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J Barrett

Publications and source records attributed to J Barrett.

At least 109 records · Page 6Linked to original sources
PubMed1999

Molecular remission of chronic myeloid leukaemia following a non-myeloablative allogeneic peripheral blood stem cell transplant: in vivo and in vitro evidence for a graft-versus-leukaemia effect.

Two patients with chronic myeloid leukaemia (CML) received a non-myeloablative preparative regimen of cyclophosphamide and fludarabine, followed by an unmanipulated, G-CSF-mobilized, peripheral blood stem cell transplant from an HLA-identical sibling. Chimaerism, evaluated in myeloid and T-lymphoid lineages by PCR of minisatellite variable regions, showed day 14 post-transplant haemopoietic recovery to be 90% autologous in both patients. On day 30 the bone marrow showed only 1/20 and 2/18 donor metaphases. By day 100 post transplant both had 100% donor myeloid and lymphoid lineages as assessed by karyotype and minisatellite chimaerism analysis. They subsequently became RT-PCR negative for BCR-ABL. Both survive 7 and 14 months post transplant in molecular remission of CML. In one, donor T cells, stimulated with pre-transplant CML cells, induced 30-50% inhibition of pre-transplant leukaemic CFU-GM, but did not inhibit CFU-GM in the day 60 marrow (46% Ph-negative recipient, 54% donor). These results show that a non-myeloablative allotransplant can induce molecular remissions of CML through a graft-versus-leukaemia effect.

Adult↗
PubMed1999

The utility of head computed tomography after minimal head injury.

OBJECTIVE: To determine if patients who present with a history of loss of consciousness who are neurologically intact (minimal head injury) should be managed with head computed tomography (CT), observation, or both. METHODS: We prospectively studied patients who presented to our urban Level I trauma center with a history of loss of consciousness after blunt trauma and a Glasgow Coma Scale score of 15. All patients underwent CT of the head and were subsequently admitted for 24 hours of observation. RESULTS: A total of 1,170 patients with minimal head injury were studied during a 35-month period. All patients had Glasgow Coma Scale scores of 15 on arrival and had a history of either loss of consciousness or amnesia to the event. Two hundred forty-seven patients (21.1%) were intoxicated with drugs or alcohol on admission; 39 patients (3.3%) had abnormalities detected by CT, including 18 intracranial bleeds; 21 patients (1.8%) had changes in therapy as a direct result of their CT results, including 4 operative procedures. No patient with negative CT results deteriorated during the subsequent observation period. CONCLUSION: CT is a useful test in patients with minimal head injury because it may lead to a change in therapy in a small but significant number of patients. Subsequent hospital observation adds nothing to the CT results and is not necessary in patients with isolated minimal head injury.

Accidents↗
PubMed1999

Optimal prosthetic for acute replacement of the abdominal wall.

OBJECTIVE: To compare two prostheses for use in acute abdominal wall replacement in the presence and absence of peritonitis. MATERIALS AND METHODS: Forty male Sprague-Dawley rats underwent full-thickness removal of a 2 x 3 cm portion of their anterior abdominal wall. Twenty rats had intraperitoneal contamination with stool slurry. Ten rats in each group (contaminated and noncontaminated) had a 2 x 3 cm piece of Gore-Tex dual-mesh expanded polytetrafluoroethylene (PTFE) sewn full-thickness to cover the abdominal wall defect. The remaining 10 rats in each group had replacement with a 2 x 3 cm piece of Dexon polyglycolic acid mesh (PGA). The rats were then awakened and returned to their cages. Rats were humanely killed at the end of a 3-week observation period or at the time of fistula formation or evisceration. At necropsy, the density of intraabdominal adhesions was graded on a scale of 0 to 3, and the extent of reepithelialization was noted. Results were analyzed with the Student's t test or Fisher's exact method of chi2 test as indicated. RESULTS: Nineteen PTFE rats and 10 PGA rats survived the observation period, The PTFE rats had significantly fewer adhesions (0.10+/-0.30 vs. 1.27+/-1.49,p < 0.005) and significantly more reepithelialization of their wounds (78.2+/-23.4% vs. 43.6+/-50.4%,p < 0.05) than the PGA rats. Evisceration and fistula formation occurred more frequently in the PGA group. The mortality in the PTFE rats was significantly less than the PGA rats (5% vs. 50%,p < 0.001.) Notably, the contaminated PGA rats had a significantly higher mortality (90%,p < 0.001) than any of the other subgroups. CONCLUSION: PTFE is superior to PGA as a replacement prosthesis for acute abdominal wall defects. There are significantly fewer adhesions, improved epithelialization of the wound, and less morbidity and mortality when PTFE is used. This finding is especially true in the presence of intraperitoneal fecal soilage.

