Women seropositive for human immunodeficiency virus type 1 (HIV-1) are at an increased risk for a number of adverse perinatal outcomes. Although efforts to reduce mother-to-child transmission of HIV (MTCT) remain a priority in resource-limited countries, HIV testing and treatment have led to steep declines in MTCT in well-resourced countries. Even so, HIV seropositive pregnant women in the United States continue to deliver a disproportionately high number of preterm and low birth weight infants. In this mini-review, we address the role of the placenta in such HIV-related perinatal sequelae. We posit that adverse perinatal outcomes may result from two mutually non-exclusive routes: (1) HIV infection of the placenta proper, potentially leading to impaired maternal-fetal exchange; and (2) infection of the maternal decidual microenvironment, possibly disrupting normal placental implantation and development. Further research into the relationship between HIV-1 infection and placental pathology may lead to the development of novel strategies to improve birth outcomes among HIV-1 seropositive parturients.

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This report represents a summary of a seminar presentation at Nippon Medical School on September 24, 2012. It is a synopsis of some of our research on trophoblast fusion.

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Macrophages hold a key role in both regulating and executing the body's own immune response under various conditions. Hence, although endometriosis, preeclampsia and abortions are clinically different, all three are regarded to involve highly complex immunological processes. The aim of our current work was to evaluate the role of macrophages within these gynaecological disorders. Macrophages have been shown to invade endometriosis lesions and to mediate propagation of endometriotic cyst growth. However this is the first time that significant GPER up-regulation in macrophages is demonstrated. This highlights a potential alternative way through which estrogen may modulate immune response of macrophages in endometriosis. In addition, during spontaneous miscarriages the macrophage population increases significantly. This deregulation may possibly support an inflammatory scheme further triggering abortive procedures. Macrophage-mediated apoptosis of extravillous trophoblasts (EVT) has been associated with preeclampsia. Larger numbers of apoptotic EVT were detected in preeclamptic placentas compared with normal. In preeclamptic placentas, decidual macrophages were found to be Fas ligand (FasL)-positive. Our results highlight a new aspect of macrophage biology in endometriosis and pregnancy physiology and patho-physiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact. Our data strongly indicate that macrophages hold key roles in various gynaecological disorders and might be crucial to further elucidate their patho-physiology.

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Sleep disorder is a common medical problem. Sleep disorder has been associated with several diseases, including pulmonary disease, gastroesophageal reflux disease (GERD) and fibromyalgia. Interest in sleep phenomenology and gastrointestinal functioning has recently increased, because sleep disorder causes significant morbidity, as evidenced by the increased need for general medical and mental health treatment for emotional problems. A number of studies have found an association between sleep disorders and functional gastrointestinal (GI) disorders. Although arousal from sleep serves several protective roles, such as increase in the speed of esophageal clearance and in airway refluxes to prevent aspiration, awakening from sleep unfortunately induces impairment of sleep quality. Some investigations about the relationship between psychogenic factors and gut motility are controversial. In addition, reports of alterations in gut motility during sleep have also been contradictory. We have evaluated sleep disorder in functional dyspepsia (FD) patients using Pittsburgh Sleep Quality Index (PSQI) score. In our recent data, PSQI score of FD patients was significantly higher compared to that in healthy volunteers. Another study has reported that the distribution of subjects who thought that they got enough sleep was significantly lower for the FD/irritable bowel syndrome (IBS) subjects than for control subjects. Several studies have reported that anti-acid therapy and prokinetic agents are effective for certain FD patients. In addition, previous study has reported tricyclic antidepressants (TCA) drugs are effective for some FD patients. Finally, new drug, actiamide, a muscarinic antagonist and cholinesterase inhibitor, significantly improves Postprandial Distress Syndrome (PDS) symptoms. It might be critical issues for determination of precise mechanism for functional gastrointestinal disorders to clarify the relationship between gut motility and sleep disorders.

