bluuebunny/crossref_metadata_2025 huggingface dataset:
Corneometric, sebumetric and TEWL measurements following the cleaning of atopic skin with a urea emulsion versus a detergent cleanser
Authors: Rudolph Reimar , Kownatzki Eckhard
Published: July 2004

A non‐detergent urea emulsion cleanser and a detergent cleanser with added moisturizers were compared for their effects on stratum corneum moisture, surface lipids and transepidermal water loss (TEWL) of atopic skin. Following a single wash with either cleanser, low corneometry and sebumetry values increased and elevated TEWL values decreased. Over the course of more than 6 h, all induced changes gradually returned to their starting points. In all instances, the changes induced by the urea emulsion lasted significantly longer than those caused by the detergent cleanser. The sebumetry increase after a wash with the lipid‐free detergent cleanser indicated that this method recognized not only true lipids but also the lipid‐derived and skin lipid‐depleting detergents. The transient TEWL normalization with either cleanser could not be attributed to a passing barrier restoration nor to an occlusion. It is speculated that the TEWL changes were related to stratum corneum water binding capacity.
Content of oak moss allergens atranol and chloroatranol in perfumes and similar products
Authors: Rastogi Suresh C. , Bossi Rossana , Johansen Jeanne D. , Menné Torkil , Bernard Guillaume , Giménez‐Arnau Elena , Lepoittevin Jean‐Pierre
Published: July 2004

Chloroatranol and atranol have been identified as the main allergens in the fragrance material of botanical origin, oak moss absolute. A previous study has shown that nearly all individuals sensitized to chloroatranol will elicit to 5 μg/ml. in a repeated open application test and that 50% will get a reaction to 0.15 µg/ml under patch test conditions. Thus, chloroatranol is known as a potent allergen. The aim of the current investigation was to quantify exposure to chloroatranol and the chemically related substance atranol in some popular perfumes, eaux de parfum and eaux de toilette available on the European market. In total, 31 products were analysed by liquid chromatography‐electrospray ionization‐tandemmass spectrometry (LC‐ESI‐MS‐MS) for their contents of atranol and chloroatranol. The 2 substances were found in 87% (n = 27) of the products. The median concentration of atranol in perfumes was 0.502 µg/ml and 0.012 µg/ml in eaux de toilette, and 0.235 µg/ml and 0.006 µg/ml for chloroatranol, respectively, in perfumes and eaux de toilette. Chloroatranol was found at a maximum concentration of 53 µg/ml and atranol at one of 190 µg/ml. The wide exposure to oak moss allergens, together with significant amounts of these potent allergens in at least half of perfumes and some eaux de toilettes explains the high frequencies of oak moss absolute allergy. It is suggested that regulations should be introduced aimed directly at these substances, and not just at oak moss absolute.
Formaldehyde and formaldehyde releasers: How much avoidance of cross‐reacting agents is required?
Authors: Herbert Courtney , Rietschel Robert L.
Published: July 2004

We investigated whether or not individuals who are allergic to formaldehyde and various formaldehyde‐releasing preservatives must avoid exposure to another closely related formaldehyde‐releasing allergen to which they were patch test negative. We found that in over 86% of cases a broad restriction of all formaldehyde‐releasing preservatives was not required if the patch test was negative. Usually the patch test is predictive of which materials need to be totally avoided. Restriction of exposure to all of the formaldehyde‐releasing preservatives may be overly restrictive.
Calcipotriene and Corticosteroid Combination Therapy for Vitiligo
Authors: Travis Lisa B. , Silverberg Nanette B.
Published: July 2004

Abstract:  Corticosteroids and photochemotherapy, using a combination of psoralen and ultraviolet A (PUVA) exposure, are the most widely prescribed therapies for vitiligo. These treatments are not uniformly effective and many patients have inadequate responses. Calcipotriene has been shown to be effective in adults and children with psoriasis when used as monotherapy and in combination with corticosteroids and phototherapy. We hypothesized that since the mechanisms of action for calcipotriene and corticosteroids are different, patients may develop more repigmentation with a combination of the two agents, while decreasing the side effects from both agents.

Twelve patients with vitiligo (average age 13.1 years) were advised to use topical corticosteroids in the morning and topical calcipotriene in the evening. Of the 12 patients, 83% responded to therapy, with an average of 95% repigmentation by body surface area. Four of the patients who responded had previously failed trials of topical corticosteroids alone. All of the patients in this group had repigmentation. Eyelid and facial skin responded best to this therapy. None of the patients had adverse reactions to the treatment. Our results show that topical calcipotriene in combination with corticosteroids can repigment vitiligo, even in those patients who were previous topical corticosteroid failures.
Responsive and Proactive Market Orientation and New‐Product Success*
Authors: Narver John C. , Slater Stanley F. , MacLachlan Douglas L.
Published: August 2004

What is the relationship between market orientation and new‐product success? This important question has not been examined adequately to date because the concept of market orientation has been measured too narrowly. The concept of market orientation implies both responsive market orientation, which addresses the expressed needs of customers, and proactive market orientation, which addresses the latent needs of customers—that is, opportunities for customer value of which the customer is unaware. In the numerous market orientation–performance studies to date, the measure of market orientation has consisted virtually entirely of behaviors related to satisfying customers' expressed needs rather than satisfying their latent needs as well.

