MRI evaluation of myocardial viability.

Cardiac magnetic resonance imaging (MRI) has become an accurate noninvasive imaging procedure for the study of postischaemic residual cardiac function, thanks to the evolution of MRI machines, postprocessing software and, above all, sequences. After infarction, and in chronic myocardial ischaemia, the degree of contractile dysfunction is one of the main determinants of longterm survival. The identification and quantification of viable dysfunctional myocardium and the possibility of improving its contractility after revascularisation improves patient prognosis and quality of life. In current clinical practice, myocardial viability is evaluated with stress echocardiography and nuclear methods. Thanks to its intrinsic characteristics and to the delayed-enhancement technique (DE-MRI), MRI has recently emerged as the only noninvasive modality able to provide a three-dimensional (3D) evaluation of cardiac viability with a multiparametric approach.

Radioguided sentinel lymph node detection in vulvar cancer.

Lymph node status is the most important prognostic factor in vulvar cancer. Histologically, sentinel nodes may be representative of the status of the other regional nodes. Identification and histopathologic evaluation of sentinel nodes could then have a significant impact on clinical management and surgery. The aim of this study was to evaluate the feasibility and diagnostic accuracy of sentinel lymph node detection by preoperative lymphoscintigraphy with technetium-99 m-labeled nanocolloid, followed by radioguided intraoperative detection. Nine patients with stage T1, N0, M0, and 11 patients with stage T2, N0, M0 squamous cell carcinoma of the vulva were included in the study. Only three cases had lesions exceeding 3.5 cm in diameter. Sentinel nodes were detected in 100% of cases. A total of 30 inguinofemoral lymphadenectomies were performed, with a mean of 10 surgically removed nodes. Histological examination revealed 17 true negative sentinel nodes, 2 true positive, and 1 false negative. In our case series, sentinel lymph node detection had a 95% diagnostic accuracy, with only one false negative. Based on literature evidence, the sentinel node procedure is feasible and reliable in vulvar cancer; however, the value of sentinel node dissection in the treatment of early-stage vulvar cancer still needs to be confirmed.

Thallium-201 myocardial scintigraphy in patients with Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White syndrome (WPW) is known to cause abnormal rest electrocardiogram and stress test. Thallium-201 myocardial scintigraphy has been particularly indicated for the noninvasive evaluation of coronary artery disease in these patients. The study group consisted of 11 WPW patients with abnormal ST-segment depression at rest electrocardiogram and/or stress test, with the absence of signs or symptoms of coronary artery disease. All the patients underwent exercise thallium-201 imaging associated with stress test by bicycle ergometer: 7 of them had ST-segment depression, but without other signs or symptoms of coronary artery disease. Transient and moderate myocardial perfusion defects were found in 5 of 11 patients. Perfusion defects in patients with WPW could derive from dyssynergy of ventricular activation, which could modify myocardial perfusion scintigraphy despite the absence of angiographic coronary stenosis. Previous reports and our data concluded that transient perfusion defects during exercise thallium-201 testing in WPW patients without cardiovascular disease may be observed. Thus, thallium-201 myocardial scintigraphy could present some limitations as a helpful adjunctive method for assessment of coronary artery disease in WPW patients.

Technetium-99m-sestamibi scintigraphy in multiple myeloma and related gammopathies: a useful tool for the identification and follow-up of myeloma bone disease.

