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Biomedical subjects

K Saunders

Publications and source records attributed to K Saunders.

At least 37 records · Page 2Linked to original sources

A nanovirus-like DNA component associated with yellow vein disease of Ageratum conyzoides: evidence for interfamilial recombination between plant DNA viruses.

Yellow vein disease of Ageratum conyzoides, a weed species that is widely distributed throughout Asia, has been attributed to infection by the geminivirus Ageratum yellow vein virus (AYVV). In addition to a single AYVV genomic component (DNA A), we have previously demonstrated that infected plants contain chimeric defective viral components, comprising DNA A and nongeminiviral sequences, that act as defective interfering DNAs. A database search has revealed that the nongeminiviral sequences of one such defective component (def19) show significant homology with sequences of nanovirus components that encode replication-associated proteins (Reps). Primers designed to hybridise to the nongeminiviral DNA were used to PCR-amplify a full-length nanovirus-like component, referred to as DNA 1, from an extract of infected A. conyzoides. DNA 1 is unrelated to AYVV DNA A but resembles nanovirus components that encode Reps and is most closely related (73% identity) to a nanovirus-like DNA recently isolated from geminivirus-infected cotton. DNA 1 is dependent on AYVV DNA A for systemic infection of A. conyzoides and Nicotiana benthamiana and can systemically infect N. benthamiana in the presence of the bipartite geminivirus African cassava mosaic virus. A. conyzoides plants coinfected with AYVV DNA A and DNA 1 remain asymptomatic, indicating that additional factors are required to elicit yellow vein disease. Our results provide direct evidence for recombination between distinct families of plant single-stranded DNA viruses and suggest that coinfection by geminivirus and nanovirus-like pathogens may be a widespread phenomenon. The ability of plant DNA viruses to recombine in this way may greatly increase their scope for diversification.

Amino Acid Sequence↗

Bean yellow dwarf virus RepA, but not rep, binds to maize retinoblastoma protein, and the virus tolerates mutations in the consensus binding motif.

It has previously been reported that complementary-sense gene products of wheat dwarf virus (WDV), a geminivirus of the genus Mastrevirus that infects monocotyledonous plants, bind to human and maize retinoblastoma (Rb) protein. Rb proteins control cell-cycle progression by sequestering transcription factors required for entry into S-phase, suggesting that the virus modifies the cellular environment to produce conditions suitable for viral DNA replication. Using a yeast two-hybrid assay, we have investigated whether the complementary-sense gene products of bean yellow dwarf virus, a mastrevirus that is adapted to dicotyledonous plants, also bind maize Rb protein. We demonstrate that whereas RepA binds to Rb protein, Rep does not, suggesting that RepA alone regulates host gene expression and progression of cells to S-phase. RepA mutants containing L --> I, C --> S, C --> G, and E --> Q mutations within the consensus Rb protein binding motif LXCXE retained the ability to bind to Rb, but with reduced efficiency. Most notably, the E --> Q mutation reduced binding by approximately 95%. Nonetheless, all LXCXE mutants were able to replicate in tobacco protoplasts and to systemically infect Nicotiana benthamiana and bean, in which they produced wild-type symptoms.

Binding Sites↗

Costs of health care use by women HMO members with a history of childhood abuse and neglect.

BACKGROUND: Early childhood maltreatment has been associated with adverse adult health outcomes, but little is known about the magnitude of adult health care use and costs that accompany maltreatment. We examined differences in annual health care use and costs in women with and without histories of childhood sexual, emotional, or physical abuse or neglect. METHODS: A random sample of 1225 women members of a health maintenance organization completed a 22-page questionnaire inquiring into childhood maltreatment experiences as measured by the Childhood Trauma Questionnaire. Health care costs and use data were obtained from the automated cost-accounting system of the health maintenance organization, including total costs, outpatient and primary care costs, and emergency department visits. RESULTS: Women who reported any abuse or neglect had median annual health care costs that were $97 (95% confidence interval, $0.47-$188.26) greater than women who did not report maltreatment. Women who reported sexual abuse had median annual health care costs that were $245 (95% confidence interval, $132.32-$381.93) greater than costs among women who did not report abuse. Women with sexual abuse histories had significantly higher primary care and outpatient costs and more frequent emergency department visits than women without these histories. CONCLUSION: Although the absolute cost differences per year per woman were relatively modest, the large number of women in the population with these experiences suggests that the total costs to society are substantial.

Adolescent↗

Effect of sleep state on the flash visual evoked potential. A case study.

