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Biomedical subjects

C Crawford

Publications and source records attributed to C Crawford.

At least 19 recordsLinked to original sources
PubMed2006

The immune response to disialoganglioside GD3 vaccination in normal dogs: a melanoma surface antigen vaccine.

As a result of its metastatic potential, canine malignant melanoma like its human counterpart like its human counter part, has a poor response to conventional treatment protocols. This prompted us to investigate the possibility of enhancing the immune response against the melanoma cell surface antigen, disialoganglioside GD3. Initially a flow cytometric study was designed in which the incidence of GD3 on the cell surface, recognized by the monoclonal antibody Mel-1 (R24), was established in canine melanoma cell lines. Results from the flow cytometry found GD3 to be highly expressed (94.2%) in six out of seven canine melanoma cell lines. Since it was thus potentially a good target, a study in which normal dogs were vaccinated intradermally with a vaccine containing GD3 plus adjuvants was designed. The adjuvant included CpG oligodeoxynucleotide (CpG-ODN) sequences and RIBI-adjuvant, which are known to target toll-like receptors (TLR) of the innate immune system. From a cohort of 10 dogs, 4 were vaccinated 3 times, at 4 weekly intervals with GD3 plus adjuvant, and 4 received only RIBI-adjuvant, and 2 phosphate buffered saline. Caliper measurements were collected to assess skin reaction at the vaccination site and sera assayed for IgM and IgG antibodies against GD3 and cell-mediated cytotoxicity against a melanoma cell line. Results from the study found significant differences (P<0.05) in the vaccine site reactions, IgM/IgG levels and cell-mediated cytotoxicity in the vaccinated versus unvaccinated dogs. The addition of CpG-ODN sequences and increasing GD3 concentration in the vaccine increased the inflammation response at the injection site. GD3 IgG and IgM antibodies in vaccinated dogs showed increasing titers over time and achieved significance at weeks 9 and 12, respectively. Cell-mediated cytotoxicity was only detected in peripheral blood mononuclear cells from vaccinated dogs. In conclusion, by combining the tumor antigen GD3 (a known weak self-antigen) and an adjuvant, tolerance was overcome by an innate and adaptive immune response in this population of normal dogs.

Adjuvants, Immunologic↗
PubMed2004

Time course of mycobacterial infection of dendritic cells in the lungs of intranasally infected mice.

SETTING: Dendritic cells (DC) could regulate between the protective and pathogenic immune responses following tuberculous infection. In this paper we investigated if their early infection in the lungs represents a plausible alternative to cross-priming with mycobacterial antigens acquired from infected macrophages. OBJECTIVE: To determine the extent and time course of infection of lung DCs following intranasal inoculation of BALB/c mice with green fluorescent protein (GFP) tagged Bacillus Calmette-Guerin (BCG). RESULTS: A fraction of GFP-BCG infected lung cells were classified as monocytic DCs with the CD11c+IA+33D1+CD8a- phenotype. These cells represented 5-18% of the total GFP+ cells, the bulk of which were macrophages. The infected DCs could be separated by cell size into two fractions with similar cell surface staining properties during the 2-72 h period after infection. An unexpected difference was observed for the time course of infection between DCs and macrophages: DC infection peaked at 48 h followed by decline at 72 h, while the proportion of infected macrophages remained steady during the same period. CONCLUSION: The presented results are direct evidence that monocytic DCs are recruited to the lungs and take up live bacilli within 48 h of intranasal infection with GFP-BCG. This finding is pertinent for the regulation of pulmonary and systemic immune responses and possibly for the dissemination of mycobacterial infection by DCs.

Administration, Intranasal↗
PubMed2003

Cross-section measurement of charged-pion photoproduction from hydrogen and deuterium.

