Toxicity of norpethidine in sickle cell crisis.
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Adolescent↗
Biomedical subjects
R Carson
Publications and source records attributed to R Carson.
Cerebral glucose metabolic rates after 30 and 45 minute acquisitions: a comparative study.
This study was undertaken to determine if measurements of absolute regional cerebral metabolic rate for glucose (rCMRglc) and variance of rCMRglc are independent of time between 30 and 45 min following injection of the radiotracer. Sixteen subjects received two sets of 18FDG PET scans commencing 30 and 45 min following intravenous injection of 18FDG. No statistically significant differences were detected in either absolute rCMRglc or rCMRglc variance between the two sets of scans. These data demonstrate that for most FDG PET studies, scanning can commence 30 min after injection of the radiotracer without compromising the metabolic data.
Adult↗
Distribution and kinetics of 3-O-methyl-6-[18F]fluoro-L-dopa in the rhesus monkey brain.
Most attempts to model accurately [18F]-DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [18F]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered 18F-labeled 3-OM-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective 18F regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one-compartment, three-parameter model was adequate to describe the kinetics of [18F]3-OM-DOPA. In conclusion, assumptions concerning [18F]3-OM-DOPA's behavior in brain appear acceptable for [18F]DOPA modeling purposes.
Animals↗
A database review in C-L psychiatry: characteristics of hospitalized suicide attempters.
A computerized database was used to study the characteristics of psychiatric consultations in patients admitted to nonpsychiatric services. The authors reviewed a consultation practice with suicide attempters over a four-year period and compared the patients with a patient sample matched for gender and age also seen by the service. For suicide attempters, the time elapsed between admission to the service and the consultation, as well as the lengths of stay, were significantly shorter. Suicide attempters were significantly more likely to have mood disorders and Axis II disorders. The authors review the role of consultation psychiatrists with these patients and suggest that a triage model fits the services provided and the needs of nonpsychiatric physicians.
Adult↗
Diagnostic characteristics and dispositions in suicidal hospitalized medical and surgical patients.
Suicidal ideation is frequently identified in psychiatric consultation patients, but the outcomes of patients with suicidal ideation are infrequently discussed. We reviewed 4 years of consultations and identified two groups of suicidal patients, those admitted following suicide attempts and those with medical illnesses. These groups and the remaining nonsuicidal patients were analyzed for lengths of stay, diagnoses, and outcomes. Suicidal patients were younger (p less than 0.001), and had earlier consultations (p less than 0.001) and shorter stays (p less than 0.001). There were more affective disorders (p less than 0.001) and Axis II disorders (p less than 0.001) in suicidal patients, but more adjustment disorders (p less than 0.005) in nonsuicidal patients.
Adjustment Disorders↗
Differential regulation of right and left ventricular levels of atrial natriuretic factor mRNA and peptide.
Over a 16-day period post-hypophysectomy both atrial natriuretic factor (ANF) mRNA and peptide levels were quite differently regulated in right and left ventricles. In the right ventricle ANF mRNA levels showed a large increase 2 days post-hypophysectomy, and returned to control levels by day 8. In the left ventricle mRNA levels doubled by day 2, and continued to rise to reach plateau levels (approximately 3-fold control) 8-16 days post-hypophysectomy. Tissue levels of ANF peptide were also measured by radioimmunoassay over the same time period. Right ventricular ANF levels rose 10-fold 2 days post-hypophysectomy, and returned to 3 times control levels by 8 days, mirroring the changes in mRNA. In the left ventricle, however, ANF peptide levels did not change significantly from intact values over the entire 16-day period following hypophysectomy despite the progressive increase in ANF mRNA levels in this tissue, suggesting that the dichotomy between mRNA and peptide levels in the left ventricle reflects an increased rate of peptide secretion.
Animals↗
Protoporphyrinaemia and decreased activities of 5-aminolevulinic acid dehydrase and uroporphyrinogen I synthetase in erythrocytes of a Vitamin B6-deficient epileptic boy given valproic acid and carbamazepine.
