Mycolactone toxin induces an inflammatory response by targeting the IL-1ß pathway: Mechanistic insight into Buruli ulcer pathophysiology.

Mycolactone, a lipid-like toxin, is the major virulence factor of Mycobacterium ulcerans, the etiological agent of Buruli ulcer. Its involvement in lesion development has been widely described in early stages of the disease, through its cytotoxic and immunosuppressive activities, but less is known about later stages. Here, we revisit the role of mycolactone in disease outcome and provide the first demonstration of the pro-inflammatory potential of this toxin. We found that the mycolactone-containing mycobacterial extracellular vesicles produced by M. ulcerans induced the production of IL-1ß, a potent pro-inflammatory cytokine, in a TLR2-dependent manner, targeting NLRP3/1 inflammasomes. We show our data to be relevant in a physiological context. The in vivo injection of these mycolactone-containing vesicles induced a strong local inflammatory response and tissue damage, which were prevented by corticosteroids. Finally, several soluble pro-inflammatory factors, including IL-1ß, were detected in infected tissues from mice and Buruli ulcer patients. Our results revisit Buruli ulcer pathophysiology by providing new insight, thus paving the way for the development of new therapeutic strategies taking the pro-inflammatory potential of mycolactone into account.

Cutaneous basidiobolomycosis: Seven cases in southern Benin.

BACKGROUND: Cutaneous basidiobolomycosis is the most common form of entomophthoramycosis. Herein we report seven cases of cutaneous basidiobolomycosis. PATIENTS AND METHODS: A retrospective observational study was conducted at the Buruli ulcer treatment centre in Pobè and at the national teaching hospital in Cotonou from 2010 to 2015. RESULTS: Seven cases of cutaneous basidiobolomycosis were diagnosed. The mean patient age was 9.53 years. There were 4 female and 3 male patients, all from southeast Benin. Clinically, the disease presented in all cases as a hard, well-defined, subcutaneous plaque with little inflammation, and which could easily be lifted from the deep structures but remained attached to the surface structures. The overlying skin was hyperpigmented. Plaques were localized to the buttocks or thighs. All patients had inflammatory anaemia with an accelerated erythrocyte sedimentation rate (30 to 70mm over the first hour), and a low haemoglobin count (8.7 to 11.4g/dL). Blood hypereosinophilia (650 to 3784elements/mm3) was present in six of the seven subjects. Histopathology (performed for 5 of the 7 subjects) showed granulomatous lesions with foreign-body giant cells, and inflammatory cells, with occasional eosinophils surrounding fungal hyphae (Splendore-Hoeppli phenomenon). Mycological analysis revealed Basidiobolus ranarum in three cases. The patients were treated with ketoconazole (5/7) and itraconazole (2/7), with good outcomes after 10 to 24 weeks of therapy. DISCUSSION: Cutaneous basidiobolomycosis is uncommon in southern Benin, with only seven cases being diagnosed over 6 years. The diagnosis of cutaneous basidiobolomycosis is a challenge in the field in Benin due to the non-specific clinical presentation, the lack of technical resources, and the existence of numerous differential diagnoses. CONCLUSION: Cutaneous basidiobolomycosis is an uncommon fungal infection in southern Benin chiefly affecting children.

[Teaching and perception of urology by medical students at the end of the second cycle: an appraisal]. / Enseignement et perception de l'urologie à la fin du deuxième cycle des études médicales: état des lieux.

