bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily versus intermittent application of high‐concentration tacalcitol ointment in combination with low‐dose cyclosporin for psoriasis vulgaris
Authors: ABE Masatoshi , SYUTO Tomoko , HASEGAWA Michiko , SOGABE Yoko , YOKOYAMA Yoko , ISHIKAWA Osamu
Published: March 2006

In this study, we aimed to compare the clinical effectiveness of highly‐concentrated tacalcitol ointment daily versus intermittent application in patients with psoriasis vulgaris who simultaneously took a low dose of cyclosporin. All the patients in both groups showed significant improvements, and the patients in the intermittent application group obtained more patient satisfaction in cost performance. The treatment cost of low‐dose cyclosporin and intermittent application of highly‐concentrated tacalcitol ointment was less than half of that of high‐dose cyclosporin and daily application of highly‐concentrated tacalcitol ointment. This preliminary study suggests that the combination therapy with low‐dose cyclosporin administration and intermittent application of highly‐concentrated tacalcitol is effective, safe and provides acceptable costs for the treatment.
Papulonecrotic tuberculid with spontaneous remission
Authors: MITSUISHI Tsuyoshi , IIDA Kazumi , KAWANA Seiji
Published: March 2006

We describe a 62‐year‐old Japanese woman who had skin lesions involving her extremities, chest and back that showed spontaneous remission. The skin lesions consisted of slightly atrophic scars and crusted, reddish or necrotic papules. A tuberculin test showed induration and bulla, which was regarded as strongly positivity. Histopathologically, a tuberculoid granuloma with necrosis was present in the upper dermis and the deep dermis, including the adipose tissues. Bacterial cultures were not positive from sputum, urine or stool, and the chest X‐P was also normal. After skin biopsy, all the lesions disappeared within 1 month. No relapse was noted in the entire body.
Contact dermatitis due to orchids (Cymbidium and Oncidium)
Authors: IWATA Masahiro , KANEKURA Takuro , GUSHI Akira , KANZAKI Tamotsu
Published: March 2006

A 64‐year‐old male who cultivated orchids as a hobby, had noticed itchy erythematous lesions on both hands since 6 months earlier. His eruptions had gradually worsened and scales and fissures had appeared. Although he was treated with topical corticosteroids by a doctor, his erythema showed no improvement. Patch tests with the orchids he cultivated, fertilizers, antiseptics and insecticides showed positive reactions to the stems of Cymbidium and Oncidium orchids. A diagnosis of contact dermatitis attributable to the cultivated orchids was made.
Primary cutaneous amyloidosis of the auricular concha: Case report and review of published work
Authors: SHIMAUCHI Takatoshi , SHIN Ji hyun , TOKURA Yoshiki
Published: March 2006

A 70‐year‐old Japanese female developed tiny papules on her bilateral ears 2 years previously. A histological study of a biopsy specimen revealed that amorphous materials were present in the widened dermal papillae. Because these materials were positive for both Congo red and Dylon, we diagnosed the lesion as primary cutaneous amyloidosis of the auricular concha. Immunohistochemically, the amyloid substance stained positively with 34βE12 (cytokeratin 1/5/10/14), suggesting that it had an epidermal origin. Seven reported cases of this unique disorder were also reviewed.
Crusted scabies in an adult T‐cell leukemia/lymphoma patient successfully treated with oral ivermectin
Authors: YONEKURA Kentaro , KANEKURA Takuro , KANZAKI Tamotsu , UTSUNOMIYA Atae
Published: March 2006

We report an adult T‐cell leukemia/lymphoma (ATL) patient whose crusted scabies was successfully treated with oral ivermectin. This 63‐year‐old man had previously been treated with oral prednisolone, sobuzoxane and etoposide for approximately 1 year. When he developed crusted scabies, he received two doses of oral ivermectin (200 µg/kg) 10 days apart and the concomitant topical application of crotamiton containing 30% benzyl benzoate. This produced remarkable results, suggesting that oral ivermectin should be considered for the treatment of crusted scabies even in immunocompromised patients. While ivermectin may be useful for treating intractable scabies, attention must be paid to the possible appearance of ivermectin‐resistant mites.
A case of infectious eccrine hidradenitis
Authors: OONO Takashi , MATSUURA Hironori , MORIZANE Shi , YAMASAKI Osamu , IWATSUKI Keiji
Published: March 2006

We report a case of “infectious” neutrophilic eccrine hidradenitis who developed papules on the upper arm and trunk. Histological findings revealed vacuolar degeneration and necrosis of epithelial cells in the eccrine sweat ducts and neutrophils that had migrated through ductal epithelium to the lumen. A microabscess was also seen in the eccrine sweat gland coil. Our patient had received no chemotherapy such as cytarabine. Gram‐positive cocci were present in the lesional eccrine duct indicating an infective origin of the disease. Human beta defensin‐2, one of epithelial antimicrobial peptides, was present in the lesional epidermis and eccrine duct.
Cutaneous ciliated cyst of the inguinal area in a man
Authors: LEE Joong Sun , KIM You Chan , LEE Eun So
Published: March 2006

