Effects of scan parameters on the accuracies of iodine quantification and hounsfield unit values in dual layer dual-energy head and neck computed tomography: A phantom study conducted in a hospital in Japan.

INTRODUCTION: No study has investigated scan parameters in head and neck dual layer dual-energy computed tomography (DL-DECT). This study aimed to select the appropriate scan parameters in head and neck imaging by evaluating the scan parameter effects on the accuracies of CT numbers and conduct iodine quantification in DL-DECT. METHODS: A multi-energy phantom was scanned using a dual layer CT (DLCT) scanner. Reference materials of iodine, blood, calcium, and adipose were used. A helical scan was performed by using reference and several protocols. Iodine density and virtual monochromatic images (VMIs) at the energy of 50, 70, and 100 keV were reconstructed. The iodine concentrations and CT numbers in each protocol were measured. Moreover, the absolute percentage errors (APEs) of iodine quantifications and CT numbers (reference vs. each protocol) were compared. Equivalence was observed when APEs between reference and each protocol was within 5%. Statistical analysis was performed using appropriate software. RESULTS: The APEs between the high-tube-voltage and reference protocol were 23.7, 14.0, 8.8, and 8.1% for iodine reference materials with concentrations equal to 2, 5, 10, and 15 mg/ml, respectively. At 50 keV, APEs between the high-tube-voltage and reference protocols were greater than 5% except for calcium and adipose. At 100 keV, APEs between the high-tube-voltage and reference protocols were greater than 5% except for blood and calcium. CONCLUSIONS: The high-tube-voltage protocol improved the accuracies of the measurement for iodine quantification and CT numbers. Additionally, the scanning parameters except for tube voltage had no effect on accuracies of iodine quantitation and CT numbers in the DLCT scanner. IMPLICATIONS FOR PRACTICE: The use of the high-tube-voltage protocol will be recommended for more accurate material decomposition in head and neck DL-DECT.

[Complete resection of an advanced mediastinal nonseminomatous germ cell tumor with multiple distant metastases after down-staging by chemotherapy].

A mediastinal nonseminomatous germ cell tumor was completely resected after down-staging by chemotherapy despite the presence of multiple distant metastases. A 22-year-old female was admitted for superior vena cava (SVC) syndrome. Her SVC was obstructed by a large anterior mediastinal tumor; she also exhibited distant metastases on a left rib, in the liver, and multiple in the lung. The blood alpha-fetoprotein (AFP) level was extremely elevated to 57,530 ng/ml. Four courses of BEP therapy [cisplatin (CDDP), bleomycin (BLM), etoposide (VP-16)] and a high dose chemotherapy followed by a peripheral blood stem cell transplantation made the tumor become smaller and effected its down-staging. Residual mediastinal tumor with an intravascular tumor in SVC was completely resected. The SVC was reconstructed by an artificial vessel graft. A mediastinal nonseminomatous germ cell tumor, even though it has multiple distant metastases, can achieve down-staging and complete resection by a chemotherapy based on scientific evidence.

Epidemiological Survey of Listeria monocytogenes in a gravlax salmon processing line / Epidemiologia de Listeria monocytogenes em uma linha de processamento de salmão gravlax

Listeria monocytogenes is a cause of concern to food industries, mainly for those producing ready-to-eat (RTE) products. This microorganism can survive processing steps such as curing and cold smoking and is capable of growing under refrigeration temperatures. Its presence in RTE fish products with extended shelf life may be a risk to the susceptible population. One example of such a product is gravlax salmon; a refrigerated fish product not exposed to listericidal processes and was the subject of this study. In order to evaluate the incidence and dissemination of L. monocytogenes 415 samples were collected at different steps of a gravlax salmon processing line in São Paulo state, Brazil. L. monocytogenes was confirmed in salmon samples (41 percent), food contact surfaces (32 percent), non-food contact surfaces (43 percent) and of food handlers' samples (34 percent), but could not be detected in any ingredient. 179 L. monocytogenes isolates randomly selected were serogrouped and typed by PFGE. Most of L. monocytogenes strains belonged to serogroup 1 (73 percent). 61 combined pulsotypes were found and a dendrogram identified six clusters: most of the strains (120) belonged to cluster A. It was suggested that strains arriving into the plant via raw material could establish themselves in the processing environment contaminating the final product. The wide dissemination of L. monocytogenes in this plant indicates that a great effort has to be taken to eliminate the microorganism from these premises, even though it was not observed multiplication of the microorganism in the final product stored at 4ºC up to 90 days.

