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Breast Neoplasms/MO/*RT/SU; Carcinoma/MO/*RT/SU; Comparative Study; Female; Follow-Up Studies; Human; Mastectomy; Neoplasm Recurrence, Local/*PC; Postoperative Care/*; Radiotherapy Dosage; Radiotherapy, High-Energy; Time Factors.

Is it necessary to irradiate the breast after conservative surgery for localized cancer?

JOURNAL ARTICLE.

Two hundred one patients with operable breast cancer received postoperative irradiation after limited surgery and were followed up for five years. Fifty-three patients (26%) had positive margins. The breast cancer recurrence rate at five years was 14%, less than half the incidence reported for patients treated by limited surgery only. Those with positive margins who received irradiation had a recurrence rate of only 13%. Another 324 patients with tumors (less than or equal to 3 cm) N0 who were treated similarly were evaluated for distant dissemination in relation to local control. Patients who remained free of local disease or developed recurrences more than five years after treatment had significantly better distant disease-free and overall survival than patients who failed locally within five years. Breast irradiation after conservative surgery resulted in decrease in local recurrence and reduced the need for salvage mastectomy. Long-term follow-up of a large number of patients is necessary to determine the relation between local control and the decreased risk of distant dissemination.

Ghossein NA; Vilcoq J; Stacey P; Asselain B.

Arch Surg 8712; 122(8):913-7

Adult; Aged; Bacteria/IP; Bile/ME/MI; Biliary Tract/*SU; Biliary Tract Surgery/*; Cefazolin/*AD/AE/ME; Cholecystectomy; Clinical Trials; Comparative Study; Double-Blind Method; Female; Gallbladder/ME; Human; Male; Middle Age; Moxalactam/*AD/AE/ME; Premedication/*; Prospective Studies; Random Allocation; Surgical Wound Infection/EP.

Single-dose antibiotic prophylaxis for biliary surgery. Cefazolin vs moxalactam.

CLINICAL TRIAL; JOURNAL ARTICLE.

Cefazolin was compared with moxalactam for single-dose prophylaxis against infection in a double-blind, prospective, randomized trial of 90 patients undergoing cholecystectomy. Risk factors for infection were present in 65 (72%) of the 90 patients and were evenly distributed. Antibiotic levels in plasma, bile, and tissue measured when the cystic duct was divided were similar for both drugs. Age greater than 65 years but not recent cholecystitis or type of antibiotic was predictive of recovery of bacteria from bile cultures. Wound infections occurred in two patients receiving cefazolin and one patient receiving moxalactam for an overall infection rate of 3%. No toxic reactions to antibiotics, including bleeding disorders, were observed. In conclusion, no significant difference in prophylactic efficacy was detected in this comparison of a first-generation with a third-generation cephalosporin. Because of its lower cost and narrower antimicrobial spectrum, however, cefazolin should remain the agent of choice.

Kellum JM; Duma RJ; Gorbach SL; Sugerman HJ; Haynes BW Jr; Gervin A; Newsome HH.

Arch Surg 8712; 122(8):918-22

Animal; Carbon Dioxide/BL; Comparative Study; Escherichia coli Infections/CO; Female; Hemodynamics/DE; Leukocyte Count; Lung/DE; Male; Naloxone/PD/*TU; Oxygen/BL; Respiration/DE; Respiratory Insufficiency/*PC; Shock, Septic/*CO; Swine; Ventilation-Perfusion Ratio.

Prevention of septic ventilatory depression with naloxone.

JOURNAL ARTICLE.

Little is known of the endorphins' role in sepsis-induced respiratory distress and naloxone's effect as a treatment of it. Thirteen piglets were infused with live Escherichia coli at a rate of 2 to 10 X 10(8) colony-forming units per hour for six hours or until death and were divided into two groups: the septic control group (n = 8), and the naloxone-treated group (n = 5), which received 8 mg/kg/h of naloxone by continuous infusion. Hemodynamic parameters, the intrapulmonary shunt fraction (QS/QT), physiologic dead space (VD/VT), minute ventilation, and blood gas levels were measured. Lung lymph flow was obtained by cannulating the right lymphatic duct. The extravascular lung water weight was also measured. The results showed a significant reduction of QS/QT, VD/VT, and arterial carbon dioxide pressure at one hour and a significant increase of arterial carbon dioxide pressure and minute ventilation at 1, 3, and 4 hours in the naloxone-treated group, compared with the untreated septic group. None of the piglets in the naloxone-treated group developed ventilatory depression, while 75% of those in the untreated septic group did. Among the latter piglets, three died of apnea within one hour. These beneficial effects of naloxone are likely related to its action on the central and peripheral respiratory regulatory mechanisms. A transient protection of the cardiac output and relatively decreased extravascular lung water with naloxone treatment may also, in part, improve the ventilation-perfusion maldistribution and secondarily reduce QS/QT and VD/VT. We conclude that endorphins play a role in septic ventilatory depression and that naloxone is effective in ameliorating it.

