Impact of surgical resection rate on survival in gastric cancer: nationwide study.

BACKGROUND: There are marked geographical variations in the proportion of patients undergoing resection for gastric cancer. This study investigated the impact of resection rate on survival. METHODS: All patients with potentially curable gastric cancer between 2006 and 2017 were identified from the Swedish National Register of Oesophageal and Gastric Cancer. The annual resection rate was calculated for each county per year. Resection rates in all counties for all years were grouped into tertiles and classified as low, intermediate or high. Survival was analysed using the Cox proportional hazards model. RESULTS: A total of 3465 patients were diagnosed with potentially curable gastric cancer, and 1934 (55.8 per cent) were resected. Resection rates in the low (1261 patients), intermediate (1141) and high (1063) tertiles were 0-50.0, 50.1-62.5 and 62.6-100 per cent respectively. The multivariable Cox analysis revealed better survival for patients diagnosed in counties during years with an intermediate versus low resection rate (hazard ratio (HR) 0.81, 95 per cent c.i. 0.74 to 0.90; P < 0.001) and high versus low resection rate (HR 0.80, 0.73 to 0.88; P < 0.001). CONCLUSION: This national register study showed large regional variation in resection rates for gastric cancer. A higher resection rate appeared to be beneficial with regard to overall survival for the entire population.

Prognosis and clinicopathologic features in patients with gastric stump cancer after curative surgery.

Background: Gastric stump ("remnant") cancer is the development of a malignancy related to previous gastric surgery. Prognosis in gastric stump cancer, compared with that in primary gastric cancer, is still controversial. Methods: From January 1988 to December 2012 at a single medical centre in Taiwan, 105 patients with gastric stump cancer, including 85 with previous peptic ulcer disease and 20 with previous gastric cancer, were analyzed for clinicopathologic characteristics and overall survival (os). Results: The 5-year os rates for patients with gastric stump cancer and with primary gastric cancer were 51.2% and 54.5% respectively (p = 0.035). Analysis of clinicopathologic characteristics indicated that, compared with patients having primary gastric cancer, those with gastric stump cancer had more lymph node metastasis (p < 0.001) and had been diagnosed at a more advanced stage (p = 0.047). Multivariate analysis with os as an endpoint showed that age [p = 0.015; hazard ratio (hr): 2.300; 95% confidence interval (ci): 1.173 to 4.509], tumour size (p = 0.037; hr: 1.700; 95% ci: 1.031 to 2.801), stromal reaction (p = 0.021; hr: 1.802; 95% ci: 1.094 to 2.969), and pathologic N category (p = 0.001; hr: 1.449; 95% ci: 1.161 to 1.807) were independent predictors in gastric stump cancer. The os rates for patients with gastric stump cancer who previously had gastric cancer or peptic ulcer disease were 72.9% and 50.0% respectively (p = 0.019). The Borrmann classification was more superficial (p = 0.005), lymph node metastases were fewer (p = 0.004), and staging was less advanced (p = 0.025) in patients with gastric stump cancer who previously had gastric cancer than in their counterparts who previously had peptic ulcer disease. Conclusions: Survival is poorer in patients with gastric stump cancer who previously had peptic ulcer disease than in those who previously had primary gastric cancer. Patients with gastric stump cancer who previously had gastric cancer and could receive curative gastrectomy tended to have a better prognosis because of a more superficial Borrmann classification. Regular follow-up in patients who have undergone gastric surgery is recommended for the early detection of gastric stump cancer.

Geographical differences in cancer treatment and survival for patients with oesophageal and gastro-oesophageal junctional cancers.

