Results of T-cell receptor β-chain repertoire analysis, gene expression profiling studies of CD34-positive cells from patients with aplastic anemia, and other cytokine data have shown that the major pathogenic mechanism of acquired aplastic anemia is stem cell injury by morbid T-cells. Several proteins, such as kinectin and diazepam-binding inhibitor-related protein 1, have been found to be related to the onset as self-antigens. With these findings and additional new clues the pathogenesis of aplastic anemia will soon be clarified. The current strategies to treat severe aplastic anemia are stem cell transplantation and immunosuppressive therapy with anti-thymocyte globulin and cyclosporine. These methods have both benefits and some problems, so it is sometimes not easy to determine which therapy should be applied to patients. Some data suggest that the presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in patient's peripheral blood heralds a good response to immunosuppressive agents. PHN clones may be a useful tool for selecting therapy. For stem cell transplantation, an HLA-identical sibling is the best donor candidate, but such a donor is available for only 30% of patients. Recently, HLA-mismatched related or HLA-matched unrelated bone marrow cells and HLA-mismatched umbilical cord blood cells have been used as alternative stem cell sources if an HLA-identical sibling donor is not available. However, greater efforts must be made to reduce the mortality and morbidity rates of stem cell transplantation. In this paper recent progress in the basic research and treatment of aplastic anemia are reviewed.

View full abstract

Alzheimer's disease (AD) is the most common cause of dementia in older people. Cerebral deposition of amyloid plaques containing amyloid beta-peptide (Aβ) has traditionally been considered the central feature of AD. γ-Secretase is the pivotal enzyme in generating the C terminus of Aβ, that determines its aggregability and propensity for deposition. Drugs that regulate the production of Aβ by inhibiting gamma-secretase activity could provide an effective therapeutics for AD, however we can't use these drugs clinically now. Anti-amyloid immunotherapy for AD has received considerable attention following reports that amyloid pathology was reduced in an amyloid precursor protein (APP) transgenic mouse model on vaccination with aggregated Aβ42. Clinical trials were terminated after four early reports of autoimmune meningoencephalitis, but a post-mortem study in one patient showed evidence of plaque reduction. Currently, no effective pharmacologic interventions have been researched enough to support their use in prevention of AD. Many epidemiological studies suggest that apolipoprotein E type 4 allele, diabetes, obesity, hypertension, and hyperlipidemia were associated the risk factor for late onset AD. Two key treatment approaches for AD have been driven by retrospective epidemiology: non-steroidal anti-inflammatory drugs and cholesterol-lowering statins. In both cases, the exact target in the disease cascade remains to be elucidated. In constant, only one acetylcholinesterase inhibitor, donepezil has been proven effective and used for patients with mild or moderate AD in Japan. Donepezil have demonstrated the effectiveness in stabilizing cognitive function and delaying behavioral symptoms. Given the likelihood that agents will become available that reliably delay onset and/or slow progression of AD, it will be important to detect preclinical AD as early as possible for maximal treatment effect. Cognitive function is generally examined by Mini-mental State Examination (MMSE), revised version of Hasegawa's Dementia Rating Scale (HDS-R) and Wechsler adult intelligence scale-revised (WAIS-R). The positron emission tomography or the single photon emission computed tomography were used for diagnosis of early stage AD. Caregivers should analyze behaviors and environmental factors which precede harmful abnormal conduct and try to avoid them.

View full abstract

The early and differential diagnosis of senile dementia is still a problem. To encourage the early referral and identification of patients with treatable conditions, an outpatient memory disorders clinic is held at our university hospital. The most frequent cause of dementia is Alzheimer's disease, followed by vascular dementia. Alzheimer's disease and vascular dementia account for 90% of causes of dementia. In 1999 donepezil hydrochloride, an acetylcholinesterase inhibitor, was approved for inhibiting disease progression in patients with Alzheimer's disease. Since then a role of an outpatient memory disorders clinic has been more important. This paper gives an outline of the clinical findings about Alzheimer's disease and vascular dementia and describes how we diagnose various types of dementia.

