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Biomedical subjects

B S Allen

Publications and source records attributed to B S Allen.

At least 73 records · Page 4Linked to original sources

Electron microscopic studies: importance of embedding techniques in quantitative evaluation of cardiac mitochondrial structure during regional ischemia and reperfusion.

This study applies the low protein-denaturation embedding technique for mitochondrial preparation to analyze control cardiac tissue, heart muscle subjected to 6 hours of regional ischemia without reperfusion, and myocardial tissue subjected to 4 to 6 hours of ischemia followed by reperfusion either with normal blood, with the heart in the beating, working state, or with substrate-enriched blood cardioplegia during total vented bypass. Parallel specimens of cardiac tissue were analyzed for ultrastructure by the conventional osmium tetroxide fixation method. Results following conventional tissue preparation with osmium tetroxide showed extensive ultrastructural damage in all hearts subjected to ischemia, with no correlation between ultrastructural findings and methods of reperfusion or functional recovery. In contrast, results following tissue preparation by the low protein-denaturation method showed reperfusion with normal blood in working hearts to cause severe mitochondrial damage, cardiac mitochondria that were intact structurally after 6 hours of ischemia and after controlled reperfusion, a logical sequence of mitochondrial structural changes that may lead to irreversibility, and a new method of quantification of such changes.

Animals↗

High oxygen requirements of dyskinetic cardiac muscle.

This study assesses the regional oxygen requirements of muscle segments that are beating and working, beating and empty, arrested and decompressed, and nonischemic that move dyskinetically. Regional oxygen demands were evaluated by producing a dyskinetic segment by infusing regional cardioplegic solution through a left anterior descending coronary artery catheter with and without extracorporeal circulation. The results show that the O2 demands of the perfused dyskinetic cardiac muscle segment (4 to 8 ml/100 gm/min) are approximately 55% of the contracting (beating, working) segment (7 to 12 ml/100 gm/min) and are fivefold more than when the same muscle segment is arrested and decompressed by total vented bypass (0.8 to 1.2 ml/100 gm/min). Additional studies showed that ischemia for 2 hours (left anterior descending coronary artery ligation) produced severe dyskinesia (-24% control systolic shortening), which failed to recover after reperfusion with the heart in the beating, working state. In contrast, lowering O2 demands by reperfusion during bypass restored occasional contractile function as a consequence of left ventricular decompression. Dyskinetic muscle segments have a high oxygen requirement that may affect their capacity to be salvaged if reperfusion is conducted without left ventricular decompression. These observations suggest that the value of revascularization in the working heart (i.e., streptokinase with or without angioplasty) may be limited unless the left ventricle is decompressed during reperfusion and provide an explanation for the delayed recovery of mechanical function in hearts reperfused surgically with normal blood during cardiopulmonary bypass.

Animals↗

Regional blood cardioplegic reperfusion during total vented bypass without thoracotomy: a new concept.

This study tests the hypothesis that immediate functional recovery is possible after 2 to 3 hours of regional ischemia by control of the conditions of reperfusion (i.e., total vented bypass) and the composition of the reperfusate (substrate-enriched blood cardioplegic solution) by either central cannulation with thoracotomy or peripheral cannulation without thoracotomy. Total vented bypass could be established successfully in each of 14 experiments (100%) in which the peripheral cannulation method was tested. Regional function (evaluated by ultrasonic crystals in open-chest animals) recovered comparably when substrate-enriched blood cardioplegic solution was given either globally or regionally (46% versus 36%) and total vented bypass was accomplished by either central cannulation or peripheral cannulation technique (i.e., left ventricle decompressed through a transaortic vent catheter, right atrium cannulated through the femoral vein, femoral artery perfusion). In contrast, systolic bulging persisted (-23% control systolic shortening) following normal blood reperfusion in beating, working hearts. Controlled reperfusion (either global or regional) also minimized postischemic edema (81% versus 83% water content, p less than 0.05). The effectiveness of controlled reperfusion (substrate-enriched blood cardioplegic solution during total vented bypass) versus uncontrolled reperfusion (normal blood in beating, working hearts) was assessed also in closed-chest dogs with 3 hours of regional ischemia (i.e., balloon inflation in the left anterior descending coronary artery). Results after controlled reperfusion showed complete recovery of contractility (as shown by echocardiography) at 24 hours, in comparison with only minimal recovery in three of eight dogs receiving uncontrolled reperfusion, and minimal histochemical damage (less than 5% triphenyltetrazolium chloride nonstaining), in comparison with 34% necrosis after uncontrolled reperfusion. These studies suggest that control of the reperfusion conditions and reperfusate composition can be achieved comparably in either the catheterization laboratory or the operating room, and a proposed clinical model for the treatment of patients with acute myocardial infarction is presented for evaluation.

