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Biomedical subjects

G D Griffiths

Publications and source records attributed to G D Griffiths.

At least 19 recordsLinked to original sources
PubMed2006

Multiple vaccine and pyridostigmine interactions: effects on EEG and sleep in the common marmoset.

Following active service during the 1990/1991 Gulf conflict, a number of UK and US veterans presented with a diverse range of symptoms, collectively known as Gulf Veterans' Illnesses (GVI). The administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB), given to Armed Forces personnel during the Gulf conflict has been implicated as a possible factor in the aetiology of these illnesses. The possibility that long-term health effects may result from the administration of these vaccines (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B, meningococcal meningitis and cholera) and/or PB, have been investigated using a non-human primate model, the common marmoset. This paper reports the results from two aspects of the study, brain electrical activity (EEG, collected during performance of a touchscreen mediated discrimination task) and sleep. There were no marked long-term changes in EEG or sleep patterns that could be attributed to vaccines and/or PB administration. The changes that were detected were predominantly time related and independent of treatment. Where statistical differences were detected between treatments, the magnitudes of the difference were relatively minor and therefore not regarded as having long term biological significance.

Animals↗
PubMed2006

Multiple vaccine and pyridostigmine interactions: effects on cognition, muscle function and health outcomes in marmosets.

Following active service during the 1990/1991 Gulf Conflict, a number of UK and US veterans presented with a diverse range of symptoms, collectively known as Gulf Veterans Illnesses (GVI). The administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB), given to armed forces personnel during the Gulf Conflict has been implicated as a possible factor in the aetiology of these illnesses. The possibility that long-term health effects may result from the administration of these vaccines (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B, meningococcal meningitis and cholera) and/or PB, have been investigated using a non-human primate model, the common marmoset. This paper reports the results from three aspects of the study, cognitive behaviour (performance of a touchscreen mediated discrimination task), muscle function (performance of a simple strength test) and general health. There were no marked long-term changes in cognition, muscle function or health that could be attributed to vaccines and/or PB administration. Statistical differences related to treatments were only observed in two aspects of cognition and one of clinical chemistry. These changes were transient in nature and their magnitude were minor and, in consequence, was not regarded as having long-term biological significance.

Acetylcholinesterase↗
PubMed2006

Modified virtual reality technology for treatment of amblyopia.

PURPOSE: The conventional patching/occlusion treatment for amblyopia sometimes gives disappointing results for a number of reasons: it is unpopular, prolonged, frequently resulting in poor or noncompliance, and also disrupts fusion. The aim of this research was to develop a novel virtual-reality (VR)-based display system that facilitates the treatment of amblyopia with both eyes stimulated simultaneously. METHODS: We have adopted a multidisciplinary approach, combining VR expertise with a team of ophthalmologists and orthoptists to develop the Interactive Binocular Treatment (I-BiT) system. This system incorporates adapted VR technology and specially written software providing interactive 2D and 3D games and videos to the patient via a stereo (binocular) display, and a control screen for the clinician. RESULTS: We developed a prototype research system designed for treatment of amblyopia in children. CONCLUSIONS: The result is a novel way to treat amblyopia, which allows binocular treatment. It is interactive, and as it is partially software based, can be adapted to suit the age/ability, and needs of the patient. This means that the treatment can be made captivating and enjoyable. Further research is on-going to determine the efficacy of this new modality in the treatment of amblyopia.

Amblyopia↗
PubMed2006

Preliminary results from the use of the novel Interactive binocular treatment (I-BiT) system, in the treatment of strabismic and anisometropic amblyopia.

BACKGROUND: We have developed a novel application of adapted virtual reality (VR) technology, for the binocular treatment of amblyopia. We describe the use of the system in six children. METHODS: Subjects consisted of three conventional treatment 'failures' and three conventional treatment 'refusers', with a mean age of 6.25 years (5.42-7.75 years). Treatment consisted of watching video clips and playing interactive games with specifically designed software to allow streamed binocular image presentation. RESULTS: Initial vision in the amblyopic eye ranged from 6/12 to 6/120 and post-treatment 6/7.5 to 6/24-1. Total treatment time was a mean of 4.4 h. Five out of six children have shown an improvement in their vision (average increase of 10 letters), including those who had previously failed to comply with conventional occlusion. CONCLUSIONS: Improvements in vision were demonstrable within a short period of time, in some children after 1 h of treatment. This system is an exciting and promising application of VR technology as a new treatment for amblyopia.

