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Biomedical subjects

L J Morrison

Publications and source records attributed to L J Morrison.

At least 19 recordsLinked to original sources
PubMed2005

International Resuscitation Network Registry: design, rationale and preliminary results.

There is a lack of high-quality information about the effectiveness of resuscitation interventions and international differences in structure, process and outcome after out-of-hospital cardiac arrest and cardiopulmonary resuscitation because data are not collected uniformly. An internet-based international registry could make such evaluations possible, and enable the conduct of large randomized controlled trials of resuscitation therapies. A prospective international cohort study was performed that included 571 infants, children and adults (a) who experienced cardiac arrest requiring chest compressions or external defibrillation, (b) outside the hospital in the study communities and (c) upon whom resuscitation was attempted by EMS personnel. Cardiac arrest was defined as lack of responsiveness, breathing or movement in individuals for whom the EMS system is activated for whom an arrest record is completed. All data were collated via a secure and confidential web-based method by using automated forms processing software with appropriate variable range checks, logic checks and skip rules. Median number of missing responses for each variable was 0 (interquartile range 0, 0). Twenty-seven percent of the patients had a first recorded rhythm of ventricular fibrillation or ventricular tachycardia, 60% had a witnessed arrest, and 34% received bystander CPR. Mean time from call to arrival on scene was 7.1+/-5.1 min. Six percent of the patients survived to hospital discharge. The resuscitation process was highly variable across centers, and survival and neurological outcome were also significantly and independently different across centers. This study shows that it is possible to collect data prospectively describing the structure, process and outcome associated with cardiac arrest in multiple international sites via the internet. Therefore, it is feasible to conduct adequately powered randomized trials of resuscitation therapies in international settings.

Adolescent↗
PubMed2005

What the genome sequence is revealing about trypanosome antigenic variation.

African trypanosomes evade humoral immunity through antigenic variation, whereby they switch expression of the gene encoding their VSG (variant surface glycoprotein) coat. Switching proceeds by duplication of silent VSG genes into a transcriptionally active locus. The genome project has revealed that most of the silent archive consists of hundreds of subtelomeric VSG tandem arrays, and that most of these are not functional genes. Precedent suggests that they can contribute combinatorially to the formation of expressed, functional genes through segmental gene conversion. These findings from the genome project have major implications for evolution of the VSG archive and for transmission of the parasite in the field.

Animals↗
PubMed2004

Clinical value of obtaining sputum and cough swab samples following inhaled hypertonic saline in children with cystic fibrosis.

Prompt detection and treatment of lower respiratory tract infection are essential in the management of patients with cystic fibrosis (CF), who often have signs or symptoms of respiratory infection without any pathogens being isolated from sputum or cough swab specimens. The aims of this study were to assess the efficacy and clinical value of obtaining sputum and oropharyngeal cough swab samples following induction with hypertonic saline (HS) in this group of patients. Forty-three outpatients with CF, mean age 7.2 years (range, 1.8-12.9 years), were recruited over a 2-year period. Nebulized salbutamol was administered, followed by 6% HS. Sputum was preferentially obtained before and after HS induction if possible. If the patient was not able to expectorate, oropharyngeal cough swabs were taken instead. Four patients were able to expectorate sputum before and 19 after HS induction. The procedure was tolerated in 41 of 43 patients. Pathogens were isolated from 13 patients' HS-induced samples, but not from their corresponding preinduced specimens, and 4 patients' preinduced specimens cultured organisms which were not identified from their HS-induced samples. Significant changes were made in the management of 13 (30.2%) patients directly resulting from the positive culture of pathogens only from HS-induced samples. Cultures from oropharyngeal cough swab or expectorated sputum specimens following inhalation of HS provide additional microbiological information which is of clinical value and may lead to changes in patient management.

Administration, Inhalation↗
PubMed2001

Redefining emergency medicine procedures: Canadian competence and frequency survey.

