Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia.

Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was > or =240 mg/dl and the average LDL-C concentration was > or =160 mg/dl. The incidence of coronary events increased in the patients with TG concentration > or =300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and >40 mg/dl for HDL-C.     

Strategy for treating elderly Japanese with hypercholesterolemia*

Background: It has been widely accepted that control of serum cholesterol levels is effective for prevention of cardiovascular events. Recent data have suggested that this is also the case in the elderly. Methods: A research group (chaired by T. Kita) was organized as part of the Comprehensive Research on Aging and Health conducted by the Japanese Ministry for Health, Labour, and Welfare in 1999–2002 to determine the best strategy for control of cholesterol levels in elderly Japanese with hypercholesterolemia. In order to do this a review of the literature was conducted. Conclusion: The research group concluded: (i) Japanese patients aged 65–74 years with hypercholesterolemia should be treated by following the Guideline for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases by the Japan Atherosclerosis Society (2002), as cholesterol‐lowering therapy would bring a similar, or even larger, preventive effect to the elderly, whose absolute risk of cardiovascular events is higher than that in the younger population; (ii) target cholesterol levels in elderly Japanese aged ≥ 75 years with hypercholesterolemia should be determined individually according to their physical activities. It is noted that the elderly are more susceptible to drug‐related adverse effects than the younger since renal and liver functions, required for metabolizing drugs, in the elderly are relatively weaker.     

Effects of gabapentin enacarbil on restless legs syndrome and leg pain in dementia with Lewy bodies

Restless legs syndrome (RLS) is a common neurological disorder. Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease. Both RLS and DLB can be effectively treated by dopaminergic medications, suggesting the role of dopamine dysfunction in the pathogenesis of both diseases. Here, I report on a Japanese woman with probable DLB and RLS who was treated with gabapentin enacarbil, a non‐dopaminergic agent. Because a dopamine agonist, a first‐line therapy for moderate to severe RLS, caused the occurrence of metamorphopsia, an alternative treatment of gabapentin enacarbil was used; this treatment improved the patient's RLS without worsening her psychiatric symptoms. An alternative treatment is desirable for DLB patients with RLS because they often experience intolerable side‐effects with a dopamine agonist, especially visual hallucinations. Administering gabapentin enacarbil also improved the continuous leg pain that occurred in conjunction with the development of RLS. Although the neurobiological mechanism in the development of pain remains unclear, a range of non‐dopaminergic structures likely mediated pain processing in DLB in the present case based on neuropharmacological results. This is the first report reporting the effects of gabapentin enacarbil for RLS and leg pain in a DLB patient with psychiatric symptoms.     

Three presenile patients in which neuropsychological and neuroimaging examinations suggest possible progression to dementia with Lewy bodies

We report three presenile patients who were initially suspected of having Alzheimer's disease (AD) or being in the prodromal stage of AD, regardless of visuoperceptual dysfunctions in daily living, because they lacked the core features and prodromal non‐motor symptoms of dementia with Lewy bodies. Subsequently, progression to dementia with Lewy bodies was suspected based on neuropsychological and neuroimaging findings; additionally, one of the three patients suffered from visual hallucinations. Neuropsychological examinations such as subjective contours, cube copying and block design in the Wechsler Adult Intelligence Scale‐III revealed visuoperceptual dysfunction in all three patients even when other cognitive functions were rather preserved. Brain magnetic resonance imaging revealed no significant brain atrophy, including in the parieto‐occipital area and the hippocampus, while brain ¹⁸F‐fluorodeoxyglucose positron emission tomography demonstrated right dominant metabolic reductions in the occipital lobe, including the primary visual cortex, in all three patients. We suggest the possibility of progression to dementia with Lewy bodies, but not AD or posterior cortical atrophy. Regardless of the presence of core features and prodromal non‐motor symptoms, this progression is suggested when there are difficulties only in higher‐level visual processing such as subjective contours and block design in the Wechsler Adult Intelligence Scale‐III, no significant atrophy of the parieto‐occipital area and hippocampus on brain magnetic resonance imaging, and hypometabolism in the occipital lobe including the primary visual cortex on brain ¹⁸F‐fluorodeoxyglucose positron emission tomography.     

A case of acute septic arthritis of the hip joint caused by Panton-Valentine leukocidin-positive ST772 community-acquired methicillin-resistant Staphylococcus aureus

Acute septic arthritis (ASA) caused by Staphylococcus aureus can lead to fulminant arthritis and cause permanent joint destruction. In particular, infection caused by methicillin-resistant Staphylococcus aureus (MRSA) becomes intractable and severe owing to limitation of therapeutic drugs. Here, we report the case of a young patient with ASA without any record of overseas travel, who was infected by the Panton-Valentine leukocidin-positive Bengal-Bay clone, which is a predominant community-acquired MRSA in India.     

