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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 991 records · Page 55Linked to original sources

The use of etomidate in the management of severe head injury.

The effects of continuous and supplementary bolus dose administration of etomidate have been investigated in ten artificially ventilated patients in traumatic coma. Continuous infusion of etomidate (5-25 micrograms/kg/min) proved to be a practical and safe means of sedating these patients and appeared to control moderately elevated ICP. Additional bolus doses of etomidate (0.2 mg/kg) always reduced acutely elevated ICP (greater than 20 mmHg), which fell by a mean of 33%. However, MAP usually fell, and occasionally serious hypotension occurred. Of a total of 61 bolus dose administrations which were analysed, CPP rose on 40 occasions, fell on 19 and was unchanged twice. There was a weak correlation between the control level of ICP and the magnitude of the fall in ICP in response to the bolus dose of etomidate (r = 0.51, p less than 0.001). Bolus doses of etomidate given just before noxious stimulation, for example chest physiotherapy, prevented or limited the expected rise in ICP (with bolus mean change in ICP = -2.7 +/- 6.9 mmHg, without bolus mean change in ICP = +7.0 +/- 6.4 mmHg). Again MAP tended to fall following the bolus dose. Overall CPP tended to fall slightly following stimulation whether or not a bolus dose was administered (-3.2 +/- 11.1 mmHg and -4.9 +/- 11.5 mmHg respectively). However, when the bolus of etomidate was not given, occasional dramatic and dangerous rises in ICP were seen, in spite of the infusion, during which CPP fell to critical levels. This very rarely occurred when the bolus had been given. Furthermore, serious episodes of hypotension in response to etomidate administration appeared to occur mainly in patients who were relatively hypo-volaemic.

Adolescent↗

A study of the ovulation-inhibiting effects of dexamethasone in the domestic hen.

Laying hens were injected with a series of graded doses of dexamethasone following the terminal oviposition of a sequence to determine the effect of this compound on the time of ovulation. It was found that injection of 10-500 micrograms of dexamethasone/kg inhibited ovulation but there was no evidence of an ovulation-inducing effect when the dose was reduced below 10 micrograms/kg. The results for dexamethasone are in contrast to the effects of corticosterone which inhibits ovulation at high doses and induces ovulation at lower doses providing the hens are injected at the stage of the ovulatory cycle used in this study. It is suggested that the ovulation-inducing action of corticosterone involves a target site remote from the hypothalamic-pituitary axis.

Animals↗

A pharmaceutical profile of diabetic patients.

Although there have been innumerable studies documenting various aspects of the morbidity caused by diabetes mellitus in the population, very little attention has been paid to patterns of therapeutic management of diabetic patients. The United States Public Health Service Ambulatory Care Data System (USPHS ACDS), a computerized patient information entry and recording system with a complete pharmaceutical record for each patient, was used to compare patterns of pharmaceutical consumption among diabetic patients as opposed to non-diabetic patients in a population of approximately 90,000 individuals. Drug use by diabetics was significantly higher than by non-diabetics. Cardiovascular drug use, in particular, was considerably higher. Substantially higher consumption of anti-lipemic agents, anti-gout drugs, anti-hypertensives, sedatives and tranquilizers was also found in the diabetic population. The higher use of all drugs by diabetics could be partially explained by a demonstrably higher frequency of out-patient visits by diabetics. However this factor alone could not account for very much higher use of certain selective drug groups by the diabetics. In most cases, these selective increases among the diabetics paralleled expected patterns of disease for which those drug groups are prescribed. The investigation of pharmacotherapeutic profiles of the diabetic population adds a new dimension to the epidemiological study of this disease.

Adult↗

Studies on the local immune response of the lactating ewe infected with Ostertagia circumcincta.

Changes in the flow and composition of gastric lymph were monitored in groups of lactating and non-lactating ewes which were repeatedly infected with Ostertagia circumcincta. As judged by faecal egg counts and worm burdens the lactating group was more susceptible than the non-lactating controls to the challenge infection. Increased amounts of pepsinogen as well as larger numbers of eosinophils and neutrophils entering the gastric lymph indicated considerable abomasal damage and inflammation in the lactating ewes. However, measurement of the flow of lymphocytes as well as the amount of IgA and IgA antibody in the lymph did not indicate that these aspects of the local immune response were impaired during lactation; in fact the output of IgA-containing lymphocytes as well as IgA itself was usually raised in the lactating sheep. Lymph flow was increased and lymph globulin concentrations proportionally decreased in lactating ewes, irrespectively of whether they were infected with worms. It is suggested that these changes were caused by the increase in voluntary food intake which occurs during lactation.

