Quality of dietary intake in relation to body composition in patients with chronic obstructive pulmonary disease eligible for pulmonary rehabilitation.

BACKGROUND/OBJECTIVES: A poor dietary quality may accelerate disturbances in body composition in chronic obstructive pulmonary disease (COPD), but only limited studies have investigated dietary intake from this perspective. The objective of the current study was to investigate dietary intake in relation to low fat-free mass and abdominal obesity in COPD. SUBJECTS/METHODS: Dietary intake was assessed by means of a cross-check dietary history method in 564 COPD patients referred for pulmonary rehabilitation. The Dutch Food Composition Database was used to calculate nutrient intake, which was compared with the 2006 recommendations from the Dutch Health Council. Body composition was assessed by DEXA scan. RESULTS: In general, the reported intake of macronutrients represented a typical western diet. With regard to micronutrients, vitamin D and calcium intakes were below the recommended levels in the majority of patients (>75%), whereas vitamin A, C and E intakes were below the recommended levels in over one-third of patients. Patients with inadequate vitamin D intake more frequently reported a low intake of protein (P=0.02) and micronutrients (P<0.001). Patients with a low fat-free mass index (FFMI) more often had low intake of protein, while abdominally obese patients more often had low intake of protein and most micronutrients (P<0.05). Patients with both low FFMI and abdominal obesity appeared most often to be consuming a poor-quality diet. CONCLUSIONS: Our data indicate that dietary quality is low in COPD patients referred for pulmonary rehabilitation and differs between patients with different body composition profiles.

Vitamin D, vitamin D binding protein, lung function and structure in COPD.

RATIONALE: Vitamin D and vitamin D binding protein (DBP) have been associated with COPD and FEV1. There are limited data regarding emphysema and vitamin D and DBP. OBJECTIVE: This is a pilot study of a portion of the subjects in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study designed to examine the relationship between vitamin D status, DBP, FEV1 and emphysema in COPD patients. METHODS: We measured serum 25(OH)D and DBP in 498 ECLIPSE subjects. Subjects were distributed amongst smoker controls, non-smoker controls, and GOLD stages 2, 3 and 4. Within each GOLD stage, the subjects were equally divided amongst high and low emphysema burden. The associations between 25(OH)D, DBP, and free vitamin D with FEV1, CT-defined emphysema, biomarkers and clinical data including CT-measured bone attenuation were assessed. MEASUREMENTS: 25(OH)D and DBP were measured using tandem mass spectroscopy and competitive enzyme-linked immunosorbent assay, respectively, MAIN RESULT: 25(OH)D was correlated with FEV1 (p = 0.01) and with severity of emphysema (p < 0.01). 25(OH)D was also associated with six-minute walk (p = 0.02), bronchodilator response (p = 0.04), and Clara cell secretory protein (CC-16) (p = 0.01). 25(OH)D levels were not associated with CT-measured bone attenuation, however DBP was associated with bone attenuation in subjects with emphysema. DBP was not associated with FEV1 or emphysema. 25(OH)D and DBP were inversely associated (p = 0.01). CONCLUSION: This is the first study to demonstrate a relationship between emphysema and vitamin D. We also provide further evidence for a relationship between vitamin D and FEV1.

Enhanced anabolic response to milk protein sip feeding in elderly subjects with COPD is associated with a reduced splanchnic extraction of multiple amino acids.

BACKGROUND & AIMS: We previously observed in elderly subjects with Chronic Obstructive Pulmonary Disease (COPD) an enhanced anabolic response to milk protein sip feeding, associated with reduced splanchnic extraction (SPE) of phenylalanine. Milk proteins are known for their high Branched-chain Amino Acids (BCAA) content, but no information is present about splanchnic extraction and metabolism of the individual BCAA in COPD. OBJECTIVE: To investigate whether BCAA metabolism and SPE of the individual BCAA are altered in COPD during milk protein sip feeding. DESIGN: In elderly subjects with COPD and in healthy age-matched elderly SPE, endogenous rate of appearance (Raendo) of the leucine (LEU), isoleucine (ILE) and valine (VAL) were measured before and during sip feeding of a Whey protein meal. To study the effect of aging, the healthy elderly were compared to a group of healthy young subjects. Stable isotopes of l-[(2)H(3)]-LEU, l-[1-(13)C]-ILE and l-[1-(13)C]-VAL were given on two separate test days orally or intravenously. Simultaneously, l-[ring-(2)H(5)]-phenylalanine (PHE) and l-[ring-(2)H(2)]-tyrosine (TYR) were given to determine the whole body protein breakdown (WbPB), synthesis (WbPS) and NetPS. RESULTS: SPE of all BCAA, TYR, and PHE (p < 0.01) were lower in the COPD group, and the increase in netPS during feeding was higher in the COPD group (P < 0.01) due to higher values for PS (P < 0.001). Raendo of all BCAA, PHE and TYR were higher in the COPD than the healthy elderly group (P < 0.05) before and during feeding (P < 0.001). Sip feeding resulted in a reduction of Raendo of PHE, ILE and VAL (P < 0.05). Postabsorptive Raendo was not different for any of the measured amino acids between the healthy elderly and young group, while sip feeding resulted in a reduction of Raendo of PHE. Only SPE of TYR was higher in the elderly (P < 0.05) and the increase in netPS during sip feeding was independent of aging. CONCLUSION: The enhanced anabolic response to milk protein sip feeding in normal-weight COPD patients is associated with a reduced splanchnic extraction of multiple amino acids including all branched-chain amino acids. Registration ClinicalTrials.gov = NCT01418469.

