Clinical benefit of nomogram for predicting positive resection margins in breast conserving surgery.

PURPOSE: Previously, we reported a nomogram for the prediction of positive resection margin (RM) after breast conserving surgery (BCS). This study was conducted to evaluate the clinical usefulness of the nomogram. METHODS: Prospective patients who underwent operations using the nomogram between July 2012 and August 2013 (nomogram group; N = 260) were compared with past control patients who underwent operations between July 2010 and October 2011 and underwent frozen section biopsy (FSB) without use of the nomogram (N = 266). In the nomogram group, an intraoperative assessment of RM using FSB was only performed when the nomogram score was higher than predefined cut-off (>80). In addition, we conducted retrospective analysis of additional 181 patients who received BCS in another institute (Kyoto University Hospital). These patients did not undergo FSBs for RMs. RESULTS: Of 260 patients, 161 (61.9%) presented low nomogram scores and avoided FSB. The surgical decision to use the nomogram did not significantly increase reoperation rate due to positive RM compared with the control FSB group (4.6% vs. 3.8%, p = 0.47). The surgery time was significantly reduced by 18.1% (mean 14.7 min) in nomogram group (p < 0.001). Of 99 nomogram high-score patients, 14 presented with positive RM on FSB and 11 of them avoided reoperation. In the Kyoto cohort, the reoperation rate was significantly lower in low-score patients than in high-score patients (2.7% vs. 11.4%, p < 0.001). CONCLUSIONS: We showed that our nomogram is useful to reduce FSBs without increasing reoperation rate for surgeons who perform routine FSBs. For most surgeons, it can give useful information about the possibility of tumor-positive RMs.

Simultaneous determination of water-soluble whitening ingredients and adenosine in different cosmetic formulations by high-performance liquid chromatography coupled with photodiode array detection.

OBJECTIVE: The Korean Cosmetic Act regulates the use of functional cosmetics) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high-performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) was employed for the simultaneous detection of arbutin (and its decomposition product, hydroquinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether and adenosine in functional cosmetic products such as creams, emulsions and lotions. METHODS: Separation by HPLC-DAD was conducted using a C18 column with a gradient elution of 5 mm KH2PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside and ethyl ascorbyl ether were 283, 289, 261, 257, 238 and 245 nm, respectively. RESULTS: This method exhibited good linearity (R(2) ≥ 0.999), precision (expressed as relative standard deviation (RSD) < 2%) and mean recoveries (89.42-104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. CONCLUSION: The method developed herein is simple and can be used for market survey and quality control of functional cosmetics.

Temperature dependence of the electronic structure of two-dimensional Na gas on the Si(111)-7 × 7 surface.

The temperature dependence of the irreversible phase transition from a two-dimensional gas to an ordered zero-dimensional solid on the Si(111)-7 × 7 surface was studied using photoemission spectroscopy. With increasing Na coverage, the two-dimensional Na gas, which is a state of highly mobile Na atoms, undergoes a phase transition into ordered zero-dimensional magic nanoclusters at room temperature. The critical Na coverage of the phase transition was found to increase with reduced temperature. This was used to develop a gas-solid phase diagram of Na atoms on the Si(111)-7 × 7 surface as a function of Na coverage and sample temperature based on the electronic structure. The temperature dependence of the phase transition can be ascribed to the suppression of the thermal energy that is required to overcome the energetic barrier between the two-dimensional gas and the zero-dimensional solid at low temperature, where three different hopping mechanisms are related to the phase transition.

Multiple gastrointestinal stromal tumours presenting as a haemoperitoneum in a patient with Type 1 neurofibromatosis: MDCT findings.

We report multidetector row CT images of multiple gastrointestinal tumours in a patient with Type 1 neurofibromatosis who presented with haemoperitoneum. The use of CT demonstrated multiple, variably sized, ovoid, relatively well-enhancing masses in the intramural or subserosal location of the jejunum. The largest mass that showed a haemorrhagic necrosis caused haemoperitoneum. These imaging features are unique and differ from previous imaging features that have been reported in the radiological literature.

