Mitotic and meiotic detection of radiation-induced translocations in mouse stem cell spermatogonia using fluorescencein situ hybridization

The efficiency of two methods of detection of translocations induced in mouse stem cell spermatogonia by X-ray doses of 2, 5 and 7 Gy was compared: classical multivalent analysis at diakinesis-metaphase I of meiosis and observation via fluorescencein situ hybridization analysis of mitotic or meiotic stages. Specific DNA libraries for chromosomes 1, 11 and 13 were used. The results obtained indicate that (a) chromosomes 1, 11 and 13 are more involved in multivalent formation than expected on the basis of DNA content and (b) if the mitotic FISH analysis data are corrected for the observed over-representation, the frequencies of induced translocations are similar to those recorded in the classical multivalent studies, suggesting equal scoring efficiencies in both systems.     

The reliability of the 3-phase bone scan in suspected scaphoid fracture: an inter- and intraobserver variability analysis.

In the diagnosis of scaphoid fracture, the dynamic phase of the radionuclide bone scan alone has been recommended as an early test. To evaluate the independent reliability of the dynamic and static phases of the 3-phase bone scan in this diagnosis, 3 examiners reviewed the 3-phase bone scans of a series of 60 patients with clinical signs of fracture of the carpal scaphoid and with negative or non-diagnostic initial radiographs. The interpretation was performed independently and without the benefit of additional data. The bone scans were reviewed after 1 year by the same observers. The results were analyzed using kappa statistics. The bone scan was suspicious of fracture of the scaphoid in 15 patients. Irrespective of training and experience, the kappa values of the dynamic bone scan between any 2 observers did not exceed 0.57. The kappa values increased significantly when the static phase of the bone scan was examined (> 0.81). The intraobserver variability showed a similar pattern. We conclude that in suspected scaphoid fracture, the dynamic phase of the radionuclide bone scan alone cannot be used as a reliable diagnostic approach because of the low inter- and intraobserver agreement in the interpretation, irrespective of the experience and training of the observer.     

Radiography of the carpal scaphoid. Experimental evaluation of "the carpal box" and first clinical results.

RATIONALE AND OBJECTIVES. The authors describe a new device ("the carpal box") for the radiographic detection of occult scaphoid fracture. METHODS. Fractures in the scaphoid of five cadaver specimens were mechanically produced. Subsequent examinations included conventional scaphoid radiography, multi-angle radiography, and radiography using the new device. The anatomic analysis of the specimens served as the standard for comparison. A pilot study was performed in six consecutive patients with suspected scaphoid fracture. RESULTS. Neither scaphoid radiography nor multi-angle radiography could confirm a fracture in two specimens, whereas all fractures were recognized on the carpal box radiographs. All scaphoid fractures were visualized by carpal box radiography, whereas scaphoid radiography was equivocal in one patient and negative in the other. CONCLUSIONS. Carpal box radiography may have additional value in the diagnosis of occult scaphoid fracture. This may lead to a reduction in costs and inconvenience for patients with clinically suspected scaphoid fracture and negative scaphoid radiography.     

The Development of a Decision Tool for the Empiric Treatment of Suspected Urinary Tract Infection in Frail Older Adults: A Delphi Consensus Procedure

Objectives

Nonspecific signs and symptoms combined with positive urinalysis results frequently trigger antibiotic therapy in frail older adults. However, there is limited evidence about which signs and symptoms indicate urinary tract infection (UTI) in this population. We aimed to find consensus among an international expert panel on which signs and symptoms, commonly attributed to UTI, should and should not lead to antibiotic prescribing in frail older adults, and to integrate these findings into a decision tool for the empiric treatment of suspected UTI in this population.

Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot of interest as an anti-hyperglycemic therapy in type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties and may behave as an immobilized anti-coagulant on endothelial cells. Here, we studied the expression and activity of endothelial DPP4 in human myocardial infarction in relation to a prothrombogenic endothelial phenotype. Using (immuno)histochemistry, DPP4 expression and activity were found on the endothelium of intramyocardial blood vessels in autopsied control hearts (n?=?9). Within the infarction area of AMI patients (n?=?73), this DPP4 expression and activity were significantly decreased, coinciding with an increase in Tissue Factor expression. In primary human umbilical vein endothelial cells (HUVECs), Western blot analysis and digital imaging fluorescence microscopy revealed that DPP4 expression was strongly decreased after metabolic inhibition, also coinciding with Tissue Factor upregulation. Interestingly, inhibition of DPP4 activity with diprotin A also enhanced the amount of Tissue Factor encountered and induced the adherence of platelets under flow conditions. Ischemia induces loss of coronary microvascular endothelial DPP4 expression and increased Tissue Factor expression in AMI as well as in vitro in HUVECs. Our data suggest that the loss of DPP4 activity affects the anti-thrombogenic nature of the endothelium.     

