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Biomedical subjects

J R Simpson

Publications and source records attributed to J R Simpson.

At least 19 recordsLinked to original sources
PubMed1997

Subgenual prefrontal cortex abnormalities in mood disorders.

Pathological disturbances of mood may follow a 'bipolar' course, in which normal moods alternate with both depression and mania, or a 'unipolar' course, in which only depression occurs. Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established. Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the prefrontal cortex ventral to the genu of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume, as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs.

Adult↗
PubMed1996

Race and prognosis of brain tumor patients entering multicenter clinical trials. A report from the Radiation Therapy Oncology Group.

We investigated the possible influence of race on the survival of patients with malignant gliomas enrolled in three consecutive trials of the Radiation Therapy Oncology Group (RTOG) retrospectively using the group's statistical database. There were no statistical differences between the survival rates for black patients with glioblastoma multiforme (GBM) and those for the white patients. The limited influence of therapy on this disease may be responsible in part for this result.

Adult↗
PubMed1995

Blood flow changes in human somatosensory cortex during anticipated stimulation.

Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decreased in parts of the primary somatosensory cortex map located outside the representation of the skin area that was the target of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in blood flow occurred in the region of the cortex representing the skin locus of the awaited stimulation. These results are concurrent with a model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

Adult↗
PubMed1995

Feasibility and acceptability of a proposed infant feeding intervention trial for the prevention of type I diabetes.

OBJECTIVE: To determine the feasibility of a randomized double-blind controlled trial of an infant formula without intact cow's-milk protein for preventing type I diabetes in high-risk children. RESEARCH DESIGN AND METHODS: We surveyed 83 people who either were parents of a child with type I diabetes or were pregnant women with type I diabetes in the ambulatory diabetes and obstetrics clinics in a university hospital. After a written and verbal description of the cow's milk-diabetes hypothesis, participants were asked to sign a sham consent form. A questionnaire designed to explore factors affecting their decision to either sign or not sign the consent form, as well as infant-feeding patterns, was subsequently administered. RESULTS: Overall, 69.9% (95% confidence interval, 60.0-79.8%) consented to participation in the proposed randomized trial. The decision to consent was not affected by the degree of belief in the cow's milk-diabetes hypothesis, the child's risk of diabetes, the respondent's demographic data, or infant feeding habits. CONCLUSIONS: A randomized feeding intervention study is an acceptable and feasible way to determine whether avoidance of cow's-milk protein during the first 6 months of life prevents type I diabetes in North American children.

Animals↗
PubMed1995

Stereotactic external beam irradiation using a linear accelerator: the Washington University experience.

From February 1989 to December 1993, 139 patients with a variety of brain lesions were treated with stereotactic external beam irradiation using a 6MV linear accelerator. The largest group consisted of patients with recurrent brain metastases (n = 46). Twenty seven patients had malignant gliomas, most of which were recurrent. Several benign conditions were treated, including arteriovenous malformations (n = 27), acoustic neuromas (n = 9), meningiomas (n = 7), and pituitary adenomas (n = 2). Durable responses were seen in the majority of patients with transient, mild, side effects. This experience suggests that stereotactic external beam irradiation is a safe, reliable, and effective method for non-invasive treatment of selected patients with small, localized brain lesions.

Academic Medical Centers↗
PubMed1994

Assurance of high quality linac-based stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery is generally a single, high-dose radiation treatment for the brain requiring targeting accuracy on the order of a millimeter. From the initial implementation of radiosurgery, therefore, quality assurance is an ongoing process of paramount importance. In this paper, we outline the basic elements of a quality assurance program for our linear accelerator that has been in use at Washington University Medical Center over the past 2 years. METHODS AND MATERIALS: Various devices and procedures have been developed to verify the accuracy and safety of the stereotactic radiosurgery regimen. Specifically, we present methods for assessing the attainment of spatially correct patient images, the reliability of the computerized treatment planning system, achieving physical safety for the patient, as well as the proper operation of the radiation treatment device. RESULTS: Our procedures have allowed us to assure quality patient treatments and, additionally, has permitted monitoring our performance for continual improvement. For example, a plot of targeting accuracy with the number of patients shows an asymptotic approach to a value within 0.6 mm of that ideally expected. CONCLUSION: To maintain high-quality patient care, one must review critical aspects of the treatment regimen on a periodic basis. Providing for the appropriate level of staff training, periodic reviews of procedures and maintenance of forms are also very important.

