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Biomedical subjects

J Paul

Publications and source records attributed to J Paul.

At least 19 recordsLinked to original sources
PubMed2006

Invasive group A streptococcal infection in injecting drug users and non-drug users in a single UK city.

OBJECTIVES: Injecting drug users (IDU) represent an increasing proportion of patients with invasive group A streptococcal (GAS) disease. Our aims were to characterise the clinical presentation and strains causing GAS bacteremia in IDU from a single UK city (Brighton and Hove), and to compare this patient group with non-drug users (non-DU) with GAS bacteremia. METHODS: Consecutive GAS blood culture isolates from twenty-two IDU and twenty-two non-DU presenting to the city hospital were studied. Clinical features, strain emm typing and superantigen toxin genotyping were investigated. RESULTS: GAS invasive disease presented differently in IDU compared to non-DU with a predominance of injection site abscesses and lower mortality in IDU. GAS strains from IDU were predominantly emm82 and emm83 types, which are uncommon in the UK and emm82 strains appeared clonal. The non-DU GAS strains demonstrated a broader range of emm types including most frequently emm1 and emm89. There was no major difference in superantigen gene profile between the isolate groups. CONCLUSION: The distinct presentation of invasive GAS disease in IDU compared with non-DU was associated with distinct emm types, a predominance of abscesses, and low mortality, although the small numbers preclude definitive conclusions. Further study is required to establish if these findings reflect strain differences or epidemiological differences in colonisation patterns and injecting practice.

Adolescent↗
PubMed2006

Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies.

The prognostic impact of p53 immunostaining in a large series of tumours from epithelial ovarian cancer patients in a two-centre study was analysed. The study population (n=476) comprised of a retrospective series of 188 patients (Dutch cohort) and a prospective series of 288 patients (Scottish cohort) enrolled in clinical trials. P53 expression was determined by immunohistochemistry on tissue microarrays. Association with progression-free survival (PFS) and overall survival (OS) was analysed by univariate and multivariate Cox regression analysis. Aberrant p53 overexpression was significantly associated with PFS in the Dutch and Scottish cohorts (P=0.001 and 0.038, respectively), but not with OS in univariate analysis. In multivariate analysis, when the two groups were combined and account taken of clinical factors and country of origin of the cohort, p53 expression was not an independent prognostic predictor of PFS or OS. In this well-powered study with minimal methodological variability, p53 immunostaining is not an independent prognostic marker of clinical outcome in epithelial ovarian cancer. The data demonstrate the importance of methodological standardisation, particularly defining patient characteristics and survival end-point data, if biomarker data from multicentre studies are to be combined.

Adult↗
PubMed2006

SCOTROC 2A: carboplatin followed by docetaxel or docetaxel-gemcitabine as first-line chemotherapy for ovarian cancer.

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

Adult↗
PubMed2006

Contamination of disposable tonometer prisms during tonometry.

AIM: Due to the theoretical possibility of prion transmission in applanation tonometry, many ophthalmological units in the United Kingdom now use disposable tonometer prisms. We have investigated the potential for bacterial and viral transmission from the health practitioner to the patient via disposable prisms. METHODS: All staff who perform applanation tonometry at the Sussex Eye Hospital (SEH) received a questionnaire to evaluate if the applanating face of the prism is touched during tonometry and the ease of use of the disposable prism compared to the reusable prisms that were previously used. We then cultured prisms handled by a random sample of staff members for common bacteria. Finally, we constructed a model to investigate the possibility of interpatient adenoviral transmission via disposable tonometer prisms. RESULTS: The questionnaire revealed that almost 50% of the staff admit to touching the applanating face of the tonometer prism prior to applanation. Cultures of the prisms grew a range of bacteria including Staphylococcus epidermidis, Staphylococcus aureus, and Bacillus species. The viral model suggested that adenovirus could be transmitted by applanation tonometry. CONCLUSION: The use of disposable prisms for applanation tonometry may reduce the risk of prion transmission but is not bacteriologically or virologically aseptic. This is a potential infection risk to patients.

