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Biomedical subjects

J A Davis

Publications and source records attributed to J A Davis.

At least 19 recordsLinked to original sources

Fistula injury to the bladder at repeat cone biopsy by laser.

A 33-year-old woman underwent repeat cone biopsy of the cervix with a carbon dioxide (CO2) laser. At operation the laser caused multiple full thickness fenestrations of the bladder, creating multiple small vesico-vaginal fistulae. The cone biopsy was completed and the fistulae were converted into a single defect which was immediately repaired. The patient went home 'dry'. We believe this is the first such report in the English-language literature.

Adult

Pre-season physiological characteristics of English first and second division soccer players.

This investigation was undertaken in an effort to establish physiological characteristics of soccer players and to relate them to positional roles. A total of 135 footballers (age 24.4 +/- 4.6 years) were assessed for body mass, % body fat, haemoglobin, maximal oxygen uptake (VO2 max), leg power, anaerobic capacity and speed prior to an English league season. The sample included 13 goalkeepers, 22 full-backs, 24 centre-backs, 35 midfield players and 41 forwards. The goalkeepers were significantly heavier (86.1 +/- 5.5 kg; P < 0.01) than all groups except the centre-backs, had significantly higher estimated body fat percentages than centre-backs, forwards, midfield players (P < 0.01) or full-backs (P < 0.05), significantly lower estimated VO2 max values (56.4 +/- 3.9 ml kg-1 min-1; P < 0.01) and were slowest over 60 m (12.71 +/- 0.42 s). The midfield players had the highest predicted VO2 max values (61.4 +/- 3.4 ml kg-1 min-1), this being significantly greater (P < 0.05) than for the centre-backs. The forwards were the fastest group over 60 m (12.19 +/- 0.30 s), being significantly quicker than goalkeepers or centre-backs (P < 0.01) and full-backs (P < 0.05). Anaerobic power, as well as knee extensor torques (corrected for body mass) and extensor-flexor ratios, were similar between groups. No difference in estimated body fat percentage was observed between any of the outfield players, and haemoglobin concentrations were similar among players of all positions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus. Case report and literature review from the plasmapheresis era.

Although thrombotic thrombocytopenic purpura (TTP) has been described in patients with systemic lupus erythematosus (SLE), the relationship between these 2 diseases is controversial. We recently treated a patient with longstanding SLE who developed TTP. The patient responded to therapy with aggressive plasmapheresis. Review of the literature revealed that TTP may occur in the setting of either active or inactive SLE. Survival in SLE associated TTP correlated with the use of plasma therapy (plasma infusion or plasmapheresis) rather than with the activity of the underlying autoimmune disease. We conclude that TTP and SLE represent distinct clinical entities that may occur together in an immunologically predisposed host. The use of plasma therapy appears to have had a significant impact on survival in these patients.

Adolescent

Protection of human umbilical vein endothelial cells by glycine and structurally similar amino acids against calcium and hydrogen peroxide-induced lethal cell injury.

Cultured human umbilical vein endothelial cells treated with either the calcium ionophore, ionomycin, or ionomycin plus cyanide-m-chlorophenylhydrazone had immediate severe depletion of adenosine triphosphate, (ATP) and increases of cytosolic free calcium (Caf) and then sustained lethal cell injury as manifested by release of lactate dehydrogenase and failure to exclude vital dyes within 15 minutes. Inclusion of glycine in the experimental medium prevented the enzyme leakage for at least 60 minutes without altering the ATP depletion or increases of Caf. The physiologic glycine concentration of 0.25 mmol/l gave 50% protection, and protection was complete at 1 mmol/l. Several other small neutral amino acids, L- and D-alanine, beta-alanine, 1-aminocyclopropane-1-carboxylate, alpha-aminoisobutyrate, and L-serine, had effects similar to glycine, but other amino acids and metabolic substrates did not. The endothelial cells were relatively resistant to damage from hydrogen peroxide, but sensitivity could be increased by preloading with Fe2+. In both non-loaded and Fe(2+)-loaded cells, hydrogen-peroxide-induced lactate dehydrogenase (LDH) release developing over 180 minutes was prevented by glycine in a fashion analogous to that seen with ionomycin damage. Mn2+ also partially protected against hydrogen peroxide injury but was not required for glycine's effects. These data demonstrate that striking modulatory effects of glycine and structurally similar amino acids that have previously been characterized in most detail using kidney tubule cells are strongly expressed in human umbilical vein endothelial cells and are involved in their response to Ca2+ and oxidant-mediated damage. These amino acid effects must be considered in the design of in vitro studies of endothelial cell injury and may contribute to endothelial cell pathophysiology in vivo.

