A large inferior mesenteric-caval shunt via the internal iliac vein

A large portosystemic shunt between the inferior mesenteric vein and the right internal iliac vein in a 28-yr-old non-cirrhotic man is presented. This collateral was discovered by ultrasound done as a screening examination for gastrointestinal bleeding. The direct communication of the inferior mesenteric vein with the internal iliac vein was demonstrated by computed tomography and percutaneous transhepatic portography. Surgical ligation of the collateral, performed to prevent future portosystemic encephalopathy, resulted in reduction of serum ammonia level and cessation of long-standing hemorrhoidal bleeding.     

Neonatal exposure to MK‐801 reduces mRNA expression of mGlu3 receptors in the medial prefrontal cortex of adolescent rats

Schizophrenia is considered as a “neurodegenerative” and “neurodevelopmental” disorder, the pathophysiology of which may include hypofunction of the N‐methyl‐d ‐aspartate receptor (NMDA‐R) or subsequent pathways. Accordingly, administration of NMDA‐R antagonists to rodents during the perinatal period may emulate some core pathophysiological aspects of schizophrenia. The effect of 4‐day (postnatal day; PD 7–10) administration of MK‐801, a selective NMDA‐R antagonist, on gene expression in the medial prefrontal cortex (mPFC), hippocampus, and amygdala was evaluated using quantitative polymerase chain reaction methods. Specifically, we sought to determine whether genes related to Glu transmissions, for example those encoding for NMDA‐Rs, metabotropic Glu receptors (mGluRs), or Glu transporters, were altered by neonatal treatment with MK‐801. Model rats showed downregulation of the mGluR3 subtype in the mPFC around puberty, especially at PD 35 in response to MK‐801 or during ontogenesis without pharmacological manipulations. Genes encoding for other mGluRs subtypes, that is NMDA‐Rs and Glu transporters, were not affected by the neonatal insult. These results suggest that NMDA‐R antagonism in the early course of development modulates the expression of mGluR3 in mPFC around puberty. Thus, mGluR3 may serve as a potential target to prevent the onset and progression of schizophrenia. Synapse 68:202–208, 2014 . © 2014 Wiley Periodicals, Inc.     

Changes in Na(+) channel expression and nodal persistent Na(+) currents associated with peripheral nerve regeneration in mice

Patients with peripheral neuropathy frequently suffer from positive sensory (pain and paresthesias) and motor (muscle cramping) symptoms even in the recovery phase of the disease. To investigate the pathophysiology of increased axonal excitability in peripheral nerve regeneration, we assessed the temporal and spatial expression of voltage-gated Na(+) channels as well as nodal persistent Na(+) currents in a mouse model of Wallerian degeneration. Crushed sciatic nerves of 8-week-old C57/BL6J male mice underwent complete Wallerian degeneration at 1 week. Two weeks after crush, there was a prominent increase in the number of Na(+) channel clusters per unit area, and binary or broad Na(+) channel clusters were frequently found. Excess Na(+) channel clusters were retained up to 20 weeks post-injury. Excitability testing using latent addition suggested that nodal persistent Na(+) currents markedly increased beginning at week 3, and remained through week 10. These results suggest that axonal regeneration is associated with persistently increased axonal excitability resulting from increases in the number and conductance of Na(+) channels.     

Compartmentalization of the chick cerebellar cortex based on the link between the striped expression pattern of aldolase C and the topographic olivocerebellar projection

The avian cerebellum is organized into multiple longitudinal stripes defined by expression profiles of aldolase C (zebrin II) in Purkinje cells. The relationship between the aldolase C striped pattern and the olivocerebellar projection pattern is crucial in understanding cerebellar functional compartmentalization. We identified all aldolase C stripes across all lobules with the serial section alignment analysis method and then looked at this relationship by anterograde and retrograde labeling of olivocerebellar axons in the chick cerebellum. Aldolase C stripes were generally consistent and continuous from lobule I through VII and to the medial part of lobules VIII–IXb. The dorsal and ventral lamellas (DL, VL) of the inferior olive projected to the stripes in these areas with a simple mediolateral topographic relation. A few aldolase C stripes appeared at the lateral edge of lobules VI–VIII. Several more stripes were added in the lateral parts of lobules IXa–IXb and IXc–X. The medial column (MC) of the inferior olive projected to the stripes in lobules VIII–X, including the added lateral stripes, with a complex topographic relation. Sharp boundaries between aldolase C‐positive and ‐negative stripes often accompanied a gap in the Purkinje cell layer and bordered topographically distinct groups of axons. Although the compartmental organization of the chick cerebellum is comparable to that of the mammalian cerebellum, several significant differences in the organization suggest partly separate evolutionary lineages of the mammalian and avian cerebella. We propose that rostral lobules may be evolved by rostral extension of medial stripes from caudal lobules in the avian cerebellum. J. Comp. Neurol. 523:1886–1912, 2015 © 2015 Wiley Periodicals, Inc.     

Phase II Study of Panitumumab Monotherapy in Chemotherapy‐Naïve Frail or Elderly Patients with Unresectable RAS Wild‐Type Colorectal Cancer: OGSG 1602

Lessons Learned

• Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild‐type unresectable colorectal cancer.
• It is especially effective for left‐sided tumors; therefore, panitumumab as first‐line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin‐based or irinotecan‐based combination regimens.

BackgroundFirst‐line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy‐naïve frail or elderly patients with unresectable RAS wild‐type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first‐line treatment.MethodsWe conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression‐free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities.ResultsThirty‐six patients (median age: 81 [range, 67–88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty‐three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty‐eight patients (77.8%) had left‐sided CRC, whereas eight (22.2%) had right‐sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4–67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5–87.7). The RR of patients with left‐ and right‐sided tumors was 65.4% (95% CI, 44.3–82.8) and 0.0% (95% CI, 0.0–36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%).ConclusionPanitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.     

