Prevalence of mid-gastrointestinal bleeding in patients with acute overt gastrointestinal bleeding: multi-center experience with 1,044 consecutive patients

Background  Video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) enable the detection of small intestinal lesions. Aim  To examine causes of acute overt gastrointestinal (GI) bleeding and the prevalence of mid-GI bleeding, defined as small intestinal bleeding from the ampulla of Vater to the terminal ileum, in a multi-center experience in Japan in the VCE/DBE era. Methods  Data were collected retrospectively from consecutive patients with acute overt GI bleeding in ten participating hospitals. All patients were examined by esophagogastroduodenoscopy and/or colonoscopy. When the source of bleeding was not identified after these procedures, patients suspected to have mid-GI bleeding were referred to our hospital and VCE/DBE was performed to determine the source of bleeding. Results  Of the 1044 patients with acute overt GI bleeding, 524 (50.2%) patients were diagnosed with upper GI bleeding, 442 (42.3%) with lower GI bleeding, and 13 (1.2%) with mid-GI bleeding. Gastric ulcer was the most common cause of bleeding (20.4%). Among cases of mid-GI bleeding, ulcers were found in 4 (30.8%) patients, erosions in 3 (23.1%), angiodysplasia in 3 (23.1%), submucosal tumor in 2 (15.4%), and hemangioma in one (7.7%). Seven lesions were located in the jejunum, 5 in the ileum, and one in both the jejunum and ileum. Analysis of age-related cause showed that the prevalence of mid-GI bleeding among younger patients under 40 years of age was higher (5%) than in other age groups (1–2%). Conclusion  mid-GI bleeding is rare among Japanese patients with acute overt GI bleeding.     

Sonic hedgehog relates to colorectal carcinogenesis

Aim

The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum.

Methods

Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group.

Results

Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression.

Conclusion

This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.     

Effect of aripiprazole, risperidone, and olanzapine on the acoustic startle response in Japanese chronic schizophrenia

Background  

Studies have also shown that differences in the kind of the antipsychotics influenced disruption of the sensorimotor gating system, including prepulse inhibition (PPI), acoustic startle reflex (ASR), and habituation (HAB). We investigated the influence on startle response in chronic schizophrenia in 20 patients with schizophrenia taking risperidone, 21 patients with schizophrenia taking olanzapine, and 20 patients with schizophrenia taking aripiprazole.     

Intranasal administration of adjuvant‐combined vaccine protects monkeys from challenge with the highly pathogenic influenza A H5N1 virus

The effectiveness in cynomolgus macaques of intranasal administration of an influenza A H5N1 pre‐pandemic vaccine combined with synthetic double‐stranded RNA (polyI/polyC12U) as an adjuvant was examined. The monkeys were immunized with the adjuvant‐combined vaccine on weeks 0, 3, and 5, and challenged with the homologous virus 2 weeks after the third immunization. After the second immunization, the immunization induced vaccine‐specific salivary IgA and serum IgG antibodies, as detected by ELISA. The serum IgG antibodies present 2 weeks after the third immunization not only had high neutralizing activity against the homologous virus, they also neutralized significantly heterologous influenza A H5N1 viruses. The vaccinated animals were protected completely from the challenge infection with the homologous virus. These results suggest that intranasal immunization with the Double stranded RNA‐combined influenza A H5N1 vaccine induce mucosal IgA and serum IgG antibodies which could protect humans from homologous influenza A H5N1 viruses which have a pandemic potential. J. Med. Virol. 82:1754–1761, 2010. © 2010 Wiley‐Liss, Inc.     

Medial frontal cortex perfusion abnormalities as evaluated by positron emission tomography in women with climacteric symptoms

OBJECTIVE: To identify functional changes in the brains of women with climacteric symptoms. Images of regional cerebral blood flow (rCBF) were compared statistically between women with and women without symptoms to identify changes in rCBF. Results may provide a better understanding of the neural basis of the symptoms, which are divided into three symptom clusters: vasomotor, psychological, and somatic. DESIGN: The study participants consisted of 12 women with moderate to severe climacteric symptoms (age 47.5 +/- 5.9 years, mean +/- SD) and 7 women with no symptoms (control group; age 49.6 +/- 4.2 years, mean +/- SD). The study participants were patients at a menopause clinic, and the latter were healthy volunteer nurses and hospital staff. Climacteric symptoms were evaluated by an assessment of the severity of 17 symptoms immediately before positron emission tomography examination of rCBF. The symptoms had been used previously to generate the Kupperman Kohnenki Shogai Index, a modified Kupperman Menopausal Index adapted to Japanese women. rCBF was measured by positron emission tomography with the CO2 dynamic inhalation method. RESULTS: Reductions in relative rCBF in the patient group were observed in the bilateral rectal gyrus and in the left subcallosal gyrus on a voxel-by-voxel basis as compared with the control group. CONCLUSIONS: The present study revealed reductions in relative rCBF of the prefrontal cortex of Japanese women with moderate to severe climacteric symptoms. This area is close to that previously addressed in studies of familial bipolar depression and familial unipolar depression, although our participants did not satisfy criteria for depression. This reduction of rCBF may be related to the three climacteric symptom clusters, but further studies are needed for evaluation of its significance. Our results should stimulate investigations into the positron emission tomography rCBF change of these women as to the integration of multiple entities in climacteric symptoms.     