Cutaneous ciliated cysts are rare, predominantly occurring on the lower extremities of young women. Most of them have been regarded as müllerian remnants. Cases in men are rarely reported. We report a case of a cutaneous ciliated cyst involving the inguinal area of a 56‐year‐old man and briefly review the published work.
Dose‐dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine: Possible contribution of nitric oxide‐associated oxidative DNA damage
Authors: Okazaki Kazushi , Ishii Yuji , Kitamura Yasuki , Maruyama Satoshi , Umemura Takashi , Miyauchi Makoto , Yamagishi Megumi , Imazawa Takayoshi , Nishikawa Akiyoshi , Yoshimura Yoshihiro , Nakazawa Hiroyuki , Hirose Masao
Published: March 2006

Dose‐dependent promotion effects of combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) on gastric carcinogenesis were examined in rats pretreated with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). Groups of 15 6‐week‐old F344 male rats were given 0.01% MNNG in their drinking water for 10 weeks to initiate carcinogenesis in the glandular stomach and a single intragastric administration of 100 mg/kg/bodyweight of MNNG by stomach tube at week 9 to initiate carcinogenesis in the forestomach. From week 11, they received either drinking water containing 0.05, 0.1 or 0.2% NaNO2 and a diet supplemented with 0.1 or 0.2% AsA in combination, each individual chemical alone or a basal diet until the end of week 42. In the forestomach, the incidence of hyperplasia was increased dose dependently by the treatment with NaNO2 alone. Incidences of neoplastic lesions were dramatically increased by the combined treatment with NaNO2 and AsA in a dose‐dependent manner, but AsA itself had no effect. In the glandular stomach, only toxicity and regenerative changes were increased by the high‐dose combination. In a second short‐term experiment conducted for sequential observation, necrosis and strong inflammation were found in the forestomach epithelium shortly after commencing combined treatment with 1.0% AsA and 0.2% NaNO2, followed by hyperplasia, whereas there were no obvious effects in the glandular stomach. In addition, after a 4 h treatment with 1.0% AsA and 0.2% NaNO2, a slight increase in the 8‐hydroxy‐deoxyguanosine levels in the forestomach epithelium was observed by high‐performance liquid chromatography and an electrochemical detection system, albeit without statistical significance. In vitro, electron spin resonance demonstrated nitric oxide formation during incubation with NaNO2 and AsA under acidic conditions. Thus, NaNO2 was demonstrated to exert promoter action in the forestomach, with AsA acting as a strong copromoter through cytotoxicity and regenerative cell proliferation, possibly mediated by oxidative DNA damage, but the combined treatment with NaNO2 and AsA had little influence on glandular stomach carcinogenesis. (Cancer Sci 2006; 97: 175 –182)
Novel orthotopic implantation model of human malignant pleural mesothelioma (EHMES‐10 cells) highly expressing vascular endothelial growth factor and its receptor
Authors: Nakataki Emiko , Yano Seiji , Matsumori Yuka , Goto Hisatsugu , Kakiuchi Soji , Muguruma Hiroaki , Bando Yoshimi , Uehara Hisanori , Hamada Hironobu , Kito Katsumi , Yokoyama Akihito , Sone Saburo
Published: March 2006

Malignant pleural mesothelioma (MPM) is closely related to exposure to asbestos, and a rapid increase in the number of MPM patients in Japan is estimated in the years 2010–2050. The purpose of the present study was to establish a clinically relevant animal model that shows human patient‐like progression of MPM. Here, we demonstrate that a human MPM cell line (EHMES‐10) inoculated orthotopically (thoracic cavity) into severe combined immunodeficiency (SCID) mice produces highly vascularized thoracic tumors with pleural dissemination and bloody pleural effusions by 5 weeks, suggesting a patient‐like progression of this cell line after orthotopic inoculation. EHMES‐10 cells overexpressed vascular endothelial growth factor (VEGF), a molecule responsible for malignant effusions, and its receptor. Treatment with cisplatin, but not gemcitabine, significantly inhibited the production of pleural effusions, but it was not effective for thoracic tumors, consistent with chemotherapy refractory characteristics of MPM in patients. Our patient‐like orthotopic model using EHMES‐10 cells overexpressing VEGF and its receptor may be useful for examining the molecular pathogenesis of MPM and may contribute to the development of novel treatment strategies for MPM. (Cancer Sci2006; 97: 183 –191)
Pharmacokinetics and pharmacodynamics of protein‐unbound docetaxel in cancer patients
Authors: Minami Hironobu , Kawada Kenji , Sasaki Yasutsuna , Igarashi Tadahiko , Saeki Toshiaki , Tahara Makoto , Itoh Kuniaki , Fujii Hirofumi
Published: March 2006

α1‐Acid glycoprotein, a plasma protein that binds docetaxel, is a significant determinant of the clearance and activity of docetaxel, but its serum levels in cancer patients are variable. This emphasizes the importance of investigating the pharmacokinetics of unbound drug rather than total drug in the plasma. In the present study, the pharmacokinetics and pharmacodynamics of unbound docetaxel were investigated in cancer patients. Docetaxel was infused over a 1‐h period in 69 patients. The concentration of unbound docetaxel was measured in the plasma ultrafiltrate at the end of infusion and the unbound fraction (fu) was calculated. The pharmacokinetics of total docetaxel in the plasma was investigated. The area under the concentration–time curve (AUC) of unbound docetaxel was calculated by multiplying fu by the AUC of total docetaxel. The peak concentration at the end of infusion (Cmax) and AUC of total and unbound drug were compared between patients who did or did not experience grade 4 neutropenia. The median of fu was 4.0%, ranging from 1.2 to 22.6% (5–95% percentile; 1.4–10.5%). Grade 4 neutropenia was observed in 24 patients. Although Cmax and AUC of total drug were not different in patients with or without grade 4 neutropenia, patients who experienced grade 4 neutropenia had significantly greater Cmax (92.3 vs 63.3 ng/mL, P = 0.01) and AUC (0.137 vs 0.104 µg × h/mL, P = 0.05) of unbound docetaxel. In a logistic regression analysis, the unbound Cmax and α1‐acid glycoprotein were determinants of grade 4 neutropenia. Pharmacokinetics of unbound drug rather than total drug is a better predictor of neutropenia for docetaxel. (Cancer Sci 2006; 97: 235–241)
Propagation of orographic barriers along an active range front: insights from sandstone petrography and detrital apatite fission‐track thermochronology in the intramontane Angastaco basin, NW Argentina
Authors: Coutand Isabelle , Carrapa Barbara , Deeken Anke , Schmitt Axel K. , Sobel Edward R. , Strecker Manfred R.
Published: March 2006