Humans↗
PubMed1994

Management of the axilla in patients with breast cancers one centimeter or smaller.

Very small breast cancers are being diagnosed with increased frequency, and, until recently, little information regarding the incidence of axillary lymph node metastases in these most favorable tumors was available. Moreover, scarce data exist regarding axillary failure in this cohort as a function of initial treatment, be it surgery, radiation, or simply observation. In the present study, limited to women with invasive cancers measuring no more than 10 mm, the incidence of pathologically positive axillary nodes was 12.3%. The incidence of nodal metastases was influenced by tumor size (albeit not quite significantly, p = .08); not one patient with a tumor < or = 5 mm had axillary node metastases, compared to 14.7% in those with cancers 6 to 10 mm. The histologic grade and tumor location were also important in predicting nodal positivity. The incidence of positive nodes was 38% in those with poorly differentiated cancers, compared to 8% and 7% in women with well and moderately differentiated cancers, respectively, p = .03. Axillary nodal positivity was seen in 17% of outer quadrant vs 3% of central and inner quadrant primaries, p < .01. The axilla was managed with surgery alone (76%), radiation alone (6%), surgery and radiation (6%), or simply observation (10%). With a median follow-up of 55 months, not one patient has suffered a nodal recurrence, and in our experience, survival free of distant relapse was not adversely affected by the omission of axillary surgery.

Axilla↗
PubMed1993

Age as a prognostic factor for breast and regional nodal recurrence following breast conserving surgery and irradiation in stage I and II breast cancer.

PURPOSE: To evaluate the association between age and breast/regional nodal relapse following breast conserving surgery and irradiation. METHODS AND MATERIALS: The results of treatment in 511 patients with 519 Stage I and II breast cancers treated at Mallinkrodt Institute of Radiology and affiliated hospitals between 1958 and 1988 were reviewed. RESULTS: Seventy women, of whom 96% had axillary dissections, were 39 years of age or younger. These young patients were more likely to have chemotherapy (p < 0.0001), and tumor bed reexcision (p < 0.01), and less likely to have an undissected axilla (p < 0.01), or estrogen receptor positive tumor (p = 0.02) than the older women (> 40 years). Although breast recurrence tended to appear earlier in the younger patients (12% at 5 years for those < 40 years vs. 6% at 5 years for those older), by 7 years the breast failure rate for the two groups was the same (12%), p = 0.13. In the 37 women 35 years of age or younger, the actuarial rate of breast recurrence was 9% at 7 years. Compared to other series in the literature, in which cancers were grossly excised without regard to the microscopic margins of resection, and reexcision was not routinely performed, young women treated with breast conserving surgery and irradiation at our institution frequently underwent reexcision of the tumor bed (57%), and had negative pathologic margins of resection (75%). Regional nodal relapse was in general uncommon, and not seen with increased frequency in the youngest cohort. CONCLUSION: Our experience suggests that young age is not a contraindication to breast conserving surgery and irradiation. Although breast cancers in this cohort may have certain features rendering them prone to local failure, we believe this risk can be mitigated by appropriate patient selection and optimal surgical resection.

Adult↗
PubMed1993

Advances in 3-dimensional radiation treatment planning systems: room-view display with real time interactivity.