OBJECTIVE: To redefine the Royal College of Physicians and Surgeons (RCPS) procedural skills list for Canadian emergency medicine (EM) residents through a national survey of EM specialists to determine procedural performance frequency and self-assessment of competence. METHODS: The survey instrument was developed in three phases: 1) an EM program directors survey identified inappropriate or dated procedures, endorsing 127 skills; 2) a search of EM literature added 98 skills; and 3) an expert panel designed the survey instrument and finalized a list of 150 skills. The survey instrument measured the frequency of procedure performance or supervision, self-reported competence (yes/no), and endorsement of one of four training levels for each skill: undergraduate (UG), postgraduate (PG), knowledge only, or unnecessary (i.e., too infrequently performed to maintain competence). RESULTS: All 289 Canadian EM specialists were surveyed by mail; 231 (80%) responded, 221 completed surveys, and 10 were inactive. More than 60% reported competence in 125 (83%) procedures, and 55 procedures were performed at least three times a year. The mean competence score was 121 (SD +/- 17.7, median = 122) procedures. Competence score correlation with patient volume was r = 0.16 (p = 0.02) and with hours worked was r = 0.19 (p = 0.01). Competence score was not associated with year or route (residency vs grandfather) of certification. Each procedure was assigned to a training level using response consensus and decision rules (UG: 1%; PG: 82%; unnecessary: 17%). CONCLUSIONS: A survey of EM clinicians reporting competence and frequency of skill performance defined 127 procedural skills appropriate for Canadian RCPS postgraduate training and EM certification.

Attitude of Health Personnel↗
PubMed2000

Improving the emergency department detection rate of domestic violence using direct questioning.

The purpose of this study was to compare the domestic violence (DV) rate identified with simple direct questioning to a historical cohort of patients receiving routine emergency department (ED) care. One thousand ED charts of female patients were retrospectively reviewed. Each patient in the prospective cohort was asked five DV specific questions. The historical cohort revealed a DV prevalence rate of 0.4%. The prospective study group of 302 patients identified 11 (3.6%) patients who admitted to acute DV on direct questioning. Ten of these patients accepted help. Twenty (6.6%) were identified as probable DV and 12 (4%) admitted to past violence. The total number of victims of DV, past, present, and probable was 43 (14.2%). This increase in detection from 0.4% (4/1000) to 14.2% (43/302) is significant at p < 0.001. Only 1.3% of patients refused to participate in the DV specific questions. The conclusion of the study indicated that the use of simple, direct questioning significantly improves the detection rate of DV in the ED.

Adult↗
PubMed2000

Facial composite production: a comparison of mechanical and computer-driven systems.

Computer-driven systems for constructing composite faces of suspects (E-fit; Mac-a-Mug) have largely replaced mechanical systems (Photofit; the Identikit) in police use, yet little is known of their comparative effectiveness in rendering an accurate likeness. Participants (N = 24) constructed 2 of 4 familiar or unfamiliar faces, for one of which they used Photofit and for the other, E-fit. A likeness of each face was made first under target-absent conditions and then with photographs of the target present. The accuracy of the resulting composites was assessed by familiarity ratings, names elicited, and matching accuracy. The computer-driven system showed consistent superiority only when a familiar face was constructed in the presence of photographs; when participants worked from memory, E-fit was no better than Photofit. The implications of these findings for theories of face retrieval and the operational use of composites are discussed.

Adult↗
PubMed1999

Response of paramedics to terminally ill patients with cardiac arrest: an ethical dilemma.

BACKGROUND: In an environment characterized by cuts to health care, hospital closures, increasing reliance on home care and an aging population, more terminally ill patients are choosing to die at home. The authors sought to determine the care received by these patients when paramedics were summoned by a 911 call and to document whether do-not-resuscitate (DNR) requests influenced the care given. METHODS: The records of a large urban emergency medical services system were reviewed to identify consecutive patients with cardiac arrest over the 10-month period November 1996 to August 1997. Data were abstracted from paramedics' ambulance call reports according to a standardized template. The proportion of these patients described as having a terminal illness was determined, as was the proportion of terminally ill patients with a DNR request. The resuscitative efforts of paramedics were compared for patients with and without a DNR request. RESULTS: Of the 1534 cardiac arrests, 144 (9.4%) involved patients described as having a terminal illness. The mean age of the patients was 72.2 (standard deviation 14.8) years. Paramedics encountered a DNR request in 90 (62.5%) of these cases. Current regulations governing paramedic practice were not followed in 34 (23.6%) of the cases. There was no difference in the likelihood that cardiopulmonary resuscitation (CPR) would be initiated between patients with and those without a DNR request (73% v. 83%; p = 0.17). In patients for whom CPR was initiated, paramedics were much more likely to withhold full advanced cardiac life support if there was a DNR request than if there was not (22% v. 68%; p < 0.001). INTERPRETATION: Paramedics are frequently called to attend terminally ill patients with cardiac arrest. Current regulations are a source of conflict between the paramedic's duty to treat and the patient's right to limit resuscitative efforts at the time of death.

Adolescent↗
PubMed1997

Safety-modified episomal vectors for human gene therapy.

