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Biomedical subjects

E B Smith

Publications and source records attributed to E B Smith.

At least 55 records · Page 3Linked to original sources

Topical antifungal drugs in the treatment of tinea pedis, tinea cruris, and tinea corporis.

Topical treatment of fungal infections took a step forward in the 1960s with the introduction of biologically active agents with specific antifungal mechanisms of action. Most modern broad-spectrum antifungal agents act by blocking specific steps in the synthesis of fungal cell membrane components. The broad-spectrum topical antifungal drugs now in use include the imidazoles (e.g. clotrimazole and miconazole), a pyridone-ethanolamine salt, dimethylmorpholines, and the newest class, the allylamines (e.g., naftifine and terbinafine). The topical allylamines have been shown in comparative studies to produce higher cure rates and more rapid responses in dermatophyte infections than many of the older agents.

Antifungal Agents↗

Fibrinogen and atherosclerosis.

Fibrin appears to be a multi-potential component of atherogenesis, intervening at virtually all stages of lesion development. Fibrin and microthrombus deposition on normal intima is associated with endothelial disruption and intimal oedema, and oedema is a primary characteristic of early proliferative lesions. Fibrin strands on or in the intima encourage smooth muscle cell (SMC) migration and proliferation, and contribute to the growth of plaques. Fibrin also provides a continuing source of fibrin degradation products (FDP), and these have mitogenic activity which will sustain SMC proliferation in growing plaques, and act as chemoattractants for blood leucocytes. Accumulation of the lipid core in fibrous plaques may also be influenced by fibrin which appears to bind the lipoprotein Lp(a) with high affinity, thereby immobilizing its lipid moiety within the lesion.

Arteriosclerosis↗

Fibrin degradation products in growth stimulatory extracts of pathological lesions.

We have previously shown that similar patterns of fibrin degradation products (FbDP) by gel electrophoresis and immunoblotting are present in extracts of human atherosclerotic plaques, human and experimental wounds and breast cancers. Such extracts were also shown to stimulate cell proliferation including angiogenesis in the chick chorioallantoic membrane, now shown also for breast cancers. Removal of FbDP from plaque extracts by an anti-fibrinogen affinity column, or by an anti-fragment E column, reduced activity. Human FbDP prepared in vitro were active, but not FgDP. Fibrin fragment E was active, and we also showed that admixture of FbDP with a polyclonal rabbit anti-fibrin E but not anti-fibrin D neutralized activity. However attempts to raise comparable monoclonal blocking antibodies were hindered by species similarities. The response of the Balb/c mouse was predominantly directed at minor D contaminants, in contrast to the Sprague-Dawley rat which responded to fibrin fragment E in our antigen preparation.

Animals↗

Angiogenic activity of fibrin degradation products is located in fibrin fragment E.

The source of angiogenic activity of fibrin degradation products has been sought in a series of experiments, applying degradation products from different types of fibrin and fibrinogen to the chick chorioallantoic membrane. The presence of platelets or fibronectin during clotting was not essential for activity, and neither was crosslinking. Fibrinogen degradation products were non-stimulatory, as was serum. Molecular sieve column chromatography indicated a range of active fragments. Admixture of active fibrin degradation products with antifibrin fragment E, but not D, antiserum neutralized activity. Preparations containing only fibrin fragment E retained activity. A commercial preparation of fibrinogen fragment E was inactive until treated with thrombin. These experiments point to fibrin fragment E being the source of angiogenic activity, with thrombin cleavage being the essential step in generating activity.

Animals↗

Fibrinogen/fibrin in atherogenesis.

Fibrin is a major component of many atherosclerotic plaques. Within the intima there is continuous formation of fibrin, and continuous fibrinolysis. In aortic lesions, a lipoprotein bound to fibrin can be released by incubation with plasmin. Most of this lipoprotein is accounted for by Lp(a). The atherogenicity of Lp(a) may be more associated with lipid deposition than with inhibition of fibrinolysis. Fibrin degradation products may be chemotactic to monocyte-macrophages and stimulate smooth muscle cell proliferation.

Antigens↗

Surgical results and complications in elderly patients with benign lesions of the spinal canal.

OBJECTIVE: To describe the long-term outcome and complications of spinal surgery in a population of elderly patients. DESIGN: Retrospective chart review and clinical follow-up. SETTING: A 700-bed tertiary care midwestern hospital. PATIENTS: Patients 70 years of age or older who underwent elective surgical procedures for the treatment of benign lesions of the spinal canal. MAIN OUTCOME MEASURES: Data obtained from chart review included age, sex, nature and duration of neurological symptoms, activities of daily living (ADL), associated illnesses, length of hospitalization, type of surgery, and complications attributable to surgery. Outcome measurements included changes in neurological symptoms and ADL and a standardized scale obtained from consecutive outpatient visits, telephone interviews, or written responses. RESULTS: Seventy-eight patients with lumbar canal stenosis or soft disc herniations underwent laminectomies, foraminotomies or discectomies. Eleven patients underwent cervical laminectomies for multilevel spondylitic myelopathy. Limb and spine pain were the most common neurological symptoms in patients with lumbar lesions; diminished ADLs were present in eight patients with cervical myelopathies. Six patients died of unrelated causes, and 78 were followed for an average of 27.1 months. Twenty-three (85.2%) of 27 patients with lumbar disc herniations reported improvements or resolution of limb pain while 35 (81.4%) of 43 patients with lumbar canal stenosis reported fair or good results. Five of eight patients with multilevel cervical spondylosis reported improvements of myelopathic symptoms. Twenty-six (28.6%) complications were attributable to 91 surgical procedures including five severe complications and one fatality. Patients with three or more associated illnesses demonstrated a significantly higher incidence of postoperative complications. CONCLUSIONS: Elderly patients with benign lesions of the spinal canal may achieve significant reduction in limb pain and increases in ADL following appropriate surgery, with a tolerable rate of severe complications. The preoperative physical condition of the elderly patient served as an indicator for operative morbidity.

