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Biomedical subjects

M A Bernstein

Publications and source records attributed to M A Bernstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

mu-Opioid receptor down-regulation and cAMP-dependent protein kinase phosphorylation in a mouse model of chronic morphine tolerance.

Results of radioligand binding and transfected receptor studies indicate that mu-receptor down-regulation and phosphorylation may be critical to the expression of morphine tolerance. In this study, an animal model of morphine tolerance was used to correlate antinociception with changes in receptor number and phosphorylation state. mu-Opioid receptor protein was quantitated by Western immunoassay of brainstem tissue from morphine-treated mice. Degree of receptor phosphorylation was assessed using immunoprecipitation (IP) of the receptor followed by back-phosphorylation. Acutely administered morphine produced no changes in mu-receptor quantity. Chronic morphine administration resulted in a 50% reduction in receptor protein quantity over placebo-treated samples. Back-phosphorylation experiments showed a drop in cAMP-dependent protein kinase A (PKA)-induced receptor phosphorylation shortly after acute morphine administration, followed by a naloxone-reversible increase in phosphorylation of the receptor that correlated with the onset of antinociception. Chronic morphine administration resulted in a decrease in PKA-induced phosphorylation of the mu-receptor. Since it has been shown that PKA activity is enhanced in the brains of morphine-tolerant mice, this decrease in mu-receptor phosphorylation suggests that the mu-receptor may be structurally or conformationally altered in the morphine-tolerant state.

Animals↗
PubMed1997

Effects of spinal versus supraspinal administration of cyclic nucleotide-dependent protein kinase inhibitors on morphine tolerance in mice.

The consequences of becoming tolerant to the analgesic effects of morphine include increased risk of unwanted side effects, such as respiratory depression, because the patient is required to take larger doses of the opioid to get the same relief from pain. Many studies suggest that phosphorylation plays a role in the neuroplasticity associated with opioid tolerance. This study examines the effect of inhibiting cyclic nucleotide-dependent protein kinase activity in the brain or spinal cord of morphine-tolerant mice. KT5720, a cyclic adenosine monophosphate (cAMP)-dependent protein kinase inhibitor, or KT5823, a cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor, was centrally administered in morphine-tolerant and placebo-treated mice prior to a systemically administered challenge dose of morphine. KT5720 completely reversed morphine tolerance in the tail-flick assay when the pretreatment was administered intracerebroventricularly (i.c.v.); KT5823 had no effect on morphine via this route. When either of these drugs was administered intrathecally (i.t.), the activity of morphine was greatly diminished in the tolerant animals, with no effect on morphine antinociception in the placebo group. These data suggest that cAMP-dependent protein kinase activity may be upregulated in the brain with morphine tolerance, and that this upregulation is critical to the expression of tolerance to the antinociceptive effects of morphine. In the spinal cord, however, the activity of cyclic nucleotide dependent protein kinases, and possibly their substrate proteins, may be affected by chronic morphine exposure such that inhibition of these kinases produces hyperalgesia.

Alkaloids↗
PubMed1997

Flow quantification using fast cine phase-contrast MR imaging, conventional cine phase-contrast MR imaging, and Doppler sonography: in vitro and in vivo validation.

OBJECTIVE: Our purpose was to assess the accuracy of measurements of flow velocity and volume flow rate in an in vitro phantom and in healthy human volunteers using a cardiac-gated, segmented K-space, fast cine phase-contrast (PC) MR imaging technique with view sharing (fast PC). We compared this method with conventional cine PC MR imaging and Doppler sonography. SUBJECTS AND METHODS: Pulsatile flow was generated in a flow phantom that consisted of a cylindric tube having various degrees of tapered stenosis. Phase-encoded velocity maps were obtained using cine PC and fast PC MR imaging. Doppler sonography was also performed. Measurements of aortic and pulmonary artery peak systolic and minimum diastolic velocity and volume flow rate were then compared in eight healthy volunteers using the three imaging techniques. RESULTS: We found excellent agreement between fast PC and cine PC measurements of peak systolic velocity when regions of interest were drawn to exclude vessel margins (r > .99 for phantom studies, and r = .80 for human studies). Correlation between minimum diastolic velocity measurements by MR imaging was limited by noise that resulted from high encoding velocity settings. However, such correlation improved with signal averaging. When compared with predicted values of volume flow rates, both cine PC (r > .99) and fast PC (r = .97) MR imaging were more accurate than Doppler sonography (r = .78) in vitro. Measurements of cardiac output were adversely affected by low signal to noise, especially during diastole; estimates based on systolic forward flow resulted in better agreement between the two MR imaging methods. CONCLUSION: Fast PC MR flow quantification may prove to be a useful adjunct to routine MR studies for measurements of peak flow velocity. However, estimates of volume flow rate using fast PC MR imaging are limited because of increased noise during low diastolic flow as well as edge artifacts.

