bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning curve for Doppler assessment of ductus venosus flow at 11 + 0 to 13 + 6 weeks' gestation
Authors: Maiz N. , Kagan K. O. , Milovanovic Z. , Celik E. , Nicolaides K. H.
Published: March 2008

Objective

To determine the number of scans necessary for training sonographers to examine accurately the ductus venosus at 11 + 0 to 13 + 6 weeks' gestation.

Methods

Ten sonographers with prior extensive experience in the measurement of nuchal translucency thickness were given practical training in the accurate assessment of the ductus venosus. They were then asked to examine the ductus venosus during the routine 11 + 0 to 13 + 6 weeks' scan. Each scan was assessed by an experienced sono‐ grapher and classified as being successful or unsuccessful (failure to obtain a waveform, poor quality image with contamination or wrong classification of the A‐wave). Each sonographer performed a total of 300 examinations, the data were analyzed in 15 groups of 20 examinations and in each group the percentage of unsuccessful examinations was calculated.

Results

In the total 3000 cases examined by the 10 sonographers there were 2849 (95.0%) successful examinations and 151 unsuccessful, including 104 failures to obtain a waveform, 30 cases where the quality of the image was considered to be inadequate and 17 cases in which the classification of the A‐wave was wrong. The overall frequency of unsuccessful examinations decreased significantly with the number of scans carried out (r = 0.982, P < 0.0001). The sonographers required an average of 80 examinations before they could successfully examine the ductus in at least 19 of a group of 20 scans. Although one of the 10 trainees achieved this standard within the first block of 20 scans some of the sonographers required training in 100 cases.

Conclusion

Competence in Doppler assessment of the ductus venosus is achieved only after extensive supervised training. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Three‐dimensional ultrasound improves the interobserver reliability of antral follicle counts and facilitates increased clinical work flow
Authors: Jayaprakasan K. , Campbell B. K. , Clewes J. S. , Johnson I. R. , Raine‐Fenning N. J.
Published: March 2008

Objectives

To compare the interobserver reliability of antral follicle counts made using real‐time two‐dimensional (2D) ultrasound with offline counts made from stored three‐dimensional (3D) data and to assess the time required for such counts.

Methods

Two observers conducted transvaginal ultrasound examinations in 45 subfertile women in the early follicular phase of the menstrual cycle. Antral follicles were counted using real‐time 2D ultrasound and the time taken was recorded. A 3D volume was then acquired from each ovary and stored for subsequent offline analysis using the multiplanar view. The time taken for each step was recorded and the total time was calculated. Intraclass correlation coefficients (ICC) and limits of agreement were used to assess reliability.

Results

There was no difference in the mean antral follicle counts using real‐time 2D (16.51 ± 11.51) and 3D (16.33 ± 12.13) ultrasound. According to ICCs, there was a significantly higher interobserver reliability for counts made using 3D (mean, 0.992; 95% CI, 0.986–0.996) compared with real‐time 2D (mean, 0.961; 95% CI, 0.940–0.977) (P < 0.01) ultrasound. 3D ultrasound was also associated with narrower limits of agreement (−2.7 to + 3.1) than was 2D ultrasound (−6.9 to + 6.4). Whilst the total time taken was significantly longer for the 3D technique (239.3 ± 71.4 s vs. 103.1 ± 28.6 s, P < 0.001), the time required for the actual ultrasound examination was significantly less (46.4 ± 7.4 s vs. 103.1 ± 28.6 s, P < 0.001).

Conclusions

3D ultrasound significantly improves the interobserver reliability of antral follicle counts. While this is at the expense of time overall, the duration of the actual ultrasound examination and patient exposure is significantly reduced using 3D compared with real‐time 2D ultrasound. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Iranian Mothers’ Perceptions of Their Lives with Children with Mental Retardation: A Preliminary Phenomenological Investigation
Authors: Kermanshahi S. M. , Vanaki Z. , Ahmadi F. , Kazemnejad A. , Mordoch E. , Azadfalah P.
Published: March 2008

This phenomenological study explored Iranian mothers’ lived experiences of having a child with mental retardation (MR). Six mothers parenting a child with MR who attended a School for Exceptional Children were interviewed. Semi-structured interviews which encouraged the mothers to describe their experiences were audiotaped, transcribed and analyzed in accordance with Colaizzi’s (Existential phenomenological alternatives for psychology, New York, Oxford University Press, 1978) procedural steps. Six major themes were found in the data: Challenging the process of acceptance, painful emotional reactions, the inter-relatedness of the mother’s health and the child’s well being, struggles to deal with oneself or the child, inadequate support from the family and community, and anxiety related to the child’s uncertain future. Findings from this study contribute to a preliminary understanding of Iranian mothers’ experiences and needs. The results suggest introductory changes in nursing practice, staff education and program development to best serve mothers and their children with MR.
Laboratory Studies on Membrane Deoiling of Lecithin
Authors: Manjula S. , Subramanian R.
Published: March 2008

