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Biomedical subjects

C A Jackson

Publications and source records attributed to C A Jackson.

At least 19 recordsLinked to original sources
PubMed2001

RNA replicons derived from poliovirus are directly oncolytic for human tumor cells of diverse origins.

The failure and/or toxicity of conventional therapies for many types of human cancers underscore the need for development of safe and effective alternative treatments. Toward this goal, we describe the direct oncolytic activity of RNA-based vectors derived from poliovirus, termed replicons, which are genetically incapable of producing infectious virus. These replicons are cytopathic in vitro for human tumor cells originating from brain, breast, lung, ovary, and skin (melanoma). The cytopathic effects in a malignant glioma cell line were associated with nuclear DNA condensation, indicative of cells undergoing apoptosis. Injection of replicons into established xenograft flank tumors in scid mice resulted in oncolytic activity and extended survival. Inoculation of replicons into established intracranial xenograft tumors in scid mice resulted in tumor infection within 8 h and extended survival. Histological analysis revealed that replicons had infected tumor cells at the site of inoculation and, most importantly, diffused to infect tumor cells that had metastasized from the initial site of implantation. The wide spectrum of cytopathic activity for human tumors combined with effective distribution after in vivo inoculation establishes the therapeutic potential of poliovirus replicons for a variety of cancers.

Animals↗
PubMed2001

Repetitive intrathecal injections of poliovirus replicons result in gene expression in neurons of the central nervous system without pathogenesis.

Poliovirus-based vectors (replicons) can be used for gene delivery to motor neurons of the CNS. In the current study, a replicon encoding green fluorescent protein (GFP) was encapsidated into authentic poliovirions, using established procedures. Intrathecal delivery of encapsidated replicons encoding GFP to the CNS of mice transgenic for the human poliovirus receptor did not result in any functional deficits as judged by behavioral testing. Histological analysis of the CNS of mice given a single intrathecal injection of poliovirus replicons encoding GFP revealed no obvious pathogenesis in neurons (or other cell types) within the CNS. The expression of GFP was confined to motor neurons throughout the neuroaxis; a time course of expression of GFP revealed that expression was detectable 24 hr postinoculation and returned to background levels by 120 hr postinoculation. A procedure was devised to allow repetitive inoculation of replicons within the same animal. Behavioral testing of animals that had received 6 to 13 independent inoculations of replicons revealed no functional deficits. Histological analysis of the CNS from animals that had received 6 to 13 sequential inoculations of replicons revealed no obvious abnormalities in neurons or other cell types in the CNS; expression of GFP was demonstrated in neurons 24 to 72 hr after the final inoculation of the replicon. Furthermore, there was no obvious inflammatory response in the CNS after the multiple inoculations. These studies establish the safety and efficacy of replicons for gene delivery to the CNS and are discussed with respect to use of replicons as new therapeutic strategies for spinal cord injuries and/or neurological diseases.

Animals↗
PubMed2001

The Life Events Inventory: re-scaling based on an occupational sample.

The objective of this study was to compare the validity of the original weightings used by the Life Events Inventory (LEI) with those obtained from a contemporary occupational sample. Fifty male and 62 female manufacturing employees (age range 16-55 years) assigned scores to each item on a slightly modified version of the LEI scale. The current sample consistently assigned higher weights to events/items than did the original sample, but there was high agreement in terms of item ranking. Some distinct age and gender differences in scoring were apparent, and are discussed further. It was concluded that when separate weightings are employed for age and gender groups, the LEI remains a useful tool for quantifying background levels of stress in both workplace stress audits and epidemiological studies where statistical control for non-occupational sources of stress is required.

Adolescent↗
PubMed2001

Effect of a tongue-tie on upper airway mechanics in horses during exercise.

OBJECTIVE: To determine the effect of a tongue-tie on upper airway mechanics in exercising horses. ANIMALS: 5 Standardbreds. PROCEDURE: Peak inspiratory and expiratory tracheal and pharyngeal pressures and airflow were measured while horses exercised on a treadmill with and without a tongue-tie. Respiratory rate was also measured. Horses ran at speeds that corresponded to 50 (HR50), 75, 90 (HR90), and 100% of maximal heart rate. The tongue-tie was applied by pulling the tongue forward out of the mouth as far as possible and tying it at the level of the base of the frenulum to the mandible with an elastic gauze bandage. Peak inspiratory and expiratory tracheal, pharyngeal, and translaryngeal resistance, minute ventilation, and tidal volume were calculated. Data were analyzed by use of 2-way repeated-measures ANOVA. For post hoc comparison of significant data, the Student-Newman-Keuls test was used. RESULTS: We were unable to detect significant differences between groups for peak inspiratory or expiratory tracheal or pharyngeal resistance, peak pressure, peak expiratory flow, tidal volume, respiratory rate, or minute ventilation. Horses that ran with a tongue-tie had significantly higher peak inspiratory flows, compared with horses that ran without a tongue-tie. In the post hoc comparison, this effect was significant at 4 m/s, HR50, and HR90. CONCLUSION AND CLINICAL RELEVANCE: Application of a tongue-tie did not alter upper respiratory mechanics in exercising horses and may be beneficial in exercising horses with certain types of obstructive dysfunction of the upper airways. However, application of a tongue-tie does not improve upper airway mechanics in clinically normal horses.

