PubMed Health⌕ Search

Biomedical subjects

J B Zimmerman

Publications and source records attributed to J B Zimmerman.

At least 19 recordsLinked to original sources
PubMed2000

Quantitative measurements of medical images for pharmaceutical clinical trials: comparison between on-site and off-site assessments.

OBJECTIVE: In pharmaceutical clinical trials, quantitative measurements on medical images are often conducted to confirm drug efficacy. This study aims to compare the quantitative image analysis performance of an off-site core laboratory with the performance of investigators from multiple clinical sites. MATERIALS AND METHODS: In a phase I clinical trial, 25 healthy subjects underwent dynamic brain single-photon emission computed tomography (SPECT) scintigraphy with 123I-Altropane, a cocaine analogue with high affinity and selectivity for dopamine transporter sites in the striatum. In 20 patients examined on-site and off-site, a total of 80 measurements were made to calculate the drug's binding potential. A trained technologist off-site at a central core laboratory and on-site investigators at different clinical sites performed the image analysis. These results were compared with measurements made by a subspecialty radiologist whose assessments were the reference standard. Statistical analysis was performed using multiple regression analysis. RESULTS: Measurements from the central core laboratory (off-site) highly correlated (r = 0.95) with measurements of the reference standard. Measurements from the clinical sites (on-site) grouped together had lower correlation (r = 0.84) with the reference standard. This difference was statistically significant (p < 0.05). CONCLUSION: Training and experience in the specific type of image analysis are critical in obtaining consistent data. Quantitative analysis by dedicated personnel at a core laboratory provides highly reproducible results. The findings support off-site assessment of medical images in pharmaceutical clinical trials.

Adult↗
PubMed1999

Targeting effect compartment or central compartment concentration of propofol: what predicts loss of consciousness?

BACKGROUND: An effect compartment has been postulated, and the ke0 has been quantified for several intravenous anesthetic drugs using electroencephalography (EEG) as the measure of effect. The authors wanted to validate that loss of responsiveness (LOR) was related to targeting an effect compartment concentration rather than a central compartment (plasma) concentration. METHODS: Twenty American Society of Anesthesiologists physical status I and II patients were randomized to receive propofol administered to a target central compartment or target effect compartment site concentration of 5.4 microg/ml propofol administered by a target-controlled infusion (TCI) using a previously validated set of pharmacokinetic parameters and a ke0 of 0.63 min(-1). Every 30 s for the first 5 min and every minute for the second 5 min the patients were asked to open their eyes. The time to LOR was measured by a blinded investigator. The authors also simulated the time to reach the desired target effect site concentration using varying ke0 values. RESULTS: The median time to LOR in the group targeted to a predicted plasma propofol concentration was 3.02 min and 1.23 min in the group targeted to a predicted effect compartment propofol concentration (P < 0.05). LOR to command in both groups occurred at a predicted median effect compartment concentration of 4.55 microg/ml. Simulations demonstrated that the time predicted to LOR targeting an effect site concentration of 5.4 microg/ml is markedly altered by the value chosen for the ke0. CONCLUSIONS: This study confirms the utility of the ke0 value to describe the effect compartment for propofol. The authors also illustrate the importance of selecting the correct ke0 value for the pharmacokinetic parameters used within the TCI system.

Adolescent↗
PubMed1993

Principles of voltammetry and microelectrode surface states.

In vivo voltammetry is approaching the end of its second decade as a technique to explore extracellular concentrations in the brain. The issues of selectivity and sensitivity, which caused considerable discussion and confusion in the early 1980s, are now resolved. It is clear that in vivo voltammetry and dialysis are complimentary tools to understand neurotransmitter dynamics. The two chief advantages of voltammetry compared to dialysis, improved temporal resolution and reduced tissue damage, make this technique exceptionally well suited for providing information which is complementary to that obtained by single-unit recording and is uniquely capable of providing information on the short-term regulation of extracellular levels of biogenic amines.

Animals↗
PubMed1992

Evoked neuronal activity accompanied by transmitter release increases oxygen concentration in rat striatum in vivo but not in vitro.