Animals↗

Reperfusate composition: benefits of marked hypocalcemia and diltiazem on regional recovery.

This study tests the hypothesis that improved muscle salvage is possible by markedly reducing the ionic calcium (Ca++) of the reperfusate (less than 250 mumol/L) and adding a calcium channel-blocking drug (diltiazem). Preliminary pilot studies showed that a 20-minute infusion of markedly hypocalcemic substrate-enriched blood cardioplegic solution (less than 250 mumol/L Ca++) did not affect left ventricular function adversely and that a 150 to 250 mumol/L substrate-enriched blood cardioplegic solution, delivered during total vented bypass with diltiazem, 300 micrograms/kg body weight, produced the most consistent functional recovery and the least histochemical evidence of damage (triphenyltetrazolium chloride nonstaining) after 2 hours of regional ischemia. Experimental studies of 2 hours of regional ischemia were followed by either regional normocalcemic (1000 to 1200 mumol/L) blood cardioplegic reperfusion in bypassed hearts, with or without diltiazem, or hypocalcemic (150 to 150 mumol/L) blood cardioplegic reperfusion with diltiazem for 20 minutes. Results showed that hypocalcemic blood cardioplegic solution with diltiazem produced superior recovery of systolic shortening (58% versus 11% systolic shortening, p less than 0.05) and limitation of histochemical damage (11% versus 54%, p less than 0.05), in comparison with normocalcemic blood cardioplegic solution without diltiazem. These studies suggest that modifying the regional reperfusate by markedly reducing ionic calcium levels and adding calcium channel-blocking drugs is safe and may improve myocardial salvage more than using substrate-enriched blood cardioplegic solution alone.

Animals↗

Reperfusate composition: supplemental role of intravenous and intracoronary coenzyme Q10 in avoiding reperfusion damage.

This study tests the hypothesis that the oxygen radical scavenger coenzyme Q10 can be given both intravenously and in the cardioplegic solution and can improve muscle salvage following surgical revascularization. Pilot studies were carried out in dogs undergoing 40 minutes of coronary artery ligation with reperfusion with normal blood, with the heart in the beating, working state. Intravenous infusions of coenzyme Q10 (10 mg/kg) 5 minutes before reperfusion resulted in improved recovery of creatine phosphate, adenosine triphosphate, total adenine nucleotide, and myocardial function reverse estimated by postextrasystolic potentiation, in comparison with the degree of recovery in untreated dogs. Experimental studies were done on 27 dogs undergoing 2 hours of left anterior descending coronary artery occlusion and subsequent reperfusion with and without total vented bypass. Thirteen dogs received intravenous coenzyme Q10 10 minutes before extracorporeal circulation, six received substrate-enriched blood cardioplegic solution with added coenzyme Q10, and six received normal blood reperfusate. Six others had cardioplegic reperfusion without coenzyme Q10. The systolic bulging that occurred during ischemia (ultrasonic crystals) persisted after reperfusion with normal blood (-25% systolic shortening, p less than 0.05), and 44% transmural triphenyltetrazolium chloride nonstaining occurred in the area at risk. Conversely, hearts receiving substrate-enriched blood cardioplegic solution recovered 37% contractility (p less than 0.05), with the least, and only, subendocardial triphenyltetrazolium chloride nonstaining (25% of area at risk) occurring with intravenous coenzyme Q10 before bypass and coenzyme Q10 supplementation of the cardioplegic solution. Intravenous coenzyme Q10, given just before reperfusion (possibly in transit to the operating room), enhances the role of substrate-enriched blood cardioplegic solution (especially when added to the cardioplegic solution) in salvaging ischemic myocardium and allowing immediate functional recovery.

Adenosine Triphosphate↗

Reperfusate composition: interaction of marked hyperglycemia and marked hyperosmolarity in allowing immediate contractile recovery after four hours of regional ischemia.

