Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middle-aged cancer patients shortly after chemotherapy.

PURPOSE: To evaluate the effectiveness of a supervised home-based flexible training program on cardiorespiratory fitness (CRF), mental distress, and health-related quality of life (HRQOL) parameters in young and middle-aged cancer patients shortly after curative chemotherapy. PATIENTS AND METHODS: One hundred eleven patients age 18 to 50 years who had received chemotherapy for lymphomas or breast, gynecologic, or testicular cancer completed the trial. These patients were randomly allocated to either an intervention group (n = 59), which underwent a 14-week training program, or a control group (n = 52) that received standard care. Primary outcome was change in CRF, as determined by Astrand-Rhyming indirect bicycle ergometer test (maximum oxygen uptake [VO(2max)]), between baseline (T0) and follow-up (T1). Secondary outcomes were mental distress, as assessed by the Hospital Anxiety and Depression Scale, and HRQOL, as assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire. Two-way analysis of covariance was used to analyze changes from T0 to T1. RESULTS: VO(2max) increased by 6.4 mL/kg(-1)/min(-1) in patients in the intervention group and by 3.1 mL/kg(-1)/min(-1) in patients in the control group (P < .01). The fatigue score decreased by 17.0 points in the control group compared with only 5.8 points in the intervention group (P < .01). There were no intergroup differences in mental distress or HRQOL. CONCLUSION: A supervised, home-based, flexible training program has significant effect on CRF in young and middle-aged cancer patients shortly after curative chemotherapy, but it has no favorable effect on patients' experience of fatigue, mental distress, or HRQOL.

Chronic poisoning by copper in tap water: I. Copper intoxications with predominantly gastointestinal symptoms.

Copper can induce acute and chronic intoxications in humans. Copper in tap water has caused a series of severe systemic diseases in Germany in recent years (copper induced liver cirrhosis). Besides cirrhosis, another type of disease with predominantly gastrointestinal symptoms has occurred which likewise appeared to be induced by copper in tap water. - In a retrospective investigation we looked for additional indications and proof that chronic copper poisoning has been the cause of the observed gastrointestinal diseases. All patients suffering from this type of disease had copper plumbing in their houses. - The patients (children and adults) suffered from nausea, vomiting, colic, and diarrhoea. In the group of infants, one refused formula milk (prepared with tap water) and the others suffered from persistent restlessness, unexplainable screaming (especially at night) and/or long lasting diaper rash. - We accept the diagnosis of chronic copper intoxication as the cause of the gastrointestinal symptoms when at least one of the following criteria were fulfilled: 1. first manifestation, remission and relapse of the disease depend on intake and a non-intake of water containing copper, respectively. 2. hypercupric state of the patients (i.e. pathological high concentrations of the non-ceruloplasmin-bound copper in serum and/or elevated copper levels in urine) 3. signs of systemic copper intoxication in the same patient 4. signs of systemic copper intoxication or hypercupric states in members of the patient s family or in his neighbourhood (non-relatives) - We found that the disease can even be caused by copper concentrations below the allowed concentration given by the German Guidelines for Drinking Water (Trinkwasserverordnung). - The data prove that copper in drinking water can cause gastrointestinal diseases and not only the better known systemic diseases (i.e. copper induced liver cirrhosis). Copper poisoning must be considered as a possible cause of chronic gastrointestinal diseases in those countries in which copper plumbing is common.

Chronic poisoning by copper in tap water: II. Copper intoxications with predominantly systemic symptoms.

