bluuebunny/crossref_metadata_2025 huggingface dataset:
Pelvic floor disorders and quality of life in women with self‐reported irritable bowel syndrome
Authors: WANG J. , VARMA M. G. , CREASMAN J. M. , SUBAK L. L. , BROWN J. S. , THOM D. H. , Van Den EEDEN S. K.
Published: October 2009

Aliment Pharmacol Ther 31, 424–431

Background  Quality of life among women with irritable bowel syndrome may be affected by pelvic floor disorders.

Aim  To assess the association of self‐reported irritable bowel syndrome with urinary incontinence, pelvic organ prolapse, sexual function and quality of life.

Methods  We analysed data from the Reproductive Risks for Incontinence Study at Kaiser Permanente, a random population‐based study of 2109 racially diverse women (mean age = 56). Multivariate analyses assessed the association of irritable bowel syndrome with pelvic floor disorders and quality of life.

Results  The prevalence of irritable bowel syndrome was 9.7% (n = 204). Women with irritable bowel had higher adjusted odds of reporting symptomatic pelvic organ prolapse (OR 2.4; 95% CI, 1.4–4.1) and urinary urgency (OR 1.4; 95% CI, 1.0–1.9); greater bother from pelvic organ prolapse (OR 4.3; 95% CI, 1.5–11.9) and faecal incontinence (OR 2.0; 95% CI, 1.3–3.2); greater lifestyle impact from urinary incontinence (OR 2.2; 95% CI, 1.3–3.8); and worse quality of life (P < 0.01). Women with irritable bowel reported more inability to relax and enjoy sexual activity (OR 1.8; 95% CI, 1.3–2.6) and lower ratings for sexual satisfaction (OR 1.8; 95% CI, 1.3–2.5), but no difference in sexual frequency, interest or ability to have an orgasm.

Conclusions  Women with irritable bowel are more likely to report symptomatic pelvic organ prolapse and sexual dysfunction, and report lower quality of life.
Symptoms and quality of life in obese children and adolescents with non‐alcoholic fatty liver disease
Authors: KISTLER K. D. , MOLLESTON J. , UNALP A. , ABRAMS S. H. , BEHLING C. , SCHWIMMER J. B. ,   for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
Published: October 2009

Aliment Pharmacol Ther 31, 396–406

Background  Data on the quality of life (QOL) of children with non‐alcoholic fatty liver disease (NAFLD) are needed to estimate the true burden of illness in children with NAFLD.

Aim  To characterize QOL and symptoms of children with NAFLD and to compare QOL in children with NAFLD with that in a sample of healthy children.

Methods  Quality of life and symptoms were assessed in children with biopsy‐proven NAFLD enrolled in the NASH Clinical Research Network. PedsQL scores were compared with scores from healthy children. For children with NAFLD, between‐group comparisons were made to test associations of demography, histological severity, symptoms and QOL.

Results  A total of 239 children (mean age 12.6 years) were studied. Children with NAFLD had worse total (72.8 vs. 83.8, P < 0.01), physical (77.2 vs. 87.5, P < 0.01) and psychosocial health (70.4 vs. 81.9, P < 0.01) scores compared with healthy children. QOL scores did not significantly differ by histological severity of NAFLD. Fatigue, trouble sleeping and sadness accounted for almost half of the variance in QOL scores. Impaired QOL was present in 39% of children with NAFLD.

Conclusions  Children with NAFLD have a decrement in QOL. Symptoms were a major determinant of this impairment. Interventions are needed to restore and optimize QOL in children with NAFLD.
Informed consent document improvement does not increase patients' comprehension in biomedical research
Authors: Paris Adeline , Brandt Christian , Cornu Catherine , Maison Patrick , Thalamas Claire , Cracowski Jean‐Luc
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Before enrolment, an informed consent (IC) document must be given to all participants by the investigator.

• Most IC documents are long, contain much information and are difficult to understand.

• Some methods to improve comprehension were tested, but they had limited effects.

WHAT THIS STUDY ADDS

• We failed to show that improving IC document comprehension through a lexicosyntactic approach or by a working group leads to better comprehension in our patient population, whichever method was used.

• We confirm too that a study in real conditions is necessary.

AIMS International guidelines on ethics in biomedical research require that the informed consent of all enrolled participants is obtained. A written document describing the research, the informed consent (IC) document, must be given to all participants by the investigator. Most IC documents are long, containing much information. The aim of the present study was to determine whether the modification of the IC document by a working group or systematic improvement in its lexicosyntactic readability can improve comprehension of the written information given to patients participating in biomedical research.

METHODS One hundred and fifty‐nine patients were randomized to read one of the three versions of the IC document: unchanged document, document modified using systematic improvement of lexicosyntactic readability and document modified by a working group.

RESULTS Neither the improvement in the lexicosyntactic readability, nor the intervention of the working group significantly improved the score of objective comprehension for the subjects included in this study: it was 66.6 (95% confidence interval 64.0, 69.2) for the control group, 68.8 (66.2, 71.4) for the group with the document improved for lexicosyntactic readability and 69.2 (66.0, 72.4) for the group who read the document improved by the working group (P= 0.38).

CONCLUSIONS We failed to show that improving IC document comprehension through a lexicosyntactic approach or by a working group leads to better comprehension.
Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration
Authors: Soyinka Julius O. , Onyeji Cyprian O. , Omoruyi Sharon I. , Owolabi Adegbenga R. , Sarma Pullela V. , Cook James M.
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Malaria is widespread across some areas of the world, most of which also bear the brunt of the human immunodeficiency virus (HIV) pandemic, resulting in a high incidence of co‐infection of both diseases.

