[The efficacy and safety of different antimicrobial regimens in carbapenem-resistant Klebsiella pneumoniae bloodstream infections].

Objective: To evaluate the efficacy and safety of different antimicrobial regimens in patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: The clinical date of patients with CRKP bloodstream infections were retrospectively analyzed at the First Affiliated Hospital of Zhejiang University Medical College between January 2017 and January 2018. All subjects were separated into three groups based on antibiotics regimens over 72 hours, including meropenem 2.0 g every 8 hours, tigecycline 200 mg as initial dose and 100 mg every 12 hours, and polymyxin B 1.25 mg/kg every 12 hours as salvage treatment of tigecycline. Results: A total of 86 patients were finally recruited, including 14, 52 and 20 patients in groups of meropenem, tigecycline and polymyxin B salvage, respectively. All of the strains were resistant to meropenem and susceptible to tigecycline and polymyxin B initially, while 2 of them became resistant to tigecycline during treatment. The 28-day mortality was significantly higher in meropenem group (13/14) than that in tigecycline group and polymyxin B salvage group (61.5%, 32/52) and (12/20), respectively (P<0.01), while as no significant difference was seen in the last two groups (χ(2)=0.014, P>0.05). The incidences of hepatic impairment [3.8%(2/52) vs. 1/20] and renal dysfunction (0 vs. 1/20) between tigecycline group and polymyxin B salvage group were both comparable (P>0.05). Conclusion: The meropenem-based therapy is not recommended for CRKP-related bloodstream infections. Tigecycline-based therapy is still disappointing despite salvage use of polymyxin B after 72 hours. Hepatic and nephretic toxicities caused by additional polymyxin B are acceptable.

First Report of Peanut Pod Rot Caused by Neocosmospora vasinfecta in Northern China.

From 2006 to 2010, peanut (Arachis hypogaea) pod rot became more prevalent in northern China, especially in the Sha River drainage area. The incidence of pod rot ranged from 30 to 100%. Typical symptoms were black rot of the pods, but no obvious morphological abnormality of the aboveground parts of infected plants was observed. Brown or black spots appeared on many pods when initially infected and then all peanut pods became black and rotten. The same fungus was isolated from 54 surface-disinfested lesions (85.2% of all lesions) on potato dextrose agar (PDA) media. One isolate, designated as HBXLb, was chosen for further characterization. In culture, both anamorph and teleomorph were present. Mycelia of the fungus grew quickly (colonies were 3.2 cm in diameter in 3 days) and became white and floccose on PDA at 28°C. The hyaline, elongated-to-cylindrical conidia aggregated on the slimy heads of conidiogenous cells that developed on undifferentiated hyphae after incubation for 3 to 4 days. Conidial sizes varied from 5 to 10 × 1.5 to 3 µm (n = 50) and were mostly single celled. Some conidia appeared slightly curved. The morphology was consistent with Acremonium spp. Numerous ascomata (perithecia) formed within 10 to 14 days when incubated at 28°C under light and dark conditions. Perithecia were orange-brown, strawberry shaped (300 to 400 µm in diameter), and ostiolate on the top. Cylindrical asci, with an average size of 90 to 110 × 7.5 to 9 µm, were present inside the ascomata with each containing eight ascospores in a row. The ascospores were brownish, spherical to ellipsoidal, and 10 to 15 × 8 to 12 µm. The cultural and morphological characteristics of isolate HBXLb matched the description of N. vasinfecta (2). The internal transcribed spacer (ITS) region of rDNA was amplified by the primer pairs ITS4/ITS5. A 525-bp amplicon (ITS4-5.8s-ITS5) was obtained and sequenced (GenBank Accession No. HM461901). The ITS sequence was a 100% match to N. vasinfecta strain N-JXLN01 (GenBank Accession No. GU213063) by BLASTn in GenBank. Pathogenicity tests were conducted on detached pods of peanut cultivar Jihua 4. Forty surface-disinfested peanut pods were soaked in a conidial suspension (105 conidia per ml) for 2 min and 40 pods were soaked in sterile water as a control. Then all peanut pods were maintained in moist petri dishes under darkness for 14 days at 28°C. Brown or black spots appeared on all pods inoculated with the fungus within 10 days, while the controls remained healthy. Symptoms were similar to those originally observed in the field, and N. vasinfecta could be reisolated from all infected pods. This fungus previously has been reported as the pathogen of foot rot of peanut in South Africa (1), Taiwan (4), and Australia (3). To our knowledge, this is the first report of peanut pod rot caused by N. vasinfecta in China. References: (1) S. W. Baard et al. Phytophylactica 17:49, 1985. (2) O. A. Cornely et al. Emerg. Infect. Dis. 7:149, 2001. (3) M. F. Fuhlbohm et al. Australas. Plant Dis. Notes 2:3, 2007. (4) J. W. Huang et al. Plant Pathol. Bull. 1:203, 1992.

