Time to achieve a prostate-specific antigen nadir of ≤0.2 ng/mL and related factors after permanent prostate brachytherapy

PurposeThe purpose of this study was to identify the time to achieve a prostate-specific antigen (PSA) nadir of ≤0.2 ng/mL and the related factors to achieve this goal.Materials and MethodsWe retrospectively reviewed 2218 Japanese prostate cancer patients who received ¹²⁵I brachytherapy with or without external beam radiotherapy between 2003 and 2013 at one institution. Among them, patients followed up for ≥72 months and without luteinizing hormone–releasing hormone (LH-RH) agonist/antagonist were included (total of 1089 patients). The time to a PSA nadir of ≤0.2 ng/mL (months) was defined as the time between the date of implantation and the first time the lowest PSA value reached ≤0.2 ng/mL. Biochemical recurrence (BCR) was determined using the Phoenix definition. Multivariate linear regression analysis was performed to detect the related factors to achieve this nadir.ResultsWe assigned 409, 592, and 88 patients to the low-, intermediate-risk, and high-risk groups, respectively. The median followup time was 9.5 years. The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 (95% confidence interval: 42.3–45.7) months. The percentage of patients that achieved the nadir was 89.1%. BCR was noted in 107 (9.8%) patients. In the multivariate analysis of patients without BCR, younger age, larger prostate volume at implantation, higher initial PSA level, and monotherapy were significantly associated with longer time to achieve the PSA nadir.ConclusionThe median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 months. Some patients, however, may require a lengthy period of time to do so.     

A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder

BackgroundCUL3 encodes cullin-3, a core component of a ubiquitin E3 ligase. CUL3 mutations have recently been associated with autism spectrum disorder (ASD); however, the detailed clinical courses have been described in only a limited number of patients with CUL3 mutations and neurodevelopmental diseases, including ASD.Case reportA 21-month-old Japanese girl presented with febrile status epilepticus and thereafter exhibited developmental regression, including loss of her verbal ability, eye contact, and skills in activities of daily living. Trio-based exome sequencing identified a de novo two-base insertion in CUL3, c.1758_1759insTG, p.(Thr587*).ConclusionWe report a case of a patient with ASD and a stop-gain CUL3 variant. Screening of CUL3 variants is worth considering for patients with ASD, especially those with Rett-like developmental regression.     

Influence of androgen deprivation therapy on prostate volume in patients with prostate cancer undergoing prostate brachytherapy with permanent seed implantation

OBJECTIVE: Enlarged prostate often causes pubic arch interference during needle insertion on transperineal interstitial permanent prostate brachytherapy. Pre-treatment hormonal therapy is necessary for downsizing the prostate gland in such cases. The degree of prostate downsizing with anti-androgen treatment before iodine 125 permanent seed implant brachytherapy and its relation to clinical as well as pathological parameters were assessed. METHODS: From September 2003 to March 2005, 110 patients underwent permanent seed implantation and 86 patients of all received antiandrogen depriviation prior to the treatment at our institute. Prostate volume was measured using transrectal ultrasound at the time of cancer diagnosis and before the seed implant. Correlations between prostate downsizing and clinical as well as pathological parameters were evaluated. RESULTS: Mean percent volume of the prostate after the size reduction with average of 6.0 months antiandrogen monotherapy, 7.7 months LHRH agoniost and 8.2 months maximum androgen blockage (MAB) was 83%, 63%, and 60%, respectively. Mann-Whitney U test revealed that the degree of prostate downsizing is significantly correlated with the prostate volume in patients with prostate cancer utilizing LHRH agonists. CONCLUSIONS: Antiandrogen monotherapy can be an alternative for prostate downsizing before interstitial brachytherapy. Utilizing LHRH agonists or MAB is recommended for cases with larger gland volume.     

Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids

Inhibitory effects of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), and cannabinol (CBN) on the catalytic activities of human recombinant cytochrome P450 (CYP) 2A6 and CYP2B6 were investigated. Δ⁹-THC, CBD, and CBN noncompetitively inhibited coumarin 7-hydroxylase activity of recombinant CYP2A6 with the apparent K _i values of 28.9, 55.0, and 39.8 μM, respectively. On the other hand, Δ⁹-THC, CBD, and CBN inhibited 7-benzoxyresorufin O-debenzylase activity of recombinant CYP2B6 in a mixed fashion with the K _i values of 2.81, 0.694, and 2.55 μM, respectively. Because the inhibition of CYP2B6 by CBD was the most potent, investigation was conducted to determine which moiety of the CBD structure was responsible for the inhibition. Olivetol and d-limonene, the partial structure of CBD, inhibited the CYP2B6 activity to some extent. Inhibitory effects of CBD-2′-monomethyl ether and CBD-2′,6′-dimethyl ether attenuated with the number of methylations on the phenolic hydroxyl groups in the resorcinol moiety of CBD. Cannabidivarin, a CBD analogue having a propyl side chain, inhibited the CYP2B6 activity less potently than CBD possessing a pentyl side chain. Therefore, both structures of pentylresorcinol and terpene moieties of CBD were suggested to play important roles in the CYP2B6 inhibition. Δ⁹-THC, CBD, and CBN showed metabolism-dependent inhibition for CYP2A6 but not for CYP2B6. Furthermore, Δ⁹-THC and CBN were characterized as mechanism-based inhibitors for CYP2A6. The k _inact and K _I values of Δ⁹-THC were 0.0169 min⁻¹ and 0.862 μM, respectively; the k _inact and K _I values of CBN were 0.00909 min⁻¹ and 1.01 μM, respectively. These results indicated that Δ⁹-THC, CBD, and CBN showed differential inhibition against CYP2A6 and CYP2B6.     

