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Biomedical subjects

E F Bernstein

Publications and source records attributed to E F Bernstein.

At least 19 recordsLinked to original sources

Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries.

Decreased fibrinolytic capacity has been suggested to accelerate the process of arterial atherogenesis by facilitating thrombosis and fibrin deposition within developing atherosclerotic lesions. Type 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor of tissue-type plasminogen activator and has been found to be increased in a number of clinical conditions generally defined as prothrombotic. To investigate the potential role of this inhibitor in atherosclerosis, we examined the expression of PAI-1 mRNA in segments of 11 severely diseased and 5 relatively normal human arteries obtained from 16 different patients undergoing reconstructive surgery for aortic occlusive or aneurysmal disease. Densitometric scanning of RNA (Northern) blot autoradiograms revealed significantly increased levels of PAI-1 mRNA in severely atherosclerotic vessels (mean densitometric value, 1.7 +/- 0.28 SEM) compared with normal or mildly affected arteries (mean densitometric value, 0.63 +/- 0.09 SEM; P less than 0.05). In most instances, the level of PAI-1 mRNA was correlated with the degree of atherosclerosis. Analysis of adjacent tissue sections from the same patients by in situ hybridization demonstrated an abundance of PAI-1 mRNA-positive cells within the thickened intima of atherosclerotic arteries, mainly around the base of the plaque. PAI-1 mRNA could also be detected in cells scattered within the necrotic material and in endothelial cells of adventitial vessels. In contrast to these results, PAI-1 mRNA was visualized primarily within luminal endothelial cells of normal-appearing aortic tissue. Our data provide initial evidence for the increased expression of PAI-1 mRNA in severely atherosclerotic human arteries and suggest a role for PAI-1 in the progression of human atherosclerotic disease.

Aorta

Failure of aspirin plus dipyridamole to prevent restenosis after carotid endarterectomy.

OBJECTIVE: To evaluate therapy with aspirin plus dipyridamole in reducing restenosis after carotid endarterectomy. PATIENTS: A total of 163 patients having 175 surgical carotid endarterectomies. INTERVENTION: Eighty-three patients (90 endarterectomies) were randomly assigned to receive oral aspirin, 325 mg, plus dipyridamole, 75 mg, beginning 12 hours preoperatively, followed by a second dose administered within 8 hours after the operation, and given three times daily thereafter for 1 year. Eighty patients (85 endarterectomies) received placebo medication that was identical in appearance to the study drugs. MEASUREMENTS: After the adequacy of the surgical procedure was confirmed by intraoperative angiography, restenosis at the endarterectomy sites was evaluated using serial duplex ultrasound studies before hospital discharge and at 3-month intervals postoperatively for 1 year. RESULTS: Based on the time for developing identifiable restenosis and on efficacy analysis, greater than 50% restenosis developed in 11 operated vessels (16%) in the treated group and in 10 arteries (14%) in the placebo group, yielding an observed risk increase of 14% (95% CI, -52% to 167%; P greater than 0.2). By intention-to-treat analysis, greater than 50% restenosis developed in 16 of 90 operated vessels in treated patients and in 10 of 85 arteries in patients receiving placebo (26% for the treated group and 12% for the placebo group; P = 0.18, Mantel-Haenszel statistic), representing an observed risk increase of 110% (CI, -5% to 365%). Similar differences were observed for greater than 20% restenosis and for the comparison of patients rather than operated vessels by either intention-to-treat or efficacy analyses. CONCLUSIONS: Because therapy not only failed to reduce carotid restenosis but may have actually increased its frequency, treatment with aspirin plus dipyridamole probably has no clinically important benefit on restenosis in patients having carotid endarterectomy.

Aged

Recurrent neutrophilic eccrine hidradenitis.

Neutrophilic eccrine hidradenitis (NEH) is a neutrophilic dermatosis primarily affecting the eccrine glands, and most commonly seen in patients undergoing chemotherapy for treatment of a malignancy. Rapid diagnosis may avert unnecessary changes in therapy to treat conditions which clinically mimic NEH. We describe a patient who developed NEH on three separate occasions provoked by two different chemotherapeutic agents--cytarabine and mitoxantrone. The lesions were morphologically distinct and differed in their anatomical distribution during each episode. The response to intravenous corticosteroids was dramatic, but lesions recurred after their withdrawal. This case illustrates the potential diversity of clinical lesions in a single patient with NEH, and its response to systemically administered corticosteroids.

