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Biomedical subjects

R K Smith

Publications and source records attributed to R K Smith.

At least 55 records · Page 3Linked to original sources

Contribution of demographic and environmental factors to the etiology of gastroschisis: a hypothesis.

We examined the clinical literature on congenital abdominal wall defects to confirm our impression that gastroschisis had become more common than omphalocele. We then examined the teratology literature and noted that congenital abdominal wall defects were frequently induced by teratogens. This lead us to review the antenatal history of 19 infants with gastroschisis and 54 control infants born with a congenital anomaly unrelated to gastroschisis. When compared to controls, mothers of infants with gastroschisis were more likely to have used aspirin during pregnancy and to have been taking oral contraceptives at the time of conception. Additionally, an increased incidence of illegal drug use (particularly cocaine) was noted among the study mothers. We conclude that gastroschisis is becoming the more common congenital abdominal wall defect, and that it could be related to exposure to an environmental teratogen.

Abdominal Muscles↗

Isolation of coordinately regulated genes that are expressed in discrete stages of B-cell development.

We have utilized subtractive hybridization to isolate 16 distinct cDNA sequences representing genes expressed in pre-B-cell lines but not myeloma cell or fibroblast lines. These sequences represent RNA transcripts that vary in abundance in pre-B-cell lines from 0.001% to 0.05%. Five of these sequences were not related to any known genes. One was related to but distinct from known myosin regulatory light chain genes and another encoded a protein with lectin domains. Three represented previously identified genes encoding carbonic anhydrase type II, thymosin, and CD2; these genes were not previously known to be specifically expressed in early stages of B-cell development. Other isolated genes corresponded to pre-B-cell-specific or pre-B-cell/B cell-specific genes recently described by others. The isolated cDNA sequences may be divided into two general categories--those representing genes expressed only in the pre-B-cell stage of B-cell development and those expressed in both the pre-B-cell and B-cell stages. The in vivo expression patterns of the identified genes suggest that some function specifically in lymphocytes while others may have roles in additional lineages.

Animals↗

Ouabain-induced lethal proximal tubule cell injury is prevented by glycine.

Exposure to 1 mM ouabain for greater than 30 min caused lethal cell injury to isolated rabbit proximal tubules as measured by increased lactate dehydrogenase release. Addition of 2 mM glycine or glutathione to the incubation medium prevented this injury and a sharp fall of cell ATP that accompanied it. Glycine and glutathione did not alter rapid, early effects of ouabain to deplete cell K+ and inhibit respiration. Preservation of cellular glutathione was not required for protection. Glycine did not ameliorate ouabain-induced increases of cell water and did not prevent lethal cell injury associated with cell swelling produced by incubation in a high K+ concentration medium. In contrast, 100 mM mannitol, which at least partially ameliorated swelling in both ouabain and high-K+ medium, prevented lethal injury in high-K+ medium and decreased it in the presence of ouabain. The combination of glycine and mannitol completely prevented ouabain-induced lethal injury and cell water increases. These observations indicate that glycine, unlike mannitol, does not protect against primary volume-induced insults. Ouabain-induced lethal cell injury results from a process that includes both a volume component ameliorated by mannitol and a volume-independent component that is prevented by glycine and is closely associated with accelerated ATP depletion.

Glutathione↗

Analysis of the third and fourth cell cycles of mouse early development.

The third (4-cell) and fourth (8-cell) cell cycles of early mouse development have been analysed in populations of blastomeres synchronized to the preceding cleavage division. DNA content was measured microdensitometrically. The entry of blastomeres into these cell cycles showed considerable heterogeneity both within and between individual embryos. This heterogeneity was greater in the fourth than in the third cell cycle. The component phases of the third cell cycle were estimated as G1 = 1 h, S = 7 h, and G2 + M = 2-5 h, and those of the fourth cell cycle as G1 = 2 h, S = 7 h, and G2 + M = 1-3 h.

Animals↗

Misuse of tetanus immunoprophylaxis in wound care.

