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Biomedical subjects

R James

Publications and source records attributed to R James.

At least 37 records · Page 2Linked to original sources
PubMed2002

Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer.

We investigated the activity of irinotecan given with a more convenient modified bimonthly de Gramont regimen of bolus and infusional 5-fluorouracil [IrMdG] in advanced or metastatic colorectal cancer in the first and second line setting. Irinotecan 180 mg m(-2) was infused over 90 min. L-folinic acid 175 mg or d,l folinic acid 350 mg was given over 2 h followed by a bolus of 5-fluorouracil (400 mg m(-2)) and a 46 h continuous infusion of 5-fluorouracil (2.4-2.8 g m(-2)). Forty-six previously untreated patients (Group A) and 36 who had received 5-fluorouracil for metastatic disease (Group B) were recruited. Seventy-eight patients were evaluable for response. A partial response was seen in 13 out of 43 (30% [95%CI 28.1-31.9%]) in Group A and 8/35 (23% [95% CI 17.9-28.1%]) in Group B. 40% (95%CI 38.1-41.9%) of Group A and 26% (95% CI 20.9-31.1%) of Group B patients achieved disease stabilisation. The median progression free survival from the start of this treatment was 7 months (95% CI 4.4-9.6 months) in Group A and 5 months (95% CI 2.8-7.2 months) in Group B. Median overall survival was 14 months (95% CI 9.0-18.9) in Group A and 11 months (95% CI 5.9-16.1) in Group B. Grade 3-4 toxicity in both treatment groups were similar; leucopenia 17% and diarrhoea 7-8%. Grade 3-4 mucositis was not seen and severe alopecia affected only three patients. IrMdG is an active and well-tolerated regimen for both the first and second line treatment of advanced colorectal cancer.

Adult↗
PubMed2002

Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. a review of phase II/III trials.

Raltitrexed (Tomudex), a thymidylate synthase inhibitor, is an alternative to 5-fluorouracil (5-FU)/leucovorin (LV) for the first-line treatment of advanced colorectal cancer. Following the completion of four phase III studies with raltitrexed at the recommended dose of 3.0 mg/m(2), it is opportune to review the efficacy and tolerability data of raltitrexed and suggest guidelines for appropriate patient management. Data are analysed from four phase III and five phase II studies including over 1300 patients with advanced colorectal cancer, some of whom were elderly or received higher doses of raltitrexed. Median survival with raltitrexed was comparable to that of bolus or infusional 5-FU/LV in three of the four randomised studies and objective response rates in the four trials were similar for the two agents. Response rates were at least comparable in elderly patients in phase II studies. For the majority of patients, treatment with raltitrexed was well tolerated even at doses higher than that recommended or in the elderly. As with other cytotoxic agents, serious and potentially life-threatening side-effects can occur; nevertheless, adherence to simple patient guidelines should minimise the incidence of serious side-effects with raltitrexed; these include the assessment of renal function before each and every treatment, dosage adjustment in the presence of renal impairment and close monitoring with prompt treatment of toxicities, particularly diarrhoea and neutropenia.

Adult↗
PubMed2002

Is muscle power related to running speed with changes of direction?

BACKGROUND: The purpose of this study was to identify the relationships between leg muscle power and sprinting speed with changes of direction. METHODS EXPERIMENTAL DESIGN: the study was designed to describe relationships between physical qualities and a component of sports performance. SETTING: testing was conducted in an indoor sports hall and a biomechanics laboratory. PARTICIPANTS: 15 male participants were required to be free of injury and have recent experience competing in sports involving sprints with changes of direction. MEASURES: subjects were timed in 8 m sprints in a straight line and with various changes of direction. They were also tested for bilateral and unilateral leg extensor muscle concentric power output by an isokinetic squat and reactive strength by a drop jump. RESULTS: The correlations between concentric power and straight sprinting speed were non-significant whereas the relationships between reactive strength and straight speed were statistically significant. Correlations between muscle power and speed while changing direction were generally low and non-significant for concentric leg power with some moderate and significant (p<0.05) coefficients found for reactive strength. The participants who turned faster to one side tended to have a reactive strength dominance in the leg responsible for the push-off action. CONCLUSIONS: The relationships between leg muscle power and change-of-direction speed were not consistent. Reactive strength as measured by the drop jump appears to have some importance for lateral change-of-direction speed, possibly because of similar push-off actions. It was concluded that reactive strength of the leg extensor muscles has some importance in change-of-direction performance but the other technical and perceptual factors than influence agility performance should also be considered.

