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J M Johnston

Publications and source records attributed to J M Johnston.

At least 19 recordsLinked to original sources
PubMed2004

Identifying barriers to the adoption of evidence-based medicine practice in clinical clerks: a longitudinal focus group study.

OBJECTIVE: To identify and explore common barriers to the adoption of evidence-based medicine (EBM) practice in the undergraduate setting. DESIGN: Nested longitudinal, focus group-based, qualitative study. Setting The University of Hong Kong Medical School, Hong Kong, China. PARTICIPANTS: A group of 39 Year 4 medical undergraduates who participated in an EBM intervention cluster randomised crossover trial. MAIN OUTCOME MEASURES: Students' attitudes, opinions and perceptions of barriers to EBM use. RESULTS: General attitudes towards EBM and the teaching intervention were positive. Four sets of barriers to greater EBM use were identified as follows. (1) Learning environment including prevailing norms for student learning involving examination-oriented, textbook learning, prior availability of clinical practice guidelines, lack of encouragement from teachers and economy of time by utilising teacher expertise. (2) Limitations of evidence consisting of poor point-of-care access to medical literature, difficulty in locating evidence and the perceived low relevance of overseas evidence to Chinese patients. (3) Lack of opportunity to practise EBM due to lack of continuity of care and anxieties about negative teacher attitudes towards EBM use at the point-of-care. (4) Time constraints such as competing study demands and long evidence search time. CONCLUSIONS: Significant barriers to the successful implementation of EBM learning in the clinical clerkship setting were identified. These can be specifically targeted to ameliorate any inhibition of clinical learning they may impose.

Attitude↗
PubMed2003

Production of dopaminergic neurons for cell therapy in the treatment of Parkinson's disease.

Dopaminergic cell therapy is a potential viable treatment for Parkinson's disease. However, lack of a well-characterized cell preparation of known phenotypic composition containing a high percentage of dopaminergic neurons, has prevented a definitive, controlled, pilot clinical trial from being conducted. We report the successful in vitro expansion of rat E12 mesencephalic progenitors to produce 5-fold the normal number of dopaminergic neurons. The expanded neurons (MAP2+) were detached, resuspended, and formed into small aggregates of 10-200 neurons containing 25-50% of dopaminergic neurons (TH+) that will likely be optimal for use in successful cell therapy. After storage in DPBS, in 0 mM Ca(2+) for up to 24 h at room temperature, aggregated cells were still 90% viable. These results demonstrate that it might be feasible to use a similar protocol to expand human dopaminergic progenitors in vitro. If successful, the requisite large numbers of dopaminergic neurons required to conduct a pilot clinical trial for Parkinson's disease will be produced in vitro. Indications are that the cells can be maintained at optimal viability for the duration of the neural transplantation procedure, under real operating conditions.

Animals↗
PubMed2002

Effect of prior revascularization on outcome following percutaneous coronary intervention; NHLBI Dynamic Registry.

AIMS: An increasing number of patients undergoing percutaneous coronary intervention (PCI) have experienced previous revascularization procedures. Their outcome after PCI has seldom been compared to that of patients without prior procedures. This study investigates which elements of prior revascularization affect in-hospital and long-term outcome after PCI. METHODS AND RESULTS: Baseline characteristics as well as in-hospital and 1-year outcomes were compared in 4010 consecutive patients undergoing PCI in the NHLBI Dynamic Registry, categorized by type of prior procedure. In-hospital mortality was lowest and procedural success highest among patients with prior PCI only. Patients with prior coronary artery bypass grafting (CABG) had higher rates for the combined endpoint of death and myocardial infarction (MI) at 1 year compared to patients with no prior procedures. However, in multivariate regression analysis adjusting for potential confounders, neither prior PCI nor prior CABG were independent predictors of death or death/MI at 1 year. Patients with prior procedure had higher rates for repeat PCI and patients with prior PCI had higher rates for CABG during the year following the index procedures. These associations persisted after adjustment for potential confounders. Finally, patients with prior procedures had a higher prevalence of angina at 1 year. CONCLUSIONS: Due to adverse baseline characteristics, patients with prior CABG have higher rates for death/MI during the first year after PCI and both groups of patients with prior procedures have higher revascularization rates. However, only the associations with repeat revascularization persist after adjustment for baseline and procedural factors.

