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Biomedical subjects

S M Jones

Publications and source records attributed to S M Jones.

At least 19 recordsLinked to original sources
PubMed2006

Severe vocal cord dysfunction resistant to all current therapeutic interventions.

Vocal cord dysfunction (VCD) is characterised by paradoxical vocal cord adduction during inspiration or throughout the respiratory cycle, it results in wheeze, stridor, cough and dyspnoea. Although asthma and VCD can coexist, patients with VCD are frequently misdiagnosed with refractory asthma. It can severely restrict an individual's level of activity and effective therapeutic control can be difficult to achieve. We report the case of a patient who was treated with all available therapeutic interventions, including intralaryngeal botulinum toxin injection, but failure resulted in a permanent trachesotomy.

Adult↗
PubMed2006

Kinetics of the immune response to the (F1+V) vaccine in models of bubonic and pneumonic plague.

Protection against aerosol challenge with > 300 MLD of Yersinia pestis was observed 7 days after a single immunisation of mice with the F1+V vaccine. At day 60, mice were protected against injected challenge (10(7)MLD) in a vaccine dose-related manner. Recall responses to rV in splenocytes ex vivo at day 98 correlated significantly (p<0.001) with the immunising dose-level of V antigen; no memory response or anti-V serum IgG was detected in killed whole cell vaccine (KWCV) recipients. This may explain the susceptibility of KWCV recipients to aerosol challenge and the enhanced protection conferred by the F1+V sub-unit vaccine, particularly since the anti-F1 responses induced by either vaccine were similarly IgG1-polarised.

Animals↗
PubMed2006

Exploring the relationship between severity of dysphonia and voice-related quality of life.

OBJECTIVES: To explore whether severity and/or consistency of dysphonia are linked to voice-related quality of life. DESIGN: Cross-sectional study. SETTING: Specialist voice clinics, University Teaching Hospital. PARTICIPANTS: Sixty adult patients attending with a primary complaint of dysphonia. Exclusion criteria were those below 16 years of age, transexual patients and those with a persistent dysphonia of >2 years. MAIN OUTCOME MEASURES: Voice-related quality of life as assessed by VoiSS. EXPLANATORY FACTORS: Severity of dysphonia as judged by perceptual ratings of voice (GRBAS); a visual analogue scale to judge best, worst and today's voice. RESULTS: There was a highly significant correlation between perceptual dysphonia severity as assessed by GRBAS and the total, impairment and emotional subsets of the VoiSS questionnaire (r from 0.48 to 0.64). There was a similar and highly significant correlation between best, worst and today's self-rated voice and the total, impairment and emotional subsets of the VoiSS questionnaire (r from -0.40 to -0.60). However, none of the self-rated parameters was demonstrably better at explaining the effect on quality of life. CONCLUSIONS: An increasingly negative effect on quality of life appears to be associated with an increase in the severity of dysphonia. Further research on the role of quality of life measures in the assessment and treatment of dysphonia would be of value.

Adult↗
PubMed2005

A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor 1 (CR1).

Complement receptor 1 (CR1) on the surface of human erythrocytes facilitates intravascular clearance of complement-opsonized pathogens. The need for complement activation can be circumvented by directly coupling the organism to CR1 using a bispecific monoclonal antibody heteropolymer (HP). Lack of a functional homologue to CR1 on mouse erythrocytes has made it difficult to study HP-dependent clearance of pathogens in small animals. We have developed a transgenic mouse that expresses human CR1 on erythrocytes. CR1 antigen is of appropriate size and in a clustered distribution as confirmed by immunoblotting and fluorescence microscopy, respectively. HP that immobilized bacteriophage PhiX174 prototype pathogen to erythrocyte CR1 of the transgenic mice increased the rate of clearance of the virus compared with HP that bound bacteriophage, but not CR1. This transgenic mouse model will allow evaluation of different HPs for their in vivo efficacy and potential as human therapeutics.

Animals↗
PubMed2005

Human immune response to a plague vaccine comprising recombinant F1 and V antigens.

