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Biomedical subjects

D Fischman

Publications and source records attributed to D Fischman.

11 recordsLinked to original sources

[Paraneoplastic neuropathy with positive anti-Hu].

The case of a 72-year-old woman presenting sensory neuropathy and anti-Hu antibodies is reported. She was admitted in November 1995 with a one year history of sensory neuropathy. Her first symptoms were painful numbness and dysesthesias in both feet. She experienced progression of the sensory symptoms affecting upper limbs, and clumsiness of gait. One month before admission she complained of diminished strength in both hands. The neurologic examination showed anicocoric fixed pupils, with no reaction to light; convergence miosis was evident in the right eye (Argyll-Robertson pupil). In the lower limbs she had very mild distal weakness, and tendon reflexes were universally abolished. Pin and touch sensation, position sense and pallesthesia were absent in all four limbs. Romberg test was elicited, and a tabetic gait was patent. Pseudoathetotic movements were observed in hands and feet. An ulcer was present in the fifth finger of the right foot. Routine blood biochemistry and hematology showed a ESR of 105 and an increased IgG in the immune-electrophoretic run. Neurophysiologic evaluation disclosed a mild demyelinating neuropathy. Positive anti-Hu antibodies were found in the serum (Western blot - Athena Diagnostics); CSF was normal but not tested for anit-Hu. An abdominal CT scan disclosed multiple hypodense nodules in liver, right adrenal gland and peritoneum. A chest CT scan showed a hyperdense mass in the lower right pulmonary lobe and enlarged retrocava-pretracheal lymph nodes. A biopsy of the peritoneal nodule was performed, showing a metastatic small cell carcinoma. The patient died eight days after discharge. Although multiple organs were affected, she was independent until death, showing an indolent clinical course.

Aged↗

Retrospective comparative study of primary intracoronary stenting versus balloon angioplasty for acute myocardial infarction.

Balloon angioplasty has been shown to be an effective therapy for the treatment of acute myocardial infarction but is associated with a high restenosis rate, substantial early recoil, persistent thrombus and need for intracoronary thrombolysis, and a high rate of reclosure. Because many of the limitations of balloon angioplasty in the noninfarction setting are addressed by intracoronary stenting, we examined the results of primary stenting of 18 consecutive patients treated for acute myocardial infarction, and compared the results to those achieved with primary balloon angioplasty in 18 prior cases. Despite the presence of thrombus prior to angioplasty in 13 of the stented patients, no intracoronary thrombolytic therapy was required. Mean percent stenosis using quantitative coronary angiography was 17.7 +/- 10.2% after primary stenting compared with 43.7 +/- 20.3% after primary balloon angioplasty (P < .001). One stent patient who had all anticoagulant and antiplatelet therapy withdrawn early suffered subacute thrombosis. Patients were followed up to 3 yr. Complications were similar in two groups. We conclude that primary stenting for acute myocardial infarction results in superior angiographic appearance as well as resolution of thrombus without the need for routine thrombolysis, and is associated with a low complication rate and excellent short-term clinical patency.

Aged↗

Performance standards and edge detection with computerized quantitative coronary arteriography. The Lovastatin Restenosis Trial Group.

Quantitative coronary angiography (QCA) has become an important tool for evaluating coronary angiograms. Many methodologic factors, such as the choice of frame to analyze, the selection of the "normal," segment and the method of edge detection used may affect the results of QCA. The sequential steps in performing QCA, including a comparison of visual and automated edge-detection methodologies, were evaluated using 12 precision-drilled phantoms and 20 patient films. Normal diameter, minimal lumen diameter, and diameter stenosis were measured. In the phantom studies, the measurements from both visual and automated systems correlated well with the true measurements of the phantoms and between systems (all r values >0.92). To study the difference between methodologies on QCA results as influenced by the choice of frame and normal segment analyzed, the patient films were analyzed independently in 3 separate rounds of interpretation. In round 1, each system's operator individually chose frames and normal segments for analysis. In round 2, both systems analyzed the same preselected frames, but independently chose normal segments. In round 3, both systems analyzed the same preselected normal segments and frames. The intersystem correlations between visual and automatic systems for rounds 1, 2, and 3 were: normal diameter, r = 0.25, r = 0.37, and r = 0.75, respectively; minimal lumen diameter, r = 0.79, r = 0.86, and r = 0.85, respectively; and diameter stenosis, r = 0.65, r = 0.73, and r = 0.87, respectively. The manual edge-detection and automated edge-detection systems used in this study are reasonably accurate and consistent on phantom studies. In patient studies, the nonautomated processes (choice of frame and normal segment for analysis) produced significant differences in the QCA results, thus illustrating that operator-dependent factors other than edge detection are very important in QCA.