The arid Puna plateau of the southern Central Andes is characterized by Cenozoic distributed shortening forming intramontane basins that are disconnected from the humid foreland because of the defeat of orogen‐traversing channels. Thick Tertiary and Quaternary sedimentary fills in Puna basins have reduced topographic contrasts between the compressional basins and ranges, leading to a typical low‐relief plateau morphology. Structurally identical basins that are still externally drained straddle the eastern border of the Puna and document the eastward propagation of orographic barriers and ensuing aridification. One of them, the Angastaco basin, is transitional between the highly compartmentalized Puna highlands and the undeformed Andean foreland. Sandstone petrography, structural and stratigraphic analysis, combined with detrital apatite fission‐track thermochronology from a ∼6200‐m‐thick Miocene to Pliocene stratigraphic section in the Angastaco basin, document the late Eocene to late Pliocene exhumation history of source regions along the eastern border of the Puna (Eastern Cordillera (EC)) as well as the construction of orographic barriers along the southeastern flank of the Central Andes.

Onset of exhumation of a source in the EC in late Eocene time as well as a rapid exhumation of the Sierra de Luracatao (in the EC) at about 20 Ma are recorded in the detrital sediments of the Angastaco basin. Sediment accumulation in the basin began ∼15 Ma, a time at which the EC had already built sufficient topography to prevent Puna sourced detritus from reaching the basin. After ∼13 Ma, shortening shifted eastward, exhuming ranges that preserve an apatite fission‐track partial annealing zone recording cooling during the late Cretaceous rifting event. Facies changes and fossil content suggest that after 9 Ma, the EC constituted an effective orographic barrier that prevented moisture penetration into the plateau. Between 3.4 and 2.4 Ma, another orographic barrier was uplifted to the east, leading to further aridification and pronounced precipitation gradients along the mountain front. This study emphasizes the important role of tectonics in the evolution of climate in this part of the Andes.
Atmospheric nitrogen deposition in world biodiversity hotspots: the need for a greater global perspective in assessing N deposition impacts
Authors: PHOENIX GARETH K. , HICKS W. KEVIN , CINDERBY STEVE , KUYLENSTIERNA JOHAN C. I. , STOCK WILLIAM D. , DENTENER FRANK J. , GILLER KEN E. , AUSTIN AMY T. , LEFROY ROD D. B. , GIMENO BEN S. , ASHMORE MIKE R. , INESON PHILIP
Published: March 2006

Increased atmospheric nitrogen (N) deposition is known to reduce plant diversity in natural and semi‐natural ecosystems, yet our understanding of these impacts comes almost entirely from studies in northern Europe and North America. Currently, we lack an understanding of the threat of N deposition to biodiversity at the global scale. In particular, rates of N deposition within the newly defined 34 world biodiversity hotspots, to which 50% of the world's floristic diversity is restricted, has not been quantified previously. Using output from global chemistry transport models, here we provide the first estimates of recent (mid‐1990s) and future (2050) rates and distributions of N deposition within biodiversity hotspots. Our analysis shows that the average deposition rate across these areas was 50% greater than the global terrestrial average in the mid‐1990s and could more than double by 2050, with 33 of 34 hotspots receiving greater N deposition in 2050 compared with 1990. By this time, 17 hotspots could have between 10% and 100% of their area receiving greater than 15 kg N ha−1 yr−1, a rate exceeding critical loads set for many sensitive European ecosystems. Average deposition in four hotspots is predicted to be greater than 20 kg N ha−1 yr−1. This elevated N deposition within areas of high plant diversity and endemism may exacerbate significantly the global threat of N deposition to world floristic diversity. Overall, we highlight the need for a greater global approach to assessing the impacts of N deposition.
Soil‐atmospheric exchange of CO2, CH4, and N2O in three subtropical forest ecosystems in southern China
Authors: TANG XULI , LIU SHUGUANG , ZHOU GUOYI , ZHANG DEQIANG , ZHOU CUNYU
Published: March 2006