We have measured the differential cross section for the gamman-->pi(-)p and gammap-->pi(+)n reactions at theta(c.m.)=90 degrees in the photon energy range from 1.1 to 5.5 GeV at Jefferson Lab (JLab). The data at E(gamma) greater, similar 3.3 GeV exhibit a global scaling behavior for both pi(-) and pi(+) photoproduction, consistent with the constituent counting rule and the existing pi(+) photoproduction data. Possible oscillations around the scaling value are suggested by these new data. The data show enhancement in the scaled cross section at a center-of-mass energy near 2.2 GeV. The cross section ratio of exclusive pi(-) to pi(+) photoproduction at high energy is consistent with the prediction based on one-hard-gluon-exchange diagrams.

Journal Article↗
PubMed2002

Low-volume exercise rehabilitation improves functional capacity and self-reported functional status of dialysis patients.

OBJECTIVE: The purpose of this study was to examine the effects of a program of low-volume exercise rehabilitation on the functional capacity and self-reported functional status of nonanemic dialysis patients. DESIGN: This was a controlled study in a clinical setting with a repeated measures design. Functional capacity and functional status were assessed before and after 12 wk of exercise rehabilitation or 12 wk of normal activity for two groups of dialysis patients. RESULTS: Mixed-model repeated measures analysis of variance revealed significant group by time interactions characterized by improvements for the exercise rehabilitation group alone in total walk, stair-climb, and stair-descent times of 15+/-5.8%, 22+/-11%, and 18+/-12% respectively. Self-reported walking speed, walking impairment-leg weakness, and walking impairment-shortness of breath were also observed to improve significantly for the exercise rehabilitation group alone by 15+/-13%, 25+/-11%, and 28+/-16%, respectively. CONCLUSION: Low-volume exercise rehabilitation can improve activity of daily living-related functional capacity and self-reported functional status of nonanemic dialysis patients.

Activities of Daily Living↗
PubMed2001

Precision measurement of the spin-dependent asymmetry in the threshold region of 3He(e, e').

We present the first precision measurement of the spin-dependent asymmetry in the threshold region of 3He(e,e') at Q2 values of 0.1 and 0.2 (GeV/c)2. The agreement between the data and nonrelativistic Faddeev calculations which include both final-state interactions and meson-exchange current effects is very good at Q2 = 0.1 (GeV/c)2, while a small discrepancy at Q2 = 0.2 (GeV/c)2 is observed.

Journal Article↗
PubMed2001

Observation of plasma focusing of a 28.5 GeV positron beam.

The observation of plasma focusing of a 28.5 GeV positron beam is reported. The plasma was formed by ionizing a nitrogen jet only 3 mm thick. Simultaneous focusing in both transverse dimensions was observed with effective focusing strengths of order tesla per micron. The minimum area of the beam spot was reduced by a factor of 2.0+/-0.3 by the plasma. The longitudinal beam envelope was measured and compared with numerical calculations.

Journal Article↗
PubMed2001

A survey of medical students' opinions about complementary and alternative medicine.

OBJECTIVE: We wished to determine third-year medical students' opinions and knowledge related to complementary and alternative medicine (CAM) in a school with no formal or elective course on the subject. STUDY DESIGN: A questionnaire was offered to third-year medical students during their 8-week rotation on obstetrics and gynecology. RESULTS: Most students had been exposed to CAM therapies, knew that the majority of the American public was using CAM, believed that some CAM interventions were useful, and did not believe CAM therapies were a threat to public health. Most students had insufficient knowledge or understanding of the safety or lack of it for 10 of the more common CAM modalities. Most respondents thought these interventions were useful, but would not refer the patient nor dissuade her from using them. There were no significant differences in responses between men and women or related to the time in the year of the clerkship. CONCLUSION: Medical students in this school self-identified an interest about the clinical usefulness of 10 CAM modalities, but did not have sufficient knowledge about the safety for 10 of the more common CAM modalities. Including CAM topics in the medical school curriculum would better prepare physicians to respond to patient inquiries about CAM and thereby to fulfill their role as patient advocates.

