RENEX: an expert system for the interpretation of 99mTc-MAG3 scans to detect renal obstruction.

A renal expert system (RENEX) has been developed to assist physicians detect renal obstruction in patients undergoing pre- and postfurosemide 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) scans. RENEX uses quantitative parameters extracted from the dynamic renal scan data and heuristic rules in the form of a knowledge base (KB) obtained from expert interpreters to conclude whether a kidney is obstructed. METHODS: Normal limits were established for 47 quantitative parameters extracted from the 99mTc-MAG3 scans of 100 potential renal donors. From these data the domain expert estimated 5 boundary conditions for each parameter: (i) definitely abnormal, (ii) probably abnormal, (iii) equivocal, (iv) probably normal, and (v) definitely normal. A sigmoid-type curve was then generated from these 5 boundary conditions, creating a parameter knowledge library used for converting the value of a prospective patient's individual quantitative parameters to a certainty factor (CF). Sixty heuristic rules were extracted from the domain expert to generate the KB for detecting obstruction. A forward-chaining inference engine was developed using the MYCIN combinatories (an approximation of Bayes theorem) to determine obstruction. A justification engine was implemented, which recorded the sequence of each rule that was fired and the current CF value of all input and output parameters at the time of instantiation to track and justify the logic of the conclusions. The entire system was fine tuned and tested using a pilot group of 32 patients (11 males, 21 females; mean age, 56.8 +/- 17.2 y; 63 kidneys) deemed by an expert panel to have 41 unobstructed kidneys, 13 obstructed kidneys,and 9 equivocal findings. RESULTS: RENEX agreed with the expert panel in 92% (12/13) of the obstructed kidneys, 93% (38/41) of the unobstructed kidneys, and 78% (7/9) of the kidneys interpreted as equivocal for obstructions. Processing time per patient was practically instantaneous using a 3.0-GHz personal computer programmed using interactive data language. CONCLUSION: We have developed a renal expert system for detecting renal obstruction using pre- and postfurosemide 99mTc-MAG3 renal scans, at a standardized expert level. These encouraging preliminary results warrant a prospective study in a large population of patients with and without renal obstruction to establish the diagnostic performance of this system.     

Cardiac efficiency and oxygen consumption measured with 11C-acetate PET after long-term cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a treatment option in patients with severe heart failure and left bundle-branch block (LBBB). This study evaluated the effects of 4 and 13 mo of CRT on myocardial oxygen consumption (MVO2) and cardiac efficiency as compared with mild heart failure patients without LBBB. METHODS: Sixteen patients with severe heart failure and LBBB due to idiopathic cardiomyopathy were studied at baseline and after 4 and after 13 mo of therapy. Thirteen patients with mild heart failure without LBBB served as a comparison group. The clearance rate (k2) of 11C-acetate was measured with PET to assess MVO2. Stroke volume was derived from the dynamic PET data according to the Stewart-Hamilton principle and, furthermore, cardiac efficiency using the work metabolic index. RESULTS: After 4 mo of CRT, stroke volume index (SVI) increased by 50% (P = 0.012) and cardiac efficiency increased by 41% (P < 0.001). Global k2 remained unchanged but regional k2 demonstrated a more homogeneous distribution pattern. The parameters showed no significant changes during therapy. Under CRT, cardiac efficiency, SVI, and the distribution pattern of regional k2 did not differ from mild heart failure patients without LBBB. CONCLUSION: CRT improves cardiac efficiency for at least 13 mo, as demonstrated by a higher SVI, whereas MVO2 remains unchanged. Cardiac efficiency, SVI, and the MVO2 distribution pattern reach the level of patients with mild heart failure without LBBB. The unfavorable hemodynamic performance in heart failure with LBBB is effectively restored by long-term CRT to the level of an earlier disease state.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Terminal transverse limb defects and early chorionic villus sampling: Evaluation of 4,300 cases with completed follow-up

Data from 4,300 consecutive cases following prenatal diagnosis by transcervical (TC) CVS (n = (1,570) and transabdominal (TA) CVS (n = 2,370) were evaluated. In the follow-up study only infants examined by a physician were included. Gestational age varied between 8.5 and 11.6 weeks (mean 10.3 weeks) for TC-CVS and between 9.3 and 20 weeks (mean 12.3 weeks) for TA-CVS 98% of TC-CVS was performed at 9–10 weeks, 80.7% of TA-CVS procedures were carried out at 12–15 weeks. Selective termination took place in 97 cases of TC-CVS (6.1%) and in 72 cases of TA-CVS (2.6%). Another 8 Women had a termination for psychosocial reasons, resulting in 4,123 (1,469 TC, 2,645 TA) continuing pregnancies. The overall fetal loss rare <28 weeks was 5.4% (n = 80) for TC-CVS and 2.6% (n = 70) for TA-CVS. The overall incidence of congenital abnormalities after birth was 0.9%. Two terminal transversal limb defects were detected in the TC-CVS group (0.14%) against one (0.04%) in the TA-CVS group. © 1993 Wiley-Liss, Inc.     

