Biomedical subjects
Jérôme Clerc
Publications and source records attributed to Jérôme Clerc.
[Thyroid nodule].
The thyroid nodule is a frequent, most often benign, chronic, multifocal and slowly progressive disease. The first line strategy is to diagnose cancerous nodules (<5%) and relies upon fine needle aspiration (FNA), a specialised technique which in trained hands has a false negative rate of below 5%. The interest to explore small thyroid nodules is controversial since the prognosis of thyroid cancer is excellent for lesions measuring less than 20 mm. Though imaging accuracy is quite limited in assessing the diagnosis of thyroid cancer, both ultrasounds (US) and thyroid scan are helpful to enhance nodular identification (>30%), to sort the nodules relevant for cytological sampling and to optimize the follow-up, the major source of health costs. Suspicious and non contributive FNAs must have a control FNA within 6 months. Nodules with a non suspicious FNA (>85%) require long term follow-up. This follow-up is mainly morphological. New or evolutive nodules, as assessed by palpation or US, will require iterative FNAs or should be considered for surgery. In patients with hyperfunctioning nodules on the scan (10 to 20%), a yearly evaluation of the TSH level is sufficient. These nodules account either for autonomously functioning ones, which slowly develop towards thyrotoxicosis, or for hyperplastic nodules frequently disclosing a lymphocytic thyroiditis. Morbidity due to thyroid autonomy is still underestimated especially in aging patients with TSH levels < or =0.60 mU/L. An algorithmic approach to the diagnostic and follow-up evaluation of thyroid nodule is suggested.
Long-term radioiodine retention and regression of liver cancer after sodium iodide symporter gene transfer in wistar rats.
Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS) gene delivery has been proposed as a potential application of gene therapy. However, it seems to be precluded by the rapid efflux of taken up iodine from most transduced xenografted tumors. We present an in vivo kinetic study of NIS-related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body iodine distribution by repeated imaging of live animals. We constructed a rat NIS (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove expression of a functional NIS protein by hepatocytes and allowed marked (from 20 to 30% of the injected dose) and sustained (>11 days) iodine uptake. This contrasts with the massive iodine efflux found in vitro in human hepatic tumor cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a rapid iodine efflux from the liver, indicating that the sustained uptake was not attributable to an active retention mechanism but to permanent recycling of the effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the complete regression of small nodules, and prolonged survival of hepatocarcinoma-bearing rats. This demonstrates for the first time the efficacy of NIS-based radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.
Hydroquinidine therapy in Brugada syndrome.
OBJECTIVES: We sought to assess hydroquinidine (HQ) efficacy in selected patients with Brugada syndrome (BrS). BACKGROUND: Management of asymptomatic patients with BrS and inducible arrhythmias remains a key issue. Effectiveness of class Ia antiarrhythmic drugs, which inhibit the potassium transient outward current of the action potential, has been suggested in BrS. METHODS: From a cohort of 106 BrS patients, we studied 35 who received HQ (32 men; mean age 48 +/- 11 years). Patients had asymptomatic BrS and inducible arrhythmia (n = 31) or multiple appropriate shocks from an implantable cardioverter-defibrillator (ICD) (n = 4). Asymptomatic patients with inducible arrhythmia underwent electrophysiologic (EP)-guided therapy. When ventricular tachycardia (VT)/ventricular fibrillation (VF) inducibility was not prevented, or in case of HQ intolerance, an ICD was placed. RESULTS: Hydroquinidine prevented VT/VF inducibility in 76% of asymptomatic patients who underwent EP-guided therapy. Syncope occurred in two of the 21 patients who received long-term (17 +/- 13 months) HQ therapy (1 syncope associated with QT interval prolongation and 1 unexplained syncope associated with probable noncompliance). In asymptomatic patients who received an ICD (n = 10), one appropriate shock occurred during a follow-up period of 13 +/- 8 months. In patients with multiple ICD shocks, HQ prevented VT/VF recurrence in all cases during a mean follow-up of 14 +/- 8 months. CONCLUSIONS: Hydroquinidine therapy prevented VT/VF inducibility in 76% of asymptomatic patients with BrS and inducible arrhythmia, as well as VT/VF recurrence in all BrS patients with multiple ICD shocks. These preliminary data suggest that preventive treatment by HQ may be an alternative strategy to ICD placement in asymptomatic patients with BrS and inducible arrhythmia.