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Biomedical subjects

D M Smith

Publications and source records attributed to D M Smith.

At least 325 records · Page 18Linked to original sources
PubMed1986

A numerical model of temporomandibular joint loading.

A numerical model of the mandible, its articulating surfaces, and the forces exerted by the primary masticatory muscles has been developed for the purpose of investigating loading of the temporomandibular joint. Evidence is presented which shows that the temporomandibular joint. Evidence is presented which shows that the temporomandibular joint is a load-bearing joint over the normal functional range of bite-force positions and angles. In this investigation, temporomandibular joint loads were found to vary from a maximum appositional force of 60% of the bite force (when bite forces were applied to the incisors) to a distracting force of about 5% of the bite force (when applied to the distal surfaces of the third molars). TMJ loads tended to reach a minimum as a result of vertically directed bite forces positioned at the second molars. A range of conditions in which bite forces were directed parallel to or within approximately 20 degrees of the mid-sagittal plane was found to be conducive to stability of the temporomandibular joint. This stability included symmetry in the direction and in the magnitude of condylar loads as well as the presence of small forces tending to oppose the condyle and articular eminence. TMJ loads tended to reach a maximum in response to mediolaterally directed bite forces. This result is consistent with the fact that no muscle of mastication exhibits a spatial orientation in which the muscle fibers are predominantly mediolateral in direction.

Bite Force↗
PubMed1986

Increasing prescribed office visits. A controlled trial in patients with diabetes mellitus.

Patients who fail to show for scheduled visits or who fail to contact their provider when warning symptoms occur pose important problems for the primary care physician. A group of interventions was examined to determine the effectiveness in increasing the number of prescribed office visits in patients with diabetes mellitus. This group of interventions included mailed packets with information on how to use the clinic, providers' names and phone numbers, after-hours phone numbers, a list of early warning signs, and a booklet on managing diabetes mellitus; mailed appointment reminders; and intense follow-up of visit failures for prompt rescheduling. Eight hundred fifty-nine patients on drug therapy for diabetes mellitus were stratified by risk of hospitalization and randomly assigned within strata to control and intervention groups. The intervention group received all interventions. After 1 year, the intervention group averaged 12% more total contacts than the control group (5.8 vs. 5.2, P = 0.01), due largely to an increase in kept scheduled visits (4.1 vs. 3.6, P = 0.006). These effects were greatest in those patients at higher risk of hospitalization. Also, visit failures were reduced only in high-risk patients. The effect of the interventions did not diminish during the year of study. This systematic and repetitive intervention appears effective in increasing prescribed office visits and is especially effective in patients requiring more frequent care.

Clinical Trials as Topic↗
PubMed1986

Trial of high-dose cytarabine, cyclophosphamide, total-body irradiation, and autologous marrow transplantation for refractory lymphoma.

Twenty-one patients with advanced non-Hodgkin's lymphoma or Hodgkin's disease who had failed to be cured with standard therapy were the subjects of this clinical trial. The patients received cytarabine (3 g/m2 at 12-hour intervals for six or eight doses), cyclophosphamide (90 mg/kg once), and total-body irradiation (one 900-cGy fraction or five 250-cGy fractions). Bone marrow was aspirated and cryopreserved before treatment and reinfused after the completion of radiotherapy. Eighteen patients (86%) had objective response and 12 (57%) achieved complete response. Three patients remain in continuous complete remission for 566+, 604+, and 1035+ days after marrow infusion. Six complete responders had tumor recurrence. One of these patients developed a localized lymphoma of another histology that was successfully treated with local radiotherapy and the patient is currently well 1004+ days after marrow infusion. Another relapsing patient responded to a brief course of salvage chemotherapy and is in remission at 1271+ days. Three of the complete responders died from infectious complications. This regimen was associated with significant toxicity. Six patients died from sepsis during the period of aplasia and three others died from interstitial pneumonia 42-105 days after marrow infusion. Although this regimen demonstrated a high level of antitumor activity, the value of adding high-dose cytarabine to the combination of cyclophosphamide and total-body irradiation remains unclear and would require a randomized clinical trial to demonstrate.

Adolescent↗
PubMed1986

In vivo action of enzyme-activated irreversible inhibitors of glutamic acid decarboxylase and gamma-aminobutyric acid transaminase in retina vs. brain.