PURPOSE: We describe our 3-dimensional (3-D) radiation treatment planning system for external photon and electron beam 3-D treatment planning which provides high performance computational speed and a real-time display which we have named "room-view" in which the simulated target volumes, critical structures, skin surfaces, radiation beams and/or dose surfaces can be viewed on the display monitor from any arbitrary viewing position. METHODS AND MATERIALS: We have implemented the 3-D planning system on a graphics superworkstation with parallel processing. Patient's anatomical features are extracted from contiguous computed tomography scan images and are displayed as wireloops or solid surfaces. Radiation beams are displayed as a set of diverging rays plus the polygons formed by the intersection of these rays with planes perpendicular to the beam axis. Controls are provided for each treatment machine motion function. Photon dose calculations are performed using an effective pathlength algorithm modified to accommodate 3-D off-center ratios. Electron dose calculations are performed using a 3-D pencil beam model. RESULTS: Dose distribution information can be displayed as 3-D dose surfaces, dose-volume histograms, or as isodoses superimposed on 2-D gray scale images of the patient's anatomy. Tumor-control-probabilities, normal-tissue-complication probabilities and a figure-of-merit score function are generated to aid in plan evaluation. A split-screen display provides a beam's-eye-view for beam positioning and design of patient shielding block apertures and a concurrent "room-view" display of the patient and beam icon for viewing multiple beam set-ups, beam positioning, and plan evaluation. Both views are simultaneously interactive. CONCLUSION: The development of an interactive 3-D radiation treatment planning system with a real-time room-view display has been accomplished. The concurrent real-time beam's-eye-view and room-view display significantly improves the efficacy of the 3-D planning process.

Computer Systems↗
PubMed1993

Regional nodal management and patterns of failure following conservative surgery and radiation therapy for stage I and II breast cancer.

PURPOSE: To determine the incidence, pattern of regional nodal failure, and treatment sequelae as determined by the extent of lymphatic irradiation. METHODS AND MATERIALS: The records of 511 patients with 519 Stage I and II breast cancers treated with breast conserving surgery with or without axillary dissection and irradiation were reviewed. The extent of nodal irradiation was at the discretion of the attending radiation oncologist and varied considerably over the years. Management of the axilla consisted of axillary dissection alone in 351, axillary dissection and supplemental irradiation in 74, irradiation alone in 75, and simply observation in 21 patients. RESULTS: Overall, axillary recurrence was uncommon (1.2%), but was slightly more frequent after irradiation alone (2.7%) than after surgery alone (0.3%), p = 0.14. There was no benefit for supplemental axillary irradiation after an axillary dissection yielding negative or 1 to 3 positive nodes. In the 21 patients in whom the axilla was observed, axillary recurrence was not observed. Supraclavicular failures were rare in women with negative or 1 to 3 positive axillary lymph nodes (0.5%), and not significantly affected by elective irradiation. Internal mammary node recurrence was seen in only one patient, and was not significantly influenced by elective internal mammary irradiation. Both arm and breast edema were significantly more common in women having breast and nodal irradiation than after breast irradiation alone. These sequelae were not influenced significantly by the number of lymph nodes obtained in the axillary dissection specimen. Radiation pneumonitis was seen with increased frequency with more extensive nodal radiotherapy. Pneumonitis was not found to be affected by the administration or sequencing of chemotherapy. CONCLUSION: There is little justification for axillary or supraclavicular irradiation following an axillary dissection which yields negative or minimally involved (1 to 3 positive) lymph nodes. There were too few patients with extensive axillary node metastases (> or = 4 positive) in our series to draw conclusions about the optimal extent of nodal irradiation in this subset. Elective internal mammary lymph node irradiation increases technical complexity, does not appear to be advantageous, and when combined with supraclavicular irradiation places the patient at highest risk for pneumonitis.

Adult↗
PubMed1993

Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials.

