Pulmonary lipoblastoma: a case report.
We report a case of pulmonary lipoblastoma in a 2-year-old child. This pathology has not been previously reported in the English literature.
Biomedical subjects
Publications and source records attributed to G Thomas.
We report a case of pulmonary lipoblastoma in a 2-year-old child. This pathology has not been previously reported in the English literature.
AIM: The present prospective study analysis whether preoperative abciximab treatment 1) increases perioperative risks, 2) alters the quality of the surgical treatment, 3) whether secondary organ complications occur and 4) whether and how the perioperative surgical management has to be modified. METHODS: The perioperative results of patients operated upon after preoperative abciximab treatment (n = 31, 1/1994-4/2000) were compared with an optimal control group (elective patients and no preoperative intervention in the hemostaseological system) and with other patients (elective, urgent, emergency operations) receiving different strategies of preoperative hemostaseological interventions (n = 926, 1/1994-4/2000). All patients were operated upon with a well-defined strategy (one surgeon). 1100 perioperative items/patient were prospectively recorded and analyzed. The 30-day and 6 month follow-up was complete. RESULTS: The mean time interval between end of abciximab therapy and onset of operation was 4.3 h (range: 36-0.5 h, median: 2 h). As compared with the optimal control group (n = 81), perioperative blood loss and the need for substitution of blood and blood products was increased. However, as compared with those patients receiving any type of preoperative intervention in the hemostaseological system (the majority of the patients), no difference was observed regarding intraoperative parameters (duration of extracorporeal circulation and of the operation) and postoperative results (neurological, renal complications, myocardial infarction, psychiatric disturbances, etc.) when abciximab patients were compared with the reference populations. No patient of the abciximab group died within 30 days or during the 6 month follow-up period. CONCLUSION: The data show that coronary artery bypass grafting can be performed with similar results in abciximab-pretreated patients as in patients with other types of preoperative anticoagulation. Only slight modifications of the surgical management are recommended. As indicated by similar use IMA-grafts the quality of surgical treatment was not reduced.
This article reviews our current knowledge of the role of ribosomal protein S6 phosphorylation and the S6 kinase (S6K) signaling pathway in the regulation of cell growth and proliferation. Although 40S ribosomal protein S6 phosphorylation was first described 25 years ago, it only recently has been implicated in the translational up-regulation of mRNAs coding for the components of protein synthetic apparatus. These mRNAs contain an oligopyrimidine tract at their 5' transcriptional start site, termed a 5'TOP, which has been shown to be essential for their regulation at the translational level. In parallel, a great deal of information has accumulated concerning the identification of the signaling pathway and the regulatory phosphorylation sites involved in controlling S6K activation. Despite this knowledge we are only beginning to identify the direct upstream elements involved in growth factor-induced kinase activation. Use of the immunosupressant rapamycin, a bacterial macrolide, in conjunction with dominant interfering and activated forms of S6K1 has helped to establish the role of this signaling cascade in the regulation of growth and proliferation. In addition, current studies employing the mouse as well as Drosophila melanogaster have provided new insights into physiological function of S6K in the animal. Deletion of the S6K1 gene in mouse cells led to an animal of reduced size and the identification of the S6K1 homolog, S6K2, whereas loss of dS6K function in Drosophila demonstrated its paramount importance in development and growth control.
Studies have shown that hemoglobin (Hb) level is a prognostic factor for outcomes following definitive radiotherapy in patients with a variety of tumors. We conducted a retrospective study on patients with carcinoma of the cervix to evaluate the relationships among Hb level, response to radiation, and effect on local control and survival. Data from 3 years (1989, 1990, 1992) were collected at seven institutions across Canada from women who received definitive radiotherapy, > or = 3,500 cGy, for carcinoma of the uterine cervix. The collected data included Hb levels at presentation and during radiation treatment specific for the time course of anemia and blood transfusion practice, patient demographics, details of the treatment regimen, and outcomes. Of 630 patients reviewed, 605 were eligible and were included in the analyses; median follow-up was 41 months. Twenty-five percent of patients received blood transfusions, most frequently when Hb decreased to below 100 g/L. Baseline Hb > or = 120 g/L was shown on univariate analysis to be significant for higher rates of pelvic disease control and disease-free survival. On multivariate analysis, baseline Hb was not a significant prognostic factor, but average weekly nadir Hb (AWNH) levels during radiotherapy were shown to be significant, and second only in importance to tumor stage. Five-year survival rates were similar if AWNH levels were > or = 12 g/L, regardless of whether baseline Hb was lower than 120 g/L (70%) or > or = 120 g/L (74%); the difference in 5-year survival between patients with lower AWNH (< 120 g/L) and higher AWNH (> or = 120 g/L) was significant. Patients with higher AWNH had significantly lower rates of overall relapse, local recurrence, and distant metastases. A stepwise significant increase was noted in overall survival rate as AWNH levels increased, regardless of transfusion status. Hemoglobin levels > or = 120 g/L during radiotherapy were shown to be a significant prognostic factor for successful radiotherapy and disease-free survival. There was no difference in outcomes relative to transfusion status.
