Minimalism through stereotactic technique.
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Humans↗
Biomedical subjects
D A Ross
Publications and source records attributed to D A Ross.
Vitamin A and measles vaccination.
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Child, Preschool↗
Low grade gliomas: preliminary analysis of failure patterns among patients treated using 3D conformal external beam irradiation.
PURPOSE: The pattern of failure of low grade gliomas following radiotherapy is less well known than that of the high grade gliomas. Stereotactic histologic studies have suggested that tumor cells extend beyond imaging abnormalities, and that large margins would be required for radiotherapy target volumes to encompass all of the neoplasm. Our experience using computerized tomography (CT)- and magnetic resonance (MR)-planned irradiation of low grade gliomas was reviewed to determine the pattern of tumor recurrence, in an effort to clinically define the minimum margin required. METHODS AND MATERIALS: Forty-six patients with low grade supratentorial gliomas were treated between April 1985 and November 1992 using three-dimensional (3D) conformal CT- or MR-planned external beam radiotherapy. Fields were designed to encompass a target volume created by adding a margin to the tumor in three dimensions. Generally, patients were treated using shrinking fields with an initial target (tumor plus a 1 to 3 cm margin) treated to a dose of 45 to 50.4 (median 50.4) Gy, and a boost (tumor plus a 0 to 2 cm margin) treated to a total of 54 to 59.4 (median 59.4) Gy. Median follow-up was 32.9 months. RESULTS: There have been 11 failures; all of these occurred within the radiographic abnormality (either T2 prolongation or CT hypodensity) visualized at the time of treatment planning (i.e., all failures were within the boost volume). Median time to failure was 53 months. Because all failures were local, there was no relationship between the amount by which the tumor volumes were expanded to create target volumes and the eventual outcome. CONCLUSION: Despite pathologic data suggesting that low grade glioma cells can be found outside the MR T2-signal abnormality in many cases, our results demonstrate that conformal external beam radiotherapy, in which the high dose volume is limited, does not result in increased marginal or out-of-field failures. Until control of tumor within the radiographically abnormal volume can be achieved, the need for large fields to treat prophylactically microscopic disease beyond the visualized tumor volume is questionable. The use of conformal fields might be associated with reduced toxicity, and thereby allow delivery of higher total doses to the central tumor.
Adolescent↗
Genomic copy number changes of DNA repair genes ERCC1 and ERCC2 in human gliomas.
Abnormalities of the genomic region of chromosome 19q13.2-13.4 are a common occurrence in brain malignancies and contain a possible tumor suppressor gene involved in gliomas. Since abnormalities of DNA repair are associated with malignancy, we assessed DNA status of the nucleotide excision repair genes located in this area, viz. ERCC1 and ERCC2. Radiodensitometry was used to assess gene copy number in samples obtained from brain tumor specimens from 24 patients. Nine tumors were of lower grade histology (3 pilocytic astrocytomas, 2 gangliogliomas, 4 astrocytomas); 15 tumors were pathologically higher grade (4 anaplastic astrocytomas, 11 glioblastomas). Tumor samples were obtained prior to radiation or chemotherapy. Abnormalities of gene copy number of ERCC1 and ERCC2 were observed in 11/24 specimens (46%). Whereas increased and decreased copy numbers were observed for ERCC1, only decreases in copy number of ERCC2 were seen. Three tumors (all lower grade) showed concurrent allelic loss of ERCC1 and ERCC2. Abnormalities of copy number for these genes were not associated with response to subsequent therapy nor survival. However, allelic loss of ERCC2 was associated with younger age at diagnosis when compared to those specimens which did not show loss. There were no significant differences between lower grade and higher grade tumors with respect to these investigations. Abnormalities in copy number of ERCC1 and ERCC2 are common in glial tumors. Further study of this genomic region is necessary to define the importance of these observations in tumor pathophysiology and treatment.
Adult↗
p53 status of head and neck cancer: relation to biological characteristics and outcome of radiotherapy.
p53 status was investigated in 99 patients with squamous cell carcinoma of the head and neck region uniformly treated with accelerated radiotherapy and in whom tumour cell proliferation and DNA aneuploidy were assessed using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Seventy-six percent of tumours were immunohistochemically positive for p53 protein, but heterogeneity was noticed both in the percentage of cells positive for p53 and in their level of expression. However, tumours which were either essentially all positive or all negative or showed sporadic positivity for p53 protein showed no differences in their level of aneuploidy, proliferation rate, tissue organisation or outcome with radiotherapy. There was a trend for those p53-positive tumours with the strongest expression to have more DNA aneuploidy and deregulation of proliferation organisation than weaker expressors; but there were no differences in proliferation rate or outcome of radiotherapy. These studies suggest that p53 protein stabilisation as assessed by immunohistochemistry does not have any major relationship with the biological characteristics and outcome of squamous cell cancer treated by accelerated radiotherapy.
