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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 37 records · Page 2Linked to original sources
PubMed2001

17 beta-estradiol inhibits cytokine, chemokine, and chemokine receptor mRNA expression in the central nervous system of female mice with experimental autoimmune encephalomyelitis.

Cytokines and chemokines govern leukocyte trafficking, thus regulating inflammatory responses. In this study, the anti-inflammatory effects of low dose 17 beta-estradiol were evaluated on chemokine, chemokine receptor, and cytokine expression in the spinal cords (SC) of BV8S2 transgenic female mice during acute and recovery phases of experimental autoimmune encephalomyelitis (EAE). In EAE protected mice, 17 beta-estradiol strongly inhibited mRNA expression of the chemokines RANTES, MIP-1 alpha, MIP-2, IP-10, and MCP-1, and of the chemokine receptors CCR1, CCR2 and CCR5 at both time points. Conversely, ovariectomy, which abrogated basal 17 beta-estradiol levels and increased the severity of EAE, enhanced the expression of MIP-1 alpha and MIP-2 that were over-expressed by inflammatory mononuclear cells in SC. 17 beta-estradiol inhibited expression of LT-beta, TNF-alpha, and IFN-gamma in SC, but had no effect on IL-4 or IL-10, indicating reduced inflammation but no deviation toward a Th2 response. Interestingly, elevated expression of CCR1 and CCR5 by lymph node cells was also inhibited in 17 beta-estradiol treated mice with EAE. Low doses of 17 beta-estradiol added in vitro to lymphocyte cultures had no direct effect on the activation of MBP-Ac1-11 specific T cells, and only at high doses diminished production of IFN-gamma, but not IL-12 or IL-10. These results suggest that the beneficial effects of 17 beta-estradiol are mediated in part by strong inhibition of recruited inflammatory cells, resulting in reduced production of inflammatory chemokines and cytokines in CNS, with modest effects on encephalitogenic T cells that seem to be relatively 17 beta-estradiol insensitive.

Animals↗
PubMed2001

Estrogen treatment down-regulates TNF-alpha production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice.

A shift toward Th2 cytokine production has been demonstrated during pregnancy and high dose estrogen therapy and is thought to be the primary mechanism by which estrogen suppresses the development of experimental autoimmune encephalomyelitis. However, low dose estrogen treatment is equally protective in the absence of a significant shift in cytokine production. In this study cytokine-deficient mice were treated with estrogen to determine whether a shift in Th2 cytokine production was required for the protective effects of hormone therapy. Estrogen effectively suppressed the development of experimental autoimmune encephalomyelitis in IL-4 and IL-10 knockout mice and in wild type littermate mice with a similar potency of protection. Significant disease suppression was also seen in IFN-gamma-deficient mice. The decrease in disease severity was accompanied by a concomitant reduction in the number of proinflammatory cytokine- and chemokine-producing cells in the CNS. Although there was no apparent increase in compensatory Th2 cytokine production in cytokine-deficient mice, there was a profound decrease in the frequency of TNF-alpha-producing cells in the CNS and the periphery. Therefore, we propose that one mechanism by which estrogen protects females from the development of cell-mediated autoimmunity is through a hormone-dependent regulation of TNF-alpha production.

Amino Acid Sequence↗
PubMed2001

Are all wheezing disorders in very young (preschool) children increasing in prevalence?

BACKGROUND: Distinct wheezing disorders co-exist in young (preschool) children, some of which (early transient wheeze and viral wheeze) are thought to be unrelated to atopy. Investigation of changes in prevalence of wheezing disorders in preschool children could provide important clues about underlying mechanisms responsible for increasing prevalence of asthma in schoolchildren. METHODS: Repeated population surveys of the prevalence of respiratory symptoms were done by parent-completed postal questionnaires in random samples of 1650 (1990) and 2600 (1998) caucasian children aged 1-5 years living in the county of Leicestershire, UK. FINDINGS: The response rates were 86% (1422 of 1650) in 1990 and 84% (2127 of 2522) in 1998. Between 1990 and 1998, there was a significant increase in the prevalance of reported wheeze ever (16% to 29%, p<0.0001), current wheeze (12% to 26%, p<0.0001), diagnosis of asthma (11% to 19%, p<0.0001), treatment for wheeze (15% to 26%, p<0.0001), and admission for wheeze or other chest trouble (6% to 10%, p<0.0001). The increase occurred both in children with viral wheeze (9% to 19%) and in those with the classic asthma pattern of wheezing with multiple triggers (6% to 10%). There was also an increase in transient early wheezers (3% to 5%), persistent wheezers (5% to 13%), and late-onset wheezers (6% to 8%), and in all severity groups. The increase could not be accounted for by putative household risk factors because these declined between the 2 years. INTERPRETATION: The fact that all preschool wheezing disorders increased (including viral wheeze) makes it probable that factors unrelated to atopy are implicated in the changing epidemiology of wheeze in childhood.

