Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study.

BACKGROUND: Previous studies showed that 5 µg of ramosetron, a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist, is only effective in male patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D). We hypothesized that either dose 1.25, 2.5, or 5 µg of ramosetron would be effective in female patients with IBS-D. METHODS: This randomized, double-blind, placebo-controlled, phase II dose-finding exploratory trial included 409 female outpatients with IBS-D treated in Japan. They were administered oral placebo (n=102), or 1.25 µg (n=104), 2.5 µg (n=104), or 5 µg (n=99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rates of global improvement of IBS symptoms in the first month. Secondary endpoints included global improvement in the other months, abdominal pain/discomfort, weekly mean changes in the Bristol Stool Form Scale (BSFS), and IBS-QOL. KEY RESULTS: Middle dose (2.5 µg) of ramosetron significantly improved abdominal pain/discomfort at second month (62.5%, P=.002), third month (60.6%, P=.005), and the last evaluation point (63.5%, P=.002) and weekly BSFS (P<.05) except at Week 8, 11, and 12 than placebo. IBS-QOL did not change. Ramosetron induced more constipation than placebo. CONCLUSIONS & INFERENCES: The trial suggested that 2.5 µg of ramosetron is the most effective and least harmful option for treating female patients with IBS-D (Clinicaltrials.gov ID: NCT01274000).

Branched-chain amino acids supplementation attenuates the accumulation of blood lactate dehydrogenase during distance running.

AIM: We investigated the effect of branched-chain amino acids (BCAA) supplementation on tissue damage during distance running. METHODS: Eight male distance runners (mean +/- standard deviation; age: 20.4+/-1.2 years, body weight: 58.4+/-4.2 kg) participated in a double blinded cross over designed study conducted during training camp. During each intervention period, the subjects were asked to participate in a 25-km run, and the blood BCAA and lactate dehydrogenase (LDH) level, an index of tissue damage, were measured pre- and post-run. Either a drink containing BCAA (0.4% BCAA in a 4% carbohydrate solution) or an iso-calorie placebo drink was provided to the subjects 5 times during the run without any restriction in the volume. RESULTS: The total volume of the drink consumed by the subjects did not differ substantially between the trials: 591+/-188 (2.36 g BCAA) vs 516+/-169 mL in BCAA and placebo trial, respectively. During the run, the blood BCAA concentration was maintained in the BCAA trial. However, the blood BCAA concentration level tended to decrease in the placebo trial (P<0.1). The extent of the blood LDH increase in the BCAA trial was significantly less than that of the placebo trail (48% vs 58%, P<0.05). CONCLUSION: Maintaining the blood BCAA level throughout a long distance run contributes to a reduction in the LDH release and, therefore, the effect of BCAA supplementation is suggested to reduce the degree of muscle damage.

The high integration and differentiation potential of autologous neural stem cell transplantation compared with allogeneic transplantation in adult rat hippocampus.

Cell therapy is thought to have a central role in restorative therapy, which aims to restore function to the damaged nervous system. The purpose of this study was to establish an autologous neural stem cell (NSC) transplantation model using adult rats and to compare survival, migration, and differentiation between this system and allogeneic NSC transplantation. Furthermore, we compared the immunologic response of the host tissue between autologous and allogeneic transplantation. NSCs were removed from the subventricular zone of adult Fischer 344 rats using stereotactic methods. NSCs were expanded and microinjected into normal hippocampus in the autologous brain. Allogeneic NSC (derived from adult Wistar rats) transplantation was performed using the same procedure, and hippocampal sections were analyzed immunohistologically 3 weeks post-transplantation. The cell survival and migration rate were higher for autologous transplantation than for allogeneic transplantation, and the neuronal differentiation rate in the autologous transplanted cells far exceeded that of allogeneic transplantation. Furthermore, there was less astrocyte and microglia reactivity in the host tissue of the autologous transplantation compared with allogeneic transplantation. These findings demonstrate that immunoreactivity of the host tissue strongly influences cell transplantation in the CNS as the autologous transplantation did not induce host tissue immunoreactivity; the microenvironment was essentially maintained in an optimal condition for the transplanted cells.

Induction of vasculogenesis in breast cancer models.

