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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 505 records · Page 28Linked to original sources
PubMed1988

Simple canine model of arterial thrombosis with endothelial injury suitable for investigation of thrombolytic agents.

Three separate studies were done to evaluate a new canine model of arterial thrombosis with endothelial injury. Endothelial injury was produced by exposing the luminal surface of a 2-cm segment of femoral artery to 100 degrees C saline for 5 min. There was no disruption of proximal or distal blood flow with this model, and thrombolysis was continuously monitored by measuring 125I-labelled fibrin gamma emissions from the thrombus. Study No. 1 showed that complete endothelial denudation was achieved with this model. Study No. 2 demonstrated 1) adherence of the experimentally induced thrombus to subendothelial connective tissue, and 2) endogenous thrombolysis of approximately 9% during the initial 2 h after thrombus formation. Study No. 3 tested the usefulness of the model for evaluating the thrombolytic efficacy of urokinase. Urokinase (30,000 U/Kg, bolus IV injection) caused 38 +/- 5.4% thrombolysis within 90 min of drug administration versus 5.9 +/- 2.4% for a saline-treated control group. We conclude that this model provides a technically simple and reproducible method for the laboratory investigation of thrombosis and thrombolysis in arteries with endothelial injury.

Animals↗
PubMed1988

Effect of phorbol ester on prostaglandin regulation of proliferation in rabbit endometrial cells.

We have proposed that two of the endogenously synthesized endometrial prostaglandins, prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E1 (PGE1), play a regulatory role in growth control of the endometrium. PGF2 alpha increases DNA synthesis and PGE1 inhibits that effect. Primary cultures of rabbit endometrial cells were used here to examine the effects of the tumor-promoting, diacylglycerol mimicking, phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), on the prostaglandin control of cell proliferation. TPA treatment of these cultures results in: a decrease in control levels of proliferation and complete inhibition by TPA of PGF2 alpha stimulated DNA synthesis; a reduction in [3H]PGF2 alpha binding with short term treatment but an increase to above control binding level with long term treatment; an inhibition of the normal PGF2 alpha stimulated inositol polyphosphate synthesis; and a small increase in accumulation of PGF2 alpha in the culture media. Furthermore, in this culture system, TPA does not down regulate [3H]PGE1 binding; it does not alter the normal PGE1 stimulation of cAMP synthesis; and it has no effect on the normal endogenous PGE1 synthesis by these cultures. The above results are consistent with our previous observations that PGF2 alpha works through the intracellular messengers inositol polyphosphate/diacylglycerol whereas PGE1 works through cAMP.

Alprostadil↗
PubMed1988

A progressive shuttle run test to estimate maximal oxygen uptake.

The purpose of the present study was to examine the validity of using a 20 m progressive shuttle run test to estimate maximal oxygen uptake. Running ability was described as the final level attained on the shuttle run test and as time on a 5 km run. Maximal oxygen uptake (VO2 max) was determined directly for seventy-four volunteers (36 men, 38 women) who also completed the shuttle run test. Maximal oxygen uptake values were 58.5 +/- 7.0 and 47.4 +/- 6.1 ml.kg-1.min-1 for the men and women respectively (mean +/- SD, P less than 0.01). The levels attained on the shuttle run test were 12.6 +/- 1.5 (men) and 9.6 +/- 1.8 (women; P less than 0.01). The correlation between VO2 max and shuttle level was 0.92. The correlation between VO2 max and the 5 km run was -0.94 and the correlation between both field tests was -0.96. The results of this study suggest that a progressive shuttle run test provides a valid estimate of VO2 max and indicates 5 km running potential in active men and women.

Adult↗
PubMed1988

Unusual dual genital duct remnants in true hermaphroditism.

A case of true hermaphroditism is reported in which a 46,XY karyotype was associated with a testis and an ovotestis. The dual presence of a Fallopian tube and a vas deferens on the side of the ovotestis is documented as a previously unreported finding.