Adenoviridae↗
PubMed2005

A randomised comparison of treosulfan and carboplatin in patients with ovarian cancer: a study by the Scottish Gynaecological Cancer Trials Group (SGCTG).

The management of older and unfit women with advanced ovarian cancer requires post-operative chemotherapy but many of these patients are not suitable for high-dose cisplatin-based regimes. Carboplatin has been an easier alternative and can be given in the ambulatory setting. Historical data suggests that oral alkylating agents to be just effective with similar efficacy. In this study we have compared platinum-based carboplatin to the alkylating agent treosulfan in a population unfit to receive high-dose cisplatin. The trial randomised patients to either intravenous carboplatin or treosulfan as single agent. The trial was stopped prematurely after the interim analysis showed improved survival and response rates in the carboplatin arm. We conclude that carboplatin is a safe and effective drug in a population that is unfit for high-dose cisplatin. Treosulfan showed limited activity but may be considered along with other oral drugs in limited circumstances. With the exception of myelosuppression, toxicity was mild in both arms. Carboplatin remains the gold standard in this older and less fit group of patients.

Aged↗
PubMed2005

Optical spectra of lactoperoxidase as a function of solvent.

The iron of lactoperoxidase is predominantly high-spin at ambient temperature. Optical spectra of lactoperoxidase indicate that the iron changes from high-spin to low-spin in the temperature range from room temperature to 20 K. The transformation is independent of whether the enzyme is in glycerol/water or solid sugar glass. Addition of the inhibitor benzohydroxamic acid increases the amount of the low-spin form, and again the transformation is independent of whether the protein is in an aqueous solution or a nearly anhydrous sugar. In contrast to lactoperoxidase, horseradish peroxidase remains high-spin over the temperature excursion in both solvents and with addition of benzohydroxamic acid. We conclude that details of the heme pocket of lactoperoxidase allow ligation changes with temperature that are dependent upon the apoprotein but independent of solvent fluctuations. At low pH, lactoperoxidase shows a solvent-dependent transition; the high-spin form is predominant in anhydrous sugar glass, but in the presence of water, the low-spin form is also present in abundance. The active site of lactoperoxidase is not as tightly constrained at low pH as at neutrality, though the enzyme is active over a wide pH range.

Binding Sites↗
PubMed2005

Congenital epulis.

Congenital epulis or gingival granular cell tumour is a rare lesion occurring in the newborn, affecting females eight times more than males and arising more commonly from the maxillary than the mandibular alveolar ridge. We report the case of a five-day-old girl who presented to us with a large mass arising from the gingival mucosa of the mandible, causing feeding difficulty. Immediate surgical excision was followed by an uneventful recovery. The case is reported to make clinicians aware of this uncommon but easily treatable condition.

Female↗
PubMed2005

Space geodetic evidence for rapid strain rates in the New Madrid seismic zone of central USA.

In the winter of 1811-1812, near the town of New Madrid in the central United States and more than 2,000 km from the nearest plate boundary, three earthquakes within three months shook the entire eastern half of the country and liquefied the ground over distances far greater than any historic earthquake in North America. The origin and modern significance of these earthquakes, however, is highly contentious. Geological evidence demonstrates that liquefaction due to strong ground shaking, similar in scale to that generated by the New Madrid earthquakes, has occurred at least three and possibly four times in the past 2,000 years (refs 4-6), consistent with recurrence statistics derived from regional seismicity. Here we show direct evidence for rapid strain rates in the area determined from a continuously operated global positioning system (GPS) network. Rates of strain are of the order of 10(-7) per year, comparable in magnitude to those across active plate boundaries, and are consistent with known active faults within the region. These results have significant implications for the definition of seismic hazard and for processes that drive intraplate seismicity.

Journal Article↗
PubMed2005

Specific properties of heavy fraction of mitochondria from human-term placenta - glycerophosphate-dependent hydrogen peroxide production.