The present study extends the measurement of market orientation to match the full scope of the concept—to measure both responsive market orientation and proactive market orientation. Using data from a sample of technologically diverse businesses, the present study develops a measure of proactive market orientation, refines the extant measure of responsive market orientation, and analyzes the relationship of a business's responsive and proactive market orientation to its new‐product success. The study findings imply that for any business to create and to sustain new‐product success, a responsive market orientation is not sufficient and, thus, that a proactive market orientation plays a very important positive role in a business's new‐product success. These findings make intuitive sense. For if in developing its new products a business relies solely on what customers state as their new product needs, the business is very vulnerable economically. Such a business is vulnerable not only for relying on customers' best guesses for new products, many or most of which may have little long‐term economic value for either party, but also to competitors' parallel new product responses and the inevitable resulting price competition. A business that relies solely on customers' expressed needs to develop its new products creates no new insights into value‐adding opportunities for the customer and thereby creates little or no customer dependence and foundation for customer loyalty. The important role for proactive market orientation in new‐product success is intuitively obvious—and is supported empirically in this study.
Esophageal Duplication Cyst: A Challenging Diagnosis of a Paracardiac Mass
Authors: Accadia Maria , Ascione Luigi , De Michele Mario , Saulino Carmela , Alabiso Maria Eleonora , Tuccillo Bernardino
Published: August 2004

We present a case of esophageal duplication cyst, echocardiographically appearing as a mass above the roof of the left atrium and behind the right pulmonary artery. The differential diagnosis and the management of such disease are discussed.
An arthritogenic monoclonal antibody to type II collagen, CII‐C1, impairs cartilage formation by cultured chondrocytes
Authors: Amirahmadi S Fatemah , Pho Minh Hue , Gray Robyn E , Crombie Duncan E , Whittingham Senga F , Zuasti Beltzane Biurrun , Van Damme Marie‐Paule , Rowley Merrill J
Published: July 2004

Antibodies to type II collagen (CII) cause articular damage in collagen‐induced arthritis (CIA) in mice as judged by passive transfer to naive animals of mAb to CII. We tested the hypothesis that mAb degrade cartilage structure by reacting with functionally important regions of the collagen molecule by examining the effects of an arthritogenic mAb to CII, CII‐C1, on cultured bovine chondrocytes at high density, at days 7 and 14. The effects were compared of CII‐C1, an isotype‐matched control mAb, or medium alone, on chondrocyte proliferation and viability, cell morphology, matrix structure by light and electron microscopy, and matrix synthesis by metabolic labelling with 3H‐proline for collagen or 35SO4 for proteoglycans. Chondrocytes in culture remained viable, proliferated, and produced an extracellular matrix in which CII was the major collagen. The addition of CII‐C1, but not a control mAb, increased the synthesis of CII and proteoglycan, and caused disorganization of the extracellular matrix and thin collagen fibrils ultrastructurally. Moreover, using a cell‐free assay, CII‐C1 inhibited the normal self‐assembly of collagen fibrils from CII in solution. The finding that the mAb to CII, CII‐C1 has striking degradative effects in vitro on cartilage synthesis suggests that antibodies to collagen perpetuate the chronic phase of CIA and that, in mice at least, such antibodies are an important component of pathogenesis.
The CD11/CD18 (β2) integrins modulate neutrophil caspase activation and survival following TNF‐α or endotoxin induced transendothelial migration
Authors: Yan Sen Rong , Sapru Kusum , Issekutz Andrew C
Published: July 2004

Neutrophils (PMN) are short‐lived cells but their survival is often prolonged in inflammation. The β2 (CD11/CD18) integrins are involved in PMN migration into inflammation but their role in PMN survival is not well understood. We investigated the role of β2 integrins in PMN caspase activation, a key enzyme cascade in apoptosis. After 20 h, caspase activation (Western blotting) was markedly decreased in PMN cultured on fibrinogen, a ligand for Mac‐1 (CD11b/CD18), but not on fibronectin or albumin. In the presence of TNF‐α or endotoxin (LPS), blockade of CD18 (β2 chain) with mAb markedly increased caspase activation in PMN on fibrinogen. PMN which migrated through endothelium in vitro in response to TNF‐α, LPS, IL‐1α, IL‐8 or C5a contained 58% fewer active caspase positive PMN after 20 h than non‐migrated PMN remaining on the endothelium. When β2 (CD18) integrin or lymphocyte function antigen (LFA)‐1 (CD11a) plus Mac1 (CD11b) were blocked by mAb (intact or Fab′), the proportion of migrated PMN (but not of non‐migrated PMN) with active caspases was significantly increased (2−4‐fold) and this was associated with accelerated PMN apoptosis and death. Thus, engagement of ligands on extracellular matrix and endothelium by the β2 integrins Mac‐1 and LFA‐1 plays a role in delaying apoptosis in PMN recruited in response to LPS and TNF‐α. Inhibition of β2 integrin function may not only inhibit PMN infiltration, but also accelerate PMN clearance from inflamed tissue.
Cellular mechanism of renin release
Authors: Schweda F. , Kurtz A.
Published: July 2004

In this review we aim to give a comprehensive overview over the current knowledge of the cellular control of renin release. We hereby focus on the inhibitory effects of calcium on the exocytosis of renin. After a short introduction into general aspects of the regulation of renin release, including a brief summary on the role of the second messengers cAMP and cGMP, we will discuss parts of the literature on the effects of calcium on the renin system together with recent studies from our laboratory, investigating putative calcium influx and extrusion pathways of juxtaglomerular cells. Finally, as the precise mechanisms by which calcium inhibits the exocytosis of renin are far from being understood, we will present some hypotheses on the intracellular events being involved in the suppression of renin release by calcium.
Tumour necrosis factor‐α receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab
Authors: Pierik M. , Vermeire S. , Steen K. V. , Joossens S. , Claessens G. , Vlietinck R. , Rutgeerts P.
Published: July 2004

Background : The role of tumour necrosis factor‐α in the pathogenesis of inflammatory bowel disorders is well‐known and is underscored by the effectiveness of antitumour necrosis factor‐α treatment. Tumour necrosis factor‐α exerts its effect by binding TNFR1 and TNFR2, which genes map to inflammatory bowel disorders susceptibility loci.