Disorders of Sex Development↗
PubMed1988

Precocial neural function in the growth-retarded fetal lamb.

Clinical studies suggest that growth-retarded prematurely delivered infants are neurologically precocious. We investigated this paradoxical observation in the fetal lamb. Somatosensory and brainstem auditory-evoked potentials were studied in chronically instrumented fetal lambs in late gestation with varying degrees of growth retardation induced by preconception uterine carunclectomy. The components of the brainstem auditory-evoked response appeared earlier (p less than 0.05) in fetuses at least 2 SD less than the mean weight for gestational age (n = 5) compared to normal controls (n = 8) or carunclectomized fetuses of normal size (n = 7). Several waveforms of both the somatosensory (N20, P/N 30, and P200) and the brainstem auditory-evoked response (I, III, IV, and V) demonstrated shorter (p less than 0.05) latencies in growth-retarded fetuses relative to normal-sized fetuses. The ability to follow increasing stimulus rates for both stimuli also demonstrated precocial maturation (p less than 0.05) in growth-retarded as compared to normal-sized fetuses. Growth retardation is thus associated with precocial neurologic maturation in utero.

Animals↗
PubMed1988

Postmarketing surveillance in rheumatology: analysis of purpura and upper abdominal pain.

A system of postmarketing surveillance of antirheumatic drugs employing prospective protocol based consecutive patient cohorts is described, together with use of recursive partitioning techniques for statistical adjustment for potentially confounding variables. An analysis of 2 side effects (purpura and upper abdominal pain) is presented. Purpura was found to be associated with age, sex, disease duration, and amount of disability. The combination of aspirin and prednisone was associated with the highest prevalence of purpura. Upper abdominal pain also varied across drug classes. Within the nonsteroidal antiinflammatory drug category, there were clinically important differences in the relative prevalence of upper gastrointestinal pain between specific drugs.

Abdomen↗
PubMed1987

Requirement for prostaglandin F2 alpha in 17 beta-estradiol stimulation of DNA synthesis in rabbit endometrial cultures.

We have hypothesized that two of the endogenously synthesized endometrial prostaglandins (PGs), prostaglandin F2 alpha (PGF2 alpha), and prostaglandin E1 (PGE1), play a regulatory role in growth control of the rabbit endometrium. PGF2 alpha increases DNA synthesis and PGE1 inhibits that effect. Primary cultures of rabbit endometrial cells were used to examine the possible role of these PGs in the mechanism of action of 17 beta-estradiol on DNA synthesis. Towards this end, binding, second messenger and DNA synthesis experiments were performed. 17 beta-estradiol stimulation resulted in a time dependent (optimal: approximately 6 h) and 17 beta-estradiol concentration dependent (optimal: approximately 10(-7) M 17 beta-estradiol in phenol red-containing medium) increase in [3H]PGF2 alpha binding. Scatchard type analysis of the binding data revealed an increase in receptor number while the receptor affinity for [3H]PGF2 alpha remained the same as in the control treated cultures. This 17 beta-estradiol stimulated increase in PGF2 alpha receptor allowed a suboptimal concentration of PGF2 alpha (10(-9) M) to increase intracellular levels of inositol polyphosphates, while by itself this concentration of PGF2 alpha caused no significant change in intracellular inositol polyphosphate levels. 17 beta-estradiol, alone among the several studied steroid hormones, could increase [3H]PGF2 alpha binding. Proliferation studies revealed that, in these primary cultures of rabbit endometrium, 17 beta-estradiol could increase DNA synthesis but not in the presence of indomethacin, unless PGF2 alpha was added to the medium at a concentration (10(-10) M) near or above what is normally accumulated in the medium by these cultures. In the absence of 17 beta-estradiol stimulation, addition of these same low concentrations of PGF2 alpha had no effect on DNA synthesis. Apparently, through its effect on the PGF2 alpha receptor, 17 beta-estradiol enhances the PGF2 alpha stimulated DNA synthesis response approximately 100 fold. The DNA synthesis induced by 17 beta-estradiol can be inhibited by PGE1, as can PGF2 alpha-induced DNA synthesis. We propose that 17 beta-estradiol may be mediating its mitogenic effect through an alteration of the prostaglandin agonist:antagonist control of proliferation in rabbit endometrial cultures. In addition we suggest that, if 17 beta-estradiol acts to increase PGF2 alpha, receptors as part of its mode of action, this may be of importance in other tissues possessing both prostaglandin and 17 beta-estradiol receptors.