Aneuploidy↗
Vitamin A supplementation and childhood malaria in northern Ghana.
Two companion, randomized, placebo-controlled trials of prophylactic vitamin A supplementation provided the opportunity to assess the impact of supplementation on malaria parasitemia, morbidity, and mortality in young children in northern Ghana. In the mortality study, 21,906 children were visited every 4 mo over 2 y, and in the morbidity study 1455 children were visited weekly for 1 y. There was no difference between children supplemented with vitamin A and those given placebo in malaria mortality rates (rate ratio = 1.03; 95% CI 0.74, 1.43) or fever incidence based on reported symptoms. Malaria parasitemia rates, parasite densities in children with a positive blood smear, and rates of probable malaria illness also did not differ between treatment groups. There was no correlation between serum retinol at the beginning of the trial and subsequent malaria parasitemia in children who received placebo (r = 0.01). It is concluded that vitamin A supplementation had no impact on malaria in this population.
Child↗
Vitamin A supplementation, morbidity, and serum acute-phase proteins in young Ghanaian children.
The association of vitamin A supplementation with concentrations of positive acute-phase proteins in the serum was investigated in the Child Health Study of the Ghana Vitamin A Supplementation Trials, a randomized, controlled trial of the effect of vitamin A on morbidity in children aged < 5 y. Mean serum concentrations of alpha 1-acid glycoprotein, serum amyloid A, and C-reactive protein did not differ overall between the vitamin A-supplemented and placebo-treated groups. Treatment groups were then subdivided according to what symptoms children had experienced in the week before blood sampling. Acute-phase-protein responses to fever and cough were not affected by vitamin A supplementation. There was a tendency for vitamin A-supplemented children, but not placebo children, to have elevated acute-phase proteins in association with reported vomiting or severe diarrhea. The failure of unsupplemented children to mount an acute-phase response may have contributed to their increased morbidity from gastrointestinal symptoms.
Acute-Phase Proteins↗
Risk factors for child mortality in northern Ghana: a case-control study.
BACKGROUND: A population-based case-control study was carried out to investigate potential risk factors for post-neonatal and child mortality in northern Ghana were child survival rates are among the lowest in Africa. METHOD: Cases were post-neonatal infant and child deaths identified within a large population under continuous demographic surveillance. For each case, one living control, matched for age, sex and locality, was selected from the demographic database. Mothers of each case and control were interviewed to obtain information on social, enconomic, demographic, environmental and other possible risk factors. Matched analyses of the 317 cases and their controls were performed using discordant pairs analysis and conditional logistic regression. RESULTS: The mortality rate for children aged 6 months to 4 years was estimated as 23.9/1000 children/year. An increased risk of death was observed where the delivery was not performed by a trained person (OR = 1.8, 95% CI: 1.0-3.2), if the preceding birth interval was < 24 months (OR = 2.2, 95% CI: 1.1-3.9), if the father beat the child's mother (OR = 4.3, 95% CI: 1.2-15.6) or if the water source was unprotected (OR = 1.6, 95% CI: 1.0-2.7). No association was found between weaning practices, parental education, or any of the socioeconomic or hygiene variables considered. CONCLUSIONS: Few strong risk factors for mortality were identified, perhaps because living conditions within the study population are relatively homogeneous. While mortality rates may be reduced by targeted interventions, such as increasing deliveries by trained people, more general improvements in the socioeconomic status in the region are essential.
Age Factors↗
Nutrient uptake by the hindlimb of growing pigs treated with porcine somatotropin and insulin.
