University Hospitals Sharon Health Center

Cholesterol-4-(14)C was injected intravenously into a series of normal men, untreated hyperlipidemic patients, and hyperlipidemic patients being treated with cholestyramine. The specific radioactivity of plasma total cholesterol was measured during the ensuing 10 wk. 16 studies were carried out in 10 subjects. Analysis of the turnover curves of plasma cholesterol revealed that in every study the turnover of plasma cholesterol conformed to a two-pool model. Each turnover curve was analyzed in terms of this model, as expressed by the equation: specific activity = C(A)e(-alphat) + C(B)e(-betat). The parameters which were calculated included the constants C(A), C(B), alpha, and beta; the size of the first pool (M(A)); the rate constants for the total rate of removal of cholesterol from each pool (k(AA) and k(BB)); and the production rate in pool A (PR(A)). In two normal men and five untreated patients the average size of pool A was 25g. The effect of cholestyramine was assessed by comparing the results obtained without therapy with those obtained during therapy in five subjects studied under both conditions. Cholestyramine therapy produced a large increase in PR(A) (from 0.98 to 1.98 g/day) and in the rate of removal of cholesterol from pool A. Cholestyramine did not significantly alter the size of pool A. It is not possible to calculate the size of the total body exchangeable pool of cholesterol from the turnover curve of plasma cholesterol. It is also not possible to calculate the metabolic turnover rate, i.e., the rate of cholesterol degradation and excretion, in the whole body. This parameter can, however, be estimated by assuming that cholesterol is removed from the body only by way of the tissue pools that comprise pool A. Under these conditions the metabolic turnover rate is equal to the production rate in pool A.

BACKGROUND: Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies. OBJECTIVES: This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States. METHODS: In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates. RESULTS: In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (<1%) and coronary revascularization (1% to 3%), across all years of study follow-up. In contrast, patients with ischemia+/LGE+ experienced a >4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers. CONCLUSIONS: In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891).

Abstract A comparison has been made of human serum lipoprotein analysis by agarose gel and paper electrophoresis with a standard method of analytical ultracentrifugation. Samples were obtained from 28 patients with various disorders of lipoprotein metabolism. Correspondence was shown between the following electrophoretic and ultracentrifugal fractions: β and S f 0–20; pre‐β and S f 20–400; α 1 and total HDL. The deviations observed with the electrophoretic methods, though sizable, were smaller than the usual clinically significant abnormalities. Semiquantitative application is there fore justified. Agarose gel electrophoresis is slightly more difficult than paper electrophoresis, but gives improved resolution of pre‐β‐ and β‐lipoproteins and better densitometric scans. Evidence was also presented that the agarose method, when used in conjuction which ultracentrifugation, may be a valuable research technique for the study of lipoprotein properties.

Accuracy of the automated fluorometric measurement of triglyceride by the technique of Kessler and Lederer is limited by the instability of the baseline. Concentration of the alcoholic KOH reagent was modified, and the pump tube manifold altered to provide on-stream mixing of the KOH reagent, which overcame this difficulty. A relatively inexpensive fluorometer with the solid-state photomultiplier microphotometer, modified to provide dual-scale sensitivity, was used to increase precision of measurements. Analytical results for 30 serum samples, taken from three pools of frozen serum, show the accuracy of the measurements to be ±8 mg/100 ml and the standard deviation ±9 mg/100 ml for a single determination.

Abstract Accuracy of the automated fluorometric measurement of triglyceride by the technique of Kessler and Lederer is limited by the instability of the baseline. Concentration of the alcoholic KOH reagent was modified, and the pump tube manifold altered to provide on-stream mixing of the KOH reagent, which overcame this difficulty. A relatively inexpensive fluorometer with the solid-state photomultiplier microphotometer, modified to provide dual-scale sensitivity, was used to increase precision of measurements. Analytical results for 30 serum samples, taken from three pools of frozen serum, show the accuracy of the measurements to be ±8 mg/100 ml and the standard deviation ±9 mg/100 ml for a single determination.