Mitochondrial respiratory chain enzyme Complexes are present in placenta at proportion similar to other tissues with exception of glycerophosphate dehydrogenase (mGPDH) which is expressed at a very high rate. As shown by Western blot quantification and respiratory chain enzyme activity measurements, the specific content of mGPDH is similar to that of succinate dehydrogenase or NADH dehydrogenase. Using fluorometric probe dichlorodihydrofluorescein diacetate we found that placental mitochondria display high rate of glycerophosphate-dependent hydrogen peroxide production. This was confirmed by oxygraphic detection of glycerophosphate-induced, KCN- or antimycin A-insensitive oxygen uptake. Hydrogen peroxide production by mGPDH was highly activated by one-electron acceptor, potassium ferricyanide and it was depressed by inhibitors of mGPDH and by cytochrome c. Our results indicate that mGPDH should be considered as an additional source of reactive oxygen species participating in induction of oxidative stress in placenta.

Animals↗
PubMed2005

A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer.

Menopausal symptoms are a major survivorship issue for patients treated for breast cancer. There are increasing concerns over the use of hormone replacement therapy (HRT) in this setting and a growing consumer interest in "natural" therapies. It had been suggested that soy phyto-oestrogens might be beneficial in the treatment of menopausal symptoms. Seventy-two patients with a histologically confirmed pre-existing diagnosis of breast cancer who were having menopausal symptoms were randomised between 12 weeks of treatment with soy capsules or placebo. Quality of life and menopausal symptom scores were assessed at baseline, 4, 8 and 12 weeks. There was no statistical difference in menopausal symptom scores or quality of life between the two arms of the study.

Adult↗
PubMed2004

Compact sources as the origin of the soft gamma-ray emission of the Milky Way.

The Milky Way is known to be an abundant source of gamma-ray photons, now determined to be mainly diffuse in nature and resulting from interstellar processes. In the soft gamma-ray domain, point sources are expected to dominate, but the lack of sensitive high-resolution observations did not allow for a clear estimate of the contribution from such sources. Even the best imaging experiment revealed only a few point sources, accounting for about 50% of the total Galactic flux. Theoretical studies were unable to explain the remaining intense diffuse emission. Investigating the origin of the soft gamma-rays is therefore necessary to determine the dominant particle acceleration processes and to gain insights into the physical and chemical equilibrium of the interstellar medium. Here we report observations in the soft gamma-ray domain that reveal numerous compact sources. We show that these sources account for the entirety of the Milky Way's emission in soft gamma-rays, leaving at most a minor role for diffuse processes.

Journal Article↗
PubMed2004

Bleomycin, vincristine, cisplatin/bleomycin, etoposide, cisplatin chemotherapy: an alternating, dose intense regimen producing promising results in untreated patients with intermediate or poor prognosis malignant germ-cell tumours.

Patients with poor and intermediate prognosis metastatic germ-cell tumours (MGCTs) are at a significant risk of relapse after standard platinum-based chemotherapy. Novel treatment regimens are required to improve survival. Dose intense, alternating combinations of drugs with known activity in germ-cell tumours represents one approach. In all, 43 patients with IGCCCG intermediate/poor prognosis MGCT were treated with a dose intense regimen alternating bleomycin, vincristine, cisplatin (BOP) with bleomycin, etoposide, cisplatin (BEP) to a maximum of three cycles. Data were collected on the maintenance of dose intensity, toxicity, response, progression-free (PFS) and overall survival (OS). The complete response rate was 58%; a further 7% of patients being rendered disease free by resection of viable residual tumour. With a median follow-up of more than 4 years in surviving patients, 3-year OS and PFS rates of 81% (95% CI: 66-91%) and 72% (95% CI: 56-83%) are seen, respectively. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) was well tolerated, with 86% of patients completing all planned courses. Toxicity was predominantly haematological with common toxicity criteria grade III neutropenia in 90% of patients. Cisplatin neuropathy and bleomycin-induced pulmonary toxicity represented the most significant nonhaematological toxicity. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) represents a practicable, well-tolerated, dose intense chemotherapy regimen with significant activity in intermediate and poor prognosis MGCT.

