bluuebunny/crossref_metadata_2025 huggingface dataset:
Sperm competition within a dominance hierarchy: investment in social status vs. investment in ejaculates
Authors: TAMARA MONTROSE V. , Edwin Harris W. , MOORE A. J. , MOORE P. J.
Published: July 2008

There is increasing recognition that male–male competition can take many forms, but as yet the form is not predictable a priori. Many recent studies have focused attention on how males in disadvantaged mating roles compensate through sperm competition. However, mating systems in which subordinate males are reproductively suppressed, particularly through the stress of social interactions, may limit the ability of males to respond by increasing investment in sperm quality. We examined the interaction between social status and ejaculate tactics in Nauphoeta cinerea, a cockroach that has a mating system with well‐characterized dominance hierarchies. Both social experience with other males and social status influenced aspects of ejaculates. The stress of social interactions reduced the size of the ejaculate and number of sperm inseminated. In ejaculates formed prior to social experience, however, males that go on to become dominant inseminated more sperm than males that go on to become subordinate, suggesting innate differences among males. Our results show that though selection for increased success in sperm competition for subordinate males in a hierarchy can occur, both the traits and the way in which the balance between pre‐ and post‐copulatory strategies is negotiated will depend on specific details of the mating system. These details will include how the physiological effects of social interactions may limit selection through male–male competition.
Condition dependence of sexually dimorphic colouration and longevity in the ambush bug Phymata americana
Authors: PUNZALAN D. , COORAY M. , HELEN RODD F. , ROWE L.
Published: July 2008

Sexually selected traits that are costly are predicted to be more condition dependent than nonsexually selected traits. Assuming resource limitation, increased allocation to a sexually selected trait may also come at a cost to other fitness components. To test these predictions, we varied adult food ration to manipulate condition in the colour dimorphic bug, Phymata americana. We compared the degree of condition dependence in a sexually selected trait expressed in males to a nonsexually selected trait expressed in males and females. We also evaluated the effects of condition on longevity of both sexes. We found that the expression of these colour pattern traits was strongly influenced by both diet and age. As expected, the strength of condition dependence was much more pronounced in the sexually selected, male‐limited trait but the nonsexual trait also exhibited significant condition dependence in both sexes. The sexually selected male trait also exhibited a higher coefficient of phenotypic variation than the nonsexually selected trait in males and females. Diet had contrasting effects on male and female longevity; increased food availability had positive effects on female lifespan but these effects were not detected in males, suggesting that males allocated limited resources preferentially to sexually selected traits. These results are consistent with the expectation that optimal allocation to various fitness components differs between the sexes.
The expression of genes involved in the ergosterol biosynthesis pathway in Candida albicans and Candida dubliniensis biofilms exposed to fluconazole
Authors: Borecká‐Melkusová Silvia , Moran Gary P. , Sullivan Derek J. , Kucharíková Soňa , Chorvát Jr Dušan , Bujdáková Helena
Published: July 2008

The expression of the ERG1, ERG3, ERG7, ERG9, ERG11 and ERG25 genes in response to incubation with fluconazole and biofilm formation was investigated using reverse‐transcription PCR and real‐time PCR in Candida albicans and Candida dubliniensis clinical isolates. The viability of biofilm was measured using an 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide (XTT) reduction assay and confocal scanning laser microscopy (CSLM). Expression of the ERG11 gene was found to be low or moderate and it was regulated by fluconazole addition more so than by biofilm formation. Very low or non‐detectable expression of ERG1, ERG7 and ERG25 genes was detected in C. albicans. The expression of the ERG9 increased in the presence of fluconazole in some isolates. Following incubation with fluconazole, formation of biofilm by C. dubliniensis was coupled with up‐regulation of the ERG3 and ERG25 genes as have been observed previously in C. albicans. Planktonic cells of both Candida species released from biofilm displayed similar resistance mechanisms to fluconazole like attached cells. The XTT reduction assay and CSLM revealed that although incubation with fluconazole decreased the biofilm thickness, these were still comprised metabolically active cells able to disseminate and produce biofilm. Our data indicate that biofilm represents a highly adapted community reflecting the individuality of clinical isolates.
Carriage rate and virulence attributes of oral Candida albicans isolates from patients with oral lichen planus: a study in an ethnic Chinese cohort
Authors: Zeng Xin , Hou Xiaohui , Wang Zhi , Jiang Lu , Xiong Chunrong , Zhou Min , Chen Qianming
Published: July 2008