Animals↗
PubMed1987

Regional variations in the extent and timing of motoneuron cell death in the lumbosacral spinal cord of the chick embryo.

We have examined the distribution of motoneurons in different segments of the chick lumbosacral spinal cord before and after the period of motoneuron cell death. The extent of cell death was found to be greatest at the boundaries of the lumbosacral cord where over 60% of the motoneurons died and least in the central region where only 30% died. After cell death at stage 40 the number of motoneurons in each segment was linearly correlated with segment length, suggesting that growth of the segment and motoneuron numbers may be regulated by a common factor. The time of completion of motoneuron cell death exhibited a rostrocaudal gradient along the lumbar cord. Cell death was complete in the anterior segments by stage 35 but not until stage 38 in the caudal 4 segments. The regional variations in the extent and timing of motoneuron cell death suggest that the relative importance of the factors mediating cell death vary in different regions of the lumbar cord.

Animals↗
PubMed1987

Influence of single-leg training on muscle metabolism and endurance during exercise with the trained limb and the untrained limb.

We have previously shown that single-leg training results in improved endurance for exercise with the untrained leg (UTL) as well as for exercise with the trained leg (TL). The purpose of this study was to see whether the improved endurance of the untrained leg could be explained on the basis of changes in muscle metabolism. Exercise time to exhaustion at 80% of maximum oxygen uptake (VO2 max) was determined for each leg separately, pre- and post-training. Muscle metabolite concentrations were measured pre- and post-training in biopsy samples obtained immediately before this endurance test and at the pre-training point of exhaustion (END1). After six weeks of single-leg training endurance time was increased for both the UTL and the TL (UTL 34.0 +/- 16.4 min vs 97.9 +/- 26.3 min, P less than 0.01; TL 28.3 +/- 10.1 min vs 169.0 +/- 32.6 min, P less than 0.01). No changes in muscle metabolite concentrations were found in resting muscle. Training increased muscle ATP (P less than 0.05) and glycogen (P less than 0.01) concentrations and decreased muscle lactate concentration (P less than 0.05) in the TL at END1. No significant changes in muscle metabolite concentrations were found for the UTL. The improved endurance of the contralateral limb after single-leg training could not be explained on the basis of changes in muscle metabolism.

Adult↗
PubMed1987

Hepatobiliary and pancreatic complications of cyclosporine therapy in 466 renal transplant recipients.

