Biomedical subjects

J Friedman

Publications and source records attributed to J Friedman.

At least 109 records · Page 6Linked to original sources

PubMed1994

Gated technetium-99m sestamibi for simultaneous assessment of stress myocardial perfusion, postexercise regional ventricular function and myocardial viability. Correlation with echocardiography and rest thallium-201 scintigraphy.

OBJECTIVES: This study compares technetium-99m sestamibi (sestamibi) electrocardiographic (ECG) gated single-photon emission computed tomography (gated SPECT) and echocardiography for the evaluation of myocardial function and assesses the feasibility of single-injection, single-acquisition stress perfusion/rest function technetium-99m sestamibi-gated SPECT as an alternative to conventional stress/rest imaging for assessment of myocardial perfusion and viability. BACKGROUND: Simultaneous assessment of stress perfusion and rest function is possible with gated SPECT acquisition of stress-injected technetium-99m sestamibi. METHODS: Rest thallium-201 SPECT followed by stress sestamibi-gated SPECT (acquired 0.5 to 1 h after sestamibi injection) was performed in 58 patients. Echocardiography was performed immediately after or before gated SPECT in 43 of the patients. All studies were analyzed by semiquantitative visual scoring. Sestamibi-gated SPECT studies were read for stress perfusion and rest wall motion and thickening. Reversibility on sestamibi-gated SPECT was defined as the presence of a definite stress defect with normal or mildly impaired wall motion or thickening on gated SPECT: RESULTS: There was high segmental score agreement between gated SPECT and echocardiography for wall motion (91%, kappa = 0.68, p < 0.001) and thickening (90%, kappa = 0.62, p < 0.001). Correlation for global wall motion (r = 0.98, p < 0.001) and thickening (r = 0.96, p < 0.001) scores between the two modalities was excellent. In 32 patients without previous myocardial infarction, there was excellent agreement for reversibility between stress sestamibi-gated SPECT and rest thallium-201/stress sestamibi (98%, kappa = 0.93, p < 0.01). However, in 26 patients with previous infarction, discordance between the two approaches was frequent, with 26% (20 of 78) of nonreversible defects by stress sestamibi-gated SPECT being reversible by rest thallium-201/stress sestamibi and 21% (23 of 112) of reversible defects by stress sestamibi-gated SPECT being nonreversible by rest thallium-201/stress sestamibi. CONCLUSIONS: Gated SPECT of stress-injected sestamibi correlates well with echocardiographic assessment of regional function and thus adds information to perfusion SPECT: In patients without previous myocardial infarction, a single-injection stress perfusion/rest function approach using sestamibi-gated SPECT can substitute for conventional stress/rest myocardial perfusion imaging, adding a rest perfusion study only if there are nonreversible defects or consideration of attenuation artifacts. In patients with previous myocardial infarction, the gated SPECT approach does not replace the need for a rest perfusion study.

Aged↗

PubMed1994

Low dose estrogen replacement therapy in early postmenopausal women effect on urinary magnesium and calcium: creatinine ratios.

The purpose of this study was to investigate whether treatment for prevention of osteoporosis by means of postmenopausal hormone replacement therapy (HRP) and daily exercise, had any effect on ratios of urinary calcium:creatinine (Ca:Cre) and magnesium:creatinine (Mg:Cre). A group of 33 early postmenopausal women (menopause onset 12-18 months previously), mean age 49.12 years, were treated during 6 months with low doses of transdermal estrogen (Estraderm TTS 25 micrograms, Ciba-Geigy) opposed by oral progestogen (Duphaston 10 mg, 10 days every month), and daily exercise (walking for 1 hour). Despite HRT's statistically significant lowering effect on Ca:Cre and Mg:Cre ratios, these returned to pretreatment levels 6 months after withdrawal from HRT. The mechanism by which HRT affects magnesiuria and calciuria is discussed.

Administration, Cutaneous↗

PubMed1994

Idiopathic fibrosing pancreatitis causing obstructive jaundice in young adults: two case reports and literature review.

