Biomedical subjects

G R Davies

Publications and source records attributed to G R Davies.

At least 19 recordsLinked to original sources

PubMed2003

Quantitative magnetization transfer mapping of bound protons in multiple sclerosis.

Quantitative analysis of magnetization transfer images has the potential to allow a more thorough characterization of the protons, both bound and free, in a tissue by extracting a number of parameters relating to the NMR properties of the protons and their local environment. This work develops previously presented techniques to produce estimates of parameters such as the bound proton fraction, f, and the transverse relaxation time of the bound pool, T(2B), for the whole brain in a clinically acceptable imaging time. This is achieved by limiting the number of data collected (typically to 10); to collect 28 5-mm slices with a reconstructed resolution of 0.94 x 0.94 mm. The protocol takes 82 sec per data point. The fitting technique is assessed against previous work and for fitting failures. Maps and analysis are presented from a group of seven controls and 20 multiple sclerosis patients. The maps show that the parameters are sensitive to tissue-specific differences and can detect pathological change within lesions. Statistically significant differences in parameters such as T(2B) and f are seen between normal-appearing white matter, multiple sclerosis lesions, and control white matter. Whole-brain histograms of these parameters are also presented, showing differences between patients and controls.

Adolescent↗

PubMed2003

Preliminary magnetic resonance study of the macromolecular proton fraction in white matter: a potential marker of myelin?

We report on a new quantitative magnetization transfer (MT) technique that allows for the in vivo estimation of the macromolecular proton fraction (f) and the bound pool T2 relaxation time (T2b), whilst permitting whole brain coverage. In this pilot study, five subjects with multiple sclerosis (MS) and five healthy controls were studied. Both f and T2b were significantly different between MS lesions and normal control white matter (WM). Relationships between f and T1 relaxation time [Spearmans rank correlation coefficient (r(s)) = -0.97, P < 0.001] and f and the magnetization transfer ratio (MTR; r(s) = 0.80, P < 0.001) were observed. Compared with MTR, f and T2b have the potential advantage of relative independence from MT acquisition protocol while offering more pathologically specific information. In particular, f may provide a more direct indication of myelin content in WM.

Adult↗

PubMed2002

An investigation into the use of pilocarpine as a sialagogue in patients with radiation induced xerostomia.

BACKGROUND: Radiation therapy to the head and neck region can be an effective form of treatment for malignancies. Unfortunately damage to salivary glands may occur. Treatment of resultant dry mouth is at present very poor. The purpose of this pilot study was to investigate whether pilocarpine dissolved in artificial saliva and administered in a mouth spray would be effective in relieving such symptoms. METHODS: Twenty-three patients with radiation induced hyposalivation were recruited for this randomized, double-blind investigation. Subjects were randomly allocated to placebo or control medicaments used for eight weeks. All subjects were evaluated for the severity of their xerostomia associated symptoms prior to administration of the spray and again eight weeks later. RESULTS: The questionnaire and the visual analogue scale did not reveal any improvements in the dry mouth symptoms between cases and controls. Side-effects were reported among cases, mostly mild and tolerable. All patients taking pilocarpine (with base salivary flow rates > 0ml/min) demonstrated improvement in stimulated and unstimulated salivary flow rates. Candida counts decreased among the cases and controls although decrease among the cases was much greater. CONCLUSIONS: The results obtained indicate that provided residual functioning salivary tissue exists, pilocarpine used as formulated is effective and warrants further investigation.

Aerosols↗

PubMed2001

Continuous-wave magnetic resonance imaging of short T(2) materials.

There is growing interest in the use of magnetic resonance imaging (MRI) to examine solid materials where the restricted motion of the probed spins leads to broad lines and short T(2) values, rendering many interesting systems invisible to conventional 2DFT pulsed imaging methods. In EPR T(2) seldom exceeds 0.1 mus and continuous-wave methods are adopted for spectroscopy and imaging. In this paper we demonstrate the use of continuous-wave MRI to obtain 2-dimensional images of short T(2) samples. The prototype system can image samples up to 50 mm in diameter by 60 mm long and has been used to image polymers and water penetration in porous media. Typical acquisition times range between 10 and 40 min. Resolution of 1 to 2 mm has been achieved for samples with T(2) values ranging from 38 to 750 mus. There is the possibility of producing image contrast that is determined by the material properties of the sample.