Frequency of Treponema pallidum invasion into cerebrospinal fluid in primary or secondary early-stage syphilis

Frequency of Treponema pallidum invasion into cerebrospinal fluid (CSF) has not been clear at this present. Since it is impossible to culture T. pallidum in vitro at this present, we need molecular based-approach to detect it in CSF. Additionally, neurosyphilis is usually a late sequela, however it might result in asymptomatic neurosyphilis even at primary or secondary syphilis. This study was to reveal the frequency of T. pallidum invasion into CSF especially at primary or secondary syphilis with polymerase chain reaction (PCR) test.All patients were visited the Aichi Medical University Hospital or Izumi ladies' clinic between 2016 and 2017. Clinical CSF samples were collected from patients with early and late stages of syphilis. The PCR was done using primers targeting the tpN47gene.CSF samples were collected from 9 patients (4 patients with primary syphilis, 3 with secondary syphilis, and 1 early latent syphilis and 1 with late latent syphilis). PCR showed positive reaction in 2 of 7 (28.6%) primary and secondary syphilis patients, in 1 of 1 (100%) early latent syphilis patients, and in 1 of 1 (100%) late latent syphilis patients.Despite its lack of sensitivity for use alone as a diagnostic test, this PCR test should be preferred for the diagnosis of neurosyphilis. Because, T. pallidum was detected in the 28.6% CSF of patients at primary and secondary syphilis, which indicated that they invade the central nervous system from the early stages of infection. However, studies in a larger population are required to confirm these preliminary results.     

Bacterial flora in the uterine endometrial cavity of healthy subjects on the first and fifth days of the puerperium

This study was designed to investigate bacterial flora of the endometrial cavity in healthy puerperae. Thirty puerperae who underwent an uneventful course in pregnancy, delivery or postpartum were subjects for this study. Intrauterine contents were collected on the first and fifth days of the puerperium and submitted for microbiologic examination. On the puerperal first day, a total of 76 strains (53 strains of aerobic bacteria, 21 strains of anaerobic bacteria, and 2 strains of fungi) were detected in the uteri of the 30 subjects. More than 2 strains were detected in 97% (29/30 subjects). The incidence of aerobic gram-positive cocci, aerobic gram-negative bacilli, and anaerobic bacteria was 51%, 16%, and 28% of 76 strains, respectively. On the puerperal fifth day, a total of 102 strains (68 strains of aerobic bacteria, 30 strains of anaerobic bacteria, and 4 strains of fungi) were detected in the uteri of the 30 subjects. More than 2 strains were detected in 97% (29/30 subjects). The incidence of aerobic gram-positive cocci, aerobic gram-negative bacilli, and anaerobic bacteria was 46.1%, 18.6%, and 29.4% of the 102 strains, respectively. The population of the former seemed to decrease, and that of the latter 2 seemed to increase during the postpartum course. However, the number of strains detected for these 3 classifications of bacteria increased from the first to fifth postpartum day. There is no significance between bacterial strains and frequency detected, using the 2×39 chi-square test (P=0.571). There is no significance between classification of bacteria and frequency detected, using the 2×7 chi-square test.     

Antitumor Effect of Gemcitabine on Orthotopically Inoculated Human Gallbladder Cancer Cells in Nude Mice

Background The prognosis of gallbladder carcinoma is poor; therefore, investigating the efficacy of new chemotherapy agents is essential for the treatments for this tumor. Recently, several studies have reported clinical trials using gemcitabine as treatment for advanced gallbladder cancers. However, the antitumor effects of gemcitabine on gallbladder carcinoma have not been examined in in vitro and in vivo model systems. Methods We examined the cytotoxicity of gemcitabine in four biliary tract cancer cell lines using the WST-1 assay. In addition, we examined the effect of gemcitabine on gallbladder cancers resulting from orthotopic inoculation of NOZ gallbladder tumor cells into nude mice. One week after transplantation, the mice were randomized into two groups: In Group A, the mice were treated by an intra-peritoneal injection of 0.9% sodium chloride for three weeks after inoculation (control). In Group B, the mice were treated by an intra-peritoneal injection of gemcitabine (125 mg / kg) for three weeks. All mice were sacrificed one week after the end of treatment, and macroscopic and histological findings were evaluated. The expression levels of proliferating-cell nuclear antigen (PCNA) were examined to investigate cellular proliferation activity, and Tunnel assays were performed to determine apoptotic status. Survival duration of the mice after gemcitabine treatment was compared to that of untreated mice. Results The gemcitabine sensitivity of the four biliary tract cancer cell lines was similar in a dose dependent manner. In the in vivo models, the Group A mice showed huge tumors of the gallbladder, with liver invasion and lymph node metastases. However, there were no abdominal tumors in the Group B mice, and microscopic gallbladder cancer could only be detected from histological findings. The mean percent of PCNA-positive tumor cells was significantly higher in tumors from mice in Group A (71.9%) compared to those of Group B (34.7%). The mean percent of Tunnel-positive tumor cells was significantly lower in mice from Group A (2.0%) than those from Group B (5.7%). Survival duration was prolonged significantly in the gemcitabine-treated mice relative to untreated mice. Conclusions Gemcitabine treatment may inhibit tumor progression and prolong survival in gallbladder cancer by inhibiting cell proliferation and inducing apoptosis.     

Simultaneous ipsilateral fractures of distal and proximal ends of the radius

We treated a patient with a rare combination of ipsilateral fractures of the distal and proximal ends of the radius. A woman aged 52 years had simultaneous fractures of the distal and proximal ends of the radius (radial head and neck) after she fell from a high place. The fracture of the radial head was treated by open fixation with a cancellous bone screw, and the fractured distal end of the radius was treated by bone graft, with the subsequent application of an external fixator. At the 1-year follow up, the patient had minor residual limitation of forearm pronation and elbow joint extension, but she had no pain on movement, and had a good result based on Cooney's score (90 points). Received: December 20, 2000 / Accepted: April 4, 2001     

A case of uterine endometritis caused by Atopobium vaginae

Although Atopobium vaginae has been reported as a causative organisms in patients with bacterial vaginosis and/or tubo-ovarian abscess, clinical significance of Atopobium species has not been defined to date. Here we report the case of uterine endometritis caused by A. vaginae.