Recently, there have been reports of postnatal vasculogenesis in cases of ischaemia models. The aim of the present study is to provide evidence of postnatal vasculogenesis in breast-cancer-bearing mice. Based on cell surface antigen expression, we isolated endothelial precursor cells from bone marrow, peripheral blood and tumour-infiltrating cells from mice that had received six human breast cancer xenografts. In all three areas (bone marrow, peripheral blood and tumour-infiltrating cells), endothelial precursor cell population was elevated in all transplanted mice. Differentiation and migration activities of endothelial precursor cells were measured by comparing levels of the endothelial precursor cell maturation markers Flk-1, Flt-1, Tie2, VE-cadherin and CD31 among these three areas. The endothelial precursor cell population was 14% or greater in the gated lymphocyte-size fraction of the inflammatory breast cancer xenograft named WIBC-9, which exhibits a hypervascular structure and de novo formation of vascular channels, namely vasculogenic mimicry (Shirakawa et al, 2001). In vitro, bone marrow-derived endothelial precursor cells from four human breast cancer xenografts proliferated and formed multiple clusters of spindle-shaped attaching cells on a vitronectin-coated dish. The attaching cells, which incorporated DiI-labelled acetylated low-density lipoprotein (DiI-acLDL) and were negative for Mac-1. The putative bone marrow derived endothelial precursor cell subset, which was double positive of CD34 and Flk-1, and comparative bone marrow derived CD34 positive with Flk-1 negative subset were cultured. The former subset incorporated DiI-acLDL and were integrated with HUVECs. Furthermore, they demonstrated significantly higher levels of murine vascular endothelial growth factor and interleukin-8 in culture supernatant on time course by enzyme-linked immunosorbent assay. These findings constitute direct evidence that breast cancer induces postnatal vasculogenesis in vivo.

Effect of resistive knee extension training on postural control measures in middle aged and elderly persons.

The purpose of the present study was to determine whether knee extension strength gain in middle-aged and elderly persons is associated with improvement in the limits of stability when leaning his/her body in various directions. The resistance training group (EXT; 4 males, 17 females) completed two bilateral knee extension training sessions, consisting of one set of exercises, per week for 10 weeks. The non-training control group (CONT; 4 males, 3 females) were instructed not to train their legs during the 10-week control period. One set of exercises consisted of 8-12 repetitions of a dynamic resistance exercise until volitional fatigue for knee extension. The initial load for training was set at 70% of the one-repetition maximum (1-RM). The thickness of the rectus femoris (RF) and vastus lateralis (VL) muscles were measured using a B-mode ultrasound apparatus. The postural control measures, obtained using the Balance Master system, included the percentage limits-of-stability (%LOS) and path length (%Path). The 1-RM in EXT was increased significantly by resistance training (p < 0.001). In addition, significant differences were observed between the percentage increase of 1-RM in EXT and those in CONT at wk 5 and at wk 10 of resistance training (p < 0.001). However, no significant increase in muscle thickness of RF or VL was found in EXT. The %LOS to the rear target in EXT was increased significantly by resistance training (p < 0.05-0.01). In addition, the percentage change in %Path was decreased significantly by resistance training (p < 0.001). Therefore, strength gain in quadriceps femoris appears to be associated with improvement in the %LOS and %Path for the rear. In conclusion, strength gain in quadriceps femoris is thought to possibly enable accurate movement of the COG farther from the center target towards the rear, suggesting that strength gain has a positive influence on a person's perception of their ability to avoid falls.

Gliosarcoma of the posterior cranial fossa: MRI findings.

We report the MR findings of a biopsy-proven gliosarcoma of the posterior cranial fossa. Multiple homogeneously enhancing lesions had shaggy margins and broad-based dural attachments, which may reflect the gliomatous and sarcomatous element of this tumour.

Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations.

We have examined the associations between levels of plasma apolipoprotein (apo) AI, apo CIII and apo AIV and genetic variation in the apo AI-CIII-AIV gene cluster in 162 boys and young men from Belgium aged from 7 to 23 years. Genotypes were determined for six restriction enzymes XmnI, PstI, SstI, PvuIIA-CIII, PvuIIB-AIV and XbaI, and for the G to A substitution at -75 bp in the 5' region of the apo AI gene. The polymorphism most strongly associated with apo AI levels was the G to A substitution (P = 0.025, R2 x 100 = 3.6%) confirming previous observations. The polymorphism most strongly associated with apo CIII levels was that of PvuIIA-CIII (P = 0.023, R2 x 100 = 2.9%) in the apo CIII gene. This novel association must be interpreted with caution until it has been confirmed in an independent sample. The polymorphism associated with the largest effect on apo AIV levels was that detected with XbaI in the apo AIV gene, but this association was not statistically significant. Previously reported associations between the SstI polymorphism and triglyceride levels, and between the PstI polymorphism and apo AI levels, were weakly detected in the present sample. Our results show that variation associated with some of the polymorphisms in the apo AI-CIII-AIV cluster makes a small, but statistically significant, contribution to the determination of apo AI and apo CIII levels in this sample of young men and boys. These observations may, in part, explain reported associations between polymorphisms in this gene cluster, differences in plasma lipid and lipoprotein levels, and prevalence of coronary artery disease.