Journal Article↗

PubMed2001

Interleukins 7 and 12 are expressed in head and neck squamous cancer.

Interleukin 7 (IL-7) and IL-12 have major roles in cell-mediated tumour immunity. In head and neck squamous cell cancer, depressed cell-mediated immunity is well documented and may account for the poor prognosis. This is the first study to assess intratumour expression of IL-7 and IL-12 in head and neck squamous cell cancer (HNSCC). Immunohistochemistry was used to identify IL-7 and IL-12 expression in snap-frozen tumour specimens from 25 patients with HNSCC and the results of immunohistochemical staining were semiquantitatively graded. Both IL-7 and IL-12 were expressed in all tumour samples and expression was not related to tumour stage or site. A trend towards better survival was associated with high expression of IL-7 and IL-12, this being more pronounced with IL 7. The universal expression suggests that the depressed cell-mediated immunity in HNSCC is not caused by reduced production of IL-7 and IL-12. Further studies with larger cohorts, especially of IL-7, are certainly warranted.

Adult↗

PubMed2000

Recurrence and malignant degeneration of 89 cases of inverted papilloma diagnosed in a non-tertiary referral population between 1975 and 1995: clinical predictors and p53 studies.

Eighty-nine patients with sinonasal inverted papilloma presenting between 1975 and 1995 were reviewed with the aims of studying predictors of tumour behaviour and correlating outcome with p53 expression. Correlation of clinical, radiological features and p53 status was made using chi2 and multiple logistic regression analysis with recurrence and malignant degeneration as the main outcome measures. Two patients had synchronous malignancy but no malignant degeneration was seen. There was no significant difference in recurrence between minor intranasal procedures and more extensive surgery for the first event. Younger patients were more likely to recur. (P = 0.0493, odds ratio 0.43). Those who smoked showed a trend towards multiple recurrence. p53 was expressed in 41% but did not predict recurrence. Morbidity was related to the extent of surgery. Inverted papilloma presenting to a non-tertiary centre is more benign than previously reported. Initial management by less extensive endoscopic surgery may reduce morbidity.

Adolescent↗

PubMed1999

Twice-weekly, directly observed treatment for HIV-infected and uninfected tuberculosis patients: cohort study in rural South Africa.

OBJECTIVE: To determine the effectiveness of twice-weekly directly observed therapy (DOT) for tuberculosis (TB) in HIV-infected and uninfected patients, irrespective of their previous treatment history. Also to determine the predictive value of 2-3 month smears on treatment outcome. METHODS: Four hundred and sixteen new and 113 previously treated adults with culture positive pulmonary TB (58% HIV infected, 9% combined drug resistance) in Hlabisa, South Africa. Daily isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice a week to 2 months and HR twice a week to 6 months in the community. RESULTS: Outcomes at 6 months among the 416 new patients were: transferred out 2%; interrupted treatment 17%; completed treatment 3%; failure 2%; and cured 71%. Outcomes were similar among HIV-infected and uninfected patients except for death (6 versus 2%; P = 0.03). Cure was frequent among adherent HIV-infected (97%; 95% CI 94-99%) and uninfected (96%; 95% CI 92-99%) new patients. Outcomes were similar among previously treated and new patients, except for death (11 versus 4%; P = 0.01), and cure among adherent previously treated patients 97% (95% CI 92-99%) was high. Smear results at 2 months did not predict the final outcome. CONCLUSION: A twice-weekly rifampicin-containing drug regimen given under DOT cures most adherent patients irrespective of HIV status and previous treatment history. The 2 month smear may be safely omitted. Relapse rates need to be determined, and an improved system of keeping treatment interrupters on therapy is needed. Simplified TB treatment may aid implementation of the DOTS strategy in settings with high TB caseloads secondary to the HIV epidemic.

