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Biomedical subjects

J Dewar

Publications and source records attributed to J Dewar.

At least 19 recordsLinked to original sources
PubMed2006

Identification of viral agents causing diarrhea among children in the Eastern Center of Tunisia.

Viral diarrhea remains a major cause of childhood morbidity and mortality worldwide. In Tunisia, no comprehensive studies of all viral agents related to diarrhea in children have yet been conducted. The present study was performed to investigate the role of enteric viruses in acute diarrhea in the country. Six hundred thirty-eight stool samples were collected from children under 5 years of age seeking medical care for acute diarrhea between October 2003 and September 2005 in hospitals from the Eastern-Center Tunisia. All samples were tested for rotavirus, astrovirus, and adenovirus using commercial antigen enzyme immunoassays (EIAs). Positive samples for rotavirus and astrovirus were confirmed by an "in-house" reverse transcriptase-polymerase chain reaction (RT-PCR). Samples positive for adenovirus antigen were subjected to further EIA screening for species F enteric adenovirus types 40 and 41. At least one viral agent was found in 30% of the specimens. The frequency of rotavirus, astrovirus, and adenovirus was 20%, 7%, and 6%, respectively. Of the stool samples containing adenovirus, 57% (20/35) were found to be positive for species F adenovirus types 40/41. Dual infections were found in 9% (17/191) of the positive samples. Enteric viruses appear to play an important role in pediatric diarrhea in Tunisia. The introduction of affordable viral diagnosis in pediatric hospitals will improve patient care by reducing the unnecessary use of antibiotics.

Acute Disease↗
PubMed2006

Molecular characterisation of the rotavirus strains prevalent in Maua, Meru North, Kenya.

BACKGROUND: Rotavirus is the most common cause of severe infantile diarrhoea disease in infants and young children below five years worldwide. Rotavirus is associated with high cases of morbidity and mortality and it is estimated that up to 650,000 deaths in young children occur annually in the less developed countries and approximately 150,000-200,000 deaths occur in Africa alone. OBJECTIVE: To characterise the circulating rotavirus strains in Maua, Meru North district, Kenya. DESIGN: A prospective study to investigate and characterise rotavirus serotypes/genotypes and electropherotypes in infants and children with severe diarrhoea hospitalised and/or attending the outpatient department of Maua Methodist Hospital during the period April 2004 to September 2005. SETTING: Maua Methodist Hospital, Meru North, Kenya. SUBJECTS: Faecal samples were collected from 135 infants and children with acute diarrhoea and were screened first for the presence of human Group A rotavirus antigen using commercially available enzyme linked immunosorbent assay kit (ELISA). The positive samples were evaluated by sodium dodecyl polycrylamide gel electrophoresis (SDS-PAGE) to determine the viral RNA electropherotype profile. Rotavirus strains were also genotyped using reverse transcriptase polymerase chain reaction (RT-PCR) of the VP7 gene. RESULTS: Assay of these samples with commercial ELISA showed that 17.8% (24/135) were positive for group A rotavirus antigen. Twenty of these ELISA positive samples were also analysed by SDS-PAGE of which 75% (15/20) gave detectable electropherotype pattern with the long electropherotype being predominant 80.0% (12/15) followed by the short RNA profile 20.0% (2/ 15). Seventeen of the ELISA positive samples were genotyped for VP7 and the results showed that G9 was the most predominant genotype comprising 47.1% (8/17) followed by G8 29.4% (5/17), GI 17.4% (3/17) and the mixed genotype was G8/G9 5.9% (1/17). Most patients with rotavirus infection were of the age of 3 - 60 months, with 79% being less than 18 months old. CONCLUSION: The overall prevalence of rotavirus infection in young children with diarrhoea hospitalised and/or attending the out-patient department of Maua Methodist Hospital was 17.8% with the predominant serotype being G9. These results show that rotavirus plays an important role in severe viral diarrhoea in young children in Maua Meru North district, Kenya. Furthermore, this high G9 rotavirus prevalence in Kenya may require vaccine trials to be held in Kenya so as to determine the efficacy of new rotavirus vaccine candidates that do not include the G9 serotype.

