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Biomedical subjects

Carol Bodian

Publications and source records attributed to Carol Bodian.

At least 19 recordsLinked to original sources

The fate of the distal aorta after repair of acute type A aortic dissection.

OBJECTIVES: The residual aorta's behavior after repair of acute type A dissection is incompletely understood. We analyzed segmental growth rates, distal reoperation, and factors influencing long-term survival. METHODS: One hundred seventy-nine consecutive patients (70% male; mean age, 60 years) with acute type A dissection underwent aggressive resection of the intimal tear and open distal anastomosis (1986-2003). Hospital mortality was 13.4%. Survivors had serial computed tomographic scans: digitization yielded distal segmental dimensions. Segment-specific average rates of enlargement and factors influencing faster growth were analyzed. Distal reoperations and patient survival were examined. RESULTS: Eighty-nine (57%) patients had imaging data sufficient for growth rate calculations. The median diameters after repair were as follows: aortic arch, 3.6 cm; descending aorta, 3.7 cm; and abdominal aorta, 3.2 cm. Subsequent growth rates were 0.8, 1.0, and 0.8 mm/y, respectively. Initial size of greater than 4 cm (P = .005) and initial diameter of less than 4 cm with a patent false lumen (P = .004) predicted greater growth in the descending aorta, and male sex (P = .05) significantly affected growth in the abdominal aorta. No significant factors were found for the aortic arch. There were 25 distal aortic reoperations (16 patients), and risk of reoperation was 16% at 10 years. Risk factors reducing long-term survival after repair of acute type A dissection included age (P < .0001), new neurological deficit at presentation (P = .04), absence of preoperative thrombus in the false lumen of the ascending aorta (P = .03), and a patent distal false lumen postoperatively (P = .06) but not distal reoperation. CONCLUSIONS: Growth of the distal aorta after repair of acute type A dissection is typically slow and linear. Distal reoperation is uncommon, and late risk of death is approximately twice that of a healthy population.

Acute Disease↗

How time affects the risk of rupture in appendicitis.

BACKGROUND: Increasing time between symptom onset and treatment may be a risk factor for a ruptured appendix, but little is known about how the risk changes with passing time. This study aimed to determine the changes in risk of rupture in patients with appendicitis with increasing time from symptom onset to treatment to help guide the swiftness of surgical intervention. STUDY DESIGN: We conducted a retrospective chart review of physician office, clinic, emergency room, and inpatient records of a random sample of 219 of 731 appendicitis patients operated on between 1996 and 1998 at 2 inner-city tertiary referral and municipal hospitals. Conditional risks of rupture were calculated using life table methods. Logistic regression was used to assess factors associated with rupture, and linear regression was used to assess factors affecting time from first examination to treatment. RESULTS: Rupture risk was < or = 2% in patients with less than 36 hours of untreated symptoms. For patients with untreated symptoms beyond 36 hours, the risk of rupture rose to and remained steady at 5% for each ensuing 12-hour period. Rupture was greater in patients with 36 hours or more of untreated symptoms (estimated relative risk [RR]=6.6; 95% CI: 1.9 to 8.3), age 65 years and older (RR=4.2; 95% CI: 1.9 to 6.1), fever > 38.9 degrees C (RR=3.6; 95% CI: 1.2 to 5.7), and tachycardia (heart rate > or = 100 beats/minute; RR=3.4; 95% CI: 1.8 to 5.4). Time between first physician examination and treatment was shorter among patients presenting to the emergency department (median, 7.1 hours versus 10.9 hours; p<0.0001), and those for whom a physician's leading diagnostic impression was appendicitis (6.3 hours versus 11.3 hours; p<0.0001). Patients sent for CT scan experienced longer times to operation (18.6 hours versus 7.1 hours; p<0.0001). CONCLUSIONS: Risk of rupture in ensuing 12-hour periods rises to 5% after 36 hours of untreated symptoms. Physicians should be cautious about delaying surgery beyond 36 hours from symptom onset in patients with appendicitis.

Adolescent↗

Diabetes mellitus is associated with hepatic encephalopathy in patients with HCV cirrhosis.

