Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction.

We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 µg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 µg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 µg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 µg/ml. In conclusion, achievement of Cmin of 15-30 µg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.

IL-8 in cerebrospinal fluid from children with acute encephalopathy is higher than in that from children with febrile seizure.

We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)-1beta, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon-gamma, tumour necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL-8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL-8 in CSF was also higher than serum IL-8, suggesting that increased IL-8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL-8 in CSF in encephalopathy may protect against severe brain damage.

Implementation of a hospital-wide project for appropriate antimicrobial prophylaxis.

The aim of this study was to confirm the effect of implementing a hospital-wide project for appropriate use of antimicrobial prophylaxis (AMP) to reduce the rate of antibiotic-resistant organisms. Fifteen different manuals for each surgical department have been simultaneously implemented since February 2007. Compliance rate was compared between pre- and postintervention periods (3 months for each period). As an effect of this intervention, we analyzed changes in the rates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus among organisms isolated postoperatively. The number of operations was 1,627 in both periods. Among patients whose surgeries were longer than 3 h in duration, 75% received an additional intraoperative antimicrobial dose in the postintervention period and 23% in the preintervention period (P < 0.001). Although most patients received postoperative AMP with an interval of q12 h in the preintervention period, 63% of the patients received AMP with an interval of q8 h in the postintervention period. The duration of AMP use was reduced from 2.4 ± 1.9 to 1.6 ± 1.5 days (P < 0.001). Forty-seven percent of patients discontinued AMP within 24 h and 81% within 48 h. Isolation rates of P. aeruginosa among all gram-negative organisms significantly decreased from 13% (68/538 patients) to 7.3% (37/509 patients) (P = 0.004). Execution of a hospital-wide project to promote the appropriate use of AMP, including shortening the duration of AMP use, was useful to decrease the rate of P. aeruginosa isolated postoperatively.

[Uncontrollable midbrain hemorrhage due to brain metastasis of pulmonary pleomorphic carcinoma].

A 54-year-old man who had been treated hypertension admitted our hospital due to midbrain hemorrhage. Pulmonary abnormal shadow was also found by chest radiological examinations and it was diagnosed as stage IB (T2N0M0) non-small-cell lung cancer. Right upper lobectomy with combined resection of azygos vein and parietal pleura facing to the tumor was conducted because the direct invasion of the tumor was strongly suspected. Pathological diagnosis was pleomorphic carcinoma. Although, postoperative course was uneventful, midbrain hemorrhage recurred 3rd postoperative day. Since the hemorrhage continued in spite of the conservative treatment, the craniotomy was performed on the 13th postoperative day. The pathological examination revealed the hemorrhage to be caused by the brain metastasis.

Hard x-ray photoemission study of Yb1-x Zr x B12: the effects of electron doping on the Kondo insulator YbB12.

We have carried out hard x-ray photoemission spectroscopy (HAXPES) of Yb1-x Zr x B12 ([Formula: see text]) to study the effects of electron doping on the Kondo insulator YbB12. The Yb valences of Yb1-x Zr x B12 at 300 K estimated from the Yb 3d HAXPES spectra decreased after substituting Yb with Zr from 2.93 for YbB12 to 2.83 for Yb0.125Zr0.875B12. A temperature dependent valence decrease was found upon cooling for all doping concentrations. We found peak shifts of the B 1s and Zr 3d5/2, and Yb3+ 4f spectra toward the deeper binding-energy with increasing Zr concentration, which indicates a shift of the Fermi level to the higher energy and that of the Yb 4f hole level close to the Fermi level, respectively, due to electron doping. These results qualitatively show the enhanced hybridization between the Yb 4f and conduction-band states with Zr substitution, consistent with magnetic susceptibility measurements.

[Diaphragmatic hernia following pneumonectomy; report of a case].

We report a case of diaphragmatic hernia following left pleuropneumonectomy. A 70-year-old man was referred to our hospital after tube drainage for 3 months due to left pyothorax. He had a past history of left lung tuberculosis. Pleuropneumonectomy with partial resection of the muscle layer of the diaphragm was performed because adhesion of pleurae was severe. On the 19th postoperative day, he started to develop a slight fever. Chest X-ray and computed tomography (CT) demonstrated diaphragmatic hernia. On the 22nd postoperative day, we performed surgery because panperitonitis developed. At laparotomy, the transverse colon was pierced by the cut end of the rib. We successfully repaired the diaphragm and established transverse colostomy. The patient has been in good health for more than 10 years after the surgery.

[Mediastinal lymph node metastasis of thyroid cancer occurring 15 years after the initial operation; report of a case].

