bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of CYP3A4in vitrodata to predict clinical drug–drug interactions; predictions of compounds as objects of interaction
Authors: Youdim Kuresh A. , Zayed Aref , Dickins Maurice , Phipps Alex , Griffiths Michelle , Darekar Amanda , Hyland Ruth , Fahmi Odette , Hurst Susan , Plowchalk David R. , Cook Jack , Guo Feng , Obach R. Scott
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Numerous retrospective analyses have shown the utility ofin vitrosystems for predicting potential drug–drug interactions (DDIs).

• Prediction of DDIs fromin vitrodata is commonly obtained using estimates of enzymeKi, inhibitor and substrate concentrations and absorption rate for substrate and inhibitor.

WHAT THIS STUDY ADDS

• Using a generic approach for all test compounds, the findings from the current study showed the use of recombinant P450s provide a more robustin vitromeasure of P450 contribution (fraction metabolized,fm) than that achieved when using chemical inhibitors in combination with human liver microsomes, for the prediction of potential CYP3A4 drug–drug interactions prior to clinical investigation.

• The current study supported the use of SIMCYP®, a modelling and simulation software in utilizing thein vitromeasures in the prediction of potential drug–drug interactions.

AIMS

The aim of this study was to explore and optimize thein vitroandin silicoapproaches used for predicting clinical DDIs. A data set containing clinical information on the interaction of 20 Pfizer compounds with ketoconazole was used to assess the success of the techniques.

METHODS

The study calculated the fraction and the rate of metabolism of 20 Pfizer compounds via each cytochrome P450. Two approaches were used to determine fraction metabolized (fm); 1) by measuring substrate loss in human liver microsomes (HLM) in the presence and absence of specific chemical inhibitors and 2) by measuring substrate loss in individual cDNA expressed P450s (also referred to as recombinant P450s (rhCYP)) The fractions metabolized via each CYP were used to predict the drug–drug interaction due to CYP3A4 inhibition by ketoconazole using the modelling and simulation software SIMCYP®.

RESULTS

Whenin vitrodata were generated using Gentest supersomes, 85% of predictions were within two‐fold of the observed clinical interaction. Using PanVera baculosomes, 70% of predictions were predicted within two‐fold. In contrast using chemical inhibitors the accuracy was lower, predicting only 37% of compounds within two‐fold of the clinical value. Poorly predicted compounds were found to either be metabolically stable and/or have high microsomal protein binding. The use of equilibrium dialysis to generate accurate protein binding measurements was especially important for highly bound drugs.

CONCLUSIONS

The current study demonstrated that the use of rhCYPs with SIMCYP®provides a robustin vitrosystem for predicting the likelihood and magnitude of changes in clinical exposure of compounds as a consequence of CYP3A4 inhibition by a concomitantly administered drug.
Prevalence and treatment of isolated and concurrent hypertension and hypercholesterolaemia in the United Kingdom
Authors: MacDonald Thomas M. , Morant Steven V.
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The 1998 and 2003 Health Survey for England revealed a high prevalence of hypertension and hypercholesterolaemia in the population of England.

• Major changes in the reimbursement of primary care for the management of both hypertension and hypercholesterolaemia have occurred in the UK.

WHAT THIS STUDY ADDS

• Using a GP database we have examined the proportion of subjects diagnosed and treated for hypertension and hypercholesterolaemia over time. To examine the true population rates and primary care data we compared the results of the Health survey for England in both 1998 and 2003 with the recorded data on GP computers.

• Despite current guidelines, many patients with hypertension and/or hypercholesterolaemia are under‐treated and, even amongst those who are treated, many do not achieve their blood pressure and/or lipid targets.

• Although treatment rates in the UK have improved recently, particularly for lipid‐lowering therapies, they remain suboptimal.

AIMS

To determine the prevalence and treatment of hypertension, dyslipidaemia and both together in the UK between 1998 and 2006.

METHODS

We used The Health Improvement Network (THIN) a general practice‐based database from 1998 to 2006 and we compared the 1998 and 2003 data to that taken from the Health Survey for England (HSE) in 1998 and 2003.

RESULTS

The prevalence (treatment) of hypertension was 25.3% (11.4%) in 1998, 27.8% (15.1%) in 2003 and 26.9% (16.2%) in 2006 in THIN. In HSE it was 37.3% (9.6%) in 1998 and 32.9% (13.8%) in 2003. For dyslipidaemia the figures were 8.6% (1.9%), 18.5% (6.5%) and 24.4% (9.8%) for THIN and 67.8% (2.3%) and 74.9% (7.0%) for HSE. Concurrent hypertension and dyslipidaemia in THIN increased from 5.5% (1.1%) in 1998 to 13.5% (4.5%) in 2003 and 17.4% (7.1%) in 2006. The prevalence of both conditions was 30.6% (0.7%) in HSE in 1998 and 28.7% (3.1%) in 2003.