We have studied the accumulation of hydrogen peroxide in rice leaves in response to salicylic acid (SA) treatment. H(2)O(2) accumulation was localized in the veins. While the activity of the H(2)O(2) degrading enzyme peroxidase was inhibited in response to SA, superoxide dismutase activity, which generates H(2)O(2), did not show any change. An increase in the activity of glutathione reductase, a peroxide degrading enzyme, was observed upon SA treatment, similar to the response reported by accumulation of active oxygen species. In rice leaves transformed with CaMV-GUS fusions, we found that SA treatment induced transcriptional activation through as-1 element. As-1 has been implicated in protective mechanisms that operate during some types of oxidative stress and the hypersensitive response (HR). Expression of rice pathogenesis-related protein 5 (PR5), one of the PR genes associated with systemic acquired resistance, was induced by SA. This induction seems to be independent of the H(2)O(2) accumulation induced by SA. Inoculation of rice leaves with the rice blast fungus, Magneporthe grisea, also led to the accumulation of H(2)O(2) in the veins, suggesting the presence of common signals between SA and pathogen responses. Thus SA application seems to induce oxidative stress in rice through H(2)O(2); a signal molecule implicated in biotic and abiotic stress responses.
The Iowa Dental Surgical Simulator is a haptic simulator to train dental students in the haptic skills of dentistry. The initial design emphasizes the detection of carious lesions. This work describes the software and implementation of the prototype system, the design tradeoffs' and the technical issues associated with haptic and graphics subsystems. The work also describes the current system performance, including a formal evaluation by practicing dentists and performance measures. A discussion of the limitations of the current system is followed by an analysis of opportunities to improve the quality of the simulator. The results should be of interest to designers of medical haptic simulation systems and other simulation designers.
The present study is the first report on a client-treatment matching protocol (CMP) to guide admissions to residential and outpatient substance abuse treatment settings. Two cohorts, a field test sample (n = 318) and cross-validation (n = 407) sample were drawn from consecutive admissions to nine geographically distributed multisetting therapeutic communities (TCs). A passive matching design was employed. Clients received the CMP on admission, but agencies were "blind" to the CMP treatment recommendation (i.e., match) and assigned clients to treatment by the usual intake procedures. Bivariate and logistical regression analyses show that positive treatment dispositions (treatment completion or longer retention in treatment)) were significantly higher among the CMP-matched clients. The present findings provide the empirical basis for studies assessing the validity and utility of the CMP with controlled designs. Though limited to TC-oriented agencies, the present research supports the use of objective matching criteria to improve treatment.
Association study is the method of choice to identify genes involved in complex processes that result from the interaction of environmental and genetic factors. However, because of biases that increase the risk of false positive reports, preliminary positive conclusions have to be reproduced on other populations to be validated as firm conclusions. In 1994, certain alleles of two genes, APOE (Apolipoprotein E) and ACE (angiotensin converting enzyme), were reported to be more frequent in French centenarians, suggesting an association with such a complex polyfactorial process as longevity. Enlargement of the French centenarian cohort allows a new assessment of this hypothesis on 563 centenarians. In contrast to APOE, the ACE association was not confirmed. Retrospective analysis of the initial study revealed discrepancies that may in part explain this observation. Risk of reporting false positive associations is discussed and recommendations to set up a rigorous experimental design are proposed.