The magnitude, temporal, and spatial patterns of soil‐atmospheric greenhouse gas (hereafter referred to as GHG) exchanges in forests near the Tropic of Cancer are still highly uncertain. To contribute towards an improvement of actual estimates, soil‐atmospheric CO2, CH4, and N2O fluxes were measured in three successional subtropical forests at the Dinghushan Nature Reserve (hereafter referred to as DNR) in southern China. Soils in DNR forests behaved as N2O sources and CH4 sinks. Annual mean CO2, N2O, and CH4 fluxes (mean±SD) were 7.7±4.6 Mg CO2‐C ha−1 yr−1, 3.2±1.2 kg N2O‐N ha−1 yr−1, and 3.4±0.9 kg CH4‐C ha−1 yr−1, respectively. The climate was warm and wet from April through September 2003 (the hot‐humid season) and became cool and dry from October 2003 through March 2004 (the cool‐dry season). The seasonality of soil CO2 emission coincided with the seasonal climate pattern, with high CO2 emission rates in the hot‐humid season and low rates in the cool‐dry season. In contrast, seasonal patterns of CH4 and N2O fluxes were not clear, although higher CH4 uptake rates were often observed in the cool‐dry season and higher N2O emission rates were often observed in the hot‐humid season. GHG fluxes measured at these three sites showed a clear increasing trend with the progressive succession. If this trend is representative at the regional scale, CO2 and N2O emissions and CH4 uptake in southern China may increase in the future in light of the projected change in forest age structure. Removal of surface litter reduced soil CO2 effluxes by 17–44% in the three forests but had no significant effect on CH4 absorption and N2O emission rates. This suggests that microbial CH4 uptake and N2O production was mainly related to the mineral soil rather than in the surface litter layer.
High thermal acclimation potential of both photosynthesis and respiration in two lowland Plantago species in contrast to an alpine congeneric
Authors: ATKIN O. K. , SCHEURWATER I. , PONS T. L.
Published: March 2006

Thermal acclimation of photosynthesis and respiration can enable plants to maintain near constant rates of net CO2 exchange, despite experiencing sustained changes in daily average temperature. In this study, we investigated whether the degree of acclimation of photosynthesis and respiration of mature leaves differs among three congeneric Plantago species from contrasting habitats [two fast‐growing lowland species (Plantago major and P. lanceolata), and one slow‐growing alpine species (P. euryphylla)]. In addition to investigating some mechanisms underpinning variability in photosynthetic acclimation, we also determined whether leaf respiration in the light acclimates to the same extent as leaf respiration in darkness, and whether acclimation reestablishes the balance between leaf respiration and photosynthesis. Three growth temperatures were provided: constant 13, 20, or 27°C. Measurements were made at five temperatures (6–34°C). Little acclimation of photosynthesis and leaf respiration to growth temperature was exhibited by P. euryphylla. Moreover, leaf masses per area (LMA) were similar in 13°C‐grown and 20°C‐grown plants of the alpine species. In contrast, growth at 13°C increased LMA in the two lowland species; this was associated with increased photosynthetic capacity and rates of leaf respiration (both in darkness and in the light). Alleviation of triose phosphate limitation and increased capacity of electron transport capacity relative to carboxylation were also observed. Such changes demonstrate that the lowland species cold‐acclimated. Light reduced the short‐term temperature dependence (i.e. Q10) of leaf respiration in all three species, irrespective of growth temperature. Collectively, our results highlight the tight coupling that exists between thermal acclimation of photosynthetic and leaf respiratory metabolism (both in darkness and in the light) in Plantago. If widespread among contrasting species, such coupling may enable modellers to assume levels of acclimation in one parameter (e.g. leaf respiration) where details are only known for the other (e.g. photosynthesis).
The distributions of a wide range of taxonomic groups are expanding polewards
Authors: HICKLING RACHAEL , ROY DAVID B. , HILL JANE K. , FOX RICHARD , THOMAS CHRIS D.
Published: March 2006

Evidence is accumulating of shifts in species' distributions during recent climate warming. However, most of this information comes predominantly from studies of a relatively small selection of taxa (i.e., plants, birds and butterflies), which may not be representative of biodiversity as a whole. Using data from less well‐studied groups, we show that a wide variety of vertebrate and invertebrate species have moved northwards and uphill in Britain over approximately 25 years, mirroring, and in some cases exceeding, the responses of better‐known groups.
Evaluating disease management programme effectiveness: an introduction to the regression discontinuity design
Authors: Linden Ariel , Adams John L. , Roberts Nancy
Published: March 2006

Although disease management (DM) has been in existence for over a decade, there is still much uncertainty as to its effectiveness in improving health status and reducing medical cost. The main reason is that most programme evaluations typically follow weak observational study designs that are subject to bias, most notably selection bias and regression to the mean. The regression discontinuity (RD) design may be the best alternative to randomized studies for evaluating DM programme effectiveness. The most crucial element of the RD design is its use of a ‘cut‐off’ score on a pre‐test measure to determine assignment to intervention or control. A valuable feature of this technique is that the pre‐test measure does not have to be the same as the outcome measure, thus maximizing the programme's ability to use research‐based practice guidelines, survey instruments and other tools to identify those individuals in greatest need of the programme intervention. Similarly, the cut‐off score can be based on clinical understanding of the disease process, empirically derived, or resource‐based. In the RD design, programme effectiveness is determined by a change in the pre–post relationship at the cut‐off point. While the RD design is uniquely suitable for DM programme evaluation, its success will depend, in large part, on fundamental changes being made in the way DM programmes identify and assign individuals to the programme intervention.
Measuring diagnostic and predictive accuracy in disease management: an introduction to receiver operating characteristic (ROC) analysis
Authors: Linden Ariel
Published: March 2006