Copper can induce acute and chronic intoxications in humans. Copper in tap water has caused a series of severe systemic diseases in Germany in recent years (chronic copper poisoning, CCuP). From the clinical point of view it has been difficult to establish the diagnosis on the basis of clinical and laboratory methods. In a retrospective study, we therefore looked for essential clinical signs as well as laboratory findings which might be typical and essential for the diagnosis of CCuP. - We observed that in patients with severe systemic CCuP not only the liver but also several other organs have been the target of copper. As a proof copper overload has been measured. The latter results are presented here. - During or shortly after exposure "free" serum copper (= non-ceruloplasmin-bound copper) was significantly elevated in all patients (range 5.1 to 47.1 micromol/l, or 25.7 to 56.2 % of total serum copper). The normal upper limits in infants according to Salmenperä (8) are: 0.3 micromol/l, or 1.6 % of total serum copper. - Total serum copper was elevated in 14/16 patients: 13.7 to 30.1 micromol/l in sick infants (normal upper level: 12.6 micromol/l), and 17.0 to 27.2 in sick children (normal upper level for children and adults: 21.4 micromol/l). - Urine copper excretion was found elevated in 9/10 patients, with a range of 11 to 456 microg/dl (normal upper level in adults: 15 microg/dl). - Our results show that patients with systemic CCuP are in a "hypercupric" state. The data thus firstly prove that indeed the putative agent copper is found in excess in the patients and secondly show that the estimation of "free" copper in serum and the measurement of copper in urine are reliable diagnostic methods. Elevation of total serum copper (even though not specific) can give a first hint to the diagnosis. - The hypercupric state of systemic CCuP can be differentiated from that of Wilson's disease by (1) normal levels of ceruloplasmin and (2) the observation that values for free copper in serum or urinary copper normalize in an environment without copper in tap water, for instance in a hospital.

Beneficial effect of amrinone on the size of acute regional ischemia in isolated rabbit hearts.

The effect of inotropes on myocardial ischemia is difficult to predict because they may influence the determinants of myocardial O2 demand and O2 supply differently. Several PDE-inhibitors have been reported to possess antiischemic properties related to their hemodynamic and O2-sparing effects. To assess whether PDE-inhibitors also possess direct cardioprotective properties, the effects of amrinone (2.5 x 10(-5) mol/L) in comparison to isoproterenol (5 x 10(-9) mol/L) and ouabain (1.5 x 10(-7) mol/L) were studied in isolated rabbit hearts perfused according to Langendorff at a constant pressure (70 cmH2O) and electrically driven at a constant pacing rate. Regional ischemia was induced by coronary artery ligation and quantified by epicardial NADH fluorescence. All substances significantly increased the actively developed left ventricular pressure to a similar extent (+20%) (P < 0.05). Coronary flow was significantly decreased by ouabain (-15%) and significantly increased by isoproterenol (+25%) and particularly by amrinone (+50%) (P < 0.05). Neither ouabain nor isoproterenol significantly changed the intensity or the distribution pattern of NADH fluorescence, whereas the size of the ischemic zone was significantly reduced by amrinone (-25%) (P < 0.05). The PDE-inhibitor amrinone was shown to possess a direct cardioprotective effect by improving myocardial perfusion and O2 supply in isolated rabbit hearts.

Influence of dihydropyridine-type calcium agonists on hemodynamics and myocardial ischemia in isolated rabbit hearts.

Calcium (Ca) agonists like Bay k 8644 ((-)-S-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (CAS 93468-89-4), may represent a new principle in the treatment of heart failure. Because of marked vasoconstrictive properties, these agents may have a deleterious effect on myocardial ischemia (MI). It was however demonstrated that contractility enhancement and coronary flow (CF) reduction do not automatically enlarge MI. Therefore, we investigated the influence of Bay k 8644 (10(-8) mol/l) in comparison to ouabain (1.5 x 10(-7) mol/l) in non-arrhythmogenic concentrations on MI in electrically paced isolated rabbit hearts (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l, 180 beats/min). MI was induced by coronary artery ligation and quantified by epicardial NADH-fluorescence. Left ventricular pressure (LVP) was significantly increased by ouabain (+10-20%) but slightly diminished by Bay k 8644 (-10%) (p < 0.05). CF reduction after Bay k 8644 (-30%) was more pronounced than after ouabain (-10%) (p < 0.05), but both substances did reduce relative CF (CF/LVP x heart rate) to the same extent (-20-30%) (p > 0.05). Nevertheless, ouabain did not significantly influence epicardial NADH-fluorescence area or intensity (p > 0.05), whereas MI was significantly enlarged by Bay k 8644 (+30%) (p < 0.05). It is concluded that in isolated rabbit hearts ouabain and Bay k 8644 might influence CF-distribution differently with a more pronounced diminuation of the nutritive CF induced by Bay k 8644.