CONCLUSIONS

There has been a progressive improvement in the detection and treatment of hypertension, dyslipidaemia and both conditions together between 1998 and 2006. However, much still needs to be done to improve the diagnosis and treatment of hypertension, hypercholesterolaemia and concurrent hypertension and hypercholesterolaemia in the United Kingdom.
Physiological response of the copepod Pseudocalanus sp. in the Baltic Sea at different thermal scenarios
Authors: ISLA JOSÉ ALEJANDRO , LENGFELLNER KATHRIN , SOMMER ULRICH
Published: February 2008

We studied the physiological response of Pseudocalanus sp. under four different temperature elevation regimes: +0, +2, +4 and +6 °C above the decadal average temperature in the Western Baltic Sea. We measured fecal pellet (FP) production rates, which was taken as a proxy of ingestion, egg production (EPR) and respiration rates. Experiments lasted from mid‐February to end April, corresponding most of the observations to the postspring bloom phase. We combined small scale incubations with the use of big (ca. 1400 L) mesocosms, which have previously been shown to be appropriate when studying phyto‐ and zooplankton succession, and the water used for the incubations was taken from the mesocosm tanks. Given that the phytoplankton succession varied between the four thermal scenarios, we evaluated (excepting in the case of the respiration rates, where incubations were carried out using 0.2 μm filtered water) both the temperature and the associated food concentration effects. Respiration and ingestion rates were found to increase with temperature. As for EPR, they also increased with temperature during the bloom, but remained at low and constant values during the postbloom in all the four treatments due to the food limitation. Linked to the temperature rise, we also detected an increase in instantaneous mortality rates and a reduction in the net growth efficiency. Finally, we discuss the potential implications of our findings for the spring phyto‐ and zooplankton succession under the forecasted climate warming, as well as for the fisheries in the Baltic Sea, where Pseudocalanus sp. is a key species.
Scaling‐up knowledge of growing‐season net ecosystem exchange for long‐term assessment of North Dakota grasslands under the Conservation Reserve Program
Authors: PHILLIPS REBECCA L. , BEERI OFER
Published: February 2008

Scaling‐up knowledge of land‐atmosphere net ecosystem exchange (NEE) from a single experimental site to numerous perennial grass fields in the Northern Great Plains (NGP) requires appropriate scaling protocols. We addressed this problem using synoptic data available from the Landsat sensor for 10 growing seasons (April 15 to September 30) over a North Dakota field‐site, where we continuously measured CO2 exchange using a Bowen Ratio Energy Balance (BREB) system. NEE observed during the growing season at our field‐site from 1997 to 2006 vacillated with drought and deluge, with net carbon (C) losses to the atmosphere in 2006. We used stepwise linear regression with 10 years of Landsat and NEE data to construct and validate a model for estimating grassland growing‐season NEE from field to landscape scales. Eighty‐nine percent of the variability in NEE was explained by year, live biomass, carbon : nitrogen ratio, day of image acquisition, and annual precipitation. We then applied this model on 20 620 ha of North Dakota perennial grass fields enrolled in the Conservation Reserve Program (CRP), including 1272 fields east of the Missouri River and 165 fields west‐river. Growing‐season NEE for individual CRP fields was highly variable from 1997 to 2006, ranging from −366 to 692 g C m−2 growing season−1. Mean annual growing‐season fluxes over 10 years for CRP fields located east‐river and west‐river were 317 g C m−2 growing season−1 and 239 g C m−2 growing season−1, respectively. Average cumulative growing‐season NEE modeled for fields east‐ and west‐river diverged from one another in 2002–2006, when west‐river fields received < 70% of the long‐term annual average precipitation during these years. Results indicate assessment of conservation practices on grassland CO2 exchange during the growing season can be remotely estimated at field and landscape scales under variable environmental conditions and should be followed up with similar, spatially explicit investigations of NEE during the dormant season.
Where did the northern peatland species survive the dry glacials: cloudberry (Rubus chamaemorus) as an example
Authors: Ehrich Dorothee , Alsos Inger Greve , Brochmann Christian
Published: February 2008

Aim  During the last ice age large parts of the north boreal and subarctic zones were covered by ice, while the climate in ice‐free regions of northern Asia was extremely cold and dry. The extensive peatlands of these zones with their characteristic vegetation developed at the beginning of the Holocene. We combine a phylogeographical approach with maps of pollen records to identify regions where Rubus chamaemorus, a plant of moist, peaty soils, was likely to grow during this period.

Location  Circumarctic/circumboreal.

Methods  Samples were collected from 45 locations throughout much of the range of R. chamaemorus and 398 plants were analysed with amplified fragment length polymorphism (AFLP). Estimates of diversity and differentiation, principal coordinates analysis and Bayesian clustering methods were used for the analysis of genetic data. Dated pollen records were retrieved from the European and the Global Pollen Databases.

Results  The plants from Sakhalin are highly divergent from the rest of the material and represent the previously described var. pseudochamaemorus. The main genetic division in R. chamaemorus sensu stricto is found in the Taymyr region in central Eurasia. Genetic diversity and the relative number of rare markers are highest in central Siberia and eastern Asia and decrease towards Europe and to a lesser extent eastwards through North America. Pollen dating back to the last ice age is found in central and eastern Siberia and Alaska. The maximum observed clone size is about 250 m, and more than one clone is found in nearly every local population.

