Spontaneous Regression of Recurrent Undifferentiated Carcinoma of the Endometrium.

We herein report a very rare case of spontaneous regression of recurrent undifferentiated carcinoma of the endometrium. An 80-year-old woman had undergone total hysterectomy with bilateral adnexectomy for undifferentiated carcinoma of the endometrium. The cancer recurred locally 10 months after surgery and then metastasized to the lung and liver. After she and her family elected to receive supportive care without active treatment, the local recurrences dramatically decreased, and the metastases of the lung, liver, and peritoneum also disappeared. This case showed that spontaneous regression can occur even with malignant tumors showing an extremely poor prognosis, such as undifferentiated carcinoma of the endometrium.

A Victim of the Great East Japan Earthquake Identified with the Preserved Medical Samples of Her Deceased Mother.

On March 11, 2011, a magnitude 9.0 earthquake and huge tsunami occurred near the Pacific coast of northeast Japan, in which more than 18,000 people died or went missing and more than 120,000 buildings were destroyed. In Taro district, one of the areas struck hardest by the tsunami, a middle-aged woman was found deceased in the rubble. Generally, a family physician can recognize victims based on their appearance; the place where they were found; their home or work address; their belongings; the identifying marks on their clothes; their dental charts; and their living biological parents, children, or multiple siblings through DNA analysis. However, in this case, the middle-aged woman remained the area's sole unidentified person for months, because her appearance was different, her body was slightly swollen, and she was missing some teeth. The district's medical and dental facilities were destroyed and almost all medical records and dental charts lost. Fortunately, a family physician who had worked in the district for many years survived the disaster, and was available to provide background information about the victim, her family, and their relationship. He recalled the existence of tissue samples of her mother who had died several years earlier. Subsequently, the individual was identified through the DNA analysis of her blood and mother's tissue samples. As demonstrated in the case, appropriately managed medical information and samples from previously deceased relatives can aid disaster victim identification. The destruction caused by the Great East Japan Earthquake forms our investigation's background.

Recommendation of Repeated Ammonia Tests for Intrahepatic Portal-Systemic Shunt Without Cirrhosis in Elderly Patients With Psychiatric Symptoms.

We report an elderly male patient with hyperammonemia induced by intrahepatic portal-systemic shunt without cirrhosis (IPSSwoC). The occasional emergence of his erratic behaviors was misdiagnosed as a psychiatric disorder. Regardless of his uneven symptoms, IPSSwoC was suspected due to his hyperammonemia. The contrast computed tomography of the abdomen revealed a congenital type of IPSSwoC. As blood ammonia levels are inconstant, repeated blood tests are recommended when this disease is suspected in elderly patients with psychiatric symptoms.

Improving the Quality of Postgraduate Education in Traditional Japanese Kampo Medicine for Junior Residents: An Exploratory Survey Conducted in Five Institutions in the Tohoku Area.

Traditional Japanese (Kampo) medicine has been widely applied in general medicine in Japan. In 2001, the model core curriculum for Japanese medical education was revised to include Kampo medicine. Since 2007, all 80 Japanese medical schools have incorporated it within their programs. However, postgraduate training or instruction of Kampo medicine has not been recognized as a goal for the clinical training of junior residents by Japan's Ministry of Health, Labour and Welfare; little is known about postgraduate Kampo medicine education. This exploratory study investigated attitudes about Kampo medicine among junior residents in Japanese postgraduate training programs. A questionnaire survey was administered to junior residents at five institutions in the Tohoku area of Japan. Questions evaluated residents' experiences of prescribing Kampo medicines and their expectations for postgraduate Kampo education and training. As a result, 121 residents responded (response rate = 74%). About 96% of participants had previously received Kampo medicine education at their pre-graduate medical schools and 64% had prescribed Kampo medications. Specifically, daikenchuto was prescribed to prevent ileus and constipation after abdominal surgery and yokukansan was prescribed to treat delirium in the elderly. Residents received on-the-job instruction by attending doctors. Over 70% of participants indicated that there was a need for postgraduate Kampo medicine education opportunities and expected lectures and instruction on how to use it to treat common diseases. In conclusion, we have revealed that junior residents require Kampo medicine education in Japanese postgraduate training programs. The programs for comprehensive pre-graduate and postgraduate Kampo education are expected.

