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The article presents a study of the quick time (QT) interval adoption in response to exercise in pediatric patients with congenital long-QT syndrome (LQTS). A total of 158 patients were divided into three groups wherein each patient underwent a uniform exercise protocol with a cycle ergometer. The study concluded that genotype-specific changes in repolarization response to exercise and recovery exist in the pediatric population and are of diagnostic utility in LQTS.

Named for Philippe Gaucher, the French physician who in 1882 first described the hepatosplenomegaly characteristics of the genetic disorder, Gaucher disease is incurable. Yet enzyme replacement therapy and other treatments have resulted in symptom relief for many of those afflicted with it. [ABSTRACT FROM AUTHOR]

Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non-high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor., Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category., Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; P interaction =0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; P interaction =0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; P interaction =0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; P interaction =0.661)., Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402.

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome., Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death., Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths ( P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events ( P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P interaction =0.007). In the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend)., Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01663402.

Objective: The aim of the study was to estimate the excess cost of guideline nonadherent cervical cancer screening in women beyond the recommended screening ages or posthysterectomy in a single healthcare system., Materials and Methods: All Pap tests performed between September 1, 2012, and August 31, 2014, in women younger than 21 years, older than 65 years, or after hysterectomy, were coded as guideline adherent or nonadherent per the 2012 America Society of Colposcopy and Clinical Pathology guidelines. We assumed management of abnormal results per the 2013 America Society of Colposcopy and Clinical Pathology management guidelines. Costs were obtained from a literature review and Center for Medicare and Medicaid Services data and applied to nonadherent screening and subsequent diagnostic tests., Results: During this period, 1,398 guideline nonadherent Pap tests were performed (257 in women <21 years, 536 in women >65 years, and 605 after hysterectomy), with 88 abnormal results: 35 (13.5%) in women younger than 21 years, 14 (2.6%) in women older than 65 years, and 39 (6.5%) in women after hysterectomy. The excess cost for initial screening, diagnostic tests, and follow-up was US $35,337 for 2 years in women younger than 21 years, US $54,378 for 5 years in women older than 65 years, and US $77,340 for 5 years in women after hysterectomy, resulting in a total excess cost of US $166,100 for 5 years. Of the 1,398 women who underwent guideline nonadherent screening, there were only 2 (0.1%) diagnoses of high-grade dysplasia (VaIN3)., Conclusions: Guideline nonadherent cervical cancer screening in women beyond the recommended screening ages and posthysterectomy resulted in costs exceeding US $160,000 for screening, diagnostic tests, and follow-up with minimal improvement in detection of high-grade dysplasia.

Objective: To estimate the proportion of guideline nonadherent Pap tests in women aged younger than 21 years and older than 65 years and posthysterectomy in a single large health system. Secondary objectives were to describe temporal trends and patient and health care provider characteristics associated with screening in these groups., Methods: A retrospective cross-sectional chart review was performed at Fairview Health Services and University of Minnesota Physicians. Reasons for testing and patient and health care provider information were collected. Tests were designated as indicated or nonindicated per the 2012 cervical cancer screening guidelines. Point estimates and descriptive statistics were calculated. Patient and health care provider characteristics were compared between indicated and nonindicated groups using χ and Wilcoxon rank-sum tests., Results: A total of 3,920 Pap tests were performed between September 9, 2012, and August 31, 2014. A total of 257 (51%; 95% confidence interval [CI] 46.1-54.9%) of tests in the younger than 21 years group, 536 (40%; 95% CI 37.7-43.1%) in the older than 65 years group, and 605 (29%; 95% CI 27.1-31.0%) in the posthysterectomy group were not indicated. White race in the older than 65 years group was the only patient characteristic associated with receipt of a nonindicated Pap test (P=.007). Health care provider characteristics associated with nonindicated Pap tests varied by screening group. Temporal trends showed a decrease in the proportion of nonindicated tests in the younger than 21 years group but an increase in the posthysterectomy group., Conclusion: For women aged younger than 21 years and older than 65 years and posthysterectomy, 35% of Pap tests performed in our health system were not guideline-adherent. There were no patient or health care provider characteristics associated with guideline nonadherent screening across all groups.