Asthma↗
PubMed2001

The quality of home spirometry in school children with asthma.

BACKGROUND: Handheld electronic spirometers provide the opportunity for more comprehensive monitoring of lung function at home than has hitherto been available. The aim of this study was to assess the quality of spirometric data collected at home by 90 asthmatic schoolchildren aged 7-14 years. METHODS: After training, children carried out twice daily recordings at home for four consecutive periods of 4 weeks using a data storage spirometer (Vitalograph), encouraged by 4-weekly visits from a research nurse. Compliance (proportion of blows recorded at correct time of day), technical quality (by machine criteria), and valid data recorded (the multiple of compliance and technical ability) were assessed. RESULTS: Mean compliance declined from 81.4% to 70.4% (p<0.001) between the first and last month, although the technical quality of the manoeuvres (81.9% and 80.1%, respectively) did not change significantly (p=0.48). CONCLUSIONS: There was a steady reduction of valid data over the four periods (from 73.6% to 64.3%, 59.7%, and 57.6%) with wide individual differences. Even under ideal conditions, home spirometry provides an incomplete (and therefore potentially biased) picture of long term changes in pulmonary function.

Adolescent↗
PubMed2001

Analysis of the harmonic content of the tidal flow waveforms in infants.

The aim of this study was to examine whether the spectral characteristics of tidal flow waveform reflect the interaction between the control of breathing and lung mechanics in 10 healthy infants (H), 10 infants with a history of wheezing disorders (W), and 10 infants with chronic lung disease (CLD). From the flow waveform, we calculated a shape index, the harmonic distortion (k(d)), which quantifies the extent to which a periodic signal deviates from a sine wave. The k(d) of the entire tidal flow waveform did not significantly discriminate between diagnostic groups. However, k(d) was sensitive to maturation: it increased from 0.26 at 1 mo to 0.37 at 6 mo of age (P < 0.002). Furthermore, the frequency (f) spectra of the flow (V) amplitudes between 0.13 and 10 Hz followed a power law: V(f) approximately f(-s), where s (slope) is the exponent in the power law. The exponent of the healthy infants s(H) was 4.24 [95% confidence interval (CI) = 0.2] at 1 mo, 4.39 (CI = 0.16) at 6 mo, and 4.35 (CI = 0.19) at 12 mo and not significantly changing with age. The mean value of s(W) was marginally lower (4.09 +/- 0.28; P < 0.05) than that of s(H). The mean s(CLD) was significantly lower (3.04 +/- 0.31; P < 0.001). Lower values of s and higher values of k(d) indicate an increased complexity of the feedback mechanisms determining tidal flow waveform and may be associated with disease.

Algorithms↗
PubMed2001

A model of viral wheeze in nonasthmatic adults: symptoms and physiology.

Episodic wheezing associated with viral infections of the upper respiratory tract (URT) is a common problem in young children but also occurs in adults. It is hypothesized that an experimental infection with human coronavirus (HCoV), the second most prevalent common cold virus, would cause lower respiratory tract (LRT) changes in adults with a history of viral wheeze. Twenty-four viral wheezers (15 atopic) and 19 controls (seven atopic) were inoculated with HCoV 229E and monitored for the development of symptoms, changes in airway physiology and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). At baseline, viral wheezers were similar to controls in PC20 (mean+/-SD log2PC20: 5.1+/-1.9 and 5.8+/-1.4 g x L(-1), respectively) but had a lower FEV1 than controls (mean+/-SD 85.8+/-11.4 and 95.6+/-13.2% predicted, respectively p < 0.05). Nineteen viral wheezers and 11 controls developed colds. Viral wheezers with colds reported significantly more URT symptoms than controls (median scores (interquartile range): 24 (10-37) and 6 (4-15), respectively p = 0.014). Sixteen viral wheezers and no controls reported LRT symptoms (wheeze, chest tightness and shortness of breath). The viral wheezers with colds had small (3-4%) reductions in FEV1 and peak expiratory flow on days with LRT symptoms (days 3-6), but a progressive reduction in PC20 from baseline on days 2, 4 and 17 after inoculation (by 0.82, 1.35 and 1.82 doubling concentrations, respectively). The fall in PC20 affected both atopic and nonatopic subjects equally. There were no changes in FEV1 or PC20 in controls. An adult model of viral wheeze that is independent of atopy and therefore, of classical atopic asthma was established.