Animals↗
PubMed2000

A consensus Porphyromonas gingivalis promoter sequence.

We have determined the transcription start points (tsp) for recently identified Porphyromonas gingivalis W50 genes, kgp, rgpA, rgpB (formerly designated prtK, prtR, and prtRII respectively), fetB and the mcmAB operon. Alignment of the DNA upstream of these tsp and those from the literature has enabled us to identify consensus sequences that may represent a P. gingivalis promoter. There is a potential -10 hexamer sequence, 5'-TATATT-3' centred on average at -10/11 nt which is repeated at -19/20 nt and an upstream consensus, 5'-CAGAT(A/G)-3' which is centred at -39/40 nt.

Bacterial Outer Membrane Proteins↗
PubMed2000

Cytokine production in motor neurons by poliovirus replicon vector gene delivery.

Poliovirus replicon vectors transiently express foreign proteins selectively in motor neurons of the anterior horn of the spinal cord. Here we intraspinally inoculated mice transgenic for the poliovirus receptor (PVR) with replicons encoding murine tumor necrosis factor alpha (mTNF-alpha). We detected high-level expression of mTNF-alpha in the spinal cords of these animals at 8-12 h post inoculation; this returned to background by 72 h. The mice exhibited ataxia and tail atony, whereas animals given a replicon encoding green fluorescent protein (GFP) exhibited no neurological symptoms. Histology of spinal cords from mice given the replicon encoding mTNF-alpha revealed neuronal chromatolysis, reactive astrogliosis, decreased expression of myelin basic protein, and demyelination. These animals recovered with only slight residual damage. This study shows that replicon vectors have potential for targeted delivery of therapeutic proteins to the central nervous system and provide a new approach for treatment of spinal cord trauma and neurological disease.

Animals↗
PubMed2000

Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves).

Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function.

Airway Obstruction↗
PubMed1998

Subspecialty distributions of ophthalmologists in the workforce.

OBJECTIVE: To describe the distribution of the supply and requirements for subspecialty ophthalmologists. METHODS: Estimates from the Eye Care Workforce Study were used to provide subspecialty-based assessments of the supply and public health need, as well as market demand, for care provided by subspecialists. Reconciliation with the boundary models (optometry first, ophthalmology first) of the Eye Care Workforce Study and current market status also were performed. RESULTS: Whether subspecialists are in excess depends first on which boundary model most closely approximates the current market conditions. Under an optometry-first model, 70% of all ophthalmologists are in excess, although subspecialists (39%) are relatively less in excess than comprehensive ophthalmologists (91% excess). Under an ophthalmology-first model, no ophthalmologists would be in excess. Extrapolating from current market conditions, a slight excess of ophthalmologists exists, probably proportional across subspecialists and comprehensive ophthalmologists. Future growth in the ophthalmologist supply will be almost entirely among subspecialists. CONCLUSION: Under current market conditions, substantial excesses in subspecialist ophthalmologists are likely to develop and grow worse over time, given current training levels.

Health Services Needs and Demand↗
PubMed1998

Work time estimates for ophthalmic diagnoses and procedures. Results from the Eye Care Workforce Study.

OBJECTIVE: To provide estimates of patient-level annual ophthalmologist work times for the care of common ophthalmic conditions and patient-level global surgical care time for common or important ophthalmic procedures. METHODS: A random sample of the domestic membership (excluding members-in-training) of the American Academy of Ophthalmology, stratified by self-designated practice concentration, was surveyed in 1994 to provide estimates of work times for common ophthalmic services. RESULTS: Comprehensive and subspecialty-specific results were obtained for ophthalmic diagnoses, services, and surgical procedures. For ophthalmic diagnoses and services, initial and follow-up visit work times are reported for comprehensive and subspecialty ophthalmologists separately. For common surgical procedures, aggregate results based on comprehensive and subspecialist survey responses are reported. CONCLUSIONS: These ophthalmology-specific survey results can be used for a variety of purposes, including practice management, "benchmarking," health plan administration and national workforce planning. Such surveys should be repeated as techniques and practice patterns change over time.