The effects of low s.c. doses of gamma-acetylenic gamma-aminobutyric acid (GAG) on glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid transaminase (GABA-T) activities, as well as of gamma-vinyl GABA (GVG) and gabaculine on GABA-T activities, were examined using preparations from retina and several other regions of rat central nervous system (CNS). GAG, in doses of 5 to 50 mg/kg, inactivated retinal GAD to a significantly greater degree than GAD from any other CNS region studied. Retinal GABA-T activities were also differentially inactivated by 1 to 50 mg/kg of GAG, 50 mg/kg of GVG, or 1 and 5 mg/kg of gabaculine. GAG, in doses of 25 and 50 mg/kg, more completely inactivated GAD and GABA-T in frontal cortex than in other brain regions. Frontal cortical GABA-T was not differentially inactivated by 10 and 50 mg/kg of GVG or 1 and 5 mg/kg of gabaculine. The effects of GAG on retinal GABA enzymes were long-lasting and not reversed by dialysis. The GAD and GABA-T activities from 1:1 mixes of control and GAG-treated retinal preparations were comparable to the means of the GAG-treated and control activities. The effects documented in this study, therefore, probably reflect irreversible in vivo changes. After peripheral administration, GAG, GVG and gabaculine might reach higher levels in the retina than in the brain. Alternatively, the differential effects of these compounds might be due to the relative proportions of catalytically active GABA enzymes in different CNS regions. On the basis of the foregoing results, the retina might be a particularly suitable region of the CNS for enzyme-activated irreversible inhibitors to label catalytically active enzymes of GABA metabolism.

4-Aminobutyrate Transaminase↗
PubMed1985

Transforming growth factors from a human tumor cell: characterization of transforming growth factor beta and identification of high molecular weight transforming growth factor alpha.

Intracellular transforming growth factors (TGFs) were extracted from a human rhabdomyosarcoma cell line and purified to apparent homogeneity by using gel filtration, cation-exchange, and high-performance liquid chromatography. Two types of transforming growth factor activities, TGF-alpha and TGF-beta, were detected. The intracellular polypeptides which belonged to the TGF-alpha family required TGF-beta for full activity in inducing nonneoplastic normal rat kidney fibroblasts to grow in soft agar. These peptides also bound to the membrane receptor for epidermal growth factor. As determined by sodium dodecyl sulfate-polyacrylamide gels, the apparent molecular weight of these intracellular TGF-alpha's was 18 000. Intracellular TGF-beta required either epidermal growth factor or TGF-alpha for stimulation of soft agar growth. The intracellular TGF-beta was purified to homogeneity as judged by a single peak after reverse-phase high-performance liquid chromatography and a single band on a sodium dodecyl sulfate-polyacrylamide gel. The intracellular TGF-beta from the human tumor cell line was similar in all respects tested (migration on sodium dodecyl sulfate-polyacrylamide gels, stimulation of soft agar growth, binding to the membrane receptor for TGF-beta, and amino acid composition) to intracellular TGF-beta from normal human placenta.

Amino Acids↗
PubMed1985

The effects of 6 hours of hypoxia on protein synthesis in rat tissues in vivo and in vitro.

Rates of protein synthesis were measured in vivo in several tissues (heart, skeletal muscles, liver, tibia, skin, brain, kidney, lung) of fed rats exposed to O2/N2 (1:9) for 6 h starting at 08:00-11:00 h. Protein synthesis rates were depressed by 15-35% compared with normoxic controls in all of the tissues studied. The decreases were greatest in the brain and the skin. Although hypoxia inhibited gastric emptying, its effects on protein synthesis could probably not be attributed to its induction of a starved state, because protein-synthesis rates in brain and skin were not decreased by a 15-18 h period of starvation initiated at 23:00 h. Furthermore, we showed that protein synthesis was inhibited by hypoxia in the rat heart perfused in vitro, suggesting a direct effect. The role of hypoxia in perturbing tissue nitrogen balance in various physiological and pathological states is discussed.

Animals↗
PubMed1985

Regional variation and differential sensitivity of rat heart protein synthesis in vivo and in vitro.

In vivo, fractional rates of protein synthesis in atrial muscle of hearts taken from fed rats were 70% greater than in ventricular muscle. After 3 days starvation, atrial protein synthesis is inhibited, but the inhibition is less than in ventricles. A crude subcellular fractionation of the aqueous homogenates by centrifugation at 32000g showed that the supernatant and precipitate proteins were synthesized at the same rate in the ventricles. The fractional rates of protein synthesis and RNA/protein ratios in the right ventricle were 10% greater than in the left ventricle. Protein synthesis in both of these regions was inhibited equally by starvation. In vitro, rates of protein synthesis in atria and ventricles of anterogradely perfused rat hearts were stimulated by saturating insulin concentrations and were inhibited by starvation, but the effects in atria were smaller than in ventricles. Rates of protein synthesis in atria in vitro were 80-95% of rates in vivo. The heart therefore shows considerable regional variation in rates of protein synthesis in vivo and in vitro, and the sensitivity of protein synthesis in the various regions to interventions such as insulin and starvation differs.

