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Biomedical subjects

C Hutchison

Publications and source records attributed to C Hutchison.

11 recordsLinked to original sources
PubMed1998

Cancer surveillance in the U.S.: can we have a national system?

Cancer-related services are consuming ever-increasing health resources; along with this trend, health care costs are rising. As health care planners, researchers, and policymakers formulate strategies to meet this challenge, they are looking to cancer registries and the health information system built around them as collectors of the most extensive information regarding cancer treatment in the U.S. Currently, there are multiple programs collecting and reporting data regarding cancer incidence, morbidity, mortality, and survival. This report profiles cancer surveillance efforts in the U.S. and describes the National Coordinating Council for Cancer Surveillance, which was organized in 1995 to facilitate a collaborative approach among the organizations involved.

American Cancer Society↗
PubMed1998

Durable remission of locally advanced breast cancer with multimodality management.

We treated 20 women with locally advanced breast cancer between January 1991 and September 1996. The treatment regimen included 4 cycles of intensive doxorubicin (30 mg/m2/d on 3 consecutive days every 2 weeks with G-CSF support), followed by appropriate surgery, followed by high dose therapy with cyclophosphamide, carboplatin and thiotepa (STAMP V, CTCb). Of the 20 patients, seven presented with inflammatory breast cancer, three with Stage IIIB, seven with stage IIIA, one with multifocal Stage IIB and two with Stage IV M1 (ipsilateral supraclavicular lymph node involvement) (including one who had an inflammatory primary) disease. Six patients had not undergone mastectomy at the time of entering the protocol. These six received the doxorubicin in a neoadjuvant fashion and were thus evaluable for tumor response. The remaining 14 received doxorubicin as adjuvant therapy prior to intensification and transplantation. All patients underwent local-regional radiation therapy and were placed on oral tamoxifen. Doxorubicin was well tolerated in this schedule with all but three patients receiving all their cycles on schedule. Both BM and PBPC were easily collected after this regimen and, when reinfused, resulted in the prompt recovery of granulocytes (median 11 days to 500 absolute granulocyte count) and platelets (median 13 days to 20,000 platelets). The six patients who received doxorubicin prior to mastectomy all had major clinical responses, but were found to have microscopic focii of breast cancer in the mastectomy specimens. The overall treatment was well tolerated with the exception of one treatment-related death (5%). The overall and relapse free survival are 70% and 58% respectively with a median follow-up of 40 months (range 12-74 months). When the Stage IV patients are censored, the relapse-free survival rate is 69%. In the bone marrow transplant phase of treatment, the major non-hematologic toxicities were stomatitis (70%) and anorexia requiring parental nutrition (75%).

Adult↗
PubMed1998

Phase I trials in cancer patients: participants' perceptions.

There is controversy surrounding the ethics of performing phase I clinical trials with cancer patients and limited research concerning patients' attitudes when participating in such trials. The aim of this study was to determine how cancer patients perceive phase I clinical trials in reference to trial participation and trial information received. Cancer patients (n = 28) were interviewed 2-4 weeks after consenting to participate, using a questionnaire which contained open and closed questions. Responses were analysed using non-parametric statistical tests. The results demonstrated that although the majority of patients participated in experimental treatment because it offered hope that they might be helped, their expectations from the new drug were realistic. Patients found that there were benefits related to participating in phase I trials and felt that the amount and quality of both nursing and medical care was superior in a phase I trial as compared to standard treatment in non-experimental settings. There were varying opinions among patients with regard to information giving by nursing and medical staff. It can be concluded that phase I trials employing cancer patients can be ethical.

Adult↗
PubMed1997

Objective structured assessment of technical skill (OSATS) for surgical residents.

BACKGROUND: The technical skill of surgical trainees is not well assessed. This study aimed (1) to compare the reliability of three scoring systems, (2) to compare live and bench formats and (3) to assess construct validity of a test of operative skill. METHODS: Parallel examinations of operative skill, one using live animals and one using simulations, were developed. Performance was graded using operation-specific checklists, detailed global rating forms and pass/fail judgements. Twenty surgical residents each took both formats. RESULTS: Disattenuated correlations between live and bench scores were high (0.69-0.72). Mean interrater reliability across stations ranged from 0.64 to 0.72. Internal consistency was moderate to high (alpha: 0.61-0.74) for the live format using the checklist and for live and bench formats using global ratings. Global ratings discriminated between resident levels for both formats (bench: F(2,17) = 4.45, P < 0.05; live: F(2,17) = 3.55, P < 0.05), checklists did not. CONCLUSION: This preliminary study suggests that the Objective Structured Assessment of Technical Skill can reliably and validly assess surgical skills. Global ratings are a better method of assessment than task-specific checklists. Bench model simulation gives equivalent results to use of live animals for this test format.

Clinical Competence↗
PubMed1995

The factor V Leiden mutation which predisposes to thrombosis is not common in patients with antiphospholipid syndrome.

