Electron beam computed tomography screening of the coronary arteries: experience with 3,263 patients at Walter Reed Army Medical Center.

The U.S. Department of Defense desires to reduce the impact of coronary atherosclerosis on its active duty, retired, and dependent populations. Electron beam computed tomography (EBCT) is currently the best way to noninvasively image the coronary arteries directly. Between August 1997 and February 1999, a total of 3,263 patients were scanned by EBCT in the Radiology Department at Walter Reed Army Medical Center. Scans were performed on 2,415 men (74%) and 848 women (26%). The most common age group was 50 to 54 years (25%). Coronary calcification was found in approximately half of the patients (46%), and the magnitude of the score was strongly associated with age and male gender. Average scores increased exponentially with age, doubling every 7 years. In men, average scores ranged from 17 units in those aged 35 to 39 years to 842 in those older than 70 years old. In women, average scores ranged from 1 in those 35 to 39 years to 162 in those older than 70 years. Significant numbers of patients fell into the high-risk categories, with 8% of men in their 40s, 20% of men in their 50s, 33% of men in their 60s, and 49% of men in their 70s with high scores. Scores of more than 400 units were seen in 368 patients (8%) overall. There is a large amount of coronary calcium present in military personnel and their dependents, in patterns that are consistent with previous studies. Many patients had very high scores that are consistent with advanced coronary artery disease. EBCT should play a central role in the identification of occult calcific atherosclerosis of the coronary arteries in military, retired, and dependent patients.

C-reactive protein is not associated with the presence or extent of calcified subclinical atherosclerosis.

BACKGROUND: Both high-sensitivity C-reactive protein (hsCRP) and electron beam computed tomography (EBCT) coronary artery calcification (CAC) are valid markers of cardiovascular risk. It is unknown whether hsCRP is a marker of atherosclerotic burden or whether it reflects a process (eg, inflammatory fibrous cap degradation) leading to acute coronary events. METHODS: A nested case-control study was performed of 188 men enrolled in the Prospective Army Coronary Calcium study. The serum hsCRP levels (latex agglutination assay) were evaluated in subjects with CAC (CAC score >0, n = 94) and compared with age- and smoking status-matched control subjects (CAC score 0, n = 94). RESULTS: Levels of hsCRP in the highest quartile were related to the following coronary risk factors: smoking status, low-density lipoprotein cholesterol, body mass index, glycosylated hemoglobin, fibrinogen, and homocysteine. The mean hsCRP level was similar in cases (+CAC, 0.20 +/- 0.22 mg/dL) and controls (-CAC, 0.19 +/- 0.21 mg/dL; P =.81) and was unrelated to the log-transformed CAC score (r < 0.01, P =.91). Multivariable analysis controlling for standard risk factors, aspirin, and statin therapy found only that low-density lipoprotein cholesterol was related to CAC. CONCLUSIONS: Despite associations with standard and emerging cardiovascular risk factors, hsCRP is unrelated to the presence and extent of calcified subclinical atherosclerosis. This implies that CAC (a disease marker) and hsCRP (a process marker) may be complementary for the prediction of cardiovascular risk.

Lack of correlation between psychological factors and subclinical coronary artery disease.

BACKGROUND: The relation between psychological variables and clinically evident coronary artery disease has been studied extensively, although the potential mechanisms of such a relation remain speculative. We studied the relation between multiple psychological variables and subclinical coronary artery disease to assess the possible role of such variables in atherogenesis. METHODS: We conducted a prospective study of 630 consecutive consenting, active-duty U.S. Army personnel, 39 to 45 years of age, without known coronary artery disease. Each participant was assessed for depression, anxiety, somatization, hostility, and stress. Subclinical coronary artery disease was identified by electron-beam computed tomography. RESULTS: The mean (+/-SD) age of the subjects was 42+/-2 years; 82 percent were male, and 72 percent were white. The prevalence of coronary-artery calcification was 17.6 percent (mean calcification score, 10+/-49). The prevalence of prior or current psychiatric disorders was 12.7 percent. There was no correlation between the coronary-calcification score and the scores measuring depression (r= -0.07, P=0.08), anxiety (r=-0.07, P=0.10), hostility (r=-0.07, P=0.10), or stress (r=-0.002, P=0.96). Somatization (the number and severity of durable physical symptoms) was inversely correlated with calcification scores (r=-0.12, P=0.003), even after we controlled for age and sex. In multivariate logistic-regression models, a somatization score greater than 4 (out of a possible 26) was independently associated with the absence of any coronary-artery calcification (odds ratio, 0.49; 95 percent confidence interval, 0.25 to 0.96). CONCLUSIONS: Our data suggest that depression, anxiety, hostility, and stress are not related to coronary-artery calcification and that somatization is associated with the absence of calcification.