The effect of major railway accidents on the psychological health of train drivers—I. Acute psychological responses to accident

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).

Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.     

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

CD15 (LeuM1) immunoreactivity: Prognostic factor for sporadic and hereditary medullary thyroid cancer?

Patients treated for sporadic and hereditary medullary thyroid carcinoma (MTC) have varying rates of persistent disease, recurrence, and survival. The aim of this study was to correlate the immunoreactivity of the monoclonal antibody CD15 (LeuM1) to initial clinical findings and the outcome of treatment. The primary tumors of 75 patients with sporadic MTC, 7 with hereditary disease, and 3 members of MEN 2A families were studied. Of these subjects 74 (87%) showed no or little immunoreactivity (<15% positive cells; score 0) in most tumors. The remaining 13% had surgery for tumors with more than 15% cells with positive staining (score I). There was no correlation between LeuM1 immunoreactivity and sex, age, and type of MTC. There was, however, a significant correlation with the pTNM classification and UICC staging. The prognosis for patients with score 0 was significantly better than score 1 patients. CD15 immunoreactivity appears to be a predictive factor in sporadic and hereditary MTC. Lymph node dissection seems to be more successful in patients with score 0 tumors than in those with score 1 tumors. The question of reoperation in patients with recurrence of disease (especially with biochemical recurrence or persistence) should be discussed on the basis of CD15 immunoreactivity.

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Resumen Los pacientes tratados para carcinoma medular, esporádico y hereditario, de la glándula tiroides (CMT) exhiben grandes variaciones en las tasas de enfermedad persistente, recidiva y sobrevida. El propósito del presente estudio fue establecer la correlación entre la inmunorreactividad del anticuerpo CD15 (LeuM1) y los hallazgos clínicos iniciales, así como con el resultado final del tratamiento.Se estudiaron los tumores primarios de 75 pacientes con CMT esporádico, de siete con enfermedad hereditaria y de 3 miembros de familias con síndrome NEM2A.Setenta y cuatro pacientes (87%) exhibieron ninguna o muy baja inmunorreactividad (menos de 15% de células positivas; puntaje 0) en la mayoría de los tumores. El 13% restante fue sometido a cirugía por tumores con más de 15% de las células con coloración positiva (puntaje 1). No se evidenció correlación entre la inmunorreactividad LeuM1 y el sexo, edad o tipo del CMT. Sin embargo, sí apareció una correlación significativa con la clasificiación pTNM y la estadificación de la UICC. El pronóstico de los pacientes con puntaje 0 resultó significativamento mejor que el de los pacientes con puntaje 1.La inmunorreactividad CD15 parece ser un factor de predicción de pronóstico en el CMT esporádico y familiar. La disección ganglionar parece ser más exitosa en pacientes con tumores de puntaje 0 que en los que portan tumores con puntaje 1.El interrogante en cuanto a reoperación en pacientes con recidiva de la enfermedad (especialmente cuando hay recidiva o persistencia bioquímica) debe ser considerada con base en la inmunorreactividad CD15.

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Résumé Les taux de maladie persistante, de récidive et de survie chez des patients traités pour cancer médullaire sporadique et héréditaire de la thyroïde (CMT) sont très variables. Le but de cette étude a été de corréler l'immunoréactivité des anticorps monoclonaux CD15 (LeuM1) à des données cliniques initiales et l'évolution finale du traitement des CMT. On a étudié 75 patients ayant un CMT primitif, sept ayant une maladie héréditaire, et trois membres d'une famille MEN 2A. Soixante quatre patients (87%) avaient peu ou pas d'immunoréactivité (moins de 15% de cellules positive: score = 0). Les 13% restants ont eu une chirurgie pour les tumeurs ayant un pourcentage > 15 (score = 1). Il n'y avait aucune corrélation entre l'immunoréactivité LeuM1 et le sexe, l'âge et le type de CMT. Il y avait, en revanche, une corrélation significative entre la classification pTMN et le stage UICC. Le pronostic des patients ayant un score = 0 était significativement meilleur que celui des patients ayant un score = 1. L'immunoréactivité CD15 apparaît comme étant un facteur pronostique des CMT. Le curage lymphatique

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Members and institutions are listed in Table 1.     

