Pulmonary infiltrates and eosinophilia associated with sulfasalazine

Asymptomatic pulmonary infiltrates and eosinophilia developed in a patient with chronic ulcerative colitis 1 month after therapy with sulfasalazine had been instituted. The abnormalities resolved completely after use of the drug was discontinued. The sulfapyridine component of the sulfasalazine was the likely causative agent because 41 years earlier, the patient had experienced fever, myalgias, and eosinophilia after taking a sulfonamide. Ten previous cases of sulfasalazine pulmonary toxicity, including one fatality, have been reported.     

Simulation for trauma and combat casualty care.

Training medical providers to care for traumatically injured patients is a difficult undertaking and currently used training strategies are often suboptimal. The further strains placed on trauma care in the military environment only add to the challenge. Simulation applications ranging from simple physical models to complex, computer-based virtual reality systems have either been developed or are being developed to help support and improve trauma care training. Several of these applications have been shown to be as good as or better than the standard training methods they are designed to replace. Simulators are available for training in the treatment of disorders of the airway, difficulty with breathing, and problems dealing with circulation as well as various non-life-threatening but disabling injuries. Some of these simulators have already drastically changed how the standard Advanced Trauma Life Support course is taught. Advances in both technology and application of simulators will continue to affect trauma skills training for the foreseeable future.     

Comparison of the mechanical performance of three types of external fixators: linear, circular and hybrid

Different configurations of the Monticelli-Spinelli and Ilizarov external fixation systems were tested to define their mechanical properties. In five configurations the external fixator consisted of rings with tensioned wires (circular), while in one configuration two pairs of the tensioned wires and their correspondent ring were replaced by threaded pins (hybrid). Testing was performed in axial compression, bending and torsion. The results were compared to the characteristics of a selected linear fixator group. Both the circular and the hybrid configurations were non-linear in compression. In bending, circular fixators had a similar pattern in both anteroposterior and oblique loading directions. The bending load-displacement pattern for the hybrid fixators was similar to the linear fixators, higher stiffness in the plane of the pins. Torsion was linear for both circular and hybrid fixators, as for the linear fixators. By combination of wires and pins (hybrid configuration), the mechanical behaviour had characteristics from both linear and circular fixators. It is concluded that the three studied groups own different mechanical performance and can be considered as different types of fixators. While it has been demonstrated that osteogenesis can be achieved independently of the mechanical behaviour of the fixator, this study supports the suggestion that some complications can be related to the mechanical behaviour of the fixator.     

Development of a combination drug-eluting bead: towards enhanced efficacy for locoregional tumour therapies

Drug-eluting beads (DEBs) are becoming a mainstay locoregional therapy for hepatic malignancies but are currently loaded with single drugs alone. Here, we wished to prepare DEB containing different drug combinations, to screen their efficacy using an in-vitro cell culture assay and to include any promising combinations that demonstrate additive efficacy in an in-vivo model of locoregional tumour treatment. A modified in-vitro assay was used based upon the use of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) with either HepG2 liver cancer or PSN1 pancreatic cancer cell lines. The comparative cytotoxicity of DEB combinations prepared containing doxorubicin, irinotecan, topotecan and rapamycin was evaluated. Those combinations that demonstrated an additive cytotoxicity effect were investigated in vivo using a nude mouse xenograft model of pancreatic cancer. Although many of the DEB combinations showed either no effect or a slight antagonistic effect, the combination of doxorubicin and rapamycin DEBs demonstrated synergistic activity. On the basis of these findings, a method was developed to prepare a doxorubicin/rapamycin dual-loaded DEB, which was shown to possess the same drug-loading capacities, drug elution properties and HepG2 cell cytotoxicity synergy as the single drug-loaded DEB combination. Evaluation of this dual-loaded combination DEB versus the respective single drug-loaded DEBs in a mouse xenograft model of pancreatic cancer showed an equivalent tumour volume reduction as the doxorubicin DEB, but with less toxicity than the rapamycin DEB. The doxorubicin/rapamycin combination DEB offers great potential for enhanced efficacy in the locoregional treatment of malignant tumours.     

Effects of acrylamide exposure on serum hormones, gene expression, cell proliferation, and histopathology in male reproductive tissues of Fischer 344 rats

Acrylamide (AA) is a reactive monomer used in many technological applications, but it is the incidental formation during cooking of common starchy foods that leads to pervasive human exposure, typically in the range of 1 μg/kg body weight (bw)/day (d). AA is carcinogenic in multiple organs from both sexes of several rodent models and a consistent body of evidence points to a genotoxic mechanism based on metabolism to a DNA-reactive epoxide, glycidamide (GA). In F344 rats, tumorigenesis occurs in several hormonally regulated tissues (thyroid, mammary gland, and peri-testicular mesothelium), which has prompted speculation about endocrine dysregulation as a possible mechanism. The present study evaluated the effects of a 14 d exposure to AA administered through the drinking water on reproductive tissues and the hypothalamic-pituitary-testes (HPG) axis in male F344 rats. The doses selected encompass a range from approximately 2.5 mg/kg bw/d, which is carcinogenic after lifetime exposure, to 50 mg/kg bw/d, a maximally tolerable dose that causes hind limb paralysis. AA caused significant changes in serum hormones, histopathology, testicular gene expression, and cell proliferation, especially at the highest dose. Despite strong evidence for activation of the HPG axis subsequent to decreases in testosterone levels, and histopathological changes associated with significant effects on Leydig and germ cells, with concomitant mRNA expression changes, the precise mechanism(s) for AA-induced testicular toxicity remains unclear; however, the absence of evidence for increased proliferation of the peri-testicular mesothelium (Ki-67 immunoreactivity) does not support hormonal dysregulation as a contributing factor to the predisposition of this tissue to the carcinogenic effects of AA.