In Vivo Imaging of Enhanced Leukocyte Accumulation in Atherosclerotic Lesions in Humans

Background

Understanding how leukocytes impact atherogenesis contributes critically to our concept of atherosclerosis development and the identification of potential therapeutic targets.

Objectives

The study evaluates an in vivo imaging approach to visualize peripheral blood mononuclear cell (PBMC) accumulation in atherosclerotic lesions of cardiovascular (CV) patients using hybrid single-photon emission computed tomography/computed tomography (SPECT/CT).

Methods

At baseline, CV patients and healthy controls underwent ¹⁸fluorodeoxyglucose positron emission tomography-computed tomography and magnetic resonance imaging to assess arterial wall inflammation and dimensions, respectively. For in vivo trafficking, autologous PBMCs were isolated, labeled with technetium-99m, and visualized 3, 4.5, and 6 h post-infusion with SPECT/CT.

Results

Ten CV patients and 5 healthy controls were included. Patients had an increased arterial wall inflammation (target-to-background ratio [TBR] right carotid 2.00 ± 0.26 in patients vs. 1.51 ± 0.12 in controls; p = 0.022) and atherosclerotic burden (normalized wall index 0.52 ± 0.09 in patients vs. 0.33 ± 0.02 in controls; p = 0.026). Elevated PBMC accumulation in the arterial wall was observed in patients; for the right carotid, the arterial-wall-to-blood ratio (ABR) 4.5 h post-infusion was 2.13 ± 0.35 in patients versus 1.49 ± 0.40 in controls (p = 0.038). In patients, the ABR correlated with the TBR of the corresponding vessel (for the right carotid: r = 0.88; p < 0.001).

Conclusions

PBMC accumulation is markedly enhanced in patients with advanced atherosclerotic lesions and correlates with disease severity. This study provides a noninvasive imaging tool to validate the development and implementation of interventions targeting leukocytes in atherosclerosis.     

Weight Loss After Laparoscopic Adjustable Gastric Banding is not Caused by Altered Gastric Emptying

Background  In order to know the role of gastric emptying in the mechanism of weight loss and early satiety after a restrictive surgical procedure for treatment of morbid obesity, a consecutive series of patients were scintigraphically investigated before and after laparoscopic adjustable gastric banding. Methods  Sixteen patients undergoing laparoscopic adjustable gastric banding underwent preoperatively, and at 6 months postoperatively, a gastric emptying study (solid meal and single isotope). Esophageal retention time, lag phase, peak activity time, gastric emptying rate, fundus emptying rate, and weight loss were recorded. Upper GI symptom assessment was carried out by using a standardized questionnaire. Gastric emptying parameters were correlated with the upper GI symptoms. Results  Gastric band placement showed no significant influence on postoperative gastric emptying rate [median % (interquartile range): 42 (23.3–59) preoperatively vs 38 (31–71) postoperatively and fundus emptying rate: 59(37–91) preoperatively vs 70 (53–89) postoperatively]; however, an increase in early satiety was found. Neither gastric emptying rate nor fundus emptying rate showed a relation with early satiety or weight loss. Furthermore, no correlation was found between early satiety and lag phase, esophageal retention time, start of activity, and peak activity time in proximal stomach. Conclusion  Laparoscopic adjustable gastric banding seems not to affect gastric emptying. Neither a relation between postoperative gastric emptying rate and weight loss nor between early satiety and weight loss was found. Therefore, it is unlikely that gastric emptying plays a role in the mechanism of weight loss following laparoscopic adjustable gastric banding. The authors disclose that there was no commercial interest and declare that there was no financial or material support.     

Endothelial signaling by Ig-like cell adhesion molecules

The migration of leukocytes across the endothelial lining of the vascular wall requires a complicated series of adhesion and signaling events. Endothelial Ig-like cell adhesion molecules (IgCAMs) such as intercellular adhesion molecule-1 play an important role, not only as ligands for leukocyte integrins, but also as signaling initiators. Clustering these IgCAMs triggers a wide range of events in the endothelial cells' interior, of which activation of Rho-like GTPases, induction of cytoskeletal changes, and the transient modulation of cell-cell contact are key events. This review discusses recent insights into this IgCAM-driven endothelial signaling and its consequences for leukocyte transendothelial migration.