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Biomedical subjects

J C Craig

Publications and source records attributed to J C Craig.

At least 19 recordsLinked to original sources

Ceftriaxone for paediatric bacterial meningitis: a report of 62 children and a review of the literature.

AIM: The purpose of this prospective study was to document the efficacy of ceftriaxone in the treatment of childhood bacterial meningitis in a general paediatric unit. METHODS: All children presenting with bacterial meningitis to Christchurch Hospital between January 1987 and June 1991 were enrolled in this prospective study and received ceftriaxone 100 mg/kg/d for seven days. Outcome was defined by parameters including mean time to fever defervescence, prolonged fever, days in hospital, seizures, and other acute neurological sequelae, requirement for ventilation, mortality and morbidity. Audiology was performed at six weeks and again at three months if abnormal. Neurodevelopmental assessment was performed at three months. Side effects were recorded. RESULTS: There were 62 evaluable children. The mortality rate was 4.8% (3 children). Two children (3.4%) had clinically detectable neurological sequelae at the three month assessment. The mean duration of stay was 8.7 nights. Five children (8%) required ventilation. Mild self limiting diarrhoea occurred in 29%. CONCLUSIONS: Ceftriaxone is an effective, safe and well tolerated antimicrobial for the treatment of childhood meningitis. It compares favourably with other equipotent antimicrobials. With a relatively long half life once daily administration is possible with a cost advantage.

Amoxicillin

Perceptual processing of adjacent and nonadjacent tactile nontargets.

Previous research has shown that subjects appear unable to restrict processing to a single finger and ignore a stimulus presented to an adjacent finger. Furthermore, the evidence suggests that, at least for moving stimuli, an adjacent nontarget is fully processed to the level of incipient response activation. The present study replicated and expanded upon these original findings. The results of Experiment 1 showed that an equally large response-competition effect occurred when the nontarget was presented to adjacent and nonadjacent fingers (on the same hand). The results of Experiment 2 showed that the effects observed in Experiment 1 (and in previous studies) were also obtained with stationary stimuli. Although small, there was some indication in the results of Experiment 2 that interference may dissipate more rapidly with distance with stationary stimuli. An additional finding was that interference effects were observed in both experiments with temporal separations between the target and nontarget of up to 100 msec. In Experiment 3, target and nontarget stimuli were presented to opposite hands. Although reduced, interference was still evident with target and nontarget stimuli presented to opposite hands. Varying the physical distance between hands did not produce any change in the amount of interference. The results suggest that the focus of attention on the skin extends nearly undiminished across the fingers of one hand and is not dependent upon the physical distance between sites of stimulation.

Adult

Response competition: a major source of interference in a tactile identification task.

Two experiments investigated the ability of subjects to identify a moving, tactile stimulus. In both experiments, the subjects were presented with a target to their left index fingerpad and a nontarget (also moving) to their left middle fingerpad. Subjects were instructed to attend only to the target location and to respond "1" if the stimulus moved either to the left or up the finger, and to respond "2" if the stimulus moved either right or down the finger. The results showed that accuracy was better and reaction times were faster when the target and nontarget moved in the same direction than when they moved in different directions. When the target and nontarget moved in different directions, accuracy was significantly better and reaction times were significantly faster when the two stimuli had the same assigned response than when they had different responses. The results provide support for the conclusion that movement information is processed across adjacent fingers to the level of incipient response activation, even when subjects attempt to focus their attention on one location on the skin.

Adult

Antimalarial activity of optical isomers of quinacrine dihydrochloride against chloroquine-sensitive and -resistant Plasmodium falciparum in vitro.

Both enantiomers of quinacrine and the racemic form of the drug showed equal activity in vitro against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, without detectable stereoselectivity. This contrasts with observations on chloroquine, where a similar lack of stereoselectivity in vitro is accompanied by a 10-fold loss of activity against the resistant strain. The observed in vivo differences reported for the enantiomers of chloroquine and the observations on the optically active metabolites of chloroquine and quinacrine may therefore be ascribed to a difference in the pharmacokinetics of their enantiomers.

Animals

Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) proteinase.