Inhibition of Atherosclerotic Plaque Development by Oral Administration of α-Glucosyl Hesperidin and Water-Dispersible Hesperetin in Apolipoprotein E Knockout Mice

Objective: Hesperidin, an abundant flavonoid in citrus fruit, and its aglycone, hesperetin, have been reported to possess various physiological activities, including antioxidant, anti-inflammatory, hypolipidemic, and antihypertensive activities. In this study, we investigated whether α-glucosyl hesperidin and water-dispersible hesperetin have protective effects on atherosclerotic progression in apolipoprotein E knockout (Apo-E KO) mice.

Methods: Ten-week-old male Apo-E KO mice were randomly assigned a regular high-fat diet, a high-fat diet with 0.5% α-glucosyl hesperidin, or a high-fat diet with 0.1% water-dispersible hesperetin for 12?weeks. Measurement of plasma total cholesterol levels, histological staining of aortic root, and immunohistochemistry for macrophages were performed to evaluate atherosclerotic plaque formation. Vascular reactivity of mouse aortic rings was also measured.

Results: Both α-glucosyl hesperidin and water-dispersible hesperetin reduced plasma total cholesterol level. They also reduced plaque formation area, adipose deposition, and macrophage infiltration into atherosclerotic lesion. Vascular-endothelium-dependent relaxation in response to acetylcholine was improved in both experimental diet groups compared to the high-fat diet group.

Conclusions: Our study suggests that both α-glucosyl hesperidin and water-dispersible hesperetin exert protective effects on atherosclerotic progression in Apo-E KO mice because they exhibit hypolipidemic activity, reduce inflammation through macrophages, and prevent endothelial dysfunction.     

An attempt to measure the diametric relationship between slow and quick phases of nystagmus

Objective: To investigate whether our original method can precisely evaluate the angle between slow and quick phases of nystagmus (vector angle) and to determine whether vector angle analysis is helpful in differentiating between horizontal nystagmus and mixed nystagmus with horizontal and vertical components.

Methods: We included 20 healthy volunteers, 17 patients with horizontal nystagmus, and 15 patients with mixed nystagmus. Caloric nystagmus was recorded in healthy volunteers; positional nystagmus was recorded in each patient. We extracted the velocity of nystagmus from eye movement of each subject and analysed the vector angle.

Results: In caloric nystagmus, the vector angle approached 180 degrees as slow-phase velocity increased, suggesting that our vector angle measurement is more reliable with faster nystagmus. Importantly, in horizontal nystagmus from peripheral vestibular disease, the vector angle similarly approached 180 degrees as slow-phase velocity increased; in contrast, the vector angle in cases of mixed nystagmus from vertebrobasilar insufficiency or spinocerebellar degeneration significantly differed from the angle of caloric nystagmus.

Conclusions: Vector angle analysis using our original algorithm can precisely evaluate the diametric relationship in vestibular nystagmus; it may be helpful in diagnosis of non-peripheral vestibular disorders.     

Influence of the menstrual cycle on compression-induced pain during mammography: correlation with the thickness and volume of the mammary gland

In mammography, breast compression is necessary and an important factor influencing image quality. The purpose of this study was to determine the influence of the menstrual cycle on compression-induced pain during mammography and to evaluate the association between the thickness and volume of the mammary gland and pain. We examined basal body temperature and categorized the menstrual cycle into five phases. We executed breast compression in the craniocaudal view using a customized compression plate, to which we introduced an opening. We measured the thickness of the mammary gland under compression using echography. Immediately after releasing the compression, we evaluated pain using the visual analogue scale. We performed magnetic resonance imaging (MRI) on the same day and measured the volume of the mammary gland. The thickness of the mammary gland, pain, and the volume of the mammary gland were minimal in the late follicular phase and maximal in the late luteal and early follicular phases. It was shown that the changes in the thickness and volume of the mammary gland during the menstrual cycle accounted for the changes in compression-induced pain. On MRI examination of each breast quadrant, the same changes were observed in areas A and C. In area A, it was shown that both the anatomical characteristics and the increase in volume of the mammary gland were associated with pain. We concluded that the late follicular phase constitutes the optimal timing for mammography.     

Glucose intolerance and adenomas of the sigmoid colon in Japanese men (Japan)

Objectives: The purpose was to investigate the relation between glucose tolerance and risk of sigmoid colon adenomas, a well-established precancerous lesion, in Japanese men.Methods: In the consecutive series of 7,637 men aged 48 to 59 years who received a preretirement health examination at four hospitals of the Self Defense Forces (SDF) in Japan from 1986 to 1994, we identified 821 cases of sigmoid colon adenomas and 4,372 controls with normal sigmoidoscopy or colonoscopy at 60 cm or more from the anus. Glucose tolerance status was classified as normal, impaired glucose tolerance (IGT), newly diagnosed non-insulin dependent diabetes mellitus (NIDDM), or diabetes mellitus under treatment, based ona75g oral glucose tolerance test and medical history. Statistical adjustment was made for body mass index (wt/ht2), cigarette smoking, alcohol use, rank of the SDF, and hospital.Results: Modest increases in adenoma risk were observed for newly diagnosed NIDDM and diabetes mellitus under treatment while there was no association between IGT and adenoma risk. When small (< 5 mm in diameter) and large (5+ mm) adenomas were analyzed separately, increased risk associated with newly diagnosed NIDDM was more pronounced for small adenomas, and diabetes mellitus under treatment showed a slightly stronger association with large adenomas.Conclusions: The findings suggest that NIDDM is associated with modestly increased risk of sigmoid colon adenomas, and add to evidence that hyperinsulinemia increases colon cancer risk.