AIDS-Related Opportunistic Infections↗

PubMed1999

Periodontal attachment loss in HIV-infected patients is associated with the major histocompatibility complex 8.1 haplotype (HLA-A1,B8,DR3).

Periodontal attachment loss is mediated by overproduction of tumour necrosis factor (TNF) and interleukin (IL)-1, and appears to have a genetic component. The 8.1 major histocompatibility complex (MHC) ancestral haplotype (HLA-A1,B8,TNFA-308(2),DR3) is associated with elevated TNF production and predisposes carriers to several autoimmune/immunopathological disorders, including rapid progression of HIV disease, but not early onset periodontal disease in healthy individuals. Rather a high proportion of subjects with severe periodontal disease carry allele 2 at IL-1A-889 and IL-1B+3953. We predicted that genetic associations may be different or clearer in HIV patients, as they often show elevated production of TNF and IL-1 and periodontal attachment loss. Hence periodontal parameters and IL-1 polymorphisms were assessed in HIV-positive subjects expressing HLA-B8 with or without other markers of the 8.1 haplotype. Of 16 HLA-B8 subjects, 13 demonstrated elevated probing pocket depth and clinical attachment loss. The difference was statistically significant and did not correlate with smoking, age, CD4 T-cell counts, HIV viral load or levels of dental plaque. As TNFA-308 (allele 2) was present in four non-B8 subjects who had minimal attachment loss, it may not mediate the effect of the 8.1 haplotype. Moreover, polymorphisms at IL-1A-889 and IL-1B+3953 did not significantly affect periodontal parameters. Thus a central MHC gene characteristic of the 8.1 haplotype was the clearest determinant of periodontal attachment loss in HIV-infected individuals.

Adult↗

PubMed1999

Non-steroidal anti-inflammatory drugs inhibit Helicobacter pylori-induced human neutrophil reactive oxygen metabolite production in vitro.

BACKGROUND: Helicobacter pylori infection is associated with increased production of gastric mucosal reactive oxygen metabolites which have been implicated in mucosal damage and carcinogenesis. In vitro, neutrophils produce reactive oxygen metabolites following activation by H. pylori. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit neutrophil activation by several factors, e.g. N-formyl-methionyl-leucyl-phenyalanine (f-MLP). AIM: To examine the effect of NSAIDs on H. pylori-induced reactive oxygen metabolite production by human peripheral blood neutrophils. METHODS: Neutrophils were stimulated by H. pylori (NCTC 11637) water extract or f-MLP in the presence or absence of NSAIDs. Reactive oxygen metabolite activity was measured by luminol-enhanced chemiluminescence. RESULTS: H. pylori water extract stimulated a sevenfold increase in chemiluminescence which was inhibited dose-dependently by diclofenac. All six NSAIDs studied (at 10-4 M) significantly inhibited H. pylori-and f-MLP-stimulated neutrophil reactive oxygen metabolite production. Meclofenamic acid and diclofenac had the greatest inhibitory effects on both H. pylori and f-MLP-stimulated neutrophil reactive oxygen metabolite production. The inhibitory effects of other NSAIDs varied with the activation stimulus. NSAIDs did not quench reactive oxygen metabolites generated in a cell-free xanthine:xanthine oxidase assay. CONCLUSION: Several NSAIDs attenuate H. pylori-induced neutrophil reactive oxygen metabolites production in vitro. This may be relevant to a potential chemopreventative role in gastric cancer and to a possible lack of synergy between H. pylori and NSAID use regarding peptic ulceration.

Adult↗

PubMed1999

Emergence of multidrug-resistant tuberculosis in a community-based directly observed treatment programme in rural South Africa.

