Radiation Therapy Oncology Group (RTOG).
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Clinical Trials, Phase III as Topic↗
Biomedical subjects
C Scott
Publications and source records attributed to C Scott.
Acute gastrointestinal bleeding due to Meckel's diverticulum heterotopic gastric mucosa.
Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract occurring in approximately 2% of the population. In our retrospective study, we analyzed 58 surgical specimens of Meckel's diverticulum operated on in our hospital. Heterotopic gastric mucosa was found in ten. Aim of this study was to establish the aetiopathogenesis of inflammation and consequent haemorrhage in Meckel's diverticulum with heterotopic gastric mucosa. Some studies showed that Helicobacter-like bacteria could play an important role in determining local phlogosis in heterotopic gastric mucosa of Meckel's diverticulum, however, none were found in our biopsy specimens. Analyzing patients with acute intestinal haemorrhage (4 out of 10 with heterotopic gastric mucosa) in Meckel's diverticulum a history of previous oral administration of NSAID's was positive in 3 of them. Although in the recent literature there were few case reports on the use of NSAID's and bleeding from Meckel's diverticulum, our results suggest that even short-term use, in small quantities, of NSAID's can play an important role in determining acute bleeding from Meckel's diverticulum with heterotopic gastric mucosa.
Acute Disease↗
RTOG's first quality of life study--RTOG 90-20: a phase II trial of external beam radiation with etanidazole for locally advanced prostate cancer.
PURPOSE: To assess institutional and patient compliance with quality of life (QL) instruments in RTOG clinical trials. To assess feasibility of using the Functional Assessment Cancer Therapy (FACT), Sexual Adjustment Questionnaire (SAQ), and Changes in Urinary Function (CUF) QL instruments in a prostate clinical trial and to compare patient self-report of symptoms to medical professional ratings of the same symptoms using the RTOG acute toxicity rating scales. METHODS AND MATERIALS: Three self-assessment QL instruments, the FACT, the SAQ, and CUF, were to be administered to patients on a Phase II locally advanced prostate trial at specified time points. Specific instructions for both data managers and for patients on when, how, and why to fill out the questionnaires were included. RESULTS: Sixty-seven percent (24 out of 36) of patients accrued to RTOG 90-20 completed both the initial FACT and SAQ. Eighty-five percent completed FACT at end of RT and 73% at 3 months. Eighty-one percent completed SAQ at end of treatment, while 69% completed this form at 3 months. Compliance drops off thereafter. Seventy-five percent of patients who had their symptom of dysuria rated by a medical professional as 0 on the RTOG toxicity rating scale self-reported the same. Only 56% of patient self-reports on FACT regarding diarrhea were in agreement with the medical professional's RTOG rating of 0 toxicity. The measures were determined to be in moderate agreement when the patient evaluated a symptom as a 1 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG toxicity rating scale. There was moderate agreement in 13% of patients with dysuria and 31% of patients with diarrhea. Low agreement occurred when the patient evaluated a symptom as a 2 or 3 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG scale. Low agreement occurred in 13% of both patients reporting dysuria and diarrhea. Differences between how medical professionals and patients were able to rate erectile function make direct comparisons difficult, but the trend towards significant discrepancies is still noteworthy. CONCLUSIONS: Quality of life assessments are necessary and attainable in RTOG clinical trials. Compliance rates for both institutional and patient participation were acceptable at initial and 3 month follow-up. Reasons for noncompliance were predominantly institution related and not patient related. Strategies to address both institution and patient compliance have been developed and implemented within the RTOG. Serious disagreement between patient self-reports of symptoms on the FACT QL scale and medical professional ratings on the RTOG acute toxicity rating scales of the same symptoms was 13% at 3 months follow-up. This warrants continued use of QL self-assessments in clinical trials.
Adenocarcinoma↗
Pit-1 exhibits a unique promoter spacing requirement for activation and synergism.
The developmentally regulated Pit-1 transcription factor is involved in the activation of prolactin, growth hormone, and TSH beta expression. Using templates with spacing mutations to program an in vitro transcription system, the activity of a single Pit-1 proximal binding site within the rat prolactin promoter was shown to have a unique bimodal distance requirement. Transcription activity rapidly decreased with each 5-base pair (bp) addition to the spacing between the binding site and the TATA box. When positioned 20 bp upstream from its normal -36 position in the prolactin promoter, the activity of the Pit-1 binding site is reduced to basal levels. Placement of the site at a position 30 bp upstream resulted in a return of Pit-1-mediated activation. Using transient transfection assays in GH3 cells, the prime bimodal sites are also a requirement for optimum expression of chimeric prolactin-luciferase reporter constructs. Interestingly, optimal synergism of transcription in vivo by the prolactin distal enhancer, containing four Pit-1 binding sites and an estrogen-responsive element, is also sensitive to the placement of the proximal Pit-1 binding site. These data have important implications for Pit-1 activator function in pituitary cells and for general models of transcription synergism.
