recommended dose for further clinical trials is 5600 ng/kg twice weekly. Based on the short half-life of the recombinant protein observed in this trial, the exploration of prolonged infusion schedules of aviscumine is warranted.
Adjuvants, Immunologic↗
Randomized phase III study for the treatment of advanced indolent non-Hodgkin's lymphomas (NHL) and mantle cell lymphoma: chemotherapy versus chemotherapy plus rituximab.
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Adolescent↗
Prospective observational study of antiphospholipid antibodies in acute lung injury and acute respiratory distress syndrome: comparison with catastrophic antiphospholipid syndrome.
Detection of antiphospholipid (aPL) antibodies in bronchoalveolar lavage fluid (BALF) of patient with acute respiratory distress syndrome (ARDS) suggests involvement of autoimmune mechanisms in the pathogenesis of ARDS. We investigated whether aPL antibodies could be detected in the serum as well as BALF of patients with acute lung injury (ALI) and ARDS. IgG anticardiolipin, IgG anti-beta2-glycoprotein I, IgG antiphosphatidic acid and IgG antiphosphatidylserine antibodies were detected by ELISA in low titers within the normal range in the BALF and serum of nine patients with ALI and 17 patients with ARDS. However, one out of 27 patients investigated had high levels of aPL antibodies in both BALF and serum. This patient suffered from severe ARDS due to sepsis. The high aPL antibody levels in serum possibly triggered by sepsis were associated with high aPL antibody levels in BALF, which can be explained by high capillary-alveolar permeability. Computed tomography scan revealed widespread infarctions in brain, spleen and kidneys, and pulmonary thromboembolism, suggesting the diagnosis of catastrophic antiphospholipid syndrome.
Adult↗
Protracted infection of pacemaker leads with development of large vegetations: three years follow up. Case report.
A case history of a patient with permanent pacemaker reports inaccurate diagnosis of inflammation at the site of operation wound and a protracted infection of pacemaker leads. Inadequate therapy led to protracted inflammation with the leads fixed in the superior vena cava and the development of large vegetations in the right heart. Finally, the condition was resolved by surgical explantation and long-term antibiotic therapy. This case history describes infectious complications related to the implantation of a permanent pacemaker and the role of echocardiography in diagnosis of vegetations and points out the surgical treatment as a method of choice.
Aged↗
[Chronic lymphatic leukemia. Current therapy concepts].
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Antibodies, Monoclonal↗
Costs of toxicity during chemotherapy with CHOP, COP/CVP, and fludarabine.
The costs of chemotherapy toxicity were analyzed in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL). A total of 91 specialists regularly treating NHL were interviewed by telephone to identify the most commonly used treatment regimens. Retrospective case record forms providing data on 424 patients with relapsed low-grade NHL were used to assess adverse event (AE) frequency and management. Data on one cycle of treatment was collected for each patient, and unit costs were assessed and extrapolated for six cycles to estimate AE costs for an average course of treatment. Average AE management costs were evaluated by country and treatment regimen. Toxicity costs were substantial for the most commonly used chemotherapy regimens, namely CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), COP/CVP (cyclophosphamide, vincristine, prednisone), and fludarabine therapies. In Canada CHOP-associated AEs costs (EUR 5.036 per patient) were more than twofold greater than drug acquisition costs, and cost more than AEs associated with COP/CVP (EUR 3.252) or fludarabine (EUR 1.273). In Germany CHOP-associated AE costs (EUR 2.515) were comparable to to those associated with COP/CVP (EUR 2.658). In Italy CHOP-associated AE costs (EUR 2.179) were considerably less than those associated with fludarabine treatment (EUR 4.908). Neutropenia and fever/infection AEs were the most common and more expensive to treat than nausea and vomiting, anaemia, thrombocytopenia, or other AEs in all three countries. This study shows that management of neutropenia and fever/infection are the most expensive AE costs associated with conventional chemotherapeutic treatment of relapsed low-grade NHL. AE management costs are substantial and are likely to be an important cost driver in all countries.
Journal Article↗
Tumour necrosis factor-alpha plasma levels in elderly patients with Type 2 diabetes mellitus-observations over 2 years.
AIMS: The cytokine tumour necrosis factor-alpha (TNF-alpha) is involved in the development of obesity-linked insulin resistance. TNF-alpha plasma levels rise with increasing age and might thus also be related to metabolic control in Type 2 diabetes mellitus. We have studied the relationship of TNF-alpha plasma levels to glycaemic control in elderly patients with Type 2 diabetes over 2 years. METHODS: Clinical and laboratory data of 53 patients (26 women, 27 men) with Type 2 diabetes (mean age 71.6 +/- 5.6 years) were regularly evaluated over 2 years, and the relationship to anti-diabetic treatment regimens analysed. TNF-alpha plasma level was measured by a solid-phase enzyme amplified sensitivity immunoassay. RESULTS: TNF-alpha plasma levels increased significantly from 16.2 +/- 9.6 pg/ml at baseline to 28.0 +/- 13.8 pg/ml after 2 years (P = 0.028). HbA1c values also increased from 6.4 +/- 1.2% to 7.7 +/- 1.6% (P = 0.046). Mean body mass index of the patients remained almost constant, while a moderate increase in the percentage of body fat (34.5 +/- 7.0% to 35.3 +/- 6.9%; P= 0.061) and in waist-hip ratio was observed (0.86 +/- 0.04 to 0.88 +/- 0.04; P= 0.052). After adjustment for covariates multivariate analysis demonstrated that TNF-alpha plasma levels are positively related to the HbA1c values of the whole study population at the baseline control and after 2 years. TNF-alpha also revealed a positive correlation to the percentage of body fat. CONCLUSIONS: In elderly patients with Type 2 diabetes TNF-alpha plasma levels revealed a continuous increase during an observation period of 2 years. This increase in TNF-alpha plasma levels might add another aspect to the worsening of glycaemic control in the progression of Type 2 diabetes.
Adipose Tissue↗
Osteocalcin: a marker of disease activity in ankylosing spondylitis?
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Adult↗
Efficacy and safety of a combined rituximab chemotherapy during pregnancy.
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Adult↗
Serum 25-hydroxyvitamin D and parathyroid hormone in patients with ankylosing spondylitis before and after a three-week rehabilitation treatment at high altitude during winter and spring.
Does a sojourn at high altitude during the winter and spring improve vitamin D status (and possibly suppress parathyroid hormone [PTH]) in patients with ankylosing spondylitis (AS)? In 73 patients with AS, serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and PTH were determined before and after a three-week rehabilitation treatment at Bad Gastein (1000 m above sea level). At the first examination, serum 25(OH)D was median (25th, 75th percentile) 15.5 ng mL-1 (10.0 ng mL-1, 20.6 ng mL-1). Thirteen patients (18%) had a 25(OH)D concentration below 8 ng mL-1. In 53 patients (73%) the level was below 20 ng mL-1. After the sojourn, 25(OH)D significantly (p = 0.02) increased to 19.7 (11.3, 24.6) ng mL-1. PTH did not change significantly, being 32 (22.4, 43.9) pg mL-1 before and 30.3 (24.1, 39.9) pg mL-1 after the sojourn. Analysing different periods of sojourn, a significant (p < 0.001) increase in 25(OH)D was found in April but not in the other months. Patients with ankylosing spondylitis may have extremely low levels of 25(OH)D. The results of the present study suggest that a sojourn at high altitude in early spring is liable to reduce vitamin D deficiency.
25-Hydroxyvitamin D 2↗