Abdominal Muscles↗
PubMed1999

Evisceration after abdominal stab wounds: is laparotomy required?

OBJECTIVES: To determine the incidence of intra-abdominal injury requiring laparotomy after an abdominal stab wound with evisceration. To identify clinical signs that increase the likelihood of an intra-abdominal injury in the presence of such a wound. METHODS: Information was collected prospectively over an 8-year period on all patients who presented to our urban level I trauma center with an abdominal stab wound and evisceration. This information included which organ eviscerated, presence of other indications for laparotomy, organs injured, and postoperative complications. All comparisons used the Fisher's exact chi2. RESULTS: A total of 81 patients were admitted with evisceration after an abdominal stab wound. Sixty-one patients (75%) had eviscerated omentum, 18 patients (22%) had eviscerated small bowel, and 2 patients (2%) had eviscerated colon. Sixty-two patients (76%) had evisceration as the sole indication for laparotomy, the remaining 19 patients (24%) had another indication such as hypotension or peritonitis. Overall, 63 patients (78%) had an intra-abdominal injury that required repair. This was true regardless of organ eviscerated (omentum = 77% vs. viscus = 80%, not significant) or clinical presentation (no other indication = 76% vs. another indication = 84%, not significant). CONCLUSION: The majority of patients who present with an evisceration after a stab wound to the abdomen require a laparotomy. This is true regardless of what has eviscerated or the presence of other clinical indications to operate. Evisceration should continue to prompt operative intervention.

Abdominal Injuries↗
PubMed1999

A proposed consent process in studies that use an exception to informed consent.

Federal regulations allow an exception to informed consent when it is not feasible to obtain informed consent in certain emergency research circumstances. A multicenter, randomized, single-blinded, normal saline procedure-controlled efficacy trial of diaspirin cross-linked hemoglobin (DCLHb) in acute traumatic hemorrhagic shock was conducted. The study intended to include 850 of the most severely injured trauma patients with hemorrhage and persistent hypoperfusion as demonstrated by vital signs suggestive of vascular collapse or a base deficit that signified prolonged hypoperfusion. It was anticipated that some patients would be unable to provide informed consent, and that identification and availability of some patients' legally authorized representatives (LARs) would be unlikely within the therapeutic window of the intervention. Each participating institution therefore developed a process to implement exception to informed consent. Each hospital's proposed process was reviewed by the institutional review board, the sponsor, the FDA, and the study's data monitoring committee chair. The goal was the development of local implementation processes by which the best interests of patients and their families could be fulfilled using prospective informed consent, the exception to informed consent, and consent to continue in emergency research, as appropriate for each individual patient. This paper describes the proposed implementation method developed for Cook County Hospital. It includes several important features, 1) prospective informed consent by the patient, when feasible; 2) the ability of the patient to decline participation, even when deemed incompetent to provide prospective informed consent; 3) prospective consent by the family/LAR, when feasible; 4) the use of a scripted abbreviated consent by the patient family/ LAR in life-threatening situations when it is possible only to briefly discuss the research being conducted; 5) independent approval for the use of the consent exception by a second physician immediately prior to patient enrollment; 6) the repeated use of consent to continue (both for the family/LAR and by the patient) when an exception to consent has been utilized; and 7) ongoing review of the informed consent process on a case-by-case basis by the institution's scientific review committee. The authors believe this proposed informed consent process maximizes the communication between investigators, patients and their proxies, and the institution's scientific review committee. Multiple mechanisms exist that allow for consent to be provided or declined, both prior to and after enrollment in the research protocol. The ongoing immediate review of the process allows for process enhancements to be made as needed.

