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Biomedical subjects

P Chapman

Publications and source records attributed to P Chapman.

At least 19 recordsLinked to original sources
PubMed2001

The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision.

The possibility of altering the pathophysiology of keloid scars was investigated in 11 patients, using a single application of 5-fluorouracil solution for 5 minutes after extralesional excision was performed. Similar excisional wounds treated with phosphate-buffered saline for 5 minutes served as synchronous controls. An objective scoring system and subjective assessment were made to assay the change in the quality of the wound-healing and scar tissue produced by this treatment. A keloid scar score was used at regular time intervals after treatment to assess the quality of scar produced, thereby enabling the treated and control scars to be clinically compared. Biopsies were taken of the control and treated scars 1 month after treatment; the biopsy specimens were then subjected to immunohistochemical analysis as well as a functional assessment of cultured keloid fibroblasts. The immunohistochemical antigens assayed were Ki-67 (also called MIB-1; a marker of cell proliferation); vascular cell adhesion molecule-1 (a marker of inflammation); transforming growth factor beta-1 (a factor involved in scarring) and CD-68 (a macrophage-specific marker). Fibroblast-populated collagen lattices provided a functional assessment of fibroblast contraction. All treated and control wounds healed without any dehiscence or infection. The keloid scar score revealed that there was a perceived improvement in condition for those treated with 5-fluorouracil, compared with the control specimens, during the 6-month follow-up period in the five patients who attended all their clinic appointments; data on later recurrence are not complete as yet. The wounds treated with 5-fluorouracil produced scars that had a significant (p < 0.01) reduction in all the markers assayed, apart from CD-68. Functionally, the keloid fibroblasts from three of five of the treated patients showed reduced contractile capacity. This pilot study demonstrates that a "single-touch" technique with 5-fluorouracil can produce a change in the characteristics of the healing keloid wound after extralesional excision. Long-term studies are required to elucidate the correct dosage and time of exposure to improve the efficacy of this potential treatment.

Adult↗
PubMed2000

Epidemiologic study of pulmonary obstruction in workers occupationally exposed to ethyl and methyl cyanoacrylate.

The association between pulmonary obstruction (e.g., asthma) and occupational exposure to methyl cyanoacrylate (MCA) and ethyl cyanoacrylate (ECA) was examined in an occupational cohort of 450 persons at an adhesive production facility in Puerto Rico. Employee medical records containing information on physical examinations and pulmonary function tests (PFTs), as well as occupational histories, on each employee over a period of about 17 yr and industrial hygiene measurements were evaluated. The cohort analysis was based on a Cox proportional hazards model. Workers exposed to ECA or MCA were compared to workers unexposed to these chemicals with respect to their risk of becoming an "incident case." An "incident case" was defined as any person whose PFTs were normal at the time of employment, but later demonstrated an obstructive pattern, which was defined as a decline in the ratio of forced expiratory volume exhaled in 1 s to forced vital capacity (FEV1/FVC) below 70%. A separate case-control analysis was also conducted that compared "suspected cases," defined as all those whose PFTs ever demonstrated an obstructive pattern (e.g., asthma), to persons whose PFTs remained within normal limits throughout their employment with respect to their past peak and cumulative exposures to cyanoacrylates. All of these analyses showed no evidence that exposure to average short-term concentrations of ECA or MCA of less than 0.5 ppm and occasional daily peak exposures of at least 1.5 ppm (usually 10 min or less), with occasional higher concentrations during spills, were associated with an increased risk of pulmonary obstruction. However, the study suggested that persons occupationally exposed to cyanoacrylates were more likely to have some reversible eye or upper airway irritation than persons who were unexposed.

Adhesives↗
PubMed2000

Linkage and LOH studies in 19 cylindromatosis families show no evidence of genetic heterogeneity and refine the CYLD locus on chromosome 16q12-q13.

Familial cylindromatosis is an autosomal dominant predisposition to multiple neoplasms of the skin appendages. The susceptibility gene has previously been mapped to chromosome 16q12-q13 and has features of a recessive oncogene/tumour suppressor gene. We have now evaluated 19 families with this disease by a combination of genetic linkage analysis and loss of heterozygosity in cylindromas from affected individuals. All 15 informative families show linkage to this locus, providing no evidence for genetic heterogeneity. Recombinant mapping has placed the gene in an interval of approximately 1 Mb. There is no evidence, between families, of haplotype sharing that might be indicative of common founder mutations.

Carcinoma, Adenoid Cystic↗
PubMed2000

Adult medulloblastoma: prognostic factors and patterns of relapse.