OBJECTIVES: Our purpose was to determine how the medical students from the second cycle perceived urology and what their learning methods were. MATERIAL AND METHODS: An e-questionnaire was sent to 1600 students in 16 teaching faculties during the last year of their second cycle. RESULTS: Overall, we obtained 590 answers (36.8%). In our population, 70.2% of the students were women. Of them, 24.1% had been already enrolled in an academic urology unit. Urology was defined as a medical, surgical and medico-surgical discipline by 3.7%, 37.8% and 58% of the students, respectively. Urology was considered as very important, important, not very important and not important at all by 5.1%, 54.4%, 37.5% and 2.4% of the students. The teaching methods used to learn urology were duplicated-notes for ENC preparation (45.3%), conferences for ENC (French national ranking exam) preparation (43.7%), courses of the national urology college (38.6%) and courses of the faculty (32%). The best mastered items were lithiasis disease (86.3%), voiding dysfunction (76.3%) and urological cancers (56.7%). On the contrary, only 34.7% and 28% considered their knowledge sufficient on the erectile dysfunctions and on renal transplantation. Lastly, 7.3% intended to become urologists. Having a work experience in a urology unit was significantly associated to the feeling of being prepared to become an intern (p<0.001) and to the project of becoming a urologist (p<0.001). CONCLUSION: Urology was considered like an important discipline by half of the students at the end of the second cycle even though it is under-represented in the national teaching programme for ENC. A third of the students used courses from the faculty to learn urology and a quarter of them had a work experience in a urology unit during their second cycle.

[Evidence-based medicine and French medical students: an appraisal]. / Evidence-based medicine et étudiants en médecine français : état des lieux.

INTRODUCTION: Nowadays, evidence-based medicine (EBM) is essential to learn and to practice medicine. The aim of the current study was to investigate the baseline level of knowledge of French students regarding EBM. MATERIALS AND METHODS: Between April and May2008, a questionnaire was sent by e-mail to 900students in their last year of medical study. RESULTS: On 327 answers, 297 (91%), 94 (29%) and 85 (26%) students declared they read, write and speak medical English. Ninety (28%) read an article of a French medical review once a month and 43 (13%) read an article of an international medical review once a month. Three hundred and eleven (95%) knew the bases of medical research on the Internet and 219 (67%) used them. Twenty-four (7%) had already participated in a editorial staff of a medical article, 7 (2%) had been co-authors. Two hundred and seventy-two (83%) had made an oral presentation during a medical staff and 3 (1%) during a congress. Finally, 237 (73%) understood the interest of the critical analysis of an article at the ECN and 70 (21%) thought they were prepared. CONCLUSION: The incapacity of learning EBM is one of the limits of the French medical training system. The introduction of the reading critical of an article at the ECN is the concrete beginning of an answer to this problem.

[Evaluation of the practical skills of final year medical students: example of bladder catheterization]. / Evaluation des compétences pratiques en fin de deuxième cycle des études médicales: exemple du drainage du bas appareil urinaire.

INTRODUCTION: When performed incorrectly, bladder catheterization can cause iatrogenic complications, especially urinary tract infections and trauma. The objective of this study was to determine the capacity of final year medical students to perform the various bladder catheterization techniques. MATERIAL AND METHODS: Between January and March 2007, a catheterization self-administered questionnaire was sent by e-mail to a representative sample of final year medical students, two months before the national classifying examination. RESULTS: Two hundred and seventy-seven questionnaires were returned and analysed. Seventy-two students (26%) considered that they were able to perform bladder catheterization in males and 106 (38.3%) in females at the end of their medical training. Seventy-one out of 277 (25.5%) students had completed an urology term during their training and 53.5% of them considered that they had acquired the indwelling catheter technique in males (p<0.001) versus 39 (54.9%) in females (p<0.001). Seventy-three students (26.4%) considered that they were able to perform intermittent catheterization in males or females and only one student was able to perform suprapubic catheterization. CONCLUSION: Teaching of catheterization procedures is inappropriate during medical training and young doctors consider themselves unable to perform these techniques at the end of their training. This is unfortunate, as all doctors should be able to perform catheterization as part of their daily practice, especially in hospital. This study indicates the need for improved teaching of essential medical procedures during undergraduate medical training.

C-cell hyperplasia.

