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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 343 records · Page 19Linked to original sources

Electro-oculographic abnormalities in amblyopia.

BACKGROUND: Electrodiagnostic tests have been used to investigate retinal function in amblyopia but previous results have been conflicting. METHODS: It was decided to investigate whether the electro-oculogram (EOG) showed any abnormalities in 12 adult amblyopes and 12 age and sex matched controls with normal vision. The mean amplitudes of the EOG recordings from each eye during 12 minutes of darkness and 18 minutes of light were compared. RESULTS: The mean values from the amblyopic eyes were lower than those from the fellow non-amblyopic eyes. At most time points the difference was significant (p < 0.05). After normalisation of the data to minimise intersubject variation, the reduction in EOG amplitudes of the amblyopic eyes at all time points was significant (p < 0.05). There was no significant difference between the mean values obtained from the right and left control eyes at any time point, either before or after normalisation. CONCLUSIONS: These results provide evidence for a retinal abnormality in amblyopia and implicate the retinal pigment epithelium as being involved. A deficiency in retinal dopaminergic function in amblyopia is proposed as a possible mechanism causing these results.

Adult↗

Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period.

Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the production of cytokines in bone or bone marrow. However, controversy remains on the role of candidate factors, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF). As IL-1 and TNF have many additive and/or synergistic effects in bone, we tested the hypothesis that the simultaneous block of IL-1 and TNF is required to prevent the initial phase of rapid bone loss that follows ovariectomy (ovx). To this aim, rats were ovariectomized and treated for 2 weeks with either IL-1 receptor antagonist (IL-1ra), an inhibitor of IL-1, or TNF-binding protein (TNFbp), an inhibitor of TNF. Ovx increased bone marrow cell secretion of IL-1 and TNF and decreased the bone density of the distal femur, as measured by dual energy x-ray absorptiometry. Ovx-induced bone loss was decreased by both IL-1ra and TNFbp and completely prevented by simultaneous treatment with IL-1ra and TNFbp. Combined treatment with IL-1ra and TNFbp decreased urinary pyridinoline cross-links, a marker of bone resorption that reflects osteoclast number and osteoclast activity, whereas treatment with either inhibitor alone was less effective. Both IL-1ra and TNFbp decreased the number of osteoclasts on the endocortical surfaces and stimulated bone formation, but the two inhibitors had no additive effects on these indexes, suggesting that inhibition of osteoclastogenesis and stimulation of bone formation do not account for the additive bone-sparing effects of IL-1ra and TNFbp. These inhibitors had no effect in sham-operated rats, indicating that they specifically blocked estrogen-dependent events. In conclusion, these data indicate that in the early post-ovx period, IL-1 and TNF play a critical causal role in inducing bone loss and do so by stimulating bone resorption and inhibiting bone formation.

Absorptiometry, Photon↗

Benefit-cost analysis of drug abuse prevention programs: a macroscopic approach.

To date, benefit-cost analysis has rarely been used to justify the drug abuse prevention field. However, there is an increasing demand for this type of analysis as the field of substance abuse prevention enters a new phase--a phase characterized by a competitive marketplace, an increased demand for accountability, and the desire to measure return on the money invested in prevention. In response, an effort is made to stimulate discussion and further research on the topic. This article first determines the overall strategy for initiating benefit-cost analysis (BCA), followed by definitions of BCA and cost-effectiveness analysis (CEA). This is followed by the determination of some of the major variables used in BCA along with the algorithm for determining the benefit-cost efficiency ratio (R) as it applies to the macro level analysis. In estimating a value for the R, a decision has been made to incorporate uncertainty into the BCA. In a macroscopic approach to BCA, four independent variables are identified for computing R. These independent and dependent variables are assumed to be random variables with normal distributions. The population means and standard deviations pertaining to these independent variables are estimated from the existing literature. In order to incorporate uncertainty into the computation of R, ten measurements have been randomly selected for each of the four independent variables. Following this procedure, fifteen benefit-cost efficiency ratios are calculated by selecting one of the ten values at random per variable used in the R equation. In this way, we were able to determine the most likely population benefit-cost efficiency ratio of 15:1, indicating that there is a $15 savings on every dollar spent on drug abuse prevention. The 95 percent confidence level pertaining to the R has an interval from $13.7 to $16.1. This indicates that the population R resides within the range 95 percent of the time.

Confidence Intervals↗

Concurrent paclitaxel/cisplatin with thoracic radiation in patients with stage IIIA/B non-small cell carcinoma of the lung.