Antarctic bryophyte communities presently tolerate physiological extremes in water availability, surviving both desiccation and submergence events. We investigated the relative ability of three Antarctic moss species to tolerate physiological extremes in water availability and identified physiological, morphological, and biochemical characteristics that assist species performance under such conditions. Tolerance of desiccation and submergence was investigated using chlorophyll fluorescence during a series of field- and laboratory-based water stress events. Turf water retention and degree of natural habitat submergence were determined from gametophyte shoot size and density, and d13C signatures, respectively. Finally, compounds likely to assist membrane structure and function during desiccation events (fatty acids and soluble carbohydrates) were determined. The results of this study show significant differences in the performance of the three study species under contrasting water stress events. The results indicate that the three study species occupy distinctly different ecological niches with respect to water relations, and provide a physiological explanation for present species distributions. The poor tolerance of submergence seen in Ceratodon purpureus helps explain its restriction to drier sites and conversely, the low tolerance of desiccation and high tolerance of submergence displayed by the endemic Grimmia antarctici is consistent with its restriction to wet habitats. Finally the flexible response observed for Bryum pseudotriquetrum is consistent with its co-occurrence with the other two species across the bryophyte habitat spectrum. The likely effects of future climate change induced shifts in water availability are discussed with respect to future community dynamics.

Grape phylloxera (Daktulosphaira vitifoliae Fitch) is a root-feeding pest of grapevines. In Australia, phylloxera-infested vineyards are subjected to quarantine restrictions and early detection remains vital for the timely implementation of post-outbreak quarantine protocols. Current detection methods rely on time-consuming ground surveying, which involves detailed examination of grapevine (Vitis vinifera L.) root systems. Leaf pigment composition is often a sensitive indicator of plant stress. The increasing popularity of remote sensing systems, which exploit those changes in pigments observed with plant stress, offers a real possibility for the development of a phylloxera-specific remote detection system. Our objective was to investigate changes in grapevine leaf pigments associated with phylloxera infestation and to relate any changes to appropriate reflectance indices. This was achieved with a glasshouse experiment in which the responses of two vine cultivars (Cabernet Sauvignon and Shiraz) to phylloxera infestation were compared with their responses to water and nitrogen deficiencies. The responses of leaf pigments to phylloxera infestation were also investigated in Pinot Noir and Cabernet Sauvignon grapevines grown under field conditions. A reduction in the leaf chlorophyll content and an increase in photoprotective pigment concentrations were observed in leaves of phylloxera-infested grapevines compared with uninfested vines. The photochemical reflectance index (PRI) was found to be most closely associated with the ratio of total carotenoid to chlorophyll in these vines.

The two types of adipose tissue in humans, white and brown, have distinct developmental origins and functions. Human white adipose tissue plays a pivotal role in maintaining whole-body energy homeostasis by storing triglycerides when energy is in surplus, releasing free fatty acids as a fuel during energy shortage, and secreting adipokines that are important for regulating lipid and glucose metabolism. The size of white adipose mass needs to be kept at a proper set point. Dramatic expansion of white fat mass causes obesity--now become a global epidemic disease--and increases the risk for the development of many life-threatening diseases. The absence of white adipose tissue or abnormal white adipose tissue redistribution leads to lipodystrophy, a condition often associated with metabolic disorders. Brown adipose tissue is a thermogenic organ whose mass is inversely correlated with body mass index and age. Therapeutic approaches targeting adipose tissue have been proven to be effective in improving obesity-related metabolic disorders, and promising new therapies could be developed in the near future.

