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Biomedical subjects

W D Brown

Publications and source records attributed to W D Brown.

At least 37 records · Page 2Linked to original sources

Proteus syndrome: craniofacial and cerebral MRI.

The Proteus syndrome is a rare hamartoneoplastic syndrome that may affect the brain, skull, and extracranial head and neck. We present a case with severe, characteristic findings. Brain abnormalities are not common in Proteus syndrome; when present, hemimegalencephaly and migrational disorders are typically seen, commonly with an associated seizure disorder. Maxillary and mandibular dysmorphism may occur, including unilateral condylar hyperplasia. Subcutaneous fatty, fibrous, lymphangiomatous masses commonly seen in this syndrome may involve the neck and face, leading to disfigurement and potential airway compromise.

Brain↗

Mate choice in tree crickets and their kin.

Mate choice theory has become a major field of research in behavioral ecology. Tree crickets provide excellent opportunities for studying the diversity and variability of mate choice. The evidence for female mate choice in tree crickets is reviewed, and broad comparisons with other orthopteran groups are made. The evidence shows that female choice may occur during several different stages of mating and may target several different criteria. Song preferences are perhaps dominated by stabilizing preferences for the cues of species recognition, but there is a growing body of evidence for directional preferences based on sensory biases or mate quality. Mate rejection during courtship and forms of postcopulatory choice may favor males, based both on phenotypic quality and on the amount of nutritious courtship gifts they provide, and may differ with the value of mating incentives. Understanding the balance and trade-offs between different forms of mate choice may help in understanding their evolutionary causes.

Journal Article↗

Effects on regional brain metabolism of high-altitude hypoxia: a study of six US marines.

Previous studies of brain glucose metabolism in people indigenous to high-altitude environments uncovered two response patterns: Quechuas native to the high Andes of South America sustained modest hypometabolism in most brain regions interrogated, whereas Sherpas, native to the Himalayas and considered by many biologists to be most effectively high-altitude adapted of all humans, showed brain metabolic patterns similar to lowlanders, with no acclimation effects noted. In the present study, the database was expanded to include hypoxia acclimation effects in lowlanders. Positron emission tomography (PET) and [(18)F]-2-deoxy-2-fluro-D-glucose (FDG) imaging techniques were used to assess regional cerebral glucose metabolic rates (rCMR(glc)) in six US marines (Caucasian lineage) before and after a 63-day training program for operations at high altitudes ranging from 10,500 to 20,320 ft. Significant changes in rCMR(glc) were found for 7 of 25 brain regions examined. Significant decreases in absolute cerebral glucose metabolism after high-altitude exposure were found in five regions: three frontal, the left occipital lobe, and the right thalamus. In contrast, for the right and left cerebellum significant increases in metabolism were found. The magnitudes of these differences, in terms of absolute metabolism, were large, ranging from 10 to 18%. Although the results may not be solely the result of lower oxygen levels at high altitude, these findings suggest that the brain of healthy human lowlanders responds to chronic hypoxia exposure with precise, region-specific fine tuning of rCMR(glc). The observed short-term hypoxia acclimation responses in these lowlanders clearly differ from the long-term hypoxia adaptations found in brain metabolism of people indigenous to high-altitude environments.

Adult↗

Extrapontine myelinolysis with involvement of the hippocampus in three children with severe hypernatremia.

Central pontine myelinolysis is a disorder of unknown etiology linked to overly aggressive correction of hyponatremia. In addition to the typical location of demyelination with preservation of neurons and axon cylinders in the basis pontis, similar lesions have been described in extrapontine locations. Central pontine myelinolysis and extrapontine myelinolysis usually occur together, and are identified at autopsy rather than in life because symptoms of extrapontine myelinolysis are often masked in the critically ill patient. Central pontine myelinolysis is described in children, usually in the clinical setting of hyponatremic dehydration. Extrapontine myelinolysis has not been described in children previously. We report three children with severe hypernatremia and extrapontine myelinolysis involving various combinations of thalamus, basal ganglia, external and extreme capsules, and cerebellar vermis. All three had additional involvement of the hippocampus seen on T2-weighted magnetic resonance imaging. None of the three had detectable pontine lesions. Clinical features of the three cases were dehydration in a 28-month-old girl, respiratory syncytial virus bronchiolitis in a 14-month-old girl, and acute respiratory failure due to anaphylaxis after consumption of walnuts in a 3-year-old boy. Peak sodium values in each child were 195, 168, and 177 mmol/L, respectively; each received aggressive treatment for hypernatremia. We believe this to be the first report of extrapontine myelinolysis in children, the first report of extrapontine myelinolysis without central pontine myelinolysis in children, and the first report in children of hippocampal formation involvement. The pathogenesis of the central and extrapontine myelinolysis complex in children is more complicated than previously believed, and might differ significantly from that of adults.