Amblyopia↗
PubMed2005

A simple method for assessing muscle function in common marmosets.

A novel method of assessing muscle function in the common marmoset was developed as part of a multidisciplinary long-term study. The method involved home cage presentation of a weight-pulling task. Over a 4-5 month period, 38 of 42 animals were successfully trained to displace weights of up to 920 g (mean 612+/-20 g). Performance, following initial training, was stable and independent of gender or body weight.

Animals↗
PubMed2004

Randomized clinical trial of distal anastomotic interposition vein cuff in infrainguinal polytetrafluoroethylene bypass grafting.

BACKGROUND: The aim was to examine the effect of a Miller vein cuff at the distal anastomosis on the medium- to long-term patency and limb salvage rates of femoral to above-knee and femoral to below-knee popliteal artery polytetrafluoroethylene (PTFE) bypasses. METHODS: This study involved extended follow-up of the original cohort of patients included in a previously reported multicentre randomized clinical study. Outcome measures were bypass graft patency and limb salvage. RESULTS: Two hundred and sixty-one bypass operations were originally randomized. For this study, full data were available on 235 (120 with a Miller cuff, 115 without). The cumulative 5-year patency rate for above-knee bypasses with a Miller cuff was 40 per cent, compared with 42 per cent for non-cuffed bypasses (P = 0.702). The cumulative 3-year patency rate for below-knee bypasses with a Miller cuff was 45 per cent, compared with 19 per cent for non-cuffed bypasses (P = 0.018). A Miller cuff had no significant effect on limb salvage for above-knee or below-knee bypasses. CONCLUSION: Three-year patency rates of femoral to below-knee popliteal PTFE bypasses were improved by a Miller cuff. Miller cuffs had no effect on patency rates for femoral to above-knee popliteal bypasses at 5 years and did not improve limb salvage in either group.

Aged↗
PubMed2003

Growth factors in the treatment of diabetic foot ulcers.

BACKGROUND: Chronic foot ulceration is a major source of morbidity in diabetic patients. Despite traditional comprehensive wound management, including vascular reconstruction, there remains a cohort of patients with non-responding wounds, often resulting in amputation. These wounds may benefit from molecular manipulation of growth factors to enhance the microcirculation. METHODS: A review of the current literature was performed using Pubmed, with secondary references obtained from key articles. RESULTS AND CONCLUSION: There has been a generally disappointing clinical outcome from growth factor trials, although topical platelet-derived growth factor has shown significant benefit and should be considered in non-healing, well perfused ulcers after failure of conventional wound care. The modulatory role of the extracellular matrix in the cellular response to growth factors and data from regenerative-type fetal wound healing are further areas of interest. The chemical induction of microvessel formation may become a future therapeutic option.

Diabetic Foot↗
PubMed2001

An extensive monoclonal antibody panel for the phenotyping of leukocyte subsets in the common marmoset and the cotton-top tamarin.

New World monkeys are valuable animal models to study human diseases. To determine the phenotype of cells involved in immune responses, we used flow cytometry to screen a large panel of anti-human monoclonal antibodies (mAb) for cross-reactivity with cells of the common marmoset and the cotton-top tamarin. Certain antigens (e.g., CD2, CD8, CD20) are well conserved. However, CD10, CD23, and CD33 showed a clear discrepancy in their reaction patterns in both species, indicating that significant differences on the epitope level occurred during evolution. Epstein-Barr virus-transformed B-cell lines were shown to be a valuable tool for screening B-cell-specific reagents. In some cases, fluorescein isothiocyanate (FITC) and phycoerythrin (PE) modification of mAbs had a negative effect on the binding capacity, which stressed the importance of choosing the right label. Despite the fact that some CD antigens were not detected, adequate numbers of cross-reactive mAbs were identified to perform extensive studies on immunological functions in both the common marmoset and the cotton-top tamarin.

Animals↗
PubMed2001

Variability in measurement of internal carotid artery stenosis by arch angiography and duplex ultrasonography--time for a reappraisal?