OBJECTIVES: An increased ammonia level of gut bacterial origin is an important mediator in the pathogenesis of hepatic encephalopathy (HE), and constipation is a frequent precipitant of hepatic coma. Because diabetes mellitus (DM) may be associated with delayed gastrointestinal transit, we speculated that its presence in patients with HCV-related cirrhosis would predispose to and exacerbate HE. METHODS: Sixty-five patients (50 men, 15 women) with HCV-related cirrhosis attending a liver transplantation clinic were assessed for severity of liver disease and presence of DM in a cross-sectional study. A modified Child-Pugh score that excluded HE was calculated. Frequency and severity of HE (absent, mild, and severe) in diabetic and nondiabetic patients were assessed. Clinical severity of cirrhosis and results of neuropsychometric testing in diabetic and nondiabetic patients with mild and severe HE were compared. RESULTS: Fifty-four patients (83%) had HE (33 mild, 21 severe). Twenty patients (31%) had DM. HE was present in 19 (95%) patients with diabetes and 35 (78%) patients without diabetes (p = 0.087). Severity of HE was greater in diabetic (35% mild, 60% severe) than in nondiabetic patients (58% mild, 20% severe) (p = 0.007). In both the mild and severe HE categories, severity of liver disease in diabetic patients was otherwise milder than in the nondiabetic patients. CONCLUSIONS: Diabetic patients with HCV cirrhosis have more severe HE. Diabetic patients have severe HE at earlier stages of biochemical decompensation and portal hypertension compared with nondiabetic patients.

Adult↗

Accelerated hepatitis C virus kinetics but similar survival rates in recipients of liver grafts from living versus deceased donors.

This study tested the hypothesis that hepatitis C virus (HCV) RNA and core antigen levels rise more rapidly after liver transplantation (LT) in recipients of grafts from living donors (LD) versus deceased donors (DD). Eleven consecutive LD and 15 DD recipients were followed prospectively. Before LT, median HCV RNA levels were similar: 5.42 (LDLT) and 5.07 (DDLT) log(10) IU/mL (P = NS). During the first 7 hours after LT a trend toward a greater HCV RNA decrease in LDLT patients was seen, although they received fewer blood replacement products during surgery. HCV RNA levels rose more rapidly in LDLT patients between days 1 and 3 (P = .0059) and were higher in this group on days 2, 3, 4, and 5. Core antigen levels were significantly higher in LDLT patients on days 3 and 5, although they were similar before LT (P = NS). Alanine aminotransferase (ALT) values were higher among LDLT patients from 8 to 14 days and from 4 to 24 months. Two-year graft and patient survival were 73% for LDLT patients and 80% for DDLT patients (P = NS). In conclusion, viral load rose more rapidly in LD recipients and reached higher levels shortly after surgery. Greater ALT elevations were evident in the LDLT group, but survival rates were similar. The trend toward a greater initial viral load decrease in patients with LD grafts and the significantly sharper increase suggest that the liver plays a predominant role in both HCV clearance and replication.

Adolescent↗

Histopathology and clinical correlates of end-stage hepatitis B cirrhosis: a possible mechanism to explain the response to antiviral therapy.

In chronic liver disease associated with histological necroinflammation, clinical severity is frequently greater in those with higher grades of activity. Conventional wisdom assumes that necroinflammation is mild or absent in patients with end-stage hepatitis B virus (HBV) cirrhosis due to the frequent presence of mildly elevated aminotransferase levels, the absence of hepatitis B e antigen (HBeAg), and low or undetectable HBV deoxyribonucleic acid (DNA) levels. However, a histopathologic analysis of such patients has not been undertaken. The aims of this study were 1) to assess severity and histological features of inflammation, 2) to correlate the severity of inflammation with biochemical and virologic parameters, and 3) to define the relationship between inflammation and clinical severity in explanted livers from patients undergoing liver transplantation for HBV cirrhosis. Characteristics of 34 consecutive patients undergoing liver transplantation for HBV cirrhosis were correlated with inflammation and immunohistological findings in the explanted livers. High-grade inflammation (grades 3 and 4) was found in many cases (47.1% interface hepatitis; 14.8% lobular inflammation; and 20.6% portal inflammation). The presence of positive cytoplasmic staining for hepatitis B core antigen (HBcAg) was associated with grade 3 or 4 interface hepatitis (P = .046) and lobular hepatitis (P = .005). There was no correlation between inflammatory activity and age, Asian ethnicity, aminotransferase levels, total bilirubin levels, HBeAg seropositivity, and detectable HBV DNA level. Patients with high-grade inflammation had greater degrees of hepatic decompensation. In conclusion, high-grade inflammation is common in end-stage HBV cirrhosis, but it is not readily detected by biochemical and virologic parameters. High-grade inflammation is associated with a greater degree of hepatic decompensation.

