Calculation of the cardiothoracic ratio from portable anteroposterior chest radiography

Cardiothoracic ratio (CTR), the ratio of cardiac diameter (CD) to thoracic diameter (TD), is a useful screening method to detect cardiomegaly, but is reliable only on posteroanterior chest radiography (chest PA). We performed this cross-sectional 3-phase study to establish reliable CTR from anteroposterior chest radiography (chest AP). First, CD(Chest PA)/CD(Chest AP) ratios were determined at different radiation distances by manipulating chest computed tomography to simulate chest PA and AP. CD(Chest PA) was inferred from multiplying CD(Chest AP) by this ratio. Incorporating this CD and substituting the most recent TD(Chest PA), we calculated the 'corrected' CTR and compared it with the conventional one in patients who took both the chest radiographies. Finally, its validity was investigated among the critically ill patients who performed portable chest AP. CD(Chest PA)/CD(Chest AP) ratio was {0.00099 × (radiation distance [cm])} + 0.79 (n = 61, r = 1.00, P < 0.001). The corrected CTR was highly correlated with the conventional one (n = 34, difference: 0.00016 ± 0.029; r = 0.92, P < 0.001). It was higher in congestive than non-congestive patients (0.53 ± 0.085; n = 38 vs 0.49 ± 0.061; n = 46, P = 0.006). Its sensitivity and specificity was 61% and 54%. In summary, reliable CTR can be calculated from chest AP with an available previous chest PA. This might help physicians detect congestive cardiomegaly for patients undergoing portable chest AP.     

Primary signet ring cell carcinoma of the uterine cervix: A case report

Rationale:Primary signet ring cell carcinoma of the uterine cervix is extremely rare and the clinical characteristics and prognosis are not well known and there are no specific guidelines for treatment.Patient concerns:A 43-year-old woman was referred to our hospital for abnormal uterine bleeding lasting 1 month.Diagnoses:Histological examination revealed a signet ring cell carcinoma of the uterine cervix. After evaluation of extragenital origin, the patient was diagnosed International Federation of Gynecology and Obstetrics stage IIIC1 primary signet ring cell carcinoma or the uterine cervix.Intervention:The patient was prescribed concomitant chemo-radiation followed by intracavitary brachytherapy.Outcomes:She showed no evidence of disease after treatment but, it recurred after 7 months of last treatment.Lessons:Different approaches to diagnosis and treatment of this rare disease are needed and molecular pathological studies related to the onset of the disease are required.     

Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia

Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damages in the brain. In the present study, ischemia-induced changes in GLP-1R immunoreactivity in the gerbil hippocampal CA1 region were evaluated after transient cerebral ischemia; in addition, the neuroprotective effect of the GLP-1R agonist exendin-4 (EX-4) against ischemic damage was studied. GLP-1R immunoreactivity and its protein levels in the ischemic CA1 region were highest at 1 day after ischemia/reperfusion (I/R). At 4 days after I/R, GLP-1R immunoreactivity was hardly detected in CA1 pyramidal neurons, and its protein level was lowest. GLP-1R protein level was increased again at 10 days after I/R, and GLP-1R immunoreactivity was found in astrocytes and GABAergic interneurons. In addition, EX-4 treatment attenuated ischemia-induced hyperactivity, neuronal damage, and microglial activation in the ischemic CA1 region in a dose-dependent manner. EX-4 treatment also induced the elevation of GLP-1R immunoreactivity and protein levels in the ischemic CA1 region. These results indicate that GLP-1R is altered in the ischemic region after an ischemic insult and that EX-4 protects against ischemia-induced neuronal death possibly by increasing GLP-1R expression and attenuating microglial activation against transient cerebral ischemic damage.     

Fat Cell�CSpecific Ablation of Rictor in Mice Impairs Insulin-Regulated Fat Cell and Whole-Body Glucose and Lipid Metabolism

OBJECTIVE

Rictor is an essential component of mammalian target of rapamycin (mTOR) complex (mTORC) 2, a kinase that phosphorylates and activates Akt, an insulin signaling intermediary that regulates glucose and lipid metabolism in adipose tissue, skeletal muscle, and liver. To determine the physiological role of rictor/mTORC2 in insulin signaling and action in fat cells, we developed fat cell–specific rictor knockout (FRic^−/−) mice.

RESEARCH DESIGN AND METHODS

Insulin signaling and glucose and lipid metabolism were studied in FRic^−/− fat cells. In vivo glucose metabolism was evaluated by hyperinsulinemic-euglycemic clamp.

RESULTS

Loss of rictor in fat cells prevents insulin-stimulated phosphorylation of Akt at S473, which, in turn, impairs the phosphorylation of downstream targets such as FoxO3a at T32 and AS160 at T642. However, glycogen synthase kinase-3β phosphorylation at S9 is not affected. The signaling defects in FRic^−/− fat cells lead to impaired insulin-stimulated GLUT4 translocation to the plasma membrane and decreased glucose transport. Furthermore, rictor-null fat cells are unable to suppress lipolysis in response to insulin, leading to elevated circulating free fatty acids and glycerol. These metabolic perturbations are likely to account for defects observed at the whole-body level of FRic^−/− mice, including glucose intolerance, marked hyperinsulinemia, insulin resistance in skeletal muscle and liver, and hepatic steatosis.