Aims and methods : Since TNFR1 and TNFR2 are good candidate genes for inflammatory bowel disorders, we studied the functional TNFR2T587G and the TNFR1A36G mutation in 344 Crohn's disease and 152 ulcerative colitis patients and investigated the relation with disease phenotypes. An association with response to infliximab was evaluated in 166 Crohn's disease patients.

Results : The TNFR2 587G allele was more frequent in ulcerative colitis compared with controls (P = 0.03). Both single nucleotide polymorphisms were negatively associated with smoking at diagnosis in Crohn's disease (TNFR1A36G odds ratio: 0.614, 95% confidence interval: 0.452, 0.99 and TNFR2T587G odds ratio: 0.572, 95% confidence interval: 0.820, 0.875). There was a positive association between pancolitis and the TNFR1A36G polymorphism in ulcerative colitis (odds ratio: 5.341, 95% confidence interval: 1.484, 19.39). The biological response to infliximab was lower in patients carrying TNFR1 36G (odds ratio: 0.47, 95% confidence interval: 0.234, 0.946).

Conclusion : The TNFR2 587G allele was more frequent in ulcerative colitis. Both single nucleotide polymorphisms were negatively associated with smoking in Crohn's disease. A relation between TNFR1A36G and pancolitis was found in ulcerative colitis. There was no clear effect of the polymorphisms on infliximab response although, the TNFR1 minor was associated with a lower response to infliximab.
A new questionnaire for constipation and faecal incontinence
Authors: Bharucha A. E. , Locke G. R. , Seide B. M. , Zinsmeister A. R.
Published: July 2004

Background : The prevalence, severity and risk factors of faecal incontinence in women in the community are incompletely characterized.

Aim : To develop and validate a self‐report questionnaire (faecal incontinence and constipation assessment) to address these issues.

Method : Eighty‐three women completed the instrument; 20 randomly selected patients answered the faecal incontinence and constipation assessment again 6 weeks later. A gastroenterologist also completed the faecal incontinence and constipation assessment in all 83 subjects after a detailed clinical assessment. Concurrent validity was evaluated by comparing the patient's self‐report to a doctor interview for every question. Reproducibility was evaluated by a test–retest approach for every question. The severity of faecal incontinence was rated by incorporating the frequency and type of faecal incontinence, rectal urgency and use of sanitary devices.

Results : The questionnaire was well‐understood. Reproducibility [median κ statistic, 0.80 (interquartile range: 0.66–0.90)]; and concurrent validity [0.59 (0.47–0.67)] were acceptable. For the index question on faecal incontinence, the κ for reproducibility and concurrent validity was 0.90 and 0.95, respectively. The faecal incontinence severity score was also valid (κ = 0.5).

Conclusion : The faecal incontinence and constipation assessment has excellent reproducibility and reasonable validity for assessing the presence, risk factors and severity of faecal incontinence and associated bowel disorders in women when compared against clinical assessment.
In vivo evaluation of a novel pH‐ and time‐based multiunit colonic drug delivery system
Authors: Bott C. , Rudolph M. W. , Schneider A. R. J. , Schirrmacher S. , Skalsky B. , Petereit H.‐U. , Langguth P. , Dressman J. B. , Stein J.
Published: July 2004

Background : Targeted drug delivery to the colon is important for topical treatment of inflammatory bowel diseases. Established targeting systems predominantly focus on either pH‐ or time‐dependent release, or bacterial degradation.

Aim : To perform a three‐phase, crossover design trial evaluating a novel combined pH‐ and time‐based multiunit delivery system.

Methods : Twelve healthy male volunteers each received 200 mg of caffeine as either uncoated immediate release tablets, coated pellets with pH‐dependent rapid release (EUDRAGIT FS 30D), and pellets with pH‐ and time‐based release (inner layer EUDRAGIT RL/RS 30D; outer layer EUDRAGIT FS 30D). Orocecal transit time was measured using lactose‐[13C]ureide. Serum concentrations of caffeine were measured by high‐performance liquid chromatography.

Results : In contrast to the uncoated tablet, both coated systems reached the ileocecal region almost at the same time (3.19 ± 0.71 and 3.33 ± 0.81 h). Serum caffeine profiles were significantly prolonged for the pH and time delivery system compared with the pH‐only based system (median tmax 12.0 vs. 5.5 h; P < 0.001). This was further reflected by a lower Cmax value and a lower area under the curve within 24 h after application.

Conclusion : Compared with the conventional delivery systems, drug release from the new dosage form may offer a new dimension for the oral treatment of mid to distal ulcerative colitis.
Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non‐selected adult population
Authors: Hillilä M. T. , Färkkilä M. A.
Published: July 2004

Background : Prevalence of irritable bowel syndrome shows great variation among epidemiological studies, which may be due to different diagnostic criteria.

