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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 325 records · Page 18Linked to original sources
PubMed1989

Clinical use of home and ambulatory blood pressure monitoring.

Blood pressure measurements made in the physician's office with a mercury-column sphygmomanometer traditionally have been the standard for diagnosis of hypertension and determination of the efficacy of antihypertensive agents. The utility of this measurement is limited, however, by the characteristic variability of blood pressure; office blood pressure readings are not always reliable indicators of pressures occurring throughout the course of the day. Therefore, blood pressure measurements performed by patients or family members at home and automatic ambulatory blood pressure monitoring are two supplementary methods used in the clinical management of hypertension. In this article, the role of these methods in the diagnosis of hypertension and other cardiovascular disorders as well as in the evaluation of the efficacy of antihypertensive therapy is addressed.

Antihypertensive Agents↗
PubMed1989

Shoulder kinesthesia after anterior glenohumeral joint dislocation.

The purpose of this study was to examine kinesthesia in normal (uninjured) shoulders and in shoulders with a history of glenohumeral joint dislocations. Both shoulders of 10 healthy subjects and 8 subjects with a history of unilateral anterior dislocation were tested for accuracy of angular reproduction, threshold to sensation of movement, and end-range reproduction using a motor-driven shoulder-wheel apparatus. An analysis of variance revealed significant differences (p less than .001) between the injured and uninjured shoulders for all three tests. Post hoc analysis showed significant differences (p less than .02) between the involved shoulders and all uninvolved shoulders. No significant difference was found among the uninvolved shoulders. The results of this study indicate that kinesthetic deficits occur after glenohumeral dislocation and may result in abnormal neuromuscular coordination and subsequent reinjury of the shoulder. Clinicians should consider rehabilitation of shoulder kinesthesia using therapeutic activation of the shoulder joint and muscle receptors when treating patients with previous dislocations.

Adult↗
PubMed1989

Variable metabolism of pinacidil: lack of correlation with the debrisoquine and trimethylamine C- and N-oxidative polymorphisms.

1. The urinary excretion of pinacidil and its N-oxide in man was found to vary over a five-fold range. 2. Studies in individuals with inherited deficiencies for C-hydroxylation (debrisoquine type) and trimethylamine N-oxidation showed that the N-oxidation of pinacidil did not co-segregate with these oxidative polymorphisms. 3. It is concluded that the variable N-oxidation of pinacidil is most likely to be due to variations in the activity of the P-450 isozymes rather than in the microsomal flavoprotein containing mixed-function amine oxidase of Ziegler which is considered to be responsible for the N-oxidation of trimethylamine.

Adult↗
PubMed1989

Prognosis of patients with AIDS requiring intensive care.

The Acute Physiology and Chronic Health Evaluation (APACHE) II classification, a measure of severity of illness in patients requiring intensive care, was devised before the rapid expansion of the acquired immunodeficiency syndrome (AIDS) epidemic. To determine the applicability of the APACHE II system to AIDS, we related observed in-hospital death rates to those predicted by APACHE II in 83 patients with AIDS. In a control group of patients without AIDS (n = 166) mean predicted and observed death rates (34.1 vs 31.3 percent) were similar. For the AIDS group overall observed mortality (63.9 percent) was significantly greater than that predicted by APACHE II (45.8 percent). The subgroup with Pneumocystis pneumonia requiring mechanical ventilation (n = 37) had an observed mortality (86.5 percent) that significantly exceeded the predicted value (44.3 percent), whereas all other AIDS patients (n = 46) showed similar predicted and observed death rates (47.0 vs 45.7 percent). APACHE II prediction of death rate also matched observed mortality in mechanically ventilated patients without Pneumocystis infection. The discrepancy between predicted and observed mortality in patients with Pneumocystis pneumonia requiring mechanical ventilation is most likely due to the lack of an APACHE II diagnostic category that accurately reflects the severity of this disease. A new diagnostic category that provides accurate outcome prediction in this patient group would form a basis for evaluation of new therapeutic interventions.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Induction of articular cartilage degradation by recombinant interleukin 1 alpha and 1 beta.