Listeria monocytogenes é um patógenode grande preocupação para as indústrias alimentícias, principalmente aquelas produtoras de alimentos prontos para consumo (RTE). Este microrganismo pode sobreviver às etapas de cura e defumação a frio, além de tolerar temperaturas de refrigeração. A presença de L. monocytogenes em pescados RTE com vida de prateleira longa representa um risco para a população susceptível, sendo o salmão gravlax deste tipo de produto. No presente estudo avaliou-se a incidência e disseminação de L. monocytogenes em 415 amostras de salmão gravlax obtidas de diferentes etapas de processamento de uma indústria localizada no Estado de São Paulo. A presença de L. monocytogenes foi confirmada em amostras de salmão (41 por cento), superfícies de contato (32 por cento) e não contato (43 por cento) e manipuladores (34 por cento), porém não se isolou o microrganismo em nenhum ingrediente. Do total de cepas isoladas, 179 destas foram escolhidas aleatoriamente e submetidas a sorologia e tipagem por PFGE. A maioria dos isolados pertenceu ao sorogrupo 1 (73 por cento), sendo identificados 61 pulsotipos quando se combinou os resultados de sorologia e PFGE e 6 clusters foram distribuídos em um dendrograma. O cluster A agrupou a maioria das cepas (120). Pode-se sugerir que as cepas foram introduzidas na linha de processamento por meio da matéria prima e contaminando o produto final. Estes resultados indicam que a eliminação de L. monocytogenes deste estabelecimento requer um grande esforço, ainda que o microrganismo não se multiplicou no produto final estocado a 4ºC por 90 dias.

Epidemiological Survey of Listeria monocytogenes in a gravlax salmon processing line.

Listeria monocytogenes is a cause of concern to food industries, mainly for those producing ready-to-eat (RTE) products. This microorganism can survive processing steps such as curing and cold smoking and is capable of growing under refrigeration temperatures. Its presence in RTE fish products with extended shelf life may be a risk to the susceptible population. One example of such a product is gravlax salmon; a refrigerated fish product not exposed to listericidal processes and was the subject of this study. In order to evaluate the incidence and dissemination of L. monocytogenes 415 samples were collected at different steps of a gravlax salmon processing line in São Paulo state, Brazil. L. monocytogenes was confirmed in salmon samples (41%), food contact surfaces (32%), non-food contact surfaces (43%) and of food handlers' samples (34%), but could not be detected in any ingredient. 179 L. monocytogenes isolates randomly selected were serogrouped and typed by PFGE. Most of L. monocytogenes strains belonged to serogroup 1 (73%). 61 combined pulsotypes were found and a dendrogram identified six clusters: most of the strains (120) belonged to cluster A. It was suggested that strains arriving into the plant via raw material could establish themselves in the processing environment contaminating the final product. The wide dissemination of L. monocytogenes in this plant indicates that a great effort has to be taken to eliminate the microorganism from these premises, even though it was not observed multiplication of the microorganism in the final product stored at 4°C up to 90 days.

Treatment of gastric hemorrhage by pulverized omeprazole and antacid--concomitant administration via a nasogastric tube.

Gastroesophageal reflux (GER) is a common episode in pediatric patients with severe motor and intellectual disabilities (SMID) and occasionally leads to a severe clinical state accompanied with nausea, hematemesis, melena, wheezing, pneumonia, anemia and/or failure to thrive. We report here a case of a 14-year-old male with Lennox syndrome who had been treated with a histamine H2 blocker intravenously or via a nasogastric tube for repeated gastric hemorrhage due to severe GER. Since his gastric hemorrhage became resistant to the H2 blocker, we decided to replace it with a proton pump inhibitor (PPI). Although lansoprazole can be decapsulated for administration via a nasogastric tube, it tends to block fine tubes. The acid-sensitive drug omeprazole, another oral PPI, is commercially available as enteric-coated tablets. Therefore, we pulverized the tablets and administered omeprazole, mixed with a small amount of antacid, via a nasogastric tube. The patient's gastric hemorrhage was dramatically improved. Thus, administration of pulverized omeprazole concomitantly with antacid via a fine nasogastric tube may provide a novel approach for the treatment of chronic GER in pediatric patients with SMID.

No evidence of PEG1/MEST gene mutations in Silver-Russell syndrome patients.

Silver-Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (alpha and beta) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST alpha coding region, and there were no significant mutations in the 5'-flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST alpha were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS.

The ultrastructure of contractile tubules in the heliozoon Actinophrys sol and their possible involvement in rapid axopodial contraction.

We employed an improved fixation procedure for electron microscopy using ruthenium red, and found a bundle of contractile tubules inside the axopodia of the heliozoon Actinophrys sol. Upon food uptake, the tubules shorten and transform into a mass of small granules when rapid axopodial contraction occurs, suggesting that these structures are involved in the process of axopodial contraction. The relationship between transformation of the contractile tubules and accompanying disassembly of the axonemal microtubules was studied by examining the ultrastructure of the contractile tubules after disassembly of the microtubules was artificially induced by cold or colchicine treatment. Granulation of the contractile tubules was induced by cold but not by colchicine treatment. During recovery from cold treatment, granular forms of the contractile tubules became re-elongated and their initial tubular appearance was restored. These results suggest that the contractile tubules in heliozoon axopodia play a role in repetitive cytoplasmic contraction.

