Impact of Carotid Artery Angioplasty and Stenting on Management of Recurrent Carotid Artery Stenosis

Citing the higher perioperative risk of redo carotid surgery, balloon angioplasty and stenting of the carotid artery (CAS) has been advocated for recurrent carotid stenosis (RCS). To examine the impact of CAS on the management and outcome of recurrent stenosis, a retrospective review of a prospectively compiled database was performed. From a registry of patients treated for carotid disease, 105 procedures were performed from 1992 to 2002 for RCS. For comparison, two study groups were examined. Time I consisted of 77 reoperations performed through 1998, before CAS was introduced at our institution. Time II included 12 reoperations and 16 CAS procedures performed for RCS from 1999 through 2002. Using perioperative stroke as a measure of outcome, the results for time II were poorer than for time I (7.2% vs. 5.2%, p = NS). Overall, the risk of perioperative stroke was the same for reoperation (5/89) and CAS (1/16) (5.6% vs. 6.3%, p = NS). Although not statistically significant, there was a trend toward a higher risk of perioperative stroke for patients treated with reoperation during the latter time period (8.3% vs. 5.2%, p = NS). This probably relates to the finding that during time II, CAS was most likely to be used in asymptomatic patients (68.6% vs. 41.7%, p = NS) with early (<3 years) RCS (87.5% vs. 41.7%, p = 0.01). No patient with asymptomatic, early RCS had a perioperative stroke with either surgery or CAS (0/35 cases, 0%). The presence of preoperative neurologic symptoms was significantly predictive of a perioperative stroke among all procedures performed for RCS (13.6% vs. 0%, p = 0.004). Contrary to suggestions that CAS might improve the management of RCS, a review of our data shows the overall risk of periprocedural stroke to be no better since CAS has become available. The bias for using CAS for asymptomatic myointimal hyperplastic lesions, and reoperation for frequently symptomatic late recurrent atherosclerotic disease, makes direct comparisons of the two techniques for treating RCS difficult. It is expected that the overall risk for redo carotid surgery will increase, as fewer low-risk patients will be receiving open procedures. However, the increased risk among symptomatic patients undergoing reoperation suggests that endovascular techniques should be investigated among this group of cases as well.Presented at the Twenty-eighth Annual Meeting of the Peripheral Vascular Surgery Society, Chicago, IL, June 7, 2003.     

Activation kinetics of the slow afterhyperpolarization in hippocampal CA1 neurons

The activation of the slow afterhyperpolarization (sAHP) in CA1 neurons was studied using whole-cell recordings in the presence of inhibitors of the fast and medium-duration AHPs. The amplitude of the slow afterhyperpolarization current (IsAHP) increased as a function of duration and magnitude of the depolarizing voltage pulse reflecting graded increases in Ca²⁺ influx through voltage-dependent Ca²⁺ channels. Therefore, the time constant for activation, _max, determined from a family of IsAHPs as a function of pulse duration, was voltage dependent decreasing several-fold within the range of –20 to 20 mV and was dependent on extracellular [Ca²⁺]. The IsAHP displayed a pronounced rising phase that was well fit by a single exponential with a time constant, _rise, that was invariant of pulse duration, voltage, IsAHP amplitude, or external [Ca²⁺] and was significantly slower than the _max. In current clamp, the magnitude of the sAHP increased with the number of evoked action potentials, yet _rise of the sAHP was invariant of action potential number and was similar to the _rise of the IsAHP recorded in voltage-clamp. The results suggest that there are two components to the development of the IsAHP, a rapid, voltage- and Ca²⁺-dependent step, the magnitude and rate of which reflects the voltage dependence of the Ca²⁺ channels, that triggers a second rate-limiting, voltage-independent process that dictates the slow IsAHP rise kinetics.     

Pharmacoeconomics: the cost of prophylactic migraine treatments

Migraine preventive medications considered effective reduce headache frequency by 50 percent in approximately 50 percent of treated patients. In spite of similar effectiveness, these medications vary tremendonsly in their prices. Knowledge of medication prices and employing cost-effective strategies may greatly reduce treatment costs.     

Successful management of carotid stenosis in a high-risk population at an inner-city hospital

This is a retrospective review of all carotid endarterectomies (CEA) (n=91) done from 1993 to 2002 at an inner-city hospital (Group I). This group was compared to a randomly selected group of patients (n=445) treated at a private hospital (Group II). The same high-volume surgeons performed CEAs at both hospitals. The majority of Group I patients (71.4%) were members of racial minority groups. They were also more likely to be younger (p<0.001), hypertensive (p<0.03), diabetic (p<0.001), and current smokers (p<0.001); have contralateral carotid artery occlusion (p=0.04); and present with stroke (p<0.001) than Group II patients. Despite this, the incidence of postoperative myocardial infarction (2.2% vs 0.2%, p=0.08), stroke (1.1% vs 1.6%, NS), and death (1.1% vs 0%, NS) was comparable between the 2 groups. Aggressive preoperative workup for occult cardiac disease in Group I revealed an incidence of 25.9% (n=15). Of these, 5 (33.3%) were found to have coronary artery disease severe enough to warrant intervention before CEA. In an inner-city population with increased medical comorbidities, more severe cerebrovascular disease, and relatively low volume of carotid surgery, the results of CEA were comparable to those in patients treated at a high-volume private hospital. The presence of high-volume surgeons, operating at the low-volume municipal hospital, may contribute to the low complication rate. Finally, aggressive preoperative cardiac workup in this underserved population revealed a meaningful incidence of occult coronary artery disease requiring intervention before CEA.     