Aspirin↗
PubMed1999

Immunomodulation by viruses: the myxoma virus story.

Myxoma virus is a poxvirus pathogen of rabbits that has evolved to replicate successfully in the presence of an active immune response by an infected host. To accomplish this, the virus has developed a variety of strategies to avoid detection by or obstruct specific aspects of the antiviral response whose consolidated action is antagonistic to virus survival. We describe two distinct viral strategies carried out by viral proteins with which myxoma virus subverts the host immune response. The first strategy is the production of virus-encoded proteins known as viroceptors or virokines that mimic host receptors or cytokines. These seek to actively block extracellular immune signals required for effective virus clearance and produce a local environment in the infected tissue that is "virus friendly". The second strategy, carried out by intracellular viral proteins, seeks to retard the innate antiviral responses such as apoptosis, and hinder attempts by the infected cell to communicate with the cellular arm of the immune system. By studying these viral strategies of immune evasion, the myxoma system can provide insights into virus-host interactions and also provide new insights into the complex immune system.

Amino Acid Sequence↗
PubMed1999

Successful treatment of metastatic renal cell carcinoma with a nonmyeloablative allogeneic peripheral-blood progenitor-cell transplant: evidence for a graft-versus-tumor effect.

PURPOSE: A 50-year-old man developed progressive pulmonary metastasis resistant to interferon alfa-2b treatment 7 months after he underwent left nephrectomy for stage III renal cell carcinoma. We performed a nonmyeloablative allogeneic peripheral-blood stem-cell transplant in this patient to exploit a possible graft-versus-tumor effect from allogeneic lymphocytes. MATERIALS AND METHODS: The conditioning regimen consisted of fludarabine and cyclophosphamide followed by a T-cell replete, granulocyte-colony stimulating-factor-mobilized peripheral-blood stem-cell transplant from his HLA-identical brother. Cyclosporine was administered from days -4 to +45 to prevent graft rejection and acute graft-versus-host disease (GVHD). RESULTS: Serial polymerase chain reaction analysis of hematopoietic lineage-specific minisatellites initiallyshowed mixed chimerism in CD14(+) and CD15(+) myeloid cells, CD3(+) T cells, and CD34(+) progenitor cells, with rapid conversion to 100% donor T-cell chimerism by day +60 and 100% donor myeloid cells by day +100. Serial computed tomography scans of the chest showed stable disease at day +30, slight regression of pulmonary lesions at day +63, and complete disappearance of all pulmonary metastatic disease by day +110. Mild transient acute GVHD disease of the skin occurred on day +60 and limited chronic GVHD of the skin occurred by day +200. CONCLUSION: The complete regression of metastatic disease, which has now been maintained for more than 1 year, is compatible with a graft-versus-tumor effect.

Antineoplastic Agents↗
PubMed1999

Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias.