Two hundred twenty-eight patients from a total of 466 (49%) receiving renal allografts under cyclosporine/prednisone (CsA/Pred) immunosuppression experienced at least one episode of posttransplant hepatotoxicity. All patients were documented to have normal serum bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), lactic acid dehydrogenase (LDH), and alkaline phosphatase (AP), as well as negative results of biliary ultrasound and upper gastrointestinal contrast examinations prior to transplantation. Hepatotoxic episodes usually were self-limited (82%), and generally occurred during the very early posttransplant period (76%). Liver function abnormalities included hyperbilirubinemia (48% of patients), elevated SGOT (47%), SGPT (73%), LDH (84%), and AP (59%). The CsA serum trough radioimmunoassay (RIA) was relatively high among hepatotoxic patients with a mean value of 225 +/- 17 ng/ml. Pharmacokinetic parameters, including bioavailability and drug clearance, were significantly altered among this group of patients. The management strategy of CsA dose reduction was effective; however, 11 patients (2.4%) developed biliary calculous disease posttransplant while under CsA/Pred immunosuppression. Seven patients had cholelithiasis, and two patients underwent choledochoduodenostomy because of primary choledocholithiasis. The results contrast with 279 renal transplant recipients from an overlapping nonrandomized group treated with azathioprine (Aza)/Pred in whom cholelithiasis was not identified. Pancreatic abnormalities were relatively common, but clinical pancreatic disease occurred in only six patients. There were two episodes of acute pancreatitis, three patients developed pancreatic abscess, and one patient developed a pancreatic pseudocyst. The apparent proclivity of CsA-treated patients to develop biliary calculous disease, and the occurrence of serious pancreatic complications in a small percentage of patients did not affect the majority of CsA-treated patients. They may, however, represent important problems associated with the use of this immunosuppressive agent.

Adult↗
PubMed1987

Heat stability of lyophilized C1 inactivator concentrates.

Heat stability of lyophilized C1 inactivator (C1-INA) concentrates of intermediate and high purity has been investigated under several heat treatment protocols that include heating for 96 and 192 h at 68 degrees C and for 10 h at 80, 90 and 100 degrees C. Both types of concentrate showed high stability in functional activity, with not more than 5% loss in any of the time-temperature combinations evaluated. However, the C1-INA antigen from both concentrates showed small but progressive changes in crossed immunoelectrophoretic pattern, in proportion to the intensity of heat treatment. High-pressure size-exclusion chromatography revealed only minimal signs of aggregation in the high-purity concentrate, but a significant and progressive aggregation of nonspecific protein contaminants present in the intermediate-purity concentrate, making the high-purity concentrate preferable for heat treatment.

Complement C1 Inactivator Proteins↗
PubMed1987

High intensity training and treadmill sprint performance.

Twelve county standard hockey players completed a 30 second sprint on a non-motorised treadmill and an uphill treadmill running test to determine maximum oxygen uptake (VO2 max) before and after 6 weeks of high intensity training (fast runs 3-5 miles, intervals 30-300 m and circuit training), whilst 11 club standard players completed the same tests without any additional training. For the county standard group there was an 11.1% and 5.0% improvement in peak running speed and distance covered on the sprint treadmill respectively, a 4.2% improvement in VO2 max and an 11.5% improvement in run time to exhaustion during the VO2 max test (all p less than 0.01). No changes were observed for the club standard group. There were large increases in blood lactate (county group 13.26 +/- 1.83 mM) and blood glucose (county group 1.56 +/- 0.71 mM) concentrations as a result of the treadmill sprint, but there were no additional changes in these variables as a result of training. Thus, the mechanism of adaptation in this type of brief maximal exercise remains in question.

Adult↗
PubMed1987

Determinants of five kilometre running performance in active men and women.

Previous studies of elite endurance athletes have suggested that success in distance running is attributable to the possession of a high maximal oxygen uptake (VO2 max), the utilisation of a large fraction of the VO2 max and to running economy. The purpose of the present study was to examine the relationships between these physiological characteristics and running performance in active but not elite men and women. Maximal oxygen uptake values were 57.6 +/- 6.2 and 46.6 +/- 4.8 ml . kg.-1 min-1 for the men and women respectively (p less than 0.01). Running performance was assessed as a 5 km time trial and the men completed this distance in 19.77 +/- 2.27 min and the women in 24.44 +/- 3.19 min (p less than 0.01). Maximal oxygen uptake showed strong correlations (p less than 0.01) with running performance (men, r = -0.85; women, r = -0.80) but there was only a modest relationship between running economy and performance (men, r = 0.39; women, r = 0.34). The results of the present study suggest that the faster 5 km performance times recorded by the men were best explained by their higher VO2 max values.

Female↗