Adult↗
PubMed2001

Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni.

Substance P (SP) regulates interferon-gamma (IFN-gamma) production through interaction with the SP receptor NK1 (SPr) on T cells at sites of inflammation. Using murine schistosomiasis, we evaluated whether SPr expression was subject to immunoregulation. Splenocytes from schistosome-infected mice cultured for < or =18 h did not express SPr, as determined by quantitative polymerase chain reaction assay. However, exposure to schistosome egg antigen (SEA) for < or =4 h induced strong receptor expression. Experiments using splenocytes fractionated with antibody-coupled, paramagnetic beads showed that induction localized exclusively to T cells. Receptor protein expression was confirmed with Western blot. Interleukin 12 (IL-12) also induced strong T-cell SPr expression. Both SEA and IL-12 remained strong inducers of T-cell SPr in lymphocytes from the IL-12 (p40) and IFN-gamma R double-knockout mouse, which suggested that SEA did not require IL-12 to induce SPr and that both worked independently of IFN-gamma. Splenocytes from wild-type mice cultured with SEA and neutralizing anti-IL-12 monoclonal antibody (mAb) also showed SPr induction. However, anti-Ia mAb inhibited SEA induction of SPR: Thus, SPr is inducible on T cells. SEA induces SPr through interaction with T-cell receptor (TCR), independently of IL-12 and IFN-gamma. IL-12 induces SPr independently of TCR activation and IFN-gamma expression. SP and its receptor, which regulate IFN-gamma production, are probably part of the IL-12-Th1 circuit.

Animals↗
PubMed2000

Alterations in sleep physiology in young children with insulin-dependent diabetes mellitus: relationship to nocturnal hypoglycemia.

OBJECTIVES: To examine the effect of diabetes per se and nocturnal hypoglycemia on sleep in children with insulin-dependent diabetes mellitus (IDDM). DESIGN: Overnight polysomnography was performed on 3 occasions in 29 children with IDDM - twice during metabolic profiling. Sleep data were analyzed from 14 children (median [range], 8.7 [5.9 to 12.9] years) with a night of hypoglycemia and a nonhypoglycemic night. Seven children in the control group (9 [5.6 to 11.4] years) underwent 2 nights of polysomnography, once during metabolic profiling (to assess the effects of metabolic profiling), and 15 members of the control group had polysomnography only (to assess the effects of diabetes per se and to compare with the index group). RESULTS: Children with IDDM had disrupted sleep compared with the control group (short wakes, percentage of sleep time, 0.8 [0.5 to 1.9] vs 0.0 [0.0 to 0.3], median [interquartile range], IDDM vs control group, respectively, P =.001; long wakes, 1.2 [0.7 to 3. 0] vs 0.0 [0.0 to 0.0], P =.033; total number of wakes, 6 [3.5 to 11. 5] vs 1 [0 to 2], P =.002). Blood sampling disrupted sleep with increased long wakes as percentage of sleep time (0.3 [0.0 to 3.8] vs 4.3 [3.1 to 16.9], nonsampling vs sampling night, respectively, P =.003). Episodes of hypoglycemia were profound, with a glucose nadir of 2.0 [1.4 to 3.3] mmol/L (35.0 [24.5 to 57.8] mg/dL) and prolonged, 308 [30 to 630] minutes, with no effect on sleep. CONCLUSIONS: Children with diabetes had disrupted sleep compared with a control group, but there was no effect of profound nocturnal hypoglycemia on sleep quality. J Pediatr 2000;137:233-8)

Blood Glucose↗
PubMed2000

Patients' rights and the law of contract in eighteenth-century England.