First Report of Neocosmospora striata Causing Peanut Pod Rot in China.

In 2008, an outbreak of pod rot of peanut (Arachis hypogaea L.) occurred on most of the peanut cultivars in the Old Yellow River drainage area, the largest peanut-growing region in China. Disease incidence reached as high as 90% in some fields, causing severe yield losses. The black rot of pods and blackened, nonrotting taproots is similar to symptoms of peanut black rot caused by Cylindrocladium parasiticum, but the reddish orange perithecia of C. parasiticum were not found on the taproots close to the surface of the soil. The foliage of affected plants was generally asymptomatic, but some plants turned greener. This pod rot disease was further investigated in 2008 and 2010. Twenty-three Fusarium-like isolates were obtained from symptomatic, surface-disinfested pods with a frequency of 82%. These isolates were fast growing, with flat, thin, and grayish white colonies when cultured on potato dextrose agar (PDA) at 28°C for 3 to 4 days. The hyaline, elongated to cylindrical conidia, aggregated in slimy heads on conidiogenous cells developed from undifferentiated hyphae when observed with the light microscope. The size of conidia (single celled or one septum) varied from 3 to 9 µm long and 1.5 to 3.5 µm wide on the basis of the measurement of 50 spores. Some conidia appeared slightly curved. Ascomata formed within 10 to 14 days, with a punctate appearance on the colony. The cerebriform ascomata were dark brown, pyriform, ostiolate, glabrous, 120 to 170 × 90 to 130 µm, and with necks 30 to 50 µm long. Asci measured 60 to 90 × 6 to 10 µm, were cylindrical to cylindric-clavate, thin walled, and had an apical ring. Ascospore arrangement was obliquely uniseriate or partially biseriate, very pale yellow to hyaline, ellipsoidal, and measured 8 to 12 × 4.5 to 6 µm. Some spores had a median transverse straight or curved septum and were slightly constricted at the septum, with 6 to 10 thin, transverse, hyaline flanges. Morphological characteristics of the isolates with ascomata dark brown and ascospores with 6 to 10 transverse hyaline flanges matched the description for Neocosmospora striata (1). The internal transcribed spacer (ITS) region of rDNA was amplified from extracted template DNA with primer pairs ITS4/ITS5 and sequenced. A 591-bp amplicon (GenBank Accession No. HM461900) had 99% sequence identity with Fusarium solani (HQ607968 and HQ608009) and N. vasinfecta (GU213063), which indicated that these fungi belong to the genus Neocosmospora or Fusarium, although there is no direct sequence evidence that they are N. striata. N. striata has only been previously reported in Japan (2). This species is unique because of the dark brown ascomata and there is no comparable species (1). Koch's postulates were completed by surface-disinfesting 80 peanut pods of cv. Jihua 9813 and soaking them in conidial suspensions (105 conidia/ml) for 2 min. Another 80 other pods soaked in sterile water served as controls. All peanuts were incubated in moist petri dishes under darkness at 28°C. Symptoms similar to those originally observed in the field formed within 10 days on all inoculated peanut pods and not the controls. N. striata was reisolated from all affected peanut pods. To our knowledge, this is first report of N. striata causing peanut pod rot in China and the first description of the anamorph of the fungus. References: (1) P. F. Cannon et al. Trans. Br. Mycol. Soc. 82:673, 1984. (2) S. Udagawa et al. Trans. Mycol. Soc. Jpn. 16:340, 1975.

MicroRNA-296 functions as a tumor suppressor in breast cancer by targeting FGFR1 and regulating the Wnt/ß-catenin signaling pathway.

