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Biomedical subjects

V Dhawan

Publications and source records attributed to V Dhawan.

At least 91 records · Page 5Linked to original sources
PubMed1993

Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease.

Regional and global metabolic rates for glucose were estimated using 18F-fluorodeoxyglucose and positron emission tomography in 10 patients with a clinical likelihood of striatonigral degeneration (2 men and 8 women; mean age, 61.8 +/- 6.9 years; mean disease duration, 4.7 +/- 2.2 years; mean Hoehn and Yahr score, 3.5 +/- 0.8). Measures of brain glucose metabolism in these patients were compared with those for 10 age-matched normal volunteers, 10 disease severity-matched patients with Parkinson's disease (PD), and 10 disease duration-matched patients with PD. Normalized glucose metabolism was significantly reduced in the caudate (p < 0.03) and putamen (p < 0.003) as compared with that in normal and PD control subjects, and discriminated patients with striatonigral degeneration from control subjects (p < 0.002). Putamenal hypometabolism in patients with striatonigral degeneration correlated significantly with quantitative ratings of motor disability (p < 0.02). These results suggest that quantitative 18F-fluorodeoxyglucose positron emission tomography techniques may be useful in supporting a diagnosis of striatonigral degeneration in life, and in objectively assessing disease severity and potential therapeutic interventions.

Aged↗
PubMed1993

Positron emission tomographic findings in Filipino X-linked dystonia-parkinsonism.

Regional and global metabolic rates for glucose (rCMRGlc and GMR) were estimated using [18F]fluorodeoxyglucose and positron emission tomography in 3 patients with Filipino X-linked dystonia-parkinsonism (lubag). In all 3 patients a selective reduction in normalized striatal glucose metabolism (rCMRGlc/GMR) was observed compared with 15 normal volunteer subjects. Presynaptic nigrostriatal function was assessed in these patients using [18F]fluorodopa and positron emission tomography. Striatal rate constants for [18F]flurodopa uptake were found to be in the normal range in all 3 patients with lubag. These findings suggest that the extrapyramidal manifestations of lubag are metabolically localized to the striatum and that clinical parkinsonism in these patients may be secondary to extranigral factors.

Adult↗
PubMed1993

Striatal 18F-dopa uptake: absence of an aging effect.

L-[18F]6-Fluoro-DOPA (L-[18F]6-fluoro-3,4-dihydroxyphenylalanine; FDOPA) has been used with quantitative positron emission tomography (PET) to assess presynaptic nigrostriatal dopaminergic function in life. The relationship of estimated kinetic rate constants for striatal FDOPA uptake [Ki(FDOPA)] to the normal aging process has been the subject of conflicting reports. Resolution of this issue has been hampered by methodological differences in previous FDOPA/PET investigations. We studied 19 healthy normal subjects (aged 27-77 years) and measured striatal Ki-(FDOPA) according to each of the earlier methods. While significant correlations (p < 0.005) existed between Ki(FDOPA) values estimated by the various techniques, none correlated with normal aging. We conclude that normal striatal Ki(FDOPA) values estimated using quantitative FDOPA/PET are uncorrelated with the aging process.

Adult↗
PubMed1993

Noninvasive quantitative fluorodeoxyglucose PET studies with an estimated input function derived from a population-based arterial blood curve.

The authors have developed a technique to estimate input functions from a population-based arterial blood curve in positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose (FDG). A standardized pump injection was used in 34 subjects. A population-based blood curve was generated based on the first 10 subjects. In the remaining 24 subjects, an estimated input function (EIFa) was obtained by scaling the population-based curve with two arterial blood samples, one obtained at 10 minutes and the other at 45. Time integrals for EIFa and the real arterial input function (RIF) were in excellent agreement (r = .998, P < .0001). Cerebral metabolic rates for glucose calculated with EIFa and RIF and the autoradiographic method also correlated excellently (r = .992, P < .0001). Analogous correlations were achieved with arterialized venous samples as scaling factors. These results suggest that individually scaled, population-derived input functions may serve as an adequate alternative to continuous arterial blood sampling in quantitative FDG-PET imaging.

