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Biomedical subjects

J M Smyth

Publications and source records attributed to J M Smyth.

17 recordsLinked to original sources
PubMed2004

Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study.

AIMS: To characterize the population pharmacokinetics of indometacin in preterm infants with symptomatic patent ductus arteriosus and to investigate the influence of various factors on the response to treatment. METHODS: Data were collected from 35 infants (gestational age 25-34 weeks; postnatal age 1-77 days) in neonatal units in Belfast and Copenhagen. Infants received an initial course of up to three doses of intravenous indometacin (0.1-0.2 mg kg(-1)) as considered appropriate by the treating physician. For those infants who did not respond to therapy or in whom the ductus reopened, a second course was sometimes given. Population analysis of the 185 plasma concentrations obtained was conducted using NONMEM and pharmacokinetic and demographic differences between responders and nonresponders were compared. RESULTS: The concentration-time course of indometacin was best described by a one-compartment model. The final population parameter estimates of clearance (CL) and volume of distribution (V) (standardized to the median weight of 1.17 kg) were 0.00711 l h(-1) and 0.266 l, respectively. CL increased from birth by approximately 3.38% per day and V by approximately 1.47% per day. Concomitant digoxin therapy resulted in a 30% decrease in V. Interindividual variability in CL and V was 41% and 21%, respectively. Interoccasion variability for CL was 43%. Residual variability corresponded to a standard deviation of 0.148 mg l(-1). Closure occurred in 75% of infants with a plasma concentration > or = 0.4 mg l(-1) 24 h after the last dose. CONCLUSIONS: Dosing regimens for indometacin should take into account the weight and postnatal age of the infant and any concomitant digoxin therapy. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indometacin that should increase the probability of achieving a 24 h plasma concentration > or = 0.4 mg l(-1). Although the pharmacokinetic estimates will be affected by both interindividual and within-individual variation, it is anticipated that this approach will decrease the variability of exposure and optimize treatment outcome.

Cardiovascular Agents↗
PubMed2001

Sexual trauma and personality: developmental vulnerability and additive effects.

Two types of sexual trauma, sexual abuse in childhood and rape in adulthood, were investigated in terms of possible effects on personality. Four groups of participants were studied: women who had experienced sexual abuse in childhood, women who had experienced rape as adults, women who had experienced both of these sexual traumas, and a control group of women who had experienced no sexual trauma. Personality functioning was assessed using the Dimensional Assessment of Personality Pathology. Groups who had experienced childhood sexual abuse displayed the highest degree of personality disturbance; however, the additive effects of repeated sexual trauma were limited. These findings may reflect the outcome of specific adversity in childhood on the psychobiological constructs underlying personality.

Adult↗
PubMed2000

Structured writing about stressful events: exploring potential psychological mediators of positive health effects.

In a previous study, the authors found that structured writing about stressful events improved symptomatology in 112 patients with rheumatoid arthritis and asthma relative to patients who did not write (J. Smyth, A. Stone, A. Hurewitz, & A. Kaell, 1999). However, little is currently known about the pathways from the intervention to alterations in outcomes. In addition to measuring symptom outcomes after the intervention in the previous study, the authors monitored perceived stress, quality of sleep, affect, substance use, and medication use on a momentary basis for the 7 days prior to writing, during the 3 intervention days, and for the 14 days following the intervention (N = 105). These variables were tested in a secondary data analysis to determine whether they mediated the effects observed in the J. Smyth, A. Stone, et al. study. No evidence was found supporting mediation, and the mechanism underlying structured writing about stressful events remains unknown.

Adaptation, Psychological↗
PubMed1999

Effects of writing about stressful experiences on symptom reduction in patients with asthma or rheumatoid arthritis: a randomized trial.