OBJECTIVE: Although little studied in developing countries, multidrug-resistant tuberculosis (MDR-TB) is considered a major threat. We report the molecular epidemiology, clinical features and outcome of an emerging MDR-TB epidemic. METHODS: In 1996 all tuberculosis suspects in the rural Hlabisa district, South Africa, had sputum cultured, and drug susceptibility patterns of mycobacterial isolates were determined. Isolates with MDR-TB (resistant to both isoniazid and rifampicin) were DNA fingerprinted by restriction fragment length polymorphism (RFLP) using IS6110 and polymorphic guanine-cytosine-rich sequence-based (PGRS) probes. Patients with MDR-TB were traced to determine outcome. Data were compared with results from a survey of drug susceptibility done in 1994. RESULTS: The rate of MDR-TB among smear-positive patients increased six-fold from 0.36% (1/275) in 1994 to 2.3% (13/561) in 1996 (P = 0.04). A further eight smear-negative cases were identified in 1996 from culture, six of whom had not been diagnosed with tuberculosis. MDR disease was clinically suspected in only five of the 21 cases (24%). Prevalence of primary and acquired MDR-TB was 1.8% and 4.1%, respectively. Twelve MDR-TB cases (67%) were in five RFLP-defined clusters. Among 20 traced patients, 10 (50%) had died, five had active disease (25%) and five (25%) were apparently cured. CONCLUSIONS: The rate of MDR-TB has risen rapidly in Hlabisa, apparently due to both reactivation disease and recent transmission. Many patients were not diagnosed with tuberculosis and many were not suspected of drug-resistant disease, and outcome was poor.

Antitubercular Agents↗

PubMed1999

Who fails to complete tuberculosis treatment? Temporal trends and risk factors for treatment interruption in a community-based directly observed therapy programme in a rural district of South Africa.

SETTING: Hlabisa Tuberculosis Programme, Hlabisa, South Africa. OBJECTIVE: To determine trends in and risk factors for interruption of tuberculosis treatment. METHODS: Data were extracted from the control programme database starting in 1991. Temporal trends in treatment interruption are described; independent risk factors for treatment interruption were determined with a multiple logistic regression model, and Kaplan-Meier survival curves for treatment interruption were constructed for patients treated in 1994-1995. RESULTS: Overall 629 of 3,610 surviving patients (17%) failed to complete treatment; this proportion increased from 11% (n = 79) in 1991/1992 to 22% (n = 201) in 1996. Independent risk factors for treatment interruption were diagnosis between 1994-1996 compared with 1991-1993 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.6-2.4); human immunodeficiency virus (HIV) positivity compared with HIV negativity (OR 1.8, 95%CI 1.4-2.4); supervised by village clinic compared with community health worker (OR 1.9, 95%CI 1.4-2.6); and male versus female sex (OR 1.3, 95%CI 1.1-1.6). Few patients interrupted treatment during the first 2 weeks, and the treatment interruption rate thereafter was constant at 1% per 14 days. CONCLUSIONS: Frequency of treatment interruption from this programme has increased recently. The strongest risk factor was year of diagnosis, perhaps reflecting the impact of an increased caseload on programme performance. Ensuring adherence to therapy in communities with a high level of migration remains a challenge even within community-based directly observed therapy programmes.

Adolescent↗

PubMed1998

Pediatric tuberculosis in rural South Africa--value of directly observed therapy.

Tuberculosis is a major cause of mortality and morbidity among children in resource-poor settings. A strategy of community-based, directly observed therapy employed in a rural health district in South Africa since 1991 is described. Most children (75 per cent) diagnosed with tuberculosis were treated in the community and most of them (85 per cent) completed treatment. Supervision was either by clinic-based health workers (26 per cent), community health workers (20 per cent), or volunteer lay people (46 per cent). Among children diagnosed with tuberculosis who were also HIV infected, the case-fatality rate was higher than among the HIV uninfected, and a larger proportion of the HIV infected failed to complete treatment.

Adolescent↗

PubMed1998

Impact of the human immunodeficiency virus epidemic on mortality among adults with tuberculosis in rural South Africa, 1991-1995.

