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C Brown

Publications and source records attributed to C Brown.

At least 109 records · Page 6Linked to original sources
PubMed2000

Prefrontal regions play a predominant role in imposing an attentional 'set': evidence from fMRI.

fMRI was used to determine whether prefrontal regions play a predominant role in imposing an attentional 'set' that drives selection of task-relevant information. While monitoring for an atypical item, individuals viewed Stroop stimuli that were either colored words or colored objects. Attentional demands were varied, being greater when the stimuli contained two distinct and incongruent sources of information about the task-relevant attribute (e.g., when attending to color, seeing the word 'blue' in red ink) as compared to only one source (e.g., seeing the word 'late' in red ink). Prefrontal but not anterior cingulate regions exhibited greater activation on incongruent than neutral trials, suggesting that prefrontal cortex has a major role in imposing an attentional 'set'. In addition, we found that prefrontal activation is most likely to occur when that attentional set is difficult to impose.

Attention↗
PubMed2000

Early outcomes after allogeneic stem cell transplantation for leukemia and myelodysplasia without protective isolation: a 10-year experience.

Although it is common practice to use some form of isolation to protect allogeneic stem cell transplant patients from infection, the necessity for these practices in all environments has not been demonstrated. The current study evaluated patterns of infection and 100-day transplant-related mortality in 288 patients with myelodysplasia and leukemia transplanted without isolation. Patients were allowed out of hospital at any time within constraints of the medication schedule. Fever, foci of infection, and positive cultures within 28 days and death within 100 days because of the transplant procedure were recorded. Fever occurred in 57% of patients, and 10% had a clinical or radiographic focus of infection. Most infections were apparently endogenous; blood cultures from 24% of recipients grew organisms, 87% of which were gram-positive bacteria. Four patients (1%) died with aspergillus infection in circumstances indicating that isolation would not have been helpful. Twenty percent of patients remained without evidence of infection throughout. Transplant-related mortality at 100 days was 1% for 108 patients with early leukemia receiving transplants from matched siblings. For patients at higher risk, by virtue of donor and/or disease status, mortality was 21%. These figures compare favorably with those reported to the International Bone Marrow Transplant Registry, the majority of patients having been subjected to some form of isolation. We conclude that allogeneic stem cell transplantation can be safely performed in some environments without confining patients continuously to the hospital.

Adolescent↗
PubMed2000

The isolation and characterisation of human monoclonal HLA-A2 antibodies from an immune V gene phage display library.

Molecular cloning techniques and V gene phage display have revolutionised the production of human monoclonal antibodies. Antibodies of a defined specificity can be obtained by selecting phage display libraries on antigen in a process known as panning. We have applied these techniques to the isolation of three HLA-A2-specific single chain variable domain fragments (scFv) from a patient alloimmunised by blood transfusion. Analysis of specificity with cells of HLA genotyped donors revealed the following: i) in addition to the major reactivity with HLA-A2, cross-reactivity with the HLA-A28 epitope; and ii) inhibition of scFv binding to the antigen by the patients' antibodies. The heavy chain variable genes of all three were derived from the germline gene Cos-3, carry the hallmarks of somatic hypermutation, and are most likely derived from clonally related B cells. The light chain variable domains were encoded by DPK1 and DPK8 from the VkappaI family. These data show that phage display can be used to clone HLA-specific alloantibodies that recognise the native antigen from alloimmunised patients.

Amino Acid Sequence↗
PubMed2000

An approach to the control of disease transmission in pig-to-human xenotransplantation.

Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ-source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ-source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved.

Animals↗
PubMed2000

Identification of the familial cylindromatosis tumour-suppressor gene.

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

Amino Acid Sequence↗
PubMed2000

The CD34+90+ cell dose does not predict early engraftment of autologous blood stem cells as well as the total CD34+ cell dose.