The study of 34 lawsuits between practitioners and patients shows how the law relating to contracts was brought to bear on convicts over medical practice in eighteenth-century England. It shows that patients in this period had rights, and explores them though the practice of the courts. The article illuminates two substantial changes: the decline of the contract of cure, and the creation of the patient's right to disregard bills for fees from physicians and apothecaries. It argues that the common law created a medical market-place that was differentiated by the legal status of the patient, and that this affected the character of many healing relationships, even though the legal scrutiny of a patient-practitioner encounter was a relatively infrequent occurrence. The inability of married women and minors to make contracts, along with the legal and customary responsibility of employers for the health of servants and apprentices, meant that many patients in eighteenth-century England were not the autonomous consumers of medical care that existing histories of the patient in this period suggest. The essay thus investigates the impact of the law on the culture of medicine, whilst using legal sources to address questions about power in healing relationships.

Contracts↗
PubMed2000

Evolutionary psychology: counting babies or studying information-processing mechanisms.

Evolutionary psychology focuses on the study of adaptations. Its practitioners put little credence in the study of reproductive success in recent and current environments, and argue for an information-processing, cost-benefit conception of adaptation. Because ancestral and current environments differ, it is necessary to distinguish between innate and operational adaptations and between concurrently contingent and developmentally contingent behaviors. These distinctions lead to an evolutionary classification of behaviors into true pathologies, pseudopathologies, quasinormal behaviors, and adaptive-culturally-variable behaviors. I argue that a complete study of the functioning of a behavioral adaptation involves modeling ancestral selection pressures, cross-cultural research, experimental studies of mental processes, and studies of the proximate biological correlates of information-processing adaptations. Finally, I claim that evolutionary psychology can help us avoid making both naturalistic and moralistic fallacies.

Adaptation, Psychological↗
PubMed2000

Arousal norms for children age 5-16 years based on home polysomnography.

Fragmentation of sleep by brief arousals has become an acknowledged aspect of poor quality sleep but there is a shortage of normative data on such arousals, especially for children. Norms for arousals (defined according to American Sleep Disorders Association criteria) were compiled for 61 children age 5-16 years using the Oxford Medilog system for a single night of home polysomnography. No significant differences were seen between the five age subgroups considered in average number of arousals per hour of sleep although individual differences were apparent at each age level and arousal duration was somewhat longer at younger ages. The low arousal rates in the children studied are in keeping with other evidence that arousal rates increase throughout life. Boys were no different from girls in either arousal frequency or duration. Arousal frequency was correlated with PSG awakenings but only to a modest extent. These new normative values should be useful in clinical practice and research for the assessment of the quality of children's sleep.

Adolescent↗
PubMed1999

Zimmerman-Laband syndrome: An unusually early presentation in a newborn girl.

We report on a female newborn, the youngest patient with Zimmermann-Laband syndrome hitherto reported. She had gingival hyperplasia, bulbous soft nose and ears, hypoplastic toenails, and hyperextensibility of the joints, as well as deep palmar and plantar creases, a sign not previously described in literature.

Abnormalities, Multiple↗
PubMed1998

Current microbiological status of 'health foods' sold in Canada.

A follow-up survey was conducted across Canada to evaluate the current status of 'health foods' sold in Canada. A total of 1239 sample units of 'health foods' were analysed for a variety of bacteria, including aerobic colony counts (ACC), coliforms, aerobic and anaerobic sporeformers, Escherichia coli and Bacillus cereus. Results presented indicate that 16.8-18.4% of the 'health foods' exceed ACC guidelines, 16.0-17.8% exceeded coliform guidelines, 35.7% exceeded aerobic sporeformer guidelines, 81.4% exceeded anaerobic sporeformer guidelines, and 9% exceeded B. cereus guidelines. Some ACC were further identified and found to be opportunistic pathogens, including the genera Bacillus, Enterococcus, and Staphylococcus. It was concluded that more extensive surveillance of this industry by health officials is needed.

Bacillus↗
PubMed1998

A double-blind, placebo controlled, dose ranging study to evaluate the safety and biological efficacy of the lipid-DNA complex GR213487B in the nasal epithelium of adult patients with cystic fibrosis.

