Search PubMed⌕ Search

Biomedical subjects

C J Thompson

Publications and source records attributed to C J Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Evaluation of the ECAT EXACT HR+ 3-D PET scanner in H2(15)O brain activation studies: dose fractionation strategies for rCBF and signal enhancing protocols.

We evaluated the performance of the ECAT EXACT HR+ 3-D whole-body positron emission tomography (PET) scanner when employed to measure brain function using H2(15)O bolus activation protocols that are completed in single same-day data acquisition sessions. Using vibrotactile and auditory stimuli as independent activation tasks, we studied the scanner performance under different imaging conditions in five healthy volunteers. Cerebral blood flow images were acquired from each volunteer using H2(15)O bolus injections of activity varying from 5-20 mCi. One-session dose-fractionation strategies were analyzed for rCBF, standard activity-concentration, switched, and cold-bolus/switched protocols. Performance characteristics. The scanner dead time grew linearly with injected dose from 10% to 25%. Random events varied from 30% to 50% of the detected events. Random and scattered events were corrected adequately at all doses. Estimated noise-effective-count curves plateau at about 10 mCi. One-session 12-injection bolus PET activation protocols. Using an acquisition protocol that accounts for the scanner performance and the practical aspects of imaging volunteers and neurological patients in a single same-day session, we assessed the correlation between the significance of activation foci and the dose/injection used. The one-session protocol employs 12 bolus injections/subject. We present evidence suggesting that when an rCBF protocol is used, image noise is reduced significantly when the activity injected increases from 5 to 10 mCi. Increasing the dose from 10 to 15 or 20 mCi yielded further but smaller reductions. Our observations also suggest that image noise will be strongly reduced if a 20-mCi dose/injection is used when data are collected using protocols that employ long acquisition times such as a switched or a cold-bolus/switched protocol.

Adult↗
PubMed1998

Technique to obtain positron emission mammography images in registration with x-ray mammograms.

X-ray mammograms reveal abnormal tissue densities, while metabolic images identify regions of abnormal metabolism. Conventional nuclear medicine and radiologic breast images must be acquired at different times with different patient positions making coregistration difficult. Accurate coregistration of metabolic and x-ray images of the breast is likely to be important when acquiring information about the location and diagnosis of suspicious lesions or tumors. Our PEM-1 (positron emission mammography) system detects metabolic activity within the breast. The two planar detectors are integrated into a conventional x-ray mammography unit. This arrangement simplifies the image registration process by allowing a breast metabolic image to be acquired immediately after performing an x-ray mammogram. The patient is not moved between procedures. A coregistration tool has also been developed. A thin plastic sheet with a wire frame protrudes from the side of the upper PEM detector. With the tool positioned over the suspicious area of the breast, a magnified film density image is made using the available x-ray equipment. A radio-opaque rectangular outline of the wire frame is visible on the film image. During a positron emission metabolic scan, detectors acquire a 49 x 59 mm2 image of the same region. The PEM detectors can be positioned anywhere along the width of the breast. This provides an image of a particular region of interest. Several contiguous images may be combined to provide a complete scan.

Breast Neoplasms↗
PubMed1998

Insertion element IS3-based PCR method for subtyping Escherichia coli O157:H7.

An Escherichia coli O157:H7 subtyping method based on PCR amplification of variable DNA sequences between the repetitive element IS3 was developed. Template DNA was prepared by boiling cells in Chelex. Two separate IS3 PCR amplifications were performed for each isolate: one with a single primer (primer IS3A) and one with two primers (primers IS3A and IS3B). The IS3 PCR subtyping method was applied to 35 epidemiologically related and unrelated E. coli O157:H7 isolates that had been previously characterized by pulsed-field gel electrophoresis (PFGE). PFGE identified 25 different subtypes (difference of one or more bands). PCR with single primer IS3A and primer pair IS3A-IS3B identified 6 and 14 different subtypes, respectively. By combining the results of the two PCR amplifications, 15 different IS3 PCR subtypes were identified. While not as sensitive as PFGE, IS3 PCR subtyping grouped all outbreak-related isolates. IS3 PCR banding patterns were reproducible between amplifications and between subcultures. IS3 PCR could serve as a simple, rapid screening method for the identification of unrelated E. coli O157:H7 isolates.

