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Biomedical subjects

D Barrett

Publications and source records attributed to D Barrett.

At least 37 records · Page 2Linked to original sources
PubMed2000

Occupational physical activities and osteoarthritis of the knee.

OBJECTIVE: To assess the risk of knee osteoarthritis (OA) associated with kneeling, squatting, and other occupational activities. METHODS: We compared 518 patients who were listed for surgical treatment of knee OA and an equal number of control subjects from the same communities who were matched for sex and age. Histories of knee injury and occupational activities were ascertained at interview, height and weight were measured, and the hands were examined for Heberden's nodes. Data were analyzed by conditional logistic regression. RESULTS: After adjustment for body mass index (BMI), history of knee injury, and the presence of Heberden's nodes, risk was elevated in subjects who reported prolonged kneeling or squatting (odds ratio [OR] 1.9; 95% confidence interval [95% CI] 1.3-2.8), walking >2 miles/day (OR 1.9; 95% CI 1.4-2.8), and regularly lifting weights of at least 25 kg (OR 1.7; 95% CI 1.2-2.6) in the course of their work. The risks associated with kneeling and squatting were higher in subjects who also reported occupational lifting, and appeared to interact multiplicatively with the risk conferred by obesity. People with a BMI of > or =30 kg/m2 whose work had entailed prolonged kneeling or squatting had an OR of 14.7 (95% CI 7.2-30.2), compared with subjects with a BMI <25 kg/m2 who were not exposed to occupational kneeling or squatting. CONCLUSION: There is now strong evidence for an occupational hazard of knee OA resulting from prolonged kneeling and squatting. One approach to reducing this risk may lie in the avoidance of obesity in people who perform this sort of work.

Aged↗
PubMed2000

Burkitt lymphoma is immunophenotypically different from Burkitt-like lymphoma in young persons.

INTRODUCTION: Burkitt-like lymphoma (BLL) is a provisional category of B-cell lymphoma which is morphologically intermediate between Burkitt lymphoma (BL) and large B-cell lymphoma (LBCL). The clinical significance of this morphology is controversial. PATIENTS AND METHODS: We examined 41 cases of pediatric B-cell lymphoma by immunohistochemistry for proteins associated with proto-oncogenes c-myc, BCL-2 and BCL-6 and a subset of cases (with adequate slides) for a proliferation-associated marker (Ki-67) and for apoptosis (Apop-Tag). Sixteen cases of BLL, thirteen cases of BL and twelve cases of LBCL were examined. RESULTS: Our results showed BCL-6 expression in 16 of 16 BLL, 4 of 13 BL, and 9 of 12 LBCL; c-myc expression in 14 of 15 BLL, 9 of 13 BL, and 12 of 12 LBCL; and BCL-2 expression in 2 of 16 BLL, 9 of 13 BL, and 6 of 12 LBCL. Mean apoptotic index for BLL was 10.3% (n = 6); for BL was 17.1% (n = 5); and for LBCL was 10.9% (n = 6). Ki-67 was diffusely reactive in all cases tested. There was a significantly higher proportion of BLL than BL which expressed BCL-6 (P = 0.0001). CONCLUSIONS: Labeling for BCL-6 distinguishes BLL from BL. It is likely that in children in North America, BLL is biologically distinct from BL and more closely resembles a subset of LBCL.

Adolescent↗
PubMed2000

30-year retrospective review of frontal sinus fractures: The Charity Hospital experience.

BACKGROUND AND OBJECTIVES: The optimal method of treating frontal sinus fractures has remained undetermined. The purpose of this retrospective review is to compare the mechanism of injury, diagnostic techniques, methods of fracture management, complications, and long-term results in different types of frontal sinus fractures. METHODS AND MATERIALS: Over 4,000 records of patients with frontal bone or skull fractures, treated during a 30-year period in an academic nonprofit tertiary Level I trauma center, were considered. From these, the authors selected 150 patients with frontal sinus fractures--with complete records and adequate follow-up time--and conducted a retrospective review. RESULTS AND/OR CONCLUSIONS: For anterior fractures, observation alone had a high rate of complications (18.2%). Reconstruction with obstruction of the nasofrontal ostia by vascularized tissue was found to be the best treatment, followed by osteogenesis (9.1%) or obliteration (7.7%). Cranialization was the safest form of management for posterior table fractures that were either comminuted or involved the nasofrontal ostia. The preferred obliteration materials were vascularized flaps, cancellous bone, temporalis muscle, and fat; hydroxyapatite cement was a good alloplastic alternative.

