Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients

BACKGROUND: Secondary hyperparathyroidism is a common complication among long-term dialysis patients. The method of predicting future parathyroid function has not yet been established. Fibroblast growth factor-23 (FGF-23) is a newly found humoral phosphaturic factor. METHODS: One hundred and three nondiabetic dialysis patients whose plasma intact parathyroid hormone (PTH) levels were below 300 pg/mL were included in the study. Blood samples were stored at -80 degrees C for 2 years. Meanwhile, each physician in charge decided upon the strategy of medical therapy for maintaining intact PTH levels between 150 and 300 pg/mL. Patients were judged 2 years after the sample collection with regard to whether the hyperparathyroidism responded to the medical therapy. The definition of refractory secondary hyperparathyroidism was either (1) retaining intact PTH levels greater than 300 pg/mL 2 years after sample collection, or (2) having received the parathyroid intervention therapy during the observation period. Serum FGF-23 levels were determined with a sandwich enzyme-linked immunosorbent assay system that detects biologically active human FGF-23. RESULTS: Seventeen patients with intact PTH levels greater than 300 pg/mL were judged as having secondary hyperparathyroidism refractory to medical therapy. A stepwise regression analysis revealed that only serum levels of FGF-23 were significantly related to the prognosis of parathyroid function. A receiver-operated characteristic analysis demonstrated that the area under the curves obtained from FGF-23 (7099.9) was significantly greater than that obtained from intact PTH (6306.4, P < .01) and Ca x Pi (5670.3, P <.0001). Although the plasma intact PTH levels at the beginning of the observation period were comparable to each other, the intact PTH levels at 2 years after the sample collection were significantly higher in the patients with FGF-23 >/=7500 ng/L than in those with FGF-23 <7500 ng/L (P < .0001). CONCLUSION: Serum FGF-23 level was found to be the most useful factor in predicting future development of refractory secondary hyperparathyroidism in long-term dialysis patients with mild secondary hyperparathyroidism. The measurement of serum FGF-23 levels is a promising laboratory examination that can be applied in the clinical practice of uremic secondary hyperparathyroidism.     

Gastropleural fistula due to gastric perforation after lobectomy for lung cancer

We report a case of acute gastropleural fistula due to gastric perforation after a left lower lobectomy for lung cancer. A 76-year-old male, who received a left hemicolectomy 20 years previously, came to our hospital for surgical treatment of lung cancer, which was performed uneventfully as a left lower lobectomy with combined resection of the diaphragm. On the postoperative day 2, acute dilatation of the stomach followed by gradual cardiopulmonary collapse, and then gastric perforation into the thorax occurred. The perforated stomach wall and diaphragm became paper-thin and necrotic, though the abdominal cavity was free of contamination. This life-threatening condition was treated by an emergency thoracotomy and partial gastrectomy through the thorax, as the left hemidiaphragm was remarkably elevated. An oeganoaxial torsion gastric volvulus caused by anatomic rotation following the lobectomy was speculated as the disease process, with loss of suspended tissue of the gastro-colic ligament from the left hemicolectomy being a possible predisposing factor. Such an episode is rare, however, it should be looked for during perioperative care following a lobectomy.     

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.     

Future outlook for OTC examination (test)

As the primary prevention of disease has been emphasized, there may be a growing need for well-conditioned development and spread of OTC test equipment, OTC test reagent and remote healthcare. Some typical examples of "simple and rapid examination items, which can be done at home by established technology" are explained in this paper and may be required in the near future by the whole Japanese population with a view to the current status of OTC test and the coming relaxation of governmental regulation. The reasons why these examination items should be commercialized as Switch OTC and the epidemiological background are further discussed. In relation to metabolic syndrome derived from super spreader-like visceral mature adipocyte: SSVMAC, visceral fat rate measurement by bioelectrical impedance technology, postprandial blood glucose determination/urinary glucose determination, and urinary microalbumin detection, are explained with an example, together with the importance of early morning blood pressure recording. In the field of cancer and infectious diseases, immunological fecal occult blood determination as a marker of distal colorectal cancer, in which both higher survival rate and recovery rate by early detection have been established, Helicobacter pylori IgG antibodies or antigen examination including an examination of gastroduodenal disorder, prostate-specific antigen (PSA) and genital chlamydia are emphasized.     

Feasibility study of imaging of intraductal papillary mucinous tumors of the pancreas based on integral photography

BACKGROUND/AIMS: The principle of integral photography was first proposed by Lippman in 1908. Recently, the three-dimensional display system based on the principle of integral photography was developed. It projects three-dimensional objects using a lens array called a fly's eye lens and photographic film. Some groups have used it for surgical navigation in brain surgery. In this study, we tried to generate integral photographic images of intraductal papillary mucinous tumors of the pancreas, and evaluated the feasibility of this method. METHODOLOGY: Five patients with an intraductal papillary mucinous tumor of pancreas were studied. We used MRI data as three-dimensional data. MRI data were acquired with a 1.5-T clinical imager (Signal.5; GE Medical Systems, U.S.A). We used multi-slab single-shot fast spin-echo sequences. Section thickness was between 2 and 3mm in the coronal plane. From these data, integral photographic images were generated on a liquid crystal display by a three-dimensional rendering algorithm. RESULTS: Three-dimensional images using the principle of integral photography could be generated in all 5 cases. We could recognize these images as three-dimensional images by slightly moving the viewpoint to up, down, left, and right. From these images, we were able to grasp the three-dimensional relationship between the tumor, bile duct, and pancreatic duct. Using these three-dimensional images, a variety of minimally invasive surgical procedures were performed for intraductal papillary mucinous tumor of the pancreas, more safely and speedily than formerly. CONCLUSIONS: The images based on integral photography are suitable for medical imaging and are useful for surgical planning.     

Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism

Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23(-/-) mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)2D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism.     

The overview of robot surgery

Surgical operations have developed in the method which skillful surgeon's hands and eyes are used. However, to realize a new surgical therapy in the 21st century, it is necessary to use various advanced technologies; surgical robots, three dimensional medical images, computer graphics, computer simulation technology and others. Three dimensional medical image for surgical operation provides surgeons with advanced vision. Surgical robots provide surgeons with advanced hand, but it is not a machine to do the same action of a surgeon using scissors or a scalpel. The advanced vision and hands available to surgeons are creating new surgical fields which are minimally invasive surgery, non-invasive surgery, virtual reality micro-surgery, tele-surgery, fetus surgery, neuro-informatics surgery and others in the 21st century.     

Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay

Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes.     

Profound ionized hypomagnesemia induced by therapeutic plasma exchange in liver failure patients

BACKGROUND: Various adverse effects, including cardiac arrest, have been induced by plasma exchange (PE). Electrolyte derangement is frequently observed. The purpose of this study was to assess the effect of PE on the serum ionized magnesium (Mg2+) concentration in acute liver failure patients. STUDY DESIGN AND METHODS: Seven liver failure patients requiring PE were enrolled in this study. PE was performed 21 times in total. Blood samples were drawn before PE and serially after the start of the PE. Serum Mg2+ was measured by the ion- selective electrode method. RESULTS: After PE was started, Mg2+ concentrations began to fall significantly. The low Mg2+ blood concentration continued during PE. After PE, the Mg2+ level recovered to about 80 percent of the control value within 2 hours in six patients. However, in one patient, the Mg2+ concentration was still low even at 2 hours after PE. This patient complained of chest discomfort during PE and ECG analysis showed sporadic supraventricular premature contractions. CONCLUSION: Profound ionized hypomagnesemia was induced by PE in liver failure patients.