OBJECTIVES: to determine the inter- and intra-observer variability of ICA stenosis measurement using duplex, ECST and NASCET methods. DESIGN: a retrospective review of arch angiograms and carotid duplex scans in 50 patients. MATERIALS AND METHODS: carotid stenoses were calculated by three independent observers according to NASCET and ECST methods. Variation between observers for NASCET and ECST was determined. For each observer, the variation between NASCET and ECST was determined. The variation between duplex and both NASCET and ECST was determined. RESULTS: inter-observer agreement on the degree of ICA stenosis was clinically and statistically good for NASCET but was poorer for ECST. For each observer, comparison between NASCET and ECST showed 95% limits of agreement of around 50 percentage points. Comparison of duplex with NASCET and ECST showed similar 95% limits of agreement. CONCLUSIONS: arch angiography allows reproducible measurement of carotid stenosis by the NASCET method between different observers. For the ECST method, reproducibility is not so good. Variations in results between NASCET and ECST and between angiography and duplex are significant. In view of the similar results of the NASCET and ECST trials, this suggests that degree of stenosis may only be a surrogate marker for outcome following carotid endarterectomy.

Angiography↗
PubMed2000

Characterization of ricin heterogeneity by electrospray mass spectrometry, capillary electrophoresis, and resonant mirror.

Electrospray mass spectrometry (ES/MS), capillary-zone electrophoresis (CZE), capillary isoelectric focusing (CIEF), and multianalyte resonant mirror are used to evaluate the heterogeneity of samples of ricin toxins extracted from five horticultural varieties of Ricinus communis seeds: R. communis zanzibariensis, carmencita, impala, sanguineus, and gibsonii. The investigation is also extended to the geographical provenance of the beans. Combining mass spectrometry, CE techniques, and resonant mirror results in a powerful analytical tool capable to characterize and differentiate between different varieties of ricin toxins. Each technique complements the others, adding another level of information. This study reveals a large extent of heterogeneity for each cultivar, demonstrating that ricin toxins consist of a series of glycosylated proteins most likely originating from a multigene family. By combining these techniques, it is possible to differentiate between zanzibariensis and the other four varieties, and that variations in the functional characteristics may be observed between the different cultivars. This study demonstrates that knowledge of the variety of R. communis beans used and their geographical provenance is essential before any type of investigation of ricin toxins is carried out. Consequently, any unusual behavior observed can only be attributed to that particular cultivar studied and not automatically extended to include all R. communis varieties.

Biosensing Techniques↗
PubMed1999

Comparison of the quality of protection elicited by toxoid and peptide liposomal vaccine formulations against ricin as assessed by markers of inflammation.

Ricin is a very toxic substance which inhibits protein synthesis and produces severe tissue damage and inflammation. It is very potent when inhaled as an aerosol and protection has been examined in a series of studies using vaccine candidates including a formaldehyde inactivated ricin toxoid and the A chain of ricin, a polypeptide equivalent to half of the toxin molecule. Initially, subcutaneous injections of both compounds were found to protect against inhaled ricin but not without some subsequent adverse signs. Intra-pulmonary vaccination using liposomal formulations of these compounds was investigated with a view to improving lung condition following challenge. Using the humoral and local pulmonary immune responses as indices of vaccine performance, no significant difference between toxoid or peptide vaccines was found. In the third and current study, the quality of lung protection by vaccines was assessed using markers of inflammation. Thus, the profiles of inflammatory cell and protein influx into the lung were determined following intratracheal (i.t.) challenge with ricin of rats treated with liposomal vaccine formulations. Results showed that liposomal ricin toxoid offered a better quality of protection with a significantly lower influx of polymorphonuclear leucocytes (neutrophils) and little pulmonary oedema compared with the A chain/liposome formulation. Further, there was no significant difference between the quality of protection offered by the A chain when administered subcutaneously or locally into the lung by i.t. instillation. Liposomal ricin toxoid is a good candidate vaccine and optimised pulmonary delivery by inhalation should be further examined.

Animals↗
PubMed1998

Local and systemic responses against ricin toxin promoted by toxoid or peptide vaccines alone or in liposomal formulations.