BACKGROUND AND OBJECTIVES: Technetium-99m 2-methoxy-isobutyl-isonitrile ((99m)Tc-sestamibi) has recently been proposed as a potential tracer in patients with multiple myeloma (MM), as its increased uptake in the bone marrow has been reported as indicator of myeloma activity. We evaluated the role of (99m)Tc-sestamibi scintigraphy in the detection of myeloma bone disease in MM and related gammopathies, and also assessed its relationship with clinical status and stage of the disease, focusing in particular on the early follow-up of a small series of MM patients treated with high-dose therapy. DESIGN AND METHODS: Forty-six consecutive patients affected by MM or monoclonal gammopathy of undefined significance (MGUS) were studied by whole body scans obtained 20 minutes after administration of 740 MBq of (99m)Tc-sestamibi. A semiquantitative uptake score was used and scintigraphic findings were correlated with clinical and laboratory data. RESULTS: All the MGUS patients showed a negative (99m)Tc-sestamibi scan. Among the 32 MM patients (25 with active disease and 7 in clinical remission) 24 showed a positive scan, while 8 presented only a physiologic uptake of the tracer. The uptake score correlated significantly with all the most relevant clinical variables. In the follow-up of 8 MM patients treated with high-dose chemotherapy (99m)Tc-sestamibi closely paralleled the activity of myeloma bone disease. Comparison with X-ray skeletal survey showed discordant results in 14 out of the overall 56 scans obtained (27%), with 10 cases of negative (99m)Tc-sestamibi scans but lytic bone lesions revealed by X-ray (7 of them were in clinical remission), and 4 negative X-ray surveys in patients with positive (99m)Tc-sestamibi scans. Overall sensitivity and specificity of (99m)Tc-sestamibi scintigraphy in detecting myeloma bone disease were 90% and 88%, respectively. INTERPRETATION AND CONCLUSIONS: This study provides additional evidence indicating that (99m)Tc-sestamibi scintigraphy closely reflects myeloma disease activity in bone marrow, with very high sensitivity and specificity. (99m)Tc-sestamibi scintigraphy is therefore suggested as a reliable new tool for the staging and follow-up of myeloma bone disease.

Localization of the sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue dye and intraoperative gamma probe.

Axillary lymph node status represents the most important prognostic factor in patients with operable breast cancer. A severe limitation of this technique is the relatively high rate of false negative sentinel lymph nodes (>5%). We studied 284 patients suffering from breast cancer; 264 had T1 tumors (16 T1a, 37 T1b and 211 T1c), while 20 had T2 tumors. All patients underwent lymphoscintigraphy 18-h before surgery. At surgery, 0.5 mL of patent blue violet was injected subdermally, and the sentinel lymph node (SN) was searched by gamma probe and by the dye method. The surgically isolated SN was processed for intraoperative and delayed examinations. The SN was successfully identified by the combined radioisotopic procedure and patent blue dye technique in 278/284 cases (97.9%). Analysis of the predictive value of the SN in relation to the status of the axillary lymph nodes was limited to 191 patients undergoing standard axillary dissection irrespective of the SN status. Overall, 63/191 (33%) identified SNs were metastatic, the SN alone being involved in 37/63 (58.7%) patients; a positive axillary status with negative SN was found in 10/73 (13.7%) patients with metastatic involvement. In T1a-T1b patients the SN turned out to be metastatic in 9/53 patients (17.0%). In 7/9 patients the SN was the only site of metastasis, while in 2/9 patients other axillary lymph nodes were found to be metastatic in addition to the SN. None of the 44 patients in whom the SN proved to be non-metastatic showed any metastatic involvement of other axillary lymph nodes. Our results demonstrate a good predictive value of SN biopsy in patients with breast cancer; the predictive value was excellent in those subjects with nodules smaller than 1 cm.

Different sites and modes of tracer injection for mapping the sentinel lymph node in patients with breast cancer.

Several studies have been published describing the techniques of identification of the "sentinel lymph node" (SN). There are marked differences in the techniques used by different investigators. Although agreement exists about the tracer particle size and the volume of injection, it is unknown what is the best site where to inject the tracer or the vital dye. The aim of the present study was to define the influence of different sites of injection on imaging of the lymphatic ducts and their SNs. We performed a pilot study in 30 consecutive patients with breast cancer who underwent SN biopsy by means of radioguided surgery and vital blue dye mapping. The patients were divided into six groups of five patients each; each patient was given a subdermal (ID) or peritumoral (IP) injection of radiotracer (300 microCi in 150 mL of 99mTc-HSA microcolloids; Albures, Amersham Sorin) above the tumor site in order to localize the SN. After the identification of the SN, a second injection of radiotracer was performed, which was different in each patient subset. In some cases more than one lymph node appeared on the lymphoscintigraphic scans after the second injection of radiotracer. When the peritumoral route was used it took longer to visualize the lymphatic pathways. For the ID route, injection at the exact skin projection over the tumor is optimal. Internal mammary lymph nodes were identified by both IP (2) and ID (1) injection, irrespective of the quadrant in which the tracer was injected. Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific SN. The subdermal route is more accurate than the intraparenchymal route, as it allows faster identification of the lymphatic vessels and SN. We believe these observations should be taken into account for the proper selection of the injection site of either vital dye or radiopharmaceuticals.