BACKGROUND: Only around one-quarter of patients with cancer of the oesophagus and the gastro-oesophageal junction (GOJ) undergo surgical resection. This population-based study investigated the rates of treatment with curative intent and resection, and their association with survival. METHODS: Patients diagnosed with oesophageal and GOJ cancer between 2006 and 2015 in Sweden were identified from the National Register for Oesophageal and Gastric Cancer (NREV). The NREV was cross-linked with several national registries to obtain information on additional exposures. The annual proportion of patients undergoing treatment with curative intent and surgical resection in each county was calculated, and the counties divided into groups with low, intermediate and high rates. Treatment with curative intent was defined as definitive chemoradiation therapy or surgery, with or without neoadjuvant oncological treatment. Overall survival was analysed using a multilevel model based on county of residence at the time of diagnosis. RESULTS: Some 5959 patients were included, of whom 1503 (25·2 per cent) underwent surgery. Median overall survival after diagnosis was 7·7, 8·8 and 11·1 months respectively in counties with low, intermediate and high rates of treatment with curative intent. Corresponding survival times for the surgical resection groups were 7·4, 9·3 and 11·0 months. In the multivariable analysis, a higher rate of treatment with curative intent (time ratio 1·17, 95 per cent c.i. 1·05 to 1·30; P < 0·001) and a higher resection rate (time ratio 1·24, 1·12 to 1·37; P < 0·001) were associated with improved survival after adjustment for relevant confounders. CONCLUSION: Patients diagnosed in counties with higher rates of treatment with curative intent and higher rates of surgery had better survival.

ANTECEDENTES: En los pacientes con cáncer en el esófago y de la unión gastroesofágica (gastroesophageal junction, GOJ), solamente en una cuarta parte se practica una resección quirúrgica. Este estudio de base poblacional analizó las tasas de tratamiento con intención curativa y de resección y su asociación con la supervivencia. MÉTODOS: A partir del Registro Nacional Sueco de Cáncer de Esófago y Estómago (National Register for Oesophageal and Gastric Cancer, NREV), se identificaron los pacientes diagnosticados de cáncer de esófago y de la GOJ entre 2006-2015. El NREV se cruzó con otros registros nacionales para obtener información adicional. Se calculó la proporción anual de pacientes tratados con intención curativa o mediante resección quirúrgica en cada una de las áreas territoriales de los condados y se categorizaron en baja, intermedia y alta. El tratamiento con intención curativa se definió como la quimiorradioterapia definitiva (definitive chemoradiation therapy, dCRT) o la cirugía, con o sin tratamiento oncológico neoadyuvante. Se analizó la supervivencia global con un modelo multinivel basado en el condado de residencia en el momento del diagnóstico. RESULTADOS: Se incluyeron 5.959 pacientes, de los que 1.503 (25,2%) fueron tratados quirúrgicamente. La mediana de supervivencia global después del tratamiento con intención curativa fue de 7,7, 8,8 y 11,1 meses para los condados de volumen bajo, intermedio y alto. Para el grupo de cirugía fue de 7,4, 9,3 y 11,0 meses, respectivamente. En el análisis multivariable, una mayor tasa de tratamiento con intención curativa y una mayor tasa de resección se asociaron con una mejor supervivencia (tiempo ganado 1,17; i.c. del 95% 1,05-1,30, P < 0,001 y tiempo ganado 1,24; i.c. del 95% 1,12-1,37, P < 0,001) después del ajuste para los factores principales de confusión. CONCLUSIÓN: Los pacientes diagnosticados en condados con tasas altas de tratamiento con intención curativa y de cirugía tuvieron una mejor supervivencia.

Nationwide study of the impact of D2 lymphadenectomy on survival after gastric cancer surgery.

