Search PubMed⌕ Search

Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 73 records · Page 4Linked to original sources
PubMed2001

Ceruminolytic efficacy in adults versus children.

OBJECTIVES: An inexpensive, nontoxic ceruminolytic with reasonable efficacy that can be used by the patient or their caregivers at home could represent significant financial saving for patients and health care systems. The purpose of this study was to compare two simple ceruminolytics for in vitro efficacy. STUDY DESIGN: Randomized controlled trial. METHODS: Thirty-six children and 33 adults presenting to a community family practice clinic who had cerumen occluding at least one external auditory canal were randomly assigned to compare use of 10% aqueous sodium bicarbonate and 2.5% aqueous acetic acid as ceruminolytics in occlusive cerumen. RESULTS: We were unable to demonstrate a difference between in vivo efficacy of these two ceruminolytic solutions, but both solutions were significantly more efficacious in children than adults. CONCLUSIONS: There is a role for these ceruminolytics in children with occlusive cerumen, but adults would be better treated in another way.

Acetic Acid↗
PubMed2001

Trimethylaminuria: the fish malodor syndrome.

The fish malodor syndrome (also known as the fish odor syndrome and trimethylaminuria) is a metabolic disorder characterized by the presence of abnormal amounts of the dietary-derived tertiary amine, trimethylamine, in the urine, sweat, expired air, and other bodily secretions. Trimethylamine itself has the powerful aroma of rotting fish, and this confers upon the sufferer a highly objectionable body odor, which can be destructive to the personal, social, and work life of the affected individual. In recent years, much progress has been made at all levels-clinical, epidemiological, biochemical, and genetic-in our understanding of this unfortunate condition. The present article summarizes this progress, draws attention to the different types of fish malodor syndrome, and highlights the current needs in the treatment of such patients.

Humans↗
PubMed2000

Echocardiographic predictors of survival in low gradient aortic stenosis.

Echocardiographic predictors of long-term survival for patients with low gradient aortic stenosis who undergo aortic valve replacement have not been previously reported. This study shows that patients with larger pre- and postoperative left ventricular volumes, a lower mean preoperative aortic pressure gradient, and failure of volumes to decrease and ejection fraction to increase postoperatively may have a poor prognosis.

Adult↗
PubMed2000

G-protein activity requirement for polymethylmethacrylate and titanium particle-induced fibroblast interleukin-6 and monocyte chemoattractant protein-1 release in vitro.

Periprosthetic granulomatous membranes consisting of fibroblasts, macrophages, lymphocytes, foreign body giant cells, and abundant particulate debris occur at sites of implant loosening. Previous studies demonstrate that fibroblasts respond to particulate debris through the release of interleukin-6 (IL-6), prostaglandin E(2), and matrix metalloproteinases in vitro. C-C chemokines are observed in granulomatous tissue surrounding loosened prosthetic implants and are released by macrophages and fibroblasts in response to particle challenge in vitro. This study tested the hypothesis that G protein activity is required for fibroblast activation by titanium and polymethylmethacrylate (PMMA) particles, and that inhibition of G protein activity would alter IL-6 and and monocyte chemoattractant protein-1 (MCP-1) release from activated fibroblasts. The specific inhibitor of G protein activity, pertussis toxin, was added to the fibroblasts to examine the effects of G protein activity with respect to the production of IL-6 and MCP-1 by orthopedic biomaterial-challenged fibroblasts in vitro. Interleukin-1beta (IL-1beta), a proven activator of MCP-1 and interleukin-6, was used as a positive control. Exposure of fibroblasts to titanium and polymethylmethacrylate (PMMA) particles resulted in a dose-dependent release of MCP-1 and IL-6. Challenge with PMMA particles at doses of 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 7-, 19-, and 22-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with PMMA particles at doses of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1-6 by 2.5-, 3.6-, 4. 3-, and 4.5-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Challenge with titanium particles at concentrations of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 2.6-, 6.4-, 9.6-, and 10. 0-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with titanium particles at concentrations of 0.038%, 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1 by 2.9-, 3.1-, 5.8-, 5.4-, and 5. 8-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Pretreatment of fibroblasts with pertussis toxin inhibited the release of interleukin-6 and MCP-1 from PMMA and titanium particle challenged fibroblasts in a dose-dependent manner. PMMA particle induced fibroblast IL-6 release was inhibited by 23.6% and 35.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle induced fibroblast IL-6 release was inhibited by 48.2% and 56.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. PMMA particle-induced fibroblast MCP-1 release was inhibited by 36.0%, 50.4%, and 60.1% with 2-, 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle-induced fibroblast MCP-1 release was inhibited by 15.5%, 53.2%, and 64.6% with 2-, 20-, and 200-ng/mL doses of pertussis toxin, respectively. This study suggests that fibroblasts localized in periprosthetic membranes are a source of macrophage chemoattractant factors and proinflammatory mediators that may influence granuloma formation and lead to periprosthetic bone resorption. Furthermore, this study shows that G proteins are involved in particle-induced fibroblast activation, as evidenced by decrease levels of particle induced IL-6 and MCP-1 release following pertussis toxin treatment. (c) 2000 John Wiley & Sons, Inc.