Constriction, Pathologic↗

Peripheral vascular complications after intracoronary stent placement: prevention by use of a pneumatic vascular compression device.

Peripheral vascular complications are a significant source of morbidity after coronary artery stent implantation. The goal of this study was to assess the incidence, risk factors, and management of vascular complications after stent placement. The study population consisted of 101 consecutive patients who underwent stent placement for either elective or bailout indications. All patients received a standardized anticoagulation regimen of aspirin, dipyridamole, low molecular weight dextran, heparin, and warfarin. Peripheral vascular access sites were examined daily until hospital discharge. Vascular complications occurred in 16 of 101 (16%) patients, including femoral artery pseudoaneurysm (n = 11), hematoma requiring transfusion or surgery (n = 4), and arteriovenous fistula (n = 1). Intervention was required in 14 of 16 (88%) patients with complications. These included transfusion (n = 7), ultrasound-guided compression (n = 8), and/or vascular surgery (n = 7). Length of hospital stay was prolonged in patients with complications (14 +/- 9 vs. 8 +/- 5 d, P < 0.001). The development of peripheral vascular complications did not correlate with clinical or procedural variables such as age, cardiovascular risk factors, arterial sheath size, or elective vs. bailout indication. After the introduction of a pneumatic vascular compression device (FEMOSTOP, C.A. Bard, Billerica, MA), a significant reduction in vascular complications was observed. Complications occurred in only 1 of 41 (2.4%) patients in whom the compression device was used in contrast to 13 of 58 (22.4%) patients compressed manually (P < 0.01). Thus peripheral vascular complications are frequent after coronary artery stent placement and are associated with serious morbidity and prolongation of hospital stay. These complications are significantly reduced by the use of a pneumatic vascular compression device despite intensive systemic anticoagulation.

Hemostasis, Surgical↗

Inter-series differences in the restenosis rate of Palmaz-Schatz coronary stent placement: differences in demographics and post-procedure lumen diameter.

Restenosis rates following Palmaz-Schatz stenting vary between 13 and 36%. To determine whether the nearly three-fold interseries difference in restenosis rates reflects systematic factors (demographic and procedural variables such as post-treatment lumen diameter) rather than random variation, we pooled 486 lesions treated with the Palmaz-Schatz coronary stent in the U.S. Multicenter Registry (n = 259) with the single-center Beth Israel Hospital experience (n = 227) and analyzed the combined series using a continuous geometric model of restenosis. A greater proportion of lesions (66 vs. 50%; P < 0.001) in the Multicenter cohort represented restenosis after a prior intervention. The Multicenter experience also showed a smaller minimum lumen diameter following stent placement (2.61 vs. 3.43 mm; P < 0.001), higher post-stent percent stenosis (16 vs. -2%; P < 0.001), and less acute gain (1.79 vs. 2.67 mm; P < 0.001) than lesions treated in the Beth Israel cohort. At 6-month follow-up, the angiographic restenosis rate (> or = 50% diameter stenosis) was significantly higher in the Multicenter group (35 vs. 27%; P = 0.05), despite the development of less absolute late loss (0.96 vs. 1.32 mm; P < 0.001). Multivariable modeling, however, showed that the only independent predictors of restenosis were a post-procedure lumen diameter < 2.80 mm (odds ratio = 1.57; P = 0.04), diabetes mellitus (odds ratio = 3.55; P < 0.001), and prior restenosis (odds ratio = 1.84; P = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗

A sarcomeric alpha-actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes.