BACKGROUND: Gastrectomy including D2 lymphadenectomy is regarded as the standard curative treatment for advanced gastric cancer in Asia. This procedure has also been adopted gradually in the West, despite lack of support from RCTs. This study sought to investigate any advantage for long-term survival following D2 lymphadenectomy in routine gastric cancer surgery in a Western nationwide population-based cohort. METHODS: All patients who had a gastrectomy for cancer in Sweden in 2006-2017 were included in the study. Prospectively determined data items were retrieved from the National Register of Oesophageal and Gastric Cancer. Extent of lymphadenectomy was categorized as D1+/D2 or the less extensive D0/D1 according to the Japanese Gastric Cancer Association classification. Overall survival was analysed and, in addition, a variety of possible confounders were introduced into the Cox proportional hazards regression model. RESULTS: A total of 1677 patients underwent gastrectomy, of whom 471 (28·1 per cent) were classified as having a D1+/D2 and 1206 (71·9 per cent) a D0/D1 procedure. D1+/D2 lymphadenectomy was not associated with higher 30- or 90-day postoperative mortality. Median overall survival for D1+/D2 lymphadenectomy was 41·5 months with a 5-year survival rate of 43·7 per cent, compared with 38·5 months and 38·5 per cent respectively for D0/D1 (P = 0·116). After adjustment for confounders, in multivariable analysis survival was significantly higher after D1+/D2 than following D0/D1 lymphadenectomy (hazard ratio 0·81, 95 per cent c.i. 0·68 to 0·95; P = 0·012). CONCLUSION: This national registry study showed that long-term survival after gastric cancer surgery was improved after gastrectomy involving D1+/D2 lymphadenectomy compared with D0/D1 dissection.

ANTECEDENTES: En Asia, la gastrectomía con linfadenectomía D2 asociada se considera el tratamiento curativo estándar para el cáncer gástrico avanzado. Este procedimiento se ha adoptado gradualmente también en el mundo occidental a pesar de la falta de apoyo de los ensayos clínicos aleatorizados. En este estudio hemos tratado de investigar cualquier ventaja sobre la supervivencia a largo plazo tras la linfadenectomía D2 de rutina en una cohorte de base poblacional de cirugía del cáncer gástrico en un país occidental. MÉTODOS: Se incluyeron todos los pacientes que fueron sometidos a gastrectomía por cáncer en Suecia desde 2006-2017. Se recuperaron datos registrados prospectivamente del Registro Nacional de Cáncer de Esófago y Estómago. La extensión de la linfadenectomía se categorizó en D1+/D2 o cuando fue menos amplia en D0/D1 de acuerdo con la clasificación de la Japanese Gastric Cancer Association. Se analizó la supervivencia global y, además, se introdujeron diversos factores de confusión en un modelo de regresión de riesgos proporcional de Cox. RESULTADOS: Un total de 1.677 pacientes fueron sometidos a gastrectomía, de los cuales 471 (28%) fueron clasificados como D1+/D2 y 1.206 (72%) como D0/D1. La linfadenectomía D1+/D2 no se asoció con una mayor mortalidad postoperatoria a los 30 y 90 días. La mediana de la supervivencia global para la linfadenectomía D1+/D2 fue de 41,5 meses con una tasa de supervivencia a los 5 años de 44% comparado con 38,5 meses y 39%, respectivamente, para D0/D1 (P = 0,116). Después de ajustar por los factores de confusión en el análisis multivariable, la supervivencia fue significativamente más alta en la linfadenectomía D1+/D2 comparada con D0/D1 (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,68-0,95), P = 0,012)). CONCLUSIÓN: Este estudio del registro nacional mostró que la supervivencia a largo plazo tras cirugía del cáncer gástrico mejoró después de una gastrectomía que incluya linfadenectomía D1+/D2 en comparación con la disección D0/D1.

Characterization and topical delivery of phenylethyl resorcinol.

