Kay T. Kimball

Soluble Cell Adhesion Molecules in Hypertriglyceridemia and Potential Significance on Monocyte Adhesion

Hypertriglyceridemia may contribute to the development of atherosclerosis by increasing expression of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as markers for CAMs. In this study, we examined the association between sCAMs and other risk factors occurring with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels, and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhesion in vitro. Compared with normal control subjects (n=20), patients with hypertriglyceridemia and low HDL (n=39) had significantly increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316+/-28.8 versus 225+/-16.6 ng/mL), sVCAM-1 (743+/-52.2 versus 522+/-43.6 ng/mL), and soluble E-selectin (83+/-5.9 versus 49+/-3.6 ng/mL). ANCOVA showed that the higher sCAM levels in patients occurred independently of diabetes mellitus and other risk factors. In 27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for > or =7 months, triglyceride level was reduced by 47+/-4.6%, sICAM-1 level was reduced by 9+/-3.4% (P=.02), and soluble E-selectin level was reduced by 16+/-3.2% (P<.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that disorders in triglyceride and HDL metabolism influence CAM expression and treatment with fish oils may alter vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1 at the concentration seen in patients significantly inhibited adhesion of monocytes to interleukin-1-stimulated cultured endothelial cells under conditions of flow by 27.5+/-7.2%. Thus, elevated sCAMs may negatively regulate monocyte adhesion.

Increased independence and decreased vertigo after vestibular rehabilitation

OBJECTIVE: We sought to determine the effectiveness in decreasing some symptoms, such as vertigo, and increasing performance of daily life skills after vestibular rehabilitation. STUDY DESIGN AND SETTING: Patients who had chronic vertigo due to peripheral vestibular impairments were seen at a tertiary care center. They were referred for vestibular rehabilitation and were assessed on vertigo intensity and frequency with the use of the Vertigo Symptom Scale, the Vertigo Handicap Questionnaire, the Vestibular Disorders Activities of Daily Living Scale, and the Dizziness Handicap Inventory. They were then randomly assigned to 1 of 3 home program treatment groups. RESULTS: Vertigo decreased and independence in activities of daily living improved significantly. Improvement was not affected by age, gender, or history of vertigo. CONCLUSION: For many patients a simple home program of vestibular habituation head movement exercises is related to reduction in symptoms and increasing independence in activities of daily living.

Nondieting Versus Dieting Treatment for Overweight Binge-Eating Women

This study evaluated the effectiveness of nondieting versus dieting treatments for overweight, binge-eating women. Participants (N = 219) were randomly assigned to 1 of 3 groups: diet treatment (DT), nondiet treatment (NDT), or wait-list control (WLC). DT received a balanced-deficit diet reinforced with behavioral strategies. NDT received therapy designed to help participants break out of their dieting cycles. Treatment in both conditions was administered in weekly groups for 6 months, followed by 26 biweekly maintenance meetings, for a total of 18 months of contact. At 6 months posttreatment, DT lost 0.6 kg while NDT gained 1.3 kg. Both treatment groups reduced their Binge Eating Scale scores significantly more than WLC. At 18-month follow-up, both treatment groups experienced weight gain but maintained similar reductions in binge eating. Results indicate that neither intervention was successful in producing short- or long-term weight loss. Therapist biases, which may have affected treatment integrity, and other methodological issues are discussed in relation to the small weight losses achieved.

Blood pressure and symptoms of depression and anxiety: a prospective study

This study investigated whether symptoms of depression and anxiety were related to the development of elevated blood pressure in initially normotensive adults. The studys hypothesis was addressed with an existing set of prospective data gathered from an age-, sex-, and weight-stratified sample of 508 adults. Four years of follow-up data were analyzed both with logistic analysis, which used hypertension (blood pressure > or =140 mm Hg systolic or 90 mm Hg diastolic) as the dependent variable, and with multiple regression analysis, which used change in blood pressure as the dependent variable. Five physical risk factors for hypertension (age, sex, baseline body mass index, family history of hypertension, and baseline blood pressure levels) were controlled for in the regression analyses. Use of antidepressant/antianxiety and antihypertensive medications were controlled for in the study. Of the 433 normotensive participants who were eligible for our study, 15% had missing data in the logistic regression analysis focusing on depression (n = 371); similarly, 15% of the eligible sample had missing data in the logistic regression using anxiety as the psychological variable of interest (n = 370). Both logistic regression analyses showed no significant relationship for either depression or anxiety in the development of hypertension. The multiple regression analyses (n = 369 for the depression analysis; n = 361 for the anxiety analysis) similarly showed no relationship between either depression or anxiety in changes in blood pressure during the 4-year follow-up. Thus, our results do not support the role of depressive or anxiety symptoms in the development of hypertension in our sample of initially normotensive adults.

