Loss of lower extremity muscle strength based on diabetic polyneuropathy in older patients with type 2 diabetes: Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes: Phase 2 study.

AIMS/INTRODUCTION: Diabetic polyneuropathy (DPN) is a factor that reduces lower extremity muscle strength (LEMS) in older type 2 diabetes patients. This relationship remains unclear in longitudinal studies. Therefore, we longitudinally investigated the apparent effects of DPN on changes in LEMS. Furthermore, we cross-sectionally examined relationships among DPN, LEMS, mobility and health-related quality of life. MATERIALS AND METHODS: Bodyweight-normalized (relative) knee extension force (KEF) was examined in 51 DPN and 54 non-DPN patients (68.9 ± 5.6 and 70.2 ± 5.9 years, respectively) at baseline and follow up at 3.6 ± 0.6 years. At follow up, mobility was measured using a 25-question geriatric locomotive function scale. Health-related quality of life was assessed using the five-dimensions of EuroQol for quality-adjusted life years calculation. RESULTS: Relative KEF in the DPN group was significantly lower at follow up (1.22 ± 0.47 Nm/kg) than at baseline (1.31 ± 0.47 Nm/kg; P < 0.05). DPN significantly affected changes in relative KEF. Mobility decreased by 41 and 65% in the non-DPN and DPN groups, respectively. Quality-adjusted life years were significantly lower in the DPN group (0.856 ± 0.131) than in the non-DPN group (0.920 ± 0.105; P < 0.01). Relative KEF was a significant independent variable that explained quality-adjusted life years. CONCLUSIONS: DPN clearly reduced LEMS in older type 2 diabetes patients within 4 years. Furthermore, DPN resulted in a loss of LEMS and decrease in mobility. Therefore, DPN development should be monitored closely, with glycemic control and LEMS kept at a high level to maintain health-related quality of life in older patients with type 2 diabetes.

Isometric knee extension force in Japanese type 2 diabetic patients without apparent diabetic polyneuropathy: Data from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study.

OBJECTIVES: To determine standard reference values for isometric knee extension force using a cohort of Japanese type 2 diabetic patients without diabetic polyneuropathy. METHODS: Patient data were collected from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study and compared with previously published data of healthy control subjects. In total, we enrolled 898 patients with type 2 diabetes aged 30-87 years, who did not have diabetic polyneuropathy. The control group included 510 healthy subjects aged 30-88 years. Maximum isometric knee extension force (KEF) values were obtained by using a hand-held dynamometer with belt stabilization. In addition, KEF (kgf) was adjusted for bodyweight (kg) to calculate %KEF. RESULTS: KEF and %KEF decreased with age in both patients with diabetes and healthy control subjects. The mean values of KEF and %KEF in patients with diabetes were reduced by 9.7% and 20.8%, respectively, in males, and by 11.6% and 23.0%, respectively, in females compared to the values in healthy control subjects. CONCLUSION: KEF and %KEF in patients with type 2 diabetes without diabetic polyneuropathy may reduce by approximately 10% and 20%, respectively, compared to these values in healthy control subjects. This study provides reference values for isometric KEF with respect to sex in a population covering a wide age range.

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. METHODS: In a systematic review of OVID MEDLINE-with additional hand-searching of relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5-24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. FINDINGS: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36-0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46-11·60; p<0·0001), antiplatelet use (1·68, 1·06-2·66; p=0·026), and anticoagulant use (3·48, 1·96-6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75-0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95-6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03-0·07). INTERPRETATION: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials. FUNDING: UK Medical Research Council and British Heart Foundation.

Assessment of lower extremity muscle mass, muscle strength, and exercise therapy in elderly patients with diabetes mellitus.

The increase in the proportion of elderly people in the population is one of the most remarkable sociodemographic phenomena of the twenty-first century. The number of patients with diabetes is also increasing worldwide with this demographic change. Given these facts, consideration of the problems the general elderly population is facing in the management of diabetes is essential. In this review article, we focus on sarcopenia, which is the decrease in lower extremity muscle mass and muscle strength accompanying aging, describe the relationship between sarcopenia and diabetes, and highlight the specific factors through which diabetes contributes to loss of muscle strength. The quantitative methods for evaluating lower extremity muscle strength will also be described. These methods hold the key to assessing the effectiveness of exercise therapy and optimizing the assessment of the degree of autonomy in the activities of daily living. Exercise is one of the basic treatments for type 2 diabetes and may also prevent and improve sarcopenia. This review discusses the aspects common to the two health conditions and elucidates the effectiveness and necessity of exercise as a preventive measure against diabetes among the elderly.