Routine calcitonin assay programs and recent studies on the natural history of familial medullary thyroid carcinoma (MTC) have greatly added to our understanding of C-cell hyperplasia (CCH) and refined its classification. This article is an update on CCH physiopathology related to clinical presentation. With this combined approach, two types of CCH that differ by their physiological characteristics can be identified: neoplastic CCH and reactive (also called physiological) CCH. Neoplastic CCH is caused by a germline mutation of the RET protooncogene in a multiple endocrine neoplasia type 2 (MEN 2) syndrome. It progresses to MTC following a time line that depends on the RET mutation involved. CCH may actually be a misnomer for a neoplastic condition that some authors have proposed to call "in situ-MTC". Reactive CCH is considered to be caused by a stimulus that is external to the C-cell, and its premalignant potential is not documented. Many situations such as hypercalcemia, hyperparathyroidy, chronic lymphocytic thyroiditis or follicular tumors have been associated with reactive CCH, the pathogenesis of which remains unclear. But C-cell density in normal patients is subject to important variability, and several studies have demonstrated the dramatic male predominance in physiological CCH when hypercalcitoninemia was a random discovery. These data suggest that a number of conditions which were previously associated with reactive CCH might be purely fortuitous. Our clinical/pathological confrontation contributes to appropriately distinguishing between various CCH types, and in turn to identify the best way of managing patients.

[Evaluation of the attitude towards disabled persons of 3rd and 4th year medical students using the "Attitude towards disabled persons" questionnaire. Effect of courses and rotations in physical medicine and rehabilitation departments]. / Evaluation de l'attitude vis-à-vis des personnes handicapées des étudiants en médecine de 3e et 4e année par le questionnaire "Attitude towards disabled persons". Effets de l'enseignement théorique et de stages dans les services de médecine physique et réadaptation.

UNLABELLED: Modifications of the medical curriculum have included a compulsory course on disability. OBJECTIVE: To determine whether attendance in a course on disability and/or rotations in physical medicine and rehabilitation departments modify the attitude of medical students towards disabled people. METHODS: All third- and fourth-year students completed a translated version of the ATDPb. This questionnaire rates items evaluating attitude towards disabled people on a 6-point scale (minimum 0; maximum 180). Retro-translation was performed to control the translation. During the second year, all students had attended a general course in ethics. Fourth-year students had attended a 17 hours course on disability, and 21 of 78 had spent 9 weeks in the physical medicine and rehabilitation department. The study compares fourth-year students to third-year students, considered as controls, and students having spent a rotation in the physical medicine and rehabilitation department to others. RESULTS: The mean score of all students was 108.86+/-15.84 (73-160) on the ATDP scale. Males and females did not differ significantly, and the score did not change from that before the course on disability (109.95+/-14.98 vs 107.6+/-16.65, P=0.23) nor after a rotation in the physical medicine and rehabilitation department (113.52+/-11.42 vs 108.54+/-16.03, P=0.14). CONCLUSION: Development and validation of scores that would fit better to the European cultural context would be useful. The present method of theoretical courses and rotations do not improve the attitude of students towards disabled people and should be modified if this objective is to be achieved.

Presence of renin, angiotensinogen, and converting enzyme in human pituitary lactotroph cells and prolactin adenomas.

Renin, angiotensinogen, and converting enzyme were detected in 10 normal human pituitary glands by immunohistochemical techniques. Renin was stained by polyclonal and monoclonal antibodies directed against human renin, and an antibody directed against the renin prosegment revealed the presence of prorenin. Immunoreactive angiotensinogen and angiotensin I-converting enzyme were found in the same cells as renin. Using serial sections and double immunohistochemical labeling with a PRL antiserum, all of the proteins of the renin-angiotensin system appeared to be localized within the lactotroph cells, and no component of the renin system was detected in any of the other pituitary cells. Renin, angiotensinogen, and angiotensin I-converting enzyme also were found in 6 PRL-secreting adenomas as well as in a mixed PRL/GH-secreting adenoma. The renin content of a PRL adenoma was about 1/100th that of a normal kidney. Renin activity could be blocked by an anticatalytic human renin antibody. No renin, angioten-sinogen, or angiotensin I-converting enzyme was found in 6 GH-secreting adenomas, 1 corticotroph adenoma, or 10 nonsecreting pituitary adenomas. The colocalization of proteins of the renin-angiotensin system suggests production of angiotensin II within the lactotroph cells and favors the hypothesis of a paracrine action of this peptide.

