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B Carvalho

Publications and source records attributed to B Carvalho.

At least 19 recordsLinked to original sources

Cross-platform array comparative genomic hybridization meta-analysis separates hematopoietic and mesenchymal from epithelial tumors.

A series of studies have been published that evaluate the chromosomal copy number changes of different tumor classes using array comparative genomic hybridization (array CGH); however, the chromosomal aberrations that distinguish the different tumor classes have not been fully characterized. Therefore, we performed a meta-analysis of different array CGH data sets in an attempt to classify samples tested across different platforms. As opposed to RNA expression, a common reference is used in dual channel CGH arrays: normal human DNA, theoretically facilitating cross-platform analysis. To this aim, cell line and primary cancer data sets from three different dual channel array CGH platforms obtained by four different institutes were integrated. The cell line data were used to develop preprocessing methods, which performed noise reduction and transformed samples into a common format. The transformed array CGH profiles allowed perfect clustering by cell line, but importantly not by platform or institute. The same preprocessing procedures used for the cell line data were applied to data from 373 primary tumors profiled by array CGH, including controls. Results indicated that there is no apparent feature related to the institute or platform and that array CGH allows for unambiguous cross-platform meta-analysis. Major clusters with common tissue origin were identified. Interestingly, tumors of hematopoietic and mesenchymal origins cluster separately from tumors of epithelial origin. Therefore, it can be concluded that chromosomal aberrations of tumors from hematopoietic and mesenchymal origin versus tumors of epithelial origin are distinct, and these differences can be picked up by meta-analysis of array CGH data. This suggests the possibility of prospectively using combined analysis of diverse copy number data sets for cancer subtype classification.

Chromosome Aberrations↗

A survey of labor patient-controlled epidural anesthesia practice in California hospitals.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) offers many advantages over continuous epidural infusions for labor analgesia including fewer physician interventions, improved analgesia and satisfaction, and reduced local anesthetic doses. However, anesthesiologists have been slow to adopt this technique, first described in 1988. No previous studies have evaluated specific labor patient-controlled epidural analgesia practices in the United States. The aim of this study was to determine labor epidural and patient-controlled epidural analgesia practices among California hospitals. METHODS: Following institutional review board exemption approval, an online survey was created using freeonlinesurveys.com. An anonymous survey was sent via e-mail to 230 California Society of Anesthesiologists' members chosen at random to represent their hospitals' labor analgesia practices. RESULTS: We received 133 replies from the 230 survey requests sent, a 58% response rate. The median labor epidural rate among the hospitals involved was 65% (range 0-95%). Overall, only 25% of California hospitals use patient-controlled epidural analgesia for analgesia in labor, with greater use among hospitals with dedicated obstetric anesthesia coverage and larger numbers of deliveries. Reasons given for not using patient-controlled epidural analgesia include cost, clinician preference, safety concerns and the inconvenience of change. CONCLUSIONS: Despite the potential advantages of patient-controlled epidural analgesia over continuous epidural infusions for labor analgesia, patient-controlled epidural analgesia has not been widely adopted in California hospitals. Education regarding this technique is needed to encourage its increased use.