Child, Preschool↗
PubMed2005

Pathology reporting of breast cancer: trends in 1989-1999, following the introduction of mammographic screening in Western Australia.

BACKGROUND: A survey of pathology reporting of breast cancer in Western Australia in 1989 highlighted the need for improvement. The current study documents (1) changes in pathology reporting from 1989 to 1999 and (2) changes in patterns of histopathological prognostic indicators for breast cancer following introduction of mammographic screening in 1989. METHODS: Data concerning all breast cancer cases reported in Western Australia in 1989, 1994 and 1999 were retrieved using the State Cancer Registry, Hospital Morbidity data system, and pathology laboratory records. RESULTS: Pathology reports improved in quality during the decade surveyed. For invasive carcinoma, tumour size was not recorded in 1.2% of pathology reports in 1999 compared with 16.1% in 1989 (p<0.001). Corresponding figures for other prognostic factors were: tumour grade 3.3% and 51.6% (p<0.001), tumour type 0.2% and 4.1% (p<0.001), vascular invasion 3.7% and 70.9% (p<0.001), and lymph node status 1.9% and 4.5% (p = 0.023). In 1999, 5.9% of reports were not in a synoptic/checklist format, whereas all reports were descriptive in 1989 (p<0.001). For the population as a whole, the proportion of invasive carcinomas <1 cm was 20.9% in 1999 compared with 14.5% in 1989 (p<0.001); for tumours <2 cm the corresponding figures were 65.4% and 59.7% (p = 0.013). In 1999, 30.5% of tumours were histologically well-differentiated compared with 10.6% in 1989 (p<0.001), and 61.7% were lymph node negative in 1999 compared with 57.1% in 1989 (p = 0.006). Pure ductal carcinoma in situ (DCIS) constituted 10.9% and 7.9% of total cases of breast carcinoma in 1999 and 1989, respectively (p = 0.01). CONCLUSIONS: Quality of pathology reporting improved markedly over the period, in parallel with adoption of standardised synoptic pathology reports. By 1999, recording of important prognostic information was almost complete. Frequency of favourable prognostic factors generally increased over time, reflecting expected effects of mammographic screening.

Adenocarcinoma↗
PubMed2005

Detection of group a rotavirus strains circulating in calves in Tunisia.

Faecal samples were collected from 89 dairy calves to determine the prevalence of rotavirus infection in Tunisia and the genomic diversity of bovine rotavirus strains. After screening of all faecal samples by enzyme-linked immunosorbent assay, rotavirus strains were analysed by RNA polyacrylamide gel electrophoresis and characterized antigenically by monoclonal antibodies to the VP6 subgroup. The VP7 genotype was determined by nested RT-PCR. Of the 89 calves tested, 27 (30%) were positive for rotavirus antigen. Four different long electrophoretypes were identified. All VP6 typeable strains carried the subgroup I specificity. G8 genotype was the most prevalent, but G6 and mixed strains G(6 + 8) were also detected.

Animals↗
PubMed2005

Cisplatin and gemcitabine induction chemotherapy followed by concurrent chemoradiotherapy or surgery for locally advanced non-small cell lung cancer.

BACKGROUND: We report a study of induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIA/IIIB non-small cell lung cancer. METHODS: Patients received two cycles of induction chemotherapy with cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. If the disease was resectable [corrected] surgery was followed with two further cycles. If unresectable, patients received cisplatin 100 mg/m(2) day 1, 29 with 5-fluorouracil 1000 mg/m(2) per 24 h continuous infusion for 96 h on days 2-5 and days 30-33 of the radiotherapy administration. Radiation therapy consisted of 63 Gy, 35 fractions, 7 weeks. RESULTS: Of 48 patients, 40% had a partial response to induction chemotherapy. Four of eleven patients with stage IIIA tumours had resectable disease. The remaining seven patients plus 37 with stage IIIB disease had chemoradiotherapy. Response at the completion of all therapy was 62% (IIIA 73%, IIIB 59%). For all patients the median survival was 15.3 months: 1 year and 3 years, 58% and 25%, respectively. Those with IIIB disease responding to induction chemotherapy had significantly superior survival to those that did not respond (37 months vs 11 months; P = 0.005). This remained significant from a landmark at 8 weeks after the start of treatment (P = 0.01). CONCLUSION: These results are equivalent to other studies using induction chemotherapy prior to concurrent chemoradiotherapy. Response to induction chemotherapy may have major prognostic significance.