OBJECTIVE: Breast cancer (BC) is a common malignancy all over the world. However, the detailed mechanism underlying BC progression remains incompletely understood. MicroRNAs (miRNAs) have been observed to play crucial roles in tumorigenesis. The present study aimed to determine the expression and function of miR-296 in BC. PATIENTS AND METHODS: MiR-296 expressions in BC tissue samples and cell lines were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After that, we performed functional assays, including MTT (3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays, to show the functions of miR-296 in BC cell proliferation, invasion and migration. Immunological histological chemistry (IHC) assays were carried out to detect the expression levels of fibroblast growth factor receptor 1 (FGFR1) in BC tissue samples. Western blot was used to explore potential mechanisms of miR-296 in regulating BC progression. A Luciferase reporter assay was carried out to confirm the target gene of miR-296. RESULTS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) results demonstrated a significant decrease of miR-296 expressions in BC when compared to the corresponding normal controls. In addition, the decreased miR-296 was correlated with the malignant phenotypes and poorer prognosis of BC patients. The functional assays indicated that miR-296 restoration could repress the proliferation, invasion and migration abilities of BC cells. Moreover, the results of the current study revealed that miR-296 exerted the repressive functions in BC cells via regulating FGFR1, the Wnt/ß-catenin signaling pathway and EMT. Additionally, miR-296 up-regulation could inhibit in vivo BC cell growth. CONCLUSIONS: All these findings indicated that miR-296 exerted anti-BC functions, providing novel therapeutic strategies in BC treatment.

Role of two recently cloned rat liver GSH transporters in the ubiquitous transport of GSH in mammalian cells.

Recently our laboratory has cloned both the rat canalicular and sinusoidal GSH transporters (RcGshT and RsGshT, respectively; Yi, J., S. Lu, J. Fernandez-Checa, and N. Kaplowitz. 1994. J. Clin. Invest. 93:1841-1845; and 1995. Proc. Natl. Acad. Sci. USA. 92:1495-1499). The current work characterized GSH transport and the expression of these two GSH transporters in various mammalian cell lines. The average cell GSH levels (nmol/10(6) cells) were 25, 22, 32, 13, and 13 in HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. GSH efflux was temperature dependent and averaged 0.018, 0.018, 0.012, 0.007, and 0.019 nmol/10(6) cells/min from HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. Dithiothreitol (DTT), which stimulates rat sinusoidal GSH efflux, stimulated GSH efflux only in HepG2 and HeLa cells which was partially reversed by subsequent cystine treatment. GSH uptake (1 mM plus 35S-GSH) was temperature dependent, linear up to 45 min, and Na+-independent with average rates of 1.12, 0.91, 0.45, and 0.45 nmol/10(6) cells/30 min for HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. BSP-GSH (2mM), which cis-inhibits sinusoidal GSH uptake in rat liver and HepG2 cells, inhibited GSH uptake only in HeLa cells. mRNA and polypeptide of RcGshT are expressed in all cells whereas those of RsGshT are expressed only in HepG2 and HeLa cells. In conclusion, bidirectional GSH transport, mediated by the "canalicular" GSH transporter, is ubiquitous in mammalian cells. Sinusoidal GSH transporter expression is more restricted, being present in HepG2 and HeLa cells. DTT and BSP-GSH affect GSH transport only in cells expressing the sinusoidal transporter confirming their selective action on this transporter.

Study of exclusive charmless semileptonic B decays and |Vub|.

We study semileptonic B decay to the exclusive charmless states pi, rho/omega, eta, and eta;{'} using the 16 fb(-1) CLEO Upsilon(4S) data sample. We find B(B0-->pi-l+nu)=(1.37+/-0.15stat+/-0.11sys)x10(-4) and B(B0-->rho-l+nu)=(2.93+/-0.37stat+/-0.37sys)x10(-4) and find evidence for B+-->eta'l+nu, with B(B+-->eta'l+nu)=(2.66+/-0.80stat+/-0.56sys)x10(-4). From our B-->pilnu rate for q2>16 GeV2 and lattice QCD, we find |Vub|=(3.6+/0.4stat+/0.2syst-0.4thy+0.6)x10(-3) [corrected]

Effect of acute acoustic stress on anorectal function sensation in healthy human.