Analysis of a non-functional HNF-1alpha (TCF1) mutation in Japanese subjects with familial type 1 diabetes.

Mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha; gene symbol TCF1) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic beta-cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non-autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1alpha. The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF-1alpha protein. Reporter gene analysis indicated that the mutant HNF-1alpha had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1alpha may lead to severe forms of diabetes like type 1 diabetes.

Novel site on sodium channel alpha-subunit responsible for the differential sensitivity of grayanotoxin in skeletal and cardiac muscle.

We searched for sites on the alpha-subunit of the fast Na(+) channel responsible for the difference in GTX (grayanotoxin) sensitivity of the skeletal- and cardiac-muscle Na(+) current. cDNA clones, encoding the skeletal or cardiac isoforms of the alpha-subunit, were inserted into a mammalian expression vector and transiently transfected into human embryonic kidney cells. The expressed channels were measured using whole-cell patch-clamp techniques and examined for GTX sensitivity. As a measure of GTX sensitivity, we used relative chord conductance (ratio of maximum chord conductance of noninactivating GTX-modified Na(+) currents to that of unmodified peak currents). Wild-type channels from skeletal muscle (mu 1) were more sensitive to GTX modification than wild-type cardiac channels (rH1) by a factor of 1.6. To facilitate exploration of alpha-subunit sites determining GTX sensitivity, we used SHHH, a chimera of skeletal muscle (S) domain D1 and heart muscle (H) domains D2D3D4 with supernormal sensitivity to GTX I (1.5-fold of wild-type mu 1). Successive replacement of Ser-251 (D1S4-S5 intracellular loop) and Ile-433 (D1S6 transmembrane segment), with corresponding rH1 residues Ala and Val, reduced, in a stepwise manner, the GTX sensitivity of the chimera and related mutants to that of wild-type rHl. We concluded that, in addition to Ile-433, known as the GTX-binding site, Ser-251 represents a novel site for GTX modification.

Development of growth hormone and adrenocorticotropic hormone deficiencies in patients with prenatal or perinatal-onset hypothalamic hypopituitarism having invisible or thin pituitary stalk on magnetic resonance imaging.

A gradual loss of anterior pituitary hormones is suspected in patients treated with irradiation due to brain tumors. Development of growth hormone deficiency (GHD) with age has been documented in patients with idiopathic GHD. A gradual loss of adrenocorticotropic hormone (ACTH) secretion has been also shown in a patient with severe GHD and an invisible pituitary stalk on magnetic resonance imaging (MRI). The purpose of this longitudinal and cross-sectional study was to evaluate the gradual loss of growth hormone (GH) and ACTH in a homogeneous group of patients with hypopituitarism. Twenty-eight patients (23 males, 5 females) from four hospitals were diagnosed as having prenatal or perinatal-onset hypothalamic hypopituitarism. They had an abnormal pituitary stalk on MRI (invisible in 18 patients, thin in 10 patients) without any other organic disease of the brain. Each patient had GHD upon initial evaluation. Height (n=20) was analyzed as standard deviation score (SDS). Longitudinal (n=8) and cross-sectional (n=28) GH secretion capacity was evaluated by GH peaks, in response to insulin tolerance test (ITT) and growth hormone releasing factor test (GRF test). Longitudinal (n=10) and cross-sectional (n=28) ACTH secretion capacity was evaluated by cortisol peaks in response to ITT. Height SDS decreased each year in all the untreated patients after birth. GH peaks decreased gradually with age. Longitudinal data showed decreased GH peaks with age in seven out of eight patients using ITT and in all four patients using GRF tests. Cortisol peaks also decreased gradually together with signs and symptoms for adrenal deficiency such as general fatigue. Cortisol peaks of less than 414 nmol/L (15 microg/dl) in response to ITT were seen in 24% of the tests before age 10 and 56% before age 25. In conclusion, GHD and ACTH deficiency developed gradually in patients with prenatal or perinatal-onset hypothalamic hypopituitarism who had invisible or thin pituitary stalks examined by MRI.

Novel wasp toxin discriminates between neuronal and cardiac sodium channels.

Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that beta-PMTX modifies rat brain type II Na+ channel alpha-subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart alpha-subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by beta-PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of beta-PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+ channels.

Regressive effect of intralesional injection of a moderate dose of recombinant interleukin-2 on carcinoma erysipeloides from gastric carcinoma.