OBJECTIVE: Usefulness and risks of incomplete versus complete revascularization are still matters of ongoing discussions. Because an increasing number of elderly patients are undergoing coronary artery bypass grafting (CABG), the question arises whether a less extensive surgical approach is more prudent than complete revascularization. METHODS: Of 6531 patients undergoing isolated CABG, 859 were 75 and older at the time of operation. Mean age of the 859 patients was 77+/-2.7 years (median: 76 years); 65% were men. Follow-up enquiry by questionnaire was performed at the 180th postoperative day with a completeness of 95.6%. Assessment of the impact of incomplete revascularization utilized both multivariable analysis and propensity score matching to account for selection factors. RESULTS: Incomplete revascularization was performed in 133 patients (16%). The most common reasons for incomplete revascularization were small vessels (55%) and massive calcification (32%). Mortality until 180 days after CABG was higher (n=32; 24%) after incomplete than after complete revascularization (n=105; 15%; P=0.005). By logistic multivariable regression, incomplete revascularization was identified as an independent risk factor for death (Odds ratio, 1.8; P=0.015). By time-related analysis, incomplete revascularization predominantly affected the early period after CABG (P=0.001). Aortic cross clamping time was only slightly shorter for the group with incomplete (59+/-27 min (median: 55 min) vs. 63+/-26 min (median: 58 min); P=0.1). CONCLUSIONS: Incomplete revascularization increases the early risk of death after CABG in patients aged 75 years and older. The potential compensating benefit of the shorter aortic cross clamping time does not outweigh the advantages of complete revascularization. Thus, in the era of high-volume interventional approaches and minimally invasive techniques, the advantages of complete revascularization need to be considered.
It is well established that most invasive oral cancers arise from precancerous lesions such as leukoplakia, erythroplakia and oral submucous fibrosis. One of the approaches for control of oral cancer is to detect oral precancerous lesions early in their development and prevent their malignant transformation to invasive cancer either by chemoprevention or by surgical excision of the lesions, with concurrent control of tobacco and alcohol use and other specific aetiological factors. However, the value of specific approaches such surgery in long-term control of lesions and prevention of malignant transformation is not known. We describe our experience with cold knife surgical excision of 59 cases of non-homogeneous leukoplakia of the oral cavity diagnosed in the context of a community-based oral cancer cluster randomised oral cancer screening trial in Kerala, India. Two-thirds of these revealed dysplasia on histology. After a minimum follow-up of 12 months (range 12-37 months) after surgical excision, 44 (74.8%) were remaining disease free with no evidence of recurrent/new lesions; during follow-up, three (5%) developed new luekoplakic lesions, and six (10.1%) developed recurrent lesions, while six (10.1%) could not be traced after treatment. There was no event of malignant change during follow-up. The proportion of subjects remaining with no evidence of disease at 3 years by Kaplan-Meier method of analysis was 62.1% (95% CI: 0.36-0.87). Accrual and long-term follow-up of large number of surgically treated cases may provide valuable leads to management policies of oral leukoplakia, since, as of now, the added value of specific treatments over and above primary prevention by tobacco and alcohol control remains to be established.
Oral cancer ranks first among all cancers in males and is the third most common among females in India. Tobacco-derived carcinogens are involved in the development of oral cancer. Environment-gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study looked at the significance of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in patients with oral cancer. The study included 98 oral cancer patients and 60 age and sex matched healthy controls. Genotypes of CYP1A1, GSTM1 and GSTT1 were determined by PCR-RFLP. GSTM1 null deletion was observed in 49% of oral cancer cases and 33% of control subjects. For GSTT1, 18% of carcinomas and 8% of controls had the null genotype. In the case of CYP1A1 m2 allele, 51% of oral cancers and 17% of normal controls, respectively, had one or both alleles with the isoleucine-->valine substitution. Digestion of the PCR products with enzyme Nco1 revealed polymorphism for CYP1A1 m2 with bands at 263 bp. There was no association between genotypes with tumor size, stage, grade, and age. Since null genotype individuals may possibly be poor detoxifiers with reduced ability to neutralise the reactive carcinogenic intermediates, they may be a high risk category. The frequency distribution of CYP1A1 m2 (Ile/val) genotypes among oral cancer patients was significantly different that from normal controls. The risk of CYP1A1 can be supported by the functional difference between presence of valine and isoleucine; valine type has higher catalytic and mutagenic activity towards benzo[a] pyrene than the isoleucine type. In conclusion, our results suggest that polymorphism in CYP1A1 m2 gene and/or GSTM1 and GSTT1 null genotype may confer an increased risk for oral cancer.