Long-term studies (32-49 wk) of the turnover of plasma cholesterol were conducted in 24 subjects. Eight subjects were normilipidemic, six had hypercholesterolemia, eight had hypercholesterolemia and hypertriglyceridemia, and two had hypertriglyceridemia alone. 10 of the hyperlipidemic patients had a definite familial disorder. In all subjects (except one for whom complete data were not available), the same three-pool model previously described gave the best fit for the data. The parameters of the three-pool model observed in the normal subjects were compared with the model parameters found in the patients with the different kinds of hyperlipidemia. In addition, single and multiple regression analyses were conducted to explore the relationships between the model parameters and various physiological variables, including age, body size, and serum lipid concentrations. Using this approach, significant differences between groups, or correlations with serum lipid levels were seen for several parameters of the three-pool model: the production rate (PR); the size of the rapidly exchanging pool 1 (M1); all estimates of the size of the most slowly equilibrating pool 3 (M3); and the rate constant k21. The PR in normal subjects (1.14 +/- 0.19 g/day, mean +/- SD) was not significantly different from that found in patients with hypercholesterolemia, with or without hypertriglyceridemia. The major determinant of cholesterol PR was overall body size, expressed either as total body weight or as surface area. The correlations between PR and indices of adiposity (percent ideal weight and excess weight), although statistically significant, were much weaker in this nonobese population. After adjustment for body size variation, cholesterol PR was not correlated with the serum cholesterol concentration but was probably (P less than 0.05) correlated with the triglyceride concentration. When the two patients with very high triglyceride concentrations were excluded, however, no correlation was observed between adjusted PR and triglyceride level. It is probable that hypertriglyceridemic patients represent a heterogeneous population, in which the majority do not show increased cholesterol PR. M1 was correlated with all body size variables, but most strongly with excess weight. After adjusting for the effects of body size, M1 was also correlated and triglyceride. Major differences were found in the relationships between the physiological variables and the sizes of pools 2 and 3. M2 was correlated neither with any of the indices of body size or adiposity, nor with the serum levels of either cholesterol or triglyceride. In contrast, all estimates of M3 were correlated with indices of adiposity (but not of overall body size) and with the serum cholesterol concentration. Thus, the amount of cholesterol in slowly equilibrating tissue sites appears to particularly increase with elevations of the serum cholesterol level. The results also confirm previous data that adipose tissue cholesterol is an important part of pool 3.

This research aimed to identify the skills required by primary health care (PHC) professionals to provide effective chronic condition prevention and self-management support, according to the perceptions of a sample of Australian consumers and carers. Qualitative data were collected and integrated from a focus group, key informant interviews and National Stakeholder meetings and a National Workshop, supported by an extensive literature review. With the exception of health professionals specifically trained or currently working in this area, consumers and carers perceive there is a lack of understanding, competence and practice of chronic condition prevention and self-management support among PHC professionals. The PHC workforce appears not to have the full set of skills needed to meet the growing burden of chronic conditions on the health system. Recommendations include education and training that focuses on improved communication skills, knowledge of community support resources, identification of consumers’ strengths and current capacities, collaborative care with other health professionals, consumers and carers and psychosocial skills to understand the impact of chronic conditions from the person’s perspective.

Studies were conducted to determine the effects of colestipol hydrochloride, a new bile acid-sequestrant resin, on some of the parameters of cholesterol turnover and metabolism in man. Three normal volunteers and eight hyperlipidemic patients participated in three sets of cholesterol turnover studies carried out at intervals of approximately 1 yr. The effects of colestipol were assessed by comparing the results obtained before therapy with those obtained on repeat study after several months of resin therapy. Colestipol treatment significantly reduced the serum cholesterol concentration (mean reduction 21%), and produced a large increase in the production rate of cholesterol (mean 86%) and in the turnover rate of cholesterol in pool 1 (mean 46%). The values of the intercompartmental rate constants and of the size of the rapidly exchangeable pool were unchanged with therapy. The turnover studies were carried out for 12-13 wk, and were analyzed according to a two-pool model. Although long-term studies of cholesterol turnover conform to a three-pool, rather than a two-pool model, the present studies probably provide a valid estimate of the effects of therapy on certain parameters, namely the production rate, the size, and the turnover rate of pool 1. Repeated studies in four untreated subjects showed a striking constancy with time for the kinetic parameters for each subject. The production rate was particularly constant from year to year for a given subject, and showed a pooled standard deviation of only 3%. The findings suggest that the total body turnover of cholesterol is under close homeostatic control in an integrated manner. Combined drug therapy with colestipol plus clofibrate further reduced the serum cholesterol level in three of four patients, and reduced the triglyceride level in all four patients. Addition of clofibrate to the treatment program produced only small decreases in the production rate, which were not significantly different from the small decreases seen in two patients who were continued (and restudied) on colestipol alone. The findings do not support the suggestion that clofibrate can block the increased rate of cholesterol synthesis and turnover resulting from bile acid-sequestrant treatment. The effects on serum lipids, however, make the combined drug therapy potentially quite useful.

