胃、结直肠癌术前区域性动脉化疗几个相关问题

胃、结直肠癌根治性切除术复发转移是严重影响术后5 a生存率提高的重要原因.以手术为主综合治疗已成为新的趋势,其中术前区域性动脉化疗(preoperative regional-arterial chemotherapy,PRAC)尤为值得重视.本文介绍了术前PRAC的概念、作用机制和影响区域性动脉化疗疗效的相关因素,并就术前区域性动脉化疗在胃、结直肠癌综合治疗中的评价进行讨论.     

Classification of burn injuries using near-infrared spectroscopy

Early surgical management of those burn injuries that will not heal spontaneously is critical. The decision to excise and graft is based on a visual assessment that is often inaccurate but yet continues to be the primary means of grading the injury. Superficial and intermediate partial-thickness injuries generally heal with appropriate wound care while deep partial- and full-thickness injuries generally require surgery. This study explores the possibility of using near-infrared spectroscopy to provide an objective and accurate means of distinguishing shallow injuries from deeper burns that require surgery. Twenty burn injuries are studied in five animals, with burns covering <1% of the total body surface area. Carefully controlled superficial, intermediate, and deep partial-thickness injuries as well as full-thickness injuries could be studied with this model. Near-infrared reflectance spectroscopy was used to evaluate these injuries 1 to 3 hours after the insult. A probabilistic model employing partial least-squares logistic regression was used to determine the degree of injury, shallow (superficial or intermediate partial) from deep (deep partial and full thickness), based on the reflectance spectrum of the wound. A leave-animal-out cross-validation strategy was used to test the predictive ability of a 2-latent variable, partial least-squares logistic regression model to distinguish deep burn injuries from shallow injuries. The model displayed reasonable ranking quality as summarized by the area under the receiver operator characteristics curve, AUC = 0.879. Fixing the threshold for the class boundaries at 0.5 probability, the model sensitivity (true positive fraction) to separate deep from shallow burns was 0.90, while model specificity (true negative fraction) was 0.83. Using an acute porcine model of thermal burn injuries, the potential of near-infrared spectroscopy to distinguish between shallow healing burns and deeper burn injuries was demonstrated. While these results should be considered as preliminary and require clinical validation, a probabilistic model capable of differentiating these classes of burns would be a significant aid to the burn specialist.     

Giant Asian honeybee or Bambara stings causing myocardial infarction,bowel gangrene and fatal anaphylaxis in Sri Lanka: a case series

The sting of Giant Asian honeybee (Apis dorsata) or Bambara in Sinhala and Karunge Kulavi in Tamil is a common environmental hazard in Sri Lanka known to cause immediate allergic reactions, which could be fatal in sensitized individuals. We reported myocardial infarction, bowel gangrene and fatal anaphylaxis in a prospectively proven case series and the association of these uncommon complications with delayed removal of stingers from the patients' skin.     

Significant variability in response to inhaled corticosteroids for persistent asthma

BACKGROUND: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. OBJECTIVE: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. METHODS: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day. RESULTS: Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). CONCLUSIONS: Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Attachment in infancy and preschool in low socioeconomic status rural Appalachian children: stability and change and relations to preschool and kindergarten competence

Attachment classifications were obtained from the Strange Situation at 15 months and at 4 years for a sample of 82 low socioeconomic status rural Appalachian children. The rate of secure attachment in infancy was 50.5%, and the majority of insecure infants were disorganized. At 4 years of age 61.2% of children were secure; early secure relationships were likely to be maintained, and about half of the insecure infants changed to a secure classification by 4 years. Overall, there was low but significant stability in attachment at the level of secure/insecure. Comparisons of (a) children who changed from insecure to secure with those who were stable insecure and (b) stable secure children with those who changed from secure to insecure identified contextual, child, and maternal interaction factors associated with attaining secure attachment. Assessments of cognitive and socioemotional competence at 4 years and kindergarten age suggested a protective effect of secure infant attachment but little benefit from secure preschool attachment.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells

Innate lymphoid cells (ILCs) expressing the nuclear receptor RORγt are essential for gut immunity presumably through production of interleukin-22 (IL-22). The molecular mechanism underlying the development of RORγt(+) ILCs is poorly understood. Here, we have shown that the aryl hydrocarbon receptor (Ahr) plays an essential role in RORγt(+) ILC maintenance and function. Expression of Ahr in the hematopoietic compartment was important for accumulation of adult but not fetal intestinal RORγt(+) ILCs. Without Ahr, RORγt(+) ILCs had increased apoptosis and less production of IL-22. RORγt interacted with Ahr and promoted Ahr binding at the Il22 locus. Upon IL-23 stimulation, Ahr-deficient RORγt(+) ILCs had reduced IL-22 expression, consistent with downregulation of IL-23R in those cells. Ahr-deficient mice succumbed to Citrobacter rodentium infection, whereas ectopic expression of IL-22 protected animals from early mortality. Our data uncover a previously unrecognized physiological role for Ahr in promoting innate gut immunity by regulating RORγt(+) ILCs.