The effectiveness of ongoing gene therapy trials may be limited by the expression characteristics of viral and plasmid-based vectors. To enhance levels of heterologous gene expression, we have developed a safety-modified episomal expression vector that replicates extrachromosomally in human cells. This vector system employs a simian virus 40 (SV40) large T antigen mutant (107/402-T) that is deficient in binding to human tumor suppressor gene products, including p53, retinoblastoma, and p107, yet retains replication competence. These SV40-based episomes replicate to thousands of copies by 2-4 days after gene transfer in multiple types of human cell lines, with lower activity in hamster cells, and no detectable activity in dog, rat, and murine cell lines. Importantly, 107/402-T has enhanced replication activity compared with wild-type T antigen; this finding may be due, in part, to the inability of p53 and retinoblastoma to inactivate 107/402-T function. We demonstrate that the level and duration of 107/402-T expression regulates the observed episomal copy number per cell. Compared with standard plasmid constructs, episomes encoding 107/402-T yield approximately 10- to 100-fold enhanced levels of gene expression in unselected populations of transient transfectants. To determine if 107/402-T-based episomes replicate extrachromosomally in vivo, tumor explants in nude mice were directly injected with liposome/DNA complexes. Using a PCR-based assay, we demonstrate that SV40-based episomes replicate in human cells after direct in vivo gene transfer. These data suggest that safety-modified SV40-based episomes will be effective for cancer gene therapy because high level expression of therapeutic genes in transient transfectants should yield enhanced tumor elimination.

Animals↗
PubMed1994

p53 mutations in bladder carcinoma cell lines.

Point mutations and deletions in the p53 tumor suppressor gene occur frequently in advanced stage bladder tumors. To extend these observations to an in vitro model of bladder tumorigenicity, we have evaluated the presence of p53 mutations in a panel of bladder carcinoma cell lines. p53 alleles were cloned using the reverse transcriptase-polymerase chain reaction method, and exons 2-11 were sequenced. Of 11 cell lines examined, 5 cell lines had missense point mutations, and each overexpressed p53 protein on western blot analysis. Except for the HT-1197 cell line, these point mutations occurred in evolutionarily conserved domains, which are characteristic hot spots for mutations. HT-1197 encodes an unusual C-terminal point mutation in codon 365, within the basic motif tetramerization domain, suggesting a linkage between induction of a mutant p53 conformation and alterations in protein oligomerization. Six of 11 cell lines had wild-type levels of p53 expression, with 4 producing p53 proteins having either internal deletions or truncations, and 2 producing wild-type p53. Presence of wild-type p53 was found only in cell lines derived from either a low-grade, papillary tumor (RT4) or fetal bladder (FHs 738Bl). The T24 cell line was found to contain a novel p53 mutant having an in-frame deletion of tyrosine 126. This p53 mutant does not bind SV40 large T antigen, yet is expressed at low levels, comparable to cell lines containing wild-type p53 alleles. Our findings characterize p53 mutations in a panel of bladder carcinoma cell lines, and provide a model for testing the role of wild-type or mutant p53 cDNA to suppress or induce tumorigenic properties.

Animals↗
PubMed1993

Increased transcription of interleukin-6 in the brains of mice with chronic enterovirus infection.

An animal model of chronic enteroviral infection was established by using PCR to detect viral genomes in animal tissues and to compare levels of transcription of a variety of cytokines in the brain. Chronic coxsackie-virus B1 infection was found in both brain and skeletal muscle of mice infected as neonates. The viral infection cleared by 240 days post-infection. Elevated levels of tumour necrosis factor alpha and interleukin-6 (IL-6) would appear to be linked to acute and chronic infection respectively. Levels of IL-6 return to normal upon clearance of the virus.

Animals↗
PubMed1992

Search for retrovirus in the chronic fatigue syndrome.

AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus. METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus. CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.

Blotting, Southern↗
PubMed1991

Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome.

We analysed peripheral blood CD56+ natural killer (NK) cell subsets in 23 carefully characterized patients with post-viral fatigue syndrome (PFS), compared with 19 healthy controls, using fluorochrome-conjugated, specific monoclonal antibodies and the FACScan. We found significantly increased percentages of CD56+, and especially CD56bright+ NK cells in PFS patients. We also found significantly increased percentages of CD56+ high affinity interleukin-2 (IL-2) receptor (CD25)+ and CD56+ transferrin receptor (CD71+) subsets of cells, most of which also stained brightly for CD56. Also, we found an increased percentage of CD56+ CD3+ cells, many of which stained brightly for CD56, although there was no increase in the percentage of CD56- CD3+ T cells in these patients. These observations, in conjunction with very low percentage of CD56- CD25+ cells, suggest that there is a preferential involvement of this minor subset of CD56+ CD3+ T cells in PFS. Finally, a decreased percentage of CD56+ Fc gamma receptor (CD16)+ NK cells was identified, which suggests a reduced capacity of antibody-dependent cellular cytotoxicity in PFS patients. Subsets of CD56+ NK cells co-expressing CD2, CD4 or CD8 did not show any significant difference between PFS patients and healthy controls. These phenotypic changes provide laboratory evidence of immunological abnormalities in this syndrome, and, we suggest, may be consistent with persistent viral infection.

