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Biomedical subjects

J West

Publications and source records attributed to J West.

At least 73 records · Page 4Linked to original sources
PubMed2000

Molecular definition of a small amplification domain within 3q26 in tumors of cervix, ovary, and lung.

A common amplification target encompassing chromosome region 3q25 to q27 has been identified by comparative genomic hybridization analyses in tumors of the cervix, ovary, endometrium, lung, and head and neck. Because this segment spans at least 30 megabases, we undertook a molecular analysis of copy number to more precisely define the amplification domain. Our Southern blot and fluorescence in situ hybridization results with the use of 17 markers confirmed the presence of low-level 3q amplification events in cervical, ovarian, and variant SCLC tumors. Most of the tumor types studied appeared to have similar, broad amplification domains centered within 3q26.2, suggesting that the same target is being affected in all. The ovarian carcinoma cell line NIH:OVCAR3 had a highly restricted amplification domain spanned by four overlapping YAC clones, suggesting a small target. The region of highest amplification included the gene for the RNA component of telomerase (hTR), supporting it as a potential target. Although the importance of low-level amplification is unknown, the consistent and reproducible nature of this event in a variety of carcinomas suggests that 3q26.2 harbors an oncogene whose low-level amplification has a significant influence on tumor biology.

Blotting, Southern↗
PubMed2000

Time perception in boys with attention-deficit/hyperactivity disorder according to time duration, distraction and mode of presentation.

In a recent theoretical model of attention-deficit/hyperactivity disorder (ADHD), Barkley (1997a) predicted that ADHD children experience impairments in their psychological sense of time. This was demonstrated in a series of experiments by Barkley, Koplowicz, Anderson, and McMurray (1997). The present study sought to investigate the effects of ADHD subtype, stimulus duration, mode of presentation (visual versus auditory) and distractors on the performance of a simple time reproduction task. Data were obtained from 44 ADHD children (14 predominantly inattentive and 30 combined type) and 44 age-matched Controls using the Time Perception Application version 1.0 (Barkley, University of Massachusetts Medical Center, 1998). Results revealed that the ADHD children made significantly larger errors on Visual time reproduction tasks than the Controls, regardless of ADHD subtype or the presence of distractors. Furthermore, ADHD children were more likely to overestimate the shorter time intervals (0.5 and 2 s) and underestimate the longer time intervals (3, 4 and 6 s) relative to Controls. No group differences were observed on the auditory time reproduction task, with both ADHD and Control groups consistently underestimating the durations to be reproduced. The results of this study provide further support for the prediction that children with ADHD have an impaired sense of time.

Acoustic Stimulation↗
PubMed2000

Room number six.

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype.

Breast cancer risk has been hypothesized to increase with exposure to heterocyclic aromatic amines (HAAs) formed from cooking meat at high temperature. HAAs require enzymatic activation to bind to DNA and initiate carcinogenesis. N-acetyltransferase 2 (NAT2) enzyme activity may play a role, its rate determined by a polymorphic gene. We examined the effect of NAT2 genetic polymorphisms on breast cancer risk from exposure to meat by cooking method, doneness and estimated HAA [2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)] intake. Women were recruited with suspicious breast masses and questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses. For 114 cases with breast cancer and 280 controls with benign breast disease, NAT2 genotype was determined using allele-specific PCR amplification to detect slow acetylator mutations. HAAs were estimated from interview data on meat type, cooking method and doneness, combined with a quantitative HAA database. Logistic regression models controlled for known risk factors, first including all controls, then 108 with no or low risk (normal breast or no hyperplasia) and finally 149 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Meat effects were examined within NAT2 strata to assess interactions. We found no association between NAT2 and breast cancer. These Californian women ate more white than red meat (control median 46 versus 8 g/day). There were no significant associations of breast cancer with red meat for any doneness. White meat was significantly protective (>67 versus <26 g/day, OR 0.46, 95% CI 0.23-0.94, P for trend = 0.02), as was chicken, including well done, pan fried and barbecued chicken. MeIQx and DiMeIQx were not associated with breast cancer. A protective effect of PhIP was confounded after controlling for well done chicken. Results were unchanged using low or high risk controls or dropping 30 in situ cases. There was no interaction between NAT2 and HAAs. These findings do not support a role for HAAs from meat or NAT2 in the etiology of breast cancer. Further research is needed to explain the white meat association.

