Virtual colon dissection with CT colonography compared with axial interpretation and conventional colonoscopy: preliminary results

OBJECTIVE: The aim of this study was to determine whether a new virtual colon dissection 3D visualization technique for CT colonography has a shorter analysis time and better sensitivity for detection of colonic polyps than interpretation of axial CT images. SUBJECTS AND METHODS. CT colonography was performed in 22 patients using 4-MDCT followed by conventional colonoscopy on the same day. The CT colonography data sets were analyzed by virtual colon dissection, which virtually bisects and unfolds the colon along its longitudinal axis to inspect the inner colonic surface for polyps. The same CT data sets were independently evaluated using axial interpretation. All data sets were independently interpreted by two radiologists in a blinded manner. RESULTS: Conventional colonoscopy revealed 31 colonic lesions in 20 patients. Twenty two of the lesions were smaller than 10 mm; nine were 10 mm or larger. Two of the original 22 patients were excluded, one because of residual stool and fluid and the other because of an impassable stenosing rectal wall cancer. For virtual colon dissection, the per-lesion sensitivity was 42% for observer 1 and 68% for observer 2; for axial interpretation, the respective sensitivities were 48% and 61%. For polyps 10 mm or larger, the respective sensitivities were 67% and 89% for virtual colon dissection and 89% and 100% for axial interpretation. The average time for reconstruction and analysis of virtual colon dissection was 36.8 min versus 29.2 min for axial images. Virtual colon dissection was feasible in both the supine and the prone positions in 45.5% of colonic segments, in either the supine or the prone position in 24.5%, and in neither position in 30% of segments. CONCLUSION: Although virtual colon dissection may facilitate detection of colonic polyps in isolated cases, its detection rate is not superior to axial interpretation, which is mainly attributable to failed rendering of insufficiently distended colonic segments or regions with residual feces. Virtual colon dissection is also the more time-consuming of the two procedures. With further improvement of path-finding and image segmentation, however, virtual colon dissection has the potential to be a useful interpretation tool for CT colonography.     

Enhanced efficacy of tumor cell vaccines transfected with secretable hsp70

Tumor immunotherapy has exploited the ability of heat shock proteins to chaperone precursors of antigenic peptides to antigen-presenting cells and to activate efficiently an immune response against tumor-associated antigens. The most common strategy is based on the purification of heat shock protein-peptide complexes from tumor cell lines or from tumor surgical samples for in vivo administration. In this article, we have modified the murine-inducible hsp70 into a secreted protein and engineered tumor cells to secrete constitutively their antigenic repertoire associated with the hsp70 protein. In vitro studies showed that the relocalization of hsp70 from the cytoplasm to the secretory pathway did not modify the ability of hsp70 to interact with peptides derived either from natural tumor-associated antigens or model antigens, and that antigen-presenting cells specifically took up the secreted hsp70 and presented the chaperoned epitopes to T cells. In vivo studies showed that tumors secreting hsp70 displayed increased immunogenicity, with induction of a strong and specific CTL response. Mice injected with hsp70-secreting tumors showed increased survival and impaired tumor take compared with mice bearing parental tumors. More than 70% of mice rejected tumor cells secreting hsp70 through mechanisms that involve T lymphocytes and natural killer cells, with the induction of a memory response in the case of T lymphocytes. Moreover, hsp70 secretion increased the immunogenic potential of tumor cell vaccines.     

Failure of gamma-hydroxybutyric acid both to increase neuroactive steroid concentrations in adrenalectomized-orchiectomized rats and to induce tolerance to its steroidogenic effect in intact animals