Deoiling of lecithin using a nonporous membrane was examined in a favorable solvent (hexane) medium with soy and rice bran lecithins. During the membrane process, the acetone insoluble (AI) content of soy lecithin increased from 63.2 to 81.0% in a single step batch operation. The membrane exhibited an excellent selectivity since phospholipid (PL) reverse micelles formed in the system were rejected almost completely due to low solubility probably aided synergistically by size exclusion. Diafiltration achieved greater oil removal from lecithin as reflected in terms of higher AI and PL contents in the deoiled lecithin. In discontinuous diafiltration, the PL content increased from 33.3 to 85.5% in rice bran lecithin (150% dilution to feed) and 56.6 to 85.7% in soy lecithin (200% dilution), respectively. The simulated continuous diafiltration run showed slightly greater PL content in soy lecithin (91.3%) compared to discontinuous diafiltration (89.7%) besides offering higher productivity. The membrane showed a color reduction of ~60% in soy lecithin but there was no improvement in rice bran lecithin due to the retention of degradation products. The proposed integrated membrane process with nonporous (deoiling) and nanofiltration (solvent recovery) membranes could be an attractive preposition besides being an acetone free process.
Oxidized proteins in plasma of patients with heart failure: Role in endothelial damage
Authors: Banfi Cristina , Brioschi Maura , Barcella Simona , Veglia Fabrizio , Biglioli Paolo , Tremoli Elena , Agostoni PierGiuseppe
Published: March 2008

Background:

Oxidative stress is increased in the failing heart, and this might contribute to the pathogenesis of myocardial remodelling and heart failure (HF).

Aim:

To identify the oxidized proteins in plasma of chronic HF patients and to evaluate their possible role in endothelial damage.

Methods:

Plasma levels of oxidized proteins were measured by immunoassay and by analysis in albumin and immunoglobulin depleted plasma using a proteomic approach, in 40 HF patients and in 20 age‐matched normal subjects. Analysis of the effects of proteins oxidized in vitro on human endothelial cell (EC) viability was also performed.

Results:

Plasma levels of oxidized proteins were significantly higher in HF patients than in controls (p < 0.01). We identified two proteins, α‐1‐antitrypsin and fibrinogen, which underwent oxidation. Oxidation of α‐1‐antitrypsin resulted in loss of its protease inhibitor activity, thus leading to EC death in the presence of elastase. Fibrinogen, when oxidized, became otherwise cytotoxic and induced apoptosis in EC.

Conclusions:

This study shows that plasma levels of oxidized proteins are increased in HF, and permitted the identification of two proteins, namely α‐1‐antitrypsin and fibrinogen, which underwent oxidation. In vitro results highlighted the potential role of oxidized proteins in the EC damage that occurs in HF.
Responders to cardiac resynchronization therapy with narrow or intermediate QRS complexes identified by simple echocardiographic indices of dyssynchrony: The DESIRE study
Authors: Cazeau Serge J. , Daubert J‐Claude , Tavazzi Luigi , Frohlig Gerd , Paul Vince
Published: March 2008

Background:

Cardiac resynchronization therapy (CRT) is recommended for patients with NYHA class III–IV refractory heart failure (HF), ejection fraction <35% and a QRS >120ms. We attempted to identify responders to CRT from echocardiographic (echo) indices of mechanical dyssynchrony in patients with QRS < 150 ms.

Methods and results:

The study enrolled 51 men and 9 women (mean age: 64.5years) in NYHA class III (n=54) or IV (n=6) presenting with a mean ejection fraction: 25.7%, LV end‐diastolic diameter: 69.1mm, and QRS = 121 ± 19 ms. All patients were implanted with a CRT system and followed for 1year. Implantation was preceded and followed by clinical, functional and Doppler (D)‐echo evaluation. The primary combined endpoint included 1) death from any cause, 2) HF‐related hospitalisations, and 3) NYHA class at 6 months. Before implant, 27 patients had ≥ 1 echo criterion of mechanical dyssynchrony (DES+ group) and 33 had no evidence of dyssynchrony (DES− group). At 12months, 8 patients (4 per group) had died, 7 from HF. As regards the primary endpoint at 6 months, 33 patients (55%) had improved, 10 (16%) were unchanged, and 17 (29%) had deteriorated. Clinical improvement was observed in 19 of 27 DES+ (70%), versus 14 of 33 DES− (42%) patients (P<0.04). Baseline QRS duration did not predict response to CRT.

Conclusions:

In this population of HF patients with QRS < 150 ms, the presence of mechanical dyssynchrony at baseline D‐echo examination, but not the QRS width, predicted 6‐month clinical response to CRT.
Identification of operator sites within the upstream region of the putative mce2R gene from mycobacteria
Authors: Vindal Vaibhav , Ashwantha Kumar Enjapoori , Ranjan Akash
Published: March 2008

Mycobacterium tuberculosis harbors four mce operons. Among them, mce2 operon is preceded by a FadR‐like regulator mce2R (Rv0586). Here, we report the operator sites of the mce2R and its orthologs in other sequenced mycobacteria and non‐mycobacterial species Nocardia farciana. All the identified DNA motifs illustrate the FadR subfamily specific nucleotide preference. Moreover, these motifs from the upstream region share sequence conservation, which is in agreement with the similarity of their DNA binding domain. Using electrophoretic mobility shift assay, we demonstrate that the predicted DNA motifs specifically interact with the recombinant Mce2R–Rv0586. Our present study has implications in the understanding of cis‐regulatory elements and the auto‐regulatory nature of the FadR subfamily of regulators.
t-to-rin West Yorkshire English
Authors: BROADBENT JUDITH M.
Published: March 2008

This article investigatest-to-rin West Yorkshire (WY) English and traces its course from a productive process in the nineteenth century to a lexically restricted fossil in contemporary WY. Nineteenth-century sources suggest that by the end of that century this process was already in decline. During the course of the twentieth centuryt-glottalling became a feature of the variety and so this article explores the possibility that as thefrequency of useoft-glottalling increased, this would quickly overshadowt-to-rusage. Paradoxically,frequency of useis also responsible for thet-to-rphenomenon manifested today. More specifically,t-to-rremains in a small group of frequent words which are related by phonological shape. As a consequence of their frequency and shape, they have lexical strength and this is why at-to-rfossil is maintained in WY today.
Vardenafil protects isolated rat hearts at reperfusion dependent on GC and PKG
Authors: Maas O , Donat U , Frenzel M , Rütz T , Kroemer H K , Felix S B , Krieg T
Published: March 2008

Background and purpose: The type‐5 PDE inhibitor vardenafil reduces myocardial infarct size in situ, following ischemia/reperfusion, when applied at reperfusion in animal models. Little is known about the underlying protective signaling. Here, we test whether vardenafil is protective in rat isolated hearts and in a cell model of calcium stress.