Adult↗
PubMed1992

Free radicals in myocardial injury: experimental and clinical studies.

The exposure of cardiac cells to OFR generated artificially, showed a marked decrease (p less than 0.01) in cellular utilization of glucose along with a significant decrease in calcium uptake (p less than 0.05). We have also provided evidence for a direct relationship of neutrophil OFR production with the extent of myocardial ischemia in patients of myocardial infarction. Our data provides evidence for implication of OFR in myocardial injury and the pivotal role played by modulators like calcium, ECGF and prostaglandins in potentiating damage to the myocardium.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Hydrolytic enzymes in leprosy sera.

Serum samples collected from 45 untreated leprosy patients and 10 healthy subjects were studied for the activities of alkaline phosphatase, N-acetyl beta-glucosaminidase and beta-glucuronidase. A highly significant increase in the specific activity of these enzymes was observed in all types of leprosy patients as compared to controls. Increase in the level of circulatory hydrolytic enzymes could be a tissue damaging factor and may be responsible for many of the lesions seen in leprosy.

Acetylglucosaminidase↗
PubMed1992

Sodium and potassium content of liquid antacids.

Sodium and potassium contents of 37 commercially available liquid antacid preparations were estimated. Only nine preparations had sodium content below 60 mmol/L. The potassium content was below 1 mmol/L in 26 preparations. We conclude that caution should be exercised in selecting liquid antacid preparations in whom critically ill patients for electrolyte overload could prove harmful.

Antacids↗
PubMed1992

Effect of indomethacin on serum lipids, lipoproteins, prostaglandins and the extent and severity of atherosclerosis in rhesus monkeys.

The present study evaluated indomethacin therapy--a nonsteroidal anti-inflammatory drug--on experimental hyperlipidemia and atherosclerosis in Rhesus monkeys. Twenty-four monkeys were divided randomly into four groups of six. Two groups received stock pellet diet and two were given an atherogenic diet for six months. After this period, one stock diet-fed group and one atherogenic diet-fed group were treated with oral indomethacin (2.5 mg) on alternate days for a further six months. Serum lipids and lipoproteins were markedly elevated in atherogenic diet-fed monkeys. Generally, indomethacin did not exert a hypocholesterolemic effect; however, liver cholesterol was decreased (P less than 0.05) in atherogenic diet-fed monkeys treated with indomethacin. High density lipoprotein cholesterol was increased in stock diet-fed, indomethacin-treated monkeys but not in atherogenic diet-fed, indomethacin-treated monkeys. Apoprotein A-I was not affected by indomethacin in either stock or atherogenic diet-fed monkeys; however, the drug produced a significant (P less than 0.01) reduction of serum thromboxane B2 in stock diet-fed monkeys, without restoring the 6-keto-prostaglandin F1 alpha to pretreatment levels. A protective role of the drug was noted on both the extent and severity of aortic and coronary atherosclerosis.

Animals↗
PubMed1991

Abnormal cerebral glucose metabolism in long-term survivors of childhood acute lymphocytic leukemia.

Chemotherapy and radiation treatment of the central nervous system may cause delayed neurotoxicity in children with acute lymphocytic leukemia. We evaluated 12 long-term survivors of childhood leukemia using [18F]fluorodeoxyglucose positron emission tomography, computed tomography scans, clinical neurological examinations, and neuropsychological tests. Regional cerebral metabolic rate for glucose (rCMRGlc) values for white matter were lower in the older long-term survivors (greater than 18 years old) treated with cranial radiation and intrathecal chemotherapy than in normal control subjects or survivors who had been treated with intrathecal chemotherapy alone. The ratio of white matter: cortex rCMRGlc values was lower than control values in the long-term survivors treated with cranial radiation and intrathecal chemotherapy, regardless of age, but not in those treated with intrathecal chemotherapy alone. By contrast, thalamic rCMRGlc values were lower than control values in older survivors regardless of treatment, and the ratio for thalamus:cortex rCMRGlc values was lower in all the treatment groups than in the control subjects. The highest rCMRGlc values were found in the youngest children, indicating an important effect of age on cerebral glucose metabolism. No neuropsychological deficits were identified in patients treated only with intrathecal chemotherapy; however, lower IQ scores were found in the long-term survivors who had been treated with cranial radiation and intrathecal chemotherapy. Treatment of the central nervous system with cranial radiation and intrathecal chemotherapy may cause prolonged alterations in white-matter and thalamic rCMRGlc, which may permit the identification and assessment of neurotoxicity in long-term survivors of acute lymphocytic leukemia by [18F]fluorodeoxyglucose positron emission tomography.

