bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of fine‐needle aspiration for diagnosis of carcinoma associated with multinodular goitre
Authors: Ríos Antonio , Rodríguez José Manuel , Galindo Pedro José , Montoya Mariano , Tebar Francisco Javier , Sola Joaquín , Canteras Manuel , Parrilla Pascual
Published: December 2004

background  Fine‐needle aspiration (FNA) is a useful method for evaluating a solitary thyroid nodule; however, this is not an agreed method for a multinodular goitre (MNG). The aim of this study was to assess the utility of preoperative FNA for detecting malignancy in MNG.

patients and method  We analysed operated MNGs in which FNA had been performed. Puncture was carried out on the dominant nodule and any other nodules with features suggesting malignancy. The diagnosis was classed as colloid, follicular or Hürthle proliferation, suggestive of malignancy, haematic and inadequate. The thyroid FNA results, grouped into suggestive of malignancy (positive result) and other diagnoses (negative result), were compared to those of the final histological study in order to calculate the value of the test in diagnosing malignancy.

results  FNA was performed in 432 MNGs, of which 42 (9·7%) were associated with carcinoma. Overall, the results of the test were poor, revealing a sensitivity of 17%, specificity of 96% and diagnostic accuracy of 88%, with a positive predictive value of 32% and negative predictive value of 88%. When the values were recalculated with the exclusion of microcarcinomas −considering their minor clinical importance − there was a slight improvement in the results: the sensitivity increased to 26%, diagnostic accuracy to 93% and negative predictive value to 96%. However, the specificity remained at 96%, and the positive predictive value fell from 32% to 25%. The results of the test improved in multifocal carcinomas.

conclusions  Thyroid fine needle aspiration is not useful for differentiating MNG with malignant degeneration from benign MNG, as more than 80% of carcinomas go unnoticed; it provides a sensitivity of 17% for detecting carcinomas, rising to 26% if microcarcinomas are excluded. We therefore suggest that clinical criteria should prevail over FNA.
Expression of a novel DnaJA1 alternative splicing in human testis and sperm
Authors: Hu Yanqiu , Zhou Zuomin , Huang Xiaoyan , Xu Min , Lu Li , Xu Zhiyang , Li Jianmin , Sha Jiahao
Published: December 2004

Using cDNA microarray hybridization from a human testicular cDNA library, one gene exhibiting threefold difference at expression level between adult and embryo human testes was named nDnaJA1 (a new alternative isoform of human DnaJA1 which was also named HDJ2/Hsdj/dj2, a human HSP40 homologue), which was believed to be involved in testis development and spermatogenesis. Multiple tissue polymerase chain reaction (PCR) results showed that nDnaJA1 expressed highly in testis and lung but low in thymus, prostate, colon and liver. The results of the other members of DnaJA1 family (GenBank accession numbers: D13388 and BC008182) showed that they were widely expressed. D13388 and BC008182 were highly expressed in sperm while nDnaJA1 was faintly expressed by reverse transcriptase PCR. Protein motif analysis of nDnaJA1 sequence revealed motifs of DnaJ. nDnaJA1 was considered as type I DnaJ like the other members of DnaJA1 family.
The role of potential splicing factors including RBMY, RBMX, hnRNPG‐T and STAR proteins in spermatogenesis*
Authors: Elliott David J.
Published: December 2004

Investigations into the RBM gene family are uncovering networks of protein interactions which regulate RNA processing, and which might operate downstream of signal transduction pathways. Similar pathways likely operate in germ cells and somatic cells, with RBMY, hnRNPGT and T‐STAR proteins providing germ cell‐specific components. These pathways may be important for normal germ cell development, and might be compromised in men with Y chromosome deletions affecting RBMY gene expression. The STAR proteins have multiple functions in pre‐mRNA splicing, signalling and cell cycle control. These processes might have to be very finely regulated during germ cell development, which involves both two sequential meiotic divisions (meiosis I and II) as well as mitotic (spermatogonial) cell divisions, and which is controlled by paracrine signalling within the testis from Sertoli cells.
Consistent presence of two normally distributed sperm subpopulations within normozoospermic human semen: a kinematic study
Authors: Chantler Eric , Abraham‐Peskir Joanna , Roberts Chris
Published: December 2004

Sperm motion analysis was performed using computer‐aided semen analysis (CASA) on nine normozoospermic human ejaculates following six fractionation schemes that included Percoll discontinuous gradient centrifugation, swim‐up, hyper and hypo‐osmotic stress in which 4600–13 400 tracks were analysed (depending on the scheme). In addition, the effect of ageing for 2 h in seminal plasma or re‐addition of seminal plasma, on the kinematic properties was investigated. Analysis following sorting of the swimming velocity at 5 μm/sec intervals revealed the presence of two discrete normally distributed subpopulations selected on the basis of path velocity (VAP): these subpopulations were also present in the track speed (VCL) and progressive velocity (VSL) distributions. The validity of the two subpopulations was examined using a two‐component normal mixture model and found to be highly statistically significant (p < 0.00001). The basis for the subpopulations was independent from the possession of midpiece vesicles or hyperactivation. Swim‐up produced subpopulations of sperm that were significantly different from those obtained by Percoll separation. Compared with sperm in seminal plasma, swim‐up and Percoll separation significantly increased the level of hyperactivated sperm at 2 h. Hyperactivation was inhibited by the re‐addition of seminal plasma. Swim‐up enhanced the proportion of sperm in the fast VAP subpopulation (independently of the level of hyperactivation) and whilst this altered distribution was maintained following the addition of homologous seminal plasma the mean velocity of the fast fraction was significantly decreased. Both swim‐up and Percoll separation significantly increased the mean velocity of the fast subpopulation but the increase was greater with swim‐up. This analysis highlights a way in which subpopulations may be detected and analysed. The procedure revealed fundamental differences in the kinematic properties of sperm processed by different methods that are used in assisted reproductive technology and showed that these were independent of hyperactivation.
Inhibitory effects of stress on postprandial gastric myoelectrical activity and vagal tone in healthy subjects
Authors: Yin J. , Levanon D. , Chen J. D. Z.
Published: December 2004