Aim : To assess prevalence of irritable bowel syndrome according to various diagnostic criteria and to study differences in symptom severity, psychopathology, and use of health care resources between subjects fulfilling different diagnostic criteria.

Methods : A questionnaire was mailed to 5000 randomly selected adults. Presence of irritable bowel syndrome was assessed by four diagnostic criteria: Manning 2 (at least two Manning symptoms), Manning 3 (at least three Manning symptoms), Rome I and Rome II.

Results : Response rate was 73%. Prevalence of irritable bowel syndrome by Manning 2, Manning 3, Rome I and Rome II criteria was 16.2%, 9.7%, 5.6%, and 5.1% respectively. Of those fulfilling Rome II criteria, 97% fulfilled Manning 2. Severe or very severe abdominal pain was reported by 27–30% of Manning‐positive subjects, and 44% of Rome‐positives. Prevalence of depression in Manning 2, and Rome II groups was 30.6 and 39.3%.

Conclusions : Prevalence of irritable bowel syndrome by Rome II criteria is considerably lower than by Manning criteria. Subjects fulfilling Rome criteria form a subgroup of Manning‐positive subjects with more severe abdominal symptoms, more psychopathology, and more frequent use of the health care system.
Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis
Authors: Russo A. , Stevens J. E. , Giles N. , Krause G. , O'Donovan D. G. , Horowitz M. , Jones K. L.
Published: July 2004

Background : KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans.

Aim : To evaluate the acute effects of KC 11458 on gastric emptying in diabetic gastroparesis.

Methods : Twenty‐nine patients (6 type 1 and 23 type 2) with gastroparesis underwent assessments of: (i) gastric emptying of a solid/liquid meal using scintigraphy, (ii) glycaemic control (blood glucose at 0, 30, 60, 90 and 120 min during the gastric emptying measurement) and (iii) upper gastrointestinal and ‘meal‐related’ symptoms (questionnaire), at baseline and after treatment with KC 11458 in a dose of 8 mg t.d.s., or placebo for 8 days.

Results : KC 11458 had no statistically significant or clinically relevant effect on gastric emptying of either the solid intragastric retention at 100 min (T100) (P = 0.87) or liquid 50% emptying time (T50) (P = 0.17) components of the meal. KC 11458 slightly worsened (P = 0.04) upper gastrointestinal symptoms when compared with placebo. The magnitude of the change in solid gastric emptying correlated with the change in the blood glucose concentration (r = 0.49; P < 0.05).

Conclusions : KC 11458, in a dose of 8 mg t.d.s. for 8 days, does not accelerate gastric emptying in patients with diabetic gastroparesis. The absence of efficacy may relate to an effect of hyperglycaemia.
The evolving role of liver biopsy
Authors: Campbell M. S. , R. Reddy K.
Published: July 2004

Liver biopsy is traditionally the ‘gold standard‘ for the evaluation of liver diseases. There are several situations in which its role is being challenged. In hepatitis C, liver biopsy helps assess prognosis and treatment candidacy. An important exception is genotype 2 or 3 because treatment is more likely to succeed and therapy is relatively short in duration. For hepatitis B, liver biopsy gives some prognostic information, but serologic tests and hepatic biochemical tests are the primary determinants of treatment candidacy. Non‐alcoholic fatty liver disease can be accurately diagnosed without a liver biopsy and, furthermore, there are no specific therapies available. The role of liver biopsy to assess methotrexate‐associated hepatotoxicity remains controversial. Finally, patients with focal liver lesions usually do not require biopsy and, in the case of hepatocellular carcinoma, biopsy carries a risk of needle‐track seeding. In short, the need for liver biopsy depends on the specific situation and should be performed when there is sufficient uncertainty about diagnosis, severity of disease, prognosis, and treatment decisions.
Reproducibility of a symptom response to omeprazole therapy in functional dyspepsia evaluated by a random‐starting‐day trial design
Authors: Madsen L. G. , Bytzer P.
Published: July 2004

Background : Satisfactory treatment options for functional dyspepsia are lacking. Single subject trial designs may identify subgroups of patients with a uniform response to therapy.

Aim : To test reproducibility of response in a new random‐starting‐day trial design developed to identify acid‐related symptoms in functional dyspepsia.

Methods : One hundred and nineteen patients with functional dyspepsia completed a 12‐day, double‐blind random‐starting‐day trial with an initial placebo run‐in followed by switch to omeprazole on a randomized and blinded day (between days 5 and 9) with active treatment continuing for the rest of the trial. Response was defined as a sustained ≥50% reduction of a daily symptom‐score within 3 days of active treatment. Fifty‐nine patients repeated the random‐starting‐day trial at relapse of symptoms.

Results : After exclusion of placebo responders, 14% (15 of 106) were classified as responders in the first and 20% (10 of 50) in the subsequent random‐starting‐day trial series. Sixty‐eight per cent (40 of 59) of the patients reproduced their initial response with a chance‐corrected agreement of 0.29. Comparing response patterns using different symptom rating‐scales showed good correlation (kappa 0.60).

