National Comparative Audit of Blood Use in Elective Primary Unilateral Total Hip Replacement Surgery in the UK

INTRODUCTION

Blood is a scarce and expensive product. Although it may be life-saving, in recent years there has been an increased emphasis on the potential hazards of transfusion as well as evidence supporting the use of lower transfusion thresholds. Orthopaedic surgery accounts for some 10% of transfused red blood cells and evidence suggests that there is considerable variation in transfusion practice.

PATIENTS AND METHODS

NHS Blood and Transplant, in collaboration with the Royal College of Physicians, undertook a national audit on transfusion practice. Each hospital was asked to provide information relating to 40 consecutive patients undergoing elective, primary unilateral total hip replacement surgery. The results were compared to indicators and standards.

RESULTS

Information was analysed relating to 7465 operations performed in 223 hospitals. Almost all hospitals had a system for referring abnormal pre-operative blood results to a doctor and 73% performed a group-and-save rather than a cross-match before surgery. Of hospitals, 47% had a transfusion policy. In 73%, the policy recommended a transfusion threshold at a haemoglobin concentration of 8 g/dl or less. There was a wide variation in transfusion rate among hospitals. Of patients, 15% had a haemoglobin concentration less than 12 g/dl recorded in the 28 days before surgery and 57% of these patients were transfused compared to 20% with higher pre-operative values. Of those who were transfused, 7% were given a single unit and 67% two units. Of patients transfused two or more units during days 1–14 after surgery, 65% had a post transfusion haemoglobin concentration of 10 g/dl or more.

CONCLUSIONS

Pre-operative anaemia, lack of availability of transfusion protocols and use of different thresholds for transfusion may have contributed to the wide variation in transfusion rate. Effective measures to identify and correct pre-operative anaemia may decrease the need for transfusion. A consistent, evidence-based, transfusion threshold should be used and transfusion of more than one unit should only be given if essential to maintain haemoglobin concentrations above this threshold.     

Prediction of the effect of erythromycin, diltiazem, and their metabolites, alone and in combination, on CYP3A4 inhibition

Predictive models of complex drug-drug interactions between multiple inhibitors and their metabolites have not been evaluated. The purpose of this study was to evaluate an interaction model for cytochrome P450 3A4 (CYP3A4) that incorporated the simultaneous reversible and irreversible inhibition by multiple inhibitors. Erythromycin (ERY) and diltiazem (DTZ), and their major metabolites, N-desmethylerythromycin (nd-ERY) and N-desmethyldiltiazem (nd-DTZ), were chosen to evaluate the model. k(inact) (rate constant for maximal inactivation), K(I) (inhibitor concentration at 50% maximal inactivation), and K(i) (reversible inhibition constant) were estimated for ERY, DTZ, nd-ERY, and nd-DTZ, respectively, using cDNA-expressed CYP3A4 and human liver microsomes under optimal experimental conditions. To evaluate the interaction model, combinations of inhibitors and metabolites were incubated at concentrations equal to K(I), (1/2)K(I), and 2K(I) of each inhibitor for specified durations in both enzyme systems. The models were further evaluated by the incubation of combinations of inhibitors with the substrate testosterone for 10 min. CYP3A4 inhibition in the presence of drug mixtures was predicted from the inhibition parameters determined for each drug or metabolite alone. The CYP3A4 activity in the presence of multiple inhibitors was well predicted by the model incorporating additive irreversible inhibition as modified by mutual competitive inhibition (percent mean error and percent mean absolute error ranged from -0.06 to 0.04 and from 0.03 to 0.09, respectively). In conclusion, the additive model predicted the combined effect of multiple inhibitors on CYP3A inhibition in vitro. However, simultaneous reversible and irreversible inhibition effects should be taken into account in a reaction mixture of substrate and multiple inhibitors of CYP3A4.     

Ultrastrukturelle Veränderungen am Nierenparenchym durch ESWL unter Acetylsalicylsäure (ASS)

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.     