Experimental approach: Infarct size in rat isolated hearts was measured after a 30 min regional ischemia and 120 min reperfusion. Vardenafil (1 nM–1 μM) was infused during reperfusion. HL‐1 cardiomyocytes were loaded with tetramethylrhodamine ethyl ester (TMRE), a fluorescent marker of mitochondrial membrane potential (ψm).

Key results: Vardenafil at reperfusion reduced infarct size as percentage of the ischemic zone from 45.8±2.0% in control hearts to 26.2±2.7% (P<0.001) only at 10 nM, whereas higher or lower dosages failed to protect. This protective effect was blocked by co‐administration of either the GC inhibitor, 1H‐(1,2,4)oxadiazolo(4,3‐a)quinoxalin‐1‐one (ODQ), or the PKG inhibitor, KT‐5823. HL‐1 cardiomyocytes, loaded with TMRE, were treated for 80 min with the calcium ionophore, calcimycin, to induce calcium stress. This reduced the mean cell fluorescence to 63.3±3.8% of baseline values and vardenafil protected against this fall (78.6±3.6%, P<0.01). The vardenafil‐induced protection of HL‐1 cells was blocked by ODQ, KT‐5823 or the PKG‐inhibiting peptides DT‐2 and DT‐3, confirming a role for GC and PKG.

Conclusions and implications: These results further support the hypothesis that PDE‐5 inhibitors are protective in ischemic hearts, in addition to their known clinical effects in the treatment of erectile dysfunction in men.
Endothelium removal augments endothelium‐independent vasodilatation in rat mesenteric vascular bed
Authors: Iwatani Y , Kosugi K , Isobe‐Oku S , Atagi S , Kitamura Y , Kawasaki H
Published: March 2008

Background and purpose: The vascular endothelium regulates vascular tone by releasing various endothelium‐derived vasoactive substances to counteract excess vascular response. We investigated whether the vascular endothelium regulates vasodilatation via released endothelium‐derived contracting factors (EDCFs), by examining the effect of endothelium removal on responses to periarterial nerve stimulation (PNS) and various vasodilator agents.

Experimental approach: The rat mesenteric vascular bed was perfused with Krebs solution. Vasodilator responses to PNS and 5 min perfusion of vasodilator agents in preparations with endothelium were compared with those in the same preparations without endothelium. The endothelium was removed by 30 s perfusion with sodium deoxycholate.

Key results: Endothelium removal significantly augmented vasodilator responses to PNS and calcitonin gene‐related peptide (CGRP), isoprenaline (β‐adrenoceptor agonist), SNP and 8‐bromo‐cGMP (8‐Br‐cGMP; cGMP analogue) but not BAY41‐2272 (soluble guanylate cyclase activator). The augmentation of SNP‐induced vasodilatation after denudation was much greater than that of CGRP‐ or isoprenaline‐induced vasodilatation. In the preparations with an intact endothelium, L‐NAME (nitric oxide synthase inhibitor) significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and 8‐Br‐cGMP, but not BAY41‐2272. Indomethacin (cyclooxygenase inhibitor) and seratrodast (thromboxane A2 receptor antagonist), but not phosphoramidon (endothelin‐1‐converting enzyme inhibitor) or BQ‐123 (selective endothelin type A receptor antagonists), significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and BAY41‐2272.

Conclusion and implication: These results suggest that the endothelium in rat mesenteric arteries regulates and maintains vascular tone via counteracting not only vasoconstriction through releasing endothelium‐derived relaxing factors, but also vasodilatation, in part by releasing an EDCF, thromboxane A2.
Serotonin decreases HIV‐1 replication in primary cultures of human macrophages through 5‐HT1A receptors
Authors: Manéglier B , Guillemin G J , Clayette P , Rogez‐Kreuz C , Brew B J , Dormont D , Advenier C , Therond P , Spreux‐Varoquaux O
Published: March 2008

Background and purpose: 5‐HT (serotonin) is known to be involved in neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV) targets cells such as monocytes/macrophages, which colocalize with 5‐HT‐releasing cell types, mostly platelets. In this study, we investigated the effects of 5‐HT on HIV‐1‐infected macrophages in vitro.

Experimental approach: Human macrophages cultured in serum‐free medium were treated over 7 days with 5‐HT at three concentrations (0.01, 1 and 100 μM) with or without agonists and antagonists of 5‐HT1A and 5‐HT2 receptors. After 7 days of treatment, macrophages were infected with HIV‐1/Ba‐L and virus replication was monitored over 16 days and expression of proviral HIV DNA was investigated by PCR after 24 h of infection. Cell surface expression of HIV‐1/Ba‐L receptor (CD4) and coreceptor (CCR5) was investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein‐1α (MIP‐1α), was quantified by ELISA in cell culture supernatants and MIP‐1α mRNA expression was assessed by reverse transcriptase‐PCR.