Adult↗
PubMed2000

Transforming growth factor-beta type II receptors and smad proteins in follicular thyroid tumors.

OBJECTIVE: Resistance to transforming growth factor (TGF)-beta-mediated cell growth inhibition is a well-known pathogenic mechanism in epithelial neoplasia. TGF-beta signaling requires normal function of downstream mediators such as TGF-beta receptors (TbetaRs) and Smad proteins. The goal of this study is to investigate the expression of components of the TGF-beta signaling pathway in follicular tumors of the thyroid. STUDY DESIGN: Twenty follicular thyroid neoplasms were classified as adenomas (11) or minimally invasive follicular carcinomas (9) according to current pathological criteria. Protein expression was evaluated to identify differences between benign and malignant tumors that could be used as an adjunct to histopathological analysis. METHODS: Paraffin-embedded tissue sections containing tumor and adjacent nonneoplastic parenchyma were analyzed by immunohistochemistry for the expression of TbetaR type II (TbetaR-II) and Smad2, Smad4, Smad6, and Smad7. Expression of each protein in the tumor was compared with that of the corresponding adjacent nonneoplastic thyroid parenchyma. RESULTS: TbetaR-II expression was lost in 78% of the carcinomas. In the remaining 22%, TbetaR-II was preserved but Smad2 expression was lost. In all conventional adenomas, however, TbetaR-II expression was maintained. Furthermore, all tumors with normal expression of all proteins were adenomas. CONCLUSIONS: Downregulation of TbetaR-II is a consistent abnormality in follicular carcinomas and can be used to differentiate minimally invasive carcinomas from adenomas. Also, downregulation of Smad proteins is another mechanism by which carcinomas can become independent from TGF-beta-mediated growth inhibition.

Adenocarcinoma, Follicular↗
PubMed2000

A randomized controlled study of the use of transscleral diode laser and cryotherapy in the management of rhegmatogenous retinal detachment.

PURPOSE: Cryotherapy, the most common modality used to create a chorioretinal adhesion during retinal reattachment surgery, is associated with the dispersion of viable pigment epithelial cells and breakdown of the blood-ocular barrier, which are thought to be causative in a number of postoperative events, including macular pucker, proliferative vitreoretinopathy (PVR), and cystoid macular edema. Transscleral diode laser has been used successfully to create a chorioretinal adhesion in retinal reattachment surgery (diopexy) and experimentally has been shown to cause less pigment dispersion and blood-ocular barrier breakdown than cryotherapy. The authors carried out a prospective randomized study to compare the results and complication rates of transscleral diopexy with those of cryopexy during surgery for rhegmatogenous retinal detachment (RRD). METHODS: Data from 120 patients with recent onset RRD without significant PVR who were suitable for scleral buckling surgery and randomized to treatment using diode laser or cryotherapy were analyzed. The primary outcome measure was reattachment at 6 months with one operation. Secondary outcome measures were pain and swelling on the first postoperative day, cystoid macular edema as assessed angiographically at 6 weeks, and visual acuity, macular epiretinal membrane, and pigment migration under the fovea at 3 months. RESULTS: There was no significant difference between the primary and secondary outcome measures between the two treatment groups, with a primary success rate of 83% in the diode group and 92% in the cryotherapy group. Pain and postoperative swelling on the first postoperative day were equivalent. Cystoid macular edema was angiographically present in 12% in the diode group and 14% in the cryotherapy group. Visual acuity of at least 20/40 was achieved in 54% of patients in both groups. The rate of PVR was 5% in the diode group and 3% in the cryotherapy group. CONCLUSION: In this study of patients with uncomplicated RD without significant preoperative PVR, the experimentally shown benefits of transscleral diode laser did not result in significant improvement in the results of reattachment surgery compared with cryotherapy.