Adolescent↗
PubMed2004

Prospects for cleaning ash in the acidic effluent from bioleaching of sulfidic concentrates.

Leaching of ashes in sulfuric acid (pH 1.0, liquid-to-solid (L/S) ratio 10:1, 25 degrees C) has been characterized with respect to the neutralizing capacity and the dissolution of dominant ions and trace elements. The conditions mimic the oxidation stage of a biohydrometallurgical process for base metal production from sulfidic mineral concentrates. Direct acid leaching of ash, integrated with this metallurgical process, offers a feasible route to the sustainable handling of metal-rich ashes. The treated ash will be deposited together with the inert mineral residue. Cd, Co, Cu, Ni and Zn are effectively leached and can be recovered utilizing existing hydrometallurgical technology, but the recovery of other readily dissolved metals, notably Mn, U and V, requires that additional steps are implemented. We make two recommendations for industrial processes. The first is to replace limestone with ash from biofuels, except peat, for pH control in biohydrometallurgical processing. This requires a modest increase of fresh alkali compared with limestone. The second is to implement sulfuric acid leaching of fly ash from the combustion of solid waste and other metal-rich fuels (used wood, tires), thereby avoiding costly ash-deposits. There is a significant economic incentive for these changes, since no costly ash-deposits and less limestone will be needed.

Hazardous Waste↗
PubMed2004

Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin.

BACKGROUND: Nitric oxide (NO) has a wide range of functions in the skin, and topical NO donors have several potential clinical applications. However, currently available donors are either unstable on the skin surface, release low concentrations of NO, or have a short duration of action. Endogenous S-nitrosothiols (RSNOs) store and transport NO within the body and can be used as exogenous sources of NO. OBJECTIVES: To study in vitro and in vivo the chemical and biological behaviour of two RSNO species, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC), in an easily applied hydrogel, and to correlate dermal nitrite concentration with erythema following application of the RSNOs. To assess the suitability of GSNO and SNAC as biologically effective NO donors for clinical research and as potential therapeutic agents. METHODS/PATIENTS: GSNO (0.3 mol g(-1)) and SNAC (0.6 mol g(-1)) were incorporated in Synperonic F-127 hydrogels (Uniquema, Belgium). The in vitro kinetics of decomposition were measured by spectrophotometry at 37 degrees C. The RSNO-containing hydrogels were applied to the forearm skin of eight subjects. Blood flow was measured by laser Doppler for 3 h following application of NO donors and dermal nitrite simultaneously measured in microdialysate in four subjects. RESULTS: The mean peak blood flow achieved was 250. At blood flow values of < 250, dermal nitrite correlated closely with blood flow and could be defined by the equation: blood flow = (nitrite concentration x 0.66) + 120, (P = 0.013). At higher blood flows there was a paradoxical fall in dermal nitrite concentration. CONCLUSIONS: Topical RSNOs produce a consistent, sustained and biologically effective release of NO on human skin in vivo, which offers advantages over currently available topical NO donors. Dermal nitrite concentration--the oxidation product of NO--is directly correlated with blood flow at low and moderate levels of blood flow. At high levels of blood flow, there is a reduction in dermal nitrite, which is presumed to be due to increased blood scavenging.

Acetylcysteine↗
PubMed2004

A randomized study (WOS MM1) comparing the oral regime Z-Dex (idarubicin and dexamethasone) with vincristine, adriamycin and dexamethasone as induction therapy for newly diagnosed patients with multiple myeloma.