Animals↗
PubMed1985

In vitro fertilization and embryo transfer: an individualized approach to ovulation induction.

Because of the inherent marked individual responsiveness to ovulatory stimulating agents, a highly individualized approach to ovulation induction for in vitro fertilization has been utilized. The starting time for medication was varied according to the previous mean cycle length. The dose of clomiphene citrate was adjusted to the body weight. The dose and duration of both clomiphene and human menopausal gonadotropin (hMG) were adjusted as early as treatment day 5 in accordance with the ultrasonic findings. The day of human chorionic gonadotropin (hCG) administration was varied according to a combination of ultrasonic findings and plasma estradiol levels. This approach resulted in a mean retrieval of four oocytes per laparoscopy, 75% of which were mature, a fertilization rate of 78%, and a pregnancy rate of 14% of laparoscopies.

Adult↗
PubMed1985

Nonelective readmissions of medical patients.

Because it is difficult to predict the course of patients discharged from the hospital, we studied 1646 consecutive patients discharged from the medicine service to the care of the hospital's medical staff. Conditions serious enough to warrant urgent or emergent (nonelective) readmissions developed in 278 (16.9%) within 90 days. Multivariate analyses including 14 characteristics of patients at the time of discharge showed five to be significantly associated with readmissions: more frequent ER visits in the 6 months prior to admission, higher BUN levels, arterial PO2 less than 80 mmHg, WBC greater than or equal to 12,000/mm3, and anemia. Using scores from the derived discriminant function, patients could be separated into groups with levels of risk for readmission varying from 7.3% to 38.0%. Nonelective readmission was found to be a frequent and early complication after hospital discharge. The characteristics identified provide a way to recognize high risk patients for clinical interventions.

Adult↗
PubMed1985

Rates of synthesis of actomyosin in atria and ventricles of the perfused working rat heart.

Actomyosin from hearts perfused in vitro with [U-14C] phenylalanine and the remaining plasma amino acids was purified by standard techniques. The rate of actomyosin synthesis was expressed relative to actomyosin protein, to total protein and to total RNA. The rate of atrial total protein synthesis was twice the ventricular rate correlating with the RNA/protein ratios of the compartments. The actomyosin contents relative to total protein were not significantly different in atria and ventricles. The rate of actomyosin synthesis in atria was 2 to 3 times greater than in the ventricles when expressed relative to actomyosin or total protein. Synthesis rates of actomyosin expressed relative to total RNA were similar in the two compartments. These results suggest that the rate of turnover of actomyosin in the atria is 2 to 3 times the ventricular rate and that the greater rate of synthesis of total protein synthesis in atria is reflected in the rate of synthesis of specific intramyocytic proteins.

Actomyosin↗
PubMed1985

Predictors of myocardial infarction in emergency room patients.

To develop a decision rule to aid in the diagnosis of myocardial infarction, we evaluated clinical and ECG data on 540 adults treated in an urban hospital emergency room for acute chest pain. Of 62 (11.5%) patients who had acute infarctions, 54 were admitted to intensive care (sensitivity 87%); 103 of 478 patients without infarctions were also admitted to intensive care (specificity 78%). Thirty-four percent of all patients admitted had infarctions. Multivariate analysis identified only four clinical variables which carried independent information predicting infarction: two from the ECG and two from the clinical history. A predictive model based on these four variables had significantly greater specificity (86% vs. 78%, p = .003) and accuracy of overall patient classification (88% vs. 79%, p = .013) but somewhat lower sensitivity (81% vs. 87%, p = .46) than physician judgments. However, a decision rule which would have admitted to intensive care those patients with a high probability of infarction who were not admitted by the emergency room physicians, would have increased the sensitivity for detecting infarction to 95% with no appreciable decrease in specificity or yield of infarctions among patients admitted to intensive care.

Adult↗
PubMed1985

Application of an objective biological assay of human interferons to clinical specimens and a survey of a normal population.