CONTEXT: Nonpharmacological treatments with little patient cost or risk are useful supplements to pharmacotherapy in the treatment of patients with chronic illness. Research has demonstrated that writing about emotionally traumatic experiences has a surprisingly beneficial effect on symptom reports, well-being, and health care use in healthy individuals. OBJECTIVE: To determine if writing about stressful life experiences affects disease status in patients with asthma or rheumatoid arthritis using standardized quantitative outcome measures. DESIGN: Randomized controlled trial conducted between October 1996 and December 1997. SETTING: Outpatient community residents drawn from private and institutional practice. PATIENTS: Volunteer sample of 112 patients with asthma (n = 61) or rheumatoid arthritis (n = 51) received the intervention; 107 completed the study, 58 in the asthma group and 49 in the rheumatoid arthritis group. INTERVENTION: Patients were assigned to write either about the most stressful event of their lives (n = 71; 39 asthma, 32 rheumatoid arthritis) or about emotionally neutral topics (n = 41; 22 asthma, 19 rheumatoid arthritis) (the control intervention). MAIN OUTCOME MEASURES: Asthma patients were evaluated with spirometry and rheumatoid arthritis patients were clinically examined by a rheumatologist. Assessments were conducted at baseline and at 2 weeks and 2 months and 4 months after writing and were done blind to experimental condition. RESULTS: Of evaluable patients 4 months after treatment, asthma patients in the experimental group showed improvements in lung function (the mean percentage of predicted forced expiratory volume in 1 second [FEV1] improved from 63.9% at baseline to 76.3% at the 4-month follow-up; P<.001), whereas control group patients showed no change. Rheumatoid arthritis patients in the experimental group showed improvements in overall disease activity (a mean reduction in disease severity from 1.65 to 1.19 [28%] on a scale of 0 [asymptomatic] to 4 [very severe] at the 4-month follow-up; P=.001), whereas control group patients did not change. Combining all completing patients, 33 (47.1%) of 70 experimental patients had clinically relevant improvement, whereas 9 (24.3%) of 37 control patients had improvement (P=.001). CONCLUSION: Patients with mild to moderately severe asthma or rheumatoid arthritis who wrote about stressful life experiences had clinically relevant changes in health status at 4 months compared with those in the control group. These gains were beyond those attributable to the standard medical care that all participants were receiving. It remains unknown whether these health improvements will persist beyond 4 months or whether this exercise will prove effective with other diseases.

Adaptation, Psychological↗
PubMed1999

Rheumatoid arthritis patients show weather sensitivity in daily life, but the relationship is not clinically significant.

While the majority of rheumatoid arthritis (RA) patients report that their pain is influenced by the weather, studies examining the impact of weather on RA pain have yielded equivocal results. It is not clear from the existing studies if the mixed results are due to limited statistical power (e.g. small sample sizes and restricted variability in weather indices) or the failure to consider individual differences. The current study addressed these weaknesses by having 75 RA patients (mean age = 52.7; 71% female) record their daily pain severity for 75 consecutive days. Objective weather indices including temperature, barometric pressure, relative humidity, and percentage of sunlight were obtained for the same dates from a local weather service. The results indicate that for the entire sample, pain levels were highest on cold, overcast days and following days with high barometric pressure. Pain levels also increased as a function of change in relative humidity from one day to the next. Individual difference analyses revealed significant variability between patients in their weather sensitivity patterns. In general, patients with higher levels of self-reported pain demonstrated more weather sensitivity. When considering the magnitude of these effects, however, weather variables accounted for only a small amount of change in pain scores. This pattern was true even for patients with the most pronounced pain-weather relationships. Thus, although weather sensitivity was found, the effect sizes were not clinically meaningful.

Adult↗
PubMed1999

Daily psychosocial factors predict levels and diurnal cycles of asthma symptomatology and peak flow.

This study examines the relationship among psychosocial factors, asthma symptoms, and peak expiratory flow rate (PEFR) in the natural environment. Twenty adult asthmatics wore preprogrammed wristwatches that prompted them to assess PEFR, asthma symptoms, and psychosocial factors five times a day for 10 days. Psychosocial variables (activities, locations, social contacts, mood, and stressors) were strongly related to PEFR and asthma symptoms, suggesting that they may play a more important role in disease expression than has been previously thought. Diurnal cycles of asthma symptoms and PEFR were observed. However, statistically controlling for psychosocial factors eliminated diurnal cycles for PEFR or asthma symptoms, indicating that psychosocial factors are a major contributor to the observed diurnal cycle in PEFR and symptoms. These relationships underscore the need to include psychosocial factors in future asthma research.