Animals↗
Quality-adjusted survival analysis of malignant glioma. Patients treated with twice-daily radiation (RT) and carmustine: a report of Radiation Therapy Oncology Group (RTOG) 83-02.
PURPOSE: To quantify the quality of life of malignant glioma patients treated on a randomized Phase I/II trial of twice-daily radiation therapy (RT) and carmustine, using a modified quality adjusted survival (QAS) model, and to compare the QAS among assigned treatment arms. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) accrued 786 malignant glioma patients to a Phase I/II randomized dose escalation trial of twice-daily RT with carmustine from 1983 to 1989. Patients were randomized to one of four arms of hyperfractionated RT in 1.2 Gy twice daily (BID) fractions (64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.6 Gy) or to either of two accelerated hyperfractionated RT arms in 1.6 Gy BID fractions (48.0 or 54.4 Gy). Although preliminary toxicity and survival data have been published, little information is available regarding the quality of these patients' lives during and following such therapy. QAS is a refinement of the methodology for assessing survival quality among breast cancer patients receiving adjuvant chemotherapy. The QAS method allows for inclusion of both improvement and decline in neurologic functional status. Patients were scored by the presence or absence of 15 neurologic signs and symptoms at on-study and at every follow-up. Within each category were gradations of severity, with the quality survival time (Q-TIME) adjusted according to any changes in these neurologic findings. The summation of all changes in signs and symptoms were weighted by 1/15th and incorporated into the QAS model as QAS = Q-TIME-TOX-RRX. TOX was the time spent with treatment-related toxicities, and RRX was the time spent in recovery from subsequent therapy. RESULTS: Of 747 evaluable patients, the average QAS time was 18.5 months. The average QAS for the hyperfractionated arms of 64.8 Gy, 72.0 Gy, 76.8 Gy, and 81.6 Gy were 15.6, 20.8, 10.0, and 13.7 months, respectively. For the accelerated hyperfractionated RT arms of 48.0 and 54.4 Gy, the average QAS times were 13.1 and 13.4 months. The QAS time of the 72.0 Gy arm was significantly longer than that of all other groups, except the 64.8 Gy arm. As expected, the QAS times were strongly discriminated by both age and Karnofsky Performance Scores (KPS) (p < 0.001). Younger patients and patients with high KPS benefited most from assignment to the 72.0 Gy arm; QAS time was not significantly longer in any treatment arm among patients over age 50 or with KPS scores of 80 or less. CONCLUSIONS: This quality-adjusted survival methodology can be successfully applied to malignant glioma patients and permits a quantitative assessment of the influence of investigational therapies on patient quality of life. This analysis confirms the potential benefit of intermediate dose (72.0 Gy) hyperfractionated RT for selected malignant glioma patients.
Adult↗
Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer.
BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.
Adult↗
Small bowel transplantation.
Small bowel transplantation (SBT) presents a formidable challenge to perioperative nurses. Patients who survive these procedures have difficult postoperative courses with lengthy intensive care stays. They also are at significant risk for graft rejection and long-term immunosuppression complications. The option for SBT is reserved for patients who otherwise face the prospect of life-long total parenteral nutrition (TPN). Advances in donor and recipient surgical techniques and improvements in immunosuppressive therapies have raised hopes that patients with intestinal failures who undergo SBT procedures will be allowed to resume full oral nutrition and independence from TPN.
Animals↗
Inhibition of hepatocyte growth factor-induced motility and in vitro invasion of human colon cancer cells by gamma-linolenic acid.