Adult↗
PubMed1996

A quantitative study of ramped radio frequency, magnetization transfer, and slab thickness in three-dimensional time-of-flight magnetic resonance angiography in a patient population.

RATIONALE AND OBJECTIVES: The authors compare the effectiveness of various magnetic resonance (MR) angiography acquisition strategies in enhancing the visibility of small intracranial vessels. METHODS: Blood vessel contrast-to-noise ratio (CNR) in time-of-flight MR angiography was studied as a function of vessel size and several selectable imaging parameters. Contrast-to-noise measurements were made on 257 vessel segments ranging in size from 0.3 mm to 4.2 mm in patients who recently had undergone intraarterial cerebral angiography. Imaging parameters studied included magnetization transfer, spatially variable radio frequency (RF) pulse profile (ramped RF), and imaging slab thickness. RESULTS: The combination of thin slabs (16 slices/slab), ramped RF, and magnetization transfer resulted in the highest CNR for all but the smallest vessel sizes. The smallest vessels (< 0.5 mm) had the highest CNR, using the thick slab (64 slices/slab) with ramped RF and magnetization transfer. Magnetization transfer always improved vessel CNR, but the improvement diminished as the slab thickness was reduced. The CNR increased with a decrease in slab thickness for all but the smallest vessel sizes. CONCLUSIONS: Overall, the results provide a quantitative demonstration that inflow enhancement of blood is reduced for small vessels. Thus, whereas magnetization transfer is important at all vessel sizes, it becomes the primary factor in improving the visibility of the smallest vessels.

Adult↗
PubMed1996

Coronary flow reserve: noninvasive measurement in humans with breath-hold velocity-encoded cine MR imaging.

PURPOSE: To measure coronary vasodilator reserve with breath-hold velocity-encoded cine magnetic resonance (MR) imaging. MATERIALS AND METHODS: Eight healthy adult volunteers underwent 1.5-T MR imaging. Velocity-encoded cine images were acquired at seven to 13 temporal phases in 25 seconds, with k-space segmentation and view-sharing reconstruction (+/- 1 m/sec velocity-encoding value) (repetition time msec/echo time msec = 16/9). Flow velocity in the left anterior descending (LAD) artery was measured twice before and twice after administration of dipyridamole (0.56 mg per kilogram of body weight). RESULTS: Peak diastolic coronary flow velocity in the LAD artery was 14.8 cm/sec +/- 1.9 (mean +/- standard deviation) in the baseline state. It increased significantly (P< .01) to 46.3 cm/sec +/- 10.2 after dipyridamole administration, with an average coronary reserve of 3.14 +/- 0.59. Interstudy and interobserver reproducibilities for measurement of peak diastolic velocity were, respectively, 9.5% +/- 1.6 and 7.0% +/- .2.5 in the baseline state and 6.8% +/- 2.2 and 3.4% +/- 1.5 after dipyridamole administration. CONCLUSION: Breath-hold velocity-encoded cine MR imaging provided reproducible assessment of coronary flow reserve in humans.

Adult↗
PubMed1996

Is complete laparoscopic colectomy superior to laparoscopic assisted colectomy?

