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Biomedical subjects

R A Brooks

Publications and source records attributed to R A Brooks.

At least 19 recordsLinked to original sources

T1 and T2 of ferritin at different field strengths: effect on MRI.

Nuclear magnetic relaxation times T1 and T2 were measured in ferritin solutions at field strengths from 0.04 to 1.5 T. T1 was relatively constant, but 1/T2 increased linearly with field strength, in agreement with earlier MRI observations in the monkey brain. This finding supports the theory that ferritin is responsible for T2 shortening in brain nuclei containing iron. The linear dependence of 1/T2 on magnetic field is unique and not explained by present theories of the magnetic properties of ferritin.

Animals

Cerebellar diaschisis revisited: pontine hypometabolism and dentate sparing.

A unilateral supratentorial lesion may cause hypometabolism in the contralateral cerebellar hemisphere (crossed cerebellar diaschisis). We analyzed glucose metabolism, measured by PET-FDG, in the posterior fossa in 67 patients (78 PET studies) with primary unilateral supratentorial brain tumors selected for visually obvious metabolic asymmetry in the cerebellar hemispheres. We found that glucose utilization was 17% lower in the contralateral cerebellar cortex (compared with the ipsilateral one), consistent with the selection criterion, and 19% lower in the ipsilateral pons, wherein lie the first order synapses of the corticopontocerebellar pathway. This finding helps to validate the prevalent view that cerebellar diaschisis is due to interruption of afferent input from the corticopontocerebellar pathway. However, glucose metabolism in the contralateral dentate nucleus was relatively preserved--only 2% less than the ipsilateral dentate. This "dentate sparing" suggests preservation of afferent input to the largest of the deep cerebellar nuclei from the Purkinje cells in the cortex, despite interruption of the major excitatory input to the Purkinje cells.

Adolescent

PET-fluorodeoxyglucose of cranial and spinal neuromas.

Five patients with eighth nerve, one with ninth nerve and one with cervical neuromas were studied with PET and [18F] fluorodeoxyglucose (FDG). Four of the patients had had surgery prior to the PET study, and six patients had subsequent surgery. All tumors were well-visualized on the PET images. Only one patient with bilateral acoustic neuroma exhibited tumor recurrence or growth after the PET study; these two lesions showed the highest FDG uptakes in the PET studies (tumor-to-cerebellum ratio of 0.93-0.98). All other tumors were relatively hypometabolic (tumor-cerebellum ratios of 0.43-0.65) and showed no tumor growth or recurrence during follow-up periods ranging from 5 to 8 yr. These results suggest that PET-FDG may be of value in the evaluation of cranial and spinal schwannomas.

Adolescent

Characterization of release of basic fibroblast growth factor from bovine retinal endothelial cells in monolayer cultures.

Release of basic fibroblast growth factor (bFGF) was investigated in bovine retinal endothelial cells (BREC) maintained in monolayer culture. Confluent cells released bFGF into serum-free culture medium or medium containing 5% serum at rates of up to 105.2 and 61.3 pM/day respectively. bFGF release coincided with a decrease in monolayer cell number and increases in lactate dehydrogenase (LDH) concentration and cells and cell-debris particles in the medium, which suggested that cell damage and lysis were responsible for growth-factor release. Maximum bFGF release at 24 h (230 +/- 10 pM) occurred when the cells were treated with lipopolysaccharide (10 micrograms/ml), which also produced the greatest changes in parameters of cell damage. Sub-confluent cells showed little overt damage at 24 h, but released bFGF (78 +/- 20 pM) along with LDH, indicating that some cell lysis had occurred. Insulin-like growth factor 1 (IGF-1) was also released into serum-free culture medium at a rate of 0.34 nM/day, but not into medium containing serum or when the cells were treated with lipopolysaccharide. This implies that the mechanism of IGF-1 release is different from that of bFGF and is not related to cell damage. Culture medium conditioned by BREC stimulated the proliferation of these cells, as measured by an increase in their incorporation of [methyl-3H]thymidine from 7550 +/- 479 to 10467 +/- 924 d.p.m. These results demonstrate that bFGF is released from damaged BREC and that medium conditioned by these cells can stimulate retinal-endothelial-cell proliferation. This strengthens the case for an involvement of this growth factor in retinal neovascularization.

Animals

Computed tomography, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose in multiple system atrophy and pure autonomic failure.

