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.

[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.

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.

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.

[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.

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.

Regulated endoplasmic reticulum-associated degradation of a polytopic protein: p97 recruits proteasomes to Insig-1 before extraction from membranes.

Polytopic membrane proteins subjected to endoplasmic reticulum (ER)-associated degradation are extracted from membranes and targeted to proteasomes for destruction. The extraction mechanism is poorly understood. One polytopic ER protein subjected to ER-associated degradation is Insig-1, a negative regulator of cholesterol synthesis. Insig-1 is rapidly degraded by proteasomes when cells are depleted of cholesterol, and its degradation is inhibited when sterols accumulate in cells. Insig-2, a functional homologue of Insig-1, is degraded slowly, and its degradation is not regulated by sterols. Here, we report that a single amino acid substitution in Insig-2, Insig-2(L210A), causes Insig-2 to be degraded in an accelerated and sterol-regulated manner similar to Insig-1. In seeking an explanation for the accelerated degradation, we found that proteasomes bind to wild type Insig-1 and mutant Insig-2(L210A) but not to wild type Insig-2, whereas the proteins are still embedded in cell membranes. This binding depends on at least two factors, ubiquitination of Insig and association with the ATPase p97/VCP complex. These data suggest that p97 recruits proteasomes to polytopic ER proteins even before they are extracted from membranes.

Endocrinological and MRI features of pituitary adenomas with marked xanthogranulomatous reaction.

INTRODUCTION: The study aims to describe the endocrinological and magnetic resonance imaging (MRI) features of the rarely reported xanthogranulomas associated with pituitary adenoma. METHODS: Of 231 consecutive pituitary adenomas treated surgically, those with xanthogranulomatous reaction on histology were reviewed. RESULTS: Five patients (2.2%) had an adenoma with marked xanthogranulomatous reaction. They were all nonfunctioning macroadenomas and presented with anterior pituitary insufficiencies. On MRI, all adenomas showed mixed signal intensities on T1- and T2-weighted images with heterogeneous gadolinium enhancement, reflecting their complex histological features: Cholesterol clefts typically showed T1 high- and T2 low-signal intensities. Preoperative diagnosis was difficult in a case predominantly featuring xanthogranuloma. Although none of them had episodes of pituitary apoplexy, hemosiderin deposits and cysts with xanthochromic-like fluid were observed in five and four cases, respectively. CONCLUSIONS: Xanthogranulomatous reaction may develop in macroadenomas, probably triggered by hemorrhagic processes despite no apoplectic episodes. They typically exhibit complex mixed signal intensity on MRI, particularly T1 high- and T2 low-signal intensities, and patients present with pituitary dysfunction.

Cerebellar infarction caused by primary central nervous system angiitis of childhood: case report.

BACKGROUND: Cerebellar infarction of childhood is rare, and is difficult in pathological diagnosis. We describe a case of radiographically diagnosed primary central nervous system angiitis of childhood. SUMMARY: A 7-year-old boy experienced dizziness and headache persisting for 7 days. Diffusion-weighted images of magnetic resonance (MR) showed high signals in the left cerebellar hemisphere and vermis. The MR angiogram (MRA) findings were normal. A conventional angiogram demonstrated severe stenoses and occlusions at distal portion of left posterior inferior cerebellar artery, and irregularity in the wall of the cervical portion of the left vertebral artery (VA). Although he recovered without any neurologic deficits, an angiogram 3 months after admission showed occlusion at the cervical portion of left VA and filling of the distal VA with collateral arteries from the deep cervical artery. He was doing well, with no additional changes demonstrated on MRA, 12 months after the onset. CONCLUSION: Although MRA can detect abnormality within the proximal intracranial vessels, angiography is essential, especially in cases with distal stenoses. Repeated angiography in primary central nervous system angiitis of childhood is necessary at least 3 months after the onset, even if the patient has no symptom.

A case of an intraventricular inflammatory pseudotumor presumably caused by Epstein-Barr virus infection.

BACKGROUND: Inflammatory pseudotumor primarily affecting the CNS is an extremely rare lesion with uncertain etiology in most cases. CASE DESCRIPTION: A 67-year-old man developed involuntary movement disorder of the left upper extremity. On MRI, a solid homogeneously-enhanced tumor was noted in the right lateral ventricle adjacent to the thalamus. He had histories of right thalamic hypertensive hemorrhage and recurrent chronic nasal sinusitis associated with an orbital mass lesion, presumably an IP. Partial removal of the tumor yielded a diagnosis of IP associated with EBV infection. CONCLUSION: The simultaneous occurrence of multiple IPs was presumably because of an exaggerated immune process after EBV infection. Inflammatory pseudotumor should be considered in any case of intraventricular mass lesion.

Surgical management of giant trigeminal schwannomas extending into the parapharyngeal space.

