The relationship between repeated measurements of HbA1c and risk of coronary events among the common haptoglobin phenotype groups: the Action for Health in Diabetes (Look AHEAD) study.

BACKGROUND: In the ACCORD study, participants with the haptoglobin (Hp) 2-2 phenotype and glycated hemoglobin (HbA1c) ≥ 8.0% had a higher risk of coronary artery disease (CAD) compared to those with HbA1c 7.0-7.9%. However, this association was not observed in participants without the Hp2-2 phenotype. The optimal glycemic target for CAD prevention for the Hp phenotypes remains uncertain and may vary based on demographic and clinical factors. OBJECTIVE: To investigate how reaching clinically relevant HbA1c targets relates to the risk of CAD in different Hp phenotype groups among a diverse cohort of individuals with T2DM (the Look AHEAD study, HbA1c ≤ 11% at baseline). METHODS: Cox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA1c (< 6.5%, 6.5-6.9%, and ≥ 8.0% compared to 7.0-7.9%), updated at years 1-4, 6, 8, and 10, and incident CAD in the Hp2-2 (n = 1,587) and non-Hp2-2 (n = 2,944) phenotypes separately. Further pre-specified subgroup analyses by age, sex, history of cardiovascular disease (CVD), race, and diabetes duration were performed in each Hp phenotype group separately. RESULTS: Compared with HbA1c 7.0-7.9%, having HbA1c < 6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 phenotype (adjusted HR 0.71, 95% CI 0.55-0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 phenotype who were male (0.60, 0.44-0.83), who did not have a history of CVD (0.65, 0.47-0.90), who were aged ≥ 65 years (0.64, 0.44-0.94), who were White (0.68, 0.51-0.91), or who had diabetes duration > 10 years (0.58, 0.35-0.95). HbA1c ≥ 8.0% was associated with CAD risk only among participants with the Hp2-2 phenotype who had a history of CVD (1.79, 1.00-3.20). No associations were found between the other HbA1c targets and CAD risk when participants with the Hp2-2 phenotype were grouped together or divided into subgroups. CONCLUSION: The differences in our results compared to our previous findings may be due to variations in the study populations and factors associated with weight loss, making it difficult to draw definitive conclusions. Our current findings should be considered in the context of hypothesis generation, and ideally, will encourage additional research in this field.

Myocardial fat overgrowth in Proteus syndrome.

Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are rare in this syndrome and only two prior cases have been reported. Many patients with PS followed at our institution underwent transthoracic echocardiograms for preoperative evaluation or as work-up for associated pulmonary disease. Some were noted to have prominent, focal echodense areas in the myocardium. We further investigated cardiac findings in a cohort of children and adult patients with PS. Patients with abnormal echocardiograms were referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise treadmill testing. Twenty children and adults with PS, age 24 months to 50 years old, underwent transthoracic echocardiograms. Seven patients (35%) had focal bright echodense areas within the myocardium suggesting fatty infiltration. The majority of patients had significant involvement of the interventricular septum. The cardiac characteristics of all patients with fatty infiltration on transthoracic echocardiograms were compared to Proteus patients without these findings. There were no significant differences in chamber sizes, mass, systolic or diastolic function. No increased risk of conduction defects or arrhythmias was found. This study shows that abnormal fat overgrowth is a common finding in the myocardium in patients with Proteus syndrome; however, it is not associated with functional derangements or arrhythmias. Further evaluation of a larger number of Proteus patients is needed in order to determine the frequency and prognosis of cardiac involvement. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Parental attitudes, values, and beliefs toward the return of results from exome sequencing in children.

Exome sequencing is being offered for children with undiagnosed conditions to identify a primary (causative) variant. Parental preferences for learning secondary (incidental) variants are largely unexplored. Our objective was to characterize values and beliefs that shape parents' preferences for learning their children's sequencing results. We conducted semi-structured interviews with 25 parents of 13 minor probands with a variety of rare genetic conditions. Parents were asked to discuss their preferences to receive four types of results from exome sequencing. Many parents preferred to receive all types of results. Parents had the most positive attitudes toward learning about variants that predispose to disorders treatable or preventable in childhood. They had reservations about learning about predispositions for untreatable adult-onset conditions and carrier status for recessive conditions. Parents described their success in coping with their child's condition as evidence for an ability to manage any additional negative health information. They felt responsible for learning about secondary variants, desiring a gain in control over their child's health. Our findings suggest that investigators should incorporate parents' perceptions of the value in receiving secondary variant information about their children when designing studies employing exome sequencing.