Main conclusions  The genetic data are consistent with the pollen records and indicate that R. chamaemorus was growing in several areas of northern central Siberia and Beringia during the last glaciation. This finding suggests that sufficient humidity for this and other species of peaty soils was present locally in different parts of the generally dry ice‐free areas of northern Asia, as had been previously documented for Beringia. The AFLP data show that var. pseudochamaemorus, which is also morphologically quite divergent, clearly represents a distinct genetic entity.
Reconstructing the biogeographical history of two plant genera with different dispersion capabilities
Authors: Katinas Liliana , Crisci Jorge V.
Published: February 2008

Aim  The pappus is one of the most distinctive features of the genera belonging to the sunflower family, and is an efficient mechanism for dispersion by wind. The pappose Holocheilus (seven species) and the non‐pappose Panphalea (nine species) are two genera of the monophyletic subtribe Nassauviinae (Asteraceae, Mutisieae), which overlap in their areas of distribution. This paper aims to reconstruct the biogeographical histories that shaped the distribution of these two genera, which are phylogenetically and geographically related, but differ in their means of dispersion. Our initial expectation was that the dispersion capability of the pappus should be reflected in more dispersal events in Holocheilus than in Panphalea.

Location  South‐eastern Brazil, Paraguay, Uruguay and Argentina.

Methods  Morphological data were acquired from the literature and by analysis of specimens. Two cladistic analyses, one for Holocheilus and one for Panphalea, were based on morphological characters, and data matrices were analysed with the Fitch parsimony algorithm of paup. The ancestral distributions were reconstructed using diva ver. 1.1 according to the dispersal–vicariance optimization method.

Results  The Paranense‐fields were identified as the most likely ancestral area of Holocheilus and Panphalea. Biogeographical reconstruction of Holocheilus shows several dispersal events from the Paranense‐fields: two ancestral dispersal events to the Yungas, followed by vicariance events (Paranense‐fields/Yungas) and numerous terminal dispersals to the surrounding areas such as Chacoan, Pampean and Espinal. diva reconstruction of Panphalea distribution also shows frequent terminal dispersals, with no vicariant events, from the Paranense‐fields to the other areas: (1) to Espinal, Pampean‐Uruguayan, Pampean‐oriental; (2) to Paranense‐hills; (3) to Pampean‐Uruguayan; and (4) to Paranense‐pine lands.

Main conclusions  In the past, both genera probably originated in the Paranense‐fields area, which was subject to the dry and humid cycles of the Quaternary glaciations. Dispersal was the process that predominantly shaped the distribution of Panphalea and Holocheilus, with approximately the same number of dispersal events in both genera, despite differing ranges of dispersion. The main barriers to dispersal were the dry Cerrado and Chaco, the latter promoting vicariance in Holocheilus. The lack of a pappus in Panphalea was a limitation for its dispersion compared with Holocheilus.
Biogenesis of Fe/S proteins and pathogenicity: IscR plays a key role in allowing Erwinia chrysanthemi to adapt to hostile conditions
Authors: Rincon‐Enriquez Gabriel , Crété Patrice , Barras Frédéric , Py Béatrice
Published: February 2008

The Erwinia chrysanthemi genome is predicted to encode three systems, Nif, Isc and Suf, known to assist Fe/S cluster biogenesis and the CsdAE cysteine desulphurase. Single iscU, hscA and fdx mutants were found sensitive to paraquat and exhibited reduced virulence on both chicory leaves and Arabidopsis thaliana. Depletion of the whole Isc system led to a pleiotropic phenotype, including sensitivity to both paraquat and 2,2′‐dipyridyl, auxotrophies for branched‐chain amino acids, thiamine, nicotinic acid, and drastic alteration in virulence. IscR was able to suppress all of the phenotypes listed above in a sufC‐dependent manner while depletion of the Isc system led to IscR‐dependent activation of the suf operon. No virulence defects were found associated with csdA or nifS mutations. Surprisingly, we found that the sufC mutant was virulent against A. thaliana, whereas its virulence had been found altered in Saintpaulia. Collectively, these results lead us to propose that E. chrysanthemi possess the Fe/S biogenesis strategy suited to the physico‐chemical conditions encountered in its host upon infection. In this view, the IscR regulator, which controls both Isc and Suf, is predicted to play a major role in the ability of E. chrysanthemi to colonize a wide array of different plants.
Sources of verticillium wilt resistance in wild olive germplasm from the Mediterranean region
Authors: Colella C. , Miacola C. , Amenduni M. , D’Amico M. , Bubici G. , Cirulli M.
Published: February 2008

Fifty‐seven wild olive accessions collected from the Mediterranean basin were screened under greenhouse conditions for their resistance to verticillium wilt. Plants were root‐dip inoculated. One defoliating and one non‐defoliating isolate of Verticillium dahliae, both obtained from diseased plants in southern Italy, were used. Plants of the highly susceptible cv. Cima di Mola, frequently used as a rootstock in Apulia, were also included in this test. Disease reactions were evaluated on the basis of external symptoms, vascular browning and by calculating areas under disease progress curves (audpc). On the basis of audpc values and external symptom severity, accessions were grouped into four phenotypic groups: highly resistant, moderately resistant, susceptible and highly susceptible. Three accessions showed high resistance to both V. dahliae pathotypes. Forty resistant plants were selected from accessions that had shown the highest levels of resistance. Clones were obtained from each of these plants by in vitro micropropagation for further testing. Ten clones showed the resistance characteristics of their original mother plants, while others suffered greater levels of disease severity than their mother plants. Several new olive rootstocks were identified that were highly resistant to verticillium wilt and could be included in breeding programmes for resistance of olive to V. dahliae.
Overexpression of membrane‐associated acyl‐CoA‐binding protein ACBP1 enhances lead tolerance in Arabidopsis
Authors: Xiao Shi , Gao Wei , Chen Qin‐Fang , Ramalingam Sathishkumar , Chye Mee‐Len
Published: February 2008