Multidisciplinary airway stent team: a comprehensive approach and protocol for tracheobronchial stent treatment.

Tracheobronchial stents are being used with increasing frequency to treat major airway obstruction from both malignant and benign processes. Traditionally, stents have been placed via rigid bronchoscopy, flexible bronchoscopy, or fluoroscopy by members of various individual disciplines. We describe a novel multidisciplinary airway stent team (MAST) protocol for tracheobronchial stent placement and endoscopic management of major airway obstruction. A patient with symptoms of airway obstruction is generally first evaluated with a computed tomography scan and a videotaped flexible bronchoscopy. These studies are reviewed by the team otolaryngologist, pulmonologist, and interventional radiologist. A treatment plan, including the type and location of stents and the need for adjuvant therapies, is formulated. Stent placement is performed in the operating room under general anesthesia. Rigid bronchoscopy, with flexible bronchoscopy and fluoroscopy as needed, allows precise stent placement and the best use of various therapeutic methods. The MAST protocol combines the skills, knowledge, and unique therapeutic options of specialists from otolaryngology, pulmonology, and interventional radiology. This approach allows optimal stent placement and the use of other endobronchial therapies, including laser ablation, balloon dilation, photodynamic therapy, cryotherapy, and brachytherapy. A protocol with representative case reports is presented, along with a review and comparison of several of our most commonly used stents. Otolaryngologists who practice bronchoesophagoscopy, by virtue of their operative skill and knowledge of airway management, are well equipped to become leaders of MASTs and are encouraged to initiate MASTs at their institutions.

Rationale and design of the Prospective Army Coronary Calcium (PACC) Study: utility of electron beam computed tomography as a screening test for coronary artery disease and as an intervention for risk factor modification among young, asymptomatic, active-duty United States Army Personnel.

BACKGROUND: Screening for coronary artery calcium with electron beam computed tomography (EBCT) has potential diagnostic and prognostic implications. Most prior research on this technology has been done on selected, high-risk populations. The goal of the Prospective Army Coronary Calcium (PACC) study is to determine the utility of EBCT for the detection of coronary calcium as a screening test for coronary artery disease and as an intervention for risk factor modification among young, asymptomatic, active-duty personnel undergoing the United States Army's Cardiovascular Screening Program. METHODS AND RESULTS: Three study designs will be used to address the objectives of this investigation: (1) a cross-sectional study of 2000 unselected, consecutive participants to determine the prevalence and extent of coronary calcification in the 40- to 45-year-old Army population, (2) a randomized, controlled trial with a 2 x 2 factorial design involving 1000 participants to assess the impact of EBCT information on several dimensions of patient behavior, with and without intensive risk factor case management, and (3) a prospective cohort study of 2000 participants followed for at least 5 years to establish the relation between coronary calcification and cardiovascular events in an unselected, "low-risk" (by conventional standards) Army population. CONCLUSIONS: We present a review of the literature on the clinical utility of EBCT, with a focus on the limited research in young, asymptomatic populations. The details of the PACC study (begun in October1998) are presented. The results of the PACC study will determine the clinical utility of EBCT in young, asymptomatic patients.

Evaluation of the aortic root by MRI: insights from patients with homozygous familial hypercholesterolemia.