In this study we have determined the effects of the n-6 essential fatty acid gamma-linolenic acid (GLA) on the motility and invasive/metastatic nature of the human colon cancer cell lines HT115, HT29 and HRT18. Cell motility was induced by hepatocyte growth factor/scatter factor (HGF/SF) and measured by both colony scattering and dissociation from carrier beads. Invasiveness was measured in vitro by cellular invasion into extracellular matrix. At concentrations up to 100 microM (which had no effect on cell growth over the duration of the experiments) both cell motility and invasion induced by HGF/SF were markedly reduced by GLA and its lithium salt. The attachment of these cells to the extracellular matrix components (Matrigel and fibronectin) was also inhibited. There were also changes in the cell-surface E-cadherin, but not fibronectin receptor at similar concentrations. It is concluded that n-6 essential fatty acids have the ability to inhibit both motility and invasiveness of human colon cancer cells, perhaps by modifying cell-surface adhesion molecules.
Arachidonic Acid↗
The effect of nedocromil sodium on childhood asthma during the viral season.
Viral-induced symptomatic respiratory infections (SRI) frequently cause exacerbations of asthma in children. This study investigated the protective effects of 0.5% nedocromil sodium nebulizer solution given three times a day in preventing asthma exacerbations associated with SRI. Ninety-three mild-moderate asthmatic children (6 to 12 yr of age) received either 0.5% nedocromil sodium or placebo for 24 wk during the viral season. The nedocromil sodium group was symptom-free 58% of the days, and the placebo-treated patients were symptom-free 45% of the days (p = 0.027). During Weeks 1-12, significant differences favored nedocromil sodium for asthma summary score (means: nedocromil sodium = 0.61, placebo = 0.92; p = 0.026), and daytime asthma (nedocromil sodium = 0.78, placebo = 1.22; p = 0.03). Significant differences were noted during monthly intervals for cough (Weeks 1-4: nedocromil sodium = 0.61, placebo = 0.92, p = 0.027) and peak expiratory flow rate (PEFR) (nedocromil sodium 262, placebo = 254 L/min, p = 0.041 Weeks 9-12). Patients in the active treatment group reduced their need for rescue inhaled beta 2-agonist by 10%, whereas patients treated with placebo demonstrated a 24% increase. There was a strong correlation between asthma symptoms and SRI symptoms (r = 0.47; p < 0.001). During SRIs, patients in the nedocromil sodium group demonstrated more rapid resolution of asthma symptoms immediately following infection (p = 0.033 summary score, p = 0.039 sleep difficulty). No serious adverse events were noted. Nedocromil sodium did not prevent the infection or exacerbation of asthma symptoms during SRI.(ABSTRACT TRUNCATED AT 250 WORDS)
Anti-Asthmatic Agents↗
Continuing risk for hepatitis B virus transmission among Southeast Asian infants in Louisiana.
OBJECTIVE: Implementation and evaluation of a hepatitis B vaccination program for Southeast Asian infants in Louisiana. METHODS: A baseline seroprevalence survey of hepatitis B virus (HBV) infection in US-born Southeast Asian children was conducted in 1991 before the implementation of a vaccination program. Hepatitis B vaccination and postvaccination serologic testing of survey participants 10 years of age and younger was performed. Eighteen months after the hepatitis B vaccine was integrated into infant immunization schedules in July 1993, a vaccination coverage survey was performed. RESULTS: Baseline serologic testing was conducted on 96% of persons from 225 randomly selected households in a Southeast Asian community in Louisiana. Of 676 US-born children, 28 (4.1%) had chronic HBV infection; 61% of children with chronic HBV infection were born to hepatitis B surface antigen (HBsAg)-negative women. Among children born to HBsAg-negative women, the prevalence of chronic HBV infection increased with age, reaching 7.3% for children 13 to 16 years of age. Children born to HBsAg-negative women and living with carriers were 5.4 times more likely to have evidence of HBV infection than were children who did not live with carriers. Before the survey, only one child had received three doses of hepatitis B vaccine. In July 1993, 43% of Southeast Asian infants 9 to 18 months of age born in Louisiana had received three doses of hepatitis B vaccine. Infants who received immunizations from private providers were more likely to be fully vaccinated than were infants who received services from public sector clinics (prevalence ratio, 2.1; 95% confidence interval, 1.4, 3.1). CONCLUSIONS: HBV transmission occurs throughout childhood in US-born Southeast Asian children, and the prevalence of chronic HBV infection approaches that of the country of origin. Few US-born Southeast Asian children have received hepatitis B vaccine. Because of the high rates of early childhood HBV transmission and the high risk of chronic infection in Asian and Pacific Islander communities, prevention efforts should be enhanced to ensure that all Asian and Pacific Islander infants receive hepatitis B vaccine in the first 12 months of life and that older children are vaccinated.