We prospectively studied medical personnel compliance with antitetanus prophylaxis in 211 patients with wounds in three emergency departments. The guidelines were incorrectly followed in 13.4% of the patients, with 88.9% of the mistakes resulting from overimmunization. The most common mistake was the practice of giving tetanus and diphtheria toxoid (Td) to a patient with a clean wound who had complete primary immunization and a booster within ten years. This mistake accounted for 63% of the mistakes. The next most common, accounting for 18.5%, was the practice of giving Td and tetanus immune globulin to the never-immunized patient who had sustained a clean wound. Overimmunization increases the possibility of adverse reactions, and undertreatment places the patient at risk for tetanus.

Data Collection↗

DNA replication and compaction in the cleaving embryo of the mouse.

The effects of aphidicolin, a reversible inhibitor of DNA polymerase alpha, both on replication and on development of the mouse embryo from the 2- and 4-cell stages to the compacted late 8-cell stage have been assessed. The continuous presence of aphidicolin from G1 of the 4-cell stage resulted in inhibition of DNA replication and prevention of division from 4 to 8 cells, but was without effect on the timing or incidence of cell flattening, surface polarization and cytoplasmic polarization. The continuous presence of aphidicolin from G1 of the 2-cell stage resulted in inhibition of DNA replication, division, and polarization. Some slight intercellular flattening in a few embryos did occur. If addition of aphidicolin was delayed by 10 h to early in G2 of the 2-cell stage, further rounds of replication were blocked and some embryos failed to cleave to 4-cells. Nevertheless, almost all embryos showed evidence of flattening and polarization regardless of cell number. In contrast, if aphidicolin was added in G1 of the 2-cell stage and removed after 10 h, the cells showed delayed DNA replication, little evidence of division, and no cell flattening or polarization. We conclude that DNA replication at the 2-cell stage may be essential for the components of compaction studied, but that DNA replication at the 4- and 8-cell stages is not.

Animals↗

Osseous adaptation to continuous loading of rigid endosseous implants.

Titanium implants, with an acid-etched surface, were screwed into holes 3 mm in diameter, about 1 cm apart, carefully prepared with an internally irrigated, surgical bur in the femurs of 3- to 6-month-old rabbits. During the first 3 days after surgery, fluorescent bone labels revealed extensive bone formation, particularly at the endosteal margin of the surgical defect, indicating preservation of a high degree of osteogenic capacity. A lattice of coarse, woven bone began encapsulating the implant within 3 days. By the end of 6 weeks, mature, lamellar bone filled voids at or near the implant surface and a rigid bone/implant interface was routinely achieved. Nonspecific, subperiosteal bony hypertrophy was noted within 6 weeks after implants were placed in young, growing animals (3 months old), but not in adults (6 months old). After 6 to 12 weeks of healing, a 100-gm load was applied for 4 to 8 weeks by stretching a stainless steel spring between the implants. All but one of twenty loaded implants remained rigid. Immediate loading of four pairs of implants resulted in spontaneous spiral-type ("torsional") fractures of the femur within 1 week. These results indicate that (1) relatively simple and inexpensive titanium implants develop a rigid osseous interface, (2) 6 weeks is an adequate healing period, prior to loading, to attain rigid stability and avoid spontaneous fracture, (3) continuously loaded implants remain stable within the bone, (4) bone formation is observed on periosteal surfaces subjected to concave flexure (compression), (5) cancellous-type bone orients perpendicularly between loaded implants, apparently corresponding to lines of stress, (6) new secondary osteons are propagated at or near the surface of loaded implants, (7) the remodeling (turnover) cycle for rabbit compact bone is about 6 weeks, and (8) endosseous implants have potential as a source of firm osseous anchorage for orthodontics and dentofacial orthopedics.

Animals↗

Kinetics of inhibition of ethanol metabolism in rats and the rate-limiting role of alcohol dehydrogenase.