Abstract  The aim was to investigate gastric myoelectrical activity (GMA) and vagal activity in response to stress. The study was performed in 10 healthy subjects in three sessions (control, relaxation and stress). The control session was composed of 30‐min recordings before and 30‐min recordings after a test meal. The protocol of two other sessions was similar except that the fasting recording was extended to 60 min and the subjects were continuously watching a horror movie (stress) or guided meditation tape (relaxation) after the 30‐min baseline. GMA was recorded using electrogastrography and heart rate variability (HRV) was derived from the electrocardiogram. Meal resulted in a postprandial increase in the dominant frequency (2.91 cpm vs 3.17 cpm, P < 0.007), dominant power (30.0 dB vs 32.5 dB, P < 0.05), and percentage of normal slow waves (79.8%vs 87.4%, P = 0.09). Similar responses were found in the relaxation session. Stress inhibited all these normal postprandial response and reduced the regularity of gastric slow waves (82.0%vs 66.0%, P < 0.01). In addition, spectral analysis of the HRV demonstrated an inhibition of postprandial vagal activity and an increase of postprandial sympathetic activity with stress. Stress has an inhibitory effect on postprandial GMA and this may involve both vagal and sympathetic pathway.
Vanilloid receptor 1 antagonists attenuate disease severity in dextran sulphate sodium‐induced colitis in mice
Authors: Kimball E. S. , Wallace N. H. , Schneider C. R. , D'Andrea M. R. , Hornby P. J.
Published: December 2004

Neurogenic mechanisms have been implicated in the induction of inflammatory bowel disease (IBD). Vanilloid receptor type 1 (TRPV1) has been visualized on nerve terminals of intrinsic and extrinsic afferent neurones innervating the gastrointestinal tract and local administration of a TRPV1 antagonist, capsazepine, reduces the severity of dextran sulphate sodium (DSS)‐induced colitis in rats (Gut 2003; 52: 713–91). Our aim was to test whether systemically or orally administered TRPV1 antagonists attenuate experimental colitis induced by 5% DSS in Balb/c mice. Intraperitoneal capsazepine (2.5 mg kg−1, bid), significantly reduced the overall macroscopic damage severity compared with vehicle‐treated animals (80% inhibition, P < 0.05); however, there was no effect on myeloperoxidase (MPO) levels. An experimental TRPV1 antagonist given orally was tested against DSS‐induced colitis, and shown to reverse the macroscopic damage score at doses of 0.5 and 5.0 mg kg−1. Epithelial damage assessed microscopically was significantly reduced. MPO levels were attenuated by approximately 50%, and diarrhoea scores were reduced by as much as 70%. These results suggest that pharmacological modulation of TRPV1 attenuates indices of experimental colitis in mice, and that development of orally active TRPV1 antagonists might have therapeutic potential for the treatment of IBD.
Options for patients with irritable bowel syndrome: contrasting traditional and novel serotonergic therapies
Authors: Johanson J. F.
Published: December 2004

Abstract  This article reviews the efficacy and tolerability of traditional therapies for irritable bowel syndrome (IBS) and concludes that they are limited by both poor efficacy and adverse effects. Serotonin, a neurotransmitter found mainly in the gut, appears to represent a link in IBS pathophysiological processes – altered gut motility, abnormal intestinal secretion and visceral hypersensitivity. Recently, available treatments for IBS have targeted serotonin receptors that are involved in motor, sensory and secretory functions of the gut. Serotonergic agents, such as alosetron (a 5‐HT3 receptor antagonist) and tegaserod (a selective 5‐HT4 receptor partial agonist), provide global relief of the multiple symptoms of IBS with diarrhoea and IBS with constipation, respectively, and represent important additions to the IBS treatment armamentarium.
Constitutive and functional expression of cyclooxygenase 2 in the murine proximal colon
Authors: Porcher C. , Horowitz B. , Ward S. M. , Sanders K. M.
Published: December 2004

Abstract  Recent reports suggest that cyclo‐oxygenase (COX)‐2, an inducible COX isoform may be constitutively expressed in gastrointestinal tissues. This study has evaluated the expression and function of COX‐2 in the tunica muscularis of the murine proximal colon. Cyclo‐oxygenase‐2‐like (COX‐2‐LI) immunoreactivity was found in a subpopulation of neurones in the myenteric and submucosal ganglia and in interstitial cells of Cajal within the muscle layers (IC‐IM). Reverse transcriptase polymerase chain reaction (RT‐PCR) verified expression of COX‐2 in colonic muscles, and quantitative PCR demonstrated that COX‐1 transcriptional expression was greater than COX‐2. To test the functional significance of COX‐2 expression, the effects of a COX‐2 inhibitor were compared with the effects of indomethacin (COX‐1/COX‐2 inhibitor) on circular muscle contractions. The experiments indicate that indomethacin and the specific COX‐2 inhibitor, GR253035X, increased the amplitude of phasic contractions, suggesting production of inhibitory prostaglandins tonically dampen contractile activity. The effects of indomethacin were reduced when tested on phasic contractions of muscles from COX‐2 knockout mice. GR253035X did not affect contractions in muscles of COX‐2 knockout animals. These studies demonstrate constitutive expression of COX‐2 in the tunica muscularis of the proximal colon. The COX‐2 appears to contribute a significant amount of the prostaglandins that affect the contractile behaviour of colonic muscles.
Gastric distension alters frequency and regularity but not amplitude of the gastric slow wave
Authors: Zhu H. , Chen J. D. Z.
Published: December 2004