Aged↗
PubMed2002

Repeat-cycle study of high-dose intravenous 4162W94 anti-CD4 humanized monoclonal antibody in rheumatoid arthritis. A randomized placebo-controlled trial.

OBJECTIVE: Results of an earlier open-label pilot study showed that 4162W94 was a relatively non-depleting anti-CD4 monoclonal antibody that induced >80% down-modulation of CD4 molecules from the surface of T lymphocytes. This placebo-controlled repeat-cycle study was conducted in active rheumatoid arthritis (RA) patients to determine the duration of CD4 blockade required to achieve lasting clinical benefit. METHODS: Following DMARD washout, 48 patients (i.e. three cohorts of 16 patients) with ACR-defined RA were to be dosed with 1 (cohort 1), 2 (cohort 2) or 3 (cohort 3) cycles of 5x300 mg 4162W94 or placebo (12 and 4 patients per cohort respectively) at monthly intervals. There was at least 3 months of follow-up after dosing. Clinical outcome was assessed in evaluable patients (receiving at least 80% of each dose course) using ACR20 criteria (required on two consecutive visits). CD4 lymphocyte counts and adverse events were also monitored. RESULTS: Sixteen patients were dosed in each of the first two cohorts; however, the dose was reduced in cohort 3 after five patients had received up to two dose cycles due to accumulating evidence of a high frequency of skin rash. These patients were analysed according to the number of cycles received. A further eight patients received 5x100 mg for one to three cycles prior to stopping the study for administrative reasons. Four of 13 (P=0.119 vs placebo) and 7/13 (P=0.015 vs placebo) in cohorts 1 and 2 respectively achieved ACR20 response on at least two consecutive occasions. No patient receiving 5x100 mg/day or placebo achieved ACR20. Four patients were still responding at the end of the 3-month follow-up period. CD4 lymphocyte suppression (<0.2x10(9)/l on at least two successive occasions) occurred in 11/34 patients who received 4162W94 vs none on placebo. Rash occurred in 21/34 monoclonal antibody-treated patients, including one case of biopsy-confirmed cutaneous vasculitis and 1/11 placebo patients. CONCLUSION: 4162W94 demonstrated significant clinical efficacy in this study. However, because of unacceptable CD4 lymphopenia and rash, the original hypothesis that prolonged CD4 blockade would give lasting clinical benefit was not tested.

Adult↗
PubMed2001

Incidence of Alzheimer's disease in a rural community in India: the Indo-US study.

OBJECTIVE: To determine overall and age-specific incidence rates of AD in a rural, population-based cohort in Ballabgarh, India, and to compare them with those of a reference US population in the Monongahela Valley of Pennsylvania. METHODS: A 2-year, prospective, epidemiologic study of subjects aged > or =55 years utilizing repeated cognitive and functional ability screening, followed by standardized clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for the diagnosis, and the Clinical Dementia Rating scale for the staging, of dementia and AD. RESULTS: Incidence rates per 1000 person-years for AD with CDR > or =0.5 were 3.24 (95% CI: 1.48-6.14) for those aged > or =65 years and 1.74 (95% CI: 0.84-3.20) for those aged > or =55 years. Standardized against the age distribution of the 1990 US Census, the overall incidence rate in those aged > or =65 years was 4.7 per 1000 person-years, substantially lower than the corresponding rate of 17.5 per 1000 person-years in the Monongahela Valley. CONCLUSION: These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow-up, cultural factors, and other potential confounders suggest caution in interpreting this finding.

Age Factors↗
PubMed2001

Molecular basis of mucopolysaccharidosis type IIIB in emu (Dromaius novaehollandiae): an avian model of Sanfilippo syndrome type B.