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Background and Purpose: Primary brain damage, caused by acute ischemic changes during initial hemorrhage, is an important cause of death and disability following subarachnoid hemorrhage (SAH). However, the mechanism underlying the reduction in cerebral circulation in patients in the acute stage of SAH remains unclear. The goal of this study was to clarify this mechanism with the aid of perfusion computed tomography (CT).
Methods: We prospectively evaluated 21 patients who had been undergone perfusion CT within 3 hours of SAH onset. Mean transit time (MTT) was estimated. Forty circular regions of interest 5 mm in diameter were delineated in the cortical region of the bilateral hemispheres on perfusion CT images. Neurological condition was graded with the Hunt and Hess scale, and initial CT findings were graded with the Fisher scale. We defined a good outcome as a modified Rankin scale (mRs) score of ≤2at 3 months after SAH onset.
Results: Global MTT was an independent predictor of outcome. The global MTT of patients with poor outcomes was longer than that of patients with good outcome. Furthermore, global MTT correlated significantly with Hunt & Hess grades, and disturbances in higher cerebral function.
Conclusion: Hemodynamic disturbances frequently occur after SAH. These abnormalities probably reflect the primary brain damage caused by initial hemorrhage. Perfusion CT is valuable for detecting hemodynamic changes in the acute stages of SAH.

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Background: Hemodialysis is a treatment in which uremic toxins and excess water content are removed from the blood with a dialyzer and dialysis fluid. The efficiency of hemodialysis is strongly influenced by the following 3 parameters: the blood flow rate (Q_B), the dialysis fluid flow rate (Q_D), and the overall mass transfer area coefficient (K₀A), an index of a dialyzer's performance. The flow ratio (Q_B : Q_D) to obtain a well-balanced dialysis efficiency is generally said to be 1 : 2. In Japan, the Q_B is controlled independently (from 200 to 250 mL/min) depending on individual conditions. However, the Q_D is usually set at around 500 mL/min regardless of the Q_B.
Materials and Methods: To investigate the effect on dialysis efficiency of decreasing the Q_D from 500 to 400 mL/min, 12 patients were divided into two groups: one in which the Q_B was 150 mL/min, with 1.3-m² membranes; and another in which the Q_B was 200 mL/min, with 1.6-m² membranes. We defined the conditions with the Q_D of 500 mL/min as condition A, and that with the Q_D of 400 mL/min as condition B. Each operating condition was assigned for 2 weeks as crossover trials. To evaluate solute removal, we calculated clearance, reduction rate, removal amount, clear space, the clear space rate, and albumin leakage. Furthermore, when dialysis efficiency decreased in condition B, we performed a supplementary test: we calculated the Q_B with the K₀A equation to achieve a dialysis efficiency equivalent to that in condition A, defined as condition B', as the operating condition with the calculated Q_B and a Q_D of 400 mL/min, and re-evaluated.
Results: In condition B, a Q_B of 150 mL/min had no effect on the dialysis efficiency;whereas with a Q_B of 200 mL/min, slight yet significant differences were observed in the clearance of small molecular weight solutes. Condition B' (Q_B=210 mL/min) showed an equivalent or greater dialysis efficiency and demonstrated an association with theoretical values.
Conclusions: In hemodialysis, the flow ratio (Q_B : Q_D) should be maintained at 1 : 2 to obtain a well-balanced dialysis efficiency. The present study has shown that the Q_D can be decreased while maintaining this flow ratio. A well-balanced Q_D setting can be financially and environmentally conscious. In addition, use of the K₀A equation is a highly effective method to calculate a Q_B that allows an expected dialysis efficiency to be achieved in case the Q_D needs to be decreased uniformly, as when dialysis fluid is in short supply during times of disaster.

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Background: Dexmedetomidine has shown beneficial effects in several inflammatory models, including ischemia-reperfusion injury (IRI). This study investigated whether the continuous infusion of dexmedetomidine could improve renal IRI in rats.
Methods: Rats were subjected to either a sham operation and given pentobarbital (10 mg/kg/h; n=6) or were subjected to 45 minutes of renal ischemia and anesthetized with pentobarbital (10 mg/kg/h; n=6), dexmedetomidine (10 or 20 μg/kg/h; both n=6), or both pentobarbital (10 mg/kg/h) and dexmedetomidine (1.0 μg/kg/h; n=6) for 6 hours of reperfusion. Blood urea nitrogen and serum creatinine were measured 6 hours after reperfusion. Gene expression mediated by inflammatory systems in the kidney was measured with the real-time reverse-transcriptase polymerase chain reaction.
Results: Treatment with 10 or 20 μg/kg/h of dexmedetomidine reduced renal dysfunction. The increases in the messenger RNA expression of interleukin-6, intercellular adhesion molecule 1, and inducible nitric oxide synthase caused by renal IRI were suppressed. Under In rats under pentobarbital anesthesia, 1.0 μg/kg/h of dexmedetomidine also improved renal dysfunction after renal IRI.
Conclusion: The present study demonstrates that continuous infusion of dexmedetomidine improves renal IRI. Moreover, with pentobarbital anesthesia, a dose of dexmedetomidine lower than the sedative dose also improves renal IRI.