Background: Preservation of myocardial perfusion during general anesthesia is likely important in patients at risk for perioperative cardiac complications. Data related to the influence of general anesthesia on the normal myocardial circulation are limited. In this study, we investigated myocardial microcirculatory responses to pharmacological vasodilation and sympathetic stimulation during general anesthesia with sevoflurane in healthy humans immediately before surgical stimulation., Methods: Six female and 7 male subjects (mean age 43 years, range 28-61) were studied at baseline while awake and during the administration of 1 minimum alveolar concentration sevoflurane. Using myocardial contrast echocardiography, myocardial blood flow (MBF) and microcirculatory variables were assessed at rest, during adenosine-induced hyperemia, and after cold pressor test-induced sympathetic stimulation. MBF was calculated from the relative myocardial blood volume multiplied by its exchange frequency (β) divided by myocardial tissue density (ρT), which was set at 1.05 g·mL(-1)., Results: During sevoflurane anesthesia, MBF at rest was similar to baseline values (1.05 ± 0.28 vs 1.05 ± 0.32 mL·min(-1)·g(-1); P = 0.98; 95% confidence interval [CI], -0.18 to 0.18). Myocardial blood volume decreased (P = 0.0044; 95% CI, 0.01-0.04) while its exchange frequency (β) increased under sevoflurane anesthesia when compared with baseline. In contrast, hyperemic MBF was reduced during anesthesia compared with baseline (2.25 ± 0.5 vs 3.53 ± 0.7 mL·min(-1)·g(-1); P = 0.0003; 95% CI, 0.72-1.84). Sympathetic stimulation during sevoflurane anesthesia resulted in a similar MBF compared to baseline (1.53 ± 0.53 and 1.55 ± 0.49 mL·min(-1)·g(-1); P = 0.74; 95% CI, -0.47 to 0.35)., Conclusions: In otherwise healthy subjects who are not subjected to surgical stimulation, MBF at rest and after sympathetic stimulation is preserved during sevoflurane anesthesia despite a decrease in myocardial blood volume. However, sevoflurane anesthesia reduces hyperemic MBF, and thus MBF reserve, in these subjects.

Background: Excessive accumulation of retinol-based toxins has been implicated in the pathogenesis of geographic atrophy (GA). Fenretinide, an orally available drug that reduces retinol delivery to the eye through antagonism of serum retinol-binding protein (RBP), was used in a 2-year trial to determine whether retinol reduction would be effective in the management of geographic atrophy., Methods: The efficacy of fenretinide (100 and 300 mg daily, orally) to slow lesion growth in geographic atrophy patients was examined in a 2-year, placebo-controlled double-masked trial that enrolled 246 patients at 30 clinical sites in the United States., Results: Fenretinide treatment produced dose-dependent reversible reductions in serum RBP-retinol that were associated with trends in reduced lesion growth rates. Patients in the 300 mg group who achieved serum retinol levels of ≤ 1 μM (≤ 2 mg/dL RBP) showed a mean reduction of 0.33 mm in the yearly lesion growth rate compared with subjects in the placebo group (1.70 mm/year vs. 2.03 mm/year, respectively, P = 0.1848). Retinol-binding protein reductions <2 mg/dL correlated with further reductions in lesion growth rates (r = 0.478). Fenretinide treatment also reduced the incidence of choroidal neovascularization (approximately 45% reduction in incidence rate in the combined fenretinide groups vs. placebo, P = 0.0606). This therapeutic effect was not dose dependent and is consistent with anti-angiogenic properties of fenretinide, which have been observed in other disease states., Conclusion: The findings of this study and the established safety profile of fenretinide in chronic dosing regimens warrant further study of fenretinide in the treatment of geographic atrophy.

Ultrasound contrast agents are gas-filled microbubbles that enhance visualization of cardiac structures, function and blood flow during contrast-enhanced ultrasound (CEUS). An interesting cardiovascular application of CEUS is myocardial contrast echocardiography, which allows real-time myocardial perfusion imaging. The intraoperative use of this technically challenging imaging method is limited at present, although several studies have examined its clinical utility during cardiac surgery in the past. In the present review we provide general information on the basic principles of CEUS and discuss the methodology and technical aspects of myocardial perfusion imaging.