Conclusion : Reproducibility of response in a random‐starting‐day trial was imperfect, mainly because of the low response rates and strict response criteria. Lack of symptom stability impairs the value of the random‐starting‐day trial and only patients with frequent and stable symptoms should be evaluated in this design.
Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen‐negative chronic hepatitis B
Authors: Gaia S. , Marzano A. , Smedile A. , Barbon V. , Abate M. L. , Olivero A. , Lagget M. , Paganin S. , Fadda M. , Niro G. , Rizzetto M.
Published: July 2004

Aim : To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen‐negative chronic hepatitis B.

Methods : Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively.

Results : The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non‐responders. Overall 7.4% of patients developed a hepatocellular carcinoma.

Conclusion : Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non‐responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.
Increased thrombin generation and circulating levels of tumour necrosis factor‐α in patients with chronic Helicobacter pylori‐positive gastritis
Authors: Consolazio A. , Borgia M. C. , Ferro D. , Iacopini F. , Paoluzi O. A. , Crispino P. , Nardi F. , Rivera M. , Paoluzi P.
Published: July 2004

Background : Conflicting data have been reported concerning the relationship between Helicobacter pylori infection and coronary heart disease.

Aim : To evaluate clotting system activation and plasma levels of tumour necrosis factor‐α, a procoagulant cytokine, in patients with H. pylori‐positive and ‐negative gastritis.

Methods : Three groups of patients were identified: 38 with H. pylori‐positive gastritis, 18 with H. pylori‐negative gastritis, and 40 H. pylori‐negative controls with normal gastric mucosa. Plasma levels of prothrombin fragment 1 + 2 (F1 + 2) and tumour necrosis factor‐α were assayed. Patients were also controlled after 2 and 6 months following standard H. pylori eradication treatment.

Results : At baseline, fragment 1 + 2 and tumour necrosis factor‐α levels in H. pylori‐positive patients were significantly higher than those in H. pylori‐negative patients with gastritis (P < 0.05 and P < 0.01, respectively). After H. pylori eradication, fragment 1 + 2 and tumour necrosis factor‐α levels showed a significant decrease at 2 months (P = 0.03 and P = 0.02, respectively) and a further reduction at 6 months, reaching levels observed in H. pylori‐negative patients and controls.

Conclusions : The increase thrombin generation rate and the correlation of plasma fragment 1 + 2 and tumour necrosis factor‐α levels in H. pylori‐positive patients suggest a role for inflammation in mediating the relationship between H. pylori infection and activation of the clotting system.
Helicobacter pylori and molecular events in precancerous gastric lesions
Authors: Nardone G. , Rocco A. , Malfertheiner P.
Published: July 2004

Gastric cancer can be divided into intestinal type and diffuse type that differ substantially in epidemiology and pathogenesis. The most important aetiological factor associated both with intestinal and diffuse gastric cancer, is Helicobacter pylori.

Exposure of gastric epithelial cells to H. pylori results in an inflammatory reaction with the production of reactive oxygen species and nitric oxide that, in turn, deaminates DNA causing mutations. The complex interplay between H. pylori strain, inflammation and host characteristics may directly promote diffuse type gastric cancer or induce a cascade of morphological events, i.e. atrophy, intestinal metaplasia and dysplasia, finally leading to intestinal type gastric cancer. Two mechanisms, genetic and epigenetic have been held to play a role in the molecular alterations underlying gastric carcinogenesis. The former, comprising changes in the DNA sequence, is irreversible; the latter, involving DNA methylation, is potentially reversible by eliminating the triggering agents. If H. pylori is eradicated before development of stable mutations, the risk of gastric cancer will likely be prevented. Thus, eradication of H. pylori might immediately reduce the risk of diffuse type gastric cancer, whereas prevention of intestinal type gastric cancer may be less effective if patients are treated later in the evolution of the carcinogenic process.
Health‐related quality of life of patients with gastrointestinal symptoms
Authors: Bovenschen H. J. , Laheij R. J. F. , Tan A. C. I. T. L. , Witteman E. M. , van Rossum L. G. M. , Jansen J. B. M. J.
Published: July 2004

Background : Little is known about the variation in health‐related quality of life among patients with different presentations of gastrointestinal symptoms.

Aim : To study the association between health‐related quality of life and presentations of gastrointestinal symptoms.

Methods : Health‐related quality of life and demographic information was obtained from 873 patients referred to the hospital for endoscopy, using a questionnaire.

Results : A total of 436 patients (50%) reported predominantly upper gastrointestinal symptoms, 344 (39%) predominantly lower symptoms, and 93 (11%) patients reported both upper and lower symptoms. Patients with mild, moderate and severe symptoms, reported mean scores on a 100‐point visual analogue scale (95% CI) of 90 (79–100), 75 (64–86) and 64 (53–76), respectively (P < 0.001). Mean visual analogue scale scores (95% CI) almost linearly declined from 81 (77–85) to 49 (46–52) for those with one to those with more than eight symptoms. Patients who reported upper gastrointestinal symptoms and in particular epigastric pain, bloating and vomiting had significantly impaired health status in comparison to patients without these symptoms (P < 0.05).

Conclusions : Severity of gastrointestinal symptoms is the most important factor in affecting health status, followed by the numbers and type of gastrointestinal symptoms.
Helicobacter pylori eradication in children and adolescents by a once daily 6‐day treatment with or without a proton pump inhibitor in a double‐blind randomized trial
Authors: Tindberg Y. , Casswall T. H. , Blennow M. , Bengtsson C. , Granström M. , Sörberg M.
Published: July 2004

Aim : To evaluate two simplified Helicobacter pylori eradication treatment alternatives for children and adolescents.

