Forward problem solution for electrical conductivity imaging via contactless measurements

The forward problem of a new medical imaging system is analysed in this study. This system uses magnetic excitation to induce currents inside a conductive body and measures the magnetic fields of the induced currents. The forward problem, that is determining induced currents in the conductive body and their magnetic fields, is formulated. For a general solution of the forward problem, the finite element method (FEM) is employed to evaluate the scalar potential distribution. Thus, inhomogeneity and anisotropy of conductivity is taken into account for the FEM solutions. An analytical solution for the scalar potential is derived for homogeneous conductive spherical objects in order to test FEM solutions. It is observed that the peak error in FEM solutions is less than 2%. The numerical system is used to reveal the characteristics of the measurement system via simulations. Currents are induced in a 9x9x5 cm body of conductivity 0.2 S m(-1) by circular coils driven sinusoidally. It is found that a 1 cm shift in the perturbation depth reduces the field magnitudes to approximately one-tenth. In addition, the distance between extrema increases. Further simulations carried out using different coil configurations revealed the performance of the method and provided a design perspective for a possible data acquisition system.     

Designer broad-spectrum polyimidazolium antibiotics

For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positive Staphylococcus aureus we obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogen Pseudomonas aeruginosa, PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.

AMPs and AMP mimics have attracted considerable attention as candidates for therapeutic development (1). The basic design elements include a region of charged residues, generally cationic residues, enabling interaction with bacterial cell surfaces, combined with a hydrophobic nature in AMPs (2). Unfortunately, AMPs and related polymers, in general, have one or more issues that limit their use as broad-spectrum antibiotics. Some are quite toxic to human cells, the potency of some is not adequate for human administration, others are sensitive to salt at levels present in human fluids, and some are too difficult and expensive to synthesize (3, 4). One broad-spectrum antimicrobial peptide, CST has seen increased recent use as a last resort antibiotic. CST is believed to kill bacteria by virtue of its ability to disrupt membrane integrity (5). This antibiotic requires intravenous administration and is nephrotoxic (6). The emergence of CST-resistant pathogens has also become a significant problem (7). We are unaware of any new broad-spectrum AMPs that have advanced to clinical trials.Imidazolium (IM) salts are antimicrobials (8), and there is an emerging literature on antimicrobial activity of side-chain and main-chain polyimidazolium (PIM) salts with chemical structures that are in some ways similar to those we describe. Although PIMs are potent antimicrobials, there are biocompatibility problems hindering their development, and some have somewhat limited activity spectra. As with other AMPs, there have been toxicity issues, potency issues, and delivery issues as many have large molecular masses, and there is little known about mammalian cell toxicity or mechanism of action (9–12).Here we show that members of a series of PIMs we designed and synthesized are potent broad-spectrum antibacterial compounds. We selected two for further analysis and showed they retain activity even against pan-antibiotic-resistant bacteria. Unlike CST and many other AMPs, which disrupt bacterial membranes, our model PIM is bactericidal without disrupting bacterial membranes. Our experiments provide insights about mechanism of action, the potential for the emergence of PIM resistance, and indicate PIMs are effective against a model gram-negative and a model gram-positive pathogen in murine infection models.     

Three ventriculoplasty techniques applied to three left-ventricular pseudoaneurysms in the same patient

A 59-year-old male patient underwent surgery for triple-vessel coronary artery disease and left-ventricular aneurysm in 1994. Four months after coronary artery bypass grafting and classical left-ventricular aneurysmectomy (with Teflon felt strips), a left-ventricular pseudoaneurysm developed due to infection, and this was treated surgically with an autologous glutaraldehyde-treated pericardium patch over which an omental pedicle graft was placed. Two months later, under emergent conditions, re-repair was performed with a diaphragmatic pericardial pedicle graft due to pseudoaneurysm reformation and rupture. A 3rd repair was required in a 3rd episode 8 months later. Sternocostal resection enabled implantation of the left pectoralis major muscle into the ventricular defect. Six months after the last surgical intervention, the patient died of cerebral malignancy. Pseudoaneurysm reformation, however, had not been observed. To our knowledge, our case is the 1st reported in the literature in which there have been 3 or more different operative techniques applied to 3 or more distinct episodes of pseudoaneurysm formation secondary to post-aneurysmectomy infection. We propose that pectoral muscle flaps be strongly considered as a material for re-repair of left-ventricular aneurysms.     

