Biomedical subjects

D Stephens

Publications and source records attributed to D Stephens.

At least 91 records · Page 5Linked to original sources

PubMed1997

Inhibition of HIV-1 replication using a mutated tRNALys-3 primer.

Cellular tRNALys-3 serves as the primer for reverse transcription of human immunodeficiency virus, type 1 (HIV-1). tRNALys-3 interacts directly with HIV-1 reverse transcriptase, is packaged into viral particles and anneals to the primer-binding site (PBS) of the HIV-1 genome to initiate reverse transcription. Therefore, the priming step of reverse transcription is a potential target for antiviral strategies. We have developed a mutant tRNALys-3 derivative with mutations in the PBS-binding region such that priming specificity was re-directed to the highly conserved TAR stem-loop region. This mutant tRNA retains high-affinity binding to HIV-1 reverse transcriptase, viral encapsidation, and is able to prime at both the targeted TAR sequence and at the viral PBS. Constitutive expression of mutant tRNA in T-cells results in marked inhibition of HIV-1 replication, as determined by measurements of viral infectivity, syncytium formation, and p24 production. Inhibition of retroviral replication through interference with the normal process of priming constitutes a new anti-retroviral approach and also provides a novel tool for dissecting molecular aspects of priming.

Base Sequence↗

PubMed1997

Hospitalization patterns in severe acute asthma in children.

We set out to determine associations between hospitalization and disease severity before and 2 hours after initiation of asthma therapy in the Emergency Department, and to describe the outcome of patients admitted and discharged. This is a retrospective review of data and charts from a randomized, double blind, placebo-controlled trial (R.C.T.) of 120 asthmatics 5-17 years of age with baseline forced expiratory volume in 1 second (FEV1) < 50% predicted, treated with 3 or 1 or 0 doses of nebulized ipratropium added to three albuterol nebulizations administered over 1 hour. None of the clinical parameters measured at baseline were associated with hospitalization. However, by 2 hours after initiation of therapy, both the FEV1 percent of predicted values (% pred.) and the total asthma score were associated with likelihood of hospital admission. Baseline O2 saturation < 92% indicated a longer hospital stay (75.3 +/- 51 hours vs. 43.0 +/- 24.4 hours, P = 0.015) and a later onset of infrequent nebulizations (46.7 +/- 35.1 vs. 26.6 +/- 17.4 hours, P = 0.006). By 2 hours, those with a post-treatment FEV1 % pred < or = 30% and an asthma score > or = 6 of 9 had a high likelihood of hospitalization (86 and 80%, respectively, combined probability 100%), whereas FEV1 % pred > or = 60% and total asthma score < 3 were associated with successful discharge (probability of 92 and 83%, respectively). We conclude that pre-treatment assessments were not associated with hospitalization, while patients with post-treatment FEV1 % pred < or = 30% and a score > or = 6 had high likelihood of hospitalization.

Administration, Inhalation↗

PubMed1997

Economic evaluation of respiratory syncytial virus infection in Canadian children: a Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study.

OBJECTIVES: To quantify the cost and distribution of health care resources consumed annually in management of Canadian children from birth to 4 years of age with respiratory syncytial virus (RSV) infection. STUDY DESIGN: Estimates of direct medical expenditures (in 1993 U.S. dollars) were collected from a prospective cohort study of hospitalized children with RSV and from national and provincial databases. RESULTS: The annual cost of RSV-associated illness was almost $18 million. The largest component of direct expenditures (62%) was for inpatient care for the estimated 0.7% of all infected children ill enough to require admission. Physician fees comprised only 4% of inpatient expenses. Expenditures for ambulatory patients accounted for 38% of direct costs. CONCLUSIONS: The greatest reductions in the economic cost of RSV infections will be found in interventions that reduce duration of or prevent hospital stay. Costs for management of RSV infection in children in the Canadian health care system are considerably less than charges reported in the United States.

Absenteeism↗

PubMed1997

Effectiveness of prophylactic inhaled steroids in childhood asthma: a systemic review of the literature.