Ro 31-8959 inhibits the spread of HIV infection and the production of cytopathic effects in cultures of acutely infected cells. IC50 values for these effects are in the range 0.5-6.0 nM and IC90 values are in the range 6.0-30.0 nM. This inhibitor is effective even when added to cultures at a late stage of infection, after syncytia have started to form. Virus antigen, virus particles and virus cytopathic effects can largely be cleared from cultures treated with compound from 3 days until 6 days post infection. In chronically-infected cells, inhibition of virus maturation can be detected after 24 hours' treatment with 10 nM Ro 31-8959. In addition, a significant reduction of the proteolytic processing of p56 to p24 can be demonstrated in these cells with compound at picomolar concentrations. These properties indicate that Ro 31-8959 is highly effective against HIV with the potential to inhibit acute, established acute and chronic infections.

Antiviral Agents

Evaluation of a principal-components tactile aid for the hearing-impaired.

Principal component analysis, a statistical data reduction technique which can be used to eliminate redundant information, has shown promising results as a speech coding strategy in auditory perceptual studies. The present study describes the development, modification, and evaluation of a principal components-based tactile aid for speech perception by the hearing-impaired. In this device, the first two principal components of an input speech signal were displayed on two-dimensional arrays of vibrators contacting either the fingertip or the forearm. Initial testing of the device with closed-set recorded speech tokens showed fair recognition performance, reaching 57% for three consonants and 56% for four vowels. Modifications to the processor algorithm designed to improve vowel recognizability resulted in higher levels of performance (66% for eight vowels). A real-time prototype was constructed implementing the revised algorithm. Live-voice testing was conducted with six normal-hearing subjects, three of whom had previous training with the Queen's University vocoder, a multichannel tactile vocoder that has shown promising results. Performance of these "trained" subjects for both single-item and connected speech tasks was excellent, equalling levels obtained with the Queen's vocoder. These results suggest that a principal components design may be a promising alternative to a vocoder strategy for a tactile aid. Results for the "naive" subjects did not reach the levels attained by the trained subjects, a finding partially attributed to the short training period available to the naive subjects. The higher level of performance for the trained subjects, together with the similarity of performance for the principal components aid and the Queen's vocoder for these subjects, suggests that they were able to transfer previous learning with the Queen's vocoder to the principal components device.

Adult

Tactile attention and the perception of moving tactile stimuli.

Three experiments investigated the ability of subjects to identify the direction of movement of a pattern across the skin. In Experiments 1 and 2, subjects were required to identify the direction of movement of a pattern presented to one fingerpad while another moving pattern was being presented to an adjacent fingerpad. Subjects were instructed to attend only to the target location. The results showed that accuracy was consistently higher and reaction times were consistently faster when the two patterns moved in the same direction than when they moved in opposite directions. Both effects were largest when the two patterns were presented simultaneously. In Experiment 3, the nontarget location was the contralateral hand. In this case, performance was not affected by the presentation of the nontarget. Combined, the results suggest that movement information is processed across adjacent fingers even when subjects are explicitly instructed to attend only to one finger. Subjects do appear to be able to restrict attention to a single hand.

Attention

Rational design of peptide-based HIV proteinase inhibitors.

A series of peptide derivatives based on the transition-state mimetic concept has been designed that inhibit the proteinase from the human immunodeficiency virus (HIV). The more active compounds inhibit both HIV-1 and HIV-2 proteinases in the nanomolar range with little effect at 10 micromolar against the structurally related human aspartic proteinases. Proteolytic cleavage of the HIV-1 gag polyprotein (p55) to the viral structural protein p24 was inhibited in chronically infected CEM cells. Antiviral activity was observed in the nanomolar range (with one compound active below 10 nanomolar) in three different cell systems, as assessed by p24 antigen and syncytium formation. Cytotoxicity was not detected at 10 and 5 micromolar in C8166 and JM cells, respectively, indicating a high therapeutic index for this new class of HIV proteinase inhibitors.

Amino Acid Sequence

Smooth muscle actin expression during P19 embryonal carcinoma differentiation in cell culture.

