Biomedical subjects

D W Smith

Publications and source records attributed to D W Smith.

At least 91 records · Page 5Linked to original sources

PubMed1998

Engineering the healing of the rabbit medial collateral ligament.

A biological approach to improve healing of the medial collateral ligament (MCL) was investigated by exploring the use of therapeutic growth factors based on in vitro and in vivo experiments. The in vitro cell culture studies involved screening a variety of growth factors to select those that exhibit the most positive effects on cell proliferation and extracellular matrix synthesis. The selected growth factors were applied in vivo to a rabbit model where the MCL was ruptured. Biomechanical and histological evaluations are performed to determine whether the selected growth factors can enhance the properties of the healed MCL, whether these improvements are dose dependent, and whether combinations of growth factors can enhance MCL healing to a greater extent than individual growth factors. In vitro studies showed that epidermal growth factor (EGF) and platelet derived growth factor-BB (PDGF-BB) have the greatest effect on ligament fibroblast proliferation, whereas transforming growth factor-beta 1 (TGF-beta 1) superiorly promotes extracellular matrix synthesis. These growth factors were then applied in vivo at different dosages, in isolation and in combination, and the ligaments were evaluated six weeks post-operatively. Tensile testing of the femur-MCL-tibia complexes (FMTCs) revealed that the specimens treated with a high dose of PDGF-BB have ultimate load, ultimate elongation and energy absorbed to failure values that are significantly greater than those from the other groups. The high dose of PDGF-BB was more effective than the low dose, indicating a dose dependency. The addition of TGF-beta 1 to PDGF-BB did not lead to any further increases in the structural properties of the FMTC. These encouraging results suggest that PDGF-BB may be a potential growth factor to enhance the quality of the healing ligament.

Animals↗

PubMed1998

Supplemental iron exacerbates aminoglycoside ototoxicity in vivo.

There is increasing evidence to suggest that free radical generation is central to a variety of pathological processes, including drug toxicity. Studies demonstrating the ability of gentamicin to facilitate the generation of radical species suggest that this process plays an important role in aminoglycoside-induced ototoxicity. Because transition metals, particularly iron, play an important role in the production of free radicals and the generation of reactive oxygen species, we sought to determine whether gentamicin-induced ototoxicity is exacerbated by increases in serum iron levels. To this end, we assessed the effects of supplemental iron administration (2 mg/kg/day and 6 mg/kg/day) on changes in auditory function induced by co-administration of gentamicin (100 mg/kg/day for 30 days). Experiments were carried out on pigmented guinea pigs initially weighing 250-300 g. Changes in cochlear function were characterized as shifts in compound action potential (CAP) thresholds, estimated every third day throughout the treatment period by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results showed that animals receiving iron in combination with gentamicin demonstrated a more rapid and profound elevation in CAP thresholds compared with animals receiving gentamicin alone. This effect occurred in a dose-dependent manner. Animals receiving supplemental iron alone maintained normal CAP thresholds throughout the treatment period. There was no statistically significant difference in serum gentamicin levels between groups receiving gentamicin alone or gentamicin plus iron. These results provide further evidence of the recently reported intrinsic role of iron in aminoglycoside ototoxicity, and highlight a potential risk of aminoglycoside administration in patients with elevated serum iron.

Animals↗

PubMed1998

Roles of community organizations in improving cancer prevention instruction in schools.

Health education can be an important factor in the development of appropriate health behaviors in children. Community agencies that have not traditionally supported school health education can be of significant influence in improving school health education. This study examined the relationships between the involvement of the American Cancer Society (ACS) in schools and the degree of implementation of cancer prevention curricula. School health specialists from 41 metropolitan school districts in Texas were surveyed regarding the coverage of topical areas related to cancer prevention, health instructional patterns in districts, and collaborative efforts with the ACS. Tobacco use was widely covered in all levels of schools (elementary, middle, and high school), as was nutrition. Cancer detection and the concepts of cancer as a disease received most extensive coverage in high schools, and there were no significant grade level differences regarding coverage of the risks of sun exposure. School personnel had little training and felt little district support for school health education. Most respondents felt that teachers saw the ACS primarily as a resource for cancer information and resources than as a collaborative partner in health education efforts. Community organizations can play three roles in supporting school health education. First, the organization must certainly provide disease-specific information (in this case, cancer). They must also promote comprehensive school health education in general. Lastly, the study illustrates that community organizations must act as advocates for broader change in schools by supporting the development of organizational capacity within schools and districts to implement quality school health education, enlisting community support for quality school health education, and supporting policy initiatives that strengthen school health education activities.

