ABSTRACT
Recent X-ray crystallographic determination of the HIV-1 envelope glycoprotein gp41 core structure opened up a new avenue to discover antiviral agents for chemotherapy of HIV-1 infection and AIDS. We have undertaken a systematic study to search for anti-HIV-1 lead compounds targeted to gp41. Using molecular docking techniques to screen a database of 20 000 organic molecules, we found 16 compounds with the best fit for docking into the hydrophobic cavity within the gp41 core and with maximum possible interactions with the target site. Further testing of these compounds by an enzyme-linked immunosorbent assay and virus inhibition assays discerned two compounds (ADS-J1 and ADS-J2) having inhibitory activity at micromolar concentrations on the formation of the gp41 core structure and on HIV-1 infection. These two compounds will be used as leads to design more effective HIV-1 inhibitors targeted to the HIV-1 gp41 core structure.
Subject(s)
Anti-HIV Agents/chemical synthesis , HIV Envelope Protein gp41/chemistry , Anti-HIV Agents/chemistry , Anti-HIV Agents/metabolism , Anti-HIV Agents/pharmacology , Cell Fusion/drug effects , Cell Line , Enzyme-Linked Immunosorbent Assay , HIV Envelope Protein gp41/metabolism , HIV-1/drug effects , Humans , Models, Molecular , Molecular Conformation , Naphthalenesulfonates/chemistry , Structure-Activity Relationship , Triazines/chemistryABSTRACT
In a series of 183 emergency operations in which intraoperative autotransfusion was used, 14 patients received blood contaminated by intestinal contents. Six of the 14 patients died early in the postoperative period, four of whom had received more than 16 liters of blood. Only two of the eight survivors had received comparable amounts of blood (13 and 17.5 liters). All eight received antibiotics upon admission; four had positive blood cultures within 24 hours of operation. Complications included acute tubular necrosis in three patients and bowel obstruction with intra-abdominal abscess in another. One of the patients with acute tubular necrosis died six weeks later; all others recovered. We believe this procedure may be life-saving in some cases.
Subject(s)
Blood Transfusion, Autologous/adverse effects , Wounds and Injuries/therapy , Female , Humans , Male , Wounds, Gunshot/therapy , Wounds, Nonpenetrating/therapy , Wounds, Stab/therapyABSTRACT
Poor results in the treatment of lung cancer have led to the development of several techniques designed to obtain tissue for diagnosis and to determine the feasibility of resection. Although mediastinoscopy has obtained great popularity, we have been dissatisfied with it because of the low yield of positive results and the attendant increases in length of operations and hospitalizations. We have modified the old technique of thoracoscopy, using a sterilized sigmoidoscope inserted through an intercostal space with the patient positioned and prepared for thoracotomy. Although most frequently used in patients with lung cancer, this procedure also has been helpful in patients with coin lesions, mediastinal tumors, and penetrating wounds of the chest. Although we agree that mediastinoscopy is useful in selected patients, we believe that thoracoscopy offers a greater number of patients a reliable means of obtaining the proper diagnosis more efficiently.
Subject(s)
Thoracoscopy , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Mediastinal Neoplasms/diagnosis , Mediastinoscopy , Sigmoidoscopy , Solitary Pulmonary Nodule/diagnosis , Sympathectomy , Thoracic Injuries/diagnosis , Thoracic Surgery , Thoracoscopy/methods , Thorax/surgeryABSTRACT
Barrett esophagus is the term describing the presence of an abnormal columnar epithelium in a portion of the esophagus. We have treated 19 patients within the past three years, representing almost 20% of all our esophageal experience; This one pathologic entity has presented as several different clinical pictures: benign stricture, peptic ulceration of the esophagus, intractable esophagitis, and malignancy. One half the patients were under 50 years old, and most were male. The benign lesions have responded well to surgical therapy. There has been an unusually high incidence of malignancy-26.3%. The reasons for the infrequent diagnosis of Barrett esophagus are confusion with "short esophagus" and failure to biopsy the proper site.
Subject(s)
Esophageal Stenosis/surgery , Adult , Aged , Epithelium/pathology , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery , Esophageal Stenosis/diagnostic imaging , Esophageal Stenosis/pathology , Esophagitis, Peptic/diagnostic imaging , Esophagitis, Peptic/surgery , Esophagus/pathology , Female , Hernia, Hiatal/surgery , Humans , Jejunum/transplantation , Male , Middle Aged , Peptic Ulcer/diagnostic imaging , Peptic Ulcer/surgery , Radiography , Transplantation, AutologousABSTRACT
Although interest in intraoperative autotransfusion increased when commercial equipment became available, this technique still is utilized rarely in most hospitals. Our experience began with sporadic use in 1972 and has evolved to regular use at least ten times a month. The machine is operated by a technician, and we heparinize the autotransfusion system (ATS) reservoir. Our series includes 47 patients who had elective vascular operations and 141 who had emergency operations, usually for trauma. In the latter group, seven patients who were autotransfused with blood contaminated by intestinal contents survived near fatal injuries and did not develop complications attributable to the procedure. Morbidity and mortality rates in both groups did not appear to be increased as a result of intraoperative autotransfusion. Controversy over methods of anticoagulation and apprehension about effect on blood are not valid reasons for underutilization of this technique. Although significant administrative commitments are required to implement its use and to treat the coagulopathy that accompanies massive reinfusions, they are justified by the value of intraoperative autotransfusion in most cases in which two or more units of blood would be required ordinarily.