Carbamazepine (CBMZP) has been implicated as an inhibitor of the activities of 5-aminolaevulinic acid dehydratase (ALA-D) and uroporphyrinogen I synthetase (URO-S). In an epileptic boy undergoing long-term treatment with valproic acid (VPA), 1.3 g/d, CBMZP, 0.9 g/d and folic acid, 7.5 mg/d, decreased activities of ALA-D and URO-S coincided with increased levels of erythrocyte protoporphyrin (EP) in the absence of Pb poisoning, iron depletion and erythropoietic protoporphyria. A progressive fall in plasma pyridoxal 5'-phosphate (B6-P) to 7.7 nmol/L (lower reference limit, 14.6 nmol/L) prompted implementation of pyridoxine HCl (B6-HCl), 87.5 mg/d followed by administration of both B6-HCl and preformed B6-P (50 mg/d each). This permitted the eventual withdrawal of VPA and a net reduction of CBMZP to 450 mg/d. During these manipulations, ALA-D and URO-S activities, EP and urinary porphyrins and their precursors were measured serially. An assay system utilizing red cell ALA-D for generation of porphobilinogen (PBG) from added ALA at pH 7.4 was used for determination of ALA-D and URO-S activities in separate aliquots of the same assay mixture both in the absence and presence of Zn and dithiothreitol (DTT). One unit (U) for ALA-D = 1 nmol PBG/L RBC/s; for URO-S = 1 nmol porphyrin/L/s; minimum normal level for ALA-D = 135 U; for URO-S = 6 U. B6-HCl alone entailed increases in ALA-D and URO-S prior to any reduction of CBMZP. After administration of both B6-HCl and B6-P and withdrawal of VPA, the overall increase in ALA-D was from 54.59 to 197.2 U (-Zn; -DTT) and from 50.76 to 217.3 U (+Zn; +DTT). The overall increase in URO-S was from 2.67 to 8.90 U (-Zn; -DTT) and from 3.02 to 8.66 U (+Zn; +DTT). During stepwise reduction of VPA, EP remained elevated to values as high as 2.48 mumol/L (upper reference limit, 1.33 mumol/L). Only after permanent withdrawal of VPA did concentrations of EP fall to normal levels. Values for porphyrins and their precursors in urine were normal throughout. Since both VPA and B6-P are strongly protein-bound, it is suggested that VPA displaced B6-P from protective protein binding sites and that the resulting deficit in B6-P (rather than CBMZP) reduced ALA-D and URO-S activities via primary reduction of ALA-synthetase activity. Increases in EP emerge as a hitherto unappreciated effect of VPA warranting further investigation.
Ammonia-Lyases↗
The lead program at CPRI.
A lead (Pb) screening program in operation at CPRI in London, Ontario, since 1977 involves simultaneous measurement of blood Pb and erythrocyte protoporphyrin (EP) in a randomized population of physically and/or mentally handicapped children and adolescents on admission, discharge and during outpatient visits. This 11-year study has yielded a large database for computerized evaluation. Based upon log normal transformation of data obtained from the admission and outpatient groups, the normal curve yielded a mean and standard deviation (SD) for blood Pb of 0.36 +/- 0.27 mumol/L (n = 4188). This fosters a downward revision of the upper reference limit to 0.89 mumol/L (95% confidence level). The overall mean for EP was 0.35 +/- 0.37 mumol/L and suggests an upper reference limit of 1.09 mumol/L. The direct correlation between annual means of blood Pb and EP retained its significance (r = 0.80; P less than 0.004). For both blood Pb and EP, there was no significant difference in values between admissions (n = 1455), discharges (n = 1310) and outpatient visits (n = 2963). Only in the case of blood Pb was the overall mean value of males (n = 3822) higher (0.46 +/- 0.34 mumol/L) than that of females (0.39 +/- 0.25 mumol/L; n = 1906), but by t-test the difference was not significant. Although annual means of both blood Pb and EP were highest in 1978 and 79 and lowest in 1987, there was no significant difference between any two years.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Workshop on schizophrenia, PET, and dopamine D2 receptors in the human neostriatum.