Adult↗

Long-term integrity of teflon felt-supported suture lines in aortic surgery.

BACKGROUND: Although the ultimate success of aortic operations depends upon the integrity of graft-to-aorta anastomoses, little is known about different techniques used to assure their longevity. We report the incidence of reoperation for suture line disruptions arising from anastomoses using reinforcement with Teflon felt. METHODS: Since 1987, 1475 patients underwent 2281 anastomoses in the thoracic aorta (mean 1.55/anastomoses per patient). All patients were followed with at least yearly computed tomographic scans, for a total follow-up of 6483.8 patient-years. Those requiring reoperation were reviewed retrospectively for evidence of suture line disruption. RESULTS: Only 34 patients, with a mean age of 55.1 years old (range 26-85 years old) underwent reoperation for suture-line disruptions following vascular graft-to-aorta anastomosis using Teflon felt. The previous operation was a Bentall procedure in 15 (44%); ascending aorta replacement in 9 (26%); total arch replacement in 6 (18%); descending aorta replacement in 2 (6%); thoracoabdominal repair in 1 (3%); and sinus of Valsalva repair in 1 (3%). The incidence of suture line disruption was 0.0052 per patient-year, and 0.0034 per anastomosis-year. The mean interval between operations was 55.9 months (range 4-180 months). In 21%, the pseudoaneurysm originated from the proximal anastomosis; in 71% from the distal anastomosis; in 3% from both; in 3% from the innominate artery; and in 3% from a sinus of Valsalva repair. In only 1 patient was there evidence of infection. Reoperation involved ascending aorta replacement in 11 patients, and total arch replacement in 13 patients. Adverse outcome, such as hospital death or permanent stroke, occurred in 8% (3 patients). CONCLUSIONS: Use of Teflon felt to support aortic suture lines yields a very low incidence of suture line disruptions: 1 per 191 patient-years, or 1 per 296 anastomosis-years. Teflon felt reinforcement provides a secure, long-lasting graft-to-aorta anastomosis with minimal risk of infection.

Adolescent↗

Composite aortic root replacement in acute type A dissection: time to rethink the indications?

OBJECTIVE: The indications for aortic root replacement in acute type A dissection are unclear. We reviewed the immediate and long-term outcome of consecutive patients in a series in which a low-threshold policy of composite aortic root replacement had evolved. METHODS: From a prospectively compiled aortic surgery database, we identified 162 patients who had either supracoronary interposition grafting, Group A (n=89), or composite root replacement, Group B (n=73) for acute type A dissection. Patients receiving total arch replacements were excluded. Operative and clinical details were analyzed and patient survival was compared to an age and gender matched census cohort. Need for reoperation on the proximal or distal aorta was also noted. Follow-up totaled 795.5 patient-years. RESULTS: Hospital mortality rates were identical in both groups (12.3%: 11 deaths in group A; 9 in group B). Chronic pulmonary disease, diabetes, malperfusion, hemodynamic compromise and aortic root dilatation were independent risk factors for hospital death. Actuarial survival estimates at 1, 5 and 10 years were 79% (71-88%), 64% (53-75%), and 55% (41-68%) for group A, and 79% (70-86%), 73% (62-83%), and 65% (52-78%) for group B (P=0.48). Age and operative patency of the ascending false lumen were independent risk factors for death after hospital discharge. Proximal aortic reoperation was required for four patients in group A and none in group B (P=0.085). CONCLUSION: A strategy of replacement rather than repair of the dissected aortic root for specific indications in type A dissection yielded high survival and low proximal reoperation rates. These results support an aggressive policy of composite root replacement in acute type A dissection.

Acute Disease↗

Optimal pH strategy for selective cerebral perfusion.