OBJECTIVE: Phenylethyl resorcinol (PR) has been used widely in the personal care industry as a novel skin lightening ingredient. Surprisingly, there is only limited information describing the physicochemical properties of this active. Therefore, the primary objective of this study was to perform a comprehensive characterization of PR. A secondary objective was to investigate the delivery of this molecule to mammalian skin. METHODS: Phenylethyl resorcinol was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and nuclear magnetic resonance (NMR). A new high-performance liquid chromatographic (HPLC) method for analysis of PR was developed and validated. The log P (octanol water partition coefficient), value, solubility and short-term stability of PR in a series of vehicles were also determined using HPLC. The evaporation of the selected vehicles was examined using dynamic vapour sorption (DVS). The permeation profiles of PR were investigated under finite dose conditions in porcine and human skin. RESULTS: The melting point of PR was determined to be 79.13 °C and the measured log P (octanol water partition coefficient) at 21 °C was 3.35 ± 0.03. The linearity of the HPLC analytical method was confirmed with an r2 value of 0.99. Accuracy of the method was evaluated by average recovery rates at three tested concentrations, and the values ranged from 99 to 106%. The limit of detection (LOD) and limit of quantification (LOQ) were 0.19 and 0.57 µg mL-1 , respectively. The solubility of PR in PG, DMI, glycerol was within the range of 367 to 877 mg mL-1 . The stability of PR in tested solvents was also confirmed by the 72 h stability studies. From the DVS studies, 70-125% of applied formulations were recovered at 24 h. The permeation through porcine skin at 24 h ranged from 4 to 13 µg cm-2 , while the corresponding amounts of PR delivered through human skin were 2 to 10 µg cm-2 . CONCLUSION: The physicochemical properties of PR confirm it is suitable for dermal delivery. In this study, propylene glycol was the most promising vehicle for PR delivery to human skin. Future work will expand the range of vehicles studied and explore the percutaneous absorption from more complex formulations.

OBJECTIF: Le phényléthyl résorcinol (PR) est largement utilisé dans le secteur des soins personnels comme ingrédient éclaircissant pour la peau. Pour autant, on ne dispose que d'informations limitées concernant les propriétés physicochimiques de ce principe actif. C'est pourquoi cette étude avait pour objectif principal de réaliser une caractérisation exhaustive du PR. Son objectif secondaire était d'étudier l'administration de cette molécule à la peau de mammifères. MÉTHODES: Le phényléthyl résorcinol a été caractérisé par calorimétrie différentielle à balayage (CDB), analyse thermogravimétrique (ATG) et par résonance magnétique nucléaire (RMN). Pour analyser le PR, une nouvelle méthode de chromatographie liquide à haute performance (CLHP) a été développée et validée. On s'est servi de la CLHP pour déterminer les propriétés suivantes du PR : log P (coefficient de partage octanol/eau), valeur, solubilité et stabilité à court terme du PR dans plusieurs véhicules. L'évaporation des véhicules sélectionnés a été examinée par sorption de vapeur dynamique (DVS). Les profils de perméabilité du PR ont été étudiés dans des conditions de dose finie dans des peaux porcine et humaine. RÉSULTATS: On a pu déterminer que le point de fusion du PR était de 79,13 °C et le log P (coefficient de partage octanol/eau) à 21 °C était de 3,35 ± 0.03. La linéarité de la méthode analytique de la CLHP a été confirmée avec une valeur r2 de 0,99. L'exactitude de la méthode a été évaluée par les taux moyens de récupération à trois concentrations testées, avec des valeurs résultantes comprises entre 99 et 106 %. La limite de détection (LD) et la limite de quantification (LQ) ont été déterminées à 0,19 et 0,57 µg/ml_ 1, respectivement. La solubilité du PR dans le PG, le DMI et le glycérol reste dans une plage comprise entre 367 et 877 mg/ml _ 1. La stabilité du PR dans les solvants testés a également pu être confirmée par les études de stabilité à 72 h. Parmi les formulations appliquées lors des études de DVS, 70 à 125 % de celles-ci ont été récupérées à 24 h. La pénétration par la peau porcine à 24 h était comprise entre 4 et 13 µg/cm_ 2, tandis que les quantités de PR correspondantes délivrées à travers la peau humaine étaient de 2 à 10 µg/cm_ 2. CONCLUSION: Les propriétés physicochimiques du PR confirment qu'il est adapté à l'administration dermique. Dans le cadre de cette étude, le propylène glycol est apparu comme le véhicule le plus prometteur pour l'administration de PR dans la peau humaine. De futurs travaux étudieront davantage de véhicules et examineront l'absorption percutanée lors de l'emploi de formulations plus complexes.