Recently, two research groups published numbers for D2 receptor sites in the neostriatum of drug-naive schizophrenic patients, obtained in vivo by positron emission tomography (PET). One study appeared to confirm the increase of D2 receptor numbers, while the other study did not. A workshop was convened in Montreal to examine the reasons for the discrepancy between the results obtained by the two groups. The workshop considered patient populations, PET instrumentation and scanning methods, pharmacology, and modeling. The workshop identified differences between the approaches of the two groups that could contribute to the divergent results, including age and chronicity of the patient samples, brain region selected for study, metabolism of the different radioligands in blood and brain, reversibility of binding, PET instrumentation, and complexity of data analysis. The workshop concluded that these initial efforts had made considerable progress in establishing the role of PET in the understanding of the biochemical processes underlying mental illness. In particular, the unique ability to quantify regional neuroreceptor density at different stages in the evolution of the disease has been implemented. At the same time, the work so far and this conference served to identify the main sources contributing to the different findings from the two centers. This information will be important in designing the next phase of the research which will build upon and reconcile these apparent discrepancies.
Adult↗
Plasma levels of neuropeptide tyrosine Y (NPY) are increased in human sepsis but are unchanged during canine endotoxin shock despite raised catecholamine concentrations.
Alterations in levels of adrenal vein and circulating immunoreactive neuropeptide tyrosine Y (NPY), as well as systemic catecholamine concentrations, have been investigated in the dog after endotoxin administration. Eighteen dogs were anaesthetized with alpha-chloralose and allowed to breathe spontaneously. Severe shock was produced by the administration of a large bolus of Escherichia coli endotoxin followed by a continuous infusion. In two further animals the left lumbar adrenal vein was cannulated and an intermittent choke allowed retrograde sampling of the adrenal effluent. The production of hypodynamic shock was associated with marked increases in systemic catecholamine concentrations but there were no consistent changes in adrenal vein or systemic immunoreactive NPY levels. In contrast, circulating concentrations of immunoreactive NPY were markedly raised above the normal range in five patients with septic shock.
Animals↗
Ligands for imaging opioid receptors in conscious humans by positron emission tomography (PET).
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Animals↗
Assessment of goals and obstacles in data acquisition and analysis from emission tomography. Report of a series of international workshops. III. Biomathematical aspects of physiological brain imaging.
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Brain↗
Relation of measured brain glucose utilisation and cerebral atrophy in man.
The effect of cerebral atrophy on measured cerebral metabolic rates for glucose (CMRglc), as determined with positron emission tomography (PET), was examined in 49 healthy males aged 21-83 years. Global CMRglc and regional CMRglc for 34 grey matter regions parallel to and from 30 to 80 mm above the inferior orbital meatal (IOM) line were measured under resting conditions, using [18F]-fluorodeoxyglucose and an ECAT II positron emission tomograph. Using a GE 8800 CT/T scanner, slices parallel to and from 30 to 80 mm above the IOM line were analysed for CSF volume. Cerebral atrophy, indicated by increased CSF volume, was correlated significantly with global CMRglc, but accounted for no more than 13% of the variance in the CMRglc measurements. Methods for correcting for inter-subject variation in CSF volume were proposed. Global values for CMRglc, uncorrected or corrected for CSF volume, were found to be age invariant. These findings indicate that (a) cerebral atrophy has a small, but statistically significant effect on CMRglc as measured with PET; (b) CMRglc is age invariant in healthy males.
Adult↗
Functional ability and equipment use among patients with neuromuscular disease.
The relationship between graded functional ability of a neuromuscular disease patient and his routine daily activities remains unknown. Mobility equipment use may provide an indirect measure of routine daily activities. In this study 110 neuromuscular disease patients were evaluated for both functional grade (Brooke upper extremity and Vignos lower extremity scales) and equipment use. Although several of the Vignos and Brooke categories did not describe significant numbers of these patients, the Vignos scale was able to predict whether or not a given patient would use a wheelchair with 94% accuracy, while the Brooke scale was only 85% accurate. It was not possible to predict manual vs electric wheelchair use based on functional rating scores. Patients with proximal weakness, regardless of diagnosis, displayed a similar pattern of functional outcome and equipment use, which was significantly different from the pattern displayed by groups with distal weakness. As expected, as functional ability diminished, wheelchair use increased; however, wheelchair use began at surprisingly high functional levels. Patients generally preferred a combination of manual and electric wheelchair use.