Porcine dentin matrix protein 1: gene structure, cDNA sequence, and expression in teeth

Dentin matrix protein 1 (DMP1) is an acidic non-collagenous protein that is necessary for the proper biomineralization of bone, cartilage, cementum, dentin, and enamel. Dentin matrix protein 1 is highly phosphorylated and potentially glycosylated, but there is no experimental data identifying which specific amino acids are modified. For the purpose of facilitating the characterization of DMP1 from pig, which has the advantage of large developing teeth for obtaining protein in quantity and extensive structural information concerning other tooth matrix proteins, we characterized the porcine DMP1 cDNA and gene structure, raised anti-peptide immunoglobulins that are specific for porcine DMP1, and detected DMP1 protein in porcine tooth extracts and histological sections. Porcine DMP1 has 510 amino acids, including a 16-amino acid signal peptide. The deduced molecular weight of the secreted, unmodified protein is 53.5 kDa. The protein has 93 serines and 12 threonines in the appropriate context for phosphorylation, and four asparagines in a context suitable for glycosylation. Dentin matrix protein 1 protein bands with apparent molecular weights between 30 and 45 kDa were observed in partially purified dentin extracts. In developing teeth, immunohistochemistry localized DMP1 in odontoblasts and the dentinal tubules of mineralized dentin and in ameloblasts, but not in the enamel matrix.     

Change of excitability in brainstem and cortical visual processing in migraine exhibiting allodynia

BACKGROUND: Clinical and neurophysiological manifestations of information processing associated with central sensitization are little known. Allodynic migraine (AM) can be caused by the sensitization of trigeminal neuron, but no study has reported on AM between attacks using blink reflex (BR) and pattern-reversal visual evoked potentials (PVEPs). OBJECTIVE: We explored the characteristics of AM between attacks associated with central sensitization using BR and PVEP. METHODS: We recruited 13 patients with interictal AM and 15 patients with nonallodynic migraine (NA), and 30 healthy subjects (HS). BRs were obtained using paired pulses delivered at the interstimulus interval (ISI) of 150, 300, and 500 ms. The ratio of the area in the R2 of the second to R2 of the first shock was measured for each ISI. PVEP were recorded with 2 spatial frequencies (0.5 and 4.0 cpd) and 2 low and high contrasts (29% and 98%, respectively). Amplitudes of P100 were measured. RESULTS: For BR, there were no significant differences in the ratio of the area of the R2 between the sides of stimulation, and the sides of headache. AM patients had less suppression of the R2 at the ISI of 150 and 300 ms when compared with the NA patients and HS. For PVEP, at 0.5, there were significant differences of amplitude between AM patients and HS, and between NA patients and HS in low and high contrast. At 4.0 cpd, there were significant differences of amplitude between AM patients and HS in low contrast, and between AM patients and HS, and NA patients and HS in high contrast. In AM patients, there was a significant difference of amplitude ratio between 0.5 and 4.0 cpd. Conclusions.-Our BR and PVEP study showed that migraine patients exhibiting allodynia may show central sensitization of brainstem trigeminal neuron and have contrast modulating dysfunction during the cortical visual processing of striate and extrastriate on visual cortex in-between attacks.     

Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia-reperfusion injury

OBJECTIVE: Ischemia-reperfusion injury is known to cause organ failure, but the mechanisms of pathogenesis remain unclear. Inflammation is a factor in tissue destruction in ischemia reperfusion injury, and interleukin (IL)-1 is a key promoter of inflammation. DESIGN: Prospective, randomized, and controlled study. SETTING: University laboratory. SUBJECTS: Male mice 6-8 wks of age, in which genes for IL-1alpha and IL-1beta (IL-1alpha/beta deficient) and IL-1 receptor antagonist (IL-1RA deficient) are deleted by homologous recombination, and wild-type controls on a Balb/c background. INTERVENTIONS: In this study, the role of IL-1 on inflammatory cascades, including chemokine expression, inflammatory cell infiltration, and tissue destruction, was investigated in 45 mins of unilateral renal ischemic injury using IL-1alpha/beta-deficient mice and IL-1RA-deficient mice. In addition, the effects of IL-1 on chemokine expression in cultured tubular epithelial cells were investigated. MEASUREMENTS AND MAIN RESULTS: In vivo study revealed that the number of interstitial infiltrated neutrophils and macrophages, which accompanied the increase of the serum levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-1alpha, respectively, significantly increased in IL-1RA-deficient mice. The number of interstitial infiltrated neutrophils correlated well with serum levels of KC at 24 hrs after reperfusion, whereas the number of interstitial infiltrated macrophages correlated well with the serum levels of MIP-1alpha and monocyte chemoattractant protein (MCP)-1 at 24 and 48 hrs after reperfusion, respectively. Likewise, in vitro study revealed that stimulation of tubular epithelial cells by IL-1beta and/or H2O2 sequentially induced KC, MIP-1alpha, and MCP-1 in both protein and messenger RNA levels, which is consistent with in vivo results. CONCLUSION: IL-1-dependent inflammatory cascades, followed by inflammatory cell infiltration and subsequent tissue destruction, may affect pathogenesis of renal ischemia-reperfusion injury.