Blood corticosteroids in Australian marsupial and placental mammals and one monotreme.

Peripheral blood corticosteroid levels were determined in nine species of Australian marsupial (Eastern grey kangaroo, black-tailed, Bennett's and pademelon wallabies, quokka, wombat, koala and Western native and tiger cats), one species of monotreme (echidna) and one placental Australian mammal (dingo). Animals were obtained or bled with minimal disturbance and came from areas considered to have adequate sodium content of the vegetation. Aldosterone, corticosterone, cortisol, 11-deoxycorticosterone and 11-deoxycortisol were measured and levels found to be similar to five introduced eutherian species (sheep, cow, dog, fox and man) with the exception of the koala and the wombat. Cortisol was the predominant corticosteroid, except in the koala, which produced corticosterone in relatively the greatest quantity, and the wombat which produced more 11-deoxycortisol. Steroid levels were generally low in the wombat. ACTH administered to the koala changed its pattern of corticosteroid secretion from predominantly corticosterone to cortisol. In the dingo, administration of ACTH caused rises in corticosteroid levels similar to those seen in most other eutherian mammals.     

Determinants of Intima-Media Thickness in the Young: The ALSPAC Study

ObjectivesThis study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years.BackgroundGreater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood.MethodsAssociations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.ResultsFat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: ?0.0032; 95% CI: 0.004 to ?0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor?associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.ConclusionsSubtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.     

Successful medical management of a patient with multiple hepatic abscesses due to Edwardsiella tarda.

Isolation of Edwardsiella tarda in humans has been associated with an asymptomatic carrier state as well as mild, self-limited diarrheal illness. Extraintestinal manifestations have included soft-tissue infections, meningitis, osteomyelitis, cholangitis, and sepsis. Only three cases of patients who had documented hepatic abscess due to E. tarda have been reported in the English-language literature; two patients died, and the third required a laparotomy and drainage. We report what is, to our knowledge, the first autochthonous case of hepatic abscess due to E. tarda in the United States and the first case that was successfully managed with antibiotic therapy alone.     

Diurnal variation in plasma concentrations of testosterone, 5α-dihydrotestosterone,and corticosteroids in the Australian brush-tailed possum, Trichosurus vulpecula (Kerr)

Plasma concentrations of testosterone, 5α-dihydrotestosterone, and total adrenal corticosteroids were measured in intact and castrated males and female possums over a 24-h period. In males, testosterone levels varied diurnally, being significantly higher in the morning than in the evening, with an overall mean concentration of 3.30 ± 0.43 (SEM) ng/ml. Levels of 5α-dihydrotestosterone showed a similar variation but of lower magnitude and the overall mean plasma concentration was 0.63 ± 0.10 ng/ml. Total adrenal corticosteroid concentrations in males also appeared to cycle, but inversely to the androgens with a peak in the early evening, and the overall mean concentration was 0.61 ± 0.08 μg/100 ml. Testosterone concentrations averaged 0.46 ± 0.02 and 0.35 ± 0.01 ng/ml in castrated males and females, respectively, and the corresponding values for 5α-dihydrotestosterone were 0.20 ± 0.03 and 0.21 ± 0.03 ng/ml. These measurements indicate that plasma testosterone levels of the marsupial possum fall within the range reported for eutherian species.     