Adolescent↗
PubMed2001

Mechanism and cleavage specificity of the H-N-H endonuclease colicin E9.

Colicin endonucleases and the H-N-H family of homing enzymes share a common active site structural motif that has similarities to the active sites of a variety of other nucleases such as the non-specific endonuclease from Serratia and the sequence-specific His-Cys box homing enzyme I-PpoI. In contrast to these latter enzymes, however, it remains unclear how H-N-H enzymes cleave nucleic acid substrates. Here, we show that the H-N-H enzyme from colicin E9 (the E9 DNase) shares many of the same basic enzymological characteristics as sequence-specific H-N-H enzymes including a dependence for high concentrations of Mg2+ or Ca2+ with double-stranded substrates, a high pH optimum (pH 8-9) and inhibition by monovalent cations. We also show that this seemingly non-specific enzyme preferentially nicks double-stranded DNA at thymine bases producing 3'-hydroxy and 5'-phosphate termini, and that the enzyme does not cleave small substrates, such as dinucleotides or nucleotide analogues, which has implications for its mode of inhibition in bacteria by immunity proteins. The E9 DNase will also bind single-stranded DNA above a certain length and in a sequence-independent manner, with transition metals such as Ni2+ optimal for cleavage but Mg2+ a poor cofactor. Ironically, the H-N-H motif of the E9 DNase although resembling the zinc binding site of a metalloenzyme does not support zinc-mediated hydrolysis of any DNA substrate. Finally, we demonstrate that the E9 DNase also degrades RNA in the absence of metal ions. In the context of current structural information, our data show that the H-N-H motif is an adaptable catalytic centre able to hydrolyse nucleic acid by different mechanisms depending on the substrate and metal ion regime.

Amino Acid Motifs↗
PubMed2001

Childhood morbidity and air pollution in the Teplice program.

BACKGROUND: A study of morbidity of children aged 0 to 3 years was conducted in two districts in the Czech Republic. Comparisons were made between children living in Teplice district, known for its high air pollution, and children living in Practice, a district with consistently lower particulate and SO2 exposures. METHODS AND RESULTS: The children were selected for the follow up based on deliveries from May 1994 to December 1966. Childhood morbidity during the first three years of life of 452 children was extracted from their pediatric records. Diagnoses were coded using the International Classification of Diseases--10th edition, and categorized into broad groupings. Children born in Teplice experienced a significantly higher rate of otitis media and otalgia, gastrointestinal infections, upper respiratory infections, and pneumonia, but did not differ in their risk for bronchitis or for viral infections such as varicella. These findings remained after multiple linear regression models adjusted for education, maternal age, maternal smoking, and other smokers in the household, breastfeeding, and attendance at day care. CONCLUSIONS: Air pollution may alter early childhood susceptibility to infection, but other differences between the districts must be considered: systematic diagnostic differences for several health outcomes comparing pediatricians in Teplice vs. Practice, differences in health-care seeking behavior by the parents, and inadequate control for confounding.

Air Pollution↗
PubMed2001

TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence.

TENB2 encodes a putative transmembrane proteoglycan, related to the EGF/heregulin family of growth factors and follistatin, which has been identified through the application of a differential display technique to a xenograft model of prostate cancer. Northern analysis and competitive PCR were used to demonstrate significantly increased TENB2 expression (p = 0.0003) on the acquisition of androgen independence in the model system. TENB2 is also overexpressed in clinical prostate carcinoma vs. its benign counterpart (p < 0.0001), with particular prominence in high-grade tumours, and shows a high degree of tissue specificity, being detected on a multitissue Northern array exclusively in brain and prostate material. Studies of recombinant protein expression demonstrate that TENB2 is a chondroitin sulphate proteoglycan. The presence of an EGF and 2 follistatin domains suggests a role in the regulation of growth factor signalling either as a ligand precursor, a membrane-bound receptor or as a binding protein for growth factors. These data are indicative of a significant role for TENB2 in the progression of poorly differentiated tumour types, with implications for prostate cancer detection, prognosis and therapy.