Questionnaire-Based Development of an Educational Program of Traditional Japanese Kampo Medicine.

Traditional Japanese Kampo medicine has been widely used in clinical practice in Japan. Though it is a compulsory subject in Japanese medical schools, a standard educational program in Kampo medicine does not exist. Tohoku University has incorporated Kampo medicine into clinical education via didactic lectures since 2003; however, student evaluations have been lower for Kampo than for all other clinical specialties. We administered a questionnaire about a Kampo medicine course for fifth-year students from 2009 to 2012 and developed an educational program based on feedback obtained. The questionnaire consisted of nine questions (a clear training plan; opportunities for learning, practice, and patient contact; acquisition of medical knowledge and physical examination; learning professionalism; understanding the specialty; overall assessment) that were rated on a 5-point Likert scale along with open-ended questions about the course's strengths and weaknesses. The students responded to the questionnaire after clinical practice in Kampo medicine and other clinical specialty courses. Scores for Kampo medicine and the average of other clinical specialties were compared. All 389 students who participated in Kampo clinical practice answered the questionnaire. In 2009, scores for Kampo medicine for nine questions were lower than for the average of the other clinical specialties. After curriculum reformation involving hands-on training in 2012, all scores except "opportunities to learn about clinical cases" and "opportunities to practice involvement" were higher than the average of all other clinical specialties. In conclusion, we have successfully developed a Kampo medicine educational program for our university through this survey study.

Candidemia from an upper urinary tract infection complicated by candida endophthalmitis.

A 51-year-old Japanese woman developed candidemia as an outpatient secondary to a Candida albicans upper urinary tract infection complicated by previously undiagnosed type 2 diabetes mellitus with poor glycemic control and ureterolithiasis. The patient did not have any risk factors typically associated with candidemia, such as an indwelling vascular catheter, parenteral nutrition or broad-spectrum antibiotic use. During the clinical course, her condition was complicated by unilateral candida endophthalmitis, which progressed despite the administration of systemic antifungal agents and ultimately required vitreous surgery. The etiology of candidemia in this patient and the reason she developed progressive ocular symptoms after starting antifungal treatment are reviewed.

The traditional kampo medicine tokishakuyakusan increases ocular blood flow in healthy subjects.

The aim of this study was to examine the effects of oral administration of kampo medical formulas on ocular blood flow (OBF). A crossover protocol was used to randomly administer five grams of yokukansan, tokishakuyakusan (TSS), keishibukuryogan, or hachimijiogan to 13 healthy blinded subjects (mean age: 37.3 ± 12.3 years). The mean blur rate, a quantitative OBF index obtained with laser speckle flowgraphy, was measured at the optic nerve head before and 30 minutes after administration. Blood pressure (BP) and intraocular pressure (IOP) were also recorded. No significant changes were observed in mean BP or IOP after the administration of any of the kampo medical formulas. There was a significant increase in OBF 30 minutes after administration of TSS (100% to 103.6 ± 6.9%, P < 0.01). Next, TSS was administered to 19 healthy subjects (mean age: 32.0 ± 11.0 years) and OBF was measured before and 15, 30, 45, and 60 minutes after administration. Plain water was used as a control. OBF increased significantly after TSS administration compared to control (P < 0.01) and also increased from 30 to 60 minutes after administration compared to baseline (P < 0.05). These results suggest that TSS can increase OBF without affecting BP or IOP in healthy subjects.

The role of integrative medicine and Kampo treatment in an aging society: experience with Kampo treatment during a natural disaster.