Whilst infusional vincristine, adriamycin and dexamethasone (VAD) is an effective treatment for patients with multiple myeloma (MM), administration may be complicated by line-associated infections and thromboses. The oral regime, Z-Dex (idarubicin and dexamethasone) has been shown to be efficacious in MM. We conducted a randomized study comparing Z-Dex with VAD as induction therapy in newly diagnosed MM patients. A total of 106 patients (median age, 56 years; range: 37-73; Durie-Salmon stage II/III) were randomized to receive four to six cycles of Z-Dex or VAD. Central line complications were reported in 38 patients on 57 cycles, primarily because of infection. Neutropenia (all grades) was more common in the Z-Dex arm (P = 0.009) although grade III/IV neutropenia was not significantly different between the treatment groups (P = 0.06). Infections (all grades) were more commonly seen in the VAD arm (P = 0.001) although grade III/IV infections were not significantly different between the two groups (P = 0.081). The responses to therapy (complete/partial response) in evaluable patients were: VAD 74% vs. Z-Dex 58%, with an estimated difference in response of 16% (95% CI -2-33, P = 0.075). VAD recipients (15%) suffered early treatment-related mortality compared with 12% of Z-Dex recipients. Overall, 45 patients have died: disease progression (Z-Dex n = 13, VAD n = 10), regimen-related toxicity (Z-Dex n = 2, VAD n = 2), infection (Z-Dex n = 0, VAD n = 3), other causes (Z-Dex n = 7, VAD n = 2), unknown (Z-Dex n = 3, VAD n = 2). This study demonstrated that Z-Dex might be a suitable oral alternative to VAD for treating newly diagnosed MM patients, although definitive evidence for equivalence is not provided.

Adult↗
PubMed2004

Outbreak of influenza A (H3N2) in a highly-vaccinated religious community: a retrospective cohort study.

An outbreak of influenza occurred at the end of the 2001-2 winter season in a highly-vaccinated, semi-enclosed, religious community. On the basis of retrospective self reporting, 43% met the case definition (151/350) and 81% (25/31) of throat swabs from cases were polymerase chain reaction (PCR) -positive for influenza A (H3N2). The risk of developing influenza in people aged 65 or more was lower than that of children aged 2 years and under (odds ratio 0.1, 95% confidence interval 0.02 to 0.38). The risk of developing symptoms of influenza was not significantly different between people who had been vaccinated in the United Kingdom and those who had not been vaccinated (OR 1.14, CI 0.41 to 3.14). Chronic disease was an independent risk factor for developing symptoms of influenza (OR 1.9, CI 1 to 3.63). Timing of the outbreak, the age structure and mode of communal living may have influenced the efficacy of the influenza vaccine, which was well matched to circulating strains at the time of the outbreak. It is important to consider the diagnosis of influenza even in a highly-vaccinated community.

Adolescent↗
PubMed2003

A phase II trial of capecitabine (Xeloda) in recurrent ovarian cancer.

Oral capecitabine is a highly active, well-tolerated and convenient treatment for breast and colorectal cancer. This trial assessed the efficacy and safety of single-agent capecitabine in patients with previously treated ovarian cancer. A total of 29 patients with platinum-pretreated relapsed ovarian cancer were enrolled in this prospective, open-label, single-centre, phase II study. Patients received oral capecitabine 1250 mg m(-2) twice daily on days 1-14 of a 21-day cycle. Tumour response was evaluated using serum CA125. Out of 29 enrolled patients, 28 were evaluable, and a response was observed in eight patients (29%, 95% confidence interval (CI), 13-49%). Median progression-free and overall survivals were 3.7 (95% CI, 2.8-4.6) and 8.0 (95% CI, 4.1-11.8) months, respectively. After 6 months of treatment, 28% (95% CI, 13-48%) of patients remained progression-free and 62% (95% CI, 42-79%) were still alive. The most common clinical adverse events were hand-foot syndrome (HFS), nausea and diarrhoea. Grade 3 HFS occurred in 14% of patients, grade 3 vomiting in 10%. Efficacy and safety of capecitabine compare favourably with other monotherapies in platinum-refractory epithelial ovarian cancer. The convenience and improved safety profile of capecitabine compared with intravenous. regimens make it an ideal agent for administration in the outpatient setting.

Administration, Oral↗