Dopamine and oxygen (O2) were measured in the caudate nucleus of anesthetized rats and in striatal slices during electrical stimulation. Simultaneous electrochemical detection of dopamine and O2 was accomplished with fast-scan cyclic voltammetry at a Nafion-coated carbon-fiber microelectrode. Stimulation of the medial forebrain bundle resulted in synaptic overflow of dopamine in the caudate nucleus. At the same time, O2 concentration increased in the extracellular fluid with two separate phases. The amplitude of the initial increase directly correlated with the frequency of the stimulus, with the time of maximum concentration reproducible across a range of frequencies. The second increase occurred at later times with a more random amplitude and with a broad, variable shape. Agents which blocked vasodilation affected both phases: atropine attenuated the initial increase, while the second feature was nearly absent after theophylline. Yohimbine and alpha-methyl-p-tyrosine did not affect the O2 responses. Local electrical stimulation of the slice preparation also resulted in dopamine overflow, but a prolonged decrease in O2 concentration accompanied this event. Striatal field stimulation in vivo produced changes in O2 concentration dependent on the relative position of the stimulating and working electrodes, but none of the responses resembled that seen in the caudate slice. Thus, while measurements in brain slices show O2 consumption as a result of stimulated neuronal activity, an apparent elevation of local cerebral blood flow during and after stimulation dominate the in vivo response.

Animals↗
PubMed1991

Simultaneous electrochemical measurements of oxygen and dopamine in vivo.

Fast-scan cyclic voltammetry, a demonstrated analytical method for the in vivo detection of catecholamine neurotransmitters, is extended to the simultaneous determination of molecular oxygen (O2). Cyclic voltammograms were recorded at a scan rate of 400 V/s at carbon-fiber disk electrodes coated with a perfluorinated ion-exchange material. The peak current for O2 occurs near -1.2 V under these conditions. In flow-injection experiments, these electrodes respond to step changes in dopamine and O2 with a half-rise time of less than 200 ms. The voltammetric peak current is independent of flow rate, indicating a diffusion-limited response unaffected by convection. Several compounds present in the in vivo matrix (adenosine, glutathione, and NAD and glutamic, lactic, and uric acids) were tested and shown not to interfere with the voltammetric signal for O2. These electrodes maintain a stable response in vivo for at least 6 h. They have been used to measure transient increases in both dopamine and O2 in the extracellular fluid of the caudate nucleus of an anesthetized rat in response to an electrical stimulus.

Animals↗
PubMed1990

MR image time-intensity relations in spleen and kidney: a comparative study of GdDTPA, albumin-(GdDTPA), and Gd2O3 colloid.

Magnetic resonance images were performed using a gradient recalled echo sequence with acquisition of images every 30 s in anesthetized rats before and after intravenous bolus injections of 100 microns/kg GdDTPA, 60 microns/kg albumin-(GdDTPA), and 60 microns/kg Gd2O3 colloid. All three agents caused significant enhancement of the renal cortex, and even greater enhancement of the spleen. GdDTPA showed an early peak at 11 s followed by a wash-out as blood concentrations fell, whereas albumin-(GdDTPA) and Gd2O3 showed sustained tissue enhancement. The enhancement in each organ was equivalent for albumin-(GdDTPA) and Gd2O3 which stay intravascular; but 30% less for GdDTPA which enters the interstitial space. In addition GdDTPA showed an initial enhancement of the renal medulla but then a subsequent loss of signal, whereas albumin-(GdDTPA) resulted in a greater enhancement of the medulla as compared to the cortex. We conclude that time-intensity studies of local tissue response to MR indicators reflect tissue physiological parameters such as perfusion, blood volume, and concentrating ability in a semiquantitative manner.

Albumins↗
PubMed1989

A psychophysical comparison of two methods for adaptive histogram equalization.

Adaptive histogram equalization (AHE) is a method for adaptive contrast enhancement of digital images. It is an automatic, reproducible method for the simultaneous viewing of contrast within a digital image with a large dynamic range. Recent experiments have shown that in specific cases, there is no significant difference in the ability of AHE and linear intensity windowing to display gray-scale contrast. More recently, a variant of AHE which limits the allowed contrast enhancement of the image has been proposed. This contrast-limited adaptive histogram equalization (CLAHE) produces images in which the noise content of an image is not excessively enhanced, but in which sufficient contrast is provided for the visualization of structures within the image. Images processed with CLAHE have a more natural appearance and facilitate the comparison of different areas of an image. However, the reduced contrast enhancement of CLAHE may hinder the ability of an observer to detect the presence of some significant gray-scale contrast. In this report, a psychophysical observer experiment was performed to determine if there is a significant difference in the ability of AHE and CLAHE to depict gray-scale contrast. Observers were presented with computed tomography (CT) images of the chest processed with AHE and CLAHE. Subtle artificial lesions were introduced into some images. The observers were asked to rate their confidence regarding the presence of the lesions; this rating-scale data was analyzed using receiver operating characteristic (ROC) curve techniques. These ROC curves were compared for significant differences in the observers' performances. In this report, no difference was found in the abilities of AHE and CLAHE to depict contrast information.

Contrast Media↗
PubMed1989

Rapid MR imaging of renal perfusion: a comparative study of GdDTPA, albumin-(GdDTPA), and magnetite.

