Management of cancer-related anemia in patients with breast or gynecologic cancer: new insights based on results from the European Cancer Anemia Survey

The incidence, prevalence, and treatment of anemia (hemoglobin [Hb] <12 g/dl) in women with breast cancer and gynecologic cancer were evaluated using data from the European Cancer Anemia Survey (ECAS). Adult patients with newly diagnosed treated or untreated disease, persistent/recurrent disease, and disease in remission were enrolled and followed for up to six chemotherapy cycles or six evaluation points within a 6-month period. At enrollment, 30.4% of breast cancer patients and 49.1% of gynecologic cancer patients were anemic. A significant correlation was shown between low Hb level and poor performance status (World Health Organization criteria) at enrollment for both breast cancer and gynecologic cancer patients. In all, 62.4% of breast cancer patients and 81.4% of gynecologic cancer patients were anemic at some time during the survey. The incidence of anemia, determined in a carefully defined population, was 59.8% for breast cancer patients and 74.8% for gynecologic cancer patients. Despite the high prevalence and incidence of anemia, only 26.3% and 42.7% of patients in the respective groups received anemia treatment. In breast cancer patients, the mean Hb trigger was 10 g/dl for epoetin treatment and 8.6 g/dl for transfusion; corresponding values for gynecologic cancer patients were 10.1 g/dl and 9.1 g/dl. Logistic regression analyses in the overall ECAS population identified five factors as significant and suitable predictors of anemia: lower initial Hb, having lung or gynecologic cancer versus gastrointestinal/colorectal cancer, any other cancer versus gastrointestinal/colorectal cancer, treatment with platinum chemotherapy, and being female. The ECAS data highlight the need for greater awareness of the adverse impact of anemia on cancer patients and for optimal anemia management to ensure maximal patient quality of life.     

Sodium retention in cirrhotic rats is associated with increased renal abundance of sodium transporter proteins

BACKGROUND: Liver cirrhosis with ascites is associated with a decrease in renal sodium excretion and therefore sodium retention. METHODS: In this paper, we utilize transporter-specific antibodies to address the hypothesis that dysregulation of one or more sodium transporters or channels is associated with sodium chloride (NaCl) retention in a rat model of cirrhosis induced by repeated exposure to carbon tetrachloride. Age-matched controls and cirrhotic rats were pair fed to ensure identical NaCl and water intake for 4 days prior to euthanasia for quantitative immunoblotting studies. RESULTS AND CONCLUSION: The rats manifested marked extracellular fluid volume expansion with massive ascites. Plasma aldosterone levels were markedly elevated. Analysis of immunoblots revealed marked increases in the abundances of both of the major aldosterone-sensitive apical transport proteins of the renal tubule, namely the thiazide-sensitive NaCl cotransporter NCC and the epithelial sodium channel alpha subunit (alpha-ENaC). These results are consistent with an important role for hyperaldosteronism in the pathogenesis of sodium retention and ascites formation in cirrhosis. In addition, we observed a large decrease in cortical NHE3 abundance (proximal tubule) and a large increase in NKCC2 abundance (thick ascending limb), potentially shifting premacula densa sodium absorption from proximal tubule to loop of Henle (which powers urinary concentration and dilution).     

Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine

BACKGROUND: Tenofovir (TDF) and didanosine (ddI) are both adenosine analogues with convenient posology, strong potency and a relatively high genetic barrier for resistance. The popularity of this combination, however, has been questioned due to concerns about pharmacokinetic interactions and increased risk of pancreatitis and hyperglycemia. Less information is available about other possible side effects. PATIENTS AND METHODS: HIV-infected individuals who initiated a protease inhibitor-sparing regimen between September 2002 and June 2003 at five hospitals, and had at least one subsequent visit within the next 12 months, always with complete virus suppression, were retrospectively assessed. Only drug-naive individuals and patients who simplified a prior successful antiretroviral regimen were analysed. RESULTS: Outcomes were analysed in 570 individuals according to treatment modality (98 drug-naive versus 472 simplified); the nucleoside analogue (NA) backbone (298 with TDF + ddI, 88 with ddI, 44 with TDF, and 140 with neither ddI nor TDF); and the third agent used (378 with non-nucleoside analogues versus 192 with NA). Significant CD4+ T-cell declines were seen in patients taking ddI + TDF with respect to all other NA combinations, including ddI or TDF separately. Patients exposed to high ddI doses or taking a third NA showed more pronounced CD4 declines. Plasma levels of ddI correlated with the extent of CD4+ T-cell loss. CONCLUSION: Patients receiving ddI + TDF-based combinations show CD4+ T-cell declines despite achieving complete virus suppression. This effect generally progresses with time. An imbalance in adenosine metabolites within CD4+ T lymphocytes may explain this phenomenon, which resembles the genetic purine nucleoside phosphorylase deficiency syndrome.     

Differences in chromosome susceptibility to aneuploidy and survival to first trimester

The purpose of this study was to find specific rates of aneuploidy in cleavage-stage embryos compared with first trimester data and to evaluate post-zygotic selection against aneuploidy. A total of 2058 embryos were analysed by flurorescence in-situ hybridization (FISH), and specific aneuploidy rates were obtained for 14 chromosomes. Data from morphologically abnormal embryos could be pooled with data from preimplantation genetic diagnosis (PGD) cycles because it was observed that they had similar rates of aneuploidy; thus, for the purpose of studying aneuploidy they could be, and were, pooled. Specific chromosome aneuploidy rates were not related to morphology or development of the embryos. The average maternal age of patients with aneuploid embryos was significantly higher than the overall analysed population. Monosomy appeared more commonly than trisomy. The chromosomes most frequently involved in aneuploidy were (in order) 22, 16, 21 and 15. When compared with first trimester pregnancy data, aneuploidies detected at cleavage stage seem to die in excess of 90% before reaching first trimester, with the exception of chromosome 16 and gonosomes (76% and 14% respectively). Differences in chromosome-specific aneuploidy rates at first trimester conceptions are probably produced by different chromosome-specific aneuploidy rates at cleavage stage and different survival rates to first trimester.     

Chronic overexposure to cadmium fumes associated with IgA mesangial glomerulonephritis

BACKGROUND: Cadmium is a metal used in the zinc, copper and steel industries, and in the manufacture of electric batteries and solar cells. Acute cadmium poisoning is characterized by irritation of the respiratory tract, while in chronic poisoning the main target organ is the renal tubule. AIMS: We report a patient with chronic work overexposure to cadmium, who presented a IgA mesangial glomerulonephritis with no respiratory or renal tubule involvement. Case report A 39-year-old patient was referred to our hospital for evaluation of a glomerular nephropathy. For the past 12 years he had worked as a welder, using cadmium electrodes. The patient had no respiratory symptoms and the chest X-ray was normal. Tests showed a proteinuria of 2 g in 24 h with microhaematuria [150 red blood cells/high power field (rbc/hpf)], with preservation of the renal function (creatinine clearance of 137 ml/min). The concentrations of cadmium in blood and urine were 45 micro g/l and 25 micro g/g creatinine, and an environmental study showed that levels of cadmium in the workplace were 52 micro g/m(3). A renal biopsy showed an IgA mesangial glomerulonephritis. The patient ceased to work with cadmium, and 1 year later cadmium levels had decreased and renal function was found to be stable. CONCLUSIONS: IgA mesangial glomerulonephritis is a disease of unknown aetiology which has been associated with other diseases. Chronic overexposure to cadmium may contribute to the development of this nephrophathy.     

Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites in human samples including the catechol-type metabolite (3,4-dihydroxymethamphetamine).