Adolescent↗

PubMed1998

Effect of behavior modification on patient compliance in orthodontics.

The purpose of this study was to evaluate the effects of a reward system for improving patient compliance in orthodontic treatment. The sample consisted of 144 orthodontic patients (63 male, 81 female, average age 12.8 years), 6 to 12 months into their treatment. The sample was divided into above-average and below-average compliers, based on the orthodontic patient cooperation scale (OPCS). Each group was further divided into three subgroups: (a) a control group, which received only standard instructions; (b) an award group, which received compliance instructions and a written evaluation of compliance; and (c) a reward group, which received compliance instructions, a report card, and eligibility to receive rewards for adherent behavior. Two measurements of patient compliance were used: (1) the OPCS, which divided the sample into high and low compliers and was used to compare compliance before and after the 6-month experimental period; and (2) a clinical evaluation of compliance that was based on oral hygiene, appointment punctuality, appliance wear, and appliance maintenance. Evaluations were completed at each monthly appointment. Average compliance scores of above-average compliers showed no significant improvement with rewards. The average scores of patients with below-average compliance did not improve significantly. Only oral hygiene scores in the low compliance reward group were better than in the low compliance control group. Academic performance in school was found to be correlated (p < 0.001) with compliance. Above-average compliers remained above average in their compliance. The award/reward system may help motivate below-average compliers to comply with prescribed instructions.

Achievement↗

PubMed1998

Finding intron/exon splice junctions using INFO, INterruption Finder and Organizer.

INFO, INterruption Finder and Organizer, has been used to find coding sequence intron-exon splice junctions in human and other DNA by comparing the six conceptual translations of the input DNA sequence with sequences in protein databanks using a similarity matrix and windowing algorithm. Similarities detected both delineate position of the gene and provide clues as to the function of the gene product. In addition to use of a standard similarity matrix and windowing algorithm, INFO uses two novel steps, the MiniLibrary and Reverse Sequence steps, to enhance identification of small exons and to improve precision of junction nucleotide delineation. Exons as small as about 30 bases can be reliably found, and > 90% of junctions are precisely identified when canonical splice junction information is used. With the MiniLibrary and Reverse Sequence steps, INFO parameters need not be optimized by the user. In comparative test runs using 19 human DNA sequences, INFO found 108 of 111 exons, with 0 reported false positives, compared with 111 exons and 51 false positives for BLASTX, 99 exons and 6 false positives for GRAIL II, 77 exons and 24 false positives for GeneMark, 61 exons and 9 false positives for GeneID, and 105 exons and 6 false positives for PROCRUSTES. The correlation coefficient for finding and positioning these 111 exons was greater than 98% for INFO. Comparable results were obtained in test runs of 13 nonhuman DNA sequences. INFO is applicable to DNA from any species, will become more robust as sequence databanks expand, and complements other heuristic approaches.

Algorithms↗

PubMed1998

Attenuation of neomycin ototoxicity by iron chelation.

Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside-iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential (CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.

Animals↗

PubMed1998

Topical gentamicin and ethacrynic acid: effects on cochlear function.

OBJECTIVE: To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the aminoglycoside antibiotic gentamicin applied topically on the round window. STUDY DESIGN: The authors studied the effects on cochlear sensitivity of co-administered intracardiac ethacrynic acid (40 mg/kg) and high-dose topical gentamicin solution (100%) applied to the round window. Comparisons were made with animals receiving ethacrynic acid plus systemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gentamicin alone; and intravenous ethacrynic acid alone. METHODS: Experiments were carried out on pigmented guinea pigs weighing 400 to 500 g. Changes in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. RESULTS: After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demonstrate a significant deterioration in cochlear sensitivity, whereas all animals receiving systemic gentamicin plus ethacrynic acid experienced profound increases in CAP thresholds. CONCLUSIONS: This study supports the contention that ethacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph. In addition, this study answers important clinical concerns regarding the safety of the use of topical aminoglycoside agents in combination with loop diuretics.

