Aberrant adrenal sensitivity to multiple ligands in unilateral incidentaloma with subclinical autonomous cortisol hypersecretion: a prospective clinical study

BACKGROUND: Incidentally discovered adrenal tumours are frequently associated with subclinical autonomous cortisol hypersecretion of unknown origin. Aberrant hormone receptors have been observed in case reports of overt Cushing's syndrome. The question arises as to whether such receptors may be present in the functioning adrenal incidentaloma, which is common and might be a subclinical stage of Cushing's syndrome. PATIENTS AND METHODS: Twenty-one consecutive patients with a unilateral incidentaloma, the biochemical features of subclinical cortisol hypersecretion and/or the scintigraphic features of an autonomously functioning adrenal adenoma were investigated for plasma cortisol responses to various stimuli: upright posture, meal, combined hypothalamic-hormones, the vasopressin analogue terlipressin, glucagon, angiotensin II, the serotonin 5-HT4 agonist cisapride, and ACTH. Six normal controls were similarly investigated. All subjects were studied during 8 mg per day dexamethasone in order to avoid any ACTH-dependent variation of plasma cortisol. RESULTS: The most constant responses in adrenal incidentalomas were observed after stimulation by terlipressin (18/20 patients, 28-415% cortisol increase) and cisapride (17/21 patients, 25-364% cortisol increase). Eighteen out of 21 patients responded to several stimuli (cortisol increase >or= 25%), and all responded to at least one stimulus other than ACTH, while such responses were absent in the controls. Plasma ACTH remained suppressed in all subjects throughout the study. CONCLUSIONS: Aberrant membrane receptors detected by in vivo stimulation tests appear to be common in autonomously functioning unilateral adrenocortical adenomas. These receptors may be involved in the modulation of cortisol secretion in adrenal incidentaloma, with potential therapeutic consequences for the control of subclinical cortisol hypersecretion.     

Inducibility of Atrial Fibrillation After GP Ablations and “Autonomic Blockade”: Evidence for the Pathophysiological Role of the Nonadrenergic and Noncholinergic Neurotransmitters

Autonomic Blockade and Atrial Fibrillation . Background: Recent clinical reports that used cholinergic and adrenergic blockade (CAB) as an alternative to ganglionated plexi (GP) ablation to terminate atrial fibrillation (AF) showed mixed results. We investigated the role of other neurotransmitters in AF inducibility. Methods: In 23 pentobarbital anesthetized dogs, a left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins and atrial appendages (AA). Programmed stimulation was used to determine the effective refractory periods (ERP) and AF inducibility, measured by the window of vulnerability (WOV). AF duration in response to acetylcholine (Ach; 100 mM) applied to the AA was measured before and after GP ablation + CAB and with vagus nerve stimulation (VNS). After GP ablation + CAB, Ach induced AF duration was determined in response to vasoactive intestinal peptide (VIP) and its specific antagonist ([Ac‐Tyr1,D‐phe2]‐VIP). Results: GP ablation + CAB significantly prolonged ERP, eliminated WOV, and suppressed the duration of Ach induced AF (P ≤ 0.01 for all). Also slowing of the heart rate by VNS was essentially blocked; however, with Ach 100 mM applied to the AA, VNS, and VIP applied to the AA markedly prolonged AF duration. This effect was blocked by the VIP antagonist. Conclusions: Neither GP ablation nor CAB can fully suppress AF inducibility arising from the atrial neural network. Our findings suggest that other neurotransmitters, such as VIP released during VNS, can promote sustained AF despite GP ablation and “autonomic blockade,” which may further define the substrate for AF outside the pulmonary vein‐atrial junctions. (J Cardiovasc Electrophysiol, Vol. 24, pp. 188‐195, February 2013)     

人类染色体17p13.3位点新克隆基因HC56,HC71 和HC90在白血病细胞的表达

为研究人类染色体17p13．3位点新克隆的基因HC56，HC71和HC90在白血病细胞中的表达，应用同位素标记的、以βM2基因作为内参的半定量RT—PcR法，检测35例急性白血病和4株白血病细胞系的Hc56，Hc70和HC90基因的表达。结果显示，急性淋巴系白血病病人的HC90基因和T淋巴系白血病细胞系Jurkat细胞HC90基因表达水平降低。急性髓系白血病病人HC71基因表达水平降低。HC56基因表达在急性白血病和正常对照间未见显差异。结论：在人类白血病有HC70和HC90的基因表达异常。     

Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection

HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10(-4)) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4(+) T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4(+) T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir.     