Diagnostic or predictive accuracy concerns are common in all phases of a disease management (DM) programme, and ultimately play an influential role in the assessment of programme effectiveness. Areas, such as the identification of diseased patients, predictive modelling of future health status and costs and risk stratification, are just a few of the domains in which assessment of accuracy is beneficial, if not critical. The most commonly used analytical model for this purpose is the standard 2 × 2 table method in which sensitivity and specificity are calculated. However, there are several limitations to this approach, including the reliance on a single defined criterion or cut‐off for determining a true‐positive result, use of non‐standardized measurement instruments and sensitivity to outcome prevalence. This paper introduces the receiver operator characteristic (ROC) analysis as a more appropriate and useful technique for assessing diagnostic and predictive accuracy in DM. Its advantages include; testing accuracy across the entire range of scores and thereby not requiring a predetermined cut‐off point, easily examined visual and statistical comparisons across tests or scores, and independence from outcome prevalence. Therefore the implementation of ROC as an evaluation tool should be strongly considered in the various phases of a DM programme.
Referral to and discharge from cardiac rehabilitation: key informant views on continuity of care
Authors: Grace Sherry L. , Krepostman Suzan , Brooks Dina , Jaglal Susan , Abramson Beth L. , Scholey Pat , Suskin Neville , Arthur Heather , Stewart Donna E.
Published: March 2006

Objectives  To assess the system‐level barriers and facilitators of continuity of care from acute care to cardiac rehabilitation (CR), and from CR discharge to follow‐up with primary health care providers.

Method  Semi‐structured individual interviews with 24 key informants including CR staff, research scientists, policy makers, cardiologists and other doctors from a regional to international level were conducted regarding the processes of referral to and discharge from cardiac rehabilitation. Key informant interviews were audio taped, transcribed, and imported into QSR N6 software for Grounded analysis.

Results  Themes that emerged related to communication, referral and discharge processes, health care provider practices, inter‐ and intra‐institutional relationships, and alternative models of delivery to improve continuity.

Conclusions  Ramifications for enhancing referral of patients to beneficial CR services and follow‐up by primary care providers to ensure maintenance of functional and health‐related gains are discussed.
Quality and productive efficiency in simple laceration treatment
Authors: Kuwabara Kazuaki , Imanaka Yuichi , Ishizaki Tatsuro
Published: March 2006

Objectives  The surgical management and outcome of outpatient care for patients with simple lacerations were compared across three institutions. We examined the variations in wound infection rate, total charge and medical resource use in terms of prophylactic antibiotic prescription, frequency of outpatient visits and required days for stitch removal.

Design  Retrospective and consecutive chart review.

Study participants Patients receiving treatment for simple lacerations in the outpatient departments of three institutions in Japan between June 2000 and August 2001.

Outcome measures and method  The basic patient characteristics, treatment method for the laceration and incidence of wound infection were collected. Variations in the wound infection rate were examined across the institutions. We then examined the variations in the medical resource use and total charge for patients without wound infection among the institutions by multiple linear regression model.

Results  A total of 479 patients were reviewed. The proportion of patients with blunt injury, patients with simple lacerations to the head or face, and those with underlying medical disease were significantly different among the three institutions. The wound infection rate did not significantly differ (1.9% in Institution A, 1.3% in B, 3.0% in C, P = 0.555). The medical resource use for patients without wound infection was significantly different and small in Institution A.

Conclusion  We identified variations in the resource use for completing wound care among three institutions, whereas the wound infection rate revealed no significant difference among the institutions. There existed some room for improvement in the productive efficiency of simple laceration treatment.
In tobacco leaf epidermal cells, the integrity of protein export from the endoplasmic reticulum and of ER export sites depends on active COPI machinery
Authors: Stefano Giovanni , Renna Luciana , Chatre Laurent , Hanton Sally L. , Moreau Patrick , Hawes Chris , Brandizzi Federica
Published: March 2006

Trafficking of secretory proteins between the endoplasmic reticulum (ER) and the Golgi apparatus depends on coat protein complexes I (COPI) and II (COPII) machineries. To date, full characterization of the distribution and dynamics of these machineries in plant cells remains elusive. Furthermore, except for a presumed linkage between COPI and COPII for the maintenance of ER protein export, the mechanisms by which COPI influences COPII‐mediated protein transport from the ER in plant cells are largely uncharacterized. Here we dissect the dynamics of COPI in intact cells using live‐cell imaging and fluorescence recovery after photobleaching analyses to provide insights into the distribution of COPI and COPII machineries and the mechanisms by which COPI influences COPII‐mediated protein export from the ER. We found that Arf1 and coatomer are dynamically associated with the Golgi apparatus and that the COPII coat proteins Sec24 and Sec23 localize at ER export sites that track with the Golgi apparatus in tobacco leaf epidermal cells. Arf1 is also localized at additional structures that originate from the Golgi apparatus but that lack coatomer, supporting the model that Arf1 also has a coatomer‐independent role for post‐Golgi protein transport in plants. When ER to Golgi protein transport is inhibited by mutations that hamper Arf1‐GTPase activity without directly disrupting the COPII machinery for ER protein export, Golgi markers are localized in the ER and the punctate distribution of Sec24 and Sec23 at the ER export sites is lost. These findings suggest that Golgi membrane protein distribution is maintained by the balanced action of COPI and COPII systems, and that Arf1‐coatomer is most likely indirectly required for forward trafficking out of the ER due to its role in recycling components that are essential for differentiation of the ER export domains formed by the Sar1‐COPII system.
Improved knowledge and practices among end‐users of mother‐to‐child transmission of HIV prevention services in rural Zimbabwe
Authors: Orne‐Gliemann J. , Mukotekwa T. , Perez F. , Miller A. , Sakarovitch C. , Glenshaw M. , Engelsmann B. , Dabis F.
Published: March 2006

Objective  To evaluate the influence of a prevention of mother‐to‐child transmission of HIV advocacy and mobilization campaign on awareness and knowledge levels within the community.

