Stimulus timing by people with Parkinson's disease.

Previous literature suggests that Parkinson's disease is marked by deficits in timed behaviour. However, the majority of studies of central timing mechanisms in patients with Parkinson's disease have used timing tasks with a motor component. Since the motor abnormalities are a defining feature of the condition, the status of timing in Parkinson's disease remains uncertain. Data are reported from patients with mild to moderate Parkinson's disease (both on and off medication) and age- and IQ-matched controls on a range of stimulus timing tasks without counting. Tasks used were temporal generalization, bisection, threshold determination, verbal estimation, and a memory for duration task. Performance of patients was generally "normal" on all tasks, but significant differences from performance of controls were found on the memory for duration task. Among the "normal" effects noted were arithmetic mean bisection, asymmetric temporal generalization gradients, and subjective shortening on the memory for duration task. The results suggest (a) that some previous reports of timing "deficits" in Parkinson's patients were possibly due to the use of tasks requiring a timed manual response and (b) small differences between patients and controls may be found on tasks where two stimuli are presented on each trial, whether patients are on medication or off it.

The contribution of non-ocular response inhibition to visual inhibition of return.

Inhibition of return (IOR) refers to slowed responses to targets presented at the same location as a preceding stimulus. IOR is typically investigated using a cue-target design, in which subjects respond only to the second stimulus of a pair. In such tasks, the measurement of 'true' IOR may be confounded by the effect of non-ocular response inhibition, because the participant must suppress any tendency to respond (e.g. key press) to the first stimulus. This confound may be eliminated using a target-target design, in which responses are made to both stimuli. We assessed the contribution of non-ocular response inhibition to visual IOR, measured in a cue-target task, by testing participants on both cue-target and target-target detection tasks, with identical timings and stimuli. Significant IOR was obtained in both tasks but, at a stimulus onset asynchrony (SOA) of 1400 ms, IOR magnitude was significantly greater in the cue-target condition than in the target-target condition. However, at an SOA of 1800 ms, there was no significant difference in the magnitude of IOR between the two tasks. Thus, a proportion of the total IOR effect observed in visual cue-target tasks can be attributed to non-ocular response inhibition, but this process appears to decay more rapidly than does 'true' IOR, having dissipated by 1800 ms following cue onset.

Tactile inhibition of return: non-ocular response inhibition and mode of response.

Inhibition of return (IOR) refers to the slowing of responses to stimuli presented at the same location as a preceding cue. However, the cue-target paradigm used in most previous studies may have overestimated the contribution of eye movement programming to IOR, due to the existence of manual response inhibition effects. This confound can be circumvented by using a target-target paradigm in which participants respond to all stimuli. Here, we compared IOR magnitude from tactile cue-target and target-target tasks involving identical interstimulus intervals of 1,400 and 1,800 ms. Reaction times were measured using a foot pedal toe-lift response and a vocal response. Tactile IOR was observed using both modes of response, demonstrating IOR for the first time using a non-spatial, vocal response. Moreover, IOR effects were significantly smaller in target-target compared to cue-target conditions, thereby confirming the existence of the response inhibition confound.

Effects of a moderate dose of alcohol on simulated laparoscopic surgical performance.

BACKGROUND: In medicine, there is no professional regulation of the drinking of alcohol, nor a body of experimental evidence on which such regulation might be based. Here we report the acute and longer-term ("hangover") effects of a moderate dose of alcohol on performance, as assessed objectively on a laparoscopic surgical simulator. METHODS: In a single-blind, experimental study, medical student subjects were assigned randomly to an alcohol (1.05 mg/kg) or a placebo condition (n = 14 in each). The effects of alcohol on performance on the MIST Virtual Reality surgical simulator were examined 60-90 min and 600-630 min (after a night's sleep) following its ingestion. Measures of the number of errors, time taken, hand movement economy, and excessive use of diathermy were recorded. RESULTS: On each measure, performance was significantly impaired 60-90 min following alcohol ingestion, but there was no hangover effect 600-630 min later, following a night's sleep. This impairment could not be attributed to between-group differences in either predrink performance, expertise or estimated sleep duration during the night preceding the experimental session. CONCLUSIONS: Simulated surgical performance is impaired severely when estimated blood alcohol concentration (BAC) is just above the UK legal limit for driving. These results contribute new, objective and quantitative evidence to the current debate about the use and misuse of alcohol within the medical profession.