P19 embryonal carcinoma (EC) cells can be induced in vitro to differentiate into cells resembling those normally formed in the embryo. Among these cell types is one whose morphology is fibroblast-like. Using indirect immunofluorescence and Western blot analysis with antibodies directed against various isoforms of actin, many of these fibroblast-like cells were found to express smooth muscle actin isoforms. Northern blot analysis of RNA indicated the presence of a smooth muscle-specific isoform of myosin heavy-chain mRNA in immortal lines of these fibroblast-like cells. These results suggest that these fibroblast-like cells resemble fetal myofibroblastic or myoepithelial cells, which have a wide distribution during embryonic development.

Actins

Temporal order and tactile patterns.

Temporal order judgments (TOJs) were obtained for tactile stimuli presented to subjects' fingerpads. In one set of measurements, pairs of spatial patterns were presented successively to a single fingerpad (same-site condition), to two fingers on the same hand (ipsilateral condition), or to two fingers on opposite hands (bilateral condition). The subjects were instructed to report which one of the two patterns was presented first. TOJs were more accurate in the same-site condition than in either the ipsilateral or the bilateral conditions. In the ipsilateral and bilateral conditions, performance improved when judging which one of two locations received a stimulus first, although performance levels were still lower than in the same-site condition. Increasing the size of the pattern set from which the two patterns to be judged were drawn had only a slight effect on same-site performance and no effect on ipsilateral/bilateral performance; however, changing the nature of the patterns had a considerable effect on same-site performance and a smaller effect on ipsilateral/bilateral performance. Introducing an intensity imbalance between members of the pair of stimuli also had a large effect on same-site TOJs: a less intense stimulus tended to be judged as being presented first. In the bilateral condition, however, there was a small effect in the reverse direction: more intense stimuli tended to be judged as being presented first. The intensity imbalance had no effect in the ipsilateral condition. The results suggest that different mechanisms are responsible for TOJs for patterns presented to the same-site and to separate sites and, furthermore, that separate sites may constitute separate channels for spatial information.

Adult

Breast fluid cholesterol and cholesterol beta-epoxide concentrations in women with benign breast disease.

Because cholesterol 5,6-epoxides have been reported to be mutagenic, carcinogenic, and cytotoxic, we investigated the relationship of these substances in breast fluid to histopathologically defined breast disease. We measured cholesterol and its oxidation product, 5 beta,6 beta-epoxide, in breast fluids from 68 women with biopsied benign breast disease (BBD) and 135 women with no history of breast disease (controls). Each biopsy was classified according to the most severe epithelial change: (a) nonproliferative epithelia; (b) hyperplasia without atypia; or (c) hyperplasia with atypia. Similar to our previous findings in control women, breast fluid cholesterol and beta-epoxide concentrations in women with BBD were associated with factors of interest in relation to breast cancer: concentrations increased with age and were higher in white than nonwhite women and in women who were past or current smokers; concentrations were lower in women who had given birth or breastfed within 2 yr. Increased breast fluid cholesterol and beta-epoxide concentrations were significantly associated with proliferative BBD (hyperplasia with or without atypia) compared to controls. After adjustment for covariates, the odds ratio for proliferative BBD associated with detectable versus nondetectable beta-epoxide concentrations was 8.5 (95% confidence intervals, 1.1, 68.8). Our findings suggest that the histological progression from normal epithelium to hyperplasia without atypia to atypical hyperplasia is associated with progressively increasing concentrations of both cholesterol and cholesterol beta-epoxide.

Adult

The suitability of different microtitre plates for detection of antibody to virus antigens by indirect ELISA.

To optimize enzyme linked immunosorbent assays (ELISAs) for the detection of virus-specific antibodies, a range of commercially available microtitre plates was evaluated for their ability to bind virus antigen. Rinderpest virus and foot-and-mouth disease virus were investigated as target antigens. Binding capacity for antigen, binding ratios (attachment of specific antibody versus that of non-immune antibody) and the variation in the results of the tests within and between plates were measured. Binding capacity was found to be greater with rinderpest virus (RPV) antigen than with foot-and-mouth disease virus (FMDV) antigen, although higher binding ratios were obtained with FMDV antigen. Variation within and between plates was generally less with RPV antigen than with FMDV antigen. One plate could not be said to out-perform the other plates in all tests. For our purpose, that is the detection of monoclonal antibody production against a variety of virus antigens, a number of plates were found to be suitable (e.g. Dynatech M129B, Flow 77-172-05 and Nunc 4-39454). The differences in the performances of the microtitre plates with these two virus antigens highlights the need for consideration of the solid phase as part of the standardization procedures for ELISAs.