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Introduction: Human serum (HS) has attributes similar to fetal bovine serum (FBS) in the proliferation and differentiation of human adipose-derived stem cells (hASCs) when compared in vitro. The purpose of this study was to determine what types of HS, with respect to the concentrations of endogenous growth factors, could be made available for hASC proliferation.
Methods: HS was collected from 2 groups of healthy donor (freshly isolated HS [n=9], and HS preserved for 4 years [n=7]). All sera were isolated with a Cellaid^® HS isolation device (JMS Co., Ltd, Hiroshima, Japan) and then classified into 3 groups based on the concentrations (high, middle, and low) of platelet-derived growth factor (PDGF)-AB, PDGF-BB, and transforming growth factor-beta 1 (TGF-β1) by means of enzyme-linked immunoassay screening. The hASCs were isolated from subcutaneous fat using a collagenase enzymatic digestion process and were cultured in control media, each supplemented with HS from a different group. Cell numbers were counted on days 2, 4, 7, and 14, and the relationship between cell proliferation and the level of each growth factor was investigated.
Results: The proliferation of hASCs correlated with the concentration of each growth factor. The cut-off points for PDGF-AB, PDGF-BB, and TGF-β1 in HS [necessary for hASC proliferation when compared with FBS] were 10 ng/mL, 1.5 ng/mL, and 15 ng/mL, respectively. There was no correlation between the storage period of HS and the proliferation potential of hASCs.
Conclusions: These results suggest that the effectiveness of HS on hASC proliferation depends on the concentrations of endogenous PDGFs. In addition, the Cellaid^® device used in this study allows the simultaneous release of several growth factors from platelets, and our results have shown that it can be used to collect HS for future hASC-based therapies.

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Background: Frey's procedure might be a good alternative to pylorus-preserving pancreaticoduodenectomy (PPPD) for patients with an inflammatory mass of the head of the pancreas, because it is technically easy and associated with low morbidity and good pain relief.
Purpose: To analyze the short-term and long-term outcomes of Frey's procedure in comparison with PPPD and to evaluate the efficacy of Frey's procedure against preoperative locoregional complications.
Patients and Methods: From August 1997 through December 2007, 6 patients underwent Frey's procedure (as described by Frey and Smith), and 10 patients underwent PPPD. The mean follow-up times were 70.8 months (Frey's procedure) and 119.8 months (PPPD). Preoperative biliary stricture and duodenal stenosis were observed in 4 and 3 patients, respectively, of patients undergoing Frey's procedure. Pain intensity was assessed with a pain scoring system. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of-Life Questionnaire-Core 30. Exocrine and endocrine pancreatic function was measured during follow-up.
Results: Significant reductions in total pain scores and all QOL scale scores were observed immediately after surgery in all patients (P<0.05). Frey's procedure was superior to PPPD with regard to physical status 7 years after surgery (P<0.05). One patient in the Frey group had a grade B pancreatic fistula, and 2 patients in the PPPD group had intra-abdominal bleeding and delayed gastric emptying. There were no re-operations or surgery-related deaths in either group. Diabetes developed postoperatively in 2 patients in the PPPD group. No patients with preoperative duodenal or biliary stricture or both had a relapse. Three patients in the PPPD group died during follow-up of diseases unrelated to chronic pancreatitis.
Conclusion: Frey's procedure is safe and effective with regard to pain relief, preservation of pancreatic function, and improvement of QOL over the long term. Moreover, this procedure can also be used to treat preoperative biliary stricture and duodenal stenosis associated with an inflammatory mass of the pancreatic head.