Much debate has centered around what constitutes a true laparoscopic colon resection. Purists argue that intracorporeal division of the mesentery and anastomosis confer a benefit over a "laparoscopic assisted" procedure. The aim of this study was to further examine this issue. Data were prospectively collected on 102 consecutive laparoscopic colon resections. Five procedures were converted to open cases and were excluded from analysis. Procedures were divided into two groups. Group 1 (n = 34) consisted of complete laparoscopic procedures (no abdominal incision was made): abdominoperineal resection (3), Hartmann's reversal (3), end colostomy (7), low anterior resection (5), proctectomy (1), sigmoid colectomy (15). Group 2 (n = 63) consisted of laparoscopic "assisted" procedures (i.e., an incision was made to facilitate anastomosis, division of the mesentery, and/or specimen retrieval): Ileocolic resection (6), restorative proctocolectomy (26), right colectomy (19), subtotal colectomy/end ileostomy (5), subtotal colectomy/ileorectal anastomosis (7). Length of hospitalization and duration of postoperative ileus were compared. A subset analysis of right colectomy (intracorporeal mobilization and extracorporeal division of the mesentery and anastomosis) versus sigmoid colectomy (intracorporeal mobilization, division of the mesentery and anastomosis) was also performed. There were no statistically significant differences in length of hospital stay (Group 1, 7.47 +/- 2.75 days; Group 2, 7.78 +/- 5.55 days) or duration of postoperative ileus (Group 1, 3.24 +/- 1.56 days; Group 2, 3.68 +/- 1.58 days). Similarly, in the sigmoid colectomy versus right colectomy subset analysis, there were no statistically significant differences in length of hospital stay (sigmoid colectomy, 7.92 +/- 2.90 days; right colectomy, 6.40 +/- 1.50 days) or duration of postoperative ileus (sigmoid colectomy, 3.36 +/- 1.39 days; right colectomy, 3.18 +/- 1.07 days). Our data demonstrate that intracorporeal division of the mesentery and anastomosis confer no advantage over the laparoscopic assisted procedures. Data were prospectively collected on 102 consecutive laparoscopic colon resections. There were no statistically significant differences in length of hospital stay or duration of postoperative ileus regardless of whether intracorporeal or extracorporeal mesenteric division and anastomosis were undertaken. These data demonstrate that a completely laparoscopic procedure does not appear to offer any advantage as compared to a laparoscopic assisted one.

Abdomen↗
PubMed1995

Alterations in L-type calcium channels in the brain and spinal cord of acutely treated and morphine-tolerant mice.

Opiate tolerance has been associated with changes in neuronal intracellular calcium levels. In vivo studies have indicated the involvement of dihydropyridine (DHP)-sensitive ('L-type') voltage-gated calcium channels in the morphine-tolerant state. In this study, we assessed how the morphine-tolerant state would affect the antinociception produced by intrathecal administration of two agents (Bay K 8644 and thapsigargin) that increase intracellular calcium. Morphine-tolerant mice displayed a 7-fold greater ED50 for Bay K 8644 antinociception than placebo-treated animals; no difference was found in the dose-response curve for thapsigargin. To further explore the role of the L-type channel in morphine tolerance development, we performed radiolabeled nitrendipine binding studies in the spinal cord and brain regions associated with pain modulation from acutely treated, tolerant, and control mice. Our treatment protocol produced a 4-fold shift in the ED50 for s.c. morphine antinociception, as determined by the tail-flick procedure. Binding site number and affinity were determined using Scatchard analysis for the following timepoints: 20 min and 60 min after s.c. injection of morphine or vehicle, as well as after 4 days of chronic administration, and after naloxone-precipitated withdrawal. Although some changes were observed in the affinity of nitrendipine for its receptor, a significant change in these measures was found only following naloxone administration, which produced increases in Bmax in both placebo- and morphine-treated mice.

Analgesics, Opioid↗
PubMed1995

Improved ejection fraction and flow velocity estimates with use of view sharing and uniform repetition time excitation with fast cardiac techniques.

PURPOSE: To improve the accuracy of ventricular volume estimates and effective temporal resolution in fast cardiac acquisitions. MATERIALS AND METHODS: Data sets at intermediate temporal phases were generated by means of sharing of views from two temporally adjacent data sets. A simulated model was used, and studies with patients and volunteers were conducted. View sharing was implemented in both fast gradient-echo and fast phase-contrast cine acquisitions; breath holding was used when possible. RESULTS: Uniform repetition time (TR) radio-frequency (RF) excitation allowed a better assessment of the end-diastolic ventricular volume. In addition, view sharing provided a better estimate of end-systolic ventricular volume in cases in which rapid changes in volume occurred at or about the temporal boundary of the source images. View sharing also provided a much smoother representation of dynamic cardiac motion when viewed in a cine loop. CONCLUSION: View sharing and uniform TR RF excitation improve the accuracy of end-systolic and end-diastolic ventricular volume measurements by improving the effective temporal resolution.