BACKGROUND: In homozygous familial hypercholesterolemia (HFH), the aortic root is prone to develop atherosclerotic plaque at an early age. However, the aortic wall and plaque have not yet been assessed in this condition by MRI. We evaluated the aortic root by use of MRI in 17 HFH patients and 12 normal control subjects in a prospective, blinded, controlled study. METHODS AND RESULTS: Morphological assessment of the aortic root was done with spin-echo and gradient-echo MRI scanning. Comparisons were made with a number of measures of disease severity, including cholesterol-year score, calcium score on electron-beam CT (EBCT), and size of Achilles tendon xanthomas. Atherosclerotic plaque, visible on fat-suppressed images but never on water-suppressed images, was present in 9 HFH patients (53%). Supravalvular aortic stenosis was present in 7 patients with HFH (41%). Maximum supravalvular aortic wall thickness was significantly greater and OD and lumen cross-sectional area (CSA) were smaller in patients than in control subjects (P=0.006, 0.0005, and 0.06, respectively). Maximum wall thickness was associated with a greater calcium score on electron-beam CT (P=0.02). Although the cumulative exposure of the aortic root to cholesterol (the cholesterol-year score) was significantly correlated with the Achilles tendon CSA and vascular calcification, this score did not correlate with the wall thickness or aortic CSA. CONCLUSIONS: This study not only demonstrates the utility of MRI for detecting and characterizing aortic root atherosclerotic plaque and supravalvular aortic stenosis in HFH patients but also suggests that the LDL receptor plays a direct or indirect role in aortic mural development and vascular growth.

Aortic hypoplasia in homozygous familial hypercholesterolemia.

Diagnosis of hypoplastic aortic root with ultrafast computed tomography provides important clinical information in homozygous familial hypercholesterolemic patients with supravalvular aortic stenosis.

Prospective sonographic evaluation of interleukin-2-induced changes in the gallbladder.

PURPOSE: To describe the changes in the gallbladder induced by interleukin-2 (IL-2) therapy and to correlate the findings with the clinical course. MATERIALS AND METHODS: Twenty-five men with human immunodeficiency virus (HIV) infection were examined prospectively with right upper quadrant ultrasonography (US) before and after receiving IL-2 therapy. Four patients also underwent US after a second course of IL-2. The gallbladder was evaluated for wall thickening, echotexture, and intramural and pericholecystic fluid. Correlation was made between the clinical signs and symptoms, IL-2 dose, CD4 cell count, and the US appearance of the gallbladder. RESULTS: There was significant correlation between symptoms of right upper quadrant pain during IL-2 therapy and US abnormalities of the gallbladder, including an increase in wall thickening (P = .012) and the development of intramural (P = .015) and pericholecystic (P = .006) fluid. More severe abnormalities were seen with higher IL-2 doses. All symptoms resolved with cessation of IL-2 therapy. In patients who underwent repeat US, the gallbladder reverted to a normal appearance. No correlation was found between the CD4 cell count and the development of symptoms or the US appearance of the gallbladder. CONCLUSION: IL-2-induced changes resolve rapidly with cessation of therapy, and no surgical intervention is needed. These changes can be avoided or reduced by decreasing the IL-2 dose during subsequent cycles.

Safety and efficacy of strength training in patients with sporadic inclusion body myositis.

We studied the effects of a 12-week progressive resistance strength training program in weakened muscles of 5 patients with sporadic inclusion body myositis (IBM). Strength was evaluated with Medical Research Council (MRC) scale ratings and quantitative isometric and dynamic tests. Changes in serum creatine kinase (CK), lymphocyte subpopulations, muscle size (determined by magnetic resonance imaging), and histology in repeated muscle biopsies were examined before and after training. After 12 weeks, the values of repetition maximum improved in the least weakened muscles, 25-120% from baseline. This dynamic effect was not captured by MRC or isometric muscle strength measurements. Serum CK, B cells, T-cell subsets, and NK cells remained unchanged. Repeat muscle biopsies did not reveal changes in the number and degree of degenerating fibers or inflammation. The size of the trained muscles did not change. We conclude that a supervised progressive resistance training program in IBM patients can lead to gains in dynamic strength of the least weak muscles without causing muscle fatigue and muscle injury or serological, histological, and immunological abnormalities. Even though the functional significance of these gains is unclear, this treatment modality is a safe and perhaps overlooked means of rehabilitation of IBM patients.

Crystalluria and urinary tract abnormalities associated with indinavir.