Abstract  The aim of this study was to assess effects of gastric distension on gastric slow waves using internal and cutaneous electrodes and the correlation between these two measurements. The study was performed in five dogs implanted with one pair of serosal electrodes and a gastric cannula. Gastric slow waves were recorded using both cutaneous and internal electrodes in several sessions with different volumes (150–600 mL) of gastric distension with a barostat balloon. Bethanechol was injected in one of sessions. The results revealed that (i) Gastric distension reduced slow wave frequency in a volume‐dependent manner and induced bradyarrhythmia at a volume of 600 mL, but had no effects on the amplitude of gastric slow waves. (ii) The cutaneous electrogastrogram (EGG) was significantly correlated with the internal recording in slow wave frequency (r = 0.88, P < 0.001) and regularity (r = 0.44, P = 0.035). (iii) The EGG amplitude was not increased when the stomach was distended but increased after bethanechol. Gastric distension volume dependently reduces slow wave frequency and induces gastric dysrhythmia at a large volume. The frequency and rhythmicity of the slow wave measured from the EGG are significantly correlated with those recorded from the internal electrodes. Relative increase in EGG amplitude reflects contractility rather than the distension of the stomach.
Effects of long‐term intravenous and intragastric l‐arginine intervention on jejunal motility and visceral nitric oxide production in the hyperdynamic compensated endotoxaemic pig
Authors: Bruins M. J. , Luiking Y. C. , Soeters P. B. , Lamers W. H. , Akkermans L. M. A. , Deutz N. E. P.
Published: December 2004

Abstract  Alterations in l‐arginine availability and nitric oxide (NO) synthesis in the intestinal muscularis may contribute to disturbed small intestinal motility that is observed during endotoxaemia. The aim of this study was to evaluate the effect of l‐arginine infusion on visceral NO production and jejunal motility in hyperdynamic compensated endotoxaemic pigs. Fasted and saline‐resuscitated pigs were intravenously infused for 24 h with endotoxin (lipopolysaccharide, 50 ng kg−1 min−1) or saline (n = 6). Endotoxaemic pigs received either intravenous l‐arginine (n = 6, 5.3 μmol kg−1 min−1) or l‐alanine (isocaloric, n = 6). After 24 h, intravenous l‐arginine or l‐alanine infusion was continued intragastrically for 32‐h in an enteral meal. During (0–24 h) and 1 day postendotoxaemia (48–56 h), jejunal motility was recorded by manometry and analysed for migrating motor complex (MMC) characteristics. Visceral NO production was measured at 24 and 48 h by 15N2‐arginine‐to‐15N‐citrulline conversion. Visceral NO production was increased during endotoxaemia and was higher in l‐arginine than in l‐alanine‐treated pigs. One day postendotoxaemia, visceral NO synthesis was still increased in l‐arginine but not in l‐alanine‐treated animals. Endotoxaemia shortened the MMC cycle duration and accelerated the MMC propagation velocity. Both were restored by l‐arginine. Similar motility disturbances were observed one day postendotoxaemia and were also compensated by l‐arginine infusion.
Diagnostic pitfalls in food allergy in children
Authors: Niggemann B. , Beyer K.
Published: December 2004

Currently, the diagnostic work‐up of suspected food allergy includes skin prick tests, the measurement of food specific immunoglobulin E (IgE), and the atopy patch test, and double‐blind, placebo‐controlled food challenges. However, all of these methods, even double‐blind, placebo‐controlled food challenges (DBPCFC), may sometimes be misleading. This overview describes several pitfalls for standard diagnostic methods such as problems with irritative skin reactions mimicking IgE‐mediated symptoms, the problem of non‐IgE‐mediated reactions, pitfalls arising from the way foods are prepared or processed, effects of the route of exposure, the role of augmentation factors lowering the threshold value for clinical reactions, the noncomparability of specific IgE decision points, the influence of the timing of diagnostic measures. In addition, the problem of alternative diagnostic measures is discussed. In conclusion, there are several pitfalls in the diagnostic work‐up of food allergy, which may be misleading for the physician. Properly performed controlled oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals in order to avoid both unjustified diets, which may lead to severe impairments in growth and development, and to avoid unnecessary symptoms if an underlying food allergy is not correctly identified as a cause for the symptoms of the patient.
Characterization of the T‐cell epitopes of a major peanut allergen, Ara h 2
Authors: Glaspole I. N. , De Leon M. P. , Rolland J. M. , O'Hehir R. E.
Published: December 2004

Background:  The development of safe and effective immunotherapy for peanut allergy has been complicated by the high anaphylactic potential of native peanut extracts. We sought to map the T‐cell epitopes of the major peanut allergen, Ara h 2 in order to develop T‐cell targeted vaccines.