Analgesia, Epidural↗

"Ultra-light" patient-controlled epidural analgesia during labor: effects of varying regimens on analgesia and physician workload.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) offers many advantages over continuous epidural infusions for maintenance of labor analgesia. Some of these benefits may depend on the PCEA settings. This study evaluated several regimens for "ultra-light" (0.125%) PCEA with basal continuous infusion (CI) in labor with goals of minimizing physician interventions while providing good analgesia. METHODS: Two hundred and twenty ASA I-II women receiving epidural analgesia during active labor (cervical dilation <5 cm) were randomly assigned in a double-blind manner to four treatment groups (n=30 in each). Analgesia was maintained with a PCEA/CI pump using bupivacaine 0.0625% + sufentanil 0.35 microg/mL. PCEA settings were: group A: CI 10 mL/h, PCEA bolus 6 mL, 8-min lockout; group B: CI 10 mL/h, PCEA bolus 12 mL, 16-min lockout; group C: CI 15 mL/h, PCEA bolus 6 mL, 8-min lockout; group D: CI 15 mL/h, PCEA bolus 12 mL, 16-min lockout. RESULTS: In groups A, B, C and D, 76, 77, 75 and 85% of parturients respectively, required no physician rescue boluses. Pain scores were low and maternal satisfaction was high in all groups, with minimal differences among them. Spontaneous vaginal delivery occurred in 78% of patients overall, instrumental (forceps or vacuum) delivery in 10% and cesarean section in 12%. CONCLUSIONS: These ultra-light PCEA regimens provided excellent analgesia with minimal physician workload and a high spontaneous delivery rate. Use of moderate to high-volume, ultra-light PCEA/CI techniques should facilitate provision of labor analgesia in busy obstetric units.

Adult↗

DNA copy number changes at 8q11-24 in metastasized colorectal cancer.

BACKGROUND: C-Myc, a well-known oncogene located on 8q24.12-q24.23, is often amplified and over-expressed in both primary and metastasizing colorectal cancer. In addition, PRL-3 (also known as PTP4A3), a tyrosine phosphatase located on 8q24.3, is amplified in colorectal cancer metastasis. Beside PRL-3 and c-myc, other oncogenes located on the 8q23-24 region might be involved in this process. Therefore, the present study aims to correlate DNA copy number status of a series of genes at 8q23-24 in colorectal cancer at high resolution in correlation to metastatic disease. MATERIALS AND METHODS: Thirty-two cases of colorectal cancer, 10 stage B1, 10 B2 and 12 D (Astler-Coller) with their corresponding liver metastasis and one colorectal cell line (colo205, previously analyzed by array-CGH), were included in this study. A chromosome 8 specific MLPA probe mixture was used to analyze the presence of DNA copy number changes. The probe mixture contained 29 probes covering 25 genes on chromosome 8, as well as 6 control probes on other chromosomes. RESULTS AND DISCUSSION: MLPA results obtained of the colo205 colorectal cell line were comparable with previous array-CGH results, thus validating the MLPA probe mixture. Astler-Coller B1 and B2 colorectal cancers differed significantly in DNA copy number of the genes, MOS (p=0.04), MYC (p=0.007), DDEF1 (p=0.004), PTK2 (p=0.02) and PTP4A3 (p=0.04). When comparing these with Astler-Coller D primary tumors, significant differences were seen for several genes as well (MYC (p<0.000), DDEF1 (p<0.000), SLA (p<0.000), PTK2 (p<0.000), PTP4A3 (p=0.002), and RECQL4 (p=0.01)). When comparing primary Astler-Coller D tumors and their corresponding liver metastases, a similar pattern of gains and losses was observed. Most of the liver metastases showed higher DNA copy number ratios than the corresponding primary tumors, but this difference was only significant for TPD52 (p=0.02) and EIF3S6 (p=0.007). CONCLUSION: In addition to c-myc, multiple genes on chromosome 8 differed significantly between primary colorectal cancers with and without liver metastases. This observation is consistent with the concept that clinical behaviour, like risk of liver metastasis, is determined by the genomic profile that is already present in the primary tumor.

Base Sequence↗

Neonatal chest wall rigidity following the use of remifentanil for cesarean delivery in a patient with autoimmune hepatitis and thrombocytopenia.

Remifentanil is a useful adjunct in general anesthesia for high-risk obstetric patients. It provides effective blunting of the rapid hemodynamic changes that may be associated with airway manipulation and surgical stimulation. There have been no previous reports of opioid-related rigidity in the neonate delivered by a parturient receiving intraoperative remifentanil. We present a case of short-lived neonatal rigidity and respiratory depression following remifentanil administration during cesarean section to a parturient with autoimmune hepatitis complicated by cirrhosis, esophageal varices and thrombocytopenia.