Diabetic polyneuropathy is a risk factor for decline of lower extremity strength in patients with type 2 diabetes.

AIMS/INTRODUCTION: The present study elucidated the effect of diabetic polyneuropathy (DPN) on lower extremity strength in a wide age range of type 2 diabetes patients. MATERIALS AND METHODS: Participants (n = 1,442) were divided into three age groups (30-49 years, 50-69 years and 70-87 years), and comparisons were made separately for each sex. Lower extremity strength was measured in terms of knee extension force (KEF) with a hand-held dynamometer. KEF was compared according to the presence or absence of DPN. Furthermore, the effect of DPN on KEF with other diabetic complications (diabetic retinopathy and diabetic nephropathy), diabetes status (diabetes duration and glycated hemoglobin) and habitual behavior (regular exercise, smoking and drinking behaviors) as explanatory variables was analyzed using multiple regression analysis in several models. RESULTS: The frequency of DPN differed among age groups, ranging from 14.3 to 49.6%, and increasing with age. There was no significant difference in KEF between patients aged 30-49 years with and without DPN. However, among both men and women aged 50-69 years and 70-87 years, patients with DPN showed significantly diminished KEF (11.0-12.9% and 11.9-16.6%, respectively) compared with those without DPN (P < 0.01-0.001). In women aged 50-69 years and 70-87 years, and in men aged 50-69 years, DPN was a significant explanatory variable for KEF in all multiple regression analysis models. CONCLUSION: DPN might reinforce a KEF decline in middle-aged and elderly type 2 diabetes patients.

Regular exercise behavior is related to lower extremity muscle strength in patients with type 2 diabetes: Data from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study.

Owing to several contributing factors, continuation of exercise therapy is difficult for patients with type 2 diabetes. One potential factor that has not been well examined is the influence of muscle strength on regular exercise behavior. We examined the relationship between regular exercise behavior and knee extension force (KEF) in 1,442 patients with type 2 diabetes. In sex-specific univariate analysis, KEF was significantly higher in patients who regularly exercised than in patients who did not regularly exercise. However, age, but not exercise behavior, was significantly different between KEF quartiles. Accordingly, KEF and age might strongly influence exercise behavior. In the multivariate analyses using age and other parameters as covariates, KEF was a significant explanatory variable of regular exercise in both men and women, suggesting that muscle strength could influence regular exercise behavior.

Aging, physical activity, and diabetic complications related to loss of muscle strength in patients with type 2 diabetes.

Patients with type 2 diabetes may have motor dysfunctions such as loss of muscle strength. Compared with non-diabetic subjects, patients with diabetes show decreased lower extremity muscle strength. The aim of this review was to describe the influence of factors associated with loss of muscle strength in patients with type 2 diabetes. Aging promotes an accelerated loss of muscle strength in patients with diabetes. Physical inactivity may cause a decline in muscle strength in patients with diabetes. Gradual loss of muscle strength is related to the presence and severity of diabetic neuropathy. Diabetic nephropathy may be a factor contributing to loss of muscle strength, because decrease in skeletal muscle mass is a hallmark of end-stage renal disease. Resistance exercise is an essential component of diabetes treatment regimens and also plays a role in the prevention and management of sarcopenia. Intensive physical therapy intervention should be provided to patients with diabetes having decreased muscle strength.

Evaluation of unmet medical need among Japanese patients with type 2 diabetes mellitus and efficacy of Lixisenatide treatment among Asian type 2 diabetes mellitus patients.