Hyperphagia among patients with Bardet-Biedl syndrome.

BACKGROUND: The importance of hyperphagia as a cause for energy imbalance in humans with Bardet-Biedl syndrome (BBS) has not been established. We therefore compared hyperphagic symptoms in patients with BBS vs. controls. METHODS: We studied 13 patients with BBS and 23 non-syndromic controls with similar age, sex and body mass index (BMI) z-score. A 13-item hyperphagia questionnaire was completed by patients' parents/guardians. RESULTS: Total hyperphagia questionnaire score was higher in BBS than controls (27.6 ± 9.0 vs. 19.1 ± 7.9, P = 0.005). Behaviour and drive subscales were higher for BBS than controls (12.5 ± 4.1 vs. 7.8 ± 3.2, P = 0.001, and 11.2 ± 4.1 vs. 8.3 ± 3.8, P = 0.04, respectively); severity was not significantly different between groups (3.8 ± 1.5 vs. 3.0 ± 1.3, P = 0.072). After adjustment for demographic variables and BMI z-score, total and behaviour subscale scores remained significantly different between groups, suggesting food-seeking activity, rather than preoccupation with food may be the main hyperphagic feature among patients with BBS. CONCLUSION: Appetite dysregulation may contribute to obesity in BBS.

The structure of microbial evolutionary theory.

The study of microbial phylogeny and evolution has emerged as an interdisciplinary synthesis, divergent in both methods and concepts from the classical evolutionary biology. The deployment of macromolecular sequencing in microbial classification has provided a deep evolutionary taxonomy hitherto deemed impossible. Microbial phylogenetics has greatly transformed the landscape of evolutionary biology, not only in revitalizing the field in the pursuit of life's history over billions of years, but also in transcending the structure of thought that has shaped evolutionary theory since the time of Darwin. A trio of primary phylogenetic lineages, along with the recognition of symbiosis and lateral gene transfer as fundamental processes of evolutionary innovation, are core principles of microbial evolutionary biology today. Their scope and significance remain contentious among evolutionists.

Ulnar artery thrombosis: a 6-year experience.

Thrombosis of the ulnar artery can be a cause of significant morbidity. Most often a consequence of blunt trauma to the hypothenar eminence of the hand, it may be attributable to one traumatic event or to repetitive insults. Surgery is often required. We reviewed the presentation and diagnosis of ulnar artery thrombosis and evaluated the effectiveness of treatment by ulnar artery excision with interposition vein grafting. Retrospective chart analysis from 1989 to 1995 at the Medical Center of Central Georgia showed that nine patients (eight male, one female) were treated for ulnar artery thrombosis. Three had associated ulnar artery aneurysms. Eight of the nine were treated with artery excision and interposition vein grafting. Four also received stellate ganglion blocks before surgery. One was treated with stellate ganglion blocks alone. All patients had symptomatic relief and resolution of physical findings. We conclude that ulnar artery thrombosis can be managed with ulnar artery excision and interposition vein grafting when conservative measures fail.

Electrophysiology and anatomic characterization of an epicardial accessory pathway.

Pericardial access permitted epicardial catheter mapping and ablation of a rapidly conducting posteroseptal accessory pathway (AP) that had failed repeated ablation attempts. Transient block was achieved at the site of an AP potential. The AP was visible at surgery and resected. Histologic examination revealed cells typical of specialized cardiac conduction tissue. The location, size, and presence of conduction tissue likely account for failure of catheter ablation and resistance to drug therapy.

Nodular fasciitis and solitary fibrous tumor of the oral region: tumors of fibroblast heterogeneity.

