Biomedical subjects

D Pearson

Publications and source records attributed to D Pearson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Cross-calibration, precision and patient dose measurements in preparation for clinical trials using dual energy X-ray absorptiometry of the lumbar spine.

Large, multicentre clinical trials using DXA to monitor bone density following intervention are now common. At the same time, several different bone densitometers and calibration phantoms are currently in use. The aim of this study was to document the technical information required on cross-calibration of equipment, reproducibility and patient dose before commencing a multicentre clinical trial. To this end, we obtained an in vitro and in vivo cross-calibration of two machines (a Hologic QDR 2000 and a Lunar DPX-L) that were not significantly different. Interobserver and intraobserver precision, and radiation dose were also measured and three commonly used phantoms assessed for their usefulness in cross-calibration and quality assurance. Measured in vitro precision on the two machines (0.3-0.7%) was better than that specified by the manufacturers. In vivo precision was worse (1.4-2.1%), as might be expected in patients with reduced bone mass. Mean entrance skin radiation doses on each machine were 280 microSv for the QDR 2000 and 38 microSv for the DPX-L. No one phantom is ideal, but the European Spine Phantom or Lunar Aluminium Spine Phantom will provide an adequate cross-calibration for a clinical trial. This study demonstrates that an adequate cross-calibration can be obtained for use in groups of patients and that the equipment used is reproducible with a low radiation output.

Absorptiometry, Photon↗

PubMed1999

Hepatotoxicity in cancer patients receiving erb-38, a recombinant immunotoxin that targets the erbB2 receptor.

To exploit overexpression of erbB2 in human cancers, we constructed a single-chain immunotoxin (erb-38) that contains the Fv portion of monoclonal antibody e23 fused to a truncated form of Pseudomonas exotoxin A. In a Phase I study, five breast cancer patients and one esophageal cancer patient received three doses of erb-38 at 1.0 and 2.0 microg/kg. Hepatotoxicity was observed in all patients. Immunohistochemistry showed the presence of erbB2 on hepatocytes explaining the liver toxicity of erb-38. We suggest that targeting of tumors with antibodies to erbB2 armed with radioisotopes or other toxic agents may result in unexpected organ toxicities due to erbB2 on normal cells.

ADP Ribose Transferases↗

PubMed1998

The relationship between bone mineral density and ultrasound in postmenopausal and osteoporotic women.

The aim of this cross-sectional study was to use a novel method of data analysis to demonstrate that patients with osteoporosis have significantly lower ultrasound results in the heel after correcting for the effect of bone mineral density (BMD) measured in the spine or hip. Three groups of patients were studied: healthy early postmenopausal women, within 3 years of the menopause (n = 104, 50%), healthy late postmenopausal women, more than 10 years from the menopause (n = 75, 36%), and a group of women with osteoporosis as defined by WHO criteria (n = 30, 14%). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness wer measured using a Lunar Achilles heel machine, and BMD of the lumbar spine and left hip was measured using dual-energy X-ray absorptiometry (DXA). SOS, BUA and Stiffness were regressed against lumbar spine BMD and femoral BMD for all three groups combined. The correlation coefficients were in the range 0.52-0.58, in agreement with previously published work. Using a calculated ratio R, analysis of variance demonstrated that the ratio was significantly higher in the osteoporotic group compared with the other two groups. This implied that heel ultrasound values are proportionately lower in the osteoporotic group compared with the other two groups for an equivalent value of lumbar spine and femoral neck BMD. We conclude that postmenopausal bone loss is not associated with different ultrasound values once lumbar spine or femoral neck BMD is taken into account. Ultrasound does not give additional information about patterns of bone loss is postmenopausal patients but is important in those patients with osteoporosis and fractures.

Absorptiometry, Photon↗

PubMed1998

Bone density: is it affected by orchidectomy and radiotherapy given for stage I seminoma of the testis?

A cross-sectional study of bone density involving 30 patients who had undergone orchidectomy and para-aortic radiotherapy for Stage I seminoma of the testis, has been performed. Bone density measurements were made of the whole body, lumbar spine and hips, including all irradiated areas. Comparison was made with previously obtained standard sex and age matched control data. The 30 patients treated for seminoma had a significantly increased mean bone density compared with age matched normal values. No significant differences were demonstrated between the mean bone densities of the irradiated and non-irradiated hips. There was no significant relationship between bone density measurement and time since orchidectomy or radiotherapy. These results suggest that nodal irradiation for seminoma has little long term effect on bone density.

Absorptiometry, Photon↗

PubMed1998

Implementation of the Henry J. Kaiser Family Foundation's Community Health Promotion Grant Program: a process evaluation.