BACKGROUND: Indinavir, a protease inhibitor widely used to treat patients with HIV infection, has been associated with nephrolithiasis. Distinctive urinary crystals and a spectrum of urologic disorders were noted in patients receiving indinavir. OBJECTIVE: To determine the composition of urinary crystals and the frequency of asymptomatic crystalluria and urinary tract symptoms in patients receiving indinavir. PATIENTS: Patients with HIV infection who were enrolled in studies conducted at the National Institutes of Health. MEASUREMENTS: Microscopic urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry of urinary crystals and stones, and clinical evaluation of patients with urologic symptoms. RESULTS: Of 240 patients receiving indinavir, 142 provided urine specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir. Of 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7 (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed syndromes: crystalluria associated with dysuria and crystalluria associated with back or flank pain. Four of the patients with the latter syndrome had radiographic evidence of intrarenal sludging. CONCLUSIONS: Indinavir forms characteristic crystals in the urine. This crystalluria may be associated with dysuria and urinary frequency, with flank or back pain associated with intrarenal sludging, and with the classic syndrome of renal colic.

Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy.

Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28- subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = -.02), whereas CD4+ T-cell number was inversely related to age (R = -.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+ v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

Lipoprotein lipase correlates positively and hepatic lipase inversely with calcific atherosclerosis in homozygous familial hypercholesterolemia.

Homozygous familial hypercholesterolemia (FH) is a rare genetic disorder that leads to premature atherosclerosis due to a defective LDL receptor. There is, however, a large degree of phenotypic heterogeneity at the level of atherosclerosis even in patients with identical mutations of the LDL receptor protein. Lipoprotein lipase (LPL) and hepatic lipase (HL) are crucial enzymes in lipoprotein metabolism, and both have been proposed as having proatherogenic as well as antiatherogenic effects. To evaluate a potential role for these enzymes in the severity of atherosclerosis, we correlated postheparin LPL mass and activity as well as HL activity with the volume of total calcific atherosclerosis (heart and thoracic aorta), coronary artery calcific atherosclerosis, and Achilles tendon width as measured by computed tomography in 15 FH homozygotes. LPL dimer and total mass were positively correlated with all three parameters (r = .65 to .87, P < .01) as was LPL activity (r = .52 to .63, P < .05). HL activity was negatively correlated with total and coronary artery calcified lesion volume (r = -.55 to .57, P < .05). In a multiple regression model of the coronary artery lesion volume, LPL dimer mass and HL activity together accounted for 84% of the variability (r = .92, P < .0001). In a multiple regression model of the total calcified lesion volume, HL activity, total cholesterol, age, and LPL dimer mass together accounted for 85% of the variability (r = .92, P = .0005). These data demonstrate a significant correlation of LPL mass and activity with the extent of calcific atherosclerosis in homozygous FH. It is not clear whether LPL is the cause or consequence of the observed correlation, but if the association between LPL and coronary artery lesions is also present in patients with other genetic dyslipoproteinemias, LPL could constitute a new risk factor for cardiovascular disease.

Strength gains without muscle injury after strength training in patients with postpolio muscular atrophy.

We evaluated changes in the dynamic and isometric strength in the newly weakened quadriceps muscles and asymptomatic triceps muscles of 6 patients with postpolio muscular atrophy (PPMA) after 10 weeks of progressive resistance strength training. Alterations in muscle size were determined with magnetic resonance imaging. Serum creatine kinase levels were measured throughout training, and histological signs of muscle injury and changes in muscle fiber size and types were assessed with muscle biopsies before and after training. Exercise training led to an increase in dynamic strength of 41% and 61% for the two knee extensor tests, and 54% and 71% for the two elbow extensor tests. Up to 20% of the improvement was maintained 5 months after cessation of training. Isometric strength, whole muscle cross-sectional areas of quadriceps and triceps muscles, and serum muscle enzymes did not change. No destructive histopathological changes were noted in the repeat muscle biopsies, and no consistent changes in muscle fiber size or fiber type percentages were observed. These results demonstrate that a supervised resistance training program can lead to significant gains in dynamic strength of both symptomatic and asymptomatic muscles of PPMA patients without serological or histological evidence of muscular damage.

Morphing radiologic images: applications on a desktop computer.