Method  We used a knowledge, attitudes and practices survey to collect baseline data in November 2002 and again in July 2004 for evaluation purposes.

Results  A total of 351 women attending healthcare services were interviewed each time. The proportion of women aware of the service increased from 48.0% in 2002 to 82.8% in 2004 (OR = 4.9, 95% CI 3.3–7.3, P = 0.001). Exclusive breastfeeding was identified as a mother‐to‐child transmission risk factor by 27.1% in 2002 and by 55.8% of respondents in 2004 (OR = 2.9, CI 2.1–4.2, P = 0.001). Although most interviewees agreed that the prevention of sexual transmission of HIV was the best strategy for prevention of mother‐to‐child transmission of HIV (88.3% in 2002 and 96.4% in 2004), few reported having ever used a male condom (24.8% in 2002 vs. 29.8% in 2004, P = 0.16).

Discussion  Prevention of mother‐to‐child transmission of HIV strategies at both individual and community level were still insufficiently understood and applied. Targeted educational messages and communication for social change need to be combined. Knowledge, attitudes and practices surveys can be used to monitor programme progress.
Handwashing and risk of respiratory infections: a quantitative systematic review
Authors: Rabie Tamer , Curtis Valerie
Published: March 2006

Objective  To determine the effect of handwashing on the risk of respiratory infection.

Methods  We searched PubMed, CAB Abstracts, Embase, Web of Science, and the Cochrane library for articles published before June 2004 in all languages. We had searched reference lists of all primary and review articles. Studies were included in the review if they reported the impact of an intervention to promote hand cleansing on respiratory infections. Studies relating to hospital‐acquired infections, long‐term care facilities, immuno‐compromised and elderly people were excluded. We independently evaluated all studies, and inclusion decisions were reached by consensus. From a primary list of 410 articles, eight interventional studies met the eligibility criteria.

Results  All eight eligible studies reported that handwashing lowered risks of respiratory infection, with risk reductions ranging from 6% to 44% [pooled value 24% (95% CI 6–40%)]. Pooling the results of only the seven homogenous studies gave a relative risk of 1.19 (95% CI 1.12%–1.26%), implying that hand cleansing can cut the risk of respiratory infection by 16% (95% CI 11–21%).

Conclusions  Handwashing is associated with lowered respiratory infection. However, studies were of poor quality, none related to developing countries, and only one to severe disease. Rigorous trials of the impact of handwashing on acute respiratory tract infection morbidity and mortality are urgently needed, especially in developing countries.
Can malaria be controlled where basic health services are not used?
Authors: Unger Jean‐Pierre , D'Alessandro Umberto , Paepe Pierre De , Green Andrew
Published: March 2006

Objective  To assess the potential of integrating malaria control interventions in underused health services.

Methods  Using the Piot predictive model, we estimated malaria cure rates by deriving parameters influencing treatment at home and in health facilities from the best‐performing African malaria programmes and applying them to Yanfolila district, Mali.

Results  Without any malaria control intervention, the population cure rate is 8.4% with home treatment, but would be 13% if access to timely treatment were improved (as in Kenya). A further 3.2% of malaria patients could be cured in institutional settings with more sensitive diagnosis, timely start of treatment, better compliance (as in Uganda, Tanzania, Ghana) and 80% chloroquine efficacy. Applied in a setting where 7.6% of malaria patients seek institutional care, these assumptions would result in a total population cure rate of 14.5%. Increasing the health service user rate from 0.17 in Yanfolila to 0.95 new cases/inhabitant/year (as in Namibia) would result in half of all malaria patients attending professional services, raising the cure rate to 26.1%.

Conclusion  If malaria patients are to be treated and followed‐up early and appropriately, basic health services need to deliver integrated care and be attended by an adequate pool of users. Improved service user rates and case management can increase malaria cure rates far more than isolated control interventions can. This has implications for international policies endorsing a narrow disease‐based approach.
Growth of Parietaria debilis in fallow and in undisturbed areas
Authors: PURICELLI E , PAPA J C
Published: March 2006

Parietaria debilis is a dominant annual weed in many non‐tillage fallow and undisturbed areas in Argentina. Herbicides control P. debilis inconsistently. A study on the growth of P. debilis, in a fallow in a soyabean–maize rotation including glyphosate‐resistant cultivars and in an undisturbed area without crops or weed control, was conducted in the central soyabean area of Argentina. The biomass dynamics of all species in the community, as well as biomass, density and growth traits of P. debilis were assessed. Biomass of several species including P. debilis and total biomass were greater in undisturbed than in fallow plots in both years of the study. Diversity was greater in undisturbed plots in 2000, but no differences in diversity were observed in 2001. In both treatments, P. debilis emergence began in March and finished in October and density increased from March to May. High mortality occurred in June and July, particularly in undisturbed plots. In the fallow plots, no other tall weed species were present and light interception was higher in spring when fruit production was at its peak. Conversely, in the undisturbed plots, P. debilis was substantially taller and had greater leaf area due to lower light interception by the high canopy of the rest of the community. In fallow, P. debilis is favoured by single applications of glyphosate, because the herbicide eliminates competitors. Control, if applied, should be directed to both fallow and undisturbed environments, as the weed produces considerable numbers of seeds and can invade extensively managed areas.
Spray retention, foliar uptake and translocation of glufosinate and glyphosate in Ambrosia artemisiifolia
Authors: GRANGEOT M , CHAUVEL B , GAUVRIT C
Published: March 2006

