Successful remission using metyrapone in an elderly patient with Cushing disease accompanied by generalized edema

An 82-year-old woman was referred to our hospital because of hypoalbuminemia and generalized edema. Hypercortisolemia was subsequently found as the levels of serum cortisol and plasma adrenocorticotropic hormone (ACTH) sampled in a fasting morning were 140 pg/mL and 41.9 μg/dL, respectively. These hormones were not suppressed after taking low-dose dexamethasone the previous night and increased to a mild extent in response to administration of corticotrophin-releasing hormone, suggesting presence of pituitary adenoma producing ACTH (Cushing's disease). However, intrasella localization of pituitary adenoma could not be determined by magnetic resonance imaging. Soon after administration of metyrapone was started in an attempt to reduce her cortisol levels, the patient suffered from severe pneumonia. The pulmonary infection and peripheral edema were improved with decreases in cortisol levels by continuing metyrapone administration with antibiotics and finally she was discharged from the hospital on foot. Metyrapone is a useful therapeutic choice to achieve a remission of cortisol levels in the elderly patients with Cushing's disease in association with serious hypercortisolemia impending severe infection.     

Dialysate Vascular Endothelial Growth Factor Is an Independent Determinant of Serum Albumin Levels and Predicts Future Withdrawal From Peritoneal Dialysis in Uremic Patients

Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis (PD) therapy in end stage renal disease (ESRD) patients. We have found that pigment epithelium‐derived factor (PEDF) has anti‐vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor (VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty‐seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate (P = 0.002), serum albumin (inversely, P < 0.001) and dialysate PEDF levels (P < 0.001). In multiple stepwise regression analysis, age (P = 0.002) and dialysate VEGF levels (P < 0.001) were independent determinants of serum albumin levels. High VEGF (>27 pg/mL), low serum albumin (≤3.31 g/dL) and low hemoglobin (≤11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 (P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients.     

The efficiency of interference of Potato virus X infection depends on the target gene

RNA silencing is a natural defense response against viral infection. This phenomenon has been used to interfere with viral infections by exploiting fragments of viral genomes as sources of RNA silencing. Agrobacterium-mediated transient expression of a hairpin RNA derived from the TGBp1 gene of Potato virus X (PVX) induced RNA silencing of the TGBp1 gene and resulted in interference of PVX infection. The interference was induced in the infiltrated leaves but not in the upper non-infiltrated leaves. Transient expression of a CP hairpin RNA also induced interference of PVX. The TGBp1 hairpin RNA showed more efficient interference of PVX infection than the CP hairpin RNA.     

VAMP4 and its cognate SNAREs are required for maintaining the ribbon structure of the Golgi apparatus

Background

The Golgi apparatus is at a crossroads between anterograde and retrograde trafficking. It exhibits a twisted ribbon-like network in the juxtanuclear region of vertebrate cells. Vesicle-associated membrane protein 4 (VAMP4) is a unique v-SNARE expressed exclusively in trans-Golgi networks (TGN), where it regulates retrograde trafficking from the early endosome to the TGN with its cognate SNARE partners Syntaxin 6, Syntaxin 16, and Vti1a.

Unilateral high-frequency jet ventilation during one-lung ventilation for thoracotomy

One-lung ventilation is indicated during thoracic operations for bronchopleural fistula, pulmonary abscess, and pulmonary hemorrhage in spite of the possibility of the development of severe hypoxemia. To evaluate methods for improving oxygen transport during one-lung ventilation, we applied high-frequency jet ventilation (HFJV) and continuous positive airway pressure (CPAP) to the nondependent lung following deflation to atmospheric pressure in each procedure, and measured the effects on cardiac output and arterial oxygenation. In each case, the dependent lung was ventilated with conventional intermittent positive pressure ventilation (IPPV). Eight patients were studied during posterolateral thoracotomy using double-lumen endobronchial tubes. HFJV or CPAP to the nondependent lung improved arterial oxygenation significantly during both closed and open stages of the surgical procedures (p less than 0.008). When the chest was open, HFJV maintained satisfactory cardiac output, whereas CPAP usually decreased cardiac output (p less than 0.008). There were no significant differences in mean partial pressure of arterial carbon dioxide between HFJV, CPAP, and deflation to atmospheric pressure. In conclusion, HFJV to the nondependent lung provides not only satisfactory oxygenation but also good cardiac output, thereby maintaining better oxygen transport than CPAP or deflation to atmospheric pressure, while the dependent lung is ventilated with IPPV during one-lung ventilation for thoracotomy.     

KRAS mutations in tongue squamous cell carcinoma

Background: p16^INK4a (p16) expression in tongue cancer (TC) is reportedly not associated with human papilloma virus (HPV). Mutations of KRAS in cancer cells are most frequently observed within codon 12. However, few reports have investigated the association between KRAS mutations and p16 status in TC.

Objectives: This study aimed to evaluate the influence of KRAS mutations on TC.

Methods: Clinical records and surgically resected specimens of 85?TC patients were analyzed. Tumor samples were analyzed for mutations of KRAS located within codons 12 and 13. p16 staining was performed and considered positive in cases with moderate to strong nuclear and cytoplasmic staining.

Results: Positive p16 staining was observed in 10 cases (11.8%). A KRAS mutation was detected in one case (1.2%). The case with KRAS mutation showed negative p16 staining. Despite being at an early stage, the patient died of lung metastasis at 43 months from initial treatment.