Bacterial Typing Techniques↗
PubMed1998

Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus.

A 45-year-old man, with a 10-year history of manic depression treated with lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year history of polyuria and polydipsia, during which time urinalysis had been negative for glucose. After recovery from hyperglycaemia, he remained polyuric despite normal blood glucose concentrations; water deprivation testing indicated nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that when this man developed type 2 diabetes, chronic polyuria due to nephrogenic diabetes insipidus was sufficient to precipitate hyperosmolar dehydration.

Antimanic Agents↗
PubMed1998

Dose-dependent reduction of cerebral blood flow during rapid-rate transcranial magnetic stimulation of the human sensorimotor cortex.

Rapid-rate transcranial magnetic stimulation (rTMS) was used to stimulate the primary sensorimotor cortex in six healthy volunteers while regional changes in cerebral blood flow (CBF) were simultaneously measured by means of positron emission tomography. A figure-eight TMS coil (Cadwell Corticoil) was positioned, using frameless stereotaxy, over the probabilistic location of the left primary sensorimotor cortex, and a series of brief 10-Hz trains of TMS was delivered at subthreshold intensity during each of six 60-s scans. The scans differed in the number of trains delivered, namely 5, 10, 15, 20, 25, and 30 trains/scan, respectively. In the left primary sensorimotor cortex, CBF covaried significantly and negatively with the number of stimulus trains. These CBF decreases may reflect TMS-induced activation of local inhibitory mechanisms known to play a role in TMS-related phenomena, such as the electromyographic silent period.

Adult↗
PubMed1998

Signal-enhancing switched protocols to study higher-order cognitive tasks with PET.

UNLABELLED: We tested the effectiveness of a switched protocol when it is used to detect signals that result from the study of a higher-order cognitive task with PET. Using language tasks that have been studied extensively in our laboratories, we compared the signal-to-noise ratio (S/N) and statistical significance of the activation signals detected in PET images of regional cerebral blood flow (rCBF), obtained using a standard activation protocol, and of activity concentration, obtained using a switched protocol. METHODS: Four volunteers were studied with PET while they were performing synonym-generation and word-repetition tasks (activation and baseline tasks, respectively). Each volunteer had three activation/baseline and three baseline/ activation scans. Data for each scan were collected in two frames (60 and 120 sec long). During the first 60 sec, data were collected using a standard activation protocol. Subjects then switched tasks, and acquisition continued for 120 sec. Two images were obtained from each scan: an rCBF image using the first frame and an activity-concentration image using both frames. Images were transformed into Talairach space, subtracted and averaged within and across subjects. Parametric t-statistic images were generated for each protocol, and the magnitude and significance of the activation signals yielded by the two acquisition methods were compared. RESULTS: All the activation foci detected using measurements of rCBF were detected when the switched protocol was used; this protocol, in addition, yielded better S/N values. The cognitive component introduced by task-switching in switched protocols did not yield extra statistically significant foci. In single subjects, the average improvement in the signal significance from regions of activation, at a 95% confidence level, was between 6% and 25%. When scans were averaged across subjects, the switched protocol yielded improvements in signal statistical significance of up to 38%. CONCLUSION: We present evidence suggesting that switched protocols can be used to study higher-order cognitive tasks and that they yield activation foci with S/N values that are greater than those of equivalent foci detected using an rCBF protocol. Switched protocols appear to be easy to apply to the testing of higher-order cognitive functions. However, the extra cognitive requirement of switching tasks during data acquisition may be a limiting factor when switched protocols are used to study memory processes.

Adult↗
PubMed1997

Transcranial magnetic stimulation during positron emission tomography: a new method for studying connectivity of the human cerebral cortex.

We describe a new technique permitting the mapping of neural connections in the living human brain. The method combines two well established tools of brain research: transcranial magnetic stimulation (TMS) and positron emission tomography (PET). We use TMS to stimulate directly a selected cortical area while simultaneously measuring changes in brain activity, indexed by cerebral blood flow (CBF), with PET. The exact location of the stimulation site is achieved by means of frameless stereotaxy. In the first study using this technique, we found significant positive correlations between CBF and the number of TMS pulse trains at the stimulation site, namely the left frontal eye field (FEF) and, most importantly, in the visual cortex of the superior parietal and medial parieto-occipital regions. The pattern of these distal effects was consistent with the known anatomic connectivity of the monkey FEF. We suggest that the combined TMS/PET technique offers an objective tool for assessing the state of functional connectivity without requiring the subject to engage in any specific behavior.

