Methicillin resistant S. Aureus in autopsy cases

Objective: To determine whether hospital stay predisposes to nasal colonisation with Staphylococcus aureus and Methicillin Resistant S. aureus (MRSA). Method: Nasal swabs were taken from cadavers undergoing post-mortem examinations at the mortuary of St. Luke’s Hospital. The swabs were taken to the Bacteriology Laboratory where attempts were made to culture S. aureus. Vitek® Gram Positive Susceptibility Cards were used for antibiotic susceptibility. MRSA positive organisms were tested using Penicillin Binding Protein Latex Agglutination. Key Findings: Ninety-three swabs were taken. The proportion of S. aureus nasal carriage was similar in both hospitalised and non-hospitalised groups. However, 8 out of 15 (53%) S. aureus carriers in the hospitalised group were MRSA positive, compared to 4 out of 19 (21%) S. aureus carriers in the non-hospitalised group. Conclusion: Hospitalisation increases the incidence of MRSA carriage compared to the non-hospitalised population.peer-reviewe

Placement of trans-sternal wires according to an ellipsoid pressure vessel model of sternal forces

Funding from the University of Malta Medical School (Grant IMF/014/11) and University of Malta Research Fund (Grant 31/389/10) is gratefully acknowledged.Dehiscence of median sternotomy wounds remains a clinical problem. Wall forces in thin-walled pressure vessels can be calculated by membrane stress theory. An ellipsoid pressure vessel model of sternal forces is presented together with its application for optimal wire placement in the sternum. Sternal forces were calculated by computational simulation using an ellipsoid chest wall model. Sternal forces were correlated with different sternal thicknesses and radio-density as measured by computerized tomography (CT) scans of the sternum. A comparison of alternative placement of trans-sternal wires located either at the levels of the costal cartilages or the intercostal spaces was made. The ellipsoid pressure vessel model shows that higher levels of stress are operative at increasing chest diameter (P < 0.001). CT scans show that the thickness of the sternal body is on average 3 mm and 30% thicker (P < 0.001) and 53% more radio-dense (P < 0.001) at the costal cartilage levels when compared with adjacent intercostal spaces. This results in a decrease of average sternal stress from 438 kPa at the intercostal space level to 338 kPa at the costal cartilage level (P = 0.003). Biomechanical modelling suggests that placement of trans-sternal wires at the thicker bone and more radio-dense level of the costal cartilages will result in reduced stress.peer-reviewe

Mechanism of sternotomy dehiscence

Research funded by the University of Malta.OBJECTIVES Biomechanical modelling of the forces acting on a median sternotomy can explain the mechanism of sternotomy dehiscence, leading to improved closure techniques. METHODS Chest wall forces on 40 kPa coughing were measured using a novel finite element analysis (FEA) ellipsoid chest model, based on average measurements of eight adult male thoracic computerized tomography (CT) scans, with Pearson's correlation coefficient used to assess the anatomical accuracy. Another FEA model was constructed representing the barrel chest of chronic obstructive pulmonary disease (COPD) patients. Six, seven and eight trans-sternal and figure-of-eight closures were tested against both FEA models. RESULTS Comparison between chest wall measurements from CT data and the normal ellipsoid FEA model showed an accurate fit (P < 0.001, correlation coefficients: coronal r = 0.998, sagittal r = 0.991). Coughing caused rotational moments of 92 Nm, pivoting at the suprasternal notch for the normal FEA model, rising to 118 Nm in the COPD model (t-test, P < 0.001). The threshold for dehiscence was 84 Nm with a six-sternal-wire closure, 107 Nm with seven wires, 127 Nm with eight wires and 71 Nm for three figure-of-eights. CONCLUSIONS The normal rib cage closely fits the ellipsoid FEA model. Lateral chest wall forces were significantly higher in the barrel-shaped chest. Rotational moments generated by forces acting on a six-sternal-wire closure at the suprasternal notch were sufficient to cause lateral distraction pivoting at the top of the manubrium. The six-sternal-wire closure may be successfully enhanced by the addition of one or two extra wires at the lower end of the sternotomy, depending on chest wall shape.peer-reviewe

