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Biomedical subjects

C Scott

Publications and source records attributed to C Scott.

At least 127 records · Page 7Linked to original sources
PubMed1998

Henoch-Schönlein purpura: a review.

Henoch-Schönlein purpura is an IgA-mediated, autoimmune, hypersensitivity vasculitis of childhood that results in a triad of symptoms, including a purpuric rash occurring on the lower extremities, abdominal pain or renal involvement, and arthritis. However, any of the triad may be absent, which often leads to confusion in diagnosing the condition. Although the cause is unknown, Henoch-Schönlein purpura is often associated with infectious agents such as group A streptococci and Mycoplasma. It has also been associated with food reactions, exposure to cold, insect bites and drug allergies. Treatment is supportive, and children affected by this disorder need close follow-up of renal status.

Diagnosis, Differential↗
PubMed1998

The development of theory of mind in deaf children.

Deaf children aged 4 to 16 years were given a false-belief test of theory of mind. Although the children experienced difficulty with the test, relative to hearing children, confirming a report by Peterson and Siegal (1995), performance was age-related, with a significantly higher proportion of 13- to 16-year-olds passing the test. It was concluded that deaf children raised in a spoken language environment show a developmental delay in theory of mind acquisition. This delay is consistent with the assumption that their early opportunities for learning about mental states are relatively restricted and that the normal development of theory of mind is dependent upon such opportunities.

Adolescent↗
PubMed1997

When is a negative study not negative?

Results of Phase III randomized clinical trials can be categorized into three groups: positive, null, and negative. The jargon used in discussing results of comparative studies requires clarification because misclassification can result in incorrect interpretation. A positive result indicates that the experimental therapy(ies) is(are) superior to standard therapy. A null result indicates that no statistically significant difference between therapies was found; hence, standard therapy should not be replaced. A negative result indicates that the experimental therapy had a deleterious effect compared to standard therapy. This article presents a discussion of these categories and examples of each.

Clinical Trials, Phase III as Topic↗
PubMed1997

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.

PURPOSE: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. METHODS AND MATERIALS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. RESULTS: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm. CONCLUSION: Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.

Adult↗
PubMed1997

Genetic influences determining progenitor cell mobilization and leukocytosis induced by granulocyte colony-stimulating factor.

The mechanisms involved in the mobilization of progenitor cells into the blood by granulocyte colony-stimulating factor (G-CSF) and other cytokines are poorly understood. To identify important influences on this complex process, in vivo murine models were used. Granulocyte-macrophage colony-stimulating factor (GM-CSF) transgenic, Max41 transgenic, W/Wv, Mpl-null, GM-CSF receptor (beta chain)-null mice, wild-type littermate controls, and six inbred strains of mice were injected with 200 microg/kg/d G-CSF for 5 days. Three parameters of response were monitored: white blood cell count (WCC), peripheral blood progenitor cell (PBPC) numbers, and spleen weight. In all genotypes studied, G-CSF induced increases in these three parameters. However, PBPC mobilization in W/Wv and Mpl-null mice was only 30% and 9%, respectively, of that observed in wild-type mice. In contrast, perturbations of GM-CSF signalling had no demonstrable effect on in vivo responses to G-CSF. Broad variability was evident between inbred strains for each parameter of the response to G-CSF. A 10-fold range in response was observed for circulating progenitor cell numbers, similar to that observed for normal human subjects receiving G-CSF. The interstrain differences were in the distribution of mature and progenitor cells between peripheral blood, bone marrow, and spleen rather than in the total numbers of these cells in the body. Results of an F2 intercross of low-responding C57BL/6 and intermediate-responding SJL mice indicated that regulation of progenitor cell mobilization is a complex genetic trait, that there is a correlation between this trait and WCC response (r2 = .5), and that this approach may serve as a useful model for the identification of genes involved in the mobilization process.

Animals↗
PubMed1997

Quality of life and neuropsychological evaluation for patients with malignant astrocytomas: RTOG 91-14. Radiation Therapy Oncology Group.