PURPOSE: The nucleoside analogs fludarabine, 2'-deoxycoformycin (DCF), and 2-chlorodeoxyadenosine (CdA), commonly used in the treatment of patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL), are associated with myelosuppression and profound and prolonged immunosuppression. These complications raise the possibility of an increase in secondary malignancies in patients whose disease already places them at greater risk. The purpose of the present study was to assess the frequency of second tumors in patients with CLL who are treated with fludarabine and in patients with HCL who are treated with DCF and CdA. PATIENTS AND METHODS: We reviewed the long-term follow-up data for 2,014 patients treated on National Cancer Institute Group C protocols with fludarabine for relapsed and refractory CLL and with DCF and CdA for HCL using a Second Cancer Report. The numbers of observed and expected secondary tumors were compared. RESULTS: Median follow-up periods for the DCF (n = 409), fludarabine (n = 724), and CdA (n = 979) studies were 6.9, 7.4, and 5.1 years, respectively. The 111 malignancies were most commonly lymphoma (25 patients), prostate (19), lung (15), colorectal (nine), bladder (six), and breast (six), but also CNS, stomach, ovary, head and neck, melanoma, sarcoma, testicular, and myeloid leukemias. Compared with age-adjusted 1994 Surveillance and Epidemiology End-Results rates for the general population, the observed/expected frequencies for DCF, fludarabine, and CdA were 1.43 (95% confidence interval [CI], 0.93 to 2.10), 1.65 (95% CI, 1.04 to 2.47), and 1.50 (95% CI, 1.14 to 1.93), respectively, indicating a significant (at P =.05) increase in risk for patients treated on the latter two protocols compared with a normal population. However, these values are consistent with the increase already associated with these diseases. CONCLUSION: Despite their immunosuppression, nucleoside analogs can be safely administered to patients with CLL or HCL without a significantly increased risk of secondary malignancies.

Aged↗
PubMed1999

Disability in patients with early inflammatory polyarthritis cannot be "tracked" from year to year: an examination of the hypothesis underlying percentile reference charts.

OBJECTIVE: To determine whether disability in patients with early inflammatory polyarthritis (IP) can be charted or "tracked" over time. The disability score was also adjusted in an attempt to exclude the influence of current disease activity, with the aim of ascertaining that component of disability relating to other factors such as psychosocial factors and joint damage. METHODS: Four hundred thirty-three patients with early IP referred to the Norfolk Arthritis Register (NOAR) were followed annually using the Health Assessment Questionnaire (HAQ) for 5 years. HAQ scores at each year were divided into quartiles. The number of patients remaining in the same quartile from year to year was examined. The relationship between disease activity, assessed by swollen and tender joint counts, and HAQ was modelled, with the residual HAQ attributed to psychosocial factors and joint damage. RESULTS: From year to year, there was considerable within-individual variation in quartile, with only 48-65% of patients remaining in the same quartile. With increasing time, a greater proportion of patients remained in the same quartile. A statistically valid activity-adjusted HAQ score could not be computed. CONCLUSION: Disability in patients with early IP cannot be easily tracked over time. It is therefore not appropriate to construct longitudinal reference charts for disability in the early years, although it may be feasible for more established disease.

Adolescent↗
PubMed1999

Risk of developing certain malignancies is related to duration of immunosuppressive drug exposure in patients with rheumatic diseases.

OBJECTIVE: To investigate the relationship between the cumulative duration of exposure to immunosuppressive drugs and the risk of developing and/or dying from malignancy in patients with rheumatic diseases attending rheumatology practices throughout Europe. METHODS: Patients with rheumatic diseases who first started an immunosuppressive drug between 1979 and 1990 were studied. They were followed annually for up to 10 years through their rheumatologists. Information was collected on vital status, the development of malignancy, and starting and stopping dates of immunosuppressive drugs. Person-years of observation were attributed to one of 4 groups according to the cumulative duration of exposure to immunosuppressives. Age and sex adjusted incidence rate ratios (IRR) were calculated by comparing each of the higher 3 groups with the baseline exposure category. RESULTS: In total 1773 patients, from 15 countries, contributed 12,266 person-years of followup. The principal drugs used were azathioprine, methotrexate, cyclophosphamide, and chlorambucil. Patients in the highest cumulative exposure group had an IRR of 3.74 (95% CI 1.48-9.47) of developing a neoplasm of the immune system or skin or bladder cancer compared to those in the lowest category. A similar pattern was seen when the analysis was confined to patients who took only azathioprine. The risk estimates were unchanged after adjustment for disease duration since first treatment. CONCLUSION: In addition to any increased risk of malignancy that may be conferred by individual rheumatic diseases, there is a further risk of specific types of malignancy that is related to the duration of exposure to immunosuppressive drugs.

Aged↗
PubMed1998

Risk and benefit.

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Biotechnology↗
PubMed1998

Synergistic transcriptional activation of the MCK promoter by p53: tetramers link separated DNA response elements by DNA looping.

