Serous borderline tumor of the ovary with isolated cardiophrenic lymph node spread at diagnosis.

•Serous borderline tumor outside of the peritoneal cavity is rare.•Involvement of cardiophrenic lymph nodes with serous borderline tumor can occur.•Preoperative imaging may aid surgical planning even in serous borderline tumor cases.•Sequencing can help confirm a diagnosis of serous borderline tumor at distant sites.

Safety and efficacy of vesatolimod (GS-9620) in patients with chronic hepatitis B who are not currently on antiviral treatment.

Vesatolimod is an oral agonist of toll-like receptor 7 designed to minimize systemic exposure and side effects. We assessed the safety and efficacy of vesatolimod in viremic chronic hepatitis B (CHB) patients not currently on oral antiviral treatment (OAV) in a phase 2, multicentre, double-blind, randomized, placebo-controlled study. A total of 192 patients stratified by HBeAg status and alanine aminotransferase level were randomized 2:2:2:1 to receive oral vesatolimod (1-, 2- or 4-mg) or placebo once weekly for 12 weeks; tenofovir disoproxil fumarate (300-mg daily) was administered daily for 48 weeks. Efficacy was assessed by quantitative serum HBsAg decline at Week 24 from baseline. In addition to safety assessments, changes in whole-blood interferon-stimulated gene (ISG) transcripts and serum cytokines were explored. Most patients were male (64.1%) and HBeAg-negative (60.9%) at baseline. Among vesatolimod-treated patients, most (60.4%-69.1%) experienced ≥1 treatment-emergent adverse event; the majority were mild or moderate in severity. No clinically meaningful differences in HBsAg changes from baseline were observed between treatment groups. No patients experienced HBsAg loss, while 3 patients experienced HBeAg loss and hepatitis B e-antibody seroconversion at week 48. HBV DNA suppression rates were similar across all treatment arms at Week 24. ISG15 induction was dose-dependent and did not correlate with HBsAg changes. A small proportion of patients exhibited dose-dependent interferon-α induction that correlated with grade of influenza-like adverse events. Overall, vesatolimod is safe and well tolerated in CHB patients. Although consistent dose-dependent pharmacodynamic induction of ISGs was demonstrated, it did not result in clinically significant HBsAg decline.

No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment.

A major hurdle in the long-term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted. Patients in studies GS-US-174-0102 (HBeAg-) and GS-US-174-0103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF through year 8. Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1-2 to <4% over years 3-8. Forty-one episodes of virologic breakthrough (VB) occurred throughout the study, with most (n=29, 70%) associated with nonadherence to study medication. Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41/165, 24.8%) or conserved (17/165, 10.3%) site changes in pol/RT, with six patients developing lamivudine and/or ADV resistance-associated mutations. No accumulation of conserved site changes was detected. The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years, with no evidence of TDF resistance or accumulation of conserved site changes.

Effect of recovery duration from prior exhaustive exercise on the parameters of the power-duration relationship.

The physiological equivalents of the curvature constant (W') of the high-intensity power-duration (P-t(LIM)) relationship are poorly understood, although they are presumed to reach maxima/minima at exhaustion. In an attempt to improve our understanding of the determinants of W', we therefore aimed to determine its recovery kinetics following exhaustive exercise (which depletes W') concomitantly with those of O(2) uptake (V(O(2)), a proxy for the kinetics of phosphocreatine replenishment) and blood lactate concentration ([L(-)]). Six men performed cycle-ergometer exercise to t(LIM): a ramp and four constant-load tests, at different work rates, for estimation of lactate threshold, W', critical power (CP), and maximum V(O(2)). Three further exhausting tests were performed at different work rates, each preceded by an exhausting "conditioning" bout, with intervening recoveries of 2, 6, and 15 min. Neither prior exhaustion nor recovery duration altered V(O(2)) or [L(-)] at t(LIM). Postconditioning, the P-t(LIM) relationship remained well characterized by a hyperbola, with CP unchanged. However, W' recovered to 37 +/- 5, 65 +/- 6, and 86 +/- 4% of control following 2, 6, and 15 min of intervening recovery, respectively. The W' recovery was curvilinear [interpolated half time (t(1/2)) = 234 +/- 32 s] and appreciably slower than V(O(2)) recovery (t(1/2) = 74 +/- 2 s) but faster than [L(-)] recovery (t(1/2) = 1,366 +/- 799 s). This suggests that W' determines supra-CP exercise tolerance, its restitution kinetics are not a unique function of phosphocreatine concentration or arterial [L(-)], and it is unlikely to simply reflect a finite energy store that becomes depleted at t(LIM).

