Concordance in the interpretation of PET after chemotherapy in advanced stage Hodgkin lymphoma.

UNLABELLED: The aim was to analyze the degree of agreement between the central review panel and the local PET interpretation within the HD15 trial and its impact on subsequent treatment and progression free survival. PATIENTS, METHODS: The analysis set consisted of 739 patients with residues ≥ 2.5 cm after 6 or 8 cycles of BEACOPPesc from the HD15 trial performed by the German Hodgkin Study Group. The recommendation for or against further radiotherapy was based on the central [(18)F]FDG-PET interpretation. Central PET interpretation was compared to the local PET interpretation and concordance was measured using Cohen's Kappa coefficient. Prognostic impact of the analysis of concordance between local and central PET interpretations was evaluated using progression free survival (PFS); groups were compared with the log rank test. RESULTS: The central panel rated 548 of 739 patients (74%) as PET negative. Of these, 513 were also rated as PET negative in the local PET interpretation. PET positivity was seen by central reviewers in the remaining 191 patients (26%), in concordance with local reviewers in 155 cases. Even though substantial agreement was found (Cohen's Kappa 0.81), the interpretation of the central PET review panel led to a different therapeutic recommendation in 71/739 (10%) patients. PFS was equally high in groups in which the therapeutic regime had been changed on the basis of the central panel decision. CONCLUSION: High concordance is found between local and central reviewers with regard to PET interpretation in residual tissue after intense chemotherapy. The existence of the central PET review panel allows the identification of additional patients as PET negative so that radiotherapy can be safely omitted (35 of 548 patients = 4.7%).

Longitudinal study of the effects of teat condition on the risk of new intramammary infections in dairy cows.

Machine milking-induced alterations of teat tissue may impair local defense mechanisms and increase the risk of new intramammary infections. The objective of the current study was to assess the influence of short-term and long-term alterations of teat tissue and infectious status of the udder quarter on the risk of naturally occurring new intramammary infections, inflammatory responses, and mastitis. Short-term and long-term changes in teat condition of right udder quarters of 135 cows of a commercial dairy farm in Saxony-Anhalt, Germany, were recorded monthly for 10 mo using simple classification schemes. Quarter milk samples were collected from all examined quarters at each farm visit. Bacteriological culture results and somatic cell counts of quarter milk samples were used to determine new inflammatory responses (increase from ≤100,000 cells/mL to >100,000 cells/mL between 2 samples), new infections (detection of a pathogen from a quarter that was free of the same pathogen at the preceding sampling), and new mastitis (combination of new inflammatory response and new infection). Separate Poisson mixed models for new inflammatory responses, new infections, and new mastitis caused by specific pathogens or groups of pathogens (contagious, environmental, major, minor, or any) were used to estimate risk ratios and 95% confidence intervals. Data preparation and parameter estimation were performed using the open source statistical analysis software R. We observed no effect of any variable describing teat condition on the risk of new intramammary infections, inflammatory responses, or mastitis. Intramammary infections of the same udder quarter in the preceding month did not affect risk either.

Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin's lymphoma: an analysis from the German Hodgkin Study Group.

BACKGROUND: The optimal treatment of elderly patients with Hodgkin's lymphoma (HL) is still a matter of debate. Since many of these patients receive combined modality treatment, we evaluated the impact of different radiation field sizes, that is extended-field (EF) or involved-field (IF) technique when given after four cycles of chemotherapy. PATIENTS AND METHODS: In the multicenter HD8 study of the German Hodgkin Study Group, 1204 patients with early-stage unfavorable HL were randomized to receive four cycles of chemotherapy followed by either radiotherapy (RT) of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). A total of 1064 patients were assessable for the analysis. Of these, 89 patients (8.4%) were 60 years or older. RESULTS: Elderly patients had a poorer risk profile. Acute toxicity from RT was more pronounced in elderly patients receiving EF-RT compared with IF-RT [World Health Organization (WHO) grade 3/4: 26.5% versus 8.6%)]. Freedom from treatment failure (FFTF, 64% versus 87%) and overall survival (OS, 70% versus 94%) after 5 years was lower in elderly patients compared with younger patients. Importantly, elderly patients had poorer outcome when treated with EF-RT compared with IF-RT in terms of FFTF (58% versus 70%; P = 0.034) and OS (59% versus 81%; P = 0.008). CONCLUSION: Elderly patients with early-stage unfavorable HL generally have a poorer risk profile and outcome when compared with younger patients. Treatment with EF-RT instead of IF-RT after chemotherapy has a negative impact on survival of elderly patients and should be avoided.