BACKGROUND AND OBJECTIVES: After the Great East Japan Earthquake, elderly individuals, who are particularly vulnerable during natural disasters, experienced difficulty while evacuating the area. This report discusses the Kampo treatments provided to elderly individuals in the disaster areas, and the role of integrative medicine and Kampo treatment. METHODS: The changes in symptoms and Kampo treatment contents were summarized using the medical records of treatments provided in the evacuation centers until 10 weeks after the earthquake. RESULTS: Infectious diseases, the common cold and hypothermia were frequently observed in most patients for first two weeks after the disaster. Allergies increased two weeks later, and mental distress was commonly observed six weeks later. We prescribed several Kampo formulas to treat the individual symptoms. DISCUSSION: Many elderly individuals were treated using Western medications, but the symptoms persisted; however, after Kampo formulas were included in the treatment, the symptoms of many patients improved. Unlike Western medications, Kampo formulas warmed the bodies of elderly individuals who often had a reduced basal metabolism and low body temperatures due to exposure to the cold tsunami waters. Therefore, the Kampo formulas may have improved the immunity of those who were under psychological and physical stress because they had spent several days in the evacuation centers. CONCLUSION: Many studies have reported the effectiveness of Kampo formulas. Therefore, the combined usage of both Western and Kampo medicine may be used in a mutually complementary manner, and these combination treatments may play an important role in preserving the victims overall health after natural disasters.

Treatment of posttraumatic stress disorder using the traditional Japanese herbal medicine saikokeishikankyoto: a randomized, observer-blinded, controlled trial in survivors of the great East Japan earthquake and tsunami.

The Great East Japan earthquake and tsunami caused immense damage over a wide area of eastern Japan. Hence, many survivors are at high risk for posttraumatic stress disorder (PTSD). This randomized, observer-blinded, controlled trial examined the efficacy and safety of the traditional Japanese herbal formula saikokeishikankyoto (SKK) in the treatment of PTSD among survivors of this disaster. Forty-three participants with an Impact of Event Scale-Revised (IES-R) score ≥ 25 were randomized into SKK (n = 21) and control (n = 22) groups. The primary endpoint was the change in IES-R scores from baseline till after 2 weeks of treatment. Intergroup statistical comparisons were performed. The magnitude of changes in total IES-R scores differed significantly between the two groups (P < 0.001). Post hoc analysis showed that the total IES-R score improved significantly in the SKK group from 49.6 ± 11.9 to 25.5 ± 17.0 (P < 0.001). Subscale scores improved significantly in the SKK group (avoidance, P = 0.003; hyperarousal, P < 0.001; intrusion, P < 0.001). Two-week treatment with SKK significantly improved IES-R scores among PTSD patients. This traditional medicine may be a valid choice for the treatment of psychological and physical symptoms in PTSD patients.

Molecular characteristics of extended-spectrum ß-lactamase-producing Escherichia coli in Japan: emergence of CTX-M-15-producing E. coli ST131.

We investigated the molecular characteristics of ESBL-producing Escherichia coli in Japan. A total of 101 clinical isolates of ESBL-positive E. coli collected in Japan between June 2008 and November 2009 were studied. Among the 101 strains, 97 were positive for CTX-M, while 47 and two were positive for TEM and SHV, respectively. Sequencing revealed that CTX-M-14 was most common (49/101), followed by CTX-M-27 (22/101) and CTX-M-15 (8/101). Based on MLST data, seven of eight CTX-M-15 producers belonged to ST131. This is the first report about clinical isolates of E. coli ST131 possessing CTX-M-15 in Japan.

Production of lentiviral vectors in protein-free media.

The use of lentiviral vectors for transgene delivery in vitro and in vivo for applications in neuroscience, hematology, developmental biology, stem cell biology, and transgenesis has become commonplace. Lentiviral vectors provide an attractive tool for transgene delivery in part because of their ability to incorporate (integrate) into the genomic DNA of target cells with high efficiency, especially in cells that are not actively dividing. In addition, lentiviral vector-mediated transgene )expression can be maintained for long periods of time. In this unit, we describe protocols for lentiviral vector production in protein-free media using polyethylenimine (PEI)-mediated transfection, resulting in consistent lentiviral vector stocks. Such stocks are then concentrated by ultracentrifugation. We also provide reliable QPCR protocols to titrate lentiviral vectors based on vector DNA copies present in genomic DNA extracted from transduced cells. The vector production and titration protocol described here can be completed within 8 days.