CONCLUSIONS

Rictor/mTORC2 in fat cells plays an important role in whole-body energy homeostasis by mediating signaling necessary for the regulation of glucose and lipid metabolism in fat cells.Mammalian target of rapamycin (mTOR) is a serine/threonine (S/T) kinase that is a key regulator of cell growth and metabolism (1). mTOR is found in two separate multiprotein complexes: mTOR complex (mTORC) 1, in which mTOR interacts with raptor, mLST8, and PRAS40; and mTORC2, formed by mTOR interaction with rictor, mLST8, and mSin (1–3). mTOR kinase activity associated with mTORC1 can be specifically inhibited by rapamycin (1). When mTOR binds to rictor it is not inhibited by rapamycin (1), but long-term treatment with rapamycin inhibits the formation of mTORC2 in some cell types (4). Both mTORCs are mediators of insulin and growth factor signaling in cultured cells through the classical tyrosine kinase receptor/phosphatidylinositol-3-kinase (PI3K) pathway (1). mTOR complexes phosphorylate and activate a subgroup of the AGC family of protein kinases, including the mTORC1 target S6 kinase 1 (S6K1) (5) and the mTORC2 substrate Akt (also known as protein kinase B) (6). The mTORC1/S6K1 arm of insulin signaling is known to be involved in the regulation of cell growth and protein synthesis (5). Akt mediates insulin regulation of glucose and lipid metabolism in adipose tissue, skeletal muscle, and liver (7).Full activation of Akt kinase activity requires phosphorylation at S473 by mTORC2 and T308 by phosphoinositide-dependent kinase (PDK1) (8). In cell culture models, short-hairpin RNA (shRNA)-mediated depletion of rictor results in loss of mTORC2-mediated Akt S473 phosphorylation (6). Interestingly, loss of S473 phosphorylation after rictor knockdown in cultured cells reduced the phosphorylation of some, but not all, Akt substrates. The effects of the loss of rictor on insulin-mediated metabolic responses were not tested. Because Akt is downstream of mTORC2 in the insulin signaling pathway and is a mediator of insulin''s effect on metabolic processes, we were interested in determining the role of mTORC2 in controlling glucose and lipid metabolism in insulin target tissues. Since whole-body rictor knockout mice are embryonic lethal (9,10), we previously developed mice in which rictor expression was ablated specifically in skeletal muscle (MRic^−/−) (11). MRic^−/− mice exhibited impaired insulin-stimulated Akt S473 phosphorylation and glucose transport defects in skeletal muscles that resulted in mild glucose intolerance.Recently, adipose tissue has gained increased attention not only for storing body''s excess energy but also as an endocrine organ secreting adipokines, such as leptin, adiponectin, and resistin (12). The adipokines, as well as nonesterified fatty acids (NEFAs) formed during lipolysis in fat cells, impact whole-body insulin sensitivity and insulin secretion by pancreatic β-cells (13). mTOR has been implicated in fat cell function (1). Patients treated with rapamycin have elevated circulating NEFAs, suggesting that mTORC1 plays a role in the regulation of fat cell lipolysis (14,15). However, because chronic rapamycin treatment can affect the activity of both mTORC1 and mTORC2 (4), it was unclear which complex was involved in the regulation of lipolysis in adipocytes. As demonstrated in fat cell–specific GLUT4 (insulin-responsive GLUT) knockout mice (16), glucose transport by fat cells is critical for the maintenance of whole-body glucose homeostasis. Our study with MRic^−/− mice had shown a role for rictor/mTORC2 in the regulation of glucose uptake (11). To determine the role of rictor/mTORC2 in fat cell function and the regulation of glucose and lipid metabolism, we developed mice in which rictor expression was specifically ablated in fat cells (FRic^−/− mice).     

Rufinamide pretreatment attenuates ischemia-reperfusion injury in the gerbil hippocampus

Objectives: Rufinamide, a voltage-gated sodium channel (VGSC) blocker, is widely used for the clinical treatment of seizures associated with Lennox-Gastaut syndrome. Previous studies have demonstrated that VGSC blockers have neuroprotective properties against ischemic damage following experimental cerebral ischemia. However, protective effects of rufinamide against cerebral ischemic insults have not been addressed. Therefore, in the present study, we firstly examined neuroprotective effects of rufinamide using a gerbil model of transient global cerebral ischemia.

Methods: Gerbils were established by the occlusion of common carotid arteries for 5 min. The gerbils were divided into vehicle-treated sham-operated group, vehicle-treated ischemia-operated group, 50 and 100 mg/kg rufinamide-treated sham-operated groups, and 50 and 100 mg/kg rufinamide-treated ischemia-operated groups. Rufinamide was administrated intraperitoneally once daily for 3 days before ischemic surgery. To examine neuroprotective effects of rufinamide, we carried out cresyl violet staining, neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, we examined gliosis using immunohistochemistry for glial fibrillary acidic protein (a marker for astrocytes) and ionized calcium-binding adapter molecule 1 (a marker for microglia).