The human immune response to a new recombinant plague vaccine, comprising recombinant F1 (rF1) and rV antigens, has been assessed during a phase 1 safety and immunogenicity trial in healthy volunteers. All the subjects produced specific immunoglobulin G (IgG) in serum after the priming dose, which peaked in value after the booster dose (day 21), with the exception of one individual in the lowest dose level group, who responded to rF1 only. Three subjects, found to have an anti-rV titer at screening, were excluded from the overall analysis. Human antibody functionality has been assessed by quantification of antibody competing for binding to rV in vitro and also by the transfer of protective immunity in human serum into the naive mouse. Human and macaque IgG competed for binding to rV in vitro with a mouse monoclonal antibody, previously shown to protect mice against challenge with plague, suggesting that this protective B-cell epitope on rV is conserved between these three species. Total IgG to rV in individuals and the titer of IgG competing for binding to rV correlated significantly at days 21 (r = 0.72; P < 0.001) and 28 (r = 0.82; P < 0.001). Passive transfer of protective immunity into mice also correlated significantly with total IgG titer to rF1 plus rV at days 21 (r(2) = 98.6%; P < 0.001) and 28 (r(2) = 76.8%; P < 0.03). However, no significant vaccination-related change in activation of peripheral blood mononuclear cells was detected at any time. Potential serological immune correlates of protection have been investigated, but no trends specific to vaccination could be detected in cellular markers.

Adult↗
PubMed2005

Advances in wound healing: topical negative pressure therapy.

In clinical practice many wounds are slow to heal and difficult to manage. The recently introduced technique of topical negative pressure therapy (TNP) has been developed to try to overcome some of these difficulties. TNP applies a controlled negative pressure to the surface of a wound that has potential advantages for wound treatment and management. Although the concept itself, of using suction in wound management is not new, the technique of applying a negative pressure at the surface of the wound is. This paper explores the origins and proposed mechanisms of action of TNP therapy and discusses the types of wounds that are thought to benefit most from use of this system.

Acute Disease↗
PubMed2004

Sprouting and synaptic reorganization in the subiculum and CA1 region of the hippocampus in acute and chronic models of partial-onset epilepsy.

Repeated seizures induce permanent alterations in the hippocampal circuitry in experimental models and patients with intractable temporal lobe epilepsy (TLE). Most studies have concentrated their attention on seizure-induced reorganization of the mossy fiber pathway. The present study examined the projection pathway of the CA1 pyramidal neurons to the subiculum, which is the output of the hippocampal formation in five models of TLE. We examined the laminar pattern of Timm's histochemistry in the stratum lacunosum-moleculare of CA1 in three acute and two chronic models of TLE: intraventricular kainic acid (KA), systemic KA, systemic pilocarpine, chronic electric kindling and chronic i.p. pentylenetetrazol. The laminar pattern of Timm histochemistry in the stratum moleculare of CA1 was permanently remodeled in epileptic models suggesting sprouting of Timm containing terminals from the adjacent stratum lacunosum. Ultrastructural examination confirmed that Timm granules were localized in synaptic terminals. As the source of Timm-labeled terminals in this region was not known, sodium selenite, a selective retrograde tracer for zinc-containing terminals, was iontophoretically injected in vivo in rats exposed to systemic pilocarpine, systemic KA or chronic pentylenetetrazol. The normal projection of CA1 pyramidal neurons to the subiculum is topographically organized in a lamellar fashion. In normal rats, the extent of the injection site (terminals) and the retrogradely labeled pyramidal neurons (cell soma) corresponded to the same number of lamellas. In epileptic rats, the retrograde labeling extended 42-67% farther than the normal dorso-ventral extent including lamellas above and below the expected. This is direct evidence for sprouting of CA1 pyramidal axons into the subiculum and stratum lacunosum-moleculare of the CA1 region confirming the alterations of the laminar pattern of Timm's histochemistry. Sprouting of the CA1 projection to subiculum across hippocampal lamellas might lead to translamellar hyperexcitability, and to amplification and synchronization of epileptic discharges in the output gate of the hippocampal formation.