• Ritonavir, a HIV protease inhibitor, and quinine, an antimalarial agent effective against multidrug‐resistantPlasmodium falciparum, are likely to be administered concurrently for treatment of patients with HIV and malaria.

• Both drugs are metabolized to a significant extent by CYP3A4 and ritonavir is a potent inhibitor of this enzyme.

WHAT THIS STUDY ADDS

• With increasing access to antiretroviral drugs, it is important that potential interactions between therapies for HIV and malaria infections are investigated.

• In this study, concurrent administration of ritonavir with quinine was found to be associated with marked elevation in the plasma levels of the antimalarial and a pronounced decrease in plasma concentrations of 3‐hydroxyquinine, the major metabolite of quinine.

• There was also a modest but significant increase (P< 0.05) in plasma concentrations of ritonavir in the presence of quinine.

AIMSTo evaluate the pharmacokinetic interactions between ritonavir and quinine in healthy volunteers.

METHODSTen healthy volunteers were each given 600‐mg single oral doses of quinine alone, ritonavir alone (200 mg every 12 h for 9 days), and quinine in combination with ritonavir, in a three‐period pharmacokinetic nonrandomized sequential design study. Quinine was co‐administered with the 15th dose of ritonavir. Blood samples collected at predetermined time intervals were analysed for ritonavir, quinine and its major metabolite, 3‐hydroxyquinine, using a validated high‐performance liquid chromatography method.

RESULTSConcurrent ritonavir administration resulted in about fourfold increases in both theCmaxand AUCT[Cmax2.79 ± 0.22vs.10.72 ± 0.32 mg l−1, 95% confidence interval (CI) 7.81, 8.04; AUC 50.06 ± 2.52vs.220.47 ± 6.68 mg h−1 l−1, 95% CI 166.3, 175.3], a significant increase (P< 0.01) in the elimination half‐life (11.15 ± 0.80vs.13.37 ± 0.33 h, 95% CI 1.64, 2.77) and about a 4.5‐fold decrease in CL/F(12.01 ± 0.61vs.2.71 ± 0.09 l h−1) of quinine. Also, with ritonavir, there was a pronounced reduction of AUC(metabolite)/AUC(unchanged drug) ratio of quinine (1.35 ± 0.10vs.0.13 ± 0.02) along with a marked decrease inCmax(1.80 ± 0.12vs.0.96 ± 0.09 mg l−1) and AUC0–48h(62.80 ± 6.30vs.25.61 ± 2.44 mg h−1 l−1) of the metabolite. Similarly, quinine caused modest but significant increases (P< 0.01) in theCmax, AUC and eliminationT½of ritonavir.

CONCLUSIONSDownward dosage adjustment of quinine appears necessary when concurrently administered with ritonavir.
Potential genetic risk factors in angiotensin‐converting enzyme‐inhibitor‐induced angio‐oedema
Authors: Bas Murat , Hoffmann Thomas K. , Tiemann Bernd , Dao Vu Thao‐Vi , Bantis Christos , Balz Vera , Schultz‐Coulon Hans‐Jürgen , Stark Thomas , Schuler Patrick , Greve Jens , Ivens Katrin , Bier Henning , Kojda Georg
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Angiotensin‐converting enzyme inhibitor (ACEi)‐induced angio‐oedema is an underestimated clinical life‐threatening problem.

• The incidence of this non‐allergic, bradykinin‐induced drug side‐effect is 1 : 4000.

• Although most ACEi‐treated patients probably have an increased bradykinin plasma concentration, only 0.5% of them develop an angio‐oedema and nothing is known about potential risk factors.

WHAT THIS STUDY ADDS

• In our attempt to elucidate the unpredictable character of ACEi‐induced angio‐oedema, we investigated bradykinin B2 receptor 2/3 and c.C181T polymorphisms as well as the ACE insertion/deletion polymorphism in combination with serum ACE activity in 65 patients.

• ACE insertion/deletion and bradykinin B2 receptor polymorphisms are not involved in the development of ACEi‐induced angio‐oedema.

• Further studies should be carried out to clarify whether a combination of these polymorphisms might be a risk factor for ACEi‐induced angio‐oedema.

AIMS

The pathophysiology of angiotensin‐converting enzyme inhibitor (ACEi)‐induced angio‐oedema remains unclear. We have investigated the impact of ACE insertion/deletion (I/D) polymorphism in combination with serum ACE activity as well as the bradykinin B2 receptor 2/3 and c.C181T polymorphisms.

METHODS

We analysed the ACE I/D as well as bradykinin B2 (2/3 and C181T) receptor polymorphisms in 65 patients with documented episodes of ACEi‐induced angio‐oedema and 65 patients matched for age and sex being under ACEi treatment without history of angio‐oedema. Furthermore, we determined serum ACE activity in 47 of the 65 angio‐oedema patients 3 months after the angio‐oedema attack and compared these values with 51 healthy individuals (control II).

RESULTS

No risk association was identified between ACE I/D (I‐allele: 0.42 vs. 0.41, D‐allele: 0.58 vs. 0.59; P= 0.095) or bradykinin B2 receptor polymorphisms and the development of angio‐oedema during ACEi treatment. We found a trend of lower serum ACE activity in ACE I/I genotypes in comparison with control II (I/I: 28 ± 4.5 vs. 33 ± 1.8 U l−1; ID: 39 ± 3.3 vs. 41 ± 1 U l−1; DD: 56 ± 6.7 vs. 52 ± 1.8 U l−1; P= 0.9).