Methods : Study subjects were identified by enzyme‐linked immunosorbent assay and immunoblot in a family screening project. Helicobacter pylori infected 10–21 year olds were offered treatment, individuals with abdominal pain underwent upper endoscopy and those with peptic ulcers were excluded. Participants were randomized to either azithromycin 500 mg daily and tinidazole 500 mg two tablets daily in combination with lansoprasole 30 mg daily for 6 days (ATL‐group) or with placebo (ATP‐group). Urea Breath Test was performed at inclusion and after a minimum of 6 weeks after end of therapy.

Results : In total, 131 individuals were randomized, of whom 31 (24%) had undergone upper endoscopy. Full compliance was achieved in 93% (122 of 131). The intention‐to‐treat eradication rate was 67% (44 of 66) and 58% (38 of 65) for the ATL‐ and the ATP‐group, respectively.

Conclusion : The double‐blind randomized clinical trial did not identify a simplified, successful once daily H. pylori treatment for children and adolescents. Thus, twice daily proton pump inhibitor (PPI)‐based triple therapies for 7 days remain as the choice of treatment in children. Further, powerful and controlled studies are needed to elucidate the best treatment strategies for H. pylori eradication in this age group.
Economic analysis of strategies in the prevention of non‐steroidal anti‐inflammatory drug‐induced complications in the gastrointestinal tract
Authors: Lanas A.
Published: July 2004

Background : It is unclear what the best therapeutic approach is in patients who require non‐steroidal anti‐inflammatory drugs. In clinical practice, choice of prescriptions are often based on drug costs.

Aim : To evaluate costs per upper gastrointestinal bleeding avoided with different prevention strategies.

Methods : Two major strategies have been considered (coxibs vs. non‐steroidal anti‐inflammatory drugs plus generic/brand gastroprotective agent). The number of patients needed to treat to prevent a bleeding event, the cost of the drug and duration of treatment were used to estimate costs.

Results : Based on hospitalization costs of a bleeding event, no therapeutic strategy is cost‐effective in patients without risk factors. All strategies (including omeprazole + coxib) are cost‐effective in patients with bleeding ulcer history. With other risk factors, all strategies are cost‐effective but prevention of events is twice as expensive in patients <75 years of age. No strategy shows superiority unless the cheapest generics are prescribed or a 50% reduction in the incidence of lower gastrointestinal complications with coxibs is confirmed.

Conclusions : Current prevention strategies to reduce serious non‐steroidal anti‐inflammatory drug‐associated gastrointestinal events are only cost‐effective in patients with risk factors. No strategy shows superiority, but coxib strategy would be more cost‐effective if it were associated with a reduction of events of the lower gastrointestinal tract.
Hepatic hydrothorax
Authors: Cardenas A. , Kelleher T. , Chopra S.
Published: July 2004

Patients with cirrhosis and portal hypertension often have abnormal extracellular fluid volume regulation, resulting in accumulation of fluid as ascites, oedema or pleural effusion. These complications carry a poor prognosis with nearly half of the patients with ascites dying in the ensuing 2–3 years. In contrast to what happens in the abdominal cavity where large amounts of fluid (5–8 L) accumulate with the patient only experiencing only mild symptoms, in the thoracic cavity smaller amounts of fluid (1–2 L) cause severe symptoms such as shortness of breath, cough and hypoxaemia. Hepatic hydrothorax is defined as a pleural effusion, usually >500 mL, in patients with cirrhosis without cardiopulmonary disease. The pathophysiology involves the direct movement of ascitic fluid from the peritoneal cavity into the pleural space through diaphragmatic defects. The estimated prevalence among cirrhotic patients is 5–10%. The effusion, which is a transudate, most commonly occurs in the right hemithorax. The mainstay of therapy is similar to that of portal hypertensive ascites and includes sodium restriction and administration of diuretics. Refractory hydrothorax can be managed with transjugular intrahepatic portosystemic shunt in selected cases. Pleurodesis is not routinely recommended. Suitable patients with hepatic hydrothorax should be considered candidates for liver transplantation.
A novel option in proton pump inhibitor dosing: lansoprazole orally disintegrating tablet dispersed in water and administered via nasogastric tube
Authors: Freston J. W. , Kukulka M. J. , Lloyd E. , Lee C.
Published: August 2004

Background : Lansoprazole orally disintegrating tablet, which rapidly disintegrates on the tongue or in water, provides a dosing alternative for patients with difficulty in swallowing. Gastric and nasogastric tubes are increasingly placed in patients with more severe swallowing disorders.

Aim : This study assessed the pharmacokinetic profile of lansoprazole orally disintegrating tablet dispersed in a small volume of water and administered through a small‐bore nasogastric tube.

Methods : Forty healthy adult men and women (18–43 years) received two single 30 mg lansoprazole orally disintegrating tablet doses (one administered directly onto the tongue without water, and one dispersed in water and administered via nasogastric tube) in a randomized, crossover fashion.

Results : The total plasma exposure to lansoprazole was comparable following both dosing regimens; mean AUC values for the lansoprazole orally disintegrating tablet nasogastric dispersion were ≤8.6% greater than those for the intact lansoprazole orally disintegrating tablet. Lansoprazole Cmax for the lansoprazole orally disintegrating tablet nasogastric dispersion was 20.9% greater than that for the intact lansoprazole orally disintegrating tablet, a difference of no clinical significance.