The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.

3D-printed Franz type diffusion cells.

OBJECTIVE: Franz cells are routinely used to measure in vitro skin permeation of actives and must be inert to the permeant under study. The aim of the present work was to develop and manufacture transparent Franz-type diffusion cells using 3D printing. Printouts were then tested using a range of model active compounds. The study also aims to identify the critical 3D-printing parameters necessary for the process, including object design, choice of printing resin, printout curing and post-curing settings and introduction of model coatings. METHODS: Transparent Franz cells were constructed using an online computer aided design program and reproduced with different stereolithography 3D printers. The two acrylate-based resins used for the fabrication process were a commercially available product and a polymer synthesised in-house. Comparative studies between glass and 3D-printed Franz cells were conducted with selected model actives: terbinafine hydrochloride (TBF), niacinamide (NIA), diclofenac free acid (DFA) and n-methyl paraben (MPB). In preliminary studies, MPB showed the lowest recovery when exposed to the receptor compartment of 3D printed cells. Consequently, in vitro permeation studies were carried out using only MPB with polydimethylsiloxane (PDMS) membrane. RESULTS: A decrease in the amounts of selected compounds was observed for transparent 3D-printed Franz cells compared to glass cells. MPB showed the lowest recovery (53.8 ± 13.1%) when compared with NIA (74.9 ± 4.0%), TBF (81.5 ± 12.0%) and DFA (90.2 ± 12.9%) after 72 h. Permeation studies conducted using 3D-printed transparent cells with PDMS membrane also showed a decrease in MPB recovery of 51.4 ± 3.7% for the commercial resin and 94.4 ± 3.5% for the polymer synthesised in-house, when compared to glass cells. Although hydrophobic coatings were subsequently applied to the 3D-printed cells, the same reduction in MPB concentration was observed in the receptor solution. CONCLUSION: Transparent Franz cells were successfully prepared using 3D printing and were observed to be robust and leak-proof. There are few resins currently available for preparation of transparent materials and incompatibilities between the actives investigated and the 3D-printed cells were evident. Hydrophobic coatings applied as barriers to the printed materials did not prevent these interactions.

Neuropsychiatric symptoms in Alzheimer's disease: associations with caregiver burden and treatment outcomes.

BACKGROUND: Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities. AIM: To address the impact of neuropsychiatric symptoms of patients in different stages of AD on their caregivers' burden. DESIGN: This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center. METHODS: All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI. RESULTS: The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively). CONCLUSIONS: The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.

Alternative optical concept for electron cyclotron emission imaging.

The implementation of advanced electron cyclotron emission imaging (ECEI) systems on tokamak experiments has revolutionized the diagnosis of magnetohydrodynamic (MHD) activities and improved our understanding of instabilities, which lead to disruptions. It is therefore desirable to have an ECEI system on the ITER tokamak. However, the large size of optical components in presently used ECEI systems have, up to now, precluded the implementation of an ECEI system on ITER. This paper describes a new optical ECEI concept that employs a single spherical mirror as the only optical component and exploits the astigmatism of such a mirror to produce an image with one-dimensional spatial resolution on the detector. Since this alternative approach would only require a thin slit as the viewing port to the plasma, it would make the implementation of an ECEI system on ITER feasible. The results obtained from proof-of-principle experiments with a 125 GHz microwave system are presented.

Enhancement of the Schottky barrier height of Au/ZnO nanocrystal by zinc vacancies using a hydrothermal seed layer.