CONCLUSIONS

Our data suggest that polymorphism of ACE I/D and the bradykinin B2 receptor polymorphisms are not involved in the development of ACEi‐induced angio‐oedema when considered individually. Further studies should be carried out to clarify whether a combination of these polymorphisms might be a risk factor for ACEi‐induced angio‐oedema.
Drugs, money and society (Part II)
Authors: Walley Tom
Published: October 2009

Pharmacoeconomics started as marketing but has developed into a valuable tool in the fuller assessment of drug therapies. Its principles are now widely accepted, and many countries have government‐funded agencies with responsibility for its application, most notably the National Institute for Health and Clinical Excellence in England. Many clinical pharmacologists are active in this area, and the discipline itself is part of the clinical pharmacology trainees' curriculum. Further developments will include value‐based pricing and its use in cost sharing arrangements between health service and manufacturers.
Co‐administration of the JAK inhibitor CP‐690,550 and methotrexate is well tolerated in patients with rheumatoid arthritis without need for dose adjustment
Authors: Cohen Stanley , Zwillich Samuel H. , Chow Vincent , LaBadie Robert R. , Wilkinson Bethanie
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• CP‐690,550 is a novel JAK inhibitor in development as a therapy for rheumatoid arthritis.

• Methotrexate is the cornerstone of combination treatment for rheumatoid arthritis.

• The safety and tolerability of co‐administration of CP‐690,550 with methotrexate have not been addressed to date.

WHAT THIS STUDY ADDS

• This study in patients with rheumatoid arthritis shows that there are no clinically relevant effects on the pharmacokinetics of either drug following short‐term co‐administration.

• Co‐administration of CP‐690,550 and methotrexate was safe and well tolerated.

AIMS

To investigate the effects of methotrexate (MTX) on the pharmacokinetics (PK) of CP‐690,550, a novel Janus kinase (JAK) inhibitor in development as a therapy for rheumatoid arthritis (RA), to determine the effects of multiple doses of CP‐690,550 on the PK of MTX, and to evaluate the short‐term safety and tolerability of co‐administration of CP‐690,550 and MTX.

METHODS

This was a fixed‐dose drug–drug interaction study. Twelve patients diagnosed with RA for at least 6 months were enrolled in a Phase I, open‐label study of the PK of multiple doses of CP‐690,550 (30 mg b.i.d.) and single doses of MTX (15–25 mg per week).

RESULTS

All patients completed the study and were evaluated for PK and safety. CP‐690,550 exposure was not affected by co‐administration with MTX; AUC12 ratio (CP‐690,550 + MTX/CP‐690,550) was 103.06% [90% confidence interval (CI) 99.00, 107.29]. MTX exposure decreased by 10%; AUC12 ratio (CP‐690,550 + MTX/MTX) was 89.53% (90% CI 77.38, 103.57), which was not considered clinically significant. Co‐administration of CP‐690,550 and MTX was safe and well tolerated. There were no serious adverse events or withdrawals from the study and there was no trend in the incidence or severity of adverse events across treatments.

CONCLUSIONS

Co‐administration of CP‐690,550 and MTX was safe and well tolerated. There was no clinically significant effect on the PK profile of either drug. Therefore, dose adjustments should not be required when co‐administering CP‐690,550 and MTX.
Misdiagnosis and mistreatment of a common side‐effect – angiotensin‐converting enzyme inhibitor‐induced cough
Authors: Vegter Stefan , De Jong‐van den Berg Lolkje T. W.
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Dry cough is a common and well‐documented side‐effect of angiotensin‐converting enzyme inhibitor (ACEi) treatment.

• The recommended course of action in case of ACE‐induced cough is substitution of the ACEi with other antihypertensive agents.

• Misdiagnosis and mistreatment of ACEi‐induced cough has not been studied before.

WHAT THIS STUDY ADDS

• In the general population, a significant and clinically relevant proportion of patients with ACE‐induced cough are treated with antitussive agents.

• These results suggest misdiagnosis and mistreatment of a well‐known side‐effect.

• The estimated frequency of antitussive treatment of ACEi‐induced cough is 15%.

AIMS

Angiotensin‐converting enzyme inhibitors (ACEi) are frequently prescribed for various cardiovascular and renal diseases. A common side‐effect of these drugs is a persistent dry cough. Physicians who fail to recognize a dry cough to be ACEi‐related may attempt to treat it with antitussive agents instead of recommended ACEi substitution. Prescription behaviour in the general population considering treatment of the side‐effect with antitussive agents has not been studied before.

METHODS

Drug dispensing data between 2000 and 2007 were retrieved from the IADB.nl database. A prescription sequence symmetry analysis was used to determine whether antitussive agents were prescribed more often following ACEi initiation than the other way around. A logistic regression model was fitted to determine predictors.

RESULTS

We identified 27 446 incident users of ACEi therapy. One thousand and fifty‐four patients were incident users of both ACEi and antitussives within a half‐year time span. There was an excess of patients being prescribed antitussive agents after ACEi initiation (703 vs. 351), adjusted sequence ratio 2.2 [confidence interval (CI) 1.9, 2.4]. Female patients were more likely to be prescribed antitussive agents following ACEi therapy initiation, odds ratio 1.4 (CI 1.1, 1.9), age and co‐medications were not significant predictors.