Pentagastrin stimulation test and early diagnosis of medullary thyroid carcinoma using an immunoradiometric assay of calcitonin: comparison with genetic screening in hereditary medullary thyroid carcinoma.

A pentagastrin stimulation test using a calcitonin (CT) immunoradiometric assay was performed in 38 healthy subjects and in the following 50 patients: 25 subjects from families with at least 2 known cases of medullary thyroid carcinoma (MTC), 11 subjects from families with apparently sporadic MTC, 2 pheochromocytoma carriers, 1 primary hyperparathyroidism, 8 patients with thyroid nodules, and 3 others with various diseases. In healthy volunteers, basal CT values were always less than 10 ng/L; the response to pentagastrin was below 30 ng/L for 36, and for the remaining 2, the peaks reached 30 for 1 subject and 48 ng/L for the other. The pentagastrin-stimulated CT peak was above 30 ng/L in each of the patients presented here, and all were thyroidectomized. In screening the 25 relatives of patients with familial MTC, a CT peak level over 30 ng/L was constantly associated with C-cell disease (23 cases of MTC and 2 of C-cell hyperplasia). A response to pentagastrin above 100 ng/L was observed in 15 patients among the 23 with MTC. In 8 of the 10 patients with a peak CT level between 30-100 ng/L, pathological examination showed a MTC; the other 2 had C-cell hyperplasia and a negative linkage study analysis. In the 25 other patients in the study without familial MTC, the pentagastrin-stimulated CT level was over 100 ng/L in 11 of the 14 subjects with MTC. The abnormal CT response to pentagastrin, which has been used as a criterion for surgical treatment, is currently determined by an immunoradiometric assay. Our study confirms that subjects with a peak CT level above 100 ng/L should undergo surgery whatever the reason for the test. In the context of inherited MTC, our results suggest that for patients with a CT peak level between 30-100 ng/L, surgery may actually be postponed when their probability of being gene carriers is low. Recent progress with the characterization of specific mutations in affected individuals will make familial screening much easier in the next few months.

Sex-related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study.

We report a prospective quantitative image analysis study of C cells in 57 normal autopsy thyroid glands, serially sectioned and wholly embedded in paraffin; all slides were immunohistochemically stained for calcitonin. Computerized quantitative image analysis was performed on 47 cases to measure C cell surface area and parenchymatous surface area after immunoperoxidase staining for calcitonin. The method was time-effective, with a good reproducibility. C cells were mainly found in the middle third of each lobe. Important inter-individual variations were observed; the maximum C cell surface area in a section (Amax) ranged from 28 x 10(3) to 470 x 10(3) microns2 (mean, 167 x 10(3) microns2) among 42 adults. Of particular interest was the important difference observed between sexes; Amax was twice as high in men (mean, 201 x 10(3) microns2) as in women (mean, 91 x 10(3) microns2; P = 0.0009). Moreover, 14 (33%) adult subjects [2 women (15%) and 12 men (41%)] fulfilled C cell hyperplasia criteria, i.e. at least 3 fields at x 100 magnification containing more than 50 C cells, suggesting that a substantial part of the normal adult population could have C cell hyperplasia.

Interest of routine measurement of serum calcitonin: study in a large series of thyroidectomized patients. The French Medullary Study Group.