Background: Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST., Methods and Results: The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020+/-283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2+/-2.4 mm(2) and evidence of vessel remodeling (index, 1.6+/-0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263+/-149 white blood cells per high-power field) and eosinophils (DES, 20+/-24 eosinophils per high-power field; sirolimus-eluting stents, 34+/-28; paclitaxel-eluting stents, 6+/-6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20+/-24) than in those from spontaneous acute myocardial infarction (7+/-10), early bare-metal stent ST (1+/-1), early DES ST (1+/-2), and late bare-metal stent ST (2+/-3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm(2) increase in ISA cross-sectional area., Conclusions: Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition.

Purpose of Review: Disturbances in the mitochondrial oxidative phosphorylation pathway most often lead to devastating disorders with a fatal outcome. Of these, complex I deficiency is the most frequently encountered. Recent characterization of the mitochondrial and nuclear DNA-encoded complex I subunits has allowed mutational analysis and reliable prenatal diagnosis. Nevertheless, complex-I-deficient patients without a mutation in any of the known subunits remain. It is assumed that these patients harbour defects in proteins involved in the assembly of this largest member of the oxidative phosphorylation complexes. This review describes current understanding of complex I assembly, new developments and future perspectives., Recent Findings: The first model of human complex I assembly has been proposed recently. New insights into supercomplex assembly and stability may help to explain combined deficiencies. Recent functional characterization of some of the 32 accessory subunits of the complex may link these subunits to complex I biogenesis and activity regulation., Summary: Research on complex I assembly is increasing rapidly. However, comparison between theoretical and experimental models of complex I assembly is still problematic. The growing understanding of complex I assembly at the subunit and supercomplex level will clarify the picture in the future. The elucidation of complex I assembly, by combining patient data with new experimental methods, will facilitate the diagnosis of (and possibly therapy for) many uncharacterized mitochondrial disorders.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

It has been supposed that there are differences with regard to clinical course and outcome due to the underlying etiological factor in acute pancreatitis. Therefore, the objective of this study was to analyze the severity of the disease, serum enzymes, indicators of necrosis, systemic complications, and mortality in acute pancreatitis with regard to the etiology. One hundred ninety patients with acute pancreatitis (127 male, 63 female) were studied prospectively and subdivided into three etiological groups: (i) alcohol, (ii) gallstones, and (iii) other causes and idiopathic acute pancreatitis. Severity scores (Ranson and Bank) and findings by contrast-enhanced computed tomography were similar in all three groups. Analysis of serum enzymes [lipase, aspartate aminotransferase (ASAT)] and indicators of necrosis (C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, and lactate dehydrogenase) showed only for ASAT within 24 h significantly higher levels in biliary acute pancreatitis in comparison with the other groups. There were no differences in the rate of infected pancreatic necrosis and mortality in alcohol-related acute pancreatitis (31 and 5.3%), biliary acute pancreatitis (38 and 10%) and acute pancreatitis due to other etiological factors (43 and 5.5%). In conclusion, this study clearly showed that once the pathogenetic mechanisms have initiated the disease, the course and outcome of acute pancreatitis are not influenced by the underlying etiological factor.