Adult↗
PubMed1997

Identification of procaryotic developmental stages by statistical analyses of two-dimensional gel patterns.

Multivariate statistical comparisons of two-dimensional protein (2-D) gel patterns were used for the first time to define stages of a biological developmental system. The differentiating procaryote, Streptomyces coelicolor, was radiolabeled in liquid cultures at 16 intervals during development, and radioactive proteins were separated and quantified on 2-D gels. Cluster, principal component, and correlation analyses classified these gel patterns into four distinct groups, each reflecting a pattern of gene expression specific for a stage of development. These studies focused our attention on a phase of arrested growth as a key regulatory transition leading to secondary metabolism and a phase of renewed growth. Proteins whose synthesis was switched on or off during the "transitional" phase (some 21 and 18, respectively) were identified and will be the focus of future studies designed to identify their physiological or regulatory function.

Algorithms↗
PubMed1997

Motion correction of PET images using multiple acquisition frames.

Positron emission tomography (PET) is a relatively lengthy brain imaging method. Because it is difficult for the subject to stay still during the data acquisition, head motion during scans is a source of image degradation. A simple data acquisition technique to reduce the effect of this problem is described. The technique associates the incoming data with the real-space position of the head. During the PET scan, the head position is constantly monitored with two video cameras and compared to its initial position. Every time the displacement for a region within the field of view (FOV) is larger than a specified threshold displacement, the PET data acquisition system starts to save the PET data in a new frame. The total number of frames required for a complete study depends on the magnitude of the head motion during the study and on the threshold displacement. At the end of the study, all the acquired frames are reconstructed independently and each image is rotated and translated to coincide with the initial position. When these images are summed, they produce a final image with fewer motion artefacts.

Artifacts↗
PubMed1997

Persistent nephrogenic diabetes insipidus following lithium therapy.

We report the case of a patient who developed severe hypernatraemic dehydration following a head injury. Ten years previously he had been diagnosed to have lithium-induced nephrogenic diabetes insipidus, and lithium therapy had been discontinued. He remained thirsty and polyuric despite cessation of lithium and investigations on admission showed him to have normal osmoregulated thirst and vasopressin secretion, with clear evidence of nephrogenic diabetes insipidus. Lithium induced nephrogenic diabetes insipidus is considered to be reversible on cessation of therapy but polyuria persisted in this patient for ten years after lithium was stopped. We discuss the possible renal mechanisms and the implications for management of patients with lithium-induced nephrogenic diabetes insipidus.

Bipolar Disorder↗
PubMed1997

Hypopituitarism following coronary artery bypass surgery.

Coronary artery bypass surgery (CABS) is a common operation, which is often complicated by neurological sequelae. Disturbances of cerebral blood flow have been reported up to eight days after surgery and pituitary apoplexy has previously been reported. We report a case of hypopituitarism without pituitary apoplexy, which developed after a period of sustained arterial hypotension, during coronary artery bypass surgery.

Aged↗
PubMed1997

Quantification of left ventricular function with thallium-201 and technetium-99m-sestamibi myocardial gated SPECT.

UNLABELLED: Myocardial gated SPECT with 99mTc-sestamibi has been used to quantify left ventricular function. The purpose of this study was to determine if myocardial gated SPECT with 201Tl was possible and reliable to quantify left ventricular function. METHODS: One hundred and four patients referred for a myocardial perfusion study were included. Myocardial gated SPECT acquisition was performed 15 min after the intravenous injection of 111 MBq (3mCi) 201Tl and at 1 hr postinjection of 925 MBq (25 mCi) 99mTc-sestamibi. A commercially available automated myocardial gated SPECT processing software was used. Parameters evaluated were left ventricular ejection fractions (LVEF), end-diastolic volumes (EDV), end-systolic volumes (ESV) and stroke volumes (SV). RESULTS: The correlation between gated SPECT with 201Tl and gated SPECT with 99mTc-sestamibi was: r = 0.93 for LVEF, 0.92 for EDV, 0.96 for ESV and 0.68 for SV. CONCLUSION: Myocardial gated SPECT quantification of left ventricular function with 201Tl was possible and as reliable as gated SPECT with 99mTc-sestamibi. There was excellent correlation between gated SPECT with 201Tl and gated SPECT with 99mTc-sestamibi. In addition to assessment of myocardial perfusion, myocardial function and viability can be quantified in a single gated 201Tl study.