Adult

CHAT analysis of the influence of specific risk factors on late results after carotid endarterectomy.

The CHAT classification separates various current and historical presentations of cerebrovascular disease in an effort to determine important prognostic clues for management and prognosis. To evaluate known risk factors for late stroke and death, we followed up for an average of 44 months 633 patients who had undergone 714 carotid operations. We analyzed the indication for surgery (by CHAT) and the effect of preoperative risk factors (age, hypertension, cardiac disease, tobacco use, diabetes, hyperlipidemia, renal disease, pulmonary disease, and total risk factor score) on the end points of late stroke and death. Ipsilateral stroke was uncommon after carotid endarterectomy: with life-table analysis, the probability of late stroke at 5 years after carotid endarterectomy was 3%. Among the 127 patients with amaurosis fugax, the incidence of late stroke and of mortality was a combined total of 1% per year, and the 17 patients who had been first seen with permanent ocular stroke (blindness) fared equally well. The 28 patients who were first seen with vertebrobasilar symptoms and were treated by carotid endarterectomy also fared particularly well, with no late strokes or deaths within the first 5 years. Logistic regression analyses revealed that the various indications for carotid endarterectomy were associated with differing patterns of risk factors as significant predictors of late stroke or death. For patients first seen with asymptomatic lesions, only diabetes was an important predictor for late stroke (p = 0.05) and renal disease was the only marker for early death (p = 0.05). On the other hand, those factors were not significant risk factors for patients first seen with amaurosis fugax, for whom tobacco use was a negative predictor for stroke (p = 0.06) and male gender a negative predictor for early death (p = 0.03). After cortical transient ischemic attacks and carotid endarterectomy, there were no risk factors predictive of late stroke or of death. For patients with prior stroke, age was a very strong predictor of stroke (p = 0.01) and both age and a history of cardiac disease were significant risk factors for early death (p = 0.007). In contrast to the results in reports of patients treated medically for transient ischemic attacks and stroke, we found that several risk factors appeared to play relatively minor roles. In conclusion, stroke after carotid endarterectomy was uncommon, least common after ocular symptoms, and most likely after permanent cortical stroke. Specific risk factors were less important for patients after carotid endarterectomy than for the medically treated stroke patient.

Analysis of Variance

Treatment-resistant psoriasis due to a mastectomy sleeve: an extensive Koebner response.

The Koebner or isomorphic response refers to the appearance of a dermatosis at sites of trauma. This process was first described by Heinrich Koebner in a man with psoriatic plaques in areas of trauma. Many types of trauma are capable of producing koebnerization. We report a case of extensive koebnerization in response to the wearing of a mastectomy sleeve, worn to reduce lymphedema. Both the chronic pressure produced by the device and the trauma of applying the sleeve produced the necessary dermal and epidermal trauma to elicit the Koebner response.

Adult

Combined carotid endarterectomy and coronary artery revascularization: a sobering review.

The clinical outcome of 99 patients who underwent combined single-stage carotid thromboendarterectomy and coronary artery bypass grafts in three different hospitals over a 15-year period was analyzed. Coronary revascularization was elective in 16 patients, urgent in 46 and emergent in 37 patients. Asymptomatic carotid artery stenosis of greater than or equal to 80% was detected in 79% of patients. Sequential reconstruction of the carotid artery circulation followed by restoration of the coronary circulation was performed in all patients by two separate surgical teams. The population included 79 men and 20 women, with a mean age of 67 +/- 6 years, of whom 53% had a previous myocardial infarction, 59% had hypertension and 49% had a history of smoking. Three or more coronary arteries were revascularized in 90% of patients. The overall major neurological complication rate was 25%, with an 11% stroke rate ipsilateral to the operated carotid. Other major complications included respiratory failure (5%), multisystem failure (8%), and myocardial infarction (8%). The overall mortality was 12%. Ten of the 12 deaths were directly related to the cardiac operation, and 2 died as a result of stroke. We conclude that a combined carotid and coronary artery operation results in a high morbidity and mortality in institutions with excellent records for each operation when performed separately. Whenever possible, these high risk patients should be carefully assessed regarding the need for both procedures, since prophylactic carotid endarterectomy has not been shown to significantly reduce the neurologic risk of coronary bypass.