Controversy exists regarding the influence of sleep state on the flash visual evoked potential. This study recorded the visual evoked potential in a new-born infant in four different sleep states; wakefulness. drowsiness, active sleep and quiet sleep over a five hour period. The infant's heart rate, breathing rate and breathing regularity were also recorded. It was clear that when this subject was awake the VEPs recorded differed substantially from those recorded when sleeping. Two of the four main components had shorter peak latencies, one component was prolonged and one of the peak to trough amplitudes was consistently smaller when alert. This study highlights an important and often overlooked aspect of developmental research that the state of the infant may affect developmental measures.

Evoked Potentials, Visual↗

Headache medication-use among primary care headache patients in a health maintenance organization.

OBJECTIVE: Medication-use among headache patients 2 and 5 years after a primary care headache visit is assessed, and the pattern of medication-use compared before and after the introduction of subcutaneous sumatriptan among migraineurs. SETTING AND PATIENTS: The study was carried out among headache patients visiting a primary care physician at the Group Health Cooperative of Puget Sound in 1989-90. METHODS: We report medication-use patterns 2 and 5 years later for the 530 subjects completing both a 2-year (1991-92) and a 5-year (1994-95) follow-up interview. Medication-use was determined by self-report for the month prior to the interview. Medication-use to control or prevent headache is shown for all headache patients and for those meeting International Headache Society criteria for migraine at the 2-year and the 5-year follow-up. RESULTS: The overall pattern of medication-use was similar at the 2-year and the 5-year follow-up, before and after the introduction of subcutaneous sumatriptan (March, 1993). There was a modest but statistically significant decline in the use of opioid and sedative-hypnotic medications, and in the use of ergotamine. At 5 years, 11% of migraineurs reported use of sumatriptan in the prior month. The large majority of study patients used symptomatic medications, usually non-prescription analgesics, sedative-hypnotics, and opiates. Only one-fifth of the migraineurs reported use of a prophylactic medication for headache. CONCLUSIONS: Continuing use of symptomatic headache medications was characteristic of patients with migraine and other common forms of headache. The introduction of subcutaneous sumatriptan was not associated with notable change in this pattern, although a modest reduction in use of sedative-hypnotics and opiates was observed. Overall, the pattern of use of headache medications was similar before and after the introduction of subcutaneous sumatriptan.

Adolescent↗

A randomized trial of a lay person-led self-management group intervention for back pain patients in primary care.

STUDY DESIGN: Randomized, controlled trial. OBJECTIVE: To evaluate a four-session self-management group intervention for patients with pain in primary care, led by trained lay persons with back pain. The intervention was designed to reduce patient worries, encourage self-care, and reduce activity limitations. BACKGROUND DATA: Randomized trials of educational interventions suggest that activating interventions may improve back pain outcomes. Expert opinion increasingly regards effective self-management of back pain as important in achieving good outcomes. In this study, an educational intervention designed to activate patients and support effective self-management was evaluated. METHODS: Six to 8 weeks after a primary care visit for back pain, patients were invited to participate in an educational program to improve back pain self-management. Those showing interest by returning a brief questionnaire became eligible for the study. Participants (n = 255) randomly were assigned to either a self-management group intervention or to a usual care control group. The effect of the intervention, relative to usual care, was assessed 3, 6, and 12 months after randomization, controlling for baseline values. The intervention consisted of a four-session group applying problem-solving techniques to back pain self-management, supplemented by educational materials (book and videos) supporting active management of back pain. The groups were led by lay persons trained to implement a fully structured group protocol. The control group received usual care, supplemented by a book on back pain care. RESULTS: Participants randomly assigned to the self-management groups reported significantly less worry about back pain and expressed more confidence in self-care. Roland Disability Questionnaire Scores were significantly lower among participants in the self-management groups relative to the usual care controls at 6 months (P = 0.007), and this difference was sustained at 12 months at borderline significance levels (P = 0.09). Among self-management group participants, 48% showed a 50% or greater reduction in Roland Disability Questionnaire Score at 6 months, compared with 33% among the usual care controls. CONCLUSIONS: Self-management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries, producing positive attitudes toward self-care, and reducing activity limitations among patients with back pain in primary care.

Activities of Daily Living↗

Assessing the feasibility of using computerized pharmacy refill data to monitor antidepressant treatment on a population basis: a comparison of automated and self-report data.