Cryotherapy↗
PubMed2000

Detecting gene copy number fluctuations in tumor cells by microarray analysis of genomic representations.

In this work, we explore the use of representations in conjunction with DNA microarray technology to measure gene copy number changes in cancer. We demonstrate that arrays of DNA probes derived from low-complexity representations can be used to detect amplifications, deletions, and polymorphic differences when hybridized to representations of genomic DNA. The method is both reproducible and verifiable, and is applicable even to microscopic amounts of primary tumors. We also present a mathematical model for array performance that is useful for designing and understanding DNA microarray hybridization protocols. The future applications and challenges of this approach are discussed.

Breast Neoplasms↗
PubMed2000

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone.

OBJECTIVE: The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. DESIGN: The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. PROCEDURE: Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. RESULTS: Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. CONCLUSIONS: Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.

Administration, Oral↗
PubMed2000

The nurse practitioner endoscopist.

Most upper and lower gastrointestinal endoscopies in Great Britain and Ireland are performed by surgeons, physicians or radiologists. Since the introduction of the 'nurse endoscopist' by the British Society of Gastroenterology Working Party, few centres in the UK have adopted this policy. We have reviewed the anxiety about nurse practitioner endoscopists among patients and physicians. Finally, the role and future of the nurse practitioner endoscopist in the UK is discussed.

Attitude of Health Personnel↗
PubMed2000

Recombinant VIIa concentrate in the management of bleeding following prothrombin complex concentrate-related myocardial infarction in patients with haemophilia and inhibitors.

Prothrombin complex concentrates (PCCs) and, more recently, activated prothrombin complex concentrates (APCCs), are widely used for the treatment of active bleeding in haemophiliacs with inhibitors. Myocardial infarction (MI), associated with the use of these concentrates, is a well-recognized, but uncommon, complication. We review the 14 previous cases published in the literature and describe two additional patients. MI related to the use of activated and non-activated PCCs predominantly affects young patients who often have no preceding history of, or risk factors for, MI and tends to be associated with large cumulative doses of concentrate. The most frequent pathological finding is myocardial haemorrhage, with no evidence of coronary artery atheroma or thrombosis. The management of further bleeding in these patients is difficult. We have safely used recombinant factor VIIa to treat bleeding in the immediate and long-term period following PCC-related MI.

Abdomen↗
PubMed2000

The impact of open access flexible sigmoidoscopy: a comparison of two services.

BACKGROUND: Open access flexible sigmoidoscopy (OAFS) is an integral part of colorectal cancer services. This study compares the impact of two types of open-access flexible sigmoidoscopy services on the utilisation of barium enema and tumour-stage migration. METHODS: This was a non-randomised comparison (over two one-year periods, four years apart) of two unselected groups of patients, with different inclusion criteria, in adjacent similarly populated health districts. One offered a nurse practitioner endoscopy service while the other had a doctor-led colorectal clinic. RESULTS: The doctor-led service with its broad inclusion criteria detected more colorectal cancers [13.2% versus 0.7%; OR = 16.05; 2.16-119.2]. Neither nurse practitioner (130 cases) nor doctor-led (262 cases) flexible sigmoidoscopy reduced the total number of barium enemas [Odds Ratio (OR) = 1.16 (95% CI 1.03-1.3)]. However, the doctor-led service did reduce the number of barium enemas requested by general practitioners (from 249 to 152). The total number of colorectal cancers (detected by all available methods) were similar [OR = 0.82 (0.53-1.25)] and both services resulted in a similar tumour-stage migration [OR = 1.39 (0.31-6.23)]. CONCLUSION: Open access flexible sigmoidoscopy services have minimal impact on the utilisation of radiology services. Broader inclusion criteria of doctor-led services produce a higher cancer-yield. Tumour-stage migration may be related to greater awareness of colorectal cancer symptoms rather than to the type of OAFS.

Barium Sulfate↗
PubMed1999

Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA-1 erythroid transcription factor.