Conclusions : Dispersion of the lansoprazole orally disintegrating tablet in a small volume of water and administering via nasogastric tube does not reduce the pharmacokinetic profile of the intact lansoprazole orally disintegrating tablet. This alternative dosing method may be useful in patients with nasogastric or gastric tubes.
The impact of immigration on the increasing incidence of hepatocellular carcinoma in the United States
Authors: Kulkarni K. , Barcak E. , El‐Serag H. , Goodgame R.
Published: August 2004

Aims : To assess if the rising incidence of hepatocellular carcinoma in the United States can be accounted for by immigration and an ageing population, or is a true increase among the USA‐born residents.

Methods : Design– A retrospective chart review. Setting– Urban, multiethnic hospital and specialty clinics in a large indigent health system in Houston, Texas. Subjects– Approximately 23 000 admissions and 143 000 out‐patient clinic visits each year from 1992 through 2001 were assessed. A total of 494 patient records were selected and reviewed because of suspicion of hepatocellular carcinoma. Analysis– Hepatocellular carcinoma was confirmed by histopathology, α‐fetoprotein level >400 ng/mL, and suggestive imaging studies. The age‐adjusted incidence was determined and causative factors were identified.

Results : About 111 cases of confirmed hepatocellular carcinoma were found. The age‐adjusted incidence rose from 3.44 per 100 000 hospital admissions during 1992–1996 (95% confidence interval: 2.86–4.02) to 5.19 during 1997–2001 (95% confidence interval: 4.41–5.97). The proportion of patients of non‐USA place of birth decreased between 1992–1996 and 1997–2001 (46–24%, respectively, P = 0.03). Fifty‐two per cent and 68% were hepatitis C virus‐positive respectively; 37% and 34% were hepatitis B surface antigen‐positive respectively; 46% and 59% had a history of alcohol abuse; and 22% and 11% had no identifiable risk factors.

Conclusions : The incidence of hepatocellular carcinoma within the greater Houston area has increased during the past decade, rising by 51% from 1992–1996 to 1997–2001. This increase is not from immigration or population ageing but represents a true rise among the native born population. Hepatitis C and alcoholic cirrhosis are associated with a majority of cases, particularly in the latter half of the decade.
Rationale and proposed algorithms for symptom‐based proton pump inhibitor therapy for gastro‐oesophageal reflux disease
Authors: Bytzer P. , Blum A. L.
Published: August 2004

Gastro‐oesophageal reflux disease and non‐erosive reflux disease are chronic, highly prevalent conditions requiring long‐term treatment that is both effective and practical. On‐demand therapy with a proton pump inhibitor may meet that need. It is becoming a mainstay of long‐term treatment because it reduces the risk of over‐ and under‐treatment, is cost‐effective and user friendly. Epidemiological and clinical observations speak also in its favour. However, for the anticipated benefits of on‐demand therapy to accrue in clinical practice, on‐demand treatment algorithms are required. These algorithms must specify the initial evaluation and treatment of candidates, and follow‐up protocols for an on‐demand strategy. Our group has developed such algorithms, which are presented here.
A review of the potential uses for recombinant human TSH in patients with thyroid cancer and nodular goiter
Authors: Woodmansee Whitney W. , Haugen Bryan R.
Published: July 2004

Recombinant human TSH (rhTSH) has revolutionized the care of patients with differentiated thyroid cancer. Since its approval for clinical use in 2001 in Europe (1998 in the USA), rhTSH has greatly enhanced the surveillance of these patients by allowing the avoidance of hypothyroidism for TSH stimulation. Previously, a hypothyroid state was required for TSH stimulated diagnostic whole‐body radio‐iodine scans (DxWBS) and thyroglobulin (Tg) levels. Patients generally prefer rhTSH as a mechanism for TSH stimulation because symptoms of hypothyroidism can be completely avoided. Currently, rhTSH is only approved for diagnostic monitoring of differentiated thyroid cancer patients. There are many other potential uses for rhTSH, including facilitation of treatment of patients with thyroid cancer and nodular goiter. The diagnostic and therapeutic role of rhTSH in patients with differentiated thyroid cancer and nodular goiter will be discussed in this review.
Aldosterone synthase gene variation and adrenocortical response to sodium status, angiotensin II and ACTH in normal male subjects
Authors: Kennon Brian , Ingram Mary C. , Friel Elaine C. , Anderson Niall H. , MacKenzie Scott M. , Davies Eleanor , Shakerdi Loai , Wallace A. Michael , Fraser Robert , Connell John M. C.
Published: July 2004

objective  Aldosterone synthase, a key enzyme in the terminal steps of aldosterone synthesis, is encoded by the CYP11B2 gene. A polymorphism in the 5′ coding region of this gene (−344 C/T) is associated with hypertension, particularly with elevation of the aldosterone to renin ratio. A second polymorphism (a conversion in intron 2 to resemble that of the neighbouring 11β‐hydroxylase (CYP11B1) gene) is found in close linkage dysequilibrium with the variant at −344 C/T. The mechanism by which these variants predispose to cardiovascular disease and the precise intermediate phenotype associated with them remains speculative.

design  We performed a focused physiological study in normal volunteers stratified by CYP11B2 genotype.

patients  Twenty‐three subjects homozygous for the T allele and 21 homozygous for the C allele of the −344 C/T polymorphism of CYP11B2 were studied.