Amino Acids

Prevalence of Chlamydia trachomatis infection in women having cervical smear tests.

OBJECTIVE: To determine the prevalence of sexually transmitted diseases in patients with normal and abnormal cervical smears. DESIGN: A prospective study of asymptomatic women with normal cervical smears attending their general practitioner and newly referred patients with abnormal smears attending a colposcopy clinic. SETTING: A hospital based colposcopy clinic and an urban general practice (list size 5500) in north west Glasgow. SUBJECTS: 197 asymptomatic women attending their general practitioner for cervical smear tests and 101 randomly selected patients attending the colposcopy clinic for investigation of abnormal smears. MAIN OUTCOME MEASURES: Presence of various sexually transmitted infections as determined by culture and serological tests. RESULTS: Of the 101 women with cytological abnormalities, six had current chlamydial infection proved by culture and none had gonococcal infection; of the 197 women with normal smears, 24 (12%) had a chlamydial infection and two had gonorrhoea. Serological studies for Chlamydia trachomatis specific antibody also indicated that a large proportion of patients had been exposed to this agent in both groups. There was no significant difference between the groups in the prevalence of any sexually transmitted disease studied. CONCLUSION: A high prevalence of chlamydial infection is present in women in north west Glasgow irrespective of their cervical cytological state.

Adult

Effect of work rate increment on peak oxygen uptake during wheelchair ergometry in men with quadriplegia.

The purpose of this study was to determine the effect of work rate increment on peak oxygen uptake (VO2 peak) during wheelchair ergometry (WCE) in men with quadriplegia due to cervical spinal cord injuries (CSCI). Twenty-two non-ambulatory subjects (aged 20-38 years) with CSCI were divided into two groups based on wheelchair sports classification (n = 12 for IA group and n = 10 for IB/IC group). Subjects underwent three different, continuous graded exercise tests (spaced at least 1 week apart) on an electronically braked wheelchair ergometer. Following a 3-min warmup, the work rate was increased 2, 4, or 6 W.min-1 for the IA group and 4, 6, or 8 W.min-1 for the IB/IC group. Ventilation and gas exchange were measured breath-by-breath with a computerized system. Repeated-measures ANOVA showed no significant difference among the three protocols for VO2 peak in the IA group (P greater than 0.05). The mean (SD) VO2 peak values (ml.kg-1.min-1) were 9.3 (2.4), 9.4 (3.2), and 8.4 (2.6) for the 2, 4, and 6 W.min-1 protocols, respectively. In contrast, the IB/IC group showed a significant difference among the protocols for VO2 peak (P less than 0.05). The mean (SD) VO2 peak values (ml.kg-1,min-1) were 15.1 (4.0), 14.1 (4.4), and 12.7 (4.0) for the 4, 6, and 8 W.min-1 protocols, respectively. Post hoc analysis revealed a difference between the 4 and 8 W.min-1 protocols. Our results suggest that graded exercise testing of men with quadriplegia due to CSCI, using WCE, should employ work rate increments between 2 and 6 W.min-1 and that work rate increments of 8 W.min-1 or greater will result in an underestimate of VO2 peak.

Adult

A classification of developmental activities of academic family medicine supported by federal grants.

Substantial funds have been awarded to academic departments of family medicine through the federal Establishment of Departments of Family Medicine grants program, initiated in 1980 under the Public Health Service Act. In 1989 the authors analyzed the successful grant applications in a sample of 61 institutions variously funded or re-funded for the grant cycles from 1980 through 1986 in order to classify the supported developmental activities. Three dimensions for explicating this activity emerged: (1) the functional area of the activity (e.g., curricular development); (2) the objectives of the activity (e.g., improving relevance of instruction); and (3) the strategies to be used to attain the objectives (e.g., addition of specialized faculty). This classification scheme provides a tentative but useful framework for characterizing departmental development.