Antiphospholipid syndrome is associated with venous, arterial, and placental thrombosis, possibly through autoantibody impairment of phospholipid-dependent protein C activation. Recently, a missense mutation in the factor V gene (1691 G-->A) has been identified that results in an abnormal factor V product (1). This mutation, known as the Leiden mutation, causes an amino acid substitution of glutamine for arginine at position 506 in the factor V molecule and renders the protein resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis (2, 3). We hypothesized that some individuals with antiphospholipid syndrome may also carry the Leiden mutation, and thus have a "second hit" predisposition to thrombosis. To test this hypothesis, allele-specific hybridization and allele-specific restriction analysis were used to test for the Leiden mutation in thirty women with the antiphospholipid syndrome, 10 of whom had a history of thrombosis. None of the women were heterozygous or homozygous for the factor V mutation. We conclude that the presence of the factor V Leiden mutation is not a prerequisite for the thrombotic events in patients with antiphospholipid syndrome, due to the occurrence of thrombosis seen in patients lacking the factor V mutation.

Alleles↗
PubMed1993

Nuclei that lack a lamina accumulate karyophilic proteins and assemble a nuclear matrix.

Xenopus egg extracts, which support nuclear assembly and DNA replication in vitro, were physically depleted of lamin B3 using monoclonal antibodies linked to magnetic beads. Depleted extracts were still able to support nuclear envelope assembly around demembranated sperm heads but the resulting pronuclei lacked a lamina and were unable to initiate semiconservative DNA replication or to assemble replicases, confirming previous data. Immunoblotting analysis of isolated nuclei and nuclear matrix fractions indicated that lamin-depleted nuclei still accumulated nucleoporins and PCNA. Furthermore, the rate of PCNA uptake was identical in lamin-depleted and control nuclei. However, neither the nucleoporins nor the PCNA was associated with nuclear matrix fractions. The major protein components of sperm pronuclear matrix fractions were characterized by two-dimensional gel electrophoresis. Of these proteins only three out of 22 species, other than the lamins, were significantly reduced in lamin-depleted nuclei, indicating that these nuclei do assemble a nuclear matrix.

Animals↗
PubMed1990

Plasmid origin of replication of herpesvirus papio: DNA sequence and enhancer function.

Herpesvirus papio (HVP) is a lymphotropic virus of baboons which is related to Epstein-Barr virus (EBV) and produces latent infection. The nucleotide sequence of the 5,775-base-pair (bp) EcoRI K fragment of HVP, which has previously been shown to confer the ability to replicate autonomously, has been determined. Within this DNA fragment is a region which bears structural and sequence similarity to the ori-P region of EBV. The HVP ori-P region has a 10- by 26-bp tandem array which is related to the 20- by 30-bp tandem array from the EBV ori-P region. In HVP there is an intervening region of 764 bp followed by five partial copies of the 26-bp monomer. Both the EBV and HVP 3' regions have the potential to form dyad structures which, however, differ in arrangement. We also demonstrate that a transcriptional enhancer which requires transactivation by a virus-encoded factor is present in the HVP ori-P.

Animals↗
PubMed1989

Changes in the nuclear distribution of DNA polymerase alpha and PCNA/cyclin during the progress of the cell cycle, in a cell-free extract of Xenopus eggs.

The nuclear distribution of DNA polymerase alpha and PCNA/cyclin in embryonic nuclei has been investigated, in a cell-free extract of Xenopus eggs that recapitulates a basic cell-cycle in vitro, by indirect immunofluorescence microscopy. Both antigens co-distribute with the chromatin in S-phase nuclei; however, as DNA replication is completed and nuclei progress into a G2 state anti-PCNA fluorescence disappears and anti-DNA polymerase alpha fluorescence becomes resolved into bright spots. These spots are initially associated with the chromatin strands and can be seen to share both anti-PCNA and anti-DNA polymerase alpha fluorescence, but as anti-PCNA fluorescence fades the spots become dissociated from the chromatin and are redistributed throughout the nucleus until they are dispersed during nuclear envelope breakdown. The loss of anti-PCNA fluorescence and displacement of anti-DNA polymerase alpha fluorescence from the chromatin can be prevented by inhibiting DNA synthesis with aphidicolin. Under these conditions both antigens remain associated with the chromatin even after nuclear envelope breakdown and lamin dispersal. The association of these antigens with mitotic figures appears to be functional, as both biotin-11-dUTP and [32P]dCTP can be incorporated efficiently into DNA during the mitotic period.

Animals↗
PubMed1987

Large numbers of random point and cluster mutations within the adenovirus VA I gene allow characterization of sequences required for efficient transcription.

We have isolated clones with well over 100 randomly dispersed point mutations distributed throughout the 5' half of chemically synthesized adenovirus type 2 VA I genes. In addition, we have isolated clusters of mutations targeted to the regions corresponding to the A and B block consensus sequences of eukaryotic tRNA and adenovirus VA genes. In vitro analyses of these constructs have allowed us to survey in detail the importance of DNA sequence to transcriptional efficiency. Our analyses demonstrate that certain constructs with radically substituted A block regions can be transcribed efficiently. In contrast, there is little tolerance for variation in the sequence within the B block region. We propose that the B block sequence should be R-G-A/T-T-C-R-A-N-N-C for optimal transcriptional efficiency of the VA I gene in mammalian cells.

Adenoviruses, Human↗