Little is known about the effects of acute acoustic stress on anorectal function. To determine the effects of acute acoustic stress on anorectal function and sensation in healthy volunteers. Ten healthy volunteers (7 M, 3 F, mean age 34 +/- 3 years) underwent anorectal manometry, testing of rectal compliance and sensation using a barostat with and without acute noise stress on separate days. Rectal perception was assessed using an ascending method of limits protocol and a 5-point Likert scale. Arousal and anxiety status were evaluated using a visual analogue scale. Acoustic stress significantly increased anxiety score (P < 0.05). Rectal compliance was significantly decreased with acoustic stress compared with control P (P < 0.000001). In addition, less intraballoon volume was needed to induce the sensation of severe urgency with acoustic stress (P < 0.05). Acoustic stress had no effect on hemodynamic parameters, anal sphincter pressure, threshold for first sensation, sensation of stool, or pain. Acute acoustic stimulation increased anxiety scores, decreased rectal compliance, and enhanced perception of severe urgency to balloon distention but did not affect anal sphincter pressure in healthy volunteers. These results may offer insight into the pathogenesis of stress-in-induced diarrhoea and faecal urgency.

Relation between postprandial satiation and antral area in normal subjects.

The factors influencing appetite in humans are poorly understood. There is a weak relation between appetite and gastric emptying in normal subjects. Recent studies have shown that fasting and postprandial antral areas increase in patients with functional dyspepsia compared with normal subjects. We evaluated the hypothesis that antral area, and hence antral distention, is a significant determinant of postprandial fullness. Fourteen normal subjects had simultaneous measurements of gastric emptying by scintigraphy and antral area by ultrasound after ingestion of 350 mL 20% glucose. Fullness and hunger were assessed by visual analog scales. Measurements of the gastric-emptying half time (t1/2) by scintigraphy and ultrasound were not significantly different (129.6 +/- 11.8 min compared with 115.6 +/- 11.4 min). Fullness increased (P < 0.001) and hunger decreased (P < 0.001) after the drink. Both fullness and the magnitude of the increase in fullness after the drink were related to antral area (r > 0.56, P < 0.05), the increase in antral area (r > 0.59, P < 0.05), and the scintigraphic content of the distal stomach (r > 0.57, P < 0.05), but not to the ultrasound or scintigraphic t1/2 values. In contrast, hunger and the magnitude of the decrease in hunger after the drink were not related to either antral area, the increase in antral area, or the rate of gastric emptying. We conclude that postprandial fullness, but not hunger, was closely related to antral distention in normal subjects.

A retrospective study of the effects of pelvic irradiation for gynecological cancer on anorectal function.

PURPOSE: To evaluate the prevalence of anorectal dysfunction following therapeutic pelvic irradiation. METHODS AND MATERIALS: Anorectal function was evaluated in 15 randomly selected patients (aged 47-84 years) who had received pelvic irradiation for treatment of carcinoma of the uterine body and cervix 5 and 10 years earlier. The following parameters were assessed in each patient: (a) anorectal symptoms (questionnaire), (b) anorectal pressures at rest and in response to rectal distension, voluntary squeeze, and increases in intraabdominal pressure (multiport anorectal manometry with concurrent electromyography of the anal sphincters), (c) rectal sensation (rectal balloon distension) and, (d) anal sphincteric morphology (ultrasound). Results were compared with those obtained in nine female control subjects. RESULTS: Ten of the 15 patients had urgency of defecation and 4 also suffered fecal incontinence. Basal anorectal pressures measured just proximal to the anal canal (p = 0.05) and anorectal pressures generated in response to voluntary squeeze measured at the anal canal were less (p < 0.01) in the patients. The fall in anal pressures in response to rectal distension was greater in the patients (p < 0.05) and the desire to defecate occurred at lower rectal volumes (p < 0.05). The slope of the pressure/volume relationship in response to rectal distension was greater (p < 0.05) in the patients, suggestive of a reduction in rectal compliance. In 14 of the 15 patients at least one parameter of anorectal motor function was outside the control range. There was no difference in the thickness of the anal sphincters between the two groups. CONCLUSION: Abnormal anorectal function occurs frequently following pelvic irradiation for gynecological malignant diseases and is characterized by multiple dysfunctions including weakness of the external anal sphincter, stiffness of the rectal wall, and a consequent increase in rectal sensitivity.

Bidirectional glutathione transport by cultured human retinal pigment epithelial cells.