Acute Disease↗
PubMed2004

Evidence for macular gravity receptor modulation of hypothalamic, limbic and autonomic nuclei.

Mice lacking normal vestibular gravity reception show altered homeostatic, circadian and autonomic responses to hypergravity (+G) exposure. Using c-Fos as a marker of neuronal activation, the current study identifies CNS nuclei that may be critical for initiating and integrating such responses to changes in vestibular signaling. This experiment utilized the mutant C57BL/6JEi-het mouse (het), which lacks macular otoconia and thus gravity receptor function. Following 2 h of 2G (2x Earth's gravity) exposure (via centrifugation) the neuronal responses of the het mice were compared with wildtype mice similarly exposed to 2G, as well as het and wildtype 1G controls. Wildtype mice exposed to 2G demonstrated robust c-Fos expression in multiple autonomic, hypothalamic and limbic nuclei, including: the lateral septum, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamus, dorsomedial hypothalamus, arcuate, suprachiasmatic hypothalamus, intergeniculate leaflet, dorsal raphe, parabrachial and locus coeruleus. The het mice exposed to 2G demonstrated little to null c-Fos expression in these nuclei with a few exceptions and, in general, a similar pattern of c-Fos to 1G controls. Data from this study further support the existence of a complex and extensive influence of the neurovestibular system on homeostatic, circadian and possibly autonomic regulatory systems.

Animals↗
PubMed2004

Setting up a store-and-forward telemedicine service for acute trauma in a hospital trust.

Telemedicine is a valuable, but as yet underused, resource for the delivery of health-care to patients. This paper describes the development of a new store-and-forward telemedicine service at the Queen Victoria Hospital, which is a tertiary referral centre for plastic surgery in the United Kingdom. The practical requirements of such a system, and the technical and legal difficulties experienced during the initial stages, are also discussed.

Database Management Systems↗
PubMed2004

Telemedicine in acute plastic surgical trauma and burns.

BACKGROUND: Telemedicine is a relatively new development within the UK, but is increasingly useful in many areas of medicine including plastic surgery. Plastic surgery centres often work on a hub-and-spoke basis with many district hospitals referring to one tertiary centre. The Queen Victoria Hospital is one such centre receiving calls from more than 28 hospitals in the Southeast of England resulting in approximately 20 referrals a day. OBJECTIVE: A telemedicine system was developed to improve trauma management. This study was designed to establish whether digital images were sufficiently accurate enough to aid decision-making. A store-and-forward telemedicine system was devised and the images of 150 trauma referrals evaluated in terms of injury severity and operative priority by each member of the plastic surgical team. RESULTS: Correlation scores for assessed images were high. Accuracy of "transmitted image" in comparison to injury on examination scored > 97%. Operative priority scores tended to be higher than injury severity. CONCLUSIONS: Telemedicine is an accurate method by which to transfer information on plastic surgical trauma including burns.

Burns↗
PubMed2003

Protective efficacy of a fully recombinant plague vaccine in the guinea pig.

A fully recombinant sub-unit vaccine comprising the protein antigens rF1 + rV has been demonstrated to protect immunised guinea pigs against exposure to 10(5) colony-forming units (CFU) of virulent Yersinia pestis. Additionally, IgG purified from rF1 + rV-immunised guinea pig serum, protected the mouse by passive immunisation against challenge with Y. pestis whereas IgG purified from the serum of guinea pigs immunised with a licensed killed whole cell (KWC) vaccine for plague, protected less well. Guinea pigs immunised with the licensed killed whole cell vaccine developed an IgG titre for fraction 1 (F1) but not for V antigen. The differential in protection conferred on the mouse by passive immunisation with guinea pig IgG, was abrogated by the use of IgG purified from guinea pigs immunised with killed whole cell vaccine supplemented with V antigen. These findings indicate that the reduced efficacy of the licensed killed whole cell vaccine formulation previously observed in the mouse can be attributed to lack of the V antigen. Cross-protection of the mouse with guinea pig IgG suggests that the recognition of neutralising epitopes in the F1 and V proteins is conserved between these two species.

