Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells

Following injury, the clearance of apoptotic and necrotic cells is necessary for mitigation and resolution of inflammation and tissue repair. In addition to macrophages, which are traditionally assigned to this task, neighboring epithelial cells in the affected tissue are postulated to contribute to this process. Kidney injury molecule-1 (KIM-1 or TIM-1) is an immunoglobulin superfamily cell-surface protein not expressed by cells of the myeloid lineage but highly upregulated on the surface of injured kidney epithelial cells. Here we demonstrate that injured kidney epithelial cells assumed attributes of endogenous phagocytes. Confocal images confirm internalization of apoptotic bodies within KIM-1-expressing epithelial cells after injury in rat kidney tubules in vivo. KIM-1 was directly responsible for phagocytosis in cultured primary rat tubule epithelial cells and also porcine and canine epithelial cell lines. KIM-1 was able to specifically recognize apoptotic cell surface-specific epitopes phosphatidylserine, and oxidized lipoproteins, expressed by apoptotic tubular epithelial cells. Thus, KIM-1 is the first nonmyeloid phosphatidylserine receptor identified to our knowledge that transforms epithelial cells into semiprofessional phagocytes.     

Volar locking plates versus Kirschner wires for distal radial fractures—A cost analysis study

Background

There is an increasing trend for managing dorsally angulated distal radial fractures with locked volar plate fixation in fractures that may have previously been managed with percutaneous Kirschner wire (K-wire) fixation. There has been no prospective randomised trial comparing locked volar plate fixation with percutaneous K-wire fixation. In the absence of data guiding management with regard to clinical effectiveness, we have examined the cost of each technique.

Methods

Patients’ details were collected retrospectively between June 2007 and June 2008. Ten consecutive patients who underwent percutaneous K-wire fixation for a distal radius fracture and the 10 who were treated by locked volar plate fixation were identified and their hospital notes retrieved. All patients had a closed extra-articular distal radial fracture with dorsal angulation. The duration and type of operation, including number of wires or screws used, were recorded.

Results

The mean age of the patients was 54 years for the locking plate group and 34 years for the percutaneous K-wire group. The mean time taken to perform percutaneous K-wire fixation with an average of two K-wires was 56 min. The mean time for applying a volar locked plate was 121 min. The cost of a pack of 10 K-wires was £3. The total cost of a standard volar locking plate and screws used was £787.

Discussion

In the absence of research comparing clinical end points, cost must play a major factor in determining the type of operation offered. A 56-min operation to percutaneously fix a distal radial fracture with K-wires costs £662. This compares to a cost of £2212 for a 121-min locked volar plate fixation. There is a calculated difference of £1549 and 65 min.

Conclusion

With use of a locked volar plate for patients under the age of 70 years there is a loss of £652 for the Trust with the present NHS tariffs.     

FIRST-DOSE RESPONSE TO ANGIOTENSIN-CONVERTING ENZYME INHIBITION IN CONGESTIVE CARDIAC FAILURE: A MALAYSIAN EXPERIENCE

Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg ± SD) were placebo 5.89 ± 2.65, perindopril 5.29 ± 2.49, enalapril 13.28 ± 3.31, lisinopril 15.04 ± 5.74 and captopril 16.76 ± 5.74 (all p< 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.     

Hemoglobin Nigeria (alpha-81 Ser replaced by Cys):a new variant associated with alpha-thalassemia

Hematologic evaluation of a Nigerian obstetrical patient disclosed the presence of sickle-cell trait as well as evidence of a hemoglobin alpha- chain abnormality. Hemoglobins containing the variant alpha-chain were isolated by DEAE-cellulose column chromatography, and analysis of the purified alpha-chain demonstrated a ser replaced by cys substitution at alpha-81. The abnormal alpha-chain represented approximately 45% of the total, and hemoglobins containing this alpha-chain appeared to have normal stability and functional properties. In addition to the abnormal hemoglobins that were identified in this patient, she also was found to have persistent microcytosis in the absence of iron deficiency, and the percentage of HbS in her erythrocytes was less than that usually present in individuals with sickle cell trait. These findings, together with a reduced alpha/beta globin synthesis ratio from her peripheral blood reticulocytes, indicated that the presence of alpha-thalassemia trait. Hematologic findings from members of the patients's family suggest that an alpha-thalassemia gene may be linked to that of the structurally abnormal alpha-chain.