Chuang GJ; Gao CX; Mulder DS; Chiu RC.

Arch Surg 8712; 122(8):940-5

Adolescence; Adult; Child; Child, Preschool; Clinical Trials; Comparative Study; Cost-Benefit Analysis; Human; Muscles/PP; Muscular Dystrophy/*DT/PP; Prospective Studies; Random Allocation; Research Design; Respiratory Function Tests; Software; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors.

Clinical investigation of Duchenne muscular dystrophy. A methodology for therapeutic trials based on natural history controls.

CLINICAL TRIAL; JOURNAL ARTICLE.

Between 1979 and 1987 we documented the natural history of Duchenne muscular dystrophy in 170 patients, aged from 3 to 23 years, by making serial measurements in over 5000 individual evaluations. This database makes it possible to design and conduct therapeutic trials using natural history controls. Such trials do not replace the need for randomized placebo-controlled trials of promising agents but they do require fewer patients, are cost-effective, and permit the use of high-risk therapy where toxicity monitoring may be important. Natural history-controlled trials, therefore, may serve as a screening method for new therapeutic agents. Drugs showing a significant benefit can then be evaluated in a randomized controlled trial.

Mendell JR; Province MA; Moxley RT 3d; Griggs RC; Brooke MH; Fenichel GM; Miller JP; Kaiser KK; King W; Robison J; et al.

Arch Neurol 8712; 44(8):808-11

Autoantibodies/*AN; Blood Coagulation Factors/AN/*IM; Cardiolipins/*IM; Cerebral Ischemia/IM; Chorea/IM; Eye/BS; Female; Human; Ischemia/IM; Lupus Erythematosus, Systemic/*IM; Male; Migraine/IM; Myositis/IM; Nervous System Diseases/*IM; Phospholipids/*IM; Polyradiculoneuritis/IM; Seizures/IM; Spinal Cord Diseases/IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S..

The spectrum of neurologic disease associated with antiphospholipid antibodies. Lupus anticoagulants and anticardiolipin antibodies.

JOURNAL ARTICLE; REVIEW.

Lupus anticoagulants and anticardiolipin antibodies are antiphospholipid immunoglobulins, predominantly of the IgG, IgM, or mixed class. Recently, these antiphospholipid autoantibodies have been associated with neurologic conditions including focal cerebral and ocular ischemia, the myelopathy of lupoid sclerosis and Degos' disease, Guillain-Barre syndrome, migraine, chorea, and seizures. We review the neurologic manifestations associated with this group of antibodies. Recognition of these conditions may lead to further insights into pathogenesis and therapy.

Levine SR; Welch KM.

Arch Neurol 8712; 44(8):876-83

Animal; Arachidonic Acids/ME; Biomechanics; Endophthalmitis/ET; Glaucoma/DT; Human; Intraocular Pressure/*DE; Prostaglandins/AE/*PD/PH/TU; Regional Blood Flow/DE; Sclera/BS; Support, U.S. Gov't, P.H.S.; Uvea/BS.

Prostaglandins. Old concepts and new perspectives.

JOURNAL ARTICLE.

Lupus anticoagulants and anticardiolipin antibodies are antiphospholipid immunoglobulins, predominantly of the IgG, IgM, or mixed class. Recently, these antiphospholipid autoantibodies have been associated with neurologic conditions including focal cerebral and ocular ischemia, the myelopathy of lupoid sclerosis and Degos' disease, Guillain-Barre syndrome, migraine, chorea, and seizures. We review the neurologic manifestations associated with this group of antibodies. Recognition of these conditions may lead to further insights into pathogenesis and therapy.

Bito LZ.