Animals↗
PubMed2003

Progression of peripheral joint disease in psoriatic arthritis: a 5-yr prospective study.

OBJECTIVE: To assess the evolution of disease subgroups and the frequency of progression of peripheral joint disease in a prospectively studied cohort of patients with psoriatic arthritis (PsA). METHODS: The cohort was identified as the first consecutive 100 patients attending a psoriatic arthritis clinic and who had been the subject of a previously published cross-sectional retrospective study. Nine of the 100 patients had died, three declined follow-up and one could not be traced. The remaining 87 patients (49 females, 38 males) completed the study proforma at a median follow-up interval of 65 months (range 39-90). An analysis of initial plasma viscosity compared with rates of progression of joint score was performed. RESULTS: Eighteen patients changed subgroup; 11 had an increase in the number of joints involved, six a decrease, and one changed from an oligoarticular pattern to predominant spondylitis. Within the polyarticular group 37/51 patients had an increase in the number of joints involved. For the whole population, there were significant increases in the number of joints involved (median 6 vs 11, P < 0.001 Wilcoxon signed rank) and Health Assessment Questionnaire scores (median 0.375 vs 0.5, P < 0.001). The median rate of joint progression was 0.42 peripheral joints per year (range 0-7.2). However, the rate of peripheral joint involvement was highest in the first year of arthritis (median 4.0 joints/yr) as measured in 13 patients who had onset within 12 months of baseline assessment. There were no significant differences in skin and nail scores although nine more patients had developed nail disease. There was a significant correlation between the initial viscosity and rate of progression of joint damage (Spearman correlation, P < 0.011). CONCLUSIONS: Peripheral joint disease is progressive in the majority of patients with PsA and reinforces the need for effective monitoring and treatment.

Adolescent↗
PubMed2002

Delayed ovulation and parturition in a viviparous alpine lizard (Niveoscincus microlepidotus): morphological data and plasma steroid concentrations.

The southern snow skink, Niveoscincus microlepidotus, exhibits an unusual biennial reproductive cycle with an extended gestation period of approximately 1 year. Morphological data were gathered on a monthly basis, providing a detailed picture of the reproductive cycle. Vitellogenesis begins in spring, immediately after parturition. Maximum follicular diameter is reached before the winter hibernation period and ovulation occurs the following spring. Embryos are fully developed and reach maximum size by early autumn. Yolk reserves are depleted before winter. Birth of between one and four young occurs the following spring. Plasma progesterone concentrations are low (2.7 +/- 0.9 ng mL(-1)) in post-partum females, begin to rise in autumn in vitellogenic females and peak (38.5 +/- 7.9 ng mL(-1)) in pre-ovulatory females after hibernation. Concentrations are high (15.4 +/- 5.9 ng mL(-1)) in early pregnancy and decline to basal levels before winter and well before birth in spring. Plasma oestradiol concentrations peak during vitellogenesis (1.0 +/- 0.3 ng mL(-1)) and decline to basal levels during pregnancy (0.2 +/- 0.03 ng mL(-1)). A second oestradiol peak occurs before parturition (0.7 +/- 0.2 ng mL(-1)). Thus, functional completion of vitellogenesis and gestation is achieved by autumn in successive years. The mechanisms that defer ovulation and parturition by a further six months are unknown.

Animals↗
PubMed2002

Tumour necrosis factor-alpha polymorphism and the HLA-Cw*0602 allele in psoriatic arthritis.

