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.     

粉防已碱对大鼠心肌微粒体ATPases的作用

体外在常规反应条件下,粉防已碱(Tet)对大鼠心肌微粒体Na⁺,K⁺-ATPase活性无明显影响,但浓度依赖性抑制Mg²⁺-ATPase(IC₅₀=179μmol/L).Tet 10和100μmol/L使哇巴因(Oua)抑制Na⁺,K⁺-ATPase的量效曲线平行右移.Tet 100μmol/L可显著提高低K⁺或高Ca²⁺浓度时的Na⁺,K⁺-ATPase活性,但未能明显增加低Na⁺浓度时该酶的活性.动力学分析提示Tet 100μmol/L增加Na⁺,K⁺-ATPase对ATP的亲和力,但不改变其最大反应速度。     

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.     

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.     

No association between nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow: a cross‐sectional general population study

Background In theory, all pigmented make‐up products may contain metal allergens including nickel. Eyelid dermatitis has previously been observed among nickel allergic dermatitis patients following exposure to nickel containing mascara and eye shadow. However, an association between nickel eyelid dermatitis and nickel in make‐up products remains controversial. Objective This cross‐sectional patch test study investigated whether the frequency of self‐reported cosmetic dermatitis from mascara or eye shadow use was higher among nickel allergic Danish women than women without nickel allergy. Methods In 2006, a total of 1843 18–69 year old women completed a postal questionnaire including questions on cosmetic dermatitis and were patch tested with nickel sulphate. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results The prevalence of nickel allergy was similar among women who reported cosmetic dermatitis from eye shadow or mascara and among women who did not report such symptoms. Cosmetic dermatitis was positively associated with self‐reported atopic dermatitis and age. Conclusion Overall, no association between having nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow use was found in the general population. This does not exclude a causal relationship in selected cases.     

Congenital heart disease: gated MR imaging in 72 patients

Seventy-two patients (aged 2 months to 75 years; mean 23 years) with a variety of congenital anomalies of the heart and great vessels underwent ECG-gated magnetic resonance (MR) imaging using the multisectional spin-echo technique (0.35 Tesla). The ability to define segmental anatomy and intracardiac anomalies on transverse, sagittal, and coronal images was evaluated. MR images were graded as excellent, diagnostic, or nondiagnostic, and MR findings were corroborated by angiography and/or two-dimensional echocardiography. Studies that were considered to be excellent or diagnostic were obtained in 96% of the cases. Visceroatrial situs, the type of ventricular loop, and the relationship of the great vessels could be identified in all patients with studies encompassing the entire heart. Forty-four of 47 abnormalities at the level of the great vessels were identified with MR, including coarctation of the aorta and vascular rings. MR showed 32 of 35 ventricular abnormalities; 2 small ventricular septal defects and 1 Ebstein anomaly were not demonstrated. All of the abnormalities at the atrial level and those of systemic and pulmonary venous return were seen on MR images. Complex cardiac anomalies, such as single ventricles, and the status of the pulmonary arteries were clearly demonstrated, and a good assessment of total and palliative postoperative anatomy was provided.     

Adhesion of platelets to human artery subendothelium: effect of factor VIII-von Willebrand factor of various multimeric composition

The relationship between the multimeric size of factor VIII-von Willebrand factor (FVIII-vWF) and the support of platelet adhesion to subendothelium was studied in an annular perfusion chamber, employing human renal and umbilical arteries. Commercial factor VIII concentrates containing multimers of low molecular weight that had been shown not to correct the bleeding time upon infusion into patients with von Willebrand's disease did not support platelet adhesion in the perfusion chamber. Cryoprecipitate and two experimental FVIII-vWF concentrates containing multimers of high molecular weight supported platelet adhesion. Factor VIII-vWF purified from cryoprecipitate was subdivided into three fractions of different molecular weights (6.0-14.0, 4.0-9.0, and 3.0-7.5 X 10(6) dalton). These fractions appeared to bind equally well and to be equally effective in supporting platelet adhesion. Factor VIII-vWF with multimers of low molecular weight (0.5-1.5 X 10(6) dalton) were prepared by partial reduction. Binding of FVIII-vWF to subendothelium was not impaired, and the support of platelet adhesion appeared to be more resistant to the effect of reduction than the ristocetin cofactor activity. At high shear rate (2,500 sec-1), increased platelet adhesion was observed with partially reduced FVIII- vWF. These data indicate that the ability of FVIII-vWF preparations to correct the bleeding time is reflected in enhanced platelet adhesion to subendothelium in a perfusion chamber. These data also emphasize that multimeric size is not the only factor determining whether FVIII-vWF will support platelet adhesion.     

A Novel Neutrotrophic Property Of Glucagon-Like Peptide 1: A Promoter Of Nerve Growth Factor-Mediated Differentiation In PC12 Cells

The insulinotropic hormone glucagon-like peptide-1 (7-36)-amide (GLP-1) has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation and is presently in clinical trials as a therapy for type 2 diabetes mellitus. We report on the effects of GLP-1 and two of its long-acting analogs, exendin-4 and exendin-4 WOT, on neuronal proliferation and differentiation, and on the metabolism of two neuronal proteins in the rat pheochromocytoma (PC12) cell line, which has been shown to express the GLP-1 receptor. We observed that GLP-1 and exendin-4 induced neurite outgrowth in a manner similar to nerve growth factor (NGF), which was reversed by coincubation with the selective GLP-1 receptor antagonist exendin (9-39). Furthermore, exendin-4 could promote NGF-initiated differentiation and may rescue degenerating cells after NGF-mediated withdrawal. These effects were induced in the absence of cellular dysfunction and toxicity as quantitatively measured by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays, respectively. Our findings suggest that such peptides may be used in reversing or halting the neurodegenerative process observed in neurodegenerative diseases, such as the peripheral neuropathy associated with type 2 diabetes mellitus and Alzheimer's and Parkinson's diseases. Due to its novel twin action, GLP-1 and exendin-4 have therapeutic potential for the treatment of diabetic peripheral neuropathy and these central nervous system disorders.