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Biomedical subjects

G Stuart

Publications and source records attributed to G Stuart.

At least 19 recordsLinked to original sources
PubMed2004

A whole genome perspective on the phylogeny of the plant virus family Tombusviridae.

Most current classifications of viruses are based on single gene analysis of capsid protein or polymerase. The comparison of entire genomes is a more balanced approach that should provide a more complete picture of relatedness. We have used a singular value decomposition (SVD)-based analysis to generate phylogenetic trees using whole genome protein sequences from a family of single-stranded RNA plant viruses. Our dataset includes the 26 species of the family Tombusviridae, 25 of which have complete genome sequences cataloged in GenBank. The resulting phylogenetic tree agrees well with current taxonomic classifications, but with significant exceptions. One previously unassigned virus within this family, Maize necrotic streak virus, is definitively placed within the genus Tombusvirus by this analysis. In addition, the analysis defines two distinct subsets within the genus Necrovirus. Future datasets will be expanded to include other icosahedral positive strand RNA plant viruses, and then perhaps all positive strand RNA plant viruses.

Amino Acid Sequence↗
PubMed2002

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

Adult↗
PubMed2002

Incidental radiological findings on brain magnetic resonance imaging in first-episode psychosis and chronic schizophrenia.

OBJECTIVE: To investigate whether patients with first-episode psychosis or chronic schizophrenia have an increased incidence of magnetic resonance imaging (MRI) brain abnormalities compared with control subjects. METHOD: Totally 340 clinical MRI reports [Controls (n=98), first-episode psychoses (n=152), chronic schizophrenia (n=90)] were reported by a neuroradiologist blind to diagnosis and subsequently categorized using referral criteria (immediate, urgent, routine or no referral). RESULTS: Thirty percent of all scans were reported by a neuroradiologist as abnormal, but the majority required no referral. Patients with chronic schizophrenia were more likely to have clinically significant abnormal scans than patients with first episode psychosis or control subjects. In four patients the MRI findings led to the discovery of previously unsuspected pathology. CONCLUSION: Patients with chronic schizophrenia have an increased prevalence of incidental brain abnormalities. A small proportion of patients with chronic schizophrenia and first-episode psychosis benefitted directly from MRI scanning.

Adult↗
PubMed2001

Anti-lymphoma immunity: relative efficacy of peptide and recombinant DNA vaccine.

The efficacy of vaccines consisting of (1) Ig idiopeptides of a murine B-lymphoblastoma, 2C3, and (2) a corresponding scFV-expressing DNA construct was determined on the basis of their ability to induce anti-tumor immune response and protection against tumor growth. Peptide-KLH complexes and a plasmid expressing single-chain variable fragment (scFv) corresponding to 2C3 Ig VH and VL chains were used separately as vaccines. Immunized BALB/c mice were bled and then challenged with live 2C3 tumor. Survival of various challenged groups was also determined. The results indicate that CDR3-H (VH3) peptides, and the plasmid DNA when given with GM-CSF, only moderately retarded tumor growth, whereas killed 2C3 tumor vaccine induced lasting protection, as shown earlier. Both peptides and scFv-plasmid induced circulating anti-Id antibodies, but no specific cytotoxic T-cell (CTL) activity was detected. However, in spite of their inability to induce CTL activity, both idiopeptides and the scFv-expressing plasmid DNA displayed epitopes recognized by an Id-specific long-term splenic CTL line (A102) obtained from mice vaccinated with killed 2C3 tumor.

Animals↗
PubMed2000

Phase II feasibility study of sequential couplets of Cisplatin/Topotecan followed by paclitaxel/cisplatin as primary treatment for advanced epithelial ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group Study.

PURPOSE: Despite the improved results in advanced ovarian cancer achieved with the addition of paclitaxel to frontline therapy, there remains room for improvement. One approach is to add new agents such as topotecan. Because myelosuppression limits the delivery of topotecan with paclitaxel/cisplatin in a three-drug combination, we explored giving sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin. PATIENTS AND METHODS: Forty-four patients with residual epithelial ovarian carcinoma after primary surgery were studied. Cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1 through 5 were administered at 21-day intervals for four cycles, followed by interval debulking surgery (if optimal debulking was not achieved with primary surgery), and then paclitaxel 135 mg/m(2) over 24 hours on day 1 and cisplatin 75 mg/m(2) on day 2 at 21-day intervals for four cycles. RESULTS: Such sequential couplets are feasible. Myelotoxicity was the major toxic effect, but it was of short duration. The granulocyte nadir with topotecan/cisplatin occurred late (median, day 18), so retreatment on day 21 was not always possible. There was no unexpected nonhematologic toxicity. The regimen was active in this group of patients who had undergone largely suboptimal debulking surgery. In 34 patients with clinically measurable disease, the overall response rate was 78%, and 30 (77%) of the 39 patients with elevated CA 125 levels at baseline had normalization of CA 125 levels by the end of therapy. CONCLUSION: Sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin are feasible. The efficacy data in this suboptimal group of patients has encouraged us to proceed with a randomized study based on this approach.