We investigate here the effects of the incorporation of the nucleoside analogs araC (1-beta-D-arabinofuranosylcytosine) and ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl] guanine) into the DNA binding recognition sequence for the GATA-1 erythroid transcription factor. A 10-fold decrease in binding affinity was observed for the ganciclovir-substituted DNA complex in comparison to an unmodified DNA of the same sequence composition. AraC substitution did not result in any changes in binding affinity. 1H-15N HSQC and NOESY NMR experiments revealed a number of chemical shift changes in both DNA and protein in the ganciclovir-modified DNA-protein complex when compared to the unmodified DNA-protein complex. These changes in chemical shift and binding affinity suggest a change in the binding mode of the complex when ganciclovir is incorporated into the GATA DNA binding site.

Animals↗
PubMed1999

Improved survival following massive transfusion in patients who have undergone trauma.

HYPOTHESIS: Survival following massive transfusion in patients who have undergone trauma has improved during the past 10 years. DESIGN: Retrospective cohort study. SETTING: Academic level I trauma center in an urban community. PATIENTS: All patients who underwent trauma and who received greater than 50 U of packed red blood cells or whole blood in the 48 hours following admission to the emergency department. INTERVENTIONS: Data were obtained from blood bank records, the trauma registry, patient medical records, and hospital purchasing records. Patients were divided into 2 groups for comparison (early [1988-1992] and late [1993-1997] periods). MAIN OUTCOME MEASURES: Survival and changes in trauma care provision. RESULTS: Survival following massive transfusion in patients who have undergone trauma has significantly increased during the past 10 years (16% vs 45%, early vs late period, P = .03). Factors associated with poor outcome included male sex, major vascular injury, high Injury Severity Score, severe acidosis, prolonged hypotension, refractory hypothermia, and decreased use of platelet transfusion (all P<.05). In the later period, there was more aggressive correction of coagulopathy, more efficient use of warming measures, decreased operative times for the initial operation, and increased use of component therapy (all P<.05). CONCLUSIONS: Survival following massive transfusion has significantly (P = .03) increased during the past 10 years. Factors that may have contributed to this include more effective and efficient rewarming procedures, improved application of damage control techniques, more aggressive correction of coagulopathy, and improved blood banking procedures.

Adult↗
PubMed1999

Assessment of immune response to meningococcal disease: comparison of a whole-blood assay and the serum bactericidal assay.

A whole-blood assay (WBA), which assesses the complete bactericidal activity of blood, was compared with the serum bactericidal assay (SBA), which measures antibody and complement mediated cell lysis. Twenty children infected with serogroup B strains and 25 infected with serogroup C strains were studied 8-12 weeks after disease, and 29 healthy children were used as controls. The infecting strain (convalescent children only) and two reference strains, MC58 (B:15:P1.7, 16) and NCTC 8554 (C:NT:P1.5) were used. In children previously infected with a serogroup B strain, bactericidal activity was detected in 95% and 85% to their infecting strain by the WBA (>50% killing) and the SBA (s), respectively. Bactericidal activity to the reference serogroup B and C strain was detected by WBA in 70 and 75% of children, respectively, and the SBA in 45% and 20%. In contrast bactericidal activity was detected to both serogroup C strains in >80% of children previously infected with a serogroup C strain using either assay and in 48% (WBA) and 20% (SBA) to the reference serogroup B strain. Levels of bactericidal activity were detectable in fewer control children. Children convalescing from meningococcal disease develop an immune response to their infecting strain, detectable by both the WBA and SBA, which is independent of age. However, the WBA appears to be a more sensitive measure of bactericidal activity to heterologous strains than the SBA.

Adolescent↗
PubMed1999

Adjuvant dose-intense chemotherapy with peripheral blood stem cell support in stage II-III breast cancer with five to nine involved axillary lymph nodes.