Adaptation, Psychological↗
PubMed1998

Consensus among experts and research synthesis. A comparison of methods.

A comparison of two assessment methods, consensus among experts and research synthesis of the scientific literature, was performed using a surgical procedure, carotid endarterectomy (CE), as an example. These two methods have been widely advocated as being scientifically valid. While the comparison revealed a number of areas of general agreement, important differences between the two methods emerged. For example, 30-day mortality for asymptomatic patients was considered an effective outcome (ranked first) by the synthesis, but only "equivocal" (ranked third) of six major indicators reported by the consensus method. The synthesis results are also consistent with other literature reviews as well as with recent large-scale randomized trial results. A number of factors that could account for differences between the two methods were examined. Overall, use of consensus panels may be appropriate early in the development of an intervention where the evidence is sparse, while quantitative research synthesis is preferable when a number of high-quality studies have been performed.

Consensus Statements as Topic↗
PubMed1998

Written emotional expression: effect sizes, outcome types, and moderating variables.

A research synthesis was conducted to examine the relationship between a written emotional expression task and subsequent health. This writing task was found to lead to significantly improved health outcomes in healthy participants. Health was enhanced in 4 outcome types--reported physical health, psychological well-being, physiological functioning, and general functioning--but health behaviors were not influenced. Writing also increased immediate (pre- to postwriting) distress, which was unrelated to health outcomes. The relation between written emotional expression and health was moderated by a number of variables, including the use of college students as participants, gender, duration of the manipulation, publication status of the study, and specific writing content instructions.

Affect↗
PubMed1997

Individual differences in the diurnal cycle of cortisol.

This study investigated individual differences in the diurnal cycle of cortisol and explored their relation to several psychosocial variables and to upper-respiratory symptoms. Cortisol and daily experience were assessed for 2 days in 109 healthy employed and unemployed community residents (mean age = 36.4 +/- 12.1, 69% female); self-report upper respiratory illness (URI) symptoms were assessed for an additional 10 days. Fifty-six (51%) participants showed typical declines in cortisol during both days, 19 (17%) showed no significant diurnal pattern on both days, and 34 (31%) showed different diurnal patterns on the 2 days. Individuals with no cycles did not differ from those with normal or inconsistent cycles on demographic factors, baseline psychological measures, health behaviors, or daily experiences over the two assessment days. Individuals without cortisol cycles, however, reported fewer URI symptoms than the remaining subjects. That 17% of our sample did not exhibit diurnal cycles of cortisol was surprising, given established views of normal endocrine function. Although average daily level of cortisol is related to a number of psychosocial and psychiatric factors (e.g. stress and depression), pattern of diurnal cycle was not related to any demographic or psychosocial measures in this study. The finding that flat cycles were related to fewer reports of URI symptoms suggests that perturbations in cycle may be related to processes associated with symptom susceptibility or symptom expression.

Adult↗
PubMed1995

Exploratory research synthesis--methodological considerations for addressing limitations in data quality.

Exploratory meta-analysis or research synthesis has been advocated as a way of developing important hypotheses for further study. An exploratory research synthesis was conducted on the carotid endarterectomy (CE) literature to illustrate this method. The CE scientific literature is similar to that of many other new medical interventions because it contains numerous limitations to data quality. Exploratory research synthesis of such literature necessitates a number of methodological and statistical considerations to address these limitations, including the problems of missing data, appropriate unit of analysis, nonnormal distribution of outcomes, and lack of controlled studies. Strengths and limitations of the exploratory research synthesis approach are discussed within the context of public policy decisions for assessing medical technologies.

Data Collection↗
PubMed1994

Analysis of the molecular basis of neuropathogenesis of RNA viruses in experimental animals: relevance for human disease?