Methods:  A panel of eight peanut‐specific CD4+ T‐cell lines (TCL) was derived from eight peanut‐allergic subjects and proliferative and cytokine responses to stimulation with a set of overlapping 20‐mer peptides representing the entire sequence of Ara h 2 determined. Proliferation was assessed in 72 h assays via tritiated thymidine incorporation, while interleukin (IL)‐5 and interferon (IFN)‐γ production were assessed via sandwich enzyme‐linked immunosorbent assay (ELISA) of cell culture supernatants.

Results:  Eight of the 17 Ara h 2 peptides were recognized by one or more subjects, with the two peptides showing highest reactivity [Ara h 2 (19–38) and Ara h 2 (73–92)] being recognized by three subjects each. Adjoining peptides Ara h 2 (28–47) and Ara h 2 (100–119) induced proliferative responses in two subjects. Each of these peptides was associated with a Th2‐type cytokine response.

Conclusion:  Two highly immunogenic T‐cell reactive regions of Ara h 2 have been identified, Ara h 2 (19–47) and Ara h 2 (73–119), providing scope for the development of safe forms of immunotherapy for peanut allergy.
Scoring atopic dermatitis in infants and young children: distinctive features of the SCORAD index
Authors: Pucci N. , Novembre E. , Cammarata M. G. , Bernardini R. , Monaco M. G. , Calogero C. , Vierucci A.
Published: December 2004

Background:  Atopic dermatitis (AD) affects infants, children, and adults with a wide degree of severity; several scoring systems have been used in trials and clinical practice. Infants and young children have a typical distribution of the lesions, but a correlation among skin surface involvement, intensity and subjective symptoms has not been reported in age groups.

Aims of the study:  To evaluate the clinical features of AD in infants and young children, by using the SCORAD index. A simplified scoring method for clinical practice is also discussed.

Methods:  The SCORAD index was assessed in 63 infants and young children with AD [mean age (±SD) 17.5 ± 11.15 months]; the single parameters of the index were evaluated, and compared with each other. Serum eosinophil cationic protein (s‐ECP) and urinary eosinophil protein X (u‐EPX) levels were determined and correlated with the SCORAD index.

Results:  The presence of erythema, edema/papulation, and oozing/crust was significantly high in these patients. A strong positive correlation resulted among the three SCORAD index parameters (extent‐intensity: P < 0.001; extent‐subjective symptoms: P < 0.001; intensity‐subjective symptoms: P < 0.001). S‐ECP and u‐EPX levels positively correlated to almost every single parameter of the SCORAD index as well as to its total.

Conclusions:  Distinctive intensity items were found in infants and young children with AD. A strong correlation resulted among the extent, intensity, and subjective symptoms; each of the three parameters was positively correlated with the total SCORAD. Immunologic parameters positively correlated to each of the SCORAD index items, which remains the gold standard for assessing disease severity in clinical trials.
Urinary inflammatory mediators and inhalation of hypertonic saline in children
Authors: Mai X.‐M. , Böttcher M. F. , Bruhammar M. , Nilsson L. , Zetterström O.
Published: December 2004

Background:  The inflammatory mechanisms of hypertonic saline‐induced bronchoconstriction are not well understood.

Methods:  Seventeen asthmatics with (n = 11) and without bronchial hyperresponsiveness (BHR) (n = 6) and 18 randomly selected nonatopic nonasthmatic controls without BHR were evaluated by urine samples collected before and 1 h after hypertonic saline provocation test. Histamine, 11β‐PGF2α, and LTE4 were analysed by enzyme immunoassay (EIA) and eosinophil protein X (EPX) by radioimmunoassay (RIA).

Results:  The levels of leukotriene E4 (LTE4) increased significantly after the challenge tests, both in the asthmatics (median: 354 pg/mg pre‐challenge vs. 628 pg/mg post‐challenge; P = 0.05) and in the controls (median: 294 pg/mg pre‐challenge vs. 460 pg/mg post‐challenge; P < 0.01). The levels of histamine also increased significantly in the latter (median: 299 μmol/mg pre‐challenge vs. 569 μmol/mg post‐challenge; P = 0.03). However, the levels of 11β‐PGF2α and EPX did not change significantly after the challenge tests either in the asthmatics or in the controls.

Conclusions:  The inhalation of hypertonic saline increased urinary excretion of LTE4 both in the asthmatics and in the controls. The slight increase of leukotrienes was enough to induce airway obstruction in some of the asthmatics, because of the hyperresponsiveness in their airways.
Mustard allergy confirmed by double‐blind placebo‐controlled food challenges: clinical features and cross‐reactivity with mugwort pollen and plant‐derived foods
Authors: Figueroa J. , Blanco C. , Dumpiérrez A. G. , Almeida L. , Ortega N. , Castillo R. , Navarro L. , Pérez E. , Gallego M. D. , Carrillo T.
Published: December 2004

Background:  Mustard IgE‐mediated allergy is supposed to be a rare cause of food allergy, and its clinical features and cross‐reactivities have not been fully elucidated.

Methods:  A prospective study was carried out, recruiting mustard allergic patients, and paired control subjects. A clinical questionnaire was administered, and skin‐prick tests (SPT) with panels of aeroallergens and foods, serum extraction for in vitro tests and double‐blind placebo‐controlled food challenges (DBPCFC) were performed.