OBJECTIVES: To investigate polymorphisms in the genes for tumour necrosis factor alpha (TNFA), interleukin 10 (IL10) and tumour necrosis factor receptor II (TNFRII) in patients with psoriatic arthritis (PsA) and their relationship to the HLA-Cw*0602 allele and to the ages at onset of psoriasis and arthritis and the pattern of joint involvement. METHODS: One hundred and twenty-four well-characterized patients with PsA were studied. Controls were 101 cadaveric organ donors. All were genotyped for single-nucleotide polymorphisms in TNFA (positions -308, -238, +488), IL10 (-1082, -819, -592) and in the 3'-untranslated region of TNFRII (+1663, +1668, +1690). The HLA-Cw*0602 allele was detected by polymerase chain reaction-based techniques. The frequencies of the respective variants were compared between patients and controls and in relation to the ages at onset of psoriasis and arthritis, to clinical subsets of the disease and to the presence of erosions. RESULTS: HLA-Cw*0602 was significantly increased in frequency in PsA (40 vs 26%; P<0.05) and was associated with younger age of onset of psoriasis (P<0.05). There was no significant increase in any of the polymorphisms studied within TNFA, IL10 or TNFRII in the total PsA group. Although the frequency of TNFA allele -238A was not increased in the total PsA group or in patients with a younger age of onset of psoriasis, TNFA allele -238A was absent in the spondyloarthritis group and increased in frequency in patients with peripheral polyarthritis. However, these latter findings could be explained by linkage disequilibrium as all TNFA -238A alleles (23/23) in patients with PsA were HLA-Cw*0602-positive (P<0.0001). CONCLUSIONS: An association between young age of onset of psoriasis and HLA-Cw*0602 is confirmed in patients with PsA. The uncommon TNFA -238A allele is strongly linked to HLA-Cw*0602 and as such is associated with the development of peripheral polyarthritis rather than spondylitis. Further investigation of possible HLA-Cw*0602 linked genes in PsA is warranted.

Adult↗
PubMed2002

Passive protection against Burkholderia pseudomallei infection in mice by monoclonal antibodies against capsular polysaccharide, lipopolysaccharide or proteins.

Burkholderia pseudomallei, the aetiological agent of melioidosis, is endemic in south-east Asia and northern Australia, where it is an important cause of human disease. There is no vaccine available and antibiotic therapy is associated with high relapse rates. A panel of seven monoclonal antibodies (MAbs) that recognise capsular polysaccharide, lipopolysaccharide or proteins was produced and their ability to protect mice passively against experimental melioidosis was evaluated. The MAbs were capable of protecting mice against intra-peritoneal challenge with 10(4) cfu/250 MLD of a virulent strain of B. pseudomallei (NCTC 4845), when pooled, and four of the MAbs were individually protective. However, at a higher B. pseudomallei challenge level of 10(6) cfu none of the MAbs afforded protection and only the anti-exopolysaccharide MAbs produced a significantly delayed time to death.

Animals↗
PubMed2001

Primordial rhythmic bursting in embryonic cochlear ganglion cells.

This study examined the nature of spontaneous discharge patterns in cochlear ganglion cells in embryonic day 13 (E13) to early E17 chicken embryos (stages 39-43). Neural recordings were made with glass micropipettes. No sound-driven activity was seen for the youngest embryos (maximum intensity 107 dB sound pressure level). Ganglion cells were labeled with biotinylated dextran amine in four embryos. In two animals, primary afferents projected to hair cells in the middle region along the length of the basilar papilla in which, in one cell, the terminals occupied a neural transverse position and, in the other, a more abneural location. Statoacoustic ganglion cells showing no spontaneous activity were seen for the first time in the chicken. The proportion of "silent" cells was largest at the youngest stages (stage 39, 67%). In active cells, mean spontaneous discharge rates [9.4 +/- 10.4 spikes (Sp)/sec; n = 44] were lower than rates for older embryos (19 +/- 17 Sp/sec) (Jones and Jones, 2000). Embryos at stages 39-41 evidenced even lower rates (4.2 +/- 5.0 Sp/sec). The most salient feature of spontaneous activity for stages 39-43 was a bursting discharge pattern in >75% of active neurons (33 of 44). Moreover, in 55% of these cells, there was a clear, slow, rhythmic bursting pattern. The proportion of cells showing rhythmic bursting was greatest at the youngest stages (39-42) and decreased to <30% at stage 43. Rate of bursting ranged from 1 to 54 bursts per minute. The presence of rhythmic bursting in cochlear ganglion cells at E13-E17 provides an explanation for the existence of such patterns in central auditory relays. The bursting patterns may serve as a patterning signal for central synaptic refinements in the auditory system during development.

Acoustic Stimulation↗