In Arabidopsis thaliana, a family of six genes encodes acyl‐CoA‐binding proteins (ACBPs) that show conservation at the acyl‐CoA‐binding domain. They are the membrane‐associated ACBP1 and ACBP2, extracellularly targeted ACBP3, kelch‐motif‐containing ACBP4 and ACBP5, and 10‐kDa ACBP6. The acyl‐CoA domain in each of ACBP1 to ACBP6 binds long‐chain acyl‐CoA esters in vitro, suggestive of possible roles in plant lipid metabolism. We addressed here the use of Arabidopsis ACBPs in conferring lead [Pb(II)] tolerance in transgenic plants because the 10‐kDa human ACBP has been identified as a molecular target for Pb(II) in vivo. We investigated the effect of Pb(II) stress on the expression of genes encoding Arabidopsis ACBP1, ACBP2 and ACBP6. We showed that the expression of ACBP1 and ACBP2, but not ACBP6, in root is induced by Pb(II) nitrate treatment. In vitro Pb(II)‐binding assays indicated that ACBP1 binds Pb(II) comparatively better, and ACBP1 was therefore selected for further investigations. When grown on Pb(II)‐containing medium, transgenic Arabidopsis lines overexpressing ACBP1 were more tolerant to Pb(II)‐induced stress than the wild type. Accumulation of Pb(II) in shoots of the ACBP1‐overepxressing plants was significantly higher than wild type. The acbp1 mutant showed enhanced sensitivity to Pb(II) when germinated and grown in the presence of Pb(II) nitrate and tolerance was restored upon complementation using an ACBP1 cDNA. Our results suggest that ACBP1 is involved in mediating Pb(II) tolerance in Arabidopsis with accumulation of Pb(II) in shoots. Such observations of Pb(II) accumulation, rather than Pb(II) extrusion, in the ACBP1‐overexpressing plants implicate possible use of ACBP1 in Pb(II) phytoremediation.
Rice SVP‐group MADS‐box proteins, OsMADS22 and OsMADS55, are negative regulators of brassinosteroid responses
Authors: Lee Shinyoung , Choi Sang Chul , An Gynheung
Published: February 2008

Most short vegetative phase (SVP)‐group MADS‐box genes control meristem identity and flowering time. Among the three SVP‐group genes in rice, OsMADS47 has been reported as a negative regulator of brassinosteroid (BR) responses. Here, we investigated the functional roles of two close homologs, OsMADS22 and OsMADS55, by generating single, double and triple RNAi lines and overexpression lines. Analyses of the plants showed that their roles in regulating meristem identity are well conserved; however, the involvement of these genes in determining flowering time has diversified. Most importantly, OsMADS55 works as a major negative regulator of BR responses, and OsMADS22 functions to support OsMADS55. Whereas single OsMADS55 RNAi plants display weak BR responses in the lamina joint (LJ), OsMADS22‐OsMADS55 double and OsMADS22‐OsMADS47‐OsMADS55 triple RNAi plants manifest dramatic BR responses with regard to LJ inclination, coleoptile elongation and senescence. Stem elongation is also notably reduced in the double and triple RNAi plants, probably because of BR oversensitivity. Expression analyses indicate the diversified roles in age‐dependent BR responses. Altogether, our study demonstrates that all three rice SVP‐group genes work as negative regulators of BR responses, but that their spatial and temporal roles are diversified.
Intertriginous plasmacytosis with plasmoacanthoma: report of a typical case and review of the literature
Authors: Senol Mustafa , Ozcan Atilla , Aydin N. Engin , Hazneci Ersoy , Turan Nergiz
Published: February 2008

Clinical manifestations of benign (reactive) plasma cell proliferations of the skin and mucosa consist of a relatively rare and distinct group in dermatologic disorders. They have generally been named according to their localization. We report a typical case of mucocutaneous plasmacytosis located on intertriginous areas of the skin as well as mucosa with a perianal tumoral mass diagnosed as plasmoacanthoma. To our knowledge, this is the first detailed case report, at least in English literature.
Two courses of rituximab (anti‐CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris
Authors: Faurschou Annesofie , Gniadecki Robert
Published: February 2008

Background  Pemphigus vulgaris (PV) is a severe autoimmune blistering disease involving the skin and mucous membranes. The response to therapy varies greatly amongst patients and treatment may be challenging. Rituximab is a chimeric monoclonal antibody that selectively targets cell surface antigen CD20, thus depleting mature B cells in vivo.

Methods  We report the results of rituximab treatment in two patients with severe PV. In both patients, high‐dose oral prednisolone and adjuvant therapy with intravenous immunoglobulins and mycophenolate mofetil failed to control disease activity. Consequently, the patients were treated with two courses of four weekly intravenous infusions of rituximab (375 mg/m2) with a 6‐month interval.

Results  Clinical improvement was already noticeable 3–6 weeks after the first infusion. After the second course, complete remission was achieved. Oral prednisolone was reduced and treatment with mycophenolate mofetil was continued. The patients remained in full remission 6 months after the last rituximab infusion.

