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Biomedical subjects

B E Jones

Publications and source records attributed to B E Jones.

At least 73 records · Page 4Linked to original sources

III. Intracellular signaling in response to toxic liver injury.

Toxin-induced liver injury was formerly considered a passive biochemical event, but recent evidence has demonstrated that signal transduction pathways actively modulate the hepatocyte's response to this form of injury. Investigations have examined the effects of a variety of toxins on the activation of receptor-coupled signal transduction, mitogen-activated protein kinases, and Fas signaling, as well as the generation of second messengers such as ceramide and nitric oxide. Many of these pathways culminate in the activation of transcription factors such as activator protein-1, c-Myc, or nuclear factor-kappaB. This Themes article discusses the effects of toxic injury on these signaling pathways and their known functions in regulating hepatocyte death and proliferation following injury.

Animals↗

Binding of the catabolite repressor protein CcpA to its DNA target is regulated by phosphorylation of its corepressor HPr.

Catabolite repression of a number of catabolic operons in bacilli is mediated by the catabolite control protein CcpA, the phosphocarrier protein HPr from the phosphoenolpyruvate-dependent sugar transport system (PTS), and a cis-acting DNA sequence termed the catabolite-responsive element (cre). We present evidence that CcpA interacts with HPr that is phosphorylated at Ser46 (Ser(P) HPr) and that these proteins form a specific ternary complex with cre DNA. Titration experiments following the circular dichroism signal of the cre DNA indicate that this complex consists of two molecules of Ser(P) HPr, a CcpA dimer, and the cre sequence. Limited proteolysis experiments indicate that the domain structure of CcpA is similar to other members of the LacI/GalR family of helix-turn-helix proteins, comprised of a helix-turn-helix DNA domain and a C-terminal effector domain. NMR titration of Ser(P) HPr demonstrates that the isolated C-terminal domain of CcpA forms a specific complex with Ser(P) HPr but not with unphosphorylated HPr. Based upon perturbations to the NMR spectrum, we propose that the binding site of the C-terminal domain of CcpA on Ser(P) HPr forms a contiguous surface that encompasses both Ser(P)46 and His15, the site of phosphorylation by enzyme I of the PTS. This allows CcpA to recognize the phosphorylation state of HPr, effectively linking the process of sugar import via the PTS to catabolite repression in bacilli.

Bacterial Proteins↗

Patterns of tuberculosis transmission in Central Los Angeles.

CONTEXT: Recent studies suggest that many tuberculosis cases in urban areas result from recent transmission. Delineation of the epidemiologic links between patients is important to optimize strategies to reduce tuberculosis transmission. OBJECTIVE: To identify epidemiologic links among recently infected urban patients with tuberculosis. DESIGN: Prospective evaluation of patients with tuberculosis. SETTING: Central Los Angeles, Calif. PATIENTS: A total of 162 patients who had culture-proven tuberculosis. INTERVENTIONS: Patients were prospectively interviewed to identify their contacts and whereabouts. The IS6110-based and pTBN12-based restriction fragment length polymorphism analyses were performed on Mycobacterium tuberculosis isolates. Patients whose isolates had identical or closely related restriction fragment length polymorphism patterns were considered a cluster. Unconditional logistic regression was used to identify independent predictors of clustering. MAIN OUTCOME MEASURES: Relationship of clinical and epidemiologic variables to clustering. RESULTS: A total of 96 (59%) of 162 patients were in 8 clusters. Only 2 of the 96 clustered patients named others in the cluster as contacts. The degree of homelessness was an independent predictor of clustering. Compared with nonclustered patients, patients in 6 clusters were significantly more likely to have spent time at 3 shelters and other locations when at least 1 patient in the cluster was contagious, and these locations were independent predictors of clustering. Among nonhomeless persons, clustered patients were significantly more likely than nonclustered patients to have used daytime services at 3 shelters. CONCLUSIONS: (1) Traditional contact investigation does not reliably identify patients infected with the same M tuberculosis strain, and (2) locations at which the homeless congregate are important sites of tuberculosis transmission for homeless and nonhomeless persons. Measures that reduce tuberculosis transmission should be based on locations rather than on personal contacts.

