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Biomedical subjects

D J Brown

Publications and source records attributed to D J Brown.

At least 19 recordsLinked to original sources
PubMed2006

Male fertility and sexual function after spinal cord injury.

Spinal cord injury has an enormous impact upon the sexual relationship of a man and his partner. Erection may be partial or absent, orgasm altered or impossible, and fertility severely impaired. New understanding of the physiology of sexual function and improved treatment can enable most cord-injured men to achieve erections suitable for sexual satisfaction. Modern methods of sperm collection and fertility treatment mean that many can also be fathers. The best results are obtained by a team approach involving rehabilitation and reproductive medicine clinicians, nurses, spinal cord injury specialists and counselors with the cord-injured man and his partner. Erections can be achieved by drugs, such as sildenafil, that block phosphodiesterase 5, prolonging the action of nitric oxide with resultant smooth muscle relaxation. Intracavernosal prostaglandin E1 and mechanical systems, such as vacuum pumps and constriction rings, are also effective. Sexual gratification can be promoted in the context of an understanding relationship in which the cord-injured person can gain pleasure from pleasing his partner and also from his partner's exploration of erotogenic areas not affected by the spinal cord injury. An emphasis on the broader view of sexuality in relationships allows for a continuance and strengthening of bonds between the couple. Vibration ejaculation or electroejaculation can be used to collect semen. For a limited period in the acute phase, usually for about 6-12 days after injury, normal semen can be obtained by electroejaculation from some cord-injured men. With chronic spinal cord injury the semen is of variable quality. Some patients have necrospermia, which may be improved by regular ejaculation. Others have poor quality semen or spermatogenic disorders and, in this situation, in vitro fertilization techniques must be used to achieve parenthood. Trials of assisted ejaculation help individualize cost-effective management of the infertility.

Autonomic Nervous System↗
PubMed2006

Systematic evaluation of current control devices used by people with intellectual disabilities in non-immersive virtual environments.

Virtual environments have a role to play in facilitating the acquisition of living skills in people with intellectual disabilities, improving their cognitive skills and providing them with entertainment. However, the currently recommended devices to allow navigation in and interaction with the environments are difficult to use. Using a methodology established in an earlier study, the study aims to systematically document the performance of users with the currently recommended devices in order to (i) inform the design of a usable control device or devices and (ii) act as a baseline against which they can be evaluated. 40 people with severe intellectual disabilities aged 21-67 years used four environments with an equal number of sessions with the different devices being evaluated. Results indicate that when forward movement is provided by the software using the mouse for both navigation and interaction allows better performance both initially and after exposure than using the fire button on the joystick. When the user had to initiate forward movement with the navigation device, the joystick allowed better performance than the arrows on the keyboard. Preventing slippage of the joystick base would make its use much easier and it is suggested that separate devices are retained for navigation and interaction.

Adult↗
PubMed2005

Ciprofloxacin resistance in non-typhoidal Salmonella serotypes in Scotland, 1993-2003.

OBJECTIVES: To determine the levels of resistance to ciprofloxacin among non-typhoidal salmonellae in Scotland. METHODS: Etest strips were used to determine the ciprofloxacin MICs for nalidixic acid-resistant salmonellae isolated from humans during 1993-2003. RESULTS: The percentage of nalidixic acid-resistant salmonellae isolated from human infection in Scotland has increased from 1.4% in 1993, to 8.8% in 1998 and 21.3% in 2003. Of 493 strains of nalidixic acid-resistant Salmonella tested, a single isolate of Salmonella Typhimurium RDNC was resistant to ciprofloxacin at the NCCLS breakpoint of 4 mg/L. Eleven isolates were resistant at the Scottish Salmonella Reference Laboratory breakpoint of 0.5 mg/L, while 466 isolates (94.5%) had reduced susceptibility with MICs of > or =0.125 mg/L and <0.5 mg/L. CONCLUSIONS: These results show that very few non-typhoidal isolates of Salmonella in Scotland that are resistant to nalidixic acid are also resistant to ciprofloxacin at the NCCLS recommended breakpoint of 4 mg/L. The majority of isolates examined, however, do show reduced susceptibility at 0.125 mg/L. This confirms the necessity for continuing antimicrobial surveillance of resistance to this important antibiotic.