Biocompatible Materials↗
PubMed2000

A sequence resembling a peroxisomal targeting sequence directs the interaction between the tetratricopeptide repeats of Ssn6 and the homeodomain of alpha 2.

The tetratricopeptide repeat (TPR) is a 34-aa sequence motif, typically found in tandem clusters, that occurs in proteins of bacteria, archea, and eukaryotes. TPRs interact with other proteins, although few details on TPR-protein interactions are known. In this paper we show that a portion of a loop in the homeodomain of the DNA-binding protein alpha2 is required for its recognition by the TPRs of the corepressor Ssn6. The amino acid sequence of this loop is similar to the sequences recognized by the TPRs of an entirely different protein, Pex5, which directs peroxisomal import. We further show that alpha2 can be made to bind specifically in vitro to the TPRs of Pex5 and that a point mutation that disrupts the alpha2-Ssn6 interaction also disrupts the alpha2-Pex5 interaction. These results demonstrate that two different TPR proteins recognize their target by a similar mechanism, raising the possibility that other TPR-target interactions could occur through the same means.

Base Sequence↗
PubMed2000

Esophageal dysmotility in brothers with an FG-like syndrome.

We present 4 brothers with developmental delay, minor anomalies, and symptoms due to gastrointestinal dysmotility. There was some resemblance with FG syndrome, although none of the brothers had sufficient findings to make this diagnosis. The index case presented with at age 1 month with screaming episodes, mild gastro-esophageal reflux (GER), and severe constipation. Esophageal manometry studies were consistent with the diagnosis of "nutcracker esophagus." Symptomatic and manometric improvement followed treatment with oral calcium channel blockers. Two older and less severely affected brothers had similar manometric findings but did not require treatment. A fourth brother with symptoms in infancy now has normal esophageal manometry findings. These boys in all likelihood have an X-linked syndrome with manifestations of FG syndrome, in which treatment with calcium channel blockers, produces clinical and manometric improvement. The FG syndrome is an X-linked syndrome of multiple congenital anomalies/mental retardation with facultative manifestations of gastrointestinal dysmotility, including gastro-esophageal reflux, severe feeding difficulties, and constipation. Esophageal dysmotility, in particular "nutcracker esophagus," should be suspected in infants with the FG syndrome and screaming attacks.

Abnormalities, Multiple↗
PubMed2000

Effects of local infusion of TGFbeta on bone ingrowth in rabbit chambers.

The local delivery of exogenous growth factors may help achieve a stable, long-lasting prosthetic interface around primary and revision joint replacements. This study examines the effects of local infusion of transforming growth factor beta (TGFbeta) in an in vivo model of tissue differentiation within bone. The Drug Test Chamber was implanted in the proximal medial tibial metaphysis of 8 mature rabbits unilaterally. The chamber contained a 1 x 1 x 5 mm canal for tissue ingrowth. The chamber was connected to an osmotic diffusion pump via polyvinyl tubing. 3.5 microg of recombinant TGFbeta1 was infused for 1 day or 1 week with subsequent harvesting of the ingrown tissue after 3 weeks. Each TGFbeta treatment was followed by two, 3-week infusions of carrier alone and harvesting of the ingrown tissue. TGFbeta for 1 day increased, and TGFbeta for 1 week decreased the percentage of bone in the chamber, compared to the initial control harvest after carrier alone. These changes, however, did not reach statistical significance. The number of vitronectin receptor positive cells in total, adjacent to bone and away from bone was higher after treatment with TGFbeta for 1 day, compared to 1 week. In an "unperturbed" bone ingrowth system (i.e., if bone ingrowth is not initially suppressed by other stimuli), this dose of TGFbeta did not enhance bone ingrowth using the DTC model.