Whole-body resting and exercise-induced lipolysis in sarcopenic [corrected] patients with COPD.

Impaired beta-adrenoceptor-mediated lipolysis has been reported in sarcopenic [corrected] chronic obstructive pulmonary disease (COPD) patients. This could play a role in the shift in body composition towards decreased fat-free mass (FFM) and relative maintenance of fat mass (FM). Lipolysis could be affected by chronic treatment with beta(2)-agonists or disease-related factors. Therefore, whole-body resting and exercise-induced lipolysis were investigated in sarcopenic [corrected] COPD patients with moderate disease severity. Seven sarcopenic [corrected] COPD patients (mean+/-sem forced expiratory volume in one second (FEV(1)) 53+/-5% of the predicted value; body mass index (BMI) 27.5+/-0.9 kg x m(-2)) and seven controls matched for age, sex and BMI were studied. In addition, six underweight COPD patients (FEV(1) 51+/-5% pred; BMI 20.6+/-0.7 kg x m(-2)) matched for disease severity were recruited. Lipolysis and plasma levels of catecholamines were assessed during infusion of [(2)H(5)]glycerol at rest and during submaximal cycling exercise. The proportional FM was comparable between sarcopenic [corrected] patients and controls, whereas the FFM index was significantly reduced in patients. At rest, the rate of appearance (R(a)) of glycerol (4.1+/-0.6 and 3.3+/-0.2 micromol x kg FFM(-1) x min(-1), respectively) did not differ significantly. In underweight patients, glycerol R(a) (4.3+/-0.5 micromol x kg FFM(-1) x min(-1)) was also comparable. End-of-exercise lipolytic rates did not differ significantly between groups. Glycerol R(a) was not related to FM. Resting adrenalin levels were significantly increased in underweight COPD patients and were related to resting lipolysis. Sarcopenia [corrected] in chronic obstructive pulmonary disease patients with moderate disease severity is not characterised by an abnormal lipolytic rate. Altered regulation of muscle protein turnover seems to be the trigger in the body compositional shift observed in these patients.

Reirradiation of primary brain tumours: survival, clinical response and prognostic factors.

BACKGROUND AND PURPOSE: First, the aim was to determine the survival and quality of life after reirradiation of relapsing primary malignant brain tumours. The second aim was to assess the influence of a set of potentially prognostic factors on survival. MATERIALS AND METHODS: Forty-two patients received reirradiation for recurring primary brain tumours. The interval between the two consecutive treatments was at least 1 year. External beam irradiation for the initial and recurrent tumour was usually delivered with two opposing lateral fields or two wedged fields in orthogonal directions. The median physical doses of the first and second radiation course were 50 and 46 Gy, respectively. The median cumulative biological equivalent doses (BED) were 200.4 (alpha/beta = 2 Gy) and 115.2 Gy (alpha/beta = 10 Gy). During follow-up, corticosteroid medication and the WHO-performance were registered at regular intervals. The radiological response was assessed by reviewing all available CT- and MRI-films. Potentially prognostic factors with respect to survival were evaluated by both univariate and multivariate analyses. RESULTS: A clinical response (i.e. clinical improvement) was seen in 24% of the patients. Of the evaluable patients, nearly one-third showed a complete (8%) or partial (22%) radiological response. The median overall survival (OS) and progression-free survival (PFS) after retreatment were 10.9 and 8.6 months, respectively. By multivariate analysis, four independent prognostic factors for survival were identified: (1), the WHO-score before retreatment (P = 0.002); (2), the length of the interval between treatments (P = 0.008); (3), the tumour histology; and (4), the response to initial treatment (P values, 0.04). The median survival times for patients with WHO-scores of 0-1 and > or = 2 were 14.0 and 7.4 months, respectively. Patients with oligodendrogliomas had a median OS of 27.5 months, whereas patients with astrocytomas had a median OS of 6.9 months after retreatment. Long-term complications of retreatment were seen in three patients, all of whom had a cumulative BED(2) of > 204 Gy (with alpha/beta = 2 Gy). The quality of life after retreatment, however, was well preserved in the majority of patients. They remained ambulant and capable of self-care until the time of progression which occurred after 8.6 months (median PFS). CONCLUSIONS: After an initial treatment with radiation up to tolerance levels of normal brain tissue, reirradiation of recurring primary brain tumours seems feasible. During the time until clinical progression, patients remained independent with a reasonable quality of life.

