Loss of heterozygosity of DPC4 tumor suppressor gene in human sporadic colon cancer

We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. Thirty-six cases of human sporadic colon carcinoma and corresponding normal tissue samples were examined to evaluate loss of heterozygosity at the DPC4 tumor suppressor locus using variable nucleotide tandem repeat (VNTR) analysis and three polymorphic markers. From 36 analyzed samples 35 (97%) were heterozygous or informative. Loss of heterozygosity at the DPC4 locus was detected in 18 (51%) of informative tumor DNAs. The DPC4 LOH was more frequent in smaller tumors (<5 cm) than in larger ones. There was no correlation between DPC4 LOH and age or sex of patients. There was a negative correlation between DPC4 LOH and histological grade or Dukes' stage of tumors, but without statistic significance. Observed results are in agreement with the view that malignant progression is consequence of many genetic changes. It can be concluded that inactivation of the DPC4 gene plays a role in a multistep process of outgrowth and progression of colon cancer.     

Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans

In this study, we have examined the correlation between the histological and histochemical changes of articular cartilage and bone parameters of the underlying subchondral bone. The aim was to elucidate patterns of bone parameter changes within different depths of subchondral bone in the joints with macroscopically normal cartilage and in joints with osteoarthritis (OA). Ten tibial plateaus were taken from patients during total knee replacement surgery due to severe OA. They were compared with 10 sets of tibial condyles obtained from autopsy subjects with no history of bone or joint disease. The cylindrical cartilage-bone samples were taken out from the anterior, posterior, external, and internal areas of the condyles for cartilage assessment (Mankin score) and subchondral bone histomorphometry. Four histomorphometric parameters were measured: bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.S). Our study showed that subchondral bone from the OA group had significantly higher bone volume (54.1 +/- 10.6%) than control group (37.8 +/- 8.1%) (P < 0.01). In addition, trabecular parameters from the OA subchondral bone showed a smaller number of sparsely distributed and thicker trabecules than in control group (P < 0.05). Medial and lateral condyle from the control group did not differ significantly, while medial condyle from OA group showed a high increase of bone volume (62.8 +/- 13.3) and consecutively different trabecular parameters when compared with the lateral condyle from the same group. Also, it was shown that there are regional differences (anterior, posterior, internal, and external) in bone parameters between both condyles within both, control and OA groups. Comparison of bone parameters from three different stage of articular cartilage degeneration (Mankin score) showed that higher degree of cartilage degeneration is followed by significant changes in subchondral bone architecture. Furthermore, we have found that progression of cartilage degeneration leads to changes in bone parameters which affected deeper levels of subchondral bone. According to these results, it can be suggested that changes in histomorphometric parameters of subchondral bone are secondary to cartilage damage and proceed deeper into subchondral bone with increasing cartilage degeneration.     

Pulmonary lymphohistiocytic reactions temporally related to etanercept therapy.

This report details the pulmonary pathologic findings in four patients with rheumatoid arthritis, who developed new onset of pulmonary signs and symptoms with alveolar infiltrates temporally related to the institution of etanercept therapy. Biopsy findings showed an interstitial and air space lymphohistiocytic infiltrate with non-necrotizing granulomas, in the setting of negative cultures and special stains for microorganisms. The association with etanercept therapy and granulomatous reactions is discussed along with the differential diagnosis.     

Impaired visuospatial associative memory and attention in obsessive compulsive disorder but no evidence for differential dopaminergic modulation

Rationale  

Patients with obsessive compulsive disorder (OCD) demonstrate impaired cognition in some selected domains. Although serotoninergic dysfunction has been implicated in OCD, recent evidence suggests that dopamine may play a role as well.     

Matrix metalloproteinase-9 and cell kinetics during the collection of peripheral blood stem cells by leukapheresis.

The plasma levels of matrix metalloproteinase-9 (MMP-9) were determined during 41 collections of peripheral blood stem cells (PBSC) by standard volume (two blood volumes) leukaphereses (SVL) in 29 donors (7 allogeneic and 22 autologous) mobilized with the granulocyte-colony stimulating factor (G-CSF). The association between MMP-9 levels and cell counts in donor's blood was explored. During the processing of the first blood volume (BV), MMP-9 levels declined on average by 31% and persisted at the same level during the processing of the second BV. During the collection, a slight decline of white blood cells (WBC), polymorphonuclear neutrophils (PMN) and platelets (PLT) in donor's blood was accompanied by a significant drop of CD34+ cells by 37% after 1 BV and by 44% after 2 BV had been processed (p=0.001). The drop of MMP-9 plasma levels showed a loose correlation with the decrease of WBC (r=0.68, p=0.002) and PMN counts (r=0.67, p=0.001). We conclude that the levels of MMP-9 that have been elevated by the mobilization of donors with G-CSF, decrease during the collection of PBSC by 4h SVL. The observed decrease was indirectly related to the drop of WBC and PMN counts, suggesting that certain other factors have an influence on MMP-9 kinetics during PBSC collection.     

