Impact of GSTM1, GSTT1 and GSTP1 genes polymorphisms on clinical toxicities and response to concomitant chemoradiotherapy in cervical cancer.

BACKGROUND: Certain forms of chemoradiotherapy generate toxic reactive oxygen species, which may be ameliorated by antioxidant enzymes such as glutathione S-transferase (GST). Genetic polymorphisms of GST may predict treatment outcomes and can be used as genetic marker to screen patients before treatment. We hypothesised an effect of GST polymorphisms on the response and toxicities produced by chemoradiation therapy. MATERIALS AND METHODS: GST polymorphisms were determined by multiplex polymerase chain reaction and PCR-restriction fragment length polymorphism (PCR-RFLP) in 227 women with cervical cancer receiving cisplatin based chemoradiotherapy. Treatment response and toxicities were evaluated by standard internationally recognised criteria (RECIST and RTOG). RESULTS: Severe (grade 3-4) gastrointestinal and haematological toxicities were present in 22 (9.4%) and 16 (7.0%) patients, respectively. GSTM1 null, GSTT1 null and GSTP1 AG genotypes brought marginally better non-significant associations. In single locus analysis GSTP1 AG and GG was linked to greatest risk of severe (grade 3-4) gastrointestinal toxicity (OR = 3.12, P = 0.035 and OR = 6.99, P = 0.01, respectively). In gene-gene interaction analysis, GSTM1 null-GSTP1 GG showed 4.2-fold higher risk of severe gastrointestinal toxicity (P = 0.014). GSTT1 null-GSTP1 AG reached statistical significance with a 3.9-fold higher risk of high grade gastrointestinal toxicity (P = 0.038). CONCLUSIONS: Although no significant links were found between GST polymorphism and treatment response, null genotypes of GSTM1, GSTT1 and 'G' allele of GSTP1 bring a higher risk of severe gastrointestinal toxicity due to chemoradiation therapy in cervical cancer.

Sensitization with anti-inflammatory BmAFI of Brugia malayi allows L3 development in the hostile peritoneal cavity of Mastomys coucha.

Filarial parasites survive by inducing tolerance in host but the antigens and mechanisms involved are not clear. Recently we found that BmAFI, a Sephadex G-200 eluted fraction of Brugia malayi adult worm extract, stimulates IL-10 release from THP-1 cells. In the present study, we determined the SDS-PAGE profile of BmAFI and infective 3rd stage larva (L3), investigated the effect of pre-sensitization of host with BmAFI on the survival and development of L3 in the non-permissive peritoneal cavity (p.c.) of the permissive host Mastomys coucha and in the p.c. of non-permissive Swiss mice, and studied immunological correlates for the observed effects. The parasite development and burden in p.c., was determined in sensitized infected M. coucha and Swiss mice and the release of TGF-ß, IL-4, IL-10, IL-13, IFN-γ and NO, cellular proliferative response to Con A and BmAFI and levels of IgG subclasses and IgE were determined in sensitized infected M. coucha. Cellular proliferative response to Con A and BmAFI, mRNA expression of GATA-3, CTLA-4 and T-bet were determined in sensitized Swiss mice. In addition, the parasitological parameter was also studied in BmAFI-sensitized M. coucha exposed to the infection by standard subcutaneous (s.c.) route to assess whether sensitization enhances the intensity of infection. BmAFI-sensitization permitted survival of L3 and their development to adult stage by day 60 p.i. in the p.c. of M. coucha; in non-sensitized animals L3 could molt to L4 only and no parasite could be recovered beyond day 30 p.i. In M. coucha that received infection by s.c. route, pre-sensitization with BmAFI enhanced the microfilaraemia and adult worm recovery. In sensitized Swiss mice L3 could successfully molt to L4 in p.c. with improved recovery of parasite. BmAFI sensitization upregulated TGF-ß and IL-10 release, IgG1 and IgG2b levels, GATA-3 and CTLA-4 mRNA expression, suppressed the cellular proliferative response and downregulated Con A stimulated response, IgE, IL-13, IFN-γ and NO responses. Immunoblot analysis showed that the BmAFI antiserum also strongly reacts with some L3 molecules. The results show, for the first time, that sensitization with the anti-inflammatory BmAFI which shares some of its molecules with those in L3, facilitates parasite survival in the non-permissive p.c. of the permissive host M. coucha, render a non-permissive Swiss mouse partially permissive to infection and enhances parasite load in M. coucha receiving the infection through permissive s.c. route by evoking a modified Th2 type of response and anti-inflammatory milieu. In conclusion, the findings suggest that the anti-inflammatory BmAFI fraction facilitates survival of B. malayi infection even in non-permissive environment.

