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Biomedical subjects

Michael Silverman

Publications and source records attributed to Michael Silverman.

31 records · Page 2Linked to original sources

Branching properties of the pulmonary arterial tree during pre- and postnatal development.

We measured arterial diameter as a function of generation number (#) in the arteriograms of six postmortem lung preparations from human infants aged 35 to 48 wks post-conceptional age (PCA). The log-log plot of mean diameter as a function of generation number revealed a linear decrease in mean and median diameter with increasing #, which was characterized by its slope alpha and intercept beta (linear regression). The mean arterial diameter per generation as well as the ratio (F) between mother and larger daughter branch and the relative ratio of asymmetry (A) between the larger and the smaller daughter branch was calculated. The values of F(#) and A(#) were found to be constant between 2 and 15 generations in individual lungs which is consistent with the pulmonary arterial tree exhibiting fractal properties. The averaged values (F and A within a subject) of F(#) and A(#) as well as alpha and beta were determined for each lung preparation and found to be constant from 35 to 48 weeks of age, revealing unchanged branching properties in the pre- and postnatal phase of human lung development.

Age Factors↗

Symptoms, lung function, and beta2-adrenoceptor polymorphisms in a birth cohort followed for 10 years.

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta-2 adrenoceptor (beta2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of beta2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P = 0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze <4 years but not with later wheeze. Neonatal V'maxFRC was reduced in those possessing Gln27 or Arg16 alleles, but there was no effect of beta2AR polymorphisms on FEV1 at 10 years. Wheeze after 4 years of age was typical of classical asthma, as it was strongly related to atopy and bronchial responsiveness at age 10. In conclusion, we confirmed the association of neonatal bronchial responsiveness with both early wheezing and later lung function. We also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to early measurements of lung function or bronchial responsiveness.

Analysis of Variance↗

The response to beta-agonists in wheezy infants: three methods compared.

BACKGROUND: Studies into the effects of salbutamol in the treatment of wheeze in infancy have been conflicting, possibly due to differences in outcome variables. We aimed to assess the response to salbutamol using indices derived from passive and forced expiration. METHODS: We recruited 39 infants who had a history of wheezing (mean age 43 weeks) and measured maximum flow at functional residual capacity (V'(max FRC)) by rapid thoracoabdominal compression (RTC), and forced expired volume at 0.4s (FEV0.4) using the raised-volume RTC technique (RV-RTC). We calculated passive compliance (C(rs)), resistance (R(rs)) and time constant (tau) from relaxed expirations that followed the augmented inspirations delivered during RV-RTC. Measurements were repeated after aerosol salbutamol (800 mcg). RESULTS: Data were obtained in 32 infants for V'(max FRC), 22 for FEV0.4 and 19 for passive mechanics. There were no mean changes in any index of forced expiration after salbutamol. Some individuals showed significant changes (improvement or worsening) in one or other index. Overall, there was a small increase in C(rs) after salbutamol but no change in R(rs) or tau. CONCLUSIONS: We found no consistent pattern of response in either index of forced expiration. Validated clinical scores or alternative physiological techniques may be preferable to respiratory mechanics in assessing bronchodilator response.

Adrenergic beta-Agonists↗

ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial.

OBJECTIVE: The objective of this study was to assess the safety and efficacy of a novel therapeutic, ZYC101a, for the treatment of women with histologically confirmed cervical intraepithelial neoplasia (CIN) 2/3. ZYC101a contains plasmid-DNA-encoding fragments derived from the E6 and E7 proteins of human papillomavirus (HPV) 16 and 18, and is formulated within small biodegradable microparticles. METHODS: A multicenter, double-blind, randomized, placebo-controlled trial was conducted in a group of women with biopsy-confirmed CIN 2/3. Subjects were randomized to 3 intramuscular doses of either placebo or ZYC101a (100 or 200 microg). Six months after the first injection, subjects underwent cervical conization. The primary endpoint for this study was histologically confirmed resolution of CIN 2/3. A total of 161 subjects were randomized, dosed, and evaluated for safety. After central pathology review, 127 subjects were evaluable for efficacy. RESULTS: The most common adverse events were related to the injection site, were mild to moderate, and did not worsen at later treatments. The proportion of subjects who resolved was higher in the ZYC101a groups compared to placebo (43% versus 27%), but the difference was not statistically significant (P =.12). In a prospectively defined population of women younger than 25 years (n = 43), resolution was significantly higher in the combined ZYC101a groups compared to placebo (70% versus 23%; P =.007). ZYC101a activity was not restricted to HPV-16-or HPV-18-positive lesions. CONCLUSIONS: ZYC101a was shown to be well tolerated in all patients and to promote the resolution of CIN 2/3 in women younger than 25 years. LEVEL OF EVIDENCE: I

Adolescent↗

Pulmonary Ureaplasma urealyticum is associated with the development of acute lung inflammation and chronic lung disease in preterm infants.