Various seed layers were prepared on a Si substrate using the sol-gel (SG) or hydrothermal (HT) method and then ZnO nanocrystal was grown on the seed layer by an HT process. Au/ZnO nanocrystal Schottky diodes (SDs) were fabricated to study the effects of various seed layers on the electrical properties of Au/ZnO SDs. The observations showed that large numbers of Zn vacancies were present near the interface of Au/ZnO with an HT seed layer. The Zn vacancy plays an acceptor-like role, which raises the barrier height of the Au/ZnO SDs to 0.79 eV with a rectifying ratio of more than 8000. Hence, a non-surface-treated Au/ZnO SD was achieved as compared to those of other reported oxygen-plasma treated surfaces. In contrast, oxygen vacancies appear near the interface of Au/ZnO with an SG seed layer. The O vacancy plays a donor-like role, which reduces the barrier height of Au/ZnO, leading to an Ohmic behavior in the I-V characteristics. Zn out-diffusion is found during Au evaporation by of x-ray photoelectron spectroscopy measurements.

Application of reutilization technology to waste from liquid crystal display (LCD) industry.

This investigation studies the recycling utility of two major waste products from the liquid crystal display (LCD) industry, panel glass and calcium fluoride sludge, which remain after the treatment of waste water. Waste panel glass was mixed with calcium fluoride sludge in various ratios and then subject to conditioning and melting treatment in order to yield glass-ceramics. Heavy metal leaching tests indicated that reductive conditions lowered the heavy metal concentrations in the leachate to an order of magnitude below that in the waste glass and sludge. A 5:5 (wt%) mixture of glass and sludge melted at 1200 degrees C for 60 min achieves a specific gravity, water absorption, unit mass, porosity ratio, and soundness that meet the American Society for Testing and Materials (ASTM) standard for fine aggregates. Therefore, waste panel glass can indeed be efficiently recycled into a useful construction material.

How normal is abnormal? Discrimination between deformations and natural variation in gonad morphology of European whitefish Coregonus lavaretus.

The gonad morphology of whitefish Coregonus lavaretus collected in Lake Thun, Switzerland, and two neighbouring lakes was assessed in order to differentiate between 'normal' and 'abnormal' character states of gonad morphology, which had been previously described in C. lavaretus from Lake Thun (constrictions, asymmetries, aplasia, compartmentations, fusions and hermaphroditism). In total, 4668 fish were collected and analysed using two complementary sampling schemes: (1) monthly samples of catches by the commercial fishermen and (2) samples of ripe spawners of all known 33 spawning sites of the three lakes. Considerable variation in gonad morphology in C. lavaretus populations of all lakes was found. Notably, all deviation types were observed in fish of all three lakes. Asymmetries and constrictions were frequent in all three lakes and showed systematic differences in frequency between the two sampling strategies. This indicates that asymmetries and constrictions represent to a large extent natural variation in gonad morphology of C. lavaretus and are also prone to considerable measurement error. In contrast, aplasia, fusions, compartmentations and hermaphroditism occurred predominantly in one C. lavaretus form of Lake Thun and in particular in populations spawning at great depths. This suggests that these deviation types are probably reliable indicators for gonad deformations and supports the interpretation that Lake Thun harbours a unique case of deformed gonads in C. lavaretus of yet unknown origin.

Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome.

OBJECTIVES: To compare early second-trimester maternal serum placenta growth factor concentrations in Down syndrome pregnancies and those in normal pregnancies. METHODS: A case-control study was performed to evaluate the maternal serum placenta growth factor concentrations in 36 Down syndrome and 320 normal pregnancies with matched gestational age during the second trimester. For the detection of serum concentrations of placenta growth factor, a quantitative sandwich enzyme immunoassay technique (R & D Systems Inc., Minneapolis, Minnesota, USA) was performed. RESULTS: Using a multiple linear regression model, maternal serum placenta growth factor level was associated with gestational age (p<0.001) and the existence of Down syndrome pregnancy (p<0.001). After converting maternal serum placenta growth factor concentrations of each analyte to multiples of the appropriate gestational median (MoM), placenta growth factor MoM (p<0.001) was revealed to be an independent variable for Down syndrome pregnancies after adjusting for the effects of maternal age (p<0.001), free beta-hCG (p<0.001) and AFP (p=0.014) by multivariate logistic regression analysis. CONCLUSIONS: Maternal serum placenta growth factor concentration was elevated in Down syndrome pregnancies during the early second trimester. Placenta growth factor might be a novel marker for maternal serum Down syndrome screening.