Adult↗
PubMed2000

Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans.

Altered beta-adrenergic regulation has been reported in individuals with hypertension. The variability in vascular responsiveness to beta-agonists, such as isoproterenol, observed in humans may be explained partially by beta(2)-adrenoceptor polymorphism. Individuals with the Gln27 form of the receptor may show reduced vascular reactivity because of downregulation expression of the receptor in the vasculature. We screened 127 normotensive white subjects, 37 of whom were homozygous for these alleles. Thirty-two subjects (17 Gln27 and 15 Glu27) agreed to receive brachial artery infusions of isoproterenol at doses of 1 to 300 ng. min(-1); forearm blood flow was measured by using venous occlusion plethysmography. Of these subjects, 25 (12 Glu27 and 13 Gln27) received local doses of isoproterenol (0.3 to 30.0 ng. min(-1)) via a dorsal hand vein preconstricted with norepinephrine. Compared with subjects homozygous for the Glu27 allele, subjects with the Gln27 substitution had lower baseline blood flow and, in response to isoproterenol, had a significantly attenuated increase in forearm blood flow. This pattern was more marked in veins. We also studied the relationship between the position 16 polymorphism and vascular reactivity. Homozygotes for Arg16 had significantly lower basal blood flow and attenuated increases in forearm blood flow compared with the Gly16 homozygotes. This was significant in veins but not in arteries. Thus, beta(2)-adrenoceptor genotype determines vascular responses to isoproterenol in forearm resistance vessels and in capacitance vessels. Further studies are necessary to establish whether beta(2)-adrenoceptor polymorphisms are important in the genesis of hypertension.

Adrenergic beta-Agonists↗
PubMed1999

Pre-operative chemo-radiotherapy in locally advanced rectal cancer: is this the way of future management?

The purpose of the present paper was to update a prospective analysis (H Elsaleh et al. unpubl. data, 1997) investigating the effectiveness and toxicity of pre-operative pelvic radiotherapy with modest dose 5-fluorouracil (5-FU) in locally advanced rectal cancer (T3-T4). A total of 31 patients were assessed (28 T3 and three T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy to the International Commission on Radiation Units and Measurements (ICRU) point in 25 fractions over 5 weeks. A radiosensitizing dose of 5-FU was delivered at 500 mg/m2 on days 1, 2 and 3, and days 22, 23 and 24. Mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. Patients had a low toxicity profile; an estimated 50% or greater response was seen in 24 out of 31 (two complete responses). There were no surgical difficulties achieving resection. No late complications were documented, although follow-up was short. In locally advanced rectal cancer, pre-operative chemo-radiotherapy had a low toxicity profile. Appropriately fractionated pre-operative chemo-radiotherapy is a reasonable option in this disease and should be further evaluated. The optimal method of delivery of the radiosensitizing agent (5-FU) is the subject of further investigation.

Adult↗
PubMed1999

Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study.

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

Aged↗
PubMed1999

Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.

PURPOSE: To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. RESULTS: A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P <.001), nausea or vomiting (P =.003), and fever without documented infection (P =.007), and less hospitalization for febrile neutropenia than did CMFP (P =.001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P <.0001). Overall, quality of life was similar for both treatments (P > = .07). CONCLUSION: Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.

Adult↗
PubMed1998

Effect of gap length and position on results of treatment of cancer of the larynx in Scotland by radiotherapy: a linear quadratic analysis.