Adult↗
PubMed2000

A phase I/II evaluation of tirapazamine administered intravenously concurrent with cisplatin and radiotherapy in women with locally advanced cervical cancer.

PURPOSE: This is a Phase I/II dose escalation study to determine the tolerable dose of tirapazamine (TPZ), and the toxicity of a regimen using TPZ with cisplatin, and radiotherapy in women with locally advanced cervical cancer. METHODS AND MATERIALS: Eligible women for this study were those with a diagnosis of locally advanced cervix cancer, who were less than 75 years of age, having provided informed consent, and who had undergone the necessary prestudy investigations. External-beam radiotherapy (RT) was given to a minimum dose of 4500 cGy in 25 fractions (Day 1-35), and brachytherapy then delivered to bring the total dose at point A to 8500 cGy. The first dose level of the study used TPZ 190 mg/m(2) and cisplatin 75 mg/m(2) on Days 1, 15, and 29 of RT. TPZ 160 mg/m(2) alone was used on Days 8, 10, 12 and 22, 24, 26 of RT. A conventional dose-escalation step method was then used to determine the maximum tolerated dose (MTD) of TPZ. RESULTS: Four patients were treated at Level 1, 6 at Level 2, and 5 at Level 3. Only 1 patient experienced a dose-limiting toxicity (DLT) at Level 2, but 2 of the 5 patients at Level 3 incurred DLTs. Level 2 was declared the MDT (TPZ 290 mg/m(2) on Days 1, 15, 29 and 220 mg/m(2) on Days 8, 10, 12 and 22, 24, 26). At 6 months, 13 of 15 patients had complete pelvic control of disease. CONCLUSION: Level 2 of this regime was identified as the MDT. The use of TPZ with concurrent cisplatin and pelvic radiotherapy has acceptable toxicity and should be considered for further Phase 2 testing in view of the promising responses noted.

Adult↗
PubMed2000

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Adult↗
PubMed2000

Urolithiasis following formation of a continent urostomy: case report and review of the literature.

BACKGROUND: Formation of urinary stones in a continent urostomy (Indiana pouch) has been described as a late complication. Management of a patient with symptomatic multiple large stones and review of the literature are outlined. CASE REPORT: A 32-year-old woman presented with recurrent urinary tract infections and pyelonephritis 6 years after a total pelvic exenteration and creation of a continent urostomy for central recurrent carcinoma of the cervix after radical pelvic radiation. Multiple large stones were found to be the underlying etiology. Laparotomy, enterocystotomy, and removal of stones were performed without apparent complication. CONCLUSION: It is recommended that for single calculi or multiple small stones, electroshock wave lithotripsy or the percutaneous endoscopic approach be considered. For larger stones the use of laparotomy and enterocystostomy may be appropriate.

Adult↗
PubMed2000

The effects of word co-occurrence on short-term memory: associative links in long-term memory affect short-term memory performance.

In immediate serial recall tasks, high-frequency words are recalled better than low-frequency words. This has been attributed to high-frequency words' being better represented and providing more effective support to a redintegration process at retrieval (C. Hulme et al., 1997). In studies of free recall, there is evidence that frequency of word co-occurrence, rather than word frequency per se, may explain the recall advantage enjoyed by high-frequency words (J. Deese, 1960). The authors present evidence that preexposing pairs of low-frequency words, so as to create associative links between them, has substantial beneficial effects on immediate serial recall performance. These benefits, which are not attributable to simple familiarization with the words per se, do not occur for high-frequency words. These findings indicate that associative links between items in long-term memory have important effects on short-term memory performance and suggest that the effects of word frequency in short-term memory tasks are related to differences in interitem associations in long-term memory.

Adult↗
PubMed2000

The comparative efficacy of intravenous cefotaxime and trimethoprim/sulfamethoxazole in preventing infection after neurosurgery: a prospective, randomized study. Brisbane Neurosurgical Infection Group.