The purpose of this study was to compare the effects of human recombinant interleukin 1, alpha and beta, on articular cartilage. The effects of rIL-1 alpha and rIL-1 beta on proteoglycan degradation and synthesis following treatment of bovine articular cartilage in serum-free organ culture were quantified. Purified human IL-1 and both rIL-1 alpha and rIL-1 beta induced a two-fold or greater increase in glycosaminoglycan (GAG) release from cultured articular cartilage. Levels or rIL-1 alpha as low as 15 pM induced increased proteoglycan degradation whereas identical levels of rIL-1 beta did not. Killing of the cartilage cells abolished induced GAG release by all forms of IL-1. Analysis of proteoglycan size following IL-1 treatment showed limited degradation of material released into the culture medium or remaining within cartilage. Both forms of recombinant IL-1 inhibited GAG synthesis when continually present in the culture medium. Actinomycin D and cycloheximide inhibited IL-1 dependent cartilage destruction whereas indomethacin did not.

Animals↗
PubMed1988

Poor sulphoxidation ability in patients with food sensitivity.

Patients with well defined reactions to foods were examined for their ability to carry out both sulphur and carbon oxidation reactions by using carbocisteine and debrisoquine as probe compounds. The proportion of poor sulphoxidisers (58 of 74) was significantly greater than that of a previously determined normal control population (67 of 200; p less than 0.005). The proportion of poor carbon oxidisers was not significantly different from the controls. Metabolic defects may play a part in the pathogenesis of adverse reactions to foods.

Adult↗
PubMed1988

The role of intestinal microflora in the formation of the methylthio adduct metabolites of paracetamol. Studies in neomycin-pretreated and germ-free mice.

The contribution of the gastrointestinal microflora to the formation of methylthio adducts from paracetamol has been studied by comparing the fate of this drug in conventional mice with that in germ-free and neomycin-treated animals. In both germ-free and neomycin-treated mice there was a highly significant reduction in the urinary excretion of 3-methylthioparacetamol, its glucuronic acid and sulfate conjugates and its sulfoxide, with no other systemic alteration to the overall fate of the drug. These data are consistent with the gut flora playing a major role in the C-S cleavage of paracetamol-3-cysteine, thereby reducing the excretion of the array of methylthio adducts subsequently formed by tissue enzymes from 3-thioparacetamol, the putative product of the C-S cleavage.

Acetaminophen↗
PubMed1988

Insulin resistance in denervated skeletal muscle. Inability of insulin to stimulate dephosphorylation of glycogen synthase in denervated rat epitrochlearis muscles.

We have investigated the effects of insulin and motor denervation on the phosphorylation of glycogen synthase in skeletal muscle. Rat epitrochlearis muscles were denervated in vivo 3 days before the contralateral and denervated muscles were incubated in vitro with 32Pi to label sites in glycogen synthase. The 32P-labeled synthase was rapidly immunoprecipitated from extracts under conditions which prevented changes in the phosphorylation state of the enzyme. When 32P-labeled synthase from contralateral muscles was cleaved with CNBr, essentially all of the 32P was recovered in two fragments, denoted CB-1 and CB-2. Incubating these muscles with insulin decreased the 32P content of each fragment by approximately 25%, indicating that the hormone stimulated dephosphorylation of at least two sites. Peptide mapping by reverse phase high performance liquid chromatography was performed to resolve phosphorylation sites more completely. The results suggest that the enzyme was phosphorylated in sites 1a, 1b, 2, 3(a+b+c), and 5. Insulin stimulated dephosphorylation of sites in peptides presumed to contain sites 1b, 2, and 3(a+b+c). Synthase from denervated muscles appeared to contain the same amount of phosphate as enzyme from contralateral muscles, and denervation did not detectably affect the distribution of 32P within the subunit. However, denervation abolished the effect of insulin on decreasing the 32P content of synthase. The results indicate that the insulin resistance induced by denervation involves a loss in the ability of insulin to stimulate dephosphorylation of glycogen synthase.

Animals↗
PubMed1988

Biochemistry of fusion mass consolidation in the sheep spine.

We report here the biochemistry of fusion mass consolidation in sheep spines during a 1-year period following autogenous cortical-cancellous bone grafting and stabilization with Harrington distraction rods. Biochemical analysis of vertebral fusion mass included determination of wet weight and dry weight and quantification of glycosaminoglycan, collagen, calcium, and phosphate following extraction with neutral EDTA and proteolytic hydrolysis with papain. Our results showed that at 1 week after surgery, the fusion mass consisted of original cortical and cancellous bone graft material. The cortical bone graft was partially resistant to EDTA-papain treatment, resulting in a residue containing hydroxyproline and mineral. At 12 weeks after surgery, the fusion mass had become a homogeneous material, which, like cancellous bone graft, was completely susceptible to treatment by EDTA-papain. Collagen content of consolidating fusion mass was highest at 16 weeks after surgery when normalized to dry weight; glycosaminoglycan content was highest within 6 weeks after surgery. Mineral content was lowest at the 6-week stage but by 12 weeks after surgery, it was comparable with original bone grafting material. At 24 and 52 weeks after surgery, fusion mass consolidation was characterized by an increase in the proportion of organic and mineral components resistant to EDTA-papain. The appearance of the EDTA-papain-resistant material in the fusion mass coincided with formation of lamellar bone and successful consolidation.