Adolescent↗
PubMed1999

Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems. Part III: Novel 2-alkyl substituents containing cationic heteroaromatics linked via a C-N bond.

The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 (1c), containing a two methylene spacer moiety and an imidazolio group, which possesses a balanced spectrum of antibacterial activity, including Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, FR20950 exhibited excellent urinary recovery, and comparable stability against renal dehydropeptidase-I (DHP-I) to Biapenem. DHP-I stability could be improved by introduction of a substituent on to the imidazole ring.

Animals↗
PubMed1999

Studies on anti-Helicobacter pylori agents. Part 1: Benzyloxyisoquinoline derivatives.

The synthesis and optimization of the anti-Helicobacter pylori activity of a novel series of benzyloxyisoquinoline derivatives that was discovered by a random screening process, are described. In the in vitro assay, compound 10c containing a 3-acetamido-2,6-dichlorobenzyl substituent was found to have extremely potent activity against H. pylori and no activity against other common bacteria. The anti-H. pylori activity of 10c was superior to that of amoxicillin (AMPC) (1) and clarithromycin (CAM) (2). However, 10c did not show in vivo efficacy in a mouse infection model; a feature attributed to the lack of strong bactericidal activity at short contact times.

Amoxicillin↗
PubMed1999

Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy. EuroMap Study Group.

We studied the association between acetaminophen exposure during pregnancy and the prevalence of congenital abnormalities and fetal growth. Our study included 123 women who had received a prescription of acetaminophen during pregnancy and/or 30 days before conception and 13,329 controls who did not receive any prescription at all. We found more malformations among those who received a prescription with an odds ratio of 2.3 (95% CI 1.0-5.4), but the type of malformations did not indicate a causal link. When restricting the study to first time pregnancies, we identified 58 women who received a prescription of acetaminophen during pregnancy and 30 days before conception and 7472 controls. We found no excess risk of malformation [OR = 0.7 (95% CI 0.1-5.5)], and no evidence that acetaminophen should influence fetal growth.

Abnormalities, Drug-Induced↗
PubMed1998

Discovery of a novel benzyloxyisoquinoline derivative with potent anti-Helicobacter pylori activity.

The synthesis and in vitro optimization of the anti-Helicobacter pylori activity of a novel series of benzyloxyisoquinoline derivatives discovered by a random screening process, are described. FR180102 (7f), having a 3-acetamido-2,6-dichlorobenzyl moiety, was found to have extremely potent activity against H. pylori and no effect against a series of common Gram-positive and Gram-negative bacteria.

Acetamides↗
PubMed1998

Confidential inquiry into quality of care before admission to intensive care.

OBJECTIVE: To examine the prevalence, nature, causes, and consequences of suboptimal care before admission to intensive care units, and to suggest possible solutions. DESIGN: Prospective confidential inquiry on the basis of structured interviews and questionnaires. SETTING: A large district general hospital and a teaching hospital. SUBJECTS: A cohort of 100 consecutive adult emergency admissions, 50 in each centre. MAIN OUTCOME MEASURES: Opinions of two external assessors on quality of care especially recognition, investigation, monitoring, and management of abnormalities of airway, breathing, and circulation, and oxygen therapy and monitoring. RESULTS: Assessors agreed that 20 patients were well managed (group 1) and 54 patients received suboptimal care (group 2). Assessors disagreed on quality of management of 26 patients (group 3). The casemix and severity of illness, defined by the acute physiology and chronic health evaluation (APACHE II) score, were similar between centres and the three groups. In groups 1, 2, and 3 intensive care mortalities were 5 (25%), 26 (48%), and 6 (23%) respectively (P=0.04) (group 1 versus group 2, P=0.07). Hospital mortalities were 7 (35%), 30 (56%), and 8 (31%) (P=0.07) and standardised hospital mortality ratios (95% confidence intervals) were 1.23 (0.49 to 2.54), 1.4 (0.94 to 2.0), and 1.26 (0.54 to 2.48) respectively. Admission to intensive care was considered late in 37 (69%) patients in group 2. Overall, a minimum of 4.5% and a maximum of 41% of admissions were considered potentially avoidable. Suboptimal care contributed to morbidity or mortality in most instances. The main causes of suboptimal care were failure of organisation, lack of knowledge, failure to appreciate clinical urgency, lack of supervision, and failure to seek advice. CONCLUSIONS: The management of airway, breathing, and circulation, and oxygen therapy and monitoring in severely ill patients before admission to intensive care units may frequently be suboptimal. Major consequences may include increased morbidity and mortality and requirement for intensive care. Possible solutions include improved teaching, establishment of medical emergency teams, and widespread debate on the structure and process of acute care.

