Effect of indomethacin on collagen biosynthesis by rabbit articular chondrocytes in monolayer cultures

The influence of indomethacin on collagen biosynthesis in rabbit articular chondrocyte monolayer cultures was studied. Two applications within the space of three days of therapeutic doses (10(-5) or 10(-6)M), as well as repeated applications four days running of lower doses (10(-8) or 10(-10)M), increased the biosynthesis of both collagen and non-collagen proteins. Two applications of higher doses (10(-3) or 10(-4M) decreased DNA synthesis and inhibited both collagen and non-collagen protein biosynthesis. These results might well be considered in connection with the adverse reactions observed in some patients with long-term use of indomethacin.     

Effects of dexamethasone on the growth of cultured rabbit articular chondrocytes:relation with the nuclear glucocorticoid-receptor complex.

This study reports that dexamethasone at a high dose (10(-4) mol/l) induced slowing of the in vitro proliferation of rabbit articular chondrocytes in both monolayer and clonal culture. This effect is consistent with an inhibition of DNA and RNA synthesis and was characterised by an accumulation of cells in the G0G1 phase of the cell cycle, as shown by flow cytometric analysis. Therefore we determined the extent of nuclear localisation of dexamethasone-receptor complexes. The results showed a discrepancy between 50% growth inhibitory dose (10(-4) mol/l) and the apparent affinity, KD (1.4 (SD 0.2) X 10(-9) mol/l). Thus the growth inhibition of rabbit articular chondrocytes by dexamethasone did not seem to be related exclusively to an interaction with the glucocorticoid-receptor complexes.     

Risk of Catastrophic Health Expenditure in Rwandan Surgical Patients with Peritonitis

Background

Surgical procedures are cost-effective compared with various medical and public health interventions. While peritonitis often requires surgery, little is known regarding the associated costs, particularly in low- and middle-income countries. The aim of this study was to determine in-hospital charges for patients with peritonitis and if patients are at risk of catastrophic health expenditure.

Methods

As part of a larger study examining the epidemiology and outcomes of patients with peritonitis at a referral hospital in Rwanda, patients undergoing operation for peritonitis were enrolled and hospital charges were examined. The primary outcome was the percentage of patients at risk for catastrophic health expenditure. Logistic regression was used to determine the association of various factors with risk for catastrophic health expenditure.

Results

Over a 6-month period, 280 patients underwent operation for peritonitis. In-hospital charges were available for 245 patients. A total of 240 (98%) patients had health insurance. Median total hospital charges were 308.1 USD, and the median amount paid by patients was 26.9 USD. Thirty-three (14%) patients were at risk of catastrophic health expenditure based on direct medical expenses. Estimating out-of-pocket non-medical expenses, 68 (28%) patients were at risk of catastrophic health expenditure. Unplanned reoperation was associated with increased risk of catastrophic health expenditure (p < 0.001), whereas patients with community-based health insurance had decreased risk of catastrophic health expenditure (p < 0.001).

Conclusions

The median hospital charges paid out-of-pocket by patients with health insurance were small in relation to total charges. A significant number of patients with peritonitis are at risk of catastrophic health expenditure.

     

Critical Care Management of Peritonitis in a Low-Resource Setting

Background

Management of critically ill patients is challenging in a low-resource setting. In Rwanda, peritonitis is a common surgical condition where patients often present late, with advanced disease. We aim to describe critical care management of patients with peritonitis in Rwanda.

Methods

Data were collected at a tertiary referral hospital in Rwanda on patients undergoing operation for peritonitis over a 6-month period. Data included epidemiology, hospital course and outcomes. Patients requiring admission to the intensive care unit (ICU) were compared with those not requiring ICU admission using Chi-square and Wilcoxon rank-sum test.

Results

Over a 6-month period, 280 patients were operated for peritonitis. Of these, 46 (16.4%) were admitted to the ICU. The most common diagnoses were intestinal obstruction (N?=?17, 37.0%) and typhoid intestinal perforation (N?=?6, 13.0%). Thirty-nine (89%) patients had sepsis. The median American Society of Anesthesiologist score was 3 (range 2–4), and the median Surgical Apgar Score was 4 (range 0–6). Twenty-four (52.2%) patients required vasopressors, with dopamine and adrenaline being the only vasopressors available. Patients admitted to the ICU, compared with non-critically ill patients, were more likely to have major complications (80.4 vs. 14%, p?<?0.001), unplanned reoperation (28 vs. 10%, p?<?0.001) and death (72 vs. 8%, p?<?0.001).

Conclusion

Patients with peritonitis admitted to the ICU commonly presented with features of sepsis. Due to limited resources in this setting, interventions are primarily supportive with intravenous fluids, intravenous antibiotics, ventilator support and vasopressors. Morbidity and mortality remain high in this patient population.