Antarctic mosses live in a frozen desert, and are characterised by the ability to survive desiccation. They can tolerate multiple desiccation-rehydration events over the summer growing season. As a result of recent ozone depletion, such mosses may also be exposed to ultraviolet-B radiation while desiccated. The ultraviolet-B susceptibility of Antarctic moss species was examined in a laboratory experiment that tested whether desiccated or hydrated mosses accumulated more DNA damage under enhanced ultraviolet-B radiation. Accumulation of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone dimers was measured in moss samples collected from the field and then exposed to ultraviolet-B radiation in either a desiccated or hydrated state. Two cosmopolitan species, Ceratodon purpureus (Hedw.) Brid. and Bryum pseudotriquetrum (Hedw.) Gaertn., B.Mey. & Scherb, were protected from DNA damage when desiccated, with accumulation of cyclobutane pyrimidine dimers reduced by at least 60% relative to hydrated moss. The endemic Schistidium antarctici (Cardot) L.I. Savicz & Smirnova accumulated more DNA damage than the other species and desiccation was not protective in this species. The cosmopolitan species remarkable ability to tolerate high ultraviolet-B exposure, especially in the desiccated state, suggests they may be better able to tolerate continued elevated ultraviolet-B radiation than the endemic species.

BACKGROUND: Regardless of advances in diagnosis and treatment during the past 40 years, the overall 5-year survival rates for oral and oropharyngeal squamous cancers have only slightly improved and remain around 50%. Thus, the early diagnosis and treatment of carcinoma by health care providers are essential in achieving a good prognosis. We report a case of invasive squamous cell carcinoma that presented as a benign endodontic-periodontic lesion with a 7-mm periodontal pocket on tooth #15 in a 40-year-old, non-smoking woman. The subsequent management of the case is also discussed. The study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2000. METHODS: Our patient was seen for a comprehensive periodontal examination including a periodontal charting, occlusal analysis, study casts, electronic pulp test for tooth #15, and complete mouth periapical radiographs. As there was a periapical radiolucency, an endodontic consultation was obtained. A periodontal flap surgical procedure was performed on teeth #13 to #15, and as there was bone erosion into the maxillary sinus, a biopsy of the soft tissue was submitted to the local hospital for histological analysis. RESULTS: The biopsied lesion was diagnosed as invasive, moderately differentiated squamous cell carcinoma with focal spindle and clear cell differentiation (grade II to III of IV). Bone invasion was also identified. The treatment of the carcinoma involved a hemimaxillectomy with the removal of the maxillary left posterior teeth. The patient remained free of tumor for 5 years after the initial presentation. CONCLUSIONS: Patient education and periodic oral cancer examinations by dental professionals are necessary to reduce diagnostic delay and improve prognosis. This case report emphasizes the important role of dental professionals, especially periodontists and endodontists, of being aware that squamous cell carcinoma may manifest itself clinically and/or radiographically as a common periodontal or endodontic lesion.