PURPOSE: To characterize glutathione (GSH) transport by cultured human retinal pigment epithelial (HRPE) cells. METHODS: Cultured HRPE cells were pretreated with acivicin for GSH efflux and with buthionine sulfoximine for GSH uptake to prevent the breakdown and resynthesis of GSH. Efflux was measured by the linear rate of accumulation of GSH in the supernatant; uptake was measured using [35S] GSH plus varying concentrations of GSH. Molecular forms were verified by high-performance liquid chromatography. HRPE cell mRNA was probed for the presence of the two recently cloned rat sinusoidal and canalicular GSH transporters, (RsGshT and RcGshT), by Northern blot analysis. RESULTS: Glutathione efflux was temperature dependent (undetectable at 4 degrees C), and its averaged 23 +/- 3.3 pmol/10(6) cells/minute or 10% of the total GSH effluxed per hour (total cell GSH = 13.6 +/- 1.5 nmol/10(6) cells). Efflux was not influenced by dithiothreitol or sulfobromophthalein-reduced GSH adduct, agents known to affect liver sinusoidal GSH transport. Glutathione uptake was linear up to 45 minutes and was temperature dependent. The difference between 37 degrees C and 4 degrees C uptake values represented true uptake. Glutathione uptake (2 microCi/ml + 1 mM mass) was Na independent and was inhibited significantly by phenol-3,6-dibromphthalein disulfonate. The kinetics of GSH uptake was assessed by measuring uptake with 35S-GSH and 0.05 to 40 mM extracellular GSH for 30 minutes. Uptake was saturable with Vmax = 18.7 +/- 1.7 nmol/10(6) cells/30 minutes, Km = 12.1 +/- 1.9 mM, n (binding site) = 1. On Northern blot analysis, HRPE cells express mRNA for RcGshT but not for RsGshT. CONCLUSIONS: The similarities in functional characteristics of GSH transport and the presence of RcGshT-like mRNA suggest GSH transport in HRPE cells is mediated by a RcGshT homolog. Although the transporter can operate bidirectionally, it is expected to be a net efflux pump under normal physiologic conditions because the intracellular GSH concentration is much higher.

Pharmacokinetic considerations in gastrointestinal motor disorders.

Although it has been recognised that alterations in gastrointestinal motility, whether induced by physiological or pathological processes, have significant effects on the pharmacokinetics of orally administered drugs, this subject has received inappropriately little attention. Studies relating to this topic have focused on healthy volunteers and animals and have largely been confined to the effects of single drug doses. There is limited information about the effects of disease on pharmacokinetics under steady-state conditions. Changes in gastrointestinal motility may affect the pharmacokinetics of orally administered drugs by altering the rate of delivery, bioavailability or mucosal absorption of the drug. In general the rate of absorption and time taken to achieve maximal plasma concentrations for well absorbed drugs may be modified by changes in gastrointestinal motility, but overall bioavailability is not usually affected. In these cases the therapeutic and clinical effects of the alteration in pharmacokinetics will, therefore, depend on which parameters are important for the action of the drug. For poorly absorbed drugs both the rate of absorption and bioavailability are likely to be altered by changes in gastrointestinal motility. However, the complex effects of food and disease, as well as the properties and formulation of any drug (solubility, ease of dispersion, delayed release formulation) often make the prediction of the magnitude, or even the direction, of any effect difficult to predict. Drugs with direct effects on gastrointestinal motility may influence their own patterns of absorption. In patients with gastrointestinal motility disorders, drugs administered in a controlled release formulation, or those with poor bioavailability, are most likely to have a poorly predictable therapeutic effect. Care should be taken to ensure that the formulation of the drug, its timing of administration in relation to meals and the use of coadministered drugs optimise, or at least ensure consistent absorption.

Ozone, NO, and NO2: oxidant air pollutants and more.

This article reviews the acute and chronic toxicity of the three oxidant air pollutants ozone, nitric oxide (NO), and nitrogen dioxide (NO2). The toxicity of binary mixtures of NO2 with other inhaled agents is also discussed. Newer studies are emphasized, especially those published in the last 5 years or still in press. Very recent data from our laboratory that suggest a new cellular mechanism of importance in lung injury in animals exposed to mixtures of ozone and NO2 that may have general relevance with regard to the effects of oxidant air pollutants on the lung are also presented.

Pyloric motor response to central and peripheral nitric oxide in the ferret.