     

Influence of crimping textile polyester vascular prostheses on the fluid flow kinetics. Groupe Européen de Recherche sur les Prothèses appliquées à la Chirurgie Vasculaire.

OBJECTIVES: to characterise the impact of the crimping of polyester prostheses on the fluid flow kinetics. DESIGN: an experimental in vitro study. MATERIALS AND METHODS: we investigated four models of polyester vascular prostheses in a continuous laminar flow circuit. The flow velocity was 80 ml/s for all experiments. We studied two fluids of different viscosity within the circuit. The speed of the particles was measured by a laser Doppler anemometer 2 to 52 mm from the prosthetic interface. We first established a calibrated flow-velocity profile corresponding to the study of the support inside the circuit without any prosthesis. We measured the velocity profiles for each prosthesis corresponding to four crimp densities obtained by stretching the grafts. RESULTS: the crimping of PET textile prostheses led to a decrease of flow velocity especially closer to the prosthetic surface. The decrease of flow velocity was dependent on the model of prosthesis. This decrease of flow velocity is described by the following negative exponential law: DeltaV=a times b(-x)where (a) is the crimp density and (b) the fluid viscosity. CONCLUSIONS: flow velocity near a prosthetic surface is influenced by the morphology of the crimping. The impact of crimping on the flow velocity in a vascular prosthesis can be predicted by computer simulation models. This may provide the optimal shape of crimping for each prosthesis.     

Percutaneous Left Atrial Appendage Closure With the Ultraseal Device: Insights From the Initial Multicenter Experience

Objectives

This study sought to evaluate the feasibility, safety, and efficacy of the Ultraseal device for left atrial appendage closure (LAAC) (Cardia, Eagan, Minnesota) in patients with nonvalvular atrial fibrillation at high bleeding risk.

Monolayer, tridimensional and immortalized cell line cultures as models in pharmacology and toxicology

The articular cartilage located in movable joints can be divided into cellular and intercellular components. This latter category, also called the extracellular matrix, is responsible for the mechanical properties of cartilage and results from the functional activity of the cartilaginous cells, the chondrocytes. Through changes in their metabolism, chondrocytes are able to modify the composition of cartilage in response to physiological, pathological and pharmacotoxicological stimuli. The culture of articular chondrocytes is therefore important in biological research and various methods have been proposed. Models in vitro of normal and pathological chondrocytes are now described. Normal culture can be studied in organ explants, monolayers and various types of tridimensional culture. Chondrocytes immortalized by gene transfection will provide a further model of normal cells when progress has been made in the maintenance of differentiation. Models of pathological cells involve normal cultured chondrocytes treated with cytokines or oxygen free radicals, or rendered senescent by successive passages. Such models are useful in pharmacological and toxicological research. The advantages and limitations of these different models of cultured articular chondrocytes are discussed.     

Patched1 functions as a gatekeeper by promoting cell cycle progression

Mutations in the Hedgehog receptor, Patched 1 (Ptch1), have been linked to both familial and sporadic forms of basal cell carcinoma (BCC), leading to the hypothesis that loss of Ptch1 function is sufficient for tumor progression. By combining conditional knockout technology with the inducible activity of the Keratin6 promoter, we provide in vivo evidence that loss of Ptch1 function from the basal cell population of mouse skin is sufficient to induce rapid skin tumor formation, reminiscent of human BCC. Elimination of Ptch1 does not promote the nuclear translocation of beta-catenin and does not induce ectopic activation or expression of Notch pathway constituents. In the absence of Ptch1, however, a large proportion of basal cells exhibit nuclear accumulation of the cell cycle regulators cyclin D1 and B1. Collectively, our data suggest that Ptch1 likely functions as a tumor suppressor by inhibiting G1-S phase and G2-M phase cell cycle progression, and the rapid onset of tumor progression clearly indicates Ptch1 functions as a "gatekeeper." In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors.     

Flow cytometric analysis of pentakis(aziridino)thiatriazadiphosphorine oxide (SOAz)-induced changes in cell cycle progression of HeLa and HL-60 cells

The treatment of HeLa and HL-60 cells with various concentrations of pentakis(arizidino)thiatriazadiphosphorine oxide results in inhibition of growth and modification of cell cycle distribution. These phenomena were observed at 10(-4) M and 5 X 10(-5) M for HeLa cells and 10(-5) M and 5 X 10(-6) M for HL-60 cells. The estimation of DNA content by flow cytometry showed an important shift in the distribution of cycling cells with a striking arrest in G2 for both cell lines with a concomitant late S-phase accumulation for HeLa cells. Incubation of cells in drug-free medium 3 days after treatment did not show any change in DNA distribution, suggesting the irreversibility of drug action.