A Prospective,Randomized Comparison of Modified Pulmonary Vein Isolation Versus Conventional Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation

Modified Pulmonary Vein Isolation in AF Ablation. Introduction: Pulmonary vein isolation (PVI) is the primary ablation therapy in patients with atrial fibrillation (AF). We hypothesized that high dominant frequency (DF) sites (AF nests during sinus rhythm [SR]) adjacent to the PV ostia are associated with the atrial substrate that maintains AF, and PVI incorporating the high‐frequency AF nests may have a higher efficacy. Methods and Results: In a prospective and randomized comparison, 126 symptomatic paroxysmal AF patients that underwent PVI were enrolled. We compared the efficacy of a modified PVI (ablation line: 1.0–1.5 cm from the PV ostium with encircling the AF nests [spectral analysis with DF >70 Hz during SR, Group II]) versus the anatomy‐guided conventional PVI (Group I). In Group II, the DF value along the PV ostium was lower than 70 Hz after the PVI. The primary endpoint was the freedom from symptomatic atrial arrhythmias after a single procedure. We also followed the autonomic function by a time‐domain analysis of the heart rate variability. In both groups, AF nests were observed and electric isolation was successfully obtained in all patients. With a mean duration of 16 ± 6.1 months of follow‐up, Group II had a higher single procedure efficacy without drugs (78.7% vs 66.1%, log‐rank test: P = 0.02), and fewer repeat procedures (6.6% vs 23%; P = 0.04), as compared to Group I. Conclusion: PVI incorporating the high frequency AF nests adjacent to the PV ostia had a better single procedure efficacy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1155–1162, November 2012)     

Binge drinking concurrent with anal intercourse and condom use among men who have sex with men

Men who have sex with men (MSM) are the demographic group most severely affected by HIV in the USA. Global association studies have shown that MSM who binge drink are more likely to engage in risky sexual behaviors and day- and event-level analyses have linked binge drinking to sexual risk behavior on specific days and during specific sexual encounters. Despite this strong foundation of research, no studies have examined the association between the frequency of situational binge drinking (i.e., binge drinking concurrent with sexual activity) and aggregated sexual risk over periods of longer duration. We used multivariable logistic regression to assess the relationship between situational binge drinking (i.e., binge drinking concurrent with anal intercourse) and condomless anal intercourse (CAI) and among a cross-sectional sample of 124 MSM in San Francisco, CA. There was a positive relationship between frequency of situational binge drinking and CAI (1–5 times vs. never: adjusted odds ratio?=?2.78, 95% CI?=?1.01–7.63; 6–10 times vs. never: 6.19, 1.27–30.22; more than 10 times vs. never: 11.88, 1.31–107.60). By filling a methodological gap and complementing existing global and event-level analyses, this positive situational relationship strengthens the evidence linking binge drinking and sexual risk, enhances the comparability of the existing literature, and further suggests that the integration of dual strategies that aim to prevent HIV and reduce binge drinking may be warranted.     

Clinical course of 161 untreated and tenofovir‐treated chronic hepatitis B pregnant patients in a low hepatitis B virus endemic region

Hepatitis B immunoprophylaxis failure is linked to high maternal viraemia. There is limited North American data on hepatitis B outcomes in pregnancy. Pregnant hepatitis B carriers were enrolled January 2011–December 2014 and offered tenofovir in the 3rd trimester if hepatitis B virus (HBV)‐DNA was >7‐log IU/mL. Outcomes were determined in treated vs untreated patients. In total, 161 women with 169 pregnancies (one twin, 170 infants; median age 32 years), 18% (29/161) HBeAg+ and median HBV‐DNA 2.51 log IU/mL (IQR 1.66–3.65; range 0.8–8.1) were studied. 14.3% (23/161) received tenofovir due to high viral load (16/23, median 74 days, IQR 59–110) or due to liver disease (7/23). In 10/16 treated due to high viraemia, with confirmed adherence, follow‐up HBV‐DNA showed a 5.49 log decline (P = 0.003). In treatment naïve mothers, median alanine aminotransferase (ALT) increased from 17 IU/L (IQR 12–24) to 29 (IQR 18–36) post‐partum (P = 1.5e‐7). In seven highly viraemic mothers who declined therapy (HBV‐DNA >8‐log IU/mL); median ALT increased ~3X from baseline (P < 0.01). 26% (44/169) had Caesarean section with no difference in treated vs untreated subjects. No tenofovir‐treated mothers had renal dysfunction. Data were available on 167/170 infants; in 50.8% (85/167) who completed immunoprophylaxis, 98.8% (84/85, including 12 exposed to tenofovir in utero) were HBV immune. One infant born to an HBeAg+ mother with HBV‐DNA >8‐log IU/mL failed immunoprophylaxis. In this prospective Canadian cohort study, most untreated mothers experienced mild HBV flares. Tenofovir in pregnancy is well tolerated and reduces viral load prior to parturition.     

Vascular entrapment of a multipolar basket catheter (OrionTM) during catheter ablation

The IntellaMap Orion^TM (Boston Scientific) is a 64-electrode basket catheter allowing for ultrahigh-density mapping of complex cardiac arrhythmias. We report the case of a basket catheter vascular entrapment, requiring surgical removal.