BACKGROUND: There has been no systematic appraisal of the evidence regarding the effectiveness of prophylactic inhaled steroids in childhood asthma. OBJECTIVE: We sought to evaluate the effectiveness of prophylactic inhaled steroids in childhood asthma. METHODS: A MEDLINE search from January 1966 through December 1996 was used to identify pertinent English-language publications. All randomized, double-blind, placebo-controlled trials of prophylactic inhaled steroid therapy for childhood asthma that included data on clinical outcomes (symptom scores and concomitant drug use) or laboratory outcomes (peak expiratory flow rate) were included. RESULTS: In total, 24 of 93 studies retrieved met the inclusion criteria. The overall weighted relative improvement in mean total symptom score (inhaled steroid vs placebo) was 50% (95% confidence interval [CI]: 49%, 51%), the overall weighted relative decrease in mean concomitant beta2-agonist use (inhaled steroid vs placebo) was 37% (95% CI: 36%, 38%), and the overall weighted relative decrease in mean concomitant oral steroid use (inhaled steroid vs placebo) was 68% (95% CI: 66%, 70%). The overall weighted absolute improvement in mean peak expiratory flow rate (inhaled steroid vs placebo) was 38 L/min (95% CI: 34.3 L/min, 41.7 L/min). CONCLUSIONS: Prophylactic inhaled steroids are effective, compared with placebo, in improving both clinical and laboratory outcomes in childhood asthma.

Child↗

PubMed1997

Giuseppe Gradenigo and his contributions to audiology.

Giuseppe Gradenigo (1859-1926) was an important figure in the development of Otology. Within this paper the authors consider his background and his particular contributions to the development of various aspects of audiology.

Audiology↗

PubMed1997

Pendred syndrome--100 years of underascertainment?

Pendred syndrome is an autosomal recessive condition classically characterized by deafness and goitre. Since both cochlear and thyroid pathology are required to secure the diagnosis, it is unclear whether the condition might present without the classical features. The perchlorate discharge test, the gold-standard investigation for Pendred syndrome, is non-specific, and in the absence of alternative means of confirming the diagnosis, its sensitivity is unknown. We used the recent mapping of the gene to chromosome 7q to identify pedigrees with a likely diagnosis of Pendred syndrome, and assessed the prevalence of clinical parameters of disease in affected patients. Thirty-six familial cases showed co-segregation between disease and the Pendred syndrome locus on chromosome 7q. Clinical and investigative findings were compared in index cases (n = 18) vs. affected siblings (n = 18). The overall prevalence of goitre was 73%, higher in index cases (94%) than in siblings (56%), many of whom had not previously been considered to have the condition. One perchlorate discharge test was false-negative (2.9%). Radiological malformations of the cochlea were identified in 86% of cases. Securing a diagnosis of Pendred syndrome may be difficult, especially in the single case. The perchlorate discharge test, although valuable, is difficult to undertake in the younger patient, and radiology may assist in diagnosing such patients.

Adolescent↗

PubMed1997

A tinnitus problem questionnaire in a clinic population.

OBJECTIVE: The purpose of this study was to investigate difficulties associated with tinnitus in a large sample of patients using an open-ended problem questionnaire. DESIGN: Four hundred seventy-three unselected patients referred to the Tinnitus Clinic of the Welsh Hearing Institute (1986 through 1991) completed the Tinnitus Problem Questionnaire (Tyler & Baker, 1988). Before clinical assessment, patients were invited to list problems that they associated with their tinnitus in order of importance in an open-ended questionnaire. Their responses were coded into 45 categories. The responses of 39 patients who only described their tinnitus were excluded, leaving unselected responses from 436 patients, 224 women and 212 men, whose average age was 57.1 yr. The questionnaire elicited an average 3.78 responses per patient (range 1 to 12). RESULTS: The 30 most common difficulties attributed to tinnitus are described. There was broad agreement between the problems reported in this clinic-based study and those reported by a self-help group sample (Tyler & Baker, 1983). CONCLUSIONS: Analysis of these responses into groups based on psychological (30.1%), hearing (23.5%), health (20.7%), sleep (14.6%), and situational (11.1%) difficulties highlights the need for recognition of the global consequences of tinnitus to many patients and for a broadly based tinnitus management model.

Adolescent↗

PubMed1997

Age-related hearing loss in the dependent elderly population: a model for nursing care.

Advancing nursing care through the implementation of evidence-based practice is a legitimate professional ideal. In reality there are many complex issues that need be addressed before such a goal can be achieved. This paper takes an intermediate step towards the realization of this aim in one aspect of continuing care nursing through the presentation of a procedural model. The presented model is designed to stimulate debate as to what could be, and arguably should be the role of the nurse in relation to meeting the auditory rehabilitative needs of dependent elderly patients. The model is based upon a published management model which outlines the auditory rehabilitative process within a psychosocial framework. The original model has been modified as a result of knowledge synthesis from a range of specialist disciplines including nursing. The Audiological Care Model for Nursing is intended to offer an accessible guide to this often neglected aspect of care.