Conclusions and Significance: KRAS mutations are not associated with p16 expression in TC and may predict poor prognosis in TC patients. Further analysis of mutations in regions other than codons 12 and 13 of KRAS will be necessary to determine the relationship between KRAS mutations and prognosis of this disease.     

Beneficial Effect of Partial Portal Decompression Using the Inferior Mesenteric Vein for Intractable Gastroesophageal Variceal Bleeding in Patients With Liver Cirrhosis

BACKGROUND: Use of the inferior mesenteric vein (IMV) for partial portal decompression has not been recommended as a first-line option for intractable gastroesophageal variceal bleeding because of the thin diameter of the vein. Although these indications remain relevant, few reports have compared partial portal decompression using the IMV with other therapies. We propose that partial portal decompression using the IMV is a useful alternative treatment for intractable variceal bleeding. METHODS: We performed partial portal decompression using the IMV in eight patients with intractable variceal bleeding that had been uncontrolled using medical and endoscopic therapies. All patients were classified into Child's class B or C. The surgical data, morbidity, and mortality were assessed. RESULTS: Mean portal venous pressure significantly decreased from 26.9 +/- 2.0 mmHg before the surgery to 19.8 +/- 3.9 mmHg after the surgery. The operative mortality rate was 0%. The mean duration of hospital stay was 25.5 +/- 13.3 days. Although one patient experienced recurrent bleeding, shunt patency was well maintained in all patients during the follow-up period (mean 28.9 +/- 14.1 months). Six patients are still alive and well without ascites or hepatic encephalopathy. Two of the Child's class C patients who underwent emergency shunt died owing to hepatic decompensation. CONCLUSION: Partial portal decompression using the IMV can be a safe, effective way to treat intractable variceal bleeding in patients with liver cirrhosis. However, use of the shunt procedure may have the most survival benefits for cirrhotic patients with preserved liver function.     

QUANTITATIVE ANALYSIS OF LOW‐DOSE ASPIRIN‐ASSOCIATED SMALL BOWEL INJURY USING A CAPSULE ENDOSCOPY SCORING INDEX

Aim: The major limitation of capsule endoscopy (CE) has been the lack of a standardized and validated severity scale for mucosal injury. The aim of the present study was to verify the usefulness of quantifying small bowel mucosal changes associated with giving low‐dose aspirin (LDA) using a CE scoring index. Methods: The CE score for small bowel mucosal injury was investigated to evaluate the severity of mucosal injury. Healthy volunteers and patients suspected of having small bowel disease were recruited for this study. The short‐term LDA group (V + S‐LDA group) consisted of volunteers who took low‐dose aspirin for 14 days; this group was then compared with healthy volunteers who did not receive LDA treatment (V‐Control group). The long‐term LDA group (L‐LDA group) consisted of patients with at least a 3‐month history of daily LDA use; this group was compared with non‐users of LDA (P‐Control group). Results: The CE score was significantly higher in the V + S‐LDA group than in the V‐Control group. In the V‐Control group, almost all the subjects were categorized as exhibiting a ‘normal’ change. ‘Mild’ changes were observed significantly more frequently in the V + S‐LDA group than in the V‐Control group. The CE score was significantly higher in the L‐LDA group than in the P‐Control group. ‘Mild’ or ‘moderate or severe’ changes were observed significantly more frequently in the L‐LDA group than in the P‐Control group. Conclusion: The CE scoring system was useful for evaluating LDA‐associated small bowel mucosal disease activity and for objectively scoring the small bowel inflammatory disease state.     

Metabolism of Cyanox in rat. II. Sex-related differences in oxidative dearylation and desulphuration

1. To examine the metabolites of Cyanox (O-4-cyanophenyl O, O-dimethyl phosphorothioate, cyanophos, CYAP) in brain, liver, blood cells and plasma during the early toxic period, the male and female rat was administered a single oral dose of [phenyl-¹⁴C]Cyanox at dose levels of 50?mg/kg and killed 5, 10 and 20 min thereafter. 2. Sex-related differences in the concentrations of metabolites were observed. Cyanoxon, produced by oxidative desulphuration, was observed in the brains of both sexes at all time points, but the concentrations were 2-6times higher in the male. The same metabolite was detected in the liver, blood cells and plasma of the male but not the female. The total concentrations of oxidative dearylation metabolites (4-cyanophenol +4-cyanophenylsulphate + glucuronide of 4-cyanophenol) in plasma, blood cell, brain and liver were larger in the male at all time points than those in the female, whereas the reverse was the case for demethylated metabolites (desmethylcyanox + desmethylcyanoxon) in all tissues except for the brain. 3. Studies of the in vitro metabolism of Cyanox revealed no sex-related difference for hepatic cytosolic fractions in terms of the major in vitro metabolic reaction, demethylation. On the other hand, the major reactions in microsomal fractions, oxidative desulphuration and oxidative dearylation, were significantly (2-3 times) greater in the male than in the female. 4. Oxidative desulphuration and oxidative dearylation, involving cytochrome P450 enzymes,were inhibited by male-specific ratCYP2C11 antiserum. The degreeof inhibition was more pronounced in the male case. Thus, the results strongly suggest that the 2C family of cytochrome P450 (male, CYP2C11 and CYP2C13; female, CYP2C12) contributes to oxidative desulphuration and dearylation of cyanox in the rat and that the activity of male-specific CYP2C11 (and CYP2C13) is greater than that of female-specific CYP2C12. The consequent greaterformation of cyanoxonin the male is consistent with the higher toxicity in this sex.