Child, Preschool↗

Disseminated aspergillosis involving the brain: distribution and imaging characteristics.

BACKGROUND AND PURPOSE: Systemic invasive aspergillosis involves the brain through hematogenous dissemination. A retrospective review of 18 patients with aspergillosis involving the brain was performed in order to present imaging findings and thereby broaden the understanding of the distribution and imaging characteristics of brain Aspergillus infection and to facilitate its early diagnosis. METHODS: The neuroimaging studies of 17 biopsy- or autopsy-proved cases and one clinically diagnosed case were examined retrospectively by two neuroradiologists. The studies were evaluated for anatomic distribution of lesions, signal characteristics of lesions, enhancement, hemorrhage, and progression on serial studies (when performed). Medical records, biopsy reports, and autopsy findings were reviewed. RESULTS: Thirteen of 18 patients had involvement of the basal nuclei and/or thalami. Nine of the 10 patients with lesions at the corticomedullary junction also had lesions in the basal nuclei or thalami. Callosal lesions were seen in seven patients. Progression of lesion number and size was seen in all 11 patients in whom serial studies had been performed. Enhancement was minimal or absent in most cases. There was gross hemorrhage in eight of the 18, and definite ring-enhancement in three. CONCLUSION: Among our cases, lesions in perforating artery territories were more common than those at the corticomedullary junction. Ring enhancement and gross hemorrhage may be present, but are not necessary for the prospective diagnosis.

Adult↗

Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys.

Although the role of dopamine dysfunction is well established in Parkinson's disease, the effect of nigrostriatal degeneration on motor performance during normal aging is less well understood. In this study, aged rhesus monkeys (25-27 years old) displayed significant impairments relative to young (3-5 years old) cohorts in motor function as assessed on a fine motor task and home cage activity. Additionally, the clinical motor function of aged monkeys was impaired relative to young monkeys as assessed on a clinical rating scale. Unbiased stereologic measurements of the substantia nigra revealed a significant age-related loss of tyrosine hydroxylase-immunoreactive (TH-ir; 50.3%) and dopamine transporter-immunoreactive (DAT-ir; 33.2%) nigral neurons. The monkeys performance on the fine motor task and on the clinical rating scale was correlated with TH-ir neuronal counts. The number of DAT-ir nigral neurons was correlated with activity and clinical rating scale scores. Our results suggest that age-related motor impairments in nonhuman primates are associated with spontaneous decreases in TH-ir and DAT-ir nigral cells. The correlation of motor deficits with the loss of TH-ir and DAT-ir nigral neurons suggests that aged nonhuman primates may provide a useful model for mimicking changes seen in human aging and early Parkinson's disease.

Aging↗

Influence of computed tomography on pretherapeutic tumor staging in head and neck cancer patients.

Refinements in radiographic techniques have resulted in increased use of radiographic studies in the evaluation of patients with head and neck cancer over the past 20 years. To assess the impact of such studies, we compared tumor clinical stages based solely on physical-examination findings with those obtained with the addition of CT findings. This study was accomplished through case review of 81 head and neck cancer patients who underwent CT after preliminary TNM-stage assignment as determined on the basis of physical examination alone. In this cohort, 44 patients (54%) had a change in assigned clinical stage. We reviewed individual anatomic sites to determine where CT was found to be most useful in modifying tumor stage. Changes in tumor and nodal stage were found across all major sites of the head and neck. Tumors of the hypopharynx were the most likely to change stage (90%) on the basis of CT findings, whereas tumors of the glottic larynx were least likely to undergo a change in stage (16%). The therapeutic implications of these findings are discussed in the context of the published literature.

Head and Neck Neoplasms↗

Prognostic limitations of the Daumas-Duport grading scheme in childhood supratentorial astroglial tumors.