Sanfilippo syndrome type B, or mucopolysaccharidosis (MPS) IIIB, is an autosomal recessive disease caused by a deficiency of lysosomal alpha-N-acetylglucosaminidase (NAGLU). In Dromaius novaehollandiae (emu), a progressive neurologic disease was recently discovered, which was characterized by NAGLU deficiency and heparan sulfate accumulation. To define the molecular basis, the sequences of the normal emu NAGLU cDNA and gene were determined by PCR-based approaches using primers for highly conserved regions of evolutionarily distant NAGLU homologues. It was observed that the emu NAGLU gene is structurally similar to that of human and mouse, but the introns are considerably shorter. The cDNA had an open reading frame (ORF) of 2259 bp. The deduced amino acid sequence is estimated to share 64% identity with human, 63% with mouse, 41% with Drosophila, 39% with tobacco, and 35% with the Caenorhabditis elegans enzyme. Three normal and two affected emus were studied for nucleotide sequence covering the entire coding region and exon-intron boundaries. Unlike the human gene, emu NAGLU appeared to be highly polymorphic: 19 variations were found in the coding region alone. The two affected emus were found to be homozygous for a 2-bp deletion, 1098-1099delGG, in exon 6. The resulting frameshift predicts a longer ORF of 2370 bp encoding a polypeptide with 37 additional amino acids and 387 altered amino acids. The availability of mutation screening in emus now permits early detection of MPS IIIB in breeding stocks and is an important step in characterizing this unique, naturally occurring avian model for the development of gene transfer studies.

Acetylglucosaminidase↗
PubMed2001

Soy protein isolate consumption protects against azoxymethane-induced colon tumors in male rats.

Male Sprague-Dawley rats (F2 generation) that had been fed modified American Institute of Nutrition-93G diets formulated with a single protein source of either casein or soy protein isolate for their entire life received azoxymethane once a week for 2 weeks (s.c., 15 mg/kg) starting at age 90 days. Forty weeks later, all rats were euthanized, the colon was examined visually for masses and these were subsequently evaluated histologically. Rats fed the casein diet had a 50% incidence of colon tumors compared with 12% on soy protein-based diets (P<0.05). These results suggest that consumption of soy protein-containing diets may reduce the risk of developing colon tumors.

Adenocarcinoma↗
PubMed2001

Computerization of clinical practice in Hong Kong.

The objective of this study was to assess the current level of computerization in clinical practice in Hong Kong through a population-based, physician survey conducted in 2000.A self-completed, 20-question, postal questionnaire was sent to 4850 randomly selected doctors in Hong Kong. We received 897 completed responses. Over one-third of doctors in the overall sample were already recording patient summaries, processing laboratory results and specialist reports, and preparing referral notes electronically. Patient registration (52.2%), billing systems (40.2%), appointment scheduling (39.9%), and payroll (36.9%), were the commonest administrative functions to have been computerized. Seventy per cent of doctors in solo or small-group ('individual') practices did not yet have any clinical function computerized compared with only 30.7% for those working in large, corporate organizations. Similarly, approximately two-thirds of administrative tasks in 'individual' clinics were not computerized, while corporate physicians reported a corresponding percentage of 39.3%. Younger age, male gender, specialist qualifications, more computers in the practice, higher numbers of administrative tasks already computerized, higher levels of knowledge about and positive attitudes towards computer applications in clinical practice were all positively associated with more clinical tasks already computerized in the practice. The present study has systematically documented the extent of clinical computer use in Hong Kong and identified areas for improvement as well as specific groups of physicians who might benefit from targeted efforts promoting computerization in practice.

Adult↗
PubMed2001

Exogenous NT-3 and NGF differentially modulate PACAP expression in adult sensory neurons, suggesting distinct roles in injury and inflammation.