The objectives of this study are to investigate the carriage rate of Candida albicans from the patients with oral lichen planus (OLP, erosive and non‐erosive subtypes) and the healthy control individuals in a Chinese cohort and then to compare the virulence attributes of these isolates. Oral C. albicans isolates from 300 patients with OLP as well as 128 healthy controls were isolated and a total of 112 isolates from patients with erosive OLP (62), non‐erosive OLP (24) and healthy control (26) were screened for phospholipase activity by using an in vitro plate assay method. Adhesion ability of the above isolates was also studied by using buccal epithelial cells assay. Statistically, the carriage rate of C. albicans from the patients with erosive OLP (44.29%) was higher than that of patients with non‐erosive OLP (15.00%) or the healthy control group (20.31%) (P < 0.001). The adhesion to buccal epithelial cells of the isolates from the erosive OLP group (3.950 ± 1.436) was more marked (P < 0.001) than that from healthy control (2.2112 ± 0.4833). The phospholipase activity of these isolates either from erosive (0.4170 ± 0.029) or non‐erosive OLP groups (0.4327 ± 0.028) was higher (P < 0.001) than that from healthy controls (0.5259 ± 0.074). Some C. albicans isolates with special virulence attributes might be co‐factors, which contribute to the development of OLP, especially erosive OLP.
Pseudomembranous‐like tinea of the scrotum: report of six cases
Authors: Lu Sha , Xi Li‐yan , Zhang Jun‐min , Lu Chang‐ming
Published: July 2008

Six cases of tinea of the scrotum with atypical clinical features were observed in the dermatology department of our hospital between 2001 and 2007. The age of onset ranged from 14 to 26 years. Unusual clinical presentations of pseudomembranous‐like disease were observed in every patient. Causative agents were Microsporum gypseum in five patients and Trichophyton rubrum in one patient. Three of the M. gypseum isolates had atypical morphologies. All six isolates were identified by cultural morphologies and DNA sequence analysis of the internal transcribed spacer region of the ribosomal DNA.
Growth of Candida species on complete dentures: effect of microwave disinfection
Authors: Sanitá Paula Volpato , Vergani Carlos Eduardo , Giampaolo Eunice Teresinha , Pavarina Ana Cláudia , Machado Ana Lucia
Published: July 2008

Microwave disinfection of complete dentures has been recommended to treat denture stomatitis in non‐immune compromised patients. Oral candidiasis is a frequent manifestation of HIV infection. The objective of this study is to evaluate the effectiveness of microwave irradiation on the disinfection of complete dentures inoculated with American Type Culture Collection (ATCC) and HIV isolates of five species of Candida. Fifty dentures were made, sterilised and inoculated with the tested microorganisms (C. albicans, C. dubliniensis, C. krusei, C. glabrata and C. tropicalis). After incubation (37 °C/48 h), dentures were microwaved (650 W/3 min). Non‐irradiated dentures were used as positive controls. Replicate aliquots of suspensions were plated at dilutions 10−1 to 10−4 and incubated (37 °C/48 h). Colony counts (cfu ml−1) were quantified. Dentures were also incubated at 37 °C for 7 days. Data were analysed with 2‐way anova and Tukey HSD tests (α = 0.05). Dentures contaminated with all Candida species showed sterilisation after microwave irradiation. All control dentures showed microbial growth on the plates. The cfu ml−1 for C. glabrata was higher than those of C. albicans, C. dubliniensis and C. tropicalis whereas the cfu ml−1 for C. krusei was lower. The cfu ml−1 for clinical isolates was higher than those of ATCC yeast. Microwave irradiation for 3 min at 650 W resulted in sterilisation of all complete dentures.
Susceptibility of Candida albicans to common and novel antifungal drugs, and relationship between the mating type locus and resistance, in Lebanese hospital isolates
Authors: Basma Raida , Barada Ghyda , Ojaimi Naim , Khalaf Roy A.
Published: July 2008