Academic Medical Centers

Relationships between intracellular amino acid levels and protection against injury to isolated proximal tubules.

Metabolism and cellular levels of glycine, alanine, and other relevant amino acids in proximal tubules were studied during models of acute injury and protection by glycine. Freeze-clamped, normal rabbit renal cortex was very rich in glycine (66.8 nmol/mg protein) and glutamate and also had substantial levels of taurine, alanine, glutamine, serine, and aspartate. Isolated proximal tubules were severely depleted of all these amino acids (glycine, 2.1 nmol/mg protein). During 37 degrees C incubation in presence of alanine, tubules recovered only glutamate to a level approximating that in vivo (38.8 nmol/mg protein, 15.2 mM). Glycine added to medium at levels ranging from 0.25 to 2 mM was actively concentrated four- to sixfold by tubule cells. Two millimolar glycine potently protected tubules from lethal cell injury induced by hypoxia, antimycin A, or ouabain. Glycine levels of injured tubules rapidly equilibrated with medium, irrespective of whether glycine was loaded by preincubation or was added concomitantly with the injury maneuver. Metabolism of glycine during protection, assessed by changes in total levels, gas chromatography-mass spectroscopy determination of the fate of [13C]glycine, and redistribution of label from [3H]glycine was minimal. The data suggest that glycine plays an essential, constitutive role in maintenance of tubule cell structural integrity independently of common metabolic pathways. Intracellular amino acid content is sufficiently labile for depletion of structurally essential amino acids to potentially occur in a variety of settings, but, even with severe ATP depletion or Na+ pump inhibition, supplemental glycine is readily available to intracellular sites of action.

Amino Acids

Role of increased cytosolic free calcium in the pathogenesis of rabbit proximal tubule cell injury and protection by glycine or acidosis.

To assess the role of increased cytosolic free calcium (Caf) in the pathogenesis of acute proximal tubule cell injury and the protection afforded by exposure to reduced medium pH or treatment with glycine, fura-2-loaded tubules were studied in suspension and singly in a superfusion system. The Ca2+ ionophore, ionomycin, increased Caf to micromolar levels and rapidly produced lethal cell injury as indicated by loss of lactate dehydrogenase to the medium by suspended tubules and accelerated leak of fura and failure to exclude Trypan blue by superfused tubules. Decreasing medium Ca2+ to 100 nM prevented the ionomycin-induced increases of Caf and the injury. Reducing medium pH from 7.4 to 6.9 or adding 2 mM glycine to the medium also prevented the cell death, but did not prevent the increase of Caf to micromolar levels. Cells treated with 1799, an uncoupler of oxidative phosphorylation which produced severe adenosine triphosphate (ATP) depletion, did not develop increases of Caf until just before loss of viability. Preventing these increases of Caf with 100 nM Ca2+ medium did not protect 1799-treated cells. Reduced pH and glycine protected 1799-treated cells without ameliorating the increases of Caf. These data demonstrate the toxic potential of increased Caf in the proximal tubule and show that Caf does sharply increase prior to loss of viability in an ATP depletion model of injury, but this increase does not necessarily contribute to the outcome. The potent protective actions of decreased pH and glycine allow the cells to sustain increases of Caf to micromolar levels in spite of severe, accompanying cellular ATP depletion without developing lethal cell injury.

Acidosis

Metabolic aspects of protection by glycine against hypoxic injury to isolated proximal tubules.