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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal disorder characterized by chronic complement-mediated hemolysis. The humanized anti-C5 antibody eculizumab binds to the C5 protein and suppresses hemolysis by inhibiting C5b-9 generation. Here, we report on a 27-year-old woman who was found to have PNH in 1997 (at 13 years of age), without subsequent transfusions, thrombosis, or renal disorder. She had been experiencing frequent malaise and fatigue and was sometimes unable to participate in social activities. She had also experienced repeated hemolytic episodes due to infection, and the hemoglobin level had decreased from 7.0 to 5.0 g/dL several times since February 2010. Red blood cell transfusion was necessary, and 6 months later, treatment with eculizumab was started. The hemoglobin level stabilized, and the patient became transfusion-independent. Furthermore, the patient showed significant improvements in fatigue scale scores and quality of life. Six months after the start of eculizumab therapy, the percentage of PNH-type red blood cells was found to have increased from 82.0% (1.95 × 10¹² cells/L) to 89.1% (2.78 × 10¹² cells/L). Furthermore, during treatment with eculizumab, intravascular hemolysis occurred due to a viral infection accompanied by a high fever. We also observed a persistent elevation in reticulocytes and total bilirubin levels, as well as a persistent reduction in haptoglobin levels. Extravascular hemolytic findings were also observed. Because treatment with eculizumab was started at a young age (27 years) and will be continued for many years, careful observation of the patient is required.

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We report a choledochal cyst that was successfully treated with laparoscopic surgery. A 32-year-old Japanese woman was referred to our hospital with a suspected choledochal cyst. Magnetic resonance cholangiopancreatography and computed tomography showed the common bile duct to be grossly dilated to the hepatic confluence. A diagnosis of type-Ia choledochal cyst in the Todani classification was made, and laparoscopic resection was performed. The patient was placed in the lithotomy position under general anesthesia, and 4 ports were inserted. After the cystic duct was dissected, the hepatoduodenal ligament was incised and a choledochal cyst was identified. Next, the common bile duct was mobilized and dissected away from the surrounding vessels and tissues. Taping of the common bile duct allowed better exposure and dissection of the surrounding tissues. Mobilization of the bile duct and dissection of the surrounding tissue was performed to the bifurcation of the common hepatic duct. Then the common hepatic duct was transected just distal to the choledochal cyst. The inferior common bile duct was dissected from the pancreas to identify the distal end of the choledochal cyst and the pancreaticobiliary junction behind the duodenum. The narrow segment of the choledochal cyst was identified and divided after distal closure with clips. After the gall bladder was dissected from the liver bed, the choledochal cyst and gallbladder were removed. A Roux limb was created extracorporeally via the umbilical incision. The jejunum 30 cm distal to the ligament of Treitz was removed through the transumbilical incision and transected. To create the Roux limb, the mesentery of the jejunum was also extracorporeally separated. A 50-cm Roux limb was made by means of side-to-side anastomosis with an endostapler. After a jejunostomy for hepaticojejunostomy anastomosis was created, the Roux limb was returned to the abdominal cavity. Then, pneumoperitoneum was started again, and the Roux limb was brought up laparoscopically in a retrocolic fashion. An end-to-side hepaticojejunostomy was intracorporeally established with a continuous, single-layer full-thickness 4-0 vicryl suture. Total operation time was 715 minutes. Intraoperative body fluid loss was 250 mL, and the postoperative course was uneventful with no major complications. The patient was discharged from hospital on the 12th postoperative day. She remains asymptomatic with normal liver function after 24 months of follow-up.

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We report a rare case of adenocarcinoma of the minor papilla of the duodenum treated with transduodenal minor papillectomy. A 64-year-old woman was treated for an asymptomatic duodenal tumor detected on gastroduodenoscopy. Endoscopy showed a 15-mm sessile mass in the descending duodenum proximal to the major papilla. The major papilla was a villous 24-mm-diameter polypoid tumor. Histopathologic examination of the biopsy specimen showed tubular adenoma with moderate epithelial atypia. Transduodenal major and minor papillectomies were performed. The orifice of the duct of Santorini and the pancreatic duct were re-approximated to the duodenal wall to prevent acute pancreatitis caused by scarring and stenosis of the duct orifice. Histological findings were consistent with well-differentiated adenocarcinoma limited to the minor duodenal papilla, without infiltration of the duodenal wall submucosa, and confirmed complete resection. The patient had an uneventful postoperative course and has remained asymptomatic, without evidence of tumor recurrence or stenosis of the pancreatic duct orifice, for 4 years.

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