K(+)-channel transgenes reduce K(+) currents in Paramecium, probably by a post-translational mechanism.

PAK11 is 1 of more than 15 members in a gene family that encodes K(+)-channel pore-forming subunits in Paramecium tetraurelia. Microinjection of PAK11 DNA into macronuclei of wild-type cells results in clonal transformants that exhibit hyperexcitable swimming behaviors reminiscent of certain loss-of-K(+)-current mutants. PAK2, a distant homolog of PAK11, does not have the same effect. But PAK1, a close homolog of PAK11, induces the same hyperexcitability. Cutting the PAK11 open reading frame (ORF) with restriction enzymes before injection removes this effect entirely. Microinjection of PAK11 ORF flanked by the calmodulin 5' and 3' UTRs also induces the same hyperexcitable phenotype. Direct examination of transformed cells under voltage clamp reveals that two different Ca(2+)-activated K(+)-specific currents are reduced in amplitude. This reduction does not correlate with a deficit of PAK11 message, since RNA is clearly produced from the injected transgenes. Insertion of a single nucleotide at the start of the PAK11 ORF does not affect the RNA level but completely abolishes the phenotypic transformation. Thus, the reduction of K(+) currents by the expression of the K(+)-channel transgenes reported here is likely to be the consequence of a post-translational event. The complexity of behavioral changes, possible mechanisms, and implications in Paramecium biology are discussed.

Reduction of radiation dose to patients undergoing barium enema by dose audit.

Nowadays, new fluoroscopic machines are usually equipped with a dose-area product (DAP) meter for dose measurement. In our hospital, DAP meters have been used in the Diagnostic Radiology Department for dose audit since June 1997. Demographic patient data, name of radiologist, fluoroscopic duration and DAP readings of every case were recorded by radiographers. In early 1999, questionnaires were distributed to radiologists who had performed fluoroscopic examinations during the auditing period. 23 radiologists with varying years of experience completed the questionnaire and their practice was analysed. Since familiarization with the examination technique would affect radiologists' practice, these radiologists were divided into two groups for analysis. Radiologists with less than 3 years of experience were grouped together as junior radiologists, whilst others were grouped as senior radiologists. Results of the questionnaire indicated that radiologists generally found DAP meters useful for dose evaluation in the process of technique refinement. Radiologists aware of being under continuous surveillance of their practice showed significant reduction of doses (junior radiologists 25%, p<0.005; senior radiologists 36%, p<0.05) and fluoroscopic times (junior radiologists 36%, p<0.001; senior radiologists 18%, p<0.05) compared with radiologists who were unaware that they were under surveillance but with similar radiological experience. This effect is believed to be because of increased awareness of radiation dose through audit. In addition, this "audit effect" may also affect junior radiologists in decision-making regarding the number of radiographs (p<0.05), but no effect was found for senior radiologists (p>0.5).

A TRP homolog in Saccharomyces cerevisiae forms an intracellular Ca(2+)-permeable channel in the yeast vacuolar membrane.