The Community Health Promotion Grants Program, sponsored by the Henry J. Kaiser Family Foundation, represents a major health initiative that established 11 community health promotion projects. Successful implementation was characterized by several critical factors: (1) intervention activities; (2) community activation; (3) success in obtaining external funding; and (4) institutionalization. Analysis of the program was based on data from several sources: program reports, key informant surveys, and a community coalition survey. Results indicate that school-based programs focusing on adolescent health problems were the most successful in reaching the populations they were targeting. The majority of the programs were able to attract external funding, thereby adding to their initial resource base. The programs were less successful in generating health promotion activities and in achieving meaningful institutionalization in their communities.

Adolescent↗

PubMed1998

Phase II and dose-escalation with or without granulocyte colony-stimulating factor study of 9-aminocamptothecin in relapsed and refractory lymphomas.

PURPOSE: To assess the efficacy and maximum dose-intensity of a new topoisomerase I (topo I)-targeting agent, 9-aminocamptothecin (9-AC), in patients with relapsed or refractory lymphomas. PATIENTS AND METHODS: Eligible patients had measurable disease and were considered incurable. 9-AC was infused over 72 hours at an initial dose rate of 40 microg/m2/h every 3 weeks with subsequent intrapatient escalations or reductions in 10-microg/m2/h increments based on toxicity. To assess the impact of granulocyte-colony stimulating factor (G-CSF) on dose-intensity, the first 16 patients received no G-CSF and the subsequent 29 patients received G-CSF on all cycles. RESULTS: Forty-five patients received a total of 142 cycles of 9-AC. The patients' median age was 55 years, 73% had stage IV disease, and histologies included indolent and aggressive non-Hodgkin's lymphoma (NHL) in 33% and 58% of patients, respectively, and Hodgkin's lymphoma in 9%. Patients had received a median of two prior chemotherapy regimens, and 67% of patients had chemotherapy-sensitive disease. Of 40 assessable patients, 10 (25%) achieved a partial response (PR). Chemotherapy-sensitive patients had a 32% response rate compared with 8% in chemotherapy-resistant patients. With a median follow-up duration of 35 months, the median event-free survival (EFS) and overall survival times were 1.5 and 12.5 months, respectively, and the median duration of response was 5 months (range, 1 to 10). G-CSF significantly reduced the incidence of neutropenia and diarrhea, but did not permit a significant increase in dose-intensity. CONCLUSION: 9-AC had a reasonable response rate of 25% in heavily pretreated patients. The low response rate in patients with chemotherapy-resistant disease suggests that there is cross-resistance between 9-AC and standard chemotherapy. However, there was no association between 9-AC response and the number of prior regimens. Due to dose-limiting thrombocytopenia, G-CSF support did not increase dose-intensity, although individual patients benefited from the use of G-CSF.

Adult↗

PubMed1998

Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS: Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS: The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION: The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Adult↗

PubMed1997

Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.

Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > -0.6). These findings suggest that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.

Adrenocorticotropic Hormone↗

PubMed1997

Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team.

BACKGROUND: Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine. METHODS: In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or > or =30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease. RESULTS: Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036). CONCLUSIONS: In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.

Adolescent↗

PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.

Large-scale systematic sequencing has generally depended on the availability of an ordered library of large-insert bacterial or viral genomic clones for the organism under study. The generation of these large insert libraries, and the location of each clone on a genome map, is a laborious and time-consuming process. In an effort to overcome these problems, several groups have successfully demonstrated the viability of the whole-genome random 'shotgun' method in large-scale sequencing of both viruses and prokaryotes. Here we report the sequence of Saccharomyces cerevisiae chromosome IX, determined in part by a whole-chromosome 'shotgun', and describe the particular difficulties encountered in the random 'shotgun' sequencing of an entire eukaryotic chromosome. Analysis of this sequence shows that chromosome IX contains 221 open reading frames (ORFs), of which approximately 30% have been sequenced previously. This chromosome shows features typical of a small Saccharomyces cerevisiae chromosome.

Base Composition↗

PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.