CONCLUSIONS

There was a significant and clinically relevant excess of patients receiving antitussives after ACEi initiation. The results suggest that cough as a side‐effect of ACEi is not recognized as being ACEi‐related or is symptomatically treated with antitussive agents instead of ACEi substitution. The estimated frequency of antitussive treatment of ACEi‐induced dry cough is 15%.
Time‐dependent inhibition (TDI) of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine–warfarin interaction
Authors: Fang Zhong‐Ze , Zhang Yan‐Yan , Ge Guang‐Bo , Huo Hong , Liang Si‐Cheng , Yang Ling
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Clinical cases reported to the Swedish adverse drug interactions register (SWEDIS) indicated that drug–drug interaction (DDI) existed when warfarin was co‐administered with noscapine.

• In vitrotesting with recombinant human enzyme showed that noscapine inhibited CYP3A4 and CYP2C9 with an IC50of around 1 µm.

• However, the clinical relevance of thesein vitrodata remains to be explored.

WHAT THIS STUDY ADDS

• Noscapine was demonstrated to be both a reversible inhibitor and a time‐dependent inhibitor to CYP3A4 and CYP2C9.

• DDI magnitude predicted from reversible inhibition and time‐dependent inhibition (TDI) kinetic parameters showed that the TDI might be a noteworthy factor resulting in clinical noscapine–warfarin interaction.

AIMS

To investigate the inhibition potential and kinetic information of noscapine to seven CYP isoforms and extrapolatein vivonoscapine‐warfarin interaction magnitude fromin vitrodata.

METHODS

The activities of seven CYP isoforms (CYP3A4, CYP1A2, CYP2A6, CYP2E1, CYP2D6, CYP2C9, CYP2C8) in human liver microsomes were investigated following co‐ or preincubation with noscapine. A two‐step incubation method was used to examinein vitrotime‐dependent inhibition (TDI) of noscapine. Reversible and TDI prediction equations were employed to extrapolatein vivonoscapine–warfarin interaction magnitude fromin vitrodata.

RESULTS

Among seven CYP isoforms tested, the activities of CYP3A4 and CYP2C9 were strongly inhibited with an IC50of 10.8 ± 2.5 µmand 13.3 ± 1.2 µm. Kinetic analysis showed that inhibition of CYP2C9 by noscapine was best fit to a noncompetitive type withKivalue of 8.8 µm, while inhibition of CYP3A4 by noscapine was best fit to a competitive manner withKivalue of 5.2 µm. Noscapine also exhibited TDI to CYP3A4 and CYP2C9. The inactivation parameters (KIandkinact) were calculated to be 9.3 µmand 0.06 min−1for CYP3A4 and 8.9 µmand 0.014 min−1for CYP2C9, respectively. The AUC of (S)‐warfarin and (R)‐warfarin was predicted to increase 1.5% and 1.1% usingCmaxor 0.5% and 0.4% using unboundCmaxwith reversible inhibition prediction equation, while the AUC of (S)‐warfarin and (R)‐warfarin was estimated to increase by 110.9% and 48.9% usingCmaxor 41.8% and 32.7% using unboundCmaxwith TDI prediction equation.

CONCLUSIONS

TDI of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine–warfarin interaction.
Growth differentiation factor 15 in anaemia of chronic disease, iron deficiency anaemia and mixed type anaemia
Authors: Theurl Igor , Finkenstedt Armin , Schroll Andrea , Nairz Manfred , Sonnweber Thomas , Bellmann‐Weiler Rosa , Theurl Milan , Seifert Markus , Wroblewski Victor J. , Murphy Anthony T. , Witcher Derrick , Zoller Heinz , Weiss Günter
Published: October 2009

Recently, the iron and erythropoiesis‐controlled growth differentiation factor 15 (GDF15) has been shown to inhibit the expression of hepcidin in β‐thalassaemia patients, thereby increasing iron absorption despite iron overload. To access the diagnostic and pathogenic impact of GDF15 in inflammatory anaemia the association of GDF15 expression with serum iron parameters and hepcidin was studied in patients suffering from iron deficiency anaemia (IDA), anaemia of chronic disease (ACD) and ACD subjects with true iron deficiency (ACD/IDA). GDF15 was significantly increased in both ACD and ACD/IDA, but not in IDA subjects as compared to controls. In contrast, hepcidin levels were significantly lower in IDA and ACD/IDA subjects than in ACD patients. IDA and ACD/IDA, but not ACD, showed an association between GDF15 and soluble transferrin receptor, an indicator of iron requirement for erythropoiesis. However, GDF15 did not correlate to hepcidin in either patient group. While GDF15 levels were linked to the needs for erythropoiesis and iron homeostasis in IDA, the immunity‐driven increase of GDF15 may not primarily affect iron homeostasis and hepcidin expression. This indicates that other ACD‐related factors may overcome the regulatory effects of GDF15 on hepcidin expression during inflammation.
Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy
Authors: Barahmani N. , Lopez A. , Babu D. , Hernandez M. , Donley S. E. , Duvic M.
Published: October 2009

Background. Alopecia areata (AA) is an organ-specific autoimmune disease characterized by folliculotropic T-cell infiltrates around anagen-stage hair follicles. The role of T helper (Th)1 and Th2 cytokines in the pathogenesis of AA have not been established.

Aim. To determine whether serum cytokine profiles define the severity of the AA phenotype or are affected by co-existent atopy.

Methods. In total, 17 serum cytokines were measured and compared in 269 patients with AA of varying severity with and without atopy and 18 unrelated controls.

Results. Of the 269 patients with AA, 96% had active disease and 54% were atopic. The disease phenotype was transient patchy AA in 27 patients, persistent patchy AA in 89 and alopecia totalis or alopecia universalis in 153. Levels of Th1, interleukin (IL)-1 receptor antagonist (ra) and IL-8 levels were higher in all patients with AA than in controls. IL-1α, IL-12 and tumour necrosis factor-α levels were higher in patients with AA and atopy than in patients with AA without atopy.