Animals↗
PubMed1988

Time-varying magnetic fields: effects of orientation on chondrocyte proliferation.

The purpose of this study was to determine the effect of orientation of pulsed electromagnetic fields (PEMFs) on cellular proliferation and extracellular matrix synthesis. Bovine articular chondrocytes were cultured in PEMFs (repetitive pulse at 72 Hz) generated using Helmholtz coils oriented either parallel (horizontal) or perpendicular (vertical) to the plane of cell adhesion. Dissipation of signal energy in the form of heat increased the temperature of the PEMF coils by 2 degrees C and the tissue culture medium by 1 degree C. Therefore, control coils, which emitted no PEMFs, were heated to the temperature of PEMF coils by circulating water. Chondrocytes were cultured in 16-mm-well culture plates, and the data for individual wells were pooled as triplicates. Although not observed by microscopic examination of individual wells, positionally dependent electric field effects may be minimized by this approach. PEMFs generated by coils oriented vertically significantly decreased chondrocyte proliferation. The effect was dependent on the concentration of serum in the culture media. At 3% serum concentration, the total cell number attained after 10 days of culture was reduced by 50% in stimulated cultures when compared with controls. At 5% serum concentration, there was no effect. PEMFs applied by coils oriented horizontally did not alter proliferation of articular chondrocytes. PEMFs had no effect on synthesis of extracellular matrix by chondrocytes plated at high density, irrespective of orientation.

Animals↗
PubMed1988

Quantitation of glycocalyx production in coagulase-negative Staphylococcus.

The purpose of this study was to develop sensitive and accurate methods of quantitating bacterial glycocalyx. Coagulase-negative staphylococci were cultured in trypticase soy broth. Quantitation of slime production was evaluated using various methods of fixation and staining. The amount of dye associated with bacterial slime was assessed spectrophotometrically following solubilization of the dye-biofilm complex by 0.2 M NaOH at 85 degrees C for 1 h. Carnoy's solution was optimal for fixation of the slime, and toluidine blue staining was most reproducible. Fifteen strains of Staphylococcus epidermidis showed a gradation in biofilm production ranging from high, medium, to low that was strain stable. Irrespective of the technique used, high, medium, and low producers of bacterial slime remained in the same category and always showed significantly different optical density readings (p less than 0.05). In our experiments, solubilization of a toluidine blue-bacterial biofilm complex was a direct, simple, and efficient method for reproducibily quantitating glycocalyx. This method provides a useful means of rapid quantitation of biofilm production to assess its role in the infection process and in the response to antibiotic therapy.

Acetates↗
PubMed1988

Time dependent pentylenetetrazol-like cues subsequent to diazepam administration.

Seventy male Sprague-Dawley rats were trained to discriminate which of two levers to press for milk reinforcement on a VI-20 schedule of reinforcement on the basis of whether they were injected subcutaneously with 0.75 mg/kg diazepam or 10.0 mg/kg pentylenetetrazol. Following discrimination acquisition, a dose-response function was generated for each drug during 5-min extinction periods. Subjects were then assigned to one of seven groups on the basis of their per cent responding during saline testing. Each group was injected with 5 mg/kg diazepam and then given a 5-min extinction test at intervals of 2, 4, 6, 8, 12, 16, 20, or 24 h subsequent to injection. The results indicated that at the shorter time intervals the animals responded on the diazepam lever. However, as the time interval between injection and testing lengthened, responding on the PTZ bar gradually increased until by 12 h following injection with diazepam the animals were responding as though they had received an injection of 5 mg/kg PTZ. Following this period of rebound, choice behavior returned to baseline by 24 h post-injection.

Animals↗
PubMed1988

Acylation of gelatin-agarose and the enhancement by heparin of fibronectin binding.