Progressive collapse of PMMA-augmented vertebra: a report of three cases.

Vertebroplasty using polymethylmethacrylate (PMMA) for augmentation is accepted as a safe and effective treatment for vertebral compression fracture. However, various complications related to PMMA vertebroplasty have recently been reported. We experienced three cases with progressive collapse of PMMA-augmented vertebra. Collapse progressed after augmentation in cases where PMMA conglomerated without contiguous bone interdigitation. A high viscosity of the PMMA preparation and vertebral body cavitory lesion may play a role in progressive vertebral collapse. To avoid this complication, bone cement should be injected sufficiently and permeate to contiguous bone to create strong support and anchorage.

Surgical management of spinal cord haemangioblastoma.

BACKGROUND: The surgical management of spinal cord haemangioblastomas is distinct from that of other benign spinal cord tumours and optimal surgical strategy is still being determined because of the rarity of the condition. The aim of this study is to investigate factors that affect the outcome of surgical management. PATIENTS AND METHODS: We retrospectively analysed 24 operations for symptomatic spinal cord haemangioblastomas in 20 patients. Clinical features and surgical results were investigated by medical record review, telephone interviews, angiographic images, and magnetic resonance images (MRI). The mean follow-up period was 5.6 years (range 6 months to 13.6 years). RESULTS: Patients with cystic components showed pre-operative motor weakness and sensory change more commonly than those without cystic components. Post-operative function scale had a positive correlation with pre-operative function (R(2) = 0.727; p < 0.001) and no correlation with the extent of the surgery. All subtotally removed tumours recurred, whereas totally removed tumours recurred in only 3 patients. CONCLUSION: The cystic component of spinal cord haemangioblastomas is responsible for symptom generation and is helpful for dissecting tumours. Post-operative functional status is determined by pre-operative functional status. Total removal is feasible by using the correct surgical technique and is recommended to prevent recurrence.

Outcome of surgery for a symptomatic herniated thoracic disc in relation to preoperative characteristics of the disc.

BACKGROUND: This report presents general information on herniated thoracic discs, their clinical manifestations as well as surgical treatment, and examines the differences in the surgical outcome based on disc characteristics. METHODS: This study includes 33 thoracic discectomies in 29 patients with a ventrally situated herniated thoracic disc reaching to the thoracic cord. Using preoperative computed tomography scanning and magnetic resonance imaging, the direction of the disc was classified as either central or lateral, and disc consistency classified as either soft or hard. Clinical outcome was assessed according to the Japanese Orthopedic Association (JOA) Score for thoracic myelopathy. The score was obtained by analysing motor, sensory and bladder function. Recovery rate was assessed, comparing preoperative and postoperative status based on disc characteristics. The correlations between outcome, symptom duration and recovery rate were also investigated. FINDINGS: Clinical outcome according to the JOA Score showed significant postoperative improvement, increasing from 7.0 +/- 3.1 points to 8.2 +/- 2.7 points postoperatively (p < 0.01). The mean recovery rate was 12.4 +/- 56.9%, and 16 patients (55.2%) showed improvement. In the soft disc group, there was improvement in all categories, but the hard disc group showed no improvement. The central disc group showed improvement in sensory function, but the lateral disc group showed little improvement. Regression analysis revealed a statistically significant correlation between the preoperative and postoperative score, symptom duration and recovery rate. CONCLUSIONS: Clinical outcome after surgery of a herniated thoracic disc proved successful, especially when the disc was considered to have a soft consistency. In order to decide the optimal surgical strategy and prospective surgical outcome, disc characteristics, including consistency and direction of prolapse should be considered preoperatively.

Cervical arthroplasty in a patient with Klippel-Feil syndrome.