We studied 45 patients who had autonomic failure with computed tomography, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose to characterize the neuroimaging features of multiple system atrophy and pure autonomic failure and determine the utility of these techniques in distinguishing multiple system atrophy from pure autonomic failure. There were 30 patients with multiple system atrophy and 15 with pure autonomic failure. In the multiple system atrophy group, eight patients had mainly cerebellar signs, seven extrapyramidal and 15 had combinations of cerebellar and extrapyramidal signs. Cerebellar atrophy on computerized tomography and magnetic resonance imaging, signal hypointensity in the posterolateral putamen on magnetic resonance imaging and a generalized reduction in glucose utilization rate with positron emission tomography with [18F]fluorodeoxyglucose, were the main findings and were seen only in the patients with multiple system atrophy. Decreased glucose utilization (hypometabolism) was most prominent in the cerebellum, brainstem, striatum and frontal and motor cortices. These results indicate clear differences, using neuroimaging studies, between multiple system atrophy and pure autonomic failure.

Atrophy

Pituitary microadenomas: a PET study.

Twenty cases of surgically verified pituitary microadenoma (17 with Cushing disease and three with acromegaly) were studied with positron emission tomography (PET) with use of fluorine-18-2-fluorodeoxyglucose (FDG). The diagnostic results were compared with those of other modalities, namely, computed tomography (CT), magnetic resonance (MR) imaging, and, in the cases of Cushing disease, simultaneous bilateral inferior petrosal sinus sampling (SIPS). The PET results showed 12 positive readings and one questionable reading, compared with seven positive readings and one questionable reading for CT (18 cases studied) and 13 positive and two questionable MR imaging readings. PET complemented MR imaging, in the sense that five of the positive PET readings were negative or questionable at MR imaging. PET studies of 20 healthy control subjects showed no false-positive cases, whereas other studies of healthy subjects with contrast material-enhanced CT and MR imaging have yielded, respectively, 20% and 15% positive readings, with findings suggestive of silent or occult adenomas.

Adenoma

Role of iron and ferritin in MR imaging of the brain: a study in primates at different field strengths.

The authors measured in vivo signal intensity on magnetic resonance (MR) images and postmortem iron concentrations in the brains of three young and two old rhesus monkeys. T2-weighted MR imaging was done at 0.5, 1.5, 2.0, and 4.7 T. Relative assessment of iron concentration was made from the optical density of brain sections stained with the Perls' method intensified with diaminobenzidine. MR imaging and optical density measurements were made in the centrum semiovale (white matter) and in four gray matter areas: the insular cortex, caudate nucleus, putamen, and globus pallidus, the latter three of which accumulate significant iron deposits with age. High optical density and decreased signal intensity were found in these areas, and the inverse correlation between gray matter/white matter signal ratio and optical density was in good agreement with the theory of T2 shortening caused by diffusion of water through magnetic inhomogeneities. However, the dependence of T2 shortening on field strength was not quadratic, as expected for paramagnetic iron, but instead showed a marked leveling off at higher field strengths. This magnetic "saturation" is explainable by antiferromagnetism and superparamagnetism of the ferritin core and has been observed in ferritin solutions at low temperatures. Similar observations at body temperature are needed before the iron-ferritin explanation for T2 shortening can be considered proved.

Aging

On the origin of paramagnetic inhomogeneity effects in blood.

Hydrogen, sodium, and fluorine (added F-) NMR spectra of venous and oxygenated blood were measured. The fluorine resonance was seen as a single peak in both samples, and all three resonances exhibited the same deoxy-oxy shift. Because F- exchanges slowly across the red cell membrane, and because sodium is 95% extracellular, these results suggest that the intra-extracellular field difference delta B is less than 0.1 ppm. A small value of delta B tends to rule out transmembrane exchange as an important contributor to relaxation in MRI of blood and hematomas. However, the broadening of the resonances with deoxygenation, by 0.3-0.4 ppm, indicates that both intra- and extracellular gradients are of comparable and sufficient magnitude to produce the T2-weighted hypointensity seen in clinical magnetic resonance images of hematomas at high fields.

Blood

A two-year follow-up study of serum insulinlike growth factor-I in diabetics with retinopathy.