Aged

Transforming growth factor-beta improves healing of radiation-impaired wounds.

Exogenously applied TGF-beta 1 has been shown to increase wound strength in incisional wounds early in the healing process. An impaired wound healing model was first established in guinea pigs by isolating flaps of skin and irradiating the flaps to 15 Gray in one fraction using a 4-MeV linear accelerator. Incisions made 2 d after irradiation were excised 7 d later, and showed decreased linear wound bursting strength (WBS) as compared to non-irradiated control wounds on the contralateral side of each animal (p = 0.001). The effect of TGF-beta on healing of radiation-impaired wounds was studied using this model. Skin on both left and right sides of guinea pigs was irradiated as above. A linear incision was made in each side. Collagen with either 1, 5, or 20 micrograms of TGF-beta was applied to one side prior to closure with staples, whereas the contralateral side received saline in collagen. Wounds given either 1 or 5 micrograms of TGF-beta were found to be stronger than controls at 7 d (p less than 0.05), whereas those receiving the higher 20-micrograms dose were weaker than controls (p less than 0.05). Thus, TGF-beta in lower doses improved healing at 7 d but very large amounts of the growth factor actually impaired healing. In situ hybridization done on wound samples showed increased type I collagen gene expression by fibroblasts in wounds treated with 1 micrograms TGF-beta over control wounds. These results indicate that TGF-beta improved wound healing as demonstrated by increased WBS. This improvement is accompanied by an up-regulation of collagen gene expression by resident fibroblasts.

Animals

Noninvasive assessment of cerebral collateral blood supply through the ophthalmic artery.

We assessed the potential of 2-MHz pulsed-wave transorbital Doppler ultrasonography to delineate the role of the ophthalmic artery as a source of collateral cerebral blood supply by comparing oculopneumoplethysmography, transorbital Doppler ultrasonography, periorbital continuous-wave Doppler ultrasonography, and transcranial Doppler ultrasonography in 25 patients with unilateral internal carotid artery occlusion and five controls with 10 normal internal carotid arteries. Systolic ophthalmic artery blood velocity was reduced ipsilateral to an internal carotid artery occlusion (38.2 +/- 10.2 cm/sec) compared with the contralateral and control velocities (46.0 +/- 10.3 and 47.5 +/- 6.8 cm/sec, respectively; p less than 0.05). Ophthalmic systolic pressure measured by oculopneumoplethysmography was 94.7 +/- 13.2 mm Hg ipsilateral to an internal carotid artery occlusion compared with 108.4 +/- 15.3 mm Hg on the contralateral side (p less than 0.01). Transorbital and periorbital Doppler ultrasonography detected reversed ophthalmic artery blood flow ipsilateral to an internal carotid artery occlusion in 44.0% and 40.0% of the patients, respectively. Systolic middle cerebral artery blood velocity was 55.2 +/- 22.3 cm/sec ipsilateral to an internal carotid artery occlusion compared with 79.4 +/- 23.5 cm/sec on the contralateral side (p less than 0.05) and 101.2 +/- 18.9 cm/sec in the controls (p less than 0.05). Reversed ophthalmic artery blood flow was associated with a low middle cerebral artery blood velocity and lack of major intracerebral collaterals. Transorbital Doppler ultrasonography permits noninvasive evaluation of the ophthalmic artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Noninvasive evaluation of vertebrobasilar insufficiency.