PURPOSE: The influence of tumor site, size, and extent of surgery on the survival of patients with glioblastoma multiforme treated on three consecutive prospectively randomized Radiation Therapy Oncology Group trials employing surgery and irradiation plus or minus chemotherapy was studied. METHODS AND MATERIALS: Six hundred forty-five patients with a diagnosis of glioblastoma multiforme on central pathological review were analyzed for survival with respect to known prognostic factors, that is, age and Karnofsky Performance Status, as well as extent of surgery, site, and size. Surgical treatment consisted of biopsy only in 17%, partial resection in 64%, and total resection in 19%. Tumors were located in frontal lobe in 43%, temporal lobe in 28%, and parietal lobe in 25%. Maximum tumor diameter as determined on computed tomography or magnetic resonance imaging scans was less than 5 cm for 38%, between 5-10 cm for 56% and greater than 10 cm for 6% of patients. The extent of surgical therapy was the same for tumors greater than 5 or greater than 10 cm, whereas total resection was more often performed for tumors less than 5 cm. The extent of surgery did not appear to vary with age or site. RESULTS: Patients undergoing total resection had a median survival of 11.3 months compared to 6.6 months for patients with a biopsy only. A significant difference in median survival was also found for partial resection versus biopsy only treatment (10.4 vs. 6.6 months). There was no difference in survival for the different tumor sizes. Patients with frontal lobe tumors survived longer than those with temporal or parietal lobe lesions (11.4 months, 9.1 months, and 9.6 months, respectively) (p = 0.01). A Cox multivariate model confirmed a significant correlation of age, Karnofsky Performance Status, extent of surgery, and primary site with survival. The best survival rates occurred in patients who had at least three of the following features: < 40 years of age, high Karnofsky Performance Status, frontal tumors, and total resection (17 months median). CONCLUSION: We conclude that biopsy only yields inferior survival to more extensive surgery for patients with glioblastoma multiforme treated with surgery and radiation therapy.

Adult↗
PubMed1993

Mitochondrial impairment reduces the threshold for in vivo NMDA-mediated neuronal death in the striatum.

There may be important relationships between glutamate receptor activation and neurotoxicity in neurodegenerative diseases. Previous experiments using cultured neurons have demonstrated a correlation between the metabolic status of neurons and their sensitivity to glutamate receptor-mediated cytotoxicity (Novelli et al. Brain Res. 451, 205, 1988). To examine such a relationship in vivo, we first established a dose-response curve for N-methyl-D-aspartate (NMDA)-induced neuronal death in the rat striatum. We then examined the interaction between metabolic impairment and infusion of NMDA at a dose below the threshold for neurotoxicity. Metabolic impairment was induced by intraperitoneal delivery of 3-nitropropionic acid (3-NP), an inhibitor of mitochondrial complex II (succinic dehydrogenase). Twelve hours after 3-NP delivery we performed stereotactic infusion of NMDA or vehicle into the striatum. During mitochondrial impairment, a relatively nonneurotoxic dose of NMDA (15 nmol) produced a lesion that was significantly larger than that caused by this dose under normal metabolic conditions. At a dose normally below the threshold for neurotoxicity, metabolic impairment significantly increased the likelihood of neuronal death in the striatum by a factor of 5. Lesions were characterized by neuronal loss with gliosis and sparing of traversing fiber bundles. These results demonstrate that metabolic impairment reduces the threshold for glutamate receptor-mediated neurotoxicity in vivo. This potentiation may have implications for understanding the role of "neuronal stress" produced by glutamate receptor activation in neurodegenerative diseases and normal aging.

Animals↗
PubMed1993

Intracranial ependymoma long term outcome, patterns of failure.

