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Biomedical subjects

C G Smith

Publications and source records attributed to C G Smith.

At least 19 recordsLinked to original sources
PubMed2001

Determination of the extracellular concentration of glycine in the rat spinal cord dorsal horn by quantitative microdialysis.

Two quantitative microdialysis methods were used to determine the extracellular concentration of glycine in the dorsal spinal cord of halothane-anaesthetised rats. Extracellular glycine determined by zero net flux was 2.6+/-0.3 microM and by the zero flow method was 3.3+/-0.3 microM. For comparison the glycine content of cerebrospinal fluid was determined to be 6.4+/-1.1 microM. There was no correlation between the extracellular and the cerebrospinal fluid concentrations.

Animals↗
PubMed2001

Effect of early or delayed insertion of tympanostomy tubes for persistent otitis media on developmental outcomes at the age of three years.

BACKGROUND: A main indication for the insertion of tympanostomy tubes in infants and young children is persistent otitis media with effusion, reflecting concern that this condition may cause lasting impairments of speech, language, cognitive, and psychosocial development. However, evidence of such relations is inconclusive, and evidence is lacking that the insertion of tympanostomy tubes prevents developmental impairment. METHODS: We enrolled 6350 healthy infants from 2 to 61 days of age and evaluated them regularly for middle-ear effusion. Before the age of three years 429 children with persistent effusion were randomly assigned to have tympanostomy tubes inserted either as soon as possible or up to nine months later if effusion persisted. In 402 of these children we assessed speech, language, cognition, and psychosocial development at the age of three years. RESULTS: By the age of three years, 169 children in the early-treatment group (82 percent) and 66 children in the late-treatment group (34 percent) had received tympanostomy tubes. There were no significant differences between the early-treatment group and the late-treatment group at the age of three years in the mean (+/-SD) scores on the Number of Different Words test, a measure of word diversity (124+/-32 and 126+/-30, respectively); the Percentage of Consonants Correct-Revised test, a measure of speech-sound production (85+/-7 vs. 86+/-7); the General Cognitive Index of McCarthy Scales of Children's Abilities (99+/-14 vs. 101+/-13); or on measures of receptive language, sentence length, grammatical complexity, parent-child stress, and behavior. CONCLUSIONS: In children younger than three years of age who have persistent otitis media, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at the age of three years.

Audiometry↗
PubMed2001

The relationship between critical velocity, maximal lactate steady-state velocity and lactate turnpoint velocity in runners.

In cycle exercise, it has been suggested that critical power, maximal lactate steady state, and lactate turnpoint all demarcate the transition between the heavy exercise domain (in which blood lactate is elevated above resting values but remains stable over time) and the very heavy exercise domain (in which blood lactate increases continuously throughout constant-intensity exercise). The purpose of the present study was to assess the level of agreement between critical velocity (CV), maximal lactate steady-state velocity (MLSSV), and lactate turnpoint velocity (LTPV) during treadmill running. Eight male subjects [mean (SD) age 28 (5) years, body mass 71.2 (8.0) kg, maximum oxygen uptake 54.9 (3.2) ml.kg(-1).min(-1)) performed an incremental treadmill test for the determination of LTPV (defined as a sudden and sustained increase in blood lactate concentration ([La]) at approximately equals 2.0-5.0 mM). The subjects returned to the laboratory on eight or nine occasions for the determination of CV and MLSSV. The CV was determined from four treadmill runs at velocities that were chosen to result in exhaustion within 2-12 min. The MLSSV was determined from four or five treadmill runs of up to 30 min duration and defined as the highest velocity at which blood [La] increased by no more than 1.0 mM after between 10 and 30 min of exercise. Analysis of variance revealed no significant differences between [mean (SD)] CV [14.4 (1.1) km.h(-1)], MLSSV [13.8 (1.1) km.h(-1)] and LTPV [13.7 (0.6) km.h(-1)]. However, the bias +/-95% limits of agreement for comparisons between CV and MLSSV [0.6 (2.2) km.h(-1)], CV and LTPV [0.7 (2.7) km.h(-1)], and MLSSV and LTPV [0.1 (1.8) km.h(-1)] suggest that the extent of disagreement is too great to allow one variable to be estimated accurately from another in individual subjects. Direct determination of MLSSV is necessary if precision is required in experimental studies.