Activities of Daily Living↗

PubMed1997

Pendred syndrome: evidence for genetic homogeneity and further refinement of linkage.

Pendred syndrome is the association between congenital sensorineural deafness and goitre. The disorder is characterised by the incomplete discharge of radioiodide from a primed thyroid following perchlorate challenge. However, the molecular basis of the association between hearing loss and a defect in organification of iodide remains unclear. Pendred syndrome is inherited as an autosomal recessive trait and has recently been mapped to 7q31 coincident with the non-syndromic deafness locus DFNB4. To define the critical linkage interval for Pendred syndrome we have studied five kindreds, each with members affected by Pendred syndrome. All families support linkage to the chromosome 7 region, defined by the microsatellite markers D7S501-D7S523. Detailed haplotype analysis refines the Pendred syndrome linkage interval to a region flanked by the marker loci D7S501 and D7S525, separated by a genetic distance estimated to be 2.5 cM. As potential candidate genes have as yet not been mapped to this interval, these data will contribute to a positional cloning approach for the identification of the Pendred syndrome gene.

Adolescent↗

PubMed1997

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study.

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.

Canada↗

PubMed1997

Does ribavirin impact on the hospital course of children with respiratory syncytial virus (RSV) infection? An analysis using the pediatric investigators collaborative network on infections in Canada (PICNIC) RSV database.

OBJECTIVES: To determine the relationship between receipt of aerosolized ribavirin and the hospital course of high-risk infants and children with respiratory syncytial virus (RSV) lower respiratory infection (LRI). METHODS: The 1993-1994 Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) RSV database consists of prospectively enrolled children with acute RSV LRI, admitted to nine Canadian pediatric tertiary care centers. After excluding cases with compromised immunity and/or nosocomial infection, subsets with any congenital heart disease (CHD), chronic lung disease (CLD), age </=6 weeks (INFANT), gestation </=36 weeks (PREM), or severe disease within 48 hours of admission as shown by an oxygen saturation </=90% or an FiO2 requirement of >.35 (EARLY HYPOXIA) were studied in two ways. First, each risk group subset was analyzed separately to assess the association between ribavirin receipt and measures of disease severity including duration of intensive care, mechanical ventilation, hypoxia and RSV-attributable hospital stay. Secondly, ribavirin was added as an independent variable to a previously described multiple regression model for RSV-attributable length of hospital stay and two mutually exclusive subsets were analyzed: 1) previously healthy patients with >/=1 of: INFANT, PREM, or EARLY HYPOXIA; 2) patients with CHD and/or CLD. RESULTS: Between January 1993 and June 1994, 1425 community-acquired hospitalized cases of RSV LRI were entered into the RSV database. Among these 750 (52.6%) fit into one or more of the defined subsets including 97 CHD, 134 CLD, 213 INFANT, 211 PREM, and 463 EARLY HYPOXIA. The proportion ventilated in each group was 20.6%, 20.9%, 15.5%, 15.2%, and 13.3%, respectively. Across the subsets ribavirin use ranged from 36% to 57% of ventilated patients and 6% to 39% of nonventilated patients. For nonventilated patients in each subset the median RSV-attributable hospital length of stay (RSV-LOS) was 2 to 3 days longer for ribavirin recipients and the duration of hypoxia was significantly increased. Duration of intensive care unit (ICU) stay was also increased for all ribavirin-treated subgroups except those with CHD. In contrast, for ventilated patients, ribavirin therapy was not significantly associated with any of the outcome measures regardless of risk group. In the multiple regression model, ribavirin was significantly associated with a prolonged RSV-LOS both for children with CHD and/or CLD as well as for those whose only risk factors included INFANT, PREM, and/or EARLY HYPOXIA. CONCLUSIONS: These data raise further doubts about the clinical effectiveness of ribavirin in infants and children with risk factors for severe disease. Selection bias, with ribavirin used for sicker children, may have influenced outcome. Nevertheless the long durations of hospitalization, ICU, ventilation, and oxygen supplementation in nonventilated ribavirin recipients stress the need for further randomized trials to assess its efficacy.

Antiviral Agents↗

PubMed1997

PICNIC (Pediatric Investigators Collaborative Network on Infections in Canada) study of the role of age and respiratory syncytial virus neutralizing antibody on respiratory syncytial virus illness in patients with underlying heart or lung disease.