A sensorimotor theory of temporal tracking and beat induction.

In this paper, we develop a theory of the neurobiological basis of temporal tracking and beat induction as a form of sensory-guided action. We propose three principal components for the neurological architecture of temporal tracking: (1) the central auditory system, which represents the temporal information in the input signal in the form of a modulation power spectrum; (2) the musculoskeletal system, which carries out the action and (3) a controller, in the form of a parieto-cerebellar-frontal loop, which carries out the synchronisation between input and output by means of an internal model of the musculoskeletal dynamics. The theory is implemented in the form of a computational algorithm which takes sound samples as input and synchronises a simple linear mass-spring-damper system to simulate audio-motor synchronisation. The model may be applied to both the tracking of isochronous click sequences and beat induction in rhythmic music or speech, and also accounts for the approximate Weberian property of timing.

A study of "white spotted kidneys" in cattle.

A study was performed at an abattoir in Australia, in an attempt to correlate focal chronic interstitial nephritis (FCIN) producing the so-called "white spotted kidney", with Leptospira spp. and other pathogens in cattle. Samples of kidneys, urine and blood were collected immediately after slaughter from 46 two-year-old heifers, and 72 cows and bulls with gross lesions consistent with FCIN. The same samples were also collected from nine heifers and 12 cows with no gross kidney lesions. Aqueous humour was also collected from the eye of 17 of the adult animals. The sera were processed by a microscopic agglutination test for leptospira antibodies, while all the other samples were cultured for Leptospira spp. and also processed for routine aerobic and anaerobic culture for other pathogens. Sub-samples from all the kidneys were fixed in 10% buffered formalin and processed histologically. Antibody titers of 1:400 or higher for Lepstospira borgpeterseni serovar hardjo were found in six adult animals with FCIN and in one adult animal with no gross kidney changes, while antibody titers of 1:400 to L. borgpeterseni serovar tarassovi were found in only one animal with FCIN. L. borgpeterseni serovar hardjo was isolated from the urine and kidney of one adult animal and from the urine of another adult animal, both with FCIN. No pathogens were isolated from any of the other samples. The histological lesions were consistent in most cases with FCIN. The results suggest that neither Leptospira spp. nor active infection by other bacteria are associated with the so-called "white spotted kidneys".

Human locognosic acuity on the arm varies with explicit and implicit manipulations of attention: implications for interpreting elevated tactile acuity on an amputation stump.

In Experiment 1, normal subjects' ability to localize tactile stimuli (locognosia) delivered to the upper arm was significantly higher when they were instructed explicitly to direct their attention selectively to that segment than when they were instructed explicitly to distribute their attention across the whole arm. This elevation of acuity was eliminated when subjects' attentional resources were divided by superimposition of an effortful, secondary task during stimulation. In Experiment 2, in the absence of explicit attentional instruction, subjects' locognosic acuity on one of three arm segments was significantly higher when stimulation of that segment was 2.5 times more probable than that of stimulation of the other two segments. We surmise that the attentional mechanisms responsible for such modulations of locognosic acuity in normal subjects may contribute to the elevated sensory acuity observed on the stumps of amputees.

The burns unit and theatre integration.

Disbanding the assigned burns theatre team at St John's Hospital had a major impact on perioperative care. Donna O'Boyle describes how, and what was done to rectify the situation, in her 3M/NATN Award commended work.

The virulence and protective efficacy for chickens of pasteurella multocida administered by different routes.