Expression of pituitary adenylate cyclase-activating polypeptide in sensory neurons varies with injury or inflammation. The neurotrophins NGF and NT-3 are profound regulators of neuronal peptidergic phenotype in intact and injured sensory neurons. This study examined their potential for modulation of PACAP expression in adult rat with intact and injured L4-L6 spinal nerves with or without immediate or delayed intrathecal infusion of NT-3 or NGF. Results indicate that in L5 DRG, few trkC neurons express high levels of PACAP mRNA in the intact state, but many do following injury. The elevated expression in injured neurons is mitigated by NT-3 infusion, suggesting a role for NT-3 in returning the 'injured phenotype' back towards an 'intact phenotype'. NGF dramatically up-regulated PACAP expression in trkA-positive neurons in both intact and injured DRGs, implicating NGF as a positive regulator of PACAP expression in nociceptive neurons. Surprisingly, NT-3 modulates PACAP expression in an antagonistic fashion to NGF in intact neurons, an effect most evident in the trkA neurons not expressing trkC. Both NT-3 and NGF infusion results in decreased detection of PACAP protein in the region of the gracile nuclei, where central axons of the peripherally axotomized large sensory fibers terminate. NGF infusion also greatly increased the amount of PACAP protein detected in the portion of the dorsal horn innervated by small-medium size DRG neurons, while both neurotrophins appear able to prevent the decrease in PACAP expression observed in these afferents with injury. These results provide the first insights into the potential molecules implicated in the complex regulation of PACAP expression in sensory neurons.

Afferent Pathways↗
PubMed2001

Dietary whey protein protects against azoxymethane-induced colon tumors in male rats.

Epidemiological studies have suggested a relationship between diet and colon cancer incidence. Results from animal studies suggest that whey protein, but not casein protein, may provide protective effects against experimentally induced breast cancer in animals. In the current study, we investigated the effects of casein and whey diets on chemically induced colon cancer in male rats. Pregnant female Sprague Dawley rats (days 3-4 of gestation) were maintained on modified AIN-93G diets formulated with a single protein source of either casein or whey. Life-time exposure to these diets was studied in the F1 generation (experiment A) or the F2 generation (experiment B). Male offspring were weaned to the same diets as the dams and were maintained on these diets throughout the study. At age 90 days, all rats received azoxymethane once a week for 2 weeks (s.c., 15 mg/kg). Forty weeks after the last azoxymethane injection, all rats were euthanized, the colon was examined visually for tumors, and each tumor was histologically evaluated. The weights and distribution of all of the tumors were recorded. In experiment A, rats fed the casein diet had a 56% incidence of colon tumors compared with 30% of the rats on whey-based diets (P < 0.05). In experiment B, rats fed the casein diet had 50% incidence of colon tumors compared with 29% in the whey group (P < 0.05). There were no significant effects of diet on tumor multiplicity or mass. These results suggest that consumption of whey protein-containing diets may reduce the risk of developing colon tumors.

Animals↗
PubMed2000

A prospective study of back belts for prevention of back pain and injury.

CONTEXT: Despite scientific uncertainties about effectiveness, wearing back belts in the hopes of preventing costly and disabling low back injury in employees is becoming common in the workplace. OBJECTIVE: To evaluate the effectiveness of using back belts in reducing back injury claims and low back pain. DESIGN AND SETTING: Prospective cohort study. From April 1996 through April 1998, we identified material-handling employees in 160 new retail merchandise stores (89 required back belt use; 71 had voluntary back belt use) in 30 states (from New Hampshire to Michigan in the north and from Florida to Texas in the south); data collection ended December 1998, median follow-up was 6(1/2) months. PARTICIPANTS: A referred sample of 13,873 material handling employees provided 9377 baseline interviews and 6311 (67%) follow-up interviews; 206 (1.4%) refused baseline interview. MAIN OUTCOME MEASURES: Incidence rate of material-handling back injury workers' compensation claims and 6-month incidence rate of self-reported low back pain. RESULTS: Neither frequent back belt use nor a belt-requirement store policy was significantly associated with back injury claim rates or self-reported back pain. Rate ratios comparing back injury claims of those who reported wearing back belts usually every day and once or twice a week vs those who reported wearing belts never or once or twice a month were 1.22 (95% confidence interval [CI], 0.87-1.70) and 0.95 (95% CI, 0.56-1.59), respectively. The respective odds ratios for low back pain incidence were 0.97 (95% CI, 0.83-1.13) and 0.92 (95% CI, 0.73-1.16). CONCLUSIONS: In the largest prospective cohort study of back belt use, adjusted for multiple individual risk factors, neither frequent back belt use nor a store policy that required belt use was associated with reduced incidence of back injury claims or low back pain. JAMA. 2000;284:2727-2732.