UNLABELLED: GTAB1001: A Double-Blind, Placebo Controlled, Dose Ranging Study to Evaluate the Safety and Biological Efficacy of the Lipid-DNA Complex GR213487B in the Nasal Epithelium of Adult Patients with Cystic Fibrosis. OBJECTIVES: To evaluate the effectiveness of various dosages of the lipid-DNA complex GR213487B (0.4375mg and either 4.0mg or 0.0625mg) for producing CFTR gene transfer and correcting the chloride ion transport defect in the nasal epithelium of patients with cystic fibrosis. To assess the safety and tolerability of the lipid-DNA complex GR213487B when applied to the nasal epithelium of patients with cystic fibrosis. DESIGN: Single-center, double-blind, placebo controlled, dose ranging study. DURATION: Pre-treatment evaluations will be performed during two outpatient study visits (ie. between Day -7 to -3 and at Day -2). Patients will be admitted to the Clinical Research Unit (CRU) at the University of North Carolina at Chapel Hill on Day -1 for additional pre-treatment evaluations performed the day prior to administration of double-blind treatment (ie. gene transfer) on Treatment Day 0. Patients will remain in the CRU for 7 days (Day -1 to Day 6) and will be discharged on Day 6. Patients will subsequently be followed on an outpatient basis but will return for another assessment between Days 9-11, and may also return to the CRU for two optional study visits on Days 14 and 21. All patients will return to the CRU on an out-patient basis for follow-up evaluations on Day 28 +/- 3. SETTING: Patients will receive in-patient treatment in the CRU at the University of North Carolina at Chapel Hill and will remain in the CRU for 7 days. PATIENTS: A target enrollment of 12 evaluable patients is planned. STUDY TREATMENTS: Patients who meet all entry criteria will complete pre-treatment assessments, which will take place between Day -7 to Day -1, and will serve as a baseline for specific evaluations and to ensure clinical stability. Patients will return on Day -1 for admission to the CRU the day prior to gene transfer. Each nostril of the patients will be randomly assigned in a double blind manner to receive either GR213487B liquid nasal spray or the lipid alone (ie. control administered as liposome), by topical application directed at the inferior turbinate. The first four patients will receive an initial dosage of GR213487B containing 0.4375 mg of DNA. The decision to proceed to administer a higher dose (ie. 4.0mg DNA) or a lower dose (ie. 0.0625mg DNA) in the subsequent eight patients will be determined by the Principal Investigator in association with an FDA officer serving as an independent Clinical Ombudsman, according to the study plan (see Section 5.5 and Appendix 3-Dosing Flow Chart). MEASUREMENTS: Efficacy Evaluations The primary variables to determine the efficacy of transgene expression will be: * Evidence of vector derived CFTR (cystic fibrosis transmembrane conductance regulator) mRNA, as measured by reverse transcriptase polymerase chain reaction (RT-PCR) in nasal epithelial cells obtained from nasal scrapes on Day 3 and, nasal biopsies on Day 5, if sufficient tissue is available. * Correction of chloride ion transport across the nasal epithelium as measured by the transepithelial electrical potential difference (TEPD). The baseline TEPD will initially be measured, and again subsequently following perfusion of: --zero chloride perfusion containing amiloride (to induce chloride secretion) --zero chloride perfusion containing amiloride and isoproterenol (to increase cAMP-mediated chloride secretion) Secondary measures to determine the efficacy of gene transfer will be: * Evidence of delivery of plasmid DNA in the nasal lavage (Day 1-5, Day 9-11 and Day 28) * Evidence of vector derived CFTR mRNA from nasal scrapes performed after the nasal biopsy (ie. Day 9-11 and/or Day 28) * Percentage of cells from nasal biopsies expressing vector derived CFTR mRNA as measured by in situ hybridization * Evidence of vector derived CFTR

Adult↗