Extremity fractures in the patient with a traumatic brain injury.

Extremity fractures are common in patients with traumatic brain injuries (TBIs). These injuries are often inadequately treated and occasionally are completely missed due to the unique problems inherent to the TBI patient. However, appropriate evaluation of the TBI patient allows prompt diagnosis and optimal treatment of extremity fractures. The increased survival rate of these patients has resulted in a greater emphasis on minimizing dysfunction and disability, especially that due to concomitant orthopaedic trauma. Advances in anesthestic technique permit earlier operative fixation of extremity fractures. Most injuries, particularly those in the lower extremity, require operative stabilization to allow early mobilization and rehabilitation. Upper extremity fractures are often associated with peripheral nerve injuries. Heterotopic ossification is common, especially about the elbow and hip. Contrary to prevalent belief, fracture healing is not necessarily accelerated in the TBI patient; hypertrophic callus, myositis ossificans, and heterotopic ossification occur frequently and are often misperceived as accelerated healing.

Sustained release of antimicrobial drugs from polyvinylalcohol and gum arabica blend matrix.

Synthetic polymers are widely used in biomedical applications. Polymer blends have recently paved their way in this field. An attempt to prepare blend of synthetic polymer polyvinylalcohol and natural macromolecule gum arabica is made in this paper. Characterization of these blends by NMR, DSC and viscoelastic studies reveal preparation of a blend composition with synergistic properties. The blend composition with synergistic properties was used to release various antimicrobial drugs. The duration and release of the drug depends on the amount of drug loaded in the matrix and solubility of the drug in the matrix and release medium. The advantage of this system is that the release kinetics of the drug from the system can be tailored by adjusting plasticizer, homopolymer and crosslinker composition depending on the drug to be released.

Voluntary scapulothoracic subluxation: a case report.

Dislocation of the scapula is a rare event, usually associated with massive trauma and injury. We report a case of a patient for whom dislocation was the sole presentation. The possibility of voluntary dislocation for secondary gain was suspected, but because of perceived progressive brachial plexus involvement, urgent closed reduction was undertaken and led to resolution of the neurologic symptoms. The patient returned 1 year later with similar complaints and findings, but declined another closed reduction attempt when offered only an interscalene regional block as pain relief. The diagnosis of voluntary dislocation should be considered in a patient presenting with superior and lateral migration of the scapula, without a history of trauma.

Musculoskeletal coccidioidomycosis. A review of 25 cases.

Coccidioidomycosis is a fungal infection endemic to the southwestern United States. Musculoskeletal involvement is rare, and there are few reports with clear recommendations regarding treatment. The purpose of this study was to review a series of 25 patients with musculoskeletal coccidioidomycosis and to assess their outcomes with respect to presentation and treatment. There were 36 lesions among the 25 patients, 8 located in the spine, with the remainder distributed throughout the body. Seventeen patients had a delay in diagnosis of more than 1 month. Eight patients had an elevated white blood cell count, and 10 had an elevated sedimentation rate. Only 7 of the patients had an overt pneumonia before the musculoskeletal presentation. Twenty-four patients underwent formal irrigation and debridement and 22 patients had at least 1 course of Amphotericin B. The average followup after the initiation of treatment was 3.5 years, ranging from 2 to 10 years. Seven patients had recurrent lesions that required further surgical intervention, 4 of whom had a delay in diagnosis of more than 1 month. There were 3 deaths. All surviving patients were free of disease at final followup.

Complexation reactions of pyridinols.

Complexation of iron(III) with several pyridinols has been studied and used in selective detection and determination (spectrophotometric and chelatometric) of the metal. Iron(III)-pyridinol complexes are also used as indicators in acid-base titrations. A thiol group vicinal to a phenol group in a pyridine molecule provides a reagent that is a suitable ligand for palladium(II) determination. Stability constants of bivalent metal complexes with pyridinols have been determined potentiometrically.