Ambrosia artemisiifolia plants exhibit stomata on both leaf surfaces and three types of trichomes: (i) small (<50 μm) spherical or ovoid, (ii) medium‐sized (50–100 μm) and (iii) long (100–200 μm) and sharp. Only the long and sharp trichomes were stained with AgNO3, indicating the presence of hydrophilic domains. Epicuticular waxes appeared amorphous, consistent with high levels of spray retention. Glufosinate was readily taken up by A. artemisiifolia leaves, with maximum uptake of >80% of the applied label, and half maximum uptake being reached within 6 h. The foliar uptake of glyphosate was nearly complete and half of it was attained after 3 h. Glufosinate and glyphosate were ambimobile and their translocation out of the treated leaves amounted to 13–16% and 11–15% of the absorbed radioactive label respectively. Glufosinate was mainly directed to the apical developing tissues, with less amounts reaching the tissues below the treated leaves. Glyphosate was directed towards the sink tissues (apical developing tissues and roots). The sensitivity of A. artemisiifolia to glufosinate and glyphosate can be explained by high spray retention, rapid and important foliar uptake, and appreciable migration out of the parts of the plant hit by the spray.
Anti‐HLA alloantibodies in pediatric solid organ transplantation
Authors: Girnita Alin L. , Webber Steven A. , Zeevi Adriana
Published: March 2006

Abstract: An increasing number of studies demonstrate the clinical impact of preformed andde novoanti‐human leucocyte antigen alloantibody (HLA‐Ab) in solid organ transplantation (Tx). The screening of HLA‐Ab in candidates and transplant recipients has evolved over time, with continuous improvement in the sensitivity and specificity of assays for HLA‐Ab detection. Furthermore, histologic markers of complement activation pathways are currently implemented in the diagnosis of antibody‐mediated rejection (AMR). Therapeutic strategies, including depletion of HLA‐Ab and B cells, have allowed Tx across antibody barriers, or have rescued patients with AMR. The purpose of the present review is to summarize the state‐of‐the‐art of HLA‐Ab detection, clinical significance and therapeutic strategies in pediatric solid organ Tx.
Concomitant oral findings in children after cardiac transplant
Authors: Ansari Franziska , Ferring Verena , Schulz‐Weidner Nelly , Wetzel Willi‐Eckhard
Published: March 2006

Abstract:  Heart transplantations have been performed in the Centre for Paediatric Heart Surgery at the Justus Liebig University in Giessen (Germany) since 1988. For further consultation and therapy, some affected children subsequently present at the Polyclinic for Paediatric Dentistry. In all these cases problematic oral findings were diagnosed. It was the aim of this study to describe the different findings and to create a concept for avoiding them in the future. Altogether, 10 children with cardiac transplants (three girls, seven boys) were examined and, where necessary, treated. At the time they first presented, they were between 23 and 119 months old (average = 72.2) and had all been operated on (organ transplant) in the first 6 months of life. Each child showed evidence of gingival hyperplasia in the area of the front teeth, which was because of ongoing immunosuppression. In three patients, reactive mucosal caps avoided the age‐related penetration of a permanent incisor in the upper jaw. In addition, the primary teeth of six children were affected by caries; in two of these cases, the damage was because of the nursing‐bottle syndrome. The results show that any infant with cardiac transplant has to be subjected to careful dental examination and offered comprehensive medical care in cooperation with the competent centre for child cardiac surgery. Furthermore, the parents of such children should be informed prior to transplantation about the possibility of subsequent findings and how these findings can be either avoided or, if necessary, adequately treated.
Liver transplantation in children with Alagille syndrome: Indications and outcome
Authors: Englert Cornelia , Grabhorn Enke , Burdelski Martin , Ganschow Rainer
Published: March 2006

Abstract:  An AGS is a dominant inherited multisystem disorder caused by mutations in the Notch signaling pathway (JAG1). In our center, 5.3% of liver transplantations (OLT) are performed in children with AGS. Some of the affected children fulfilled criteria for OLT, despite the absence of liver cirrhosis. The aim of our present study was to evaluate the indications and outcome for OLT in children with this complex disorder as clear criteria are difficult to establish in clinical practice. A total of 37 patients were included in a retrospective analysis. Twenty‐four children underwent OLT for chronic end‐stage liver failure (n = 8) or symptomatic liver disease (n = 16). Patient survival post‐OLT was 91.7% after 1 yr, that of graft survival was 87.5%, respectively. Significant post‐transplant vascular complications included a mid‐aortic syndrome (n = 1) and severe lethal bleeding due to suspected vascular malformation (n = 1). Severe hypercholesterolemia (>800 mg/dL) and xanthomata resolved completely in affected patients. We conclude from our data that indications for OLT in AGS should be extended to patients with severe symptomatic liver disease, even in the absence of liver cirrhosis because of the significantly improved outcome after pediatric OLT in the last decade. Future studies must identify underlying mechanisms of hypercholesterolemia and vascular malformation.
Assessment of nephrotoxicity of high‐cumulative dose of liposomal amphotericin B in a pediatric patient who underwent allogeneic bone marrow transplantation
Authors: Cesaro Simone , Zignol Matteo , Burlina Alberto B. , Tridello Gloria , Visintin Gianluca , Messina Chiara
Published: March 2006