Chronic pancreatitis is uncommon in children and adolescents. A rare syndrome of idiopathic fibrosing pancreatitis has been reported in 28 patients, ages 4 months to 17 yr. We report two young adults with this syndrome who presented with obstructive jaundice. Both were seen in adult gastroenterology practice, and one is the oldest reported patient at age 20. We review the clinical features, diagnosis, and treatment of this disorder, which merits attention by adult gastroenterologists.

Adolescent↗

PubMed1994

Comparative feasibility of separate or simultaneous rest thallium-201/stress technetium-99m-sestamibi dual-isotope myocardial perfusion SPECT.

UNLABELLED: Separate or simultaneous rest 201Tl/stress 99mTc-sestamibi dual-isotope SPECT are potentially efficient myocardial perfusion imaging protocols which combine the use of a high-resolution 99mTc tracer for stress perfusion assessment and 201Tl, the current single-photon agent of choice, for viability assessment. METHODS: To investigate the feasibility of dual-isotope myocardial perfusion SPECT protocols using rest 201Tl and stress sestamibi, 201Tl crosstalk into the 99mTc acquisition window (Group 1, n = 26 patients) and 99mTc crosstalk into 201Tl windows (Group 2, n = 25) were studied. For Group 1, treadmill exercise with sestamibi injection and poststress SPECT ("virgin" sestamibi images) were performed, followed by rest 201Tl injection and SPECT acquisition using dual-isotope windows (contaminated or "dual" images). For Group 2, the order was reversed: rest 201Tl SPECT (virgin 201Tl images) was performed first, followed by exercise sestamibi injection and dual-isotope SPECT. RESULTS: The contribution of 201Tl scatter to the dual sestamibi images (Group 1) was measured to be 2.9% +/- 2.1%, while 99mTc crosstalk contributed 26.7% +/- 13.0% to the dual 201Tl images (Group 2). Image quality was considered good to excellent in 92% of the sestamibi (virgin and dual) images and 88% of the virgin 201Tl SPECT, but only in 23% of the dual 201Tl studies. CONCLUSIONS: Technetium-99m crosstalk into 201Tl windows is substantial; therefore, simultaneous dual-isotope protocols, which involve assessment of 201Tl images contaminated by 99mTc, are not recommended. On the other hand, because of the small amount of 201Tl crosstalk into the 99mTc window, a separate acquisition dual-isotope approach employing the rest 201Tl (virgin)/stress sestamibi sequence is acceptable.

Aged↗

PubMed1994

Multicenter trial validation for quantitative analysis of same-day rest-stress technetium-99m-sestamibi myocardial tomograms.

UNLABELLED: The accuracy of an automated quantitative analysis of same-day rest/stress 99mTc sestamibi SPECT images for detection and localization of coronary artery disease (CAD) was assessed in a multicenter trial consisting of 161 patients from 7 different clinical sites utilizing various camera computer systems. METHODS: Of the 161 patients, 102 had angiographically documented coronary artery disease, 22 had normal coronary arteriograms, and 37 had a low (< 5%) likelihood of coronary artery disease based on their age, sex, symptoms and the results of their exercise electrocardiograms. The patients were studied using previously optimized image acquisition and processing protocols. An additional population consisting of 45 patients with single-vessel disease were evaluated to determine the optimal criteria for detection of CAD. RESULTS: The quantitative analysis method was associated with an overall sensitivity of 87%, specificity of 36%, and normalcy rate (true negative rate in the low likelihood patients) of 81%. Sensitivity for overall detection of disease was similar (90%) in patients with and without myocardial infarction (90% versus 89%). The sensitivities and specificities for identification of disease in individual coronary arteries were, respectively, 69% and 76% for LAD, 70% and 80% for LCX, and 77% and 85% for RCA. CONCLUSION: The results of this study demonstrate that the new objective quantitative method for analysis of same-day rest/stress 99mTc sestamibi SPECT images is accurate for detection and localization of CAD and correlates highly with expert visual interpretation.

Adolescent↗

PubMed1994

An analysis of the expression of cyclophilin C reveals tissue restriction and an intriguing pattern in the mouse kidney.

Cyclophilin C (cyp C) is a cyclosporin A (CsA) binding protein originally isolated from a mouse bone marrow stromal cell line. We have compared the expression patterns of the mammalian cyclophilins A, B, and C in mouse tissues using in situ hybridization. These studies reveal that cyp C is expressed in a restricted subset of tissues including mouse ovary, testis, bone marrow, and kidney. Within the kidney, cyp C is highly expressed in a narrow zone in the outer medulla. Using monoclonal antibodies reactive against cyp C, we find that the kidney cells expressing cyp C correspond to the S3 segment of the nephron. The S3 segment has been shown to sustain histopathological damage from high dosages of CsA, raising the possibility that cyp C may be involved in mediating this damage.

Amino Acid Isomerases↗

PubMed1993

Crystal structure of murine cyclophilin C complexed with immunosuppressive drug cyclosporin A.

Cyclophilin is a cellular receptor for the immunosuppressive drug cyclosporin A (CsA). Cyclophilin C (CyPC) is highly expressed in murine kidney, making it a potential mediator of the nephrotoxic effects of CsA. The structure of murine CyPC complexed with CsA has been solved and refined to an R factor of 0.197 at a 1.64-A resolution. Superposition of the CyPC-CsA structure with the unligated cyclophilin A (CyPA) revealed significant migration of three loops: Gln-179 to Thr-189, Asp-47 to Lys-49, and Met-170 to Ile-176. The proximity of the loop Gln-179 to Thr-189 to the CsA binding site may account for the unique binding of a 77-kDa glycoprotein, CyPC binding protein (CyCAP), to CyPC. The binding of CsA to CyPC is similar to that of CsA to human T-cell cyclophilin A (CyPA). However, the conformation of CsA when bound to CyPC is significantly different from that when bound to CyPA. These differences may reflect conformational variation of CsA when bound to different proteins. Alternatively, the previous CyPA-CsA structure at low resolution may not provide sufficient details for a comparison with the CyPC-CsA structure.

Amino Acid Isomerases↗

PubMed1993

Technetium-99m teboroxime regional myocardial washout in subjects with and without coronary artery disease.

The aim of this study was to test the hypothesis that regional myocardial washout of technetium-99m teboroxime is slowed in the presence of coronary stenosis. Washout was assessed in 33 catheterized patients and in 13 with a low likelihood of coronary artery disease, using a triple detector camera and dynamic single-photon emission computed tomography, with serial 1-minute acquisitions after injection of 20 to 25 mCi of teboroxime at the third minute of adenosine-induced hyperemia. Washout was measured as the percent change in counts between the first, second and third minutes after injection, as measured in 6 short-axis myocardial regions of interest. Myocardial regions were classified as ischemic (> or = 50% diameter stenosis and no prior myocardial infarct), infarcted, normal (no significant coronary stenosis) or "low likelihood" (from the 13 patients with a low likelihood of coronary artery disease). Teboroxime washout was significantly (p < 0.001) slowed in the ischemic myocardium (12.7 +/- 8.3%) compared with the normal (18.5 +/- 5.7%), low-likelihood (17.8 +/- 6.1%) and infarcted (17.8 +/- 4.4%) zones. There was regional variability in washout rates (% washout/min), with the anterior wall having the lowest (13.8 +/- 3.4%/min) and the inferior wall the highest (20.7 +/- 7.9%/min) values. In regard to individual coronary territories, 21 of 41 ischemic, noninfarcted territories (51%) had abnormal washout compared with 3 of 43 normal territories (7%) (p = 0.001). In conclusion, regional washout of teboroxime is detectably slowed in ischemic, noninfarcted myocardium. The clinical value of washout analysis in teboroxime single-photon emission computed tomography warrants further investigation.

Cohort Studies↗

PubMed1993

Cloning and characterization of cyclophilin C-associated protein: a candidate natural cellular ligand for cyclophilin C.

We report the protein purification and the cloning and characterization of a cDNA encoding the proteins that bind with high affinity to cyclophilin C (Cyp-C) in the absence of cyclosporin A. Transfection of this cDNA into COS cells directs the production of a glycoprotein of 77 kDa that binds to Cyp-C in the absence, but not the presence, of cyclosporin A. Homology comparisons reveal that this protein and gene, termed CyCAP for Cyp-C-associated protein, possess a cysteine-rich domain (scavenger receptor cysteine-rich domain) found in a variety of cell-surface molecules; the rest of the sequence is apparently specific. This result raises the possibility that Cyp-C serves as a mediator or regulator of an as-yet-unidentified signal or cellular process initiated via the Cyp-C-associated protein.

Amino Acid Isomerases↗

PubMed1993

[Cutaneous larva migrans].

Larva migrans is a rare cutaneous parasitic infestation, whose incidence in Israel has increased over the past few years. This is mainly due to the growing number of Israelis traveling to the Far East and to Central and South America. We present 4 such cases. The treatment of choice for this parasite is thiabendazole, an imidazole with anthelminthic properties.

Adult↗

PubMed1993

Okadaic acid induces both augmentation and inhibition of beta 2-adrenergic stimulation of cAMP accumulation in S49 lymphoma cells.

To address the role of protein phosphatases in regulating hormonal responses in mammalian cells, we investigated the effects of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, on epinephrine and prostaglandin E1 stimulation of cAMP accumulation and adenylyl cyclase in S49 WT and kin- lymphoma cells. Depending on the dose and time of okadaic acid pretreatment of both cell lines, there were two distinguishable effects on cAMP accumulation, an augmentation and an inhibition. The augmentation occurred rapidly (t1/2 < 1 min), was maximal with 3 microM okadaic acid, and was observed with concentrations of okadaic acid as low as 0.3 microM. Prolonged (t1/2 of 5-15 min) pretreatment of cells with okadaic acid caused an inhibition of epinephrine-stimulated cAMP accumulation, which was characterized by a 2-3-fold increase in the EC50 for the response to epinephrine. The EC50 for the okadaic acid-mediated inhibition was similar to that for the augmentation. In assays of adenylyl cyclase in membrane fractions prepared from okadaic acid-pretreated cells the inhibitory, but not the stimulatory, effects of okadaic acid pretreatment were observed. The data demonstrate that protein phosphatases play an important role in regulating adenylyl cyclase and suggest that cAMP-dependent protein kinase is not involved in either of its actions.

Adenylyl Cyclases↗

PubMed1993

Standardized varimax descriptors of event related potentials: basic considerations.

This paper describes a set of proposed standardized quantitative descriptors of event-related potentials, based upon principal component varimax analysis (PCVA). No claim is made that these mathematical descriptors correspond to discrete neurophysiological processes which generate the ERP. However, adoption and prospective evaluation of such a set of precise, standardized descriptors of the quantitative ERP may eventually result in advances like those which resulted from adoption of equally arbitrary standardized descriptors for QEEG. PCVA was performed on data from normal subjects and from groups of patients with a wide variety of psychiatric disorders ("Abnormals"). This yielded two sets of factor waveshapes, Normal and Abnormal, which were closely similar. Reconstruction of the normal and abnormal ERP data with either set of factors yielded almost identical allocation of variance. These results gave acceptable reassurance that factors derived from normal population could reasonably be used to describe ERP waveshapes from patients. The ERPs at each electrode of the 10/20 System in a "training group" of normal subjects were then reconstructed. The resulting distributions of factor scores were transformed to achieve Gaussianity. Mean values and standard deviations were obtained for the normative distribution of each factor score, the root mean square deviation, the residual and the absolute ERP power at each electrode. Individual ERPs could then be reconstructed with the normal factors, and the resulting factor scores rescaled to "probability of abnormal morphology" by Z-transformation. Statistical probability maps could be generated by using a color scale in standard deviation units. These methods were used to evaluate visual and auditory ERPs from an independent normal "test group" and the patients in the Abnormal sample. High specificity and sensitivity were obtained for many factor Z- scores. Multiple discriminant functions were constructed which separated normal from abnormal patients with high, replicable accuracy. Further development and testing of these descriptors may make them clinically useful.

Adolescent↗

PubMed1993

Localization of the angiogenesis inhibitor thrombospondin in human synovial tissues.

Recently, we have shown that a macrophage subpopulation isolated from the synovial tissue of patients with rheumatoid arthritis was potently angiogenic and that a secreted inhibitor of angiogenesis, which is controlled by a tumor suppressor gene in hamster cells, was similar to thrombospondin. In order to investigate the potential role of thrombospondin in human arthritic disorders, we employed immunohistochemistry to examine frozen synovial tissue sections from normal controls (n = 3), patients with rheumatoid arthritis (n = 14) and with osteoarthritis (n = 5). The synovial tissues were stained with monoclonal antibody (mAb) A2.5, which reacts with the heparin-binding domain of thrombospondin, mAb A6.1, which reacts with the epidermal growth factor repeat motif of thrombospondin, and with mAb A4.1, which reacts with the properdin-repeat domain of thrombospondin. In rheumatoid synovial tissues the anti-thrombospondin mAbs reacted with vascular endothelial cells, and to a lesser extent with vascular smooth muscle. Pericytes were stained, particularly with mAb 6.1. Reactivity was also found with isolated macrophages and with the macrophage-derived synovial lining layer in over half the tissues. In osteoarthritis synovial tissues, mAb A2.5 stained fewer macrophages than in rheumatoid arthritis synovial tissues. Slightly fewer blood vessels reacted with mAb A2.5 in normal compared to diseased synovia. The mAbs reacted with capillaries, venules and arterioles in all synovial tissues. We conclude that mAbs to thrombospondin react primarily with blood vessels and macrophages in synovial tissues. Perhaps thrombospondin may function as an adhesive glycoprotein mediating cellular interactions, or it may serve to counteract the effects of the angiogenic factors produced by cells within diseased synovial tissues.

Antibodies, Monoclonal↗

PubMed1993

Fatigue in Parkinson's disease.

Fatigue is a common but poorly understood symptom in Parkinson's disease (PD). Using previously validated scales, we asked 58 nondemented PD patients and 58 controls to fill out questionnaires assessing fatigue and depression and found that PD patients were more depressed and more fatigued than age-matched controls. Although fatigue correlated with depression but not with disease severity, many nondepressed patients had significant complaints of fatigue.

Aged↗

PubMed1993

Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera.

Technetium-99m-teboroxime is characterized by a high extraction fraction over a wide range of blood flow rates, rapid myocardial clearance and avid hepatic uptake. This study determined the imaging parameters and examined the clinical efficacy of a rapid back to back adenosine stress/rest teboroxime myocardial perfusion SPECT protocol using a triple-detector camera. Acquisition parameters were determined using cardiac phantom studies which were then applied in SPECT studies of 51 catheterized patients (22 with prior myocardial infarction) and 20 patients with a "low" (7.9% +/- 4.3%) likelihood of coronary artery disease. Technetium-99m-teboroxime (20-25 mCi) was injected at the third minute of adenosine infusion. Teboroxime (20-25 mCi) was also injected at rest, 15 min later. Stress followed by rest SPECT were completed within 25 min using a triple-detector camera and sequential, 1-min continuous rotations in alternating directions. Summed raw data from the first to second (1-2 min), second to third (2-3 min) and second to fifth (2-5 min) minutes of imaging following stress teboroxime injection were reconstructed and compared for image quality, degree of liver interference, and accuracy for diagnostic efficacy. In a subgroup of 30 patients, 2-8-min summed images were also reconstructed to compare this more conventional imaging protocol with our rapid acquisition. Image quality was fair to good in 75% of the 1-2-min, 84% of the 2-3-min and 2-5-min studies and 53% of the 2-8-min scans. The frequency of severe liver interference appeared to increase with the duration of imaging time (1-2 min: 3%; 2-3 min: 7%; 2-5 min: 8%) and was greatest (30%, p = 0.08) with 2-8-min images. Three patients (4%) had uninterpretable studies due to intense hepatic uptake. Overall sensitivity (95%) and specificity (71%) were equal for the 2-3-min and 2-5-min stress images and appeared better than in the 1-2-min images (84% and 57%, respectively). For the 2-8-min scans, vessel sensitivity (69%) and specificity (63%) appeared poorer than with 2-3-min studies (83% and 81%, respectively). Normalcy rates were 89% for the 2-3-min and 2-5-min and 79% for 1-2-min images. The back to back adenosine stress/rest teboroxime SPECT can be performed in 30 min using a triple-detector camera. Although overall high sensitivity and normalcy rates were achieved, the protocol is technically demanding. Interference due to intense liver uptake remains problematic.