The diagnosis of vertebrobasilar insufficiency (VBI) is a clinical challenge because its manifestations are subjective and difficult to quantify. We evaluate 61 patients with the clinical diagnosis of VBI and 30 control patients with other medical problems. We used duplex scanning to study the extracranial carotid, vertebral, and subclavian arteries, and a 2-MHz transcranial Doppler (TCD) to examine the intracranial vertebral and basilar arteries. Extracranial lesions were more common in VBI patients than among controls, including stenosis of the subclavian artery with and without subclavian-vertebral steal and stenosis of the vertebral artery. Intracranial abnormalities identified in the vertebrobasilar circulation included stenosis and occlusion of the intracranial vertebral artery and basilar artery steal. Overall, significant lesions were detected in 32.8% of VBI patients and 3.0% of controls (P less than 0.05). Systolic artery velocity (cm/sec) in the extracranial vertebral artery was higher in controls (65.9 +/- 23.3) than in VBI patients who had no evidence of vertebrobasilar steal (43.0 +/- 17.4, P less than 0.05). Patients with a steal mechanism had an intracranial vertebral artery systolic velocity of 90.0 +/- 38.9, compared with 53.0 +/- 15.0 in controls (2P less than 0.050). Intracranial vertebral artery systolic velocity was higher among VBI patients with significant carotid artery disease (greater than 50%, 76.7 +/- 28.8) than in those with less severe disease (less than 50%, 47.3 +/- 13.8, P less than 0.05). Evaluation and quantitation of the vertebrobasilar circulation using both intra- and extracranial noninvasive studies may afford further insight as to the pathophysiology of vertebrobasilar insufficiency and provide a readily available, direct, and simple method of initial and serial assessment of VBI patients.

Arterial Occlusive Diseases

Transcutaneous determination of tissue dihematoporphyrin ether content. A device to optimize photodynamic therapy.

Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer resulting in tissue destruction. The photosensitizer dihematoporphyrin ether is selectively retained in tumors allowing for tumor destruction while sparing normal structures. Accessibility of skin tumors makes them well suited for photodynamic therapy. Tissue and tumor dihematoporphyrin ether content is estimated based on the amount of dihematoporphyrin ether administered. In our study, skin dihematoporphyrin ether content was measured in guinea pigs transcutaneously by a hand-held fluorometer and compared with dihematoporphyrin ether determinations done on skin biopsy specimens. Fluorometry was performed on guinea pigs receiving 0, 2.5, 5, 10, and 25 mg/kg of dihematoporphyrin ether. Transcutaneous measurements of skin fluorescence increased with increasing dihematoporphyrin ether dose and correlated well with skin dihematoporphyrin ether content as determined by extracting dihematoporphyrin ether from skin samples. Transcutaneous fluorescent measurements of guinea pigs given 0 and 2.5, 2.5 and 5, 5 and 10, and 10 and 25 mg/kg of dihematoporphyrin ether differed in a statistically significant manner. Transcutaneous fluorometric determination of dihematoporphyrin ether content and extraction of dihematoporphyrin ether from skin samples were able to reflect differences in dihematoporphyrin ether dosing and presumably skin dihematoporphyrin ether content. However, transcutaneous fluorometry provides an instantaneous estimate of tissue dihematoporphyrin ether without the need for a tissue sample. This may provide a clinical tool to predict more accurately the optimal light dose necessary to maximize photodynamic therapy.

Animals

In vitro photodynamic treatment of normal and human papilloma virus-transfected keratinocytes with photofrin II and red light.

Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer to result in tissue destruction. The photosensitizer dihematoporphyrin ether and red light were used to treat normal and human papilloma virus type 18-transfected keratinocytes in vitro. Although both cell lines were sensitive to treatment, normal keratinocytes retained more dihematoporphyrin ether and were more sensitive to photodynamic therapy than were transfected cells. In vitro data fail to show the selective retention of dihematoporphyrin ether reported elsewhere in the literature in papillomas and tumors. We did not find selective uptake or retention of dihematoporphyrin ether by human papilloma virus-transfected cells, despite previously published in vivo data to the contrary. Dihematoporphyrin ether retention and thus selective photosensitivity of papillomas in vivo is not caused by individual cellular differences in the processing of dihematoporphyrin ether. In addition, because in vitro results may not parallel in vivo results, both in vivo and in vitro models must be investigated in the study of phototherapeutic agents.