Animals↗

Local immunity and Ostertagia circumcincta: changes in the gastric lymph of sheep after a primary infection.

Some aspects of the kinetics of the primary local immune response to O. circumcincta were studied by monitoring the flow and composition of gastric lymph from 4 sheep for 3 weeks after infection with 50 000 larvae. A significant increase in the frequency of lymphoblasts in the lymph showed that all the sheep were responding immunologically to the parasites from day 8 onwards. However, considerable individual variation in degree and timing was evident in other aspects of the immune response; 2 animals responded with large increases in lymphocyte output which reached a peak on day 5 or day 10, whereas the main response in the other 2 sheep appeared to be inflammatory in nature, with large increases in lymph flow and eosinophil output which occurred during the third week of infection. No significant changes in the content of IgA or IgA anti-worm antibody were detected in the lymph, but pepsinogen concentrations were significantly raised from day 12 onwards.

Animals↗

Local immunity and Ostertagia circumcincta: changes in the gastric lymph of immune sheep after a challenge infection.

Immunity to Ostertagia circumcincta was demonstrated in 5 previously infected sheep which were killed 10 days after challenge with 50 000 larvae. This immunity was expressed as a reduction in the number as well as the degree of development of the surviving parasites compared with those found in 6 control sheep. Gastric lymph was sampled from the immune group from 2 days before till 10 days after challenge and a secondary local immune response was detected. The main features of this response were a large increase in cell output in the lymph, especially in lymphoblasts and IgA-containing cells, which reached a peak on day 4 or 5, followed by a ten-fold increase in IgA immunoglobulin and IgA anti-worm antibody which reached a peak 7 or 8 days after challenge. The timing of these events suggested that the cellular, but not the IgA, response could have been involved in a putative mechanism which caused arrested development, although both components could have been implicated in mechanisms which may have caused expulsion of developing larvae.

Animals↗

Calcium excretion in feces of ungulates.

1. Fecal excretion of calcium was examined in 122 individual ungulates representing 7 species of Equidae, 3 species of Tapiridae, 3 species of Rhinocerotidae, 2 species of Elephantidae, 2 species of Hippopotamidae, 12 species of Bovidae, 2 species of Cervidae, 3 species of Camellidae and 1 species of Giraffidae. 2. Animals were fed timothy hay, a low calcium diet or alfalfa hay, a high calcium diet. 3. In a few cases oat straw or prairie hay was used instead of timothy hay. 4. Samples of feces were obtained from individuals daily for 4 days following a 20 day dietary equilibration period. 5. Feces of equids, tapirs, rhinoceros and elephants had a lower calcium concentration and a lower Ca/P ratio than feces of ruminants when the animals were fed diets of equivalent calcium content. 6. The findings suggest that the non-ruminant ungulate equids, tapirs, rhinoceros and elephants absorb a larger proportion of dietary calcium than ruminants do.

Animals↗

In vitro complementation as an assay for purification of adenovirus DNA replication proteins.

As an approach to the purification of adenovirus-encoded DNA replication proteins, we have developed in vitro complementation assays that make use of viral mutants defective in DNA replication in vivo. Nuclear extracts prepared from cells infected with H5ts36 or H5ts125, two such mutants belonging to different complementation groups, were found to be defective in viral DNA replication in vitro. However, replication activity could be restored by mixing the two extracts. Replication activity in either extract also could be restored by addition of appropriate replication-deficient fractions purified from cells infected with wild-type adenovirus. By using such assays, H5ts36- and H5ts125-complementing activities were extensively purified. As expected, purified H5ts125-complementing activity consisted of a single major polypeptide, the 72-kilodalton (kDal) adenovirus DNA binding protein. The purified H5ts36-complementing activity consisted of the 80-kDal adenovirus terminal protein precursor and two other major polypeptides with apparent molecular masses of 140 and 65 kDal. Formation of the 80-kDal terminal protein-dCMP complexes, the proposed initial step in adenovirus DNA replication, required components in the purified H5ts36-complementing fraction and a cellular factor(s) but did not require the adenovirus DNA binding protein. The complete in vitro adenovirus DNA replication reaction was reconstituted from the purified H5ts36-complementing activity, the adenovirus DNA binding protein, and an extract from uninfected cells.