Effects of prior very-heavy intensity exercise on indices of aerobic function and high-intensity exercise tolerance.

A recent bout of high-intensity exercise can alter the balance of aerobic and anaerobic energy provision during subsequent exercise above the lactate threshold (theta(L)). However, it remains uncertain whether such "priming" influences the tolerable duration of subsequent exercise through changes in the parameters of aerobic function [e.g., theta(L), maximum oxygen uptake (Vo(2max))] and/or the hyperbolic power-duration (P-t) relationship [critical power (CP) and the curvature constant (W')]. We therefore studied six men performing cycle ergometry to the limit of tolerance; gas exchange was measured breath-by-breath and arterialized capillary blood [lactate] was measured at designated intervals. On different days, each subject completed 1) an incremental test (15 W/min) for estimation of theta(L) and measurement of the functional gain (DeltaVo(2)/DeltaWR) and Vo(2peak) and 2) four constant-load tests at different work rates (WR) for estimation of CP, W', and Vo(2max). All tests were subsequently repeated with a preceding 6-min supra-CP priming bout and an intervening 2-min 20-W recovery. The hyperbolicity of the P-t relationship was retained postpriming, with no significant difference in CP (241 +/- 39 vs. 242 +/- 36 W, post- vs. prepriming), Vo(2max) (3.97 +/- 0.34 vs. 3.93 +/- 0.38 l/min), DeltaVo(2)/DeltaWR (10.7 +/- 0.3 vs. 11.1 +/- 0.4 ml.min(-1).W(-1)), or the fundamental Vo(2) time constant (25.6 +/- 3.5 vs. 28.3 +/- 5.4 s). W' (10.61 +/- 2.07 vs. 16.13 +/- 2.33 kJ) and the tolerable duration of supra-CP exercise (-33 +/- 11%) were each significantly reduced, despite a less-prominent Vo(2) slow component. These results suggest that, following supra-CP priming, there is either a reduced depletable energy resource or a residual fatigue-metabolite level that leads to the tolerable limit before this resource is fully depleted.

Absence of long-term modulation of ventilation by dead-space loading during moderate exercise in humans.

The stability of arterial PCO(2) (P(a)CO(2)) during moderate exercise in humans suggests a CO(2)-linked control that matches ventilation (V(E)) to pulmonary CO(2) clearance (VCO(2)). An alternative view is that V(E) is subject to long-term modulation (LTM) induced by "hyperpnoeic history". LTM has been reported with associative conditioning via dead-space (V(D)) loading in exercising goats (Martin and Mitchell 1993). Whether this prevails in humans is less clear, which may reflect differences in study design (e.g. subject familiarisation; V(D) load; whether or not V(E) is expressed relative to VCO(2); choice of P(a)CO(2) estimator). After familiarisation, nine healthy males performed moderate constant-load cycle-ergometry (20 W-80 W-20 W;

The development and evaluation of an ELISA for the detection of antibodies to caprine arthritis-encephalitis virus in goat sera.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of antibodies to caprine arthritis encephalitis virus (CAEV) in goat sera. The system was evaluated using some 1500 sera from flocks of known clinical history. From this data the interpretation limits of the system were determined. The ELISA system was compared with a gel precipitin test using 5800 sera. Of the positive sera, ELISA detected 97.3% and AGPT 61%. Further evaluation was made using 60 sera of known CAEV reactivity from the USA, and results agreed 100%. Indications are that antibody to the envelope glycoprotein gp135 is being detected. The ELISA system is more sensitive than the precipitin test and is presently being used in a CAEV flock accreditation scheme.

Experimental transmission of malignant catarrhal fever to red deer (Cervus elaphus).

Malignant catarrhal fever was transmitted from affected to recipient red deer (Cervus elaphus) using blood or lymphoid suspension as inoculum. Incubation periods ranged from 11 to 26 days. The disease was also transmitted using lymphoid suspension stored overnight at 4 degrees C or at -70 degrees C for 8 months. The experimental disease was characterised by fever, depression, anorexia, diarrhoea and dysentry. The course of the disease was approximately 96 hours. Major lesions consisted of acute mesenteric lymphadenitis and acute haemorrhagic typhlitis and colitis. Lesions in the caecum and colon started as multifocal mucosal haemorrhages and progressed rapidly to massive mucosal haemorrhage.