OBJECTIVE: Selective cerebral perfusion (SCP) affords brain protection superior to hypothermic circulatory arrest (HCA) for prolonged aortic arch procedures. Optimal pH strategy for HCA is controversial; for SCP it is unknown. We compared pH strategies during SCP in a survival pig model. METHODS: Twenty juvenile pigs (26+/-2.4 kg), randomized to alpha-stat (n=10) or pH-stat (n=10) management, underwent cooling to 20 degrees C on cardiopulmonary bypass (CPB) followed by 90 min of SCP at 20 degrees C. SCP was conducted with a mean pressure of 50 mmHg and hematocrit of 22.5%. Using fluorescent microspheres and sagittal sinus blood sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at the following time points: baseline, after 30 min cooling (20 degrees C), 30 min of SCP, 90 min of SCP, 15 min post-CPB and 2h post-CPB. Visual evoked potentials (VEP) were assessed at baseline and monitored for 2h during recovery. Neurobehavioral recovery (10=normal) was assessed in a blinded fashion for 7 postoperative days. RESULTS: There were no significant differences between the groups at baseline. CBF was significantly higher at the end of cooling, and after 30 and 90 min of SCP in the pH-stat group (P=0.02, 0.007, 0.03). CMRO2 was also higher with pH-stat (P=0.06, 0.04, 0.10). Both groups showed prompt return to values close to baseline after rewarming (P=ns). VEP suggested a trend towards improved recovery in the alpha-stat group at 2h post-CPB, P=0.15. However, there were no significant differences in neurobehavioral score: (alpha-stat versus pH-stat) median values 7 and 7.5 on day 1; 9 and 9 on day 4, and 10 and 10 on day 7. CONCLUSIONS: These data suggest that alpha-stat management for SCP provides more effective metabolic suppression than pH-stat, with lower CBF. Clinically, the better preservation of cerebral autoregulation during alpha-stat perfusion should reduce the risk of embolization.

Animals↗

Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine.

BACKGROUND & AIMS: Evidence suggests that mesalamine-based anti-inflammatory medicines may prevent colorectal cancer (CRC) in ulcerative colitis (UC). If mesalamine exerts its chemopreventive effect by its anti-inflammatory activity, then other medications that reduce colitis activity also should possess chemopreventive properties. Our aim was to determine the effect of the immunomodulators 6-mercaptopurine (6MP) and azathioprine (AZA) in preventing the development of dysplasia or CRC in UC. METHODS: Patients with UC who underwent a surveillance colonoscopy in 1996-1997 were identified from a gastrointestinal pathology database. A proportional hazards analysis assessing 6MP/AZA use as a time-changing covariate was performed to evaluate the effect of 6MP/AZA on: (1) progression to any neoplasia (low-grade dysplasia, high-grade dysplasia, or CRC), and (2) progression to advanced neoplasia (high-grade dysplasia or CRC). RESULTS: A total of 315 subjects met inclusion criteria and were followed for an average of 8 years from their first surveillance examination. There were no significant differences in rates of progression to advanced neoplasia or to any neoplasia between 6MP/AZA users and never-users by log-rank testing. The proportional hazards analysis resulted in hazard ratios of 1.06 (95% confidence interval, .59-1.93) and 1.30 (95% confidence interval, .45-3.75) when considering the effect of exposure to 6MP/AZA on progression to any or to advanced neoplasia, respectively. The results were unaffected by known potential confounders. CONCLUSIONS: In UC patients with no initial history of dysplasia, 6MP/AZA use appears to have little or no effect on the rate of neoplastic transformation in the colon. Importantly, the use of 6MP/AZA did not increase malignant transformation in UC.

Adult↗

Antifibrinolytic use and bleeding during surgery on the descending thoracic aorta: a multivariate analysis.

OBJECTIVES: The purpose of this study was to determine the potential benefit of antifibrinolytic (AF) therapy in improving hemostasis in descending aortic surgery in which extracorporeal distal perfusion is used. DESIGN: Retrospective database study. SETTING: University hospital. PARTICIPANTS: Seventy-two patients who underwent descending thoracic or thoracoabdominal aortic replacement during the period from January 1993 through December 1996 when the use of AF therapy was emerging. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seventy-two records met criteria for inclusion. The use of AF therapy had no significant effect on any bleeding or transfusion outcome in any model. Excessive chest tube drainage postoperatively was independently associated with repeat surgery and intraoperative hypothermia. The risk of receiving a red blood cell (RBC) transfusion was independently predicted by low preoperative hemoglobin and age > or =65 years. Cross-clamp was an independent predictor of receiving a transfusion of non-RBC products (p = 0.03). CONCLUSIONS: The authors could not show a beneficial effect of AF therapy on bleeding and transfusion, although current practice shows that this therapy continues to be used. Because heterogeneity of patient population exists and bias cannot be completely excluded, a prospective investigation evaluating efficacy and safety in this population is warranted.

