Early development of Charcot neuroarthropathy in the course of compensated diabetes mellitus--case report

Charcot neuroarthropathy (CN)--chronic and progressive, destructive disease of bones and joints, which develops on the background of neuropathy, is late and uncommon complication of diabetes. It occurs almost exclusively in patients with a mean duration of diabetes at least 10 years. We report the case of woman, who developed an acute phase of CN 11 months after recognition of diabetes. Because of recent recognition of diabetes and good glycaemic control, CN wasn't considered in the differential diagnosis of swelling, pain and warmth of feet. The initial diagnosis was missed, leading in few months, to development of irreversible deformity of both feet.     

Serum aminoterminal peptide of type III procollagen (PIIINP) and transforming growth factor-beta1 (TGF-beta1) levels in patients with chronic hepatitis B and C

Fibrosis is the process accompanying majority of chronic diseases of liver, independent of etiological factor and leading to cirrhosis and hepatic failure. Monitoring fibrosis process by liver's biopsy is limited, so many attempts are undertaken to assess concentrations of definite proteins in blood, which could be easily accessible marker of intrahepatic process. It seems, that among others, determinations of blood concentration of aminoterminal propeptide of procollagen III--index of collagen's III synthesis and TGF-beta 1--cytokine of antiproliferative action and inhibiting hepatocytes' growth, yet inducing fibroblasts' growth and stimulating fibrosis process brings out such a possibility. The aim of the study was simultaneous determination of TGF-beta 1 and PIIINP concentration in blood of patients with chronic hepatitis B and C before interferone's therapy in comparison to healthy controls, assessment of the parameters in dependence on stage of liver fibrosis and determination of correlation between TGF-beta 1 and PIIINP. Studies were performed in 40 patients with chronic hepatitis B (CAH B) and 35 patients with chronic hepatitis C (CAH C). Significantly increased serum concentrations of TGF-beta 1 as PIIINP in both groups of patients (CAH B and CAH C; grading 2-3, staging 1-2) in comparison with control group was noted. Significant positive correlation of TGF-beta 1 and PIIINP serum concentrations in both groups of patients was observed. There was not significant changes in PIIINP serum levels in patients with hepatitis B and C in dependence on stage of liver fibrosis (staging 1 vs staging 2) but TGF-beta 1 serum levels was significantly increased in CAH B and C patients with higher stage of liver fibrosis process. On the base of obtained results, it seems that changes in TGF-beta 1 concentrations in blood reflect "grading" and "staging" and can be a marker of intensification of intrahepatic fibrosis process whereas PIIINP levels in blood have rather the relation with "grading".     

Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.     

Non-full-thickness macular holes: a closer look

Lamellar macular holes and macular pseudoholes are non-full-thickness defects of retinal tissue involving the anatomic fovea, thereby affecting central visual acuity. Non-full-thickness macular holes have been associated with myriad ocular conditions. Originally, lamellar macular holes were described as secondary to diabetic macular edema and macular pseudoholes as idiopathic. The pathogenesis of secondary non-full-thickness macular defects was recently confirmed by spectral-domain optical coherence tomography. These may be mistaken for macular hole lesions, despite careful clinical examination. Careful biomicroscopic examination with a contact lens and optical coherence tomography help to ensure accurate diagnosis. Surgical management with or without air or gas tamponade improves visual acuity and foveal morphology in most eyes.     

Adhesion of cells in flowing suspensions: effects of shearing force and cell kinetic energy

The computation of the shearing force and torque operating upon L1210 leukemic cells, which adhere to the surface while flowing in a medium of a given velocity, yields information relevant to the problem of adhesion strength. The shearing force in a slowly moving fluid is too small to prevent the formation of adhesive bonds and the cell adhesion efficiency is relatively great. When the fluid velocity at a distance of 5 μm above the channel is 14 μm/sec, the shearing force is equal to 3.5 × 10⁻¹² N and the torque is 7.6 × 10⁻¹⁸ N·m. The cell adhesion efficiency in a faster medium flow is smaller and drops to insignificant values if the fluid near-wall velocity exceeds 140 μm/sec, such as when the shearing force amounts to 3.4 × 10⁻¹¹ N or more. Thus, the strength of the adhesive bonds of almost all cells is insufficient to resist the action of this force. As the above physical parameters are estimated at the very moment of the adhesive cell-surface bonding, they are not influenced by the contact time factor. For slowly moving cells the mean kinetic energy (translational and rotational motion before adhesion) is 2.2 × 10⁻²² J, approximately two orders of magnitude greater than when cells flow with a speed approaching the limits of compatibility with adhesion.     

Cancer procoagulant in patients with adenocarcinomas.

Cancer procoagulant (CP) is a cysteine proteinase that may be produced by malignant and foetal tissue. The possible role of CP in the pathogenesis of cancer-related thrombosis has been suggested recently. The purpose of the study was to evaluate coagulation prothrombotic markers and their relation to CP concentration in the blood of patients with gastrointestinal adenocarcinomas (GIAC). The study group consisted of 45 patients with confirmed diagnosis of adenocarcinoma (stomach, 18 patients; colon, 27 patients) and without evident metastatic disease. In 24 patients further observation showed metastases. The control group for CP was composed of 10 healthy subjects. Blood samples were drawn on the admission day, before any treatment. Among 45 patients with GIAC, deep venous thrombosis was observed in two (4.4%). In all patients the CP activity in the serum was found, and the mean CP activity shortened the coagulation time almost three times compared with the healthy control group. Also, the mean thrombin-antithrombin complex concentration was above the normal range. A significant elevation of the mean prothrombin fragment 1+2 plasma content in this group of patients was noticed. Despite these observations, CP remained within the normal range and did not correlate with thrombin-antithrombin complex or prothrombin fragment 1+2 plasma concentrations. A positive correlation was observed between serum CP and fibrinogen concentration, and a negative correlation between CP and free protein S plasma content (P = 0.04 and P = 0.025, respectively). A negative correlation between activated protein C resistance ratio and protein C activity in the plasma was confirmed. Protein C activity in the plasma showed a correlation with free protein S plasma content. Analysis of factors influencing the activated partial thromboplastin time revealed the presence of antiphospholipid antibodies in seven persons from the study group (in three cases of IgG and in four cases of IgM class). Our data suggest that CP is a minor risk factor for deep venous thrombosis in GIAC patients. To confirm this, however, the number of patients and controls should be larger. After 3 years of observation, the follow-up in 10 living GIAC patients showed nobody with thromboembolic disease.