The incidence of antifungal resistance is on the increase worldwide and novel drugs are constantly being developed to counter this trend. One hundred and sixteen clinical isolates of Candida albicans were collected from Lebanese hospitals in order to first determine the degree of resistance of Lebanese isolates to four common azoles: fluconazole (FL), itraconazole (IT), ketoconazole (KE), and voriconazole (VO), in addition to amphotericin B (AP) and caspofungin (CS) through the Epsilometer test method and second, determine any relationship between the allelic compositions of the mating type loci (MTLa, MTL α, MTLa/α) with drug resistance. Results showed that resistance, among C. albicans isolates, was the highest with 12% for IT, followed by 7.7% for VO, 6% for KE, 5% for FL, 1.7% for AP and 0% for CS. Three isolates (2.6%) were resistant to all azoles tested, including one that was resistant to all drugs used except CS. Eleven isolates were homozygous at the MTL locus (9.5%), five of which (45%) were resistant to at least one antifungal drug whereas 14 of the 105 heterozygous strains (13%) exhibited similar resistance (P = 0.02), indicating a strong correlation between MTL locus homozygosity and resistance.
Microbial profile and drug resistance ofCandidastrains isolated from the blood of children: an 11‐year study
Authors: Małafiej Eugeniusz , Adamiec Anna Ciebiada , Tworzyańska Urszula
Published: July 2008

The latest observations indicate a continuous increase in the frequency of fungal infections, particularly in hospital patients, accompanied by changes in both the profile of the isolated strains and their drug susceptibility. The objective of this study was to evaluate the trend in the incidence of candidaemia and susceptibility of antifungal drugs in the Polish Mother’s Memorial Hospital over an 11‐year period. Blood samples taken from the hospitalised children were sent to the Department of Clinical Microbiology for diagnostic purposes. A total of 195Candidastrains were isolated: 47.7%Candida albicansand 52.3% non‐albicans.Candida parapsilosiswas isolated in 65.7% of non‐albicansstrains. The prevalence ofCandidaspp. decreased from 16.9–20.5% in the years 1996–1997 to 3.1–2.1% in the years 2005–2006. In the years 2000–2005, non‐albicansstrains were more prevalent. AllC. albicansstrains were susceptible to amphotericin B, 2.94% of non‐C. albicansstrains were semisusceptible to amphotericin B, 98.92% ofC. albicansand 85.29% of non‐albicansstrains were susceptible to 5‐fluorocytosine.Candidaspp. strains are predominant pathogens in fungaemia in children in our hospital. Over the last few years,C. albicanshave been replaced by non‐albicansstrains (predominantlyC. parapsilosis), which exhibit a higher level of drug resistance. The number ofCandidaspp. isolated from blood decreased during the 11‐year study.
Knowledge and perceptions about sunburn and solar keratoses in Australia
Authors: Raasch Beverly A , Buettner Petra G
Published: July 2008

An omnibus telephone survey of 1200 adult Australians determined self‐reported prevalence of and attitudes to sunburn and sunspots, knowledge of the term solar keratosis and prevalence of skin checks. Half reported they had been sunburnt in the previous year. Seventy‐eight per cent considered sunburn to be extremely or very serious, while 73% considered sunspots as serious or very serious. While 29% reported currently having sunspots, 69% had never heard of the term solar keratosis, 30% had never had a skin check and 28% had their last skin check more than 12 months ago. Respondents 18–29 years old (odds ration [OR] = 2.6; P = 0.002) and men (OR = 2.4; P < 0.001) were most likely to experience multiple sunburn. Persons living in capital cities (OR = 0.63; P = 0.006) and having a university degree (OR = 0.52; P = 0.001) had reduced OR for multiple sunburns. Men (OR = 0.45; P < 0.001) were less likely to consider sunburn serious or extremely serious than women. Compared with respondents 18–29 years old, those 55 years or older were 7.4‐fold more likely to have had a skin check (P < 0.001). Sun‐protection campaigns need to continue using evidence‐based interventions targeting younger people and men to reduce sunburn. The terms used in health promotion need to be understood by the target audience.
Eosinophilic annular erythema: A subset of Wells' syndrome or a distinct entity?
Authors: Howes Renae , Girgis Laila , Kossard Steven
Published: July 2008