Aged↗

Evaluation of fatigue in U.S. patients with primary biliary cirrhosis.

OBJECTIVES: Fatigue, which may have a significant impact on quality of life, is the most common reported symptom in primary biliary cirrhosis (PBC). Multiple instruments to quantify fatigue and quality of life in liver disease have been validated, but have not been broadly applied to U.S. PBC patients. This study examines the extent of fatigue and its effect on quality of life in U.S. PBC patients. METHODS: Seventy patients with PBC were administered two validated questionnaires about quality of life (the Mayo version of the NIDDK-QA) and fatigue (the Fisk Fatigue Impact Score) and a proposed physical measure of fatigue in PBC (the grip strength test) on the day of routine physician visit. Nonparametric methods were employed. RESULTS: The fatigue and quality of life domain scores (physical functioning, liver symptoms, health satisfaction, Karnofsky index) discriminated between patients with and without self-reported fatigue (p < 0.05), as opposed to the grip strength results. Fatigue and quality of life domains correlated strongly with each other (r between 0.33 and 0.74, p</= 0.006) and not with the grip strength results. Neither quality of life nor fatigue scores correlated with age. CONCLUSIONS: The correlation between fatigue and quality of life scores suggests fatigue has an impact on quality of life in U.S. primary biliary cirrhosis patients. However, our fatigue scores suggest U.S. PBC patients have less fatigue than non-U.S. PBC patients. The grip strength is an insensitive measure of fatigue in U.S. PBC patients.

Adult↗

Predictors of transfusion requirements for cardiac surgical procedures at a blood conservation center.

BACKGROUND: Previous studies defining perioperative risk factors for allogeneic transfusion requirements in cardiac surgery were limited to highly selected cardiac surgery populations or were associated with high transfusion rates. The purpose of this study was to determine perioperative risk factors and create a formula to predict transfusion requirements for major cardiac surgical procedures in a center that practices a multimodality approach to blood conservation. METHODS: We performed an observational study on 307 consecutive patients undergoing coronary artery bypass grafting, valve, and combined (coronary artery bypass grafting and valve) procedures. An equation was derived to estimate the risk of transfusion based on preoperative risk factors using multivariate analysis. In patients with a calculated probability of transfusion of at least 5%, intraoperative predictors of transfusion were identified by multivariate analysis. RESULTS: Thirty-five patients (11%) required intraoperative or postoperative allogeneic transfusions. Preoperative factors as independent predictors for transfusions included red blood cell mass, type of operation, urgency of operation, number of diseased vessels, serum creatinine of at least 1.3 mg/dL, and preoperative prothrombin time. Intraoperative factors included cardiopulmonary bypass time, three or fewer bypass grafts, lesser volume of acute normovolemic hemodilution removed, and total crystalloid infusion of at least 2,500 mL. The derived formula was applied to a validation cohort of 246 patients, and the observed transfusion rates conformed well to the predicted risks. CONCLUSIONS: A multimodality approach to blood conservation in cardiac surgery resulted in a low transfusion rate. Identifying patients' risks for transfusion should alter patient management perioperatively to decrease their transfusion rate and make more efficient use of blood resources.

Aged↗

Time and the risk of ruptured tubal pregnancy.

OBJECTIVE: Tubal pregnancy remains an important cause of maternal morbidity and mortality. We sought to quantify the relationship of time between symptom onset and treatment and the risk of tubal rupture. METHODS: We reviewed inpatient, clinic, and physician office charts of 221 women with tubal pregnancy. We assessed the conditional risk of rupture with passing time and other factors related to rupture. RESULTS: Time between symptom onset and treatment varied from 3 hours to 66 days with an average of 7 days. There was a 32% rupture rate. The conditional risk of rupture was highest within the first 48 hours of symptom onset (5-7%). The risk dropped, leveled off, and remained fairly steady at approximately 2.5% per 24 hours of untreated symptoms. Classic tubal pregnancy signs, symptoms, and tests were not helpful in predicting rupture. CONCLUSION: The rate of rupture is highest in women with the shortest times between symptom onset and treatment. With passing time, the risk declines, but remains steady despite women's getting into care. LEVEL OF EVIDENCE: II-2

Adolescent↗

Are pANCA, ASCA, or cytokine gene polymorphisms associated with pouchitis? Long-term follow-up in 102 ulcerative colitis patients.

