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C A Walker

Publications and source records attributed to C A Walker.

At least 55 records · Page 3Linked to original sources
PubMed1985

Competition between strains of scrapie depends on the blocking agent being infectious.

Compton White mice (Sincs7) were injected twice intraperitoneally, first with the 22A strain of scrapie agent (in brain homogenates) and then, after 105 days, with the 22C strain. Incubation periods were calculated from the time of the first injection. The experiment was designed so that, with no interaction between strains, the second strain (22C) should have produced cases about 300-350 days after the first injection, depending on the dose of 22C. This was well before the limit of 470 days set by the mean incubation period minus 3 SD of 22A alone: a limit which was used to distinguish 22C from 22A clinical cases. In fact, 22A blocked 22C as shown by (i) the lengthening of 22C incubation periods, (ii) the reduced proportion of cases due to 22C, and (iii) the reduced effective titer of 22C. The blocking efficiency of 22A was not greatly reduced by physicochemical treatments that had little or no effect on its infectivity by the intraperitoneal route. However, treatment of 22A homogenates with 6 M urea virtually eliminated infectivity and also abolished blocking ability. It is concluded that competition depends on the infectivity of the scrapie strain used for blocking.

Animals↗
PubMed1983

The antiviral compound HPA-23 can prevent scrapie when administered at the time of infection.

The effects of up to 12 daily doses of HPA-23 (ammonium 5-tungsto-2-antimoniate) on scrapie were studied using five experimental models of the disease, some with widely different incubation times. Treatment of animals with HPA-23, starting just before injecting scrapie, produced survivors. In some experiments, animals were fully protected against several hundred infectious units of scrapie. Treatment of animals after infection was far less effective. Prolonging the treatment for several weeks was no more effective than treating for a few days. In a very long incubation model of scrapie, the course of 12 daily doses of HPA-23 represented less than 3 per cent of the total incubation period. HPA-23 may interact with certain cells of the lymphoreticular system, preventing infection and, perhaps, the early replication of agent.

Animals↗
PubMed1983

Disinfection studies with two strains of mouse-passaged scrapie agent. Guidelines for Creutzfeldt-Jakob and related agents.

A variety of disinfection procedures were tested on two strains of scrapie agent, treated either as brain macerates (autoclaving) or as 10% homogenates (chemical treatments). It is suggested that a given treatment should produce a titre loss, of both strains of scrapie, of at least 10(4) units before it be regarded as useful for the disinfection of the agents of scrapie and Creutzfeldt-Jakob disease (CJD). By this criterion, treatment at room temperature with about 4% Hycolin (0.6% chlorinated phenols), 0.2% permanganate, 5% Tego (dodecyl-di(aminoethyl)-glycine) or 5% sodium dodecyl sulphate (SDS) are unsuitable. However, data indicate that SDS might be used to reduce the heat stability of scrapie agent. Hypochlorite (Sterilex) was the only satisfactory chemical reagent tested. At least 10(4)-10(5) units of infectivity were lost by treatment with hypochlorite containing 1,000 ppm available chlorine after a 4-16 h exposure, or containing 10,000 ppm available chlorine after a half-hour exposure. The latter result points to the use of concentrated hypochlorite (about 2% available chlorine; approximately 20% Sterilex) to decontaminate surfaces. We suggest that the cleaning action of SDS, or other strong detergents, might also help to decontaminate surfaces, but studies on this are needed. Autoclaving at 126 degrees C for 1-2 h reduced titres by 10(3)-10(7) units, depending on the strain of agent. However, total disinfection of brain containing high titres of infectivity was approached only at 136 degrees C when titre losses of about 10(6) units were obtained by autoclaving for 4-32 min. Further studies are needed before we can make simple, general recommendations for the disinfection of CJD agents in hospital practice.

Animals↗
PubMed1983

Pathogenesis of mouse scrapie: evidence for spread of infection from central to peripheral nervous system.

The onset of replication has been studied in spinal cord, dorsal root ganglia and spinal nerves of CW mice infected intraperitoneally with the 139A strain of scrapie. The patterns obtained suggest a centrifugal spread of infection from central to peripheral nervous systems. Infectivity titres in the peripheral nervous system reached a plateau long before the end of the incubation period, and the maximum titres were much lower than in the central nervous system. This suggests that there is a restriction of replication in the peripheral nervous system similar to that already known in extraneural tissues.