OBJECTIVE: To determine the patterns of relapse and the prognostic factors for adult medulloblastomas treated in the magnetic resonance imaging era. METHODS: Between 1986 and 1996, 32 adult patients (age, > or =16 yr) with medulloblastomas confined to the craniospinal axis were treated in our institutions. Twenty cases involved classic histological features and 12 involved the desmoplastic variant. The Chang staging distribution was as follows: T1, 2; T2, 17; T3, 10; T4, 3; M0, 24; M1, 1; M2, 4; M3, 3. Brainstem invasion was present in nine patients. Lesions were midline in 13 cases and lateral in 19. Resection was complete in 17 cases, subtotal in 6, and partial in 5, with biopsy only in 4 cases. All patients received postoperative radiotherapy, with median doses of 36 Gy to the entire craniospinal axis and 55 Gy to the posterior fossa. Twenty-four patients received chemotherapy (20 before radiotherapy, 3 after radiotherapy, and 1 before and after radiotherapy). RESULTS: With a median follow-up period of 5.4 years, 17 patients experienced recurrences. At 5 and 8 years, overall survival rates were 83 and 45% and disease-free survival rates were 57 and 40%, respectively. The 5- and 8-year posterior fossa control rates were 67 and 59%, respectively. Twenty-nine percent of all relapses occurred more than 5 years after treatment. The posterior fossa was the most common site of relapses. In univariate analyses, factors adversely affecting posterior fossa control were less than complete resection (P<0.001), the presence of brainstem invasion (P = 0.02), and the use of chemotherapy (P = 0.03). The overall radiotherapy duration was marginally significant in predicting posterior fossa control, with 5-year posterior fossa control rates of 81 and 49% for durations of less than 48 days and 48 days or more, respectively (P = 0.06). In a multivariate analysis, complete resection was predictive of improved posterior fossa control (P = 0.02) and disease-free survival (P = 0.02) rates. Of the eight low-risk patients who received radiotherapy alone, three experienced recurrences in the bone as the only site of relapse. CONCLUSION: Late relapse is common among adult patients with medulloblastomas, and long-term follow-up monitoring is important. Because of the high risk of systemic failure among the low-risk patients treated with radiotherapy alone, the role of chemotherapy for this group of patients needs to be further investigated. Complete resection, the absence of brainstem invasion, and an overall radiotherapy duration of less than 48 days are important prognostic factors.

Adolescent↗
PubMed1999

Driving experience and the functional field of view.

Research has suggested that novice drivers have different search strategies compared with their more experienced counterparts, and that this may contribute to their increased accident liability. One issue of concern is whether experienced drivers have a wider field of peripheral vision than less experienced drivers. This study attempted to distinguish between people of varying driving experience on the basis of their functional fields of view. Participants searched video clips taken from a moving driver's perspective for potential hazards while responding to peripheral target lights. Hit rates for peripheral targets decreased for all participant groups as processing demands increased (i.e. when hazards occurred) and as the eccentricity of the target increased, though there was no interaction. An effect of experience was also found which suggests that this paradigm measures a perceptual skill or strategy that develops with driving experience.

Accidents, Traffic↗
PubMed1998

Genetic and functional studies of a germline TP53 splicing mutation in a Li-Fraumeni-like family.

We report an extensive Li-Fraumeni-like family in which there is an unusual spectrum of tumours at relatively late onset. A germline TP53 splice donor mutation in exon 4 is present in all affected family members available for testing. The mutation abolishes correct splicing of intron 4 and techniques of RT-PCR have identified three different aberrant transcripts from the mutant TP53 allele. Using the yeast functional assay to analyse transcripts in cells from a number of family members with the mutant allele, TP53 appears wild-type. Functional studies have been carried out on cells from patients with and without cancer who carry the germline mutation, and on cells from unaffected individuals from the same family who do not carry the mutation. Using a number of functional endpoints known to distinguish between cells carrying mutant or wild-type TP53 alleles, we were unable to discriminate normal (wt/wt) from heterozygous (wt/mut) cells by lymphocyte apoptosis and fibroblast survival following low dose rate ionising radiation exposure. However germline mutation carriers show increased sensitivity to radiation-induced chromosome damage in the G2 phase of the cell cycle, and decreased transient and permanent G1 arrest. These studies demonstrate the importance of fully characterising the effects of TP53 germline mutations, and may explain some of the phenotypic features of this family.

Adult↗
PubMed1998

Visualising E-selectin in the detection and evaluation of inflammatory bowel disease.

BACKGROUND: Vascular endothelial E-selectin expression is induced by proinflammatory cytokines and contributes to accumulation of leucocytes in tissues. AIMS: To investigate the role of E-selectin in inflammatory bowel disease (IBD). METHODS: E-selectin expression was assessed in patients with ulcerative colitis and Crohn's disease by measuring the concentration of circulating soluble E-selectin (sE-selectin) using ELISA, by immunohistochemistry of colonic biopsy specimens, and by abdominal immunoscintigraphy after injecting radiolabelled F(ab')2 fragment of a monoclonal anti-E-selectin antibody. The value of scintigraphy using anti-E-selectin was judged by a prospective comparative study of autologous leucocyte scanning and E-selectin antibody scanning in 17 patients with IBD. RESULTS: Circulating sE-selectin was elevated in patients with clinically active disease. Tissue expression of E-selectin was enhanced in patients with active inflammation, with weak or absent expression in inactive disease and healthy controls. In-111 labelled anti-E-selectin scintiscans were compared with Tc-99m labelled leucocyte scans performed 24 hours earlier. Twelve patients had areas of active inflammation on leucocyte scan while 11 patients had positive E-selectin scans. The results of the two scans were concordant in 14 patients, with those positive for both (10/17) showing similar disease localisation and extent. CONCLUSIONS: Tissue E-selectin and circulating sE-selectin are increased during active inflammatory bowel disease. Anti-E-selectin imaging with radiolabelled monoclonal antibody identified areas of inflammation in Crohn's disease and ulcerative colitis. The technique should prove useful clinically for identifying the site and extent of disease.