A 71-year-old woman was found to have an abnormal shadow on a chest X-ray. Fifteen years earlier she had undergone a subtotal thyroidectomy for thyroid cancer without any lymph node metastasis. Chest computed tomography (CT) revealed a mediastinal tumor with full of blood stream. Since the positron emission tomography (PET) disclosed an increased uptake of fluoro-2-deoxy-D-glucose (FDG) in the tumor, a malignant lymphatic tumor was therefore suspected. An immunohistological examination of biopsy specimens taken by thoracoscopic procedure demonstrated tumor to be lymph node metastasis of the previous thyroid cancer. After a tumor resection by means of a thoracotomy and total thyroidectomy, the patient was scheduled to receive radioiodine therapy. The previously reported cases are also herein reviewed.

A multi-centre retrospective study of mandibular fractures: do occlusal support and the mandibular third molar affect mandibular angle and condylar fractures?

This retrospective study was performed to investigate the influence of occlusal support and the presence, state, and position of mandibular third molars on the incidence of mandibular angle and condylar fractures. The following variables were investigated: age, sex, cause of fracture, presence and state (impaction, angulation, and the number of roots) of the mandibular third molars, site of the mandibular fracture, presence of occlusal support, duration of intermaxillary fixation, and postoperative complications. Various risk factors for mandibular angle and condylar fractures were investigated by univariate analysis. The risk of mandibular angle fracture was significantly higher in patients with occlusal support and mandibular third molars. The risk of condylar fracture was significantly higher in patients without occlusal support or mandibular third molars. The position and angulation of the mandibular third molars were not significant risk factors in mandibular angle and condylar fractures. This study demonstrated the influence of occlusal support and the presence of mandibular third molars on the incidence of mandibular angle and condylar fractures. The presence of occlusal support may be a more important factor affecting mandibular angle or condylar fractures than the position of the mandibular third molars.

[Sternal metastasis of breast cancer; report of a case].

A 51-year-old woman presented with a painful sternal lump. Nine years earlier she had undergone right modified mastectomy for breast cancer, followed by chemotherapy. Computed tomography and bone scintigraphy demonstrated a solitary sternal bone metastasis. The patient was treated by partial sternectomy. Thereafter, the sternal defect was reconstructed with Marlex mesh and rectus abdominis myocutaneous flap. The postoperative course was uneventful. The patient subsequently developed brain metastasis and died within 52 months after sternal resection. The stability of the chest wall was well preserved for the duration of follow-up.

Platelet-derived nitric oxide and coronary risk factors.

Platelet aggregation is inhibited through a negative feedback mechanism by the L-arginine/nitric oxide (NO) pathway found in platelets themselves. We have shown that long-term smoking impairs the bioactivity of platelet-derived NO (PDNO), resulting in an increased platelet aggregability. However, little is known about the relation between other coronary risk factors and PDNO release. Accordingly, this study was undertaken to examine whether other coronary risk factors are related to the impairment of PDNO bioactivity. We measured collagen-induced PDNO release with an NO-selective electrode in 61 subjects (mean age 47 years, range 24 to 74 years) who underwent complete physical and laboratory examinations. There was a significant inverse correlation between PDNO release and the number of coronary risk factors (r=-0.61, P<0. 001). Univariate analysis showed a significant inverse correlation between PDNO release and age (r=-0.33, P<0.01), mean arterial pressure (r=-0.40, P<0.002), total cholesterol level (r=-0.31, P<0. 02), and LDL-cholesterol level (r=-0.33, P<0.02). PDNO release was significantly lower in long-term smokers than in nonsmokers (P<0. 001). With multiple stepwise regression analysis, PDNO release correlated significantly and independently (r(2)=0.51), with smoking (F=37.8), age (F=7.1), and mean arterial pressure (F=5.1). Thus, we demonstrated that coronary risk factors are associated with an impairment of PDNO release by human platelets. Our findings may contribute to the understanding of the pathophysiological link between coronary risk factors and atherothrombotic disease.

Regulation of activator protein-1 activity in the mediastinal lymph node metastasis of lung cancer.

Orthotopic implantation of a metastatic cell line of Lewis lung carcinoma (LLC-MLN), which was isolated by an in vivo selection method, resulted in greater metastatic growth in mediastinal lymph nodes as compared with that of the original LLC cells. LLC-MLN cells also had increased invasive ability and activator protein-1 (AP-1) transcriptional activity as compared with the original LLC cells. This is well consistent with the previously reported finding that overexpression of AP-1 is associated with lymphatic metastasis in lung cancer patients. Oral administration of curcumin, which downregulates AP-1 transcription, significantly inhibited the mediastinal lymph node metastasis of orthotopically implanted LLC cells in a dose-dependent manner, but did not affect the tumor growth at the implantation site. Combined treatment with curcumin and an anti-cancer drug, cis-diamine-dichloroplatinum (CDDP), resulted in a marked inhibition of tumor growth at the implanted site and of lymphatic metastasis, and a significant prolongation of the survival time. The downregulation of transcriptional AP-1 activity by curcumin as seen in the dual luciferase assay caused inhibition of LLC cell invasion through the repression of expression of the mRNAs for urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR). Inhibition of AP-1 transcriptional activity may offer improved therapeutic efficacy for lung cancer patients with lymphatic metastasis.