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric motility. In 10 urethane-anaesthetized ferrets, drugs were administered directly to the CNS via a 0.5-mm-diameter cannula inserted into the 4th ventricle, approximately at the obex. Drugs were also given directly to the upper GI tract by close intra-arterial (i.a.) injection at the coeliac axis. Antropyloroduodenal pressures were recorded with a five-channel sleeve/sidehole micromanometric assembly (1.35 x 1.75 mm o.d.), which was introduced via the duodenum. Pyloric motility was stimulated throughout the main part of each study with a continuous i.v. infusion of CCK-8 (30 pmol min-1). This infusion produced an immediate and sustained increase in tonic and phasic pyloric activity, and sustained abolition of antral pressure waves. CCK-8 also induced a duodenal motor response, but this was short-lived (11.4 +/- 7.9 min). Coeliac axis injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) decreased phasic pyloric activity (from 330 +/- 35 to 148 +/- 21 mmHg min-1 after SNAP 5 micrograms, P < 0.01). By comparison central SNAP administration over the same dose range had no effect on CCK-stimulated pyloric motlity. Inhibition of endogenous NO synthase with L-Nitro Arginine Methyl Ester (L-NAME, 100 mg kg-1 close i.a.) caused a marked increase of phase pyloric motor activity from 349 +/- 59 to 1044 +/- 140 mmHg min-1 (P < 0.01). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 +/- 0.5 to 13.1 +/- 2.8 mmHg (P < 0.01). Central nervous administration of L-NAME caused modest enhancement of phasic pyloric activity (248 +/- 31 to 283 +/- 32 mmHg min-1 P < 0.05) and pyloric tone (2.6 +/- 0.5 to 3.7 +/- 0.7 mmHg, P < 0.05). Our data indicate that motor activity of the ferret pylorus is potently modulated by NO released within the upper gut. Additionally, there is potential for modulation of pyloric motility by central nervous system production of NO.

Postural changes in proximal gastric volume and pressure measured using a gastric barostat.

A barostat was used to examine the effect of changes in posture on the volume and pressure in a bag positioned in the proximal stomach of 14 normal volunteers. Volumes in the supine position were compared with those in the standing, left lateral and right lateral positions at a constant pressure 2 mmHg above basal intragastric pressure. A separate series of measurements was then used to evaluate the effects of the same postural changes on pressure within the bag whilst its volume was kept constant. Changing from the supine to the left lateral position decreased bag volume by 62% when pressure was controlled; pressure increased by 60% when volume was controlled. In contrast, movement from the supine to the right lateral position resulted in a 68% increase in bag volume and a 31% fall in pressure. Moving from supine to standing had inconsistent effects on bag volume and pressure. There was a negative correlation between the magnitudes of the changes in pressure and volume (r2 = 0.557). The observed effects of posture probably result from changes in the compression of the stomach by abdominal viscera and indicate that subject position must be specified and maintained constant in studies of proximal gastric motor function using a barostat.

In vitro exposure of tracheobronchial epithelial cells and of tracheal explants to ozone.

An in vitro system for exposing respiratory epithelial cells or explant tissues to ozone has been developed and characterized. This system is designed to generate and monitor consistent, reproducible levels of ozone, over a range of concentrations, in a humidified atmosphere, and to allow an exposure time of 24 h or longer. Based on chemical analysis, highly reproducible concentrations of ozone are delivered throughout the chamber, with a coefficient of variation of < 5% between five replicate vials exposed to 0.5 ppm of ozone for 50 min. The viability of cultured human tracheobronchial epithelial cells, as measured by the ability to oxidize a vital dye, and of rat tracheal epithelium, as measured by total numbers of necrotic cells in tracheal explants, after ozone exposure was examined in this system. Responses of cultured cells to ozone exposure as measured by bioassay were consistent with the observed low level of variability of ozone concentration between replicate incubation dishes or vials. Responses of cultured cells to ozone were proportional to duration of exposure and inversely proportional to the volume of medium covering the cells. We conclude that this newly developed in vitro exposure system will allow relatively simple and convenient exposure of cultured cells or organs to ozone or other gaseous agents under highly controlled and reproducible conditions.

Disturbances in anorectal function in patients with diabetes mellitus and faecal incontinence.