Background: Controversy exists regarding the use of magnesium in the treatment of acute myocardial infarction (AMI) because of apparent conflicting results from clinical trials. One hypothesis to explain the various clinical observations proposes that the timing of magnesium administration significantly influences its therapeutic effect; ie, supraphysiological levels of Mg2+ must be present at the time of reperfusion for magnesium to produce clinical benefit., Methods and Results: These experiments evaluated the effect of varying the timing of magnesium administration during AMI. Female Yorkshire swine (34 to 42 kg) underwent thoracotomy and 50 minutes of left anterior descending coronary artery (LAD) occlusion, followed by 3 hours of reperfusion. In the first group, MgSO4 (250 mg of magnesium diluted in 60 cm3 saline) was infused into the LAD over 12 minutes, beginning immediately with the onset of reperfusion (n = 6, Mg-early group). In the second group, MgSO4 was given after 1 hour of reperfusion (n = 6, Mg-late group). Six pigs received saline instead of magnesium and served as the control group. Lethal arrhythmias were significantly reduced in the Mg-early group. Infarct size was determined by vital staining. Infarct size was 0.16 +/- 0.05 g/kg body wt (Mg-early), 0.35 +/- 0.08 g/kg (Mg-late), and 0.42 +/- 0.04 g/kg for the control group. Compared with the control group, significant (P = .029) reduction in infarct size occurred in the Mg-early group but not in the Mg-late group., Conclusions: We conclude that intracoronary MgSO4 delivered during reperfusion can significantly diminish infarct size in swine, but the timing of administration is critical.

Background: Practitioners often assume a close relation between angiographic coronary artery stenosis and patient functional capacity. To test this unproven hypothesis, we analyzed the relation between coronary artery stenosis measured by different methods and maximal treadmill exercise tolerance in patients with single-vessel disease before and after intervention by percutaneous transluminal coronary angioplasty (PTCA)., Methods and Results: Coronary angiography and maximal exercise testing off anti-ischemic medication were performed before random assignment of 227 patients with single-vessel coronary artery disease to PTCA or drug therapy. Six months later, angiography and exercise testing were repeated with patients assigned to PTCA off anti-ischemic therapy so that the altered coronary stenosis was the only consistent variable. Patients assigned to drug therapy were exercised on drug therapy. Coronary stenosis was assessed visually by the local investigator and quantitatively by blinded caliper and computer methods in central laboratories. Variabilities of caliper and computer measurements were established in a subset read twice. Visually estimated stenosis > or = 90% at baseline was associated with shorter exercise duration (7.9 versus 9.2 minutes, P < .04). Similar segregation at baseline was not observed with caliper or computer methods. Regardless of the method of measurement used, correlation between changes of lesion severity and exercise duration from baseline to follow-up was poor. Patients were angiographically classified as "better," "unchanged," or "worse" if follow-up stenosis was below, within, or above 2 SD of mean technical variability from baseline (+/- 18.8%, caliper, +/- 14.6%, computer). Exercise duration for PTCA patients improved among those with better lesions (+2.4 minutes, n = 50, P = .001) but also among those with unchanged lesions (+1.9 minutes, n = 41, P < or = .001). Unchanged medically treated patients improved less (+0.5 minutes, n = 86, P = .04). Results were similar when patients were angiographically classified by minimum lumen diameter., Conclusions: Handheld calipers and quantitative coronary angiography are equivalent techniques for making anatomic measurements. Neither method identified patients having reduced exercise capacity at baseline as well as visual estimation. The relation between changes of coronary stenosis and exercise duration is highly variable, at least in part because of the insensitivity of angiographic methods for detecting small but potentially important changes. Minimal anatomic improvement 6 months after PTCA does not preclude a good functional outcome. Contrary to common belief, angiographic stenosis does not correlate well with functional capacity, even in patients with single-vessel disease.

Both ranitidine and metoclopramide produce neuropsychiatric side effects. Concomitant use of these drugs preoperatively may produce adverse behavioral and emotional changes. Therefore, in 123 unpremedicated patients undergoing tubal occlusion, behavior, cognitive function, and affect were studied before and after a 2-min intravenous injection of placebo (n = 30), ranitidine 50 mg (n = 32), metoclopramide 10 mg (n = 30), or both ranitidine 50 mg and metoclopramide 10 mg (n = 31). Cognitive function was evaluated by the responses to 11 statements devised to assess attitude toward anesthesia and surgery. Affect was assessed by the word chosen out of 11 word-pairs as best describing the feelings at the time. After ranitidine injection, one patient seemed restless and five seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05) and restlessness (P < 0.05). After metoclopramide injection, 6 (20%) developed akathisia, 13 (43.3%) seemed restless, and 8 (26.7%) seemed drowsy. The changes were associated with subjective sensation of jumpiness (P < 0.01) and discomfort (P < 0.05). When both ranitidine and metoclopramide were injected, 10 (32.3%) developed akathisia, 4 (12.4%) seemed restless, and 11 (35.5%) seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05), jumpiness (P < 0.05), restlessness (P < 0.01), and upset (P < 0.05). Akathisia, a side effect of metoclopramide, seemed to be more prominent when ranitidine was added.