Gamma-Hydroxybutyric acid (GHB), a drug proposed in the treatment of alcohol withdrawal syndrome, increases the cerebrocortical and plasma concentrations of the neuroactive steroids allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC). In the present study, we examined the role of hypothalamic-pituitary-adrenal (HPA) axis in the effect of GHB by measuring the concentrations of these steroids in the brain and plasma of adrenalectomized-orchiectomized (Adx-Orx) rats. The acute administration of GHB (500 mg/kg, i.p.) induced in 30 min an increase in the concentrations of allopregnanolone, THDOC and their precursors pregnenolone and progesterone in different brain areas (cerebral cortex, hypothalamus and cerebellum) and plasma of sham-operated rats but had no effect on the concentrations of these compounds in Adx-Orx rats, suggesting that activation of the HPA axis mediates the effect of GHB on brain and plasma concentrations of neuroactive steroids. Moreover, we evaluated whether repeated exposure of GHB induces tolerance to its steroidogenic effects. Chronic administration of GHB (500 mg/kg, i.p., twice a day for 10 days) to intact animals failed to affect the levels of progesterone, allopregnanolone, or THDOC measured 3 or 48 h after the last drug administration, whereas a challenge injection of GHB or ethanol was still able to increase the concentrations of these steroids in brain and plasma. These results indicate that repeated exposure to GHB fails to induce tolerance or cross-tolerance to the steroidogenic action of GHB or ethanol, respectively.     

Hepatitis C virus infection associated with liver-kidney microsomal antibody type 1 (LKM1) autoantibodies in children

OBJECTIVE: To evaluate the clinical pattern and evolution of chronic hepatitis C in children with liver/kidney microsomal antibody type 1 autoantibodies (LKM1). STUDY DESIGN: A multicenter, retrospective study, including the following groups of children with hepatitis C virus infection: (1). 21 consecutive LKM1-positive patients, (2). 42 age- and sex- matched LKM1-negative patients, and (3). 4 interferon-induced LKM1-positive cases. LKM1 reactivity to human microsomes and recombinant cytochrome P450IID6 (CYP2D6) was assayed by immunoblotting. RESULTS: Clinical and biochemical features overlapped in LKM1-positive and LKM1-negative children, but a fibrosis score >3 (range 0-6) was significantly more frequent (P =.04) in the former. Reactivity to microsomal protein and CYP2D6 was significantly (P =.02) associated with LKM1 titers >or=1:320 and was found in 39% of patients, including severe cases and both children (of 4 treated) who achieved a sustained alanine aminotransferase (ALT) normalization after steroid treatment. Five of 7 LKM1-positive children treated with interferon had an ALT exacerbation. CONCLUSIONS: LKM1-positive hepatitis C in children is characterized by a wide spectrum of biochemical, serologic, and histologic features. Whether autoimmunity may contribute to liver damage in a subgroup of patients with more severe liver disease, high LKM1 titers, and reactivity to CYP2D6 is a question deserving further investigation.     

Integrating model-based decision support in a multi-modal reasoning system for managing type 1 diabetic patients

We present a multi-modal reasoning (MMR) methodology that integrates case-based reasoning (CBR), rule-based reasoning (RBR) and model-based reasoning (MBR), meant to provide physicians with a reliable decision support tool in the context of type 1 diabetes mellitus management. In particular, we have implemented a decision support system that is able to jointly exploit a probabilistic model of the glucose-insulin system at the steady state, a RBR system for suggestion generation and a CBR system for patient's profiling. The integration of the CBR, RBR and MBR paradigms allows for an optimized exploitation of all the available information, and for the definition of a therapy properly tailored to the patient's needs, overcoming the single approaches limitations. The system has been tested both on simulated and on real patients' data.     

Infection due to extended-spectrum beta-lactamase-producing Salmonella enterica subsp. enterica serotype infantis in a neonatal unit

OBJECTIVE: To describe the investigation and control of an outbreak of extended-spectrum beta-lactamase producing Salmonella enterica subsp. enterica serotype Infantis in a neonatal unit in Brazil. METHODS: A case-control study for risk factors for Salmonella Infantis systemic infection, environmental cultures, and evaluation of staffing and overcrowding and an assessment of infection control practices were performed. RESULTS: During July 1998 to June 1999, 140 Salmonella Infantis culture-positive patients were identified in the neonatal unit. Presence of a peripheral intravascular catheter was identified as an independent risk factor (odds ratio = 4.98; 95% CI = 1.59-19.31; P =.01) and each 250-g increase in birth weight as a protective factor (odds ratio = 0.76; 95% CI = 0.57-0.95; P =.03). Hospital stay was significantly longer and costs higher in case patients than in control patients. Salmonella Infantis was isolated from multiple environmental sources. Neonatal unit personnel were observed to make several breaks in infection control practices. The unit was understaffed and overcrowded. Prompt case identification, cohorting of patients, enhanced staff hand hygiene, and environmental cleaning terminated the outbreak. CONCLUSIONS: Inadequate infection control practices, nursery overcrowding, and understaffing can have an adverse effect on patient morbidity, mortality rates, and hospital cost.     