Conclusion  These cases suggest that two courses rather than a single course of rituximab may be a preferable mode of treatment. Rituximab should be considered as a promising treatment option for recalcitrant PV.
Extramedullary granulocytic sarcoma of the skin, mediastinum, and pericardium
Authors: Diab Mohammad , Coloe Jacquelyn , Bechtel Mark
Published: February 2008

A 27‐year‐old man, with a past history of developmental delay, presented on 18 November 2005 for the evaluation of an acute onset of multiple red–violaceous nodules on the head, neck, and trunk of 5 days’ duration. The patient had no associated fever, chills, weight loss, night sweats, chest pain, dyspnea, lymphadenopathy, or organomegaly. He had no previous history of malignancies. A biopsy indicated a diagnosis of leukemia cutis (Fig. 1). His initial complete blood count (CBC) was within normal limits. The 2‐week follow‐up revealed enlargement of the previous lesions and the development of new lesions (Fig. 2). By the third week, the patient had developed dyspnea, but with normal breath sounds and oxygen saturation. Chest computed tomography demonstrated a mediastinal mass measuring 16 × 5.2 cm and pericardial thickening (Fig. 3). The diagnosis of granulocytic sarcoma of the skin lesion and mediastinal mass was established on the basis of immunohistochemical stains, with positivity to CD43 and Leder's preparation and negativity to CD3, CD4, CD5, CD8, CD10, CD20, CD23, CD30, CD34, CD56, bcl‐1, terminal deoxynucleotidyl transferase (TdT), and granzyme. The bone marrow was negative for malignant cells. CBC and chemistry panel were all normal. Nevertheless, the patient experienced increased dyspnea and developed a pericardial effusion which required a pericardial window. Cytology of the pericardial fluid was consistent with granulocytic sarcoma. Once the diagnosis of granulocytic sarcoma was established, the patient started a regimen of cytarabine, daunorubicin, and etoposide. Despite this, the skin lesions and mediastinal mass showed minimal response. Repeat computed tomography showed a mediastinal mass measuring 14.5 × 4.4 cm. The patient's respiratory status required intubation and, 2 weeks later, his family requested that he be withdrawn from life support.

Immature myelocytic infiltrate in the dermis (hematoxylin and eosin, ×4)

image

Clinical image of granulocytic sarcoma

image

Computed tomography of the chest illustrating mediastinal pericardial involvement

image
Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid
Authors: Feng Suying , Wu Qinxue , Jin Peiying , Lin Lin , Zhou Wuqing , Sang Honggui , Shao Changgeng
Published: February 2008

Background  The 180‐kDa transmembrane hemidesmosomal protein (BPAG2) has been identified as an important autoantigen in bullous pemphigoid (BP). Using the NC16A domain as the antigenic target, a highly sensitive and specific enzyme‐linked immunosorbent assay (ELISA) for the detection of autoantibodies to BP180 was developed.

Aim  To investigate the correlation of clinical severity and ELISA indices in BP.

Methods  Antibody titers in the sera from 20 patients were measured using BP180NC16a‐ELISA, and an analysis of the correlation of ELISA indices with disease activity was performed. Serum was obtained from each patient with BP at least three times: before the initiation of treatment, during complete disease control just before the decrease in corticosteroid, and when the dosage of corticosteroid was successfully decreased to half the initial dose. Of the 20 patients, three showed recurrence at a later stage, caused by their decision to stop treatment; serum was obtained at the early stage of recurrence.

Results  ELISA indices were significantly decreased after successful therapy, although indirect immunofluorescence titers did not always show apparent correlations. Indices measured using BP180NC16a‐ELISA were well correlated with disease activity. Three patients decided to stop taking their medication; subsequently (within 1–2 weeks), blisters recurred, and the levels of antibodies to BP180 increased to close to those before the initiation of treatment.

Conclusion  BP180 antibody titers showed a closer correlation than indirect immunofluorescence titers to disease activity. The titer of BP180 antibody may be a useful tool for the evaluation of disease activity and for the assessment of the effectiveness of treatments in BP.
The effect of 50% glycolic acid on the percutaneous absorption of eutectic mixture of local anesthetics (EMLA): a study of the electrofulguration‐induced pain
Authors: Suswardana, MD  , Radiono Sunardi , Chusniyati Nafiah , Rosmelia, MD  , Widodo Wirohadidjojo Yohanes
Published: February 2008

Background  EMLA has a slow onset due to its limited percutaneous absorption into an intact skin, while Glycolic acid (GA) has been known to have the capability of disrupting the skin barrier function. To the best of our knowledge, the effect of 50% GA on the percutaneous absorption of EMLA has not been studied previously.

Methods  The study used a two‐step randomized double blind controlled trial involving 20 healthy subjects each. The first step compared the pain intensity upon applying GA and placebo for 4 minutes prior to EMLA occlusive application over time. Based on findings made in the first step, second step observation focused on the effect of occlusion on EMLA percutaneous absorption after GA application in minute 30 and 45. A second of 20 mA electrofulguration induced the pain, while modified Verbal Rating Scale (VRS) measured the pain intensity.

Results  Significant VRS difference (P < 0.05) between GA and placebo group was found in minute 15, 20, 30 and 45. However, no significant VRS difference was found after minute 60 (P = 0.420). Adequate cutaneous analgesia was achieved in minute 30 in the treatment (GA) group and in minute 45 in the placebo. There was no significant VRS difference between the occlusive and non‐occlusive group in minute 30 (P = 0.214) and minute 45 (P = 0.309).