Activities of Daily Living↗

Complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy with lasers or cautery is a feasible, effective, and worthwhile operative procedure that is subject to morbidity and mortality. There is unequivocal evidence that the complication incidence is directly related to the training and experience of the surgeon, applicability of basic principles of gallbladder and common duct surgery, and preventive measures toward iatrogenic injuries in gallbladder surgery. Continued and sustained investigation in laparoscopic cholecystectomy, technological developments in equipment, and the continued education of the surgeon in the applicability and use of laparoscopic cholecystectomy, intraoperative cholangiography, and choledocholithotomy are essential. At the St Francis Medical Center, Pittsburgh, Pennsylvania 1009 laparoscopic cholecystectomies with lasers or cautery were performed between March 1989 and October 1991. There were 32 (3%) abandoned laparoscopic cholecystectomies with alternative open cholecystectomy. There were six extrahepatic ductal injuries and a complication incidence of 10.9%. The mortality rate was 0.38%. The average length of stay was 2 days. In comparison with standard cholecystectomy, laparoscopic cholecystectomy is a competitive and superior procedure in selected circumstances.

Bile Ducts↗

Does lipoprotein(a) (Lp(a)) complete with plasminogen in human atherosclerotic lesions and thrombi?

Thrombotic occlusion is the major cause of myocardial infarction (MI), and fibrin accumulation appears to play a significant role in development of atherosclerotic lesions. Any factor that reduces the lysis of fibrin may thus increase the risk of MI, and it has been suggested that this accounts for the atherogenicity of the lipoprotein variant Lp(a). The characteristic feature of Lp(a) is an apoprotein which is homologous with part of the plasminogen molecule, and experiments in vitro suggest that it interferes with uptake and activation of plasminogen on cell surfaces and fibrin. The presence of Lp(a) also seemed to offer an explanation for the apparent absence of plasminogen from 70-80% of intimal samples. We have compared the levels of Lp(a) and plasminogen in normal intima and atherosclerotic lesions. In aortic intima there was no relation between Lp(a) and plasminogen, which was absent in some samples with no Lp(a), and present in others with high levels. In intravascular thrombi plasminogen was present at a rather constant concentration (16.3 +/- 4.6 micrograms/100 mg wet tissue), whereas Lp(a) varied over a 100 fold range (0-104 micrograms/100 mg). Plasminogen binds to fibrin and is activated on the fibrin clot, so levels in extracts may not fully represent Lp(a)/plasminogen interactions. After extraction the residual tissues and thrombi were treated with 1 M epsilon-aminocaproic acid (epsilon-aca) to elute lysine-bound components. Lp(a) was eluted from all but one intimal sample, confirming previous findings on its binding to fibrin in lesions, but there was no relation between the amounts of Lp(a) and plasminogen in the tissue eluates. Paradoxically, in the thrombi there was a weak positive correlation between Lp(a) and plasminogen in epsilon-aca eluates (r = 0.504, P = 0.05). These results do not support the hypothesis that Lp(a) displaces plasminogen in vivo, but the large amount of Lp(a) eluted by epsilon-aca suggests that its atherogenicity resides in preferential binding to fibrin, leading to increased lipid accumulation in lesions.

Adult↗

Treatment of necrolytic migratory erythema in glucagonoma syndrome.

The glucagonoma syndrome is characterized by elevated serum glucagon, a pancreatic alpha-cell tumor, anemia, hypoaminoacidemia, and necrolytic migratory erythema. Necrolytic migratory erythema may cause marked morbidity and is frequently misdiagnosed. A 42-year-old white woman with a 1 1/2-year history of refractory dermatitis (most severe on the lower extremities) had the glucagonoma syndrome. Her severe morbidity was markedly relieved with the administration of intravenous amino acids. This therapy was successful in controlling the necrolytic migratory erythema through recurrences after somatostatin (SMS 201-995), surgical debulking, and chemotherapy proved inadequate.

Adult↗

Effects of general anesthetics and pressure on mammalian excitatory receptors expressed in Xenopus oocytes.

The effects of general anesthetics and pressure on receptors from the mammalian central nervous system have been investigated using oocyte expression techniques. Poly A+ mRNA extracted from rat whole brain was injected into mature Xenopus oocytes producing depolarizing responses to the fast excitatory neurotransmitters NMDA and kainate and the inhibitory neurotransmitters GABA and glycine. An apparatus was constructed to allow agonist dose-response curves to be determined at high pressures using voltage-clamped oocytes. This was used to investigate the excitatory transmitter kainate. It was found that anesthetics depress the current induced by kainate whereas pressure does not appear to affect the responses associated with this transmitter. Furthermore it was found that pressure does not reverse (or modify in any way) the changes in response brought about by application of anesthetics.

Animals↗