AIMS: This study determined the unmet medical need of basal insulin therapy among type 2 diabetes patients who participated in the ALOHA study. Also a meta-analysis of the GetGoal-Duo1, -L, and -L-Asia trials was conducted to examine the impact of lixisenatide add-on treatment to basal insulin therapy ± OADs specifically among Asian type 2 diabetes patients. METHODS: The proportions of Japanese patients with an unmet need of diabetes management, defined as not achieving an HbA1c<7% despite having a fasting plasma glucose (FPG)<130 mg/dL, and without an unmet need, defined as having an endpoint HbA1c<7%, regardless of FPG level, were determined for the ALOHA study population, which was conducted as a post-marketing survey for insulin glargine in Japan. For the meta-analysis, all Asian modified intent-to-treat patients with baseline and endpoint HbA1c measurements reported from the 3 GetGoal trials were included. RESULTS: Among 1013 Japanese type 2 diabetes patients in the ALOHA study, 36% had an unmet need. In the GetGoal-Duo1, -L, and L-Asia trials, 237 Asian patients were treated with lixisenatide add-on treatment to basal insulin and 226 received placebo. Lixisenatide add-on treatment vs. placebo was associated with the following significant mean changes in efficacy outcomes at week 24: HbA1c: -0.6%, p=0.005; FPG: -13.3mg/dL, p=0.004; PPG: -101.4 mg/dL, p<0.001; weight: -0.5 kg, p=0.018; basal insulin dose: -1.6 U, p<0.001. CONCLUSIONS: Lixisenatide add-on treatment may provide a viable option to address the unmet need of basal insulin therapy among Asian type 2 diabetes patients.

Rapid De Novo Aneurysm Formation after Rathke Cleft Cyst Rupture.

BACKGROUND: Spontaneous rupture of a Rathke cleft cyst is very rare, and rapid de novo aneurysm formation associated with pituitary apoplexy is rare. CASE DESCRIPTION: A 66-year-old woman experienced severe left temporal pain. Magnetic resonance imaging showed a Rathke cleft cyst, and transsphenoidal surgery was planned. However, the patient suddenly developed severe headache, vomiting, visual disturbance, and a lowered level of consciousness about 3 weeks after the first onset. The clinical course and neuroradiologic characteristics suggested Rathke cleft cyst rupture. The patient received hormone replacement, and the visual abnormalities resolved. However, subsequent neuroradiologic evaluation demonstrated that a de novo aneurysm in the cavernous sinus portion of the internal carotid artery had formed within 8 days after rupture of the Rathke cleft cyst. This de novo aneurysm was not apparent on initial magnetic resonance angiography. CONCLUSIONS: This case features a rare clinical presentation of rapid de novo aneurysm formation after Rathke cleft cyst rupture. The severe inflammation around the vasculature after rupture of the Rathke cleft cyst might have been involved in aneurysm formation.

Predictors for achieving target glycemic control in Japanese patients with type 2 diabetes after initiation of basal supported oral therapy using insulin glargine: sub-analysis of the ALOHA2 study, drug use surveillance in Japan.

OBJECTIVES: We aimed to identify diabetes-related factors associated with achieving HbA1c <7.0 % after the initiation of basal supported oral therapy (BOT) in insulin-naïve type 2 diabetes patients with an HbA1c value of ≥6.5 % during the previous 4 weeks, using data from Add-on Lantus® to Oral Hypoglycemic Agents 2 (ALOHA2) study, a 24-week observational study on Japanese type 2 diabetes patients. METHODS: Patients were categorized into two groups: HbA1c <7.0 % at the final evaluation point (at 24 weeks or the last visit) as HbA1c-target-achieved; HbA1c ≥7.0 % as target-not-achieved. Associations between baseline factors and HbA1c <7.0 % achievement were explored using logistic regression. RESULTS: Of the 1520 patients in the study, 400 patients (26.3 %) achieved HbA1c <7.0 %. Patients with diabetes duration of <1 year and between ≥1 and <2 years [odds ratio (OR): 5.27, 95 % confidence interval (CI): 1.13-24.51; OR: 3.77, 95 % CI 1.19-11.93, respectively], those on one pre-study orally administered antidiabetic agent (OAD) (OR: 2.42, 95 % CI 1.12-5.22), and those with absence of diabetic neuropathy (OR: 2.54, 95 % CI 1.12-5.76) were more likely to achieve HbA1c <7.0 % than those with duration of ≤15 years, ≥4 pre-study OADs, and neuropathy, respectively. Achievement of HbA1c <7.0 % among patients increased by approximately 20 % for each 1 % decrease in HbA1c level at baseline. CONCLUSIONS: Shorter diabetes duration, pre-study regimen of one OAD, absence of neuropathy, and lower HbA1c level at baseline were associated with achievement of HbA1c <7.0 %, suggesting that earlier initiation of BOT leads to good HbA1c control in insulin-naïve Japanese type 2 diabetes patients, consistent with our early ALOHA study.