To clarify the roles of butyrate and acylglycine formation in hypoxic proximal tubule cell injury and protection by glycine and to test the contribution of iodoacetate-suppressible metabolism to protection, (1) it was determined whether protection by glycine is fully expressed when glucose, lactate, alanine, and butyrate are replaced by alpha-ketoglutarate as the sole substrate for the tubules, (2) butyrate metabolism and acylglycine formation were directly measured in control and hypoxic preparations, and (3) it was assessed whether injury produced by iodoacetate, a potent inhibitor of glycolytic metabolism, is subject to protection by glycine. Susceptibility to hypoxic injury in medium with alpha-ketoglutarate as the sole substrate was similar to that seen in medium containing glucose, lactate, alanine, and butyrate. Tubules in alpha-ketoglutarate medium showed high degrees of protection by glycine against injury produced by 30-min of hypoxia, by iodoacetate alone, and by iodoacetate combined with hypoxia. Protection did not require preservation of cell ATP or glutathione. In glucose-lactate-alanine-butyrate medium, butyrate, measured by gas chromatography, was rapidly metabolized by oxygenated tubules and fully accounted for basal rates of oxygen consumption. Butyrate utilization stopped during hypoxia. Neither aspect of butyrate metabolism was altered by glycine. Formation of acylglycines was assessed by gas chromatography/mass spectroscopy. In preparations treated with glycine, butyrylglycine was detected under both oxygenated and hypoxic conditions; the quantities, however, were small and no other acylglycines were found. These observations indicate that protective effects of glycine are independent of short-chain acylglycine formation and glycolytic metabolism.

Animals

Effect of heterosis on performance of mice across three environments.

Performance of six genetic groups of mice was studied in three different environments in order to determine the effect of heterosis on consistency of performance in varied environments. Designed as a 3 x 6 factorial, data were analyzed using least squares analyses of variance. Genetic group effects, environmental effects, genetic group x environment interaction, and heterosis were examined for 42-d weight, age and weight at vaginal opening, age and weight at puberty, ovulation rate (determined by total corpora lutea), number of implantations, and number of fetuses at 10 d of gestation. Weight at vaginal opening, ovulation rate, implantation rate and total number of fetuses exhibited significant heterosis. Regression of these traits against an environmental index (mean performance of all genetic groups over environments) provided an estimate of stability of performance. In general, genetic groups exhibiting heterosis expressed more consistent performance across environments than pure lines did. We conclude that a stability model could be used to aid in identification of lines with consistent performance for production traits in variable environments.

Analysis of Variance

Modification to the RITARD surgical model.

The Removable Intestinal Tie-Adult Rabbit Diarrhea (RITARD) procedure is the surgical model of choice for studying pathogenesis of diarrheas of Campylobacter, Escherichia coli, and Aeromonas origin. Other than nonhuman primates, the RITARD rabbit is the only model that closely resembles human infection. Classically, the RITARD model is created by isolating the terminal ileum using umbilical tape placed in a slipknot fashion, and injecting the occluded segment with the organism of choice. The slipknot is removed at 4 h postinoculation and patency of the gut reestablished. We found removal of the umbilical tape to be extremely difficult, usually requiring a second surgery to gently untie the material and prevent destruction of the fragile intestinal tissue. This complication of the described procedure appeared to be related to the absorptive and abrasive nature of the tape material. The modification described uses the same idea, but a different material and a different knot pattern. The tubing was easily removed at the prescribed 4 h postsurgery, without an additional surgery. The tubing did not adhere to or damage the gut, yet did provide the occlusive seal required for a 4-h static gut. Histologically, no evidence of pressure could be found at the tie site.

Animals

Amino acid protection of cultured kidney tubule cells against calcium ionophore-induced lethal cell injury.

Treatment of two cultured renal tubule epithelial cell lines, MDCK and LLC-PK1, with ionomycin produced rapidly evolving models of lethal cell injury characterized by increases of cytosolic free calcium to the microM level within 15 minutes followed by lactate dehydrogenase release and failure to exclude vital dyes that began between 30 and 60 minutes and became extensive after 60 minutes. The pattern of injury was similar when the mitochondrial uncoupler, carbonyl cyanide-m-chlorophenylhydrazone, was added to ionomycin. Carbonyl cyanide-m-chlorophenylhydrazone alone produced severe ATP depletion but not lactate dehydrogenase release. Inclusion of glycine in the experimental medium at concentrations ranging from 0.25 mM to 5 mM did not affect the increases of cytosolic free calcium or ATP depletion but was protective against enzyme release and failure to exclude vital dyes for 180 minutes. Maximal protection was achieved at glycine concentrations between 1 and 5 mM. Several other small neutral amino acids including alanine, beta-alanine, L-serine, 1-aminocyclopropane-1-carboxylic acid, and alpha-aminoisobutyric acid also had protective effects but, glucose, pyruvate, glutamate, glutamine, leucine, valine, and taurine did not. These data indicate that potent protective effects of glycine and other small neutral amino acids previously shown in fresh tubule preparations are fully expressed in cultured tubule cells of diverse origin when appropriate acute injury models are used and the protective effects are sustained for long durations. The suitability of cultured cell lines for prolonged exposure studies will provide a powerful way of further exploring mechanisms of these effects.