Conclusions. Increased Th1 serum cytokines (IL-2, IL-12 and interferon-γ) and IL-1ra levels are associated with AA regardless of disease severity or the presence of atopy.
Pemphigus herpetiformis: analysis of the autoantibody profile during the disease course with changes in the clinical phenotype
Authors: Lebeau S. , Müller R. , Masouyé I. , Hertl M. , Borradori L.
Published: October 2009

Background. Pemphigus herpetiformis (PH) is a rare dapsone-responsive variant of pemphigus, characterized by annular and vesiculopustular cutaneous lesions. Most PH serum samples contain autoantibodies against desmoglein (Dsg)1, but not Dsg3, and the presence of the latter is almost invariably associated with mucosal involvement, as predicted based on the ‘Dsg compensation theory’.

Methods. We describe a patient with features characteristic of PH with histologically eosinophilic spongiosis who repeatedly tested positive for anti-Dsg3 but not anti-Dsg1 autoantibodies by ELISA. To investigate whether the peculiar clinical phenotype was due to a distinct immunological profile, the patient’s serum was tested by ELISA and immunoblotting using recombinant forms of Dsg3.

Results. Serum samples were found to have low and high reactivity against the EC1 and the EC4 domains of Dsg3, respectively, whereas the autoantibodies belonged predominantly to the IgG1 and IgG4 subclasses. The overall immunological profile was typical of pemphigus vulgaris. The patient finally developed isolated oral erosions 22 months after initial presentation, without significant changes in the autoantibody profile and of the targeted antigenic sites.

Conclusions. Our patient presented features characteristic of PH. Although circulating anti-Dsg3 antibodies were present, the patient had only cutaneous involvement for a long period. Our findings indicate that the proposed Dsg compensation theory cannot always explain the clinical phenotype, changes in which may occur without apparent modification of the autoantibody profile and antibody specificity. Hence, additional factors, such as Fcγ-dependent neutrophil activation, may critically affect the clinical presentation of pemphigus.
Mucosal (oral and vulval) lichen planus in women: are angiotensin-converting enzyme inhibitors protective, and beta-blockers and non-steroidal anti-inflammatory drugs associated with the condition?
Authors: Clayton R. , Chaudhry S. , Ali I. , Cooper S. , Hodgson T. , Wojnarowska F.
Published: October 2009

Aim. To determine whether there is an association between the use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and nonsteroidal anti-inflammatory drugs (NSAIDS) in women with mucosal (oral and vulval) lichen planus (LP) compared with a control population.

Methods. This was a retrospective review of medical records in dedicated vulval and oral clinics in hospitals. The study population comprised 141 women with vulval LP and 106 women with oral LP. Medications taken at the time of diagnosis were recorded.

Results. Patients with mucosal LP were more likely to be on NSAIDS and beta-blockers, but less likely to be on ACE inhibitors compared with controls. All three groups were found to have an inverse relationship with ACE inhibitors, but no association was found between patients with oral LP and beta-blockers.

Conclusions. Beta-blockers and NSAIDS are associated with LP, suggesting that withdrawal of these drugs should be considered. Further studies are needed to confirm or refute the inverse relationship between mucosal LP and use of ACE inhibitors.
The profile of dermatological problems in primary care
Authors: Kerr O. A. , Tidman M. J. , Walker J. J. , Aldridge R. D. , Benton E. C.
Published: October 2009

Background. Cutaneous disease is thought to account for 10–15% of patient consultations with general practitioners, but relatively little is known about the demography of dermatological conditions in primary care.

Aim. To assess the proportion and diagnostic profile of dermatological conditions seen in primary care in the southeast of Scotland, and to draw comparisons with secondary dermatological care.

Methods. General practitioners in 13 general practices were asked to note all skin-related consultations during a 2-week period. The case notes of these patients were reviewed, and diagnosis and treatment was recorded. Patients who had consulted for the same skin disorder on ≥ 3 occasions during the previous year were invited for assessment by a consultant dermatologist. Where possible, the case notes from 10% of all consultations during the 2-week study period were examined to assess accuracy of recording.

Results. The percentage of consultations relating to cutaneous disorders varied between practices, ranging from 3% to 18.8%, with a mean of 8.4%. Eczema accounted for 22.5%, infections 20.3% and benign tumours for 11.4% of consultations with a dermatological basis. In contrast, in secondary care, benign tumours accounted for 23.8%, malignant tumours for 16.4% and eczema for 16.3% of dermatological consultations.

Conclusions. Dermatological disorders make up a significant proportion of general practitioners’ workload. The diagnostic profile of primary-care dermatology differs markedly from that of hospital practice. General practitioners may benefit from training specifically tailored to the common primary-care dermatological conditions.
Are dark-skinned people really protected from ultraviolet radiation?
Authors: Young A. L. , Levy S. , Nighland M. , Grossman R. , Silvers D. N. , Celebi J. T.
Published: October 2009

Background. Premature ageing of the skin (photoageing) results from the action of ultraviolet radiation (UVR) on skin. One of the histopathological findings of photoageing is the presence of solar elastosis in the dermis. Skin pigmentation is protective against UVR.

Aim. To evaluate the presence of solar elastosis in dark-skinned people.

Methods. Normal facial skin biopsies of 147 dark-skinned and 140 light-skinned people were examined histopathologically for solar elastosis. The degree of solar elastosis was graded on a five-point scale by a panel of dermatopathologists blinded to patient demographics.