View full abstract

All-trans retinoic acid (ATRA) combined with anthracycline-based chemotherapy and followed by maintenance treatment with intermittent ATRA improved the cure rate in patients with newly diagnosed APL to 70% from 35% in patients treated with chemotherapy alone. Nevertheless, disease will relapse in about 20% of patients who achieve a complete remission. Arsenic trioxide (ATO) is an active drug in refractory/relapsed APL with antileukemic mechanisms of inducing partial differentiation and apoptosis. ATO monotherapy in patients with relapsed APL achieved remission rates of more than 80% with molecular remissions. The reported adverse effects (e.g., APL differentiation syndrome, hyperleukocytosis, prolongation of the QTc interval, and liver dysfunction) are few and manageable. A 74-year-old woman in whom APL complicated with subarachnoid hemorrhage was diagnosed achieved complete remission with ATRA in March 2005. Subsequently, she received postremission therapy as an outpatient. In October 2005, leukemia relapse was noted with a white blood cell count of 11.2×10⁹/L (42% blasts), a platelet count of 16×10⁹/L, and disseminated intravascular coagulation (DIC). ATO was administered at a dose of 0.15 mg/kg/day. The DIC resolved after 12 days. The white blood cell count gradually decreased. On day 41, ATO was discontinued due to neutropenia of less than 0.1×10⁹/L. After 14 days, granulocyte colony-stimulating factor (G-CSF) was administered because of sustained neutropenia. Ten days after G-CSF was started, bone marrow aspiration revealed APL cells. ATO was started again with G-CSF, and bone marrow remission was finally achieved after 20 days. ATO is a powerful and promising treatment for refractory/relapsed APL. Neutropenia has recently been reported as an adverse effect. This is the first case of APL successfully treated with ATO and G-CSF for neutropenia followed by remission.

View full abstract

We present here a case of postpartum eclampsia resulting in reversible posterior leukoencephalopathy syndrome. Fluid-attenuated inversion recovery and T2-weighted magnetic resonance images showed multiple hyperintense lesions in the posterior white matter. The patient had no complications of hypertension until the onset of eclampsia.

View full abstract

We present a case of abdominal incisional hernia that was successfully treated with laparascopic surgery. An 81-year-old woman presented with symptoms of abdominal pain and discomfort. In the past history, she had distal gastrectomy for gastric carcinoma in 1995 and total gastrectomy for the remnant of gastric carcinoma combined with a cholecystectomy in 2003. Subsequently, she developed a swelling in the abdominal region. She had consulted a local hospital and surgery was suggested, but she rejected. Finally, she visited Keihin General Hospital with the hope for a treatment by endoscopic surgery. On medical examination, longitudinal and horizontal surgical scars were observed on the upper abdominal region and an incisional hernia measuring 14×15 cm in diameters was found. Laparoscopic repair operation was performed under general anesthesia using a 19.6×24.6 cm Bard Composix Kugel Patch (Bard, Inc.), inserting through three ports of about 11 mm in diameter in the lower abdomen. At present, the patient is under follow up with no pain or recurrence. In conclusion, we report a better prognosis of a case with huge incisional hernia under laparoscopic repair operation.

View full abstract

A case of anomalous hepatomesenteric trunk and gastrosplenic trunk was found during an anatomical practice at Nippon Medical School in 2002. In 1928, Adachi¹ reported the frequency of this type of anomaly to be 0.4%. The case exhibited a gastrosplenic trunk, which consisted of the splenic and the left gastric arteries and composed the celiac trunk with the common hepatic artery, arising directly from the left side of the abdominal aorta. In addition, the common hepatic and superior mesenteric arteries, arising directly from the abdominal aorta, formed a hepatomesenteric trunk. The common hepatic artery extended upward into the liver after diverging from the hepatomesenteric trunk. The abdominal arterial anomalies and unification of the abdominal arterial branches were thought to originate from rotation of the digestive organs during embryonic development. A left accessory hepatic artery and a cystic arterial anomaly were also found.

View full abstract