PURPOSE: Trigeminal schwannomas extending into the deep parapharyngeal space are relatively rare, and a surgical approach to such tumors has not been well established. We report four cases in which the tumors were completely removed by using a combination of three approaches. METHODS: Four patients with trigeminal schwannomas extending into the extracranial space were surgically treated using a combination of the transcervical approach, anterolateral retromaxillar pathway via gingivobuccal sulcus, and epi and interdural middle fossa approach. RESULTS: The maximum diameters of the tumors ranged from 4 to 7 cm. Three tumors extended beyond the lower end of the maxillary sinus. All tumors were completely excised. The Karnofsky performance scales after surgery were more than 90% in all patients. CONCLUSION: Although the tumors extending to the deep parapharyngeal space are difficult to completely remove via a single approach, a combined approach is useful in these huge extracranial extensions.

Dural suturing for repair of cerebrospinal fluid leak in transnasal transsphenoidal surgery.

OBJECTIVE: Repair of a cerebrospinal fluid (CSF) leak after transsphenoidal surgery (TSS) is usually accomplished using various graft materials. These methods are effective in most, but not all, cases. METHODS: Since 2006, we have been directly suturing the sellar floor dura in patients with an intraoperative CSF leak. Fat and/or fascial grafts were utilized only when a major CSF leak developed. The incidence of postoperative CSF rhinorrhea was compared before and after the suture. RESULTS: Postoperative CSF rhinorrhea developed in 3.7% (7 out of 188) of cases before 2005, but never since the dural suture was introduced (0 out of 136, 0%; P = 0.0229). Although watertight closure was not achieved in some cases, narrowing the dural defect and supporting the intrasellar graft was attained in every case. Surgical time was approximately 30 min longer in patients who underwent dural suture (148 +/- 42 min) than those who did not (119 +/- 37 min; P = 0.0001). CONCLUSION: Direct suturing of the sellar dura is a simple, safe, and reliable surgical technique for repairing CSF leaks after TSS. Using this procedure, more than 70% of patients with an intraoperative CSF leak can avoid autologous tissue grafts.

Primary medulla oblongata germinoma--an unusual posterior fossa tumors in young adults.

We encountered 2 patients with germinoma arising from the medulla oblongata in whom preoperative radiological diagnosis was difficult. A 30-year-old woman presented due to aspiration pneumonia caused by bilateral lower cranial nerve palsies, and a 24-year-old man presented with headache caused by obstructive hydrocephalus. In both patients, there was a midline tumor that extended from the lower part of the fourth ventricle to the C1 lamina level. It was well-demarcated and homogeneously enhanced tumor with a slightly high density on plain CT scan. The preoperative diagnosis for both patients was ependymoma. The former patient had persistent lower cranial nerve palsies due to brain stem injury after tumor resection. Both patients achieved complete remission with adjuvant therapy. Fewer than 10 cases of germinoma affecting the medulla oblongata have been reported. Radiological findings resembling those of the pineal region germinoma were observed in the two patients reported here. We would like to stress the importance of remembering germinoma when making a preoperative differential diagnosis of fourth ventricular tumors in young adults.

Edaravone inhibits collagen-induced arthritis possibly through suppression of nuclear factor-kappa B.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease which is induced by proinflammatory cytokines or oxidative stress. The activation of nuclear factor-kappa B (NF-kappaB) that contributed to imbalance between apoptosis and proliferation of rheumatoid synovial cells (SC). Edaravone, clinically available free radical scavenger in Japan, is confirmed to be beneficial in the acute stage of stroke. We aimed to investigate the suppressive effect of edaravone on collagen-induced arthritis (CIA) mice and on the activated molecules in SC stimulated by interleukin-1beta (IL-1beta). METHODS: Edaravone was administrated intravenously at a dose of 3mg/kg of body weight to CIA mice. The progression of CIA was evaluated by the macroscopic arthritis scoring system of paws. Interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3) concentrations in culture medium of human SC were measured by enzyme linked immunosorbent assays. Caspase-3/7 activity and nuclear factor-kappa B (NF-kappaB) protein level of cultured human SC were estimated by fluorometric assay and Western blot analysis, respectively. RESULTS: Edaravone significantly decreased macroscopic arthritis score in CIA mice. Acceleration of IL-6 and MMP-3 productions and attenuation of caspase-3/7 activity in IL-1beta-stimulated SC were abated by edaravone. Activated NF-kappaB in IL-1beta-stimulated SC was suppressed by edaravone. CONCLUSION: Edaravone, antioxidants available for clinical use, appears to have therapeutic effect on RA. We suggest that the inhibitory effect of edaravone on RA might be exerted, at least in part, through suppression of activated NF-kappaB. Therefore, we expect therapeutical use of edaravone as an anti-rheumatic agent.

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.

Transient hemiballism caused by a small lesion of the subthalamic nucleus.

Hemiballism is most commonly caused by ischemic stroke and most cases have a favorable prognosis. Lesions directly involving the subthalamic nucleus (STN) are the cause of a minority of cases but are usually associated with poor prognosis. We report two patients with a small STN lesion who presented with transient hemiballism. A small lesion confined to and only focally affecting the STN may cause hemiballism yet may have excellent outcome. Precise evaluation of the affected region with MRI is useful in predicting the prognosis.

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.