Ciprofloxacin↗
PubMed2005

Health and quality of life of persons with spinal cord lesion in Australia and Sweden.

STUDY DESIGN: Cross-sectional questionnaire study. OBJECTIVES: The aim of the study was to demonstrate the value of common general health-related quality of life (HRQL) instruments, readily available for cross-cultural comparisons, in persons with spinal cord lesion (SCL) treated at spinal units in Melbourne, Australia and in Gothenburg, Sweden. Another aim was to determine as to which of the independent variables were the most powerful predictors of global QL in the two SCL groups. SETTINGS: Australia and Sweden. METHODS: Two groups consisting of 89 Australian and 71 Swedish SCL persons were surveyed. The two groups were matched according to sex, age, time since injury and level of injury. The 36-item short-form health survey (SF-36) and the Spinal Cord Injuries Quality of Life-23-item questionnaire were used to cover essential generic and specific domains of health and quality of life. Clinical and sociodemographic data were collected using questionnaires. For interpretation purpose, available general population data were used. RESULTS: The most important predictors of QL perception in the Australian group were the same as for the Swedish group; mood, physical and social functioning and problems regarding injury. In total, 61% (Australian group) and 52% (Swedish group) of the variance was explained by these variables. Despite similarities of health profiles, some areas of the SF-36 differed between the two groups. CONCLUSION: The demonstrated HRQL profiles in SCL persons have shown that valid measures can provide new information of clinical value beyond the self-evident physical and practical restrictions due to injury. Illustrative comparisons, such as those presented here between Australia and Sweden, may extend our knowledge about areas where the SCL persons themselves are the logical experts, for example, maintenance of personal roles, social interaction and emotional well-being.

Activities of Daily Living↗
PubMed2004

Transient focal cooling at the round window and cochlear nucleus shows round window CAP originates from cochlear neurones alone.

We have measured the compound action potential (CAP) evoked by very brief high-frequency tone-bursts (20 kHz, 1/4 ms) at the round window (RW) and at the surface of the cochlear nucleus (CN) in guinea pigs before, during and after a localised chilling of either the cochlea or CN, with a non-toxic 'freeze spray'. CN chilling almost abolished the negative-going component of the CAP measured in the CN (generated by the CN and here called the cochlear nucleus response or CNR), leaving a positive-going localised response from the cochlear neurones as they leave the internal auditory meatus. Within 3 min, the CNR recovered to control values. During that time, the N(1) component of the RW CAP was slightly increased and the P(1) was larger, even though the CNR was abolished, indicating that the P(1) was not due to electrotonic spread of current from the CN. The N(2) and successive peaks at the RW were also abolished, but returned after 30 s. When the cochlea was chilled, the RW CAP was initially reduced in amplitude, presumably due to a drop in the number of cochlear neurones spiking in response to sound, but recovered within 3 min to be larger than the control waveform, with a more prominent N(1) peak which was delayed slightly, making the CAP more monophasic. At the same time, the CNR was smaller, presumably due to fewer cochlear neurones responding, but overall the CN CAP was altered little in waveshape. These experiments indicate that that RW CAP is generated almost solely by cochlear neurones. We also suggest that some of the changes in the RW CAP during the chills were due to changes in the firing of the lateral olivo-cochlear system of efferent neurons.

Acoustic Stimulation↗
PubMed2004

K(+) currents produce P(1) in the RW CAP: evidence from DC current bias, K(+) channel blockade and recordings from cochlea and brainstem.