Adult↗
PubMed2000

Altered binding of mutated presenilin with cytoskeleton-interacting proteins.

The majority of familial Alzheimer's disease (AD) cases are linked to mutations on presenilin 1 and 2 genes (PS1 and PS2). The normal function of the proteins and the mechanisms underlying early-onset AD are currently unknown. To address this, we screened an expression library for proteins that bind differentially to the wild-type PS1 and mutant in the large cytoplasmic loop (PS1L). Thus we isolated the C-terminal tail of the 170 kDa cytoplasmic linker protein (CLIP-170) and Reed-Sternberg cells of Hodgkin's disease-expressed intermediate filament-associated protein (Restin), cytoplasmic proteins linking vesicles to the cytoskeleton. PS1L binding to CLIP-170/restin requires Ca(2+). Treating cells with thapsigargin or ionomycin increased the mutated PS1 in CLIP-170 immunoprecipitates. Further, PS1 and CLIP-170 co-localize in transfected cells and neuronal cultures.

Alzheimer Disease↗
PubMed2000

Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study.

BACKGROUND: The APOE*E4 allele of the gene for apolipoprotein E (APOE) has been reported as a risk factor for Alzheimer disease (AD) to varying degrees in different ethnic groups. OBJECTIVE: To compare APOE*E4-AD epidemiological associations in India and the United States in a cross-national epidemiological study. DESIGN: Case-control design within 2 cohort studies, using standardized cognitive screening and clinical evaluation to identify AD and other dementias and polymerase chain reaction to identify APOE genotyping. PARTICIPANTS: Rural community samples, aged 55 years or older (n=4450) in Ballabgarh, India, and 70 years or older (n=886) in the Monongahela Valley region of southwestern Pennsylvania. MAIN OUTCOME MEASURES: Criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable and possible AD and Clinical Dementia Rating (CDR) scale for dementia staging. RESULTS: Frequency of APOE*E4 was significantly lower (P<.001) in Ballabgarh vs the Monongahela Valley (0.07 vs 0.11). Frequency of probable or possible AD, with CDR of at least 1.0, in the Indian vs US samples, was as follows: aged 55 to 69 years, 0.1% (Indian sample only); aged 70 to 79 years, 0.7% vs 3.1%; aged 80 years or older, 4.0% vs 15.7%. Among those aged 70 years or older, adjusted odds ratios (95% confidence interval) for AD among carriers of APOE*E4 vs noncarriers were 3.4 (1.2-9.3) and 2.3 (1.3-4.0) in the Indian and US samples, respectively, and not significantly different between cohorts (P=. 20). CONCLUSION: This first report of APOE*E4 and AD from the Indian subcontinent shows very low prevalence of AD in Ballabgarh, India, but association of APOE*E4 with AD at similar strength in Indian and US samples. Arch Neurol. 2000.

Aged↗
PubMed2000

Endoglin expression as a measure of microvessel density in cervical cancer.