Animals

Assay sensitivity and differentiation of monoclonal antibody specificity in ELISA with different coating buffers.

Buffers of different pH and ionic strength were employed as coating buffers for antigen adsorption to microtitre plates. Their efficiency for coating plates with rinderpest virus (RPV) and foot-and-mouth disease virus (FMDV) antigens was studied by ELISA with polyclonal and monoclonal antibody preparations. While the adsorption and detection of RPV antigen with polyclonal antiserum was highly dependent on the ionic strength and pH of coating buffer, adsorption of antigenically active FMDV antigen was relatively unaffected by the buffering conditions. Both antigens were adsorbed optimally in 0.01 M phosphate buffer, pH 8.0. When monoclonal antibodies were used to detect antigen, there was a greater degree of dependence on the coating buffer than that found with polyclonal antisera. Moreover, when they were used to detect antigen adsorbed under several buffering conditions, monoclonal antibodies showed a variety of preferred buffers. The usefulness of this differential reactivity in distinguishing epitope specificity is demonstrated.

Antibodies, Monoclonal

Synthesis and dopaminergic activity of 2-substituted octahydrobenzo[f]quinolines.

A series of 2-substituted octahydrobenzo[f]quinolines has been synthesized and assayed for dopamine agonist activity. Only the compounds corresponding to the beta-rotameric conformation of dopamine showed biphasic activity in competition binding studies with the radioligand [3H]spiroperidol. These findings suggest that the congeners possessing the beta-rotamer conformation show receptor-binding characteristics that resemble those of the ergolines more closely than do those of the corresponding alpha-rotamer congeners.

Animals

Interference in localizing tactile stimuli.

A series of experiments investigated the ability of subjects to localize a tactile stimulus in the presence of an additional, extraneous tactile stimulus. The subject's task was to localize a tactile stimulus (target) presented at one of several locations on his or her left index fingerpad. The target stimulus, generated on a 6 x 24 array of stimulators, was presented either by itself or in the presence of an extraneous stimulus (masker) that either preceded or followed the target. The localizability of the target was affected by the temporal separation between the target and masker in much the same way as previous studies have shown identification of tactile patterns to be affected. Unlike previous identification results, presenting the masking stimulus to the same location as the target interfered with localizability, although not as much as did presenting the masker to a different location. The results are discussed in terms of their implications for identification and discrimination of tactile patterns.

Adult

A comparison of discrimination and identification of vibrotactile patterns.

Both discrimination and identification tasks have been used to assess subjects' abilities to perceive vibratory spatial patterns presented to the skin. The present study examined discrimination and identification performance under comparable conditions. In Experiment 1, subjects attempted to discriminate a pair of patterns on some blocks of trials and to identify both members of a pair on other blocks. For both tasks, the time between the members of the pair was varied. Discrimination performance could be predicted accurately from identification data. Analysis of performance on identification trials indicated that subjects used discriminability information to identify pairs. In Experiment 2, discrimination and identification were compared when the temporal separation between patterns was fixed and a masking stimulus followed each pattern after a variable delay. Results suggest that temporal masking, rather than the time available for processing pattern information, is the major limitation in both discrimination and identification of sequences of tactile patterns.

Adult

T-cell-mediated suppression of Epstein-Barr virus-induced B lymphocyte activation in multiple sclerosis.

Significantly reduced levels of T-cell-mediated "suppression" of numbers of Epstein-Barr virus (EBV)-activated B lymphocytes which secrete IgG or IgM were found in preparations of mononuclear cells (MNC) from peripheral blood of 28 patients with multiple sclerosis (MS) compared with 28 healthy subjects, all seropositive for EBV. A statistically significant correlation was not found between the suppression of EBV-induced activation of B lymphocytes and either EBV-specific T-cell-mediated cytotoxicity or numbers of T8-positive cells.

Antibody Formation