Metastatic squamous cell carcinoma of the skin in chronic myeloid leukaemia: complication of hydroxyurea therapy

Hydroxyurea is a ribonucleotide diphosphate reductase inhibitor used in the treatment of patients with myeloproliferative disorders. Hydroxyurea has some dermatological side-effects. It has recently been recognized that hydroxyurea can induce squamous cell and basal cell carcinomas of skin. We present the case of an elderly man with chronic myeloid leukaemia who was treated with hydroxyurea for 4 years, with good control of his disease. However, in addition to the appearance of various skin lesions and cutaneous squamous cell carcinoma after 3 years of therapy, he was found to have a metastatic squamous cell carcinoma after 4 years. Hydroxyurea was discontinued, and he underwent surgery and radiotherapy. The patient subsequently died of ventricular fibrillation. We present this case to draw attention to the association between hydroxyurea and secondary skin cancers and to emphasize the need for dermatological examination before and during the course of hydroxyurea therapy.     

The Influence of Different Nonsteroidal Anti-Inflammatory Drugs on Alveolar Bone in Rats: An Experimental Study

The aim

The aim of this study was to investigate the effect of dexketoprofen trometamol, meloxicam, diclofenac sodium on any untreated alveolar bone when they are used as drugs for another indication.

Materials and Methods

Twenty eight male Spraque-Dawley rats were randomized into four groups as dexketoprofen trometamol (Group I), meloxicam (Group II), diclofenac sodium (Group III) and control group. Nonsteroidal anti-inflammatory drugs (NSAID) were administered after a fibula fracture for 10 days. Untreated alveolar bone was histopathologically examined for spongious bone density, osteoclastic density and osteoblastic density.

Results

Spongious bone density was lower in study groups (Group I, group II and group III) than the control group (p<0.05). In contrast, the increase in osteoclastic density was observed in other groups apart from the control group (p<0.05). Osteoblastic density was evaluated and it was determined that group II and group III had lower results than the control group (p<0.05) but group I was equal to the control group.

Conclusion

This study showed that systemically administrated NSAIDs have the potential to affect untreated alveolar bone. This should also be considered in long term use of NSAIDs.Key Words: Non-steroidal anti-inflammatory agents, bone remodeling, osteoblast, osteoclast, maxillary bone     

Lead Exposure Is Related to Impairment of Aortic Elasticity Parameters

Arterial hypertension is one of the physical complications of chronic lead exposure. Hypertension has effects on aortic elastic properties. The aim of this study was to evaluate the aortic elastic properties in workers occupationally exposed to lead. Forty‐one workers who were exposed to lead and 39 healthy controls were included in the study. All patients underwent transthoracic echocardiography for detecting aortic elastic parameters. There were no differences in baseline characteristics between the lead‐exposure group and controls. Aortic strain (9.4%±4.5% vs 12.4%±4.2%, P=.004) and aortic distensibility (0.45±0.21 cm²/dyn vs 0.55±0.20 cm²/dyn, P=.046) were decreased in patients with lead exposure compared with controls. There was a negative significant weak correlation between aortic strain and (r=−0.294, P=.008) lead levels. There was no significant correlation between aortic distensibility and any other echocardiographic parameters. This study suggests that chronic exposure to lead is related to impairment of aortic elasticity parameters.

Lead contamination (such as that emitted from house paint, gasoline, batteries, and other sources) may cause a wide variety of body organ complications.¹ Despite the still manifested divergences of opinion, it seems that chronic exposure to lead represents a risk for arterial hypertension development. Functional changes within the arterial wall both in smooth muscles and the endothelium might result in arterial hypertension caused by chronic exposure to lead compounds.² Blood pressure (BP) was found to be increased in workers with blood lead concentrations of 7 μg/L on average.³ According to the World Health Organization (2000), the level of 400 μg/L is accepted as safe to avoid possible adverse health effects, but American Conference Governmental and Industrial Hygienists suggest an even lower value of <300 μg/L.Hypertension has effects on the aorta (decreased aortic distensibility and increased aortic stiffness). Aortic strain is a simple and useful parameter of transthoracic echocardiography. Some studies have suggested that aortic elastic parameters can be used as an independent predictor of all‐cause and cardiovascular mortality in hypertensive patients.⁴, ⁵ In previous studies, the relationship between lead exposure and arterial hypertension has been demonstrated, and findings suggest that arterial hypertension and organ complications of arterial hypertension are more frequent in workers with lead exposure. Until now, there have been no data on the effects of lead exposure on aortic stiffness. The aim of this study was to evaluate the effects of lead on aortic elasticity parameters.     

Identification of new CRF51_01B in Singapore using full genome analysis of three HIV type 1 isolates

A recent HIV-1 molecular epidemiology survey in Singapore identified a novel CRF01_AE/B recombinant form, which accounted for 13 (11.9%) of 109 patient samples. Peripheral blood mononuclear cell DNA from three of these 13 patients was used to generate near full-length sequences to characterize the novel CRF01_AE/B recombinant form. The three isolates had a recombinant structure composed of CRF01_AE and subtype B, and shared identical breakpoints. As the three patients were not epidemiologically linked, this recombinant form has been designated CRF51_01B. Identification of the novel recombinant forms indicates ongoing active HIV-1 transmission in Singapore.