Adult↗
PubMed2001

Tooth loss in periodontal patients.

OBJECTIVE: To compare tooth loss between patients who received surgical therapy for chronic periodontitis and those who received nonsurgical therapy alone. METHODS: A retrospective chart study was conducted at Dalhousie University. All patients who had periodontal treatment and were active cases for at least 10 years were included (n = 335). The sample consisted of 120 males (35.8%) and 215 females (64.2%). Ages ranged from 16 to 77 (mean = 46.1 +/- 12.0 years). All patients received nonsurgical therapy; 44.8% received periodontal surgery as well. Variables recorded were demographics, initial attachment loss, treatment type, recall frequency, patient compliance and history of extracted teeth. Independent t-tests or chi-squared tests were used to compare these for surgical and nonsurgical patients. ANOVA was used to test for interactions between initial attachment loss, age, gender, compliance and type of therapy a patient received as reasons for tooth loss. RESULTS: 521 teeth were lost in 69 patients (20.6% of sample). Of teeth lost, 61.8% were due to periodontal disease; 24.8% to caries; 13.2% to other reasons. Patients initially diagnosed with early attachment loss lost an average of 0.37 (+/- 1.33) teeth. Patients diagnosed with moderate attachment loss lost an average of 1.50 (+/- 2.54) teeth and those diagnosed with advanced attachment loss lost an average of 3.11 (+/- 3.01) teeth. Those who received surgical therapy lost more teeth (mean = 1.31 +/- 2.36) than those who received nonsurgical treatment (mean = 0.68 +/- 1.87; p = 0.001). However, initial attachment loss was the only factor that could predict tooth loss. The type of therapy (surgical or nonsurgical) was not statistically significant. CONCLUSIONS: Most periodontal patients (79.4%) who received treatment at this dental school clinic did not lose any teeth due to periodontal disease over at least 10 years. Although patients who had surgical therapy lost more teeth than those who had nonsurgical therapy alone, this was not an important predictor of tooth loss.

Adolescent↗
PubMed2000

Pumping of water with ac electric fields applied to asymmetric pairs of microelectrodes.

Bulk fluid flow induced by an ac electric potential with a peak voltage below the ionization potential of water is described. The potential is applied to an ionic solution with a planar array of electrodes arranged in pairs so that one edge of a large electrode is close to an opposing narrow electrode. During half the cycle, the double layer on the surface of the electrodes charges as current flows between the electrodes. The electrodes charge in a nonuniform manner producing a gradient in potential parallel to the surface of the electrodes. This gradient drives the ions in the double layer across the surface of the electrode and this in turn drags the fluid across the electrode surface. The anisotropic nature of the pairs of electrodes is used to produce a net flow of fluid. The flow produced is approximately uniform at a distance from the electrodes that is greater than the periodicity of the electrode array. The potential and frequency dependence of this flow is reported and compared to a simple model. This method of producing fluid flow differs from electrical and thermal traveling-wave techniques as only a low voltage is required and the electrode construction is much simpler.

Journal Article↗
PubMed2000

Language, speech sound production, and cognition in three-year-old children in relation to otitis media in their first three years of life.