Amino Acid Sequence↗
PubMed2001

[Environmental pollution and childhood morbidity].

BACKGROUND: A study of morbidity of children aged 0 to 3 years was organized in two districts in the Czech Republic. Comparisons were drawn between children living in district Teplice, known for its high air pollution, and those living in Practice, the district with consistently lower particulate and SO2 exposures. METHODS AND RESULTS: 452 children of the follow up study were born between May 1994 and December 1996. Childhood morbidity during the first three years of life was obtained from their pediatric records. Diagnoses were coded using the International Classification of Diseases--the 10th edition, and categorized into broad groups. Children born in Teplice experienced a significantly higher rate of otitis media (and otalgia), gastrointestinal infections, upper respiratory infections, and pneumonia, but they did not differ in the risk of bronchitis or that of viral infections such as varicella. These findings remained valid after the multiple linear regression models were calculated and adjusted for education, maternal age, maternal smoking, and other smokers in the household, breastfeeding, and attendance at the day care. CONCLUSIONS: Air pollution may alter early childhood susceptibility to infection, but other differences between the districts have to be considered: systematic diagnostic differences for several health outcomes between pediatricians in Teplice and Practice, differences in health-care seeking approach of parents, and some hitherto unidentified factors.

Air Pollution↗
PubMed2001

Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Palmoplantar pustular psoriasis (PPP) is a chronic, relapsing condition often recalcitrant to therapy. Synthetic retinoids have been found to be efficacious in the treatment of PPP, but their use is limited by side-effects. Liarozole is an imidazole-like compound that inhibits the retinoic acid (RA) 4-hydroxylase-mediated breakdown of all-trans RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid-mimetic drug. Liarozole has already been found to be effective in the treatment of retinoid-responsive conditions such as chronic plaque psoriasis and ichthyoses. OBJECTIVES: To assess the efficacy and side-effect profile of liarozole in the treatment of PPP. METHODS: We performed a double-blind, randomized, placebo-controlled trial of oral liarozole 75 mg twice daily for 12 weeks in the treatment of PPP. The trial was conducted at two centres and involved 15 patients. RESULTS: Using the PPP Area and Severity Index we found a statistically significant (P = 0.02) improvement in PPP in subjects on liarozole (median 3, range 1.8-14.1) as compared with placebo (median 12.1, range 5-18) by the end of the treatment phase. There was also a statistically significant difference (P = 0.006) in the number of fresh pustules after treatment for the two study groups (liarozole median 2, range 0-18; placebo median 38, range 2-75). The severity of disease (on a scale of 0-8) between the two groups was significantly different at the end of treatment (liarozole median 1, range 1-5; placebo median 3, range 2-6; P = 0.04). No patients withdrew from the trial because of adverse events. The most commonly reported side-effects were pruritus, cheilitis and xerosis but these were rarely severe and resolved rapidly on discontinuation of treatment. Laboratory results, including haematology, liver function tests and serum cholesterol and triglycerides were not significantly different between the liarozole and placebo groups. CONCLUSIONS: The results of this pilot study suggest that liarozole 75 mg twice daily is an effective and well-tolerated therapy for PPP. In addition, the pharmacokinetics of liarozole may help to circumvent side-effects associated with synthetic retinoids and allow its use in premenopausal women.

Administration, Oral↗
PubMed2001

Changes in Expanded Program for Immunization coverage for mother and child in Krakor, Cambodia 1996--1998.

We evaluated a training intervention aimed at enhancing the roles of health centre staff, Village Health Volunteers (VHVs) and Traditional Birth Attendants (TBAs) within the Expanded Program for Immunization (EPI) in the district of Krakor, Cambodia. We conducted population-based surveys to determine the coverage of the EPI at baseline (1996) and after the intervention (1998), using data from health cards for mothers and their children and history data. Statistically significant changes over the 2-year period were apparent for tetanus, BCG, polio and DTP, supporting the positive impact the training intervention had on immunization coverage in the district.

Adult↗
PubMed2001

An analysis of factors contributing to a series of deaths caused by exposure to high environmental temperatures.