We have identified three missense mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 in four French and German families with Blau syndrome. Our findings indicate that, in addition to Crohn disease, CARD15 is involved in the susceptibility to a second granulomatous disorder.
Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37x10(-4)) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.
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BACKGROUND: Our previous studies have demonstrated that renal proximal tubular epithelial cells (PTCs) may contribute to renal interstitial fibrosis by the generation of transforming growth factor-beta1 (TGF-beta1). In these in vitro experiments, TGF-beta1 was, however, secreted in its latent form. Plasmin has been implicated as a potential physiological activator of TGF-beta1. The inter-alpha-trypsin inhibitor (IalphaI) family of serum protease inhibitors together with tumor necrosis factor-stimulated gene 6 (TSG-6) recently have been implicated in the regulation of this protease pathway. The aim of the current study was to examine PTC synthesis of these proteins and to relate it to alterations of plasmin-protease activity. METHODS: PTCs were grown to confluence and stimulated under serum-free conditions with either interleukin-1beta (IL-1beta) or 25 mmol/L D-glucose. Alterations in IalphaI and TSG-6 generation were detected by Western analysis of both membrane extracts and supernatant samples. Alterations in gene expression were examined by reverse transcription-polymerase chain reaction. The effect of alteration in synthesis of TSG-6 on plasmin activity was determined by quantitating plasmin inhibitory activity of supernatant samples by in vitro calorimetric assay prior to and following TSG-6 immunoprecipitation. RESULTS: The data demonstrate that human PTCs constitutively express mRNA for bikunin and heavy chain 3 (H3) of IalphaI. Neither IL-1beta (1 ng/mL) nor 25 mmol/L D-glucose influenced their mRNA expression nor protein synthesis. In contrast, the addition of either IL-1beta or 25 mmol/L D-glucose increased TSG-6 mRNA expression. This was accompanied by an early up-regulation of TSG-6 protein expression following IL-1beta stimulation (24 h) and a late up-regulation after the addition of 25 mmol/L D-glucose (96 h) in the cell culture supernatant and associated with the cell membranes. Early induction of TSG-6 mRNA by IL-1beta was unaffected by the addition of the protein synthesis inhibitor cycloheximide. In contrast, the later glucose-stimulated induction of TSG-6 mRNA was abrogated by the addition of cycloheximide. Stimulation of TSG-6 by either IL-1beta or 25 mmol/L D-glucose was associated with an inhibition of total percentage plasmin activity. Immunoprecipitation of TSG-6 in these samples returned plasmin activity to control levels. CONCLUSIONS: : The data demonstrate that human PTCs constitutively express the bikunin and H3 components of the IalphaI family of serum protease inhibitors. Moreover, the addition of IL-1beta or 25 mmol/L D-glucose up-regulates the expression of TSG-6 in these cells, resulting in an inhibition of plasmin activity.
BACKGROUND & AIMS: To evaluate how characterization of genetic alterations can help in the elucidation of liver carcinogenesis pathways, 137 tumors were analyzed. METHODS: High-density allelotype, p53, Axin1, and beta-catenin gene mutations were determined. Alterations were analyzed according to clinical parameters. RESULTS: Tumors could be divided into 2 groups according to chromosome stability status. In the first group, demonstrating a chromosome stability, beta-catenin mutation associated with chromosome 8p losses were frequently found as the single genetic alterations. beta-catenin mutations were associated with large tumor size and with negative hepatitis B virus status. In the second group, demonstrating a chromosome instability, the most frequent allelic losses were on chromosome 1p, 4q, 6q, 9p, 13q, 16p, 16q, and 17p; Axin1 and p53 were frequently mutated. All of these alterations, except losses on 6q and 9p, were associated with hepatitis B virus infection. P53 mutations, 17p, 13q losses, and a high value of the fractional allelic loss index were associated with poor differentiated tumors, independently of risk factors. Finally, in the whole series, chromosome 9p and 6q losses were associated with poor prognosis. CONCLUSIONS: Two main pathways defined by genetic alterations show different risk factors and clinical characteristics. Furthermore, loss of chromosome 9p or 6q is an independent prognostic indicator.
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