UNLABELLED: With increasingly aggressive neurosurgical and radiation therapy modalities (gamma knife, external beam stereotactic radiation and interstitial brachytherapy with or without hyperthermia) offered to patients with malignant astrocytomas (MA), increasing national demand for medical outcome studies and rising health care costs amidst public, business, and governmental debate to cut spending, we as physicians are obligated to continue our research to find effective treatments for malignant astrocytoma (MA) and a cost-effective means to study their impact upon the patient's quality of life (QOL). PURPOSE: We report data that was collected within the Radiation Therapy Oncology Group (RTOG) on 126 patients with MA who were enrolled in RTOG 91-14. This study was undertaken to prospectively test the feasibility of performing quality of life (QOL) and neuropsychological evaluation (NPE) and collecting this data within the RTOG. RESULTS: The NPE and QOL parameters that were used in this study are cost effective. They are not only much cheaper than formal cognitive and memory testing, but also provide additional information regarding the patients' day to day functional abilities that are not provided by the current routinely used means, such as KPS. The Mini-Mental Status Exam (MMSE) provides greater sensitivity to patients' differences in neurological status and may be preferable to NFS as an eligibility criteria.

Activities of Daily Living↗
PubMed1997

Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall cell lung cancer: Radiation Therapy Oncology Group (RTOG) 92-04.

PURPOSE: The purpose of this study was to compare the severity and distribution of the toxicities associated with the two different combinations of chemotherapy and radiotherapy. METHODS AND MATERIALS: This prospective randomized trial studied toxicities associated with induction chemotherapy followed by concurrent treatment (Arm 1) vs. immediate concurrent chemotherapy/radiotherapy (CT/RT) (Arm 2). Arm 1 consisted of vinblastine (VB), 5 mg/M2 I.V. bolus weekly, weeks 1-5 and cisplatin (DDP), 100 mg/M2 days 1 and 29, DDP 75 mg/M2, days 50, 71, and 92. Daily RT started on day 50; a total dose of 63 Gy was given in 34 fractions in 7 weeks. In Arm 2 RT started day 1; a total dose of 69.6 Gy was given in 58 fractions of 1.2 Gy bid, 5 days per week for 6 weeks with DDP 50 mg/M2 i.v. days 1 and 8, and oral VP-16 50 mg b.i.d. during the first 10 days of RT. DDP/VP-16 were repeated beginning day 29. Survival was used as the Phase II endpoint. RESULTS: Between July 1992 and February 1994, 168 patients were randomized; 162 evaluable patients had minimum follow-up of 20 months. Eighty patients were registered to Arm 1 and 82 to Arm 2. Pretreatment characteristics were distributed evenly. Arm 1 had significantly more Grade 4 hematologic toxicity (62%) than Arm 2 (33%) (p = 0.021). Acute nonhematologic Grade 3+ toxicity was also greater (p = 0.018) in Arm 2 than Arm 1 due mainly to esophagitis (38 vs. 6%; p < 0.0001). Grade 3+ late esophageal toxicity was 12% on Arm 2 compared to 3% on Arm 1 (p = 0.006). There were no differences between the two arms in compliance with protocol specifications for either RT or CT. At 1 year, 31.7% of patients had in-field progression on Arm 1 compared to 19.8% on Arm 2 (p = 0.042), but overall progression-free survival rates were nearly identical; 50 and 49% for Arms I and II, respectively, at 12 months. One-year and median survivals were 65% and 15.5 months on Arm 1 compared to 58% and 14.4 months on Arm 2. CONCLUSION: Whereas hematologic toxicity was greater in Arm 1, esophageal toxicity, both acute and late, was greater in Arm 2. Infield progression was lower in Arm 2, but overall progression rates were similar and there were no significant differences in survival between the two arms. A 3-arm randomized Phase III study is underway in the RTOG to compare sequential and concurrent CT/RT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.