A 52‐year‐old woman with a 6‐year history of a persistent non‐pruritic cutaneous annular eruption, forming polycyclic and arcuate plaques that commenced as erythematous papules and nodules, is presented. Lethargy and arthralgia were associated symptoms. We have followed this patient for the last 3 years, and during this period she has continued to have a florid annular eruption of unknown cause. Laboratory tests, including an eosinophil count, examination of stool samples for parasites, and a computed tomography scan of the chest, abdomen and pelvis, failed to detect any abnormalities. Skin biopsies demonstrated a superficial to deep cellular infiltrate consisting of numerous eosinophils, with lymphocytes and isolated neutrophils. Eosinophilic dust, flame figures and granulomatous inflammation were not seen. In addition, strands of mucin were present through the dermis, and prominent basal vacuolar change was evident at the dermoepidermal junction; these features may represent new findings that help define a distinct form of eosinophilic annular erythema.
Poliosis circumscripta associated with neurofibromatosis 1
Authors: Sandoval‐Tress Cecilia , Nava‐Jiménez Gabriela
Published: July 2008

A 38‐year‐old man presented with axillary freckling, multiple café au lait macules and neurofibromas on the scalp, trunk and extremities. In addition, he had a patch of white hair on the right parieto‐occipital area overlying a scalp neurofibroma. He was diagnosed with poliosis circumscripta associated with neurofibromatosis 1.
Retention of general practitioners in rural Nepal: A qualitative study
Authors: Butterworth Katrina , Hayes Bruce , Neupane Bhusan
Published: July 2008

Objectives:  To explore the key issues that influence GP retention in rural areas of Nepal.

Design:  A qualitative study using triangulation of data from one postal questionnaire, one hand‐delivered questionnaire with semistructured interview and focus group discussions. Data from a small community survey from 13 rural districts also included.

Participants:  Sixty‐two Nepali GPs, 25 doctors in General Practice training programs, 11 individuals involved in policy development and rural health care.

Results:  The key issues identified by this study as critical to the retention of Nepali GPs in rural areas were:

• Career/promotion prospects

• Status/recognition

• Financial incentives

• Working conditions

• Education for children

• Continuing medical education

• Political stability and security

Conclusions:  The strongest theme was that of career development. This must be addressed by the Government of Nepal if there is to be any hope of improving retention of GPs in rural areas. GPs need to have a clear career ladder, with recognition of the value of service in rural areas. There is, however, no one single answer to the complex interacting factors that impact on GP retention in rural Nepal. A multifaceted, holistic response is necessary. From the level of community awareness, a career structure and financial remuneration to adequately set up hospitals, functional teams, family support, continuing professional development and a secure working environment – each area must be addressed for the whole to function.
Quality of life in Hepatitis C virus infection: Assessment of rural patients living in north‐western New South Wales
Authors: Gunasekera Sanjeevani , Fraser John , Alexander Christian
Published: July 2008

Objective:  To measure the health‐related quality of life (HRQOL) of rural Australian Hepatitis C virus (HCV)‐infected patients living in north‐western New South Wales.

Design:  A cross‐sectional survey, including the Short Form 36 (SF36) questionnaire as well as topics concerning demographic data and items relating to the perceived mode and duration of HCV infection.

Subjects:  A total of 80 patients with HCV infection were identified, using non‐random, convenience sampling, during October 2004 to June 2005. These patients attended either the Hepatitis C clinic, the Alcohol and Other Drugs clinic or general practitioner surgeries in rural north‐western New South Wales. Of the 80 patients selected, 65 completed the survey instrument, yielding a response rate of 81%.

Measurements:  HRQOL in terms of the standard eight SF36 subscores as well as aggregate physical and Mental Component Summary (MCS) scores based on the SF36.

Results:  Patients attending the Alcohol and Other Drugs clinic had a significantly (P = 0.024) lower vitality score than patients attending either the Hepatitis C clinic or the general practice surgeries. Otherwise, the three groups had similar scores in respect of the remaining seven SF36 dimensions. Most participants (86%) stated that their families are aware of their HCV status and 74% of participants mentioned that their families are supporting them in respect of their HCV status.