In vitro investigation of anti-osteoporotic bioactivity of extracts from indigenous plants and investigating whether these induce an oestrogen growth factor response

Aims: The main aim of the study is the production of an extract from a local indigenous plant that induces the differentiation of the osteoblast cell line MC3T3-E1 without inducing an estrogen growth factor response in the breast cancer cell line MCF-7. Methods: A wide range of different methodologies have been used. Methanol extraction has been utilized for the extraction process. Using the osteoblast cell line MC3T3-E1, titrations were performed so as to obtain the working concentrations for betaoestradiol, the extracts, and an already commercialized product (Lignan). To determine the cytotoxicity, XTT assays were performed on the different compounds tested. A chemiluminescence method has also been utilized to directly measure the osteogenesis rate by measuring the uptake of the stain Alizarin red for calcium mineralization (bone matrix). Western blotting is being used to measure the activation of the Estrogen Receptor (ER-alpha) by using a specific phospho-antibody. Real time-PCR will be utilized for expression studies of identified oestradiol response genes. Results: Using methanol reflux, two different extracts have been produced. The working concentrations of the test compounds have already been identified and XTT assays have showed us that none of the test compounds tested (beta-oestradiol, lignan, and carob pod extract) is cytotoxic. The osteogenesis rate has been quantified and after 15 days, a 3.6 fold increase in osteogenesis has been obtained with beta-oestradiol and a 7.6 fold increase in osteogenesis has been obtained with Lignan, when compared with a no factor control. Out of the 2 extracts produced, one of them did not produce any significant results. However, pilot studies conducted on the second extract have shown very promising results and the current experiments being performed will determine the ideal working concentration of this extract. We also confirmed the work done by Takamizawa et al (2004) where whilst ascorbic acid 2-phosphate stimulates osteogenesis, ascorbic acid showed a repressive effect depending on concentration used. Conclusions: To date we can conclude that both betaoestradiol, and Lignan increase the rate of osteogenesis. Although the primary extract did not produce any significant results, pilot studies on the secondary extract have shown us that the results are very promising. The effect of these test compounds on ER-alpha and on oestradiol response genes still needs to be determined.peer-reviewe

Is there a biomechanical cause for spontaneous pneumothorax?

OBJECTIVES: Primary spontaneous pneumothorax has long been explained as being without apparent cause. This paper deals with the effect of chest wall shape and explains how this may lead to the pathogenesis of primary spontaneous pneumothorax. METHODS: Rib cage measurements were taken from chest radiographs in 12 male pneumothorax patients and 12 age-matched controls. Another group of 15 consecutive male thoracic computerised tomography (CT) were investigated using paramedian coronal and sagittal CT reconstructions to assess apical lung shape. A finite element analysis (FEA) model of a lung apex was constructed, including indentations for the first rib guided by CT scan data, to assess pleural stress. This model was tested using different anteroposterior diameter ratios, producing a range of thoracic indexes. RESULTS: The pneumothorax patients had a taller chest (P = 0.03), wider transversely (P = 0.009) and flatter (P = 0.03) when compared with controls, resulting in a low thoracic index. Prominent rib indentations were found anteriorly and posteriorly on the lung surface, especially on the first rib on CT. FEA of the lung revealed significantly higher stress (×5-×10) in the apex than in the rest of the lung. This was accentuated (×4) in low thoracic index chests, resulting in 20-fold higher stress levels in their apex. CONCLUSIONS: The FEA model demonstrates a 20-fold increase in pleural stress in the apex of chests with low thoracic index typical of spontaneous pneumothorax patients. Mild changes in thoracic index, as occurring in females or with aging, reduce pleural stress. Spontaneous pneumothorax occurring in young male adults may have a biomechanical cause.peer-reviewe