The aim of our study was to assess the ability of routine calcitonin (CT) measurement to improve the preoperative diagnosis of medullary thyroid carcinoma (MTC) in nodular thyroid diseases. We systematically determined basal CT in 1167 patients before thyroid surgery and performed a pentagastrin (Pg) CT stimulation test in 121 of these patients whose basal CT level was normal. Sixteen MTC (1.37%) were found on histopathological examination of surgical specimens: 14 in the 34 patients (41.1%) with abnormal basal CT levels and 2 in the 1133 patients with normal basal CT levels (0.17%). An abnormal increase in Pg-stimulated CT was observed in 7 of the 121 patients tested and was related to microscopic MTC in 2 cases. Among 1167 thyroidectomized patients with nodular thyroid diseases, the prevalence of MTC was 1.37% and reached 41.1% when the basal CT level was abnormal (3% of the patients). CT evaluation detected MTC, whereas other procedures, such as fine needle aspiration cytology, failed, thus allowing early radical surgery. CT measurement should thus become a routine part of the diagnostic evaluation of nodular thyroid diseases.

Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I.

One hundred pancreatic tumors ranging in size from 0.3 to 7 cm were studied in 28 patients (17 male and 11 female patients; mean age 35 years) with multiple endocrine neoplasia, type I. An immunohistochemical study was performed on deparaffinized sections using the following antibodies: neuron-specific enolase, chromogranin A or synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, adrenocorticotropic hormone, alpha-subunit of human chorionic gonadotropin, gonadotropin-releasing factor, serotonin, and calcitonin. Among the 100 tumors (all multiple), seven were unclassified, 10 were plurihormonal, and 83 produced a predominant hormonal secretion (with 50-90% of the same cell type), including 37 "A-cell tumors" (glucagon), 27 "B-cell tumors" (insulin), 11 PP-cell tumors, one G-cell tumor (gastrin) and one vasoactive intestinal peptide (VIP)-cell tumor. These multiple tumors had a different predominant hormonal secretion in the same patient in 23 of the 28 cases. There was a preferential association of A-cell tumor and B-cell tumor. Hyperplasia of the islets of Langerhans was not detected in adjacent pancreas. Nesidioblastosis was observed in 30% of cases.

C-cell hyperplasia associated with chronic lymphocytic thyroiditis: a retrospective quantitative study of 112 cases.

Since the first description by Wolfe et al of C-cell hyperplasia (CCH) in asymptomatic relatives of patients suffering from a medullary thyroid carcinoma (MTC), several investigators have described CCH associated with a chronic lymphocytic thyroiditis (CLT) not within the context of MTC or multiple endocrine neoplasia (MEN). We report the study of C-cell density in 112 cases of CLT on retrospective surgical material to determine the frequency of the association between CCH and CLT. The cases of CLT were compared with 19 normal thyroid glands obtained at necropsy. C cells, immunoreactive with a polyclonal anti-calcitonin (CT) antibody, were counted at high magnification (X400) and the number of low-power magnification (X100) microscopic fields (LPFs) containing at least 50 C cells per slide was assessed. Image analysis was performed to determine the C-cell density expressed in number of C cells/cm2. C-cell hyperplasia was defined by the following criteria: C-cell density > 40 cells/cm2 and the presence of at least three LPFs containing more than 50 C cells. Twenty percent of the cases of CLT showed a CCH thus defined, and four of them had an elevated serum CT level. Statistical analysis showed no clinical or biological correlation with the presence of CCH. However, the frequency of CCH was higher if a follicular cell carcinoma was associated with CLT. This study confirms a pathological association between CCH and CLT, provides new criteria for the definition of CCH on surgical pathology material, and reports four cases with an elevated serum CT level not within the context of MTC or MEN.

Contribution of immunohistochemistry, electron microscopy, and cell culture to the characterization of nonfunctioning pituitary adenomas: a study of 40 cases.