OBJECTIVE: As part of a prospective study of possible effects of early-life otitis media on speech, language, cognitive, and psychosocial development, we tested relationships between children's cumulative duration of middle ear effusion (MEE) in their first 3 years of life and their scores on measures of language, speech sound production, and cognition at 3 years of age. METHODS: We enrolled 6350 healthy infants by 2 months of age who presented for primary care at 1 of 2 urban hospitals or 1 of 2 small town/rural and 4 suburban private pediatric practices. We intensively monitored the children's middle ear status by pneumatic otoscopy, supplemented by tympanometry, throughout their first 3 years of life; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated children for otitis media according to specified guidelines. Children who met specified minimum criteria regarding the persistence of MEE became eligible for a clinical trial in which they were assigned randomly to undergo tympanostomy tube placement either promptly or after a defined extended period if MEE remained present. From among those remaining, we selected randomly, within sociodemographic strata, a sample of 241 children who represented a spectrum of MEE experience from having no MEE to having MEE whose cumulative duration fell just short of meeting randomization criteria. In subjects so selected, the estimated duration of MEE ranged from none to 65.6% of the first year of life and 44.8% of the first 3 years of life. In these 241 children we assessed language development, speech sound production, and cognition at 3 years of age, using both formal tests and conversational samples. RESULTS: We found weak to moderate, statistically significant negative correlations between children's cumulative durations of MEE in their first year of life or in age periods that included their first year of life, and their scores on formal tests of receptive vocabulary and verbal aspects of cognition at 3 years of age. However, the percent of variance in these scores explained by time with MEE in the first year of life beyond that explained by sociodemographic variables ranged only from 1.2% to 2.9%, and the negative correlations were concentrated in the subgroup of children whose families had private health insurance (rather than Medicaid). We found no significant correlations in the study population as a whole or in any subgroup between time with MEE during antecedent periods and children's scores on measures of spontaneous expressive language, speech sound production, or other measured aspects of cognition. In contrast, by wide margins, scores on all measures were consistently highest among the most socioeconomically advantaged children and lowest among the most socioeconomically disadvantaged children. CONCLUSIONS: Our findings suggest either that persistent early-life MEE actually causes later small, circumscribed impairments of receptive language and verbal aspects of cognition in certain groups of children or that unidentified, confounding factors predispose children both to early-life otitis media and to certain types of developmental impairment. Findings in the randomized clinical trial component of the larger study should help distinguish between causality and confounding as explanations for our findings.language, speech, cognition, development, otitis media, middle ear effusion.

Child Language↗
PubMed1999

Adenoidectomy and adenotonsillectomy for recurrent acute otitis media: parallel randomized clinical trials in children not previously treated with tympanostomy tubes.

CONTEXT: Adenoidectomy and adenotonsillectomy are commonly performed in US children to reduce the occurrence of persistent or recurrent otitis media, but evidence supporting the efficacy of the operations is limited. OBJECTIVES: To test the efficacy of adenoidectomy and adenotonsillectomy in children with persistent or recurrent otitis media who had not previously undergone tube placement and to compare the relative efficacy of adenoidectomy alone vs adenotonsillectomy in such children. DESIGN: Two parallel randomized clinical trials. SETTING AND PARTICIPANTS: A total of 461 children aged 3 to 15 years were enrolled at Children's Hospital of Pittsburgh, Pa, between April 1980 and April 1994. Four hundred ten children were observed for up to 3 years. INTERVENTIONS: Children without recurrent throat infection or tonsillar hypertrophy (304 enrolled; 266 followed up) were randomized to either an adenoidectomy, adenotonsillectomy, or control group; children who had such conditions (157 enrolled; 144 followed up) were randomized to an adenotonsillectomy or control group. MAIN OUTCOME MEASURES: Occurrence rate of episodes of acute otitis media by treatment group and estimated proportion of time with otitis media. RESULTS: In both trials, most subjects were eligible because of recurrent acute otitis media, with or without persistent otitis media with effusion. A total of 47 children assigned to surgical treatment groups had no surgery. The efficacy of surgery in both trials was modest and limited mainly to the first follow-up year. The largest differences in that year were found in the 3-way trial between the adenotonsillectomy group and the control group: mean annual rate of episodes of acute otitis media, 1.4 vs 2.1 (P<.001); and mean estimated percentage of time with otitis media, 18.6% vs 29.9% (difference, 11.3%; 95% confidence interval, 4.4%-18.2%; P=.002). Perioperative and postoperative complications or other adverse events occurred not infrequently, especially among subjects undergoing adenotonsillectomy (14.6%). CONCLUSIONS: Our study showed limited and short-term efficacy of both adenoidectomy and adenotonsillectomy; given the risks, morbidity, and costs of these procedures, these data suggest that neither operation should ordinarily be considered as a first surgical intervention in children whose only indication is recurrent acute otitis media.