Middle latency auditory-evoked potential index monitoring of cerebral function to predict functional outcome after emergency craniotomy in patients with brain damage.

BACKGROUND: At present, no satisfactory reports on the monitoring of cerebral function to predict functional outcomes after brain damage such as traumatic brain injury (TBI) and stroke. The middle latency auditory-evoked potential index (MLAEPi) monitor (aepEX plus®, Audiomex, UK) is a mobile MLAEP monitor measuring the degree of consciousness that is represented by numerical values. Hence, we hypothesized that MLAEPi predicts neurological outcome after emergency craniotomy among patients with disturbance of consciousness (DOC), which was caused by brain damage. METHODS: The afore-mentioned patients who underwent emergency craniotomy within 12 h of brain damage and were subsequently monitored using MLAEPi were enrolled in this study. DOC was defined as an initial Glasgow Coma Scale score < 8. MLAEPi was measured for 14 days after craniotomy. Neurological outcome was evaluated before discharge using a cerebral performance category (CPC) score and classified into three groups: favorable outcome group for a CPC score of 1 or 2, unfavorable outcome group for a score of 3 or 4, and brain dead (BD) group for a score of 5. RESULTS: Thirty-two patients were included in this study (17 with TBIs and 15 with acute stroke). Regarding outcome, 10 patients had a favorable outcome, 15 had an unfavorable outcome, and 7 were pronounced BD. MLAEPi was observed to be significantly higher on day 5 than that observed immediately after craniotomy in cases of favorable or unfavorable outcome (63 ± 3.5 vs. 36 ± 2.5 in favorable outcome; 63 ± 3.5 vs. 34 ± 1.8 in unfavorable outcome). MLAEPi was significantly lower in BD patients than in those with a favorable or unfavorable outcome on day 3 (24 ± 4.2 in BD vs. 52 ± 5.2 and 45 ± 2.7 in favorable and unfavorable outcome, respectively) and after day 4. MLAEPi was significantly higher in patients with a favorable outcome than in those with a favorable or unfavorable outcome after day 6 (68 ± 2.3 in favorable outcome vs. 48 ± 2.3 in unfavorable outcome). CONCLUSION: We believe that MLAEPi satisfactorily denotes cerebral function and predicts outcomes after emergency craniotomy in patients with DOC, which was caused by acute brain damage.

Improved Treatment Satisfaction and Self-reported Health Status after Introduction of Basal-Supported Oral Therapy Using Insulin Glargine in Patients with Type 2 Diabetes: Sub-Analysis of ALOHA2 Study.

INTRODUCTION: This study aimed to assess treatment satisfaction and self-reported health status in insulin-naïve patients with type 2 diabetes mellitus (T2DM) who started insulin glargine basal-supported oral therapy (BOT) with glycated hemoglobin (HbA1c) value of ≥6.5%, using data from Add-on Lantus(®) to Oral Hypoglycemic Agents 2 (ALOHA2) study, a 24-week single-arm, observational study of Japanese patients with T2DM, conducted as drug use surveillance in Japan. METHODS: Treatment satisfaction was measured using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and change version (DTSQc) and self-reported health status using EuroQol 5 Dimension (EQ-5D). The results were compared between the groups stratified by HbA1c level at the final evaluation point: target-achieved (<7.0%) and target-not-achieved groups (≥7.0%). RESULTS: In 1251 patients (336 in the target-achieved group), scores of DTSQs, DTSQc, and EQ-5D indicated significant improvement from baseline to the final evaluation point (both P < 0.01). The mean change in DTSQs scale score, DTSQs item score, and EQ-5D index score, and mean DTSQc scale score were significantly improved in the target-achieved group compared with the target-not-achieved group (P < 0.05 for all). DTSQs scale score and HbA1c level showed the same pattern of chronological change. Data analysis in patients stratified by DTSQs score showed better glycemic control in the high satisfaction group. CONCLUSION: Following insulin glargine BOT introduction, treatment satisfaction and health status were improved from patients' perspectives despite the need for daily injections. Based on the possible association between HbA1c 7.0% level achievement, treatment satisfaction, and health status, better glycemic control may be a key to successful treatment.