Tone-burst-evoked compound action potentials (CAP) from the guinea pig round window (RW) are altered by DC current injection through the RW. The CAP waveform consists of a series of interleaved negative and positive peaks (N(1), P(1), N(2), P(2) etc.) of decreasing amplitude. During positive DC current injection (around +50 microA) the positive peaks are depressed substantially and there is an overall negative baseline shift of the waveform following the N(1). Negative current injection (around -50 microA) increased the positive peaks, in particular P(1), and produced an overall positive baseline shift following the N(1) peak. Results support our hypothesis that the first and dominant N(1) peak in the RW CAP is due to depolarising Na(+) currents into the primary afferent dendrites and axons within the cochlea, and that the P(1) potential is largely due to the exit of the hyperpolarising K(+) currents in the same cells. We have reached this conclusion on the basis of the sign and latency of the N(1) and P(1) components at the RW, beneath the myelin layers around the spiral ganglion cells, at the internal auditory meatus (IAM) within the brain case, and on the basis of the differential susceptibility of the various peaks to perfusion of lidocaine in the cochlear nucleus, sectioning of the cochlear nerve at the IAM, application of the K(+) channel blockers 4-amino-pyridine and tetraethylammonium within the cochlea, and DC current biasing at the RW.

4-Aminopyridine↗
PubMed2004

Determinants of the spectrum of the neural electrical activity at the round window: transmitter release and neural depolarisation.

In this paper we summarise the changes we have observed in the electrical activity at the round window (RW) of guinea pigs during transient cooling of the RW or cochlear nucleus (CN), transient hypoxia, low frequency acoustic biasing, ablation of the CN, and DC current injection into the basal cochlear turn. We have measured the compound action potential (CAP), the spectrum of the average CAP waveform (SAW) evoked by brief tone-bursts, and the spectrum of the neural noise (SNN). We discuss how the changes we have observed can be understood in terms of changes in transmitter release from inner hair cells (that controls stochastic neural firing), or changes in the membrane potential of the primary afferent neurones (that controls the neural firing waveshape and the spectral content of the SAW and SNN). We note that changes in sound intensity produce a simple increase in the stochastic release of transmitter from inner hair cells, without much change in the waveform of the neural response, but manipulations of the auditory brainstem, cooling and current injection all appear to alter neural firing rate and the neural response waveform, producing a baseline shift in the CAP and changes in 1000 Hz peak and low frequency content of the SAW and SNN. We also discuss the use of the CAP, SAW and SNN as an indication of cochlear and auditory brainstem neural activity.

Action Potentials↗
PubMed2004

An outbreak due to peanuts in their shell caused by Salmonella enterica serotypes Stanley and Newport--sharing molecular information to solve international outbreaks.

Salmonellosis is a global problem caused by the international movement of foods and high incidence in exporting countries. In September 2001, in an outbreak investigation Australia isolated Salmonella Stanley from imported peanuts, which resulted in a wider investigation in Canada, England & Wales and Scotland. Patients infected with Salmonella serotypes known to be isolated from peanuts and reported to surveillance systems were interviewed to determine exposure histories. Tagged image file format (TIFF) images of pulsed-field gel electrophoresis (PFGE) patterns of Salmonella isolates were shared electronically amongst laboratories. Laboratories tested packets of 'Brand X' peanuts from various lots and product lines. In total, 97 cases of S. Stanley and 12 cases of S. Newport infection were found. Seventy-three per cent (71/97) of S. Stanley cases were in persons of Asian ethnicity. Twenty-eight per cent of cases recalled eating Brand X peanuts and a further 13% had peanuts in their house in the previous month or had eaten Asian-style peanuts. Laboratories isolated S. Stanley, S. Newport, S. Kottbus, S. Lexington and S. Unnamed from Brand X peanuts. Isolates of S. Stanley from peanuts and human patients were indistinguishable by PFGE. This international outbreak resulted from a product originating from one country affecting several others. Rapid sharing of electronic DNA images was a crucial factor in delineating the outbreak; multinational investigations would benefit from a harmonized approach.