Animals↗
PubMed2000

Monocyte migration inhibitory factor synthesis and gene expression in particle-activated macrophages.

This study analysed MIF mRNA and protein expression in human macrophages exposed in vitro to polymethylmethacryate and titanium alloy particles. MIF levels released from macrophages without exposure to particles were in the range of 2-4 ng/ml. Exposure of macrophages to particles as demonstrated increased MIF release at 0. 075%-0.225% v/v particle concentration, which was maximal at 12-24 h. MIF mRNA signal levels in cells with and without particles at a concentration of 0.075% showed no significant differences in a time course experiment. The profile of MIF release in response to increasing particle concentration coincided with increased release of lactate dehydrogenase. The viability of the cells was unchanged by the addition of particles as determined by 3H-thymidine uptake. These data suggest that MIF expression may represent an independent macrophage response to locally high particle concentrations.

Alloys↗
PubMed2000

Induction of interleukin-6 release in human osteoblast-like cells exposed to titanium particles in vitro.

Orthopaedic wear debris induces release of bone-resorbing factors from macrophages and fibroblasts. However, the extent to which elemental metallic particles induce bone cells to express factors contributing to implant loosening remains unclear. This study showed that exposure of MG-63 osteoblast-like cells to titanium particles at a concentration of 0.30% v/v resulted in a 15-fold increase in IL-6 release into the culture medium after 24 hours, when compared with cells without particles. Northern blots revealed that exposure of MG-63 cells to titanium particles at a concentration of 0.30% v/v for 24 hours increased IL-6 mRNA signal levels by 9.6-fold, when compared with control cultures. Pretreatment of MG-63 cells with cytochalasin B prevented the particle-induced increase of IL-6 expression but did not alter the basal level of IL-6 release from cells cultured in the absence of particles. The protein kinase C inhibitor, H7, and the serine/threonine kinase inhibitor, genistein, abolished the particle-induced increase in IL-6 release at a concentration of 100 microM for each compound. In contrast, an inhibitor of protein kinase A, HA1004, had no effect on the particle-induced increase in IL-6 release. The transcription factors, nuclear factor IL-6 and nuclear factor kappa B, translocated into the nucleus within 1 hour of particle exposure. This study showed that osteoblast-like cells respond to titanium particles through increased expression of the proinflammatory cytokine, IL-6, in a process requiring phagocytosis and intracellular signaling pathways. These results suggest that osteoblasts play a direct role in implant loosening because of localized release of soluble mediators such as interleukin-6.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Ethylamine in human urine.

The urinary excretion of ethylamine has been measured in 200 unrelated healthy volunteers (100 male, 100 female) who maintained their normal diet. The average daily output was 7.82+/-7.03 mg (mean+/-S.D.) (8.01+/-7.40 male; 7.64+/-6.67 female) with a range of values spreading from 0.22 to 35.27 mg. Dietary studies investigating 41 food substances did not highlight any major sources of this amine, except that drinking tea increased subsequent urinary ethylamine levels.

Adult↗
PubMed2000

Effect of dietary fat on the development of non-insulin dependent diabetes mellitus in obese Zucker diabetic fatty male and female rats.

The obese Zucker diabetic fatty male rat (ZDF/Gmi¿trade mark omitted¿-fa) has become a widely used animal model of NIDDM, in contrast to the obese ZDF females that rarely develop NIDDM. However, preliminary observations suggest that obese ZDF females may become diabetic on high-fat diets. Therefore, we studied the effect of dietary fat on development of NIDDM, dyslipidemia, and alterations in organ-specific serum panels in obese ZDF males and females. Results indicated different effects of dietary fat-content on development of diabetes in males and females. Males, even on low fat-content diets, developed diabetes but the process was accelerated as a function of dietary fat-content, whereas only the highest fat-content diet induced development of NIDDM in obese ZDF females. Additionally, triglyceride/apolipoprotein B ratios demonstrated gender-specific differences in the nature of circulating lipoprotein particles independent of diabetic state with values for females approximately twice those of males indicating more highly triglyceride-enriched lipoprotein particles in females. We conclude that the obese ZDF female rat has the potential to become an important animal model of NIDDM especially in women where few models currently exist.