Action Potentials↗

PubMed1998

Australian encephalitis in the Northern Territory: clinical and epidemiological features, 1987-1996.

BACKGROUND: The last epidemic of Australian encephalitis occurred in 1974. Since then, cases have been reported from the Kimberley of Western Australia (WA). AIMS: To describe the epidemiology and clinical features of Australian encephalitis in the Northern Territory (NT) of Australia. METHODS: Review of cases of Australian encephalitis presenting to Royal Darwin Hospital from 1987-1996 and review of sentinel chicken surveillance for Australian encephalitis viruses. RESULTS: Sixteen patients were identified; ten from the NT and six from WA. Cases occurred in the years 1987, 1988, 1991 and 1993. Infection was acquired throughout northern NT below latitude 20 degrees S in the months March to July. All infections were due to Murray Valley encephalitis (MVE) virus. Eleven of the patients were children. Distinguishing features were spinal cord and brainstem involvement and the absence of seizures in adults. CT scanning was normal and EEG showed no focal activity. Five died (31%) and four (25%) have residual neurological disability. Sentinel chicken surveillance since 1992 shows yearly seroconversion to MVE virus throughout northern NT; human cases occurred simultaneously with chicken seroconversion in 1993. CONCLUSIONS: Australian encephalitis is endemic in the NT; the areas at risk are north of Tennant Creek. Outbreaks are seasonal and occur every few years. Young children are most at risk. Mortality and morbidity are high. Prevention of disease is by avoidance of mosquito exposure and vector control measures.

Adult↗

PubMed1998

Evaluation of Jump Into Action: a program to reduce the risk of non-insulin dependent diabetes mellitus in school children on the Texas-Mexico border.

Jump Into Action, a school-based non-insulin dependent diabetes mellitus (NIDDM) prevention program, encourages students to eat low-fat foods and exercise regularly to reduce their risks for developing NIDDM. A study was conducted in a school district with a predominately Hispanic enrollment to assess the effectiveness of Jump Into Action in improving fifth-graders' knowledge, self-efficacy, and behaviors regarding NIDDM prevention. Jump Into Action was found effective in increasing knowledge and self-efficacy regarding NIDDM prevention and improving dietary and exercise-related behaviors. These gains were sustained from posttest to follow-up four weeks later.

Child↗

PubMed1998

Changing causes of death of elderly people in the United States, 1950-1990.

BACKGROUND: Causes of death have changed greatly in the United States during the 20th century. OBJECTIVE: To detail these changes in elderly people during 1950-1990. METHODS: The source of data was 'Vital Statistics of the United States' for the years discussed. Mortality rates for several causes were calculated for the 85-89 age group, and the percentage of deaths attributed to several causes was calculated. RESULTS: There are large peaks about 1970 in both the mortality rate of ischemic heart disease and the percentage of total deaths attributed to this cause. The peaks have been followed by declines. Death rates from cancer and the percent of deaths attributed to cancer have increased during 1950-1990. CONCLUSIONS: The above changes coincide with major changes in medical science and care, the identification of the risk factors predisposing to ischemic heart disease and cerebrovascular diseases, and the implementation of Medicare, a program of health care benefits to all people 65 and over that is supported by the United States government.

Aged↗

PubMed1998

Nosology and vital statistics of dementing conditions of elderly people.

