Toxoplasma gondii isolates: Multi locus RFLP-PCR genotyping from human patients in Sao Paulo State, Brazil identified distinct genotypes

This study investigated the genetic characteristics of Toxoplasma gondii samples collected from 62 patients with toxoplasmosis in Sao Paulo State, Brazil. DNA samples were isolated from blood, cerebrospinal fluid and amniotic fluids of 25 patients with cerebral toxoplasmosis and AIDS, two patients with acute toxoplasmosis, 12 patients with ocular toxoplasmosis, six newborns with congenital toxoplasmosis and 17 pregnant women with acute infection. Diagnosis of toxoplasmosis was based in clinical, radiological and laboratory features. Genotyping was performed using multilocus PCR-RFLP genetic markers including SAG1, SAG2, 5`- and 3`-SAG2, alt.SAG2, SAG3, BTUB, GRA6, C22-8, c29-2, L358, PK1 and Apico. Among the 62 clinical samples, 20 (32%) were successfully genotyped at eight or more genetic loci and were grouped to three distinct genotypes. Eighteen samples belonged to ToxoDB Genotype #65 and the other two samples were identified as ToxoDB Genotypes #6 and #71, respectively (http://toxodb.org/toxo/). Patients presenting Genotypes #6 and #71 had severe and atypical cerebral toxoplasmosis, characterized by diffuse encephalitis without extensive brain lesions. These results indicate that T. gondii Genotype #65 may have a high frequency in causing human toxoplasmosis in Sao Paulo State, Brazil. This unusual finding highlights the need to investigate the possible association of parasite genotypes with human toxoplasmosis. (C) 2011 Elsevier Inc. All rights reserved.

Recommendations for the Use of Extended Criteria Donors in Lung Transplantation

Selection criteria for lung donation were based on initial experiences with lung transplantation without further studies to improve them, thereby guaranting the best use of donated organs. A definition of an extended criteria donor is therefore required to obtain more lungs to meet the demands of patients awaiting transplantation. Studies have been reviewed for the impact on survival and morbidity of age ranges, oxygen fraction, cause of death, smoking habits, x-ray findings, infection, hepatitis serology and non-heart-beating status, seeking to support physicians to make decisions regarding the use of marginal organs.

Clinical Criteria as Predictive Factors of Response to Primary Hormone Therapy in Locally Advanced Breast Cancer

This study investigates the efficacy of clinical criteria in selecting patients for primary tamoxifen therapy. A total of 60 breast cancer patients with large primary tumors and unknown hormonal receptor status were subjected to primary hormone therapy. Inclusion criteria were age over 60 years old or menopausal status for at least 10 years and no clinical evidence of inflammatory disease and fast tumor growth. The objective response rate was 55%. There was a positive correlation between the lack of clinical response and axillary lymph node metastasis (p = 0.009). Patients with objective response had significantly improved disease-free (p = 0.045) and overall (p = 0.0002) survival over those who did not have response to hormonal therapy. In multivariate analysis, the clinical response to therapy was the most powerful prognostic factor. This analysis demonstrates that clinical criteria were very effective predictor of response to neo-adjuvant hormone therapy in large breast tumors for postmenopausal women. Response to therapy is the major prognostic factor in primary tamoxifen-treated breast cancer.

Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal `dominant optic atrophy plus` variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

Finite Element Modeling for Development and Optimization of a Bone Plate for Mandibular Fracture in Dogs

This study aimed to develop a plate to treat fractures of the mandibular body in dogs and to validate the project using finite elements and biomechanical essays. Mandible prototypes were produced with 10 oblique ventrorostral fractures (favorable) and 10 oblique ventrocaudal fractures (unfavorable). Three groups were established for each fracture type. Osteosynthesis with a pure titanium plate of double-arch geometry and blocked monocortical screws offree angulanon were used. The mechanical resistance of the prototype with unfavorable fracture was lower than that of the fcworable fracture. In both fractures, the deflection increased and the relative stiffness decreased proportionally to the diminishing screw number The finite element analysis validated this plate study, since the maximum tension concentration observed on the plate was lower than the resistance limit tension admitted by the titanium. In conclusion, the double-arch geometry plate fixed with blocked monocortical screws has sufficient resistance to stabilize oblique,fractures, without compromising mandibular dental or neurovascular structures. J Vet Dent 24 (7); 212 - 221, 2010

Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography

Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector row computed tomographic coronary angiography (CTCA). We studied five HoFH patients (three females, two males, mean age 19.8 +/- 2.9 years, age range 15-23 years, with a mean low density lipoprotein (LDL) cholesterol 618 +/- 211 mg/dL) using 64 slice CTCA. None of the patients showed evidence of ischemia with standard exercise testing. Calcified and mixed atherosclerotic plaques adjacent to or compromising the coronary artery ostia were found in all study subjects. Coronary plaques causing significant obstruction were found in one patient, who had previously undergone coronary artery bypass surgery and aortic valve replacement. Two other patients were noted to have non-obstructive calcified, mixed and non-calcified coronary artery plaques. Our data suggest that CTCA could be a useful non-invasive method for detection of early aortic and coronary atherosclerosis specifically affecting the coronary ostia in HoFH subjects. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Orthodontic-surgical treatment of Class III malocclusion with extraction of an impacted canine and multi-segmented maxillary surgery

Establishment of a treatment plan is based on efficacy and easy application by the clinician, and acceptance by the patient. Treatment of adult patients with Class III malocclusion might require orthognathic surgery, especially when the deformity is severe, with a significant impact on facial esthetics. Impacted teeth can remarkably influence treatment planning, which should be precise and concise to allow a reasonably short treatment time with low biologic cost. We report here the case of a 20-year-old man who had a skeletal Class III malocclusion and impaction of the maxillary right canine, leading to remarkable deviation of the maxillary midline; this was his chief complaint. Because of the severely deviated position of the impacted canine, treatment included extraction of the maxillary right canine and left first premolar for midline correction followed by leveling, alignment, correction of compensatory tooth positioning, and orthognathic surgery to correct the skeletal Class III malocclusion because of the severe maxillary deficiency. This treatment approach allowed correction of the maxillary dental midline discrepancy to the midsagittal plane and establishment of good occlusion and optimal esthetics. (Am J Orthod Dentofacial Orthop 2010;137:840-9)

Long-term survivor mixture model with random effects: application to a multi-centre clinical trial of carcinoma

A mixture model incorporating long-term survivors has been adopted in the field of biostatistics where some individuals may never experience the failure event under study. The surviving fractions may be considered as cured. In most applications, the survival times are assumed to be independent. However, when the survival data are obtained from a multi-centre clinical trial, it is conceived that the environ mental conditions and facilities shared within clinic affects the proportion cured as well as the failure risk for the uncured individuals. It necessitates a long-term survivor mixture model with random effects. In this paper, the long-term survivor mixture model is extended for the analysis of multivariate failure time data using the generalized linear mixed model (GLMM) approach. The proposed model is applied to analyse a numerical data set from a multi-centre clinical trial of carcinoma as an illustration. Some simulation experiments are performed to assess the applicability of the model based on the average biases of the estimates formed. Copyright (C) 2001 John Wiley & Sons, Ltd.

Early-Mid Holocene climatic variations in Tasmania, Australia: multi-proxy records in a stalagmite from Lynds Cave

Mass spectrometric uranium-series dating and C-O isotopic analysis of a stalagmite from Lynds Cave, northern Tasmania, Australia provide a high-resolution record of regional climate change between 5100 and 9200 yr before present (BP). Combined delta(18)O, delta(13)C, growth rate, initial U-234/U-238 and physical property (color, transparency and porosity) records allow recognition of seven climatic stages: Stage I ( > 9080 yr BP) - a relatively dry period at the beginning of stalagmite growth evidenced by elevated U-234/U-238; Stage II (9080-8600 yr BP) - a period of unstable climate characterized by high-frequency variability in temperature and bio-productivity; Stage 111 (8600-8000 yr BP) - a period of stable and moderate precipitation and stable and high bio-productivity, with a continuously rising temperature; Stage IV (8000-7400 yr BP) - the warmest period with high evaporation and low effective precipitation (rainfall less evaporation); Stage V (7400-7000 yr BP) - the wettest period with highest stalagmite growth and enhanced but unstable bio-productivity; Stage VI (7000-6600 yr BP) - a period with a significantly reduced precipitation and bio-productivity without noticeable change in temperature; Stage VII (6600-5100 yr BP) - a period of lowest temperature and precipitation marking a significant climatic deterioration. Overall, the records suggest that the warmest climate occurred between 8000 and 7400 yr BP, followed by a wettest period between 7400 and 7000 yr BP. These are broadly correlated with the so-called 'Mid Holocene optimum' previously proposed using pollen and lake level records. However, the timing and resolution of the speleothem. record from Lynds Cave are significantly higher than in both the pollen and lake level records. This allows us to correlate the abrupt change in physical property, delta(18)O, delta(13)C, growth rate, and initial U-234/U-238 of the stalagmite at similar to8000 yr BP with a global climatic event at Early-Mid Holocene transition. (C) 2001 Elsevier Science B.V. All rights reserved.