Adolescent↗
PubMed1991

Prostaglandin-F2 alpha levels in normal saline-induced mid-trimester abortions.

In 20 mid-trimester abortion seekers induced by extra-amniotic instillation of normal saline, serial estimation of prostaglandin F2 alpha (PGF2 alpha) in the plasma and extra-ovular space were carried out. It was observed that PGF2 alpha was undetectable in both plasma and the extra-ovular space prior to the onset of induction, and was first detected in the extra-ovular fluid 2 hours after the onset of induction, prior to oxytocin infusion. In the subsequent samples, the prostaglandin concentration in plasma as well as in the extra-ovular fluid was found to rise, with levels in the latter showing a more significant rise with time as compared to the former. Thus, this study confirms the hypothesis that the mechanism of action of extra-ovular normal saline instillation in mid-trimester termination of pregnancy is the result of separation of fetal membranes from the uterine wall, leading to the release of prostaglandins which, in turn, causes uterine contractions leading to abortion.

Abortion, Induced↗
PubMed1991

Effects of percent thresholding on the extraction of [18F]fluorodeoxyglucose positron emission tomographic region-of-interest data.

Although we and others have employed a thresholding strategy to extract "peak" values from positron emission tomographic (PET) regions of interest (ROIs), the effects of peak picking on fitted fluorodeoxyglucose rate constants, regional metabolic rate for glucose (rCMRglc) profiles, patterns of regional metabolic covariation, and PET-neurobehavioral correlations have not been systematically investigated. Our results suggest that under some commonly encountered imaging conditions percent thresholding may increase sensitivity to regional activation; however, the effect of thresholding is determined by a number of factors, including the relative magnitude of regional activation, ROI size, and the specific threshold selected. The difference-annulus concept is proposed as a means to study the effects of different region drawing and thresholding strategies, and to determine if a given ROI contains one and only one source of covarying metabolic activity.

AIDS Dementia Complex↗
PubMed1991

The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography.

Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life.

Aged↗
PubMed1990

The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies.

We studied the metabolic anatomy of typical Parkinson's disease (PD) using [18F]fluorodeoxyglucose (FDG) and [18F]fluorodopa (FDOPA) and positron emission tomography (PET). Fourteen PD patients (mean age 49 years) had FDG/PET scans, of which 11 were scanned with both FDOPA and FDG. After the injection of FDOPA, brain uptake and arterial plasma radioactivity were monitored for 2 h. Striatal FDOPA uptake was analyzed with regard to a two-compartment model, and target-to-background ratios (TBRs) and TBR-versus-time slopes were also calculated. Regional patterns of metabolic covariation were extracted from FDG/PET data using the Scaled Subprofile Model (SSM). SSM pattern weights, FDOPA uptake constants (Ki), TBRs, and TBR slopes were correlated with clinical measures for bradykinesia, rigidity, tremor, gait disturbance, left-right asymmetry, dementia, and overall disease severity. In PD patients, rate constants for FDOPA uptake correlated with individual measures of bradykinesia (p = 0.001) and gait disability (p less than 0.05). SSM analysis revealed a distinct pattern of regional metabolic asymmetries, which correlated with motor asymmetries (p less than 0.001) and left-right differences in Ki (p less than 0.01). Our data suggest that in PD patients, FDG/PET and FDOPA/PET may provide unique and complementary information about underlying disease processes.

Adult↗
PubMed1990

Short-term therapy of atherosclerosis with low dose indomethacin: an experimental study.