SETTING: In the Hlabisa district tuberculosis programme, South Africa, the prevalence of human immunodeficiency virus (HIV) infection among adults with tuberculosis increased from 36.0% in 1993 to 65.9% in 1997, and the annual tuberculosis caseload increased from 321 in 1991 to 1250 in 1996. OBJECTIVE: To examine the impact of the HIV epidemic on mortality among adults with tuberculosis from 1991 to 1995. METHODS: Data were extracted from the control programme database. As the programme started in July 1991, data for this year were combined with those for 1992. RESULTS: All-cause mortality among all those diagnosed with tuberculosis increased by 45.6%, from 9.2% (55/599) in 1991/92 to 13.4% (96/714) in 1995 (P = 0.02). Among smear-positive patients only, mortality increased by 134%, from 4.4% to 10.3% (P = 0.003). The case-fatality rate (CFR) increased in most age groups of both sexes, the largest increase (157.5%) being among women aged 15-34 years. CFR was highest among those with smear-negative disease (24.7% in 1995). In multifactorial analysis, independent risk factors for mortality were increasing age (P = 0.0001), HIV infection (odds ratio [OR] 3.5, 95 % confidence interval [CI] 2.3-5.4), smear-negative disease (OR 2.5, 95%CI 1.8-3.5), and diagnosis in 1995 vs 1991/92 (OR 1.8, 95%CI 1.2-2.7). Mortality among the HIV infected continued to accrue throughout treatment, whereas non-HIV-infected patients that died did so early in treatment. CONCLUSION: The HIV epidemic is increasing tuberculosis all-cause mortality. As well as having a direct effect on individuals, increased caseloads due to HIV may also contribute to increased mortality by reducing the health system's ability to provide adequate care.

Adolescent↗

PubMed1997

Loss of cell surface microvilli on rat basophilic leukaemia cells precedes secretion and can be mimicked using the calmodulin antagonist trifluoperazine.

OBJECTIVE: We studied changes in cell surface morphology following treatment with secretagogue or trifluoperazine in a mast cell model. MATERIALS AND METHODS: Rat basophilic leukaemia (RBL) cells were treated with antigen and or the calmodulin antagonist, 0-50 microM trifluoperazine (TFP). The release of a secretory granule enzyme, beta-hexosaminidase, into the external medium was used as a measure of secretion. Quantitation of cell surface microvilli was determined by using a computer with input from a digitising tablet from scanning electron micrographs. Cytoskeletal proteins present in microvilli were analysed by confocal immunofluorescence. RESULTS: When RBL cells are stimulated to secrete with an antigen, the cell surface is transformed from a microvillous morphology to a ruffled one. The cell surface rearrangement preceded beta-hexosaminidase secretion: the majority of microvilli disappeared rapidly after stimulation (t1/2 of 39 s) whereas secretion can only be measured after a lag of 47 s. The calmodulin antagonist, TFP did not inhibit antigen-induced secretion or loss of microvilli, however TFP alone caused a similar loss of microvilli but was unable to stimulate or potentiate secretion. The microvilli mostly disappeared within 30 s, and a half-maximal effect occurred at approximately 8 microM TFP. Using immunofluorescence, calmodulin was localized to punctate structures on the dorsal cell surface which presumably correspond to the microvilli, and which also stained for F-actin and myosin I. CONCLUSIONS: Loss of cell surface microvilli on RBL cells precedes secretion and could reflect a cytoskeletal rearrangement which facilitates fusion of secretory granules with the membrane. It can be mimicked using trifluoperazine and we suggest it may involve calmodulin-binding components of the microvillus cytoskeleton such as myosin I.

Animals↗

PubMed1997

Coping with Africa's increasing tuberculosis burden: are community supervisors an essential component of the DOT strategy? Directly observed therapy.