Conclusion  Administering 50% GA prior to EMLA application enhances percutaneous absorption of EMLA, which accelerates the onset of adequate cutaneous analgesia, even without using an occlusive dressing.
Acute localized exanthematous pustulosis (ALEP) caused by amoxicillin–clavulanic acid
Authors: Betto Paola , Germi Lerica , Bonoldi Emanuela , Bertazzoni Marina
Published: February 2008

A 40‐year‐old woman was admitted to the hospital for an acute outbreak of multiple pustular lesions with an underlying erythematous base affecting cheeks and chin. These lesions were referred to as “aching”. The patient had been taking amoxicillin‐clavulanic acid (3 g a day) over the past three days for oral prophylaxis for dental treatment. Given the possible allergic reaction to the drug administered and the extension of the pustular lesions over all face and neck during the following four days, we replaced the amoxicillin‐clavulanic acid with another antibiotic with wide range (ciprofloxacin). Resolution of the pustular lesions occurred within ten days and was accompanied by light scarring and pigmentation. On the basis of the close relationship between the administration of amoxicillin‐clavulanic acid and the development of the disease, in combination with a rapid, acute resolution as soon as this treatment was interrupted, and all the histologic findings, we consider this to be an unusual type of acute generalized pustular eruption (AGEP) recently defined as acute localized pustular eruption (ALEP) due to amoxicillin‐clavulanic acid.
Treatment and outcomes for metastatic sebaceous cell carcinoma of the eyelid
Authors: Husain Amina , Blumenschein George , Esmaeli Bita
Published: February 2008

Objective  To report the management and outcomes in patients with metastatic eyelid sebaceous cell carcinoma.

Methods  The clinical records of four patients with metastatic eyelid sebaceous cell carcinoma treated between January 1999 and August 2006 were reviewed.

Results  The study included four women with a mean age of 66 years. Metastatic sites included the lung in three patients, regional lymph nodes in two, liver in two, and bone in one. Time from diagnosis of eyelid carcinoma to metastasis ranged from 0 to 62 months. Treatment of regional nodal metastasis consisted of complete neck dissection followed by radiation therapy. One patient developed lung metastasis 5 years after the diagnosis of eyelid tumor; she was treated with systemic chemotherapy followed by subtotal lung resection. Systemic chemotherapy was considered for two additional patients: in one, chemotherapy was deferred due to poor performance status and ongoing medical problems; and another patient died before chemotherapy could be started. The patient with bony metastasis was treated with radiation therapy to the spine. Two patients died during the study period. The follow‐up time from diagnosis of metastasis to last contact or death ranged from 1 month to 3 years (median of 21 months).

Conclusion  Eyelid sebaceous cell carcinoma can result in systemic metastasis and death. Metastasis can be discovered as late as 5 years after treatment of the eyelid carcinoma, warranting continued surveillance. Treatment of metastatic disease may include a combination of chemotherapy, radiation, and surgical neck dissection.
The association of dermatologist‐diagnosed and self‐reported skin diseases with skin‐related quality of life in Latino migrant farmworkers
Authors: Quandt Sara A. , Schulz Mark R. , Vallejos Quirina M. , Feldman Steven R. , Verma Amit , Fleischer Alan B. , Rapp Stephen R. , Arcury Thomas A.
Published: February 2008

Background  Skin diseases are known to affect the quality of life (QoL), but data to support this are based on clinical samples. Few data document the skin‐related QoL in the general population, and whether its association differs with self‐reported or dermatologist‐diagnosed skin ailments. Farmworkers are at high risk for skin diseases, and are an appropriate population in which to explore these associations.

Objectives  To compare the association between skin‐related QoL and workers’ self‐reports of skin conditions or dermatologist‐diagnosed skin diseases over the course of a work season.

Methods  Three hundred and four Latino farmworkers were recruited from 45 randomly selected residential sites in North Carolina, USA, for longitudinal surveillance. The participants were interviewed up to five times at 3‐week intervals and the reported skin problems and Dermatology Life Quality Index (DLQI) were recorded. Nine digital photographs were taken of each participant. A board‐certified dermatologist rated each for the presence of specific skin diseases.

Results  An impact of skin disease on QoL was reported in 16% of interviews. In multivariate analyses with self‐reported skin problems, feet or skin fungus, rash, itching, and poison ivy were predictors of QoL. Dermatologist‐diagnosed inflammatory diseases and pigmentary disorders were significant predictors of QoL. The association was stronger for self‐reported skin problems than for dermatologist‐diagnosed conditions.

Conclusions  In a population of farmworkers, skin problems had a clinically significant impact on QoL. Itch‐related conditions and cosmetic conditions, such as acne and melasma, were important determinants of QoL. Treatment for these conditions in this population may enhance QoL.
Characteristics of superficial fungal infections in the Riyadh region of Saudi Arabia
Authors: Abanmi Abdullah , Bakheshwain Saadia , El Khizzi Noura , Zouman Abdul Rahman , Hantirah Samir , Al Harthi Fahad , Al Jamal Mohammad , Rizvi Syeda Sadaf , Ahmad Mohammad , Tariq Mohammad
Published: February 2008

Background  The prevalence and characteristics of superficial fungal infections (SFIs) vary with climatic conditions, lifestyle, and population migration patterns. This study was undertaken to determine the characteristics of SFIs amongst patients visiting the dermatology clinic of Riyadh Military Hospital, Riyadh, Saudi Arabia, during the period 2003–2005.