Cutaneous metastatic diseases remain nearly incurable and a major medical challenge. It has been shown that interleukin-2 (IL-2) has potential as a therapeutic agent for various neoplastic diseases such as melanoma, renal cell carcinoma and myeloid leukaemia. However, IL-2 therapy for metastatic skin lesions has not been established yet. In the present study, we investigated the effect of recombinant IL-2 in a 79-year-old Japanese man with carcinoma erysipeloides, a rare type of cutaneous metastasis from gastric cancer. He was treated with an intralesional injection of rIL-2 (200 000 JRU) daily. Ten days after treatment, an erythematous plaque was eliminated almost completely leaving light brown pigmentation. A skin biopsy from the pigmented area revealed the absence of obvious tumour cells. These findings suggest that this cytokine should be considered for the clinical treatment of several inoperative metastatic cutaneous diseases, including gastric cancer.

Fixed drug eruption due to clarithromycin.

Clarithromycin is one of the macrolide antibiotics used for cutaneous and respiratory system infections. Only a few cases of adverse cutaneous reactions to this drug have been reported. Here we report a rare case of clarithromycin-induced fixed drug eruption which could be reproduced by a peroral provocation test, whereas patch tests on both unaffected and residual pigmented skin yielded negative results. All cutaneous lesions that recurred due to the challenge test developed the same pigmentation after a short course of intravenous corticosteroid.

Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH.

We report a 30-year-old female with adrenal unresponsiveness to ACTH. Her clinical features included no adrenal crisis despite poor drug compliance, poor pubic hair development (Tanner stage 2), well-developed breasts (Tanner stage 5), and regular menstrual cycles. Endocrinological data included blood ACTH 1500 pmol/l, cortisol 18 nmol/l, dehydroepiandrosterone sulphate below 0.26 micromol/l, activated renin 0.37 pmol/l, and aldosterone 3.4 nmol/l. Direct sequencing and allele-specific amplification revealed two novel mutations in the ACTH receptor gene. One was transition from guanine to adenine at nucleotide position 1002, resulting in substitution of aspartate for asparagine at codon 103, and the other was transition from cytosine to thymine at nucleotide 1104, leading to substitution of arginine for tryptophan at codon 137. The present findings lend additional credence to the notions that adrenal androgens play an important role in female pubic hair development and that ovarian development takes place independently of adrenarche.

Enzymatic formation of ether linkage producing shoyuflavones from genistein and (+/-)-trans-epoxysuccinic acid.

The production mechanism of shoyuflavones, conjugated ethers of isoflavones with tartaric acid and isolated from fermented soy sauce, was studied. In the high molecular weight fraction of the culture extract of Aspergillus oryzae, genistein was transformed into shoyuflavone B in the presence of (+/-)-trans-epoxysuccinic acid but not in the low molecular one. Asp. sojae and Asp. tamarii showed high activity similar to Asp. oryzae but none of Asp. niger, Rhizopus oligosporus, and Mucor praini did. The contents of epoxysuccinic acids in the starting materials of soy sauce and the cultures of various Asp. fungi were determined as dimethyl 2-chloro-3-hydroxysuccinate derivatives by GC-MS. Although epoxysuccinic acids were contained in Asp. oryzae, Asp. sojae, and Asp. tamarii cultures, they were not found in soybeans and wheat. A possible producing mechanism for shoyuflavones by enzymatically conjugating isoflavones to (+/-)-trans-epoxysuccinic acid with ether linkage was suggested.

MR imaging of the pituitary gland in children and young adults with congenital combined pituitary hormone deficiency associated with PROP1 mutations.

OBJECTIVE: The aim of this study was to clarify the relationship between morphologic changes of the pituitary gland and the genotype of Prophet of Pit-1 (PROP1), a newly discovered gene responsible for congenital combined pituitary hormone deficiency, in a series of eight humans with this disorder. CONCLUSION: Congenital hypoplasia of the anterior pituitary gland is the most common MR imaging finding in patients with combined pituitary hormone deficiency. Our findings suggest a crucial role for PROP1 in pituitary organogenesis as well as anterior pituitary cell differentiation.

On site of action of grayanotoxin in domain 4 segment 6 of rat skeletal muscle sodium channel.

Grayanotoxin I (GTX I) is a diterpenoid extracted from the family of Ericaceae that binds to Na(+) channels and causes persistent activation. We investigated the interaction of GTX I with the amino acid residues I1575, F1579 and Y1586 in transmembrane segment D4S6 of micro1. In F1579A, GTX shifted the threshold potential about 50 mV in the hyperpolarizing direction and modified Na(+) channels twice as efficiently as that in wild-type. In contrast, these GTX-effects were eliminated completely in the I1575A mutant and were reduced substantially in mutant Y1586A. Lysine substitution for F1579 significantly reduced and for Y1586 completely eradicated the GTX-effect. Our data suggest that the GTX receptor site shares overlapping but non-identical molecular determinants with BTX in D4S6 and has common molecular determinants in D1S6.