If liver alcohol dehydrogenase were rate-limiting in ethanol metabolism, inhibitors of the enzyme should inhibit the metabolism with the same type of kinetics and the same kinetic constants in vitro and in vivo. Against varied concentrations of ethanol, 4-methylpyrazole is a competitive inhibitor of purified rat liver alcohol dehydrogenase (Kis = 0.11 microM, in 83 mM potassium phosphate and 40 mM KCl buffer, pH 7.3, 37 degrees C) and is competitive in rats (with Kis = 1.4 mumol/kg). Isobutyramide is essentially an uncompetitive inhibitor of purified enzyme (Kii = 0.33 mM) and of metabolism in vivo (Kii = 1.0 mmol/kg). Low concentrations of both inhibitors decreased the rate of metabolism as a direct function of their concentrations. Qualitatively, therefore, alcohol dehydrogenase activity appears to be a major rate-limiting factor in ethanol metabolism. Quantitatively, however, the constants may not agree because of distribution in the animal or metabolism of the inhibitors. At saturating concentrations of inhibitors, ethanol is eliminated by inhibitor-insensitive pathways, at about 10% of the total rate at a dose of ethanol of 10 mmol/kg. Uncompetitive inhibitors of alcohol dehydrogenase should be especially useful for inhibiting the metabolism of alcohols since they are effective even at saturating levels of alcohol, in contrast to competitive inhibitors, whose action is overcome by saturation with alcohol.

Alcohol Dehydrogenase↗

Prevocational programming in the rehabilitation of the head-injured patient. A summary.

The purpose of this paper is to discuss the success and relevance of prevocational and transitional programming, as components of reentry for the head-injured patient, to the treatment continuum of the interdisciplinary rehabilitation team. Prevocational and transitional programming are particularly applicable to the young adult with head injury because they combine conditioning and instruction in a societal, thus a developmental, context. The societal context is described and distinguished from a purely medical or clinical model. The specific features, problems, and prerequisites of prevocational and transitional programming are discussed.

Brain Injuries↗

Tricyclic antidepressant overdose.

Overdose from tricyclic antidepressants (TCAs) is increasing. TCAs are well absorbed orally, highly protein bound, and highly lipid soluble. Clinical features of poisoning with TCAs occur within 12 hours of ingestion, usually after a dose of 20 mg/kg or more. Clinical symptomatology involves various anticholinergic, central nervous system, and cardiovascular effects. Cardiovascular toxicity accounts for the majority of the fatalities and may include a hyperdynamic response, various arrhythmias and heart blocks, or severe hypotension. Prolongation of the QRS interval of 10 msec or more implies severe toxicity. Many factors limit the usefulness of drug levels in the overdosed patient. Treatment revolves around good supportive care and general poisoning management. The physician should no longer use physostigmine precipitously. Sodium bicarbonate is effective in treating many of the cardiovascular complications. Other cardiac drugs are used but with varying efficacy. Patients with significant signs or symptoms of toxicity require monitored hospitalization until clinically free of manifestations for 24 to 48 hours.

Antidepressive Agents, Tricyclic↗

Change in electrical potential within periodontal ligament of a tooth subjected to osteogenic loading.

A tungsten microelectrode 12 microns in length and 1-2 microns in diameter was inserted into the periodontal ligament (PDL) of a maxillary molar of an anesthetized rat. The acid etched enamel surface, microelectrode shaft, and a suture for mesial traction were bonded together with composite resin. A mesial tipping load was applied by passing the suture over a pulley and attaching a 100 g weight. Cell-level potential was monitored with an electrometer modified with a variable nulling circuit. Baseline drift of 1-3 mV in 15 min was achieved prior to applying a load. When a 100 g mesial (anterior) load was applied, a relatively sharp drop of about 5-10 mV occurred within minutes. This more negative potential was maintained for as long as the load was applied up to 20 min. When the force was removed, a sharp increase in potential up to about 50-60% of preloaded levels was observed consistently. Animals monitored after breathing stopped, due to anesthetic overdose, showed only a minimal response to loading after 10 min and no effect at all after 20 min.

Animals↗

Economic indicators of mental health service utilization in rural Appalachia.

This exploratory study examined the relative predictive strengths of selected economic factors (welfare cases, banking activity, unemployment, retail sales, motor vehicle sales) for utilization of mental health services (hotline calls, intake at community mental health centers and admissions at mental hospitals) over a 78-month period in rural Appalachia. Monthly data were tested for autocorrelation and adjusted for seasonality and inflation. Regression analyses indicated that (a) economic factors did account for a considerable portion of variance in mental health factors; (b) these factors predicted mental hospital admissions and hotline calls; (c) strengths of these relationships were quite consistent across the areas sampled, but the directions sometimes were different; (d) welfare factors were the best predictors of utilization; (e) Aid to Families with Dependent Children was generally the best single predictor of utilization, especially when mental health factors were lagged by 3 months. A causative model describing the decision-making process involved in the utilization of mental health services was presented.