The Daumas-Duport grading scheme (DDGS) is a commonly used method for determining the grade of a tumor. It scores 4 histologic features and is used as a prognostic tool in adult astroglial tumors. This system of assigning children to prognostically homogeneous groups has not been evaluated. The Childhood Brain Tumor Consortium (CBTC) database includes 327 children with a CBTC assigned World Health Organization (WHO) diagnosis of supratentorial astroglial tumor and histologic features necessary for Daumas-Duport grading. We compared survival estimates for tumors within and between DDGS grades using a slightly broadened definition of endothelial prominence. The DDGS yielded only 3 histologic groups in children and only 2 prognostically differing groups. Subgroups within DDGS grades had significantly different survival distributions. The summing of 4 disparate histologic features in the DDGS is inadequate for the assessment of childhood supratentorial astroglial tumors. A classification system more fully summarizing the complete histologic content of tumors is most likely to provide diagnoses useful for clinical purposes.

Adolescent↗

Brain: supratentorial cortical anatomy.

Knowledge of the cerebral cortical lobes and gyri is critical for the localization of lesions and for the correlation of radiologic findings with neurologic symptoms and signs. This article deals with the six cerebral lobes-frontal, parietal, occipital, temporal, limbic, and insula-and the fissures and imaginary lines that divide them. The major gyri and sulci of each lobe are individually considered. Anatomy and function are correlated for a few selected areas of particular clinical importance.

Cerebral Cortex↗

Brain: supratentorial central nuclei and tracts.

This article deals with numerous gray and white matter components of the forebrain, excluding the cerebral cortex. The basal ganglia, amygdalae, and basal forebrain structures are discussed including their groupings and subdivisions, as are the thalami, hypothalamus, and other derivatives of the diencephalon. The white matter structures considered include the capsules, optic and auditory radiations, and bundles ending or arising in the hypothalamus; all the major commissural tracts; and several major long association bundles that may be accurately located even if not discretely visualized.

Amygdala↗

Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment.

UNLABELLED: This article presents dosimetry based on the measurement of fluoro-DOPA activity in major tissues and in the bladder contents in humans after oral pretreatment with 100 mg carbidopa. METHODS: Bladder activity was measured continuously by external probe and calibrated using complete urine collections. Quantitative dynamic PET scans provided time-activity curves for the major organs. Bladder wall dosimetry was calculated using the methods of MIRD Pamphlet No. 14. Effective dose was calculated as described in ICRP Publication 60. RESULTS: Mean absorbed dose to the bladder wall surface per unit administered activity was 0.150 mGy/MBq (0.556 rad/mCi) with the realistic void schedule used in our studies. The dose was 0.027 mGy/MBq (0.101 rad/mCi) to the kidneys, 0.0197 mGy/MBq (0.0728 rad/mCi) to the pancreas, and 0.0186 mGy/MBq (0.0688 rad/mCi) to the uterus. Absorbed doses to other organs were an order of magnitude or more lower than the bladder, 0.009-0.015 mGy/MBq. The effective dose per unit administered activity was 0.0199 mSv/MBq (0.0735 rem/mCi.) CONCLUSION: Urinary excretion of fluoro-DOPA was altered significantly by pretreatment with carbidopa. In general, any manipulation of tracer metabolism in the body should be expected to produce changes in biodistribution and dosimetry. The largest radiation dose was to the bladder wall, for which our estimate was one-fifth of that from the original report. The methods used reflect realistic urinary physiology and typical use of this tracer. The principles of MIRD Pamphlet No. 14 should be used in planning studies using tracers excreted in the urine to minimize the absorbed dose.

Aromatic Amino Acid Decarboxylase Inhibitors↗

Sherpa brain glucose metabolism and defense adaptations against chronic hypoxia.

The brain of hypoxia-tolerant vertebrates is known to survive extreme oxygen limitation at least in part because of very low rats of ATP utilization and ATP production. To asses whether similar adaptations are involved in healthy humans during hypoxia adaptation over generational time, we initially used positron-emission tomography measurements of glucose metabolic rates in the brain of Quechuas, whose ancestors have been indigenous to the Andes at altitudes between approximately 3,300 and 4,500 m for several hundred years. Workers in this field generally believe that the lineage of Sherpas has been indigenous to the Himalayas for even longer and that Sherpas and other peoples indigenous to the Tibetan plateau are perhaps the most exquisitely hypoxia adapted of all humans. For this reason, in this study we extended our database to include Sherpas. With the use of the same protocol as before, two metabolic states were analyzed: 1) the presumed normal (hypoxia-adapted) state, monitored as soon as possible after subjects left the Himalayas and 2) the deacclimated state, monitored after 3 wk at low altitudes. Positron-emission tomography measurements of 2-[18F]deoxy-2-fluoro-D-glucose metabolic rates, quantified in 26 regions of the brain, indicated that the Sherpas' brain metabolism differed significantly from that of Quechuas but was essentially identical to that of lowlanders. Region-by-region patterns were similar in all three groups, indicating that the regional organization of glucose metabolism in the brain is a conservative, relatively constant characteristic.