Acute Disease↗
PubMed1999

Parental stress and parent-rated child behavior in relation to otitis media in the first three years of life.

OBJECTIVE: As part of a long-term study of possible effects of early-life otitis media on speech, language, cognitive, and psychosocial development, we tested relationships between parents' ratings of parent-child stress at ages 1, 2, and 3 years, and of their children's behavior problems at ages 2 and 3 years, and the children's cumulative duration of middle-ear effusion (MEE) in their first 3 years of life. METHODS: We enrolled healthy infants by age 2 months who presented for primary care at 1 of 2 urban hospitals or 1 of 2 small-town/rural and 4 suburban private pediatric practices. We obtained standardized baseline measures of parental stress; we intensively monitored the children's middle-ear status by pneumatic otoscopy, supplemented by tympanometry, throughout their first 3 years of life; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated children for otitis media according to specified guidelines. We obtained parent ratings of parental stress using the Parenting Stress Index/Short Form when the children reached ages 1, 2, and 3 years, and parent ratings of children's behavior using the Child Behavior Checklist when the children reached ages 2 and 3 years. RESULTS: In 2278 children we found no substantial relationships between parents' ratings of parent-child stress when the children reached ages 1, 2, and 3 years, or of their children's behavior problems at ages 2 and 3 years, and the cumulative duration of the children's MEE during antecedent periods. On the other hand, ratings both of parent-child stress and of behavior problems were consistently highest among the most socioeconomically disadvantaged children and lowest among the most socioeconomically advantaged children. Ratings also tended to be highest among children whose parents' baseline stress scores were highest. CONCLUSIONS: Parent-child stress and children's behavior problems in the first 3 years of life, as rated by parents, bear little or no relationship to the children's previous cumulative duration of MEE.

Adult↗
PubMed1997

Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life.

OBJECTIVE: As part of a long-term study of possible effects of early-life otitis media on speech, language, cognitive, and psychosocial development, we set out to delineate the occurrence and course of otitis media during the first 2 years of life in a sociodemographically diverse population of infants, and to identify related risk factors. METHODS: We enrolled healthy infants by age 2 months who presented for primary care at one of two urban hospitals or one of two small town/rural and four suburban private pediatric practices. We intensively monitored the infants' middle-ear status by pneumatic otoscopy, supplemented by tympanometry, throughout their first 2 years of life; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated infants for otitis media according to specified guidelines. RESULTS: We followed 2253 infants until age 2 years. The proportions developing > or = 1 episode of middle-ear effusion (MEE) between age 61 days (the starting point for data analysis) and ages 6, 12, and 24 months, respectively, were 47.8%, 78.9%, and 91.1%. Overall, the mean cumulative proportion of days with MEE was 20.4% in the first year of life and 16.6% in the second year of life. Tympanostomy-tube placement was performed on 1.8% and 4.2% of the infants during the first and second years of life, respectively. By every measure, the occurrence of MEE was highest among urban infants and lowest among suburban infants; these differences were greatest in the earliest months of life. Overall, unadjusted mean cumulative proportions of days with MEE were higher among boys than girls, higher among black than white infants, and higher among Medicaid than private health insurance enrollees. Cumulative proportions of days with MEE varied directly with the number of smokers in the household and with the number of other children to whom infants were exposed, whether at home or in day care, and varied inversely with birth weight, maternal age, level of maternal education, a socioeconomic index, and duration of breastfeeding. After adjustment, using multivariate analysis, the only variables that each remained independently and significantly related to the cumulative proportion of days with MEE were: during the first year of life, study site grouping, sex, the socioeconomic index, breastfeeding for > or = 4 months, the number of smokers in the household, and an index rating the degree of exposure to other children at home or in day care; and during the second year of life, sex, the socioeconomic index, and the child exposure index. The duration of breastfeeding and the degree of exposure to tobacco smoke contributed little to the explained variance; most was attributable to differences in the socioeconomic index and the child exposure index. CONCLUSIONS: Contrary to findings in many previous reports, the prevalence of otitis media during the first 2 years of life among lower-socioeconomic-status black infants appears to be as high as, if not higher than among lower-socioeconomic-status white infants, and certainly higher than among middle-class white infants. Among middle-class white infants the prevalence may also be higher than commonly assumed. The most important sociodemographic risk factors for otitis media appear to be low socioeconomic status and repeated exposure to large numbers of other children, whether at home or in day care.