The relative virulence for chickens of five strains of Pasteurella multocida was evaluated. Twenty groups, each of ten chickens, were inoculated with a standard dose of 10(5) of each of five strains by the intramuscular (I.m.), intravenous (I.v.), intratracheal (I.tr.) or conjunctival (Co) routes. The highest mortality occurred in the groups dosed I.m. and I.v., followed by I.tr. inoculation. The relative virulence of each strain did not change when inoculated by the different routes. The most virulent strain, VP161, caused 100% mortality by all except the Co route. The least virulent strain, VP17, caused a single mortality by the I.v. route, but gave a high level of protection to birds inoculated by both the I.m. and I.v. routes, when challenged by intramuscular injection with (VP161). There was no protection against I.m. challenge in the birds inoculated by the I.tr. or Co routes. Serum antibody levels measured by ELISA correlated with the level of protection against virulent challenge for groups inoculated I.m. or I.v., but not I.tr. Western blots of pooled sera from each group did not show any specific antigen recognition that might explain the observed differences in protection. Inoculation with strain VP17, (both I.m. and I.tr.) also gave a high level of protection to birds challenged with strain VP161 by intratracheal instillation.

PCR detection and analysis of Pasteurella multocida from the tonsils of slaughtered pigs in Vietnam.

A total of 36 tonsil swab samples were collected from healthy swine prior to slaughter at the abattoirs in Can tho and Tien giang provinces of Southern Vietnam. The presence of Pasteurella multocida in these samples was detected by the combination of direct cultivation and isolation, mouse inoculation and the polymerase chain reaction (PM-PCR). P. multocida was detected in 16 samples by PCR, with 17 strains ultimately isolated. All samples were negative for serogroup B by HSB-PCR and conventional serotyping, with isolates identified as A:3, D:1 or D:3. In addition, all samples were determined to be negative for the P. multocida toxin (PMT). Characterisation of isolated P. multocida by REP-PCR and biotyping revealed nine distinct REP profiles and seven biotypes among the 17 isolates. Some correlation was seen with P. multocida isolated from a previous Australian outbreak of acute swine pasteurellosis, and those isolated from fowl cholera outbreaks in Vietnamese poultry.

The molecular epidemiology of four outbreaks of porcine pasteurellosis.

Biochemical profiles, restriction endonuclease analysis (REA) and ribotyping were used to investigate a total of 38 Pasteurella multocida isolates from four separate outbreaks of pasteurellosis in Australian piggeries. Six isolates were obtained from Outbreak 1, 16 from Outbreak 2 and eight each from outbreaks 3 and 4. Outbreaks 1 and 2 were cases of pneumonic pasteurellosis while outbreaks 3 and 4 involved systemic pasteurellosis. Biochemical characterisation established that a number of different types of P. multocida were present in outbreaks 1 and 3 while outbreaks 2 and 4 were associated with a single type of P. multocida. Outbreaks 1 and 3 yielded isolates of P. multocida that belonged to the subspecies multocida and gallicida, with the subspecies multocida isolates being identified as biovar 3 (6 in total) or 12 (1 in total) and the subspecies gallicida isolates (7 in total) being identified as biovar 8. All 24 isolates from outbreaks 2 and 4 belonged to the subspecies multocida and were all biovar 3. REA and ribotyping showed that, in outbreaks 1 and 3, there were three different types of P. multocida in each outbreak with no common strains between the outbreaks. The molecular methods showed that only a single strain of P. multocida was associated with outbreaks 2 and 4, although the outbreaks were associated with strains that differed in REA profiles but shared a ribotype profile. This study has shown that both, systemic and pneumonic pasteurellosis can be associated with either a single strain or multiple strains of P. multocida. The results also indicate that the molecular typing methods of REA and ribotyping are superior to biochemical characterisation for epidemiological investigation of porcine pasteurellosis.

Joint position sense is impaired by Parkinson's disease.