Key results: In vitro, 5‐HT downregulated the membranous expression of CCR5 and led to a decrease of HIV‐1 infection, probably through its action on 5‐HT1A receptors. 5‐HT (100 μM) was also able to induce overexpression of MIP‐1α mRNA leading to an increase of MIP‐1α secretion by human macrophages.

Conclusions and implications: The effects of 5‐HT on HIV infection could be a consequence of the increase in MIP‐1α concentrations and/or CCR5 receptor downregulation. These results suggest that 5‐HT can inhibit the replication of HIV‐1 in primary culture of human macrophages through its action on 5‐HT1A receptors.
Na+/Ca2+exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart
Authors: Farkas A S , Acsai K , Nagy N , Tóth A , Fülöp F , Seprényi G , Birinyi P , Nánási P P , Forster T , Csanády M , Papp J G , Varró A , Farkas A
Published: March 2008

Background and purpose:The Na+/Ca2+exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 μMSEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+concentrations in rabbit and rat hearts.

Experimental approach:The concentration‐dependent effects of SEA0400 onINa/Cawere studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff‐perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.

Key results:SEA0400 inhibited INa/Cawith similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration‐dependent manner, for example, 1.0 μMSEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.

Conclusions and implications:NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na+concentration may play an important role in the contractility response to NCX inhibition.
Managing Crises: UK Civil Aviation, BAA Airports and the August 2006 Terrorist Threat
Authors: Henderson Joan C.
Published: March 2008

The paper examines the causes, characteristics and consequences of a travel and tourism industry crisis. A case study methodology is employed and the focus is on the civil aviation sector of the UK and events there in the summer of 2006 when an alleged terrorist plot disrupted airline services. Responses to the situation by the principal parties of government, the leading airport operator and airlines are reviewed within the context of a crisis management model and outcomes are assessed. Findings confirm the vulnerability of travel and tourism to terrorism-related crises and suggest the distinctive qualities of such crises and the challenges of managing them. Crisis management planning emerges as essential and past experiences yield valuable lessons which can be incorporated into preparations for the future.
Miniature ponies: 1. Follicular, luteal and endometrial dynamics during the oestrous cycle
Authors: Gastal E. L. , Neves A. P. , Mattos R. C. , Petrucci B. P. L. , Gastal M. O. , Ginther O. J.
Published: March 2008

Follicular dynamics were studied during 12 interovulatory intervals (IOIs) and 36 preovulatory periods in Miniature mares. The percentage of IOIs with the following follicle events was: ovulatory wave with only one follicle ≥10 mm (55%), diameter deviation similar to previous reports in larger mares (25%) and minor waves emerging before or after the ovulatory wave (55%). Follicle data were compared among Miniature ponies, large ponies and Breton horses (n = 12 IOIs per breed). The IOI was longer (P < 0.001) in Miniature ponies (23.3 ± 0.9 days) and in large ponies (23.9 ± 0.5 days) than in Breton horses (20.3 ± 0.7 days). The Miniature ponies had fewer (P < 0.0001) growing follicles ≥10 mm per ovulatory wave (1.5 ± 0.3) and more (P < 0.0004) ovulatory waves (6/11) with only one follicle ≥10 mm than large ponies (9.8 ± 0.8 and 0/12) and horses (5.8 ± 0.9 and 0/12). Maximum diameter of the preovulatory follicle was smaller (P < 0.003) in the Miniature ponies (38.3 ± 0.7 mm) than in the horses (44.5 ± 1.4 mm), but the difference between breeds was slight (6%) compared with the difference in bodyweight (65%). Considering the small number of follicles per ovulatory wave, Miniature mares are a potential model for comparative studies in folliculogenesis within and among species.
Miniature ponies: 2. Endocrinology of the oestrous cycle
Authors: Ginther O. J. , Beg M. A. , Neves A. P. , Mattos R. C. , Petrucci B. P. L. , Gastal M. O. , Gastal E. L.
Published: March 2008

Plasma concentrations of FSH, LH, oestradiol and progesterone were studied daily during 12 interovulatory intervals and 21 periovulatory periods in nine Miniature ponies. The peak of the FSH surge that was temporally associated with emergence of the future ovulatory follicle occurred when the follicle was ~9 mm, compared with a reported diameter of 13 mm in larger breeds. The ovulatory LH surge involved a slow increase between Days 13 and 18 (ovulation = Day 0; 0.6 ± 0.1 ng day–1), a minimal increase or a plateau on Days 18 to 21 (0.04 ± 0.1 ng day–1), and a rapid increase after Day 21 (2.2 ± 0.4 ng day–1; P < 0.0001). The end of the plateau and the beginning of the rapid increase occurred on the day of maximum concentration in the oestradiol preovulatory surge. An unexpected mean increase and decrease in LH occurred (P < 0.04) on Days 5 to 9. Concentrations of oestradiol and progesterone seemed similar to reported results in larger breeds. Results indicated that in Miniature ponies the peak of the FSH surge associated with emergence of the future ovulatory follicle occurred at a smaller diameter of the future ovulatory follicle than in larger breeds, the ovulatory LH surge increased in three phases, and the ovulatory LH surge was followed by an LH increase and decrease during the early luteal phase.
Expression of mRNAs encoding oestrogen receptor (ER) α and ERβ, androgen receptor and progesterone receptor during gonadal and follicular development in the marsupial brushtail possum (Trichosurus vulpecula)
Authors: Haydon Lisa J. , Juengel Jennifer L. , Thomson Brian P. , Eckery Douglas C.
Published: March 2008