Serum insulinlike growth factor-I (IGF-I) concentration was evaluated prospectively over two years in 35 diabetic patients with severe background or preproliferative retinopathy (group 1) and 24 diabetics with mild background retinopathy matched for age, sex, and glycemic control (group 2). In addition, 12 normal subjects were also studied to assess the variability of individual serum IGF-I levels over two years. Mean serum IGF-I (+/- SD) micrograms/l at entry, one year, and two years was not significantly different in the patient groups (157 +/- 71 v 168 +/- 77; 166 +/- 78 v 159 +/- 87; 143 +/- 58 v 159 +/- 67) or when compared with the normal subjects (181 +/- 47, 188 +/- 30; 221 +/- 56). Eight patients in the preproliferative group and none in the mild background group developed proliferative retinopathy. In this subgroup developing retinal neovascularization, serum IGF-I at the time of the first appearance of retinal new vessels was significantly higher than 3 months (1 to 4 months) before the onset of proliferation (271 +/- 94 v 196 +/- 58; P = .036). Values at the time of proliferation were not, however, significantly different from the mean serum IGF-I value of all patients in group 1 and by 4 months (3 to 6 m) had returned to their previous values. Although a transient elevation of IGF-I occurs at the time of retinal new vessel formation, the rise in serum concentration is not sufficiently great or early enough to be of clinical value as a predictor of retinal neovascularization.

Adult

Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy.

The response to GH releasing hormone (GHRH 1-29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 micrograms by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 micrograms/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU.l-1.h-1; 209 +/- 81 vs 121 +/- 82; P = 0.01). Mean +/- SD IGF-I levels (micrograms/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2-16) pump administration (203 +/- 62 vs 60 +/- 25; P = 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.

Adult

Production of endothelin 1 by cultured bovine retinal endothelial cells and presence of endothelin receptors on associated pericytes.

Endothelinlike immunoreactivity was detected by radioimmunoassay in medium conditioned by cultured endothelial cells obtained from bovine retinal microvessels (9.2 +/- 6.5 pM, n = 4). Sephadex G-25 column chromatography and fast-protein liquid chromatography revealed that most of the endothelinlike immunoreactivity was eluted in an identical position to synthetic endothelin 1. Retinal capillary pericyte-conditioned medium contained 2.9 pM endothelinlike immunoreactivity. In contrast to endothelial cells, retinal pericytes were found to bind endothelin. The dissociation constant and binding capacity were 0.14 nM and 1.5 x 10(5) sites/cell (n = 3), respectively. These findings suggest that endothelin produced by the retinal endothelial cells binds to the pericytes, adding support to the suggestion that pericytes in the retina may have a musclelike function.

Animals

Human diabetic serum does not stimulate bovine retinal endothelial cell growth in culture.

Bovine retinal microvascular endothelial cells were cultured with serum from nondiabetic controls, patients with background, preproliferative, proliferative and inactive (treated) proliferative diabetic retinopathy. Using Coomassie Blue to measure cellular protein, we found no significant increase in retinal endothelial cell growth with serum from patients with preproliferative or proliferative retinopathy.

Animals

Computed tomography profiles of periventricular hypodensity in hydrocephalus and leukoencephalopathy.

Profiles of hypodense periventricular white matter, drawn from the interior of the frontal horns through the surrounding white matter to the peripheral gray matter, were analyzed in 65 patients. Abnormal curves were grouped into four patterns: linear, double-slope, plateau, and bimodal. The first two, found primarily in hydrocephalic patients, appear to be due to transependymal passage of cerebrospinal fluid (CSF). The linear pattern was found more frequently in acute cases and indicates breakdown of the ventricular wall as a barrier. The double-slope pattern probably indicates a persistent or restored barrier effect at the wall, with residual CSF infiltration of the parenchyma. Most of the other patients' curves showed either a plateau pattern or (especially in primary leukoencephalopathy) a bimodal ("bumpy") pattern which is believed to correspond to the nonuniform nature of the pathological process.

Cerebral Ventriculography

Tissue signatures with dual-energy computed tomography.

By providing information on two parameters, dual-energy computed tomography can offer clinically useful tissue signatures for metallic deposits (Ca) or injected iodine, as well as for different normal and abnormal types of brain parenchymal tissues and CSF. Cerebral CT was performed on 36 patients and tissue differences analyzed using Hounsfield notation.

Brain

Split-detector computed tomography: a preliminary report.

A split-detector system, consisting of a thin CaF2 scintillator followed by a thick Nal crystal, was installed in an EMI Mark I scanner. Energy discrimination is possible because the CaF2 crystal responds primarily to low-energy photons; dual-energy images can be obtained from only one scan. Calculations and preliminary experiments show that the split-detector separates energies better than the 100-140 kVp method. It was possibel with the split detector to differentiate between two weak solutions of CaCl2 and Kl which had the same computed tomography number (44 H), under normal scanning conditions.

Tomography, X-Ray Computed