Results. There were 112 of 140 (80%) light-skinned and 50 of 147 (34%) dark-skinned patients with high-grade solar elastosis. In the dark-skinned patient group, high-grade solar elastosis was seen in 29 of 61 (47.5%) Hispanic and 5 of 49 (10.2%) African American subjects.

Conclusions. Dark-skinned people are not completely protected from the effects of UVR.
c-Ski promotes skin fibroblast proliferation but decreases type I collagen: implications for wound healing and scar formation
Authors: Liu X. , Li P. , Chen X.-Y. , Zhou Y.-G.
Published: October 2009

Background. Accelerating wound healing is always accompanied by excessive scar formation. The focus in chronic wounds has been promoting the proliferation of tissue repair cells while decreasing collagen deposition. Smad3 null mice display more rapid wound closure and reduced scar formation. We hypothesized that c-Ski, acting as a co-repressor of transforming growth factor-β1/Smad3 in epithelial cells and as a complicated regulator of embryo fibroblast proliferation, may play such a role through modulation of skin fibroblast function.

Aim. To investigate the effect of c-Ski on skin fibroblast proliferation, cell-cycle progression, type I collagen secretion and myofibroblast differentiation. The potential involvement of Smad3 was also investigated.

Methods. Cultured rat skin fibroblasts were used. Immunocytochemistry and reverse transcription (RT)-PCR was used to examine the localization and expression of c-Ski. Plasmid transfection technology was used to produce c-Ski or/and Smad3 overexpression. Cell proliferation was analysed by 5-bromo-2-deoxyuridine incorporation; cell cycle by fluorescence-activated cell sorting; type I collagen expression by immunocytochemistry, RT-PCR and western blotting; and myofibroblast differentiation by western blotting.

Results. c-Ski was expressed in cultured skin fibroblasts. Overexpression of c-Ski was able to promote skin fibroblast proliferation and accelerate cell-cycle progression through inhibiting Smad3 activity. It also decreased type I collagen protein and mRNA expression through inhibiting Smad3 activity. It did not affect fibroblast–myofibroblast differentiation.

Conclusions. Because of the important role of fibroblast proliferation and collagen secretion in tissue repair and scar formation, we speculate that c-Ski may be a new candidate molecule for accelerating wound healing and decreasing scar formation.
Topical tazarotene vs. coal tar in stable plaque psoriasis
Authors: Kumar U. , Kaur I. , Dogra S. , De D. , Kumar B.
Published: October 2009

Background. The efficacy of topical tazarotene has not previously been compared with the conventional topical treatment of crude coal tar (CCT) in stable plaque psoriasis.

Aim. To assess the comparative efficacy and tolerability of topical tazarotene 0.1% gel and CCT 5% ointment in stable plaque psoriasis.

Methods. In this nonblinded side-to-side comparison study, patients with chronic stable plaque psoriasis, who had bilaterally symmetrical plaques on the limbs, applied 0.1% tazarotene gel on the right side and 5% CCT ointment on the left side once daily for 12 weeks followed by an 8-week treatment-free follow up period. Severity of psoriatic lesions and response to treatment was evaluated by scoring erythema, scaling and induration (ESI).

Results. Of 30 patients recruited, 27 could be assessed. In the per-protocol analysis, the mean percentage reduction in ESI score at the end of the treatment period was 74.15% ± 9.43 and 77.37% ± 10.93 with tazarotene and CCT, respectively (P > 0.05). A reduction in ESI score of > 75% was seen in 11 (40.74%) and 16 (59.26%) patients with tazarotene and CCT, respectively, at the end of 12 weeks. Side-effects were seen in 48.14% of patients treated with tazarotene, but in no patient treated with CCT.

Conclusions. Tazarotene 0.1% gel has comparable clinical efficacy to CCT 5% ointment. CCT ointment remains a cost-effective therapy for plaque psoriasis.
Demethylation of promoter regulatory elements contributes to CD70 overexpression in CD4+ T cells from patients with subacute cutaneous lupus erythematosus
Authors: Luo Y. , Zhao M. , Lu Q.
Published: October 2009

Background. Impaired methylation of T-cell DNA is thought to contribute to the development of systemic lupus erythematosus (SLE). CD70 (TNFSF7) is a B-cell costimulatory molecule that contributes to excessive B-cell stimulation in vitro and in vivo. CD70 is overexpressed in CD4+ T cells of patients with SLE, and DNA demethylation occurs in promoter sequences that regulate CD70 expression in SLE CD4+ T cells. However, it is unknown whether the expression and methylation of CD70 in CD4+ T cells are affected in patients with subacute cutaneous lupus erythematosus (SCLE).

Objective. To compare CD70 expression levels and the methylation status of the CD70 promoter region in CD4+ T cells from patients with SCLE and healthy controls.

Methods. We used real-time RT-PCR to compare messenger RNA levels of CD70 and flow cytometry to compare CD70 protein levels in CD4+ T cells from patients with SCLE and healthy controls. Bisulphite sequencing was used to determine the methylation status of the CD70 promoter region.

Results. CD70 is overexpressed at the surface of SCLE CD4+ T cells. Demethylation of the CD70 promoter region was seen in CD4+ T cells from patients with SCLE.