Mapping the sentinel lymph node in malignant melanoma by blue dye, lymphoscintigraphy and intraoperative gamma probe.

Eighty-eight consecutive patients (48 men and 40 women; mean age, 58.9 years; range, 16-84 years) with clinically localized cutaneous melanoma involving the trunk, extremities or head and neck underwent lymphatic mapping at our institution. The primary melanoma had a mean thickness of 2.74 mm (range, 0.95 to 9 mm). Patients were divided into two groups: group A (39 patients) underwent only vital blue dye (VBD) mapping, while group B (49 patients) underwent lymphatic mapping with VBD and radio-guided surgery (RGS) combined. In all patients 1-1.5 mL of VBD was injected subdermally around the biopsy scar 10-20 min before surgery. In group B 37 MBq in 150 microL of 99mTc-HSA nanocolloid was additionally injected intradermally 18 h before surgery (3-6 aliquots injected perilesionally). In all lymphatic basins where drainage was noted the sentinel lymph nodes (SNs) were identified and marked with a cutaneous marker. Final identification of the SN was then performed externally by a hand-held gamma probe. After the induction of anesthesia 0.5-1-0 mL of patent blue V dye was injected intradermally with a 25-gauge needle around the site of the primary melanoma. SNs were examined by routine hematoxylin and eosin (H&E) staining and immunohistochemistry. Patients with histologically positive SN(s) underwent standard lymph node dissection (SLND) in the involved lymph node basin. The SN was identified in 37/39 patients (94.9%) of group A and in 48/49 patients (98.0%) of group B. Blue dye mapping failed to identify the SN in 5 of the 88 patients (5.8%), while the radioisotope method failed in only 1 of 49 patients (2.0%). Similar results were obtained with the combined use of the two probes. The average number of SNs harvested was 1.9 per basin sampled, which does not differ significantly from the numbers reported by other authors. The SN was histologically positive in 18 patients (20.5%). None of the 12 patients with a Breslow thickness less than 1.5 mm had positive SNs, whereas 18 of the 77 patients (23.4%) with a Breslow index exceeding 1.5 mm showed metastatic SNs with H&E or immunohistochemistry. The latter all underwent SLND of the affected basin. In 10 patients (55.6%) the SN was the only site of tumor invasion; eight patients (44.4%) with positive SNs had one or more metastatic lymph nodes in the draining basin.

Mapping sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue-dye, and intraoperative gamma-probe.