Targeting the mevalonate and mammalian target of rapamycin pathways in breast cancer

Introduction: Breast cancer is the commonest cause of cancer mortality in Maltese females. The availability of eukaryotic translation initiation factor 4E (eIF4E) is reduced by mammalian target of rapamycin (mTOR) inhibitors e.g. rapamycin and metformin. Expression of 3-hydroxy-3-methylglutarylcoenzynre A reductase (HMG-CoA reductase), the mevalonate pathway rate limiting enzyme, is regulated by eIF4E. Additionally statins e.g. simvastatin, are HMG-CoA reductase inhibitors.peer-reviewe

Differential expression of breast cancer signature genes following rapamycin treatment

Introduction: Breast cancer is classified into intrinsic molecular subtypes, each relating to predictive prognostic and clinical outcomes. Rapamycin inhibits the mammalian target of rapamycin (mTOR) pathway, which is often deregulated in various types of cancer. mTOR inhibitors are associated with antiproliferation and apoptosis. Aim: Investigating the differential expression of breast cancer signature genes following rapamycin treatment in various breast cancer subtypes.peer-reviewe

In vitro investigation of osteogenesis bioactivity of extracts from indigenous plants and measurement of estrogen growth factor response

The objective of the current research is to characterise the bioactive properties of substances prepared in our laboratory from indigenous plants which could be used as an alternative to hormone replacement therapy (HRT). While the usefulness of HRT in osteoporosis is well established, it has been shown to carry serious long-term risks including that of breast cancer. Hence the need to identify phytoestrogens that induce osteoblast cell line (MC3T3-E1) differentiation without inducing an estrogen growth factor response in the breast cancer cell line (MCF-7).peer-reviewe

Totarol content and cytotoxicity varies significantly in different types of propolis

Propolis is a complex honeybee product deposited in the beehives, where it protects the hive and its occupants from microbial infection. Propolis has several reported medical applications in view of its numerous bioactive properties. The water insoluble fraction of crude Maltese honeybee propolis was extracted in methanol. Analysis by gas chromatography – mass spectrometry (GC-MS) showed the diterpenoid totarol to be the predominant constituent in all samples. The evaporated methanol residue was dissolved in dimethyl sulphoxide (DMSO) and used for cytotoxicity testing on human cancer cell lines using standard 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assays. Results obtained show that the propolis collected from Malta has cytotoxic activity in cancer cells in vitro. However, propolis collected from different sites, only a few miles apart and at different times of the year, showed marked variations in the cytotoxicity, which correlated clearly with totarol content. This reflects the differences in the species of plants, on which the bees had foraged and indicates the importance of collection site and season of collection on the bioactivity of propolis products.peer-reviewe

In vitro Apoptotic Bioactivity of Flavonoids from Astragalus verrucosus Moris

Six aglycone flavonoids and their corresponding glycosides: genistein and genistin, quercetin and rutin, apigenin and apigenin 7-O-β-D-(6-p-coumaroyl) glucoside, as well as the aglycone daidzein isolated from Astragalus verrucosus Moris, were tested for their apoptosis-inducing potential. In vitro techniques that monitor bioactivity through morphological and biochemical changes were carried out on HCT116 (human colon carcinoma) and MCF7 (human Caucasian breast adenocarcinoma) cancer cell lines. Dose-dependent cytotoxic effects were monitored through changes in mitochondrial dehydrogenase activity using the standard MTT assay. The median inhibitory concentration (GI50) determined from the dose-response curves showed that the aglycones apigenin and quercetin were the most bioactive (low GI50), whilst daidzein and genistein, which had not been previously tested on these cell lines, showed a smaller cytotoxic effect (high GI50). The remaining flavonoids, mostly glycosides, showed negligible cytotoxicity. Morphological changes were monitored by microscopic observation with a photographic record. Results showed important hallmarks of apoptosis, including cell rounding with reduction of cell volume, small condensed nuclei, membrane blebbing and formation of apoptotic bodies