Conclusions. Demethylation of regulatory elements contributes to CD70 overexpression in CD4+ T cells of patients with SCLE.
Elastic interferometry for ocean bottom cable data: Theory and examples‡
Authors: Gaiser J.E. , Vasconcelos I.
Published: October 2009

Elastic imaging from ocean bottom cable (OBC) data can be challenging because it requires the prior estimation of both compressional‐wave (P‐wave) and shear‐wave (S‐wave) velocity fields. Seismic interferometry is an attractive technique for processing OBC data because it performs model‐independent redatuming; retrieving ‘pseudo‐sources’ at positions of the receivers. The purpose of this study is to investigate multicomponent applications of interferometry for processing OBC data. This translates into using interferometry to retrieve pseudo‐source data on the sea‐bed not only for multiple suppression but for obtaining P‐, converted P to S‐wave (PS‐wave) and possibly pure mode S‐waves. We discuss scattering‐based, elastic interferometry with synthetic and field OBC datasets.

Conventional and scattering‐based interferometry integrands computed from a synthetic are compared to show that the latter yields little anti‐causal response. A four‐component (4C) pseudo‐source response retrieves pure‐mode S‐reflections as well at P‐ and PS‐reflections. Pseudo‐source responses observed in OBC data are related to P‐wave conversions at the seabed rather than to true horizontal or vertical point forces. From a Gulf of Mexico OBC data set, diagonal components from a nine‐component pseudo‐source response demonstrate that the P‐wave to S‐wave velocity ratio (VP/VS) at the sea‐bed is an important factor in the conversion of P to S for obtaining the pure‐mode S‐wave reflections.
Low‐frequency passive seismic experiments in Abu Dhabi, United Arab Emirates: implications for hydrocarbon detection
Authors: Ali Mohammed Y. , Berteussen Karl A. , Small James , Barkat Braham
Published: October 2009

Low‐frequency passive seismic experiments utilizing arrays of 3‐component broadband seismometers were conducted over two sites in the emirate of Abu Dhabi in the United Arab Emirates. The experiments were conducted in the vicinity of a producing oilfield and around a dry exploration well to better understand the characteristics and origins of microtremor signals (1–6 Hz), which had been reported as occurring exclusively above several hydrocarbon reservoirs in the region.

The results of the experiments revealed that a strong correlation exists between the recorded ambient noise and observed meteorological and anthropogenic noises. In the frequency range of 0.15–0.4 Hz, the dominant feature is a double‐frequency microseism peak generated by the non‐linear interactions of storm induced surface waves in the Arabian Sea. We observed that the double‐frequency microseism displays a high variability in spectral amplitude, with the strongest amplitude occurring when Cyclone Gonu was battering the eastern coast of Oman; this noise was present at both sites and so is not a hydrocarbon indicator. Moreover, this study found that very strong microtremor signals in the frequency range of 2–3 Hz were present in all of the locations surveyed, both within and outside of the reservoir boundary and surrounding the dry exploration well. This microtremor signal has no clear correlation with the microseism signals but significant variations in the characteristics of the signals were observed between daytime and nighttime recording periods that clearly correlate with human activity.

High‐resolution frequency‐wavenumber (f‐k) spectral analyses were performed on the recorded data to determine apparent velocities and azimuths of the wavefronts for the microseism and microtremor events. The f‐k analyses confirmed that the double‐frequency microseism originates from wave activity in the Arabian Sea, while the microtremor events have an azimuth pointing towards the nearest motorways, indicating that they are probably being excited by traffic noise. Results drawn from particle motion studies confirm these observations. The vertical‐to‐horizontal spectral ratios of the data acquired in both experiments show peaks around 2.5–3 Hz with no dependence on the presence or absence of subsurface hydrocarbons. Therefore, this method should not be used as a direct hydrocarbon indicator in these environments. Furthermore, the analyses provide no direct evidence to indicate that earthquakes are capable of stimulating the hydrocarbon reservoir in a way that could modify the spectral amplitude of the microtremor signal.
Shrub expansion may reduce summer permafrost thaw in Siberian tundra
Authors: BLOK D. , HEIJMANS M. M. P. D. , SCHAEPMAN‐STRUB G. , KONONOV A. V. , MAXIMOV T. C. , BERENDSE F.
Published: October 2009

Climate change is expected to cause extensive vegetation changes in the Arctic: deciduous shrubs are already expanding, in response to climate warming. The results from transect studies suggest that increasing shrub cover will impact significantly on the surface energy balance. However, little is known about the direct effects of shrub cover on permafrost thaw during summer. We experimentally quantified the influence of Betula nana cover on permafrost thaw in a moist tundra site in northeast Siberia with continuous permafrost. We measured the thaw depth of the soil, also called the active layer thickness (ALT), ground heat flux and net radiation in 10 m diameter plots with natural B. nana cover (control plots) and in plots in which B. nana was removed (removal plots). Removal of B. nana increased ALT by 9% on average late in the growing season, compared with control plots. Differences in ALT correlated well with differences in ground heat flux between the control plots and B. nana removal plots. In the undisturbed control plots, we found an inverse correlation between B. nana cover and late growing season ALT. These results suggest that the expected expansion of deciduous shrubs in the Arctic region, triggered by climate warming, may reduce summer permafrost thaw. Increased shrub growth may thus partially offset further permafrost degradation by future temperature increases. Permafrost models need to include a dynamic vegetation component to accurately predict future permafrost thaw.
Multiscale analysis of temporal variability of soil CO2 production as influenced by weather and vegetation
Authors: VARGAS RODRIGO , DETTO MATTEO , BALDOCCHI DENNIS D. , ALLEN MICHAEL F.
Published: October 2009

