Gadolinium contrast-enhanced MRI reveals cystic lateral semicircular canal contents

Conclusion: Contrast-enhanced magnetic resonance imaging (MRI) reveals variations in the endolymphatic morphology of the cystic lateral semicircular canal (CLSC) that correlate with inner ear function. This report is the first to suggest a relationship between the morphology and function of this common inner ear malformation in clinical cases. Objectives: This study investigated the radiological and functional findings of a common inner ear malformation using computed tomography (CT), gadolinium contrast-enhanced magnetic resonance imaging (MRI), caloric testing, and cervical and ocular vestibular evoked myogenic potential (VEMP) testing. Method: Four ears in three patients who were radiologically diagnosed with a CLSC and a normal cochlea on high-resolution CT and contrast-enhanced MRI were included. Semicircular canal and vestibular functions were analyzed using the caloric test and cervical and ocular VEMP testing. Results: Unilateral and bilateral cystic canals were found in two and one patients, respectively. In the first patient, the malformed vestibule and cystic space were separate on imaging, and perilymph filled the cystic space. The functional test results were normal. In the second patient, endolymph filled both cystic spaces, and the functional responses were poor. In the third patient, endolymph filled the cystic space, and the ear did not respond during functional testing.     

κ I light chain AL amyloidosis presenting with rapidly progressive renal and hepatic failure with unusual renal amyloid distribution

A 65-year-old man suffering from generalized edema and jaundice was admitted to our hospital. Laboratory findings revealed marked renal dysfunction with heavy proteinuria as well as liver dysfunction with severe obstructive jaundice. On renal biopsy, the diagnosis of AL amyloidosis associated with κ I light chain was made. Interestingly, amyloid deposits were restricted to the glomeruli. Although hemodialysis was initiated, the patient died due to further deterioration of hepatic function. On autopsy, severe intrahepatic cholestasis was observed, and there was marked deposition of AL amyloid in the liver. Literature reviews showed that rapidly progressive renal failure is common in AL amyloidosis patients who presented with acute hepatic failure due to severe intrahepatic cholestasis. However, the detailed renal pathology in this condition has not been documented. The present case is very interesting because rapidly progressive renal and hepatic failure was simultaneously observed, and renal amyloid deposition was restricted to the glomeruli.     

Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration.

Heparin-binding growth factor type 1 (HBGF-1; sometimes termed acidic fibroblast growth factor) is potentially an important factor in liver regeneration. HBGF-1 alone (half-maximal effect at 60 pM) stimulated hepatocyte DNA synthesis and bound to a high-affinity receptor (Kd = 62 pM; 5000 per cell). Epidermal growth factor (EGF) neutralized or masked the mitogenic effect of HBGF-1 concurrent with appearance of low-affinity HBGF-1 binding sites. HBGF-1 reduced the inhibitory effect of transforming growth factor type beta (TGF-beta) on the EGF stimulus. Nanomolar levels of HBGF-1 decreased the EGF stimulus. An increase in hepatic HBGF-1 gene expression after partial hepatectomy precedes increases in expression of the EGF homolog, TGF-alpha, and nonparenchymal-cell-derived TGF-beta in the regenerating liver. Expression of HBGF-1 mRNA occurs in both hepatocytes and nonparenchymal cells and persists for 7 days in liver tissue after partial hepatectomy. HBGF-1 acting through a high-affinity receptor is a candidate for the early autocrine stimulus that drives hepatocyte DNA synthesis prior to or concurrent with the EGF/TGF-alpha stimulus. It may allow hepatocyte proliferation to proceed in the presence of low levels of TGF-beta. An EGF/TGF-alpha-dependent change in HBGF-1 receptor phenotype and increasing levels of nonparenchymal-cell-derived HBGF-1 and TGF-beta may serve to limit hepatocyte proliferation.     

Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation of the sodium-glucose cotransporter-2 inhibitor tofogliflozin

Sodium-glucose cotransporter-2 inhibitors (SGLT2) are drugs that have been reported to have several effects through the regulation of plasma volume, for example, antihypertensive effects. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2 inhibitor tofogliflozin on estimated plasma volume (ePV), brain natriuretic peptide (BNP) and the relationship between changes in ePV, BNP and body weight (BW). Data from 157 participants with type 2 diabetes receiving tofogliflozin monotherapy in a phase 3 study were analysed. Changes in variables or correlations among them during a 52-week administration and a 2-week post-treatment period were investigated. Percent change in ePV was calculated using the Strauss formula. Significant decreases in BW, ePV and ln-transformed BNP (ln-BNP) were noted by week 52. %ΔBW was not significantly correlated with %ΔePV and Δln-BNP, while %ΔePV was significantly correlated with Δln-BNP. Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased. %ΔBW was significantly correlated with %ΔePV and Δln-BNP. Furthermore, ePV and BNP were significantly higher than baseline levels.     

Vimentin-positive gastric adenocarcinoma arising in a hyperplastic polyp

We report a case of vimentin-positive early gastric adenocarcinoma arising in a hyperplastic polyp (HP). A 72-year-old Japanese man was admitted for the detailed examination of a gastric polyp. He had a subtotal gastrectomy due to acute abdomen 12 years ago. Upper endoscopy revealed a pedunculated polyp measuring approximately 2 cm on the greater curvature of upper body of the remnant stomach. Magnifying endoscopy revealed that the microsurface pattern was irregular and partially absent accompanied with irregular microvessels at the upper end of the polyp. We speculated that the lesion was an adenocarcinoma arising in the HP. Endoscopic submucosal dissection (ESD) was performed. Histological examination of the ESD specimen revealed that the lesion consisted of well- to poorly differentiated adenocarcinoma at the protruding lesion and foveolar hyperplastic epithelia at the base of the polyp. Immunohistochemically, most of tumor cells that comprised poorly-differentiated adenocarcinoma were positive for both cytokeratin and vimentin. Although carcinomas have occasionally been found in HPs, the histological features of the present case are considered extremely unusual. To the best of our knowledge, this is the first case of vimentin-positive early gastric carcinoma arising in a HP.     

Factors associated with deep foot fissures in diabetic patients: a cross-sectional observational study

BackgroundFoot ulcers can develop from fissures in patients with diabetes. It is generally considered that fissures can develop with dry skin due to decreased perspiration associated with autonomic neuropathy. Especially, deep fissures that extend into the dermis may have a higher risk of ulceration than superficial fissures because of damage of skin barrier function. However, distinctions between superficial and deep fissures have not been well described, and specific factors involved in their development are generally unknown.ObjectiveTo investigate factors associated with the superficial and deep foot fissures in patients with diabetes.Design and methodsThis cross-sectional observational study involved 578 patients with diabetes evaluated at a university hospital between September 2007 and March 2008. Patients with foot ulcers or foot defects due to amputation were excluded. Superficial fissures were defined as narrow skin cracks limited to the epidermis. Deep fissures were defined as narrow, deep, linear skin cracks extending to the dermis, possibly with higher ulceration risk than superficial fissures. Logistic regression analysis was performed to analyze factors associated with the depth (superficial or deep) of foot fissures.ResultsThe prevalence of superficial fissures was 9.0%, and that of deep fissures was 3.8%. Presence of superficial fissures was correlated with autonomic neuropathy (OR 2.35, 95% CI 1.20–4.59, p = 0.012). Notably, presence of deep fissures was correlated with autonomic neuropathy and angiopathy (OR 2.88, 95% CI 1.11–7.48, p = 0.030; and OR 3.29, 95% CI 1.30–8.35, p = 0.012, respectively).ConclusionsOur new finding of a correlation between deep fissures and angiopathy suggests that control of blood supply should be effective for preventing deep fissures prone to ulceration. In the future, elucidation of the mechanism of the angiopathy-induced deep fissures will be needed to promote more effective preventive care of fissures.     

Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone marrow injection of autologous bone marrow cells

Objectives. Femoral head osteonecrosis (ON) is a serious complicationof steroid administration. We evaluated bone marrow transplantation(BMT) for preventing corticosteroid-induced ON. Methods. Rabbits, injected with methylprednisolone (MPSL; 20mg/kg), were divided into four groups: (i) MPSL alone; MPSLinjection only, (ii) MPSL+needling; 2 days after MPSL injection,a hole (1.2 mm diameter) was drilled from the outer cortex 2.5cm distal to the proximal end of the greater trochanter, (iii)MPSL+saline; 2 days after MPSL injection, 2 ml saline was injecteddirectly into the bone marrow cavity, and (iv) MPSL+BMT; 2 daysafter MPSL injection, 1 x 10⁷/2 ml bone marrow cells (BMCs)were injected directly into the bone marrow cavity. Platelets,fibrinogen, prothrombin time and total cholesterol in peripheralblood were measured before and after treatment. Tissues werestained with haematoxylin and eosion and terminal deoxynucleotidyl-mediateddeoxyuridine triphosphate nick-end labelling stain and immunostainedfor VEGF, while cell proliferation and viability of whole BMCsin the femur were analysed by cell cycle analysis and [³H]-thymidineuptake. Results. The ON incidence in rabbits treated with MPSL alone,MPSL+needling and MPSL+saline was 72.7, 70.0 and 66.7%, respectively,while in the MPSL+BMT group, the incidence was 0%. Serologicalfindings in the MPSL+BMT group were almost normalized. VEGFand TUNEL staining were reduced in the MPSL+BMT group comparedwith all other groups. There were significantly fewer BMCs inG1 phase from the MPSL+BMT group than the other groups, whileuptake of [³H]-thymidine was significantly increased. Conclusion. Direct injection of autologous BMCs into femursprevents corticosteroid-induced ON following treatment withhigh-dose, short-term steroids. KEY WORDS: Corticosteroid, Osteonecrosis, Animal model, Bone marrow transplantation, Bone marrow cells Submitted 10 June 2007; revised version accepted 15 January 2008.     

Intestinal ischemia induces late preconditioning against myocardial infarction: a role for inducible nitric oxide synthase

OBJECTIVE: We tested the hypothesis that occlusion of the superior mesenteric artery induces late preconditioning against myocardial infarction and examined the effects of pharmacological modifiers of inducible nitric oxide synthase activity on the late preconditioning in anesthetized rats. METHODS: Rats underwent an intestinal ischemia preconditioning protocol (30 min occlusion of the superior mesenteric artery) or were sham-operated. They were subjected to a sustained 30 min of coronary occlusion and 180 min of reperfusion 24 h later. RESULTS: In rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was 72+/-4% and 31+/-2%, respectively, in sham-operated rats, and these were significantly reduced to 44+/-4% and 23+/-2% (P<0.01) 24 h after intestinal ischemia preconditioning. Myeloperoxidase activity was significantly reduced by intestinal ischemia preconditioning. Administration of aminoguanidine (300 mg/kg, s.c.) or S-methylisothiourea sulfate (3 mg/kg, i.v.), both relative inducible NO synthase inhibitors, 60 or 30 min before sustained myocardial ischemia not only abolished the late preconditioning afforded by intestinal ischemia, but also inhibited the ability of intestinal ischemia preconditioning to significantly reduce neutrophil infiltration. A change in inducible NO synthase activity was not observed in normal myocardium 24 h after intestinal ischemia, but 30 min of coronary occlusion significantly increased the inducible NO synthase activity in the preconditioned group, which was abolished by aminoguanidine or S-methylisothiourea sulfate. CONCLUSIONS: These data provide pharmacological evidence that induction of inducible nitric oxide synthase, following intestinal ischemia, is associated with increased myocardial tolerance to infarction 24 h later.