Effect of cilobradine in cats with a first episode of congestive heart failure due to primary cardiomyopathy.

INTRODUCTION: Heart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality. OBJECTIVES: To investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP. ANIMALS: Three hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned. METHODS: Prospective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity. RESULTS: Median time to primary outcome was 84 days (95% confidence interval [CI]: 63-219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145-377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG. CONCLUSIONS: Heart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.

ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour.

The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain development, adult hippocampal neurogenesis and in cognitive functions. Lack of ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are associated with, e.g. X-linked intellectual disability. However, little is known about the effects of over-expression of ATP6AP2 in the adult brain. We hypothesized that mice over-expressing ATP6AP2 in the brain might exhibit altered neuroanatomical features and behavioural responses. To this end, we investigated heterozygous transgenic female mice and confirmed increased levels of ATP6AP2 in the brain. Our data show that over-expression of ATP6AP2 does not affect adult hippocampal neurogenesis, exercise-induced cell proliferation, or dendritic spine densities in the hippocampus. Only a reduced ventricular volume on the gross morphological level was found. However, ATP6AP2 over-expressing mice displayed altered exploratory behaviour with respect to the hole-board and novel object recognition tests. Moreover, primary adult hippocampal neural stem cells over-expressing ATP6AP2 exhibit a faster cell cycle progression and increased cell proliferation. Together, in contrast to the known deleterious effects of ATP6AP2 depletion, a moderate over-expression results in moderate behavioural changes and affects cell proliferation rate in vitro.

Medical and surgical management of paraneoplastic pyoderma gangrenosum--a case report and review of the literature.

We present a case of a 44-year-old male with pyoderma gangrenosum (PG) presenting simultaneously with diagnosis of acute leukemia. His skin disease was stabilized with corticosteroids and most lesions cleared after chemotherapy-induced remission of the malignancy, but the largest lesion remained necrotic. Surgical treatment of the large necrotic ulcer included debridement followed by split-thickness skin graft while maintaining corticoid therapy. Unfortunately, relapse of the pyoderma gangrenosum with bullous lesions heralded relapse of the ultimately fatal malignancy. This case illustrates: (1) PG presenting simultaneously with a haematologic malignancy (2) Relapse with atypical bullous lesions with return of the malignancy and (3) The use of surgical modalities in managing patients with PG, a disease notorious for surgical complications.

Acute generalized exanthematous pustulosis after pemetrexed, and recurrence after re-introduction.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous reaction, which in most cases, is related to medication. Pemetrexed is an antifolate drug, approved for treatment of metastatic non-small-cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). We present a case of AGEP caused by pemetrexed, and a recurrence of this eruption after re-introduction of pemetrexed despite use of corticosteroids.