PURPOSE: Promising results from new approaches such as radiosurgery or stereotactic surgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous Radiation Therapy Oncology Group (RTOG) brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions. METHODS AND MATERIALS: The database included 1200 patients from three consecutive RTOG trials conducted between 1979 and 1993, which tested several different dose fractionation schemes and radiation sensitizers. Using recursive partitioning analysis (RPA), a statistical methodology which creates a regression tree according to prognostic significance, eighteen pretreatment characteristics and three treatment-related variables were analyzed. RESULTS: According to the RPA tree the best survival (median: 7.1 months) was observed in patients < 65 years of age with a Karnofsky Performance Status (KPS) of at least 70, and a controlled primary tumor with the brain the only site of metastases. The worst survival (median: 2.3 months) was seen in patients with a KPS less than 70. All other patients had relatively minor differences in observed survival, with a median of 4.2 months. CONCLUSIONS: Based on this analysis, we suggest the following three classes: Class 1: patients with KPS > or = 70, < 65 years of age with controlled primary and no extracranial metastases; Class 3: KPS < 70; Class 2- all others. Using these classes or stages, new treatment techniques can be tested on homogeneous patient groups.

Adult↗
PubMed1997

Recursive partitioning analysis of 1592 patients on four Radiation Therapy Oncology Group studies in inoperable non-small cell lung cancer.

Survival outcome of 1592 analyzable patients on four Radiation Therapy Oncology Group (RTOG) studies in inoperable non-small cell lung cancer were studied utilizing a recursive partitioning analysis (RPA). This approach creates a regression tree according to prognostic variables which partitions into homogenous subsets according to survival. Four protocols, RTOG 83-11, 83-21, 84-03 and 84-07 were analyzed. 83-11 and 84-07 were studies utilizing irradiation with alterfractionation; 83-21 and 84-03 were studies evaluating thymocin with irradiation and prophylactic cranial irradiation with thoracic irradiation respectively. Nine pretreatment variables and one treatment variable were analyzed. Adjustment for radiotherapy effect was made in the accelerated treatment protocol (84-07). Overall, median survival for the entire group was 9.0 months with 17% alive at 2 years. Univariate analysis suggests that KPS, < or = 70 vs. 80-100, pleural effusion, weight loss, < or = 5% vs. 5%, age, 60+ vs. < 60, T stage (T1 and T2 vs. T3 and T4) and N stage (N- vs. N+) were important prognastic factors. Radiation dose, sex, race and histology were not univariate prognastic factors. RPA identified KPS as the most significant covariate (median survival 5.9 mos. < or = 70 vs. 9.9 mos. 80-100). Within KPS 80-100 other splits occurred for N stage, age, weight loss and radiation therapy dose. KPS < or = 70 split at pleural effusion only. The best overall RPA tree has four distinct classes with median survival times ranging from 3.3 to 12.6 months. The RPA classes were validated in an independent non-small cell lung cancer dataset. This analysis may allow more intelligent stratification and study-design for future RTOG trials in inoperable non-small cell lung cancer.

Aged↗
PubMed1997

Fatal compressional injuries from a burst tyre: an industrial death.

A young maintenance man was killed while fixing a heavy duty tyre to a fork lift. The tyre exploded, sprang off the front axle and threw the victim against a wall 7.5 m away, fatally crushing him. Autopsy revealed multiple crush injuries and, cannabinoids were detected in the victim's urine. The mechanism of the fatal pneumatically-induced compressional injuries sustained and the significance of the cannabinoids in the body fluids of the deceased are discussed in this paper. Proposals are given on how to prevent similar accidents in the workplace.

Journal Article↗
PubMed1997

All-trans-retinoic acid: a phase II Radiation Therapy Oncology Group study (RTOG 91-13) in patients with recurrent malignant astrocytoma.