OBJECTIVE: Fibroblastic proliferations of the oral cavity are extremely varied, yet they share certain features-spindle cell morphology, collagen synthesis, and fasciculation. Nodular fasciitis is a cellular fibroblastic lesion, uncommonly located in the oral submucosa, that shows smooth muscle actin (SMA) immunoreactivity. Solitary fibrous tumor expresses a CD34 fibroblast phenotype. The aim of this study is to report instances of nodular fasciitis and solitary fibrous tumor in the orofacial region and investigate immunohistochemical markers to compare and contrast fibroblastic phenotypic heterogeneity in these tumors. STUDY DESIGN: Seven benign cellular fibrogenic tumors initially diagnosed as nodular fasciitis over a 10-year period were examined. Immunohistochemical markers, including S-100 protein, SMA, CD68, CD34, and vimentin, were used to further characterize these lesions. RESULTS: All tumors occurred in adults, and the buccal mucosa was found to be the favored site. The spindle cells in these tumors showed phenotypic heterogeneity both within and between tumors. All were vimentin-reactive and harbored small populations of CD68-positive macrophage/dendrocytes. Five tumors were SMA-positive and CD34-negative; the tumor in one case was SMA-negative and CD34-positive, and that in another was SMA-positive and CD34-positive. CONCLUSION: Although rare, nodular fasciitis and solitary fibrous tumor arise in oral submucosa, usually in the cheek. The histopathologic features and immunomarkers indicative of myofibroblastic differentiation are seen in nodular fasciitis, whereas solitary fibrous tumor is CD34-positive; however, one instance was found to be positive for both markers. All of these cases harbored subpopulations of CD68-positive cells. Immunomarkers are a valuable adjunct in differentiating nodular fasciitis from solitary fibrous tumor, yet some tumors may harbor heterogeneous fibroblast phenotypes.

Freewheeling centrioles.

The century-old controversy over the reproduction and function of the centriole is examined to elucidate the conceptual and methodological issues that have made it so resistant to closure. The study of centrioles is situated in two distinct eras punctuated by the deployment of the electron microscope. From the late 19th century to the mid-20th century, centrioles were defined largely in functional terms- as self-reproducing 'central bodies' playing a directive role in mitosis. During this period, when their structure remained unknown, their universal presence in all cells was ambiguous, and their reality was seriously debated. A conceptual switch occurred after the mid-1950s. When the centriole was made visible under the electron microscope, it was defined in terms of its characteristic cart-wheel structure, but its function and manner of reproduction have remained enigmatic. The controversy over the nature of centrioles illustrates the dynamic interplay of techniques, theories, and background assumptions in the production of scientific knowledge. It also highlights the difficulties biologists face in coming to grips with problems of cell structure and intracellular morphogenesis.

Jean Brachet, l'hérédité générale and the origins of molecular embryology.

Jean Brachet's research on microsomes and the role of RNA in protein synthesis during the 1940s and 50s is placed in the context of embryological views about the role of the cytoplasm in development, and plasmagene theory based on studies of non-Mendelian inheritance in microorganisms. I show how Brachet's subsequent conception of messenger RNA evolved in the context of his conceptions of the relations between plasmagenes and nuclear genes. His theorizing on cytoplasmic organelles and viruses is further situated in the bio-political controversy over the inheritance of acquired characteristics during the Lysenko controversy.

The potential for bias due to attrition in the National Exposure Registry: an examination of reasons for nonresponse, nonrespondent characteristics, and the response rate.

This study examined attrition in the Trichloroethylene (TCE) Subregistry of the National Exposure Registry (NER). The analyses focused on 3915 persons exposed to the chemical TCE through the drinking water in their home. Baseline data were compared for subgroups of the TCE Subregistry members who were eligible to participate in the first TCE Subregistry follow-up. Study members were grouped according to their participation status in the first follow-up: remainers (n = 3494) and losses (n = 421), and three subgroups of losses: refusals, unable to locate, and unable to contact. The comparison of demographic variables of remainers and losses revealed that remainers had a higher percent of females, currently smoked less, were older, and fewer had no education and more had education beyond high school. These differences occurred for the losses subgroups unable to locate and unable to contact, however, not for refusals. The comparison of reporting rates of remainers and losses for 2.3 health outcomes revealed statistically significant decreases by losses for five health conditions but the pattern of statistically significant differences for the losses subgroups was not clear-cut. Altogether, the analyses indicated that the potential for bias due to attrition was minimal.

Contractile properties of myocardium are altered in dystrophin-deficient mdx mice.