In many nonmuscle cells, nonsarcomeric alpha-actinin is distributed in the dense bodies of stress fibers, adhesion plaques, and adherens junctions. In striated muscle, a sarcomeric isoform of alpha-actinin (s-alpha-actinin) is found in the Z-bands of myofibrils and subsarcolemmal adhesion plaques. To understand the role(s) of the alpha-actinin isoforms in the assembly and maintenance of such cytoskeletal structures, full-length or truncated s-alpha-actinin cDNAs were expressed in PtK2 cells and in primary skeletal myogenic cells. We found the following. (i) In transfected PtK2 cells the truncated s-alpha-actinin was rapidly incorporated into preexisting dense bodies, adhesion plaques, and adherens junctions. With time these structures collapsed, and the affected cells detached from the substrate. (ii) In myotubes the truncated s-alpha-actinin was incorporated into nascent Z-bands. Many of these progressively hypertrophied, forming nemaline-like bodies. With time the affected myofibrils fragmented, and the myotubes detached from the substrate. (iii) In both cell types the truncated s-alpha-actinin was significantly more disruptive of the cytoskeletal structures than the full-length molecule. (iv) Pools of "over-expressed" full-length or truncated protein did not self-aggregate into homogeneous, amorphous complexes; rather the exogenous proteins selectively colocalized with the same cohort of cytoskeletal proteins with which the endogenous alpha-actinin normally associates. The similarity among the hypertrophied Z-bands in transfected myotubes, the nemaline bodies in patients with nemaline myopathies, and the streaming Z-bands seen in various muscle pathologies raises the possibility that the genetically determined nemaline bodies and the pathologically induced Z-band alterations may reflect primary and/or post-translational modifications of s-alpha-actinin.

Actinin↗

Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty.

BACKGROUND: The balloon-expandable intracoronary stent developed by Palmaz and Schatz is undergoing clinical evaluation for use in unfavorable anatomic situations and in the prevention of restenosis. Because the stent's mechanism of action would suggest effectiveness in salvaging certain percutaneous transluminal coronary angioplasty (PTCA) failures, we retrospectively examined the results of emergency unplanned coronary artery stenting for failed PTCA procedures, including acute occlusion. METHODS AND RESULTS: The study population consisted of all US patients receiving emergency unplanned stent implantation in a nonrandomized fashion at seven centers over a 2 1/2-year period (n = 56). All available medical records and angiograms were reviewed to determine retrospectively the reason for stenting: Group 1 consisted of 23 patients with a suboptimal angioplasty result; group 2 included patients with evidence of impending vessel closure after PTCA (n = 15); and group 3 were patients with frank acute occlusion after PTCA (n = 18). The immediate and final (30-day) results of stenting were examined with respect to major complications, which included death, need for coronary artery bypass graft surgery, and occurrence of myocardial infarction. Finally, restenosis rates (greater than or equal to 50% stenosis) based on follow-up angiography were calculated. Baseline characteristics of the study population included a mean +/- SD age of 58 +/- 11 years and a large prevalence of angiographic characteristics generally considered unfavorable for PTCA, which include lesion eccentricity (49%), intimal dissection (9%), or angiographically visible thrombus (6%). After conventional balloon angioplasty, there was an increased incidence of intimal dissection (74%) and thrombus formation (38%), and overall stenosis severity was unchanged (75 +/- 12% versus 70 +/- 27%, p = NS). Successful stent deployment was achieved in 55 (98%) of 56 patients with initial success (freedom from death, surgery, and infarction) in 52 (93%) of 56 patients. The success rate at 1 month fell to 71% primarily because of the occurrence of subacute stent thrombosis (16%) and its associated complications. Overall, major complications occurred in 16 (29%) of 56 patients within 30 days. The only predictor of subacute stent thrombosis in multiple stepwise logistic regression analysis was the presence of angiographically visible thrombus after stenting (p = 0.03). Angiographic restenosis was documented in eight (23%) of 35 eligible patients. CONCLUSIONS: Emergency stenting may be a useful and effective treatment for failed angioplasty. High initial success rates (greater than 90%) can be achieved, but subsequent complications, often related to subacute thrombosis, occur in a substantial portion of patients. Patients who receive stents on an emergency basis, particularly those with previous acute occlusion, should be considered to be at greater than usual risk for complications and receive more careful anticoagulation and follow-up.