Results:  Thirty‐eight mainly adult patients, with 10.5% reporting systemic anaphylaxis, were included in the study [age (mean ± SD): 21.9 ± 8.6 years]. DBPCFC were performed in 24 patients, being positive in 14 cases (58.3%). Patients with positive outcome showed significantly greater mustard SPT than those with negative outcome (8.2 ± 3.7 vs 5.3 ± 2.4 mm, P < 0.05), and the receiver‐operating characteristic (ROC) curve analysis yielded a cut‐off value for mustard commercial SPT of 8 mm, with a specificity of 90% (95% CI, 55.5–98.3), and a sensitivity of 50% (95% CI, 23.1–76.9). A significant association between mustard hypersensitivity and mugwort pollen sensitization was found (97.4% of patients), with partial cross‐reactivity demonstrated by UniCAP System inhibition assays. All patients showed sensitization to other members of Brassicaceae family, and cross‐reactivity among them was also confirmed. Moreover, significant associations with nut (97.4%), leguminous (94.7%), corn (78.9%), and Rosaceae fruit (89.5%) sensitizations were also shown. Around 40% of these food sensitizations were symptomatic, including food‐dependent exercise‐induced anaphylaxis in six patients.

Conclusions:  Mustard allergy is a not‐uncommon disorder that can induce severe reactions. Significant associations with mugwort pollinosis and several plant‐derived food allergies are demonstrated, suggesting a new mustard–mugwort allergy syndrome. A relationship between this syndrome and food‐dependent exercise‐induced anaphylaxis is also reported.
The rise of the phoenix: the expanding role of the eosinophil in health and disease
Authors: Adamko D. J. , Odemuyiwa S. O. , Vethanayagam D. , Moqbel R.
Published: December 2004

We have entered a new phase in the evolution of our understanding of the role of the eosinophil with a greater appreciation of novel potential functions that may be ascribed to this enigmatic cell type. This review not only provides an update to our current understanding of the various immunobiological roles for the eosinophil, but also attracts attention to some novel observations predicting functions beyond its putative effector role. These observations include the intriguing possibility that the eosinophil may posses the capacity to regulate the immune and inflammatory responses in diseases such as asthma.
Efficacy of the Non‐antibiotic Paste Protexin®Hoof‐Care for Topical Treatment of Digital Dermatitis in Dairy Cows
Authors: Kofler J. , Pospichal M. , Hofmann‐Parisot M.
Published: December 2004

In this study, the efficacy of the non‐antibiotic paste Protexin®Hoof‐Care containing metallic salts and organic acids, was tested for local treatment of 26 acute digital dermatitis lesions. The control group (26 cases) was treated with local application of oxytetracycline spray. These 52 affected limbs with digital dermatitis were diagnosed in 47 dairy cows from eight different farms with slatted floors. The therapeutic effect was evaluated using a scoring system for weightbearing at stance, lameness at walk and pain of the digital dermatitis lesions. The pre‐treatment and control examination scores were documented on days 0, 4, 10 and 28. Both treatment regimens were effective, no statistical differences regarding the examined parameters was found between the group treated with the non‐antibiotic Protexin®Hoof‐Care paste and the group treated with oxytetracycline spray. Twenty‐seven digital dermatitis lesions required only one treatment with one of these products. A second topical treatment was carried out on day 4 in 13 lesions of the study group and in 12 lesions of the control group. The data of this pilot study indicate that the non‐antibiotic paste Protexin®Hoof‐Care could be a valuable alternative to topical antibiotic treatment for digital dermatitis in dairy cattle.
Explanatory case studies: Implications and applications for clinical research
Authors: Fisher Imogen , Ziviani Jenny
Published: December 2004

Explanatory case study methodology has been used to research complex systems in the fields of business, public policy and urban planning, to name a few. While it has been suggested by some that this might be a useful way to progress complex research issues in health science research, to date, there has been little evidence of this happening. The purpose of this paper is to review the explanatory case study method and present a framework for understanding how it differs from other case study methods. A review of the literature is undertaken to ascertain to what extent this method is currently being used in health science research. Finally, a model for guiding the implementation of the explanatory case study method is proposed in order to promote quality, rigour and applicability of this approach within clinical settings.
Hepatitis B and C genotyping: methodologies and implications for patient management
Authors: SABLON ERWIN , SHAPIRO FRED
Published: December 2004

Abstract The spontaneous tendency of the hepatitis B virus (HBV) and hepatitis C virus (HCV) to mutate has led in both cases to the emergence of distinct viral genotypes with uneven geographic distributions. Numerous studies point to differential impacts of these genotypes on the course of chronic liver disease and response to treatment with currently approved drugs. HCV genotype plays a pivotal role in determining an individual's response to treatment. Evidence is also accumulating that HBV genotypes influence HBeAg seroconversion rates, the natural history and severity of chronic HBV liver disease, and the development of antiviral drug‐resistance and precore/core promoter mutational patterns—all of which have an impact on disease prognosis and patient management. An overview of HBV and HCV genotypes, diagnostic methodologies for their determination, and the clinical relevance of genotypes for patient management is presented.
Relevance of HBV mutations in severity and progression of chronic hepatitis B
Authors: LOCARNINI STEPHEN
Published: December 2004

Abstract  Infection of the hepatocyte with the hepatitis B virus (HBV) results in the production of very high levels of viral replication without actually killing the infected cell directly. The HBV uses reverse transcription to copy its DNA genome, and because of a lack of proof‐reading capability, mutant viral genomes or quasispecies, emerge frequently. Particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antiviral drugs) readily select out these quasispecies which emerge as the new dominant population. Which particular viral mutations or combination of mutations play a role in the clinical outcome of infection with the HBV are not fully known but certain patterns are emerging. Further studies are needed to identify the molecular pathological basis and subsequent clinical sequelae arising from the selection of these quasispecies in infected individuals.
Splanchnic hemodynamics: cirrhotic versus non‐cirrhotic portal hypertension
Authors: SCHIEDERMAIER PETER
Published: December 2004

Abstract  Portal hypertension, defined as an increase in the hepatic venous pressure gradient above 5 mmhg, can be related to cirrhosis as well as non‐cirrhotic disorders. Based on the site of increased resistance, portal hypertension can be classified as presinusoidal, sinusoidal and postsinusoidal. Wedged hepatic venous pressure (WHVP) measurement distinguishes between presinusoidal (low WHVP reflecting normal sinusoidal pressure) and sinusoidal portal hypertension (high WHVP).