Adult↗
PubMed1994

Reconstructions of phase contrast, phased array multicoil data.

We present a reconstruction method for phased array multicoil data that is compatible with phase contrast MR angiography. The proposed algorithm can produce either complex difference or phase difference angiograms. Directional flow and quantitative information are preserved with the phase difference reconstruction. The proposed method is computationally efficient and avoids intercoil cancellation errors near the velocity aliasing boundary. Feasibility of the method is demonstrated on human scans.

Algorithms↗
PubMed1993

NMR structural studies of the tight complex between a trifluoromethyl ketone inhibitor and the 85-kDa human phospholipase A2.

Arachidonyl trifluoromethyl ketone (AACOCF3) is a slow- and tight-binding inhibitor of the human cytosolic phospholipase A2 (cPLA2) [Street et al. (1993) Biochemistry 32, 5935]. 19F and 13C NMR experiments have been carried out to elucidate the structure of the cPLA2.AACOCF3 complex. One mole of AACOCF3 per mole of enzyme is tightly bound in the active site while excess molar equivalents of the inhibitor associate loosely and nonspecifically with hydrophobic regions of the protein. Incubation of the cPLA2.AACOCF3 complex with a 10-fold molar excess of a structurally related inhibitor allows the slow dissociation of the enzyme-inhibitor complex to be followed with 19F NMR. These results establish that the bound inhibitor is in slow exchange with the free ligand and that inhibition of the cPLA2 by AACOCF3 is not due to irreversible modification of the protein. AACOCF3 labeled with 13C at the carbonyl position was used to determine the nature of the bound inhibitor species. A comparison of the 13C NMR chemical shift value obtained from labeled enzyme-inhibitor complex (delta c 101.0 ppm) with the chemical shift values obtained from model compounds suggests that the enzyme-bound inhibitor species is a charged hemiketal. These results are very similar to those obtained previously with alpha-chymotrypsin and a peptidyl trifluoromethyl ketone inhibitor [Liang, T.-C., & Abeles, R. H. (1987) Biochemistry 26, 7603] and, by analogy with the serine proteases, a structural model for the cPLA2.AACOCF3 complex is proposed.

Arachidonic Acids↗
PubMed1993

Colon and rectal cancer in pregnancy.

Colorectal carcinoma presenting in pregnancy is an uncommon disease that is reported to be associated with an extremely poor prognosis. To better characterize this disease, we surveyed the membership of the American Society of Colon and Rectal Surgeons by mailed questionnaire and reviewed the literature. Forty-one new cases of women with large bowel cancer who presented during pregnancy or the immediate postpartum period were identified. The mean age at presentation was 31 years (range, 16-41 years). Tumor distribution was as follows: right colon-3, transverse colon-2, left colon-2, sigmoid colon-8, and rectum-26. Dukes stage at presentation was A = 0, B = 16, C = 17, and D = 6 (two patients were unstaged). Average follow-up was 41 months. Stage for stage, survival was found to be similar to patients with colorectal tumors in the general population. Large bowel cancer coexistent with pregnancy presents in a distal distribution (64 percent of tumors in the current series and 86 percent of those reported in the literature were located in the rectum) and presents at an advanced stage (60 percent were Stage C or more advanced at the time of diagnosis). While patient survival is poor, it is no different stage for stage from the general population with colorectal tumors.

Adolescent↗
PubMed1993

Developing community-based program alternatives for the seriously and persistently mentally ill elderly.

The deinstitutionalization movement in the United States has traditionally neglected the rehabilitation potential of the seriously mentally ill elderly. With the proliferation of the elderly population, unique programs and community-based settings must be created and expanded to meet the mental health needs of this population in a cost-effective and humane manner. The mental health continuum presented is a model composed of programs that target the seriously mentally ill elderly in a variety of community placements including residential treatment facilities, nursing homes, retirement homes, and permanent housing.

Aged↗
PubMed1992

A data adaptive reprojection technique for MR angiography.

