Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice

Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphorus (Pi) and vitamin D metabolism, but the mechanisms by which circulating FGF-23 itself is regulated are unknown. To determine whether the serum FGF-23 concentration is regulated by dietary intake of Pi, we fed wild-type (WT), Npt2a gene-ablated (Npt2a(-/-)), and Hyp mice diets containing varying Pi contents (0.02-1.65%). In WT mice, increases in dietary Pi intake from 0.02-1.65% induced a 7-fold increase in serum FGF-23 and a 3-fold increase in serum Pi concentrations. Across the range of dietary Pi, serum FGF-23 concentrations varied directly with serum Pi concentrations (r(2) = 0.72; P < 0.001). In Npt2a(-/-) mice, serum FGF-23 concentrations were significantly lower than in WT mice, and these differences could be accounted for by the lower serum Pi levels in Npt2a(-/-) mice. The serum concentrations of FGF-23 in Hyp mice were 5- to 25-fold higher than values in WT mice, and the values varied with dietary Pi intake. Fgf-23 mRNA abundance in calvaria was significantly higher in Hyp mice than in WT mice on the 1% Pi diet; in both groups of mice, fgf-23 mRNA abundance in calvarial bone was suppressed by 85% on the low (0.02%) Pi diet. In WT mice fed the low (0.02%) Pi diet, renal mitochondrial 1alpha-hydroxylase activity and renal 1alpha-hydroxylase (P450c1alpha) mRNA abundance were significantly higher than in mice fed the higher Pi diets and varied inversely with serum FGF-23 concentrations (r(2) = 0.86 and r(2) = 0.64; P < 0.001, respectively). The present data demonstrate that dietary Pi regulates the serum FGF-23 concentration in mice, and such regulation is independent of phex function. The data suggest that genotype-dependent and dietary Pi-induced changes in the serum FGF-23 concentration reflect changes in fgf-23 gene expression in bone.     

Descriptive patterns of severe chronic pulmonary hypertension by chest radiography

BACKGROUND: To find chest roentgenographic (CXR) features to help differentiate two representative diseases with severe chronic pulmonary hypertension (PH). STUDY SUBJECTS: Thirty-six consecutive patients with chronic thromboembolic PH (CTEPH), 38 with primary PH (PPH), and 37 with left heart disease and PH. METHODS: CXRs were reviewed about 6 features (left 2nd arc protrusion, right descending pulmonary artery diameter (rPAD), cardiothoracic ratio (CTR), right 2nd arc width, avascular area and pleural abnormality). Hemodynamic data and the degree of tricuspid regurgitation (TR) on echocardiography were compared with CXR findings. RESULTS: The diagnostic pattern of CTEPH was the presence of one of two findings, an avascular area or marked rPAD (>20mm) together with pleuritic change. The diagnostic pattern of PPH was one of the two features; without pleuritic abnormality, marked left 2nd arc protrusion (>10mm) or moderate left 2nd arc protrusion (5-10mm) with marked rPAD (<20mm). The sensitivity for the diagnosis of CTEPH among the three diseases was 78% and specificity was 92%. The sensitivity for the diagnosis of PPH was 45% and specificity was 88%. CTR and right 2nd arc width were related to the degree of TR in CTEPH and PPH. CONCLUSIONS: Characteristic roentgenographic findings can help differentiate two frequent diseases associated with chronic pulmonary hypertension and reflect the severity of disease.     

Vascular smooth muscle cell apoptosis induced by 7-ketocholesterol was mediated via Ca2+ and inhibited by the calcium channel blocker nifedipine

Previous reports indicate that 7-ketocholesterol (7KCHO) induces apoptosis of cultured human vascular smooth muscle cells (SMCs). We hypothesized that calcium channel blockers will inhibit SMC apoptosis induced by 7KCHO because caspase-3 activity is Ca2+ dependent and 7KCHO stimulates caspase-3 and SMC apoptosis. So, the protective effect of the calcium channel blocker nifedipine on SMC apoptosis induced by 7KCHO was investigated. When 7KCHO (50 micromol/L) was added to SMCs, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling was positive. DNA extracted from SMCs exposed to 7KCHO showed a ladder pattern on agarose electrophoresis. In the presence of extracellular Ca2+, the Ca2+ influx, caspase-3 activity, and fragmented DNA also increased in SMCs incubated with 7KCHO dose-dependently. However, in the absence of extracellular Ca2+, no effects of 7KCHO on caspase-3 activity and fragmented DNA were observed. In the presence of nifedipine, the 7KCHO-induced increases in Ca2+ influx, caspase-3 activity, and the amount of fragmented DNA decreased significantly. These results suggest that 7KCHO-induced apoptosis of SMCs is inhibited by calcium channel blockade, and that Ca2+ influx into cells mediated by 7KCHO plays an important role in 7KCHO-induced apoptosis.     

Mechanical ventricular assist system required for sustained severe cardiac dysfunction secondary to peripartum cardiomyopathy.

A 29-year old woman developed severe congestive heart failure in the first week after an uneventful full-term delivery. Despite intense medical treatment over the next 6 months, her heart failure symptoms gradually worsened and she eventually developed cardiogenic shock. She successfully underwent the implantation of a left ventricular assist system, but because there was no sign of recovery of ventricular function, she was placed on the waiting list for heart transplantation. After 143 days of support, she suffered from brain hemorrhage, and eventually died after a total of 321 days of left ventricular support. Postmortem examination of the myocardium showed sustained diffuse fibrosis and no inflammatory reaction. This case implies that with severe peripartum cardiomyopathy heart transplantation should be considered without delay even if a mechanical assist system is available.     

