Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes

Haemoglobin (Hgb) levels are known to be associated with numerousadverse outcomes in both chronic kidney disease (CKD) and non-CKDpatients. This analysis evaluates the association of baseline haemoglobinlevels on survival in CKD patients, who are followed by nephrologists,irrespective of glomerular filtration rate (GFR), prior to initiationof renal replacement therapy (RRT) and erythropoietin hormonereplacement therapy. Analysis of data from the provincial database (PROMIS, PatientRegistration and Outcome Management Information System) in BritishColumbia, Canada, was undertaken. Records used for the analysisincluded all CKD patients at first registration: GFR <60ml/min/1.73 m², not yet on dialysis, starting from May 1998to October 2002, and who had complete data (defined as age andgender, diabetic status, eGFR and Hgb levels). The primary objective of this study was to determine the associationof Hgb and survival controlling for eGFR at first registrationvalue, age, gender and diabetic status. Multivariate Cox proportionalhazards analysis with time to death as outcome variable wasperformed. The cohort included 3028 patients: the mean age was 65 years,28% were diabetic, and the mean eGFR in the cohort was 21 ml/min/1.73m². The cohort is representative of the BC CKD and dialysispopulation regarding ethnicity: 64% Caucasian, 32% Asian. Medianfollow-up was 27 months, 1 year survival was 0.92, 2 year survivalwas 0.85. Hgb at initial registration is a statistically independentpredictor of survival (RR = 0.875 for every 10 g/l, 95% CI:0.835–0.917, P = 0.0001), after adjusting for age, gender,diabetic status and baseline eGFR. Further analysis, controllingfor RRT, demonstrated a similar association between Hgb andsurvival (RR = 0.853 for every 10 g/l, 95% CI: 0.799–0.910,P = 0.0001), after adjusting for above variables. Substantialvariation in Hgb values exists at all GFR levels. These findings underscore the importance of evaluating Hgb atall GFR levels, and the need to study the impact of modificationof Hgb at different GFR levels on survival.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Identification of a parathyroid hormone in the fish Fugu rubripes.

A PTH gene has been isolated from the fish Fugu rubripes. The encoded protein of 80 amino acid has the lowest homology with any of the PTH family members. Fugu PTH(1-34) had 5-fold lower potency than human PTH(1-34) in a mammalian cell system. INTRODUCTION: Parathyroid hormone (PTH) is the major hypercalcemic hormone in higher vertebrates. Fish lack parathyroid glands, but there have numerous attempts to identify and isolate PTH from fish. MATERIALS AND METHODS: Polymerase chain reaction (PCR) was performed with primers based on preliminary data from the Joint Genome Institute database. PCR amplification was performed on genomic DNA isolated from Fugu rubripes. PCR products were purified and DNA was sequenced. All sequence was confirmed from more than one independently amplified PCR product. Multiple sequence alignments were carried out, and the percentage of identities and similarities were calculated. An unrooted phylogenetic tree, using all the known PTH and PTH-related protein (PTHrP) amino acid sequences, was determined. Synthetic peptides were tested in a biological assay that measured cyclic adenosine 3',5'-monophosphate formation in UMR106.1 cells. Rabbit polyclonal antisera specific for N-terminal human PTHrP and one rabbit polyclonal antiserum specific for N terminus hPTH were used to test the cross-reactivity with fPTH(1-34) in immunoblots.     

Extrapulmonary and pulmonary small-cell carcinoma: Tumor biology,therapy, and outcome

Extrapulmonary small-cell cancer is a distinct clinicopathological entity from smallcell anaplastic carcinoma of the lung. Approximately 1,000 cases have been projected annually in the United States, which represents an overall incidence of between 0.1% and 0.4% of all cancer. Not surprisingly then, little information is available regarding the treatment of this disease, which presents a challenge to the clinician when it is regionally confined. The majority of patients with extrapulmonary small-cell neoplasms have only been treated with local modalities of therapy, surgery, radiation, or a combination of both. Prolonged survival is not infrequent, which is in contrast to the experience for small-cell lung cancer and surprising given our current systemic approach to patients with this disease. This report will summarize the similarities and differences in biology, natural history, and clinical characteristics of patients with extrapulmonary small-cell cancer and smallcell anaplastic carcinoma of the lung. The histogenesis of small-cell cancer is briefly reviewed. A general therapeutic approach to patients with small-cell lung cancer is reported. Lastly, recommendations for therapy of patients with regionally confined extrapulmonary small-cell cancer by primary site are outlined.