This is the first published report of a patient with Klippel-Feil syndrome treated with cervical arthroplasty. A 36-year-old man presented with posterior neck pain and myelopathic symptoms. A radiograph demonstrated congenital fusion of the vertebral bodies at C2-3, C4-5 and C5-6. On MRI, the spinal cord was compressed by a protruding cervical disc and bony spurs at C6-7. After anterior discectomy and decompression of the spinal cord at the C6-7 level, the disc was replaced with the Bryan cervical disc system (Medtronic Sofamor Danek, Memphis, TN, USA) to restore normal motion. The absence of adjacent segment degeneration and the preservation of cervical motion were noted 2 years after surgery. Arthroplasty may be performed in selected patients with Klippel-Feil syndrome in order to restore motion and to prevent degeneration of the adjacent segment by reducing hypermobility.

Clinical and radiological results following cervical arthroplasty.

BACKGROUND: This was a retrospective study of clinical and radiological results of cervical arthroplasty using the Bryan cervical disc prosthesis to evaluate the efficacy of arthroplasty in clinical applications. METHODS: A total of 46 patients underwent arthroplasty of a single level using the Bryan disc prosthesis. Clinical outcome was assessed using the visual analogue scale (VAS) and the neck disability index (NDI). All patients were evaluated using preoperative and postoperative static cervical spine radiographs to compare cervical sagittal balance. Dynamic cervical spine radiographs were used to compare movement at the level of the procedure, movement at the adjacent level and movement of the whole cervical spine. FINDINGS: With the exception of four patients with aggravated neck pain, the NDI and VAS scores decreased significantly in late follow-up evaluations. The range of movement of the whole cervical spine, the functional segmental unit, and the adjacent segments were preserved after arthroplasty. The sagittal alignment of the cervical spine showed kyphosis after surgery but restored lordosis at a later time. The postulated cause of kyphotic changes include "over-milling" at the dorsal endplate, inappropriate angle of disc insertion, structural absence of lordosis in the Bryan disc, removal of posterior longitudinal ligament, and pre-existing kyphosis. CONCLUSIONS: Arthroplasty using the Bryan disc appears to be safe and provided a favorable preliminary clinical and radiological outcome. Postoperative kyphosis can be prevented by understanding the biomechanical properties of the Bryan disc. Future studies will need to address the association between postoperative kyphosis, clinical outcome and adjacent segment disease.

Bone temperature estimation during orthopaedic round bur milling operations.

Heat generation during orthopaedic bone cutting operations may cause thermal bone damage. During the bone cutting, the maximum temperature occurs at the point of contact between the bone and the cutting tool. However, this temperature is difficult to measure. Many researchers have attempted to measure this temperature using a thermocouple; however, limitations of the thermocouple makes it difficult to determine the maximum temperature at the point of contact. In order to solve this problem, in this study, two infrared thermometers are used to measure the fresh-milled surface temperature, and the maximum temperature was extrapolated by a moving plane heat source solution. The estimated maximum temperature increment varied from 49 to 115 degrees C under various cutting conditions. These results showed that the thermal damage may reach up to 1.9 mm in depth during round bur milling. A larger feed rate and a smaller cutting depth decreased the maximum temperature.

Pancreatic carcinoid tumor with obstructive pancreatitis: multislice helical CT appearance: case report.

Carcinoid tumor of the pancreas is rare. Moreover, obstructive pancreatitis secondary to a pancreatic carcinoid tumor is extremely rare. We report a case of pancreatic carcinoid tumor in a 50-year-old male who presented with pancreatitis. On multislice helical computed tomography, the main pancreatic duct was obstructed by a small round tumor, and the main pancreatic duct proximal to the tumor was dilated. The correlation between the main pancreatic duct and the tumor was well depicted on minimum intensity projection image. This is the first report of multislice helical computed tomorgraphic and minimum intensity projection image findings of a pancreatic carcinoid tumor presenting with pancreatitis.

Small cell carcinoma of the colon: barium study and CT findings.

Extrapulmonary small cell carcinoma is a rare neoplasm. It is an aggressive malignant tumour characterized by rapid local progression and early metastasis. We report a case of small cell carcinoma arising in the transverse colon in a 34-year-old man who presented with epigastric pain. On CT, a poorly enhancing bulky mass encircling the transverse colon with extensive regional lymph node metastases was observed. A segmental annular narrowing with thick interhaustral folds of the transverse colon was found by barium enema examination. This is the first report of barium study and CT findings of extrapulmonary small cell carcinoma of the colon.