This article compares self-report and automated data as measures of dose and duration of antidepressant use in order to assess the feasibility of using automated pharmacy data in a disease management context. We used self-report and computerized refill data to identify two treatment failures-premature discontinuation of the medication and sub-optimal dosages-at time points 1 and 4 months after initiation of antidepressant therapy. The sources showed modest agreement regarding identification of current users at 1 month (kappa = .33); agreement was high at 4 months (kappa = .72). Agreement regarding dosage adequacy was also higher later in treatment, with kappas of .52 and .65 at 1 and 4 months, respectively. The two sources showed high agreement on an overall measure of acute phase treatment adequacy (kappa = .80). Data completeness was another outcome, with data on current users and overall treatment adequacy generally available from computerized files, data on dose less so. Automated pharmacy data appear to be a feasible means of monitoring treatment adequacy and quality of care as part of a disease management approach to improving care for populations of patients.

Antidepressive Agents↗

Novel defective interfering DNAs associated with ageratum yellow vein geminivirus infection of Ageratum conyzoides.

Defective DNA forms of the geminivirus ageratum yellow vein virus (AYVV) have been identified in naturally infected Ageratum conyzoides plants. Several examples of the defective DNA have been cloned from purified virus-specific supercoiled DNA and characterized by sequence analysis. All are approximately half the size of AYVV genomic DNA, and all contain intergenic region sequences and the 5' terminus of gene C1 as well as additional sequences that are unrelated to the viral genomic DNA. The chimeric nature of the defective DNA distinguishes it from previously characterized geminivirus defective and satellite DNAs. The defective DNA ameliorates disease symptoms and causes a significant delay in the accumulation of viral DNA during the early stage of infection when coinoculated with the AYW genomic DNA into Nicotiana benthamiana, suggesting a biological role as a defective interfering DNA.

Base Sequence↗

Transactivation of dianthin transgene expression by African cassava mosaic virus AC2.

We have recently described a novel strategy for engineering resistance to African cassava mosaic virus (ACMV) in transgenic Nicotiana benthamiana plants using a virus-inducible promoter to control the expression of a plant ribosome-inactivating protein (RIP) transgene (Y. Hong et al., Virology 220, 119-127, 1996). Here, we have used a potato virus X (PVX) vector to express the ACMV transactivator protein, AC2, in planta. We confirm that amplification of RIP activity in transgenic plants is mediated by AC2; disruption of AC2 expression by either the introduction of an in-frame stop codon or the deletion of 5'-terminal or 3'-terminal coding sequences reduced RIP expression to the basal level associated with PVX-infected plants. AC2 expression from the PVX vector induced necrosis in nontransformed plants as well as in plants containing the RIP transgene, suggesting that the protein can functionally interact with PVX and/or host factors. The potential of this system to provide a direct and sensitive assay to investigate AC2 function in planta is discussed.

Antiviral Agents↗

Use of exogenous hormones and risk of temporomandibular disorder pain.

Temporomandibular disorders (TMD) are common pain conditions that have their highest prevalence among women of reproductive age. The higher prevalence of TMD pain among women, pattern of onset after puberty and lowered prevalence rates in the post-menopausal years suggest that female reproductive hormones may play an etiologic role in TMD. Two epidemiologic studies were designed to assess whether use of exogenous hormones is associated with increased risk of TMD pain. Both used data from automated pharmacy records of women enrolled in a large health maintenance organization to identify prescriptions filled for post-menopausal hormone replacement therapies (Study 1) or for oral contraceptives (OCs) (Study 2). Study 1 employed an age-matched case-control design to compare post-menopausal hormone use among 1291 women over age 40 referred for TMD treatment and 5164 controls not referred. After controlling for health services use, the odds of being a TMD case were approximately 30% higher among those receiving estrogen compared to those not exposed (P = 0.002); a clear dose-response relationship was evident. The relationship of progestin use to TMD was not statistically significant. Study 2 used a similar design to examine the relationship of OC use to referral for TMD care, drawing on data from 1473 cases and 5892 controls aged 15-35. Use of OCs was also associated with referral for TMD care, with an increased risk of TMD of approximately 20% for OC users, after controlling for health services use (P < 0.05). These results suggest that female reproductive hormones may play an etiologic role in orofacial pain. This relationship warrants further investigation through epidemiologic, clinical and basic research.

Adult↗

'My beloved chloroform'. Attitudes to childbearing in colonial Queensland: a case study.