According to the equation portal pressure = portal venous flow × portal venous outflow resistance, increase in pressure can result from an increase in inflow into the portal vascular system or by an elevated portal outflow resistance. Both, blood flow and resistance to flow can be estimated by means of Doppler ultrasound. The congestion index increases with the outflow resistance in the portal vein and the hepatic and splenic arterial resistance index reflects the outflow resistance in the downstream vascular region (i.e. the hepatic parenchyma or the whole portal vascular system).

In cirrhosis, a sinusoidal form of portal hypertension, the hepatic venous pressure gradient (HVPG) is increased while portal blood flow is decreased. The congestion index of the portal vein as well as the resistance index of the hepatic artery and the spleen parenchyma are increased.

Prehepatic portal hypertension due to an increased inflow through an enlarged spleen is characterized by an increased portal blood flow, a decreased splenic resistance index and an only slightly elevated HVPG. Vice versa, splenomegaly of portal hypertensive origin is characterized by a decrease in portal blood flow and an increase in the splenic artery resistance index. In idiopathic portal hypertension or non‐cirrhotic portal fibrosis, portal and splenic blood flow are increased and there is a gradient between elevated intrasplenic and normal or only slightly elevated wedged hepatic venous pressure. Schistosomiasis, the other presinusoidal intrahepatic form of portal hypertension, is characterized by a normal wedged hepatic venous pressure and portal blood flow seems to be preserved, too.

Posthepatic portal hypertension, such as the Budd–Chiari syndrome, shows a very low HVPG due to an increase in both FHVP and WHVP together with a decrease in portal blood flow and sometimes a compensatory increase in hepatic artery flow.
Albumin dialysis for the treatment of hepatic encephalopathy
Authors: BLEI ANDRES T
Published: December 2004

Abstract  Treatment of hepatic encephalopathy is hampered by the scant therapeutic options available to the practicing physician. Albumin dialysis has been proposed to improve the management of such patients, by removing both water‐soluble and protein bound toxins. A recently completed trial of albumin dialysis in patients with severe hepatic encephalopathy offers the opportunity to evaluate the role of such a therapy. Such patients had encephalopathy associated with acute‐on‐chronic liver failure rather than the result of precipitant‐induced changes in mental state. In this entity, improvement in encephalopathy may also require correction of the hemodynamic changes associated with liver failure.
New directions in molecular diagnostics for hepatitis B: serum and tissue‐based diagnostics
Authors: BOWDEN SCOTT
Published: December 2004

Abstract  Serological assays have been the mainstay of diagnosis of hepatitis B virus (HBV) infection and have had substantial impact on public health. However, not all interpretation of hepatitis B serology is straightforward. In addition, serology has proven inadequate in determining how new anti‐HBV agents and therapeutic strategies can be assessed and compared. Some of these deficiencies can be overcome by the new HBV DNA quantification assays, using improved signal amplification or real‐time PCR and which have been standardized to the WHO HBV reference standard. Molecular diagnostics have now also turned to the examination of liver tissue. Biopsy material, usually taken for histological examination, can also be assayed to quantify intrahepatic HBV DNA replicative intermediates, in particular HBV covalently closed circular (ccc) DNA and HBV RNA transcripts. Measurement of such replicative species may offer additional options for monitoring and predicting treatment efficacy, but further validation and standardization are required before they can become truly diagnostic assays. Similar obstacles will apply to newer technologies, such as tissue‐based microarrays and gene arrays, which may lead to even more insights into HBV pathogenesis.
Establishment of authentic HCV replication systems for drug screening
Authors: YEH CHAU‐TING
Published: December 2004

Abstract  Although the interferon‐based therapeutics for chronic hepatitis C has improved remarkably over the decades, in some groups of patients the current therapeutic efficacy is far from satisfactory. Although new therapeutics is vigorously sought, the lack of appropriate cell culture systems and small animal models greatly hindered the progress of drug development. By introducing a selection marker into the HCV subgenomes, several successful replicon constructs were established. HCV replicons harboring adaptive mutations confer markedly increased efficiencies of replication. Furthermore, Huh‐7 cells carrying replicon that contained the whole genome were established but these cells were unable to secrete infectious viral particles. By use of SCID mice carrying a plasmogen activator transgene, an animal model carrying a chimeric human liver was established. These mice are permissive for HCV infection and the viral passages can be achieved successfully. However, the accessibility of this system is limited. By use of a molecular screening strategy, a hepatic factor, Sip‐L, is found to be capable of supporting HCV replication in an otherwise non‐permissive cell line. Potentially, this factor may be used to promote the infectivity and replication in other known permissive cell lines. An ex vivo assay using human liver biopsy slices has been established. This method can be used to test new anti‐HCV agents. In conclusion, although much progress has been made, culture cells permissive for highly efficient HCV infection are still lacking. An easily accessible small animal model is still in need. Much effort is still needed to establish an efficient and easily accessible authentic HCV replication system.
Autopsy case of prostate cancer with multiple endocrine neoplasia 2A
Authors: Ishida Eiwa , Nakamura Mitsutoshi , Shimada Keiji , Matsuyoshi Syuichi , Tada Kazuhiro , Okajima Eijiro , Fujimoto Kiyohide , Konishi Noboru
Published: December 2004