Methods  One hundred and nineteen patients with confirmed SFI (37 males and 82 females), aged between 5 months and 67 years, were included in this study. The diagnosis of SFI was based on clinical presentation confirmed by laboratory analysis. The type of mycotic pathogen and the site of infection were recorded as a function of age and sex.

Results  Onychomycosis (40.3%) was the most frequent infection, followed by tinea capitis (21.9%), tinea pedis (16%), tinea cruris (15.1%), and tinea corporis (6.7%). Tinea capitis was most prevalent (15.1%) in children (male to female ratio, 1 : 1.57), whereas tinea pedis was most common (11.8%) in adults (male to female ratio, 1 : 2.5). Trichophyton mentagrophytes and Microsporum canis were the most common dermatophytes responsible for tinea infections, and T. mentagrophytes, Candida spp., and Aspergillus spp. were mainly responsible for onychomycosis.

Conclusion  The prevalence of SFI was twofold greater in females than males. Children were most commonly affected by tinea capitis, whereas adults generally suffered from tinea pedis. The frequency of onychomycosis was nearly three times higher in adults. This study clearly shows that SFIs are of concern in both genders and in all age groups.
Survey assessment of parental perceptions regarding head lice
Authors: Silva Lucía , Alencar Rúbia de Aguiar , Madeira Newton Goulart
Published: February 2008

Background  Head lice constitute a problem in children. Each year, numerous cases of pediculosis occur worldwide. Little work has been performed to evaluate the understanding, opinions, and actions of populations regarding head lice. These areas are important as they enable clinicians and educators to alert parents on how to avoid treatments that are innocuous or of high risk to patients.

Methods  A cross‐sectional study was performed by interviewing the heads of households of 100 randomly chosen residences within the study area.

Results  The results obtained showed that 13% were infested during the first week of the survey, and 86% in the 24 weeks prior to the study. The number of positive cases increased with increasing resident number, and decreased in families with parents with a higher educational level. Itching was the principal clinical manifestation and caused sleep compromise in 65% of respondents. Innocuous and unhealthy practices to combat infestation, such as the use of inflammables and home insecticides, were common.

Conclusion  The results showed that certain beliefs generated worry and confusion in parents, who blamed head lice as the cause of various health problems which were not due to this insect.
CLINICAL STUDY: Prolactin response to fenfluramine in abstinent, alcohol‐dependent patients
Authors: Porter Richard J. , Sellman Doug , Joyce Peter R. , Davies Julia , Frampton Chris
Published: February 2008

It has been suggested that serotonin (5HT) function is abnormal in alcoholics even during abstinence. The prolactin response to fenfluramine (PRF) is generally believed to reflect the activity of the 5HT system and has been previously used to investigate 5HT activity in a variety of conditions, including alcoholism. The origin of the cortisol (CORT) response to fenfluramine is less clear. The objectives of this paper are to examine the prolactin (PRL) and CORT response to dl‐fenfluramine in a large cohort of males with alcohol dependence who had been abstinent for 3 weeks, and to compare this with an age‐matched control group. Ninety‐four subjects with a DSM‐III‐R diagnosis of moderate to severe alcohol dependence who had been abstinent for 3 weeks, and 23 control subjects underwent neuroendocrine challenge with dl‐fenfluramine (10 mg per 10 kg body weight). PRL and CORT responses were measured. No significant difference was found in PRF between abstinent, alcoholic patients and controls (F = 2.7, d.f. = 1.115, P = 0.10). CORT response was significantly lower in abstinent alcoholics than in controls (F = 10.0, d.f. = 1.116, P = 0.002). The results suggest no clear difference in 5HT function between abstinent alcoholics and healthy controls. The reduced CORT response in abstinent alcoholics further supports evidence of hypofunction of the adrenocortical system in this group.
Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor
Authors: Cooper Ziva D. , Haney Margaret
Published: February 2008

Awareness of cannabis dependence as a clinically relevant issue has grown in recent years. Clinical and laboratory studies demonstrate that chronic marijuana smokers can experience withdrawal symptoms upon cessation of marijuana smoking and have difficulty abstaining from marijuana use. This paper will review data implicating the cannabinoid CB1 receptor in regulating the behavioral effects of Δ9‐tetrahydrocannobinol (THC), the primary psychoactive component of cannabis, across a range of species. The behavioral effects that will be discussed include those that directly contribute to the maintenance of chronic marijuana smoking, such as reward, subjective effects, and the positive and negative reinforcing effects of marijuana, THC and synthetic cannabinoids. The role of the CB1 receptor in the development of marijuana dependence and expression of withdrawal will also be discussed. Lastly, treatment options that may alleviate withdrawal symptoms and promote marijuana abstinence will be considered.
Preclinical ex vivo expansion of peripheral blood CD34+ selected cells from cancer patients mobilized with combination chemotherapy and granulocyte colony‐stimulating factor
Authors: Lorenzon D. , Mazzucato M. , Abbruzzese L. , Cilli M. , De Angeli S. , Degan M. , Mambrini G. , Piccardi F. , Rupolo M. , Michieli M. , De Marco L. , Gattei V. , Astori G.
Published: February 2008

Background and Objectives  Ex vivo peripheral blood progenitor cell (PBPC) expansion has been proposed as a strategy to increase the number of haematopoietic progenitors available for cell transplantation. We have expanded CD34+ cells from PBPCs obtained from four patients with haematological malignancies and one patient with an Ewing's sarcoma.