Efficacy and safety of lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal-S.

AIMS/INTRODUCTION: This was a subanalysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation (GetGoal-S) study - a 24-week, randomized, placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin. MATERIALS AND METHODS: In GetGoal-S, 127 Japanese patients received the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide 20 µg/day or a matching placebo. The primary outcome was change in glycated hemoglobin. RESULTS: At week 24, lixisenatide significantly reduced mean glycated hemoglobin (least squares mean difference vs the placebo -1.1% [12 mmol/mol, P < 0.0001]), and significantly more lixisenatide patients reached glycated hemoglobin targets of <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) vs the placebo. Lixisenatide produced statistically significant reductions in 2-h postprandial plasma glucose (least squares mean difference vs the placebo -8.51 mmol/L, P < 0.0001) and glucose excursion vs the placebo, and significantly reduced fasting plasma glucose (least squares mean difference vs the placebo -0.65 mmol/L, P = 0.0454). Bodyweight decreased with both lixisenatide and the placebo (least squares mean change -1.12 kg for lixisenatide, -1.02 kg for placebo). The overall incidence of adverse events was similar for lixisenatide and the placebo (84.2 and 82.4%, respectively), the most frequent being gastrointestinal disorders (52.6% for lixisenatide vs 29.4% for placebo). The incidence of symptomatic hypoglycemia was higher with lixisenatide vs the placebo (17.1 and 9.8%, respectively), with no cases of severe symptomatic hypoglycemia in either group. CONCLUSIONS: In the Japanese subpopulation of the GetGoal-S study, lixisenatide produced a significant and clinically relevant improvement in glycated hemoglobin, with a pronounced improvement in postprandial plasma glucose, and a good safety and tolerability profile.

[Adjuvant Surgery for Initially Unresectable Locally Advanced Pancreatic Cancer following Gemcitabine and S-1 Chemotherapy--A Case Report].

A man in his 60s was admitted with obstructive jaundice. A hypovascular tumor, 55 mm in diameter, was detected in the pancreas head on imaging. The superior mesenteric vein showed severe stenosis bilaterally and the roots of all branches were invaded by the tumor. The tumor was diagnosed as unresectable pancreatic cancer, and chemotherapy of gemcitabine and S-1 was administered, resulting in a remarkable reduction of the tumor size. Following 7 courses of chemotherapy, a subtotal stomach-preserving pancreatoduodenectomy was carried out. Microscopic examination revealed no residual cancer cells in the resected specimen, indicating that pathological complete remission was obtained. Although some reports suggest that surgical treatment for patients with initially unresectable pancreas cancer who show excellent response to chemotherapy may improve the prognosis, further studies are needed.

Glycemic variability is an independent predictive factor for development of hepatic fibrosis in nonalcoholic fatty liver disease.

UNLABELLED: Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) often have metabolic disorders including insulin resistance and type 2 diabetes mellitus (T2DM). We clarified the predictive factors in glucose metabolism for progression of hepatic fibrosis in patients with NAFLD by the 75-g oral glucose tolerance test (75gOGTT) and a continuous glucose monitoring system (CGMS). One hundred sixty-nine patients (68 female and 101 male patients) with biopsy-proven NAFLD with performance with 75gOGTT were enrolled and divided into four groups according to the stage of hepatic fibrosis (F0-3). The proportion of patients with T2DM significantly gradually increased, HbA1c and the homeostasis model assessment of insulin resistance were significantly elevated, and 1,5-anhydroglucitol (1,5-AG) was remarkably decreased with the progression of fibrosis. In the 75gOGTT, both plasma glucose and insulin secretion were remarkably increased with the progression of fibrosis. The only factor significantly associated with advanced fibrosis was 1,5-AG (P = 0.008) as determined by multivariate logistic regression analysis. We next evaluated the changes in blood glucose during 24 hours by monitoring with the CGMS to confirm the relationship between glycemic variability and progression of fibrosis. Variability of median glucose, standard deviation of median glucose (P = 0.0022), maximum blood glucose (P = 0.0019), and ΔMin-max blood glucose (P = 0.0029) were remarkably higher in severe fibrosis than in mild fibrosis. CONCLUSION: Hyperinsulinemia and hyperglycemia, especially glycemic variability, are important predictive factors in glucose impairment for the progression of hepatic fibrosis in NAFLD.