Cost-benefit analysis of a plant sterol containing low-fat margarine for cholesterol reduction.

For decreasing the risk of coronary heart disease (CHD) it has been proposed to enrich food such as margarine with plant sterol esters which have been shown to reduce total and LDL cholesterol concentrations, two of the major risk factors. A Markov model was developed to assess the costs and benefits of consuming a low-fat plant sterol containing margarine (PS margarine). A health insurer's perspective was taken with a time frame of 10 years. Transition probabilities for CHD and CHD-related death were calculated on the basis of the Framingham risk equations. These were applied to a representative sample of the German population. The alteration in cholesterol levels after intake of PS margarine was estimated based on a meta-analysis of ten randomized controlled trials with parallel or crossover design that found a reduction of 5.7% in total cholesterol. Average annual costs of CHD were assumed to be at 3,000 euro. Costs for "no CHD" and "CHD-related death" were set to 0 euro since the intervention would solely be paid by the consumers. Sensitivity analyses were performed with regard to annual costs, risk estimation, PS margarine reduction in total cholesterol, discount factor, and risk of CHD-related death. The 10-year CHD risks are 6.1% (PS margarine) vs. 6.5% (control). Thus expected 10-year CHD costs are 696 euro (PS margarine) vs. 748 euro (control). The cost savings of 52 euro varied between 32 euro and 74 euro in the sensitivity analysis. A projection at the level of the population for which evidence (randomized controlled trials) exists that plant sterols lower cholesterol (25.35 million) leads to a reduction of 117,000 CHD cases over 10 years and a cost reduction of 1.3 billion euro for this time period (sensitivity analysis 0.8-1.9 billion euro).

Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects.

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response.

Successful mobilization of peripheral blood stem cells with the DHAP regimen (dexamethasone, cytarabine, cisplatinum) plus granulocyte colony-stimulating factor in patients with relapsed Hodgkin's disease.

High-dose chemotherapy followed by autologous stem cell transplantation can improve the outcome of relapsed and refractory Hodgkin's disease (HD) patients. The objective of the trial was to determine the mobilizing potential of the DHAP salvage regimen (dexamethasone, cytarabine, cisplatin) for the collection of peripheral blood stem cells (PBSC) in patients with relapsed HD. The target yield of harvesting CD34 + cells was > or =2 x 10(6)/kg in order to support the subsequent myeloablative chemotherapy. Most of the 105 patients included were intensively pre-treated with different combination chemotherapy regimens prior to mobilization. The use of DHAP followed by granulocyte colony-stimulating factor (G-CSF; 10 microg/kg) resulted in the successful collection of adequate numbers of PBSC in 97.1% of patients (102 of 105) with a median harvest of CD34+ cells of 13 x 10(6)/kg (range 2.6 - 85.1). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 65 of 103 (63%) patients after 1 apheresis, the maximum number of aphereses for all patients was 3. It was found that the optimal time of PBSC harvest was at days 13 - 16 after initiating the mobilization regimen. These results demonstrate that the salvage chemotherapy regimen, such as DHAP combined with G-CSF, can be successfully used to mobilize PBSC in HD patients.

Gas exchange during exercise in habitually active asthmatic subjects.

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency.

A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly).

In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.

Pulmonary function subsequent to expiratory muscle fatigue in healthy humans.

One of the mechanisms proposed to explain the decrement in pulmonary function often seen after exercise is fatigue of the expiratory muscles. To test the hypothesis that expiratory muscle fatigue alters lung function, several indices of pulmonary function were measured before and after expiratory muscle fatigue was induced by expiratory loaded breathing. Eight subjects completed a fatigue trial (EF) in which expiratory threshold loaded breathing was performed at an initial resistance equal to 80 % of their maximal expiratory pressure (MEP), at a respiratory rate of 13 bpm, and a duty cycle (T(I)/T(Tot)) of 0.33. MEP was taken at predefined intervals throughout the loaded breathing protocol, and loaded breathing was discontinued when MEP was less than 80 % of each subject's pre EF trial MEP (T(Lim)). FVC, FEV(1.0), FEF(25 %), FEF(25-75 %), and maximal inspiratory and expiratory pressures (MIP and MEP) were taken prior to, immediately after, and at 5, 10, and 15 min post fatigue. On a separate day a control trial (CON) was performed that was identical to each subjects EF trial with the exception that no expiratory load was utilized. At T(Lim) MEP was significantly reduced (p < 0.001) by 23.5 % from the pre-expiratory loaded breathing value (183.1 +/- 39.56 to 140.13 +/- 30.45 mmHg), whereas it remained unchanged during the CON trial (191.06 +/- 44.18 to 188.06 +/- 43.50 mmHg). FVC measured prior to and immediately after T(Lim) remained unchanged following both the EF (5349.45 +/- 1130.8 to 5387.43 +/- 1139.92 mL) and CON trials (5287.75 +/- 1220.29 and 5352.78 +/- 1191.30 mL). These results suggest that any expiratory muscle fatigue developed during exercise by itself does not result in altered pulmonary function. However, any interactions between expiratory muscle fatigue and other consequences of exercise that may alter lung function cannot be ruled out.