Extrapancreatic Glucagon and Glucagonlike Immunoreactivity in Depancreatized Dogs: A QUANTITATIVE ASSESSMENT OF SECRETION RATES AND ANATOMICAL DELINEATION OF SOURCES

The anatomical sites and the rates of extrapancreatic secretion of glucagon and of glucagon-like immunoreactivity (GLI) were assessed in dogs 2 h after pancreatectomy by catheterization of the gastrosplenic and mesenteric veins.     

Comparison of facemask and mouthpiece interfaces for multiple breath washout measurements

Background

Different interfaces (mouthpiece/nose clip vs. facemask) are used during multiple breath washout (MBW) tests in young children.

Endothelial NOS G894 T and MMP-3 5A/6A gene polymorphisms and hypertension in Serbian population

The incidence of hypertension is increasing and it is more common in man than in women. Up to date, MMP-3 5A/6A polymorphism has been associated with artery stiffening and elevated blood pressure, whereas results considering association of endothelial NOS (eNOS) G894 T polymorphism with hypertension are controversial. The aim of our study was to analyze the possible association of eNOS G894 T and MMP-3 5A/6A gene polymorphisms with hypertension in Serbian population. Study sample consisted of 172 hypertensive and 200 normotensive subjects divided by gender. Both female and male group was truncated according to age. All subjects were genotyped for MMP-3 5A/6A and eNOS G894 T polymorphism. There was a significantly higher (P < 0.05) prevalence of 5A/5A genotype in hypertensive females compared to normotensive ones (19.30 % vs. 10.84%) even more pronounced in group > or =50 years, according to its recessive effect. In young males (<40 years), we found 3.7-fold increased risk for hypertension associated with allele 6A (P < 0.01), and 8.1-fold with genotype 6A/6A (P = 0.01) according to recessive model. We found no association of eNOS G894 T polymorphism with hypertension. These results indicate that there were gender- and age-specific differences in association of MMP-3 5A/6A polymorphism with hypertension in Serbian population.     

Navigation system for robot-assisted intra-articular lower-limb fracture surgery

Purpose

In the surgical treatment for lower-leg intra-articular fractures, the fragments have to be positioned and aligned to reconstruct the fractured bone as precisely as possible, to allow the joint to function correctly again. Standard procedures use 2D radiographs to estimate the desired reduction position of bone fragments. However, optimal correction in a 3D space requires 3D imaging. This paper introduces a new navigation system that uses pre-operative planning based on 3D CT data and intra-operative 3D guidance to virtually reduce lower-limb intra-articular fractures. Physical reduction in the fractures is then performed by our robotic system based on the virtual reduction.

Methods

3D models of bone fragments are segmented from CT scan. Fragments are pre-operatively visualized on the screen and virtually manipulated by the surgeon through a dedicated GUI to achieve the virtual reduction in the fracture. Intra-operatively, the actual position of the bone fragments is provided by an optical tracker enabling real-time 3D guidance. The motion commands for the robot connected to the bone fragment are generated, and the fracture physically reduced based on the surgeon’s virtual reduction. To test the system, four femur models were fractured to obtain four different distal femur fracture types. Each one of them was subsequently reduced 20 times by a surgeon using our system.

Results

The navigation system allowed an orthopaedic surgeon to virtually reduce the fracture with a maximum residual positioning error of \(0.95 \pm 0.3\,\hbox {mm}\) (translational) and \(1.4^{\circ } \pm 0.5^{\circ }\) (rotational). Correspondent physical reductions resulted in an accuracy of 1.03 ± 0.2 mm and \(1.56^{\circ }\pm 0.1^{\circ }\), when the robot reduced the fracture.

Conclusions

Experimental outcome demonstrates the accuracy and effectiveness of the proposed navigation system, presenting a fracture reduction accuracy of about 1 mm and \(1.5^{\circ }\), and meeting the clinical requirements for distal femur fracture reduction procedures.