The objective of the investigation was to determine the comparative efficacy of cefotaxime versus trimethoprim-sulfamethoxazole in the prophylaxis of patients undergoing neurosurgical procedures. In this prospective randomized open study, 780 adult patients undergoing elective craniotomy, shunt surgery or stereotactic surgery were randomized to receive preoperative cefotaxime (1 g) or trimethoprim-sulfamethoxazole (160 mg trimethoprim, 800 mg sulfamethoxazole) as prophylaxis: 613 patients were available for analysis, of whom 315 received cefotaxime and 298 received trimethoprim-sulfamethoxazole. Forty-two patients (6.9%) experienced 49 postoperative infections, with no significant difference between treatment groups. The most common infections unrelated to neurosurgery were urinary tract infections (17 cases) and pneumonia (seven cases). Fifteen neurosurgical infections occurred, comprising 11 wound infections, two shunt infections and two cerebral abscesses. Neurosurgical infection rates were similar in the cefotaxime group (2.5%) and the trimethoprim-sulfamethoxazole group (2.3%). We concluded cefotaxime and trimethoprim-sulfamethoxazole administered as single dose prior to neurosurgery are equally effective in controlling neurosurgical infection and postoperative infection at remote sites.

Adult↗
PubMed2000

Depression diagnoses and antidepressant use in primary care practices: a study from the Practice Partner Research Network (PPRNet).

BACKGROUND: We examined the pharmacologic management and follow-up of adults with newly diagnosed depression, and the use of antidepressants among patients not diagnosed with depression in primary care practice. A total of 389 physicians in 39 practices in the Practice Partner Research Network (PPRNet), a national network of primary care physicians provided data for the study. METHODS: We performed a retrospective cohort study for the year 1996 using demographic, contact, diagnosis, and prescription data available in the December 1997 PPRNet database. We identified patients with new diagnoses of depression from the problem lists in the electronic medical record. Psychopharmacologic agents prescribed within 5 days of the diagnosis, follow-up contacts within 6 months of the diagnosis, and diagnoses of patients prescribed antidepressants without a new diagnosis of depression were also identified. We performed descriptive analyses for all practices and for individual practices. RESULTS: During 1996, there were 149,327 active adult patients in the 39 participating practices. Of the 131,141 patients without a history of depression or antidepressant prescription, 2103 (1.6%) had a new diagnosis of depression in 1996. Incidence among the 39 practices ranged from 0.4% to 4.0%. Forty-nine percent of the newly diagnosed patients received an antidepressant prescription within 5 days of diagnosis; 81% of the prescriptions were for selective serotonin reuptake inhibitors. Ninety percent of the patients prescribed antidepressants had at least one contact in the 6 months after diagnosis (mean = 5.3 contacts). One third of the patients who had not begun antidepressants within 5 days of their diagnoses started taking one by the end of 1996. Among the 149,327 active patients, 6.3% received a prescription for an antidepressant in 1996. More than 40% of these patients had never been diagnosed with depression. CONCLUSIONS: Our study highlights the high prevalence and wide interpractice variations of diagnosing depression and prescribing antidepressants in primary care. Follow-up of patients newly diagnosed with depression was common and consistent with published guidelines. Opportunities for increased detection and treatment of depression exist in approximately half of the study practices.

Adolescent↗
PubMed1999

Facilitation and inhibition arising from the exogenous orienting of covert attention depends on the temporal properties of spatial cues and targets.

On the covert orienting of visual attention task (COVAT), responses to targets appearing at the location indicated by a non-predictive spatial cue are faster than responses to targets appearing at uncued locations when stimulus onset asynchrony (SOA) is less than approximately 200 ms. For longer SOAs, this pattern reverses and RTs to targets appearing at uncued locations become faster than RTs to targets appearing at the cued location. This facilitation followed by inhibition has been termed the biphasic effect of non-predictive peripheral spatial cues. Currently, there is debate about whether these two processes are independent. This issue was addressed in a series of experiments where the temporal overlap between the peripheral cue and target was manipulated at both short and long SOAs. Results showed that facilitation was present only when the SOA was short and there was temporal overlap between cue and target. Conversely, inhibition occurred only when the SOA was long and there was no temporal overlap between cue and target. The biphasic effect, with an early facilitation followed by a later inhibition, occurred only when the cue duration was fixed such that there was temporal overlap between the cue and target at short but not long SOAs. In a final experiment, the duration of targets the temporal overlap between cue and target and the SOA were manipulated factorially. The results showed that facilitation occurred only when the SOA was short, there was temporal overlap between cue and target and the target remained visible until the subject responded. These results suggest that the facilitation and inhibition found on COVATs which use non-informative peripheral cues are independent processes and their presence and magnitude is related to the temporal properties of cues and targets.

Adult↗