The molecular identification of ion channels in internal membranes has made scant progress compared with the study of plasma membrane ion channels. We investigated a prominent voltage-dependent, cation-selective, and calcium-activated vacuolar ion conductance of 320 pS (yeast vacuolar conductance, YVC1) in Saccharomyces cerevisiae. Here we report on a gene, the deduced product of which possesses significant homology to the ion channel of the transient receptor potential (TRP) family. By using a combination of gene deletion and re-expression with direct patch clamping of the yeast vacuolar membrane, we show that this yeast TRP-like gene is necessary for the YVC1 conductance. In physiological conditions, tens of micromolar cytoplasmic Ca(2+) activates the YVC1 current carried by cations including Ca(2+) across the vacuolar membrane. Immunodetection of a tagged YVC1 gene product indicates that YVC1 is primarily localized in the vacuole and not other intracellular membranes. Thus we have identified the YVC1 vacuolar/lysosomal cation-channel gene. This report has implications for the function of TRP channels in other organisms and the possible molecular identification of vacuolar/lysosomal ion channels in other eukaryotes.

Paramecium genome survey: a pilot project.

A consortium of laboratories undertook a pilot sequencing project to gain insight into the genome of Paramecium. Plasmid-end sequencing of DNA fragments from the somatic nucleus together with similarity searches identified 722 potential protein-coding genes. High gene density and uniform small intron size make random sequencing of somatic chromosomes a cost-effective strategy for gene discovery in this organism.

Chemically charging the pore constriction opens the mechanosensitive channel MscL.

MscL is a bacterial mechanosensitive channel that protects the cell from osmotic downshock. We have previously shown that substitution of a residue that resides within the channel pore constriction, MscL's Gly-22, with all other 19 amino acids affects channel gating according to the hydrophobicity of the substitution (). Here, we first make a mild substitution, G22C, and then attach methanethiosulfonate (MTS) reagents to the cysteine under patch clamp. Binding MTS reagents that are positively charged ([2-(trimethylammonium)ethyl] methanethiosulfonate and 2-aminoethyl methanethiosulfonate) or negatively charged (sodium (2-sulfonatoethyl)methanethiosulfonate) causes MscL to gate spontaneously, even when no tension is applied. In contrast, the polar 2-hydroxyethyl methanethiosulfonate halves the threshold, and the hydrophobic methyl methanethiolsulfonate increases the threshold. These observations indicate that residue 22 is in a hydrophobic environment before gating and in a hydrophilic environment during opening to a substate, a finding consistent with our previous study. In addition, we have found that cysteine 22 is accessible to reagents from the cytoplasmic side only when the channel is opened whereas it is accessible from the periplasmic side even in the closed state. These results support the view that exposure of hydrophobic surfaces to a hydrophilic environment during channel opening serves as the barrier to gating.

Cardiovascular manifestations of pheochromocytoma.

Pheochromocytomas are rare tumors that originate in chromaffin tissue and produce their distant variant effects by secretion of catecholamines, tending to mislead the emergency physicians to a wrong diagnosis. Therefore, we analyze the clinical cardiovascular manifestations in patients with pheochromocytoma to improve the diagnostic ability of the emergency physicians. All patients presenting to the Chang Gung Memorial Hospital between January 1993 and December 1997 with a final diagnosis of pheochromocytoma had their charts reviewed. The data of 25 patients including age, sex, adrenergic stimulation presentations, electrocardiographic changes, location of the tumor, and complications were analyzed. Hypertension was the most important major manifestation and fluctuation of blood pressure drew our attention to the possibility of pheochromocytoma. Six patients had abnormal electrocardiographic ST-T segment changes. Five of them had chest pain which prompted them to undergo coronary angiography before surgery, because acute coronary syndrome (unstable angina and acute myocardial infarction) was suspected initially. However, all of them turned out to have normal coronary arteries. Right-sided pheochromocytoma was found in three of these five patients. We should maintain high index of suspicion for pheochromocytoma in patients presenting with chest pain, fluctuating blood pressure, and ischemic electrocardiogram (ECG) changes despite any typical isoenzyme changes. Pheochromocytoma should also be included in the differential diagnosis of acute coronary syndrome because acute catecholamine secretion may induce chest pain and abnormal ECG changes mimicking an ischemic episode. The right-sided pheochromocytoma may present more striking electrocardiographic abnormalities and clinical manifestations.