OBJECTIVE: To determine the effects of age and respiratory syncytial virus (RSV) antibody status on frequency and severity of RSV infections in children with underlying heart or lung disease. DESIGN: Cohort study conducted during two consecutive RSV seasons. SETTING: Ambulatory patients at eight Canadian pediatric tertiary care centers. METHODS: Subjects under 3 years old with underlying heart disease who were digoxin-dependent or had not received corrective cardiac surgery or with underlying lung disease were enrolled. Demographic information and an acute sera for RSV neutralizing antibody was obtained on enrollment. Weekly telephone follow-up consisting of a respiratory illness questionnaire was followed with a home visit to obtain a nasopharyngeal aspirate when there was new onset of respiratory symptoms. The specimen was used to detect RSV antigen. RSV illnesses were grouped as upper or lower respiratory tract infection (LRI) based on clinical and radiographic findings. RSV hospitalizations were considered to be those RSV infections that resulted in hospitalization. RESULTS: Of 427 enrolled subjects, 160 had underlying lung disease only, 253 had underlying heart disease only, and 14 had both. Eleven percent and 12% of lung and heart disease groups, respectively, had an RSV LRI. Three percent and 6% of lung and heart disease groups, respectively, were hospitalized with RSV infection. A significant decrease in frequency of RSV LRI and RSV hospitalization occurred with increasing age, with a major drop in those older than 1 year vs those younger than 1 year. Acute sera were available from 422 subjects. Geometric mean RSV antibody titers demonstrated a U-shaped distribution with increasing age. The trend to lower antibody concentrations in premature infants did not reach statistical significance. The frequency of RSV infection and RSV LRI was lower in patients with antibody at a titer more than 100, although the difference for RSV hospitalization was not statistically significant. These differences remained significant after age adjustment. CONCLUSION: Both age and RSV antibody status impact on RSV illness and LRI. Reduction in illness frequency with increasing age may lead to more informed targeting of those children most likely to benefit from RSV immune globulin prophylaxis.

Age Distribution↗

PubMed1997

Profound permanent hearing impairment in childhood: causative factors in two European countries.

A collaboration between Denmark and Wales was established in order to evaluate any differences between countries in factors causing permanent childhood hearing impairment (PCHI). Two identical 6-year birth-cohorts from 1975-1980 suffering from a permanent hearing loss > or = 90 dB HL in the better hearing ear, averaged across 0.5-4 kHz (BEHL), were included in the analysis. The overall estimated prevalence of children with this loss was 0.41/live births in Wales (n = 59). In Denmark the overall prevalence was 0.45/1,000 live births (n = 34), there being no significant differences in prevalence between the two countries. Both cohorts were subjected to a multidisciplinary investigation protocol. No significant differences were found between countries in the proportion of hearing impairment caused by the various factors, when based on uniform criteria and identical birth-cohorts. The proportion of inherited hearing loss is 47-50% in the two countries. Within inheritance the proportion of non-syndromal/syndromal inheritance differs slightly, as non-syndromal inheritance comprises 50% in Wales, and 76% in Denmark. The reported proportion of 16-34% of unknown factors causing profound PCHI emphasises the need for appropriate protocols for aetiological evaluation.

Child↗

PubMed1997

The association between visual incompetence and spinal derangement: an instructive case history.

OBJECTIVE: To discuss the difficulties encountered in the diagnosis of concentric narrowing of the visual fields. CLINICAL FEATURES: A 13-yr-old child was referred to a chiropractic clinic after an ocular examination concerning a 6-month period of minor headaches, which culminated in a more severe attack, during which she had to lie down. Her examination was essentially normal, with the exception of the presence of constricted visual fields when measured to a small stimulus. INTERVENTION AND OUTCOME: Standard outpatient spinal adjustments were followed by recovery of vision. DISCUSSION: The recovery of constricted fields of vision with spinal manipulation has now been discussed with greater frequency in the chiropractic literature. The diagnosis of constriction of the visual fields is often the factor that may decide the further management of the patient. In this instance, constriction of the visual fields could easily have been missed, even though clinical examination of the visual fields had been done. CONCLUSION: Elements in the history and physical examination will suggest when a sensitive assessment of the visual fields may be of benefit to the patient.

Adolescent↗

PubMed1997

Persistent pulmonary hypertension of the newborn: case study and pathophysiology review.

Pulmonary hypertension, though quite normal in the fetus while the burden of oxygenation is on the maternal placenta, can be rapidly fatal if severe resistance to pulmonary blood flow continues as the infant attempts to make the transition to extrauterine life. This article reviews the pathophysiology of and current management priorities for persistent pulmonary hypertension of the newborn.