Systematic sequencing of the genome of Saccharomyces cerevisiae has revealed thousands of new predicted genes and allowed analysis of long-range features of chromosomal organization. Generally, genes and predicted genes seem to be distributed evenly throughout the genome, having no overall preference for DNA strand. Apart from the smaller chromosomes, which can have substantially lower gene density in their telomeric regions, there is a consistent average of one open reading frame (ORF) approximately every two kilobases. However, one of the most surprising findings for a eukaryote with approximately 6,000 genes was the amount of apparent redundancy in its genome. This redundancy occurs both between individual ORFs and over more extensive chromosome regions, which have been duplicated preserving gene order and orientation. Here we report the entire nucleotide sequence of chromosome XIII, the sixth-largest S. cerevisiae chromosome, and demonstrate that its features and organization are consistent with those observed for other S. cerevisiae chromosomes. Analysis revealed 459 ORFs, 284 have not been identified previously. Both intra- and interchromosomal duplications of regions of this chromosome have occurred.

Base Composition↗

PubMed1997

Long-term quality control of DXA: a comparison of Shewhart rules and Cusum charts.

Long-term clinical trials using bone mineral density (BMD) measurements are now commonplace. It is important to maintain a high standard of quality control. In this study two methods of monitoring quality control measurements of dual-energy X-ray absorptiometry (DXA) equipment have been compared using receiver operating curve (ROC) analysis: Shewhart multi-rule charts and Cusum charts. Computer-generated faults within daily spine phantom measurements were used. The Charts were then applied to 3 years of quality control data from one machine and the results related to hardware faults, random events and changes in the underlying BMD measurement. In the ROC analysis the Shewhart multi-rule chart performed as well or better than the cusum chart, but the stringency of the rules must be tightened to obtain optimal performance.

Absorptiometry, Photon↗

PubMed1997

Use of pump-assisted hemofiltration in children with acute renal failure.

In critically ill children, acute renal failure (ARF) is associated with a high mortality. To assess the outcome and complications of pump-assisted hemofiltration (PAHF) using a standard volumetric pump to regulate blood flow, we retrospectively reviewed our experience in 52 patients with ARF treated with PAHF from 1989 to 1995. These patients ranged in age from < 1 month to 19 years and in weight from 2 to 125 kg. The most common underlying diagnoses were congenital heart disease and infection. The duration of PAHF averaged 9 +/- 8 days (range 24 h to 43 days). Hemodiafiltration for solute control was required in 40 patients. Total fluid intake while on PAHF was 136 +/- 95 ml/kg per day, while urine output and ultrafiltration averaged 15 +/- 24 ml/kg per day and 89 +/- 58 ml/kg per day, respectively. Management of laboratory abnormalities was efficient with only 4 patients requiring 1 or 2 additional treatments of hemodialysis for control of uremia. Complications included hyponatremia in 13 patients, hypokalemia in 14 patients, hypovolemia in 8 patients, hyperglycemia in 6 patients, and bleeding in 9 patients. No complications specifically related to use of the volumetric infusion pump for PAHF were noted. PAHF using a volumetric infusion pump for blood flow regulation in critically ill children with ARF is a practical and efficient therapy.

Acute Kidney Injury↗

PubMed1997

Long-term results from the first UKCCSG Ewing's Tumour Study (ET-1). United Kingdom Children's Cancer Study Group (UKCCSG) and the Medical Research Council Bone Sarcoma Working Party.

The aim of this study was to evaluate multimodal chemotherapy and radiotherapy in patients with Ewing's sarcoma. 142 (74 male, 68 female) patients were entered into the ET-1 study between 1978 and 1986. They were treated with vincristine, doxorubicin, actinomycin D, and cyclophosphamide with radiotherapy plus or minus surgery to the primary tumour. Of the 120 who had no metastases at diagnosis, 45 remain alive with a median follow-up of 11.2 years. Only 2 of those with metastases at diagnosis remain alive. The major prognostic factor was site of disease, but age and serum lactic dehydrogenase at diagnosis also had an influence on outcome. 45 of the 61 patients who survived 4 years or more had late effects documented. The type and extent were dependent on tumour site, type of local therapy, volume and dose of radiotherapy. 4 patients had second malignancies. Prospects for long-term survival have improved in patients treated for Ewing's sarcoma. However, late sequelae are present in the majority of patients.

Adolescent↗

PubMed1997

Changes in bone mineral density in patients with Paget's disease treated with risedronate.