Adolescent↗

GABAergic and other noncholinergic basal forebrain neurons, together with cholinergic neurons, project to the mesocortex and isocortex in the rat.

The extrathalamic relay from the brainstem reticular formation to the cerebral cortex in the basal forebrain has been thought to be constituted predominantly, if not exclusively, by cholinergic neurons. In contrast, the septohippocampal projection has been shown to contain an important contingent of gamma-aminobutyric acid (GABA)ergic neurons. In the present study, we investigated whether GABAergic neurons also contribute to the projection from the basal forebrain to neocortical regions, including the mesocortex (limbic) and the isocortex in the rat. For this purpose, retrograde transport of cholera toxin (CT) was examined from the medial prefrontal cortex for the mesocortex and from the parietal cortex for the isocortex and was combined with dual-immunohistochemical staining for either choline acetyltransferase (ChAT) or glutamic acid decarboxylase (GAD) in adjacent series of sections. Retrogradely labelled GAD+ neurons were codistributed with retrogradely labelled ChAT+ neurons through the basal forebrain from both the prefrontal and the parietal cortex, suggesting parallel, widespread cortical projections. The GAD+ cortically projecting cells were similar in size to the ChAT+ cells, thereby indicating that they comprise a contingent of the magnocellular basal cell complex. The proportions of retrogradely labelled neurons that were GAD+ (approximately one-third) were equal to or greater than those that were ChAT+ from both the prefrontal cortex and the parietal cortex. In addition, the total of GAD+ and ChAT+ neurons did not account for the total number of cortically projecting cells, indicating that another equivalent proportion of chemically unidentified noncholinergic neurons also contributes to the basalocortical projection. Accordingly, as in the allocortex, GABAergic, cholinergic, and other unidentified noncholinergic neurons may have the capacity to modulate activity in the mesocortex (limbic) and the isocortex through parallel, widespread projections.

Animals↗

Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans.

In the present study, we investigated changes in regional cerebral blood flow (rCBF) in humans during the progression from relaxed wakefulness through slow wave sleep (SWS). These changes were examined as a function of spindle (12-15 Hz) and delta (1.5-4.0 Hz) electroencephalographic (EEG) activity of SWS. rCBF was studied with positron emission tomography (PET) using the H215O bolus method. A maximum of six 60 sec scans were performed per subject during periods of wakefulness and stages 1-4 of SWS, as determined by on-line EEG monitoring. Spectral analysis was performed off-line on the EEG epochs corresponding to the scans for computation of activity in specific frequency bands. The relationship between EEG frequency band activity and normalized rCBF was determined by means of a voxel-by-voxel analysis of covariance. delta activity covaried negatively with rCBF most markedly in the thalamus and also in the brainstem reticular formation, cerebellum, anterior cingulate, and orbitofrontal cortex. After the effect of delta was removed, a significant negative covariation between spindle activity and the residual rCBF was evident in the medial thalamus. These negative covariations may reflect the disfacilitation and active inhibition of thalamocortical relay neurons in association with delta and spindles, as well as the neural substrates underlying the progressive attenuation of sensory awareness, motor responsiveness, and arousal that occur during SWS. delta activity covaried positively with rCBF in the visual and auditory cortex, possibly reflecting processes of dream-like mentation purported to occur during SWS.

Adult↗

Pneumocystis carinii pneumonia masquerading as tuberculosis.