Adolescent↗
PubMed2003

Cross-contamination with Salmonella on a broiler slaughterhouse line demonstrated by use of epidemiological markers.

AIMS: To investigate contamination of surfaces on a poultry slaughter line from infected poultry and subsequent cross-contamination of non-infected poultry. METHODS AND RESULTS: A broiler slaughterhouse was investigated for the presence of Salmonella on 17 defined points over two 1-week periods. Flocks supplied to slaughter and neck skin samples from processed chicken were likewise investigated. Salmonella was detected in 10 out of 18 flocks at ante-mortem inspection, while seven flocks tested positive in the finished products. Equipment at all but one control point at the slaughter line tested positive at least once during the study. The chicken receiving area was the most contaminated. By comparison of typing results from serotyping, plasmid profile typing and phage typing, direct evidence for cross-contamination with Salm. serotype Typhimurium, Salm. Serotype 4.12:b:- and Salm. serotype Virchow on the slaughter line was obtained for four of the flocks. The cleaning procedure in place did not remove all Salmonella from the contaminated areas. CONCLUSIONS: Evidence for contamination of equipment on a slaughter line and subsequent cross-contamination to non-infected chicken was provided by typing methods. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has provided detailed information on cross-contamination on a slaughter line by the use of phage typing and plasmid profiling. The study stresses the importance of controlling Salmonella in the primary production, as contamination of the equipment on the slaughter line will act as a vehicle to contaminate finished products. Cleaning procedures on slaughter lines cannot be expected to control this problem with the current equipment.

Abattoirs↗
PubMed2003

Investigation of human infections with Salmonella enterica serovar Java in Scotland and possible association with imported poultry.

PFGE analysis of S. Java strains (29 from humans, 30 from poultry meat) showed two major clusters. All isolates from poultry imported from the Netherlands belonged to Cluster A, which also comprised 10 human isolates. Thirty-one of the 37 isolates in this cluster had an identical JavX1 pattern, similar to the X8 profile of a particular S. Java clone predominant in poultry production in several European countries. Cluster B comprised 19 human isolates and two poultry isolates of unknown origin. These results combined with epidemiological data and information on the origins of poultry meat strongly suggested that imported poultry meat is an important source of Java infections in humans in Scotland.

Animals↗
PubMed2002

Quantitative ultrasound assessment of acute bone loss following spinal cord injury: a longitudinal pilot study.

Spinal cord injury (SCI) results in substantial and rapid osteoporosis. Given its rapid onset, assessment of bone changes in the early stages (first 6 months) following SCI is important. This is particularly pertinent if intervention is to be implemented. Quantitative ultrasound (QUS) represents a potential assessment tool for the evaluation of skeletal changes in the early stages following SCI. This longitudinal pilot study assessed changes in QUS measures of calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) in 15 male subjects (age 23.9+/-7.3 years) over a 6-week period. Their mean time since SCI was 110.3+/-34.5 days. Also assessed were bone mineral density of the calcaneus (BMDc) and proximal tibia (BMDt) using dual-energy X-ray absorptiometry (DXA). Confirming the rapid onset of bone loss following SCI, BMDc and BMDt decreased by 7.5+/-3.0% ( p<0.001) and 5.3+/-4.2% ( p<0.001), respectively. QUS was sensitive to these changes. BUA decreased by 8.5+/-6.9% ( p<0.001), whilst SOS decreased by 1.5+/- 1.3% ( p<0.001). Suggesting an influence of the material properties of bone on BUA, BUA was correlated with BMDc at both the initial ( r = 0.68, p<0.01) and final ( r = 0.62, p<0.01) assessments. There were no significant correlations in the magnitude of change over the 6-week assessment period between any of the skeletal measures (all p>0.05). This suggests that skeletal qualities other than material properties also influence QUS measures. Overall, this study confirmed the rapid onset of bone loss following SCI and showed QUS to be a useful portable measure of acute bone changes. This may allow assessment of bone loss and the efficacy of intervention on this loss in the early stages following injury, a period where traditional axial DXA assessment is limited by practical constraints.