OBJECTIVES: To study changes in bone mineral density (BMD) in patients with Paget's disease of bone treated with risedronate. METHODS: Whole body dual energy x ray absorptiometry (DXA) scans were carried out on 20 patients with Paget's disease treated with oral risedronate. DXA scanning was carried out at baseline and 11 months. Whole body bone mineral content (BMC) was measured. In addition, regions of interest were drawn around the skull, individual lumbar vertebrae, hemipelvis, femora, and tibiae to obtain BMD for these sites. An uncoupling index was also calculated as the area under the curve for serum alkaline phosphatase (ALP) divided by the area under the curve for hydroxyproline excretion (HYPRO) for the period of treatment. RESULTS: Median whole body BMC increased from 3057 g to 3156 g (p < 0.001) resulting from an increase in pagetic and non-pagetic BMD. From the analysis of regions of interest it was found that pagetic trabecular bone showed the largest increase in BMD. The pretreatment HYPRO and the uncoupling index were significantly related to the change in BMD for all pagetic sites for a patient (r = 0.65, p < 0.01 and r = 0.57, p < 0.05 respectively). CONCLUSION: Bisphosphonate treatment of Paget's disease results in an increase in BMD of pagetic bone without redistribution of mineral from non-pagetic bone. The remodelling space and extent of uncoupling are significantly related to increases in BMD at pagetic sites.

Absorptiometry, Photon↗

PubMed1997

Immunization tracking systems: experience of the CDC Vaccine Safety Datalink sites.

Recognizing the potential of large databases within HMOs for the evaluation of vaccine safety, the Centers for Disease Control and Prevention (CDC) funded the Vaccine Safety Datalink project, linking outcome and vaccine exposure information at Group Health Cooperative of Puget Sound, Kaiser Permanente Northwest, Kaiser Permanente Medical Care Program Northern California, and Southern California Kaiser Permanente. Integral to the Vaccine Safety Datalink Project was the development of Immunization Tracking Systems at each site; this report describes the effort required to establish these tracking systems. Essential requirements are the methods used to insure data quality and to educate system users. Tracking systems can be a valuable means for assessing vaccine coverage, evaluating barriers to complete immunization, and studying the effectiveness of interventions design to improve immunization coverage. Finally, we report on recent efforts to link HMO Immunization Tracking Systems with developing regional tracking systems.

California↗

PubMed1996

Synthesis, structure, and structure-activity relationships of divalent thrombin inhibitors containing an alpha-keto-amide transition-state mimetic.

A new class of divalent thrombin inhibitors is described that contains an alpha-keto-amide transition-state mimetic linking an active site binding group and a group that binds to the fibrinogen-binding exosite. The X-ray crystallographic structure of the most potent member of this new class, CVS995, shows many features in common with other divalent thrombin inhibitors and clearly defines the transition-state-like binding of the alpha-keto-amide group. The structure of the active site part of the inhibitor shows a network of water molecules connecting both the side-chain and backbone atoms of thrombin and the inhibitor. Direct peptide analogues of the new transition-state-containing divalent thrombin inhibitors were compared using in vitro assays of thrombin inhibition. There was no direct correlation between the binding constants of the peptides and their alpha-keto-amide counterparts. The most potent alpha-keto-amide inhibitor, CVS995, with a Ki = 1 pM, did not correspond to the most potent divalent peptide and contained a single amino acid deletion in the exosite binding region with respect to the equivalent region of the natural thrombin inhibitor hirudin. The interaction energies of the active site, transition state, and exosite binding regions of these new divalent thrombin inhibitors are not additive.

Amides↗

PubMed1996

Thoracoscopic splanchnicectomy for chronic pancreatitis pain.

BACKGROUND: The study was undertaken to quantitate the effects of thoracoscopic splanchnic nerve resection (SPL) on pain from chronic pancreatitis. METHODS: Patients with chronic pancreatitis pain completed an analog pain scale before operation and at postoperative visits. Midepigastric and left-sided pain was treated with left SPL; right-sided pain was treated with right-sided SPL. If pain recurred on the contralateral side, the patient underwent contralateral SPL. RESULTS: Fifteen patients underwent SPL. Eleven patients required daily narcotics for relief of pain before operation. Eight patients had unilateral SPL, whereas seven ultimately had a bilateral operation (median follow-up, 18 months). Fourteen patients had constant pain before operation, which decreased to a mean of 2.8 attacks per month (p < 0.0001). Before operation, the "worst pain within last two months" was 9.1 on pain scale (range, 0 for no pain, to 11 for constant pain). After operation this decreased to 5.1 (p < 0.002). "Current severity" of pain decreased from 6.5 before operation to 2.0 after operation (p < 0.0005). The "amount pain is interfering with daily activities" decreased from 7.3 before operation to 2.3 after operation (p < 0.0001). Seven patients (46%) no longer require narcotics and are classified as having had good results. Five patients (33%) are classified as improved and have had a major reduction in narcotic needs. Three have had no significant pain relief and are classified as having had poor results. CONCLUSIONS: Thoracoscopic SPL offers substantial promise in the therapy of pain from chronic pancreatitis.

Adolescent↗