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a designer drug commonly misused in large segments of young populations. MDMA is usually formulated in tablets of its racemate (1:1 mixture of its enantiomers) in doses ranging from 50 to 200 mg. MDMA has an enantioselective metabolism, the (S)-enantiomer being metabolized faster than the (R)-enantiomer. Different pharmacologic properties have been attributed to each enantiomer. The carbon responsible for MDMA chirality is preserved along its metabolic disposition. An analytical method has been developed to determine MDMA enantiomers and those from its major metabolites, 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymeth-amphetamine (HHMA), and 4-hydroxy-3-methoxymethamphet-amine (HMMA). It has been applied to the analysis of plasma and urine samples from healthy recreational users of MDMA who participated voluntarily in a clinical trial and received 100 mg (R,S)-MDMA. HCl orally. (R)/(S) ratios both in plasma (0-48 h) and urine (0-72 h) for MDMA and MDA were >1 and <1, respectively. Ratios corresponding to HHMA and HMMA, close to unity, deviate from theoretical expectations and are most likely explained by the ability of MDMA to autoinhibit its own metabolism. The short elimination half-life of (S)-MDMA (4.8 h) is consistent with the subjective effects and psychomotor performance reported in subjects exposed to MDMA, whereas the much longer half-life of the (R)-enantiomer (14.8 h) correlates with mood and cognitive effects experienced on the next days after MDMA use.     

Medial temporal MR spectroscopy is related to memory performance in normal adolescent subjects

In addition to the study of pathological conditions, magnetic resonance spectroscopy can provide useful information about brain-behavior relationships in normal subjects. Recently, there have been reports of correlations between N-acetylaspartate (NAA) values and cognitive functions in normal adults. We tested the possible specific relationship between the NAA/choline (Cho) ratio in the medial temporal lobe and memory performance in normal adolescents. The medial temporal NAA/Cho ratio was unrelated to age, gender and general intelligence but presented a clear correlation with several memory measures. In the regression analysis two memory variables (RAVLT learning and a face-name recognition task) explained 55.6% of NAA/Cho variance. We conclude that NAA values in the medial temporal lobe are related to memory abilities but not to global intelligence in normal adolescent subjects.     

Assessment of the potential irritation and photoirritation of novel amino acid-based surfactants by in vitro methods as alternative to the animal tests

The ultraviolet-A radiation damage effects on skin and eyes will be increased by phototoxic compounds which could be present in pharmaceutical or cosmetic formulations. Great efforts have been made in the last years to find surfactants to replace those with phototoxic potential in commercial use. Series of different in vitro models for phototoxicity, included to validated neutral red uptake (NRU) 3T3 phototoxicity assay are useful screening tools. The phototoxic effects of a novel family of glycerol amino acid-based surfactant compounds were examined via these assays. Human red blood cells and two immortalised cell lines, murine fibroblast cell line 3T3, and one human keratinocyte cell line, HaCaT, were the in vitro models employed to predict potential photoirritation. The phototoxic end-points assessed were hemolysis (human red blood cell test) and resazurin transformation to resorufin and NRU in cell culture methods. The results suggest that no phototoxic effects by any new amino acid derived-surfactants, could be identified.     

The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients

The European Cancer Anaemia Survey (ECAS) was conducted to prospectively evaluate the prevalence, incidence and treatment of anaemia (haemoglobin <12.0 g/dL) in European cancer patients, including the relationship of mild, moderate and severe anaemia to performance status. Patients were evaluated for up to 6 months. Data (N=15367) included demographics, tumour type, performance status, haemoglobin levels, cancer treatments and anaemia treatments. Prevalence of anaemia at enrollment was 39.3% (haemoglobin <10.0 g/dL, 10%), and 67.0% during the survey (haemoglobin <10.0 g/dL, 39.3%). Low haemoglobin levels correlated significantly with poor performance status. Incidence of anaemia was 53.7% (haemoglobin <10.0 g/dL, 15.2%). Anaemia was treated in 38.9% of patients (epoetin, 17.4%; transfusion, 14.9%; and iron, 6.5%). Mean haemoglobin to initiate anaemia treatment was 9.7 g/dL. Anaemia prevalence and incidence in cancer patients are high. Anaemia significantly correlates with poor performance status and many anaemic patients are not treated.