Arch Ophthalmol 8712; 105(8):1036-9

Actins/ME; Animal; Cell Adhesion; Cell Movement; Cornea/CY/ME/*PH; Epithelium/CY/ME/PH; Male; Microscopy, Fluorescence; Muscle Proteins/*ME; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't.

Vinculin in focal cell-to-substrate attachments of spreading corneal epithelial cells.

JOURNAL ARTICLE.

Vinculin is a specialized protein with a molecular weight of 130 kilodaltons that is localized to focal regions of cell-to-substrate attachment. It is located precisely at the termini of actin-containing intracytoplasmic stress fibers, which appear to insert into the inner surface of the cell membrane via the vinculin junctions. By double-labeling corneal epithelial cells in tissue culture simultaneously for vinculin and actin, the intimate association of stress fibers and cell-to-substrate adhesion foci was demonstrated. At the leading edge of the migrating epithelial sheet, discrete vinculin patches were numerous in the direction of cell movement, while vinculin was less polarized and often diffusely distributed in the cytoplasm in the less motile cells toward the center of the cell colony. This study shows that corneal epithelial cell migration and spreading during wound healing is characterized by relatively firm substrate attachments at the advancing edge, with the cells behind the edge possibly being pulled forward via cytoskeletal contractile mechanisms.

Soong HK.

Arch Ophthalmol 8712; 105(8):1129-32

Alteplase/*PD; Animal; Cornea/AH; Dose-Response Relationship, Drug; Eye/*ME; Fibrinolysis/*; Human; Osmolar Concentration; Rabbits; Recombinant Proteins/*PD; Sodium Chloride/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S..

Intraocular fibrinolysis with recombinant human tissue plasminogen activator. Experimental treatment in a rabbit model.

JOURNAL ARTICLE.

Intraocular fibrin formation following ocular surgery is a potentially binding problem. Current therapy for this postoperative fibrin response is often ineffective. In the rabbit, we developed a quantitative reproducible model for intraocular fibrin deposition. Using this model, we have tested the efficacy of human tissue plasminogen activator (tPA) in promoting intraocular fibrinolysis. Citrated rabbit plasma (0.2 mL) was injected intracamerally following paracentesis, resulting in fibrin clot formation within three hours. The fibrin clots were stable for four days, and then slowly lysed over the next four days. Approximately 24 hours after clot formation, various concentrations of human tPA were injected intracamerally. The time taken for clot lysis was dose dependent, with 1800 IU of tPA producing clot lysis in three hours. Toxicity, as measured by intraocular pressure, corneal thickness, inflammation, or cataract formation, was minimal.

Snyder RW; Lambrou FH; Williams GA.

Arch Ophthalmol 8712; 105(9):1277-80

Antigens, Surface/AN; Arthritis/IM/*PA/PP; Blood Cells/*PH; Flow Cytometry; Human; HLA-DR Antigens/AN/IM; Interferon Type II/PD; Lymphocyte Transformation/*; Monocytes/IM/*PH; Phenotype; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Synovial Fluid/*CY.

Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis. I. A cytofluorographic study of monocyte differentiation antigens and class II antigens and their regulation by gamma-interferon.

JOURNAL ARTICLE.

Recent study of the expression of monocyte differentiation antigens (MAg) and HLA-DR on peripheral blood monocytes (PBM) has led to the recognition of resting and activated monocyte phenotypes. The former is identified by the expression of large amounts of MAg (i.e., Mo2 and 63D3) and small amounts of HLA-DR, while the latter is identified by the reverse. We studied the phenotypes of PBM and synovial fluid monocytes (SFM) of patients with chronic inflammatory arthritis and found that PBM were primarily resting and SFM were usually activated. In addition, we measured the degree of modulation of MAg and HLA-DR by gamma-interferon (gamma-IFN). Patient PBM reacted the same as PBM from normal individuals (i.e., MAg decreased and HLA-DR increased after exposure to gamma-IFN). However, in patient SFM, HLA-DR did not increase with exposure to gamma-IFN because expression was already maximal. Interestingly, MAg could still be down-regulated on gamma-IFN-treated SFM, even when expression began at a very low level (i.e., activated phenotype). This independent regulation of MAg and HLA-DR suggests that macrophage activating factors other than gamma-IFN may be responsible, in part, for the activated phenotypes observed.

Firestein GS; Zvaifler NJ.

Arthritis Rheum 8712; 30(8):857-63