OBJECTIVE: The aim of this study was to determine whether a secure, privacy-preserving record linkage (PPRL) methodology can be implemented in a scalable manner for use in a large national clinical research network. RESULTS: ). As a pilot, four sites used the Datavant software to transform patient personally identifiable information (PII) into de-identified tokens. We queried the sites for patients with a clinical encounter in 2018 or 2019 and matched their tokens to determine whether overlap existed. We described patient overlap among the sites and generated a "deduplicated" table of patient demographic characteristics. Overlapping patients were found in 3 of the 6 site-pairs. Following deduplication, the total patient count was 3,108,515 (0.11% reduction), with the largest reduction in count for patients with an "Other/Missing" value for Sex; from 198 to 163 (17.6% reduction). The PPRL solution successfully links patients across data sources using distributed queries without directly accessing patient PII. The overlap queries and analysis performed in this pilot is being replicated across the full network to provide additional insight into patient linkages among a distributed research network.

Importance: The role of stress cardiac magnetic resonance (CMR) imaging in clinical decision-making by reclassification of risk across American College of Cardiology/American Heart Association guideline-recommended categories has not been established. Objective: To examine the utility of stress CMR imaging for risk reclassification in patients without a history of coronary artery disease (CAD) who presented with suspected myocardial ischemia. Design, Setting, and Participants: A retrospective, multicenter cohort study with median follow-up of 5.4 years (interquartile range, 4.6-6.9) was conducted at 13 centers across 11 US states. Participants included 1698 consecutive patients aged 35 to 85 years with 2 or more coronary risk factors but no history of CAD who presented with suspected myocardial ischemia to undergo stress CMR imaging. The study was conducted from February 18, 2019, to March 1, 2020. Main Outcomes and Measures: Cardiovascular (CV) death and nonfatal myocardial infarction (MI). Major adverse CV events (MACE) including CV death, nonfatal MI, hospitalization for heart failure or unstable angina, and late, unplanned coronary artery bypass graft surgery. Results: Of the 1698 patients, 873 were men (51.4%); mean (SD) age was 62 (11) years, accounting for 67 CV death/nonfatal MIs and 190 MACE. Clinical models of pretest risk were constructed and patients were categorized using guideline-based categories of low (<1% per year), intermediate (1%-3% per year), and high (>3% year) risk. Stress CMR imaging provided risk reclassification across all baseline models. For CV death/nonfatal MI, adding stress CMR-assessed left ventricular ejection fraction, presence of ischemia, and late gadolinium enhancement to a model incorporating the validated CAD Consortium score, hypertension, smoking, and diabetes provided significant net reclassification improvement of 0.266 (95% CI, 0.091-0.441) and C statistic improvement of 0.086 (95% CI, 0.022-0.149). Stress CMR imaging reclassified 60.3% of patients in the intermediate pretest risk category (52.4% reclassified as low risk and 7.9% as high risk) with corresponding changes in the observed event rates of 0.6% per year for low posttest risk and 4.9% per year for high posttest risk. For MACE, stress CMR imaging further provided significant net reclassification improvement (0.361; 95% CI, 0.255-0.468) and C statistic improvement (0.092; 95% CI, 0.054-0.131), and reclassified 59.9% of patients in the intermediate pretest risk group (48.7% reclassified as low risk and 11.2% as high risk). Conclusions and Relevance: In this multicenter cohort of patients with no history of CAD presenting with suspected myocardial ischemia, stress CMR imaging reclassified patient risk across guideline-based risk categories, beyond clinical risk factors. The findings of this study support the value of stress CMR imaging for clinical decision-making, especially in patients at intermediate risk for CV death and nonfatal MI.

Legionella infection is an important cause of community-acquired pneumonia in Australia. Morbidity and mortality is significant. Diagnosis remains a challenge with infection often unrecognised, particularly early in the course of illness. An understanding of available diagnostic methods and their limitations is important to public health practitioners and clinicians alike.