OBJECTIVE: To evaluate endoglin, a membrane protein and member of the transforming growth factor beta-1 receptor complex, as an endothelial marker of angiogenesis in cervical cancer tissues. METHODS: Tumor tissue was collected from 31 surgically treated stage IB nonbulky (under 5 cm) cervical cancer subjects, and samples were fixed in formalin and embedded in paraffin. Endoglin was stained on 5-microm slide sections by the DAKO Catalyzed Signal Amplification method (DAKO Corporation, Carpinteria, CA). Factor VIII was stained by standard immunohistochemistry. Positively stained microvessels were counted in "hot spots" at 200x magnification. Clinical data were correlated with vessel counts by Spearman correlation. Mean differences in counts were tested using paired t tests. RESULTS: This staining method for endoglin identified significantly more vessels than the factor VIII method (mean 92 +/- 45 versus 33 +/- 16, P <. 001). Endoglin and factor VIII counts correlated significantly with deep stromal invasion (Spearman rho 0.466 and 0.522, respectively, P <.05); however, only endoglin counts correlated significantly with lymph node metastases (rho =.495, P <.01). CONCLUSION: Endoglin is stimulated in tumor angiogenesis and might be relatively more specific than commonly used endothelial markers. The endoglin system was more sensitive for staining capillaries in neoplastic cervical tissue, better predicted lymph node metastases, and should be widely applicable for the study of other tumors.

Antigens, CD↗
PubMed2000

Pharmacokinetic, pharmacodynamic and clinical effects of a humanized IgG1 anti-CD4 monoclonal antibody in the peripheral blood and synovial fluid of rheumatoid arthritis patients.

BACKGROUND: CD4(+) T cells are important mediators in the pathogenesis of rheumatoid arthritis (RA). In this open-label, dose-escalating study, we examined the pharmacokinetic (PK), clinical, biological and immunological effects of a humanized IgG1 anti-CD4 monoclonal antibody (mAb), 4162W94, in the peripheral blood (PB) and synovial fluid (SF) of RA patients. METHOD: Twenty-four patients in four cohorts (six patients in each cohort) were allocated to be treated with five consecutive daily doses of 4162W94 (10, 30, 100 or 300 mg i.v.). Disease activity was measured by the American College of Rheumatology (ACR) criteria and disease activity score (DAS). We also measured 4162W94 concentration, the percentage of 4162W94-coated CD4(+) lymphocytes, percentage down-modulation of CD4, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha) levels in the PB and SF. RESULTS: A direct relationship between 4162W94 dose, biological response and clinical outcome was seen. Treatment with 10 and 30 mg of 4162W94 for 5 consecutive days resulted in transient coating and down-modulation of CD4(+) lymphocytes, with little effect observed beyond the final dose. However, treatment with 100 and 300 mg resulted in sustained coating and/or down-modulation for 3 weeks and 4 weeks, respectively, in PB and >4 weeks in SF in one patient from the 300 mg cohort. There was a dose-related moderate but transient depression in the CD4(+) lymphocyte count in most patients, with all but three returning to >0.40 x 10(9)/l or >75% baseline by the end of the study period. Significant clinical improvement (ACR 20%) was seen in only 1/6 patients in each of the 10- and 30-mg cohorts; however, 3/6 and 5/5 patients in the 100 and 300-mg cohorts, respectively, were ACR 20% responders. In addition, there were significant reductions in PB acute phase reactants as well as SF IL-6 and TNFalpha concentrations in parallel to clinical improvement. CONCLUSION: Data from this pilot study suggest that 4162W94 is a clinically active novel immunotherapeutic agent that may suppress inflammation in RA.

Adult↗
PubMed1999

Small head size is related to low Mini-Mental State Examination scores in a community sample of nondemented older adults.

The objective of this analysis was to determine the relationship, if any, of head size to performance on a cognitive screening test among elderly nondemented adults participating in a community-based survey. The study sample included 825 subjects (533 women, 292 men), age 70 to 95 years. Multivariate analyses, with adjustment for age and education, revealed that smaller head size was associated with low Mini-Mental State Examination (MMSE) scores (i.e., below the 10th percentile) in both men and women. For every 1-centimeter increment in head size, there was a corresponding reduction of approximately 20% in the probability of a low MMSE score.

Age Factors↗
PubMed1999

Plasma platelet-activating factor acetylhydrolase activity is not associated with premature coronary atherosclerosis.

Platelet-activating factor acetylhydrolase activity in plasma was compared between 72 subjects with angiographically normal coronary arteries and matched controls with clinically significant obstruction. No difference was seen, and we conclude that variation in plasma platelet-activating factor acetylhydrolase activity is not a risk factor for coronary artery disease.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