Comparison of Pulmonary Artery Pressure Measurements in the Supine and 60° Lateral Positions Leanne is continuing this research in her doctoral studies

Pulmonary artery pressure monitoring, with the patient in both the supine and lateral positions, is an essential element in the assessment of critically ill patients. Previous work offers conflicting results regarding the accuracy of measurements obtained with the patient in the lateral position. The purpose of this study was to determine if accurate pulmonary artery pressure measurements can be obtained in the cardiac surgical patient. Thirty-five patients underwent repositioning between the supine and both the left and right 60° lateral position while being mechanically ventilated and then breathing spontaneously. Pulmonary artery pressure measurements were recorded prior to, two minutes following and ten minutes following repositioning. Despite some variation in results the pulmonary capillary wedge pressure measurement was reliable ten minutes after repositioning in both the spontaneously breathing and mechanically ventilated patient. Other pulmonary artery pressure measurements were not so reliable in the lateral position. This study concludes that clinical practitioners can obtain accurate pulmonary capillary wedge pressure measurements in post-operative cardiac surgical patients positioned in either the left or right 60° lateral position. Further research is however required, with larger numbers from all sub-groups of the critical care population. Physiological and pathophysiological characteristics which preclude reliable pulmonary artery pressure measurements need to be identified.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

Evaluation of the introduction of a standardised protocol for the staging and follow-up of colorectal cancer on resection rates for liver metastases

INTRODUCTION

In 2004, an audit in our unit demonstrated wide variation in liver resection rates for colorectal cancer (CRC) metastases within the cancer network. Subsequently, a network-wide CT-based follow-up and referral policy was introduced for all patients. A second audit was performed to assess the impact of the guidelines on liver resection rates.

SUBJECTS AND METHODS

Analysis of prospective liver resection database between 1997 and 2004 and after the introduction of standardised guidelines between January 2005 and April 2008.

RESULTS

A total of 362 patients underwent liver resection for CRC metastases between 1997 and 2008, 237 prior to the introduction of the referral guidelines and 125 after. Liver resection rates according to referring hospital varied from 0.92 to 2.32 per 100,000 population before guidelines were introduced. After 2005, resection rates from the four district hospitals standardised (1.68–1.84 per 100,000 population), but the central unit rate (Sheffield) remained significantly higher (2.67 per 100,000 population). No significant difference in 1-year disease-free survival between patients from Sheffield and the outlying hospitals was found (P = 0.553).

CONCLUSIONS

Introduction of a referral protocol standardised resection rates from the four district hospitals, but these remain lower compared to the specialist centre. The wide-spread adoption of a policy to discuss all patients with liver metastases at an advanced disease multidisciplinary team meeting, in the presence of hepatobiliary specialists, may further increase resection rates across the UK.     

Defects in mismatch repair occur after APC mutations in the pathogenesis of sporadic colorectal tumours

The roles of the intrinsic mutation rate and genomic instability in tumorigenesis are currently controversial. In most colorectal tumours, it is generally supposed that the first mutations occur at the adenomatous polyposis coli (APC) locus; APC mutations are thought to provide cells with a selective advantage but have no known effect on the mutation rate. It has also been suggested that genomic instability is the initiating event in colorectal tumorigenesis and, if this is true, mutations of DNA mismatch repair (MMR) genes (or at similar loci) are the most likely candidates. If defective MMR precedes APC mutations, the APC mutations of colon tumours with defective MMR and hence replication errors (RER+) should differ from those of RER- tumours, in at least three specific ways: (1) a higher frequency of allele loss at APC in RER- tumours; (2) more frameshift than nonsense mutations in RER+ tumours; and (3) APC mutations in simple repeat sequences [(N)_n, (N₁N₂)_n, or (N₁N₂N₃)_n] in RER+ tumours. We found no evidence that sporadic RER+ and RER- colon cancers (including cell lines) differ in any of these three ways. Although it remains possible that MMR is abnormal in tumours from HNPCC families before APC mutations occur, it is likely that in sporadic colon tumours, APC mutations, rather than genomic instability, are the initiating events in tumorigenesis. Hum Mutat 11:114–120, 1998. © 1998 Wiley-Liss, Inc.     

Core-peripheral temperature gradient in children: does it reflect clinically important changes in circulatory haemodynamics?

Following open heart surgery, changes in core and peripheral skin temperature and changes in the core-peripheral temperature gradient were measured in 10 children. These were correlated with changes in cardiac index, systemic vascular resistance index, mean arterial pressure and urinary output. During the study intervals, which lasted 1 h each, no changes in medical management were made. Using Spearman's rank correlation, only a change in central venous pressure was found to correlate with a change in the core-peripheral temperature gradient. We conclude that a change in the core-peripheral temperature will give valuable information about the patient's intravascular volume.