Antihypertensive Medications in End‐Stage Renal Disease

Hypertension is almost universal in end‐stage renal disease (ESRD) and contributes to the substantial cardiovascular (CV) morbidity and mortality observed in these patients. The management of blood pressure (BP) in ESRD is complicated by a number of factors, including missed dialysis treatments, intradialytic changes in BP, medication removal with dialysis, and poor correlation of BPs obtained in the dialysis unit with those at home and with CV outcomes. Control of extracellular volume with ultrafiltration and dietary sodium restriction represents the principal strategy to manage hypertension in ESRD, and antihypertensive medications are subsequently added if this strategy is inadequate. While reduction in BP with medication improves CV outcomes, few head‐to‐head clinical trials have been performed to firmly establish the superiority of one antihypertensive medication class over another. Therefore, individualization of therapy is necessary, and patient comorbidities must be considered. Angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta‐blockers are reasonable first‐line agents for most patients. ACE inhibitors and ARBs exert cardioprotective effects that are independent of BP reduction. Medications that are removed with dialysis may be preferred in patients who are prone to develop intradialytic hypotension. Intradialytic hypertension can be managed with challenging the patient's dry weight and using nondialyzable medications. Within a class of antihypertensive medications, there may be large variability in drug removal with dialysis, which must be considered upon medication selection. Studies demonstrate that even thrice‐weekly dosing of medication after dialysis has robust BP‐lowering effects, which may be a useful regimen in nonadherent patients.     

Decreased Mechanical Strength and Collagen Content in SPARC‐Null Periodontal Ligament Is Reversed by Inhibition of Transglutaminase Activity

The periodontal ligament (PDL) is a critical tissue that provides a physical link between the mineralized outer layer of the tooth and the alveolar bone. The PDL is composed primarily of nonmineralized fibrillar collagens. Expression of secreted protein acidic and rich in cysteine (SPARC/osteonectin), a collagen‐binding matricellular protein, has been shown to be essential for collagen homeostasis in PDL. In the absence of SPARC, PDL collagen fibers are smaller and less dense than fibers that constitute WT PDL. The aim of this study was to identify cellular mechanisms by which SPARC affected collagen fiber assembly and morphology in PDL. Cross‐linking of fibrillar collagens is one parameter that is known to affect insoluble collagen incorporation and fiber morphology. Herein, the reduction in collagen fiber size and quantity in the absence of SPARC expression was shown to result in a PDL with reduced molar extraction force in comparison to that of WT mice (C57Bl/6J). Furthermore, an increase in transglutaminase activity was found in SPARC‐null PDL by biochemical analyses that was supported by immunohistochemical results. Specifically, collagen I was identified as a substrate for transglutaminase in PDL and transglutaminase activity on collagen I was found to be greater in SPARC‐null tissues in comparison to WT. Strikingly, inhibition of transglutaminase activity in SPARC‐null PDL resulted in increases in both collagen fiber thickness and in collagen content, whereas transglutaminase inhibitors injected into WT mice resulted in increases in collagen fiber thickness only. Furthermore, PDL treated with transglutaminase inhibitors exhibited increases in molar extraction force in WT and in SPARC‐null mice. Thus, SPARC is proposed to act as a critical regulator of transglutaminase activity on collagen I with implications for mechanical strength of tissues. © 2015 American Society for Bone and Mineral Research     

Patient Engagement in Neurological Clinical Trials Design: A Conference Summary

Objectives

The conference objectives included educating patients and advocates about clinical trials, educating the clinical research community about patient perspectives on participating in clinical trial design, and identifying strategies to increase participation in clinical trial design for neurological disorders.

Design

Observations were noted during a 1‐day conference attended by patients, patient advocates, clinical trial staff, and investigators. The conference offered didactic sessions, small, and large group discussions.

Participants

Conference participants were patients, patient advocates, clinical trial staff, students, and investigators interested in engaging patients in clinical trial design for neurological disorders.

Measures

Conference participants were asked to consider lessons learned that could increase patient engagement in clinical trial design.

Results

We found that there is growing interest in including patients in the design of clinical trials for neurological disorders. Several themes emerged on how to move forward: networking; the multifaceted roles of advocates in research; training and education; creating patient–researcher partnerships; and clinical trials regulation issues.

Conclusions

The conference provided a forum for dialogue regarding stakeholder engagement in the design of clinical trials for neurological disorders. This experience provides a template for replication and dissemination of this conference and informs next steps to accelerate the pathway from dialogue to action.