Nine patients with stage IIIB non-small cell lung cancer were entered into a phase II trial designed to determine the feasibility of giving a combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin concurrent with thoracic radiation. Paclitaxel was given as a 24-hour infusion (135 mg/m2) followed by cisplatin (75 mg/m2) every 4 weeks, for a total of four cycles. Thoracic radiation was given concurrently with the first two cycles of chemotherapy, for a total dose of 64.8 Gy over 6 weeks. Neutropenia and esophagitis were the most common toxicities, with 66% of patients experiencing grade 3 or 4 neutropenia and 55% experiencing grade 3 or 4 esophagitis. Grade 3 pulmonary toxicity developed in 33% of patients. All patients were able to receive the full dose of radiation, although half of the patients required some modification of the chemotherapy regimen. There was one complete response and four partial responses, yielding a 56% overall response rate. This study demonstrates that it is feasible to treat patients with stage IIIB non-small cell lung cancer with paclitaxel/cisplatin plus concurrent thoracic radiation, with a degree of toxicity comparable with that associated with a degree of toxicity comparable with that associated with other concurrent combined-modality regimens for this disease.

Aged↗

Biliary haptoglobin, a potent promoter of cholesterol crystallization at physiological concentrations.

BACKGROUND/AIMS: Several proteins present in human bile have been reported to promote cholesterol crystallization and thus are potentially important in the formation of cholesterol crystals as the initial stage in gallstone pathogenesis. To be physiologically relevant, such proteins must either be present in high concentration in bile or have a potent promoting activity. The current study explored several of the more abundant but unexamined biliary proteins based upon their also having sufficiently high serum concentrations that antibodies were available for both their isolation and quantitation. METHODS: Protein purification was accomplished by immunoaffinity chromatography of bile followed by delipidation. Con A affinity chromatography of bile was used to obtain the bound fraction, a portion of which was delipidated. Crystallization-promoting activity of both the purified proteins and Con A-bound glycoprotein fractions (CABG) was measured by a photometric crystal growth assay. A competitive antibody-capture ELISA assay was developed to measure concentrations of alpha 1-antitrypsin, transferrin, and haptoglobin in native bile. RESULTS: At their relevant physiological concentrations, biliary haptoglobin (15 micrograms/ml) had a crystallization-promoting activity twice that of the biliary IgM (75 micrograms/ml) used as a reference standard (P < 0.05). Biliary transferrin (20 micrograms/ml) had only modest promoting activity (P < 0.05). Biliary alpha 1-antitrypsin (50 micrograms/ml), by contrast, showed no promoting activity. Delipidation of the CABG fraction decreased its promoting activity by 75%. Biliary haptoglobin accounts for about 30% of delipidated total CABG-promoting activity. CONCLUSIONS: Biliary haptoglobin at its physiological concentration has a highly potent crystallization-promoting activity and thus becomes a candidate for major attention in understanding gallstone pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

The isolated air perfused rat heart.

A simple method has been developed for continuous monitoring of metabolic activity of an isolated, perfused rat heart by O2/CO2 respirometer. Since respirometer provides vital data on oxygen consumption and carbon dioxide production of a preserved organ on a continuous basis over a long period of time, it will be possible to use this method to monitor viability of not only isolated heart but also any given donor organ under preservation.

Air↗

The use of poly R-478 as a marker to determine gastric emptying and intestinal propulsive motility in suckling rats.

During our studies on gastrointestinal motility in suckling rats using 51Cr or 51Cr-EDTA as markers, we noticed that these markers--in contrast to studies in adult rats--"adhered" to the gastrointestinal wall of sucklings. We therefore decided to test the use of another non-absorbable marker Poly R-478 (an acetylated anthrapyridone chromophore linked to an polyamino-ethylene-sodium ethylene sulfonate copolymer backbone developed by the Dynapol Corporation (Palo Alto, CA). This new method has appeared to be useful.

Animals↗

Testing reckless drivers for cocaine and marijuana.

BACKGROUND: Driving under the influence of intoxicating drugs other than alcohol may be an important cause of traffic injuries. We used a rapid urine test to identify reckless drivers who were under the influence of cocaine or marijuana. METHODS: We conducted a consecutive-sample study in Memphis, Tennessee, in the summer of 1993. Subjects arrested for reckless driving who were not apparently impaired by alcohol (did not have an odor of alcohol, tested negative on breath analysis, or both) were tested for cocaine and marijuana at the scene of arrest. The results of the drug tests were compared with clinical evaluations of intoxication made at the scene by a police officer. RESULTS: A total of 175 subjects were stopped for reckless driving, and 150 (86 percent) submitted urine samples for drug testing at the scene of arrest. Eighty-eight of the 150 (59 percent) tested positive: 20 (13 percent) for cocaine, 50 (33 percent) for marijuana, and 18 (12 percent) for both drugs. Ninety-four of the 150 tested drivers were clinically considered to be intoxicated, and 80 of them (85 percent) tested positive for cocaine or marijuana. The intoxicated drivers had a broad range of affects and appearances. Nearly half the drivers intoxicated with cocaine performed normally on standard sobriety tests. CONCLUSIONS: Over half of the reckless drivers who were not intoxicated with alcohol were found to be intoxicated with other drugs. Toxicologic testing at the scene is a practical means of identifying drivers under the influence of drugs and is a useful adjunct to standard behavioral sobriety testing.