Adolescent↗
Antidepressants and side effects.
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Australia↗
Diagnostic laparoscopy: a 5-year experience in a hepatology training program.
Diagnostic laparoscopy continues to have a role in the evaluation and diagnosis of acute and chronic liver diseases, primary and metastatic liver tumors, and peritoneal diseases. We retrospectively reviewed the records of 1794 diagnostic laparoscopies performed at our institution from 1987 to 1992 to identify the indications, results, and safety of this procedure in our training program. A definitive diagnosis was made in 91% of cases with biopsy performed in 93%. Chronic liver disease was evaluated in 890 patients, and a diagnosis was made in 98%. Four hundred thirty-seven patients were evaluated for suspected primary or metastatic carcinoma, and a diagnosis was made in 85%. Ascites was evaluated in 73 patients, and a diagnosis was made in 82%. One-hundred sixty-four patients were evaluated for abnormal liver function tests, and a diagnosis was made in 91%. HIV-related liver function test abnormalities were evaluated in 67 patients, and a diagnosis was made in 81%. One hundred sixty-three patients underwent diagnostic laparoscopy for the evaluation of hepatomegaly, splenomegaly, unexplained portal hypertension, fever of unknown origin, and cholestasis, and a diagnosis was made in 74% of cases. Eight major complications (including abdominal viscus perforation, hemobilia, splenic laceration, bleeding) and thirty-one minor complications were seen. Our findings confirm that diagnostic laparoscopy is a safe and valuable procedure in the evaluation of chronic liver disease.
Chronic Disease↗
An interview with Clifford Scott. Interview by Virginia Hunter.
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Canada↗
Conserved amino acid residues in the complementarity-determining region 1 of the TCR beta-chain are involved in the recognition of conventional Ag and Mls-1 superantigen.
Superantigens activate T cells by interacting primarily with the V beta region of the TCR. This report describes a series of studies performed to elucidate the role of the conserved amino acid motif (Asp-His-Asn) in the complementarity-determining region 1 (CDR1) of the TCR V beta chains that recognize murine endogenous superantigen Mls-1. By using site-directed mutagenesis of the Mls-1-reactive TCR V beta 6 gene, it is shown that the alterations of the conserved CDR1 motif disrupt Mls-1 superantigen and conventional Ag recognition in vitro. The loss of V beta 6 (mutant)+ TCR reactivity to Mls-1 superantigen is apparently dependent on the partner alpha-chain in the V beta 6/V alpha 3 TCR pairing shows some reactivity to Mls-1, whereas other TCR pairings do not. The examination of the developmental fate of the mutated form of the V beta 6 chain in Mls-1+ mice by using retroviral vector-mediated gene transfer confirms the critical role played by the CDR1 residues in Mls-1 recognition in vivo. Collectively, the results indicate that the CDR1 of the TCR V beta 6 chain is involved in interacting with peptide/MHC as well as in Mls-1 recognition. The observation that the conserved residues in selective TCR V beta chains are imparting a significant contribution to Ag recognition suggests a molecular basis for the intrinsic bias of some V beta chains for MHC molecules.
Amino Acid Sequence↗
The effect of perioperative blood transfusion on survival in head and neck cancer.
This Head and Neck Intergroup analysis was undertaken to evaluate further previously reported observations linking blood transfusions, which were given to patients with head and neck cancer, to a worse prognosis. This study population represents those patients registered to the Head and Neck Intergroup Trial 0034 for previously untreated resectable squamous cell carcinoma. Additional transfusion data were obtained by one of us (D.E.S.) on 217 patients and added to the Head and Neck Intergroup data set, providing an opportunity for assessing the impact of survival by other variables. The study group was separated using 13 variables. Analysis demonstrated that transfusion did not significantly decrease the locoregional control (P = .60). Multivariate analysis indicated that T stage (P = .015), N stage (P = .004), treatment received (P = .004), and Karnofsky Performance Scale (P = .031) were the only factors that did significantly influence survival. This multivariate analysis controlling for these variables demonstrated no significant effect on survival for those patients receiving transfusion during surgery (P = .55) or after surgery (P = .39). This study of 217 patients, controlled for other variables, does not demonstrate any significant negative relation between blood transfusions and either locoregional control or survival.
Activities of Daily Living↗
Stimulation of phospholipase C in cultured microvascular endothelial cells from human frontal lobe by histamine, endothelin and purinoceptor agonists.