Health care response to the tsunami in Taro District, Miyako City, Iwate Prefecture.

PROBLEM: IN THE TARO DISTRICT (POPULATION: 4434), the great tsunami of 11 March 2011 destroyed the central region including the clinic, the sole medical facility (one physician, 13 nurses and other staff) in the district, and many citizens were forced to live in evacuation centres. CONTEXT: The Taro District experienced massive damage during the tsunamis of 1896 and 1933. Since then countermeasures to tsunamis have been implemented. The great tsunami on 11 March 2011 caused catastrophic damage to the low-lying areas where approximately 2500 people lived; 1609 buildings were completely destroyed, and approximately 200 people died or were missing across the district. ACTION: The Taro National Health Insurance Clinic, the sole medical facility in the Taro District, was required to play a central role in a variety of activities to care for residents in severely affected areas. First of all, evacuees needed to move to neighbouring hospitals or safer evacuation centres because lifeline services were cut off to the first evacuation centre. Then, the clinic staff worked in a temporary clinic; they visited the evacuation centres to assess the public health and medical situation, cared for wounded residents, managed infection control and encouraged a normal lifestyle where possible. Additional medical, pharmaceutical and logistical support was received from outside the district. OUTCOME: There was no noticeably severe damage to health, although there was manifestation of and deterioration in lifestyle-related diseases (e.g. diabetes, hypertension, obesity). Health care activities gradually returned to their pre-disaster levels. At the end of July 2011, the evacuation centres closed, and all evacuees moved to temporary accommodations. DISCUSSION: ISOLATED RURAL HEALTH PRACTITIONERS WERE REQUIRED TO BE INVOLVED IN A WIDE VARIETY OF ACTIVITIES RELATED TO THE DISASTER IN ADDITION TO THEIR ROUTINE WORK: e.g. preventive health (public health and safety activities), routine medical care, acute medical care, psychological care, post-mortems and recovery of medical facilities. Although the whole health care system returned to near-normal six months after the disaster, it is important to plan how to develop more resilient medical systems to respond to disasters, especially in rural areas. This article describes my experience and lessons learnt in responding to this disaster.

Comparative analysis of HIV-1-based lentiviral vectors bearing lyssavirus glycoproteins for neuronal gene transfer.

BACKGROUND: The delivery of therapeutic genes to the central nervous system (CNS) using viral vectors represents an appealing strategy for the treatment of nerve injury and disorders of the CNS. Important factors determining CNS targeting include tropism of the viral vectors and retrograde transport of the vector particles. Retrograde transport of equine anemia virus (EIAV)-based lentiviral vectors pseudotyped with the glycoprotein derived from the Rabies virus RabERA strain from peripheral muscle to spinal motor neurons (MNs) was previously reported. Despite therapeutic effects achieved in mouse models of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), the efficiency of this approach needs to be improved for clinical translation. To date there has not been a quantitative assessment of pseudotyped HIV-1-based lentiviral vectors to transduce MNs. Here, we describe quantitative tests to analyze the retrograde transport capacity of HIV-1 vectors pseudotyped with the G glycoprotein derived from Rabies and Rabies-related viruses (Lyssaviruses). METHODS: With a view toward optimizing the retrograde transport properties of HIV-1-based lentiviral vectors, we compared the glycoproteins from different enveloped viruses belonging to the Rhabdoviridae family, genus Lyssavirus, and evaluated their ability to transduce specific cell populations and promote retrograde axonal transport. We first tested the transduction performance of these pseudotypes in vitro in SH-SY5Y neuroblastoma cells, NSC-34 neuroblastoma-spinal cord hybrid cells, and primary mixed spinal cord and pure astrocyte cultures. We then analyzed the uptake and retrograde transport of these pseudotyped vectors in vitro, using Campenot chambers. Finally, intraneural injections were performed to evaluate the in vivo retrograde axonal transport of these pseudotypes. RESULTS: Both the in vitro and in vivo studies demonstrated that lentiviral vectors pseudotyped with the glycoprotein derived from the Rabies virus PV strain possessed the best performance and neuronal tropism among the vectors tested. CONCLUSION: Our results indicate that HIV-1-based lentiviral vectors pseudotyped with the Rabies PV glycoprotein might provide important vehicles for CNS targeting by peripheral injection in the treatment of motor neuron diseases (MND), pain, and neuropathy.