Conclusion:  Our rural HCV‐infected patients have comparable HRQOL measures to their counterparts selected from patients attending the Liver Diseases Clinic or the Infectious Diseases Clinic in Adelaide. Both groups have reduced HRQOL compared with the Australian population norm.
Glycine N‐methyltransferase is a favorable prognostic marker for human cholangiocarcinoma
Authors: Huang Yu‐Chuen , Chen Marcelo , Shyr Yi‐Ming , Su Cheng‐Hsi , Chen Chi‐Kuan , Li Anna Fen‐Yau , Ho Donald Ming‐Tak , Chen Yi‐Ming Arthur
Published: July 2008

Background and Aim:  Glycine N‐methyltransferase (GNMT) is a susceptibility gene for human hepatocellular carcinoma (HCC). We previously reported that GNMT expression is diminished in HCC. Here we report our examination of GNMT expression patterns in cholangiocarcinoma and the relationship between its expression and prognosis.

Methods:  We analyzed GNMT expression in tumor tissues from 33 cholangiocarcinoma patients (19 male) using immunohistochemistry (IHC) procedures with a GNMT monoclonal antibody (mAb 4–17). GNMT expression intensity and percentages were scored on a scale of 0 to 6. The association between GNMT expression and survival was analyzed using the Kaplan–Meier method, and prognostic factors were evaluated with a multivariate Cox proportional hazards regression model.

Results:  High GNMT expression was found in epithelial cells of normal bile ducts. Six of 33 (18.2%) cholangiocarcinoma tissues had no GNMT expression. A statistically significant difference was noted in GNMT expression between male and female patients (68.4% vs 100%, P < 0.05). Compared to patients with GNMT expression scores > 3, the death hazard ratio for patients with GNMT scores ≤ 3 was 3.68 (95% confidence interval = 1.17–11.59, P < 0.05).

Conclusions:  GNMT expression is a favorable prognosis predictor for cholangiocarcinoma.
Rapid hepatic fate specification of adipose‐derived stem cells and their therapeutic potential for liver failure
Authors: Banas Agnieszka , Teratani Takumi , Yamamoto Yusuke , Tokuhara Makoto , Takeshita Fumitaka , Osaki Mitsuhiko , Kato Takashi , Okochi Hitoshi , Ochiya Takahiro
Published: July 2008

Background and Aim:  Multipotential mesenchymal stem cells (MSC), present in many organs and tissues, represent an attractive tool for the establishment of a successful stem cell‐based therapy in the field of regeneration medicine. Adipose tissue mesenchymal stem cells (AT‐MSC), known as adipose‐derived stem cells (ASC) are especially attractive in the context of future clinical applications because of their high accessibility and minimal invasiveness during the procedure to obtain them. The goal of the present study was to induce human ASC into functional hepatocytes in vitro within a very short period of time and to check their therapeutic potential in vivo.

Methods:  In vitro generated ASC‐derived hepatocytes were checked for hepatocyte‐specific markers and functions. Afterwards, they were transplanted into nude mice with liver injury. Twenty‐four hours after transplantation, biochemical parameters were evaluated in blood serum.

Results:  We have shown here that ASC can be differentiated into hepatocytes within 13 days and can reach the functional properties of primary human hepatocytes. After transplantation into mice with acute liver failure, ASC‐derived hepatocytes can restore such liver functions as ammonia and purine metabolism. Markers of liver injury, alanine aminotransferase, aspartate aminotransferase, as well as ammonia, were decreased after ASC‐derived hepatocyte transplantation.

Conclusions:  Our data highlight the properties of ASC as having a special affinity for hepatocyte differentiation in vitro and liver regeneration in vivo. Thus, ASC may be a superior choice for the establishment of a therapy for injured liver.
Platelets contribute to the reduction of liver fibrosis in mice
Authors: Watanabe Motonobu , Murata Soichiro , Hashimoto Ikuka , Nakano Yoritaka , Ikeda Osamu , Aoyagi Yasuyuki , Matsuo Ryota , Fukunaga Kiyoshi , Yasue Hiroshi , Ohkohchi Nobuhiro
Published: July 2008

Background and Aim:  Several recent studies have reported that liver cirrhosis (LC) can be ameliorated, but few adequate strategies are available against liver fibrosis. Although LC clinically shows thrombocytopenia and hypersplenism, the correlation with liver fibrosis and platelets remains unclear. The aim of the present study was to investigate the effect of platelets on liver fibrosis in mouse models.