Previously, we have reported marked pulmonary inflammation in infants who develop chronic lung disease of prematurity. We revisited these infants who did not have clinical or laboratory evidence of infection and searched for Ureaplasma urealyticum, group B streptococci, and other microbes by reverse transcription-PCR performed on RNA extracted from 93 bronchoalveolar lavage samples. From infants ventilated for respiratory distress syndrome, 6 (gestation, 28 wk; birthweight, 880 g) were positive for U. urealyticum and 11 (25 wk, 800 g) were negative. Five (83%) positive and four (36%) negative infants developed chronic lung disease. Each infant was colonized with either biovar 1 or biovar 2 but not both. U. urealyticum was very weakly detectable in two infants on d 1 but was detected in five of six infants at d 10. Furthermore, pulmonary neutrophils, alveolar macrophages, soluble intercellular adhesion molecule-1, and IL-1beta on d 10 and IL-6 and IL-8 at d 1 were significantly increased in the positive group. A variety of organisms were identified in six samples between 14 and 21 d of age, but all samples were negative for group B streptococci. Our data suggest that U. urealyticum colonization is associated with the development of pulmonary inflammation in infants who subsequently develop chronic lung disease.

Acute Disease↗

Prevalence of symptoms of asthma and allergies in schoolchildren in Gondar town and its vicinity, northwest Ethiopia.

A low level of allergic disorders has been generally reported in children from developing countries. A survey was conducted to determine the prevalence of symptoms of asthma and allergies among schoolchildren in Gondar, northwest Ethiopia. A standardized self-administered questionnaire developed by the International Study of Asthma and Allergies in Children (ISAAC) was used. In total, 3,365 children aged 13-14 years were surveyed at school, with a response rate of 98.4%. The female to male ratio was 1.5:1. The 12-month-period prevalences of wheeze (16.2%), rhino-conjunctivitis (14.5%), and eczema (10.9%) were comparable to findings from Addis Ababa, but significantly higher than reported from Jimma. A striking seasonal pattern of rhinitis symptoms is observed during the months of September-December with a peak in November, corresponding with the main pollen season of the area. Overall, about 36% of the children reported symptoms of atopic disorders. However, the prevalence of diagnosed atopic diseases (8.6%) is less than a quarter of the symptom prevalence rate. This may reflect a generally poor awareness and low health service utilization, or underdiagnosis by health facilities. In conclusion, it appears that the prevalence of atopic diseases in Gondar area is high, and there is also wide variation within the country. This calls for further epidemiological studies with more objective assessments of atopy, such as allergen and bronchial hyperresponsiveness tests and ecological analysis.

Adolescent↗

Evaluation of three interventions to promote workplace health and safety: evidence for the utility of implementation intentions.

This article evaluates a motivational intervention based on the theory of planned behavior, a volitional intervention based on implementation intentions, and a combined motivational plus volitional intervention in promoting attendance at workplace health and safety training courses in the UK. Intervention manipulations were embedded in postal questionnaires completed by participants (N=271). Subsequent attendance over a 3-month period was determined from course records. Findings showed that the volitional and combined interventions doubled the rate of attendance compared to the motivational and control conditions (rates were 39%, 32%, 12%, and 16%, respectively). The effects of the volitional intervention were independent of the effects of previous attendance, demographic variables, employment characteristics, and variables from the theory of planned behavior.

Adult↗

Transitional B cells: step by step towards immune competence.

Transitional B cells mark the crucial link between bone-marrow (BM) immature and peripheral mature B cells. Examination reveals unexpected heterogeneity, consisting of contiguous subsets with phenotypic and functional differences. Data point to the late transitional B-cell stage as a crucial juncture at which developing B cells gain access to splenic follicles, become responsive to T-cell help and lose sensitivity to negative selection, characterizing the immature B-cell response to B-cell antigen receptor (BCR) signaling in vitro and in vivo. The biological and molecular processes directing maturation through this stage are becoming clearer through biochemical studies and murine models deficient in various components of the BCR signaling pathway.