We analyzed 31 patients with intracranial ependymoma, all verified by secondary neuropathology review. There were 12 patients with ependymomas and 19 patients with anaplastic ependymoma by the WHO classification. Eight patients received craniospinal irradiation, 22 patients received cranial irradiation alone, and one patient was treated with chemotherapy alone. The median follow-up time was 11 years. The 5- and 10-year progression-free survivals (PFS) were 60% and 48%. Those with anaplastic tumors had a decreased 10 year PFS over those with low grade lesions: 26% vs. 55% (p = 0.02). Delivering spinal irradiation in addition to cranial irradiation did not improve outcome. There were relapses in 16 patients. All patients relapsed at the primary intracranial sites with no spinal failures. Patients treated with whole brain irradiation had decreased 10 year PFS over those treated with local fields: 19% vs. 64% (p = 0.006). Those patients treated to > or = 50 Gy had an improved long-term PFS (p = 0.04). Multivariate analysis was undertaken with the following variables: extent of cranial irradiation, pathology, anatomic site of ependymoma, cranial irradiation dose, extent of surgery, and whether spinal irradiation was given. With PFS as the endpoint, only extent of cranial irradiation (favoring local fields) and pathology (favoring low grade ependymoma) were significant prognosticators. We conclude that carefully outlined local field irradiation is the therapy of choice, and elective spinal irradiation is of questionable benefit.

Adolescent↗
PubMed1993

Age dependence of striatal neuronal death caused by mitochondrial dysfunction.

Several lines of evidence point to a decline in mitochondrial efficiency with age. The relationship between age and sensitivity to Huntington disease-like neuronal death in the striatum induced by the mitochondrial inhibitor 3-nitropropionic acid (3-NP) was examined. 3-NP has been shown to cause degeneration of striatum, hippocampus, and thalamus in rat and of caudate-putamen in humans. We administered single doses of 3-NP intraperitoneally to rats of various ages. Animals older than 4 months exhibited a far greater susceptibility to striatal neurotoxicity and mortality compared with younger animals. These results are discussed in the context of age-dependent metabolic impairment, which may be a key factor in the etiology of neurodegenerative disorders such as Huntington's disease and Alzheimer's disease.

Acetylcholinesterase↗
PubMed1993

Brain metastases from non-central nervous system tumors: evaluation with PET.

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) was performed in 19 patients with brain metastases from non-central nervous system (CNS) neoplasms and one patient with a primary CNS lymphoma. Various histopathologic types were represented by the primary neoplasms in the patients with metastases. Only 21 of the 31 lesions (68%) were detected with FDG PET as discrete, metabolically active foci (relative to surrounding structures). Six of the nondetected lesions may have been nondiscernible owing to their small size and/or isointensity relative to closely apposed normal gray matter. However, four lesions of at least 1.2 cm in diameter showed frankly decreased FDG accumulation relative to normal brain. These findings suggest that studies of FDG accumulation by a variety of non-CNS neoplasms and their CNS metastases are in order and that extrapolation of the successes of FDG PET in imaging of primary glial tumors to imaging of brain metastases should proceed with caution.

Adult↗
PubMed1993

Survival following breast-conserving surgery and irradiation or modified radical mastectomy in patients with invasive breast cancers with a maximum diameter of 1 cm.

The reported relapse-free survival for women with invasive breast cancers measuring no more than 10 mm in dimension ranges from 75% to 95%, with axillary status an important prognostic factor in most series. Further study of prognostic variables in this most favorable subset is notably limited. We retrospectively reviewed the records of 168 women with invasive breast cancers < or = 10 mm treated with either breast conserving surgery+axillary dissection (AXD) and radiation therapy, or mastectomy+AXD. The actuarial survival and survival free of distant metastases (DMFS) at 7 years was 95% and 97%, respectively. Location and size of the primary tumor were most important in predicting outcome, although statistical significance was not achieved. The 5-year distant metastases-free survival (DMFS) was 100% for central and inner quadrant tumors, compared to 97% in those with outer quadrant tumors, p = 0.18. The 5-year DMFS was 100%, 95%, and 98% for patients with cancers 2-5 mm, 6-9 mm, and 10 mm, respectively, p = 0.15. Status of the axillary lymph nodes, type of breast surgery, clinical tumor status (palpable vs. nonpalpable), age, menopausal status, histologic grade, systemic therapy, or histologic type were not found to have a significant impact on prognosis.

Adult↗