A rapid, quantitative, and nonsubjective method of interferon assay is described, which can be readily applied to clinical specimens. Automated data acquisition and data reduction allowed a significant increase in volume per unit of time over existing methodologies. Plasma always yielded higher (usually 2:1) interferon values than did serum obtained simultaneously. Ranges of interferon levels in plasma in normal control populations are reported as well as ranges for clinical virology laboratory technicians and patients with terminal malignancies or collagen vascular diseases.

Biological Assay↗
PubMed1984

Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts.

A procedure has been developed for the iodination of human transforming growth factor-beta (TGF-beta) with full retention of biological activity. Using the iodinated peptide, saturable receptors have been found for TGF-beta on normal rat kidney fibroblasts, a cell line that will grow in soft agar in the presence of TGFs but not in their absence. Scatchard analysis of the binding data showed a high affinity binding site (dissociation constant equal to 25 to 30 pM with approximately 17,000 receptors per cell). The receptor was specific for TGF-beta with epidermal growth factor, insulin, insulin-like growth factors I and II, platelet-derived growth factor, and TGF-alpha being unable to compete for the binding of 125I-TGF-beta to the receptor. The binding of TGF-beta was a time- and temperature-dependent process. At 37 degrees C, maximal binding was attained within 45 to 60 min after addition of 125I-TGF-beta followed by a rapid decline in cell-associated radioactivity due to degradation of the 125I-TGF-beta. As demonstrated using ammonium acetate, a compound known to inhibit lysosomal enzymes, this degradation was most likely due to the action of proteolytic enzymes found in the lysosome. At 0 degrees C, binding reached a plateau within 2 to 3 h and maintained this level with no apparent drop during the 4-h incubation period. The receptor could be down-regulated by TGF-beta, but not by epidermal growth factor, to approximately 50% of the level initially observed.

Binding, Competitive↗
PubMed1984

Rates of protein turnover in vivo and in vitro in ventricular muscle of hearts from fed and starved rats.

Starvation of 300 g rats for 3 days decreased ventricular-muscle total protein content and total RNA content by 15 and 22% respectively. Loss of body weight was about 15%. In glucose-perfused working rat hearts in vitro, 3 days of starvation inhibited rates of protein synthesis in ventricles by about 40-50% compared with fed controls. Although the RNA/protein ratio was decreased by about 10%, the major effect of starvation was to decrease the efficiency of protein synthesis (rate of protein synthesis relative to RNA). Insulin stimulated protein synthesis in ventricles of perfused hearts from fed rats by increasing the efficiency of protein synthesis. In vivo, protein-synthesis rates and efficiencies in ventricles from 3-day-starved rats were decreased by about 40% compared with fed controls. Protein-synthesis rates and efficiencies in ventricles from fed rats in vivo were similar to values in vitro when insulin was present in perfusates. In vivo, starvation increased the rate of protein degradation, but decreased it in the glucose-perfused heart in vitro. This contradiction can be rationalized when the effects of insulin are considered. Rates of protein degradation are similar in hearts of fed animals in vivo and in glucose/insulin-perfused hearts. Degradation rates are similar in hearts of starved animals in vivo and in hearts perfused with glucose alone. We conclude that the rates of protein turnover in the anterogradely perfused rat heart in vitro closely approximate to the rates in vivo in absolute terms, and that the effects of starvation in vivo are mirrored in vitro.

Animals↗
PubMed1984

In vivo autoradiographic demonstration of beta-adrenergic binding sites in adult rat type II alveolar epithelial cells.

Adult male rats were injected intravenously with the muscarinic binding probe 3H-Quinuclidinyl benzilate (QNB) or the beta-adrenergic probe 3H-dihydroalprenolol (DHA). Other rats were pre-treated with an intraperitoneal injection of a 500-fold excess of L-isoproterenol prior to the DHA. Light microscopic autoradiography of 0.5 micron sections of lung from the QNB group demonstrated very little labelling even after 6 months of exposure. In contrast, trachealis smooth muscle from these animals contained substantial labelling. Autoradiographs of lung from rats injected with DHA demonstrated labelling which was well localized over alveolar septa and concentrated over the cytoplasm of type II cells. Quantitative analysis of labelling in the DHA groups indicated a significant reduction of labelling in animals treated with L-isoproterenol prior to DHA, in both the alveolar parenchyma in general and over type II cells. The results of this study provide morphologic evidence for the uptake and specific binding of beta-adrenergic antagonists by the adult lung in vivo, while failing to demonstrate similar binding of a muscarinic probe. In addition, the results demonstrate specific beta-adrenergic receptors on type II cells in vivo and substantiate the view of a direct effect of beta-adrenergic agonists on alveolar type II cells.

Animals↗