Materials and Methods  Cells were expanded in the Dideco ‘Pluricell system’. After 12 days in culture, we evaluated cell phenotype, total nucleated cells, CD34+ fold increase, cell apoptosis and colony assay of expanded cells. Cell engraftment has been evaluated by transplanting two groups of irradiated non‐obese diabetic/severe combined immunodeficient (NOD‐SCID) mice with expanded and non‐expanded cell populations.

Results  Total nucleated cells and CD34+ cells increased 59·5 and 4·0 times, respectively. The expanded cells were mainly constituted of myeloid and megakaryocytic cells. A significant increase in the number of colony‐forming unit–granulocyte macrophage (CFU‐GM) was observed in the CFU assay. Ten mice transplanted with expanded cells showed a best overall survival (80%) compared to 10 mice transplanted with non‐expanded cells (20%). Human CD45+ cells were detected by flow cytometry and polymerase chain reaction in bone marrow and spleen of transplanted animals. The relative low engraftment level obtained with the expanded cells suggests a loss of SCID repopulating cells maybe due to cell differentiation during expansion.

Conclusions  We have demonstrated the feasibility of the ex vivo expansion of mobilized PBPCs from cancer patients, evidencing a clonal expansion of CFUs and the ability of the expanded cells to engraft the bone marrow and spleen of immunosuppressed mice. The differentiation of the CD34+ stem cell compartment could be further minimized by ameliorating the expansion conditions.
Shifting Mosaics in Grazed Woodlands Driven by the Alternation of Plant Facilitation and Competition
Authors: Olff H. , Vera F. W. M. , Bokdam J. , Bakker E. S. , Gleichman J. M. , de Maeyer K. , Smit R.
Published: February 2008

Abstract: Free‐ranging large grazers, such as cattle and horses, are increasingly reintroduced to former agricultural areas in Western Europe in order to restore natural and diverse habitats. In this review we outline mechanisms by which large grazers induce and maintain structural diversity in the vegetation (mosaics of grasslands, shrub thickets and trees). This variation in vegetation structure is considered to be important for the conservation of biodiversity of various plant and animal groups.

The process of spatial association with unpalatable plants (as‐sociational resistance) enables palatable plants to establish in grasslands maintained by large grazers. In this way, short unattractive (thorny, low quality or toxic) species facilitate taller unattractive shrubs, which facilitate palatable trees, which in turn outshade the species that facilitated their recruitment. Established trees can, therefore, not regenerate under their own canopy, leading to cyclic patch dynamics. Since this cyclic dynamic occurs on a local scale, this contributes to shifting mosaics. The mechanisms involved in creating and maintaining the resulting shifting mosaics are described for temperate flood‐plain and heathland ecosystems, including the effects on nutrient transport within grazed landscapes. How grazing leads to shifting mosaics is described in terms of plant functional types, allowing potential generalisation to other ecosystems.

The resulting interaction web of grasses, unpalatable forbs and shrubs, palatable light‐demanding trees and shade‐tolerant trees is discussed, and was found to contain various interesting direct and indirect effects. The key process contributing to spatial diversity in vegetation structure is the alternation of positive (facilitation) interactions between plant species at one life cycle stage, and competitive displacement at another stage. Grazing thus causes directional successional sequences to change to shifting mosaics. The implications of this theory for nature conservation are discussed, including the relevant management problems, possible choices and practical solutions.

We conclude that the theoretical framework outlined in this review provides helpful insights when coping with nature conservation issues in temperate woodland habitats.
One Morphotype, Three Physiotypes: Sympatric Species of Clusia with Obligate C3 Photosynthesis, Obligate CAM and C3‐CAM Intermediate Behaviour
Authors: Lüttge U.
Published: February 2008

Abstract: Among about 150 species of the genus of Clusia, morphologically very similar neotropical shrubs and trees, 20 have been studied ecophysiologically and 39 original publications were screened here for key data on the potential performance of the various species. I have collected data on carbon isotope discrimination (873C), day‐night oscilliations of malate (Amal), citrate (Acitr) and titratable protons (AH), maximum rates of net CO2 exchange in the dark (Dark Jco2) and in the light (Light Jco2) apparent rate of photosynthetic electron transport at PS II (ETR), effective quantum yield of non‐cyclic electron transport at PS II (AF/F'm) at 1000 umol m‐2 s‐1 PPFD, and potential quantum yield of PS II of leaves adapted to short periods of darkness at midday (Fv/Fm midday) and after relaxation overnight (Fv/Fm predawn). The 20 species can be arranged from predominant C3 photosynthesis to principally CAM. There may be only a few bona fide obligatory CAM species in the genus, but it is doubtful if there are obligatory C3 species. The data were then used to provide comparisons of intrinsic capabilities for Clusia species occurring sympatrically at two sites each, in Brazil and Venezuela. No clear advantage of CAM emerges from these comparisons under the stress of high insolation and low water availability at these sites. Different Clusia species are successful in different ways and with different intrinsic ecophysiological capacities. The conventional expectations in CAM as a drought and light stress adaptation are confounded in Clusia to the extent that on some occasions C3 photosynthesis seems to be the superior strategy. However, it appears, that C3/CAM plasticity which is so widespread in the genus, with many species and potentially rapid speciation, allows a particularly wide ecological amplitude.