Adenosine Triphosphate

Protocol dependency of VO2max during arm cycle ergometry in males with quadriplegia.

The purpose of this study was to determine whether maximal oxygen uptake (VO2max) is protocol dependent during arm cycle ergometry (ACE) for quadriplegic males with spinal cord injuries (SCI). Twenty-four non-ambulatory subjects (aged 20-38 yr) with cervical SCI were divided into two groups based on wheelchair sports classification (IA group = 14; IB/IC group = 10). They underwent three different, continuous graded exercise tests spaced at least 1 wk apart on an electronically braked arm cycle ergometer. Following a 3-min, unloaded warm-up at 60 rpm, the work rate was increased 2, 4, or 6 W.min-1 for the IA group and 4, 6, or 8 W.min-1 for the IB/IC group. Ventilation and gas exchange were measured breath-by-breath with a SensorMedics 4400 computerized system. Repeated-measures ANOVA showed no significant difference among the three protocols for VO2max in the IA group (P greater than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 10.8 (+/- 3.4), 11.0 (+/- 2.7), and 10.2 (+/- 2.9) for the 2, 4, and 6 W.min-1 protocols, respectively. In contrast, the IB/IC group showed a significant difference among the protocols for VO2max (P less than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 16.8 (+/- 4.5), 15.3 (+/- 4.3), and 14.6 (+/- 4.3) for 4, 6, and 8 W.min-1, respectively. Post hoc analysis revealed a difference between the 4 and 8 W.min-1 protocols. Our results suggest that graded exercise testing of SCI persons with quadriplegia, using ACE, should employ work rate increments between 2-6 W.min-1 and that work rate increments of 8 W.min-1 or greater will underestimate VO2max.

Adult

Effects of warm-up on muscle glycogenolysis during intense exercise.

This study investigated the effects of preliminary exercise (warm-up) on glycogen degradation and energy metabolism during intense cycle ergometer exercise. After determination of VO2max, six male subjects were randomly assigned to perform warm-up (WU) and no warm-up (NWU) trials incorporating a 2 min standardized sprint ride (SR) at 120% of the power output attained at VO2max (POmax). Muscle biopsies and temperature (Tm) recordings were obtained from the vastus lateralis muscle. Tm was elevated above the resting level prior to the SR during the WU trial (37.7 +/- 0.1 vs 35.4 +/- 0.4 degrees C; P less than 0.05) and remained higher than the NWU trial after the SR (38.6 +/- 0.2 vs 37.1 +/- 0.4 degrees C; P less than 0.05). Similar trends existed for rectal temperature (Tr). The increases in Tm and Tr during the SR were both greater in the NWU trial (P less than 0.05). Muscle glycogen degradation was similar for the WU and NWU trials (30.8 +/- 3.7 vs 25.6 +/- 3.7 mmol.kg-1, respectively). When blood and muscle lactate concentrations after the SR were expressed relative to values before the SR, the WU trial resulted in a lower accumulation of blood lactate (6.5 +/- 0.9 vs 10.7 +/- 0.8 mEq.l-1; P less than 0.01) and muscle lactate (20.1 +/- 0.1 vs 23.4 +/- 2.2 mEq.kg-1 wet wt.; P less than 0.05). Furthermore, oxygen consumption during the 1st min of the SR was higher in the WU trial (2.3 +/- 0.2 vs 1.9 +/- 0.2 l.min-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult