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Biomedical subjects

M Zucker

Publications and source records attributed to M Zucker.

At least 19 recordsLinked to original sources
PubMed2001

Characterization of high-affinity [3H]TBZOH binding to the human platelet vesicular monoamine transporter.

The present study indicates that human platelets can be used as an accessible peripheral model not only for the plasma membrane serotonin transporter, but also for the vesicular monoamine transporter. The vesicular monoamine transporter (VMAT2) is responsible for the accumulation of monoamines in the synaptic vesicles. VMAT2 differs from the plasma membrane transporters in its capability to recognize serotonin, histamine, norepinephrine and dopamine with almost the same affinity. Dihydrotetrabenazine (TBZOH) is a very potent inhibitor of VMAT2 that binds with high affinity to this transporter. [3H]TBZOH has been used as a ligand to label VMAT2 in human, bovine and rodent brain. In this study we characterized the pharmacodynamic and pharmacokinetic parameters of [3H]TBZOH binding in human platelets as compared to rat brain. The density (Bmax) and affinity (Kd) of [3H]TBZOH specific binding was assessed by Scatchard analysis. Association and dissociation rate constants (k(on), K(off)) were assessed by kinetic binding studies. In this study high-affinity and saturable binding sites for [3H]TBZOH were demonstrated in human platelets. Both the affinity of [3H]TBZOH to its binding site in platelets (Kd = 3.2+/-0.5 nM) and the kinetic rate constants (K(on) = 2.8 x 10(7) M(-1) min(-1); K(off) = 0.099 min(-1)) were similar to that in rat brain (Kd(striatum) = 1.5 nM; Kd(cerebral cortex) = 1.35 nM; K(on) = 2 x 10(7) M(-1) min(-1); K(off) = 0.069 min(-1)). Only the VMAT2 blockers tetrabenazine and reserpine inhibited [3H]TBZOH specific binding.

Animals↗
PubMed2001

The pseudomonas hot-foot syndrome.

BACKGROUND: Between March and May 1998, there was an outbreak of a clinically distinct skin eruption on the soles of the feet of children who used a community wading pool. METHODS: We reviewed the medical records of 40 children in whom this syndrome developed between March and May 1998. We treated 17 children and advised the attending physicians on the care of the other 23. Follow-up data were obtained for up to one year. RESULTS: Exquisitely painful erythematous plantar nodules developed in 40 children (age, 2 to 15 years) within 40 hours after they had used a wading pool whose floor was coated with abrasive grit. Culture of the plantar pustules from one child yielded Pseudomonas aeruginosa with a pattern on pulsed-field gel electrophoresis that was identical to that of a strain of P. aeruginosa cultured from the pool water. A skin-biopsy specimen from this patient showed a perivascular and perieccrine neutrophilic infiltrate, and a specimen from another patient showed a dermal microabscess. Thirty-seven patients were treated symptomatically; three others were treated with cephalexin. All patients recovered within 14 days, but three children had recurrences of the painful plantar nodules within 24 hours after using the pool again. Folliculitis developed in one patient. CONCLUSIONS: The "pseudomonas hot-foot syndrome" is characterized by the acute onset in children of exquisitely tender plantar nodules and a benign, self-limited course. This community outbreak developed after exposure to pool water containing high concentrations of P. aeruginosa.

Adolescent↗
PubMed2001

Efficacy of single versus bilateral internal mammary artery grafting in women: a long-term study.

BACKGROUND: Coronary artery bypass grafting carries a higher operative mortality and less favorable long-term benefit in women than in men. Bilateral internal mammary artery grafting (BIMA) has been shown to yield excellent perioperative and long-term results in both women and men. However, controversy continues to exist as to the benefits of a second internal mammary artery graft in women. METHODS: A retrospective analysis was performed comparing 261 consecutive women from a single surgical practice receiving BIMA and supplemental vein grafts between January 1972 and October 1994 with a computer-matched cohort of 261 women receiving single internal mammary artery (SIMA) and vein grafts during the same period. Univariate analysis confirmed the homogeneity of the two groups based on nine preoperative variables. RESULTS: Operative mortality was comparable in the two groups, 3.8% (10 of 261 patients) in the SIMA and 3.4% (9 of 261 patients) in the BIMA group, with a markedly reduced mortality in both groups since 1990, 2.3% (2 of 86 patients) in the SIMA and 1.3% (1 of 78 patients) in the BIMA group. The mean number of distal grafts (2.78, SIMA; 3.14, BIMA), perfusion time (104 minutes, SIMA; 108 minutes, BIMA), and cross-clamp time (58 minutes, SIMA; 66 minutes, BIMA) were all comparable. There was no significant difference in the incidence of postoperative complications, including sternal wound infection. Patient follow-up ranged from 1 month to 27 years, with a mean of 10.0 years in the SIMA group and 9.1 years in the BIMA group. Clinical results were excellent, with 100% (136 of 136 patients) of the SIMA and 100% (167 of 167 patients) of the BIMA patients in Canadian Cardiovascular Society class I or II at follow-up. Rates of late myocardial infarction, percutaneous transluminal coronary angioplasty, and reoperation were similarly low in both groups: 3.7% (5 of 136 patients) versus 1.8% (3 of 166 patients), 5.4% (7 of 136 patients) versus 4.8% (8 of 166 patients), and 3.7% (5 of 136 patients) versus 1.8% (3 of 166 patients), for SIMA versus BIMA survivors, respectively. No significant difference was found in the long-term and event-free survival or in any of the eight subscales of the SF-36 quality of life survey for the two groups. CONCLUSIONS: Excellent short- and long-term results have been demonstrated with internal mammary artery grafting in women. However, the addition of a second internal mammary artery graft does not appear to confer any additional clinical benefits in a comparably matched cohort of patients.

Adult↗
PubMed2001

Changes in vesicular monoamine transporter (VMAT2) and synaptophysin in rat Substantia nigra and prefrontal cortex induced by psychotropic drugs.

We investigated the regulatory effect of the dopaminergic agent L-dopa, the mood stabilizer lithium and the nonselective monoamine oxidase inhibitor phenelzine on brain vesicular monoamine transporter (VMAT2) expression. Rats were treated chronically (21 days) with the three psychoactive drugs. VMAT2 gene expression at the protein level was assessed in the prefrontal cortex and striatum by autoradiography with high-affinity [(3)H]dihydrotetrabenazine ([(3)H]TBZOH) binding and at the mRNA level in the substantia nigra pars compacta by in situ hybridization. In addition, the effect of various treatments on the synaptophysin mRNA level was determined in the substantia nigra by in situ hybridization. Chronic administration of L-dopa resulted in a significant decrease (28%, p < 0.05) in the density of [(3)H]TBZOH binding in the prefrontal cortex but had no effect on VMAT2 and synaptophysin mRNA levels in the substantia nigra. Lithium treatment increased [(3)H]TBZOH-specific binding in the prefrontal cortex (23%, p < 0.05) but had no effect on VMAT2 and synaptophysin mRNA levels. Phenelzine did not modulate VMAT2 gene expression but reduced the synaptophysin mRNA level (19%, p < 0.05). The modulatory activities of these drugs, although relatively weak, may be relevant to the drug-induced synaptic and neuronal plasticity as well as to the molecular and cellular pathophysiology of monoamine-related neuropsychiatric disorders.

Animals↗
PubMed2001

A four-year experience with patient individualized heparin and protamine dosing using the Hemochron RxDx system.

Cardiac surgical case histories, collected over 4 years at Huntsville Hospital in Alabama, were reviewed for 2,293 patients. Patients were separated into two dosing groups for both heparin and protamine, hospital empirically dosed and Hemochron RxDx dosed. Review of the heparin dosing information found that incomplete data were collected for 47 patients, leaving 2,246 patients eligible to be evaluated for heparin dose comparison. Both RxDx recommended and empirically calculated doses were recorded, as well as the actual dose given. Of the 2,246 patients, 1671 were administered heparin according to the RxDx calculated dose, and the remaining 575 patients were dosed according to the hospital's empirical protocol. The average RxDx calculated heparin dose was 17% greater then the empirically calculated heparin dose (350 U/kg) (p < .001). Anticoagulation to target ACT (480 sec) was achieved in 92% of the patients dosed according to the RxDx recommended dose; whereas, in the empirically dosed patient group only 80% of the patients reached the target ACT after initial heparin bolus dose. Incomplete protamine dosing data was recorded for 336 patients, leaving a total of 1,957 patients available for protamine dose evaluation. All patients had an RxDx protamine calculation, empirical protamine calculation, and actual amount of protamine dosed recorded. Of the 1,953 patients, 1,764 were dosed according to the RxDx recommended dose, with the remaining 189 patients dosed empirically (1 mg protamine/100 U of heparin). In both the RxDx and the empirical groups, 96% of the patients returned to baseline following initial protamine infusion. The overall RxDx dose (293 mg) was 16% lower than the average empirical dose (348 mg). The RxDx system has been shown to be an effective method for determining patient-specific dosing for both heparin and protamine. This long-term clinical experience demonstrates the consistency and reliability of patient maintenance using this individualized dosing system, which has been shown, in other independent evaluations, to lead to improved patient outcomes.

Analysis of Variance↗
PubMed1999

Transmyocardial laser revascularization with the Holmium:YAG laser does not improve myocardial perfusion in the acutely ischemic heart: an experimental study measuring myocardial perfusion by a thermal imaging camera.

BACKGROUND: Transmyocardial laser revascularization (TMLR) is a new surgical therapy for patients with end-stage coronary artery disease refractory to conventional therapy. TMLR should act by improvement of perfusion of the lasered myocardium. Blood should be delivered from the cavity of the heart to the surface of the myocardium. The aim of this study was to measure perfusion of normal, ischemic, and ischemic myocardium after TMLR. METHOD: We used a new method of perfusion measurement by an infrared thermal imaging system in an open-chested adult sheep model with temporary and permanent occlusion of the dominant diagonal branch. RESULTS: A significant fall from normal perfusion of the myocardium to reduced after inducing ischemia (p<0.01) and a significant rise again after reperfusion (p<0.001) could be shown. Perfusion measurements after TMLR did not significantly differ from perfusion measurements after inducing ischemia (p=0.2). CONCLUSION: In the presented sheep model, laser revascularization could not improve myocardial perfusion after acute ischemia as seen by the infrared thermal imaging system.

Aluminum↗
PubMed1997

Chest teleradiology in a teaching hospital emergency practice.

OBJECTIVE: New standards for hospital accreditation and health care reimbursement may require that faculty subspecialists be more available after regular working hours to supervise residents in academic radiology departments. We designed a receiver operating characteristic study to determine whether a thoracic radiologist who evaluated computed radiography (CR) images of the chest at a home-based teleradiology workstation could add significant value to a junior resident's interpretations of films within the hospital for acutely ill patients. SUBJECTS AND METHODS: Using a hybrid cassette, we obtained analog chest films and CR images simultaneously for each of 252 acutely ill patients in the emergency department and in an intensive care unit. Interpretations of the analog films by three first-year residents were analyzed for 11 parameters deemed critical for patient management. Likewise, CR images of the same chest studies were viewed on a home teleradiology workstation by a faculty thoracic radiologist who analyzed the images for these 11 interpretive parameters. All interpretations by radiology residents and by the home-based thoracic radiologist were then compared with the interpretations of a consensus panel consisting of another thoracic radiologist and a full-time emergency department radiologist. RESULTS: Analysis of the pooled results from the three junior residents as a group failed to show significant differences between their interpretations of chest films and the interpretations of CR images by a thoracic radiologist at a home workstation. However, we observed significant differences for several image interpretation parameters between individual residents and the home-based radiology subspecialist. CONCLUSION: The data confirm that significant value can be added to the interpretations of chest films by individual junior residents when a home-based thoracic radiologist uses teleradiology to provide expert interpretations. Accordingly, it is reasonable to infer that on-line supervision by faculty subspecialists via teleradiology could be used to complement the scheduled visits that are being made now by individual faculty members of our institution to interpret films periodically with a radiology resident during overnight and weekend periods.

Emergency Service, Hospital↗
PubMed1996

Bilateral internal mammary artery grafting in women: a 21-year experience.

BACKGROUND: Coronary artery bypass grafting traditionally has carried a higher mortality rate in women than in men. It remains the leading cause of death in women despite major advances in diagnosis and treatment over the past 2 decades. METHODS: A retrospective analysis was conducted to identify risk factors that adversely influence hospital mortality, morbidity, and long-term clinical results in women undergoing bilateral internal mammary artery grafting. From January 1972 through October 1994, 327 consecutive women received bilateral internal mammary artery grafts and supplemental vein grafts. Patient age ranged from 32 to 84 years (mean, 65.7 years). There were 262 patients (80.1%) with three-vessel disease; 71 (21.7%) had substantial (> 50%) stenosis of the left main coronary artery, 65 (19.9%) had a moderately reduced (0.30 to 0.50) ejection fraction, and 11 (3.4%) had a severely reduced (< 0.30) ejection fraction. Preoperatively, 316 patients (96.6%) were in New York Heart Association class III or IV. RESULTS: There were 1,016 coronary artery grafts (mean, 3.1 per patient). The overall hospital mortality rate was 3.4% (11 of 327). Postoperative complications included myocardial infarction in 18 patients (5.5%), stroke in 5 (1.5%), pulmonary insufficiency in 11 (3.4%), reoperation for bleeding in 7 (2.1%), and sternal infection in 8 (2.4%). Independent predictors of operative death were postoperative cardiac arrest (p < 0.001), use of intraaortic balloon pump (p < 0.001), and reoperation for bleeding (p < 0.050). Follow-up was completed on 316 hospital survivors (100%) and ranged from 6 months to 21 years (mean, 5.1 years). Actuarial survival (mean +/- standard error of the mean) was 90.5% +/- 1.9% at 5 years and 65.6% +/- 6.1% at 10 years. At follow-up, 252 patients (94.0%) were asymptomatic in New York Heart Association class I, and 12 (4.5%) were in class II. CONCLUSIONS: This longitudinal study demonstrates that bilateral internal mammary artery grafting, though technically demanding, can be achieved in women with low hospital mortality and morbidity rates. Patients experienced reduced late cardiac events, excellent functional improvement, and enhanced long-term survival.

Actuarial Analysis↗
PubMed1995

Intraoperative detection of unsuspected distal coronary obstruction by thermal coronary angiography.

Intraoperative assessment of graft patency and completeness of revascularization can increase the success of coronary artery bypass grafting. A 56-year-old man underwent a quadruple bypass operation. Flow in the graft to the anterior descending artery was verified after completion of the distal anastomosis using a Doppler flow detector. Visualization of the native artery by thermal coronary angiography demonstrated that the flow passed into the second diagonal branch and not into the distal anterior descending artery, which had an unsuspected obstruction just distal to the anastomosis. The obstruction was dilated. Patency was verified with cold solution, and flow of warm blood to the entire artery was accomplished. This case demonstrates how the early (intraoperative) recognition of an unsuspected coronary obstruction using an infrared imaging system can improve the results of myocardial revascularization and avoid potential postoperative complications.

Coronary Angiography↗
PubMed1995

Comparison of hard- and soft-copy digital chest images with different matrix sizes for managing coronary care unit patients.