The objective of the present study was to determine which ovarian cells express mRNAs for oestrogen (ERα and ERβ), androgen (AR) and progesterone (PR) receptors during ovarian and follicular development in the brushtail possum. Expression of ERα and/or ERβ mRNA was observed from birth, initially in cells of the blastema, then in the medullary cords from Day 20. ERα was expressed in the oocytes and granulosa cells of secondary and antral follicles. Preovulatory follicles did not express ERα mRNA, although their oocytes were not examined for any gene. ERβ mRNA was observed in oocytes at all follicular stages examined, but was not consistently observed in granulosa or theca cells. Expression of AR mRNA before Day 40 was very faint; thereafter, expression was observed in the medullary cords, peaking between Days 60 and 120. Oocytes, granulosa cells and theca of secondary and antral, but not preovulatory, follicles expressed AR mRNA. PR mRNA was expressed throughout the gonad by Day 20. Granulosa cells of some secondary and antral follicles and theca of antral follicles expressed PR mRNA. Thus, the expression of mRNAs encoding steroidogenic receptors in a time- and cell-specific manner supports a role for steroids in the process of ovarian follicular formation and growth.
Gastric and oesophageal emptying in insulin‐dependent diabetes mellitus
Authors: HOROWITZ MICHAEL , HARDING PHILIP E. , MADDOX ANNE , MADDERN GUY J. , COLLINS PETER J. , CHATTERTON BARRY E. , WISHART JUDITH , SHEARMAN DAVID J. C.
Published: March 2008

Abstract Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 45 randomly selected insulin‐dependent diabetics and in 22 control subjects. In the diabetics, the relationships between oesophageal emptying, gastric emptying, age, duration of diabetes mellitus, upper gastrointestinal symptoms, glycaemic control and the complications, autonomic neuropathy, peripheral neuropathy and retinopathy were examined. The lag period before solid food left the stomach was not significantly different in diabetics compared with control subjects, but the percentage retention of solid food at 100 min was greater (P < 0.001) in the diabetic subjects. Both the early phase (percentage retention at 10 min) and the 50% emptying time for liquid gastric emptying were delayed (P < 0.001) in the diabetic subjects. Of the diabetics, 58% had delayed gastric emptying of either the solid and/or the liquid meal; oesophageal emptying was delayed in 42%. Upper gastrointestinal symptoms correlated poorly with both gastric and oesophageal emptying. Oesophageal emptying, solid gastric emptying and the liquid 50% emptying time correlated with the severity of autonomic nerve dysfunction (P < 0.05). The early phase of liquid emptying (retention at 10 min) was significantly slower (P < 0.05) in patients with mean plasma glucose concentrations of > 15 mmol/l during the gastric emptying test and the lag period for solid emptying correlated with both the glycosylated haemoglobin and mean plasma glucose concentrations.
Carbamazepine hepatitis: the clinicopathological spectrum
Authors: WILLIAMS S. J. , RUPPIN D. C. , GRIERSON J. M. , FARRELL G. C.
Published: March 2008

Abstract Despite 20 years of widespread use, carbamazepine has rarely been implicated as causing hepatic drug reactions. The observation of eight cases of carbamazepine hepatitis during a 3‐year period afforded an unusual opportunity to describe the clinicopathological spectrum of this reaction. The eight patients (four males, four females, aged 44–83 years) presented with fever, anorexia and malaise within 12 weeks of starting carbamazepine. Clinical features included swinging fever, jaundice (six cases) and right upper quadrant abdominal pain and tenderness which frequently led to a clinical diagnosis of cholangitis; rash and eosinophilia were not present. Serum transaminase and alkaline phosphatase values variably suggested cholestasis (three patients), predominantly hepatocellular injury (one patient) or were mixed (four patients). However, in all four patients subjected to liver biopsy, the histological picture was a granulomatous hepatitis.

Cessation of carbamazepine resulted in rapid resolution of symptoms with normalization of biochemical abnormalities within 4 weeks. In two patients who were rechallenged with carbamazepine, symptoms and abnormal serum biochemistry recurred within 24 h. It is suggested that carbamazepine causes hepatic drug reactions more commonly than has been previously recognized. Although the clinical and laboratory picture may suggest cholangitis, the usual histological finding is a granulomatous hepatitis. Prompt resolution can be expected in the majority of cases upon withdrawal of the drug.
The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension
Authors: GIBSON P. R. , MCLEAN A. J. , DUDLEY F. J.
Published: March 2008

Abstract Nitroglycerin was administered orally to seven patients with cirrhosis and portal hypertension, to determine whether portal venous pressure (PVP) may be lowered without the systemic effects associated with its intravenous or sublingual use. PVP was measured via direct cannulation of the portal vein transhepatically using a Chiba needle. PVP decreased from 29 (s.d. = 4) to 22.7 (s.d. = 3.7) mmHg (22% mean fall) following 1.2 mg nitroglycerin with onset 7–15 min following ingestion, and the response persisted for up to 150 min. This was not associated with headache in any patient. Although a decrease in blood pressure was seen in most patients, this temporally followed the fall in PVP suggesting that it was a secondary response. Sublingual nitroglycerin was given to two patients without change in PVP yet both experienced severe headache. These findings support the hypothesis that oral nitroglycerin is delivered differentially to the portal venous bed with differential effects on PVP. Further studies are needed to evaluate this agent and this strategy for their potential role in long‐term control of portal pressure.
α1‐Antitrypsin phenotypes in chronic active hepatitis
Authors: BASSETT M. L. , BRADBEAR R. A. , KERLIN P. , CLARK P.
Published: March 2008