Recent laboratory studies indicate that genetic diversity exists in human strains of Pneumocystis carinii. Structural and functional variability in infecting strains could result in differences in host-parasite interactions and the natural history of P carinii pneumonia. We report 5 unusual cases in which the clinical presentation mimicked tuberculosis. All patients were cared for at a university-based public hospital clinic in Los Angeles, Calif, during a 2-year period. These patients were chronically ill, had lost weight, and each had cavities or cystic spaces as the primary radiographic findings. None were receiving aerosol pentamidine and only one had a history of smoking. Four patients were initially treated for tuberculosis and the fifth for disseminated Mycobacterium avium complex. Pneumocystis carinii was the only pathogen identified in each case. The unusual clinical presentations delayed the diagnosis of P carinii in all 5 cases. Practitioners must be aware of the variable presentations of P carinii pneumonia.

Adult↗

Phosphorylation on histidine is accompanied by localized structural changes in the phosphocarrier protein, HPr from Bacillus subtilis.

The histidine-containing protein (HPr) of bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) serves a central role in a series of phosphotransfer reactions used for the translocation of sugars across cell membranes. These studies report the high-definition solution structures of both the unphosphorylated and histidine phosphorylated (P-His) forms of HPr from Bacillus subtilis. Consistent with previous NMR studies, local conformational adjustments occur upon phosphorylation of His 15, which positions the phosphate group to serve as a hydrogen bond acceptor for the amide protons of Ala 16 and Arg 17 and to interact favorably with the alpha-helix macrodipole. However, the positively charged side chain of the highly conserved Arg 17 does not appear to interact directly with phospho-His 15, suggesting that Arg 17 plays a role in the recognition of other PTS enzymes or in phosphotransfer reactions directly. Unlike the results reported for Escherichia coli P-His HPr (Van Nuland NA, Boelens R, Scheek RM, Robillard GT, 1995, J Mol Biol 246:180-193), our data indicate that phosphorylation of His 15 is not accompanied by adoption of unfavorable backbone conformations for active site residues in B. subtilis P-Ser HPr.

Bacillus subtilis↗

High-frequency gamma electroencephalogram activity in association with sleep-wake states and spontaneous behaviors in the rat.

The occurrence of high-frequency gamma activity (30-60 Hz) and its relationship to other frequency band activities were examined by spectral analysis of the electroencephalogram in association with sleep wake states and spontaneous behaviors in the rat. In the electroencephalogram, gamma wave activity was evident in unfiltered and high-frequency filtered recordings, in which it was prominent during attentive or active Wake episodes and during Paradoxical Sleep, when theta-like activity was also apparent. In amplitude spectra from these episodes, multiple peaks were evident within the gamma frequency band, indicating broad-band high-frequency activity, in association with a single low-frequency peak in the theta band. gamma peaks were attenuated during quiet Waking, in association with a low-frequency peak between theta and delta, and during Slow Wave Sleep, in association with a low-frequency peak in the delta band. In coherence spectra from ipsilateral cortical leads, peaks were also present within the gamma range and were significantly higher in Waking moving and Paradoxical Sleep than in Waking quiet and Slow Wave Sleep. In measures of frequency band amplitude, gamma activity (30.5-58.0 Hz) varied significantly across the sleep waking cycle, being similarly high during Wake and Paradoxical Sleep and lowest during Slow Wave Sleep. Across these states, gamma was negatively correlated with delta (1.5-4.0 Hz). In contrast, high beta (19.0-30.0 Hz) was significantly lower in Wake than in Slow Wave Sleep and was positively correlated with delta. gamma differed significantly across specific behaviors, being highest in Paradoxical Sleep with twitches and during Waking eating and moving behaviors, slightly lower in Waking attentive, lower in Waking grooming and as low in Waking quiet as during Slow Wave Sleep. These results indicate that the reciprocal variation of high-frequency gamma activity (and not beta) with low-frequency delta activity reflects the sleep waking cycle of the rat. Moreover, gamma activity reflects the degree of behavioral arousal, since it is high during active Waking, when the electromyogram is high, and low during quiet Waking, when the electromyogram is low. It also reflects cortical arousal, independent of motor activity, since it attains high levels in association with attentive immobility and maximal levels only during particular active behaviors (eating and moving and not grooming), and it also attains maximal levels during Paradoxical Sleep, when the nuchal electromyogram is minimal, but small twitches evidence dreaming. The co-variation of gamma and a slow oscillation in the theta band across states and behaviors suggests that a common system may modulate these fast and slow electroencephalogram rhythms, and that such modulation, potentially emanating from the basal forebrain, could predominate during certain states or behaviors, such as Paradoxical Sleep.