Animals↗
PubMed1983

A double-blind comparative trial of the decanoates of clopenthixol and fluphenazine in the treatment of chronic schizophrenic out-patients.

Forty-five patients were entered into a 24-week double-blind trial of clopenthixol decanoate and fluphenazine decanoate. The 24-week double-blind period was preceded by a 12-week open period. Of the 45 patients entered, 6 failed to attend the second interview and 1 left the country before the final assessment. Doses administered were in the range 100 mg 4-weekly to 400 mg 2-weekly for clopenthixol decanoate and 12.5 mg 4-weekly to 37.5 mg 3-weekly for fluphenazine decanoate. Both depot neuroleptics appeared to have an equivalent duration of action, with 200 mg clopenthixol decanoate approximately equivalent to 25 mg fluphenazine decanoate. Patients' mental state was assessed on the Brief Psychiatric Rating Scale, Clinical Global Impression, Krawiecka, Goldberg and Vaughan Rating Scale, and unwanted effects were recorded on a checklist. No differences were detected between the two drugs with regard to therapeutic activity or side-effects. It is concluded that clopenthixol decanoate is as effective and as well-tolerated a depot neuroleptic as fluphenazine decanoate.

Antipsychotic Agents↗
PubMed1982

Diurnal variation in ornithine decarboxylase activity of different brain regions of the rat.

The activity of ornithine decarboxylase (ODC) was studied in the brain of Sprague-Dawley male rats weighing 200-250 g. In this study, animals were maintained at a temperature of 21 +/- 1 degree C and a 12:12 h light--dark cycle for a minimum of 3 weeks prior to any experimentation. Animals were sacrificed at 06.00 h and 18.00 h and the brain cerebral cortex, hypothalamus, amygdala, hippocampus, midbrain, pons, medulla oblongata and cerebellum were isolated and assayed for ODC activity. The data show significant diurnal variations (P less than 0.05) in hypothalamus, midbrain, medulla oblongata and cerebellum, with peak values during the active phase of the animal. Other brain parts studied did not show any significant diurnal variations.

Amygdala↗
PubMed1982

Discontinuous counterimmunoelectrophoresis in the diagnosis of antibiotic-associated colitis.

Discontinuous counterimmunoelectrophoresis (DCIE) was employed to detect the toxin of Clostridium difficile, etiologic antibiotic-associated colitis (AAC), in bacteria-free stool filtrates from 51 patients with diarrhea. Stool samples from 31 patients contained C. difficile toxin as determined by tissue-culture assay. A positive result was obtained by DCIE in 20 of the 31 patients (65%) and was influenced by the titer of toxin present. When toxin was present by tissue-culture assay in a dilution of less than or equal to 10(-2) (11 samples), DCIE was positive in only 2 (18%). However, DCIE yielded positive results in 18 of the 20 samples (90%) containing toxin titers greater than or equal to 10(-3). The combination of DCIE and sigmoidoscopy of colonoscopy was superior to either alone in the diagnosis of AAC irrespective of the toxin titer. Nine of 11 patients (82%) whose stool samples contained C. difficile toxin in a dilution of less than or equal to 10(-2) were recognized by DCIE, endoscopy, or both. In stool samples containing toxin in titers greater than or equal to 10(-3), no false-negative results were encountered (sensitivity equals 100%). Thus, 29 of 31 patients whose stool samples contained C. difficile toxin were identified when the results of DCIE and endoscopical examination were combined (sensitivity 93.5%). Neither endoscopical examination nor DCIE yielded positive results in the 20 patients whose stool samples lacked C. difficile toxin (specificity equals 100%). DCIE is a rapid, moderately sensitive, and specific method for detecting C. difficile toxin. When DCIE is combined with endoscopy, the vast majority of patients requiring specific therapy for AAC can be identified.

Anti-Bacterial Agents↗
PubMed1982

Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection.