CD90 or Thy-1 is an antigen co-expressed with CD34+ on putative immature hematopoietic stem cells. Peak mobilization of CD34+90+ cells into the blood occurs a few days earlier than peak mobilization of total CD34+ cells. Because it is not known which cell type best correlates with engraftment, the optimal timing of apheresis remains unclear. The purpose of the study was to determine if the CD34+90+ cell dose predicts engraftment of autologous blood stem cells independent of the total CD34+ cell dose/kg, the dose of other CD34+ cell subsets (CD34+33-, CD34+38-, CD34+41+), or various clinical factors. Data were analyzed on 125 consecutive patients ranging in age from 19 to 66 years (median 46) who underwent autologous blood stem cell transplantation (ABSCT) for breast cancer (54), lymphoma (59), or other malignancies (12). By univariate analysis, neutrophil (> or = 0.5 x 10(9)/l) and platelet (> or = 20 x 10(9)/l or > or = 100 x 10(9)/l) engraftment correlated better with the total CD34+ cell dose than with the CD34+90+ cell subset. Using Cox proportional hazards models, factors independently associated with both neutrophil engraftment (> or = 0.5 x 10(9)/l) and platelet engraftment (> or = 20 x 10(9)/l and > or = 100 x 10(9)/l) were higher total CD34+ dose/kg and high-dose regimen (melphalan-containing slower than other regimens). In conclusion, the total CD34+ dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34+ subset, including CD34+90+ cells. Apheresis should continue to be timed according to peak CD34+ levels.

Adult↗
PubMed2000

Laparoscopic appendectomy for simple and perforated appendicitis in children: the procedure of choice?

BACKGROUND/PURPOSE: Whether laparoscopic appendectomy (LA) is superior to open appendectomy (OA) for simple (SA) and perforated appendicitis (PA) in children is debatable. The operative experience of 4 senior pediatric surgeons at a single institution was studied over a 6-year period during a transition from OA in all cases to LA in all cases, to answer this question. METHODS: All appendectomies from December 1993 to December 1999 were reviewed for operative technique (OA, LA), presence of perforation (SA, PA), operating time (OT), length of stay (LOS), morbidity, and mortality. RESULTS: There were 1,128 appendectomies in children aged 14 months to 19 years, including 955 LA (653 in SA, 302 in PA) and 173 OA (86 in SA, 87 in PA). OT was equal for LA and OA in SA (52 minutes), but has dropped to less than 40 minutes for LA in the past year. OT in PA was slightly longer in LA versus OA (68 v. 58 minutes; P < .001) but recently has dropped in LA to less than 60 minutes. LOS in SA was 2 days for LA and 3 days for OA; in PA, LOS was 7 days in both LA and OA, but has dropped to 5 days for LA recently. Postoperative abscess rates and incidence of bowel obstruction did not differ between LA and OA in either group. There was no mortality. CONCLUSIONS: LA is at least as safe and effective as, if not superior to, OA for both simple and perforated appendicitis. Postoperative pain is less, and recovery is faster, thereby reducing LOS and overall cost. The growing demand for this procedure can be satisfied without increase in cost, morbidity, or mortality. Laparoscopic appendectomy is our procedure of choice in children.

Acute Disease↗
PubMed2000

The burden of alcohol misuse on an inner-city general hospital.

Alcohol consumption in the UK has been increasing steadily. We prospectively studied the burden on hospital services caused by overt alcohol misuse, in an inner-city hospital in north-west England. All Accident & Emergency (A&E) patients were assessed to determine whether their hospital attendance was alcohol-related, and whether this resulted in admission and/or generated new out-patient appointments. Over 2 months, 1915 patients attended A&E with alcohol-related problems, accounting for 12% of attendances; 50% were aged 18-39 years, and acute alcohol intoxication was the commonest presenting complaint. Overall, 6.2% of all hospital admissions were due to alcohol-related problems. Over 2800 new out-patient visits were likely to have been generated over an 18-month period from initial attendance with an alcohol-related problem, mostly for orthopaedic clinics. The burden placed by overt alcohol-related problems on hospitals is enormous, both in terms of the emergency and out-patient services. The implementation of education, screening and intervention strategies in A&E departments, and employment of key trained personnel, should be considered, to optimize the clinical management of these patients.

