Molecular biology in prostate cancer

Summary Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includesex vivo corrective therapy, suicide, and antisense therapy.     

Deliberate hypotension in orthopedic surgery reduces blood loss and transfusion requirements: A meta-analysis of randomized controlled trials

PURPOSE: To determine if deliberate hypotension decreases blood loss and transfusion requirements in patients undergoing orthopedic surgery, a systematic review of all randomized trials addressing this issue was undertaken. METHODS: Electronic databases, citations lists and review articles were searched for potential articles. Relevant articles met the following inclusion criteria: English language, humans undergoing orthopedic surgery, deliberate hypotension used by any method, intraoperative blood loss measured as an outcome, and the trial methodology being randomized and controlled. Four outcomes were analyzed, including estimated blood loss, blood transfused, surgery duration, and quality of the surgical field. For all analyses, the random-effects model was used. RESULTS: Seventeen articles met the inclusion criteria. The surgeries studied included total hip arthroplasty (seven), orthognathic surgery (eight), total knee arthroplasty (one) and spinal fusion (one). A total of 636 patients were randomized across all studies. For blood loss, the overall weighted mean difference favoured treatment, with a savings of about 287 mL of blood [95% confidence interval (CI): -447, -127]. The mean differences also showed a statistically significant benefit for deliberate hypotension in reducing transfusion requirements (-667 mL of blood transfused; 95% CI: -963, -370). Deliberate hypotension was not shown to reduce the duration of surgery (-1.9 min of surgery; 95% CI: -7.2, 3.5) or improve surgical conditions (surgical field quality rating -0.5; 95% CI: -1.1, 0.2). CONCLUSION: This review provides some support for the use of deliberate hypotension in reducing blood loss and transfusion requirements in orthopedic surgery, but these results are tempered by the small sample sizes and poor methodological quality of published studies.     

Neonatal splenic necrosis not related to wandering spleen.

Splenic necrosis is extremely rare in neonates, the cases recorded so far being secondary to torsion of wandering organs. A newborn with an abdominal mass who underwent exchange transfusions through an umbilical catheter is presented here. Comprehensive investigation led to the suspicion of enteric duplication, but a splenic necrosis with no features of wandering spleen was found at laparotomy. The pathogenesis and preoperative diagnostic work-up of splenic necrosis are emphasised.     

Antibody Responses to Asian and American Genotypes of Dengue 2 Virus in Immunized Mice

The possibility of a correlation between dengue virus genotype groups and disease severity is currently under discussion. The objective of this investigation was to identify any immunogenic difference between the American and Asian dengue 2 virus genotypes through the study of antibody development (virus-binding immunoglobulin G and neutralizing antibodies) in mice. Differences in the neutralization pattern between the strains studied were observed, suggesting the presence of slight antigenic variations among them. The lack of recognition of one of the Asian genotype strains was remarkable.     

Acute resynchronization with inhaled iloprost in a pregnant woman with idiopathic pulmonary artery hypertension.

We describe the case of a pregnant woman with idiopathic pulmonary arterial hypertension, a responder in right heart catheterization, followed since the first trimester in outpatient consultations, admitted to hospital at 23 weeks gestation. She was treated with inhaled iloprost until delivery (at 34 weeks gestation) and continuous infusion of iloprost throughout the perioperative period and following days. This line of therapy has proved efficacious in previous cases. The authors present echocardiographic images that document acute changes in ventricular synchrony during inhalation of iloprost.     

Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferases, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, γ-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for γ-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisci plinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6–20 MeV electron beams. The median follow-up time for the entire group is 25 months (2–65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.