Adult↗

The metabolic responses of human type I and II muscle fibres during maximal treadmill sprinting.

1. Muscle biopsy samples were obtained from the vastus lateralis of six healthy volunteers before and after 30 s of treadmill sprinting. A portion of each biopsy sample was used for mixed-fibre metabolite analysis. Single fibres were dissected from the remaining portion of each biopsy and were used for ATP, phosphocreatine (PCr) and glycogen determination. 2. Before exercise, PCr and glycogen contents were higher in type II fibres (79.3 +/- 2.7 and 472 +/- 35 mmol (kg dry matter (DM)-1, respectively) compared with type I fibres (71.3 +/- 3.0 mmol (kg DM)-1, P < 0.01 and 375 +/- 25 mmol (kg DM)-1, P < 0.001, respectively). 3. Peak power output was 885 +/- 66 W and declined by 65 +/- 3% during exercise. Phosphocreatine and glycogen degradation in type II fibres during exercise (74.3 +/- 2.5 and 126.3 +/- 15.8 mmol (kg DM)-1, respectively) was greater than the corresponding degradation in type I fibres (59.1 +/- 2.9 mmol (kg DM)-1, P < 0.001 and 77.0 +/- 14.3 mmol (kg DM)-1, P < 0.01, respectively). The decline in ATP during exercise was similar when comparing fibre types (P > 0.05). 4. Compared with previous studies involving similar durations of maximal cycling exercise, isokinetic knee extension and intermittent isometric contraction, the rates of substrate utilization recorded in type I fibres were extremely high, being close to the rapid rates observed in this fibre type during intense contraction with limb blood flow occluded.

Adenosine Triphosphate↗

Neuronal rescue with transforming growth factor-beta 1 after hypoxic-ischaemic brain injury.

Transforming growth factor-beta 1 (TGF-beta 1) mRNA is induced from 5 h to 3 days following hypoxic-ischaemic brain injury. Cell death also develops during this time suggesting that extracellular accumulation of this peptide may be involved in the processes that regulate cell loss. We examined the effect of rhTGF-beta 1 (0,2.5, 10,50 ng) injected into the cerebral lateral ventricle of rats 2 h after severe hypoxic-ischaemic brain injury. Histological outcome and B4-isolectin histochemistry were assessed 5 and 2 days, respectively following hypoxia. Treatment with 10 ng TGF-beta 1 reduced the microglia reaction (p < 0.05), the magnitude of neuronal loss (p < 0.01) and the area of cortical infarction (p < 0.05). Exogenous TGF-beta 1 given soon after hypoxic-ischaemic brain injury may have therapeutic potential and act by inhibiting the microglial reaction.

Animals↗

A comparison of the effects of two monophasic low dose oral contraceptives on the inhibition of ovulation.

Fifty-three women were randomly allocated to one of two combined low-dose monophasic oral contraceptives (20 micrograms ethinyl estradiol with 75 micrograms gestodene or 20 micrograms ethinyl estradiol with 150 micrograms desogestrel). The ability of these formulations to inhibit ovulation was compared using hormonal parameters and ovarian ultrasound. The effects on three treated cycles were compared with pre- and post-treatment cycles. No ovulations occurred in either group during therapy. Twenty-one percent of women were observed to show some follicle-like structures accompanied by raised serum estradiol in at least one treatment cycle. No significant differences between the two preparations were demonstrated on residual ovarian function. The secretion of estradiol and progesterone was significantly reduced throughout all three treatment cycles. Mean LH and FSH concentrations were comparable with both treatments. A secondary analysis of cycle control and tolerance was undertaken. Significantly less bleeding was seen in the gestodene group during cycle 2 (p = 0.02). There were no differences between the two treatments with respect to the other cycle control parameters. Approximately half the women recorded intracyclic bleeding during the first treatment cycle. This improved during cycles 2 and 3. Both formulations were tolerated well.

Adolescent↗