The Radiation Therapy Oncology Group enrolled 30 patients with recurrent malignant astrocytomas onto a phase II study (RTOG 91-13). Patients were treated with all-trans-retinoic acid at a starting dose of 120 mg/m2 per day orally continuously until disease progression. Fourteen patients had glioblastoma, 14 had anaplastic astrocytoma, and 2 had other histologies; 53% were under 50 years of age. All patients had failed radiation therapy and/or at least one chemotherapy regimen. All patients had a Karnofsky performance status score of at least 70, but only 37% had a KPS of 90-100. Forty percent had a neurologic function status of grade 1 (able to work). A minimum of 4 weeks of all-trans-retinoic acid defined adequate treatment. Twenty-five patients received adequate therapy. Most common toxicities were dry skin, cheilitis, anemia, and headache; 3 patients had grade 3 headache requiring suspension of all-trans-retinoic acid. No grade 3 hematologic toxicity was observed. Of 25 adequately treated patients, 3 showed objective regression of tumor on magnetic resonance imaging and computed tomography scans, 3 patients remained stable, and 19 patients had disease progression. The median time to tumor progression was 3.8 months and the median survival time was 5.7 months. This study suggests that this dose of single agent all-trans-retinoic acid has modest clinical activity against recurrent malignant gliomas with tolerable side effects. A response rate of 12% and a stabilization rate of 12% are lower than expected. Future studies with higher dosage or in combination with biological response modifiers or chemotherapy may be warranted.

Antineoplastic Agents↗
PubMed1997

Teleophthalmology: rationale, current issues, future directions.

Relatively little information exists concerning the delivery of ophthalmic services via telemedicine, yet ophthalmology is particularly amenable to the utilization of such applications. This paper discusses the technological issues pertinent to the research, development, and assessment of teleophthalmology delivery systems and begins to define the parameters that will determine the sustainability of teleophthalmology. A prototype urban teleophthalmology delivery system is presented in the context of improving access to eye care for an underserved inner-city population. Potential enhancements to the prototype telephthalmology system are discussed.

Adolescent↗
PubMed1997

Impact of adding concurrent chemotherapy to hyperfractionated radiotherapy for locally advanced non-small cell lung cancer (NSCLC): comparison of RTOG 83-11 and RTOG 91-06.

A hyperfractionated radiation therapy (HFX RT) trial (1.2 Gy twice daily, b.i.d.) (HFX) for non-small cell lung cancer (NSCLC) showed that 69.6 Gy resulted in better survival than did lower total doses (Radiation Therapy Oncology Group, RTOG 83-11) and that cisplatin concurrent with irradiation improved local control and survival over RT alone (Radiation Therapy Oncology Group, RTOG 91-06). Concurrent combination chemotherapy and HFX could improve both local and systemic control. In a phase II trial (RTOG 91-06) for inoperable NSCLC, two cycles of PE were used [cisplatin 50 mg/m2 intravenously (i.v.) days 1 and 8, etoposide 50 mg orally (p.o.) b.i.d., 75 mg/day if body surface area (BSA) < 1.7 m2, days 1-14] starting on day 1 of HFX (69.6 Gy) and repeated on day 29. HFX/PE was compared with HFX (69.6 Gy) from an earlier phase II trial (RTOG 83-11). Seventy-six patients treated with HFX/PE and 203 patients who received HFX alone were compared for toxicity, response, survival, and patterns of failure. The rates of grade 4 nonhematologic toxicity were similar (3.0% for HFX/PE, 3.0% for HFX), but grade 4 hematologic toxicity occurred only with HFX/PE 56.6%. Three (3.9%) HFX/PE patients had fatal toxicity (2 pulmonary, 1 renal); 1 HFX patient had fatal esophageal toxicity. Response and metastasis rates were similar for the two treatments, but infield (p = 0.054) and overall (p = 0.04) progression-free survival rates were better with HFX/PE. Median survivals were 18.9 months with HFX/PE and 10.6 months with HFX. Two-year survival rates were 36% for HFX/PE and 22% for HFX (p = 0.014). The differences in survival between HFX/PE and HFX remained borderline statistically significant (p = 0.0593) in the multivariate model, which included weight loss, Karnofsky performance status (KPS), sex, and stage. HFX/PE is an effective regimen in patients with inoperable NSCLC, although it is considerably more toxic, and is undergoing a comparison in a three-arm randomized phase III study against induction cisplatin/vinblastine plus standard once-daily RT and against cisplatin/vinblastine concurrent with standard RT.