Alterations in pulmonary function following exercise are not caused by the work of breathing alone.

Both pulmonary function and respiratory muscle strength decrease following exercise in healthy humans. The alterations in respiratory muscle are not the same following exercise and voluntary isocapnic hyperpnea that simulates that exercise. Therefore, in this study we measured pulmonary and respiratory muscle function following maximal exercise or hyperpnea that simulated the ventilation seen during exercise. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1.0), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and handgrip strength were measured before and following voluntary hyperpnea in which minute ventilation and breathing frequency were controlled to levels identical to those obtained during the exercise test, and before and following a period of rest of equal duration to the exercise and hyperpnea tests. FVC decreased by 400 ml (7%, p<0.05) immediately post-exercise. MIP decreased by 12 mmHg (15%, p < 0.005) following exercise and remained depressed for 15 minutes. Neither MEP nor FEV1.0 decreased following exercise, and none of the variables were altered following the control or hyperpnea bouts. These data indicate that pulmonary function and respiratory muscle strength are altered following exercise but not by similar bouts of hyperpnea without accompanying exercise. Therefore, exercise affects pulmonary function independent of the respiratory muscle work done.

Effect of manipulating visual feedback parameters on eye and finger movements.

Thirteen healthy subjects were asked to maintain a constant index finger position in Experiment 1 or a constant eye position in Experiment 2 using visual feedback. The finger or eye position along with a stationary baseline target was displayed on an oscilloscope placed in front of the subject. Experiments 1 and 2 were carried out under sixteen combinations of delay and amplification of displacement on the screen (i.e., gain). In Experiment 1, increasing the gain in the visual feedback decreased the Root Mean Square (RMS) errors while increasing the delay increased these errors. An interaction between gains and delays was also observed in Experiment 1. In Experiment 2, the RMS errors were systematically higher than those recorded in Experiment 1 for the finger. No systematic pattern was recognized across all conditions of gains and delays for eye movements in Experiment 2. This study clearly illustrates differences in dynamics of motor control systems regulating eye and finger positions, respectively.

Transpapillary positioning of a large 3.2 mm biliary endoprosthesis.

An endoscopic method for positioning a large-caliber (3.2 mm) biliary endoprosthesis is described. In 3 patients with malignant jaundice the endoprosthesis provided definitive relief of jaundice until death 4 1/2, 15 and 17 weeks respectively after the introduction of the prosthesis.

Serological and clinical evidence of toxoplasmosis on the Upper Leeward Islands.

Toxoplasma infections are common on the Upper Leeward Islands (Saba, St. Maarten and St. Eustatius, Neth. Antilles) as proved by clinical evidence and serological determinations in patients and in healthy people. In schoolchildren an overall positive percentage of 45.5% was found. On St. Eustatius the highest frequency of recent infections was in the youngest age groups, in contrast with findings in the Netherlands and in Germany.

Serological and clinical evidence of toxoplasmosis in the Upper Leeward Islands

Toxoplasma infections are common on the Upper Leeward Islands (Saba, St. Maarten and St. Eustatius, Neth. Antilles) as proved by clinical evidence and serological determinants in patients and in healthy people. In schoolchildren an overall positive percentage of 45.5 percent was found. On St. Eustatius the highest frequency of recent infections was in the youngest age groups, in contrast with findings in the Netherlands and in Germany (AU)

Positioning of a plastic prosthesis under fiberendoscopic control in the palliative treatment of cardio-esophageal cancer.

A method is described for non surgical peroral positioning of a plastic prosthesis under visual control in patients with obstructing cardio-esophageal malignancy or with pulmonary-esophageal fistula. The ACMI-F7 small calibre endoscope is well suited for guiding the prosthesis mainly because of easy maneuvrability and sufficient sturdiness to withstand substantial pushing force.