Acute Disease↗
PubMed1998

Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer.

BACKGROUND: Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment in colonic crypts is reported to be one of the earliest changes in premalignant mucosa. AIMS: To assess the role of crypt cell proliferation as a phenotypic biomarker in HNPCC. PATIENTS: Thirty five patients at 50% risk of carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and hence gene carrier status was known) and 18 controls. METHODS: Crypt cell proliferation was measured at five sites in the colon using two different techniques. Labelling index was determined using the monoclonal antibody MIB1 and whole crypt mitotic index was measured using the microdissection and crypt squash technique. The distribution of proliferating cells within the crypts was also assessed. RESULTS: There were no significant differences in the total labelling index or mean number of mitoses per crypt, nor in the distribution of proliferating cells within the crypt, between the study and control groups at any site. When the 21 patients in whom gene carrier status was known were analysed separately there were no significant differences in the measured indices of proliferation between the HNPCC gene carriers and non-gene carriers. CONCLUSION: Crypt cell proliferation is not a discriminative marker of gene carriage in HNPCC.

Adolescent↗
PubMed1997

Interstitial irradiation of brain tumors, using a miniature radiosurgery device: initial experience.

OBJECTIVE: This report describes the clinical evaluation of a novel stereotactic radiosurgical device for interstitial irradiation of malignant brain tumors. METHODS: Fourteen patients with cerebral lesions less than 3.5 cm in greatest diameter were treated with a single fraction of stereotactic interstitial irradiation (average, 12.5 Gy). Clinical evaluation, Karnofsky Performance Scale ratings, and neuroimaging studies were obtained at 6-week intervals postoperatively to assess treatment response. Reduction or stabilization of tumor size on follow-up imaging was accepted as local control, whereas tumor enlargement indicated local failure. INSTRUMENTATION: This battery-powered miniature x-ray generator device produces low-energy x-ray photons that are attenuated rapidly within tissue. A dose decline rate proportional to 1/r3 yields extremely sharp dose fall-off curves with minimal exposure to surrounding tissue. Dose rates of 200 cGy per minute are possible, allowing for the administration of 12.5 Gy to a lesion 3 cm in diameter in less than 1 hour. RESULTS: Local control (stabilization or reduction in lesion size) was obtained in 10 of the 13 patients with tumors with follow-up of 1.5 to 36 months (mean, 12 mo). Of three patients with radiographic progression, recurrence was symptomatic in only one. All patients tolerated the procedure well, and most patients were discharged home the day after treatment. No new neurological deficits were noted after biopsy and irradiation. CONCLUSIONS: Preliminary experience with this novel radiosurgical device has demonstrated its feasibility and safety. Clinical efficacy of this technique is now under investigation in an international multicenter study.

Adult↗
PubMed1997

Antineutrophil cytoplasm autoantibodies against bactericidal/permeability-increasing protein in inflammatory bowel disease.

BACKGROUND: Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3). AIM: To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease. METHODS: ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls. RESULTS: Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01). CONCLUSION: BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.

Adult↗
PubMed1997

Nutrition knowledge among adolescent high school female athletes.

The purpose of this study is to evaluate the effectiveness of an original sports nutrition education program in changing the nutrition behavior of the female high school varsity football teams of the Baseline League of Southern California. A total of 72 subjects from eight teams were randomly divided into two groups, control and experimental. Only the experimental group received nutrition education. Dietary habits of the athletes were studied through a pre- and post- 24-hour recall. A comparison of pretest scores of both groups showed no significant difference in level of nutrition knowledge. The posttest scores obtained after nutrition education showed a significant difference in nutrition knowledge for the experimental group. However, there was no significant improvement in dietary intake and food choices due to the limited duration of the study.

Adolescent↗
PubMed1996

Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.

Transgenic mice overexpressing the 695-amino acid isoform of human Alzheimer beta-amyloid (Abeta) precursor protein containing a Lys670 --> Asn, Met671 --> Leu mutation had normal learning and memory in spatial reference and alternation tasks at 3 months of age but showed impairment by 9 to 10 months of age. A fivefold increase in Abeta(1-40) and a 14-fold increase in Abeta(1-42/43) accompanied the appearance of these behavioral deficits. Numerous Abeta plaques that stained with Congo red dye were present in cortical and limbic structures of mice with elevated amounts of Abeta. The correlative appearance of behavioral, biochemical, and pathological abnormalities reminiscent of Alzheimer's disease in these transgenic mice suggests new opportunities for exploring the pathophysiology and neurobiology of this disease.

Aging↗