Encouraging results in older patients receiving chemotherapy: A retrospective analysis of treatment guideline adherence in daily practice

Objective: A retrospective study was performed to determine whether patients over 60 years old who received chemotherapy were treated according to the existing treatment guidelines and to investigate the reasons for dose reductions or treatment delay. Material and methods: Three hundred and seven patients aged over 60 years old and diagnosed with colon, breast or lung cancer between 1998 and 2008 who were treated with chemotherapy in the Radboud University Medical Center were included. From the medical records we recorded the number of and the reasons for dose reductions and delays. We calculated the relative dose intensity (RDI) received. Results: RDI did not decrease significantly with age. However patients over 65 years of age had a higher probability of receiving a suboptimal dose intensity, even when treated with curative intent. There was no correlation between toxicity and age, however the comorbidity score increased with age. The average received RDI was higher in patients diagnosed more recently. Conclusion: Despite increased comorbidity, older patients receiving chemotherapy were generally treated according to protocol without high incidence of severe toxicity. We saw improvement of RDI over the time period investigated. The participation of geriatricians in multidisciplinary oncology teams could help to optimize therapy decisions for patients with comorbidity. Geriatr Gerontol Int 2012; 12: 80–85.     

Therapeutic angiogenesis with vascular endothelial growth factor in peripheral and coronary artery disease: a review

Therapeutic angiogenesis constitutes an alternative treatment for patients with extensive tissue ischaemia in whom primary vascular reconstruction procedures are not feasible or have previously failed. At present vascular endothelial growth factor (VEGF) has been the most widely used angiogenic factor in experimental and human clinical trials. Early clinical data provide evidence that gene transfer of the VEGF gene can achieve beneficial angiogenesis, with minimal side-effects. Ongoing phase III clinical studies will reveal definitive efficacy.     

Behavioral adjustment in children of diabetic mothers

The aim of this study was to evaluate whether maternal diabetes in pregnancy may adversely affect the children's behavioral adjustment, in a sample of 201 mothers (68 with pre-gestational diabetes, 50 with gestational diabetes, and 83 with non-diabetic pregnancies) and their singleton offspring. After accounting for socioeconomic status, ethnicity and maternal attitudes, none of the Child Behavior Checklist ratings correlated significantly with maternal patient group or several indices of antepartum maternal metabolism. Child obesity, a common sequela of diabetic pregnancies, correlated positively with Internalizing Behavior problems and three narrow-band sub-scales: Somatic Complaints, Anxious/Depressed, and Social Problems. Results suggest that children of diabetic mothers are at increased risk for a variety of developmental disturbances. Screening for learning and behavioral difficulties should be made at regular pediatric visits, with follow-up evaluations warranted by positive indications, excessive weight gain, or other evolving medical concerns.     

The effects of phenethyl isothiocyanate, N-acetylcysteine and green tea on tobacco smoke-induced lung tumors in strain A/J mice

Male and female strain A/J mice were exposed to a mixture of cigarette sidestream and mainstream smoke at a chamber concentration of total suspended particulates of 82.5 mg/m3. Exposure time was 6 h/day, 5 days/week for 5 months. The animals were allowed to recover for another 4 months in filtered air before sacrifice and lung tumor count. Male animals were fed either 0.2% N-acetylcysteine (NAC) or 0.05% phenethyl isothiocyanate (PEITC) in diet AIN-76A with 5% corn oil added. Female animals received normal laboratory chow and were given a 1.25% extract of green tea in the drinking water. Corresponding control groups were fed diets without NAC or PEITC or given plain tap water. Exposure to tobacco smoke increased lung tumor multiplicity to 1.1-1.6 tumors/lung, significantly higher than control values (0.5-1.0 tumors/lung). None of the putative chemopreventive agents (NAC, PEITC or green tea extract) had a protective effect. In positive control experiments, PEITC significantly reduced both lung tumor multiplicity and incidence in mice treated with the tobacco smoke-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In mice treated with three different doses of urethan and fed NAC in the diet, a significant reduction in lung tumor multiplicity was found only at one dose level. Green tea extract did not reduce lung tumor multiplicity in animals treated with a single dose of NNK. It was concluded that successful chemoprevention of tobacco smoke-induced lung tumorigenesis might require administration of several chemopreventive agents rather than just a single one.      

Glycan microheterogeneity of alpha 1-acid glycoprotein in sera and dialysates of patients on continuous ambulatory peritoneal dialysis

Total concentration and concanavalin (Con A) dependent microheterogeneity of alpha 1-acid glycoprotein (AGP) were studied in sera of eight chronic renal failure patients before the start of continuous ambulatory peritoneal dialysis (CAPD), and in sera and dialysate fluids for up to 6 months of CAPD. The glycan heterogeneity of AGP in the samples was expressed as a reactivity coefficient, i.e. the ratio of the Con A-reactive AGP components to the Con A non-reactive AGP component. Concentrations of AGP in serum and reactivity coefficients were markedly elevated in non-dialysed uraemic patients. AGP concentrations in serum increased further during the first week on CAPD, and then gradually decreased to pre-dialysis values, which were reached after 1 to 6 mth. The reactivity coefficients did not change significantly during the CAPD treatment. Dialysate AGP concentrations were low in comparison to those in serum, and there was a good correlation between the reactivity coefficients in the dialysate fluids and those in the corresponding sera. The effect of peritonitis was evaluated in a separate group of eight CAPD patients. Serum and dialysate AGP concentrations were significantly higher during than after peritonitis while the corresponding reactivity coefficients were only slightly elevated.     

Phenotypic characterization of human bone marrow granulocyte-macrophage forming progenitor cells

Cell surface antigens of the human bone marrow CFU-C have been studied. Human marrow cells were incubated with a variety of monoclonal antisera and complement prior to culture in semisolid media. By using indirect immunofluorescent studies, the percentage of bone marrow cells binding the antibodies was determined. The CFU-C phenotype is HLA+, la+, 4F2+, 3A1-, and DUALL-1-. This study provides information that is useful in the study of myeloid cell ontogeny and necessary for the use of some of these reagents in the treatment of bone marrow cells prior to human bone marrow transplantation in various clinical settings.     

罗格列酮对前驱糖尿病或非糖尿病代谢综合症血浆脂联素水平和动脉僵硬度的影响

目的噻唑烷二酮类对糖尿病患者动脉粥样硬化替代标记物如脂联素和动脉僵硬度有较好的作用。这些有益的作用是否会在非糖尿病患者(如前驱糖尿病或非糖尿病代谢综合症)出现还不明确。目前的研究是评价非糖尿病患者胰岛素致敏剂罗格列酮对循环脂肪细胞因子水平和肱踝脉搏波传递速度的作用。方法99例前驱糖尿病或非糖尿病患者随机分配到罗格列酮组和对照组(分别为50和49例)。罗格列酮组每日4mg罗格列酮,持续12周。所有患者均口服葡萄糖75 g,检测口服葡萄糖耐量试验前后肱踝脉搏波传递速度、脂联素、抵抗素和高敏C反应蛋白水平。结果相对于对照…     

Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study

To define the toxicity profile of recombinant human interleukin-6 (rhIL- 6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6- related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL- 6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.