The objective of this study was to develop a vaccine which would ultimately protect man from the lethal effects of inhaled ricin toxin. Porton rats have previously been protected from lethal quantities of inhaled ricin by subcutaneous (s.c.) ricin toxoid vaccine, but not without lung damage. This situation might be improved by an alternative vaccine such as the A chain of ricin, already known to protect against inhaled ricin. Another option would be to improve respiratory tract immunity by local vaccination in conjunction with liposomal formulation with a view to enhancing lung secretion of immune IgA. While boosted s.c. doses of ricin toxoid or A chain produced indistinguishable systemic immune responses 3 weeks later, when delivered by the intratracheal (i.t.) route, the A chain failed to elicit a specific immune response, unlike ricin toxoid. This situation was overcome by liposomal formulations and although ricin toxoid was readily encapsulated in liposomes, A chain was not. However, by simply mixing A chain and liposomes in the same weight ratio determined for liposomal toxoid, systemic immune responses for each formulation were indistinguishable 1 week after boosting. Ricin antibody responses in lung fluid monitored 1, 3, 7 and 14 days after i.t. challenge with ricin were statistically indistinguishable, but the group vaccinated with liposomal toxoid secreted 28.7% IgA compared with 0.9-14.9% for the A chain liposomal group. From this, it might be anticipated that the lungs would be better protected by liposomally-encapsulated ricin toxoid than by the A chain-liposome mixture.

Animals↗
PubMed1998

Histological study of colonic ischaemia after aortic surgery.

BACKGROUND: Colonic ischaemia is a well documented complication of abdominal aortic reconstruction. In this prospective study patients had routine preoperative and postoperative colonoscopy and biopsy, in order to determine the true incidence and implications. METHODS: Fifty-six patients undergoing elective infrarenal aortic surgery, 28 for aneurysm and 28 for occlusive disease, had colonoscopy and biopsy before and 1 week after operation. RESULTS: Colonic ischaemia was identified histologically in biopsies from 16 (30 per cent) of 53 patients. Almost half the patients had normal macroscopic appearances. Two factors exhibited a statistically significant association with the development of ischaemia: prolonged cross-clamp time (P < 0.05) and postoperative diarrhoea (P< 0.001). Co-morbidity was much higher in patients with colonic ischaemia (P< 0.005). Overall morbidity was significantly greater in the aneurysm group (P < 0.05). CONCLUSION: Colonic ischaemia is common after aortic reconstruction. When suspected, colonoscopy with biopsy is diagnostic.

Aged↗
PubMed1997

Liposomally-encapsulated ricin toxoid vaccine delivered intratracheally elicits a good immune response and protects against a lethal pulmonary dose of ricin toxin.

A small study was performed to examine whether the instillation of ricin toxoid vaccine into the lungs of Porton rats offered protection from lethal effects of subsequent intratracheal challenge with ricin toxin. Further the immune response to liposomally-encapsulated vaccine and the protection offered was compared with vaccine either adsorbed to Alhydrogel adjuvant or as a simple aqueous solution. The formaldehyde-treated ricin toxin vaccine (RTV) was administered at two dose levels, 500 and 100 micrograms kg-1 body weight to groups of rats, on two occasions by intratracheal instillation. Liposomally-encapsulated vaccine (LRTV) produced a higher titre of ricin-specific antibodies than Alhydrogel-vaccine (ARTV) and vaccine solution. When challenged with 3 LD50 of ricin by intratracheal instillation 7 weeks after the second vaccine instillation, all rats in both LRTV dose groups survived with minimal signs of incapacitation. Analysis of antibody secretion by spleen cells, 14 days post challenge, showed that the IgG isotype in the LRTV group was significantly higher than that in the ARTV and RTV groups and also that the proportion of specific IgA in lung fluid was higher in the LRTV group than in the ARTV and RTV groups. The results of this study indicate that effective vaccinations against inhaled ricin could be achieved with liposomally-encapsulated ricin toxoid, via the lung and should be investigated further.

Administration, Inhalation↗
PubMed1996

Morphology of ricin and abrin exposed endothelial cells is consistent with apoptotic cell death.