PURPOSE: This paper reports on the analysis of the effect of the length and position of unplanned gaps in radiotherapy treatment schedules. MATERIALS AND METHODS: Data from an audit of the treatment of carcinoma of the larynx are used. They represent all newly diagnosed cases of glottic node-negative carcinoma of the larynx between 1986 and 1990, inclusive, in Scotland that were referred to one of the five Scottish Oncology Centres for primary radical radiotherapy treatment. The end-points are local control of cancer of the larynx in 5 years and the length of the disease-free period. The local control rates at > or =5 years, Pc were analyzed by log linear models and Cox proportional hazard models were used to model the disease-free period. RESULTS: Unplanned gaps in treatment are associated with poorer local control rates and an increased hazard of a local recurrence through their effect on extending the treatment time. A gap of 1 day is potentially damaging but the greatest effect is at treatment extensions of 3 or more days, where the hazard of a failure of local control is increased by a factor of 1.75 (95% confidence interval 1.20-2.55) compared to no gap. The time factor for the actual time was imprecisely estimated at 2.7 Gy/day with a standard error of 13.2 Gy/day. Among those cases who had exactly one gap resulting in a treatment extension of 1 day, there is no evidence that gap position influences local control (P = 0.17). The treatment extension as a result of the gap is more important than the position of the gap in the schedule. CONCLUSIONS: Gaps in the treatment schedule have a detrimental effect on the disease-free period. A gap has a slightly greater effect than an increase in the prescribed treatment time. Any gap in treatment is potentially damaging. The position of the gap in the schedule was shown to be not important.

Appointments and Schedules↗
PubMed1998

Potentiation of the response to chemotherapy in patients with breast cancer by dietary supplementation with L-arginine: results of a randomised controlled trial.

Patients with large primary breast cancers are being treated with neo-adjuvant chemotherapy. Studies in animals have shown that responses to chemotherapy can be increased by dietary manipulation of tumour cell metabolism. Also dietary supplementation with the amino acid L-arginine, resulted in an increase in tumour metabolic activity expression of the nuclear activation antigen, Ki67, in patients with breast cancer. Therefore, we have carried out a randomised, double blind, placebo controlled trial to determine if L-arginine supplementation is beneficial in patients with breast cancer, undergoing neo-adjuvant chemotherapy. 96 patients were randomised to receive L-arginine (30 g/day) for three days (n = 48) or placebo (n = 48) prior to undergoing chemotherapy (doxorubicin, cyclophosphamide, vincristine, prednisolone), 6 pulses at 21-day intervals. Clinical and pathological responses were assessed in both groups of patients following completion of chemotherapy. The clinical response rate was 77% (23% complete and 54% partial responses) in the L-arginine treated group, compared with 71% (15% complete and 56% partial) in the placebo group of patients (p = ns). However, in patients with tumours less than 6 cm in initial diameter, there was a significant increase in the better histopathological responses in the L-arginine group, when compared with the placebo group of patients (88% vs 52%, p = 0.04). This may have important implications for clinical practice.

Adenocarcinoma↗
PubMed1997

Association between beta 2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics.

