Adult heart transplantation under tacrolimus (FK506) immunosuppression: histopathologic observations and comparison to a cyclosporine-based regimen with lympholytic (ATG) induction

BACKGROUND: Tacrolimus (FK506) is an effective immunosuppressant for human heart transplantation, but information about its effects on cardiac allograft and nonallograft kidney and liver histopathologic study is limited. METHODS: We therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were compared with 619 endomyocardial biopsy specimens and four autopsy results from 51 patients treated with cyclosporine-based immunosuppression with lympholytic induction (CLI) by use of rabbit anti-thymocyte globulin. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrospectively assessed without knowledge of the treatment regimen. The lymphocyte growth index on biopsy specimens obtained from these patients was also compared. RESULTS: In general, there were no qualitative differences in the histopathologic appearance of various allograft syndromes between tacrolimus- and CLI-treated patients. Thus histopathologic criteria used to diagnose various graft syndromes are applicable under tacrolimus immunosuppression. However, early (between 10 and 30 days) after transplantation, biopsy specimens from patients treated with tacrolimus showed a significantly higher percentage of inflamed fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and the rejection grade tended to be slightly higher (p = 0.08). In contrast, during the late transplantation period (275 to 548 days), biopsy specimens from patients treated with CLI showed a significantly higher percentage of inflamed fragments (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p = 0.01), and a higher frequency of Quilty lesions (p = 0.05). Although overall freedom from any grade 3A or higher rejection was greater in the CLI-treated arm, tacrolimus was successfully used to treat refractory rejection in three patients from the CLI-treated arm. Concern has been raised in the literature about the possibility of tacrolimus being a direct hepatotoxin and an accelerant of allograft obliterative arteriopathy. However, no evidence to support either of these contentions was detected in this patient population. In contrast, tacrolimus is clearly nephrotoxic, although similar to cyclosporine in this regard. CONCLUSIONS: Tacrolimus is an effective immunosuppressive drug for heart transplantation. The cardiac allograft histopathologic study of patients treated with tacrolimus immunosuppression does not significantly differ from those given conventional, cyclosporine-based triple therapy with lympholytic induction.     

Spatial distribution of corticospinal potentials following transcranial electric and magnetic stimulation in human spinal cord

To search for concomitant anomalies among babies with congenital hypothyroidism, 120 newborn babies with confirmed congenital hypothyroidism were studied at the Veterans General Hospital, Taipei. The incidence of concomitant anomalies was estimated to be 11.67% (14/120). Among these anomalies, cardiac and gastrointestinal systems were the most commonly involved, comprising 35.7% (5/14) and 28.6% (4/14) of all anomalies, respectively. The type (i.e. agenesis, ectopia or eutopic goiter) as well as the severity of hypothyroidism were analyzed between groups of babies with or without concomitant anomalies. No differences existed between the two groups of babies regarding these two aspects.     

Influence of panel-reactive antibody on survival and rejection after lung transplantation

BACKGROUND: Panel-reactive antibody (PRA) is commonly used before thoracic organ transplantation to estimate a potential recipient's degree of humoral sensitization. METHODS: To assess the influence of an elevated PRA on survival and the incidence of rejection in pulmonary transplantation, the records of 247 patients that underwent single or double lung transplantation were reviewed. RESULTS: Twenty-one of 247 patients (8.5%) had PRA values greater than 10%. Survival of this population was not significantly different from that of patients with low PRA levels: 74% (low PRA) vs 65% (elevated PRA) at 1 year and 58% in both groups at 3 years. The acute rejection rates (episodes/first 100 days) for the elevated and low PRA groups were 2.1 and 1.9, respectively (p = NS). Obliterative bronchiolitis developed in 38.9% of the high and 31.2% of the low PRA groups (p = NS). Six of 247 patients had a retrospective positive lymphocytotoxic cross-match result; three had PRA values greater than 10%. Patients with a positive cross-match result experienced similar survival and incidence of rejection as the remainder of the population. Among 957 patients evaluated for lung transplantation, 16 (1.7%) had a PRA (with dithiothreitol) greater than 15%. All had a history of pregnancy, blood transfusion, connective tissue disease, or previous transplantation. CONCLUSIONS: Humoral sensitization is uncommon in the lung transplantation population. A modestly elevated PRA does not predict survival or the development of acute rejection or bronchiolitis obliterans. PRA testing before lung transplantation should be reserved for those patients with specific risk factors for humoral sensitization.     

An Optimal Weight Predictor for Hierarchical Regression Models

We consider the polynomial regression model. In this model a hierarchical structure, or natural ordering, in the parameter space can be assumed.

Maximum likelihood estimators may be found for the parameters of each order model in the hierarchy. We introduce the class of estimators given by weighted combinations of these maximum likelihood estimators under certain restrictions. This class is obtained by considering a Bayes estimator class and contains the subset regression estimator as a special case.

The optimal weights which minimize the predictive mean squared error are obtained exactly, using an alternative method to that of Kanda (1985). The estimated weights which minimize the estimated predictive mean square error in a similar way to the Mallow’s C_p-statistic are also exactly presented and some numerical examples are shown.

     

Mother-infant face-to-face interaction in Japan and the United States: A laboratory comparison using 3-month-old infants.

In this cross-cultural comparison 36 Japanese and 36 American 3-month-old infant–mother dyads were videotaped in a standardized laboratory setting in their own countries. Mothers in both countries responded contingently to these infant behaviors, but there were differences in the type and timing of maternal behavior vis-à-vis infant behavior. Japanese mothers were more likely than American mothers to punctuate their facial expressions and vocalizations with looming upper-body movements and with touches and they were less likely to respond selectively to infant vocalizations. American mothers held their faces closer to the infants' and provided primarily facial and vocal displays for the infant. Japanese infants tended to display longer average durations of smiling and vocalizing with a lower rate of onsets compared with American infants. The results have implications for understanding the role of the face-to-face period in human development and the way in which cultural differences in interpersonal communicative style may guide the development of infant affective expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ventricular tachycardia originating at the right ventricular outflow tract--surgical treatment of extrasystole

A boy with Down syndrome who developed acute nonlymphocytic leukemia (ANLL/M2) at the age of 40 months is presented. Chromosomal analysis of cultured peripheral blood cells without mitogen revealed a constitutional abnormality, trisomy 21, associated with the acquired chromosome change t(8;21)(q22;q22).     

5-fluorouracil and low-dose leucovorin as surgical adjuvant therapy from viewpoint of long-term outcome

Biochemical modulation of 5-FU by leucovorin (LV) has been demonstrated to increase the therapeutic effect compared to single agent 5-FU in the treatment of patients (pts) with advanced colorectal cancer. The purpose of this study was to determine the effectiveness of the 5-FU + LV combination as adjuvant therapy following surgery in pts with Dukes' B, C colon cancer. Pts were entered in a stratified clinical trial comparing two different combination chemotherapeutic regimens to single agent 5-FU, given orally as a control. This report summarized the result of treatment in 61 pts who were 5-FU oral alone and 32 pts who were 5-FU (375 mg/m2) and low-dose LV (20 mg/m2) intravenously for 5 days with 5-FU oral intake. 5-FU with LV regimen was associated with an improved survival compared with the single agent 5-FU oral intake (p < 0.05). 5-FU with LV regimen resulted in less recurrence in liver and lung compared with single-agent 5-FU oral intake.