ABSTRACT
Acute rheumatic fever (ARF) is an autoimmune disease affecting the heart-valve endocardium in its final stage. Although rare in developing countries, ARF persists in third-world countries, particularly Senegal, where rheumatic heart diseases (RHDs) are the most common pediatric cardiovascular pathology. This study aimed to investigate mutations in MT-CYB in ARF and RHD in Senegalese patients. MT-CYB was amplified from blood samples from ARF patients at the Clinical of Thoracic and Cardiovascular Surgery of Fann National University Hospital Centre, Dakar, Senegal (control group, healthy individuals) and sequenced. More than half of the MT-CYB mutations (58.23%) were heteroplasmic. Transitions (61.67%) were more frequent than transversions (38.33%), and non-synonymous substitutions represented 38.33% of mutations. Unoperated RHD patients harbored frequent MT-CYB polymorphisms (7.14 ± 14.70 mutations per sample) and accounted for 72.73% of mutations. Paradoxically, subjects undergoing valvular replacement harbored infrequent polymorphisms (1.39 ± 2.97 mutations per patient) and lacked 36 mutations present in unoperated subjects. A genetic differentiation was observed between these two populations, and the mutations in operated subjects were neutral, while those in unoperated subjects were under positive selection. These results indicate a narrow link (perhaps even causal) between MT-CYB mutations and ARF and its complications (i.e., RHDs) and that these mutations are largely deleterious.
ABSTRACT
Taxane-induced neuropathy is a frequent complication, in particular in women with breast cancer. The incidence can be variable and ranges from 11 to 87%, depending on the taxane used and identified risk factors, such as cumulative dose, additional neurotoxic chemotherapy agents and previous nerve fragility. However, little is known about long-term outcome and interference with daily life activities. The objective of this study was to assess clinical and electrophysiological neurological evaluation (ENMG) in a cohort of patients, 1-13 years (median 3 years) after the end of the last cure. Sixty-nine women were enrolled in the lymphology unit of Cognacq-Jay's Hospital. They were 58 ± 9 years old (mean age ± SD) and had been treated by docetexel (n = 56), paclitaxel (n = 10) or both (n = 3), 1-13 years before. Sensory neuropathy occurred in 64% and totally disappeared within months for only 14% after cessation of treatment. However, if symptoms were still present at the time of examination, they were considered as minor by almost all patients, with no interference with daily life activities (grade 2 CTCAE v.3.0). ENMG was accepted by 14 patients; it was normal in 7, and showed sensory axonal neuropathy in 5 and sensory-motor neuropathy in 2. The incidence of taxane-induced neuropathy is high, more frequent with paclitaxel than docetaxel, and is characterized by minor or moderate axonal sensory polyneuropathy. When persistent, it is extremely well tolerated by the patient. When clinical motor signs occur, the patient should be referred to a neurologist.