Podocalyxin increases the aggressive phenotype of breast and prostate cancer cells in vitro through its interaction with ezrin

Podocalyxin is an anti-adhesive transmembrane sialomucin that has been implicated in the development of more aggressive forms of breast and prostate cancer. The mechanism through which podocalyxin increases cancer aggressiveness remains poorly understood but may involve the interaction of podocalyxin with ezrin, an established mediator of metastasis. Here, we show that overexpression of podocalyxin in MCF7 breast cancer and PC3 prostate cancer cell lines increased their in vitro invasive and migratory potential and led to increased expression of matrix metalloproteases 1 and 9 (MMP1 and MMP9). Podocalyxin expression also led to an increase in mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) activity. To determine the role of ezrin in these podocalyxin-dependent phenotypic events, we first confirmed that podocalyxin formed a complex with ezrin in MCF7 and PC3 cells. Furthermore, expression of podocalyxin was associated with a changed ezrin subcellular localization and increased ezrin phosphorylation. Transient knockdown of ezrin protein abrogated MAPK and PI3K signaling as well as MMP expression and invasiveness in cancer cells overexpressing podocalyxin. These findings suggest that podocalyxin leads to increased in vitro migration and invasion, increased MMP expression, and increased activation of MAPK and PI3K activity in MCF7 and PC3 cells through its ability to form a complex with ezrin.     

Lymphangiomyomatosis: CT, chest radiographic, and functional correlations

Eight patients with the diagnosis of lymphangiomyomatosis were evaluated with computed tomography (CT), chest radiography, and pulmonary function tests to determine the relationship between the extent of disease seen on imaging studies and functional status. Chest radiographic assessment included the subjective determination of disease extent and measurements of lung length and the arc of the right hemidiaphragm. Disease extent on CT scans was scored as a percentage of lung that was abnormal on the basis of visual assessment of the degree of cystic replacement of the lung parenchyma. Significant correlations were observed between CT scores and percentages of predicted forced expiratory volume in 1 second/forced vital capacity (r = -.92, P less than .002) and diffusing capacity of the lungs for carbon monoxide (r = -.80, P less than .017). No significant correlations were observed between subjective chest radiographic scores and pulmonary function tests, although measurements of lung length and percentage of predicted total lung capacity were correlated (r = .76, P less than .045). CT was more accurate than chest radiography in defining the presence and extent of parenchymal cysts and provided for greater morphologic-physiologic correlation. CT, particularly high-resolution CT, may be useful in the diagnosis and longitudinal evaluation of patients with this disease and may be more sensitive than pulmonary function tests in the early stages of lung damage.     

Miliary tuberculosis: A complication of intravesical BCG treatment

A case of miliary tuberculosis following intravesical bacillus Calmette-Guerin (BCG) treatment is described.     

Gene Probe Analysis in an Informative Family with Multiple Endocrine Neoplasia Syndrome Type 2A (MEN 2A). Improvement in Carrier Risk Estimation

Gene probe analysis of the MEN 2A locus on chromosome 10 hasbeen undertaken using the markers TB10.163, RBP 3 and TB14.34in a large kindred with familial medullary thyroid carcinomas,with or without phaeochromocytomas or primary hyperparathyroidism.A maximum LOD score of 2.97 gave strong evidence of close linkagewith zero recombination. For 12 members of the family so far not known to be affectedby any form of the disease the estimated risk of carrying thegene has been considerably decreased in all but one, whose riskhas been greatly increased.     

Medical treatment of hepatic amebic abscess: rare need for percutaneous drainage

Although amebic liver abscess can virtually always be successfully treated medically, percutaneous drainage has been advocated recently. In 96 recently treated patients, therapeutic aspiration and percutaneous drainage were rarely needed. Most cases were correctly diagnosed by means of clinical, laboratory, and sonographic findings. Abscesses in only 13 (13.5%) patients were diagnostically aspirated. An abscess in one patient was therapeutically aspirated because the patient was responding slowly to medical therapy. No patient required catheter drainage. The key to successful amebic abscess management is medical therapy. Therapeutic drainage is rarely needed. Successfully treated patients occasionally respond slowly to medical therapy, and successfully treated amebic abscesses may enlarge or become bizarre-appearing on sonograms. This should not prompt therapeutic drainage. Diagnostic aspiration is appropriate when amebic and pyogenic abscesses are indistinguishable using clinical and imaging findings. Rare indications for therapeutic aspiration or drainage include pyogenic superinfection and large, juxtacardiac abscesses (potential intrapericardial rupture).