Sucrose nonfermenting-related kinase (SNRK) is a member of the AMPK-related kinase family, and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white adipose tissue (WAT) and brown adipose tissue (BAT), but SNRK expression diminishes in adipose tissue in obesity. In this study we report novel experimental findings from both animal models and human genetics. SNRK is essential for survival; SNRK globally deficient pups die within 24 h after birth. Heterozygous mice are characterized by inflamed WAT and less BAT. Adipocyte-specific ablation of SNRK causes inflammation in WAT, ectopic lipid deposition in liver and muscle, and impaired adaptive thermogenesis in BAT. These metabolic disorders subsequently lead to decreased energy expenditure, higher body weight, and insulin resistance. We further confirm the significant association of common variants of the SNRK gene with obesity risk in humans. Through applying a phosphoproteomic approach, we identified eukaryotic elongation factor 1δ and histone deacetylase 1/2 as potential SNRK substrates. Taking these data together, we conclude that SNRK represses WAT inflammation and is essential to maintain BAT thermogenesis, making it a novel therapeutic target for treating obesity and associated metabolic disorders.

Medical examiners and coroners (ME/C) in the United States hold statutory responsibility to identify deceased individuals who fall under their jurisdiction. The computer-assisted decedent identification (CADI) project was designed to modify software used in diagnosis and treatment of spinal injuries into a mathematically validated tool for ME/C identification of fleshed decedents. CADI software analyzes the shapes of targeted vertebral bodies imaged in an array of standard radiographs and quantifies the likelihood that any two of the radiographs contain matching vertebral bodies. Six validation tests measured the repeatability, reliability, and sensitivity of the method, and the effects of age, sex, and number of radiographs in array composition. CADI returned a 92-100% success rate in identifying the true matching pair of vertebrae within arrays of five to 30 radiographs. Further development of CADI is expected to produce a novel identification method for use in ME/C offices that is reliable, timely, and cost-effective.

Objective. To report on the accuracy of reports of diabetes-related major amputations, rates per 100 000 people and trends over the 10-year period from 1998–99 to 2007–08 in Far North Queensland. Methods. Three data sources were cross-checked. Poisson regression was used to calculate the percentage change in trends in diabetes amputation hospitalisations over the period. Results. There was a discrepancy of 6 (3.7%) in 161 cases over 10 years. The number of diabetes-related hospitalisations for major lower limb amputation did not show a significant trend during this period, with an annual percentage change of –0.32%, P = 0.915. Conclusion. Amputation data in Far North Queensland were accurate. There was a modest reduction in the hospitalisation rate for major lower limb amputation over the 10-year period, demonstrating the need for improvements in the organisation of care. What is known about the topic? Diabetic foot complications resulting in amputation are recognised internationally as a costly, major health problem. Limited data are available in the Australian context, especially for regional high risk populations. What does this paper add? Accurate data on an Australian Institute of Health and Welfare recommended indicator, namely major amputations in people with diabetes. Confirmation of the accuracy of the data, enables benchmarking for future improvements. What are the implications for practitioners? A focus on major amputations is a useful indicator of the quality and safety of care for people with diabetes.

PURPOSE: To report a local outbreak of community-associated methicillin-resistant Staphylococcus aureas (CA-MRSA), discuss the incidence and the high rates of CA-MRSA-related skin and soft tissue infections in our outpatient and emergency department (ED) population, and also review the diagnosis and management of CA-MRSA in outpatients. DATA SOURCES: Case report, diagnostic evidence, scientific literature, published treatment guidelines, and a retrospective chart review. CONCLUSIONS: Clinical suspicions of high rates of CA-MRSA-related skin and soft tissue infections in our institution's outpatient and ED population was supported. Hospital-acquired MRSA (HA-MRSA) was also more prevalent than expected. Recognizing high-risk settings, patients and clinical features of CA-MRSA is essential for early identification and proper management. The most common clinical manifestation of CA-MRSA we identified was a skin or soft tissue infection. IMPLICATIONS FOR PRACTICE: It is important that clinicians have an awareness of high-risk patients, perform routine culturing of soft tissue infections, and prescribe antibiotics based on culture and sensitivities. Awareness, prevention, early diagnosis, and implementation of effective antibiotic management by nurse practitioners can help limit an epidemic of CA-MRSA.