Female↗

PubMed1996

Study of interobserver reliability in clinical assessment of RSV lower respiratory illness: a Pediatric Investigators Collaborative Network for Infections in Canada (PICNIC) study.

Randomized trials of ribavirin therapy have used clinical scores to assess illness severity. Little information on agreement for these findings between observers has been published. We decided to determine interobserver agreement for (1) a history for apnea or respiratory failure; (2) assessment of cyanosis, respiratory rate, retractions, and oximetry; and (3) determination of reason for hospitalization (requirement for medications, supportive care, underlying illness, poor home environment). At eight centers 137 RSV-infected patients were assessed by two observers blinded to the assessments by others with no interventions made between assessments. Observations were categorized, and agreement was summarized as percentage of observed agreement, Pearson correlation, or as a kappa statistic. Observed agreement for a history of either apnea or a respiratory arrest was at least 90% at all centers, with seven of the eight centers in total agreement. At all centers except one, the agreement on the reason why the patient remained in hospital was at least 80%. The observed agreement for assessing cyanosis was at least 94% at all eight centers. The correlation coefficient for respiratory rate varied from 0.42 to 0.97 across centers. The kappa values for agreement beyond chance for retractions varied from 0.05 to 1.00. The kappa values for oxygen saturation measures varied from 0.31 to 0.70. Although not statistically significant, there appeared to be more variation as the time between assessments increased. In conclusion, agreement for historical findings and assessment of cyanosis was high. However, there was wide variation in agreement in the other assessments. Training to ensure consistent and reproducible assessment by different examiners will be necessary if these findings are to be used as outcome variables in clinical trials.

Antiviral Agents↗

PubMed1996

Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of admission and management variation in patients hospitalized with respiratory syncytial viral lower respiratory tract infection.

OBJECTIVE: To describe differences in patients hospitalized with respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) at nine Canadian tertiary care hospitals. In addition, this study describes the variation in use of drug and other interventions. METHODS: Data on patients hospitalized with RSV LRI and their outcomes were prospectively collected. Demographic data were obtained on enrollment by center study nurses. Data recorded daily included clinical assessment, oxygen saturation determination, and interventions (bronchodilators, steroids, ribavirin, antibiotics, intensive care, and mechanical ventilation) received during the day. Patients were divided into those with underlying diseases including congenital heart disease, chronic lung disease, immunodeficiency, or multiple congenital anomalies and those who were previously healthy. Mean RSV-associated length of stay and the proportion of patients receiving each intervention in each group were determined by hospital. RESULTS: A total of 1516 patients were enrolled at nine hospitals during January 1 to June 30, 1993, and January 1 to April 30, 1994. Significant differences were observed among hospitals in the proportion of patients with underlying disease, postnatal age less than 6 weeks, hypoxia, and pulmonary infiltrate on chest radiograph. The mean length of stay varied among hospitals from 8.6 to 11.8 days and 4.6 to 6.7 days in compromised and previously healthy patients, respectively. Except for receipt of bronchodilators, compromised patients were significantly more likely to receive interventions than previously healthy patients. There was variation among hospitals in receipt of most interventions in compromised and previously healthy patients. This variation was statistically significant for previously healthy patients but not statistically significant in those with underlying disease, because the numbers of patients in the latter group were much smaller. The magnitude of the variation for each intervention, however, was not different between those with underlying disease compared with previously healthy patients. CONCLUSION: Differences exist among tertiary pediatric hospitals in the nature of the patients admitted with RSV LRI. Variation occurred in the use of five interventions among the hospitals, regardless of whether the patient had underlying illness or was previously healthy. Given their current widespread use, high cost, and potential side effects, randomized clinical trials are needed to determine the efficacy of different drug treatments used to treat infants hospitalized with RSV.

Adrenal Cortex Hormones↗

PubMed1996

Family and physicians' views of surrogate decision-making: the roles and how to choose.

Physicians and family members were compared on the roles played in surrogate decision-making and their views as to how choices should be made by surrogate decision-makers. Thirty-six family members of patients with Alzheimer's disease, 35 family members of patients with schizophrenia, and 34 physicians from a diversity of specialties were the respondents. There was general agreement that shared decision-making was preferred. Physicians seem to make surrogate decisions in accordance with contemporary views about their roles. Families believed they had a strong subjective appreciation of the patient's overall good. The burden of decision-making was greater for families, but that depended to some degree on the diagnosis of the patient.

Activities of Daily Living↗