Tuberculosis incidence in Africa is increasing dramatically and fragile health systems are struggling to cope. Potential coping capacity may lie within affected communities but this capacity needs to be harnessed if tuberculosis is to be controlled. Since 1991 all patients with tuberculosis in Hlabisa health district, South Africa have been eligible for community-based directly observed therapy (DOT). Patients are supervised either by a health worker (HW) in a village clinic, or in the community by a community health worker (CHW) or a volunteer lay person (VLP). Tuberculosis incidence increased from 312 cases in 1991 to 1250 cases in 1996. By December 1995, 2622 (87%) of 3006 patients had received DOT, supervised mainly by VLP (56%) but also by HW (28%) and CHW (16%). The proportion supervised by HW fell from 46% in 1991 to 26% in 1995 (P < 0.0001). More patients supervised by VLP (85%) and CHW (88%) than by HW (79%, P = 0.0008) completed treatment. Case-holding by HW declined more between 1991 and 1995 (84% to 71%, P = 0.02) than did case-holding by both CHW (95% to 90%. P = 0.7) and VLP (88% to 84%, P = 0.4). Mortality was similar (4-6%) and stable over time, irrespective of the supervisor. High tuberculosis treatment completion rates are achievable and sustainable for several years in resource-poor settings despite a massively increased case load if community resources are harnessed. Patients may be more effectively supervised by voluntary lay people than by health workers under these circumstances, without being placed at increased risk. These findings suggest that community supervisors may be an essential component of any DOT strategy.

Antitubercular Agents↗

PubMed1997

Molecular epidemiology and transmission dynamics of Mycobacterium tuberculosis in rural Africa.

The relative contribution of reactivated and recently acquired tuberculosis to the disease burden in developing countries is unknown, as are the settings within which most transmission occurs. In an attempt to answer these questions, we combined molecular techniques (restriction fragment length polymorphism analysis) and conventional epidemiology (risk factor analysis and contact tracing) to study 246 consecutive cases of smear-positive tuberculosis in rural South Africa. We estimate that 29-43% of the cases were recently acquired, as they were clustered. We were unable to identify firm transmission links between 73% of clustered cases. Our findings suggest that most smear-positive tuberculosis in rural Africa is both recently acquired and casually transmitted. Tuberculosis control may depend more on promoting early presentation, rapid diagnosis and vaccine development than on chemotherapy.

Adult↗

PubMed1997

Eicosanoids: role in gastrointestinal inflammation and cancer.

This paper contains a brief review of the metabolism and physiological actions of eicosanoids, with a discussion of the potential clinical implications of disturbances in eicosanoid metabolism, particularly in NSAID-induced upper gastrointestinal damage and inflammatory bowel disease. There follows a summary of current evidence for the role of eicosanoids in the pathogenesis of colorectal neoplasia.

Animals↗

PubMed1997

The increasing burden of tuberculosis in rural South Africa--impact of the HIV epidemic.

OBJECTIVE: To determine the impact of the HIV epidemic on tuberculosis caseload in rural South Africa. SETTING: Hlabisa health district, KwaZulu-Natal. METHODS: Demographic and clinical data were extracted from the tuberculosis database for the period, May 1991-June 1995. The attributable fraction of HIV-infected tuberculosis cases was estimated from the prevalence of HIV infection in tuberculosis cases and the prevalence of HIV infection in women attending antenatal clinics. RESULTS: Between 1991 and 1995, the annual tuberculosis caseload increased from 301 to 839 cases. Tuberculosis accounted for 4.7% of all admissions in 1989 and 8.3% in 1995 (P < 0.0001). The incidence of tuberculosis increased from 154/100,000 in 1991, to 413/100,000 in 1995. The proportion with smear-positive pulmonary disease fell from 65% to 56% (P = 0.04), and pleural tuberculosis accounted for 7.5% of disease in 1991 and 18% in 1995 (P = 0.002). The minimum HIV prevalence in patients with tuberculosis increased from 8.7% in 1991 to 28.3% in 1995, and the proportion of tuberculosis cases attributable to HIV infection was estimated to be at least 44% in 1995. CONCLUSION: The burden of HIV-related tuberculosis is increasing rapidly in rural South Africa and is exerting a negative impact. Innovative approaches to control will be needed to cope with it effectively.

AIDS-Related Opportunistic Infections↗