Adolescent↗
PubMed2000

Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer.

To determine the sensitivity, specificity, and accuracy of staging mediastinal nodal disease in potentially resectable lung cancer using fluorodeoxyglucose-positron emission tomography (FDG-PET), computed tomography (CT), or both and compare these results to surgical staging. We also assessed whether PET scanning results changed clinical management. From 1992 to 1997, 50 patients underwent CT, and PET scanning before or close to the time of surgical staging. Sensitivity, specificity, accuracy, and predictive values were then calculated based on pathology results. A retrospective review of the records was performed to determine how PET results affected clinical treatment decisions. Forty-seven of 50 patients had non-small-cell lung cancer. The prevalence of pathologically confirmed mediastinal and hilar involvement was 38%. The sensitivity, specificity, and accuracy of mediastinal disease staging were as follows: CT alone = 73%, 77%, 76%; PET alone = 73%, 94%, 87%; PET + CT = 82%, 96%, 91%, respectively. PET was more specific and accurate than CT (p = 0.025). The results of PET changed management decisions in 12 of 50 cases (24%). Using FDG-PET in conjunction with CT scanning provides the most accurate staging of mediastinal disease in lung cancer by contributing complementary information. Furthermore, PET can affect clinical decision-making and allow some patients considered unresectable a chance for resection.

Adult↗
PubMed2000

Vaginal yeasts in the era of "over the counter" antifungals.

OBJECTIVE: To establish whether there has been any rise in the prevalence of non-albicans Candida species isolated from vaginal swabs since the introduction of "over the counter" antifungal treatments. METHOD: A retrospective review looking at all positive vaginal yeast isolates collected from women attending one genitourinary medicine clinic during the 6 year period from 1993 to 1998 inclusive. All positive vaginal yeast isolates were included, regardless of whether or not the patients were symptomatic. Isolates from HIV positive women were excluded from the analysis. RESULTS: No increase in non-albicans vaginal yeast isolates was shown during the period studied. The proportion of non-albicans yeasts remained constant at approximately 5% of the total yeasts isolated. The most common non-albicans yeast isolated was C glabrata. CONCLUSION: There is no evidence from this study to suggest that the increasing use of "over the counter" antifungal treatment has selected for atypical, possibly inherently azole resistant, strains of vaginal yeasts in HIV seronegative women.

Antifungal Agents↗
PubMed2000

A genome-wide search for susceptibility loci to human essential hypertension.

We undertook a systematic search of the entire human genome with the affected sibling-pair model to identify major susceptibility loci to essential hypertension. Affected nuclear families (n=263) were recruited and divided according to definite or probable genetic contribution to hypertension depending on number of hypertensive siblings. The largest nuclear families were first screened with a set of microsatellite markers. Regions on the genome with P<0.05 were tested against the second set of smaller families. An exclusion map was generated to identify regions in which hypertension-causing genes are unlikely to reside. Sibling-pair linkage analysis identified a single locus on chromosome 11q (P<0.004) in the first pass. A second pass with nuclear families that had only affected sibling pairs was, as expected, insufficient to support linkage to 11q. Multipoint exclusion-linkage analysis showed that 3 genetic loci are necessary to explain familial aggregation of essential hypertension. Our preliminary findings suggest that no single region within the human genome contains genes with a major contribution to essential hypertension. We show that the disease is indeed polygenic, with each gene providing a relatively small risk. Our exclusion map will help future investigators to concentrate on areas likely to contain these genes. The region on chromosome 11 is the first to point to a new candidate gene for hypertension that has arisen out of a genome search, but replication of these results at a higher significance is necessary before positional cloning can be justified.

Aged↗
PubMed2000

Attempted eradication of salmonellosis from a colony of short-tail grey opossums (Monodelphis domestica).