Methods:  To induce liver fibrosis, C57BL6 female mice were injected i.p. with 1 mL/kg carbon tetrachloride (CCl4) twice a week for 8 weeks. Thrombocytosis was achieved by giving thrombopoietin or splenectomy in addition to CCl4 intoxication. At 8 weeks, whole blood and liver specimens were obtained for studies as follows: peripheral platelet counts, histopathological examination, hydroxyproline assay, immunostaining, quantification of mRNA expression, and microarray analysis.

Results:  Thrombocytosis significantly reduced liver fibrosis and hydroxyproline content of liver tissues compared to mice with CCl4 administration alone. Platelets suppressed increments in mRNA expression for transforming growth factor‐β, and increased matrix metalloproteinase‐9 expression in the liver. Microarray analysis of the liver revealed that platelets upregulated gene expressions involved in cell proliferation compared to expression in mice with CCl4 intoxication alone. Platelets also increased liver volume, proliferative cell nuclear antigen labeling index, and mitotic index in fibrotic mice.

Conclusion:  These results clearly show that platelets reduce liver fibrosis and promote liver regeneration, even under cirrhotic conditions. We, therefore, propose that platelets could offer a potent tool in the treatment of liver cirrhosis.
Discussing withdrawing and withholding of life‐sustaining medical treatment in a tertiary paediatric hospital: A survey of clinician attitudes and practices
Authors: Forbes Tom , Goeman Emma , Stark Zornitza , Hynson Jenny , Forrester Mike
Published: July 2008

Aim:  To better understand current attitudes and practices relating to discussions concerning the withholding and withdrawing of life‐sustaining medical treatment (WWLSMT) among medical staff in the paediatric setting.

Methods:  An anonymous online survey of paediatricians (senior medical staff – SMS) and paediatric trainees (junior medical staff – JMS) likely to be involved in the care of children with life limiting illness.

Results:  A total of 162 responses were obtained (response rate 42%). SMS indicated feeling more comfortable with their abilities to discuss WWLSMT than JMS. Barriers to discussing WWLSMT were numerous and included clinician concerns about family readiness for the discussion, prognostic uncertainty, family disagreement with the treating team regarding the child's prognosis/diagnosis and concerns about how to manage family requests for treatments that are not perceived to be in the child's best interests. Fifty‐eight per cent of JMS and 35.8% of SMS reported receiving no specific communication training regarding WWLSMT. Most learned through experience and by observing more senior colleagues. There was a high level of support for additional training in this area and for the provision of resources such as discussion guidelines and a structured form for documenting the outcomes WWLSMT discussions.

Conclusion:  The majority of JMS feel less comfortable with their abilities to facilitate these discussions than their senior colleagues. The results of this study suggest that although confidence correlates with experience, junior and senior clinicians are eager to improve their skills through ongoing professional development and the provision of resources. The education needs of JMS and SMS appear to be different.
Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa
Authors: Brassesco María Sol , Valera Elvis Terci , Neder Luciano , Castro‐Gamero Angel Mauricio , Arruda Darlene , Machado Hélio Rubens , Sakamoto‐Hojo Elza Tiemi , Tone Luiz Gonzaga
Published: July 2008

Cytogenetic studies of choroid plexus tumors, particularly for atypical choroid plexus papillomas, have been rarely described. In the present report, the cytogenetic investigation of an atypical choroid plexus papilloma occurring at the posterior fossa of a 16‐year‐old male is described. Comparative genome hybridization analysis demonstrated gains of genetic material from almost all chromosomes. Chromosome losses involved 19p, regional losses at chromosome X and loss of chromosome Y. The presence of polyploid cells was confirmed by fluorescence in situ hybridization analysis with probes directed to centromeric regions. Furthermore, the microscopic analysis of cultures showed nuclear buds, nucleoplasmic bridges, and micronuclei in 23% of tumor cells suggesting the presence of complex chromosomal abnormalities. Previous cytogenetic studies on choroid plexus papillomas showed either normal, hypodiploid or hyperdiploid karyotypes. To the best of our knowledge, this is the first report of polyploidy in choroid plexus papilloma of intermediate malignancy grade. Although the mechanisms beneath such genome duplication remain to be elucidated, the observed abnormal nuclear shapes indicate constant restructuring of the tumor's genome and deserves further investigation.
Erythropoietin pharmacokinetic/pharmacodynamic analysis suggests higher doses in treating neonatal anemia
Authors: Neelakantan Srividya , Widness John A. , Schmidt Robert L. , Veng‐Pedersen Peter
Published: July 2008