OBJECTIVE: Morphing is an image processing technology that transforms one image into another by generating a series of intermediate synthetic images. The ability to perform morphing, once restricted to high-end graphics workstations, is now widely available for desktop computers. We investigated the potential use of morphing for displaying radiographic images. MATERIALS AND METHODS: Morphing was performed with commercially available software (Morph 2.5; Gryphon Software, San Diego, CA) on a Macintosh (Apple Computer, Cupertino, CA) computer. Images from 26 patients with serial radiologic studies were selected, digitized, and morphed. Key points and key surfaces were identified on the images to improve the quality of the morph movie, a process that took approximately 15 min. The images were then morphed into a continuous Quick Time (Apple) movie lasting 5-7 sec. When a sequence contained more than two images, a single movie incorporating all the images was created. The intervals between segments of the movie were made proportional to the actual time elapsed between the images. Images obtained with different techniques (positron emission tomography and MR imaging) were also morphed. Three observers judged the quality of the morph movies as satisfactory, good, or excellent. RESULTS: Twenty of the 26 movies were judged to be of good or excellent quality. The movie format allowed the rapid display of multiple images in a concise 5- 7-sec time frame. Moreover, the movie allowed the recognition of several simultaneous processes more easily than was possible with static images. Morphing two images of the same anatomic site using different techniques (MR imaging and positron emission tomography) proved to be a simple method of superimposing images. CONCLUSION: Morphing is a readily available and easily learned technique for displaying serial studies. The movie format is a more interesting, intuitive, and concise summary of events than can be provided by serial static images. Morphing may be useful for displaying large numbers of serial images in a short time for occasions such as clinical conferences or teaching purposes.

Relation of cholesterol-year score to severity of calcific atherosclerosis and tissue deposition in homozygous familial hypercholesterolemia.

The high concentrations of low-density lipoprotein cholesterol in plasma lead to accelerated atherosclerosis in patients homozygous for familial hypercholesterolemia (FH). We addressed the hypothesis that lipid deposition in the arterial vasculature and in nonvascular tissues in these patients correlates with both the duration and severity of their hypercholesterolemia. The severity of calcific atherosclerosis was defined by calcification scores and a calcified volume determined by electron beam tomography. The extent of tendinous xanthomatosis was quantitated by computed tomography. A cholesterol-year score was calculated based on the age and the yearly mean serum cholesterol concentration of each patient. Seventeen patients homozygous for FH were followed up. The average total cholesterol concentration in the study group was 780 +/- 231 mg/dl (20.2 mmol/L), and the cholesterol-year scores ranged from 2,172 mg-year/dl (56 mmol-year/L) to 32,260 mg-year/dl (834 mmol-year/L). Achilles tendon width (r=0.86) and cross-sectional area (r=0.81; both p <0.001) were best correlated with the cholesterol-year score. In addition, the coronary (r=0.61; p<0.05), ostial (r=0.45; p<0.05), and total (r= 0.77; p<0.001) calcification atherosclerosis scores all were best correlated with the cholesterol-year score. Calcific atherosclerosis was not observed in these patients until the cholesterol-year score exceeded 10,000 mg-year/dl (260 mmol-year/L). These findings establish a direct association of cholesterol-year with extravascular lipid deposition in tissues of patients with FH. The cholesterol-year score may be useful in defining the risk of atherosclerosis in patients with more common forms of hypercholesterolemia.

Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy.

BACKGROUND: Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus-independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. METHODS: We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. RESULTS: There was an inverse relation between the patients' ages and the CD4+ T-lymphocyte counts six months after therapy was completed (r = -0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r = 0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P = 0.015). CONCLUSIONS: Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.

Coronary artery calcification: assessment with electron beam CT and histomorphometric correlation.

PURPOSE: To assess the reliability of electron beam computed tomography (CT) in the detection of calcific deposits in coronary arteries. MATERIALS AND METHODS: The authors quantitatively evaluated a total of 4,298 segments of coronary arteries with electron beam CT and histomorphometry. RESULTS: Regression analysis of the electron beam CT calcium score versus histomorphometric calcium area produced an r2 value of .92 (r = .96; P < .0001). Ninety-three percent (78 of 84) of all coronary arteries with stenosis of 76%-100% contained calcific deposits, and 20% (17 of 83) of all coronary arteries with stenosis of 0%-50% contained calcific deposits. CONCLUSION: The amount of calcific deposits detected with electron beam CT correlates highly with histomorphometric measurements. Also, the amount of calcific deposits correlates well with the degree of coronary artery stenosis. Electron beam CT, therefore, is a promising noninvasive technique that can help depict the presence and extent of atherosclerotic plaques.

Coronary artery disease: prediction with in vitro electron beam CT.