Absorptiometry, Photon↗
PubMed2002

Gabapentin for neuropathic pain following spinal cord injury.

STUDY DESIGN: Retrospective review of patient data. OBJECTIVE: To present two years of experience in the use of gabapentin for the alleviation of neuropathic pain in spinal cord injury patients. SETTING: Supra-regional Spinal Cord Service, Melbourne, Australia. METHOD: Data were retrieved from the medical records of all spinal cord injury patients prescribed gabapentin for neuropathic pain. Pain was assessed prior to and during treatment at 1, 3 and 6 months with a 10 cm visual analogue scale which ranged from 0 ('no pain') to 10 ('worst pain imaginable'), or by the documentation of a verbal description of pain. RESULTS: Seventy-six per cent of patients receiving gabapentin reported a reduction in neuropathic pain. In those patients with data at all four measurement points, the mean pretreatment score was 8.86. Following treatment with gabapentin the score dropped to 5.23, 4.59 and 4.13 at 1, 3 and 6 months, respectively. Where only a verbal description of pain was documented, the trend was that the pretreatment report of 'unbearable' was replaced by 'liveable' during treatment. CONCLUSION: Our experience suggests that gabapentin offers an effective therapeutic alternative for the alleviation of neuropathic pain following spinal cord injury. Controlled clinical trials are now required to confirm these observations.

Acetates↗
PubMed2001

Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.

Non-syndromic low frequency sensorineural hearing loss (LFSNHL) affecting only 2000 Hz and below is an unusual type of hearing loss that worsens over time without progressing to profound deafness. This type of LFSNHL may be associated with mild tinnitus but is not associated with vertigo. We have previously reported two families with autosomal dominant LFSNHL linked to adjacent but non-overlapping loci on 4p16, DFNA6 and DFNA14. However, further study revealed that an individual with LFSNHL in the DFNA6 family who had a recombination event that excluded the DFNA14 candidate region was actually a phenocopy, and consequently, DFNA6 and DFNA14 are allelic. LFSNHL appears to be genetically nearly homogeneous, as only one LFSNHL family is known to map to a different chromosome (DFNA1). The DFNA6/14 critical region includes WFS1, the gene responsible for Wolfram syndrome, an autosomal recessive disorder characterized by diabetes mellitus and optic atrophy, and often, deafness. Herein we report five different heterozygous missense mutations (T699M, A716T, V779M, L829P, G831D) in the WFS1 gene found in six LFSNHL families. Mutations in WFS1 were identified in all LFSNHL families tested, with A716T arising independently in two families. None of the mutations was found in at least 220 control chromosomes with the exception of V779M, which was identified in 1/336 controls. This frequency is consistent with the prevalence of heterozygous carriers for Wolfram syndrome estimated at 0.3-1%. An increased risk of sensorineural hearing loss has been reported in such carriers. Therefore, we conclude that mutations in WFS1 are a common cause of LFSNHL.

Alleles↗
PubMed2001

Proinflammatory cytokine expression by Theileria annulata infected cell lines correlates with the pathology they cause in vivo.