Hepatic-Aid is purported to ameliorate encephalopathy and promote positive nitrogen balance in protein-intolerant, cirrhotic patients by correcting their imbalanced amino acid profile. This study evaluated Hepatic-Acid by comparing a 50-g Casein diet with an identical diet with 20-g Casein/30-g Hepatic-Aid per day in a cross-over study. Four patients with biopsy-proven stable cirrhosis, encephalopathy, and under-nutrition were studied. Each study period included three days of equilibration and eight days of metabolic balance, with the following measured at baseline and on balance days 5 and 8: routine biochemistry, fasting ammonia, psychometric tests, EEG, and plasma amino acid profiles. There was no significant change in clinical status, routine biochemistry, fasting ammonia, psychometrics or EEG between the two study periods. Mean (+/-SD) nitrogen balance on the Casein diet at 1.5 +/- 1.5 g/day was not significantly different from that on the Hepatic-Aid diet at 1.5 +/- 1.2 g/day. Plasma amino acid profiles showed a significant fall (p less than 0.05) in fasting and intraprandial tyrosine (tyr) and phenylalanine (phe) on Hepatic-Aid, but only intraprandial leucine (leu), isoleucine (ile), and valine (val) were significantly increased (p less than 0.05) on Hepatic-Aid. The ratio leu + ile + val to tyr + phe was significantly increased (p less than 0.05) on Hepatic-Aid. It is concluded that Hepatic-Aid, as given in this study, maintains N balance similar to Casein, alters the amino acid profile towards normal, but does not ameliorate encephalopathy.

To evaluate the relative long-term improvement in coronary artery hemodynamics after revascularization by coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA), regional coronary flow reserve (CFR) was measured, by digital computer analysis of 35 mm cine film, in 50 men undergoing cardiac catheterization. CFR (mean +/- SEM) in 12 atherosclerotic arteries before revascularization was 1.02 +/- 0.05. Mean CFR in 29 normal arteries of men with normal coronary arteriograms was significantly higher (2.59 +/- 0.11) than that in 16 atherosclerotic arteries of patients revascularized by CABG (2.02 +/- 0.17, p less than .01) or in 14 atherosclerotic arteries of those revascularized by PTCA (1.97 +/- 0.12, p less than .01). No difference in CFR between the CABG and PTCA groups was found and variables known to influence CFR were similar between groups. Equivalent and significant long-term improvement in coronary artery hemodynamics is provided by CABG or PTCA. We postulate that the difference in CFR in the men with normal arteries and those who underwent revascularization was related to the effects of the general atherosclerotic process, which remain despite successful treatment by these techniques.

Digitalis has been shown to improve the impaired ventricular function associated with coronary artery disease as well as to increase myocardial oxygen consumption and produce coronary vasoconstriction. To elucidate the net result of these contrasting effects, six patients with coronary artery disease and left ventricular ejection fractions less than 0.50 had 1.0 mCi thallium-201 injected intravenously at rest and during three minutes of 33% of maximal handgrip, off and on 0.25 mg daily maintenance digoxin. Thallium-201 scintigram images were taken 30 minutes later and were computer processed with orthogonal linearly interpolated background subtraction and maximal count density equalization. Processed images were visually graded on a 0, 1, or 2 scale for 18 sectors--nine from the AP projections and nine from the 40 degrees left anterior oblique projections. A score resulting from the summation of the 18 sector grades was made for each study, the maximum score being 36. Off digitalis, patients performing handgrip exercise decreased their scintigram scores from 25.7 +/- 1.5 (mean +/- SEM) to 23.0 +/- 1.0, P less than 0.05. When patients were on maintenance digoxin, scores did not change significantly during handgrip exercise. Post exercise scores were significantly higher on digoxin than off (P less than 0.05), whereas, resting scores were unaffected by digoxin. These data suggest that myocardial perfusion, as measured by thallium-201 uptake, is improved in patients on digitalis who have coronary artery disease and left ventricular dysfunction.