Abstract α1‐Antitrypsin (Pi) phenotypes were determined in 58 Caucasian patients with chronic active hepatitis, in whom there was no evidence for a specific aetiological factor. Pi allele and gene frequencies were compared with frequencies in 1007 Australian Caucasian blood donors. There was an increased frequency of the M1M3 phenotype in chronic active hepatitis patients. In contrast to other studies, there was no increase in the frequency of the MZ phenotype. The chronic hepatitis patients had a gene frequency of 0.034 for Pi Z, compared to 0.012 in blood donors. The difference is not statistically significant. The Pi Z group consisted of one homozygous Pi Z patient, previously diagnosed as having chronic active hepatitis and cirrhosis due to α1‐antitrypsin deficiency, and only two heterozygous Pi Z subjects. This study fails to confirm a major association between chronic active hepatitis and heterozygous Pi Z phenotypes.
Chronic duodenal ulcer, marital status and personality pattern. A case‐control study
Authors: FUNG L. H. , GILLIGAN I. J. , TALLEY N. J. , PIPER D. W.
Published: March 2008

Abstract The aim of the study was to assess the association of chronic duodenal ulcer (DU) with marital status and psychological factors. Sixty‐six consecutive patients with DU were compared with 66 randomly selected age, sex, and social‐grade matched community controls, with regard to marital status and personality profile. Personality was assessed at interview by the Spielberger State‐Trait Anxiety Questionnaire, Beck Depression Inventory, Costello‐Comrey Personality Questionnaire and the Eysenck Personality Inventory.

It was found that patients with higher scores on the Beck Depression Inventory and patients who were unmarried were significantly more likely to have DU (odds ratio = 1.2 and 3.3, respectively). None of the other psychometric measures were statistically significant on a multivariate analysis. However, the absolute differences observed and the odds ratio for depression were small. The results suggest that the psychological factors studied were of only minor clinical importance in DU.
Clinical spectrum of chronic Budd‐Chiari syndrome and surgical relief for ‘coarctation’ of the inferior vena cava
Authors: MADANAGOPALAN N. , SOLOMON V. , JAYANTHI V. , RAGHURAM K. , BALAKUMAR M. , KANDASAMY I. , GAJARAJ A. , PANCHANADAM M.
Published: March 2008

This report presents the clinical features of 78 cases of the chronic Budd‐Chiari syndrome encountered over a period of 13 years. The diagnosis of hepatic venous outflow obstruction was confirmed by venographic studies in all cases. In 20 patients there was hepatic vein occlusion without inferior vena caval (IVC) obstruction (Group A). In 17 patients there was constriction of the IVC above the drainage site of the right hepatic vein which was patent (Group B). In 13 patients there was short segmental obstruction of the hepatic segment of the IVC along with blockage of the hepatic venous orifices (Group C). In 28 patients there was hepatic venous obstruction with long segment involvement of the IVC extending to varying lengths of the infrahepatic segment (Group D). Of particular interest are the operative findings in 12 of 17 patients of Group B of hour glass constriction of the IVC, which can be labelled as ‘coarctation of the IVC'. Dorsal cavoatrial bypass using a polytetra fluoroethylene graft has proved useful in Group B. Interesting histopathological findings of the liver in some of the cases are also described. The possible aetiology of the Group B cases is discussed.
Effect of diisopropyl 1,3‐dithiol‐2‐ylidinemalonate on rat liver and AFP‐positive cells in 3′‐Me‐DAB hepatocarcinogenesis
Authors: TAKINO TATSURO , IWAI MASAKI , OKUNO TADAO , ISHII MASARU , KOMATSU MASAMI , SUGIMOTO TATSUYOSHI
Published: March 2008

The simultaneous administration of diisopropyl, 1,3‐dithiol‐2‐ylidinemalonate (malotilate) suppressed the proliferation of AFP‐positive oval cells, the formation of hyperplastic nodules and the appearance of clusters of AFP‐positive cells in rat liver with hyperplastic nodules in 3′‐methyl‐4‐dimethylaminoazobenzene (3′‐Me‐DAB) hepatocarcinogenesis. The development of hepatocarcinoma, induced by 3′‐Me‐DAB, was delayed in rats treated with malotilate; therefore, the simultaneous administration of malotilate worked as an inhibitory effect on 3′‐Me‐DAB hepatocarcinogenesis.
Portal circulation before and after sclerotherapy for oesophageal varices studied by radionuclide angiography
Authors: SHIOMI SUSUMU , IKEOKA NAOKO , KUROKI TETSUO , HARIHARA SHIGEYOSHI , KAMATA TEISUKE , KOBAYASHI KENZO , YAMAMOTO SUKEO , MONNA TAKEYUKI , OCHI HIRONOBU
Published: March 2008

Radionuclide angiography was used to generate curves of first‐pass radioactivity vs. time for the right hepatic lobe and both kidneys following the rapid intravenous injection of 10 mCi of 99mTc‐phytate. By analysis of the right hepatic curve, the arterial and portal components of the liver circulation were calculated in 21 healthy subjects and 183 patients, 39 with chronic hepatitis and 144 with cirrhosis of the liver.

In the healthy subjects, the portal component (PC) of liver blood supply ranged from 64% to 79% (mean 71.5%). In patients with hepatitis the mean PC was 61.3%, and in patients with cirrhosis it was 37.9%. The PC was lower in cirrhotic patients with oesophageal varices than in those without (P < 0.001).