The abilities of Parkinson's disease (PD) patients, taking routine medication, and of control subjects, to discriminate bilateral differences in the static angular positions of the two elbow joints were studied during passive (subject relaxed) and active (subject contracting to hold position) conditions. On each trial, one of the subject's elbows served as the reference joint (angle 60 degrees) and the other as the test joint (angular range, 54 degrees to 69 degrees, at 3 degree intervals). Subjects, with eyes closed, were required to discriminate the relative angles of the two elbows. In Experiments 1 (passive condition) and 2 (active condition), parkinsonians (n = 12) gave significantly fewer correct responses, pooled across sides, than did controls (n = 12), both in total scores across all angles and at individual test angles of 57 degrees and 63 degrees. In Experiment 3 (passive condition), derivation of conventional psychophysical variables indicated that both the difference limen (DL; threshold) and Weber ratio (WR; discriminatory sensitivity, independent of absolute stimulus values; same as DL/PSE) values of patients (n = 6) were significantly larger than those of controls (n = 6), in the absence of a significant difference between groups in the point of subjective equality (PSE). Our results provide clear evidence of a quantitative impairment of joint position sense in PD patients.

Proprioceptive regulation of voluntary ankle movements, demonstrated using muscle vibration, is impaired by Parkinson's disease.

OBJECTIVE: To test the hypothesis that the proprioceptive regulation of voluntary movement is disturbed by Parkinson's disease, the effects of experimental stimulation of proprioceptors, using muscle vibration, on the trajectories of voluntary dorsiflexion movements of the ankle joint were compared between parkinsonian and control subjects. METHODS: Twenty one patients with Parkinson's disease, on routine medication (levodopa in all but one), and an equal number of age matched, neurologically intact controls, were trained initially to make reproducible ankle dorsiflexion movements (20 degrees amplitude with a velocity of 9.7 degrees /s) following a visual "go" cue while movement trajectories were recorded goniometrically. During 50% of the experimental trials, vibration (105 Hz; 0.7 mm peak to peak) was applied to the Achilles tendon during the ankle movement to stimulate antagonist muscle spindles; vibrated and non-vibrated trials were interspersed randomly. Subjects' performance was assessed by measuring end point position-that is, the ankle angle attained 2 seconds after the visual "go" cue, from averaged (20 trials) trajectories. RESULTS: Statistical analysis of the end point amplitudes of movement showed that, whereas the amplitudes of non-vibrated movements did not differ significantly between patients with Parkinson's disease and controls, antagonist muscle vibration produced a highly significant reduction in the amplitudes of ankle dorsiflexion movements in both the patient and control groups. However, the extent of vibration induced undershooting produced in the patients with Parkinson's disease was significantly less than that in the controls; the mean vibrated/non-vibrated ratios were 0.86 and 0.54 for, respectively, the patient and control groups. CONCLUSIONS: The present finding of a reduction of vibration induced ankle movement errors in parkinsonian patients resembles qualitatively previous observations of wrist movements, and suggests that Parkinson's disease may produce a general impairment of proprioceptive guidance.

Effects of dry cow intramammary therapy on quarter infections in the dry period.

Quarter milk samples were taken from 150 cows from three dairy farms in south-east Queensland at drying off, two, four and six weeks after drying off, at calving, and one, two and three weeks after calving. In each of the herds, the cows were randomly allocated to three groups of approximately equal size. One group had all the quarters of all the cows treated at drying off with a dry cow antibiotic infusion containing cloxacillin; the second group was given no treatment, and the third group had selected quarters treated on the basis of their high activity of N-acetyl-beta-D-glucosaminidase at drying off. Dry cow treatment resulted in a marked reduction in the number of infected quarters at two and four weeks after drying off, so that the comprehensively treated group had significantly less infected quarters at these times (P<0.02). Twelve dinical cases of mastitis were detected two weeks after drying off in the untreated groups, 10 in the untreated quarters of the selectively treated groups, and no cases in the comprehensively treated groups. These cases were due mainly to Streptococcus uberis and Streptococcus dysgalactiae. The number of infected untreated quarters increased markedly between drying off and two weeks later, but in all three groups there was a marked decrease in the number of infected quarters between six weeks after drying off and calving, suggesting that the mammary glands were more able to overcome infections at this time.