Animals↗

Modulation of cholinergic nucleus basalis neurons by acetylcholine and N-methyl-D-aspartate.

Known to exert an important modulatory influence on the cerebral cortex, the cholinergic neurons of the basal forebrain are modulated in turn by neurotransmitters which may include acetylcholine released from processes of brainstem or forebrain neurons. In the present study, we examined the effect of carbachol, a non-specific cholinergic agonist, either alone or in the presence of N-methyl-D-aspartate upon electrophysiologically identified cholinergic basalis neurons in guinea-pig basal forebrain slices. Carbachol produced a direct postsynaptic hyperpolarization, accompanied by a decrease in membrane resistance. Muscarine could mimic this hyperpolarizing effect, whereas nicotine produced a direct postsynaptic membrane depolarization. The interaction of carbachol with N-methyl-D-aspartate was subsequently tested since, in a prior study, N-methyl-D-aspartate was shown to induce rhythmic bursting in cholinergic cells when they were hyperpolarized by continuous injection of outward current. Applied simultaneously with N-methyl-D-aspartate in the absence of current injection, carbachol was also found to promote rhythmic bursting in half of the cells tested. Since the bursts under these conditions were markedly longer in duration than those observed in the presence of N-methyl-D-aspartate alone, it was hypothesized that carbachol might have another action, in addition to the membrane hyperpolarization. Using dissociated cells, it was found that brief applications of carbachol could indeed diminish the slow afterhyperpolarizations that follow single spikes, short bursts or long trains of action potentials in cholinergic basalis neurons. These results indicate that, through its dual ability to hyperpolarize cholinergic neurons and to reduce their afterhyperpolarizations, acetylcholine can promote the occurrence of rhythmic bursting in the presence of N-methyl-D-aspartate. Accordingly, whether derived from brainstem or local sources, acetylcholine may facilitate rhythmic discharge in cholinergic basalis neurons which could in turn impose a rhythmic modulation upon cortical activity during particular states across the sleep-waking cycle.

Acetylcholine↗

CD4 cell counts in human immunodeficiency virus-negative patients with tuberculosis.

We evaluated 85 human immunodeficiency virus (HIV)-negative patients with tuberculosis for clinical features and CD4 cell counts. Thirty-seven patients had low CD4 cell counts (mean +/- SD, 341 +/- 116 cells/microL), and 48 patients had normal CD4 cell counts (mean +/- SD, 830 +/- 254 cells/microL). CD4 cell counts were most strongly correlated with total lymphocyte counts (r = 0.84). If total lymphocyte count was excluded, depressed CD4 cell counts were significantly associated with low serum albumin levels, extensive pulmonary disease, low body-mass index, and low hematocrit. Of these four variables, multivariate linear discriminant analysis revealed that the serum albumin level was the best single predictor of low CD4 cell counts and that the other three variables did not improve predictive value. Because these four variables are markers of severe tuberculosis, these findings suggest that disease severity is associated with greater depression of the total lymphocyte and CD4 cell counts. The CD4 cell counts returned to normal levels in most patients after 1 month of therapy.

Adult↗

Chest radiographic findings in patients with tuberculosis with recent or remote infection.