The purpose of the present work was two-fold: 1) to evaluate the predictive value of the sentinel lymph node (sLN) versus the axillary-node status in patients with T1-T2 breast cancer, and 2) to form an experimental basis for a randomized trial in which one group of patients with non-metastatic sLN will not have axillary dissection. Of a group of 284 patients considered for this analysis, 264 had a T1 cancer (16 T1a, 37 T1b and 211 T1c), while 20 had a T2 cancer; 243 patients were in clinical stage N0 and 41 were N1. All patients underwent lymphoscintigraphy 18 hr before surgery: 10 MBq in 0.15 mL of 99mTc-human albumin nanocolloids (particle size between 50-80 nm) was injected subdermally at the cutaneous projection of the tumor. Static gamma-camera images were acquired every 10-15 minutes until scintigraphic identification of the sLN. At surgery, 1-2 mL of Patent-Blue Violet was injected subdermally, and the sLN was searched by gamma-probe and by the dye method. The surgically isolated sLN was processed for intraoperative Hematoxylin & Eosin (H&E) histology, then for delayed histological and immunohistochemical examinations. The sLN was successfully identified by the combined radioisotopic procedure and Patent-Blue dye technique in 278/284 cases (97.9%). The Patent-Blue dye technique alone identified fewer sLNs than the radioisotopic procedure alone (56.3% versus 97.2%). Analysis of the predictive value of the sLN as to the status of axillary lymph nodes was limited to 197 patients undergoing standard axillary dissection irrespective of the sLN status. Overall, 63/191 (33%) identified sLNs were metastatic, the sLN alone being involved in 37/63 (58.7%) patients; a positive axilla status with negative sLN was found in 10/73 patients with metastatic involvement (13.7% false-negative rate). In conclusion, subdermal lymphoscintigraphy was confirmed to be an effective technique for sLN mapping; the addition of Patent-Blue dye minimally improved intra-surgical identification of the sLN. There was a high, but not absolute, correlation between a negative sLN and a negative axilla.

Pattern of lymphatic drainage to the sentinel lymph node in breast cancer patients.

BACKGROUND AND OBJECTIVE: We performed a pilot study on 30 consecutive patients undergoing sentinel node (sN) biopsy by radioguided surgery and vital blue dye mapping to determine whether there is a single sN for each breast independent of tumor site or an sN specifically related to the site of the breast neoplasm. METHODS: There were 6 groups of 5 patients; each patient had a subdermal injection of radiotracer on the tumor site plus a second injection of radiotracer that was changed in every subset of patients to test whether modifying the site or the route of injection could have impaired the proper detection of the sN. RESULTS: "False" sN were detected only in patients who had a second injection of radiotracer away from the tumor site; this occurred in 2 of 5 patients (40%) in group I, in 3 of 5 patients (60%) in group II, in all patients in group III, and in 3 of 5 patients (60%) in group IV. The different route of injection (peritumoral or subdermal) always on the tumor site that was tested in groups V and VI did not impair the proper detection of the sN. CONCLUSIONS: Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific sN more than the existence of a first sN in the axillary basin, which indiscriminately drains all quadrants of the breast, like "a neck of a bottle." This should be considered for the proper selection of the injection site of either vital blue dye or radiopharmaceuticals.

Statistical evaluation of inter- and intra-laboratory variations of the Ames test, as related to the genetic stability of Salmonella tester strains.

A statistical analysis was performed on the data resulting from an international collaborative study of the Ames test according to a standardized experimental protocol, which involved the comparative testing of 4NQO (4 doses), in 3 separate experiments for each of the 38 participating laboratories, by using a common reference (R) culture and in-house laboratory (L) cultures of 5 strains of S. typhimurium. Despite some toxicity phenomena recorded at the highest dose of 4NQO, the majority of the dose-response curves in individual laboratories were linear on a bi-log scale and their mean values fitted a linear regression framework. Scattering of data around mean values of laboratories was Gaussian-like even at the highest dose of 4NQO, toxic effects being expressed as a dose-related increase of variance. A weighted least-square analysis could therefore take into account toxic effects without resorting to a sophisticated non-linear model incompatible with log transformation. Various analytical approaches--e.g. the weighted estimates of linear regression parameters, a multifactor (laboratory, experiment, dose, culture of each strain) analysis of variance with all the possible interactions, the assessment of correlations in individual laboratories and of coefficients of variation for induced and spontaneous mutability--could detect some statistically significant differences between L and R cultures. However, at a critical evaluation on an individual basis, only few of these differences, without any peculiar involvement of given strains, were convincing in view of the existence of real phenomena of genetic drift. Therefore, on the whole, the genetic drift of Salmonella tester strains appears to lend a negligible contribution to the considerable inter- and intra-laboratory variability detected in this study. With a background variability between replications averaging 26%, a dose-related variability was evident both between experiments (28-54%) and between laboratories (44-127%).