Prior to re-housing a colony of laboratory short-tail grey opossums, the animals were found to harbour salmonella. This paper describes an unsuccessful attempt to eradicate the infection from the colony by means of antibiotic treatment and hygienic measures. A pilot treatment of five animals which received enrofloxacin 10 mg/kg for 5 days appeared to be successful in that no salmonellae were recovered from faeces or organs sampled after treatment. The process was repeated on the whole colony prior to a change of accommodation but 2 animals were found to be still infected, 5 weeks after cessation of treatment.

Animals↗
PubMed2000

The association between depressive symptoms and cigarette smoking in an urban primary care sample.

OBJECTIVE: To examine the relationship between cigarette smoking and depressive symptoms in an urban primary care sample. METHODS: Eligible participants were 526 patients aged eighteen to sixty-four presenting in the waiting rooms of two university affiliated internal medicine clinics. Participants were asked to complete a brief interview which ascertained current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D), demographic information, and smoking status using a modified version of the Fagerstrom Test for Nicotine Dependence (FTND). RESULTS: Smoking status differed significantly by age, gender, education, and employment status. Mean level of depressive severity also differed by smoking status. Current smokers with nicotine dependence symptoms had significantly higher CES-D scores than those who had never smoked, ex-smokers, and non-dependent smokers. Logistic regression analyses indicated that gender, employment status, age, and smoking status were significantly associated with CES-D scores > or = 16. Exploratory analyses suggested that among smokers with a symptom of nicotine dependence, significantly more women than men had clinically significant levels of depressive symptoms. CONCLUSIONS: The association between smoking behavior and depressive symptoms in the present study is consistent with that reported in population-based and psychiatric samples. Symptoms of nicotine dependence were significantly associated with clinical levels of depressive symptoms. Primary care physicians may wish to inquire about depressive symptoms among smokers, because these symptoms may interfere with patients' efforts to quit.

Adolescent↗
PubMed2000

Opioid and benzodiazepine withdrawal syndrome in adult burn patients.

The prolonged use of continuous intravenous sedation [benzodiazepines (BZDs)] and pain medication [opioids (OPs)] is now common in intensive care units. Few studies have evaluated the characteristics that may lead to an acute withdrawal syndrome when these long-term medications are withdrawn. Those studies that have made recommendations for weaning rates to prevent withdrawal have given these recommendations with minimal data to support their recommendations. The purpose of this study was to retrospectively review the records of adult burn patients for the presence of acute BZD or OP withdrawal syndrome and to characterize whether patterns of BZD or OP administration or weaning rates contribute to the development of acute withdrawal syndrome. We found no relation of acute withdrawal syndrome to peak dose, total dose, or duration of dose of BZD/OP before the terminal withdrawal phase. There was a significant relationship between the rate of BZD/OP weaning in the terminal drug withdrawal phase and the percentage of days that patients experienced withdrawal symptoms (P < 0.005). Those patients who underwent a prolonged terminal weaning from these medications experienced fewer symptoms. The optimal rate of weaning that would allow decreased ventilator and intensive care unit length of stay without development of acute withdrawal symptoms is yet to be determined.

Adult↗
PubMed2000

Daily smoking by Louisiana students: sixth through twelfth grades, 1996-1997.

OBJECTIVES: We sought to determine the prevalence of daily smoking in Louisiana in grades 6 through 12 and to compare Louisiana students' daily smoking to that of national student and Louisiana adult rates. METHODS: A statewide, randomized, stratified classroom-based survey of 11,736 subjects was done for the school year 1996-1997. RESULTS: We found that 17.3% of sixth grade students smoked daily, increasing to 36.1% in twelfth grade. Native American (43.7%), white (37.8%), and public school (28.5%) students had the highest rates of daily smoking. Males and females smoked at similar rates. Louisiana students in grades 8, 10, and 12 smoked daily at much higher rates (331%, 193%, and 146%, respectively) than comparable national samples. In 1997, Louisiana students smoked daily at higher rates than did Louisiana adults (28.9% vs 24.6%), primarily due to higher rates of smoking in student females (27.1%) compared to adult females (20.4%). CONCLUSIONS: Student smoking in Louisiana is a significant public health problem.

Adolescent↗