Diagnostic Techniques, Ophthalmological↗
PubMed1998

Demand-based assessment of workforce requirements for orthopaedic services.

On the basis of an analysis of the supply of and demand for orthopaedic surgeons, we projected that there will be 21,134 full-time-equivalent orthopaedists in the year 2010 if training continues at current levels. We estimated a demand-based requirement of 17,012 full-time-equivalent orthopaedic surgeons, indicating a surplus of 4122 full-time equivalents. In terms of orthopaedist-to-population ratios, we estimated that there will be 7.5 full-time-equivalent orthopaedists per 100,000 population in 2010 compared with a demand-based requirement of 6.0 full-time equivalents. However, we did not include estimates of the demand for orthopaedic surgeons as assistants in the operating room in our model. If an assistant orthopaedic surgeon is required for all procedures, an additional 3906 full-time-equivalent orthopaedists would be demanded, thus eliminating the surplus. The demand for an assistant orthopaedic surgeon in only half of the procedures would still lead to a sizable reduction in the surplus.

Emergency Service, Hospital↗
PubMed1996

Prevalence of comorbid anxiety disorders in primary care outpatients.

OBJECTIVE: To estimate the extent to which anxiety disorders (eg, panic disorder, phobia, and generalized anxiety disorder [GAD]) co-occur in patients with major medical and psychiatric conditions. DESIGN: Observational study. SETTING: Offices of primary care providers in three US cities, with mental health specialty providers included for comparative purposes. PATIENTS: Adult patients (N = 2494) with hypertension, diabetes, heart disease (congestive heart failure or myocardial infarction), current depressive disorder, or subthreshold depression. MEASURES: Current (past 12 months) and lifetime panic disorder, phobia, GAD, perceived need for help for emotional or family problems, and unmet need (ie, failure to get help that was needed). METHODS: Comparisons of the prevalence of anxiety comorbidity in medically ill nondepressed patients of primary care providers and in depressed patients of both primary care and mental health specialty providers. RESULTS: Among primary care patients, those with chronic medical illnesses or subthreshold depression had low rates of lifetime (1.5% to 3.5%) and current (1.0% to 1.7%) panic disorder, but those with current depressive disorder had much higher rates (10.9% lifetime and 9.4% current panic disorder). Concurrent phobia and GAD were more common (10.4% to 12.4% current GAD), especially among depressed patients (25% to 54% current GAD). Depending on the type of medical illness or depression, 14% to 66% of primary care patients had at least one concurrent anxiety disorder. Patient-perceived unmet need for care for personal or emotional problems was high among all primary care patients (54.6% to 72.9%). CONCLUSION: Primary care clinicians should be aware of the possible coexistence of anxiety disorders (especially GAD) among their patients with chronic medical conditions, but especially among those with current depressive disorder.

Adult↗
PubMed1996

Comorbid anxiety disorder and the functioning and well-being of chronically ill patients of general medical providers.

BACKGROUND: The comorbidity of psychiatric disorders with chronic health conditions has emerged as a topic of considerable clinical and policy interest, in part owing to the evidence that anxiety disorders themselves are associated with morbidity. However, the implications for health-related quality of life that result from anxiety disorders, which are comorbid to chronic medical or psychiatric illness, are not well understood, especially in primary care samples. METHODS: A 2-year observational study of 875 adult patients with hypertension, diabetes, heart disease, and current depressive disorder or subthreshold depression receiving care from general medical providers was conducted. The unique effect of any comorbid anxiety disorder on functioning and well-being (determined with the use of the 36-Item Short-Form Health Survey [SF-36]) was estimated, as well as the differential impact at baseline, 2-year follow-up, and change over time, of any comorbid anxiety disorder for patients with chronic medical conditions or depression. RESULTS: Patients with comorbid anxiety who received general medical care had lower levels of functioning and well-being than those without comorbid anxiety. These differences were most pronounced in mental health-related quality-of-life measures and when anxiety was comorbid with chronic medical conditions rather than with depression. Hypertensive and diabetic patients with comorbid anxiety were as debilitated as patients with depression or heart disease, and this low health-related quality of life persisted over time. Comorbid anxiety had less of an effect on patients with heart disease who already had a low health-related quality of life. CONCLUSION: The finding of substantial differences in the quality of life between hypertensive and diabetic patients with and without comorbid anxiety disorder highlights the clinical and societal importance of identifying comorbid anxiety in these patients.