Intracranial chondrosarcoma--case report.

The authors report the case of a 54-year-old male who was found to have a large intracranial chondrosarcoma at the site from which chondromas had been partially removed twice, 6 and 10 years previously. On the third admission, the second through tenth and the twelfth cranial nerves on the right side were involved. Computed tomographic scans showed a large mass in the right middle and posterior fossae and the right ethmoid sinus. Angiography demonstrated an extradural mass in the right middle fossa. The tumor in the middle and posterior fossae was subtotally removed, and second, third, and eighth cranial nerve function improved postoperatively. Histological examination of tumor specimens showed active proliferation of poorly differentiated cartilagenous cells, suggestive of sarcomatous transformation of the pre-existing chondroma. It is emphasized that chondromas should be removed as completely as possible and that patients must be followed carefully after surgery.

[Cerebral artery occlusion due to blunt cervical trauma].

Three cases are reported in which cerebral infarction developed due to blunt cervical trauma. All of these patients had external signs of cervical trauma and presented focal cerebral ischemic symptoms. Cerebral angiography demonstrated characteristic findings in each case. The first case: A 27 year-old man developed left hemiparesis four days after hitting his neck against a bed rail. Cerebral angiography showed complete occlusion of the right extracranial internal carotid artery 1.5 cm distal to its origin and emboli in distal branches of the right middle cerebral artery. He was treated conservatively. The second case: A 32 year-old man developed disturbance of consciousness with motor aphasia and right hemiparesis a few hours after hitting his chest and neck against baggage hanging from a crane. Cerebral angiography showed complete occlusion of the left middle cerebral artery and no abnormalities of the left internal carotid artery. He was treated with STA-MCA anastomosis two weeks after the accident. The third case: An 84 year-old man, who failed in a suicidal hanging, was semicomatose on admission and had right hemiparesis. Computed tomography demonstrated massive cerebral infarction of the territory of both anterior and left middle cerebral arteries. Cerebral angiography showed linear shadow defect of the left extracranial internal carotid artery corresponding with the site of the ligature. He was treated conservatively. From these angiographic findings, it was thought that intimal tear, intramural hematoma, vasospasm of the internal carotid artery and emboli given might bring about cerebral infarction. In such cases of blunt cervical trauma, cerebral angiography should be undertaken as soon as possible if focal cerebral ischemic symptoms can be seen.(ABSTRACT TRUNCATED AT 250 WORDS)

[Aneurysm growth and enlargement of pre-aneurysmal lesions].

Three patients with cerebral aneurysms newly growing and enlarging for 2 to 10 years are reported. Case 1, a 54-year-old woman, had subarachnoid hemorrhage due to rupture of an intracranial aneurysm, growing from a small residual aneurysmal neck on the left internal carotid artery 10 years after the repair of the aneurysm. Case 2, a 63-year-old man, had a junctional dilatation on the left internal carotid-posterior communicating artery, developing into ruptured aneurysm about 10 years after the first hemorrhage. Case 3, a 52-year-old man, had multiple aneurysms on the bilateral bifurcations of middle cerebral arteries and left anterior cerebral artery-frontopolar artery junction. Angiography 2 years after the repair of the aneurysms revealed the new growth of a small aneurysm on the anterior cerebral artery at the junction of the fronto-orbital artery, developing from a localized vascular dilatation which had been recognized by the preoperative angiography. The existence of pre-aneurysmal lesions in arterial wall and the addition of hemodynamic impingement were thought to be one of the precipitating factors of aneurysmal formation. The pre-aneurysmal lesions in our study are as follows; a small part of thin wall of residual aneurysmal neck, a junctional dilatation, and a small evagination of arterial wall. It is necessary to discriminate a junctional dilatation and a small evagination of arterial wall from a small aneurysm with observation from multiple directions by the preoperative angiographic study. Our observations suggest that preaneurysmal lesions of the cerebral artery may develop into aneurysm and rupture, and hence the follow-up angiography is recommended for the cases with a preaneurysmal lesion or a small aneurysm for many years.