Does switching the bacillus Calmette-Guérin strain affect clinical outcome in patients with recurrent non–muscle-invasive bladder cancer after initial bacillus Calmette-Guérin therapy?

Purpose

It is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor).

The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis

Objectives

Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT).

Establishment of the optimal follow-up schedule after radical prostatectomy

Purpose

Monitoring the serum level of prostate specific antigen (PSA) is indispensable for surveillance after radical therapy, and the aim of this study was to establish the optimal follow-up schedule.

Characteristic Sonographic Findings of Early Restenosis After Carotid Endarterectomy

Objective. Restenosis of the carotid artery after carotid endarterectomy (CEA) is a major complication. The frequency, time of occurrence, and tissue characteristics of carotid restenosis were assessed with sonography. Methods. Two hundred sixteen patients who had CEA for carotid stenosis were studied; follow‐up sonography and magnetic resonance angiography were done 2 weeks, 3 months, and then every year after CEA. On sonography, restenosis was defined as an internal carotid artery (ICA) with a peak systolic velocity of 170 cm/s or greater or a maximum area of stenosis of 90% or greater. Results. During 605 artery‐years of follow‐up, 18 patients (7.5%) were found to have restenosis on sonography: 4 at 3 months, 11 at 1 year, and 3 at 2 years after CEA. At the time that restenosis was detected, in all 18 ICAs the peak systolic velocity exceeded 200 cm/s and had more than doubled since the last measurement (mean ± SD, 103 ± 27 to 321 ±107 cm/s), whereas the area of stenosis exceeded 90% in 6 patients, and magnetic resonance angiography revealed stenosis of 60% or greater in 8 patients. On sonography, all of the restenotic plaques were isoechoic and concentric. The restenosis was asymptomatic in 17 patients. Vascular risk factors or the severity of initial carotid stenosis before CEA were not associated with development of restenosis. Eleven patients had successful endovascular therapy, and the others received medical treatment. Conclusions. A marked increase in the flow velocity through an operated ICA is a good indication of restenosis. The isoechogenicity and concentricity of the restenotic plaques suggest that the restenosis is primarily the result of intimal hyperplasia.     

Lrp4 Modulates Extracellular Integration of Cell Signaling Pathways in Development

The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway.     

Estrogen treatment of prostate cancer increases triglycerides in lipoproteins as demonstrated by HPLC and immunoseparation techniques

BACKGROUND: Estrogen administration is known to increase serum triglyceride concentrations. This study measured changes in lipoproteins of patients with prostate cancer treated with estrogen to determine whether the increased triglyceride concentrations are associated with atherogenic lipoprotein patterns. METHODS: Fifteen patients (52-87 years) with histologically diagnosed prostate cancer received diethylstilbestrol diphosphate (250 mg/day). Serum samples were collected before and after 1 and 2 weeks of treatment. Cholesterol and triglyceride profiles of major lipoproteins were determined by HPLC, remnant-like particle cholesterol and triglyceride concentrations by an immunoseparation technique, and apolipoproteins by immunologic methods. RESULTS: Estrogen treatment induced a 63.3% increase in total triglyceride concentrations, which occurred in all major lipoprotein classes with significant increases in HDL-triglycerides (130.4%), LDL-triglycerides (60.7%) and VLDL-triglycerides (56.2%). HDL-cholesterol increased significantly by 26.8%, while LDL-cholesterol decreased (15.6%). Remnant-like particle triglyceride concentrations also increased significantly by 77%, whereas remnant-like particle cholesterol concentrations remained unchanged. Apolipoproteins A-I and A-II increased; apolipoprotein E and Lp(a) decreased. CONCLUSIONS: The techniques used here conveniently demonstrated that short-term estrogen treatment in prostate cancer patients resulted in triglyceride enrichment of all major lipoprotein classes but did not induce changes in the lipoprotein profiles generally recognized as increasing risk for cardiovascular disease, except for the elevation of plasma triglyceride and remnant-like particle triglyceride.     

A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia

Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy.     

Prevalence of cribra orbitalia in Pacopampa during the formative period in Peru

Cribra orbitalia is characterized by an aggregation of small apertures in the orbital roof in response to marrow hypertrophy. This pathological change is indicative of biological stress during youth. We examined the prevalence of this lesion in Pacopampa, a ceremonial center of the formative period, located in the northern highlands of Peru. Using this evaluation of cribra orbitalia, we reconstructed aspects of the population’s health and nutritional status during the formation of Andean civilization. We examined 41 orbits of 27 adult individuals (13 males, 14 females) and recorded the macroscopic presence or absence of cribra orbitalia. The presence or absence of cribra orbitalia was the same bilaterally for all 14 individuals having both orbits preserved. The pathology was present in two of the 13 males (15.4%), one of the 14 (7.1%) females, and three of 27 individuals (11.1%) for both sexes combined. There was no difference in the frequency between sexes. The prevalence of cribra orbitalia was found to be lower in Pacopampa than in the comparative data of coastal populations. It is reasonable to assume that the increase in social complexity in Pacopampa was probably unrelated to the decline in overall health of the people.