Adolescent↗
PubMed1990

Assay of complement activation in mouse serum by ELISA.

We describe a simple, sensitive and reproducible ELISA assay for complement activation in mouse serum, based on measurement of the opsonization of purified, heat-aggregated mouse gamma-globulin bound to the solid phase. This assay measures mainly classical pathway activation, and we used it to show significant differences in complement activation in sera from mice of various autoimmune, immunodeficient and immunologically normal strains. This assay has the advantage over existing methods of requiring minimal volumes of serum, and of avoiding problems of species incompatibility.

Animals↗
PubMed1990

Immunological abnormalities in BXSB mice at the onset of SLE development.

Male BXSB mice develop murine lupus spontaneously at about 3 months of age. Polyclonal B-cell activation is thought to play a major role in the development of the syndrome in these mice, but the immunological events which lead to this activation are not known. We therefore examined the immune characteristics of mice aged 10-16 weeks, at the onset of disease. We found several immunological markers, indicating polyclonal B-cell activation leading to early, preclinical, disease activity in both male and female BXSB mice, but consistent abnormalities in the percentages and function of lymphocyte subpopulations were found only in male BXSB mice. In particular, the ratio of helper to suppressor/cytotoxic T cells was found to be significantly lower in male BXSB, than in either females of this strain, or normal control DBA2 mice. We conclude that defective immunoregulation is likely to be significant in the initiation of murine lupus, since it is detectable at the onset of disease in male BXSB mice.

Animals↗
PubMed1989

A search for common immunological abnormalities at the onset of murine lupus in two genetically different strains.

Mice of the genetically different BXSB and MRL/lpr strains develop murine lupus spontaneously at about three months of age. Polyclonal B-cell activation is thought to play a major role in the development of the syndrome in each strains, but the immunological events which lead to this activation are not known. We therefore examined the immune characteristics of mice aged 10-16 weeks, at the onset of the disease. We found consistent abnormalities in the percentages of lymphocyte sub-populations in both male BXSB, and male and female MRL/lpr mice. In particular, the ratio of helper to suppressor/cytotoxic T cells was found to be significantly lower in male BXSB, and in male and female MRL/lpr mice than in normal, control, DBA2 mice. Significant increases in serum IgG and IgA concentrations, indicative of polyclonal B cell activation, were present in each strain. The histological appearance of the lymphoid organs and the functional responses to mitogen stimulation were, however, distinctly different. We conclude that defective immunoregulation is likely to be significant in the initiation of murine lupus, since it is detectable at the onset of disease in two genetically distinct strains. It may be associated, however, with different immunological phenomena in strains of different genetic backgrounds.

Animals↗
PubMed1982

Reaction of the leukocytes of melanoma patients and control donors, including pregnant women, with melanoma- and fetus-derived materials.

Using a one-stage capillary leukocyte migration inhibition assay, we examined peripheral blood leukocytes from 97 patients with malignant melanoma, 194 pregnant women, and 123 non-pregnant donors for their reactivity with materials from fetal and melanomatous tissues. As in previous studies, we found melanoma extracts selectively to inhibit melanoma patients' leukocytes. First-trimester fetal extracts also selectively inhibited melanoma patients' leukocytes, suggesting their cross-reactivity with melanoma-derived antigens. We could not localize the source of the inhibitory materials within the fetuses. We found no evidence that pregnant women were selectively immunized to fetal or melanoma extracts, regardless of their parity or the stage of their pregnancy.

Cell Migration Inhibition↗
PubMed1982

Establishment and characterization of human neuroblastoma and ganglioneuroblastoma cell lines.

The establishment in culture and characterization of 4 human neuroblastoma (NB) cell lines and 1 human ganglioneuroblastoma cell line are described. Each cell line fulfilled at least 2 of 4 criteria for malignant or transformed cells: viz., subcultured more than 70 times, high saturation density with absence of contact inhibition, population-doubling time within a range of 10-40 h, and tumour formation in nu/nu mice. Each cell line also fulfilled at least 2 of 3 criteria for neuroblastoma cells: viz., humoral and cell-mediated immune reactivity toward NB-associated cell-surface antigen, intracellular storage and extra-cellular secretion of catecholamines, and characteristic neuroblast and ganglion-cell morphology.

Animals↗