Appalachian Region↗

The advantages of delayed imaging and radiographic correlation in scintigraphic localization of gastrointestinal bleeding.

Two cases in which gastrointestinal bleeding was localized by serial scintigraphic imaging with red blood cells labeled in vivo with 99mTc-PYP are reported. The importance of both early serial imaging and delayed imaging and of the correlation with other radiographic techniques is demonstrated. Reflux of blood from the sigmoid into the proximal colon was observed in both cases. In one case, contrast material injected into a resected specimen confirmed the scintigraphic localization of the site of bleeding.

Aged↗

Effective ministry unifies spiritual, professional life.

Effective pastoral care departments are organized and periodically evaluated. Goals and objectives contribute to the department's effectiveness; they do not in themselves, however, transform the department into a religious community.

Chaplaincy Service, Hospital↗

Cell kinetics of the initial response to orthodontically induced osteogenesis in rat molar periodontal ligament.

Initial cell kinetics (15 min-20 h) of mechanically induced osteogenesis was studied with 3H-thymidine (3H-Tdr) autoradiography. Continuous orthodontic force elicited a three-stage cell proliferative reaction within rat molar periodontal ligament (PDL): (a) brief, generalized response, characterized by a burst of mitotic activity from 75 min to 2 h and a cyclic change (decrease, increase and return to control levels) in percent labeled cells from 15 to 2 h; (b) transient, generalized response, involving an increased mitotic index (MI) from 2 to 13 h, associated with elevated labeling index (LI) from 6 to 12 h; and (c) sustained, localized osteogenic response (12 h to several days) in which cell proliferation was confined primarily to the immediate area of new bone formation. These results suggest that the initial effect of mechanical perturbation on relatively quiescent adult bone progenitor cells is a generalized, transient release of G1 and G2 blocked cells. This response may correlate clinically with the regional acceleration phenomenon (RAP), which follows bone trauma, fracture, or surgical injury.

Animals↗

Detection and localization of gastrointestinal bleeding using Tc-99m-pyrophosphate in vivo labeled red blood cells.

Eighteen patients with either clinically or laboratory-detectable gastrointestinal bleeding were studied using Tc-99m-PYP in vivo labeled red blood cells. In those patients with massive gastrointestinal bleeding, the site of bleeding was usually detected within the first half-hour of scanning. Slower bleeding required longer scanning time. In several patients, bleeding sites were detected which could not be located by other means. It was experimentally determined that as little as 5 ml of ingested whole blood labeled in vivo with Tc-99m-PYP could be detected in the upper gastrointestinal tract.

Erythrocytes↗

Skeletal muscle necrosis in pressurized compartments associated with hemorrhagic hypotension.

Skeletal muscle necrosis is quantified using technetium-99m stannous pyrophosphate (99mTc-PYP) in pressurized muscle compartments after severe blood loss. Six dogs (15 to 20 kg) were anesthetized by pentobarbital sodium (25 mg/kg IV) and hemorrhaged to a hypotensive state. Left hind-leg muscle compartments were pressurized to a level of 20 mm Hg for 6 hours by infusing autologous plasma. Intracompartmental pressure was continuously monitored by the wick catheter. The right leg served as a control. Forty-eight hours following pressurization, 5 mCi of 99mTc-PYP were injected IV, and 3 hours later each dog was sacrificed and pressurized and control muscles were resected simultaneously, weighed, and counted for 99mTc-PYP uptake. Significant uptake appeared in muscle compartments pressurized for 6 hours at 20 mm Hg, indicating that 20 mm Hg in a hypotensive state produces a degree of necrosis as great as that produced by 40 to 50 mm Hg in a normotensive state. We conclude that an acute compartment syndrome occurs in a hypotensive individual at an intramuscular pressure level considerably less than the threshold pressure level in an individual with normal blood pressure.

Acute Disease↗