Annick Moisan

Aceruloplasminemia: new clinical, pathophysiological and therapeutic insights

Aceruloplasminemia is an autosomal recessive disease of iron overload associated with mutation(s) in the ceruloplasmin gene. We report here a new case of aceruloplasminemia in a woman who is a compound heterozygote for two new mutations. Besides this novel genotypic profile, this observation provides new insights on: (i) iron metabolism with normal erythroid repartition, in the absence of serum non-transferrin-bound iron and with an increase of 59Fe plasma clearance; (ii) hepatic abnormalities associated with the presence of iron-free foci; (iii) the therapeutic management of the disease, chronic subcutaneous infusion of deferrioxamine being remarkably effective at reducing hepatic iron overload.

Contribution of technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy to the diagnosis of diabetic foot infection

Abstract. We conducted a prospective study in order to evaluate the contribution of technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled leucocyte scintigraphy to the diagnosis and follow-up of osteomyelitis in the diabetic foot. The study was conducted between October 1992 and November 1996 and included 42 patients (30 men and 12 women; mean age 63 years) with diabetes mellitus (type 1, nxa0=xa022, type 2, nxa0=xa020) who had a total of 56 diabetic foot ulcers. The initial exploration included standard radiography, three-phase bone scintigraphy and 99mTc-HMPAO labelled leucocyte scintigraphy (HMPAO-LS), performed within a 3-day interval. For the 56 ulceration sites, 26 cases of osteomyelitis were diagnosed: ten on the basis of radiographic and histological/bacteriological criteria after bone biopsy, 11 after radiographic follow-up and five on the basis of biopsy results alone. No osteomyelitis was present at 30 sites, there were seven cases of cellulitis. The sensitivity and specificity of 99mTc-HMPAO-LS were 88.4% and 96.6% respectively (23 true-positives, 29 true-negatives, one false-positive, three false-negatives). The accuracy of radiography, 99mTc-methylene diphosphonate and HMPAO-LS was 69.6%, 62.5%, and 92.9%, respectively. Follow-up scintigraphy (nxa0=xa014) 4 months after initial diagnosis and 1 month after antibiotic withdrawal confirmed cure of osteomyelitis despite the absence of complete clinical regression of the ulcers. In conclusion, 99mTc-HMPAO labelled leucocyte scintigraphy was found to be an excellent method for the diagnosis of osteomyelitis in the diabetic foot. It can contribute to follow-up, particularly when clinical regression of perforating ulcers is incomplete and cure of osteomyelitis must be confirmed in order that antibiotic treatment may be discontinued.

Biodistribution of radiolabelled human dendritic cells injected by various routes

PurposeThe purpose of this study was to investigate the biodistribution of mature dendritic cells (DCs) injected by various routes, during a cell therapy protocol.MethodsIn the context of a vaccine therapy protocol for melanoma, DCs matured with Ribomunyl and interferon-gamma were labelled with 111In-oxine and injected into eight patients along various routes: afferent lymphatic vessel (IL) (4 times), lymph node (IN) (5 times) and intradermally (ID) (6 times).ResultsScintigraphic investigations showed that the IL route allowed localisation of 80% of injected radioactivity in eight to ten nodes. In three cases of IN injection, the entire radioactivity stagnated in the injected nodes, while in two cases, migration to adjacent nodes was observed. This migration was detected rapidly after injection, as with IL injections, suggesting that passive transport occurred along the physiological lymphatic pathways. In two of the six ID injections, 1–2% of injected radioactivity reached a proximal lymph node. Migration was detectable in the first hour, but increased considerably after 24xa0h, suggesting an active migration mechanism. In both of the aforementioned cases, DCs were strongly CCR7-positive, but this feature was not a sufficient condition for effective migration. In comparison with DCs matured with TNF-α, IL-1β, IL-6 and PGE2, our DCs showed a weaker in vitro migratory response to CCL21, despite comparable CCR7 expression, and higher allostimulatory and TH1 polarisation capacities.ConclusionThe IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection.

Technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy for the diagnosis of bone and joint infections: a retrospective study in 116 patients

The aim of this study was to evaluate the diagnostic value of technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy (HMPAO-LS) by means of a retrospective review of 116 patients divided into three groups of bone and joint infection. One hundred and thirty-one LS examinations were performed, and 143 sites analysed. The final diagnosis of infection was based on surgical, histological and bacteriological data and follow-up. Ninety-four suspected localizations were examined in group 1, which included 74 patients with an infection suspected to involve orthopaedic implants. In this group, there were 38 true-positives, 1 false-negative, 49 true-negatives and 6 false-positives. Surgical confirmation was obtained in 34 cases. In group 2 (24 patients with suspected osteomyelitis), there were 27 localizations of which 14 were true-positives and 13 were true-negatives (including seven surgical confirmations). In group 3 (18 patients suspected of septic arthritis) there were eight true-positives, two false-negatives, ten true-negatives and two false-positives. Overall sensitivity of99mTc-HMPAO-LS for the detection of bone and joint infection was 95%, with a specificity of 90% (group 1: sensitivity 97%, specificity 89%; group 2: 100% and 100%; group 3: 80% and 83%). It may be concluded that HMPAO-LS is an effective tool for the diagnosis of both bone infection involving implants and chronic osteomyelitis.

Comparison of Tc-99m-labelled antileukocyte fragment Fab' and Tc-99m-HMPAO leukocyte scintigraphy in the diagnosis of bone and joint infections: a prospective study.