An endocrinopathy characterized by dysfunction of the pituitary-adrenal axis and alopecia universalis: supporting the entity of a triple H syndrome.

We demonstrate the rare disorder of triple H syndrome in a 25-year-old man. He was pointed out as having short stature, at -5.9 s.d., and diagnosed as GH deficient at 6 years old. Approximately a year ago, he noticed systematic hair loss. He lost body weight by 7 kg during the last half year. He was admitted to Jichi Medical School Hospital because of unconsciousness. Physical findings showed disturbance of consciousness with Japan Coma Scale I-3. He had emaciation and alopecia universalis. Laboratory findings showed plasma glucose was as low as 1.11 mmol/l. GH and ACTH deficiency with hypoadrenocorticism were clarified. His intelligence was in the low normal range with a WAIS IQ of 70, and anterograde amnesia was suggested in the presence of a little, but not significant, morphological change in the hippocampus on a magnetic resonance imaging scan. Replacement by a physiological dose of hydrocortisone normalized plasma glucose, and restored body weight and growth of hair during the 7 month therapeutic period. The present finding strongly supports a clinical entity of triple H syndrome, including ACTH deficiency, alopecia universalis and anterograde amnesia, and that there may be some variation of the triad among the subjects.

Coronary stent deployment in a young adult with Kawasaki disease and recurrent myocardial infarction.

A 19-year-old man developed a huge coronary aneurysm and stenosis in the right coronary artery as a sequela of Kawasaki disease (KD) that resulted in recurrent episodes of myocardial infarction. Coronary ischemic events were successfully prevented after balloon angioplasty followed by coronary stent implantation into the stenotic lesion. The stent deployment may have an advantage compared with balloon angioplasty and other new devices for the treatment for patients with KD showing stenotic lesions without dense calcification.

Vasospastic angina induced by nonsteroidal anti-inflammatory drugs.

We report two cases of vasospastic angina associated with anaphylactic reaction caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Both patients exhibited anaphylactic manifestations, such as general rash and urticaria, along with angina pectoris with electrocardiographic ST-segment elevations after suppository administration of diclofenac sodium or indomethacin, the most commonly used NSAIDs. Although these patients had normal coronary arteriograms, intracoronary administration of ergonovine or acetylcholine provoked diffuse coronary artery spasms accompanied by chest pain and ischemic ST-segment changes. It is therefore suggested that an allergic mechanism may be involved as a causative factor of the coronary artery spasm induced by NSAIDs.

Palmaz-Schatz stent for hepatic artery stenosis during hepatic arterial infusion chemotherapy.

Hepatic arterial infusion chemotherapy using an implantable port system was performed on a 40 year-old man with advanced hepatocellular carcinoma. When the in-dwelling catheter was inserted into the common hepatic artery (CHA), intimal dissection occurred as a result of the catheterization causing severe stenosis. On day 55 after intimal dissection, an in-dwelling Palmaz-Schatz stent was inserted after percutaneous transluminal angioplasty (PTA). CHA blood flow was shown to have improved on Digital subtraction angiography (DSA) and Doppler ultrasound after the in-dwelling Palmaz-Schatz stent. Thus a partial response was shown. The DSA from the implantable port system showed adequate patency 6 months after. This is the first report describing the usefulness of a Palmaz-Schatz stent for the severe stenosis of the CHA caused by the technique of catheterization.

What factors are involved in the knowledge necessary for the self-management of diabetic patients?

The aim of this study is to obtain data for improving a training program for patients with diabetes mellitus. One hundred eighty-seven patients with non-insulin dependent diabetes mellitus were tested with 20 questions about their knowledge for self-management of diabetes mellitus. Then to draw out factors in their personal backgrounds relating to their correct answers, multiple regression analyses were conducted. As a result, four factors showed significant differences in the following order: Educational careers > ages > duration of disease > socioeconomic strata. The results of the present study have shown for the first time, that these four factors closely concern patients to acquire the necessary knowledge for their self-management of the disease. In addition, this study has raised some fundamental problems regarding the training program for patients: how education should be given to patients.

Complement activation pathways associated with islet cell surface antibody (ICSA) derived from child patients with insulin-dependent diabetes mellitus (IDDM).