Adenoviruses, Human↗

Comparison of assay methods used to measure antiepileptic drugs in plasma.

The various techniques used to measure the concentration of antiepileptic drugs in plasma have been compared using data from the HEATH-CONTROL external quality control scheme. Assay methods were categorized as gas-liquid chromatography with and without derivatization (GLC + D, GLC-ND), radio- and enzyme multiplied immunoassay (RIA, EMIT), thin-layer and high-pressure liquid chromatography (TLC, HPLC), and spectrophotometry and colourimetry. The accuracy of the methods was determined from differences of measurements from the levels of drugs spiked into the samples. Most methods significantly underestimated the spiked drug concentrations. Comparisons of assay precision were made with the standard deviation of measurements or from the performance of individual laboratories in a ranking procedure. Comparable significant differences were found in both analyses. RIA followed by GLC-ND were the least variable methods for phenytoin; EMIT and then GLC-ND were the best for both phenobarbitone and primidone. Spectrophotometric measurements of phenobarbitone were unacceptably variable. TLC and colourimetry performed well for carbamazepine, whereas the GLC methods were the most variable. HPLC topped the list for ethosuximide, whereas EMIT had difficulty with this drug. Methods used for valproic acid were similar in precision. GLC + D was consistently less effective for all drugs when compared with GLC-ND.

Anticonvulsants↗

Effect of electroconvulsive shock on the uptake and release of noradrenaline and 5-hydroxytryptamine in rat brain slices.

The uptake and release of [3H]noradrenaline and [3H]-5-hydroxytryptamine (5-HT) were studied in cerebral cortex slices from rats 30 min and 24 h after a single electroconvulsive shock (ECS) and 24 h after a series of five shocks given over 10 days. Both the Km and Vmax for 5-HT uptake were lower than controls 24 h after a single ECS, whereas after 5 ECS spread over 10 days both parameters remained depressed, though only the fall in Vmax was significant. Noradrenaline uptake was not altered after a single ECS, but the Vmax and Km were elevated following chronic ECS treatment. Neither ECS treatment schedule had any effect on the potassium-stimulated release of either transmitter. It is possible that the changes in monoamine uptake seen following ECS are an adaptive response to alterations in the synaptic cleft concentration of these transmitters.

Animals↗

A role for 5-hydroxytryptamine in the GABA-mimetic potentiation of alpha-flupenthixol-induced catalepsy in the rat.

1 alpha-Flupenthixol (alpha-FPT)-induced catalepsy in the rat was potentiated by diaminobutyric acid (DABA), an inhibitor of the neuronal high affinity uptake of gamma-aminobutyric acid (GABA). 2 The depletion of 5-hydroxytryptamine (5-HT) with p-chlorophenylalanine (PCPA) abolished the DABA potentiation of alpha-FPT-induced catalepsy; this response was restored with 5-hydroxytryptophan. 3 Potentiation of alpha-FPT-induced catalepsy by clonazepam was significantly reduced by methysergide. Conversely, the potentiation of catalepsy by clomipramine was significantly reduced by picrotoxin. 4 These results are interpreted as evidence supporting a role for 5-HT in modifying the GABA-ergic inhibition of dopaminergic pathways, possibly by regulating the release of GABA.

Aminobutyrates↗

The involvement of 5-hydroxytryptamine in the release of dendritic dopamine from slices of rat substantia nigra.

[3H]dopamine (DA) accumulated by slices of rat substantia nigra was released following superfusion with Krebs solution containing 5-hydroxytryptamine (5-HT) in a dose-dependent fashion with maximal release being produced by 1 X 10(-4) M. This 5-HT-induced release of [3H]DA was calcium-dependent and was inhibited by pretreatment with the 5-HT antagonist cinanserin. These results are interpreted as supporting the possibility that 5-HT has a role in regulating dopaminergic activity in the nigro-striatal pathway.

Animals↗

Shuttle cloning vectors for the cyanobacterium Anacystis nidulans.