Black People↗
PubMed1995

Effects of tubercidin and its 5'-O-methyl ether on adenosine receptors and mediator release functions in mast cells.

Tubercidin (7-deazaadenosine, Tu) is a highly cytotoxic nucleoside xenobiotic that, as the nucleoside or nucleotide derivatives, closely mimics the actions of adenosine (or its corresponding nucleotides) in a wide variety of biochemical/biological systems. In light of its acceptance in these test systems as an adenosine (Ado) surrogate, it was postulated that the compound might interact with adenosine receptors. To test this hypothesis, a nonphosphorylatable derivative (5'-O-methyl tubercidin, MeTu) was prepared and evaluated in comparison with tubercidin and Ado in a variety of biological systems. In a cell culture assay using Chinese hamster ovary cells, MeTu is approximately one-third as cytotoxic as is Ado and 10(5)-fold less cytotoxic than Tu. Both Tu and MeTu inhibited the antigen-stimulated release of beta-hexosaminidase from mouse bone marrow derived mast cells in vitro, but only Tu was active in the in vivo PCA test. The inhibitory effect of MeTu on mast cell mediator release does not appear to involve interaction with adenosine receptors or to be the result of conversion to Tu per se.

Animals↗
PubMed1995

Multifunctional regulation of the biological effects of TNF-alpha by the soluble type I and type II TNF receptors.

Two soluble receptors of tumour necrosis factor were evaluated for development as potential therapeutic agents for inflammatory disease. The recombinant human soluble Type I and Type II TNF receptors, rsTNF-RI and rsTNF-RII, were expressed at high levels in E. coli, refolded, and chromatographically purified to homogeneity. The potencies of both recombinant soluble receptors were similar to their naturally occurring soluble receptors. In in vitro cytotoxicity and competitive binding assays, both recombinant soluble receptors functioned to inhibit the biological effects of rhTNF-alpha although rsTNF-RI was a 5 to 30 fold more potent inhibitor of rhTNF-alpha than was rsTNF-RII or a truncated form of the soluble receptor, TNF-RII delta. In in vivo experiments in mice, rsTNF-RI was a better inhibitor than rsTNF-RII delta of rhTNF-alpha-stimulated changes in the percentages of circulating lymphocytes and neutrophils, influx of neutrophils into the peritoneal cavity, and serum IL-6 induction. At molar ratios of 0.1:1 and 0.01:1 (rsTNF-R:rhTNF-alpha), using the rsTNF-I or rsTNF-II delta, there was a trend towards enhancement of the induction of IL-6. However, higher ratios of either rsTNF-RI or rsTNF-RII delta significantly inhibited the rhTNF-alpha-stimulated increase in serum IL-6 levels. In a murine model of cytokine-induced shock, either rsTNF-RI or rsTNF-RII delta provided protection against the lethality of shock induced by a synergistic combination of rhTNF-alpha and rhIL-1 beta. Based on the results of these experiments, the rsTNF-RI was chosen as the better candidate for development as an anti-inflammatory agent.

