Clustering of metabolic syndrome risk factors and arterial stiffness in young adults: the Northern Ireland Young Hearts Project

OBJECTIVES: This study aimed to investigate whether the clustering of the risk factors of the metabolic syndrome (MetS) is associated with stiffness of central and peripheral arterial segments; whether these associations are similar in men and women; and whether insulin resistance and low-grade inflammation mediate any such associations. BACKGROUND: Increased arterial stiffness may explain, at least in part, the increased cardiovascular and diabetes risk associated with the MetS. However, the mechanisms linking the MetS to an increased arterial stiffness are incompletely understood, and gender differences may exist. METHODS: Cross-sectional analyses of data on 313 young men and women (mean age 23 years) from the Northern Ireland Young Hearts Project. Subjects were categorized according to the number of traits of the MetS; in addition a continuous MetS score was calculated. Arterial stiffness was assessed by measuring pulse wave velocity (PWV) in three arterial segments using a non-invasive optical method. RESULTS: The prevalence of the MetS was similar for men (10.6%) and women (10.5%). After adjustment for potential confounders and other cardiovascular risk factors, PWV of the three arterial segments investigated increased with increasing traits of the MetS in women only. Women with the MetS, as compared to those without risk factors of the syndrome, had greater PWV of the aorto-iliac (+14.0%, P = 0.016), the aorto-radial (+13.2%, P = 0.010) and aorto-dorsalis pedis (+11.8%, P = 0.011) segments. A great deal (up to 75%) of the association between the MetS and aortic-iliac PWV was mediated by heart rate, inflammation markers [C-reactive protein (CRP) and fibrinogen] and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)], whereas these variables did not explain much of the association between the MetS and PWV of the peripheral segments. CONCLUSIONS: Young women with the MetS show increased stiffness of peripheral and central arteries, a mechanism that may explain their increased cardiovascular risk. Low-grade inflammation, insulin resistance and sympathetic activation explain much of the adverse impact of the MetS on central, but not peripheral, arterial stiffness.     

Vesicular release of prolactin from preformed prolactin granules is stimulated by soluble factor(s) from the anterior pituitary of lactating rats

This study demonstrates that conditioned media (CM) from the anterior pituitary gland (AP) of lactating rats contains soluble factors that promote in vitro prolactin (PRL) release from the pituitary glands of male rats. CM-induced PRL release was confirmed by polyacrylamide gel electrophoresis, ELISA and bioassay. In cultured AP cells challenged with CM, increased intracellular staining with the dye FM1-43 was observed, suggesting vesicular PRL release and subsequent endocytosis. The percentage and hormone content of PRL-containing cells but not of growth hormone-containing cells increased in cultured male AP cells when exposed to CM. When the release of PRL, prelabeled with [3H] leucine for 30 min to 24 h was examined, no stimulatory effect of CM was observed, suggesting that released PRL originates from hormone synthesized more than 24 h earlier. Accordingly, the PRL content of mature granules from male pituitary tissues decreased after CM treatment. These findings were confirmed by electron microscopy immunogold PRL labeling. Treatment with inhibitors of protein synthesis or vesicle trafficking between the endoplasmic reticulum and the Golgi complex did not prevent the stimulatory effect of CM on PRL release. However, blockage of traffic to the plasma membrane completely abolished the effect of CM. These results suggest that CM from the AP of lactators contains soluble factor(s) capable of inducing rapid vesicular release of PRL in the male AP, which originates from preformed, mature granules by mechanisms independent of protein synthesis.     

The value of thoracic computed tomography scans in clinical diagnosis: A prospective study

BACKGROUND:

Computed tomography (CT) scans are used extensively to investigate chest disease because of their cross-sectional perspective and superior contrast resolution compared with chest radiographs. These advantages lead to a more accurate imaging assessment of thoracic disease. The actual use and evaluation of the clinical impact of thoracic CT has not been assessed since scanners became widely available.

OBJECTIVE:

To identify patterns of utilization, waiting times and the impact of CT scan results on clinical diagnoses.

DESIGN:

A before and after survey of physicians who had ordered thoracic CT scans.

SETTING:

Vancouver General Hospital – a tertiary care teaching centre in Vancouver, British Columbia.

SUBJECTS:

Physicians who had ordered CT scans.

INTERVENTION:

Physicians completed a standard questionnaire before and after the CT scan result was available.

MEASUREMENTS:

Changes in the clinical diagnosis, estimates of the probabilities for the diagnosis both before and after the CT scan, and waiting times.

RESULTS:

Four hundred fifty-four thoracic CT cases had completed questionnaires, of whom 80% were outpatients. A change in diagnosis was made in 48% of cases (25% with a normal CT scan and 23% with CT scan findings that indicated a different diagnosis). The largest change in probability scores for the clinical diagnosis before and after the CT scan was 43.9% for normal scans, while it was 36.3% for a different diagnosis and 26.3% for the same diagnosis. High-priority scans were associated with decreased waiting time (−7.89 days for each unit increase in priority).

CONCLUSIONS:

The CT scan results were associated with a change in diagnosis in 48% of cases. Normal scans constituted 25% of the total and had the greatest impact scores. Waiting times were highly correlated with increased urgency of the presenting problem.     