measurements  Basal and angiotensin II stimulated plasma and 24‐h urinary steroid excretion during low (60 mmol/day) and high (160 mmol/day) sodium intake and plasma steroids after ACTH stimulation were measured.

results  No influence of polymorphic variation on basal or stimulated plasma cortisol or aldosterone or other plasma steroid concentrations during either dietary phase was seen. However, excretion of tetrahydro‐11‐deoxycortisol (the urinary metabolite of 11‐deoxycortisol), which is the precursor of cortisol) was increased in TT subjects during sodium restriction, consistent with impairment of zona fasciculata 11β‐hydroxylation.

conclusions  We conclude that this polymorphism has no major influence on normal zona glomerulosa function but is associated with a change in 11β‐hydroxylation in the zona fasciculata. The mechanism remains uncertain, but alteration of 11‐deoxycortisol levels without change in cortisol suggests altered efficiency of 11β‐hydroxylation. In the long term, this may lead to a minor but chronic increase in ACTH drive to the gland, which may have consequences for steroid synthesis and predispose to the risk of cardiovascular disease.
Proton magnetic resonance spectroscopy and single photon emission computed tomography study of the brain in asymptomatic young hyperlipidaemic Asian Indians in North India show early abnormalities
Authors: Sinha Sanjeev , Misra Anoop , Kumar Virendra , Jagannathan N. R. , Bal C. S. , Pandey Ravindra Mohan , Singhania Rohit , Deepak
Published: July 2004

objective  To evaluate brain metabolism and cerebral blood flow in young patients with hyperlipidaemia.

patients and methods  Proton magnetic resonance spectroscopy (1H MRS) and single photon emission computed tomography (SPECT) of the brain was carried out in 19 asymptomatic young patients with hyperlipidaemia (mean age 32·6 ± 6·0 years, range 22–45 years) and 21 age‐matched healthy controls divided into the following three groups; (i) hyperlipidaemics on pharmacological treatment (group 1, n = 13), (ii) hyperlipidaemics not on pharmacological treatment (group 2, n = 6) and (iii) control group of healthy subjects (group 3, n = 21).

results  No statistical difference was observed in the brain metabolite ratios between controls and hyperlipidaemic patients (both treatment naive and treated) in the 1H NMR study. Two hyperlipidaemic patients showed a lactate peak and one had a lipid peak. The SPECT study was abnormal in seven hyperlipidaemic patients. In the pooled data, 50% subjects with high serum triglyceride (TG) levels as opposed to 14% subjects with normal serum TG levels showed cerebral hypoperfusion. The choline/creatine (Cho/Cr) ratio of the occipital region of the brain showed correlation with the excess percentage of body fat (%BF) and low levels of high density lipoprotein cholesterol (HDL‐C) compared to those with normal %BF and normal HDL‐C levels, respectively, in pooled data of all subjects. The N‐acetyl aspartate (NAA)/Cho ratio also showed correlation with hypercholesterolaemia. Serum TG levels were positively correlated with the NAA/Cr ratio (r = 0·62, P < 0·05) and the Cho/Cr ratio (r = 0·63, P < 0·05) in the parieto‐temporal area in group 1 patients.

conclusion  The study revealed no difference in the brain metabolite ratios between controls and hyperlipidaemic patients, while some hyperlipidaemic patients showed abnormalities of cerebral blood flow. Brain metabolite ratios were also influenced by certain parameters of body composition and lipids. As abnormal body composition, hypertriglyceridaemia and low levels of HDL‐C are prevalent in Asian Indians, such data are important and indicate a need for further study.
Genetics of endometriosis: a role for the progesterone receptor gene polymorphism PROGINS?
Authors: Lattuada Debora , Somigliana Edgardo , Viganò Paola , Candiani Massimo , Pardi Giorgio , Di Blasio Anna Maria
Published: July 2004

objective  Endometriosis is a steroid‐dependent disease with a particular genetic background, but the locations of possible genomic aberrations are still poorly clarified. We have investigated the potential association between endometriosis and the PROGINS 306 base pair insertion polymorphism in intron G of the progesterone receptor (PR) gene, which has been reported previously to segregate with this disease.

design  In a case‐control study, we examined the PROGINS polymorphism of the progesterone receptor gene in 131 Italian women affected by endometriosis diagnosed according to published criteria for the definition of the definite disease. Control subjects were represented by 127 Italian women without laparoscopic evidence of the disease.

measurements  Peripheral blood samples, DNA extraction and polymerase chain reaction (PCR) were used to genotype women for the presence of the PROGINS polymorphism.

results  We found a statistically significant difference in the distribution of PROGINS genotypes between patients with and without endometriosis. The frequency of the PROGINS allele T2 was 17·2% and 11%, respectively, in affected women and in controls [odds ratio (OR) = 1·7, 95% confidence interval (CI) 1·0–2·8]. This association was stronger in patients with more severe forms of endometriosis, such as an infiltrating disease or a disease characterized by severe pelvic adhesions (OR 2·4, 95% CI 1·2–4·8; and OR 2·7, 95% CI 1·4–5·3, respectively). Combination of the results from an earlier study and the current data indicates that carrying the allele variant T2 is associated with a twofold increase in the risk of developing endometriosis (OR 2·0, 95% CI 1·3–2·9).

conclusions  Our results further support the idea that the PROGINS polymorphism of the progesterone receptor may be associated with an increased risk of endometriosis.