In 1847 the anaesthetic and analgesic properties of chloroform were discovered. This technology generated a new era for midwifery: mothers could be relieved of pain in childbirth. The introduction of chloroform for childbirth saw increasing medical dominance in obstetrics, traditionally in the hands of the midwife. At the same time the use of chloroform sparked a medical and moral controversy which lasted for several decades. On the one hand women were destined by the 'curse of Eve' to experience pain during childbirth; on the other, medical humanitarians and practitioners believed that there were technical and moral reasons for alleviating pain in childbirth. In concentrating on the debate historians have largely ignored the reactions of mothers to the introduction of the technology. This paper explores changing attitudes to childbearing within the context of colonial Queensland society, 1860-90, by examining the correspondence of an upper-class mother. Her education and liberal outlook, and a certain ambivalence towards motherhood, all influenced her attitude to the use of chloroform and the process of childbirth.

Anesthesia↗

The course of back pain in primary care.

STUDY DESIGN: Review paper of outcome studies among primary care back pain patients. OBJECTIVES: To determine the short-term and long-term pain and functional outcomes of patients with back pain who are seeking treatment in primary care settings. SUMMARY OF BACKGROUND DATA: Back pain has been viewed as running either an acute or a chronic course, but most patients experience recurrent back pain. This review summarizes outcome studies in light of the episodic course of back pain. METHODS: Studies reporting pain and functional outcome data for consecutive primary care patients with back pain were reviewed. RESULTS: Back pain among primary care patients typically is a recurrent condition for which definitions of acute and chronic pain based on a single episode are inadequate. Because a majority of patients experience recurrences, describing only the outcome of the initial back pain episode may convey a more favorable picture of long-term outcome than warranted. For the short-term follow-up evaluation, most patients improve considerably during the first 4 weeks after seeking treatment. Sixty-six percent to 75% continue to experience at least mild back pain 1 month after seeking care. At 1 month, approximately 33% report continuing pain of at least moderate intensity, whereas 20-25% report substantial activity limitations. For the long-term follow-up (1 year or more) period, approximately 33% report intermittent or persistent pain of at least moderate intensity, one in seven continue to report back pain of severe intensity, and one in five report substantial activity limitations. CONCLUSION: Results from existing studies suggest that back pain among primary care patients typically runs a recurrent course characterized by variation and change, rather than an acute, self-limiting course.

Back Pain↗

Resistance to geminivirus infection by virus-induced expression of dianthin in transgenic plants.

Ribosome-inactivating proteins (RIPs) are naturally occurring plant toxins that exhibit antiviral activity against a diverse range of plant and animal viruses. Here, the action of dianthin, a potent RIP isolated from Dianthus caryophyllus, has been exploited to engineer resistance to a plant DNA virus, African cassava mosaic virus (ACMV), in transgenic Nicotiana benthamiana. To achieve this, dianthin has been expressed from the ACMV virion-sense promoter that is transactivated by the product of viral gene AC2. This avoids the need for constitutive expression of the RIP, facilitating the regeneration of phenotypically normal plants, and ensures transgene expression is localized to virus-infected cells. When challenged with ACMV, transgenic plants produce atypical necrotic lesions on inoculated leaves, indicative of dianthin expression, viral DNA accumulation is significantly reduced in these tissues, and plants exhibit attenuated systemic symptoms from which they recover. This phenotype holds for isolates of ACMV but not for other geminiviruses, suggesting that AC2 homologues from the latter are unable to efficiently transactivate the ACMV promoter.

Antiviral Agents↗

Cortical visual dysfunction in children: a clinical study.

Damage to the cerebral cortex was responsible for impairment in vision in 90 of 130 consecutive children referred to the Vision Assessment Clinic in Glasgow. Cortical blindness was seen in 16 children. Only 2 were mobile, but both showed evidence of navigational blind-sight. Cortical visual impairment, in which it was possible to estimate visual acuity but generalised severe brain damage precluded estimation of cognitive visual function, was observed in 9 children. Complex disorders of cognitive vision were seen in 20 children. These could be divided into five categories and involved impairment of: (1) recognition, (2) orientation, (3) depth perception, (4) perception of movement and (5) simultaneous perception. These disorders were observed in a variety of combinations. The remaining children showed evidence of reduced visual acuity and/ or visual field loss, but without detectable disorders of congnitive visual function. Early recognition of disorders of cognitive vision is required if active training and remediation are to be implemented.

Adolescent↗

Growth and physical outcome of children conceived by in vitro fertilization.