Activities of Daily Living↗
Upper vs lower extremity functional loss in neuromuscular disease.
Functional rating scales have been developed for evaluation of upper extremity (UE) and lower extremity (LE) function in Duchenne muscular dystrophy (DMD). The Vignos scale is accepted for LE function and the Brooke scale for UE evaluation. The assumption that UE functional loss parallels LE loss has never been tested. Furthermore, there are no studies examining the relationship between UE/LE strength. This study tests the hypothesis that UE/LE strength and functional losses are parallel in DMD and other neuromuscular disorders. Vignos grades, Brooke grades, and manual muscle test scores were determined for 27 patients with DMD, 10 patients with fascioscapulohumeral muscular dystrophy (FSH), 24 patients with myotonic muscular dystrophy (MMD) and 29 patients with other (Becker's dystrophy and limb-girdle syndrome) proximal myopathies (PM). Spearman correlation coefficients were calculated for UE vs LE functional grade and strength scores and subjected to significance analysis. While all correlations were statistically significantly different from zero (p less than 0.01), all were also significantly different from one (p less than 0.01), none representing perfect equivalence. Coefficients of determination indicated that a maximum of 86% (FSH) of variation in UE rank could be explained purely by observing LE rank. While there is a significant relationship between UE/LE strength and functional grade, these measurements were not found to be entirely equivalent. Therefore, while measures of lower body function or strength might be used as a substitute for UE measurements in drug trials in which global effects are expected, the two measurements are not equivalent when evaluating an individual's clinical status.
Child↗
Regulation of prostaglandin biosynthesis by human ovarian follicular fluid: a mechanism for ovulation?
We have studied the effect of human ovarian follicular fluid on PG production by bovine seminal vesicles in vitro and found that hFF1 contains a factor of high molecular weight (Mr greater than 30,000) which inhibits PG synthase in a dose-dependent manner. Exposure of this substance to protease activity produced a factor of lower molecular weight (Mr less than 1000) which stimulated PG synthase activity. If this is true of ovarian follicles in vivo, it is possible that increased follicular protease activity stimulates PG synthesis at the time of ovulation.
Animals↗
Relative levels of thecal blood flow in atretic and non-atretic ovarian follicles of the conscious sheep.
The relative level of blood flow through thecal capillaries (RTF) in individual atretic and non-atretic follicles greater than 1 mm was measured in conscious ewes by injecting 15 micron radioactive microspheres into the aorta near the origin of the ovarian artery, and determining the ratio of radioactivity per mg protein in theca of individual follicles to that in the non-luteal portion (stroma plus follicles less than 1 mm diameter) of the corresponding ovary. In follicles greater than 1 mm diameter, RTF in those showing advanced stages of atresia (stages IV and V) was significantly less than that in non-atretic (stage I) follicles. RTF values in non-atretic (stage I), early atretic (stage II) and moderately atretic (stage III) follicles did not differ significantly. There was no effect of follicular diameter (P greater than 0.05) on the relative level of blood flow within individual thecae or of atresia on thecal protein content. These data indicate that reduced thecal blood flow is associated with advanced atresia of antral follicles and are in accordance with the findings of previous histological studies. Whether thecal ischaemia is a factor involved in the onset of atresia, or occurs as a consequence of the degenerative process, remains uncertain.
Animals↗
Development and steroidogenic activity of preantral follicles in the neonatal rat ovary.
The neonatal rat ovary is completely devoid of antral follicles until the twelfth day of age. During this period the ovary becomes steroidogenically active and responsive to gonadotrophins. The aim of this study was to correlate the onset of ovarian androgen and oestrogen production in vitro with the first appearance of distinct granulosa and theca cells. Although ovarian aromatase activity increased significantly on day 7 of age, ovarian oestrogen production was limited by low progesterone and testosterone production until day 12 of age. Increased aromatase activity on day 7 and androgen production on day 12 were coincident with the first appearance of granulosa and theca cells respectively. These functional and morphological changes were not associated with significant alterations in ovarian weight or concentrations of LH or FSH in serum.
Animals↗