Inability to detect vessel overlap and vascular loops can compromise the interpretation of magnetic resonance angiograms. A data-adaptive ray tracing (DART) technique was developed to produce the appropriate variations in signal intensity at points of vessel overlap in order to simulate the standard angiographic representation of vessels. In this technique a threshold is utilized to identify vessels in the image slices composing a 3D angiographic data set. A mask, which defines regions slightly larger than the vessel boundaries, is obtained by blurring the vessel information surviving the initial threshold. This mask is converted to binary form prior to multiplication by the original angiographic data set. Following application of an additional threshold to the masked data, line integrals through the regions defined by the mask are performed to obtain an angiographic signal proportional to the integrated vessel signal as in conventional angiography. This integrated reprojection is then uniquely combined with a maximum intensity pixel (MIP) reprojection to produce the final DART image. The application of the DART technique to 2D time-of-flight and 3D phase-contrast angiograms successfully enabled the identification of over-lapping vessels and vascular loops. DART was also found to produce less vessel narrowing than the MIP technique.

Algorithms↗
PubMed1989

A method for correctly setting the rf flip angle.

Currently the accepted method for setting the correct rf power levels to achieve 90 degrees and 180 degrees rf pulses for MR imaging is to peak the echo amplitude of a rf spin-echo sequence. The echo amplitude of this alpha-2 alpha pulse sequence is proportional to sin3 (alpha) and has a relatively broad maximum. Recently another method for setting the rf flip angle by maximizing the ratio of the stimulated echo to the primary echo amplitudes (in a 3 alpha sequence) demonstrated accuracy similar to that of the spin-echo method using a shorter repetition time. We present a new, more sensitive, and more accurate method for setting the correct rf power levels for 90 degrees and 180 degrees rf pulses. In this method, based upon the stimulated echo pulse sequence, we are able to accurately set the rf power to within +/- 0.1 dB by minimizing the signal amplitude of the third spin echo. This null method works for both selective and nonselective rf pulses of flip angle 90 degrees or 180 degrees, allowing the user to accurately adjust the relative amplitudes of the four rf pulse types within a single pulse sequence.

Calibration↗
PubMed1989

Multiple short-echo (2.5-ms) quantitation of in vivo sodium T2 relaxation.

The MR behavior of the sodium-23 nucleus in vivo is a complex problem which has generated considerable interest over the last 20 years. Early studies on excised tissue samples revealed that the sodium nucleus exhibited a two-component T2 relaxation. This biexponential T2 relaxation was characterized by a short component with a T2 = 0.7-4.8 ms, and a long component with a T2 = 7.0-26.0 ms. We have developed a 3D pulse sequence capable of performing multiple Hahn echo in vivo sodium-23 imaging at echo times as short as 2.5 ms. This sequence obtains the shorter spin echo times by presaturating the spins outside of the desired imaging region, allowing the use of nonselective rf pulses. Using this sequence we have been able to quantify the long and short T2 components of normal brain tissue, vitreous humor of the eye, and a rabbit VX-2 carcinoma. We found that gray matter and white matter of normal brain have a monoexponential T2 relaxation with T2 = 17.6 +/- 2.4 ms. The vitreous humor T2 relaxation is also monoexponential with T2 = 56.8 +/- 2.1 ms. However, we find that some of the rabbit VX2 carcinomas exhibit a biexponential T2 decay with a short component of 3.3 +/- 4.6 ms and a long component of 22.0 +/- 9.0 ms.

Absorption↗
PubMed1988

Acute recurrent appendicitis with appendicolith.

Appendiceal disease can be acute, acute recurrent, or chronic. Acute appendicitis is the most common form. Acute recurrent appendicitis is more common than chronic appendicitis. In children the clinical manifestations of appendicitis are variable. Patients who have an appendicolith usually develop appendicitis, often with perforation. A case is presented of 3-year follow-up of a patient with an appendicolith and acute recurrent appendicitis. The literature about appendicoliths is reviewed. In the appropriate clinical setting, a history of prior episodes of similar right lower quadrant pain does not preclude the diagnosis of appendiceal disease. Awareness of the less common forms of appendicitis is important so that appropriate treatment is not delayed.

Appendectomy↗