Adenosine↗

PubMed1992

Reproducibility of stress redistribution thallium-201 SPECT quantitative indexes of hypoperfused myocardium secondary to coronary artery disease.

To determine the reproducibility of quantitative indexes of hypoperfused myocardium by exercise thallium-201 single-photon emission computed tomography, duplicate studies were performed in 16 stable patients within 1 month. Twenty-three other patients, with intervals up to 13 months between studies, were retrospectively identified from medical records. Symptoms, weight, heart rate achieved and peak systolic blood pressure during the 2 studies were similar. Maximal counts circumferential profiles' polar maps were generated and divided into 3 vascular territories. The hypoperfused myocardium was defined as the percent stress profile points below the normal level. The observed values were compared between the 2 studies for each patient. Defect size ranged from 0 to 73%. The concordance correlation coefficient (a measure of the closeness of the data points to the line of identity) and mean absolute deviation were 0.94 and 4.5%, respectively, when all patients were considered together, 0.93 and 3.2%, respectively in the reproducibility group, and 0.94 and 5.1%, respectively, in the retrospective group. Inter- and intraobserver reproducibility were also very high. For individual vessels, the concordance correlation coefficients were all > or = 0.89 and the mean absolute deviations between 3.7 and 9%. Thus, in stable patients with repeat thallium studies within a year, the percent hypoperfused myocardium is highly reproducible.

Adult↗

PubMed1992

Quantitative MRI studies for assessment of multiple sclerosis.

Although magnetic resonance imaging (MRI) is a valuable aid in the initial diagnosis of multiple sclerosis (MS), quantitatively MRI has been disappointing in staging and evaluating therapy protocols by means of serial examinations. In this study, image processing algorithms were developed for the global analysis of MR images of the cerebrum. Limited three-dimensional segmentation was achieved through histogram analysis by these algorithms, which are essentially operator independent. The effects of coil response and tip angles, patient positioning, and interslice gap thicknesses were examined for 10 MS patients with repeated examinations for a total of 72 images. Effects of technique and instrumentation errors were approximately 6%, and agreement between two independent operators for measuring the total MR pixel sum from periventricular effusions and intense MS plaques was better than 97% with a standard deviation of 2.9%.

Adipose Tissue↗

PubMed1992

Speech production, syntax comprehension, and cognitive deficits in Parkinson's disease.

Speech samples were obtained that were analyzed for voice onset time (VOT) for 40 nondemented English speaking subjects, 20 with mild and 20 with moderate Parkinson's disease. Syntax comprehension and cognitive tests were administered to these subjects in the same test sessions. VOT disruptions for stop consonants in syllable initial position, similar to those noted for Broca's aphasia, occurred for nine subjects. Longer response times and errors in the comprehension of syntax as measured by the Rhode Island Test of Sentence Comprehension (RITLS) also occurred for these subjects. Anovas indicate that the VOT overlap subjects had significantly higher syntax error rates and longer response times on the RITLS than the VOT nonoverlap subjects--F(1, 70) = 12.38, p less than 0.0008; F(1, 70) = 7.70, p less than 0.007, respectively. The correlation between the number of VOT timing errors and the number of syntax errors was significant. (r = 0.6473, p less than 0.01). VOT overlap subjects also had significantly higher error rates in cognitive tasks involving abstraction and the ability to maintain a mental set. Prefrontal cortex, acting through subcortical basal ganglia pathways, is a component of the neural substrate that regulates human speech production, syntactic ability, and certain aspects of cognition. The deterioration of these subcortical pathways may explain similar phenomena in Broca's aphasia. Results are discussed in relation to "modular" theories.

Adult↗