The nosology of dementing conditions of very old people, as described in the International Classification of Diseases, Ninth Revision (ICD-9) and reported in Vital Statistics of the United States, is examined. Methods included a questionnaire of state officials who oversee death certification that asked chiefly about death certificate entries that denote dementing conditions. Current nosology includes several dementing conditions that are commonly indistinguishable without a postmortem examination. Dementing conditions are grouped with other conditions of unrelated pathogenesis. The words "psychosis" and "dementia" are used interchangeably. The majority of state officials said that some death certificate entries denoting dementing conditions are acceptable as causes of death. The current system of nosology of dementing conditions probably results in the under-reporting of these conditions in vital statistics. The tenth revision of the International Classification of Diseases (ICD-10) classifies dementing conditions similarly to the ninth revision. An alternative system of nosology, based on dementia as a common characteristic, is suggested.

Age Factors↗

PubMed1997

The clinical significance of p21(WAF1/CIP-1) and p53 expression in pancreatic adenocarcinoma.

BACKGROUND: Wild-type p53 protein activates the WAF1/CIP-1 (p21) gene, leading to G1 arrest after DNA damage. The authors investigated the relation of p21 and p53 expression in pancreatic adenocarcinomas to disease stage, overall patient survival, and survival when chemotherapy or radiation therapy was given. METHODS: Paraffin embedded tissue sections of 75 ductal adenocarcinomas of the pancreas were immunostained for p53 and p21. Nuclear expression was scored as absent, focal (<10%), moderate (10-50%), or strong or diffuse (>50%). RESULTS: The median survival of patients whose pancreatic tumors expressed the p21 protein (43 of 75 cases, 57%) was better than that for patients whose tumors were p21 negative (32 of 75 cases, 43%) (median survival, 13.5 vs. 9.8 months, respectively; P = 0.23). No difference in survival was found with regard to p53 protein expression (43 of 75 cases, 57%); however, strong p53 expression was significantly associated with advanced disease stage (70% in Stage IV vs. 13-28% in lower stages). Expression of p21 correlated with earlier clinical stage. Stage specific comparisons showed a trend toward increased survival among p21 positive tumor patients diagnosed at clinical Stages I and III but not among those diagnosed at Stage IV. Adjuvant chemotherapy or radiation improved survival significantly if tumors expressed p21 or no p53. CONCLUSIONS: Expression of p21 is significantly associated with earlier clinical stage in pancreatic adenocarcinoma, perhaps accounting for the better survival observed in this patient group than among those whose tumors were p21 negative. Improved survival with either chemotherapy or radiation therapy was observed for patients whose tumors were p21 positive or p53 negative.

Adenocarcinoma↗

PubMed1997

Neuronally restricted RNA splicing regulates the expression of a novel GABAA receptor subunit conferring atypical functional properties [corrected; erratum to be published].

We report the isolation and characterization of a cDNA encoding a novel member of the GABA receptor gene family, epsilon. This polypeptide is 506 amino acids in length and exhibits its greatest amino acid sequence identity with the GABAA receptor gamma3 subunit (47%), although this degree of homology is not sufficient for it to be classified as a fourth gamma subunit. The epsilon subunit coassembles with GABAA receptor alpha and beta subunits in Xenopus laevis oocytes and transfected mammalian cells to form functional GABA-gated channels. alpha1beta1epsilon GABAA receptors, like alpha1beta1gamma2s receptors, are modulated by pentobarbital and the steroid 5alpha-pregnan-3alpha-ol-20-one but, unlike alpha1beta1gamma2s receptors, are insensitive to flunitrazepam. Additionally, alpha1beta1epsilon receptors exhibit rapid desensitization kinetics, as compared with alpha1beta1 or alpha1beta1gamma2s. Northern analysis demonstrates widespread expression of a large epsilon subunit transcript in a variety of non-neuronal tissues and expression of a smaller transcript in brain and spinal cord. Sequence analysis demonstrated that the large transcript contained an unspliced intron, whereas the small transcript represents the mature mRNA, suggesting regulation of expression of the epsilon subunit via neuronally restricted RNA splicing. In situ hybridization and immunocytochemistry reveal a pattern of expression in the brain restricted primarily to the hypothalamus, suggesting a role in neuroendocrine regulation, and also to subfields of the hippocampus, suggesting a role in the modulation of long term potentiation and memory.

Amino Acid Sequence↗

PubMed1997

Auditory behavioral thresholds for Japanese macaques using insert earphones.