Adult↗

High resolution microarray comparative genomic hybridisation analysis using spotted oligonucleotides.

BACKGROUND: Currently, comparative genomic hybridisation array (array CGH) is the method of choice for studying genome wide DNA copy number changes. To date, either amplified representations of bacterial artificial chromosomes (BACs)/phage artificial chromosomes (PACs) or cDNAs have been spotted as probes. The production of BAC/PAC and cDNA arrays is time consuming and expensive. AIM: To evaluate the use of spotted 60 mer oligonucleotides (oligos) for array CGH. METHODS: The hybridisation of tumour cell lines with known chromosomal aberrations on to either BAC or oligoarrrays that are mapped to the human genome. RESULTS: Oligo CGH was able to detect amplifications with high accuracy and greater spatial resolution than other currently used array CGH platforms. In addition, single copy number changes could be detected with a resolution comparable to conventional CGH. CONCLUSIONS: Oligos are easy to handle and flexible, because they can be designed for any part of the genome without the need for laborious amplification procedures. The full genome array, containing around 30000 oligos of all genes in the human genome, will represent a big step forward in the analysis of chromosomal copy number changes. Finally, oligoarray CGH can easily be used for any organism with a fully sequenced genome.

Breast Neoplasms↗

Concurrent hypermethylation of gene promoters is associated with a MSI-H phenotype and diploidy in gastric carcinomas.

Changes in the pattern of DNA methylation are among the most common alterations observed in human cancers, such as gastric carcinomas. We analysed in a series of 51 sporadic gastric carcinomas the methylation status of the promoter regions of the hMLH1, CDH1, MGMT and COX2 genes. We aimed to determine the frequency of CpG island hypermethylation and to find out whether the occurrence of concurrent hypermethylation is related to the clinicopathological features of the gastric carcinomas. Using methylation-sensitive restriction analysis/polymerase chain reaction (PCR) and methylation-specific PCR (MSP) strategies, we searched for the presence of hypermethylation on the promoter region of the 4 selected genes. All showed hypermethylation of their promoter regions with frequencies of 37, 51, 61 and 29% for hMLH1, CDH1, MGMT and COX2, respectively. Concurrent hypermethylation was more frequently observed in MSI-H (P=0.0005) and diploid (P=0.029) tumours. Hypermethylation of hMLH1 was associated with MSI-H tumours (P=0.0001), whereas hypermethylation of MGMT was associated with MSI-H (p=0.021) and diploid tumours (p=0.012). Our results indicate that concurrent hypermethylation is a common event in gastric cancer, suggesting that global methylation changes play an important role in the development of sporadic gastric carcinoma. Moreover, inactivation of different gene promoters by hypermethylation is significantly associated with microsatellite instability (MSI-H) and diploidy: hMLH1 determines MSI-H and MGMT the diploid status of gastric carcinomas.

Adaptor Proteins, Signal Transducing↗

Myocardial ischaemia precipitated by acute normovolaemic haemodilution.

Acute normovolaemic haemodilution (ANH) is widely used as part of a blood conservation strategy to minimize the use of allogenic blood in the peri-operative period. Its role has not been proven in a prospective randomized trial. The potential benefits must not blind clinicians to the possible hazards. We report a life-threatening complication of ANH prior to induction of anaesthesia for aortic aneurysm repair.

Aged↗

Novel expressed sequences obtained by means of a suppression subtractive hybridisation analysis from the 6q21 region that is frequently deleted in gastric cancer.

In our search for genomic regions that are involved in the development of gastric cancer, we recently identified a 2-cM minimal region of overlapping heterozygous deletions in 6q16.3-q23.1. Here, we describe an application of the suppression subtraction method (SSH) to search for genes in this small region of the genome, taking advantage of the fact that many human genes present on yeast artificial chromosomes (YACs) are expressed in yeast. Subtraction was performed with two virtually contiguous YACs that cover a region of approximately 2.5 Mb. Combined forward and reversed subtractions resulted in the identification of 12 clones of human origin, all of which could be confirmed by sequence analysis as originating from the 6q21 region. Expression in human tissues could be confirmed by Northern analysis for two of the clones, one of them showing a high level of expression in stomach tissue.