The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.

PURPOSE: To answer the question whether a single fraction of radiotherapy that is considered more convenient to the patient is as effective as a dose of multiple fractions for palliation of painful bone metastases. PATIENTS: 1171 patients were randomised to receive either 8 Gy x 1 (n = 585) or 4 Gy x 6 (n = 586). The primary tumour was in the breast in 39% of the patients, in the prostate in 23%, in the lung in 25% and in other locations in 13%. Bone metastases were located in the spine (30%), pelvis (36%), femur (10%), ribs (8%), humerus (6%) and other sites (10%). METHOD: Questionnaires were mailed to collect information on pain, analgesics consumption, quality of life and side effects during treatment. The main endpoint was pain measured on a pain scale from 0 (no pain at all) to 10 (worst imaginable pain). Costs per treatment schedule were estimated. RESULTS: On average, patients participated in the study for 4 months. Median survival was 7 months. Response was defined as a decrease of at least two points as compared to the initial pain score. The difference in response between the two treatment groups proved not significant and stayed well within the margin of 10%. Overall, 71% experienced a response at some time during the first year. An analysis of repeated measures confirmed that the two treatment schedules were equivalent in terms of palliation. With regard to pain medication, quality of life and side effects no differences between the two treatment groups were found. The total number of retreatments was 188 (16%). This number was 147 (25%) in the 8 Gy x 1 irradiation group and 41 (7%) in the 4 Gy x 6 group. It was shown that the level of pain was an important reason to retreat. There were also indications that doctors were more willing to retreat patients in the single fraction group because time to retreatment was substantially shorter in this group and the preceding pain score was lower. Unexpectedly, more pathological fractures were observed in the single fraction group, but the absolute percentage was low. In a cost-analysis, the costs of the 4 Gy x 6 and the 8 Gy x 1 treatment schedules were calculated at 2305 and 1734 Euro respectively. Including the costs of retreatment reduced this 25% cost difference to only 8%. The saving of radiotherapy capacity, however, was considered the major economic advantage of the single dose schedule. CONCLUSION: The global analysis of the Dutch study indicates the equality of a single fraction as compared to a 6 fraction treatment in patients with painful bone metastases provided that 4 times more retreatments are accepted in the single dose group. This equality is also shown in long term survivors. A more detailed analysis of the study is in progress.

Quality of life after radiation therapy of cerebral low-grade gliomas of the adult: results of a randomised phase III trial on dose response (EORTC trial 22844). EORTC Radiotherapy Co-operative Group.

In 1985, the EORTC Radiotherapy Co-operative Group launched a randomised phase III study comparing high-dose (59.4 Gy in 6.5 weeks) versus low-dose (45 Gy in 5 weeks) radiotherapy with conventional techniques in patients diagnosed with low-grade cerebral glioma. The primary endpoint of the study was survival. No difference in survival was observed between the two treatment strategies. A quality of life (QoL) questionnaire consisting of 47 items assessing a range of physical, psychological, social, and symptom domains was included in the trial to measure the impact of treatment over time. Patients who received high-dose radiotherapy tended to report lower levels of functioning and more symptom burden following completion of radiotherapy. These group differences were statistically significant for fatigue/malaise and insomnia immediately after radiotherapy and in leisure time and emotional functioning at 7-15 months after randomisation. These findings suggest that for conventional radiotherapy for low-grade cerebral glioma, a schedule of 45 Gy in 5 weeks not only saves valuable resources, but also spares patients a prolonged treatment at no loss of clinical efficacy.

Pain characteristics help to predict the analgesic efficacy of radiotherapy for the treatment of cancer pain.

