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Biomedical subjects

J C Craig

Publications and source records attributed to J C Craig.

At least 109 records · Page 6Linked to original sources

Acute obstructive uropathy--a rare complication of circumcision.

We report a rare complication of ritual circumcision in an 8-week-old boy. He presented 1 week after the procedure with reduced urine output, a grossly distended bladder and marked bilateral hydroureteronephrosis on ultrasonography. The acute partial urinary obstruction was due to the dressing which was applied after surgical removal of the foreskin and to oedema of the glans. He had abnormal renal function (creatinine 85 mumol/l, urea 8.5 mmol/l) and a hyperkalaemic metabolic acidosis with hyponatraemia (Na 127 mmol/l, K 6.9 mmol/l, HCO3 16 mmol/l), which were attributed to obstructive uropathy. Because of prolonged secondary bladder dysfunction he required urinary catheterisation for 1 week. There was significant post obstructive diuresis and parenteral fluid therapy was given for 7 days. Whilst urinary retention is a well recognized complication of circumcision, this is the first report of significant obstructive uropathy and renal impairment due to surgical excision of the foreskin.

Acute Kidney Injury↗

The effect of spatial orientation on the perception of moving tactile stimuli.

Previous studies have shown that the perception of spatial patterns, such as letters, presented to the hand is affected by the spatial orientation of the hand. The present study investigated how the perception of direction of motion across the fingerpads changes with the position of the hand in space. The moving stimuli were generated on two displays. In one condition, the displays were placed horizontally in front of the subject, with the subject's thumb (target site) and index finger (nontarget site) placed flat on the displays. In a second condition, the displays were vertically oriented and gripped between the thumb and index finger. Using a selective-attention paradigm in which subjects are instructed to respond only to the direction of motion at the target site, performance was still affected by the direction of motion at the nontarget site. Changing the orientation of the displays changed the effectiveness of the nontarget in interfering with the identification of the target movement. Nontarget stimuli that produced no interference in the horizontal orientation did so in the vertical, and vice versa. It appears that subjects are not using the local direction of movement across the fingerpads to judge the relative direction of movement at the two sites; rather, they are using the external direction of movement.

Attention↗

Differential binding of the enantiomers of chloroquine and quinacrine to polynucleotides: implications for stereoselective metabolism.

Interaction of the antimalarial drugs quinacrine and chloroquine with DNA has been studied extensively in order to understand the origin of their biological activity. These studies have shown that they bind to DNA through an intercalative mode and show little sequence specificity. All previous experiments were carried out using the racemic form of these drugs. We have investigated the binding of the enantiomeric forms of quinacrine and chloroquine to synthetic polynucleotides poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly (dG-dC), and found interesting differences in their binding parameters. Quinacrine enantiomers have a much higher binding affinity for the two polynucleotides compared to those of chloroquine. The negative enantiomers were found to have higher binding affinity than the positive ones. The binding constant for the binding of quinacrine(-) to poly(dG-dC).poly(dG-dC) was found to be about 3 times that of quinacrine(+). The differences in these binding affinities were further confirmed by equilibrium dialysis of the complexes of the polynucleotides with the racemic form of the drugs, which resulted in the enrichment of the dialysate with the positive enantiomer. CD spectra of the enantiomers and their polynucleotide complexes are reported. Changes in the fluorescence properties of quinacrine in the presence of the two polynucleotides are also described. Biological implications of these findings are discussed.

Chloroquine↗

Anomalous sensations following prolonged tactile stimulation.

Animal studies have demonstrated that tactile experience can alter central organization of somatosensory information. The present study examined the effect of prolonged tactile stimulation on spatial sensitivity in human subjects. Four subjects received repetitive, tactile stimulation presented on the volar surface of the forearm. The tactile stimuli were delivered through small vibrators worn by the subjects. After a period of 5-9 weeks of wearing the vibrators, three of the four subjects reported anomalous sensations when attempting to localize tactile stimuli. Subjects had difficulty in localizing stimuli and reported sensations of pressure and diffuseness. Single stimuli would sometimes evoke double and triple sensations separated by as much as 20 cm. After removing the vibrators, subjects continued to report anomalous sensations for up to 15 weeks. These results are interpreted within the framework of a model of central, neural reorganization.

Adult↗

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↗