Prognostic Value of Exercise 201Tl Tomography in Patients Treated With Thrombolytic Therapy During Acute Myocardial Infarction

BACKGROUND Although myocardial perfusion scintigraphy is of proven value in the risk stratification of patients with a recent myocardial infarction who receive conventional therapy, its value in patients undergoing thrombolytic therapy remains controversial. METHODS AND RESULTS Seventy-one patients who received thrombolytic therapy for acute myocardial infarction had exercise 201Tl tomography and coronary angiography before hospital discharge. Eleven (15%) of 71 patients had ischemic ST-segment depression during exercise, whereas 27 patients (38%) had scintigraphic ischemia. Twenty-five (37%) of 68 patients had a cardiac event consisting of either death (n = 2), recurrent myocardial infarction (n = 5), congestive heart failure (n = 7), or unstable angina (n = 11) during a follow-up of 26 +/- 18 months. Univariate predictors of cardiac events were as follows: Killip class (P = .04); left ventricular ejection fraction (P < .0005); total (P = .002) and ischemic (P < .0005) perfusion defect size; percent thallium lung uptake (P = .001); presence of infarct-zone redistribution (P = .02); and multivessel coronary artery disease (P = .01). By multivariate analysis, the significant joint predictors of risk were ejection fraction (P < .0005) and ischemic perfusion defect size (P = .005). The combination of ejection fraction and thallium tomography added significant incremental prognostic information to the clinical data, whereas angiography did not further improve a model that included clinical, ejection fraction, and tomographic variables. CONCLUSIONS Quantitative exercise 201Tl tomography provides important incremental, long-term prognostic information in patients receiving thrombolytic therapy for acute myocardial infarction.

Duodenal morphology and intensity of infection in AIDS-related intestinal cryptosporidiosis

BACKGROUND The pathogenesis of intestinal cryptosporidiosis is not known. Previous studies have shown that the intensity of infection varies between patients. The hypothesis of this study is that intestinal injury is related to the intensity of infection. METHODS The histological abnormalities associated with Cryptosporidium infection were evaluated in duodenal biopsy specimens from 18 patients with acquired immunodeficiency syndrome-associated cryptosporidiosis. The intensity of Cryptosporidium infection was assessed histologically in all patients as the percentage of mucosa covered by organisms and by quantitation of oocyst excretion in the stools of 14 patients. RESULTS Duodenal biopsy specimens from 13 patients (72%) showed normal villous architecture. In these patients, the inflammatory component of the lamina propria was either normal or moderately increased. This increase consisted mostly of lymphocytes and plasma cells. Five of 18 patients (28%) had flattening of the mucosa associated with a prominent neutrophilic infiltrate. The intensity of infection in patients with villous flattening as measured from biopsy specimens and stool was significantly higher than in those without flattening (92% vs. 12% mucosa occupied with organisms; 738 x 10(3) vs. 199 x 10(3) oocyst/mL stool) (P < 0.004 in both cases). CONCLUSIONS Most patients with intestinal Cryptosporidium infection had normal duodenal villous architecture. Severe duodenal morphological abnormalities, including flattening of the villi, were associated with high-intensity infections.

Angiographic and hemodynamic determinants of myocardial ischemia during adenosine thallium-201 scintigraphy in coronary artery disease.