Human brain microsomes: their abilities to metabolize tetrahydrocannabinols and cannabinol

In spite of the psychedelic action of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) in the brain, no report on its metabolism by human brain microsomes has been published. In this study, the metabolism of Δ⁸-THC, Δ⁹-THC and cannabinol (CBN) was studied using human brain microsomes. The metabolites formed were analyzed by gas chromatography–mass spectrometry after trimethylsilylation. The three cannabinoids were biotransformed to two main metabolites by human brain microsomes. Δ⁸- and Δ⁹-THCs were mainly oxidized at the allylic positions. The main metabolites of Δ⁸-THC were 7α-hydroxy- and 11-hydroxy-Δ⁸-THCs, whereas those of Δ⁹-THC were 8α-hydroxy- and 11-hydroxy-Δ⁹-THCs. CBN was metabolized to 8-hydroxy- and 11-hydroxy-CBNs. Although the primary metabolic pathways of the THCs and CBN in brain microsomes are different from those in liver microsomes for other mammalian species, those in human brain microsomes were similar to those in human liver microsomes.     

Symmetrical brainstem encephalitis caused by herpes simplex virus

We describe a 53-year-old man with herpes simplex virus (HSV) brainstem encephalitis diagnosed based by positive HSV immunoglobulin M antibodies from cerebrospinal fluid. The MRI findings of this case had three unique features. First, the lesions were symmetrical. Second, the lesions may have been associated with reactivation of HSV infection in the region of the trigeminal nerve. Third, diffusion-weighted and apparent diffusion coefficient (ADC) imaging, conducted for the first time on an HSV brainstem encephalitis case, suggested that the lesions were associated with vasogenic edema.     

Synchronous monitoring of external/internal respiratory motion: validity of respiration-gated radiotherapy for liver tumors

Purpose  

Four-dimensional (4D) radiotherapy, in particular respiration gating for the treatment of lung tumors, is gaining popularity. Its utility for other sites, however, has not been investigated fully. The purpose of this study was to see whether 4D therapy is feasible for liver tumors.     

A case of sensory ataxic neuropathy and polymyositis of perivascular type associated with Sj?gren's syndrome]

A 53-year old woman was admitted with of sensory disturbance and weakness of lower limbs which had progressed slowly in the previous ten years. A diagnosis of sensory ataxic neuropathy associated with Sj?gren's syndrome was made. A sural nerve biopsy showed marked loss of myelinated fibers. A muscle biopsy revealed atrophy of muscle fibers along with perivascular cellular infiltration. The dorsal root ganglia have been considered to be the main site affected in the ataxic neuropathy in Sj?gren's syndrome. However, the evidence for that was meager. The perivascular inflammatory change observed in the muscle may also have existed in the peripheral nervous system including the dorsal root ganglia.     

Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease

Objective

The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD).

Methods

Fifteen patients with AD (mean age: 80.2 ± 4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D₂ selective antipsychotic, was performed for 12 weeks.

Results

Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted.

Conclusions

Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed.     

TOCP对DFP在鸡脊髓神经细胞膜特异结合的影响

[目的]调查〔3H〕DFP在各脊髓段神经细胞膜上的特异结合。[方法]鸡曝露于Tri-o-cre-sylphosphate(TOCP)后,隔6、24、48h处死,取颈、胸、腰段脊髓,称重后制成匀浆。经超速离心,获得膜蛋白。在脊髓膜蛋白中加入8nM的〔3H〕DFP,或加入80nM的非标记DFP后又加入8nM的〔3H〕DFP,然后培养1h。用nitrocellulosefilter进行快速真空滤过,用Tris-HCl-NaCl液对滤纸冲洗,再加5mL的Aquasol-2后,计数〔3H〕DFP的结合量。[结果]对照组鸡的颈、胸、腰椎段脊髓神经细胞膜上的〔3H〕DFP特异结合量分别为832.0、857.0、864.0fmol/mg,TOCP曝露组为273.5、243.52、71.5fmol/mg。TOCP曝露组各段脊髓神经细胞膜上的〔3H〕DFP特异结合量显著低于对照组,而各段脊髓神经细胞膜之间〔3H〕DFP的特异结合量无显著性差异。随着TOCP曝露后的时间的推移,各段脊髓神经细胞膜上的〔3H〕DFP特异结合量逐渐增高,提示迟发性神经毒性有机磷化合物的特异结合膜蛋白是较均匀地分布在整个脊髓神经细胞膜上。在这些脊髓神经细胞膜上的特异性结合部位,TOCP和DFP之间有竞争性抑制作用。[结论]脊髓神经细胞膜上的特异性结合膜蛋白可能与有机磷化合物的迟发性神经毒性诱发有关。