Coronary Disease↗
PubMed1996

Nucleoside-diphosphate kinase from Streptomyces coelicolor.

Nucleoside-diphosphate (NDP) kinase was purified from crude extracts of Streptomyces coelicolor to over 90% homogeneity in a single step using an adenosine 3',5'-cyclic monophosphate (cAMP) binding column. The specific activity of protein in the fraction eluted with cAMP (400 U/mg) was about 3600-fold higher than that in the crude extract. This enzyme was autophosphorylated in the presence of [y-32P]ATP. The high-energy phosphoenzyme intermediate was stable in alkali and highly labile in acid; this suggests the presence of an N-phosphate amino acid (most probably a histidine residue). A tetrameric form of the 15-kDa protein was suggested by its apparent molecular mass (66 kDa) on a gel filtration column. The measured Michaelis constant (Km) for ATP was 85 microM. The IC50 for cAMP of 6 mM suggested weak competitive inhibition. However, no evidence that cAMP acts as an allosteric effector was obtained. The ndk gene from S. coelicolor was isolated and sequenced. The deduced amino acid sequence was very similar to other NDP kinases. However, unique characteristics were also noted, including a truncated C-terminus that makes it one of the smallest NDP kinases reported in the literature.

Amino Acid Sequence↗
PubMed1996

Characterization of the covalent binding of thiostrepton to a thiostrepton-induced protein from Streptomyces lividans.

Thiostrepton is a highly modified multicyclic peptide antibiotic synthesized by diverse bacteria. Although best known as an inhibitor of protein synthesis, thiostrepton is also a potent activator of gene expression in Streptomyces lividans. In these studies, we characterize the nature of the interaction between thiostrepton and two proteins that it induces, TipAL and TipAS. In the absence of added cofactors, thiostrepton formed a complex with either TipAL or TipAS in aqueous solution. The TipA-thiostrepton complex was not dissociated by denaturants such as SDS, urea, or disulfide reducing agents. The mass of the TipAS-thiostrepton complex as determined by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MS) was equivalent to the sum of TipAS and thiostrepton. Thiostrepton also reacted spontaneously with free cysteine (but not with other amino acids tested) to generate stable compounds having masses equivalent to thiostrepton plus 3 to 4 cysteines. Blocking experiments indicated that complex formation required dehydroalanine residues on thiostrepton and cysteine residues on TipAS. When the TipAS-thiostrepton complex was digested with trypsin and analyzed by MS, the thiostrepton adduct was found bound only to the unique cysteine-containing TipAS peptide fragment. Amino acid analysis confirmed that the TipAS-thiostrepton complex contained lanthionine, the product of a reaction between dehydroalanine and cysteine. Together, these data document a covalent attachment of thiostrepton to TipA proteins mediated by bond formation between dehydroalanine of thiostrepton and cysteine of TipAS. Implications regarding the function of TipAS as a thiostrepton (electrophile)-sequestering protein and thiostrepton-mediated activation of TipAL as a model of irreversible transcriptional activation are discussed.

Alanine↗
PubMed1996

The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: The best dynamic test for the assessment of the hypothalamic-pituitary-adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic-pituitary-adrenal axis. DESIGN: Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed. SETTING: Programmed Investigation Unit. SUBJECTS: Fifty-seven healthy volunteers and 166 patients. MAIN OUTCOME MEASURES: Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycemia (plasma glucose < 2 mmol/l) during an IST. RESULTS: From normal data the mean-2SD 30-minute value during the SST was 392 nmol/l and 60-minute value was 497 nmol/l. The maximal cortisol response (mean - 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission. CONCLUSIONS: Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

Adrenal Cortex Function Tests↗