MR contrast agents injected intravenously reach the kidney very rapidly. Modification of a gradient recalled echo sequence allowed acquisition of 32 sequential MR images each 3.9 s apart on a 1.5 T clinical imager. This sequence was then used to observe the renal accumulation of contrast agent following an intravenous bolus of 100 microns/kg GdDTPA, 60 microns/kg albumin-(GdDTPA) or 9.6 and 40 mg/kg of 0.7 mu magnetic latex microspheres in rats or rabbits. Serial changes in image intensity were obtained with 3.9 s temporal and 0.08 ml spatial resolution. The renal cortical response to GdDTPA was similar to changes in blood 1/T1, but the medulla showed first a signal enhancement owing to the initial increased T1 relaxation followed by loss of signal as increased concentrations caused T2 relaxation to become predominant. Changes in intensity caused by magnetite and albumin-(GdDTPA) correlated with the 1/T1 changes observed in blood samples consistent with the predominantly intravascular location of these two agents. We conclude that MRI provides high spatial resolution with sufficient temporal resolution to record tissue response to an intravenous bolus of MR contrast agents.

Albumins↗
PubMed1987

Angiotensin II-noradrenergic interactions in renovascular hypertensive rats.

This study tested the hypothesis that interactions of endogenous angiotensin II (AII) with the noradrenergic neuroeffector junction are important in renin-dependent hypertension. In the in situ blood-perfused rat mesentery, in normal rats exogenous AII potentiated mesenteric vascular responses to periarterial (sympathetic) nerve stimulation (PNS) more than vascular responses to exogenous norepinephrine (NE). In 2-kidney-1-clip (2K-1C) rats with renovascular hypertension mesenteric vascular responses to PNS and NE were greater than in sham-operated rats, and renovascular hypertension mimicked the effects of exogenous AII with respect to enhancing responses to PNS more than responses to NE. In 2K-1C rats, but not in sham-operated rats, 1-Sar-8-Ile-AII markedly suppressed vascular responses to PNS, without influencing responses to NE. Finally, 1-Sar-8-Ile-AII attenuated sympathetic nerve stimulation-induced neuronal spillover of NE in 2K-1C rats, but not in sham-operated rats. These data indicate that renovascular hypertension enhances noradrenergic neurotransmission, and that this enhancement is mediated in part by AII-induced facilitation of NE release.

Angiotensin I↗
PubMed1984

Adaptive grey level assignment in CT scan display.

The normal method of assigning grey levels to computed tomographic (CT) numbers in CT scan display involves interactive selection of an intensity window. This method often results in the inability to visualize different types of tissue in a single image and sometimes results in unnecessary loss of contrast sensitivity. A method is described that solves these problems by automatically adapting the assignment of displayable grey levels to CT numbers in a way that varies smoothly across the image according to local needs for the presentation of contrast. The adaptation is based on local histogram equalization implemented using interpolation so as to operate on a minicomputer in a few tens of seconds. This contrast enhancement is followed by a mapping that causes the viewer's perceptual response to be linear across the display scale.

Data Display↗
PubMed1983

Prostaglandin biosynthesis does not participate in hypercapnia-induced cerebral vasodilatation in the dog.

The participation of cerebral prostaglandin biosynthesis in hypercapnia-induced cerebral vasodilation was assessed in pentobarbital-anesthetized dogs using the radioactive microsphere technique. In five dogs, administration of 5% CO2 increased pCO2 from 31.0 +/- 0.8 to 53.4 +/- 2.4 mm Hg (P less than .001) and decreased total cerebral vascular resistance from 11.2 +/- 3.0 to 2.6 +/- 0.6 mm Hg . min . 100 g . ml-1 (P less than .001). The observed increases in pCO2 and the decreases in cerebral vascular resistance during 5% CO2 inhalation were unchanged 1 hr after administration of an i.v. bolus of 0.1 M Na2CO3 (vehicle). In another group of five dogs, 5% CO2 increased pCO2 from 30.4 +/- 0.58 to 55.2 +/- 4.2 mm Hg (P less than .01) and decreased total cerebral vascular resistance from 5.7 +/- 0.6 to 1.8 +/- 0.4 mm Hg . min . 100g . ml-1 (P less than .001). In these dogs, the CO2-induced decrease in cerebral vascular resistance 1 hr after a bolus dose of indomethacin (10 mg/kg i.v.) dissolved in 0.1 M Na2CO3 was also unchanged. In both groups of dogs the patterns described for total cerebral vascular resistance were also observed in the cerebrum, cerebellum and brainstem. The dose of indomethacin used in this study abolished the vasodepressor responses to i.v. arachidonic acid and suppressed the total brain secretion rate of immunoreactive 6-keto-prostaglandin F1 alpha. Furthermore, the administration of 5% CO2 did not increase the total brain secretion rate of immunoreactive 6-keto-prostaglandin F1 alpha. We conclude that cerebral prostaglandin biosynthesis does not mediate or modulate hypercapnia-induced cerebral vasodilation in the dog.