Aortic Insufficiency and Hemocompatibility-related Adverse Events in Patients with Left Ventricular Assist Devices

AimHemocompatibility-related adverse events (HRAE) are a major cause of readmissions in patients with left ventricular assist devices (LVAD). The impact of aortic insufficiency (AI) on HRAE remains uncertain. We aimed to investigate the impact of AI on HRAE.Methods and ResultsPatients who underwent LVAD implantation between August 2014 and July 2017 and had echocardiograms 3 months post-LVAD implantation were enrolled. AI severity was assessed by measuring the systolic/diastolic ratio of flow and the rate of diastolic flow acceleration using Doppler echocardiography of the outflow cannula. Regurgitation fraction was derived from these parameters. Significant AI was defined as regurgitation fraction > 30%. Among 105 patients (median age, 56 years; 76% male), 36 patients (34%) had significant AI. Baseline characteristics were statistically not significantly different between those with and without significant AI except for higher rates of ischemic etiology and atrial fibrillation in the significant AI group (P < 0.05 for both). One-year survival free from HRAE was 44% in patients with AI compared to 67% in patients without significant AI (P = 0.018). The average hemocompatibility score, which defines the net burden of HRAE, was higher in the AI group (1.72 vs 0.64; P = 0.009), due mostly to higher tier I (mild HRAE; P = 0.034) and tier IIIB scores (severe HRAE; P = 0.011).ConclusionSignificant AI, as assessed by Doppler echocardiographic parameters, was associated with HRAE during LVAD support.     

The resection of non-hepatic intraabdominal recurrence of gastric cancer

BACKGROUND/AIMS: Surgical resection of hepatic or pulmonary metastases from gastrointestinal cancer has been recognized as a curative modality in some patients. However, the role and outcome of the surgical management of a non-hepatic intraabdominal recurrence of gastrointestinal cancer have not been clearly delineated. METHODOLOGY: We treated 5 patients for non-hepatic intraabdominal recurrence of gastric carcinoma surgically. All the resected specimens were microscopically identified as recurrent gastric cancer. Three of 5 patients received postoperative chemotherapy. The clinicopathological findings were analyzed according to the general rules for gastric cancer study. RESULTS: The lymph nodes were dissected for lymph node metastases. Surgical resection of the tumors combined with total gastrectomy, esophagectomy, or colectomy was performed for the local and peritoneal recurrences. All of the recurrent tumors were macroscopically resected with curative states. One patient died of sepsis 54 days after surgery. Three patients died of recurrent gastric cancer: 2 within 1 year of surgery and 1 after 3 years. One patient still survives disease free 3 years and 6 months after the 2nd operation. CONCLUSIONS: Surgical resection for non-hepatic intraabdominal recurrence of gastric cancer is the treatment of choice for selected patients. Surgical resection followed by adjuvant chemotherapy may improve the outcome of these patients.     

Liver metastasis of rectal cancer with intraluminal growth in the extrahepatic bile duct

Metastatic liver tumors are considered to have a tendency for expansive growth and rarely invade the bile duct. We recently encountered a resected case of liver metastasis from rectal cancer with intraluminal growth in the extrahepatic bile duct with a successful left trisegmentectomy of the liver. A 54-year-old woman underwent a posterior total pelvic exenteration for advanced rectal cancer. Ultrasonography and computed tomography four months after the first operation demonstrated a solitary occupied lesion in the liver with dilation of the left hepatic duct. Endoscopic retrograde cholangiopancreatography disclosed a filling defect in the intra- to extrahepatic bile duct. Liver metastasis from rectal cancer with intraluminal growth in the bile duct was suspected despite a consideration of primary bile duct cancer. A left trisegmentectomy of the liver and resection of the extrahepatic bile duct with a right hepatojejunostomy were performed. The tumor had invaded the intrahepatic bile duct and had developed intraluminally in the extrahepatic bile duct. Tumor thrombi were microscopically found in the bile duct of the left caudal lobe. Liver metastasis arising from colorectal cancer with intraluminal growth in the bile duct is rare, however we encountered such a case with a successful resection involving a left trisegmentectomy of the liver.     

Impact of esophageal bile exposure on the genesis of reflux esophagitis in the absence of gastric acid after total gastrectomy

OBJECTIVE: The role of duodenal contents refluxing into the esophagus in producing reflux esophagitis (RE) remains unclear. We aimed to assess the impact of esophageal bile exposure on the genesis of RE in reference to esophageal pH changes in the absence of gastric acid after total gastrectomy. METHODS: Thirty patients having undergone total gastrectomy were studied with concurrent 24-h esophageal pH and bilimetric monitoring, and were divided into two groups based on endoscopic esophageal mucosal findings: without RE, group 1 (n = 24) and with RE, group 2 (n = 6). Esophageal bile exposure was defined as bilirubin absorbance >0.14 detected in the esophagus. RESULTS: 1) The percentage total time of esophageal bilirubin absorbance >0.14 was not correlated with that of esophageal pH >7.0, >7.4, and >8.0. 2) All parameters for esophageal bilirubin absorbance >0.14 in group 2 were significantly higher than those in group 1, whereas none of the parameters for esophageal pH >7.0, >7.4, and >8.0 showed a significant difference between the two groups. 3) The percentage total time of esophageal bilirubin absorbance >0.14 was over 50% in all subjects with RE, and six of seven subjects with that over 50% had RE. CONCLUSIONS: Esophageal bile exposure plays an important role in the genesis of RE in the absence of gastric acid, which is assessed better with the measurement of esophageal bilirubin absorbance than that of esophageal pH.