Quantitative analysis of fentanyl in rat plasma by gas chromatography with nitrogen-phosphorus detection.

A sensitive assay method was developed to determine fentanyl, an opiate agonist, in rat plasma by gas chromatography with nitrogen-phosphorus detection. For the pretreatment of plasma samples, sodium hydroxide was added to denature protein and n-butyl chloride was used to extract fentanyl. The calibration curve was linear within the concentration range 0.5 to 50 ng/ml (r=0.9997). The limit of detection was 0.1 ng/ml, and 0.5 ng/ml could be quantified with acceptable precision. Furthermore, fentanyl could be determined in only 200 microl of rat plasma. The method has been successfully applied to an intramuscular pharmacokinetic study at a dose of 10 microg/kg. Therefore, the current method is a valuable analytical tool for investigating the pharmacokinetics of fentanyl at low clinical doses.

Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue.

A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of beta cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic beta cells by autoimmune responses specific to beta cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic beta cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

A novel neuroprotective mechanism of riluzole: direct inhibition of protein kinase C.

In addition to its antiexcitotoxic action, the anti-amyotrophic lateral sclerosis (ALS) neuroprotectant riluzole protects against nonexcitotoxic oxidative neuronal injury. In light of evidence that protein kinase C (PKC) mediates oxidative stress in cortical culture, we examined the possibility that riluzole's antioxidative neuroprotection involves PKC inhibition. Riluzole (30 microM) blocked phorbol 12-myristate 13-acetate (PMA)-induced increases in membrane PKC activity in cultured cortical cells. Suggesting a direct action, riluzole also inhibited the activity of purified PKC. Consistently, both PKC depletion and oxidative neuronal death induced by PMA were markedly attenuated by riluzole. The site of action of riluzole on PKC was not likely the diacylglycerol binding site but the catalytic domain, since riluzole did not alter radiolabeled phorbol-12,13-dibutyrate binding, but inhibited PKM, the catalytic domain of PKC. However, increasing ATP concentrations did not alter the inhibition of PKC by riluzole, making it unlikely that riluzole is a competitive inhibitor of ATP binding at PKM. Present results have demonstrated that riluzole directly inhibits PKC, which action may contribute to its antioxidative neuroprotective effects. In addition, it appears possible that PKC inhibition may be able to explain some of its well-known channel inhibitory and neuroprotective effects. Combined with findings that PKC activity is increased in ALS, the present results suggest that PKC may be a potential therapeutic target in ALS.

Seasonal biochemical plasticity of a flight muscle in a bat, Murina leucogaster.

Cellular and biochemical responses of the pectoral muscle to variation in seasonal activity were studied in the bat, Murina leucogaster ognevi. We collected bats in mid-hibernation (February), end-hibernation (April), and mid-summer (August) to track major activity periods in their annual cycle. Our findings indicated that myofiber cross-sectional area decreased to 68% between mid- and end-hibernation, but returned to the winter level in mid-summer. Total soluble protein and total RNA concentrations were not altered over these sampling periods. Oxidative potential gauged by citrate synthase activity increased 1.47-fold from mid- to end-hibernation and then remained at the similar level in mid-summer. Glycolytic potential gauged by lactate dehydrogenase activity changed little between mid- and end-hibernation but increased 1.42-fold in summer, compared with the winter level. Thus, the myofibers underwent disuse atrophy during hibernation, while enzymatic catalytic function recovered towards the level of mid-summer.

Catalysis of the oxidative folding of bovine pancreatic ribonuclease A by protein disulfide isomerase.