Acute septicaemic pasteurellosis in Vietnamese pigs.

Sixteen isolates of Pasteurella multocida were cultured from cases diagnosed as acute septicaemic pasteurellosis in Vietnamese pigs. The HSB-PCR assay provided rapid presumptive determination of 10 isolates of P. multocida identified as haemorrhagic septicaemia (HS) causing type B cultures (B:2, B:5, B:2,5). Serological designation using the Carter and Heddleston typing systems confirmed these findings, and identified the six HSB-PCR negative cultures as either A:1, A:3 or D:3,4. Biochemical fermentation and REP-PCR revealed phenotypic and genotypic identity between P. multocida type A:1 isolated from Vietnamese pigs and poultry. Marked homogeneity was also demonstrated among HSB-PCR positive swine isolates, which were shown to possess genotypic identity with P. multocida type B:2 from buffaloes diagnosed with HS.

Functional conservations of the alkaline nuclease of herpes simplex type 1 and human cytomegalovirus.

The herpes simplex virus type 1 UL12 gene product, alkaline nuclease (AN), appears to be involved in viral DNA processing and capsid egress from the nucleus (Shao, L., Rapp, L. M., and Weller, S. K., Virology 196, 146-162, 1993). Although the HSV-1 AN is not absolutely essential for viral replication in tissue culture, conservation of the AN gene in all herpesviruses suggests an important role in the life cycle of herpesviruses. The counterpart of HSV-1 AN for human cytomegalovirus (HCMV) is the UL98 gene product. To examine whether the HCMV AN could substitute for HSV-1 AN, we performed trans-complementation experiments using a HSV-1 amplicon plasmid carrying the HCMV UL98 gene. Our results indicate (i) HCMV AN can complement the growth of the HSV-1 AN deletion mutant UL12lacZ virus in trans; (ii) a new recombinant virus, UL12laZcUL98/99, appears to be generated by the integration of the HCMV UL98 gene into the HSV-1 UL12lacZ viral genome; (iii) in contrast to its parental HSV-1 UL12lacZ virus, capsids formed in UL12lacZUL98/99-infected Vero cells were able to transport from the nucleus to the cytoplasm and mature into infectious viruses. Our results demonstrate a functional conservation of AN between HSV-1 and HCMV.

Antibiotics for the preservation of koala (Phascolarctos cinereus) semen.

AIM: To determine the normal microbial flora of the koala ejaculate and prepuce in order to select appropriate antibiotics for addition into diluents designed for the preservation of semen. PROCEDURE: Bacteriological samples of the koala prepuce (n = 12) and ejaculate (n = 20) were submitted for microbial culture and sensitivity testing. Microbial flora of ejaculates collected by electroejaculation and artificial vagina were compared. The effects of varying concentrations of penicillin G and gentamicin on sperm motility and on the growth of bacteria in diluted semen stored at room temperature and 16 degrees C over a 24 h period were investigated. RESULTS: A range of bacteria was isolated from the koala prepuce and ejaculate. The predominant organisms in semen collected by electroejaculation and artificial vagina were Corynebacterium spp, none of which could be assigned to any recognised species. The addition of penicillin G and gentamicin to a PBS-based diluent at dose rates of 1000 to 2000 IU/mL and 100 to 200 micrograms/mL respectively, resulted in no adverse effect on sperm motility over a 24 h incubation period. Penicillin G (1000 IU/mL) and gentamicin (100 micrograms/mL) prevented growth of bacterial contaminants in diluted koala semen. CONCLUSION: By controlling the growth of bacteria in extended koala semen, penicillin G and gentamicin are likely to lengthen the period by which spermatozoa can be stored at 16 degrees C and reduce the possibility of disease transmission during artificial insemination procedures.