The enhancement of the binding of plasma fibronectin to collagen or gelatin by heparin was previously thought to be due primarily to interaction of heparin with fibronectin. We observed, however, that the elution of purified human plasma fibronectin from heparin-treated gelatin-agarose required the same high urea concentrations regardless of whether heparin treatment preceded or followed fibronectin adsorption. Acylation of gelatin-agarose with acetic anhydride or succinic anhydride had little effect upon fibronectin binding, yet the heparin enhancement of fibronectin binding was abolished by either acylation reaction. When heparin binding to gelatin-agarose was investigated with dansyl heparin, gelatin-agarose bound substantial quantities of labeled heparin which could be readily dissociated from the matrix with 2 M NaCl. Acetylated gelatin-agarose did not bind detectable amounts of dansyl heparin. We interpret these results as evidence that the stronger binding of fibronectin to gelatin-agarose in the presence of heparin is due to heparin itself binding to gelatin, thus allowing fibronectin to bind simultaneously to both immobilized ligands through appropriate domains of the glycoprotein.

Acylation↗
PubMed1988

Trimethylaminuria ('fish-odour syndrome'): a study of an affected family.

1. Beginning with a single propositus, who had been previously diagnosed at the age of 10 as suffering from trimethylaminuria (fish-odour syndrome), both her parents and two sisters were investigated biochemically with respect to their ability to N-oxidize trimethylamine (TMA), both when derived from the diet and when administered exogenously. 2. Both the propositus and a second sister were markedly deficient in their ability to N-oxidize TMA, both when derived from the diet and when given as such; furthermore, both siblings readily developed the symptoms of fish-odour syndrome as characterized by a strong objectionable breath and body odour shortly after the oral administration of TMA (300 mg). 3. At this dose level of TMA, neither of the parents nor the third sister showed any evidence of impaired N-oxidation ability nor did they experience any 'fish-odour' symptoms. 4. With an oral challenge of 600 mg of TMA, both the parents showed a clear impairment of N-oxidation capacity which was not seen in six healthy unrelated volunteers. Both parents experienced a fish-odour syndrome at this level of TMA challenge. 5. The family data support the hypothesis that trimethylaminuria is an inborn error in the ability to N-oxidize TMA which is inherited as an autosomal recessive trait. Furthermore, experience with this family suggests that an oral challenge dose with 600 mg of TMA may be used to identify carriers of the condition.

Adult↗
PubMed1988

A diffusion model of the transient response of the cochlear inner hair cell synapse.

One class of models of hair cell synaptic function that has been investigated in recent years consists of one or more reservoirs of synaptic material connected to other reservoirs and/or the synaptic cleft by means of diffusion paths. One such general model is considered here, comprising two reservoirs and a global source of synaptic material connected in series and releasing material into the synaptic cleft by a diffusion path characterized by an intensity-dependent permeability. The explicit form of the solution of the model for a sudden onset of stimulation is derived: The solution comprises two exponentially decaying terms plus a constant. This solution is shown to have a unique inverse. This allows the determination of the parameters of the model directly from experimental data from auditory-nerve fibers in the Mongolian gerbil. The behavior of the derived model parameters with variation of stimulus intensity is demonstrated, and implications for synaptic function are discussed.

Acoustic Stimulation↗
PubMed1988

Denitrification in a sand and gravel aquifer.

Denitrification was assayed by the acetylene blockage technique in slurried core material obtained from a freshwater sand and gravel aquifer. The aquifer, which has been contaminated with treated sewage for more than 50 years, had a contaminant plume greater than 3.5-km long. Near the contaminant source, groundwater nitrate concentrations were greater than 1 mM, whereas 0.25 km downgradient the central portion of the contaminant plume was anoxic and contained no detectable nitrate. Samples were obtained along the longitudinal axis of the plume (0 to 0.25 km) at several depths from four sites. Denitrification was evident at in situ nitrate concentrations at all sites tested; rates ranged from 2.3 to 260 pmol of N(2)O produced (g of wet sediment) h. Rates were highest nearest the contaminant source and decreased with increasing distance downgradient. Denitrification was the predominant nitrate-reducing activity; no evidence was found for nitrate reduction to ammonium at any site. Denitrifying activity was carbon limited and not nitrate limited, except when the ambient nitrate level was less than the detection limit, in which case, even when amended with high concentrations of glucose and nitrate, the capacity to denitrify on a short-term basis was lacking. These results demonstrate that denitrification can occur in groundwater systems and, thereby, serve as a mechanism for nitrate removal from groundwater.

Journal Article↗