Simplified lentivirus vector production in protein-free media using polyethylenimine-mediated transfection.

During the past 12 years, lentiviral vectors have emerged as valuable tools for transgene delivery because of their ability to transduce nondividing cells and their capacity to sustain long-term transgene expression. Despite significant progress, the production of high-titer high-quality lentiviral vectors is cumbersome and costly. The most commonly used method to produce lentiviral vectors involves transient transfection using calcium phosphate (CaP)-mediated precipitation of plasmid DNAs. However, inconsistencies in pH can cause significant batch-to-batch variations in lentiviral vector titers, making this method unreliable. This study describes optimized protocols for lentiviral vector production based on polyethylenimine (PEI)-mediated transfection, resulting in more consistent lentiviral vector stocks. To achieve this goal, simple production methods for high-titer lentiviral vector production involving transfection of HEK 293T cells immediately after plating were developed. Importantly, high titers were obtained with cell culture media lacking serum or other protein additives altogether. As a consequence, large-scale lentiviral vector stocks can now be generated with fewer batch-to-batch variations and at reduced costs and with less labor compared to the standard protocols.

A comparative analysis of constitutive and cell-specific promoters in the adult mouse hippocampus using lentivirus vector-mediated gene transfer.

BACKGROUND: Viral vectors provide powerful tools for transgene delivery to the mammalian brain to assess the effects of therapeutic proteins, antisense RNAs or small interfering RNAs. A key advantage of such approaches is that specific brain regions implicated in a particular disease can be independently targeted. METHODS: To optimize transgene expression in sub-regions of the mouse hippocampus and with a view towards devising gene therapy strategies for Alzheimer's disease, we designed lentivirus-based reporter vectors bearing various promoters, including constitutive and cell-specific promoters. Furthermore, we devised methods allowing a side-by-side comparison of transgene expression levels in neural cells both in vitro and in vivo. RESULTS: Following stereotaxic injection into the adult mouse hippocampus, titer-adjusted lentiviral vectors bearing constitutive promoters resulted in robust and sub-region-specific transgene expression. Our results show that the human CMV-IE promoter resulted in efficient transgene expression in the entire hippocampus whereas transgene expression mediated by the hybrid hEF1alpha/HTLV promoter was limited mainly in the dentate gyrus and the CA2/3 region. Finally, the neuron-specific human synapsin I promoter was particularly effective in the dentate gyrus. CONCLUSIONS: These findings indicate that subregion-specific transgene expression in the hippocampus can be achieved following lentivirus vector-mediated gene transfer.

Cyclooxygenase-3 gene expression in Alzheimer hippocampus and in stressed human neural cells.

The cyclooxygenase (COX) superfamily of prostaglandin synthase genes encode a constitutively expressed COX-1, an inducible, highly regulated COX-2, and a COX-3 isoform whose RNA is derived through the retention of a highly structured, G + C-rich intron 1 of the COX-1 gene. As generators of oxygen radicals, lipid mediators, and the pharmacological targets of nonsteroidal anti-inflammatory drugs (NSAIDs), COX enzymes potentiate inflammatory neuropathology in Alzheimer's disease (AD) brain. Because COX-2 is elevated in AD and COX-3 is enriched in the mammalian CNS, these studies were undertaken to examine the expression of COX-3 in AD and in [IL-1beta + Abeta42]-triggered human neural (HN) cells in primary culture. The results indicate that while COX-2 remains a major player in propagating inflammmation in AD and in stressed HN cells, COX-3 may play ancillary roles in membrane-based COX signaling or when basal levels of COX-1 or COX-2 expression persist.