Background. Myocardial ischemia attributed to coronary steal may occur in some patients receiving pharmacological coronary vasodilation. ECG ST‐segment depression is a marker of myocardial ischemia in these patients, but the factors determining the presence or absence of ischemia are not well known. Methods and Results. To examine the angiographic, hemodynamic, and scintigraphic determinants of adenosine‐induced ischemic ST‐segment depression in patients with coronary artery disease, we studied 65 consecutive patients (45 men and 20 women; mean age, 65 ± 12 years) who showed reversible perfusion defects during adenosine (140 &mgr;g · kg‐1 · min‐1 for 6 minutes) 201TI single‐photon emission computed tomography. Patients with prior myocardial infarction were excluded. Ischemic ST depression occurred in one third of the whole cohort (22 of 65 patients). The presence of coronary collateral vessels (p =0.001), systolic blood pressure at baseline (p =0.006), and adenosine‐induced anginal chest pain (p =0.011) were the only significant independent predictors of ischemic ST‐segment depression by stepwise logistic regression analysis. Rate‐pressure product at baseline, systolic blood pressure, heart rate, rate‐pressure product, increase in heart rate, and rate‐pressure product during adenosine infusion and maximal percent stenosis were variables also significantly related to ischemic ST depression by univariate analysis but were not predictive after the three primary variables were included in the regression model. Perfusion defect size, number of diseased vessels, and age did not correlate with ST‐segment depression. Conclusions. The presence of collaterals, which may predispose to coronary collateral steal, is the most significant correlate of ischemic ST‐segment depression during adenosine infusion. Systolic blood pressure at baseline, which may affect the myocardial oxygen supply/demand ratio and anginal chest pain induced by adenosine, are additional variables related to ischemic ST‐segment depression during adenosine infusion. (Circulation 1993;87:1211‐1219)

Effectiveness of treatments for benign paroxysmal positional vertigo of the posterior canal.

Objective: To determine which common, nonpharmacological, nonsurgical treatments are most effective for treatment of benign paroxysmal positional vertigo (BPPV). Study Design: Prospective, randomized, sham-controlled. Patients: Patients (n = 124) with BPPV of the posterior semicircular canal. Setting: Tertiary care center. Interventions: Random assignment to one of five groups: modified canalith repositioning maneuver (CRP), modified liberatory maneuver (LM), sham maneuver, Brandt and Daroffs exercise, and vertigo habituation exercises. Subjects received a standard educational lecture about BPPV and the purpose of the intervention. No vestibular-suppressant medication or special instructions for head positioning were used. Post-tests were given at 1 week after treatment and at approximately 3 months and 6 months later. Main Outcome Measures: Vertigo intensity and frequency. Results: Multilevel analyses showed that vertigo decreased significantly after LM, CRP, and Brandt-Daroff exercise; those three groups did not differ significantly. The habituation group did not differ from sham, Brandt-Daroff, LM, or CRP groups. Changes in scores were maintained throughout the 6-month follow-up period. Conclusion: LM, CRP, and exercises are all effective interventions; patient education plus the sham maneuver, however, had some beneficial effect. These results support two possible mechanisms of BPPV: displaced otoconia and a neural mechanism affecting interpretation of semicircular canal signals.

Application of the Vestibular Disorders Activities of Daily Living Scale

Objective Existing scales of functional performance are either insufficiently sensitive or omit some important daily life tasks. This paper demonstrates that a new scale of self‐perceived disablement in the vestibularly impaired population—the Vestibular Disorders Activities of Daily Living Scale (VADL)—differentiates between disabled and healthy persons and evaluates the associations of this assessment with other measures of vestibular disorders.

Benign Paroxysmal Positional Vertigo and Comorbid Conditions

Purpose: To determine the prevalence of comorbid disease in patients with benign paroxysmal positional vertigo (BPPV) and the relationship of comorbid disease to symptoms of vertigo, disequilibrium, and anxiety. Procedures: Patients who had posterior semicircular canal BPPV and who had been referred for vestibular rehabilitation at a tertiary care center completed a health status questionnaire and the Vertigo Symptom Scale, answered questions about level of vertigo, and were tested on computerized dynamic posturography. Results: Subjects had high rates of diabetes, mild head trauma, and probable sinus disease. Balance was generally impaired, worse in diabetics and subjects with significant vestibular weakness. Subjects who smoked or had had mild head trauma had higher levels of anxiety. Conclusions: Comorbid conditions, particularly diabetes, mild head trauma, and sinus disease, are unusually prevalent in BPPV patients. Message: Patients with comorbid disease are at risk for having increased vertigo, anxiety, and disequilibrium compared to other patients.