Ecosystem processes are influenced by weather and climatic perturbations at multiple temporal scales with a large range of amplitudes and phases. Technological advances of automated biometeorological measurements provide the opportunity to apply spectral methods on continuous time series to identify differences in amplitudes and phases and relationships with weather variation. Here we used wavelet coherence analysis to study the temporal covariance between soil CO2 production and soil temperature, soil moisture, and photosynthetically active radiation (PAR). Continuous (hourly average) data were acquired over 2 years among three vegetation types in a semiarid mixed temperate forest. We showed that soil temperature and soil moisture influence soil CO2 production differently at multiple periods (e.g. hours, days, weeks, months, years), especially after rain pulse events. Our results provide information about the periodicity of soil CO2 production among vegetation types, and provide insights about processes controlling CO2 production through the study of phase relationships between two time series (e.g. soil CO2 production and PAR). We tested the performance of empirical models of soil CO2 production using the continuous wavelet transform. These models, built around soil temperature and moisture, failed at multiple periods across the measured dates, suggesting that empirical models should include other factors that regulate soil CO2 production at different temporal scales. Our results add a new dimension for the analysis of continuous time series of biometeorological measurements and model testing, which will prove useful for analysis of increasing sensor data obtained by environmental networks.
El Niño, grazers and fisheries interact to greatly elevate extinction risk for Galapagos marine species
Authors: EDGAR GRAHAM J. , BANKS STUART A. , BRANDT MARGARITA , BUSTAMANTE RODRIGO H. , CHIRIBOGA ANGEL , EARLE SYLVIA A. , GARSKE LAUREN E. , GLYNN PETER W. , GROVE JACK S. , HENDERSON SCOTT , HICKMAN CLEVE P. , MILLER KATHY A. , RIVERA FERNANDO , WELLINGTON GERALD M.
Published: October 2009

Comparisons between historical and recent ecological datasets indicate that shallow reef habitats across the central Galapagos Archipelago underwent major transformation at the time of the severe 1982/1983 El Niño warming event. Heavily grazed reefs with crustose coralline algae (‘urchin barrens’) replaced former macroalgal and coral habitats, resulting in large local and regional declines in biodiversity. Following recent threat assessment workshops, a total of five mammals, six birds, five reptiles, six fishes, one echinoderm, seven corals, six brown algae and nine red algae reported from coastal environments in Galapagos are now recognized as globally threatened. The 2008 International Union for the Conservation of Nature (IUCN) Red List includes 43 of these species, while two additional species (Galapagos damsel Azurina eupalama and 24‐rayed sunstar Heliaster solaris) not seen for > 25 years also fulfil IUCN threatened species criteria. Two endemic species (Galapagos stringweed Bifurcaria galapagensis and the damselfish A. eupalama) are now regarded as probably extinct, while an additional six macroalgal species (Dictyota galapagensis, Spatoglossum schmittii, Desmarestia tropica, Phycodrina elegans, Gracilaria skottsbergii and Galaxaura barbata) and the seastar H. solaris are possibly extinct. The removal of large lobster and fish predators by artisanal fishing probably magnified impacts of the 1982/1983 El Niño through a cascade of indirect effects involving population expansion of grazing sea urchins. Marine protected areas with adequate enforcement are predicted to ameliorate but not eliminate ecosystem impacts caused by increasing thermal anomalies associated with El Niño and global climate change.
A histopathological study of the pulp of dogs’ teeth after induction of experimental pulp inflammation for different periods of time
Authors: SHAHRAVAN A. , GHODDUSI J. , ESLAMI B. , RATEGAR A.F.
Published: October 2009

The purpose of this study was to investigate the reaction of the pulp of dogs’ teeth after insertion of soft carious dentin from freshly extracted human teeth into the buccal cavities for short and longer periods of time. Forty‐seven mature lower and upper teeth were used in this study. On the middle of the buccal side of the teeth, 3 × 5 mm class ν cavities were prepared, soft carious dentin from freshly extracted human teeth was inserted into the floor of the cavity, and those were filled with glass ionomer. The dogs were killed after 7, 14, 28 and 47 days using vital perfusion techniques. Six‐micrometre sections were prepared and blindly evaluated by pathologist. An inflammatory reaction occurred in all of the samples. Moderate to severe inflammation were shown in all periods except in one in the 7‐day period. Insertion of soft carious dentin gathered from freshly extracted human teeth into class ν cavities produced in dogs’ teeth for 7 days is a reproducible process and could be used in study of pulp pathology.
Image analysis benchmarking methods for high‐content screen design
Authors: FULLER C.J. , STRAIGHT A.F.
Published: October 2009

The recent development of complex chemical and small interfering RNA (siRNA) collections has enabled large‐scale cell‐based phenotypic screening. High‐content and high‐throughput imaging are widely used methods to record phenotypic data after chemical and small interfering RNA treatment, and numerous image processing and analysis methods have been used to quantify these phenotypes. Currently, there are no standardized methods for evaluating the effectiveness of new and existing image processing and analysis tools for an arbitrary screening problem. We generated a series of benchmarking images that represent commonly encountered variation in high‐throughput screening data and used these image standards to evaluate the robustness of five different image analysis methods to changes in signal‐to‐noise ratio, focal plane, cell density and phenotype strength. The analysis methods that were most reliable, in the presence of experimental variation, required few cells to accurately distinguish phenotypic changes between control and experimental data sets. We conclude that by applying these simple benchmarking principles an a priori estimate of the image acquisition requirements for phenotypic analysis can be made before initiating an image‐based screen. Application of this benchmarking methodology provides a mechanism to significantly reduce data acquisition and analysis burdens and to improve data quality and information content.