This study tests the hypothesis that improved muscle salvage after prolonged ischemia (4 hours) occurs when the substrate-enriched blood cardioplegic solution is markedly hyperglycemic (greater than 400 mg/dl) and markedly hyperosmotic (greater than 400 mOsm). Thirty-five dogs underwent 4 hours of occlusion of the left anterior descending coronary artery and reperfusion during total vented bypass with substrate-enriched blood cardioplegic solution, in which the glucose concentration and osmolarity were varied in relation to one another. Spontaneous systolic shortening recovered consistently (31 +/- 6%) only when glucose was greater than 400 mg/dl and osmolarity was greater than 400 mOsm. The least recovery occurred (only one of six dogs recovering spontaneous shortening) when cardioplegic glucose was greater than 400 mg/dl and osmolarity was greater than 400 mOsm. Regional segments reperfused with our standard substrate-enriched blood cardioplegic solution had lower transmural flow rates following reperfusion (56 versus 87 ml/100 gm/min, p less than 0.05), markedly reduced mitochondrial State 3 and State 4 respiration in epicardial and endocardial muscle (p less than 0.05), and the most extensive histochemical evidence of damage (63% area of nonstaining versus area at risk, p less than 0.05). We conclude that markedly increased levels of osmolarity (greater than 400 mOsm) and glucose (greater than 400 mg/dl) improve the capacity of substrate-enriched blood cardioplegic solution to salvage myocardium after prolonged ischemia.

Animals↗

Effects of "duration" of reperfusate administration versus reperfusate "dose" on regional functional, biochemical, and histochemical recovery.

This study tests the hypothesis that improved myocardial salvage following regional ischemia occurs when attention is directed toward the duration of blood cardioplegic reperfusion rather than the reperfusate "dose". Pilot studies after global ischemia established the postischemic oxygen use pattern consistent with normal and impaired recovery; the best recovery occurred when postischemic muscle consumed oxygen in excess of basal demands. Experimental studies were then performed on 22 dogs undergoing 2 hours of left anterior descending coronary occlusion. Nine dogs received normal blood reperfusion, with the heart allowed to remain in the beating, working state. In 13 dogs, cardiac O2 demands were kept low during reperfusion by delivering a dose of 150 to 250 mumol/L Ca2++ aspartate-glutamate-enriched blood cardioplegic solution containing 250 to 350 micrograms/kg body weight diltiazem during total vented bypass. This same reperfusate dose with diltiazem was given over 10 minutes in five dogs and over 20 minutes in eight others. Persistent systolic bulging (ultrasonic crystals) of -27% (p less than 0.05) of systolic shortening followed normal blood reperfusion without bypass. During blood cardioplegic reperfusion, regional O2 uptake exceeded basal demands by 24 ml/100 gm/min at 10 minutes (p less than 0.05) and did not return to baseline until 20 minutes had elapsed. Hearts reperfused with blood cardioplegia for 20 minutes had better recovery of systolic shortening (58% versus 30%, p less than 0.05), less edema (79.8% versus 80.9% water content, p less than 0.05), and less triphenyltetrazolium chloride nonstaining (12% versus 21%, p less than 0.05) than those reperfused for 10 minutes with the same solution containing the same diltiazem dose. Continuing blood cardioplegic reperfusion until myocardial oxygen uptake reaches control levels enhances regional functional recovery after acute coronary occlusion. These results indicate that attention should be directed toward the duration of reperfusion, as well as the "dose" of cardioplegic reperfusate.

Animals↗

Reperfusion conditions: importance of ensuring gentle versus sudden reperfusion during relief of coronary occlusion.

This study tests the hypothesis that more muscle salvage after acute ischemia is possible by "gentle," temporary reperfusion than with sudden, complete revascularization. Ten dogs underwent 4 hours of left anterior descending coronary artery ligation with reperfusion during total vented bypass for 1 hour of the 2-hour reperfusion period. In five dogs, reperfusion was accomplished by release of the occlusion suddenly and completely. The five others received selective low-pressure (40 to 50 mm Hg) coronary reperfusion with normal blood for 20 minutes at 30 ml/min before the occlusion was relieved completely. Systolic shortening with ultrasonic crystals, triphenyltetrazolium chloride staining, and myocardial wet and dry weights were measured. Sudden relief of occlusion failed to restore contractility spontaneously (-7 +/- 1% systolic shortening, p less than 0.05) or with inotropic infusion (-2 +/- 4% systolic shortening, p less than 0.05) and caused the greatest amount of edema (82.2%, systolic shortening, p less than 0.05) and triphenyltetrazolium chloride nonstaining (76% area at risk, p less than 0.05). In contrast, temporary, gentle reperfusion allowed slight spontaneous recovery in four of five hearts (4 +/- 2% systolic shortening), increasing to 26 +/- 12% systolic shortening (p less than 0.05) with inotropic stimulation, limited edema (80.7%, p less than 0.05), and reduced triphenyltetrazolium chloride nonstaining to 55% (p less than 0.05). Early temporary, gentle reperfusion limits the postischemic damage that occurs with sudden, complete revascularization (aortic unclamping without control of reperfusion pressure or flow). These findings may have implications during revascularization for acute myocardial infarction when perfusion pressure and flow can be controlled.

Animals↗

Multicentric reticulohistiocytosis.