Adult↗
PubMed1998

Studies on the regulation of CTP:phosphocholine cytidylyltransferase using permeabilized HEP G2 cells: evidence that both active and inactive enzyme are membrane-bound.

To obtain more insight into the mechanisms regulating CTP:phosphocholine cytidylyltransferase (CT), we determined the effect of oleate treatment on the rate of CT release from permeabilized Hep G2 cells and the distribution of the CT remaining in the permeabilized cells. When we permeabilized untreated cells in pH 7.5 buffer containing 0.15 M KCl, the rate of CT release was much slower than the release of lactate dehydrogenase. Oleate treatment caused a further decrease in CT release from cells. In untreated cells, 70-80% of the CT remaining in cells 10 min after permeabilization was recovered as soluble CT. Oleate treatment increased the amount of bound CT but over 50% of the CT in cells 10 min after permeabilization was recovered as soluble CT. In both control and oleate-treated cells, the increase in CT release with time correlated with a decrease in the amount of CT recovered from permeabilized cells as soluble CT. These results suggested that CT existed in a form that was not immediately available for release from permeabilized cells, but was recovered in the soluble fraction after cell disruption. When cells were permeabilized in 10 mM imidazole-20% glycerol-5 mM Mg2+ pH 6.5, over 80% of CT in control and over 90% of CT in oleate-treated cells was recovered bound to the particulate fraction. Essentially no CT was released from the cells. The recovery of CT in the particulate fraction required Mg2+ to be present when permeabilization was initiated. The addition of Mg2+, after cells were disrupted, did not increase CT in the particulate fraction. In untreated cells, 50% of bound CT was active. Oleate treatment increased the amount of active CT in the particulate fraction to over 70% of total. About 50% of particulate CT in untreated cells but only 15% in oleate-treated cells was extracted with 0.15 M KCl. Inactive CT was preferentially extracted by KCl. The bound CT was recovered in isolated nuclei. Overall, the results suggested that both inactive and active CT are bound to nuclear membranes, and that the activation of CT involves conversion of CT loosely bound to membrane to a form more tightly bound to membranes perhaps by hydrophobic interaction with phospholipids. This model does not involve translocation from a soluble pool.

Biological Transport↗
PubMed1998

Aging and the immune response to tetanus toxoid: diminished frequency and level of cellular immune reactivity to antigenic stimulation.

The period of efficacious immune reactivity afforded by tetanus immunization and the need for continuing some forms of tetanus vaccination programs have been the subjects of recent debates. Our studies demonstrate that the level of antitetanus immunity based on immunological memory (i.e., cellular immune responsiveness) varies dramatically as a function of age, with older individuals constituting a population which is increasingly susceptible to tetanus infection.

Adolescent↗
PubMed1997

Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems--I. 2-Alkoxymethyl derivatives.

The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are described. As a result of these studies, we discovered that FR27743 (19j) containing a novel 2-fluoroethoxymethyl substituent possesses a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa. Furthermore, FR27743 exhibited excellent stability against renal dehydropeptidase-I (DHP-I), good urinary recovery, and superior in vivo activity compared to that for Meropenem against several systemic infections.

Animals↗
PubMed1997

Managing clinical integration in integrated delivery systems: a framework for action.

An integrated delivery system (IDS) in healthcare must coordinate patient care across multiple functions, activities, and operating units. To achieve this clinical integration, senior management confronts many challenges. This paper uses a cross-functional-process (CFP) framework to discuss these challenges. There are ten CFPs that fall into three categories: planning processes (strategy formulation, program adaptation, budget formulation), organizational processes (authority and influence, client management, conflict resolution, motivation, and cultural maintenance), and measurement and reporting processes (financial and programmatic). Each process typically spans several functional units. Senior management must consider how to improve both the functioning of each CFP, as well as its "fit" with the other nine. The result can be greater clinical integration, improved cost management, and more coordinated care for enrollees.

Budgets↗
PubMed1997

Use of an anti-ALK antibody in the characterization of anaplastic large-cell lymphoma of childhood.