To determine if chest radiographic findings differ in adult tuberculosis patients with recent and remote infection, we reviewed the chest radiographs of 103 patients with tuberculosis in Los Angeles and performed RFLP analyses of their Mycobacterium tuberculosis isolates. Patients whose isolates had identical or closely related RFLP patterns were considered a "cluster." Most patients in large clusters (more than seven patients) had tuberculosis from recent infection, whereas most unclustered patients had tuberculosis from remote infection. Mediastinal adenopathy or pleural effusions were classified as typical of recent infection, and upper lobe infiltrates, cavitation, or fibrosis were classified as characteristic of remote infection. Radiographic patterns were typical of remote infection in 62% of patients and were characteristic of recent infection in 23% of patients. The distribution of these radiographic patterns was similar in clustered and unclustered patients, both with or without human immunodeficiency virus (HIV) coinfection. However, mediastinal adenopathy and pleural effusions were significantly more common in HIV-infected patients. We conclude that: (1) chest radiographic findings in adults with tuberculosis of recent infection are similar to those in patients with remote infection; (2) the distinctive chest radiographic findings in HIV-infected patients with tuberculosis are not due to an increased frequency of recent infection.

AIDS-Related Opportunistic Infections↗

A continuous striatal infusion of 6-hydroxydopamine produces a terminal axotomy and delayed behavioral effects.

Rat models of Parkinson's disease typically employ a rapid nigral injection of 6-hydroxydopamine (6-OHDA) to produce a near-complete loss of nigrostriatal dopamine neurons, and thus, model end stage disease. The present report describes the use of a continuous, low dose infusion of 6-OHDA into the striatum which produces a terminal axotomy of nigrostriatal dopamine neurons and protracted behavioral response. A solution of 6-OHDA in 0.4% ascorbate, delivered at 37 degrees C from osmotic minipumps, was stable for 8 days as determined by its retained toxicity to a dopaminergic neuroblastoma cell line. The continuous infusion of 0.2 mu g 6-OHDA per h did not affect the striatal uptake of [3H]%GABA, [3H]choline, or [3H]glutamate but reduced [3H]dopamine uptake by 55% within 1.5 days after the start of the infusion. The striatal infusion of 6-OHDA produced a dose-dependent reduction of striatal dopamine and DOPAC levels but did not alter HVA, 5-HT, or 5-HIAA. An increase in amphetamine-induced ipsiversive rotations occurred within 1.5 days after the acute striatal injection of 20 mu g or 30 mu g of 6-OHDA but required 4 days to develop with the continuous 6-OHDA infusion. The topography of the lesion mapped by [3H]mazindol binding showed that, beginning by 1.5 days, a diffuse depletion of terminals encompassed much of the striatum in the 30 mu g acute injection group, whereas in the continuously infused rats, the lesion was apparent only by 4 days and was restricted to a smaller and more completely lesioned area. Unlike acutely lesioned animals, continuously infused rats revealed no obvious loss of dopamine neurons in the pars compacta by 5 weeks after 6-OHDA. The continuous striatal infusion of 6-OHDA can produce a topographically limited terminal axotomy of dopamine neurons and a protracted behavioral impairment.

Animals↗

Scleral matrix metalloproteinases, serine proteinase activity and hydrational capacity are increased in myopia induced by retinal image degradation.

In the avian model of myopia, retinal image degradation quickly leads to ocular enlargement. We now give evidence that regionally specific changes in ocular size are correlated with both biomechanical indices of scleral remodeling, e.g. hydration capacity and with biochemical changes in proteinase activities. The latter include a 72 kDa matrix metalloproteinase (putatively MMP-2), other gelatin-binding MMPs, an acid pH MMP and a serine protease. Specifically, we have found that increases in scleral hydrational capacity parallel increases in collagen degrading activities. Gelatin zymography reveals that eyes with 7 days of retinal image degradation have elevated levels (1.4-fold) of gelatinolytic activities at 72 and 67 kDa M(r) in equatorial and posterior pole regions of the sclera while, after 14 days of treatment, increases are no longer apparent. Lower M(r) zymographic activities at 50, 46 and 37 kDa M(r) are collectively increased in eyes treated for both 7 and 14 days (1.4- and 2.4-fold respectively) in the equator and posterior pole areas of enlarging eyes. Western blot analyses of scleral extracts with an antibody to human MMP-2 reveals immunoreactive bands at 65, 30 and 25 kDa. Zymograms incubated under slightly acidic conditions reveal that, in enlarging eyes, MMP activities at 25 and 28 kDa M(r) are increased in scleral equator and posterior pole (1.6- and 4.5-fold respectively). A TIMP-like protein is also identified in sclera and cornea by Western blot analysis. Finally, retinal-image degradation also increases (approximately 2.6-fold) the activity of a 23.5 kDa serine proteinase in limbus, equator and posterior pole-sclera that is inhibited by aprotinin and soybean trypsin inhibitor. Taken together, these results indicate that eye growth induced by retinal-image degradation involves increases in the activities of multiple scleral proteinases that could modify the biomechanical properties of scleral structural components and contribute to tissue remodeling and growth.