Abstract:  We describe a 9‐yr‐old boy who received the highest cumulative dose so far reported of liposomal amphotericin B.The patient underwent an allogeneic bone marrow transplantation (BMT) for adrenoleucodystrophy, after a conditioning regimen with busulfan, thiothepa and cyclophosphamide. Rabbit antithymoglobulin, cyclosporin and prednisone were used as prophylaxis against graft vs. host disease (GVHD). Post‐transplant Epstein–Bar‐virus‐related lymphoma was diagnosed on day +68 and was treated with donor‐derived lymphocytes. The patient developed a severe form of GVHD, and a progressive worsening of his neurological status because of progression of his underlying disease. Death from septic shock occurred 23 months after BMT. During prolonged hospitalization, 19 750 mg of liposomal amphotericin B, about 1000 mg/kg, were given for prophylactic or empirical therapeutic purposes without significant nephrotoxicity. This case suggests that liposomal amphotericin B is safe and well‐tolerated even if is administered for long periods and a cumulative dose fivefold greater than the nephrotoxic threshold of amphotericin B deoxycholate is achieved.
Option of pre‐emptive nephrectomy and renal transplantation for Bartter's syndrome
Authors: Chaudhuri Abanti , Salvatierra Oscar , Alexander Steven R. , Sarwal Minnie M.
Published: March 2006

Abstract:  Bartter's syndrome (BS) is an incurable genetic disease, with variable response to supportive therapy relating to fluid and electrolyte management. Poor control or therapy non‐compliance may result in frequent life threatening episodes of dehydration, acidosis and hypokalemia, with resultant adverse effects on patient quality of life (QOL). We report, for the first time, pre‐emptive bilateral native nephrectomies and successful renal transplantation, prior to the onset of ESRD, for severe, clinically brittle, neonatal BS, resulting in correction of metabolic abnormalities and excellent graft function. We propose that fragile BS should be considered as a possible indication for early native nephrectomies and pre‐emptive renal transplantation, procedures that results in a ‘cure’ for the underlying disease and significant improvements in patient QOL.
Cyclosporine drug monitoring with C0 and C2 concentrations in children with stable renal allograft function
Authors: Kalyoncu Mukaddes , Topaloglu Rezan , Bayrakci Umut , Bakkaloglu Aysin , Besbas Nesrin , Ozaltin Fatih , Bakkaloglu Mehmet
Published: March 2006

Abstract:  Cyclosporin A (CsA) has a narrow therapeutic window and necessitates monitoring of blood concentration. We aimed to evaluate trough (C0) and second hour (C2) level after ingestion of drug monitoring in renal allograft recipients. In this retrospective study, 12 children eight boys and four girls; mean age at transplantation 14.6 ± 3.7 yr (ranges: 7.0–19.0), mean age post‐transtplant 17.8 ± 4.9 yr (ranges: 9.0–24.0) who were transplanted >6 months were enrolled in this evaluation. Ten were recipients of a living related donor and two deceased donor grafts. While six children were receiving CsA, steroids and azathioprine, the other six received CsA, steroids and mycophenolate mofetil. Clinical course, blood pressure, renal and liver function tests were recorded. Mean C0 and C2 were 96.2 ± 59.5 and 504 ± 305.4 ng/mL respectively. Mean serum creatinine level was 1.2 ± 0.45 mg/dL and mean creatinine clearance (CrCl) was 89.2 ± 36.8 mL/min/1.73 m2. There was a correlation between serum creatinine level, CsA dose and C2 levels,whereas,there was no correlation between age, blood pressure, CrCl and C2 levels. However, no correlation was found between C0 levels and any of the above parameters. In conclusion, our data suggest that C2 levels are correlated better with dose and serum creatinine level.
Gastrointestinal tract ulcers in pediatric intestinal transplantation patients: Etiology and management
Authors: Sarkar Shampa , Selvaggi Gennaro , Mittal Naveen , Cenk Acar B. , Weppler Debbie , Kato Tomoaki , Tzakis Andreas , Ruiz Phillip
Published: March 2006

Abstract:  One of the observed complications in patients after intestinal transplantation is the occurrence of ulcers in the native or transplanted gastrointestinal tract. Previous reports have described the appearance of ulcers but have not described any systemic approach to accurately diagnose the etiology of the ulcer. We evaluated 112 intestinal transplantation patients at our institution, in which endoscopic examination identified ulcer formation in 11 patients. No common or defining demographic or clinical variables were found in the patients with ulcers. Biopsies were obtained from the ulcer edge as well as the intervening mucosa. The most common changes in the ulcers were compatible with post‐transplant lymphoproliferative disorder (PTLD), acute rejection, and viral infections. These changes could occur simultaneously and retrospective analysis showed that ulcers could have concomitant etiologies. Endoscopically directed biopsies of ulcer edges often displayed morphologic changes compatible with acute rejection of the graft. Some patients were treated for rejection based on the changes within the mucosa outside the ulcer bed, and they responded with resolution of the ulcers. Our findings demonstrate that PTLD and acute rejection are the most common causes of chronic ulcer formation and reinforce the concept that biopsy samples should be collected simultaneously from both the ulcer edge and intervening mucosa.