BACKGROUND: In-vitro studies have suggested that polymorphisms of the beta 2-adrenoceptor may influence the desensitisation induced by beta 2-agonists. We investigated the influence of beta 2-AR polymorphism on the development of bronchodilator desensitisation in asthma patients. METHODS: We carried out an analysis of 22 moderately severe stable asthmatics, mean age 38 years, FEV1 63% of predicted and FEF25-75 38% of predicted, who received a median inhaled corticosteroid dose of 1000 micrograms/day. Patients were randomly assigned inhaled placebo or inhaled formoterol 24 micrograms bid for 4 weeks each in a crossover study. Bronchodilator dose-response curves were made at the end of each treatment period by use of cumulative doses of formoterol (6-108 micrograms) with FEV1 and FEF25-75 measured 30 min after each dose, and up to 6 h after the last dose. We calculated the degree of bronchodilator desensitisation by comparing the dose-response (for maximum and 6 h) after placebo with that after formoterol, and expressed this degree as a percentage of placebo response. Patients were divided into groups according to genotype at codon 16: homozygous Arg 16 (n = 4), heterozygous Arg 16/Gly 16 (n = 8), and homozygous Gly 16 (n = 10). At codon 27: homozygous Gln 27 (n = 5), heterozygous Gln 27/Glu 27 (n = 11), and homozygous Glu 27 (n = 6). FINDINGS: We found a significantly (p < 0.05) greater degree of bronchodilator desensitisation with homozygous Gly 16 than with homozygous Arg 16 for maximal FEV1 response: -8% (Arg 16) vs 46% (Gly 16); and for maximal FEF25-75 response: -32% (Arg 16) vs 74% (Gly 16; 95% CI 15-92% and 49-164%, respectively). Bronchodilator responses at 6 h were also significantly (p < 0.05) different for FEV1 and FEF25-75 when Arg 16 and Gly 16 were compared and values for heterozygous Arg 16/Gly 16 were intermediate. There was significantly greater desensitisation with Glu 27 than with Gln 27 for maximal FEF25-75 response: -7% (Gln 27) vs 68% (Glu 27), p = 0.05; and for 6 h FEF25-75 response: 43% (Gln 27) vs 93% (Glu 27), p < 0.05 (95% CI 2-147% and 5-94%, respectively). All patients who were homozygous Glu 27 were also homozygous Gly 16. INTERPRETATION: We have found preliminary evidence that beta 2-adrenoceptor polymorphism is associated with altered beta 2-adrenoceptor expression in asthma patients. The homozygous Gly-16 form was significantly more prone to bronchodilator desensitisation than Arg 16, with the influence of Gly 16 dominating over any putative protective effects of Glu 27.

Administration, Inhalation↗
PubMed1997

Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. Australian-New Zealand Breast Cancer Trials Group.

PURPOSE: To determine whether a strategy of adding medroxyprogesterone acetate (MPA) to tamoxifen (TAM) is superior to the substitution of MPA for TAM among women with advanced breast cancer and disease progressing on TAM. To assess the patterns or response and subsequent progression in sites and tissues according to prior involvement and treatment. PATIENTS AND METHODS: Two-hundred-fifteen postmenopausal women with advanced breast cancer progressing on TAM after receiving TAM for at least six months were randomized: 109 to add MPA 500 mg/day orally (TAM + MPA), and 106 to stop TAM and to substitute MPA. RESULTS: There were no significant differences between the groups with respect to complete plus partial response rates: TAM + MPA 10%, MPA 9%, median time to progression TAM + MPA 3.0 months, MPA 4.5 months, or median overall survival, TAM + MPA 17.2 months, MPA 18.4 months. In a multivariate model, prognostic factors significant for a shorter time to disease progression were worse for performance status, involvement of more than one tissue, prior radiotherapy, and shorter time from recurrence after primary therapy to randomization. Adjusting for these factors, treatment with TAM + MPA was associated with a higher relative risk for disease progression, with a hazards ratio of 1.31, but this was not significant (95% confidence interval, 0.98 to 1.74; P = .067). However, in an exploratory analysis, the time to disease progression, among patients with progesterone receptor positive (PR+) tumors, was 6.3 months with MPA versus 2.9 months with TAM + MPA, with a hazards ratio of 1.92 (95% confidence interval, 1.12 to 3.32; P = .02). There was a significant interaction, P = .04, between PR status and treatment, indicating an advantage to treatment substitution for those who have PR+ tumors. Tumor response occurred in 14% of assessed metastatic sites. Subsequent progression occurred in a new tissue alone in 13% of patients, in both new and previously involved (old) tissues in 76%, and in old tissues only in 11%. In 23% of patients, progression occurred only at a new site, in 50% at both old and new sites, and in 27% only at old sites. No significant differences in the patterns of response or progression were seen in the different treatment groups. CONCLUSION: Among women with breast cancer whose disease is progressing after at least six months of treatment with TAM, there is no advantage to maintaining TAM when MPA is to be given. An overall effect of treatment on the pattern of failure at old sites or at new sites or tissues cannot be discerned.

Aged↗