Animals↗

Spatial relationship between neurotensinergic axons and cholinergic neurons in the rat basal forebrain: a light microscopic study with three-dimensional reconstruction.

Cholinergic neurons of the basal forebrain are known to project to the hippocampus and cerebral cortex wherein they play an important role in cortical activation, attention and memory. These neurons have been shown to possess neurotensin binding sites and to respond electrophysiologically to local application of neurotensin, indicating the presence of functional receptors on their membrane. In the present light microscopic study, the spatial relationship between neurotensinergic axons and cholinergic nerve cell bodies and proximal dendrites was investigated in the basal forebrain of the rat by dual immunostaining for neurotensin and choline acetyltransferase. Rostrally, neurotensinergic fibres were concentrated in the lateral septum and anterior substantia innominata, whereas cholinergic neurons were located in the medial septum, diagonal band of Broca and magnocellular preoptic nucleus. At high magnification, a few neurotensinergic axonal varicosities were observed in the region of cholinergic neurons, and fewer still in close proximity to cholinergic perikarya and proximal dendrites. Caudally, neurotensinergic fibres formed a dense plexus of varicose axons in the same regions where cholinergic neurons were located in the posterior substantia innominata and in the ventral and caudal aspects of the globus paltidus. At high magnification, many of these neurotensinergic varicosities were seen in close proximity to the cholinergic perikarya. These results suggest that cholinergic cells receive a much denser neurotensinergic innervation in the caudal than in the rostral aspect of the basal forebrain. This differential distribution is not reflected in the uniform density of neurotensin receptors and potent responses to neurotensin through the cholinergic cell population, suggesting the possibility that neurotensin's effects are mediated in part by a paracrine mechanism.

Animals↗

Dermatology teleconsultations to Central Prison: experience at East Carolina University.

OBJECTIVE: To review our experience with dermatology teleconsultations between East Carolina University School of Medicine in Greenville and Central Prison in Raleigh, NC. MATERIALS AND METHODS: Consultation forms kept on file in the Department of Internal Medicine served as the source of data. One physician reviewed the forms from the initial 22 months of our dermatology teleconsultation service to Central Prison. Patient demographics and the diagnoses made by the consulting physician were recorded. Recommendations were tabulated as either diagnostic or therapeutic. Diagnoses and recommendations for known HIV-positive individuals were separately recorded. RESULTS: One hundred thirty-eight dermatology teleconsultations were performed over the 22-month period. Seventy two per cent of the patients seen were African-American. The average age was 32 years. One hundred fifty-nine diagnoses were made. The most common problems were eczema and acneiform eruptions. Fifty-nine diagnostic and 252 therapeutic recommendations were made. CONCLUSION: Consultants generally were confident of their diagnoses and management decisions. Dermatologists can assist primary care physicians through telemedicine consultation.

Adult↗

Differential oscillatory properties of cholinergic and noncholinergic nucleus basalis neurons in guinea pig brain slice.