Animals↗
PubMed1995

Outbreak of brucellosis at a United States pork packing plant.

In 1992, the North Carolina Department of Environment, Health, and Natural Resources received 18 case reports of brucellosis from a county health department. All patients had potential exposure to the kill floor of one pork processing plant. A subsequent National Institute for Occupational Safety and Health health hazard evaluation surveyed 154 (99%) of 156 kill floor workers of this plant and found that 30 (19%) had evidence of recent (or persistent) brucellosis. These data show that significant exposure to Brucella is occurring among packing plant workers in North Carolina and suggest that some of the approximately 38,000 production workers in pork processing plants in the United States are at risk of contracting swine brucellosis. Additional measures may need to be taken to prevent occupational exposure to Brucella.

Adult↗
PubMed1994

Basal forebrain injections of the benzodiazepine partial inverse agonist FG 7142 enhance memory of rats in the double Y-maze.

Cholinergic replacement strategies have achieved little success in the treatment of Alzheimer's disease. It has been suggested that the mnemonic function of cholinergic neurons may be enhanced by treatments that reduce GABA-ergic inhibition, while preserving the normal pattern of activity in the cholinergic neurons. Following on these suggestions, the present study investigated the mnemonic effects of intra-nucleus basalis magnocellularis (NBM) injections of the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG 7142). Rats were surgically implanted with bilateral cannulae in the NBM prior to training in a double Y-maze. Daily training sessions continued until reference and working memory choice performance stabilized to a criterion of > or = 91% correct. Rats (n = 9) received FG 7142 bilaterally in doses of 0.2, 2.0 and 3.0 micrograms/0.5 microliter per side, muscimol (a GABAA agonist) in a dose of 0.1 microgram/0.5 microliter per side, vehicle (345 micrograms 2-hydroxypropyl-beta-cyclodextrin/0.5 microliter saline per side) or no injection in a counterbalanced order with retraining to criterion between treatments. Muscimol impaired choice accuracy on both the reference and working memory components, but the effect was bigger for working memory, replicating our previous findings. Two doses of FG 7142 (0.2 and 2.0 micrograms/0.5 microliter) enhanced choice accuracy on the working memory component. The present results suggest that benzodiazepine partial inverse agonists may enhance mnemonic function.

Animals↗
PubMed1994

Persistently elevated soluble tumor necrosis factor receptor and interleukin-1 receptor antagonist levels in critically ill patients.

The appearance of endogenously produced inhibitors against tumor necrosis factor (TNF) (soluble TNF-receptor type I, sTNFR-I) and interleukin-1 (IL-1 receptor antagonist, IL-1ra) was evaluated acutely in five normal patients after experimental endotoxemia lipopolysaccharide (LPS) and prospectively during a one to 11 week period in 12 septic, critically ill patients. Increased levels of both factors remained detectable in the circulation for up to 24 hours after LPS (2 nanograms per kilogram body weight) administration in normal patients. Despite free TNF-a activity being detected only sporadically (3 percent of the samples) and that IL-1 beta was never detectable in the patients in the intensive care unit, IL-6 bioactivity was present in 90 percent of initial samples. Circulating sTNFR-I levels up to 62,000 picograms per milliliter and IL-1ra levels of 14,800 picograms per milliliter were noted in the critically ill patients and remained consistently detectable throughout the extended period of evaluation. While there was no difference in IL-1ra levels between patients who survived or ultimately died, sTNFR-I levels were significantly (p < 0.001) lower in survivors compared with nonsurvivors. A correlation between circulating sTNFR-I and concurrent cortisol levels (r = 0.64; p < 0.002) was also noted. Furthermore, a correlation between sTNFR-I and the severity of initial insult, as assessed by APACHE II scores (r = 0.54; p < 0.01) was demonstrable. These naturally occurring cytokine antagonists likely represent additional indicators of the presence of an infectious or other inflammatory process and seem to persist in the circulation even during conditions in which their respective proinflammatory cytokines are not demonstrable.

Adolescent↗