Cultures of bovine pulmonary endothelial (BPE) cells were exposed to LC70 doses of ricin or abrin (15.5 and 4.5 pM respectively) over a period of up to 40 h. The viability of the cultures (as determined by the neutral red (NR) dye retention assay) declined after 6 h exposure to the toxins. From 15 h onwards, cellular material in toxin exposed cultures became detached from the substratum of the culture vessels. Hoffman modulation contrast photomicrography showed that this process was due to ricin and abrin exposed cells collapsing into membrane bound vesicles which retained the NR dye, became detached and floated into the medium. These apoptotic-like structural changes were further investigated by transmission electron microscopy (TEM) and by agarose gel electrophoresis of DNA from control and exposed cultures. Many of the characteristic changes associated with apoptotic cell death were seen using TEM, including heterochromatin condensation at the nuclear periphery, crenulation of the nuclear membrane and progressive degeneration of residual nuclear and cytoplasmic structures. The plasma membrane of many cells remained intact, and contained nuclear and cytoplasmic debris. Agarose gel electrophoresis of DNA extracted from toxin-treated cells revealed oligonucleosome sized DNA fragments, characteristic of apoptosis, from adherent cells at 7 h and both adherent and floating populations when harvested from 15 h; DNA from unexposed control cells did not show this fragmentation. The identification of apoptosis as being a significant additional mechanism of toxicity following exposure to ricin and abrin holotoxins raises the possibility of developing new therapeutic strategies against poisoning by these phytotoxins.

Abrin↗
PubMed1995

Protection against inhalation toxicity of ricin and abrin by immunisation.

1. Abrin and ricin are highly toxic plant proteins which are very similar in structure and function and inhibit protein synthesis in eukaryotes. 2. Rats have been immunised against either toxin using formaldehyde-toxoids by three subcutaneous injections at intervals of 3 weeks. For abrin, serum titres in 14 out of 15 rats were raised to between 1:12800 and 1:51200 after two injections, 6 weeks from the start of the experiment. Titres of between 1:256 and 1:1024 were also measured in lung washes after challenge with active abrin toxin. 3. The three major antibody classes, IgG, IgM and IgA were present in the immune sera but IgG and IgA only were detected in lung washes. The proportion of IgA to IgG was higher in the lung fluid than in sera. Rats immunised by abrin toxoid were protected against 5 LCt50's of abrin by inhalation but others exposed to ricin were not. 4. For ricin, serum titres ranged from 1:800 to 1:25600 after two injections and after a third injection the titre range was the same but population samples were weighted towards the higher titres. All rats immunised with ricin toxoid survived the challenge of 5 LCt50's of ricin toxin by inhalation over the observation period of 28 days post-challenge. 5. Representative immunised rats (abrin toxoid) were taken at various times post-exposure, humanely killed and tissues were examined for pathological changes. It was concluded that an apparently severe lung lesion occurred at a later time than in non-immunised, toxin challenged rats. This damage was not lethal over the experimental observation periods. 6. Immunisation by the sub-cutaneous route therefore protects against lethality from challenge by inhalation of ricin or abrin toxins but does not prevent significant lung damage.

Abrin↗
PubMed1994

Examination of the toxicity of several protein toxins of plant origin using bovine pulmonary endothelial cells.

The bovine pulmonary endothelial (BPE) cell line was examined as a model to study the toxicity of ricin and abrin toxins currently under investigation. The BPE cell line was examined because ricin has been shown to bind to endothelial cells. Cell viability was assessed using several different biochemical parameters including growth (DNA by binding of gentian violet stain), mitochondrial function (succinate dehydrogenase activity) using MTT and lysosomal integrity (neutral red retention assay). In order to compare toxicities and investigate potential protective compounds, concentrations of toxins causing death of 50% and 70% of the (control) cell population (LC50 and LC70, respectively) were determined. It is concluded that while ricin and abrin share a common mechanism of action ricin is slightly less toxic than abrin. BPE cells are a good model for future mechanistic studies and particularly for initial phase screening of potentially therapeutic compounds. Carbohydrates were used in an attempt to examine which receptor types were involved in the binding and uptake of ricin and abrin by the cell line. It was found that only high concentrations of galactose prevented lethality while mannose apparently had no effect. Furthermore, the molar excess of carbohydrate to toxin required in order to achieve protection indicated that this would be an impractical approach to adopt in vivo.

Abrin↗