An antiserum to soluble rat luteal LH receptors was produced in rabbits. The presence of LH receptor antibodies was shown by indirect immuno-precipitation of [125]hCG-soluble rat LH receptor-receptor antiserum complexes by antirabbit IgG. The antiserum bound LH receptors from rat ovaries and testes but not those from human or sheep ovaries. Unoccupied LH receptors competed with [125I]hCG occupied receptors in a dose-dependent fashion for antiserum binding. Extracts of rat brain and liver did not appear to bind to the antiserum. In addition, LH-dependent progesterone secretion from isolated rat ovarian cells was reduced by the antiserum although there was no change in hormone binding.

AbstractPompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype,GAAgenotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.Trial registry:ClinicalTrials.gov Identifier: NCT01526785https://clinicaltrials.gov/ct2/show/NCT01526785.Social Media Statement:Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.

Purpose To characterize clinical characteristics and genotypes of patients in the ADVANCE study of 4000 L-scale alglucosidase alfa (NCT01526785), the largest prospective United States Pompe disease cohort to date. Methods Patients aged ≥1 year with confirmed Pompe disease previously receiving 160 L alglucosidase alfa were eligible. GAA genotypes were determined before/at enrollment. Baseline assessments included histories/physical exams, Gross Motor Function Measure-88 (GMFM-88), pulmonary function tests, and cardiac assessments. Results Of 113 enrollees (60 male/53 female) aged 1–18 years, 87 had infantile-onset Pompe disease (IOPD) and 26 late-onset (LOPD). One hundred eight enrollees with GAA genotypes had 215 pathogenic variants (220 including combinations): 118 missense (4 combinations), 23 splice, 35 nonsense, 34 insertions/deletions, 9 duplications (1 combination), 6 other; c.2560C>T ( n = 23), c.−32-13T>G ( n = 13), and c.525delT ( n = 12) were most common. Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material–negative. All IOPD and 6/26 LOPD patients had cardiac involvement, all without c.−32−13T>G. Thirty-two (26 IOPD, 6 LOPD) were invasively ventilated. GMFM-88 total %scores (mean ± SD, median, range): overall 46.3 ± 33.0% (47.9%, 0.0–100.0%), IOPD 41.6 ± 31.64% (38.9%, 0.0–99.7%), LOPD: 61.8 ± 33.2 (70.9%, 0.0–100.0%). Conclusion ADVANCE, a uniformly assessed cohort comprising most US children and adolescents with treated Pompe disease, expands understanding of the phenotype and observed variants in the United States.

Purpose Pompe disease results from lysosomal acid α-glucosidase (GAA) deficiency and its associated glycogen accumulation and muscle damage. Alglucosidase alfa (recombinant human GAA (rhGAA)) received approval in 2006 as a treatment for Pompe disease at the 160 L production scale. In 2010, larger-scale rhGAA was approved for patients up to 8 years old without cardiomyopathy. NCT01526785 evaluated 4,000 L rhGAA efficacy/safety in US infantile- or late-onset Pompe disease (IOPD, LOPD) patients up to 1 year old transitioned from 160 L rhGAA. Methods A total of 113 patients (87 with IOPD; 26 with LOPD) received 4,000 L rhGAA for 52 weeks dosed the same as previous 160 L rhGAA. Efficacy was calculated as the percentage of patients stable/improved at week 52 (without death, new requirement for invasive ventilation, left ventricular mass z -score increase >1 if baseline was >2, upright forced vital capacity decrease ≥15% predicted, or Gross Motor Function Measure–88 decrease ≥8 percentage points). Safety evaluation included an extension ≤20 months. Results Week 52 data was available for 104 patients, 100 of whom entered the extension. At week 52, 87/104 (83.7%) were stable/improved. Overall survival was 98.1% overall, 97.6% IOPD, 100% LOPD; 92.4% remained invasive ventilator–free (93.4% IOPD, 88.7% LOPD). Thirty-five patients had infusion-associated reactions. Eight IOPD patients died of drug-unrelated causes. Conclusions Most Pompe disease patients were clinically stable/improved after transitioning to 4,000 L rhGAA. Safety profiles of both rhGAA forms were consistent.

Upper airway edema (UAE) occurs infrequently in hereditary angioedema (HAE), but still results in significant morbidity and mortality.To assess patients with HAE and UAE to determine whether unique features exist that can predict the risk of UAE.Clinical, laboratory, and genetic data were compared between 43 patients with HAE and 743 UAE attacks and those without UAE and normal controls after ethics committee approval.Most patients had their first episode of UAE in the second (25.6%), third (27.9%), and fourth (23.3%) decades of life, and the mean age at onset was 27.3 years. Evolution of UAE from initial to maximum symptoms was 4.6 hours on average, and most cases (69.8%) progressed within 4 hours. Dyspnea was the most frequent manifestation in per-episode (92.2%) and per-patient (97.7%) analyses. Men developed more asphyxiation attacks (19 vs 2) and underwent more tracheotomies (12 vs 2) than did women. UAE was associated with facial edema in half the studied patients. Patients with a positive family history of UAE had a high risk of UAE attacks.Symptoms limited to the upper airway should be taken seriously. Dyspnea may be the only manifestation of UAE. UAE attacks most commonly start spontaneously and usually progress rapidly, as quickly as 30 minutes, from awareness of symptoms to maximum airway involvement. Patients with a positive UAE family history are predisposed to UAE attacks, and men appear to be more apt to develop asphyxiation than women.