OBJECTIVE: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for ulcerative colitis. This study aims to analyze the frequency and characteristics of pouchitis in long-term follow-up in a large population, and to determine whether a significant association exists between five immunogenetic markers and pouchitis. METHODS: From a population of over 500 ulcerative colitis patients who had undergone ileal pouch-anal anastamosis 5-12 yr earlier, 102 subjects participated in the study. Using clinical data obtained from interviews and chart reviews, patients were classified into three groups: no pouchitis; 1-2 episodes per year; and >2 episodes per year. Coded sera from the patients were analyzed for ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies and Crohn's disease-associated anti-saccharomyces cerevesiae antibodies. Interleukin-1 receptor antagonist, tumor necrosis factor (TNF), and lymphotoxin beta (lymphotoxin) polymorphisms were also analyzed. RESULTS: Pouchitis affected 49% of the study population. Antineutrophil cytoplasmic antibodies, anti-saccharomyces cerevesiae antibodies, and lymphotoxin-beta polymorphisms were not associated with pouchitis. Carriage of interleukin-1 receptor antagonist allele 2 was significantly greater among those without pouchitis than those with pouchitis. Patients without pouchitis had a significantly greater carriage rate of TNF allele 2. CONCLUSIONS: Perinuclear antineutrophil cytoplasmic antibodies and anti-saccharomyces cerevesiae antibodies are not correlated with pouchitis, but interleukin-1 receptor antagonist and TNF may play a role in its development. Further evaluation of these markers in pouchitis will require larger populations, long-term prospective observation, and studies that correlate polymorphisms with specific immunologic functions.

Adult↗

The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients.

OBJECTIVES: We reviewed data to investigate the effect of 5-ASA drugs, metronidazole, ciprofloxacin, prednisone, 6-mercaptopurine, azathioprine, and cyclosporine on pregnancy outcomes in patients with inflammatory bowel disease (IBD). METHODS: One hundred and thirteen female patients with a total of 207 documented conceptions were studied. Treatment information included: smoking history (patient and spouse), dates of conception and termination, and outcome of pregnancy (spontaneous abortion, therapeutic abortion, maternal or fetal illness resulting in abortion, premature birth, healthy full-term birth, multiple births, ectopic pregnancy, congenital defects), weight of baby, type of delivery (cesarian section, vaginal), medication history during each trimester (mean dose, maximum dose, frequency). We analyzed the effect on pregnancy outcome of medication use during the first trimester or at any time during the pregnancy. RESULTS: Thirty-nine patients (34.5%) had ulcerative colitis (UC), 73 (64.5%) had crohn's disease (CD), and 1 patient (1%) had indeterminate colitis. For 100 of the 207 conceptions, the patients were on 5-ASA drugs at some time during the pregnancy, 49 on prednisone, 101 on an immunomodulator (6-MP/azathioprine), 27 on metronidazole, 18 on ciprofloxacin, and 2 on cyclosporine. In 85 (31%) of the conceptions, patients were on none of these medications. No significant differences were found among the groups in each pregnancy with respect to outcome (p values 0.091 to 0.9). In multivariate analyses controlling for age of mother, there was no evidence that 5-ASA type drugs or any type of drug influenced pregnancy outcome. CONCLUSIONS: In 113 female patients with 207 conceptions none of the drugs used to treat IBD is associated with poor pregnancy outcomes.

Adolescent↗

Dynamics of GPIIb/IIIa-mediated platelet-platelet interactions in platelet adhesion/thrombus formation on collagen in vitro as revealed by videomicroscopy.