The dynamics of agent replication were studied at 8 levels of spinal cord and in 9 areas of brain of mice infected intraperitoneally with the 139A strain of scrapie agent. Replication in the CNS was first detectable at 2 levels of spinal cord between thoracic vertebrae 4 and 9. The onset of replication was progressively delayed by up to 4 weeks at increasingly lower levels of spinal cord. A similar trend was seen at higher levels of spinal cord and in brain. In brain, agent replication occurred first in medulla, then in the pons and midbrain, thalamus and hypothalamus and, finally, striatum, septum, hippocampus and cerebral cortex. These results are highly suggestive of spread of infection from peripheral sites of agent replication along autonomic fibres to midthoracic cord, followed by an ascending and descending spread of agent at an apparent rate of 0.5 to 1.0 mm/day until the whole CNS is infected. However, experiments involving sympathectomy gave inconclusive results and the evidence for neural spread of scrapie in the peripheral nervous system is circumstantial.

Animals↗
PubMed1981

Circadian variation of diazepam acute toxicity in mice.

The LD50 of i.p. injected diazepam was determined every 4 h over a 24-h period in albino mice adapted to a 12-h dark/12-h light programmed illumination cycle. Results show that diazepam is more toxic during the light phase of the cycle than during the dark phase and demonstrate circadian variation in the toxicity of the compound in mice.

Animals↗
PubMed1981

The Robin anomalad (Pierre Robin syndrome)--a follow up study.

During a 10-year period 55 patients with the Robin anomalad were admitted to the Liverpool Regional Cleft Palate Units. Fourteen (25%) children died. All deaths were within 3 months of birth. Congenital abnormalities other than mandibular retrognathia and cleft palate were present in 14 (26%) children. Peripheral limb defects were particularly common. Thirty children were recalled and reviewed to assess speech, hearing, growth, and educational achievement. There was a clear association between severe nasal escape of air in speech and atypical articulatory patterns. Almost half the children tested had abnormal articulation. Only 4 (13%) of 30 children showed delayed language development. Half the children tested audiometrically showed a binaural handicap but in only one patient was this sufficiently severe to warrant amplification. There was no trend towards abnormalities of growth and only 2 children could be firmly classified as educationally subnormal.

Child Development↗
PubMed1980

Dexamethasone protection against the acute lethality of ethanol in mice.

The administration of dexamethasone (DXM, 2.00 mg/kg) 1 h prior to the injection of lethal doses of ethanol was found to offer complete protection against ethanol toxicity at doses up to 5.25 g/kg and partial protection using higher doses. It is suggested that DXM central action might be involved in the protection against ehanol toxicity.

Animals↗
PubMed1980

Twenty-four hour toxicity rhythms of sedative-hypnotic drugs in mice.

Twenty-four hour LD50 values of secobarbital, pentobarbital, phenobarbital, in male Swiss-Webster mice weighing approximately 30 g each. The animals were adapted for three weeks in an environmental room equipped with an automatically-timed photoperiod lasting from 0800 to 2000 h daily. Each mouse was injected intraperitoneally at 6 h time intervals with either phenobarbital or chloral hydrate for toxicity analysis. Secobarbital, pentobarbital and hexobarbital were injected at 3 h time intervals. Peak toxicity was reached at D-0600 with all drugs screened except chloral hydrate which was 180 degrees out of phase. The drugs were least toxic at 1200 h with the exception of chloral hydrate which was least toxic at D-0600 h. These results suggest circadian periodicity in the toxicity of sedative hypnotics. Factors that could be responsible for these variations are discussed.

Animals↗
PubMed1980

Pathogenesis of mouse scrapie: evidence for neural spread of infection to the CNS.

The replication of infectious agent has been studied in brain, thoracic cord, and lumbar cord of Compton white mice (Sinc87) infected with the 139A strain of scrapie. Nine experiments were carried out using four different peripheral routes of injection. A highly consistent pattern of results was obtained in which replication in the CNS started in the thoracic cord after about 35% of the total incubation period had elapsed (range 25 to 42%). This was followed by the simultaneous onset of replication in brain and lumbar cord which occurred 2 to 4 weeks later. It is difficult to explain these results on the basis of haematogenous spread of infection from peripheral sites of replication (e.g. in spleen) to the CNS. However, the data are consistent with spread of infection along peripheral nerves and, in particular, along nerves of the sympathetic nervous system. It is suggested, therefore, that this may be the major route by which scrapie agent invades the CNS.

Adrenergic Fibers↗