OBJECTIVE: This study was to determine whether different digital display formats for portable chest radiographs of coronary care unit patients would provide comparable information for clinical care. In particular, we tried to ascertain whether 1024 x 1024 pixel (1K) images on a picture archiving and communication system (PACS) workstation would be comparable to 1760 x 2140 pixel (2K) images on workstations or to digital films. If comparability could be proved, we hypothesized that 1K workstations could considerably lower equipment and film costs and facilitate image transmission from point to point. MATERIALS AND METHODS: Four chest radiologists read a panel of chest studies assembled from 98 coronary care unit patients, comparing 1K and 2K soft-copy images with digital hard copies. For all three image types for the 98 patients, the readers evaluated nine image parameters that the cardiologists deemed essential for clinical decision making. Two other chest radiologists reviewed each patient's three image types, historical chest images, current and prior radiologic reports, and medical record to determine the consensus, or "truth findings." RESULTS: With one exception (small pleural effusions), the receiver operating characteristic analysis showed no significant differences in the clinical information derived from the three image types. CONCLUSION: For clinical management in a coronary care unit, comparable information can be obtained from digital radiologic chest studies using a 1K x 1K soft-copy format, a 2K x 2K soft-copy format, or a hard copy (film). Substantial savings in cost and time are therefore possible by using soft-copy images and lower resolution (1K x 1K) workstations and, when necessary, by transmitting images on regular telephone lines.

Coronary Care Units↗
PubMed1992

Low-risk criteria for cervical-spine radiography in blunt trauma: a prospective study.

STUDY HYPOTHESIS: Cervical-spine radiography does not need to be performed on selected blunt trauma patients who are awake, alert, nonintoxicated, do not complain of midline neck pain, and have no tenderness over the bony cervical spine. STUDY POPULATION: One thousand consecutive patients seen in the UCLA Emergency Medicine Center with a chief complaint of blunt trauma, for whom cervical-spine films were ordered and for whom prospective data questionnaires were completed. METHODS: Clinicians completed data forms for each patient before radiograph results were known. Data items included mechanism of injury, evidence of intoxication, presence of cervical-spine pain and/or tenderness, level of alertness, presence of focal neurologic deficits, and presence of other severely painful injuries unrelated to the cervical spine. Physicians were also asked to estimate likelihood of significant cervical-spine injury. RESULTS: Twenty-seven patients with cervical-spine fracture were among the 974 patients for whom data forms were completed. A number of findings were statistically more common in the group of patients with fracture than without, but no single or paired findings identified all patients with fracture. All 27 patients with fracture had at least one of the following four characteristics: midline neck tenderness, evidence of intoxication, altered level of alertness, or a severely painful injury elsewhere. Three hundred fifty-three of 947 (37.3%) patients without cervical-spine fracture had none of these findings. CONCLUSION: Cervical-spine radiology may not be necessary in patients without spinous tenderness in the neck, intoxication, altered level of alertness, or other severely painful injury. A policy to limit films in such patients would have decreased film ordering by more than one third in this series, while identifying all patients with fracture.

Adolescent↗
PubMed1992

Distribution and kinetics of the inflammatory cell response to ocular challenge with Pseudomonas aeruginosa in susceptible versus resistant mice.

This study examined and characterized the distribution and kinetics of the inflammatory cell response to pseudomonas ocular challenge in susceptible C57BL/6J and resistant DBA/2J mice. Initially, in the cornea, the number of neutrophilic leukocytes (PMNs), macrophages/monocytes or lymphocytes was 2-2.5 times greater in resistant versus susceptible mice. The peak cellular response in the cornea was also greater in resistant than in susceptible animals. Further, resistant mice, when compared with susceptible mice, had a shorter duration of inflammatory cells as well as bacteria in the cornea. These data were similar for the cell infiltrate in the anterior chamber, with the exception that PMNs were initially greater in number in C57BL/6J than in DBA/2J mice. Collectively these data suggest that susceptible mice are, in general, cellularly hyporesponsive to pseudomonas ocular challenge when compared with resistant animals. This, together with persistence of inflammatory cells and bacteria in the cornea of susceptible animals, may contribute to their failure to restore corneal clarity following pseudomonas ocular challenge.

Animals↗
PubMed1988

Effects of a low saturated fat, low cholesterol fish oil supplement in hypertriglyceridemic patients. A placebo-controlled trial.