PURPOSE: To investigate the potential to predict coronary artery disease with electron beam computed tomography (CT). MATERIALS AND METHODS: Fifty heart specimens were examined with electron beam CT and histomorphometric techniques to measure calcific deposits as a percentage of blockage. RESULTS: In group A specimens (from cadavers of patients with symptomatic coronary artery disease), calcific deposits were identified at electron beam CT in 41% (584 of 1,426) of all segments of coronary arteries; in group B specimens (with asymptomatic coronary artery disease), in 24% (369 of 1,535) of all segments; and in the normal control specimens, in 4% (47 of 1,337) of all segments; segments (group A vs control specimens, P < .0001; group B vs control specimens, P = .02). On the basis of logistic regression analysis, coronary artery disease would be predicted if the average electron beam CT calcium score exceeds 0.32. The sensitivity and specificity of electron beam CT in the detection of calcific deposits per coronary artery was 94% and 76%, respectively. CONCLUSION: The electron beam CT calcium score appears to be an effective predictor of coronary artery disease.

Symptomatic interleukin-2-induced cholecystopathy in patients with HIV infection.

OBJECTIVE: This study reports the clinical and radiologic findings in seven patients infected with HIV who had 10 consecutive episodes of symptomatic cholecystopathy induced by infusion of interleukin-2. SUBJECTS AND METHODS: Ten episodes of right upper quadrant pain associated with gallbladder wall thickening were seen in seven of 29 HIV-infected patients who received IV interleukin-2. Patients received 6-18 million IU/day of continuous interleukin-2 infusion for 5 days. Patients with right upper quadrant pain underwent sonographic examinations, which were interpreted prospectively. Medical records and previous sonographic studies were reviewed retrospectively. Follow-up was obtained through outpatient visits and sonography. RESULTS: Right upper quadrant pain during these 10 episodes of cholecystopathy usually developed 4-5 days after starting infusion of interleukin-2. Sonography during that time showed gallbladder wall thickening (mean thickness, 12.4 mm; range, 5-18 mm) and a wide variety of sonographic appearances. Tenderness during sonography was focal in six episodes, diffuse in one, and absent in three. Sludge was identified in one episode; calculi were not seen. Findings on radionuclide biliary scans were normal in three cases. Symptoms abated rapidly in every case after infusion of interleukin-2 was reduced or stopped. No surgery was necessary. When treatment was repeated, three patients had recurrent episodes, with clinical courses and sonographic aberrations showing little variance from the initial episodes. Follow-up sonography in three episodes showed a maximal thickness of the gallbladder wall of 4 mm. No patient had a history or laboratory evidence of intrinsic biliary disease. CONCLUSION: Symptomatic thickening of the gallbladder wall during infusion of interleukin-2 can exactly mimic other forms of acalculous cholecystitis, except that when associated with interleukin-2 the thickening is rapidly reversible and surgery is not required. Radionuclide scans can be useful in clinical decision making. The process appears to be benign, and cessation of interleukin-2 therapy, along with close clinical observation, appears to be the appropriate treatment.

Detection and quantitation of calcific atherosclerosis by ultrafast computed tomography in children and young adults with homozygous familial hypercholesterolemia.

Ultrafast computed tomography (CT) is a new method for detecting calcific lesions in the coronary arteries. The ability of CT to detect and quantify coronary artery atherosclerosis in children and young adults at risk for malignant atherogenesis was evaluated. A total of 11 consecutive familial hypercholesterolemic (FH) homozygotes (3 to 37 years old) participated. Untreated total cholesterol concentrations were 488 to 1277 mg/dL (12.7 to 33.2 mmol/L). Angiography detected significant lesions in 7 of 11 patients. CT detected calcific atherosclerosis in all 9 of the patients older than 12 years of age, including all those with angina. CT was more sensitive in detecting aortic root and coronary ostial lesions, where atherosclerosis first appears in homozygous FH. The volume of calcification (in cubic millimeters) correlated with the severity and duration of the hypercholesterolemia (r = .62, P < .05) as well as with the presence of angina (P < .05). All patients with angina (7 of 7) had > 150 mm3 of calcified volume, whereas only 1 of 4 asymptomatic patients had a volume score > 150 mm3. We conclude that (1) coronary and aortic calcium phosphate deposits are common in young FH homozygotes; (2) these deposits are associated with the presence of angiographic stenoses, as has been seen in adults with coronary atherosclerosis; and (3) aortic calcific deposits are more common than calcific coronary lesions.