The objective of this study was to determine whether cardiac contractile force is altered in the dystrophin-deficient mdx mouse model of muscular dystrophy. Left atria from 12-14-week-old control and mdx mice were paced at 1 Hz in 1.25 mM external Ca2+ buffer. Twitch properties and effects of interposing intervals of 0.3 to 600 s on the force of subsequent beats (force-interval curves) were examined. Peak force and time-to-peak force were similar in both groups, but half-relaxation time was significantly prolonged in mdx heart. In control hearts, force-interval curves increased to an inflection point at about 1 s, then rose to a second peak near 60 s. In mdx heart, curves reached the early inflection more quickly, the second peak was diminished in magnitude and force was greatly depressed at long intervals. Curves were fitted to a four-parameter equation to quantify differences in shape. The parameter a, which reflects rate of rise to the first inflection, was significantly increased in mdx atria, while the parameter B, which reflects amplitude of the late peak, was significantly reduced. These differences in force production were more marked when external Ca2+ was raised to 2.5 mM. Results show contractile properties are markedly altered in atria from dystrophin-deficient mdx mice. These findings are consistent with the hypothesis that dystrophin deficiency affects cardiac contractile function, possibly through effects on SR function.

"Current topics in health sciences librarianship": a pilot program for network-based lifelong learning.

The long-term objective of this project is to make health sciences librarians more effective in their role by using emerging technologies to deliver timely continuing education (CE) programs to them regardless of their physical location. The goals of the one-year planning project at the William H. Welch Medical Library are to plan, implement, and evaluate a pilot CE program that includes (1) a three-day general-interest session organized in four tracks: Market Forces and Management, Information Technology and the Internet, Publishing and Copyright, and Education; (2) a one-day special topic session on the Informatics of the Human Genome Project; and (3) an electronic poster session in parallel with the general-interest session. The program will be offered in three simultaneous formats: (1) on-site, in a distance-learning classroom in Baltimore; (2) as a telecourse, in a similar classroom outside Washington, DC; and (3) online, via the World Wide Web. An electronic proceedings of the entire program will be published on the Web to serve as a continuously available CE resource for health sciences librarians. This paper gives an overview of the planning process, presents a status report on the programmatic and technical implementation of the pilot project at its midpoint, and discusses future directions for the program.

Incidence and hospital stay for cardiac and pulmonary complications after abdominal surgery.

OBJECTIVE: Internists frequently evaluate preoperative cardiopulmonary risk and co-manage cardiac and pulmonary complications, but the comparative incidence and clinical importance of these complications are not clearly delineated. This study evaluated incidence and length of stay for both cardiac and pulmonary complications after elective laparotomy. DESIGN: Nested case-control. SETTING: University-affiliated Department of Veterans Affairs Hospital. PATIENTS: Computerized registry of all 2,291 patients undergoing elective abdominal operations from 1982 to 1991. MEASUREMENT AND MAIN RESULTS: Strategy for ascertainment and verification of complications was systematic and explicit. The charts of all 116 patients identified by the registry as having complications and 412 (19%) randomly selected from 2,175 remaining patients were reviewed to verify presence or absence of cardiac or pulmonary complications, using explicit criteria and independent abstraction of pre- and postoperative components of charts. From these 528 validated cases and controls (23% of the cohort), 96 cases and 96 controls were matched by operation type and age within ten years. Hospital and intensive care unit stays were significantly longer (p < 0.0001) for the cases than for the controls (24.1 vs 10.3 and 5.6 vs 1.5 days, respectively). All 19 deaths occurred among the cases. Among the cases, pulmonary complications occurred significantly more often than cardiac complications (p < 0.00001) and were associated with significantly longer hospital stays (22.7 vs 10.4 days, p = 0.001). Combined cardiopulmonary complications occurred among 28% of the cases. Misclassification-corrected incidence rates for the entire cohort were 9.6% (95% CI 7.2-12.0) for pulmonary and 5.7% (95% CI 3.6-7.7) for cardiac complications. CONCLUSIONS: For noncardiac surgery, previous research has focused on cardiac risk. In this study, pulmonary complications were more frequent, were associated with longer hospital stay, and occurred in combination with cardiac complications in a substantial proportion of cases. These results suggest that further research is needed to fully characterize the clinical epidemiology of postoperative cardiac and pulmonary complications and better guide preoperative risk assessment.

Absence of radiometric differentiation between periapical cysts and granulomas.

A recent study reported that the mean density of periapical cysts was greater than that of periapical granulomas. This study, which used a larger sample size and a robust method for standardization of density and contrast between images, found no difference between the radiographic density of cysts and granulomas classified by microscopic evaluation. Cysts tend to be larger than granulomas, but there was wide variation in size of both types of lesions. There was no significant correlation between the density of a lesion and its size.