Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.     

Intracerebral hemorrhage after carotid endarterectomy: incidence, contribution to neurologic morbidity, and predictive factors

PURPOSE: With a diminishing rate of cardiac and neurologic events after carotid endarterectomy, intracerebral hemorrhage is gaining increasing importance as a cause of perioperative morbidity and mortality. To date, information has been largely anecdotal, and there has been no comparison with a control group of patients. METHODS: The records of all patients experiencing symptomatic intracerebral hemorrhage after carotid endarterectomy were reviewed and compared with data from 50 randomly selected patients who did not experience intracranial bleeding. Univariate analyses were performed, using the Fisher exact test for dichotomous data and the Student t test for continuous data. RESULTS: During a 6-year period, symptomatic intracranial hemorrhage developed in 11 (0.75%) of 1471 patients undergoing carotid endarterectomy, accounting for 35% of the 31 total perioperative neurologic events. Hemorrhage occurred a median of 3 days postoperatively (range, 0 to 18 days). Signs and symptoms included hypertension in all 11 patients, headache in 7 conscious patients (64%), and bradycardia in 6 patients (55%). Massive hemorrhage with herniation and death occurred in 4 patients (36%). Moderate hemorrhage developed in 5 patients (45%); 3 of these patients had partial recovery, and 2 had complete recovery. Petechial hemorrhage occurred in the remaining 2 patients (18%), 1 with partial and 1 with complete recovery. In comparison with the control group, there were no differences in respect to sex, indication for operation, smoking or diabetic history, and antiplatelet therapy or perioperative heparin management. Patients with intracranial hemorrhage were, however, younger, more frequently hypertensive, had a higher degree of ipsilateral and contralateral carotid stenosis, and had a higher rate of contralateral carotid occlusion. CONCLUSION: Intracranial hemorrhage occurs with notable frequency after carotid endarterectomy and accounts for a significant proportion of neurologic morbidity and mortality. Younger patients, hypertensive patients, and patients with severe cerebrovascular occlusive disease appear to be at greatest risk for the complication.     

An in vitro tissue culture bilayer model to examine early events in Mycobacterium tuberculosis infection

A tissue culture bilayer system that mimics some aspects of early alveolar infection by Mycobacterium tuberculosis was developed. This model incorporates human lung epithelial type II pneumocyte (A549) (upper chamber) and endothelial cell (lower chamber) layers separated by a microporous membrane. This construction makes it possible to observe and quantify the passage of bacteria through the two layers, to observe the interaction of the bacteria with the various cell types, and to examine the basic mechanisms of immune cell recruitment to the site of infection. After 10(7) organisms were added to the upper chamber we microscopically observed large numbers of bacteria attached to and within the pneumocytes and we determined by viable-cell counting that a small percentage of the inoculum (0.02 to 0.43%) passed through the bilayer into the lower chamber. When peripheral blood mononuclear cells were added to the lower chamber, microscopic examination indicated a migration of the mononuclear cells through the bilayer to the apical surface, where they were seen associated with the mycobacteria on the pneumocytes. The added complexity of the bilayer system offers an opportunity to define more precisely the roles of the various lung cell types in the pathogenesis of early tuberculosis.     

The role of CD8 and CD4 T cells in intestinal allograft rejection: a comparison of monoclonal antibody-treated and knockout mice

Studies were performed to determine the effects of PTH and related compounds on phosphatidylcholine (PC) hydrolysis in UMR-106 cells and the pathway by which the PTH effects occurred. The responses were compared with those of phorbol 12,13-dibutyrate (PDBu). Both bovine PTH-(1-34) [bPTH-(1-34)] and PDBu stimulated PC hydrolysis within 10 min. Significant effects were elicited by concentrations of 0.3-1 nM bPTH-(1-34) and 5 nM PDBu. Dose-dependent increases were seen at higher concentrations of both compounds, however, the response to bPTH-(1-34) was reduced at 30 nM. Bovine or human PTH-(1-34) and human PTH-related peptide-(1-34) [hPTHrP-(1-34)] were equipotent in their effects, whereas bovine [Nle(8,18)Tyr34]PTH-(3-34) amide [bPTH-(3-34)] and hPTH-(1-31) amide [hPTH-(1-31)] were less potent than bPTH-(1-34). bPTH-(3-34) did not antagonize the effects of bPTH-(1-34). Down-regulation of protein kinase C isozymes by 24-h treatment with PDBu completely prevented the stimulatory effect of PDBu on PC hydrolysis, but did not significantly affect the stimulatory effect of bPTH-(1-34). Both bPTH-(1-34) and PDBu stimulated transphosphatidylation of PC, indicating a phospholipase D-stimulated mechanism. The results suggest that in the UMR-106 cell line PTH can stimulate activation of PLD by a mechanism other than through protein kinase C.     

Unrelated donor bone marrow transplantation for chronic myelogenous leukemia: a decision analysis

BACKGROUND: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. OBJECTIVE: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. DESIGN: A markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. SETTING: Therapeutic decision at the time of diagnosis of CML. PATIENTS: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. INTERVENTION: Early transplantation, delayed transplantation, and no transplantation. MEASUREMENTS: Quality-adjusted, discounted life expectancy. RESULTS: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 53 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. CONCLUSIONS: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.