The major oxidative folding pathways of bovine pancreatic ribonuclease A at pH 8.0 and 25 degrees C involve a pre-equilibrium steady state among ensembles of intermediates with zero, one, two, three and four disulfide bonds. The rate-determining steps are the reshuffling of the unstructured three-disulfide ensemble to two native-like three-disulfide species, des-[65-72] and des-[40-95], that convert to the native structure during oxidative formation of the fourth disulfide bond. Under the same regeneration conditions, with oxidized and reduced DTT, used previously for kinetic oxidative-folding studies of this protein, the addition of 4 microM protein disulfide isomerase (PDI) was found to lead to catalysis of each disulfide-formation step, including the rate-limiting rearrangement steps in which the native-like intermediates des-[65-72] and des-[40-95] are formed. The changes in the distribution of intermediates were also determined in the presence and absence of PDI at three different temperatures (with the DTT redox system) as well as at 25 degrees C (with the glutathione redox system). The results indicate that the acceleration of the formation of native protein by PDI, which we observed earlier, is due to PDI catalysis of each of the intermediate steps without changing the overall pathways or folding mechanism.

The 5'-untranslated region of GM-CSF mRNA suppresses translational repression mediated by the 3' adenosine-uridine-rich element and the poly(A) tail.

Granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA levels are controlled post-transcriptionally by the 3'-untranslated region (UTR) adenosine-uridine-rich element (ARE). In untransformed, resting cells, the ARE targets GM-CSF mRNA for rapid degradation, thereby significantly suppressing protein expression. We used a rabbit reticulocyte lysate (RRL) cell-free system to examine translational regulation of GM-CSF expression. We uncoupled decay rates from rates of translation by programming the RRL with an excess of mRNAs. Capped, full-length, polyadenyl-ated human GM-CSF mRNA (full-length 5'-UTR AUUUA+A90) and an ARE-modified version (full-length 5'-UTR AUGUA+A90) produced identical amounts of protein. When the 5'-UTR was replaced with an irrelevant synthetic leader sequence (syn 5'-UTR), translation of syn 5'-UTR AUUUA+A90 mRNA was suppressed by >20-fold. Mutation of the ARE or removal of the poly(A) tail relieved this inhibition. Thus, in the absence of a native 5'-UTR, the ARE and poly(A) tail act in concert to block GM-CSF mRNA translation. Substitutions of different regions of the native 5'-UTR revealed that the entire sequence was essential in maintaining the highest rates of translation. However, shorter 10-12 nt contiguous 5'-UTR regions supported 50-60% of maximum translation. The 5'-UTR is highly conserved, suggesting similar regulation in multiple species and in these studies was the dominant element regulating GM-CSF mRNA translation, overriding the inhibitory effects of the ARE and the poly(A) tail.

2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity.

TRAIL is a newly identified cytokine belonging to the large tumor necrosis factor (TNF) family. TRAIL is a novel molecule inducing apoptosis in a wide variety of tumor cells but not in normal cells. To help in elucidating its biological roles and designing mutants with improved therapeutic potential, we have determined the crystal structure of human TRAIL. The structure reveals that a unique frame insertion of 12-16 amino acids adopts a salient loop structure penetrating into the receptor-binding site. The loop drastically alters the common receptor-binding surface of the TNF family most likely for the specific recognition of cognate partners. A structure-based mutagenesis study demonstrates a critical role of the insertion loop in the cytotoxic activity of TRAIL.

Substance P augments nitric oxide production and gene expression in murine macrophages.

We investigated the effects of substance P (SP) on nitric oxide (NO) synthase activity in macrophages by measuring the production of nitrite and the expression of inducible NO synthase (iNOS) mRNA and protein. In LPS-activated macrophages, SP stimulated NO production in time and concentration dependent manners. These SP effects were blocked by a specific NK-1 receptor antagonist. Furthermore, SP stimulation increased the levels of both iNOS mRNA and iNOS protein. These results demonstrate that SP can increase LPS induced NO production in macrophages by augmenting the induction of iNOS expression. We also examined the role of SP on acute-cold stress induced altered production of NO by mouse peritoneal macrophages. SP enhanced the LPS-induced macrophages NO production from stressed mice relative to the non-stressed mice. These results suggest that SP may have an important modulatory role in production of NO by macrophages.