We describe an autopsy case of a 65‐year‐old man with prostate cancer accompanied by multiple endocrine neoplasia 2A (MEN 2A), including malignant pheochromocytomas, thyroid medullary carcinomas and parathyroid hyperplasia. Metastatic lesions from the prostate primary were identified using immunohistochemistry for prostate specific antigen within both primary and metastatic pheochromocytomas in the liver. To investigate the affinity of prostate cancer for pheochromocytoma cells, immunohistochemistry was carried out using a number of antibodies and both tumors were positive for N‐cadherin. Interestingly, pheochromocytomas, thyroid medullary carcinomas and prostate cancer were all positive for the anti‐RET antibody. The immunohistochemical results suggest that the cell affinity may, in part, result from cell–cell adhesion via N‐cadherin. Although prostate cancer is rarely associated with MEN, RET activation may have participated in the tumorigenesis of this case.
Foam cells generated by a combination of hyperglycemia and hyperlipemia in rats
Authors: Sano Jun‐ichi , Shirakura Shiro , Oda Shoji , Hara Takuji , Ishihara Tokuhiro
Published: December 2004

Diabetes is a major risk factor for atherosclerosis, as well as hyperlipemia. Investigators have suggested that denatured lipoprotein in hyperglycemia transforms macrophages into foam cells, which correlates with the development or progression of atherosclerosis. In the present study, we  examined  the  generation  of  foam  cells  in  rats  caused by a combination of hyperglycemia and hyperlipemia. Streptozotocin‐induced diabetic male Wister rats were fed a high cholesterol diet (HCD) containing 1% cholesterol and 0.5% cholic acid to maintain a hyperglycemic and hyperlipemic state. Animals fed the HCD for 8 weeks or longer showed a high incidence of foam cell accumulation in the renal glomerulus, intima of aortic arch, splenic red pulp and marginal zone, liver sinusoid and intestinal lamina propria. The foam cells exhibited positive staining for antimonocyte/macrophage antibody and lipids in all these tissues. Anti‐rat apolipoprotein B (apo B) antibody revealed that positive staining existed only in the cytoplasm of glomerular foam cells. These results suggest that the origin of these foam cells can be attributed to lipid‐laden macrophages. The generation of foam cells in the hyperglycemia‐hyperlipidemia supervening rat model presented in the present study might be a useful tool for investigations of the pathogenesis of foam cells.
Choosing to practice in rural dietetics: What factors influence that decision?
Authors: Heaney Susan E. , Tolhurst Helen , Baines Surinder K.
Published: December 2004

Objective:  The present study aimed to identify those factors that influence the decision of a dietitian to consider working in a rural area.

Design:  A qualitative design using focus groups was chosen for this study to allow for in‐depth data to be obtained.

Setting:  University of Newcastle, Callaghan Campus.

Subjects:  Twenty‐three students/new graduates from the Bachelor of Health Science (Nutrition and Dietetics) degree at the University of Newcastle.

Main Outcome Measures:  Not applicable, this project was an exploratory study.

Results:  A number of factors that influence the decision of dietetic students and newly graduated dietitians to consider working in a rural area were identified. These fell into the following main thematic areas: job prospects; rural lifestyle; comfort zones; support networks; promotion opportunities/professional development; type of work/work role; rural needs; and time frame.

Conclusions:  The present study found that choosing a location to work (whether it be a rural one or not) is a complex process and involves a number of interacting factors. Also those factors that may influence one dietitian to choose a career in a rural area may also be the factors that influence another dietitian not to choose a career in a rural area.

What is already known on this subject:  Australian rural areas are understaffed with dieticians by more than 50% of optimal numbers. Rural dieticians see variety of work, rural lifestyle, and professional autonomy and responsibility as incentives for working in rural areas, and limited professional development opportunities, professional support, career structure and specialization opportunities as disincentives.

What does this paper add?:  Career choice by dietetics students is a complex process with some issues such variety of work being incentives for some students and disincentives for others. Students have a ‘comfort zone’ that is a geographical area in which they feel comfortable living and working and even if they will unemployed in an urban area some students are unwilling to move outside of their comfort zone in order to find work.
Point‐of‐care monitoring of anticoagulant therapy by rural community pharmacists: Description of successful outcomes
Authors: Jackson Shane L. , Peterson Gregory M. , House Murray , Bartlett Timothy
Published: December 2004

Warfarin is a recognised high‐risk drug for adverse events. Patients from rural and remote regions are at increased risk of these events because of problems of access to health care providers and services, and there is some reluctance to prescribe warfarin to patients in rural areas because of the difficulties in monitoring anticoagulated patients. The availability of portable international normalised ratio (INR) monitors is particularly attractive in rural or remote settings because of the lack of access to pathology services. Pharmacists and other health professionals in rural areas are ideally placed to assist general practitioners in the management of their anticoagulated patients through the use of portable INR monitors. The present article describes three cases of successful outcomes of pharmacist‐assisted anticoagulation monitoring in the rural setting. Innovative service delivery models like these are needed to meet the needs of the increasing number of rural Australians requiring warfarin therapy.