Impact of carotid intima-media thickening on risk stratification in elderly hypertensives

BACKGROUND: It has been shown that aging and arterial hypertension are both associated with an increased prevalence of carotid structural abnormalities, such as intima-media (IM) thickening or plaques, which are a powerful independent predictor of cardiovascular (CV) events. We investigated the impact of carotid IM thickening in profiling the absolute CV risk stratification according the 1999 World Health Organization/International Society of Hypertension (WHO/ISH) guidelines in elderly hypertensive patients. METHODS: Two hundred and thirty untreated elderly patients (>65 years) referred to our outpatient hospital clinic were included in the study. They underwent the following procedures: (i) medical history, physical examination and clinic blood pressure measurement; (ii) routine blood chemistry and urine analysis; (iii) electrocardiogram. The risk was initially stratified according to the routine procedures indicated by WHO/ISH guidelines and subsequently reassessed by adding the results of carotid ultrasonography (IM thickening as diffuse IM thickness >0.9 and <1.3 mm). RESULTS: According to routine classification 56% (=129) were medium-risk patients, 29% (n = 67) high-risk and 15% (n = 34) very-high-risk patients. The overall prevalence of carotid IM thickening was 54% (49% in medium-risk vs 60% in high or very high-risk patients, p < 0.05). A marked change in risk stratification was observed when IM thickening was taken in consideration: medium-risk patients decreased to 29% and high-risk rose to 56% (p < 0.01). CONCLUSIONS: Ultrasound assessment of large artery damage is extremely useful for a more accurate estimate of global CV risk in elderly hypertensives, because stratification based on diagnostic routine procedures can underestimate the overall risk in a large fraction of medium-risk subjects.     

Aberrant chemokine receptor expression and chemokine production by Langerhans cells underlies the pathogenesis of Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is characterized by a clonal proliferation and retention of cells with a Langerhans cell (LC)-like phenotype at various sites within the body. The present study set out to elucidate whether aberrant expression of chemokine receptors or dysregulation of chemokine production in LCH lesions could explain abnormal retention of these cells. Immunohistochemical analysis on 13 LCH biopsies of bone, skin, and lymph node all expressed the immature dendritic cell (DC) marker CCR6 on the lesional LCs and absence of the mature DC marker CCR7. Furthermore, regardless of the tissue site, LCH lesions markedly overexpressed CCL20/MIP-3alpha, the ligand for CCR6. The lesional LCs appeared to be the source of this CCL20/MIP-3alpha production as well as other inflammatory chemokines such as CCL5/RANTES and CXCL11/I-TAC. These may explain the recruitment of eosinophils and CD4+CD45RO+ T cells commonly found in LCH lesions. The findings of this study emphasize that, despite abundant TNF-alpha, lesional LCs remain in an immature state and are induced to produce chemokines, which via autocrine and paracrine mechanisms cause not only the retention of the lesional LCs but also the recruitment and retention of other lesional cells. We postulate that the lesional LCs themselves control the persistence and progression of LCH.     

Evaluation of simvastatin antioxidant effects

3-Hydroxy-3-methyl-coenzyme A reductase (HMG-CoA reductase) which transforms 3-hydroxy-3-methylglutaril-coenzyme A (HMG-CoA) in mevalonate, is the rate limiting enzyme in cholesterol biosynthesis. In our study, from HMG-CoA reductase's known inhibitors, we used simvastatin (ZOCOR), which is a semi synthetic derivative of the second generation. The study was performed on 25 subjects (12 men and 12 women) aged 33-67 yo, with hypercholesterolemia, which have received simvastatin, 10 mg daily for 8 months. Under treatment with simvastatin we obtained a significant decrease of total cholesterol (p < 0.0001) and an improvement of enzymatic antioxidant parameters: superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). In conclusion, simvastatin therapy determines a significant decrease in SOD, GPx, CAT, and an increase in CAT/SOD and GPx/SOD ratios.