Evidence has suggested that the nucleus basalis magnocellularis has the potential to influence the functional state of the cerebral cortex through topographically organized, widespread projections of the cholinergic cells in that nucleus. It has also been shown that, in addition to the cholinergic neurons, other non-cholinergic magnocellular basal forebrain neurons, some of which have been identified as gamma-aminobutyric acid-ergic, project into the cerebral cortex and thus may also participate in the modulation of its activity. We have performed a comparative study of the intrinsic rhythmic properties of immunohistochemically and morphologically characterized choline acetyltransferase (ChAT)-positive and ChAT-negative cells of the nucleus basalis by means of intracellular recordings in guinea pig brain slices. Our results demonstrate that relatively large, multipolar cholinergic and non-cholinergic neurons each display differential voltage-dependent properties that allow them to discharge rhythmically in spike bursts and spike clusters, respectively, at low frequencies (< 10 Hz). Cholinergic cells display bursts of 2-4 action potentials (at approximately 200 Hz) riding on low-threshold spikes recurring at a low frequency (< 5 Hz) when depolarized from a membrane potential more negative than -55 mV and display low-frequency (< 10-15 Hz) tonic firing when depolarized from a more positive level. In contrast, non-cholinergic cells fire in a unique mode, displaying non-adapting clusters of spikes interspersed with rhythmic subthreshold membrane-potential oscillations when depolarized from levels less negative than -55 mV. The spike clusters repeat rhythmically at relatively low frequencies (2-10 Hz). The intracluster spiking frequency is relatively high and coincides approximately with that of the intervening membrane-potential oscillations (approximately 20-70 Hz). The cluster frequency of the non-cholinergic cells corresponds, in the same manner as the burst frequency of the cholinergic cells, to a delta (1-4 Hz) or theta (4-10 Hz) range of activity, whereas the intra-cluster and tonic spike frequencies of the non-cholinergic cells correspond to high beta to gamma ranges of electroencephalographic activity (19-30 Hz and 30-60 Hz, respectively). We propose that the different modes of oscillatory firing by the cholinergic and non-cholinergic basal forebrain cell populations could collectively contribute to the rhythmic modulation of slow and fast rhythms within the cerebral cortex.

Animals↗

Single-photon emission computed tomography using hexamethylpropyleneamine oxime in the prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: The role of single-photon emission CT (SPECT) in the prognosis of cerebral infarction is controversial, but most studies report that SPECT using a variety of radiopharmaceutical agents gives useful prognostic information. Only one study has questioned whether acute perfusion deficits independently add to a valid clinical prognostic score. This study was limited to middle cerebral artery territory infarcts and was negative. We present data on the prognostic utility of SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO) in cerebral infarction, unselected by site. METHODS: Fifty consecutive unselected patients admitted to the hospital with acute cerebral infarction, of whom 10 died and 7 withdrew, had SPECT performed serially at onset and at 1 week and 3 months after stroke onset using 99mTc-HMPAO and the NOVO 810 dedicated high-resolution head tomograph. Clinical severity at presentation and outcome was measured with the Canadian Neurological Scale and the Barthel Index. Infarct volumes were measured from both the SPECT and CT scans. The data for the 43 subjects who completed the study or died were evaluated to determine the most powerful prognostic measures. Predictors were the Canadian Neurological Scale score at onset and 1 week, the Barthel Index at 1 week, the CT infarct volume typically done between 3 and 7 days after stroke onset, and the infarct volumes at the first and second SPECT. Outcome measures were the Canadian Neurological Scale score and Barthel Index score at 3 months, scored as zero for those patients who died. RESULTS: The clinical prognostic indicators correlated with the outcome measures, with coefficients between .617 and .821 (P < .0006 in all cases). The Canadian Neurological Scale score measured at 1 week was the best of these. Infarct volumes measured from SPECT correlated less well (coefficients between -.518 and -.683, P < .0019 in all cases). CT infarct volume was the poorest predictor. Although SPECT infarct volumes predicted outcome, they did so less well than clinical examination. Spontaneous infarct reperfusion did not affect outcome. CONCLUSIONS: Although the measurement of infarct volume on SPECT using 99mTc-HMPAO provides a predictor of stroke outcome, it is not a better predictor than the Canadian Neurological Scale score.

Acute Disease↗