What is already known on this subject:  There is clear evidence of the under use of warfarin in patients with atrial fibrillation (AF) and under use is greatest in rural areas. One of the barriers to the use of warfarin in these areas is the relative lack of access to pathology services for regular international normalised ratio (INR) testing.

What does this study add:  Through case studies, the present study demonstrates the practical utility of point‐of‐care INR monitoring in rural and remote communities. Such monitoring has the potential to lead to safer and more effective use of warfarin and therefore to better management of anticoagulated patients in rural and remote areas.
Follicular development and induction of ovulation with human chorionic gonadotropin in the pregnant rat
Authors: KAGABU SATOSI , UMEZU MOTOAKI
Published: December 2004

Aims: The number of ovarian follicles and ovulations after human chorionic gonadotrophin (hCG) was given at various doses during pregnancy were investigated in rats.

Methods: On designated days of pregnancy, rats were injected with hCG at 13.00 hours and the number of ova were observed. The same rats were then killed at 13.00 hours the next day. The ovaries were cut into complete sections. All sections were observed and the size of each follicle was measured.

Results: The number of large (≥550 µm), healthy, non‐atretic follicles (Graafian follicles) ranged from 1.5 to 11 during pregnancy. Ovulation was induced in rats at any stage of pregnancy with intramuscular injections of 40 or 50 IU hCG, but 10 IU had no effect and 20 or 30 IU had an incomplete effect. The number of ovulations after 40 IU hCG was 2–12 and there was not a significant difference between the number of ovulations and the number of large, healthy follicles at any point in the pregnancy.

Conclusion: Graafian follicles existed through the pregnancy. Results suggest that although hCG induces ovulation in large ovarian follicles (≥550 µm) during pregnancy, the responsiveness to hCG is lower than in recurrent estrus‐stage rats. (Reprod Med Biol 2004; 3: 201–204)
Bisphenol A‐induced morphological alterations in Sertoli and spermatogenic cells of immature Shiba goats in vitro: An ultrastructural study
Authors: ANDRIANA BIBIN BINTANG , TAY TAT WEI , HIRAMATSU RYUJI , AWAL MOHAMMAD ABDUL , KANAI YOSHIAKIRA , KUROHMARU MASAMICHI , HAYASHI YOSHIHIRO
Published: December 2004

Background and aims: There is no information currently available regarding the effects of bisphenol A (BPA) on testes in ruminants. Therefore, to establish and clarify the effects of BPA in ruminants, testicular tissue cultures were obtained from immature Shiba goats.

Methods: The testes of 2‐month‐old Shiba goats were cut into smaller pieces and seeded in medium. At 1, 3, 6 and 9 h after administration of various concentrations of BPA, the specimens underwent light and transmission electron microscopic observations

Results: At 1 h after BPA treatment, vacuolization and nuclear membrane rupture appeared within the nucleoplasm and cytoplasm of Sertoli cells. Such alterations tended to gradually increase in number in time‐ and dose‐dependent manners. Thus, because of BPA treatment, apoptotic spermatogenic cells, necrotic spermatogenic cells, apoptotic Sertoli cells and necrotic Sertoli cells could be identified. Particularly in the Sertoli cell, ruptured vesicles could be found within the multivesicular nuclear body.

Conclusion: The treatment with BPA at a low concentration tends to lead spermatogenic and Sertoli cells to apoptosis, whereas a higher concentration tends to lead spermatogenic and Sertoli cells to necrosis. Therefore, this study showed that testicular tissue culture is an advantageous avenue for screening the testicular toxicity of chemicals in ruminants. (Reprod Med Biol 2004; 3: 205–210)
Changes in the amount of cytoplasmic inclusions in mouse oocytes during meiotic maturation in vivo and in vitro
Authors: NIIMURA SUEO , KAWAKAMI SHIN‐YA , TAKANO HIROKO
Published: December 2004

Background and aims: The changes in cytoplasmic inclusions during meiotic maturation have only been examined in porcine oocytes. In the present study, the amount and the number of cytoplasmic inclusions (glycogen granules, lipid droplets and fibrous structures) were examined in mouse oocytes in the process of in vivo and in vitro maturation. For those inclusions that changed in amount during maturation, we also examined their content in oocytes treated with olomoucine, an inhibitor of cyclin‐dependent kinase, in order to clarify the relationship between nuclear maturation and changes in the inclusions.

Methods: Nuclear maturation in the oocytes cultured for various periods and those collected from antral follicles and oviducts was examined after staining with aceto‐orcein. For the demonstration of glycogen granules and lipid droplets, oocytes were stained with periodic acid‐Schiff or Sudan IV. Fibrous structures in the oocytes were observed under an electron microscope.

Results: The amount of glycogen granules, Sudanophilic lipid droplets and fibrous structures did not change in the oocytes matured in vivo and in vitro, whereas the number of the lipid droplets increased during maturation. In the oocytes treated with olomoucine, the resumption of nuclear maturation was inhibited, whereas the increase in the number of Sudanophilic lipid droplets was not inhibited.

Conclusion: Present findings suggest that the increase in the number of Sudanophilic lipid droplets occurs in the cytoplasm of mouse oocytes during maturation, regardless of in vivo or in vitro maturation, and that such the change in the inclusion is not related to nuclear maturation. (Reprod Med Biol 2004; 3: 231–236)