The conventional description of platelet interactions with collagen-coated surfaces in vitro, based on serial static measurements, is that platelets first adhere and spread to form a monolayer and then recruit additional layers of platelets. To obtain dynamic information, we studied gravity-driven platelet deposition in vitro on purified type 1 collagen by video phase-contrast microscopy at 22 degrees C. With untreated human and wild-type mouse platelets, soon after the initial adhesion of a small number of "vanguard" platelets, "follower" platelets attached to the spread-out vanguard platelets. Follower platelets then adhered to and spread onto nearby collagen or over the vanguard platelets. Thus, thrombi formed as a concerted process rather than as sequential processes. Treatment of human platelets with monoclonal antibody (mAb) 7E3 (anti-GPIIb/IIIa (alphaIIbbeta3) + alphaVbeta3) or tirofiban (anti-GPIIb/IIIa) did not prevent platelet adhesion but nearly eliminated the deposition of follower platelets onto vanguard platelets and platelet thrombi. Similar results were obtained with Glanzmann thrombasthenia platelets. Wild-type mouse platelets in the presence of mAb 1B5 (anti-GPIIb/IIIa) and platelets from beta3-null mice behaved like human platelets in the presence of 7E3 or tirofiban. Deposition patterns of untreated human and wild-type mouse platelets were consistent with random distributions under a Poisson model, but those obtained with 7E3- and tirofiban-treated human platelets, 1B5-treated mouse platelets, or beta3-null platelets demonstrated a more uniform deposition than predicted. Thus, in this model system, absence or blockade of GPIIb/IIIa receptors interferes with thrombus formation and alters the pattern of platelet deposition.

Animals↗

Diabetes and evidence of atherosclerosis are major risk factors for adverse outcome after elective thoracic aortic surgery.

BACKGROUND: To predict risk after elective repair of ascending aorta and aortic arch aneurysms, we studied 464 consecutive patients. METHODS: Adverse outcome (stroke or hospital death) was analyzed in 372 patients who underwent proximal repair and 92 patients who underwent aortic arch replacement from 1986 to the present. Preoperative risk factors with a P value less than.2 in a univariate analysis were entered into a multivariate model, and an equation incorporating independent risk factors was derived separately for proximal aorta and arch surgery. RESULTS: Age more than 65 years (P =.04), diabetes (P =.02), cause (P =.01), and prolonged total cerebral protection time (duration of hypothermic circulatory arrest and selective cerebral perfusion, P =.001) were significant univariate risk factors for elective proximal aortic repair. Diabetes (P =.005, odds ratio 5.1), atherosclerosis (P =.003, odds ratio 4.0), and dissection (P =.048, odds ratio 2.5) were independent factors. For elective arch surgery, female sex (P =.07), age more than 65 years (P =.04), coronary artery disease (P =.02), diabetes (P =.06), cause (P =.07), and prolonged total cerebral protection time (P =.025) were univariate risk factors. Female sex (P =.05, odds ratio 4.7), coronary artery disease (P =.02, odds ratio 6.5), diabetes (P =.13, odds ratio 4.0), and total cerebral protection time (P =.03, odds ratio 1.02/min) were independent factors. To calculate risk of adverse outcome (P), enter 1 if factor is present, 0 if absent, and estimate total cerebral protection time (in minutes). [equation: see text]. CONCLUSION: In this large series of patients, the presence of diabetes and manifestations of atherosclerosis emerge as extremely important risk factors for adverse outcome after ascending aorta or arch surgery, displacing age. Multivariate equations derived from these data allow more precise calculation of risk for each individual contemplating elective surgery.

Adolescent↗

The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study.

BACKGROUND & AIMS: 6-mercaptopurine/azathioprine is effective in IBD patients. However, data regarding toxicity associated with pregnancy are lacking, raising both patients' and physicians' concerns and sometimes resulting in elective abortion. METHODS: To evaluate potential toxicity of 6-mercaptopurine (6-MP), we reviewed the records of 485 patients who had received the drug. We contacted 462, of whom 155 had conceived at least 1 pregnancy after developing IBD. Pregnancies were analyzed as to whether the patient had taken 6-MP before, or at the time of, conception. These were compared with IBD patients who had their pregnancies before taking 6-MP. We collected data on live births, spontaneous abortions, prematurity, abortions secondary to birth defects, major and minor congenital birth defects, infections, and neoplasia. Outcomes were analyzed comparing pregnancies from men and women who had taken or were currently taking 6-MP to controls. RESULTS: There was no statistical difference in conception failures (defined as a spontaneous abortion), abortion secondary to a birth defect, major congenital malformations, neoplasia, or increased infections among male or female patients taking 6-MP compared with controls (RR = 0.85 [0.47-1.55], P = 0.59). CONCLUSIONS: 6-MP use before or at conception or during pregnancy appears to be safe. Discontinuation of the drug before and during pregnancy is not indicated.

Control Groups↗