Efficacy of a new instrument for dural defect repair in anterior skull base reconstruction: a technical note.

BACKGROUND: The anterior skull base is a deep and narrow area, which makes dural repair technically challenging. The goal of this study was to demonstrate the efficacy of a new instrument for anterior skull base dural repair. METHODS: Ten patients underwent surgery via the transbasal approach, combined with either a transfacial or a transnasal endoscopic resection. The dural repair was performed prior to tumor resection, and the new instrument was used to suture the fascia lata in an underlay fashion. The repaired dural defect was then covered with a pericranial flap. RESULTS: The follow-up period ranged from 2 to 18 months, with an average follow-up time of 8.7 months. During this period, none of the patients experienced cerebrospinal fluid leakage, meningitis, tension pneumocephalus, abscess formation, or flap necrosis. CONCLUSIONS: Our findings suggest that the use of this instrument combined with the technique of suturing the fascia lata in an underlay fashion and covering it with a pericranial flap, may be an effective alternative approach to anterior skull base reconstruction.

[Surgical treatment for gall bladder cancer with a confluence stone-a case report].

The patient was a 71-year-old man. In September 2011, he experienced abdominal pain with high fever. Abdominal computed tomography (CT) diagnosed acute cholecystitis with a confluence stone (corlette classification type II). He underwent total cholecystectomy and placement of a T-tube in the main bile duct through the gall bladder duct. However, pathological investigations revealed gall bladder cancer in the neck and body part of the gall bladder, leading to a diagnosis of gall bladder adenocarcinoma(Gbn, Flat type, tub2, INF ß,pSS, pHinf0, pBinf1, pPV0, pA0, pT3) with a confluence stone. We suspected that the tumor was present in the common bile duct. Therefore, in October 2011, he underwent choledochectomy, resection of the liver bed, lymph node dissection, and choledocho-jejunostomy. Pathological findings revealed that the tumor was present in the common bile duct. He died 8 months after the last surgery because of recurrence of peritoneal metastasis.

Evaluation of the protective effects of cyclosporin a and FK506 on abnormal cytosolic and mitochondrial Ca²âº dynamics during ischemia and exposure to high glutamate concentration in mouse brain slice preparations.

We examined the protective effects of the immunosuppressants cyclosporin A (CsA) and FK506 on abnormal cytosolic Ca²âº ([Ca²âº]c) and mitochondrial Ca²âº concentration ([Ca²âº]m) dynamics induced by ischemia or high L-glutamate concentration in mouse brain slice preparations. We used fura-4F and rhod-2 as indicators for [Ca²âº]c and [Ca²âº]m, respectively, in their acetoxymethylester form. Slice preparations loaded with either of these two indicators were exposed to ischemic artificial cerebrospinal fluid (oxygen- and glucose-deprived medium) for 12 min or to aerobic medium with high L-glutamate concentration (isotonic 20 mM L-glutamate) for 5 min. CsA (1 - 10 µM) showed significant protective effects on the maximum increase in ischemia-induced [Ca²âº]c and [Ca²âº]m. FK506 (10 µM) showed significant protective effects on the [Ca²âº]m increase, but not on the ischemia-induced [Ca²âº]c increase. Both immunosuppressants showed almost equal protective effects on the [Ca²âº]c and [Ca²âº]m increases induced by high L-glutamate concentration. These results suggest that the protective effects of CsA and FK506 on Ca²âº overloading may be dependent upon the common pharmacological sites of actions relating to their effects as immunosuppressants. The small, but significant depressant effects of these drugs could give us important clues for rescuing critical brain damage induced by Ca²âº overloading.