Animals↗
PubMed2000

Communication after laryngectomy: an assessment of quality of life.

The purpose of this study was to examine quality of life in laryngectomees using different methods of communication. A survey was mailed to all the living laryngectomees in Nova Scotia. Patients were asked to rate their ability to communicate in a number of common situations, to rate their difficulty with several communication problems, and to complete the EORTC QLQ-C30 quality-of-life assessment tool. Sixty-two patients responded (return rate of 84%); 57% were using electrolaryngeal speech, 19% esophageal speech, and 8.5% tracheoesophageal speech. These groups were comparable with respect to age, sex, first language, education level, and years since laryngectomy. There were very few differences between these groups in ability to communicate in social situations and no difference in overall quality of life as measured by these scales. The most commonly cited problem was difficulty being heard in a noisy environment. Despite the fact that tracheoesophageal speech is objectively most intelligible, there does not seem to be a measurable improvement in quality of life or ability to communicate in everyday situations over electrolaryngeal or esophageal speakers.

Aged↗
PubMed2000

Distribution of chloride channel-2-immunoreactive neuronal and astrocytic processes in the hippocampus.

The chloride homeostasis of neurons and non-neuronal cells is maintained in part by a voltage-sensitive inwardly rectifying chloride conductance through the chloride channel-2. This channel is activated by hyperpolarization and extracellular hypotonicity. In the present study, hippocampal sections were immunostained for chloride channel-2, and somata and dendrites of both pyramidal and non-pyramidal cells were found to be immunoreactive. In addition, glial processes in the vicinity of small blood vessels were also immunostained, whereas the neuropil of strata pyramidale and lacunosum-moleculare contained chloride channel-2-positive punctate structures. Electron microscopy and double immunostaining using antibodies against chloride channel-2 and glial fibrillary acidic protein confirmed that the dense network of chloride channel-2-positive processes corresponds to the end feet of astrocytes. The distribution of chloride channel-2-immunoreactive astrocytes was inhomogeneous throughout the hippocampus: strata oriens, pyramidale and lacunosum-moleculare of CA1-CA3 and the outer molecular layer of the dentate gyrus contained the majority of immunoreactive end feet, whereas the other layers showed sparse labeling. Subcellular studies demonstrated that, in addition to astrocytes, chloride channel-2 was localized in the membrane of dendrites, dendritic spines, cell bodies and axon initial segments of neurons, frequently close to, or within active zones of, symmetrical synapses.Thus, chloride channel-2 appears to be involved in transmembrane chloride movements associated with GABAergic synaptic transmission. The specific laminar distribution of chloride channel-2-positive astroglial processes coinciding with that of GABAergic axon terminals suggests that the network of astrocytes may be able to siphon and deliver Cl(-) ions to layers with intense GABAergic transmission, thereby increasing the efficacy of GABA(A) receptor-mediated inhibition.

Animals↗
PubMed2000

Ultrastructural identification of dentate granule cell death from pilocarpine-induced seizures.

Cell loss in the hippocampal formation is a common event in patients with temporal lobe epilepsy. The belief that dentate granule neurons are relatively resistant to excitotoxic injury has recently been challenged both, in epileptic patients and in animal models of temporal lobe epilepsy. The nature of dentate granule cell damage in epilepsy has been reported as either apoptotic, necrotic or both. The lack of a consensus on this topic stems from use of different animal models and different experimental techniques for characterizing the apoptotic/necrotic process. Using electron microscopy for defining the, nature of cell loss and one of the main animal models of status epilepticus (SE) we have focussed on the nature of the degenerative process in dentate granule cells. Ultrastructural morphological changes of these cells were evaluated 2.5-48 h after pilocarpine-induced status epilepticus. A variety of morphologies ranging from apoptosis to necrosis, could be seen at 2.5 h after SE onset and continued at least over the following 48 h. Some cells displayed coalescence of chromatin against nuclear membranes. In such cases however, chromatin did not have well-defined edges (as it should, if it were apoptosis). Condensation of cytoplasm. present in both processes was also frequently found. Neither obvious apoptotic budding-off of cytoplasm nor typical membrane-bound apoptotic bodies were found. Our results indicate that in the dentate granule cell layer pilocarpine-induced SE promotes a degenerative process in which apoptotic and necrotic features overlap.