Mapping of α- and β-globin genes on Antarctic fish chromosomes by fluorescence in-situ hybridization

The pathways and mechanisms of genomic change that have led to the peculiar haemoglobinless phenotype of the white-blooded Antarctic icefishes (16 species in the family Channichthyidae) constitute an important model for understanding the rapid diversification of the Antarctic notothenioid fish flock. To provide complementary structural information on genomic change at globin-gene loci in Antarctic fish species, cytogenetic studies and in-situ chromosomal mapping have been undertaken. Using a DNA probe containing one α- and one β-globin gene from the embryonic/juvenile globin gene cluster of the red-blooded species Notothenia coriiceps, we mapped the cluster on the chromosomes of Antarctic teleosts by fluorescence in-situ hybridization. As anticipated on the basis of its molecular organization, the cluster was located on a single chromosome pair in all of the red-blooded fish species probed (N. coriiceps, N. angustata, Trematomus hansoni, T. pennellii). In contrast, the α/β-globin probe did not recognize complementary sequences on the chromosomes of the white-blooded species Chionodraco hamatus and Channichthys rhinoceratus. These results represent the first example of chromosomal mapping of embryonic/juvenile globin genes in teleostean fishes. Beyond its relevance to the evolutionary history of Antarctic notothenioids, this work contributes to our understanding of the evolution of the chromosomal loci of globin genes in fishes and other vertebrates. This revised version was published online in July 2006 with corrections to the Cover Date.     

A method to remove artifacts in attenuation-corrected myocardial perfusion SPECT Introduced by misalignment between emission scan and CT-derived attenuation maps.

Nonuniform soft-tissue attenuation affects the diagnostic accuracy of SPECT in myocardial perfusion imaging. The attenuation map required for attenuation correction can be acquired using x-ray tomography (CT). Frequent findings in attenuation-corrected images are defects in the apical and anterior myocardial wall. We assume that these are artifacts produced by misalignment of SPECT images and the attenuation map. METHODS: One hundred forty patients underwent myocardial perfusion imaging with 99mTc-methoxyisobutylisonitrile. Twenty-seven of 140 showed pronounced defects in the apical or anterior wall only after CT-based attenuation correction. SPECT and corresponding CT slices were examined for misalignment in the ventrodorsal direction (y-direction) visually and by threshold-based delineation of the body surface. Mismatched studies were realigned and image reconstruction and analysis were redone. The effect of the correction was assessed visually and by semiquantitative analysis based on a 20-segment model using 4D-MSPECT. RESULTS: In 15 of 27 patients, the improved coregistration led to smaller and less-pronounced defects in the regions mentioned. In 6 of 27 patients, former defects were judged as normal. No improvement was seen in only 4 patients. In these 4 subjects, the mismatch in the y-direction was <1 pixel (7 mm), and visual inspection suggested a coincident mismatch in the craniocaudal direction. In 2 cases, coregistration was not possible because the body outline extended beyond the CT field of view. Semiquantitative analysis revealed a significant increase of the relative uptake in the apex; in the apical segments of the anterior, septal, and inferior wall; and in the mid-anterior and mid-anteroseptal segment. Basal segments of the anterolateral, lateral, and inferolateral wall and the middle inferolateral segment showed a significant decrease of relative uptake. CONCLUSION: Misalignment in the y-direction between SPECT and the attenuation map can lead to artifacts in the apical, septal, and anterior wall, which will appear as defects. It also can cause overcorrection in the basal inferior and lateral segments. There is evidence that mismatches along the other directions may have a similar effect. The coregistration of SPECT and the attenuation map needs to be verified for every patient, even when using integrated dual-modality imaging devices.     

The relationship between interviewers' characteristics and ratings assigned during a multiple mini-interview.

PURPOSE: To assess the consistency of ratings assigned by health sciences faculty members relative to community members during an innovative admissions protocol called the Multiple Mini-Interview (MMI). METHOD: A nine-station MMI was created and 54 candidates to an undergraduate MD program participated in the exercise in Spring 2003. Three stations were staffed with a pair of faculty members, three with a pair of community members, and three with one member of each group. Raters completed a four-item evaluation form. All participants completed post-MMI questionnaires. Generalizability Theory was used to examine the consistency of the ratings provided within each of these three subgroups. RESULTS: The overall test reliability was found to be .78 and a Decision Study suggested that admissions committees should distribute their resources by increasing the number of interviews to which candidates are exposed rather than increasing the number of interviewers within each interview. Divergence of ratings was greater within the pairing of community member to faculty member and least for pairings of community members. Participants responded positively to the MMI. CONCLUSION: The MMI provides a reliable protocol for assessing the personal qualities of candidates by accounting for context specificity with a multiple sampling approach. Increasing the heterogeneity of interviewers may increase the heterogeneity of the accepted group of candidates. Further work will determine the extent to which different groups of raters provide equally valid (albeit different) judgments.