Auditory event-related potentials (P300) in partial and generalized epileptic patients.

We evaluated the P300 components of event-related potentials (ERP) in 64 cryptogenic partial epilepsy (CPE) patients, and 52 idiopathic generalized epilepsy (IGE) patients as well as in their age-matched control groups. The P200, N200 and P300 latencies recorded from Cz were significantly longer in CPE patients compared with those of their control group (P = 0.0371, P = 0.0092 and P = 0.0405, respectively). The P200 and N200 latencies recorded from Fz were significantly longer than in their control group (P = 0.0448 and P = 0.0107) while the prolongation in the P300 latencies was not found to be statistically significant (P = 0.0733). All latencies were longer in IGE patients, and the amplitudes of the N200/P300 components of ERP were lower in both epileptic groups compared with their control groups, but these differences were not significant. The prolongation of the P300 latencies was not correlated with the type or serum level of antiepileptic drug or seizure control. Our findings suggest that the prolongation of the P300 latency of ERP is related to the type of epilepsy.     

T-cell-rich B-cell lymphoma: a clinicopathologic study of 21 cases and comparison with 43 cases of diffuse large B-cell lymphoma

Clinicopathologic features of 21 patients with T-cell-rich B-cell lymphoma (TCRBCL) were reviewed and compared to 43 patients with diffuse large B-cell lymphoma (DLBCL) to determine if there were distinguishing clinical characteristics and differences in response or survival to CHOP therapy. For the diagnosis of TCRBCL, the current WHO criteria was used. In all of our cases, the majority of cells are non-neoplastic T cells and <10% large neoplastic B cells are present. The initial pathologic diagnosis was nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) in two cases. Patients with TCRBCL were significantly younger (median: 46 years) and had a significantly higher incidence of B symptoms (62%), hepatomegaly (33%) and marrow infiltration (33%) at presentation when compared to DLBCL (P<0.03). The CR rate after treatment was 48% for TCRBCL patients versus 79% for the DLBCL (P<0.003). Although the CR rates in between the two groups are significant, the difference in 3 years survival rates in each CR groups was insignificant (80% versus 77%). The overall survival time in the two groups was 17 months. Event-free survival time in TCRBCL was 12 months, compared with 17 months in the DLBCL (P>0.05). The frequency of patients with TCRBCL achieving CR was 52.6% whereas that of patients with DLBCL was 79% (P<0.003). The TCRBCL 3 years event-free survival 48% and overall survival 64% were 63 and 72% for DLBCL, respectively.     

A 10.46 Mb 12p11.1-12.1 interstitial deletion coincident with a 0.19 Mb NRXN1 deletion detected by array CGH in a girl with scoliosis and autism

We present a 12-year-old girl with de novo karyotype 46,XX,del(12)(p11.1p12.1). Array CGH revealed in addition to a 10.466 Mb interstitial deletion on 12p11.1→12p12.1 a 0.191 Mb deletion on 2p16.3. The girl presented with mild facial dysmorphism consisting of microcephaly, hypertelorism, downslanting palpebral fissures, strabismus, broad nasal base, bulbous nose, short philtrum, micro/retrognathia, irregular tooth arrangement, phalangeal deformity in distal phalanges of hands, 5th finger camptodactyly, brachydactyly in feet, history of joint hypermobility, and scoliosis. She was considered to have mild to moderate mental retardation and ascertained for an autism spectrum disorder(ASD). Short arm of chromosome 12 interstitial deletions are rarely reported whereas point mutations and deletions of NRXN1, which is located on chromosome 2p16.3, are associated with ASDs. In this article we present and discuss the phenotypic consequences of a patient who was affected by deletions of two different chromosomal regions.     

PTP1B expression is an independent positive prognostic factor in human breast cancer

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has come into focus as a critical regulator of multiple signaling pathways. The role of PTP1B in breast cancer remains unclear with evidence suggesting that PTP1B can exert both tumor-suppressing and tumor-promoting effects. To better define the role of PTP1B in human breast cancer, and its relationship with HER2, we performed immunohistochemical studies on a large cohort of functionally annotated primary breast cancer specimens. 683 of 1,402 (49 %) evaluable primary breast cancers are positive for PTP1B. There is no statistically significant association between PTP1B expression and age, tumor size, T stage, histologic grade, lymph node status, or histological subtype. Of note, there is no significant association between PTP1B expression and HER2 expression (PTP1B expression 53.1 % in HER2⁺ cancers vs. 47.5 % in HER2^? cancers, p = 0.0985). However, PTP1B expression is significantly associated with estrogen receptor expression (PTP1B expression 50.7 % in ER⁺ cancers vs. 43.1 % in ER^? cancers, p = 0.0137) and intrinsic molecular subtype (PTP1B expression 53.9 % in the luminal B HER2⁺ subtype and 37.9 % in the basal-like subtype). Of note, multivariate analyses demonstrate that PTP1B is an independent predictor of improved survival in breast cancer (HR 0.779, p = 0.006). Taken together, we demonstrate in the largest study to date that (1) PTP1B is commonly expressed in breast cancer, (2) there is no association or functional impact of PTP1B expression in HER2⁺ breast cancer, and (3) PTP1B expression in breast cancer is associated with significantly improved clinical outcome. Until additional studies are performed, caution should be exercised in using PTP1B inhibitors in human breast cancer.     

Biliary precipitation during ceftriaxone therapy: frequency and risk factors

Ceftriaxone, a third-generation cephalosporin, is widely used for treating infection during childhood. It is mainly eliminated in the urine, but approximately 40% of a given dose is unmetabolized and secreted into bile. The aim of this study was to investigate the frequency, clinical characteristics, and outcome of biliary sludge (BS) in addition to potential contributing risk factors in children who receive ceftriaxone. Biliary ultrasonography was performed at the time of randomization before ceftriaxone treatment was started, on the 5th and 10th days, and at the end of the treatment. If BS was detected, patients were followed-up weekly by sonographic examination until the BS or biliary lithiasis (BL) disappeared. A total of 114 children (56 girls, 58 boys; age range: 2-180 months, mean 47.5 +/- 46.3 mos) were enrolled in the study. Fourteen (12%) subjects developed BS and 10 (9%) developed BL on the 5th day of treatment. On the 10th day of treatment, 20 (18%) subjects developed BS and 15 (13%) developed BL. In total, 35 (31%) of all subjects developed biliary precipitation (BP), of whom 20 (57%) were diagnosed as BS and 15 (43%) as BL. All subjects who developed BP were found to be asymptomatic during the course of therapy. Patient age over 12 months, daily total dose of ceftriaxone of more than 2 g, and duration of treatment longer than five days were found to be associated with BP. Ceftriaxone frequently causes transient BPs and its probability increases if the child is over 12 months of age, the dose is over 2 g/day, or the duration is over five days. Neither radiologic investigation nor the discontinuation of treatment with ceftriaxone is necessary as long as the patient is asymptomatic.     

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer

Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1⁺ TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1⁺ TIL were present in 104 (15.8 %) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1⁺ TIL was associated with a significantly worse overall survival (HR = 2.736, p < 0.001). In subset analyses, the presence of PD-1⁺ TIL was associated with significantly worse overall survival in the luminal B HER2^? subtype (HR = 2.678, p < 0.001), the luminal B HER2⁺ subtype (HR = 3.689, p < 0.001), and the basal-like subtype (HR = 3.140, p < 0.001). This is the first study to demonstrate that the presence of PD-1⁺ TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.