The purpose of this study is to determine outcomes for patients with high-risk nonmetastatic breast cancer undergoing high-dose chemotherapy with peripheral blood stem cell support. Forty-three patients with stage II-III disease, five to nine positive axillary lymph nodes, and a median age of 44 years (range, 27-60 years) were enrolled in a study that included: 1) standard dose doxorubicin, 5-fluorouracil, and methotrexate adjuvant therapy; 2) cyclophosphamide, etoposide, filgrastim, and peripheral blood stem cell harvest; and 3) high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion. All 43 patients received doxorubicin, 5-fluorouracil, and methotrexate, 42 (98%) received etoposide, and 41 (95%) received CTCb. Thirty-two patients (74%) are alive, 28 (65%) without relapse at a median of 55 months (range, 41-87 months). Two died (5%) of treatment-related causes, (subclavian catheter complication after etoposide and late radiation pneumonitis), and nine other deaths (21%) were associated with recurrent breast cancer. The probabilities of overall and event-free survival at 4 years were 0.77 and 0.67, respectively, compared with 0.82 and 0.69, respectively, for 72 similar patients with 10 or more positive axillary nodes receiving the same sequence of therapy. Thus, patients with five to nine positive axillary lymph nodes have a similar risk of failure after high-dose chemotherapy and peripheral blood stem cell support as patients with 10 or more positive axillary lymph nodes.

Adult↗
PubMed1999

Retrospective intermodality registration techniques for images of the head: surface-based versus volume-based.

The primary objective of this study is to perform a blinded evaluation of two groups of retrospective image registration techniques, using as a gold standard a prospective marker-based registration method, and to compare the performance of one group with the other. These techniques have already been evaluated individually [27]. In this paper, however, we find that by grouping the techniques as volume based or surface based, we can make some interesting conclusions which were not visible in the earlier study. In order to ensure blindness, all retrospective registrations were performed by participants who had no knowledge of the gold-standard results until after their results had been submitted. Image volumes of three modalities: X-ray computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) were obtained from patients undergoing neurosurgery at Vanderbilt University Medical Center on whom bone-implanted fiducial markers were mounted. These volumes had all traces of the markers removed and were provided via the Internet to project collaborators outside Vanderbilt, who then performed retrospective registrations on the volumes, calculating transformations from CT to MR and/or from PET to MR. These investigators communicated their transformations, again via the Internet, to Vanderbilt, where the accuracy of each registration was evaluated. In this evaluation, the accuracy is measured at multiple volumes of interest (VOI's). Our results indicate that the volume-based techniques in this study tended to give substantially more accurate and reliable results than the surface-based ones for the CT-to-MR registration tasks, and slightly more accurate results for the PET-to-MR tasks. Analysis of these results revealed that the rotational component of error was more pronounced for the surface-based group. It was also apparent that all of the registration techniques we examined have the potential to produce satisfactory results much of the time, but that visual inspection is necessary to guard against large errors.

Algorithms↗
PubMed1999

Differential patterns of executive function in children with attention-deficit hyperactivity disorder according to gender and subtype.

The present investigation examined differential patterns in executive functions of children with attention-deficit hyperactivity disorder (ADHD; no diagnosed comorbid disorders) according to subtype and gender, and identified instrumentation sensitive to executive function in children aged 6 to 12 years with ADHD. Data were obtained from 94 children diagnosed with ADHD (predominantly inattentive, n = 32, ADHD combined, n = 62), and from 28 controls. Participants with ADHD, who were unmedicated at the time of testing, were administered five tests of executive function (the Wisconsin Card Sorting Test, the Stroop Color-Word Test, the Matching Familiar Figures Test, the Trail Making Test, and the Tower of London). A two-way multivariate analysis of covariance with age as the covariate and subtype and gender as the independent variables was conducted on all of the tests administered. While children with ADHD predominantly inattentive and those with ADHD combined differed from controls, it was only the latter subtype that differed significantly in perseveration and response inhibition. The absence of diagnosed comorbidity in the children with ADHD at the time of test administration demonstrates that the impairments in executive function are clearly located in ADHD, particularly in the ADHD combined subtype, thus providing support for Barkley's proposed unifying theory of ADHD.

Attention Deficit Disorder with Hyperactivity↗