Acute renal rejection versus acute tubular necrosis in a canine model: MR evaluation

Findings of magnetic resonance (MR) imaging in acute renal rejection and acute tubular necrosis (ATN) were studied in dogs. On T1-weighted images, corticomedullary differentiation was absent in kidneys undergoing acute rejection. The loss of corticomedullary differentiation in these kidneys was secondary to a decrease in the relative signal intensity of the cortex, indicating prolongation of the T1 relaxation time of the cortex. In contrast, corticomedullary differentiation was preserved on T1-weighted images of autotransplanted kidneys and kidneys with ATN. MR imaging findings correlated with changes in water content in these three groups of kidneys. Kidneys undergoing acute rejection showed a marked increase in water content compared with kidneys in the other two groups. No change in fat content was found in any group.     

ATM, an unexpected new target in metabolic syndrome

ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
Schneider et al. (2006)
Cell Metabolism: 4 (5): 377–389     

Work in progress: the application of temporal filtering techniques to hybrid subtraction in digital subtraction angiography

Temporal filtering methods were applied to iodine signal-to-noise ratio (SNR) restoration in intravenous hybrid subtraction digital subtraction angiography (DSA). For equal detected exposure rates hybrid subtraction had approximately 35% of the SNR of temporal subtraction. When matched filtering was applied to a DSA run, the filtered result had approximately two times higher SNR than the peak contrast image in the run. Thus, when matched filtering techniques were applied to the hybrid image sequence, the resultant SNR increased to about 70% of that of temporal subtraction. With an additional factor-of-two increase in exposure rate for the hybrid run, SNR parity with temporal subtraction could be achieved. This compared with a factor-of-nine increase in exposure that would be required if no filtering were performed. Experimental hybrid matched filter results, generated with intravenous canine DSA studies, supported the predictions in SNR performance.     

Risk-stratified nosocomial infection surveillance in a neonatal intensive care unit: Report on 24 months of surveillance

Objective : To document the nosocomial infection rate in a single neonatal intensive care unit (NICU) in terms of patient workload and device utilization.
Methodology : Nosocomial infections have been identified and documented by the methodology described by the National Nosocomial Infection Surveillance System (NNIS), Centres for Disease Control, Atlanta. In addition, antibiotic usage has been surveyed in the NICU and standardized measures of patient exposure to antibiotics stratified by birthweight and gestational age have been described.
Results : Overall nosocomial infection rates compared favourably with the published NNIS figures at 6.2 infections per 100 admissions or 4.8 per 1000 patient days. Infection rates were significantly higher in lower birthweight groups. Device-related infection rates in each birthweight cohort were also very close to published figures and varied less with birthweight group. Antibiotic exposure averaged 12% of total admission days, less than previously published data.
Conclusions : The NNIS system is applicable to Australian NICU and provides an effective tool for monitoring infection episodes.     

The major determinant of exendin-4/glucagon-like peptide 1 differential affinity at the rat glucagon-like peptide 1 receptor N-terminal domain is a hydrogen bond from SER-32 of exendin-4

BACKGROUND AND PURPOSE

Exendin-4 (exenatide, Ex4) is a high-affinity peptide agonist at the glucagon-like peptide-1 receptor (GLP-1R), which has been approved as a treatment for type 2 diabetes. Part of the drug/hormone binding site was described in the crystal structures of both GLP-1 and Ex4 bound to the isolated N-terminal domain (NTD) of GLP-1R. However, these structures do not account for the large difference in affinity between GLP-1 and Ex4 at this isolated domain, or for the published role of the C-terminal extension of Ex4. Our aim was to clarify the pharmacology of GLP-1R in the context of these new structural data.

EXPERIMENTAL APPROACH

The affinities of GLP-1, Ex4 and various analogues were measured at human and rat GLP-1R (hGLP-1R and rGLP-1R, respectively) and various receptor variants. Molecular dynamics coupled with in silico mutagenesis were used to model and interpret the data.

KEY RESULTS

The membrane-tethered NTD of hGLP-1R displayed similar affinity for GLP-1 and Ex4 in sharp contrast to previous studies using the soluble isolated domain. The selectivity at rGLP-1R for Ex4(9–39) over Ex4(9–30) was due to Ser-32 in the ligand. While this selectivity was not observed at hGLP-1R, it was regained when Glu-68 of hGLP-1R was mutated to Asp.

CONCLUSIONS AND IMPLICATIONS

GLP-1 and Ex4 bind to the NTD of hGLP-1R with similar affinity. A hydrogen bond between Ser32 of Ex4 and Asp-68 of rGLP-1R, which is not formed with Glu-68 of hGLP-1R, is responsible for the improved affinity of Ex4 at the rat receptor.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.