ABSTRACT
Although diabetes can be managed clinically with the use of insulin injections, it remains an incurable and inconvenient disorder. In the long-term, it is associated with a number of clinical complications, such as cardiovascular disease, resulting in a desire for the development of new methodologies to replace defective cells and provide a lasting normality without the need for drug treatment. Stem cells, including induced pluripotent stem cells, offer the possibility of generating cells suitable for transplantation due to their capacity to differentiate into all tissue lineages. However, many issues must be addressed before this type of treatment becomes a reality, including the need for a greater understanding of the underlying biology involved in the onset of diabetes.
ABSTRACT
INTRODUCTION: Pre-operative anaemia is well recognised in patients presenting with colorectal cancer (CRC). While the benefits of long-term FeSO4 supplementation on Fe deficiency anaemia are well established, it is not known if short-course supplementation (2-3 weeks) impacts significantly on pre-operative haemoglobin (Hb) levels. This study examines the impact of short-term, oral FeSO4 supplementation on patients undergoing surgery for CRC. PATIENTS AND METHODS: All patients with CRC presenting to a single surgeon were included. At diagnosis, baseline Hb and blood film were checked on all patients who then received 200 mg tds of FeSO4. Haemoglobin was rechecked pre-operatively and daily postoperatively. Patients requiring pre-operative blood transfusions were excluded from analysis. RESULTS: Between 1 January 2004 and 31 December 2006, 117 patients were identified, 14 of whom were excluded. Patients received a median of 39 days' treatment with FeSO4. Fifty-eight (56.3%) patients were anaemic at presentation gaining a mean of 1.73 g/dl (P<0.001) from short-course FeSO4 supplementation. Right-sided tumours (lower mean Hb at presentation; P=0.008) responded more to FeSO4 when compared to left-sided tumours (P<0.017). Increase in Hb was unrelated to pathological stage. The transfusion rate for all curative resections was 0.69 units/patient. For the historical cohort (patients undergoing curative resection between 1 January 2001 and 31 December 2003), the mean transfusion rate fell from 1.69 units/patient. CONCLUSIONS: Routine short-course supplementation with iron offers improved pre-operative Hb prior to surgery in CRC, especially in right-sided lesions and those with presenting anaemia.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Colorectal Neoplasms/complications , Ferrous Compounds/therapeutic use , Hematinics/therapeutic use , Administration, Oral , Adult , Aged , Aged, 80 and over , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/etiology , Cohort Studies , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Drug Administration Schedule , Female , Ferrous Compounds/administration & dosage , Hematinics/administration & dosage , Hemoglobins/metabolism , Humans , Male , Middle Aged , Preoperative Care/methods , Treatment OutcomeABSTRACT
The urokinase receptor is a multi-functional protein that plays a central role in cell surface plasminogen activation, cell migration, and cell adhesion. We previously demonstrated that high affinity peptide ligands for the urokinase receptor, which are urokinase competitors, can be obtained from a 15mer peptide library (Goodson et al., 1994). In order to probe for additional urokinase receptor binding sites we affinity selected the same bacteriophage library on complexes of soluble urokinase receptor (suPAR) and the receptor binding domain of urokinase, residues 1-48 (uPA1-48). Bacteriophage were isolated which bound to suPAR and suPAR:uPA1-48 complexes with high yield. The peptide sequences encoded by these bacteriophage were distinct from those obtained previously on urokinase receptor expressing cells, and comprise two groups based upon effects on su-PAR:1-anilino-8-napthalene sulfonate (ANS) fluorescence, and vitronectin binding competition. Alanine scanning mutagensis of the soluble peptides was used to define minimal regions and key residues for suPAR binding by competition with the parent bacteriophage. A comparison of these results with sequences of domains of both vitronectin and integrin alpha-chains, which have been reported to be important for urokinase receptor binding, suggests that the homology with the peptide sequences selected is functionally significant.