STUDY OBJECTIVE: To determine the effects of fish oil supplements low in saturated fat and cholesterol on plasma lipid and lipoprotein levels in hypertriglyceridemic patients. DESIGN: Single-blind, placebo-controlled (safflower oil), crossover trial with 6-week treatment periods. SETTING: Outpatient lipid clinic in a university medical center. PATIENTS: Eleven adult patients had isolated hypertriglyceridemia (type IV) and seven had concomitant hypercholesterolemia (Type IIb). INTERVENTION: Twelve 1-g capsules of either fish oil or placebo (safflower oil) were taken daily during each treatment period. MEASUREMENTS AND MAIN RESULTS: Blood was drawn at the fifth and sixth week of each period and analyzed for total lipids; cholesterol in very low, low (LDL), and high density (HDL) lipoproteins (mmol/L); and apoprotein B (mg/dL). Compared with the placebo, fish oil lowered plasma triglyceride levels (4.0 +/- 1.8 to 2.5 +/- 1.0), and raised LDL cholesterol levels (3.7 +/- 1.75 to 4.25 +/- 0.85), apolipoprotein B levels (122 +/- 29 to 140 +/- 34), and the ratio of LDL cholesterol to HDL cholesterol (4.0 +/- 0.9 to 4.7 +/- 1.4) (P less than 0.05; mean +/- SD). No significant changes were seen in levels of HDL or HDL cholesterol subfractions. Similar responses were seen in patients with both type IIb and IV lipoprotein phenotypes. CONCLUSIONS: Because the fish oil supplement contributed negligible amounts of cholesterol and saturated fat to the diet, the n-3 fatty acids most likely caused the observed effects. These findings indicate that relatively small amounts of fish oil can have beneficial effects on plasma triglyceride levels in hypertriglyceridemic patients, but the increase in LDL cholesterol and apoprotein B levels, and in the LDL cholesterol to HDL cholesterol ratio suggests the need for careful monitoring of plasma lipoprotein changes during fish oil supplementation, and for a careful evaluation of their long-term benefits.

Apolipoproteins B↗
PubMed1986

Potential targets for antiviral chemotherapy.

Serendipity and random screening have been successful in producing effective antiviral agents. The increase in our knowledge of the basic biochemistry of viral replication and of virus-host interrelationships has revealed not only an understanding of the targets upon which existing antiviral agents exert their inhibitory effect, but also has uncovered new potential targets. The hope is that such molecular understanding will afford the synthesis of compounds with selective antiviral activity. A review of various viral targets which are potentially susceptible to attack, and a few approaches for development of antiviral agents are presented.

Antiviral Agents↗
PubMed1985

Congruent stress-preventing factors and anxiety in a long-term stress situation.

The relationship of state anxiety to personal and social stress-preventing factors and to criterion measure was examined in 38 family men who were recent immigrants to Israel from Western countries. As predicted, state anxiety accounted for more variance in the criterion measure of stated intention of remaining in Israel than all the stress-preventing factors combined. Moreover, approximately half of the effect of the latter factors on the criterion was achieved through the anxiety variable. Given the modest sample size, the specific findings are regarded as tentative, but the general conclusion of the study appears to be amply supported. Namely, the level of state anxiety in the individual may be regarded as an index of the effectiveness of the various stress-preventing factors operating in the situation and as a stress-preventing factor in its own right that directly affects problem-solving behavior and outcomes.

Adaptation, Psychological↗
PubMed1981

Primary adenocarcinoma of an anal gland with secondary perianal fistulas.

A case of primary mucinous (colloid) adenocarcinoma associated with multiple perianal fistulas and a supra-anal intergluteal abscess of a short duration is described. The origin of this tumor has been much debated. Some believe that the tumor occurs primarily in an anal duct or its glands with secondary fistula formation, whereas others claim that the tumor arises in a chronic fistulous tract. The present study substantiates the former concept on the basis of the mode of clinical presentation and the pathologic findings of a large tumor, without involvement of the anorectal mucosa. The residual anal ducts and glands were found in close relationship with the tumor.

Adenocarcinoma, Mucinous↗