Autopsy reports at the Forensic Science Centre, Adelaide, South Australia, were reviewed for the 8 years from January 1991 to December 1998 for cases with unusual features in which deaths had been attributed to exposure to high environmental temperatures. Amphetamine-related hyperpyrexial deaths, anesthetic deaths caused by malignant hyperpyrexia, deaths of elderly incapacitated individuals during heat waves, and deaths of children trapped in the back of cars were excluded from the study. In 9 cases, where heat-related deaths had occurred (age range 21 to 77 years; M:F = 8:1). Predisposing factors included lack of familiarity with Australian environmental conditions, excessive clothing, prolonged sun exposure, acute alcohol intoxication, obesity, benztropine and trifluoperazine medication, and underlying dementia, alcoholic liver disease, and possibly epilepsy.

Adult↗
PubMed2001

Supplementation of islet culture medium with insulin may have a beneficial effect on islet secretory function.

Recent reports suggest that apoptosis resulting from the disruption of the normal cell-matrix relationship (anoikis) during islet isolation could lead to a loss of islet tissue in culture. Insulin is known to have a role in cell growth and survival, and this study was undertaken to assess any beneficial effect on islets by supplementing the islet culture medium with insulin. Human and porcine islets were cultured in medium supplemented with 0, 10, 100, and 1,000 ng x mL(-1) insulin. Secretory function was assessed by perifusion at days 1 and 8. The results demonstrated a significant variation in stimulation index between isolations for human islets, but there was no effect relating to the concentration of insulin in the medium or time in culture. For porcine islets, there was a significant (p < 0.001) improvement in secretory function for islets cultured in 10 and 100 ng x mL(-1) insulin, relative to 0 and 1,000 ng x mL(-1) insulin. There was no interisolation variation or effect of time in culture. In conclusion, the secretory function of porcine islets benefited from the addition of 10 to 100 ng x mL(-1) insulin to the culture medium, but interisolation variation in human islet secretory function did not allow any specific effect of the insulin to be determined.

Animals↗
PubMed2001

Changes in ante-natal care and family planning in Krakor, Pursat, Cambodia, 1996-1998.

This study examines variations in ante-natal care (ANC) and family planning in Krakor, Pursat, Cambodia between 1996 and 1998. Population-based survey interviews were conducted with a total of 291 women in 1996 and 211 women in 1998. An intervention strategy designed to enhance the skills and roles of Health Centre staff, Village Health Volunteers (VHVs) and Traditional Birth Attendants (TBAs) was conducted. Over this timeframe, reported ANC access increased from 37% to 47%. Most women delivered their last child at home, usually assisted by a TBA. Few women practiced family planning, despite the fact that most reported that they did not want any further children. A range of reasons for not practicing family planning were found to be highly significant, including the lack of available services (p<0.01). The fear of side-effects decreased significantly (p<0.01), with the community education provided by the VHVs and TBAs, potentially being one contributing factor. The results of this study suggest that continual support of VHVs and TBAs will further improve the health of women in Cambodia.

Adult↗
PubMed2001

Ambivalence about health-related behaviours: an exploration in the domain of food choice.

OBJECTIVES: Interest in attitudes and ambivalence has highlighted problems with the adequacy of conceptualizing attitudes as unitary, unidimensional, evaluations. In this paper, we report an application of the Theory of Planned Behaviour (Ajzen, 1991) in the domain of dietary choice which investigates the hypothesis that ambivalence will attenuate observed attitude-intention relationships (since the evaluations influencing the expression of attitudes are more likely to differ from the evaluations influencing the expression of intentions for people who are more ambivalent. DESIGN: Participants completed a postal questionnaire which contained, inter alia, measures assessing the components of the Theory of Planned Behaviour and a measure of ambivalence. METHODS: Participants (N = 296) were recruited via advertisements placed in local newspapers, asking for volunteers to assist in a research project. Participants were randomly assigned to complete a questionnaire about either their chocolate consumption or their meat consumption. Participants were paid 4. RESULTS: The findings show considerable support for the hypothesis: there was a tendency for attitude-intention relationships to be attenuated among participants with higher levels of ambivalence, compared to participants with lower levels of ambivalence. CONCLUSIONS: The research supports the widespread view that ambivalence is an important issue, both for those involved in basic attitude research and for those who seek to use attitude theories in applied research. In particular, the findings indicate that ambivalence may often have implications for the predictive ability of attitude-intention-behaviour models, especially when applied to health-related behaviours that are characterized by motivational conflicts.

Journal Article↗