Thromboembolism (TE) occurs in about 20% of patients with rheumatic mitral valve disease, and platelet survival time in these patients has correlated with TE. In patients with mitral valve prolapse, TE appears to occur very infrequently. Platelet survival (autologous labeling with chromium-51) was performed in 26 patients with mitral prolapse. Five patients had a history of stroke, as well as normal cerebrovascular arteriography and shortened platelet survival (average half-time +/- SEM 2.3 +/- 0.18 days; normal half-time 3.7 +/- 0.03 days; n = 26; p less than 0.01). Platelet survival was shortened in seven of 21 patients without TE (33%) (3.3 +/- 0.06 days; p less than 0.01 vs patients with TE). In 138 patients with rheumatic heart disease, platelet survival was shortened in 40 of 41 (98%) with a history of TE (2.3 +/- 0.08 days) and in 76 of 97 (78%) without TE (2.9 +/- 0.07 days; p less than 0.001 vs patients with TE). In patients with mitral prolapse, sulfinpyrazone increased platelet survival (2.4 +/- 0.16 to 2.7 +/- 0.19 days; n = 7; p less than 0.05). Our results suggest that platelet survival time is shortened in patients with mitral prolapse and rheumatic heart disease who have had TE. Of those without TE there is an increased frequency of shortened platelet survival in patients with rheumatic heart disease (78%) compared with those with mitral prolapse (33%), consistent with the infrequency of TE in mitral prolapse.

Platelet survival time (SURV) has correlated with thromboembolism in patients with prosthetic cardiac valves. Sulfinpyrazone increases SURV. SURV (autologous labeling with 51Chromium) was measured in 126 patients who had aortic or mitral valve replacement. These patients were followed prospectively. Ninety-four with shortened SURV received sulfinpyrazone; 32 with normal SURV were not treated with platelet suppressants. Eighty-seven patients were anticoagulated with warfarin--67 with shortened SURV and 20 with normal SURV. Eleven patients have had thromboembolism, and all had shortened SURV (2.4 +/- 0.08 days; average half-time +/- SEM; normal 3.7 +/- 0.03 days; n = 26) none had an increase of SURV with sulfinpyrazone (2.3 +/- 0.09 days). Of 83 patients with shortened SURV who did not have embolism, sulfinpyrazone increased SURV in 59 (71%) 2.6 +/- 0.05 to 2.9 +/- 0.06 days). Of 35 patients with shortened SURV who failed to increase SURV with sulfinpyrazone, 11 (31%) had embolism; none of 59 (0%) with an increase of SURV with sulfinpyrazone had thromboembolism. These results suggest that patients with thromboembolism after prosthetic cardiac valve replacement have shortened SURV and that patients treated with slufinpyrazone who have thromboembolism do not have an increased SURV.

To determine the effect of angioplasty-induced arterial injury on regional coronary blood flow, resting and postocclusion reactive hyperemic flows were measured in the left anterior descending (LAD) and circumflex (LCx) coronary arteries of 32 dogs after one of four interventions in the LAD with a balloon angioplasty catheter: group A, no injury; group B, endothelial denudation; group C, medial injury; group D, pretreatment with 325 mg of aspirin 2 hr before medial injury. Resting flows did not change in any group. In group C, hyperemic flow decreased in both the LAD and LCx by 15% to 20% (p less than .001) over 30 to 90 min, suggesting that a circulating substance changed coronary resistance. Histologic and ultrastructural studies of the LADs demonstrated an intact endothelial cell layer in group A, endothelial disruption with a few adherent platelets in group B, medial injury with a dense layer of adherent platelets in group C, and medial injury with a few adherent platelets in group D. Thus endothelial denudation results in relatively mild platelet deposition and no change in resting or hyperemic coronary blood flow. In contrast, medial injury results in relatively marked platelet deposition and a significant decrease in hyperemic flow, both of which are prevented by platelet inhibition with aspirin.