It is recognised that radiotherapy provides relief for intractable pain in approximately 50% of patients with cancer pain. Unfortunately, traditional explanatory variables, such as age, gender, histology or radiation dose, do not help to predict which individuals will benefit from palliative radiotherapy. A non-randomised prospective clinical trial was conducted on 51 patients to evaluate the value of pain characteristics as new explanatory variables for predicting the efficacy of palliative radiotherapy for providing cancer pain relief. Two new explanatory variables were identified: the presence of radiating pain and the pain score before radiotherapy.

A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844.

PURPOSE: Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article. METHODS AND MATERIALS: For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended. RESULTS: With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p < 0.0001) on multivariate analysis. Other prognostic factors, most of which are known, have now been quantified and confirmed in this prospective study. CONCLUSION: The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup, but objective prognostic parameters are recognized. The tumor size or T parameter as used in this study appears to be a very important factor.

Effects measured in the evaluation of automated information systems.

The results of a literature search show that most of the evaluation studies of automated information systems are dealing with structure measures. Only 15 of 91 studies investigated effects on the outcome of the care process. Probably one of the reasons for this lack of investigated "outcome" measures is the fact that many of the evaluated systems were not in routine use at the moment of evaluation. It is, however, possible to obtain indicators of outcome measures by investigating the relationship between process measures and outcome measures. In the context of many developments, such as the trend of increasing attention to the evaluation of outcomes of the care process and the increasing costs of health care, the effect of automated information systems on the outcome of the health care process becomes more and more important. In the attempts to develop guidelines for the evaluation of automated information systems, it is therefore important to pay attention to the relationship between process and outcome.

Prognostic implications of bone marrow culturing in myelodysplastic syndrome: a retrospective analysis.

To assess the predictive role of bone marrow culturing in MDS in vitro data of 205 patients were correlated with progression to AML and survival. Both in vitro growth pattern and in vitro differentiation were significantly predictive for progression to AML. Other predictive parameters were FAB classification and the presence of cytogenetic abnormalities in all metaphases analysed. Since FAB classification and in vitro bone marrow culturing appeared confounding variables, the in vitro data were analysed for high risk patients, RAEB and RAEBt and low risk patients, RA and RARS. In 91/110 RAEB(t) patients the estimated chance to develop AML was 25% in cases of normal growth versus 62% if abnormal (p < 0.06). In 82/87 RA(RS) patients the estimated chance to develop AML was 5% and 40% respectively (p = 0.0004). After AML progression median survival was only 2 months (0-16.1 months). In RAEB(t) patients bone marrow culturing did not discriminate for better survival, although a trend was shown. The estimated median survival was 16 months if growth was normal versus 8 months if abnormal (p = 0.07). In RA(RS) patients the median survival also was not significantly different, 31 versus 22 months respectively (p = 0.39). However, if in vitro growth and differentiation were both normal a significant difference in median survival was observed, 35 versus 22 months (p = 0.016). In conclusion, in vitro bone marrow culturing has predictive value for AML development in RA(RS) patients. In RAEB(t), due to many patients dying early in cytopenia, the predictive value is less pronounced. Especially normal growth in RA(RS) patients makes progression to AML very unlikely and these patients should be considered for a supportive approach. In RA(RS) patients with normal growth and differentiation (about 25% of all patients) in vitro bone marrow culturing also predicts a better survival.

Irradiation and responsiveness to pain stimuli in rats.

This study evaluates whether irradiation inhibits responses to pain in an animal model. We found that irradiation with doses of 10 Gy, 15 Gy and 17.5 Gy of the lumbar enlargement of the spinal cord inhibits the behavioural responses to the stimulus of the hot-plate. These doses were otherwise without effects. This data is discussed in view of the effects of irradiation of living cells, and we propose that a modification of pain signal processing is accomplished. Similar considerations apply to the human condition.

[Prognostic significance of the histological classification and staging for patients with a malignant non-Hodgkin lymphoma]. / De prognostische betekenis van histologische classificatie en stadiëring voor patiënten met een maligne non-Hodgkin-lymfoom.