The PC was assessed in 23 of the patients with cirrhosis before and after sclerotherapy for oesophageal varices. A paired t‐test showed significant rises in this component immediately after the final treatment (P < 0.001). Two months after this treatment, the mean PC had dropped significantly, approaching the pre‐treatment value (P < 0.001). One year after treatment, the PC had not dropped further.

These findings suggest that this non‐invasive method may be useful for the assessment of portal circulatory changes in cirrhosis, and of results of sclerotherapy for oesophageal varices.
Human pepsinogens: A review of clinical and genetic aspects
Authors: WESTERVELD B.D. , PALS G. , DEFIZE J. , ERIKSSON A. E. , MEUWISSEN S. G. M.
Published: March 2008

In recent years clinical interest in the study of the proteolytic enzymes of the stomach has greatly increased. Human pepsinogens belong to the group of aspartic proteases and are categorized into two main groups: Pepsinogen A (PGA = PG I) and Pepsinogen C (PGC = PG II). Genetic models have been proposed to explain the inheritance of PGA, and a recent multigene model may be of value. PGA phenotypes in urine and gastric mucosa have been determined in healthy volunteers as well as in patients with different gastric disorders. An increased frequency of the ‘intense Pg5’ phenotype seems to be associated with gastric cancer and pre‐malignant conditions, such as atrophic gastritis. Reliable radio‐immunoassay and enzyme‐linked immunosorbent assay techniques have facilitated the study of serum levels of PGA and PGC in different patient groups; in particular, duodenal ulcer patients (high PGA levels) and patients with atrophic gastritis and/or gastric cancer (low PGA levels). The ratio serum PGA/PGC may be introduced for clinical application, being the most convenient non‐invasive marker for the detection of fundic atrophy. While the chromosome localization of pepsinogen has been established, further research is likely to concentrate on the structure and organization of the pepsinogen genes at the DNA‐level, as well as on the development of new isozyme specific monoclonal antibodies.
Gut immunity to typhoid: The immune response to a live oral typhoid vaccine Ty21a
Authors: BARTHOLOMEUSZ R. C. A. , LABROOY J. T. , JOHNSON M. , SHEARMAN D. J. C. , ROWLEY D.
Published: March 2008

Abstract The oral typhoid vaccine, Ty21a, generated an intestinal antibody response that was consistent and long‐lasting in contrast to the irregular response it generated in serum. Studies with different doses of the vaccine showed that 109 organisms appeared to be around the threshold dose required for a response and there was an increase in the consistency and magnitude of the response without side effects up to the maximum dose used of 1011 organisms. Revaccination after 6 months generated a further response though this response did not have the features of a memory response.
Delta‐agent infection in Taiwan
Authors: CHEN DING‐SHINN , SU IH‐JEN , LAI MING‐YANG , HSU HEY‐CHI , YANG PEI‐MING , SHEU JIN‐CHUAN , SUNG JUEI‐LOW
Published: March 2008

Based on observations of a limited number of patients, delta (δ) infection has been reported to be infrequent in Taiwan. To further evaluate the role of δ‐infection in patients with hepatitis B virus (HBV) infection, serum samples of 493 subjects with acute and chronic HBV infections collected in 1976–85 were studied for anti‐δ by radioimmunoassay. Intrahepatic δ‐antigen was also studied by immunofluorescence in 12 anti‐δ‐positive patients. The overall prevalence of δ‐infection was 4.7%, consistent with previous studies. δ‐Infection had an even yearly distribution in the last decade. However, there were four groups with significantly higher frequencies: (i) 24% of 41 anti‐HBe‐positive patients with chronic active hepatitis (CAH); (ii) 21% of 14 HBsAg carriers with prominent lobular hepatitis; (iii) two of three HBsAg carriers with intravenous drug abuse; and (iv) two of seven with fulminant hepatitis. On the other hand, δ‐infection was uncommon in patients with chronic persistent hepatitis, cirrhosis, hepatocellular carcinoma, classical type B hepatitis, submassive necrosis and asymptomatic HBsAg carriers. δ‐Antigen was found in only two patients with CAH; one progressed to cirrhosis, and the other had disease regression on follow‐up. Overall, at least half of the δ‐superinfected HBsAg‐positive patients had a non‐progressive course on follow‐up.

It was concluded that δ‐agent was introduced to Taiwan before 1976. Although it has played a role in some clinical settings of HBV infections, it is generally infrequent in Taiwan. The δ‐superinfection apparent in half the patients studied seems to have a non‐progressive course.
Immunogenicity study of low‐dose administration of hepatitis B virus vaccine in newborn infants: A cost reduction trial
Authors: CHUNG WHAN KOOK , CHOI KYU YONG , DON LEE CHANG , CHUNG JIN WU , SUN HEE SIK , CHUNG KYU WON , KIM BOO SUNG , CHUN CHUNG SIK , CHO KYOO HONG , KIM SEUNG JO
Published: March 2008

Different doses of hepatitis B virus vaccine—prepared by Korea Green Cross Corporation, were given to healthy infants born to HBsAg‐negative mothers at birth, 1 and 6 months of age. A dose of 2 μg was administered intradermally in Group A and, in the three other groups, the vaccine was given intramuscularly (i.m.). An adequate follow‐up observation was possible for 9 months after birth in 22, 25, 23 and 21 infants in Groups A, B, C and D, respecvely.

Group C (5 μg, i.m.) produced seroconversion most rapidly, showing the highest rate (96%) at 9 months of age. The lowest seroconversion rate (5%) was found at the age of 1 month in Group A subjects, but the rate increased to 91% after a booster dose was given at 6 months of age.