The shift in nutrient partitioning induced by porcine somatotropin (pST) is accompanied by a decrease in insulin sensitivity for whole-body glucose uptake. The relative contribution of metabolic changes in the hindlimb was investigated in eight pigs (55 kg) that had received recombinant pST (120 micrograms/kg) or excipient (control) for 7 d. Uptake of metabolites by the hindlimb was measured under basal conditions and during hyperinsulinemic-euglycemic clamps at low [14 ng/(kg.min)] and high [360 ng/(kg.min)] insulin infusion rates. Dextrose infusion rate required to maintain euglycemia was used as an index of whole-body glucose uptake in response to exogenous insulin. Effects of pST on hindlimb and whole-body glucose uptake were evident only at physiological levels of insulin (basal and low insulin infusion rate). During the low rate of insulin infusion, dextrose infusion rate was 79% lower for pST-treated pigs and glucose uptake by the hindlimb was 59% lower compared with control pigs. The decrease in glucose uptake by the hindlimb was entirely accounted for by the estimated reduction in glucose utilization by adipose tissue of the hindlimb. Glucose:oxygen quotients were reduced during basal (57%) and low insulin infusion (63%) with pST treatment, indicating a change in the pattern of substrate utilization. This is consistent with the concept that pST directs nutrients away from adipose and towards muscle growth by altering the response of tissues to homeostatic signals such as insulin.
Adipose Tissue↗
Effects of propofol sedation on seizures and intracranially recorded epileptiform activity in patients with partial epilepsy.
BACKGROUND: Case reports suggesting both pro- and anticonvulsant effect(s) of propofol have been published in recent years. The effects of sedative doses of propofol on epileptiform activities in patients suffering from intractable partial epilepsy were systematically investigated. METHODS: Fourteen patients suffering from complex partial seizures were studied. Electroencephalogram (EEG) was recorded from intracranial electrodes implanted in the hippocampi and temporal neocortex. Propofol was given as a computer-controlled infusion in four steps to achieve target plasma propofol concentrations of 0.3, 0.6, 0.9, and 1.2 micrograms/ml. Each concentration was maintained for 30 min, and steady-state kinetics were confirmed by blood levels drawn at 10th and 30th min at each level. Between the 15th and 30th min of each concentration of propofol, EEG was analyzed for presence of electroencephalographic seizure activity and/or number of interictal spikes (IIS). Effects of propofol on IIS frequency at different electrode sites were compared using a two-way repeated measures analysis of variance. A value of P < 0.05 was considered significant. RESULTS: None of the patients developed a seizure during the 2 h of propofol infusion. No "false spikes" (spikes developing with propofol infusion in areas where no spikes were seen in baseline EEG) were seen. Although effects of propofol on IIS frequency were highly variable across patients and at different propofol doses in the same patient, there was no statistically significant effect of propofol on any electrode site with any of the doses studied. CONCLUSIONS: We were unable to demonstrate a significant change in epileptiform activity with sedative doses of propofol in patients suffering from complex partial epilepsy.
Adult↗
Aplasia cutis congenita: failed conservative treatment.
Large scalp defects in aplasia cutis congenita present a management dilemma. In these lesions, prolonged conservative treatment may cause as much risk as does operative treatment. As a result of our experience, we suggest that one should be prepared to undertake early surgical intervention, rather than prolonged conservative treatment, for larger defects. Decreasing the size of the defect should decrease the risk of complications, since these appear to be related. The management of this condition should be a compromise of both operative and conservative modalities.
Bandages↗
CDC's Information Network for Public Health Officials (INPHO): a framework for integrated public health information and practice.
To strengthen the public health infrastructure, the Centers for Disease Control and Prevention (CDC) initiated the Information Network for Public Health Officials (INPHO). CDC INPHO has three goals: (1) to make communication among public health practitioners throughout the United States easy, (2) to make information accessible, and (3) to make secure data exchange as swift and smooth as contemporary technology will allow. Based on a systems approach to supporting the core functions of public health, CDC INPHO achieves its goals by creating a flexible and user-responsive infrastructure of open communications and information exchange.
Centers for Disease Control and Prevention, U.S.↗
Language mapping in epilepsy patients undergoing dominant hemisphere anterior temporal lobectomy.
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Brain Mapping↗
Limitations of flow cytometry in the analysis of CD1a/HLADR+ human oral mucosal Langerhans cells.
Suspensions of human oral epithelial cells were stained with antibodies to CD1a and HLADR conjugated with fluorochromes and analysed by flow cytometry with the aim of purifying double-labelled Langerhans cells, a population comprising approximately 2% of the cell total. Whole suspensions had high levels of autofluorescence and a wide range of forward and right angle scatter properties. The mean percentage of CD1a/HLADR+ cells was 2.1%, though the double-labelled cells did not form a discrete group and the percentages of positive cells using control antibodies were similar. Density gradient centrifugation prior to flow cytometry did not facilitate Langerhans cell identification within the suspension. The results indicate flow cytometric analysis of minority cell populations (such as Langerhans cells) within oral epithelium is limited by the autofluorescence of physically heterogeneous keratinocytes, and emphasize the importance of controls in studies of oral epithelium which use this method.