Cribra orbitalia is correlated with the meningo-orbital foramen and is vascular and developmental in nature

Cribra orbitalia is a phenomenon with interdisciplinary interest. However, the etiology of cribra orbitalia remains unclear. Recently, the appearance of cribra orbitalia was identified as vascular in nature. This study assessed the relationship between anatomical variation of vasculature, as determined by the presence of meningo-orbital foramina, and the presence of cribra orbitalia in 178 orbits. Cribra orbitalia was identified in 27.5% (49:178) of orbits (22.7%, 35:154 adult orbits and 58.3%, 14:24 subadult orbits) and meningo-orbital foramina were identified in 65.8% (100:152) of orbits. Among the 150 total intact adult orbits (i.e., orbital roof and posterior orbits both intact), cribra orbitalia was found in 35 (23.3%). Of these 35 occurrences of cribra orbitalia, 32 (91.4%) had the concurrent finding of a meningo-orbital foramen. However, in the absence of the meningo-orbital foramen, cribra orbitalia was only found in three sides out of the total sample of intact orbits (3:150; 2.0%). Fisher's exact test revealed that the presence of cribra orbitalia and the meningo-orbital foramen were statistically dependent variables (p = .0002). Visual evidence corroborated statistical findings—vascular impressions joined cribra orbitalia to meningo-orbital foramina. This study identifies that individuals who possess a meningo-orbital foramen are anatomically predisposed to developing cribra orbitalia. Conversely, cribra orbitalia is unlikely to occur in an individual who does not possess a meningo-orbital foramen. Thus, the antecedent of cribra orbitalia is both vascular and developmental in nature. This report represents an important advancement in the understanding of cribra orbitalia—there is an anatomical predisposition to the development of cribra orbitalia.     

Genetic modification of primary chronic lymphocytic leukemia cells with a lentivirus expressing CD38

Studies of the role of individual genes in chronic lymphocytic leukemia (CLL) have been hampered by the inability to consistently transfect primary tumor cells. Here, we describe a highly efficient method of genetically modifying primary CLL cells using a VSVG pseudotyped lentiviral vector. We transduced CD38 negative CLL cells with a lentiviral vector encoding CD38 which caused increased surface CD38 expression in all the samples tested (n=17) with no evidence of plasmacytoid differentiation. The mean percentage of positive cells expressing CD38 was 87%±8.5% and the mean cell viability 74%±17%. This high level of transduction of all the CLL cell samples tested demonstrates the utility of this technique which should prove applicable for the introduction and analysis of other genes in these non-dividing cells.     

Cholesterol in β-cell Dysfunction: The Emerging Connection Between HDL Cholesterol and Type 2 Diabetes

β-cell dysfunction is a critical step in the pathogenesis of type 2 diabetes. The mechanisms responsible for β-cell death and dysfunction remain incompletely understood, but include glucolipotoxicity, the deleterious metabolic milieu created by high plasma concentrations of glucose and lipid species. Recently, an important role has emerged for cholesterol in this process. In this article, we review recent advances in our understanding of the role of ABCA1 and cholesterol metabolism in β-cell function, with particular attention to insights gained from human studies.     

Gestational age-related inhibition of placental hCG, alpha hCG and steroid hormone release in vitro by a GnRH antagonist

Human placental tissues have been shown to contain gonadotrophin-releasing hormone-(GnRH)-like activity. Thus, the effect of a potent GnRH antagonist (N-Ac-Pro1,D-p-Cl-Phe2,D-Nal(2)3,6-GnRH, obtained from Syntex Laboratories) on placental hormonal release was studied. Explant cultures of placentae of 6 to 15 weeks' gestation were studied. This GnRH antagonist did not inhibit the alpha human chorionic gonadotrophin (alpha hCG), human chorionic gonadotrophin (hCG), oestrone or oestradiol release from the six- and nine-week placental cultures, but greatly suppressed the release of these hormones in the placental cultures from 13- and 15-week gestations. Synthetic GnRH partially reversed the action of this antagonist on the hormonal releases in the 15-week placental cultures. These data demonstrate a gestational age-related action of this antagonist on placental hormonal release. Thus, a role for the endogenous GnRH-like activity of the placenta in the control of placental hormonogenesis is indicated.     

Multidetector spiral high-resolution computed tomography of the lungs: distribution of findings on coronal image reconstructions

The aim of this pictorial essay is to illustrate the distribution of normal findings and various lung diseases on coronal reconstructions as compared with cross-sectional high-resolution CT images. The volumetric CT images were obtained at 120 kVp, 200 mA/rotation, pitch 6:1, and a high-spatial-frequency reconstruction algorithm. The scans were performed using 2.5-mm collimation and reconstructed at 1.25-mm intervals. Coronal reconstructions were obtained at 2.5-mm slice thickness and 2.5-mm intervals. The pictorial includes images of normal anatomy, emphysema, idiopathic pulmonary fibrosis, Langerhans cell histiocytosis, sarcoidosis, bronchiolitis obliterans organizing pneumonia, desquamative interstitial pneumonia, nonspecific interstitial pneumonia, lymphocytic interstitial pneumonia, pulmonary edema, tuberculosis, cytomegalovirus pneumonia, bronchiectasis, and panbronchiolitis.