Aged↗

Restenosis after placement of Palmaz-Schatz stents in native coronary arteries. Initial results of a multicenter experience.

BACKGROUND: Several metallic intracoronary stents are currently undergoing preliminary evaluation to ascertain potential benefit as means to reduce the 30-40% incidence of restenosis after balloon angioplasty. METHODS AND RESULTS: To determine the incidence and correlates of restenosis after placement of Palmaz-Schatz stents in native coronary arteries in the first group of patients selected for this procedure, clinical and quantitative angiographic data from 206 consecutive patients (221 stenoses) with successful stent placement (diameter stenosis < 50%) were analyzed. Six patients (2.9%) had thrombosis-mediated stent closure within 1 month after stent placement and were excluded from long-term angiographic follow-up. One hundred eighty-one (91%) of the remaining 200 patients had angiography at 5.8 +/- 2.1 months. Patients with and without follow-up did not differ in any baseline characteristic; in particular, history of restenosis at the site stented (73% versus 65%), placement of multiple overlapping stents (17% versus 20%), and mean poststent diameter stenosis (16 +/- 12% versus 14 +/- 12%). The overall incidence of restenosis (diameter stenosis > or = 50% at follow-up) in this group at high risk for restenosis was 36% (95% confidence interval, 29-43%) on a per-stenosis basis. The incidence of restenosis when a single stent was placed was 30% (95% confidence interval, 23-37%). Risk was dependent upon a history of restenosis (present versus absent 36% versus 16%, p = 0.02) and upon whether or not a poststent stenosis < or = 0% was achieved (6% versus 33%, p = 0.02). When multiple overlapping stents were placed, restenosis occurred at 64% of sites, and placement of multiple stents was discouraged during the later phases of this study as these results became apparent. CONCLUSIONS: Although multiple stents appear to yield a poor long-term result, placement of single stents may offer a benefit compared with standard coronary angioplasty, particularly if an excellent angiographic result can be obtained in patients without prior restenosis. Further randomized trials in such patients are needed.

Coronary Angiography↗

Evidence for reduced fibrinolytic activity in unstable angina at rest. Clinical, biochemical, and angiographic correlates.

BACKGROUND: The goal of this study was to evaluate the role of the fibrinolytic system in patients with unstable angina at rest associated with transient electrocardiographic changes. METHODS AND RESULTS: Tissue plasminogen activator activity in plasma was comparable among patients with unstable angina (n = 17), patients with stable exertional angina (n = 10), and control patients with normal coronary arteriograms (n = 8). In contrast, plasminogen activator inhibitor-1 (PAI-1) activity in plasma was elevated in the unstable angina group (21.67 +/- 9.52 AU/ml) as compared with either the stable angina group (12.01 +/- 7.06 AU/ml, p less than 0.02) or the controls (12.49 +/- 8.54 AU/ml, p less than 0.02). Coronary angiography performed within 24 hours after the last anginal episode showed a similar extent of coronary artery disease in the unstable and stable angina groups. However, intracoronary thrombi were observed in eight patients in the unstable angina group while no thrombus was noted in the stable angina group (chi 2 = 7.22, p less than 0.01). CONCLUSIONS: We conclude that patients with unstable angina at rest have a reduced fibrinolytic activity and an increased incidence of intracoronary thrombi. It is postulated that elevated PAI-1 activity in the presence of coronary arterial wall injury may be an important factor leading to the development of acute coronary syndromes.

Angina Pectoris↗