Control of Theileria annulata is currently best achieved by the use of live attenuated cell line vaccines. However, the mechanisms underlying attenuation are unclear and there is a need to rapidly produce new cell line vaccines, which could safely and effectively vaccinate cattle against tropical theileriosis. There is increasing evidence to suggest that proinflammatory cytokines produced by T. annulata infected cells play a central role in both pathology and immune evasion. This study aimed to test this hypothesis and to evaluate cytokine expression as a marker of virulence. The pathogenicity and protective efficacy of cloned T. annulata cell lines that expressed different levels of proinflammatory cytokines were compared. In two independent trials using different stocks of T. annulata, cell lines that expressed higher levels of proinflammatory cytokines induced severe reactions, and in some cases death, when used to vaccinate groups of cattle. In contrast, low cytokine expressing lines induced low post-vaccinal reactions. The results clearly demonstrated that cytokine expression by T. annulata infected cells could be used as a marker of virulence and provided strong evidence to support a role for cytokines in the induction of pathology. Both high and low cytokine expressing cell lines protected cattle against heterologous challenge infection, offering the possibility of using cytokine expression to rapidly select new safe, potent vaccines against tropical theileriosis without the need for culture attenuation.

Animals↗
PubMed2001

Tobravirus 2b protein acts in trans to facilitate transmission by nematodes.

Analysis of RNA2 of TRV PaY4 showed it to be recombinant, carrying 3'-terminal sequences derived from RNA1. Virus produced using an infectious cDNA clone of PaY4 RNA2 was nematode transmissible, demonstrating that natural TRV recombinant isolates are not necessarily defective. Mutations introduced into PaY4 RNA2 showed that the 2b gene, but not the 2c gene, is required for transmission by both Paratrichodorus pachydermus and P. anemones nematodes. Experiments examined whether infection of plants with two different virus clones would impact upon nematode transmission of either virus. Simultaneous inoculation with TRV clones expressing green or red fluorescent proteins revealed that mixing of the two virus populations did not occur, although, in roots, adjacent cells were found containing green- or red-tagged viruses. Subsequently, in similar experiments it was found that a TRV PaY4 2b mutant was transmitted when combined with wild-type TRV PaY4. Also, transmission of a 2b mutant of an in vitro TRV/PEBV recombinant virus (TRV-C1) occurred after coinfection with wild-type virus. Thus, the tobravirus 2b transmission protein is trans-acting. Although TRV PaY4 and TRV PpK20 are both transmitted by P. pachydermus, a 2b mutant of TRV PaY4 was not transmitted when coinoculated to plants with TRV PpK20.

Amino Acid Sequence↗
PubMed2001

Altered expression of growth factors and cytokines in keratoconus, bullous keratopathy and diabetic human corneas.

The purpose of this study was to identify the growth factors and cytokines present in normal and diseased corneas. Total RNA was isolated from normal and diseased corneas. cDNA was synthesized from individual corneas and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed with primers to IL-1alpha, 1IL-8, PDGF-B, BMP-2, BMP-4, IGF-I, TGF-beta2, FGF-2, and VEGF. After normalization to beta2-microglobulin, several factors were identified that were significantly different from normal. Antibodies to IGF-I, BMP-2, VEGF and TGF-beta2 were used for immunohistochemistry. A total of 93 corneas were used for this study including 31 normal, 20 keratoconus, 19 bullous keratopathy (pseudophakic and aphakic, PBK/ABK), and 23 diabetic corneas. The VEGF RNA levels were significantly decreased in the keratoconus and PBK/ABK corneas but increased in the diabetic corneas. BMP-2 gene expression was lower than normal in the PBK/ABK and diabetic corneas. IGF-I and BMP-4 RNA levels were increased in PBK/ABK. In the immunohistochemical studies, the protein patterns paralleled those found at the mRNA level. The only exception was IGF-I in diabetic corneas that showed increased staining in the epithelium and its basement membrane without a significant increase in mRNA levels. TGF-beta2 mRNA and protein levels were similar to normal in all diseased corneas. Thus, no alterations in the tested growth factors/cytokines were unique to keratoconus corneas. In contrast, PBK/ABK corneas had specific significant elevations of BMP-4 and IGF-I. Diabetic corneas were unique in their increased VEGF mRNA levels. These data suggest that while some growth factor/cytokine alterations are non-specific and can be found in multiple corneal diseases, there are others that are unique to that disease.

Adult↗