We studied the pathways of complement activation associated with the islet cell surface antibody (ICSA) obtained from sera of 7 patients (age less than 15 years) with insulin dependent diabetes mellitus (IDDM). The target cells were 51CR labelled rat islet cells and the complement source was human AB serum. Complement-dependent antibody mediated cytotoxicity (CAMC activity) was obtained using the percentage of cytotoxicity. CAMC activity of untreated sera was significantly inhibited by treating with EGTA or EDTA (p less than 0.001). The CAMC activity of EDTA-treated sera was significantly lower than that of EGTA-treated sera (p less than 0.001). In the inactivated human AB serum, it was lower than that of EGTA-treated sera (p less than 0.05), but not different from that of EDTA-treated sera. These results show that the complement activation associated with ICSA in patients occurred not only via the classical pathway but also via the alternative pathway.

Significance of urinary albumin index in the urine collected arbitrarily in the morning.

To evaluate urinary albumin index (UAI), the relationship between albumin excretion rate (AER) in the urine stored for 24 h and UAI in the urine collected arbitrarily on the morning of the same day was studied in 123 inpatients. The patients were admitted to our hospital from September 1, 1988 to August 31, 1989, consisting of 67 non-insulin dependent diabetics (Group 1), 40 patients with collagen disease (Group 2), and 16 patients with primary renal disease (Group 3). The relationship between log(e) AER and log(e)UAI was plotted on a graph. Pearson's rank correlation coefficients of Groups 1-3, Group 1, Group 2, and Group 3 were as follows: r = 0.725, r = 0.691, r = 0.855, and r = 0.611, respectively. The formula obtained by using Pearson's rank correlation coefficients to estimate log(e)AER from log(e)UAI in 123 cases of Groups 1-3, 67 cases of Group 1, 40 cases of Group 2, and 16 cases of Group 3 were: log(e)AER/log(e)UAI = 0.815, log(e)AER/log(e)UAI = 0.860, log(e)AER/log(e)UAI = 0.830, log(e)AER/log(e) = 0.722, respectively. In the present study, log(e)UAI was found to correlate well with log(e)AER. As AER is generally accepted to be the most reliable index to know the stage of albuminuria, UAI is considered to be clinically useful.

Dose-dependent effect of hydroxymethylglutaryl-coenzyme A reductase inhibitor on serum cholesterol with limited dietary restrictions: a case study.

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (pravastatin sodium) can selectively inhibit cholesterol biosynthesis in the liver and may lower serum cholesterol concentrations even where there are no particular dietary restrictions. A 72-year old housewife with non-insulin-dependent diabetes mellitus complicated by hyperlipaemia type IIb, who did not follow directions for diet therapy or kinesitherapy, was administered HMG-CoA reductase inhibitor. The initial dose of 10 mg/day HMG-CoA reductase inhibitor was increased by 10 mg/day every 4 weeks to 30 mg/day, maintained at 30 mg/day for 8 weeks and then reduced gradually until discontinuation after a further 27 weeks. Test results showed the changes in low-density lipoprotein cholesterol and apoprotein B to be dose-dependent. The findings represent the first clinical evidence that hypercholesterolaemia can be adequately managed by the use of HMG-CoA reductase inhibitor, even when no specific dietary restrictions are imposed, and may contribute to improvements in the quality of daily life for many patients suffering from hyperlipaemia type IIb.

Estimated urinary albumin index: a predictor of microalbuminuria in type 2 diabetes.

This study examined factors contributing to the development of microalbuminuria in diabetic patients. A total of 236 patients with Type 2 diabetes were studied: 143 were normoalbuminuric and 86 were also normotensive. Multiple regression analysis was used to identify factors influencing the urinary albumin index (UAI), an index of proteinuria based on urinary albumin adjusted for urinary creatinine. Significant factors (retinopathy, systolic blood pressure, and glycosylated haemoglobin) were used to generate a formula for estimating the log(e) UAI. Target values for systolic blood pressure and glycosylated haemoglobin to maintain the urinary albumin index at or below 22 were determined for different degrees of retinopathy. Normoalbuminuric patients were followed for 3 years to evaluate their progression to microalbuminuria. Each month, blood pressure, urinary albumin and creatinine, and glycosylated haemoglobin were measured. In normotensive, normoalbuminuric patients, initial urinary albumin index and log(e) UAI were significantly higher in patients who subsequently developed microalbuminuria. Patients with initial log(e) UAI > 3.09 or initial glycosylated haemoglobin > 6.0% also showed greater progression to microalbuminuria. Hyperglycaemia was an independent factor for the development of microalbuminuria in Type 2 diabetes. The urinary albumin index was most significantly affected by retinopathy, systolic blood pressure, and glycosylated haemoglobin. The estimated loge UAI calculated from these factors is a useful predictor of progression to microalbuminuria.