Adult↗
Temporal lobe central benzodiazepine binding in unilateral mesial temporal lobe epilepsy.
PET-demonstrated decreases in [11C]flumazenil binding occur in anterior mesial temporal structures on the side of epileptogenesis in unilateral mesial temporal lobe epilepsy. We performed quantitative autoradiography on anterior mesial and lateral temporal specimens from 11 subjects with unilateral mesial temporal lobe epilepsy and six neurologically normal controls to identify the predominant in vitro correlates of the decreased [11C]flumazenil binding. In anterior mesial temporal regions exhibiting the greatest neuronal cell loss, decreases in agonist and antagonist binding to type 1 and 2 (central) benzodiazepine binding sites were highly correlated with neuronal cell counts. Cell loss and decreased binding were particularly prominent in the lateral portion of hippocampal region CA1, adjacent to CA2. Lateral temporal central benzodiazepine binding was diffusely increased, achieving statistical significance in cortical laminae V and VI. These findings suggest that the predominant source of PET-demonstrated decreases in [11C]flumazenil binding in mesial temporal epilepsy is hippocampal sclerosis, rather than down-regulation of central benzodiazepine binding sites on surviving hippocampal neurons.
Adult↗
Child morbidity and mortality following vitamin A supplementation in Ghana: time since dosing, number of doses, and time of year.
OBJECTIVES: The impact of large-dose vitamin A supplementation given at intervals of 4 months on child mortality and morbidity was examined according to the time interval since dosing, number of doses received previously, and time of year. METHODS: Two double-blind, randomized, placebo-controlled trials of large doses of vitamin A administered at intervals of 4 months were conducted in adjacent populations in northern Ghana. RESULTS: While vitamin A supplementation significantly reduced the overall incidence of severe illnesses (especially diarrhea with dehydration), clinic attendances, hospital admissions, and mortality, there was no evidence that the impact of each dose of vitamin A was related to the number of doses the child had received previously. There was no evidence that the effectiveness of the supplement waned over the 3 to 5 months between doses. The impact on mortality did not differ significantly by the month in which the supplement had been given. CONCLUSIONS: In the study population, there was no evidence that an interval between doses of less than 4 months would have had a greater impact on severe morbidity or mortality, and the effectiveness of supplementation did not vary by time of year.
Child↗
Pathology of tumors of the cranial base.
Tumors of the skull base are varied and can be categorized into benign and malignant neoplasms. This article outlines the types of tumors found in this surgically challenging anatomic location.
Adenoma↗
In vivo MR determination of water diffusion coefficients and diffusion anisotropy: correlation with structural alteration in gliomas of the cerebral hemispheres.
PURPOSE: To determine whether a relationship exists between water diffusion coefficients or diffusion anisotropy and MR-defined regions of normal or abnormal brain parenchyma in patients with cerebral gliomas. METHODS: In 40 patients with cerebral gliomas, diffusion was characterized in a single column of interest using a motion-insensitive spin-echo sequence that was applied sequentially at two gradient strength settings in three orthogonal directions. Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes at 128 points along the column. An average ADC and an index of diffusion anisotropy (IDA = diffusion coefficientmax-min/diffusionmean) was than calculated for any of nine MR-determined regions of interest within the tumor or adjacent parenchyma. RESULTS: In cerebral edema, mean ADC (all ADCs as 10(-7) cm2/s) was 138 +/- 24 (versus 83 +/- 6 for normal white matter) with mean IDA of 0.26 +/- 0.14 (versus 0.45 +/- 0.17 for normal white matter). Solid enhancing central tumor mean ADC was 131 +/- 25 with mean IDA of 0.15 +/- 0.10. Solid enhancing tumor margin mean ADC was 131 +/- 25, with IDA of 0.25 +/- 0.20. Cyst or necrosis mean ADC was 235 +/- 35 with IDA of 0.07 +/- 0.04. CONCLUSION: In cerebral gliomas ADC and IDA determinations provide information not available from routine MR imaging. ADC and IDA determinations allow distinction between normal white matter, areas of necrosis or cyst formation, regions of edema, and solid enhancing tumor. ADCs can be quickly and reliably characterized within a motion-insensitive column of interest with standard MR hardware.
Adolescent↗