We studied 40 endocrinologically inactive pituitary adenomas by immunohistochemistry, electron microscopy, and cell culture in order to determine the incidence of gonadotropic adenomas and to classify nonfunctioning adenomas. Immunohistochemical studies using a large panel of monoclonal and polyclonal antibodies identified the following nonfunctioning adenomas: 20 gonadotropic adenomas, four silent corticotropic adenomas, one plurihormonal adenoma, and 15 nonsecreting adenomas. Among nonsecreting adenomas, ultrastructural study of 13 cases identified seven null cell adenomas and six oncocytomas. Silent corticotropic adenomas were classified into subtypes I, II, and III according to Kovacs and Horvath. Most often, gonadotropic adenomas displayed a varying number of oncocytic cells, characteristic secretory granules, and a prominent Golgi apparatus. Postembedding immunoelectron microscopy was performed on eight gonadotropic or nonsecreting adenomas, but this technique did not provide any additional information. Six gonadotropic adenomas and 10 so-called nonsecreting adenomas were studied in primary cell cultures. The six gonadotropic adenomas and seven of the 10 nonsecreting adenomas released gonadotropins in the culture medium. The use of in vitro results as a supplementary diagnostic criterion allowed classification of the 40 nonfunctioning adenomas as follows: 27 gonadotropic adenomas, four silent corticotropic adenomas, one plurihormonal adenoma, and eight nonsecreting adenomas. These results demonstrate a high proportion of gonadotropic adenomas among nonfunctioning adenomas (67.5%) and the usefulness of several techniques in characterizing this type of pituitary adenoma.

Angiotensin-I-converting enzyme in germinomas.

Angiotensin-I-converting enzyme (ACE) was detected in 18 germinomas, both of testicular or extratesticular localization, and studied by immunohistochemical methods using specific polyclonal antibodies and by enzyme activity measurements. ACE was also detected in normal human germ cells. On the other hand, it was not present in other types of testicular tumors. Biochemical studies and immunohistochemical findings suggest that at least part of the enzyme is membrane bound. Plasma ACE levels appeared to be normal, indicating that measurement of plasma ACE levels in germinomas would be of little help for the diagnosis and follow-up of patients. However, the apparent specificity of ACE detection in germinomas among germ cell tumors might help in histologic diagnosis, especially for tumors of extragonadal localization.

Stenotic intimal thickening of the external iliac artery in competition cyclists.

Twenty-three cases of an arterial disease that affects competition cyclists are reported. Patients complained of intermittent acute claudication appearing on one lower limb only at the time of a maximal strain while cycling. Doppler hemodynamic investigation on an ergometric bicycle revealed a collapse of the ankle systolic pressure. Arteriography showed a sinuous lengthening and moderate stenosis of the external iliac artery. Pathologic examination of the artery disclosed a stenotic intimal thickening due to moderately cellular loose connective tissue with a variable distribution of collagen and elastic fibers. The cells in the affected zone were readily labeled with anti-actin and anti-myosin antibodies, and electron microscopy revealed features of synthetic smooth muscle cells. The lesion observed differs from intimal fibrodysplasia and from artherosclerosis. Abnormal local hemodynamic conditions may lead to this type of lesion. Thus, stenotic intimal thickening of the external iliac artery appears to be a new arterial disease defined by clinical, arteriographic, and pathologic features.

Medullary thyroid microcarcinoma: a clinicopathologic retrospective study of 38 patients with no prior familial disease.

Thirty-eight patients (25 women, 13 men; mean age, 57.8 [32 to 91]) showing one or more medullary thyroid microcarcinomas (ie, < 1 cm), with no prior MEN II or medullary thyroid carcinoma history in their family, were reviewed. Follow-up was available for 29 patients (mean, 53.6 months [1 to 147]). 21 patients (72.4%) are alive and free of disease, four patients (13.8%) died during follow-up without disease, 2 patients are alive with disease (local recurrence and persistent hypercalcitoninemia) after 80 and 99 months, respectively, and 2 patients died of disease after 24 and 46 months. Most tumors were incidental pathological findings (19 of 38) or were discovered by systematic blood calcitonin measurement for a nodular thyroid disease (15 of 38). Only the four patients who had an unfavorable outcome were symptomatic cases (palpable micro-MTC, diarrhea, cervical lymph node metastasis and pulmonary metastatic disease). The two patients with metastatic disease at diagnosis died during follow-up. In univariate analysis, a symptomatic medullary thyroid carcinoma was a strong predictor of an unfavourable outcome (p < .00008), as were the preoperative calcitonin level (P = .007) and an elevated postoperative calcitonin level (P = .004). Among 30 histopathological criteria, only the presence of amyloid correlated with an unfavorable outcome (P = .018).

Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis).

A group of 13 pathologists belonging to the French Calcitonin Tumor Study Group (GETC: Groupe d'Etude des Tumeurs à Calcitonine) examined the histological slides and medical records of 109 proband cases of medullary thyroid carcinoma (MTC) diagnosed on clinical features. The cases belonged to the various forms of the disease (80 sporadic and 29 familial MTC). The aim of the study was to detect histological predictors for survival by comparing morphological data from patients killed by the disease versus the others. Twenty-seven histological parameters were considered, including cellular heterogeneity, shape of the cells, and cytoplasmic characteristics. Other parameters such as sex, age, and phenotype of the disease were also studied. First, predictive parameters of interest on survival function were selected by univariate analysis (Mantel-Cox test). Then, the extracted parameters were tested in a multifactorial analysis using the Cox's forward stepping proportional hazard model. Five parameters were significantly associated with a lower survival function: presence of necrosis in the tumor (P = .001), squamous pattern (P = .002), age over 45 years (P = .004), presence of oxyphil cells in the tumor and absence of cells with intermediate cytoplasm (P = .025), less than 50% of calcitonin immunoreactive cells in the tumor (P = .04).

High field magnetic resonance imaging evaluation of superparamagnetic iron oxide nanoparticles in a permanent rat myocardial infarction.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate superparamagnetic iron oxide (SPIO) nanoparticles to discriminate infarcted from normal tissue after myocardial infarction using high field MR imaging (7 tesla). MATERIALS AND METHODS: Permanent myocardial infarction was induced in rats. SPIO nanoparticles (1 mg Fe/kg) were assessed with T1-weighted gradient echo sequence to visualize the myocardial infarction 48 hours after ligature (n = 6). Furthermore, MR Imaging was performed using a T2-weighted RARE sequence and nanoparticles were injected (5 or 10 mg Fe/kg) on 36 rats 5, 24 or 48 hours after infarction. RESULTS: No changes in contrast between normal and infarcted myocardium was observed after nanoparticle injection on T1-weighted images. However, nanoparticles induced a significant contrast increase between normal and infarcted myocardium on T2-weighted images whatever the delay between infarction and imaging (2.99 +/- 1.66 preinjection vs. 7.82 +/- 1.96 after SPIO injection at a dose of 5 mg Fe/kg 5 hours postinfarction, P = 0.0001). CONCLUSIONS: Nanoparticle injection made it possible to discriminate normal from infarcted myocardium on T2-weighted images. However, the high magnetic field prevented the visualization of the T1 effect of SPIO nanoparticles.

MRI study of transient cerebral ischemia in the gerbil: interest of T2 mapping.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the diagnostic use of MRI and, more precisely, the use of quantitative T2 imaging at 7 T for the early detection of neuronal cerebral alterations after transient ischemia in the gerbil. METHODS: One hundred forty-seven Mongolian gerbils were separated into four groups for which a bicarotid artery occlusion lasted for 4, 6, 8, or 10 minutes, respectively. The animals were scanned before carotid artery occlusion and at 3, 6, 10, 24, and 48 hours and 5 days after the ischemic incident. MR images were acquired on a Bruker Avance DRX300 mini-imaging system. RESULTS: Our results show that T2 mapping is able to localize brain damage induced by transient ischemia and to detect early perturbations in water content (as early as 6 hours after ischemia). CONCLUSIONS: T2 measurements in the striata are correlated with the severity of the ischemic incident, since the changes observed on the T2 images are directly proportional to the duration of occlusion.