RNA viruses with segmented genomes were the first model used for molecular analysis of viral neuropathogenesis, since they could be analysed genetically by reassortment. Four viruses with non-segmented genomes have been used as models of neurovirulence and demyelinating disease: JHM coronavirus, Theiler's virus, Sindbis virus and Semliki Forest virus (SFV). Virus gene expression in the central nervous system of infected animals has been measured by in situ hybridization and immunocytochemistry. Cell tropism has been analysed by neural cell culture. Infectious clones have been constructed for Theiler's virus, Sindbis virus and SFV, and these allow analysis of the sequences involved in the determination of neuropathogenesis, through the construction of chimeric viruses and site-specific mutagenesis. Measles and rubella viruses have been studied in animal systems because of their importance for human disease. The importance of two recently discovered mechanisms of neuropathogenesis, antibody-induced modulation of virus multiplication, and persistence of virus in the absence of multiplication, remains to be assessed.

Animals↗
PubMed1990

Multiplication of virulent and demyelinating Semliki Forest virus in the mouse central nervous system: consequences in BALB/c and SJL mice.

The sites of multiplication in the mouse central nervous system (CNS) of the virulent L10 strain of Semliki Forest virus (SFV) and the L10-SFV-derived demyelinating M9 mutant were determined using both BALB/c and SJL mouse strains. In situ hybridization (ISH), using a cRNA probe to an SFV non-structural sequence, and immunogold-silver staining (IGSS), using polyclonal anti-SFV rabbit IgG, were the techniques utilized. For L10-SFV, viral RNA and antigen were detected in neurons and glial cells of both mouse strains. For BALB/c mice infected with M9-SFV, both neuronal and glial cell infection was less extensive than that obtained with L10. ISH or IGSS were generally not sensitive enough to detect viral RNA and antigen, respectively, in M9-SFV-infected SJL mice. M9-SFV multiplied to a similar titre in primary cultures of glial cells derived from either BALB/c or SJL mice. Following infection with M9-SFV, small plaques of demyelination in the CNS and occasional small aggregates of mononuclear leukocytes in the leptomeninges persisted for up to 12 months in SJL mice but not BALB/c mice. This was not associated with detectable persistence of infectious virus, viral antigen or viral RNA in the CNS.

Animals↗
PubMed1989

Effect of infection with the ts22 mutant of Semliki Forest virus on development of the central nervous system in the fetal mouse.

The A7 strain of Semliki Forest virus induces rapid fetal death in pregnant mice, whereas the ts22 mutant derived from it is teratogenic for a proportion of fetuses. Both A7 and ts22 induce viremia and infect the central nervous systems and fetuses of pregnant mice. Using immunogold-silver staining, a cDNA probe for a Semliki Forest virus nonstructural sequence, and a riboprobe derived from the same sequence, we showed that the skin and musculoskeletal systems of fetuses from mothers infected with ts22 were often heavily infected but the central nervous systems were not labeled before day 17 of pregnancy. Damage to the neural tube, including open-neural-tube defects, was detected in fetuses following infection of the mother at days 8 and 10 of pregnancy with both A7 and ts22. For ts22, neural tube damage induced by fetal infection before day 17 of pregnancy appeared to be indirect and caused by virus infection of mesenchymal cells surrounding the developing neural tube.

Animals↗
PubMed1988

Teratogenicity of the Semliki Forest virus mutant ts22 for the foetal mouse: induction of skeletal and skin defects.

The maximum proportion of skeletal and/or skin defects induced by the Semliki Forest virus (SFV) mutant ts22 in the 17-day-old foetal mouse occurred following infection of the mother at day 10 of pregnancy. The skeletal defects were detected using a combination of Alcian blue staining for cartilage and Alizarin red staining for bone. Using immunogold-silver staining with anti-SFV IgG and in situ hybridization with a cDNA probe to SFV non-structural sequences, we have shown that mesenchymal cells in the dermis and surrounding developing cartilaginous plates were heavily infected in most foetuses at day 17 of pregnancy, following infection of the mother at day 10. Other infected foetal tissues contained less viral antigen and nucleic acid; they included the liver, muscle (including myocardium), lung and kidney. The central nervous system contained only small amounts of viral antigen and nucleic acid. It is proposed that the skeletal and skin defects induced in mouse foetuses by ts22 infection result from the tropism of the virus for mesenchymal cells involved in the development of such tissue.

Animals↗