Administration, Oral↗
PubMed1997

Neurotrophins stimulate chemotaxis of embryonic cortical neurons.

During mammalian cortical development, neuronal precursors proliferate within ventricular regions then migrate to their target destinations in the cortical plate, where they organize into layers. In the rat, most cortical neuronal migration occurs during the final week of gestation (Bayer et al, 1991; Jacobson, 1991). At this time (E15-E21), reverse transcriptase-polymerase chain reaction demonstrated that cortical homogenates contain mRNA encoding brain derived neurotrophic factor (BDNF) and the catalytic form of its high-affinity receptor, TrkB. Immunocytochemistry and in situ hybridization of sections revealed that the catalytic TrkB receptors predominantly localize to regions containing migratory cells. Many TrkB+ cells exhibited the classic morphology of migrating neurons, suggesting that TrkB ligands play a role in cortical neuronal migration. We analysed whether TrkB ligands influence the motility of embryonic cortical cells (from E15-E21) using a quantitative in vitro chemotaxis assay. High-affinity TrkB ligands (BDNF and NT4/5) stimulated chemotaxis (directed migration) of embryonic neurons at concentrations ranging from 1 to 100 ng/ml. NT-3, a low-affinity TrkB ligand, only stimulated significant migration at high concentrations (> or =100 ng/ml). Peak migration to BDNF was observed at gestational day 18 (E18). BDNF-induced chemotaxis was blocked by either tyrosine kinase inhibitor, K252a, or the Ca2+-chelator, BAPTA-AM, suggesting that BDNF-induces motility via autophosphorylation of TrkB receptor proteins and involves Ca2+-dependent mechanisms. BDNF-stimulation of increased cytosolic Ca2+ was confirmed with optical recordings of E18 cortical cells loaded with Ca2+ indicator dye. Thus, signal transduction through the TrkB receptor complex directs neuronal migration, suggesting that, in vivo, BDNF exerts chemotropic effects that are critical to morphogenesis of the cortex.

Animals↗
PubMed1997

Acute and one-year outcome of a randomised controlled trial of brief cognitive therapy for major depressive disorder in primary care.

BACKGROUND: The consensus statement on the treatment of depression (Paykel & Priest, 1992) advocates the use of cognitive therapy techniques as an adjunct to medication. METHOD: This paper describes a randomised controlled trial of brief cognitive therapy (BCT) plus 'treatment as usual' versus treatment as usual in the management of 48 patients with major depressive disorder presenting in primary care. RESULTS: At the end of the acute phase, significantly more subjects (P < 0.05) met recovery criteria in the intervention group (n = 15) compared with the control group (n = 8). When initial neuroticism scores were controlled for, reductions in Beck Depression Inventory and Hamilton Rating Scale for Depression scores favoured the BCT group throughout the 12 months of follow-up. CONCLUSIONS: BCT may be beneficial, but given the time constraints, therapists need to be more rather than less skilled in cognitive therapy. This, plus methodological limitations, leads us to advise caution before applying this approach more widely in primary care.

Acute Disease↗
PubMed1997

Psychiatric home care for the elderly.

This study summarizes descriptive information concerning an existing psychiatric home care service and lays the foundation for more sophisticated studies of elderly depressed persons who receive this type of long term care. Using existing medical record data, the demographic and clinical characteristics of the elderly patients using a multi-site home health care service are summarized, including: (1) their functional/psychiatric status, (2) their length of stay, (3) caregiver availability, (4) scope of multidisciplinary interventions provided, and (5) reasons for discharge. Prospective research of elderly persons receiving psychiatric home care is needed in the future.

Activities of Daily Living↗