Between January and July 1998, we conducted a prospective study to compare Tc-99m-labelled antigranulocyte monoclonal antibody fragment Fab′ (LEUKOSCAN®) scintigraphy versus Tc-99m-hexamethylpropyleneamine oxime (Tc-99m-HMPAO)-labelled leukocyte scintigraphy (HMPAO-LS) for the diagnosis of unselected patients with bone and joint infection. Twenty-three patients (16 men and 7 women; mean age, 67 years) with suspected bone infection were explored successively with bone scintigraphy, HMPAO-LS and LEUKOSCAN® scintigraphy. Thirty-two foci were studied (diabetic foot = 11, prosthetic material = 8, joint disease = 4, others = diagnosed in 18 cases, eight on the basis of bacteriological and histological examination of surgical or puncture specimens, with or without radiographic signs, and 10 on the basis of clinical course and radiographic findings. Overall sensitivity, specificity and accuracy were 86%, 72% and 78%, respectively, for LEUKOSCAN® scintigraphy (12 true positives (TP), 13 true negatives (TN), 5 false positives (FP), 2 false negatives (FN)), 93%, 100% and 96%, respectively, for HMPAO-LS (13TP, 18TN, 0FP, 1FN), and 100%, 17% and 53.3%, respectively, for bone scintigraphy. In this small series, LEUKOSCAN® scintigraphy was found to be less specific for the diagnosis of osteomyelitis than HMPAO-LS. In addition, the interpretation of LEUKOSCAN® scintigraphy is more difficult than HMPAO-LS for the diagnosis of bone infection in the diabetic foot, and would appear to be less discriminating for differentiating soft tissue infection from osteitis in the case of plantar perforating ulcers.

Intratumoral consumption of indium-111-labeled platelets in a child with splenic hemangioma and thrombocytopenia.

The authors report Kasabach-Merritt syndrome (KMS) in a patient with thrombocytopenia and splenic hemangioma. A 13-month-old boy with a history of anemia, thrombocytopenia, and abdominal mass was admitted to the hospital. The scintigraphic studies showed that a large mass contiguous to the spleen was responsible for the platelet uptake. After partial splenectomy, the platelet count returned to normal. This report of KMS in a child with splenic hemangioma suggests that the scintigraphic studies are mandatory to confirm diagnosis. Indium-111-labeled platelets are useful in identifying hemangiomatous sequestration of platelets in patients with thrombocytopenia.

Development of 99mTc labelled Lipiodol: biodistribution following injection into the hepatic artery of the healthy pig

BackgroundWe develop a method for the radiolabelling of Lipiodol with 99mTc, using a lipophilic complex, [99mTc-(S2CPh)(S3Ph)2], dissolved in Lipiodol (99mTc-SSS Lipiodol). ResultsThe labelling yield is high (96±0.8%), and the radiochemical purity satisfactory (92±2.6%). This labelling is reproducible and stable for up to 24u2009h in vitro. Studies carried out after injection into the hepatic artery of the healthy pig show that the biodistribution of 99mTc-SSS Lipiodol is comparable with that observed for 188Re Lipiodol. Materials and methodsThe 99mTc-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with 99mTc, in cold lipiodol. The radiochemical purity (RCP) of the labelling was checked immediately and at 24u2009h. The 99mTc-SSS lipiodol was injected into the hepatic artery of four healthy pigs for an ex-vivo biodistribution study. An autoradiographic study was performed in two cases. ConclusionsApart from the specific interest of a Lipiodol-bearing technetiated agent for carrying out dosimetric studies, the labelling of Lipiodol with 99mTc is a preliminary step towards the use of radiolabelling with the 188Re analogue.

Indium scanning in assessment of acute Crohn's disease. A prospective study of sensitivity and correlation with severity of mucosal damage.

The aim of this study was to determine whether the sensitivity of indium-111 (111In) scanning in the assessment of the activity and extent of Crohns disease correlates with the severity of intestinal lesions as measured by the newly validated Crohns disease endoscopic index of severity (CDEIS). Nineteen patients with active (CDAI>200) colonic (N=11) or ileocolonic (N=8) Crohns disease were assessed by colonoscopy and indium scanning. The intestine was divided into five segments in both studies (rectum, sigmoid and left colon, transverse colon, right colon, and ileum). Seventy of the 86 intestinal segments seen at colonoscopy presented macroscopic lesions of Crohns disease. On third-hour scintigrams111In uptake was observed in 52 segments, 51 of which were found to be abnormal at colonoscopy. Predictive positive and negative values of scanning with respect to disease extent assessment were equal to 98% and 44%, respectively. Complete agreement between endoscopic and scintigraphic findings was observed in only six of the 19 patients (32%). Segmental endoscopic indexes of severity (SEIS) were significantly (P<0.001) lower in false negative (7.9±4.2) (mean ±sd) than in true positive (18.0±9.7) segments as defined by scintigraphy. SEIS values above which111In uptake was constantly observed did not differ in the different disease locations. When comparing macroscopically abnormal intestinal segments according to their111In uptake grade, the corresponding mean SEIS values increased significantly as the grade increased. Scintigraphic activity, as assessed by the fall in splenic activity, was equal to 23±11% (N=19). It correlated significantly with CDEIS (r=0.63,P<0.005), but even more so when the highest SEIS of each patient had been taken into account (r=0.75,P<0.0005). In conclusion, when considering disease extent and activity, scanning results correlate well with the endoscopic severity of intestinal lesions in active Crohns disease. Nevertheless, minor endoscopic lesions can be missed by111In scanning.