[Hereditary fructose intolerance]. / L'intolleranza ereditaria al fruttosio.

Two cases of hereditary fructose intolerance are reported. In the first one the symtomatology has started with an acute hepatic failure; the second one has come to our observation with a diagnosis of intrahepatic biliary duct atresia. It is underlined the difficulty of a differential diagnosis, in infants with serious hepatic failure, between infectious, metabolic and others illnesses.

[Hepatic duct hypoplasia or Alagille-Odièvre disease]. / La ipoplasia duttale epatica o malattia di Alagille-Odièvre.

Five children from one to seven years of age with intrahepatic ductular hypoplasia are presented. Clinical and biochemical characteristics of the disease are specifically considered as well as differential diagnosis. In three patients a severe hemolytic anemia, only partially corrected with vitamine E, was present. All subjects received continuous cholestyramine therapy. Variable follow up from nine months to seven years demonstrated persistent intrahepatic cholestasis with hypercholesterolemia in two cases, clinical and biochemical improvement in one case. One child died two years and six months after diagnosis was made an one patient was lost to follow up. The Authors confirm the literature clinic, diagnostic and therapeutic data concerning ductular hypoplasia, while, on the basis of their experience, the prognosis seems poor also in some cases of syndromic ductular hypoplasia.

[Kawasaki disease: a new pediatric nosological entity]. / Malattia di Kawasaki: una nuova entità nosologica pediatrica.

Kawasaki disease (KD) is a new, well characterized pediatric syndrome. In this work the last epidemiologic, diagnostic and clinical data are pointed. Especially the heart-disease and its monitoring and therapy are studied. Our casuistry (5 cases in 4 years) is also presented. The international literature and our clinical experience suggest that KD is more spread than we think and therefore in needs to be studied carefully by the pediatricians.

[A study through factor analysis of the connection between 7 variables concerning blood lipides, with a particular reference to the interpretation of the lipidograms (author's transl)]. / Studio mediante la factor analysis delle relazioni esistenti tra 7 variabili concernenti i lipidi ematici con particolare riferimento all'interpretazione del lipidogramma.

The AA. examined 7 variables concerning blood lipides and studied their internal relationship by means of a method, the Factor Analysis, which aims at determining the least amount of Common Factors which can sum up the information contained in the same variables. In this case three Common Factors (F) could be obtained, two of which were connected to the interpretation of the data of the lipidogram. The AA. discuss the signification of the determined Factors; they have even calculated the scores of the same Factors for each single individual and derived from the frequence distributions of the scores of F1 and F2 the normal values of the same Factors.

[The importance of biological standardization in clinical laboratory examinations (author's transl)]. / Importanza della standardizzazione biologica negli esami clinici di laboratorio.

The AA. consider the various causes that can give rise to different results regarding one same biological sample which has been examined various times in the same or in different laboratories. From the analysis of the possible sources of variability and from the results obtained in research performed by various laboratories in the course of a polycentric co-ordinate study, the AA. deduce some general considerations about the measures to be taken in order to reduce the different sources of variability (either fortuitous or systematic) and they especially emphasize the practic usefulness of considering the question of "laboratory errors" not only as a question of accurate dosage, but also, and primarily, as a question of biological standardization.

[Definition of normal values in medicine]. / Sulla definizione dei valori normali in medicina

The definition of the normal values of quantitative characters is discussed. Three distinct types of normality: statistical, biological and epidemiological, are examined. A method postulating the presence of several Gaussian components, one of which represents the truly normal population, in a heterogeneous population, is proposed for the statistical analysis of frequency distribution. Examples are given of the application of a relatively simple and effective graphical-numerical process. In the light of the preliminary results, systematic adoption of the process is suggested, not only for the definition of normal values in the sense of biological normality, but also in the comparison of patients and healthy subjects, whereby epidemiological normality can be defined by means of discriminant analysis. Lastly, the possibility of defining normal values for groups of variables is considered.