Hybrid plasmids capable of acting as shuttle cloning vectors in Escherichia coli and the cyanobacterium Anacystis nidulans R2 were constructed by in vitro ligation. DNA from the small endogenous plasmid of A. nidulans was combined with two E. coli vectors, pBR325 and pDPL13, to create vectors containing either two selectable antibiotic resistance markers or a single marker linked to a flexible multisite polylinker. Nonessential DNA was deleted from the polylinker containing plasmid pPLAN B2 to produce a small shuttle vector carrying part of the polylinker (pCB4). The two polylinker-containing shuttle vectors, pPLAN B2 and pCB4, transform both E. coli and A. nidulans efficiently and provide seven and five unique restriction enzyme sites, respectively, for the insertion of a variety of DNA fragments. The hybrid plasmid derived from pBR325 (pECAN1) also transforms both E. coli and A. nidulans, although at a lower frequency, and contains two unique restriction enzyme sites.

Anti-Bacterial Agents↗

Acute and chronic servo-control of renal perfusion pressure.

We describe a servo-control system for acute and chronic regulation of renal perfusion pressure or pressures in other parts of the circulation. The system employs a Dacron-reinforced inflatable silastic occluder of sufficient strength and durability to produce large pressure gradients for long periods of time (at least 10 days) in the abdominal aortas of large dogs. The occluder is inflated with an inexpensive, bidirectional DC motor syringe pump that is controlled by a comparator feedback circuit connected to the output of a driver amplifier of a Grass polygraph or any other suitable recorder. The system has a rapid response time for precise control and has been used to maintain a constant renal perfusion pressure in experiments lasting as long as 10 days. The system has diverse applications in studies of acute or chronic regulation of renal hemodynamics as well as the hemodynamics of other organ systems. The main advantages of this system, besides its durability and precision of control, are that it is very inexpensive (total cost including the syringe pump is less than $150), easy to construct, and can be used in chronic studies for servo-controlling renal perfusion pressure or pressures in other parts of the circulation.

Animals↗

Characterization of the glucocorticoid receptor translocated to the nucleus in intact AtT-20 mouse pituitary tumor cells at low temperatures.

Although low temperatures retard the nuclear translocation of glucocorticoid-receptor complexes, they do not completely inhibit it. To gain insight into the mechanism of nuclear translocation, we determined the Stokes radius and surface charge density of the receptors bound to the nucleus at 0 C and compared them with the values obtained from standard preparations of activated and unactivated glucocorticoid receptors. Specifically, intact, viable AtT-20 cells were incubated at 0 C for 3 h with 10 nM tritiated triamcinolone acetonide and the nuclear receptor extracted with 0.3 M KCl/20 mM sodium molybdate. These nuclear receptors were found to elute from an Agarose A 1.5 m column with a Stokes radius identical to that of an "activated" receptor (6.4 nm) but eluted from a DEAE column at the same position as an "unactivated" species (0.17 M KCl). From these results we hypothesize that the change in receptor structure that leads to nuclear binding is a multistep process, and although the change in molecular size may be a prerequisite for nuclear binding, the change in surface charge is not.

Animals↗

The use of metrizamide for isopyknic separation and enrichment of Plasmodium falciparum schizonts from continuous culture.

Plasmodium falciparum-parasitized erythrocytes obtained from continuous in vitro cultures were fractionated over metrizamide density gradients. Late developmental stage schizonts were isolated from uninfected erythrocytes and other intracellular blood stage forms (rings and trophozoites) by centrifugation through 15% metrizamide. Schizonts comprised, on the average, 85% of the total number of cells recovered from the top fraction of the gradient with the remaining cells being predominantly uninfected erythrocytes. The mean percentage of schizonts recovered was 27% relative to the estimated number of mature forms present before fractionation. The concentrated schizonts were viable based upon their ability to complete schizogony and undergo a new cycle of reinvasion and schizogony in vitro. In addition, in these short term synchronous cultures the newly infected cells were able to incorporate radiolabeled hypoxanthine. This function was inhibited by the addition of chloroquine to these 45- to 46-hour cultures. Metrizamide-purified schizonts should be useful for further study and characterization of the unique metabolic, biochemical, and immunological properties of the malaria parasite.

Centrifugation, Density Gradient↗