OBJECTIVE: To determine the growth and physical outcome at 2 years of age for children born after assisted reproductive techniques in the state of Victoria. DESIGN: Using a case-matched control study between January 1991 and July 1993, 314 children (196 singletons, 47 sets of twins, 8 sets of triplets) conceived after in vitro fertilization (IVF) and related techniques at the Monash IVF and Royal Women's Hospital Reproductive Biology Unit and 150 control children (113 singletons, 17 sets of twins, 1 set of triplets) randomly selected from the general population using the Victorian Perinatal Data Collection Unit records were enrolled to be examined for minor dysmorphic and major organ abnormalities. Singleton and twin cases were matched for plurality and gestation and date of birth. Triplets were not matched. RESULTS: IVF status was not a significant independent factor for physical outcomes, including malformation rates, nor for days of hospitalization postdischarge and operations. There was no significant interaction between IVF status and mean percentiles for weight and head circumference. The IVF group had a greater mean length percentile. Twins in both groups had significantly poorer physical outcomes than singletons on some measures. CONCLUSION: This study did not demonstrate an independent IVF effect on the growth and physical outcome of children at 2 years of age when matched for plurality and gestation. The poor outcomes where noted were related to the effects of multiple births. These findings must be viewed in context of the response rates and therefore representativeness of the data. The need for longitudinal studies is demonstrated.

Adult↗

Outcomes of "inadequate" antidepressant treatment.

OBJECTIVE: To examine outcomes of primary care patients receiving low levels of antidepressant treatment. DESIGN: Cohort study comparing patients receiving anti-depressant treatment within and below the recommended dosing range. SETTING: Primary care clinics of a staff-model health maintenance organization. PATIENTS: Primary care patients initiating antidepressant treatment for depression. MEASUREMENTS AND MAIN RESULTS: Of 88 patients beginning antidepressant treatment, 49 (56%) used "adequate" doses for 30 days or more. Likelihood of "adequate" pharmacotherapy was not related to patient age, gender, medical comorbidity, or baseline depression severity. All the patients showed substantial clinical improvement after four months. Compared with those using "adequate" pharmacotherapy, the patients receiving low-intensity treatment had lower likelihood of clinical response (64% vs 84%; chi-square = 4.44; df = 1; p = 0.035). At four months, however, those receiving low-intensity and those receiving higher-intensity treatment did not differ significantly in either the score on the 20-item Symptom Checklist depression scale (18.91 and 15.72, respectively; F = 1.45; df = 1.86; p = 0.23) or the proportion with persistence of major depression (10% and 4%, respectively; chi-square = 1.30; df = 1; p = 0.25). A replication sample of 157 patients (assessed only at baseline and four months) yielded similar results. CONCLUSIONS: While the patients receiving recommended levels of pharmacotherapy showed somewhat higher improvement rates, many of the patients receiving "inadequate" treatment experienced good short-term outcomes. Efforts to increase the intensity of depression treatment in primary care should focus on the subgroup of patients who fail to respond to initial treatment.

Adult↗

A chronic disease score with empirically derived weights.

Different types of medication prescribed during a 6-month period for the treatment and management of chronic conditions were utilized in the refinement and validation of a chronic disease score. Prescription data, in addition to age and sex, were utilized to develop a chronic disease score based on empirically derived weights for each of three outcomes: total cost, outpatient cost, and primary care visits. The ability of the revised chronic disease score to predict health care utilization, costs, hospitalization, and mortality was compared to an earlier version of the chronic disease score (original) that was derived through clinical judgments of disease severity. The predictive validity of the chronic disease score is also compared to ambulatory care groups, which utilize outpatient diagnoses to form mutually exclusive diagnostic categories. Models based on a concurrent 6-month period and a 6-month prospective period (ie, the 6-month period after the chronic disease score or ambulatory care group derivation period) were estimated using a random one half sample of 250,000 managed-care enrollees aged 18 and older. The remaining one half of the enrollee population was used as a validation sample. The revised chronic disease score showed improved estimation and prediction over the original chronic disease score. The difference in variance explained prospectively by the revised chronic disease score versus the ambulatory care groups, conversely, was small. The revised chronic disease score was a better predictor of mortality than the ambulatory care groups. The combination of revised chronic disease score and ambulatory care groups showed only marginally greater predictive power than either one alone. These results suggest that the revised chronic disease score and ambulatory care groups with empirically derived weights provide improved prediction of health care utilization and costs, as well as hospitalization and mortality, over age and sex alone. We recommend the revised chronic disease score with total cost weights for general use as a severity measure because of its relative advantage in predicting mortality compared to the outpatient cost and primary care visit weights.

Adult↗