Adult↗
PubMed2001

The effects of coronavirus on human nasal ciliated respiratory epithelium.

Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6-14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.

Adult↗
PubMed2001

A comprehensive investigation of barriers to adult immunization: a methods paper.

OBJECTIVE: Immunization rates for influenza and pneumococcal vaccines among the elderly (especially minority elderly) are below desired levels. We sought to answer 4 questions: (1) What factors explain most missed immunizations? (2) How are patient beliefs and practices regarding adult immunization affected by racial or cultural factors? (3) How are immunizations and patient beliefs affected by physician, organizational, and operational factors? and (4) Based on the relationships identified, can typologies be created that foster the tailoring of interventions to improve immunization rates? STUDY DESIGN: A multidisciplinary team chose the PRECEDE-PROCEED framework, the Awareness-to-Adherence model of clinician response to guidelines, and the Triandis model of consumer decision making as the best models to assess barriers to and facilitators of immunization. Our data collection methods included focus groups, face-to-face and telephone interviews, self-administered surveys, site visits, participant observation, and medical record review. POPULATION: To encounter a broad spectrum of patients, facilities, systems, and interventions, we sampled from 4 strata: inner-city neighborhood health centers, clinics in Veterans Administration facilities, rural practices in a network, and urban/suburban practices in a network. In stage 1, a stratified random cluster sample of 60 primary care clinicians was selected, 15 in each of the strata. In stage 2, a random sample of 15 patients was selected from each clinician's list of patients, aiming for 900 total interviews. CONCLUSIONS: This multicomponent approach is well suited to identifying barriers to and facilitators of adult immunizations among a variety of populations, including the disadvantaged.

Aged↗
PubMed2000

The meaning of healthy and not healthy: older African Americans and whites with chronic illness.

Qualitative in-person interviews with 114 older African Americans and whites with chronic illness were conducted to assess whether they thought of themselves as healthy or not healthy and the meanings associated with that assessment. The first and most frequently assigned attribute of healthy was the presence of functional capacities; for not healthy it was the presence of medical conditions or physical symptoms. While both African Americans and whites responded similarly regarding the assessment of whether they were healthy or not healthy, African Americans described the attributes associated with healthy or not healthy somewhat differently than whites. Also, both groups reported more varied meanings to the concept of 'healthy' than to 'not healthy', suggesting that 'healthy' may be a multidimensional construct more connected to ones' total life experiences than is 'not healthy'. This study concludes that social and cultural factors such as race, ethnicity or health experiences may influence how individuals perceive and describe their health status and the processes used in making these assessments.

Journal Article↗
PubMed2000

Prevalence of wheeze during childhood: retrospective and prospective assessment.

The question "Has your child ever had wheezing or whistling in the chest at any time in the past?" is a simple and widely used proxy measure for the lifetime prevalence of asthma. Our aim was to test its validity in a longitudinal survey, comparing retrospective recall with prospective assessment of lifetime prevalence. A population-based cohort of 1,422 children, surveyed twice previously, was studied again at age 8-13 yrs by postal questionnaire using standardized questions from the International Study of Asthma and Allergies in Childhood (ISAAC). Of those traced (1,190) questionnaires were returned by 89%. The prevalence of current wheeze was higher than in the previous surveys (20.5% versus 12.4% and 12.5%). Reported "wheeze ever" increased significantly from survey 1 (15.6%) to survey 2 (22.4%) and survey 3 (39.2%) and was very similar to the cumulative lifetime prevalence assessed prospectively over three surveys (42.8%). The retrospective question had a good negative predictive value (97%) and a reasonable positive predictive value (65%) compared to prospective assessment. Children reporting "wheeze ever" (but not current wheeze) in surveys 1 and 2 had at survey 3 an asthma prevalence higher than never-wheezers but lower than current-wheezers. It is concluded that retrospective recall of wheeze at age 8-13 yrs is a valid proxy measure for the lifetime prevalence of wheeze.

Adolescent↗
PubMed2000

Can peak expiratory flow be measured accurately during a forced vital capacity manoeuvre?