Animals↗
PubMed2000

Turning genes off by Ssn6-Tup1: a conserved system of transcriptional repression in eukaryotes.

The Ssn6-Tup1 repressor forms one of the largest and most important gene-regulatory circuits in budding yeast. This circuit, which appears conserved in flies, worms and mammals, exemplifies how a 'global' repressor (i.e. a repressor that regulates many genes in the cell) can be highly selective in the genes it represses. It also explains how, given the appropriate signal, specific subsets of these genes can be derepressed. Ssn6-Tup1 seems especially robust, bringing about a high level of repression irrespective of its precise placement on DNA or of specific features of the DNA control regions of its target genes. This high degree of repression probably results from several distinct mechanisms acting together.

Chromatin↗
PubMed2000

Threshold dependence of mortality effects for fine and coarse particles in Phoenix, Arizona.

Daily data for fine (< 2.5 microns) and coarse (2.5-10 microns) particles are available for 1995-1997 from the U.S. Environmental Protection Agency (EPA) research monitor in Phoenix, AZ. Mortality effects on the 65 and over population were studied for both the city of Phoenix and for a region of about 50 mi around Phoenix. Coarse particles in Phoenix are believed to be natural in origin and spatially homogeneous, whereas fine particles are primarily vehicular in origin and concentrated in the city itself. For this reason, it is natural to focus on city mortality data when considering fine particles, and on region mortality data when considering coarse particles, and most of the results reported here correspond to those assignments. After allowing for seasonality and long-term trend through a nonlinear (B-spline) trend curve, and also for meteorological effects based on temperature and specific humidity, a regression of mortality was performed on PM using several different measures for PM. Based on a linear PM effect, we found a statistically significant coefficient for coarse particles, but not for fine particles, contrary to what is widely believed about the effects of coarse and fine particles. An analysis of nonlinear pollution-mortality relationships, however, suggests that the true picture is more complicated than that. For coarse particles, the evidence for any nonlinear or threshold-based effect is slight. For fine particles, we found evidence of a threshold, most likely with values in the range of 20-25 micrograms/m3. We also found some evidence of interactions of the PM effects with season and year. The main effect here is an apparent seasonal interaction in the coarse PM effect. An attempt was made to explain this in terms of seasonal variation in the chemical composition of PM, but this led to another counterintuitive result: the PM effect is highest in spring and summer, when the anthropogenic concentration of coarse PM is lowest as determined by a principal components analysis. There was no evidence of confounding between the fine and coarse PM effects. Although these results are based on one city and should be considered tentative until replicated in other studies, they suggest that the prevailing focus on fine rather than coarse particles may be an oversimplification. The study also shows that consideration of nonlinear effects can lead to real changes of interpretation and raises the possibility of seasonal effects associated with the chemical composition of PM.

Aged↗
PubMed2000

The interaction of MRI contrast agents with phospholipids.

The molecular interactions of three clinically used MRI contrast agents with lipid vesicles, consisting of egg phosphatidylcholine (EPC), have been studied using high-field NMR techniques. At a molar ratio of one contrast agent molecule to five phospholipid molecules, a significant increase in the proton resonance line width occurred for certain lipid head group moieties. A large decrease in the T1 relaxation times for the head group moieties was also observed. These two effects occurred regardless of the ionic status and the chelate structure of the three contrast agents. The structure of the contrast agents did, however, affect the magnitude of the two NMR parameter changes. These NMR effects also differed in magnitude amongst the various head group entities. The NMR effects were greatest for the head group moieties at or near the vesicle-water interface. The results are discussed in terms of the structure of the phospholipid-water interface. Since the use of contrast agents has become routine in clinical MRI, our results are of importance in terms of the interaction of the agents with physiological surfaces, many of which contain phospholipids. The understanding of such interactions should be of value not only for improved diagnostics, but also in the development of new contrast agents.

Animals↗