Results: We found that pre-treatment with 100 mg/kg of rufinamide effectively protected pyramidal neurons in the hippocampal cornus ammonis 1 (CA1) area after transient global cerebral ischemia. In addition, pre-treatment with 100 mg/kg of rufinamide significantly attenuated activations of astrocytes and microglia in the ischemic CA1 area.

Discussion: These findings suggest that rufinamide can display neuroprotective effect against cerebral ischemic insults and that its neuroprotective effect may involve the attenuation of ischemia-induced glial activation.     

A pilot study to investigate the treatment of cervical human papillomavirus infection with zinc-citrate compound (CIZAR®)

Objective

In the present study the potential therapeutic effects of zinc-citrate compound (CIZAR®) in women infected with high-risk human papillomavirus (HR-HPV) was investigated.

Methods

A total of 194 women diagnosed with HR-HPV infection using the Hybrid capture (HC) II assay with no evidence of high grade squamous intraepithelial lesions (HSIL) or worse by Pap smear and colposcopy were enrolled. Among them, 76 women were treated by twice weekly self administered intra-vaginal infusion of 0.5 mM zinc citrate solution containing CIZAR® for 12 weeks and were evaluated for clearance of the HR-HPV infection compared to 118 women without treatment (Control group).

Results

The 12 weeks zinc citrate solution treatment resulted in the elimination of HR-HPV in 49/76 (64.47%) patients compared to the spontaneous clearance of 15.25% (18/118) in the control group (p = 0.000). By logistic regression analysis, the 12 week zinc citrate solution treatment reduced the risk of persistent HR-HPV infection significantly (OR 0.079; 95% CI 0.039-0.165; p = 0.000).

Conclusion

The results of this study showed for the first time that treatment with intra-vaginal infusion of a zinc-citrate compound (CIZAR®) can result in elimination of HR-HPV infection from the uterine cervix.     

Comparison of efficacy of pulsed biphasic waveform and rectilinear biphasic waveform in a short ventricular fibrillation pig model

Aim of study

The waveform designs and their relative defibrillation efficacy of external biphasic waveforms may differ remarkably among manufacturers. In this study, we compared pulsed biphasic waveform (PBW) with rectilinear biphasic waveform (RBW) and their effects on terminating ventricular fibrillation (VF).

Methods

VF was electrically induced and untreated for 10 s in 6 domestic pigs weighing between 56 and 70 kg. The animals were then randomized to attempt defibrillation with either a PBW or RBW shock at energy levels of 50–200 J. If the delivered shock failed to terminate VF, a 150 J rescue shock was delivered with the same waveform. After a recovery interval of 4 min, the sequences were repeated for a total of 60 test shocks. The 50% and 80% defibrillation thresholds (DFT) were then calculated for the compared waveforms.

Results

No differences were observed in energy DFT50 and DFT80. Although the peak current and average current of the PBW were higher than RBW, there was no change observed in ST segment following shocks with both waveforms.

Conclusion

In the setting of this experiment, there was no difference in terms of defibrillation efficacy and myocardial injury related to the electrical shocks of the two waveforms.     

High-definition imaging of trabeculectomy blebs using spectral domain optical coherence tomography adapted for the anterior segment

Background:  The aim of this work was to image trabeculectomy blebs using spectral domain optical coherence tomography (SDOCT).
Methods:  In this prospective cross-sectional study, patients who had undergone trabeculectomy with at least 3 months of follow up were included. Blebs were imaged using an adapted SDOCT system (Cirrus HD-OCT, Carl Zeiss Meditec Inc., Dublin, CA, USA) and time domain anterior segment optical coherence tomography (ASOCT) (Visante OCT, Carl Zeiss Meditec Inc.). An observer masked to clinical data assessed the utility of SDOCT and ASOCT in visualizing structures in successful and failed blebs.
Results:  Fifty-one eyes were imaged, of which 43 (84.3%) were successful. SDOCT showed wall thickening (93.0% vs. 67.4%, P  = 0.006) and discrete hyporeflective spaces in the wall (88.4% vs. 14.0%, P  < 0.0001) in a greater proportion of successful blebs than ASOCT. SDOCT showed the bleb cavity (23.3% vs. 48.8%, P  = 0.02), scleral flap (34.9% vs. 90.7%, P  < 0.0001), subflap space (20.9% vs . 72.1%, P  < 0.0001) and ostium (9.3% vs. 88.4%, P  < 0.0001) in fewer successful blebs than ASOCT. The internal ostium was not visualized in any failed bleb using SDOCT, whereas ASOCT showed the ostium in 87.5% of failed blebs ( P  = 0.001). SDOCT showed cystic spaces in the bleb wall in a greater proportion of successful blebs than failed blebs (88.4% vs. 37.5%, P  = 0.005).
Conclusions:  SDOCT imaging was able to show fine superficial features in the bleb wall. However, SDOCT had limited clinical utility in that it did not provide useful information about deep features such as flap position, bleb cavity formation or patency of the subflap space and internal ostium.