The WAF1, Cyclin G and muscle creatine kinase (MCK) genes, all contain multiple copies of the consensus p53-binding element within their regulatory regions. We examined the role of these elements in transactivation of the muscle creatine kinase (MCK) gene by p53. The MCK promoter possesses distal (-3182 to -3133) and proximal (-177 to -81) p53-binding elements within which residues -3182 to -3151 (distal) and -176 to -149 (proximal) show homology to the consensus p53-binding site. Using promoter deletion studies, we find that both proximal and distal elements are required for high level, synergistic transcriptional activation in vivo. Electron microscopy indicates that p53-p53 interactions link proximal and distal p53-binding elements and cause looping out of intervening DNA, suggesting that this DNA sequence may be dispensable for synergy. This idea was confirmed by progressive deletion of the DNA between p53-binding elements. Synergism persisted with spacing reduced to only 150 bp. Tetramerization-deficient p53 mutants were defective for transcriptional activation but still capable of synergy. Our results provide evidence for a model by which high level transcriptional activation of promoters with multiple p53 response elements is achieved.

Animals↗
PubMed1998

Utilization of rheumatology physician services by the elderly.

PURPOSE: To examine rheumatology subspecialty practice patterns, determinants of referral to rheumatologists, and utilization of aspiration and injection procedures in a population-based sample of elderly individuals. SUBJECTS AND METHODS: We obtained Medicare physician claims for all visits to rheumatologists among beneficiaries aged 65 years and older in Colorado, Massachusetts, and Virginia in 1993, and for visits to all providers by patients with coded diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We examined variations in visit frequency and aspiration/injection procedures, and we analyzed determinants of referral to a rheumatologist for RA or SLE. RESULTS: In 1 year, 144,797 visits were made to rheumatologists by 38,443 patients in the three states. An inflammatory disorder was coded in 45% of visits and a noninflammatory disorder in 50%. Half of patients with RA were seen three or fewer times in the year. For RA and SLE, African Americans were about 60% as likely to be seen by a rheumatologist as whites. Utilization of rheumatologist services for rheumatoid arthritis and systemic lupus erythematosus was highest in the state (Virginia) with the lowest per capita supply of rheumatologists. Among patients with bursitis, tendinitis, and osteoarthritis, African-American women were more likely to receive an injection or aspiration procedure than whites or African-American men. CONCLUSION: Elderly patients with rheumatologic disorders were seen by specialists less frequently than recommended by a recent rheumatology manpower survey. African-Americans with RA and SLE had fewer rheumatology visits than whites.

Aged↗
PubMed1998

Cytochrome P450 in parasitic protozoa and helminths.

Cytochrome P450 has been demonstrated in flagellate and sporozoan Protozoa. In Plasmodium there is a correlation between chloroquine resistance and cytochrome P450 mono-oxygenase activity, but there is no evidence that the malarial parasite metabolises chloroquine by an oxidative mechanism. There is no evidence for cytochrome P450 in adult helminths (nematodes and platyhelminths) based on P450 content and mono-oxygenase activity with classical substrates, although low activities may be present in free-living larval stages.

Animals↗
PubMed1998

How could the BSE crisis affect nutrient intake? Comparison of beef and non-beef eating meat eaters from the UK Women's Cohort Study.

OBJECTIVES: To compare nutrient and food intakes in a group of meat eating women who ate beef with those who did not eat beef. DESIGN: Analysis of preliminary data from the UK Women's Cohort Study, a national study of women aged 35-69 y. SUBJECTS: Three thousand and eighty-six beef meat eaters from the cohort were compared with 593 non-beef meat eaters. RESULTS: The non-beef eaters had lower energy, protein, zinc, fat, percentage of energy from fat and body mass index and higher fibre and vitamin C intakes than the beef eaters. There was no difference between the groups in consumption of carbohydrate, sugar or iron. CONCLUSION: There were differences in nutrient intake between the groups, which if reflected long term in the general population have implications for health and food policy following media revelations.

Adult↗