The goal of this study was to measure behavioral auditory thresholds in four Japanese macaques. Animals were trained using food as a reward in an operant reinforcement paradigm. Stimuli were 1-s sinusoids with 10-ms rise/fall times delivered through insert earphones (Etymotic ER-1) having expandable foam eartips. The animals generally produced threshold contours similar in shape to those reported for other macaques species, except that the low-frequency thresholds may have been slightly higher in the present studies. At middle and high frequencies, thresholds fell at the lower extreme of the range previously reported in other macaque species. The possible difference in low-frequency thresholds may have been a result of either transducer and calibration differences between studies or true species variations, or both. Though somewhat limited at high frequencies, the insert earphones used in these studies offer more reliable calibrations, less susceptibility to changes in positioning with movement of the animal, and greater interaural attenuation.

Animals↗

PubMed1997

Is avascular necrosis of the femoral head the result of inhibition of angiogenesis?

An hypothesis is offered here that the pathogenesis of avascular necrosis (AVN) of the femoral head is based on the inhibition of angiogenesis. Well-established facts supporting this hypothesis are: 1, the lesion of AVN is vascular obliteration often leading to infarction; 2, glucocorticoids, which are a risk factor for AVN, are inhibitors of angiogenesis; 3, interferons, which are now being used in the treatment of multiple sclerosis, hepatitis, leukemias, and hemangiomas are inhibitors of angiogenesis, and other endogenously produced cytokines are also inhibitors; 4, constituents of cartilage are inhibitors of angiogenesis, explaining the subchondral location of AVN; 5, angiography of the femoral head indicates the need for continual renewal of its blood supply, shows the inhibition of revascularization by steroids, and suggests that the stress of weight bearing makes the femoral head particularly vulnerable. This hypothesis has implications for the therapeutic use of inhibitors of angiogenesis.

Animals↗

PubMed1997

Synaptic specializations associated with the outer hair cells of the Japanese macaque.

Across species the innervation of outer hair cells (OHCs) shows a remarkable similarity. There are, however, notable differences in fine structure. The present work describes the normal synaptic morphology of OHCs in the Japanese macaque (Macaca fuscata), as determined by examination of serial sections with transmission electron microscopy. The nerve endings at the base of OHCs were divided primarily into two groups: vesiculated (efferent) and non-vesiculated (afferent). In addition, we found supranuclear efferent nerve endings and reciprocal synapses in all three cochlear turns. We also found presynaptic bodies in OHCs at the afferent synapse, the branching of afferent nerve fibers and axodendritic synapses between afferent and efferent fibers in the outer spiral bundle and just beneath OHCs. In terms of synaptic structure, the data indicate that that the Japanese macaque is more similar to that of the human than other species examined to date.

Afferent Pathways↗

PubMed1997

(2E,9E)-pyronaamidine 9-(N-methylimine), a new imidazole alkaloid from the northern Mariana islands sponge Leucetta sp. cf. chagosensis.

A new imidazole alkaloid, (2E,9E)-pyronaamidine 9-(N-methylimine) (4), was isolated along with the known compounds pyronaamidine (3) and kealiiquinone (5) from the yellow sponge Leucetta sp. cf. chagosensis collected near the Island of Rota, Northern Mariana Islands. Single-crystal X-ray diffraction analysis allowed the unambiguous assignment of the structure of compound 4, including the position of the exchangeable proton and the geometry of the two imino double bonds. Compound 4 exhibited mild cytotoxicity toward the A-549, MCF-7, and HT-29 human tumor cell lines.

Alkaloids↗

PubMed1997

Centenarians: human longevity outliers.

This article is about the few humans who reach very old ages--here called "longevity outliers." They are a distinct group, with lower mortality rates than most of the population. Centenarians are human longevity outliers. They are more resistant to causes of death such as heart disease and cancer than those who die at younger ages. Inheritance of life span, the present condition of centenarians, and their causes of death are considered. The maximum human life span in the future will be affected, at least marginally, as more longevity outliers survive to challenge today's maximum of 121 years.

Aged↗