1. Cultures of endothelial cells derived from the microvasculature of human frontal lobe have been investigated for phospholipase C (PLC) responses to histamine, endothelins and purinoceptor agonists. 2. Using cells prelabelled with [3H]-inositol and measuring total [3H]-inositol (poly)phosphates, histamine acting at H1 receptors stimulated a substantial response with an EC50 of about 10 microM. 3. Endothelin-1 also gave a clear stimulation of phosphoinositide-specific phospholipase C. Both concentration-response curves and binding curves showed effective responses and binding in the rank order of endothelin-1 > sarafotoxin S6b > endothelin-3, suggesting an ETA receptor. 4. Assay of total [3H]-inositol (poly)phosphates showed no response to the purinoceptor agonists, 2-methylthioadenosine 5'-trisphosphate (2MeSATP), adenosine 5'-O-(3-thiotrisphosphate) (ATP gamma S) or beta,gamma-methylene ATP. Both ATP and UTP gave a small PLC response. 5. Similarly, when formation of [32P]-phosphatidic acid from cells prelabelled with 32Pi was used as an index of both PLC and phospholipase D, a small response to ATP and UTP was seen but there was no response to the other purinoceptor agonists tested. 6. Study by mass assay of stimulation by ATP of inositol (1,4,5) trisphosphate accumulation revealed a transient response in the first few seconds, a decline to basal, followed by a small sustained response. 7. These results show that human brain endothelial cells in culture are responsive to histamine and endothelins in a manner which may regulate brain capillary permeability. Purines exert a lesser influence.
Adenosine Triphosphate↗
Dilated cardiomyopathy in children: determinants of outcome.
OBJECTIVE: To determine the outcome of dilated cardiomyopathy presenting in childhood and the features that might be useful for prognostic stratification. SETTING: Supraregional paediatric cardiology unit. DESIGN: Retrospective analysis. BACKGROUND: The natural history of dilated cardiomyopathy in children is not well characterised. Previous studies have shown a variable relation between age at presentation and outcome, and sudden death has been infrequent. METHODS: Retrospective study of 63 consecutive patients with idiopathic dilated cardiomyopathy presenting between 1979 and 1992. Survival curves were constructed by the Kaplan-Meier method. RESULTS: Age at diagnosis ranged from 1 day to 15 years (median 12 months) and follow up ranged from 1 day to 13 years (median 19 months). Actuarial survival from presentation was 79% at one year (95% confidence interval (95% CI) 66%-88%) and 61% (44%-74%) at five years. Univariate analysis showed that mural thrombus, left ventricular end diastolic pressure > 20 mm Hg, and age at presentation > 2 years were predictors of adverse outcome, but on multivariate analysis only age at presentation was significant. Left ventricular echocardiographic indices either did not improve or deteriorated in 36 children (17 of whom died, four suddenly, and three were transplanted), partially improved in 16 (three of whom died, all suddenly), and returned to normal in 11 (all of whom have survived). CONCLUSIONS: Older age at presentation and lack of improvement in systolic function are associated with an adverse outcome, and early transplantation should be considered in these patients. There is a persistent risk of late sudden death in those children in whom echocardiographic dimensions remain abnormal.
Adolescent↗
Mild sialoadenitis: a common finding in patients with hepatitis C virus infection.
BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disease of presumed viral origin; sialoadenitis has been reported to occur in hepatitis C virus (HCV) infection. METHODS: Lip biopsy specimens were graded in 32 consecutive patients with either HCV-related chronic liver disease or SS. RESULTS: Seventeen of 22 HCV-positive patients had sialoadenitis, although generally mild (15 of 17, grades I-II). Severe inflammation (grades III-IV) was observed in 8 of 10 patients with SS (chi-square = 12.6; P < 0.0005). Moreover, HCV-positive patients with sialoadenitis differed from patients with SS in female sex prevalence (6 of 17 versus 10 of 10; chi-square = 10.9; P = 0.0001) and presence of serum antinuclear autoantibodies (0 of 17 versus 9 of 10; chi-square = 23.0; P < 0.0001). Five of 13 HCV-positive patients and 7 of 8 patients with SS were HLA-DR3-positive (chi-square = 4.9; P < 0.05). CONCLUSIONS: Sialoadenitis of HCV-related liver disease is common but differs from SS with regard to predisposing genetic factors, expression of autoimmune markers, and histopathologic severity.
Adult↗