Multicentric reticulohistiocytosis is a histiocytic disorder affecting primarily skin and joints but occasionally involving other organ systems as well. A case is presented and the disease is reviewed, including discussion of historical, clinicopathologic, radiologic, etiologic, therapeutic, and prognostic aspects.

Adolescent↗

Acrodermatitis continua of Hallopeau: treatment with etretinate and review of relapsing pustular eruptions of the hands and feet.

Acrodermatitis continua of Hallopeau is considered by many to be a variant of pustular psoriasis because of similar histologic features. Its clinical picture is unique and helps to distinguish acrodermatitis from pustular psoriasis. We present a patient with acrodermatitis continua of Hallopeau resistant to conventional therapy. We describe the beneficial effect of etretinate in this patient.

Acrodermatitis↗

Junctional epidermolysis bullosa. Treatment with phenytoin.

Junctional epidermolysis bullosa (EB) is a rare, heritable, blistering disease of the skin characterized by presence of bullae at birth, lack of scarring of the lesions, and early death. To date there has been no effective treatment for the disease. Phenytoin, which decreases collagenase activity in human skin explants and fibroblast cultures, has been used successfully to treat patients with recessive dystrophic EB. We found a marked decrease in new blister formation in one child with junctional EB during phenytoin therapy.

Diagnosis, Differential↗

Phenytoin therapy for junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is a recessively inherited mechanobullous disease characterized by neonatal onset of blisters, healing without scarring or milium formation, dystrophic nails, and internal involvement in some patients. Several treatment modalities have been tried, including systemic corticosteroids and oral vitamin E, but no form of therapy has been uniformly successful. We describe a patient with JEB treated with phenytoin, followed by improvement in his skin lesions.

Adolescent↗

Use of colchicine in the treatment of Behçet's disease.

To date, various treatment modalities have failed to produce consistent improvement in patients having Behçet's disease. Recent reports in the literature, however, have shown promising results with the use of colchicine. Our patient, an 18-year-old white woman, satisfied the 1977 Istanbul Conference criteria for Behçet's disease by exhibiting ocular inflammation and a five-year history of severe, recurrent oral and vaginal ulcerations. She was treated with 0.6 mg of colchicine orally twice daily, and at the end of two weeks of treatment, the oral lesions had completely resolved, and the vaginal ulcers were reduced in diameter and depth to at least one half. Within one month all oral and vaginal ulcers were completely healed.

Adolescent↗

Various parameters for grading acne vulgaris.

Two 12-week-long double-blind placebo-controlled studies of acne treatments were performed using three judges and a total of 331 male college students. Global severity grades and papule, pustule, and comedo counts were performed every two weeks. The data were evaluated using Pearson's coefficient of correlation, and results showed a high degree of correlation between global severity grades and lesion counts, as well as among judges. These data suggest that acne grading scales and papule counts are equally reproducible methods of grading inflammatory acne and that the comedo grading scale and comedo count are equally reproducible methods of grading comedonal acne.

Acne Vulgaris↗

Topical erythromycin with zinc in acne. A double-blind controlled study.

This double-blind controlled study investigated the effectiveness of 4% topical erythromycin liquid with 1.2% zinc acetate and 4% topical erythromycin gel with 1.2% zinc octoate applied twice daily in comparison with 250 mg of oral tetracycline twice daily and placebo. One hundred forty-nine patients began and one hundred forty-one completed the study. Three judges recorded acne measurements of severity grade, papule counts, pustule counts, comedo grades, and comedo counts without mutual consultation on visits at 0, 2, 4, 6, 8, and 10 weeks. Analysis of the reduction in the acne severity grade and papule count showed that the erythromycin/zinc liquid and gel were statistically significantly better than placebo and as effective as the oral tetracycline. Analysis of comedo grades showed that at weeks 8 and 10 the 4% topical erythromycin/zinc liquid showed a reduction statistically better than placebo.

Acne Vulgaris↗

Multiple hamartoma syndrome. A report of a new case with associated carcinoma of the uterine cervix and angioid streaks of the eyes.

Multiple hamartoma syndrome is a genodermatosis with autosomal-dominant inheritance. Characteristic findings include mucocutaneous verrucoid papules, "cobblestoning" of the tongue, and hamartomas of multiple organ systems. Also reported are frequent malignancies, especially of the breast. Herein we report a case of a 42-year-old black woman with typical findings of multiple hamartoma syndrome, including an occult malignancy of the uterine cervix, an as yet unreported site of carcinoma in this syndrome. Additionally, we detail a previously unreported finding of bilateral angioid streaks of the optic fundi. Photographs displaying many of the typical features of multiple hamartoma syndrome and associated histopathology are included, along with a brief review of the literature.

Adult↗