While it can be concluded that a 5 μg i.m. dose of vaccine at 0, 1 and 6 months of age is optimum for the immunization of infants in efficacy and economy, a 2 μg intradermal dose can also be considered as an immunogenic and economical regimen, though the immune response is slower and a special technique is required for immunization.
Failure of autologous mixed lymphocyte reaction in patients with auto‐immune chronic active hepatitis
Authors: KURIHARA TAKESHI , YAMAUCHI KATSUMI , NAKANISHI TOSHIMI , OBATA HIROSHI
Published: March 2008

T cells are effectively stimulated by DR‐antigens on the surface of autologous non‐T cells. This phenomenon, referred to as an autologous mixed lymphocyte reaction (AMLR), is reported to be impaired in several auto‐immune diseases. In the present study, both AMLR and allogeneic mixed lymphocyte reaction (allo‐MLR) activities of peripheral blood mononuclear cells were examined from patients with auto‐immune chronic active hepatitis. AMLR activity in these patients was much lower than that of controls, while allo‐MLR activity of the same patients revealed no abnormality with regard to either stimulator or responder activities in comparison to controls. Furthermore, co‐culture experiments using cells from patients and their HLA‐identical siblings suggested that the defect resided in the responder T cells rather than in the stimulator non‐T cells.
Different effects of short‐ and long‐term dietary choline‐deficiency on hepatic microsomal phospholipids and drug oxidation
Authors: MURRAY MICHAEL , ZALUZNY LOUISE , CANTRILL ELIZABETH , FARRELL GEOFFREY C.
Published: March 2008

Prolonged administration of a choline‐deficient diet to male rats results in the development of hepatic cirrhosis and alterations in oxidative drug metabolism. The present study was designed to assess whether the changes in drug metabolism were related to the development of cirrhosis or merely to the effects of choline‐deficiency on hepatic microsomal lipid composition. Male rats were given a synthetic choline‐deficient diet for either 1 week (short‐term) or 30 weeks (long‐term), and results at each time were compared with age‐matched control rats given the same diet but with supplementary choline.

After both 1 week and 30 weeks of the choline‐deficient dietary regimen, the proportion of microsomal phospholipid present as phosphatidylcholine was significantly decreased, and that present as phosphatidylethanolamine was significantly increased, compared with appropriate controls. However, microsomal cholesterol content (per mg of microsomal protein) was not significantly changed at either time. Cytochrome P‐450 levels and the turnover of ethylmorphine N‐demethylase (enzyme activity/nmol cytochrome P‐450) were significantly reduced in the cirrhotic (30 week) model whereas short‐term intake of the diet did not alter the levels of cither enzyme. These findings suggest that the effects of changes in phosphatidylcholine and phosphatidylethanolamine levels in choline‐deficiency cirrhosis have minimal importance with respect to changes in drug oxidation. Instead, altered regulation of specific cytochrome P‐450 isozymes appears to be the principal cause of impaired oxidation.
Evaluation of the Crithidia assay to distinguish between auto‐immune chronic active hepatitis and systemic lupus erythematosus
Authors: LEGGETT BARBARA A. , COLLINS RUSSELL J. , COOKSLEY W. GRAHAM E. , PRENTICE ROGER L. , POWELL LAWRIE W.
Published: March 2008

The aim of this study was to determine if the Crithidia luciliae assay for auto‐antibodies to double‐stranded DNA, often positive in systemic lupus erythematosus, is always negative in auto‐immune chronic active hepatitis (CAH) as has recently been suggested. Twenty‐five patients were identified as having auto‐immune CAH. Mean duration of follow‐up was 10.5 years. Antinuclear antibodies were detected in 92%, smooth muscle antibodies in 76% and antimitochondrial antibodies in 16%. Antibodies to double‐stranded DNA were detected by the Crithidia assay in four patients (16%). Two of these patients had positive tests on only one occasion and no features of systemic lupus erythematosus. In the other two the assay was persistently positive. During follow‐up both developed arthritis and serositis but the liver lesion remained the dominant clinical feature. It was concluded that there is significant serological overlap between auto‐immune CAH and systemic lupus erythematosus making the Crithidia assay unreliable in distinguishing between them.
A reappraisal of the management of severe colitis in its fulminant phase
Authors: VICKERS CHRISTOPHER R. , GALLAGHER NEIL D. , GLENN DAVID C. , MORGAN BRIAN P. , GOULSTON STANLEY J.
Published: March 2008

The results of a policy of intensive intravenous medical treatment and early colectomy in fulminant ulcerative colitis, over a 22 year period, are described. Forty‐nine patients developed fulminant colitis; 43 received a period of intensive treatment including corticosteroids. Half (51%) of patients showed initial objective improvement. Deterioration was always heralded by a sudden increase in pulse rate, temperature or stool frequency. The mean duration of intensive medical treatment was 7.7 days. Early colectomy was performed in 20 (44%) patients because of the lack of sustained improvement and in 25 (56%) patients because of a major complication. All complications developed within the first 5 days of treatment. Toxic dilatation was present in 11 (22%) patients with only one concurrent perforation and no deaths. The perforation rate was 16% and accounted for 59% of the surgical mortality. The overall mortality in this series was 16.3% and in patients treated with the intensive medical regime 11.6%. Post‐operative complications developed in 19% of patients. No colonic perforations or deaths have occurred in 36 consecutive patients admitted since 1967. Earlier results, supporting the hypothesis that early colectomy in fulminant colitis is life‐saving, have been confirmed.