Blotting, Northern↗

The output of two sevoflurane vaporizers in the presence of helium.

BACKGROUND: Modern vaporizers are designed to deliver accurate and stable concentrations of volatile anaesthetic agents. Carrier gas composition may adversely affect the output from vaporizers. No previous study has tested helium in combination with sevoflurane vaporizers, a clinically useful combination especially in anaesthesia for upper airway obstruction. METHODS: This study evaluated the effect of increasing helium concentrations, carrier gas flow rates and varying the vaporizer dial setting on the output from Blease Datum and Drager Vapor 19.3 sevoflurane vaporizers. RESULTS: The presence of helium in the carrier gas had negligible effects on the output from both of the sevoflurane vaporizers tested. Carrier gas flow rates had the greatest effect on output but changes were within +/- 10% of baseline. CONCLUSION: Helium/oxygen mixtures can be used with these vaporizers without adversely affecting their performance.

Anesthesia, Inhalation↗

Allelic gains and losses in distinct regions of chromosome 6 in gastric carcinoma.

In gastric cancer, alterations in the long arm of chromosome 6 are a frequent event. Two regions of heterozygous loss have been described: 6q16.3-6q23 and 6q26-6q27. We have evaluated by microsatellite and FISH analyses the 6q status of three cell lines that we established from primary gastric carcinomas xenografted in nude mice, in order to elucidate the underlying mechanisms of 6q alterations. Alterations of the long arm of chromosome 6 were found in all three xenografts and corresponding cell lines. Allelic imbalance (AI) was found in the three cases, by microsatellite analysis. Fluorescence in situ hybridization analyses clearly demonstrated a duplication of the larger part of the 6q arm in all three cell lines. Two of the cell lines and the corresponding xenografts showed, in addition, complete loss of one of the parental alleles at the terminal part of 6q. Thus, the AI observed along the long arm of chromosome 6 is represented by gain of alleles in one distinct chromosomal segment and loss of alleles in another distinct segment.

Allelic Imbalance↗

'Near-miss' hyperkalaemic cardiac arrest associated with rapid blood transfusion.

A case is presented in which a relatively modest blood transfusion resulted in acute hyperkalaemia with a 'near-miss' cardiac arrest. While transfusion-related hyperkalaemia usually occurs in association with massive transfusions, several factors may have increased the risk of such an acute reaction. A high index of suspicion is required, especially in patients with risk factors. Anaesthetists should not be lulled into a false sense of security simply because modest volumes of blood are being transfused.

Aged↗

Substantial reduction of the gastric carcinoma critical region at 6q16.3-q23.1.

Deletions of the long arm of chromosome 6 are a common event in gastric carcinomas. In a previous study, deletion mapping of 6q identified two smallest regions of overlap (SROs) of heterozygous deletions: one interstitial, spanning 12-16 cM, bordered by D6S268 (6q16.3-q21) and ARG1 (6q22.3-q23.1), and one distal to IFNGR1 (6q23-q24), spanning more than 30 cM. Loss of heterozygosity (LOH) of the interstitial SRO was detected in 50% of informative tumors. We analyzed 60 primary gastric tumors with 19 highly polymorphic markers from 6q16.3-q23.3 to delimit the interstitial SRO further. Of the 50 tumors that were informative for at least one locus, 18 (36%) showed allelic imbalance (AI). The overlap of these cases allowed us to define an SRO of approximately 3 Mb flanked by D6S278 and D6S404. AI or LOH of this region occurs in all histologic types of gastric carcinoma and in early stages of development, indicating that loss of a gene from this region of 6q is a crucial step in a main route of gastric carcinogenesis. For cases with retention of 6q, alternative routes of gastric carcinogenesis may exist. Genes Chromosomes Cancer 26:29-34, 1999.

Chromosome Deletion↗