Spirometry and peak flow measurements traditionally depend on different forced expiratory manoeuvres and have usually been performed on separate, dedicated equipment. As spirometry becomes more widely used in primary care settings, the authors wished to determine whether there was a systematic difference between peak expiratory flow (PEF) derived from a short sharp exhalation (PEF manoeuvre) and from a full forced vital capacity (FVC) manoeuvre, using the same turbine spirometer (Microloop, Micro Medical, Kent, UK). Eighty children (38 with current asthma) aged 7-16 yrs were asked to perform 2 blocks of PEF and FVC manoeuvres, the order being randomly assigned. PEF obtained from a peak flow manoeuvre (PEFPF) was significantly greater than that from a forced vital capacity manoeuvre (PEFVC) in both healthy (group mean difference 20 L x min(-1); p<0.001) and asthmatic children (group mean difference 9 L.min(-1); p<0.004). For clinical purposes, a mean difference of about 3% for children with asthma is of no practical significance, and peak expiratory flow data can usefully be obtained during spirometric recordings.

Adolescent↗
PubMed2000

Acoustical properties of speech as indicators of depression and suicidal risk.

Acoustic properties of speech have previously been identified as possible cues to depression, and there is evidence that certain vocal parameters may be used further to objectively discriminate between depressed and suicidal speech. Studies were performed to analyze and compare the speech acoustics of separate male and female samples comprised of normal individuals and individuals carrying diagnoses of depression and high-risk, near-term suicidality. The female sample consisted of ten control subjects, 17 dysthymic patients, and 21 major depressed patients. The male sample contained 24 control subjects, 21 major depressed patients, and 22 high-risk suicidal patients. Acoustic analyses of voice fundamental frequency (Fo), amplitude modulation (AM), formants, and power distribution were performed on speech samples extracted from audio recordings collected from the sample members. Multivariate feature and discriminant analyses were performed on feature vectors representing the members of the control and disordered classes. Features derived from the formant and power spectral density measurements were found to be the best discriminators of class membership in both the male and female studies. AM features emerged as strong class discriminators of the male classes. Features describing Fo were generally ineffective discriminators in both studies. The results support theories that identify psychomotor disturbances as central elements in depression and suicidality.

Adult↗
PubMed2000

Induced sputum in children: feasibility, repeatability, and relation of findings to asthma severity.

BACKGROUND: The collection of induced sputum provides a non-invasive method of investigating airway inflammation. Few studies have been performed in children, so a study was undertaken to determine the feasibility of sputum induction, the repeatability of eosinophil counts and sputum eosinophil cationic protein (ECP) levels, and the relation of these to current asthma severity. For comparison, serum ECP levels were also measured. METHODS: In a cross sectional study of children aged 5-15 years, 27 healthy children and 60 with asthma underwent sputum induction using inhaled nebulised hypertonic saline. The whole sputum sample was used for analysis. Ten children with stable asthma repeated the procedure within 10 days. RESULTS: A satisfactory sample (>500 non-squamous cells) was obtained in 61% of children with asthma and in 60% of healthy controls. The limits of agreement within subjects ranged from a 0.68 to 2.8 fold difference for eosinophil differential counts and from 0.38 to 4.4 fold for sputum ECP. Despite a median of 42% squamous cells, significant differences were found between asthma and healthy controls for the eosinophil differential count (p = 0.0004), total eosinophil counts (p = 0.03), and sputum ECP level (p = 0.0001). Overall, there was no correlation between any marker of airway inflammation and asthma severity, however expressed, including lung function. CONCLUSIONS: Sputum induction is only possible in a proportion of children. The repeatability of sputum cell counts and ECP levels, measured in a small number of children, was similar to that reported in adults. Sputum analysis revealed no evidence of airway inflammation in a number of highly symptomatic children with asthma.

Adolescent↗
PubMed2000

Alterations in airway wall properties in infants with a history of wheezing disorders.

Airway diameter and airway wall mechanics (compliance) are important determinants of flow limitation and wheezing. We have previously used the high-speed interrupter technique (HIT) to measure input impedance (Zin) in infants at frequencies up to 900 Hz, including antiresonance phenomena, which are known to be related to wave propagation velocity, and have shown that the frequency at which the first antiresonance occurs (f(ar,1)) is a function of airway wall compliance. We aimed to determine whether f(ar,1) (and thus airway wall compliance) was different in infants with a history of wheezing disorders. We compared 23 asymptomatic infants (aged 36 to 81 wk) with a history of wheezing with an age-matched group of 19 healthy control infants. We found that f(ar,1) was significantly lower in infants with wheezing disorders than in the control group (p < 0. 005), implying differences in airway wall compliance, even when they were clinically asymptomatic. Developmental differences in airway wall mechanics may be important in the pathogenesis of wheezing disorders or, alternatively, alterations in airway wall mechanics might be a consequence of postinflammatory remodeling.

Airway Resistance↗