Design, synthesis, and biological evaluation of thio-containing compounds with serum HDL-cholesterol-elevating properties

A novel series of substituted sulfanyldihydroimidazolones (1) that modulates high-density lipoprotein cholesterol (HDL-C) has been reported to have HDL-elevating properties in several animal models. Concerns about the chemical and metabolic stability of 1 directed us to explore the structure-activity relationship (SAR) of a related series of substituted thiohydantoins (2). Expansion of the scope of the thiohydantoin series led to exploration of compounds in related thio-containing ring systems 3-7 and the N-cyanoguanidine derivative 8. Compounds were tested sequentially in three animal models to assess their HDL-C elevating efficacy and safety profiles. Further evaluation of selected compounds in a dose-response paradigm culminated in the identification of compound 2.39 as a candidate compound for advanced preclinical studies.     

Discussions about cognitive impairment in first medical visits: older patients' perceptions and preferences

Primary care physicians are the first medical contact for most patients with early-stage dementia. However, little is known about older patients' desire for discussions about cognitive problems or the frequency of discussions about cognitive status during primary care visits. To investigate this question, older patients and accompanying individuals were interviewed separately following the first visit with a primary care physician in an outpatient geriatric medical practice. Patients indicated that memory was discussed in 62 percent of visits. When memory was not discussed, almost one-third of patients stated that they would have wanted to discuss it. Physicians were more likely than patients to initiate discussions about memory. Patient factors, including age, gender, the presence of an accompanying individual, number of diagnoses, and the patient's statement that cognitive function was a main goal of the visit, were examined as predictors of the likelihood of discussion of memory during the first visit. Patients who identified discussing cognitive function as a goal of the visit were more likely to have a discussion about memory than those who did not.     

Changes in the auditory nerve brainstem evoked responses in a case of maple syrup urine disease

Maple syrup urine disease (MSUD) is a rare metabolic disease due to deficiency in the enzyme that breaks down branched chain amino acids. Lack of the enzyme causes accumulation of these amino acids and, if untreated, causes severe neurological damage. A case study of a 10-day old female infant, born after 40 weeks' gestation with a birthweight of 2740 g with MSUD hospitalized in the acute stage with respiratory failure and severe brain oedema is described. As part of the neurological evaluation, auditory nerve brainstem evoked response testing was conducted and revealed bilateral presence of the first wave from the auditory nerve, with no later brainstem waves. Over the course of days when her condition improved following dialysis treatment and a diet to reach balanced levels of branched chain amino acids, the later brainstem waves appeared on one side, and several weeks later they were also observed on the other side. The possible mechanisms of the reversibility of the appearance of brainstem waves in this case are discussed.     

A mouse model of episodic ataxia type-1

Episodic ataxia type-1 (EA1) is a dominant human neurological disorder characterized by stress-induced attacks of ataxia. EA1 is caused by mutations in the voltage-gated potassium channel Kv1.1, and affected individuals are heterozygous. Here we introduced the V408A EA1 mutation into mice using homologous recombination. In contrast to Kv1.1 null mice, homozygous V408A/V408A mice died after embryonic day 3 (E3). V408A/+ mice showed stress-induced loss of motor coordination that was ameliorated by acetazolamide, a carbonic anhydrase inhibitor that minimizes EA1 symptoms in human patients. We made electrophysiological recordings from cerebellar Purkinje cells in both V408A/+ mice and their wild-type littermates. V408A/+ mice showed a greater frequency and amplitude of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) than did wild type; however, the amplitude or frequency of miniature IPSCs and the basket cell firing frequency did not differ between groups. The stress-induced motor dysfunction in V408A mice is similar to that of family members harboring the EA1 allele, and our findings suggest that these behavioral changes are linked to changes in GABA release.     

A model for predicting occult carotid artery stenosis: screening is justified in a selected population

OBJECTIVES: The diagnosis and treatment of carotid artery disease is an integral part of stroke prevention. However, a population of patients who would benefit from screening for carotid artery stenosis has not been well defined. As part of an institutional stroke-screening program, a modified, rapid duplex scan was developed to evaluate patients for occult carotid stenosis. The goal of this study was to evaluate risk factors predictive of carotid stenosis in a selected population, and to identify patients who would benefit from carotid screening. METHODS: Patients were eligible for the study if they were >60 years of age and had a history of hypertension, heart disease, current smoking, or family history of stroke. A modified carotid duplex scan that had been previously validated against formal duplex scanning was utilized; this involved visualization of the carotid bulb and proximal internal carotid artery where Doppler flow velocities were obtained and recorded. RESULTS: Screening was performed on 394 patients. Thirty-eight patients (9.6%) had either unilateral or bilateral carotid stenosis of > or =50%. Risk factors evaluated included smoking, hypertension, cardiac disease, or hypercholesterolemia. If none of these risk factors was present, the incidence of carotid stenosis was 1.8%. This increased to 5.8% with one risk factor, 13.5% with two risk factors, and 16.7% with three risk factors. Two of three patients with all four risk factors had carotid stenosis (66.7%). Logistic regression and prespecified contrast statements for multiple comparisons were used to assess the relationship between the presence of risk factors and occult carotid artery stenosis. The presence of any one of these risk factors was associated with a statistically significant increase in the presence of occult carotid stenosis (P <.01). This was also statistically significant for the presence of any two risk factors (P <.01) or three risk factors (P <.05). CONCLUSION: The prevalence of carotid stenosis significantly increases with the presence of one or more identifiable demographic risk factors in a selected population. Assuming the diagnosis and treatment of carotid stenosis are fundamental to stroke prevention, screening for carotid artery disease is justified in this group of patients.