Adult↗
PubMed1996

Characteristics and service use of seriously mentally ill persons living in rural areas.

OBJECTIVE: Data from a cross-sectional survey of 210 current or former inpatients at Mississippi State Hospital and 197 informants, usually patients' family members, were used to compare the demographic, clinical, and service use characteristics of patients living in rural areas with those of patients living in nonrural areas. METHODS: All subjects completed structured face-to-face interviews. Information on recent use of community mental health center (CMHC) services was obtained from CMHC records. Characteristics of rural patients (N = 107) and nonrural patients (N = 103) were compared using chi square and t tests. RESULTS: Rural patients were less likely to have completed high school and more likely to be living with family members. Although rural and nonrural subjects were clinically similar, rural subjects were less likely to have received certain community mental health services such as case management and day treatment and were more likely to have used physical health services and to have been involved with the criminal justice system. CONCLUSIONS: Differences between rural and nonrural patients in patterns of service use are most likely a reflection of less availability or accessibility of mental health services in rural areas, resulting in spillover into physical health and criminal justice sectors. Rural community mental health centers need to formally incorporate families, local medical providers, and law enforcement officials into their network of care.

Activities of Daily Living↗
PubMed1995

Cloning, expression and sequence analysis of the genes encoding the heterodimeric methylmalonyl-CoA mutase of Porphyromonas gingivalis W50.

Two genes that encode methylmalonyl-CoA mutase (MCM) have been characterised in Porphyromonas gingivalis W50 (Pg). The genes, designated mcmA and mcmB are transcribed in an operon and encode the MCM small subunit (SS, 68,626 Da) and the MCM large subunit (LS, 78,703 Da), respectively. A recombinant Escherichia coli (Ec) clone harbouring the Pg mcmA and mcmB genes expressed MCM activity 280-times higher than that of the Ec control. The C terminus of the MCM LS has sequence homology to domains of a variety of enzymes that consume or produce methylmalonyl-CoA, suggesting that the MCM LS C-terminal domain is involved in substrate binding. The MCM LS C-terminal region also exhibits homology to other enzymes that have cobalamin-containing cofactors. It is likely, therefore, that the C terminus of the MCM LS is an important MCM domain involved in both substrate and cofactor binding.

Amino Acid Sequence↗
PubMed1995

Endothelial lipopigment as an indicator of alpha-tocopherol deficiency in two equine neurodegenerative diseases.

Two spontaneous neurodegenerative diseases of the horse, equine motor neuron disease (EMND) and equine degenerative myeloencephalopathy (EDM), have been associated with alpha-tocopherol deficiency, and both were characterized by prominent accumulations of endothelial lipopigment in the small vessels of the spinal cord. These endothelial pigment deposits appear to be reversible. In EMND horses pasture-supplemented for 9 months or more after the progression of weakness and wasting had arrested, there was very little endothelial lipopigment. The origin and the potential effects of these endothelial lipopigment accumulations are discussed.

Animals↗
PubMed1995

Estimating eye care workforce supply and requirements.

PURPOSE: To estimate the workforce supply and requirements for eye care in the United States. METHODS: Three models were constructed for analysis: supply of providers, public health need for eye care, and demand (utilization) for eye care. Ophthalmologists, other physicians, and optometrists were included in the models. Public health need was determined by applying condition-specific prevalence and incidence rates from population-based and other epidemiologic studies. Demand was determined by use of national databases, such as the National Ambulatory Care Survey, National Hospital Discharge Survey, and Medicare Part B. Time requirements for care were obtained through a stratified sample survey of the membership of the American Academy of Ophthalmology. RESULTS: Under modeling assumptions that use a work-time ratio of one between optometrists and ophthalmologists and between specialist and generalist ophthalmologists, a significant excess of eye care providers exists relative to both public health need and demand. Changes in the work-time ratio, work-hours per year per provider, care patterns for the same condition, or other factors could significantly reduce or eliminate the surplus relative to need. CONCLUSION: If optometrists are the preferred primary eye care provider, ophthalmologists would be in excess under all demand scenarios and all need scenarios where the optometrist to ophthalmologist work-time ratio is greater than 0.6. No excess of ophthalmologists would exist if ophthalmologists are the preferred primary eye care provider. Data on the appropriate work time ratio will help refine estimates of the imbalance between supply and requirements.

Eye Diseases↗