Antiviral Agents

Real-time color duplex scanning after sclerotherapy of the greater saphenous vein.

A color real-time duplex scanner was used to scan the greater saphenous vein in 89 limbs of 55 patients to study the efficacy of prior greater saphenous vein sclerotherapy. The greater saphenous vein was insonated from the saphenofemoral junction to the knee to evaluate both reflux to a standardized 30 mm Hg Valsalva maneuver and evidence of greater saphenous vein obliteration by sclerotherapy. These data were correlated with the number of sclerosing injections used (mean, 1.8; range, 1 to 6), time from the last injection (mean, 27.5 mo.; range, 3 to 55 mo), and concentration of injectant used (0.5% to 3% sodium tetradecyl sulfate). Fifty-one of 89 injected limbs (57%) demonstrated reflux through the saphenofemoral junction, and reflux down the more distal greater saphenous vein was found in 67 of 89 injected limbs (75%). Greater saphenous vein obliteration was noted in only 18 of 89 injected limbs (20%); two were totally obliterated, and 16 were partially obliterated. The greater saphenous vein was obliterated in 6% below a refluxing saphenofemoral junction and in 40% below a nonrefluxing junction. A greater saphenous vein obliteration rate of 9% was found with a refluxing greater saphenous vein, and 50% in a nonrefluxing greater saphenous vein. Femoral vein reflux was identified in 11 of the 110 limbs (10%) and in every case was associated with both saphenofemoral junction and greater saphenous vein reflux. We noted a trend toward more successful results with more concentrated injectate (3% sodium tetradecyl sulfate). Fifty percent of patients reported improvement in symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Utility of computed tomography for surveillance of small abdominal aortic aneurysms. Preliminary report.

To assess the ability of computed tomography to predict the potential for expansion of small abdominal aortic aneurysms, we analyzed the computed tomographic scans of 30 patients who had two or more abdominal computed tomographic scans at least 6 months apart between 1979 and 1989. Clinical variables and 10 defined objective characteristics of computed tomography were evaluated. Twenty-five men and five women with abdominal aortic aneurysms ranging from 30 to 64 mm (mean, 45 mm) were followed up with serial computed tomographic scans for a mean (+/- SE) of 26 +/- 3 months. In 19 patients, enlargement of aneurysm diameter of 3 mm or more on serial computed tomographic scans was noted, whereas in 11, there was little or no expansion. Of the clinical variables studied, only serum cholesterol correlated with an increased risk of expansion. Thrombus area, measured by computed tomography, was 7.3 +/- 0.9 cm2 in enlarging aneurysms vs 4.3 +/- 0.9 cm2 in stable aneurysms. Based on these preliminary data, we conclude that computed tomography may provide valuable information about the likelihood of future expansion of small abdominal aortic aneurysms.

Adult

The natural history of amaurosis fugax with minor degrees of internal carotid artery stenosis.

The natural history of amaurosis fugax with hemodynamically insignificant degrees of internal carotid artery stenosis is uncertain. Seventy-three patients over age 40 who presented with amaurosis fugax without obvious cause and had ipsilateral stenoses of 50% or less with carotid duplex scanning were followed for a mean period of 35.5 months (range 3-110) without surgical intervention. At the initial vascular laboratory duplex evaluation, 35 patients had normal arteries (47.9%), 29 had minor (0-19%) stenoses of the ipsilateral internal carotid arteries (39.7%), and 11 had 20-50% stenosis (15.1%). Four patients with 0-19% stenosis and one patient with 20-50% stenosis experienced a subsequent stroke or permanent ipsilateral blindness. When analyzed by life-table format, stroke, blindness, and early death were more frequent in patients with minor degrees of stenosis than in those with normal arteries. Investigations in all patients with amaurosis fugax should be aimed at identifying whether the symptoms are explained by arteriosclerotic, systemic, collagen, cardiac, hematologic, or ophthalmologic disease. When no other etiology is found, and localized carotid bifurcation atherosclerosis of even modest degrees is identified, an atheroembolic etiology should be considered.

Aged