OBJECTIVE: To assess the prognostic significance of histological classification, grade and stage with regard to overall survival in patients with non-Hodgkin's lymphoma (NHL). DESIGN: Retrospective analysis. SETTING: University Hospital St Radboud, Nijmegen. METHOD: All consecutive 346 patients with NHL diagnosed in the period January 1978-December 1990 were included in this one-centre study. Recorded data included histological type according to the Kiel classification, histological grading according to the International Working Formulation (IWF), Ann Arbor stage, age, sex, tumour mass, number of extranodal sites, serum LDH and ESR. Grading according to the IWF was assessed retrospectively for those patients whose primary disease had been diagnosed before 1982. The observation period ended September 1st, 1991. Overall survival was calculated according to Kaplan-Meier. The significance of the prognostic parameters was studied using both univariate and multivariate stepwise regression analysis. RESULTS: There were 209 men and 137 women with a median age of 56 years (range 15-85). No initial treatment was given to 8% of the patients. After a median follow-up of 52 months, 179 patients (52%) had died; the calculated median survival time was 49 months. Patients with low-grade NHL had a significantly better short-term prognosis than the remaining patients. Related to clinical stage, only patients with stage I disease had distinctly longer survival times than those with more advanced disease. Multivariate analysis revealed serum LDH, age, stage and histological classification to be the most important independent prognostic variables. CONCLUSION: Even in multivariate analysis, histological classification and Ann Arbor stage have prognostic significance with regard to overall survival in patients with NHL. However, serum LDH levels proved to be the most important prognostic parameter.

Histologic factors in the grading and prognosis of astrocytoma grade I-IV.

The prognostic value of histologic or cytologic features were examined in 317 patients with an astrocytic glioma. Of 46 features examined 7 morphologic characteristics of nucleus and 5 of mesenchyma correlated well with grading according to Kernohan. The morphological characteristics of nucleus are cellularity, atypical nuclei, polymorphism, multinucleated cells, hyperchromasia, gigantic nuclei and mitosis. For mesenchyma these were vascularity, vascular endothelial proliferation, vascular glomeruli, necrosis with palisade formation and necrosis without palisade formation. Scoring of these items on a scale from 0 to 4 enables us to establish a nucleus-score (max. 28) and a mesenchyma-score (max. 20). Nucleus-score + mesenchyma-score less than or equal to 10 corresponds with astrocytoma grade II, less than or equal to 20 with grade III and greater than 20 with grade IV. A low nucleus-score in grade II (less than 5) predicts a long survival (greater than 10 years), a high nucleus-score a low survival (median 0.6 year). In grade III a low mesenchyma-score predicts a median survival of 1.25 years, a high mesenchyma-score a median survival of 0.38 year. This retrospective study shows that nucleus-score and mesenchyma-score correlate to grading according to Kernohan and are highly correlative to survival.

Digiplot: a PC programme for drawing tumour volumes for radiation therapy treatment planning using computed tomography images.

Computed tomography (CT) provides explicit information for tumour localisation. However, CT data are displayed in the transverse plane, whereas on the Radiotherapy Simulation films, radiation portals are commonly directed into anteroposterior and lateral planes. Using present day radiotherapy planning computers, it is possible to read in the CT data to determine the tumour volume in anterior/posterior and lateral directions and to perform dosimetry calculations. In cases where the digital computer data cannot be used directly by the radiotherapy planning computer, (for example, owing to compatibility problems) the radiation oncologist must transfer information about tumour location from the CT hard copy images to the longitudinal planes of the simulation film by hand. This manual data transfer can now also be performed using the new personal computer programme, Digiplot, which we have developed and is described below. The application of Digiplot to the head and neck area has shown that it complies with the accuracy requirements laid down by the radiation oncologist. The clinical impact of Digiplot was tested on ten patients with a brain tumour. In two cases, Digiplot detected errors which had not been observed using the conservative (manual) method.

[Postoperative irradiation in grade III and IV astrocytoma]. / Postoperatieve bestraling bij astrocytoom graad III en IV.

The aim of this paper is to contribute to the discussion on the value of postoperative radiotherapy in patients with astrocytoma grade III-IV. One hundred and fifteen of the 243 patients with histologically proven astrocytoma grade III-IV received postoperative radiotherapy at the St. Radboud University Hospital Nijmegen. According to the protocol all patients with a fairly good performance status were irradiated. The extent of surgery consisted of biopsy alone in 11%, subtotal tumour resection in 85% and macroscopically complete tumour removal in 4%. All patients received a whole brain irradiation of 40 Gy with a boost of 10-15 Gy in the tumour. Patients with grade III who underwent surgical resection had a median survival of 2.1 months, those with grade IV 2.7 months. Patients who underwent surgical resection and radiotherapy had a median survival of 12 months (grade III) and 8.6 months (grade IV). The extent of surgery and grade of malignancy were the only prognostic factors. Because of the selection of patients this study produces no additional arguments in favour of postoperative radiotherapy. However, we continue our treatment strategy to irradiate patients with grade III-IV tumours because the median survival obtained with this strategy is high in comparison with data from literature.