Adaptation, Physiological↗

Enhanced cardiac metabolism of plasma glucose in high-altitude natives: adaptation against chronic hypoxia.

The metabolism of glucose in mammalian heart is 25-50% more O2 efficient than the metabolism of free fatty acids. To assess the role of substrate preference in adaptations to chronic hypoxia, positron emission tomographic measurements of heart regional glucose uptake rates after an overnight fast were made in volunteer Quechua subjects and in Sherpa subjects, both indigenous to altitudes of over 3,000 m, and in a group of lowlander volunteers. Highest uptake rates were found in the Quechuas on arrival and in the Sherpas after a 3-wk period at low altitude, intermediate rates in Quechuas after a 3-wk period at low altitude and in the lowlanders, and lowest rates in Sherpas on arrival. These low values were probably related to the stress of travel to the site of the experiments. Measured plasma catecholamines, hormones, and substrates indicated that glucose concentrations correlated best with observed variations in glucose uptake, with a negative correlation for the control subjects and a positive correlation for the Quechuas and Sherpas. Uptake values in Quechuas declined significantly after a 3-wk period at low altitude, but the positive correlation with glucose levels persisted. We conclude that an elevated glucose preference in heart is a true metabolic adaptation in humans adapted over generations to chronic hypoxia.

Adaptation, Physiological↗

Headache and stroke.

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Cerebrovascular Disorders↗

Medulloblastoma and Collins' law: a critical review of the concept of a period of risk for tumor recurrence and patient survival.

Collins' law (CL) states that the period of risk for recurrence for a tumor is the age of the patient plus 9 months. Originally a clinical observation in Wilms' tumor, CL has been applied to other tumors such as medulloblastoma (MB). Although CL does not apply to all childhood tumors, it seems to be a valid observation for childhood MB, despite several reports of violations or exceptions to CL in the literature. We sought to test CL in a large population of children with MB from the Childhood Brain Tumor Consortium (CBTC). We analyzed data from 602 children with MB, of whom 421 died and 181 were censored but alive at the last follow-up. We found 16 additional CL exceptions to supplement the 22 already present in the literature. This is both the greatest number of exceptions and the largest MB study population for CL reported to date. We provide clinical data on our 16 uncensored exceptions to CL and critically review those 22 cases cited previously in the literature. All of the CBTC exceptions were under 6 years of age at the time of initial diagnosis and were followed for an average of 7.5 years. All 16 CBTC exceptions died. Children older than 8 years of age could not be followed for a sufficient period of time to be able to state whether CL applies; as age at initial diagnosis increases, the period of observation required to determine CL validity becomes impractically long. Exceptions to CL are rare and amounted to 3.8% of 405 uncensored CBTC patients who died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The applicability of Collins' Law to childhood brain tumors and its usefulness as a predictor of survival.

In 1955, Collins made the observation that tumor recurrence in children with Wilms' tumor was correlated with the child's age plus 9 months. This concept of a period of risk for recurrence was later applied to a variety of tumors in children and became known as Collins' Law (CL). The law has been a successful predictor of survival for some children with neural tumors within the central nervous system and a poor predictor for others. We tested Collins' concept of a period of risk for recurrence and extended it to survival for 14 childhood neural tumors described in the Childhood Brain Tumor Consortium (CBTC) database. The CBTC data describe clinical, surgical, and histological details (over a 49-year period in 10 institutions) from 3921 patients under the age of 21 years at the time of their first surgical procedure for a brain tumor. CL was considered to be a good predictor of survival if fewer than 10% of patients who die survive beyond the expiration of the period of risk for that child. We found that CL applied to tumors such as anaplastic astrocytoma, glioblastoma, pineoblastoma, medulloblastoma or "primitive neuroectodermal tumor," teratoma, and germinoma, as well as ependymoma, papilloma, and tumors that could not be classified; it had no predictive value in craniopharyngioma, oligodendroglioma, or plain, fibrillary, pilocytic, or protoplasmic astrocytoma. We had sufficient follow-up data to determine adherence to CL when the child's age at diagnosis was less than 8 years; it is likely that CL applies to older children with these tumors, but we did not have the data to show this unequivocally.

Adolescent↗