BACKGROUND: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase inappropriately expressed in lymphoid tissue involved by CD30+ anaplastic large-cell lymphoma (ALCL) with the translocation t(2;5)(p23;q35)(, which juxtaposes the nucleophosmin gene (NPM) with that encoding ALK, resulting in a hybrid (NPM-ALK) message. PATIENTS AND METHODS: A polyclonal antibody against residues of the kinase portion of NPM-ALK (designated anti-ALK 11) was tested for clinical utility in paraffin sections of 44 cases of pediatric large-cell lymphoma (LCL) and 17 additional lymphoma cases, by streptavidin-biotin-alkaline phosphatase method. RESULTS: Nineteen of 20 CD30+ cases (the majority exhibiting anaplastic morphology) labeled with anti-ALK 11, and 5/28 CD30- cases were also ALK+ (3 T cells, 1 null cell, and 1 B cell). Sixteen of 17 B-cell pediatric LCLs were negative, as were 6/6 cases of Hodgkin's disease and 7/7 cases of adult B-cell lymphoma. In pediatric LCLs with adequate follow-up (24/44 ALK+), there was no significant association between ALK expression and two-year event-free survival, similar to the finding reported previously for CD30 expression in these cases. CONCLUSION: We conclude that the majority of pediatric CD30+ ALCLs show ALK overexpression, consistent with the presence of the t(2;5)-encoded NPM-ALK fusion, but that the clinical significance of this entity remains unproven.

Adult↗
PubMed1996

Prostate specific antigen detected prostate cancer (clinical stage T1c): an interim analysis.

PURPOSE: The majority of impalpable prostate cancers (state T1c) are biologically significant. We report the interim results in 257 patients with stage T1c prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: Prostate specific antigen progression-free survival was assessed by the Kaplan-Meier method. Multivariate analyses were performed to determine which clinical and pathological variables independently correlated with progression. Comparisons among the various clinical substages (T1a to T2b/c) were calculated. RESULTS: Of the patients with stage T1c cancers 51% had stage pT2c or less and 91% had clinically significant tumors on the basis of pathological grade, deoxyribonucleic acid ploidy and tumor volume. High preoperative prostate specific antigen, poorly differentiated tumors and nondiploid status were strong independent predictors of progression. The 5-year survival rate free of progression was 84%. Patients with clinical stage T1c cancers had a significant progression-free survival advantage compared to those with clinical stage T2b/c disease (p = 0.0005). CONCLUSIONS: Impalpable tumors should not be regarded as insignificant or innocuous on the basis of pathological analysis. Disease-free survival in the stage T1c group was similar to that in the clinical stages T1a to T2a group but significantly better than that in the T2b/c group.

Adult↗
PubMed1996

Partial reconstitution of the respiratory burst oxidase in lymphoblastoid B cell lines lacking p67-phox after transfection with an expression vector containing wild-type and mutant p67 -phox cDNAs: Deletions of the carboxy and amino terminal residues of p67-phox are not required for activity.

The respiratory burst oxidase of phagocytes and B lymphocytes in a multicomponent enzyme that catalyzes the reduction of oxygen by NADPH. It is responsible for O-(2) production in response to stimulation with phorbol 12-myristate 13-acetate (PMA). The study of patients with chronic granulomatous disease (CGD), an inherited disorder characterized by deficient of absent respiratory burst activity, has contributed greatly to our understanding of the NADPH-oxidase. The absence of any one of four components results in the clinical expression of CGD: the two membrane-bound components of the cytochrome b-558, gp91-phox and p22-phox, or the cytosolic factors, p47-phox and p67-phox. We used a system to investigate the activity of mutant p67-phox proteins expressed in a reconstitution assay. This system is characterized by the partial reconstitution of O-(2) production in an Epstein-Barr virus (EBV)-transformed lymphoblastoid B cell line from a patient with p67-phox-deficient CGD by transfection with an expression plasmid containing the 67-phox cDNA in the sense orientation. No O-(2) production was detectable in p67-phox-deficient lymphoblastoid B cell lines transfected with an antisense plasmid or in untransfected p67-phox lymphoblastoid cells stimulated by PMA. We tested two mutants, pEBOp67delta1-22 and pEBOp67delta512-526, and found that both recombinant proteins are active in our system. Thus, we conclude that the first 22 amino acid residues and the last 14 amino acid residues are not critical for initiation of O-(2) production

B-Lymphocytes↗