The effects of low dose indomethacin therapy in primary prevention of diet-induced atherosclerosis of rhesus monkeys was studied. The parameters studied were serum cholesterol concentration, thromboxane A2 (T x B2), prostacyclin (6-keto-PGF1 alpha) in serum/plasma, and the extent and intensity of coronary atherosclerosis. Although indomethacin did not affect serum cholesterol, it reduced serum T x B2 significantly (P less than 0.01). Plasma 6-keto-PGF1 alpha was not restored to the pretreatment level. A significant protective role of the drug was noted as far as coronary atherosclerosis is concerned (P less than 0.01).

6-Ketoprostaglandin F1 alpha↗
PubMed1989

The time course of steroid action on blood-to-brain and blood-to-tumor transport of 82Rb: a positron emission tomographic study.

Blood-to-brain and blood-to-tumor transport rate constants for Rb (K1) and apparent tissue blood volume (Vb) were estimated in 8 patients with primary or metastatic brain tumors before and approximately 6 hours after a 100-mg intravenous bolus injection of dexamethasone using 82Rb and positron emission tomography. Eight additional patients were studied to evaluate test-retest variability and repositioning errors. Six hours following dexamethasone administration tumor K1 (but not Vb) was significantly reduced compared with contralateral control brain regions (p less than 0.03). These data are consistent with our previously published 24-hour-postdexamethasone data and suggest that comparable effects of corticosteroids on brain/tumor capillaries may be observed at 5 to 6 and 24 hours. The time course of dexamethasone-induced alterations in brain/tumor capillary permeability supports the view that these alterations may be responsible for at least some of the antiedema effects of corticosteroids.

Adolescent↗
PubMed1989

Positron emission tomographic measurement of blood-to-brain and blood-to-tumour transport of 82Rb. I: Error analysis and computer simulations.

Unidirectional blood-to-brain and blood-to-tumour transport rate constants (K1) for 82Rb (half-life 76 s) and plasma water volume per unit mass of brain/tumour tissue (Vp) can be estimated in vivo using dynamic positron emission tomography (PET). The accuracy of these estimates depends upon the accuracy of PET measurements of regional brain/tumour radioactivity and scintillation well detector measurements of whole-blood radioactivity, which, in turn, depend upon the time course of arterial blood radioactivity. A two-compartmental model has been employed to derive estimates for K1, k2 (efflux rate constant) and Vp from 82Rb/PET data. Errors in these parameter estimates have been studied (1) qualitatively using sensitivity function analysis and (2) quantitatively using computer simulations. The effect of adding a third irreversible compartment and its unidirectional rate constant, k3, has also been investigated. The advantages and disadvantages of bolus injection vs continuous infusion protocols are discussed. Precision in estimated parameters from actual patient data is compared to that obtained from computer simulations in part II of this paper.

Blood↗
PubMed1989

Positron emission tomographic measurement of blood-to-brain and blood-to-tumour transport of 82Rb. II: Clinical data and validation of technique.

Computer simulations and error analysis of a simple two-compartment, passive-diffusion exchange model for 82Rb across the blood-brain-barrier (BBB) have demonstrated the feasibility of obtaining useful estimates of unidirectional rate constant (K1) and tissue-blood water volume (Vb) in vivo using dynamic positron tomography (PET). The coefficients of variation (CV) in parameter estimates for 20 studies on ten patients are shown to have mean values of 10% for tumour K1 and Vb, 6% for normal brain Vb and 30% for normal brain K1. Ten test-retest studies show a very high correlation (R2 greater than 0.88) between the estimated parameter values. Apparent tissue blood volume (Vb) estimates obtained from 82Rb studies underestimate the blood volumes obtained by single-breath C15O studies by approximately 15%. In normal brain the extraction of rubidium (E) is small (less than 10%), and gives rise to a linear relationship between K1 and permeability-surface area product (PS). In tumour, however, E is larger (greater than 30%), and results in a non-linear relationship between these values. For both tumour and normal brain, K1 was found to be independent of regional cerebral blood flow (rCBF). The data from these clinical studies are in agreement with the predictions of the computer simulations and suggest the suitability of 82Rb/PET in the quantification of BBB functional changes.

Adolescent↗