Animals↗

Influenza-related hospitalizations among young children in Leicestershire.

BACKGROUND: Population-based data on influenza hospitalizations are unavailable in the United Kingdom, but they represent an essential component of health economic analyses that could support the use of vaccines and antiinfluenza drugs in healthy children. We collected data on hospitalizations for influenza infections among young children in Leicester, UK. METHODS: This prospective, longitudinal, noninterventional single center study was conducted at the Children's Hospital in Leicester, which provides inpatient pediatric care to a total population of approximately 1 million. We studied children <6 years of age between October 14, 2001, and June 30, 2002, who were admitted to the hospital with an acute respiratory tract illness, seizures, specified acute febrile gastrointestinal illness or any acute febrile illness or apnea or other life-threatening events in infants <12 months of age. Nasopharyngeal swabs obtained within 24 h of hospital admission were examined for influenza, respiratory syncytial virus and human metapneumovirus by PCR. RESULTS: Of 7165 clinical episodes that were assessed in the Children's Hospital between October 1 and June 30, 2441 (34.1%) were caused by acute respiratory illness. Overall 33 (5.4%) of 613 children analyzed had an influenza A or B virus infection, including 19 (5.0%) of 381 children with acute respiratory illness and 14 (6.0%) of the remaining 232 children. CONCLUSIONS: Influenza is evidently an important cause of hospitalization among young children, even during limited outbreaks of influenza. Further analyses will enable us to estimate age-related admission rates for influenza and to compare the burden from influenza with that for respiratory syncytial virus and human metapneumovirus.

Age Distribution↗

What we see: inattention and the capture of attention by meaning.

Attention is necessary for the conscious perception of any object. Objects not attended to are not seen. What is it that captures attention when we are engaged in some attention-absorbing task? Earlier research has shown that there are only a very few stimuli which have this power and therefore are reliably detected under these conditions (for example, Mack & Rock, 1998; Moray, 1959). The two most reliable are the observer's own name and a happy face icon which seem to capture attention by virtue of their meaning. Three experiments are described which explore whether these stimuli are detected under conditions, heretofore unexamined, which either cause inattentional blindness or are associated with a perceptual failure associated with the limits of attention. The evidence obtained indicates that these stimuli have a unique capacity to capture and extend the limits of attention under conditions in which this has been deemed highly unlikely.

Adult↗

Cloning and Gene Replacement Mutagenesis of a Pseudomonas atlantica Agarase Gene.

An agarase gene (agrA) was isolated by cloning genomic DNA prepared from Pseudomonas atlantica. The agarase activity in recombinant Escherichia coli was found in cell-free culture supernatants and could pass through a 0.45-mum-pore-size membrane separating cells from agar, suggesting that the gene product was exported in E. coli. The enzyme was specific for agar and agarose and did not digest alginate or carrageenan. Mutations generated by transposon mini-Mu d1(lacZ Km) were used to define the agrA coding region, as well as the direction of transcription of the gene. A procedure was developed to produce a P. atlantica agrA mutant. This required construction of an agrA::kan insertion mutation in vitro and subsequent introduction of the defect into the chromosome of P. atlantica by recombinational exchange. Transformation of P. atlantica with plasmids containing agrA::kan utilized a Tris-polyethylene glycol 6000-CaCl(2) treatment for making competent cells. Replacement of wild-type agrA with agrA::kan resulted in loss of agarase activity. Uses of the agrA gene probe and an Agr mutant for environmental studies are discussed.

Journal Article↗

Effect of attention therapy on reading comprehension.

This study quantified the influence of visual attention therapy on the reading comprehension of Grade 6 children with moderate reading disabilities (RD) in the absence of specific reading remediation. Thirty students with below-average reading scores were identified using standardized reading comprehension tests. Fifteen children were placed randomly in the experimental group and 15 in the control group. The Attention Battery of the Cognitive Assessment System was administered to all participants. The experimental group received 12 one-hour sessions of individually monitored, computer-based attention therapy programs; the control group received no therapy during their 12-week period. Each group was retested on attention and reading comprehension measures. In order to stimulate selective and sustained visual attention, the vision therapy stressed various aspects of arousal, activation, and vigilance. At the completion of attention therapy, the mean standard attention and reading comprehension scores of the experimental group had improved significantly. The control group, however, showed no significant improvement in reading comprehension scores after 12 weeks. Although uncertainties still exist, this investigation supports the notion that visual attention is malleable and that attention therapy has a significant effect on reading comprehension in this often neglected population.

Attention↗