Can pretreatment ADC values predict recurrence of bladder cancer after transurethral resection?

Objective

The aim of this retrospective study was to investigate the association between the pretreatment apparent diffusion coefficient (ADC) value and recurrence of bladder cancer after transurethral resection.

Methods

Patients with superficial bladder cancer were identified. Mean ADC values of the tumors were compared between patients with and without recurrence following trans-urethral resection. A receiver–operator characteristic curve was used for determining the optimal cutoff ADC value. Univariate and multivariate analyses were used to determine the effect of ADC values and other factors.

Results

With a mean follow-up period of 25 months, bladder cancer recurred in 14 of 44 patients (32%). The mean ADC value of tumors in patients with recurrence was lower than in those without recurrence (1.08 mm²/s vs. 1.28 × 10⁻³ mm²/s; p = 0.003). The optimal cutoff ADC value for predicting recurrence was determined to be 1.12 × 10⁻³ mm²/s. A modest and significant negative correlation was observed between the ADC values and tumor size (r = −0.436, p = 0.008). After adjustment for size and risk groups, an ADC value equal to or less than the optimal cutoff remained a significant predictor of recurrence (odds ratio 6.3, 95% CI 1.23–32.2, p = 0.027).

Conclusion

Pretreatment ADC values may be an independent predictor of bladder cancer recurrence.     

Dramatic improvement in Down syndrome-associated cognitive impairment with donepezil

OBJECTIVE: To report 2 cases of patients with Down syndrome and severe cognitive impairment who gained dramatic improvements in quality of life (QOL) upon donepezil treatment. CASE SUMMARIES: Case 1. A 38-year-old woman with Down syndrome, diagnosed with secondary progressive dementia when her mental state had deteriorated rapidly after graduation from junior high school, started donepezil treatment. The loading dose was 3 mg/day and was increased to 5 mg/day for maintenance. One month after the dose was increased, adverse effects such as soft stool and urinary incontinence appeared. These adverse effects disappeared when the dose was decreased again to 3 mg/day. Her QOL improved dramatically with this minimal dose. She recovered verbal and written communication skills that she had lost for the past 21 years. Case 2. A 22-year-old man with Down syndrome, who had been diagnosed as having severe mental retardation, was put on donepezil therapy. Both loading and maintenance doses were 3 mg/day. His QOL had also dramatically improved, with some recovery in verbal communication. Transient agitation/violence and transient muscle weakness appeared during the first few months of treatment. DISCUSSION: Patients with Down syndrome may be more sensitive to donepezil therapy than others and may benefit from this medicine, although they may also have adverse effects more frequently. CONCLUSIONS: Donepezil may be a useful medicine for some patients with Down syndrome with severe cognitive impairment or mental retardation if the adverse effects are manageable.     

Clinical outline of Barrett's esophagus

Barrett's esophagus is one of the important gastrointestinal disease in Europe and the United States. It was recognized as not only complication of reflux esophagitis, but also pre-malignant lesion of adenocarcinoma. Recently, realization of Barrett's esophagus is attentioned in Japan, because increasing of reflux esophagitis for westernization of eating habit, living habit and aging of the population. In this section, we present general consideration and clinical research of Barrett's esophagus. We expect Barrett's esophagus will gradually increase near the future and need to research abundantly about controversial point of Barrett's esophagus. We also think it is important to accumulate intensively the clinical data of Barrett's esophagus patients.     

Angiotensin receptor vaccines

Recent clinical studies have shown that RAS inhibitors are effective not only for the prevention of end-organ damage in hypertensive patients, but also for prevention of new-onset hypertension, diabetes mellitus, and atrial fibrillation. Vaccines against the RAS have been developed since the 1950s, and a recent phase IIa placebo-controlled study has confirmed that an angiotensin vaccine causes a significant decrease in blood pressure in hypertensive patients. The results of animal experiments from our and other laboratories have suggested that vaccination against the angiotensin type 1 (AT1) receptor causes a significant decrease in blood pressure in animal models of hypertension, and also ameliorates hypertensive end-organ damage. The angiotensin receptor may therefore be an important target for the development of vaccines for the prevention of hypertension and related complications.     

TNF-alpha induces thromboxane receptor signaling-dependent microcirculatory dysfunction in mouse liver

TNF-alpha is a critical mediator of hepatic microcirculatory dysfunction during endotoxemia. The present study was to investigate the role of thromboxane A2 (TXA2) and the biological significance of thromboxane prostanoid (TP) receptor signaling in TNF-alpha-mediated hepatic microcirculatory dysfunction in male C57Bl/6 mice. The number of leukocytes adhering to the endothelial cells of the hepatic microvessels (the portal venules, sinusoids, and central venules) and the percentage of nonperfused sinusoids were determined using in vivo fluorescence microscopy. FR167653, an inhibitor of TNF-alpha, was administered 0 and 2 h after LPS injection. A TXA2 synthase inhibitor, OKY-046, was administered 30 min before TNF-alpha injection. Thromboxane prostanoid receptor knockout mice were used to investigate whether TNF-alpha-induced hepatic microcirculatory dysfunction is mediated by endogenously produced TXA2. FR167653 reduced LPS-induced leukocyte adhesion (50%-80%) and the percentage of nonperfused sinusoids (55%). The leukocyte adhesion was increased in the portal venules (8-fold), sinusoids (51-fold), and central venules (73-fold) in TNF-alpha-treated mice, accompanied with an increase in sinusoidal perfusion deficits (8-fold). Alanine aminotransferase levels rose as the adhesion of leukocytes increased. OKY-046 administration before TNF-alpha administration reduced leukocyte adhesion (41%-49% decrease) and sinusoid perfusion deficits (34% decrease). In TP receptor knockout mice, the number of adhering leukocytes, the percentage of nonperfused sinusoids, and alanine aminotransferase levels were lower (by 43%-56%, 41%, and 29%, respectively) than in wild-type counterparts. The results suggest that TP receptor signaling may promote hepatic microcirculatory dysfunction elicited by TNF-alpha. Blockade of TNF-alpha generation and TP receptor signaling may be a good strategy for managing endotoxin-induced hepatic injury.     

The EFA6 family: guanine nucleotide exchange factors for ADP ribosylation factor 6 at neuronal synapses

ADP ribosylation factor 6 (ARF6) is a member of the ARF family of small GTPases, which mediates a variety of neuronal functions accompanying the structural changes of developing and mature neurons through its regulation of actin cytoskeleton reorganization and membrane traffic. The activation of ARF6 is strictly regulated by guanine nucleotide exchange factors (GEFs). The EFA6 family is the first member that was identified to be a specific GEF for ARF6 and comprises four structurally related polypeptides (EFA6A, EFA6B, EFA6C and EFA6D). Since the cellular and subcelllular localization of GEFs is a critical determinant for the spatiotemporal activation of ARF6 in neurons, I have focused on the EFA6 family from the anatomical point of view to understand the neuronal functions of ARF6. Three members of the EFA6 family (EFA6A, EFA6C and EFA6D) are abundantly expressed in the mouse brain with distinct spatiotemporal patterns. Interestingly, they are enriched particularly in the postsynaptic density fraction, shedding light on the importance of the EFA-ARF6 pathway in neuronal synapses. Here, I will review the recent advances in the expression and functions of the EFA6 family in the nervous system.