OBJECTIVE: The pathophysiology of faecal incontinence in diabetes mellitus is poorly understood. The study was designed to document the anorectal dysfunctions in diabetic patients with faecal incontinence. METHODS: Multiport anorectal manometry and electromyography were done in 11 diabetic patients with faecal incontinence and in 20 healthy controls. RESULTS: Basal and squeeze pressures were reduced (P < 0.05) in the diabetic patients compared with the control subjects. During basal recording six patients showed regular oscillations in anal electrical activity and pressure with an amplitude of 10-40 (median: 25) cmH2O and a frequency of 6-10 (median: 8) min-1. Nine patients also exhibited spontaneous transient anal relaxations with an amplitude of 15-50 (median: 40) cmH2O and a duration of 15-720 (median: 60)s, and in six of them leakage occurred as the anal pressure fell below the rectal pressure. None of the control subjects showed oscillation or spontaneous relaxations. In patients there was a greater tendency for repetitive rectal contractions in response to rectal distension and reduced rectal compliance (P < 0.01). During rectal distension four patients showed no anal relaxation, and in the remainder relaxation occurred at an abnormally high threshold. However, the residual pressures were lower (P < 0.05) than in control subjects and often fell below rectal pressure, whereupon leakage occurred. There was no significant difference in the distension thresholds for rectal sensation between patients and control subjects, but in 9/11 patients the perception of rectal sensation was delayed by more than 2s (P < 0.05). CONCLUSION: These results indicate that aetiology of faecal incontinence in diabetic patients is multifactorial and, suggest for the first time, that instability of the internal sphincter probably plays a major role.

Hyperglycaemia affects proximal gastric motor and sensory function in normal subjects.

OBJECTIVE: Hyperglycaemia delays gastric emptying in normal subjects and patients with diabetes mellitus by uncertain mechanisms and may affect the perception of somatic sensations. The effects of hyperglycaemia on the motor function of the proximal stomach and the perception of gastric distension were evaluated in normal subjects. DESIGN: Paired studies were performed in randomized order in 10 healthy volunteers on separate days during euglycaemia and hyperglycaemia (blood glucose approximately equal to 15 mmol/l). METHODS: With a barostat and a balloon positioned in the proximal stomach, tasting subjects underwent a stepwise gastric distension. Each 2 mmHg step was maintained at a constant pressure for 2 min. The volume of the barostat balloon was measured and perception of the sensations of fullness, desire to belch, nausea, abdominal discomfort and hunger was scored at each step. RESULTS: Hyperglycaemia was associated with an increase in proximal gastric compliance (P < 0.01) evident from 2 mmHg above basal intragastric pressure. Perception scores for the sensations of nausea and desire to belch were greater during hyperglycaemia than euglycaemia (P < 0.05) in relation to both pressure at each step and volume. Hyperglycaemia did not affect perception of the sensations of abdominal discomfort, fullness or hunger. CONCLUSIONS: Hyperglycaemia increases proximal gastric compliance, reflecting a reduction in gastric tone. This may contribute to the previously observed delay in gastric emptying associated with hyperglycaemia. Hyperglycaemia appears to increase the perception of some of the sensations induced by gastric distension.

[Modelling the general relative risk models in case-control studies of primary hepatocellular carcinoma].

This paper was to analyse the effect of risk factors of primary hepatocellular carcinoma (PHC). The analysis was carried on using the family of relative risk functions to asses which scale could better explain the risk structure underlying the data. The results showed that the risk factors of PHC in south area of China were HBV infection, family history of PHC, drank pond-ditch water, while the risk factors of PHC in north area were HBV infection, family history of PHC, history of hepatitis, drank alcohol. The results suggested that the combined effect of risk factors was near to multiplicative. Being able to discriminate between risk structures has important implications on causal interpretation and public health practice.

Control of defecation in patients with spinal injuries by stimulation of sacral anterior nerve roots.

OBJECTIVE: To observe the effects of stimulation of the sacral anterior roots on anorectal and low colonic pressures and to programme implanted stimulators to produce defecation. DESIGN: Prospective study of 12 consecutive patients. SETTING: Spinal injuries unit and university gastrointestinal physiology department. PATIENTS: 12 Patients with complete supraconal spinal cord lesions. Their injuries had been sustained at least two years before the study. INTERVENTIONS: A Brindley-Finetech intradural sacral anterior root stimulator was implanted in all patients. Three months postoperatively the stimulator settings were adjusted after measurement of simultaneous anorectal and low colonic pressures. MAIN OUTCOME MEASURES: Full defecation. RESULTS: Six patients achieved complete rectal evacuation of faeces using the implant and subsequently did not require manual help for defecation. For all but one of the patients the total time taken to complete defecation was reduced, and all were free from constipation, the most prevalent gastrointestinal symptom in patients with spinal injuries. CONCLUSIONS: Sacral anterior root stimulators can be programmed to achieve complete unassisted defecation and can considerably improve the quality of life of patients with spinal injuries.