Role of plasminogen activator inhibitor-1 in promoting fibrin deposition in rabbits infused with ancrod or thrombin

The role of defective fibrinolysis caused by elevated activity of plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been well established. The present study compared the efficacy of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or thrombin; another set of normal rabbits received intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P < .01). In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma and by purified antithrombin III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote fibrin deposition in rabbits infused with ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion may be caused by decreased inhibition of procoagulant activity and not increased PAI-1 activity.     

Identification of T lymphocytes in human mixed hemopoietic colonies

The addition of a T-cell growth-promoting medium (PHA-TCM) to culture conditions that support growth of multi-lineage hemopoietic colonies enhances the proliferation of cells with lymphoid morphology within these colonies. These cells were identified as T lymphocytes by their ability to form rosettes with SRBC and their reaction with monoclonal antibodies (OKT3, OKT4) directed against T-cell-specific surface components. They continue to proliferate extensively under the influence of PHA-TCM after transfer of mixed colonies into liquid suspension culture. Supportive evidence for a common progenitor of myeloid and lymphoid cells within single mixed colonies is provided by Y-chromatin body analysis of E-rosette positive and negative cells in colonies grown in cocultures of male and female bone marrow cells.     

Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.     

Use of accurate diagnostic criteria may increase incidence of stercoral perforation of the colon

PURPOSE: Stercoral perforation of the colon is reported to be a rare disease with poor prognosis. The aim of this study was to determine the frequency of stercoral perforation of the colon, to define diagnostic criteria for stercoral perforation of the colon, and to analyze the patient outcome in a university hospital gastrointestinal surgery unit. METHODS: From November 1993 until November 1998 all surgically treated patients with a colorectal disease were prospectively recorded in a computerized database. Diagnosis of stercoral perforation of the colon was made if 1) the colonic perforation was round or ovoid, exceeded 1 cm in diameter, and lay antimesenteric; 2) fecalomas were present within the colon, protruding through the perforation site or lying within the abdominal cavity; and 3) pressure necrosis or ulcer and chronic inflammatory reaction around the perforation site were present microscopically. Any additional colon pathology led to exclusion from the diagnosis of stercoral perforation of the colon. Using the same criteria, 81 cases in the literature were found to qualify and were further analyzed. RESULTS: In a five-year period 1,295 patients underwent colorectal interventions through laparotomy. A total of 566 (44 percent) cases were emergencies, 220 (17 percent) of these caused by colonic perforation. Seven patients had stercoral perforation of the colon. The incidence of stercoral perforation of the colon was 0.5 percent of all surgical colorectal procedures through laparotomy, 1.2 percent of all emergency colorectal procedures, and 3.2 percent of all colonic perforations. The mean age of the patients was 59 (median, 64; range, 22–85) years. All perforations were situated in the left hemicolon or upper rectum. The round or ovoid perforation had a mean diameter of 3.6 cm. Fecalomas were present in all patients and protruded from the perforation site or were found within the free abdominal cavity in three of them. Generalized stercoral peritonitis was a constant finding. Using a colonic resection without immediate restoration of continuity, an extensive intraoperative lavage, and antibiotics, there was no in-hospital mortality. Analysis of the reports in the literature revealed additionally that 28 percent of patients with stercoral perforation of the colon have multiple stercoral ulcers in the colon and that substantial mortality is encountered if only minor surgical procedures of treatment are used. CONCLUSIONS: The incidence of stercoral perforation of the colon seemed to have been underestimated. The reason for this might be the lack of defined diagnostic criteria for this disease. Low mortality is obtained by early surgical eradication of the affected part of the colon, including all stercoral ulcers, and by aggressive therapy for peritonitis.Presented in part at the meeting of the Swiss Society of Surgery, Lugano, Switzerland, June 9 to 12, 1999.     

Effect of prosthetic aortic valve design on the Doppler-catheter gradient correlation: an in vitro study of normal St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves.

To evaluate the normal range of Doppler-derived velocities and gradients, their relation to direct flow measurements and the importance of prosthetic valve design on the relation between Doppler and catheter-derived gradients, five sizes of normal St. Jude bileaflet, Medtronic-Hall tilting disc, Starr-Edwards caged ball and Hancock bioprosthetic aortic valves were studied with use of a pulsatile flow model. A strong linear correlation between peak velocity and peak flow, and mean velocity and mean flow, was found in all four valve types (r = 0.96 to 0.99). In small St. Jude and Hancock valves, Doppler velocities and corresponding gradients increased dramatically with increasing flow, resulting in velocities and gradients as high as 4.7 m/s and 89 mm Hg, respectively. The ratio of velocity across the valve to velocity in front of the valve (velocity ratio) was independent of flow in all St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves when the two lowest flow rates were excluded for Hancock valves. Although Doppler peak and mean gradients correlated well with catheter peak and mean gradients in all four valve types, the actual agreement between the two techniques was acceptable only in Hancock and Medtronic-Hall valves. For St. Jude and Starr-Edwards valves, Doppler gradients significantly and consistently exceeded catheter gradients with differences as great as 44 mm Hg. Thus, Doppler velocities and gradients across normal prosthetic heart valves are highly flow dependent. However, the velocity ratio is independent of flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastroparesis after combined heart and lung transplantation.

GOALS: To determine the prevalence, severity, and outcome of gastroparesis after heart and lung transplantation (HLT). STUDY: Ten patients (five women; age range, 27-57 years) underwent HLT at Temple University Hospital from 1996 to 1999. The charts of these patients were reviewed, including results from gastric emptying scans and upper endoscopies. Symptoms were assessed with a standardized questionnaire. RESULTS: The indications for HLT included pulmonary hypertension in six patients, Eisenmenger syndrome in two, and dilated cardiomyopathy and congenital heart disease in two. Four patients died before the start of this clinical analysis. The six surviving patients constituted our study population. The patients' posttransplantation follow-up period ranged from 1.4 to 4.4 years (average, 2.6 years). Five patients (83%) were symptomatic with nausea, vomiting, and postprandial abdominal distension. Solid phase gastric emptying was delayed in all five patients with mean gastric retention of 93% at 2 hours (normal <50%). Patients generally did not respond to prokinetic agents. Four patients required pyloroplasty with J tube placement for symptom control, nutrition, and delivery of immunosuppressive medication. CONCLUSIONS: There is a high prevalence of symptomatic gastroparesis in patients after HLT. The gastroparesis is severe and often resistant to prokinetic agents.     

Opiate antagonistic properties of an octapeptide somatostatin analog.

The somatostatin analog D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-NH-CH(CH2OH)CHOHCH3 (SMS 201-995) displaces [3h[naloxone from its binding sites (IC50, 38 +/- 60 nM), being more than 200 times more potent than somatostatin. As measured by the difference between [3H]dihydromorphine, [3H][D-Ala2,D-Leu5]enkephalin, and (-)-[3H]bremazocine binding, SMS 201-995 appears to be highly specific for the opiate mu binding site. Electrophysiological data from hippocampal cultures and results from animal studies (tail flick, mydriasis) demonstrate the opiate antagonistic properties of SMS 201-995. SMS 201-995 is an opiate mu antagonist with a peptide structure. That this property is displayed by a somatostatin analog is somewhat unexpected.     

Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time. Our findings demonstrate that some patients are still experiencing long delays to diagnosis, indicating an ongoing need for improved disease awareness.