Animals↗
PubMed1982

Effects of indomethacin on beta adrenoreceptor-stimulated renin release in the dog.

The hypothesis that prostaglandins participate in beta adrenoreceptor-stimulated renin release was tested by examining the effects of prostaglandin synthesis inhibition on renal nerve stimulation (0.5-5.0 Hz)-induced renin release. In phentolamine (5 micrograms/kg/min, intrarenal artery)-treated dogs (n = 6), renal nerve stimulation produced a frequency-related increase in renal renin secretion rate, without altering renal blood flow. In phentolamine plus propranolol (0.3 mg/kg i.v. bolus + 5 micrograms/kg/min infusion)-treated dogs (n = 6), renal nerve stimulation-induced renin release was inhibited by 86% (P less than .03), 75% (P less than .03) and 73% (P less than .02) at 1, 2 and 5 Hz, respectively. In contrast to propranolol, blockade of prostaglandin synthesis with indomethacin (8 mg/kg i.v. bolus) failed to alter the renin secretory response to renal nerve stimulation in phentolamine-treated animals. These results indicate that, in a situation of intrarenal alpha adrenoreceptor blockade, renal nerve stimulation induces renin secretion by a beta adrenoreceptor mechanism that is independent of prostaglandin biosynthesis.

Animals↗
PubMed1981

6-Keto-prostaglandin E1 is more potent than prostaglandin I2 as a renal vasodilator and renin secretagogue.

Several studies indicate that prostaglandin (PG) I2 is involved in the control of renin release. This investigation was performed to determine if the active possible metabolite of PGI2, 6-keto-PGE1, is also a renin secretagogue. The relative potencies of PGI2, 6-keto-PGE1 and 6-keto-PGF1 alpha on renin secretion rate (RSR) and renal blood flow (RBF) were assessed in nonfiltering, beta adrenoreceptor blocked kidneys of seven anesthetized dogs. Intrarenal infusions of both PGI2 and 6-keto-PGE1 significantly augmented RSR in a dose-related fashion. However, 6-keto-PGE1 was approximately 5 times more potent than PGI2, producing significantly greater increases in RSR at doses from 3 X 10(-9) to 3 X 10(-8 g/kg/min (P < .03). At low infusion rates (less than 3 X 10(-8) g/kg/min), 6-keto-PGE1 enhanced RBF to a greater extent than PGI2. However, with infusion rates of 3 X 10(-8) g/kg/min, these eicosanoides enhanced RBF to an equal extent. Thus, in comparison to PGI2, 6-keto-PGF1 induced a greater increase in RSR for equivalent increases in RBF. 6-keto-PGF 1 alpha had no effect on either RSR or RBF at any of the doses infused. We conclude that, in the canine kidney, 6-keto-PGE1 is more potent than PGI2 in stimulating the juxtaglomerular cells to secrete renin.

Alprostadil↗
PubMedDate not supplied

Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake.

Advances in measurement techniques have enabled the extracellular concentration of dopamine to be monitored inside striatal structures during transient electrical stimulation of the medial forebrain bundle. The observed concentration changes can be accounted for by a mathematical model as a function of the frequency employed and the stimulus duration. Overflow curves can be described by 3 kinetic parameters: the concentration of dopamine released per stimulus pulse, and the Km and Vmax of uptake. In terms of this model, the kinetics of overflow during stimulation is found to be identical in the nucleus accumbens and caudate nucleus with the exception that the Vmax for uptake is lower in the former region. Maximal uptake is also found to be lower in animals with partial lesions of dopamine neurons. Measured concentrations vary with stimulation frequency from 10 to 60 Hz in a manner that can be predicted by the model. Competitive uptake inhibitors have their primary effect on overflow in the limit of low stimulus frequencies. In contrast, D2 antagonists, which increase the concentration of dopamine released per stimulus pulse, have a moderate effect in low and high frequency ranges, but cause a significant maximal increase in extracellular dopamine concentrations at a mid-range frequency. Both calculated response and experimental findings indicate that in the caudate nucleus, the upper frequency for observable uptake inhibition and the characteristic maximum frequency for the receptor-mediated response occur at higher values than in the nucleus accumbens. The model appears to be useful for predicting dopamine extracellular concentrations over a wide range of conditions, and its predictions may be valid when extended to more physiological situations.

Animals↗