Background: The establishment of effective treatment of neonatal anemia using recombinant human erythropoietin (r‐HuEPO) requires a thorough understanding of the physiology and mechanism of EPO’s pharmacologic effect. The purpose of the present preclinical study in sheep was to elucidate the stimulatory effect of EPO on erythroid progenitors and their differentiation into reticulocytes useful in predicting optimal r‐HuEPO dosing.

Methods: Five young adult sheep each underwent two phlebotomies spaced 4–6 weeks apart in which their hemoglobin levels were reduced from 12 g/dL to 3–4 g/dL. Endogenous EPO levels and reticulocyte counts produced in response to anemia were sampled throughout the study and analyzed using a pharmacokinetic/pharmacodynamic (PK/PD) model.

Results: The phlebotomy‐induced drop in hemoglobin resulted in a increase in EPO levels, which reached a maximum of 764 ± 55 mU/mL (mean ± %CV) in 0.5–2.6 days. The reticulocyte counts increased from baseline values of 76.9 × 103 ± 67/μL to 619 × 103 ± 30/μL in 8 days. The PK/PD analysis indicated an increased maturation time for the reticulocytes (4.88 ± 35 days) and demonstrated that the Emaxmodel for EPO’s activation of the progenitors did not show significant effect saturation at the endogenous EPO levels reached.

Conclusions: In extrapolating from the animal pilot experiment, the present study provides a case for the use of higher r‐HuEPO doses in human studies to determine if higher doses are more effective in treatment of neonatal anemia to reduce, and in some less severe cases, eliminate, the need for blood transfusions.
Growth of infants with osteogenesis imperfecta treated with bisphosphonate
Authors: Hasegawa Kosei , Inoue Masaru , Seino Yoshiki , Morishima Tsuneo , Tanaka Hiroyuki
Published: July 2008

Background:  Osteogenesis imperfecta (OI) is a heritable bone disease characterized by bone brittleness and various degrees of growth disorder. Cyclic pamidronate therapy is reportedly useful to prevent bone fracture in OI and in infants with OI, but, it remains unclear how infants with OI grow during bisphosphonate therapy.

Methods:  Height and weight measurements of OI infants treated with cyclic pamidronate therapy were taken before and every 6 months during therapy until 18 months. Vertebral morphometry and the concavity index were analyzed using X‐ray films taken simultaneously.

Results:  Among OI patients, those in the group for which the height z‐score decreased tended to have more femur fractures than those of the group for which the height z‐score increased. Morphometry of the lumbar spine showed that compression fractures occurred less during cyclic pamidronate therapy, by which the lumbar bone mineral density increased.

Conclusions:  Bisphosphonate preserved vertebral morphometry during 18 months after starting therapy in infants. Prevention of femur fracture during the infantile period might help prevent short stature; therapeutic strategies during infancy must better emphasize prevention of long bone fracture before the beginning of gait.
Time‐course changes in the liver of biliary atresia patients on magnetic resonance imaging
Authors: Takahashi Atsushi , Hatakeyama Shin‐itsu , Kuroiwa Minoru , Suzuki Norio , Toki Fumiaki , Suzuki Makoto , Suehiro Taketoshi , Shimura Tatsuo , Kuwano Hiroyuki
Published: July 2008

Background:  Using magnetic resonance imaging (MRI), changes in the livers of postoperative biliary atresia (BA) patients were investigated.

Methods:  Periodic MRI was performed in 32 postoperative BA patients. The findings were evaluated by calculating the near‐normal liver tissue area that corresponded with normal‐ or high‐signal regions on T1‐weighted imaging. The patients were divided into three groups based on the extent of near‐normal liver tissue on the final MRI: group A, n = 14; group B, n = 13; and group C, n = 5, included patients with >40%, 20–40%, and <20% area of near‐normal liver tissue, respectively. The relationship among the macroscopic and histological findings in the liver at orthotopic living donor liver transplantation (OLDLT), patient outcomes, and MRI findings were investigated.

Results:  In group A, 11 patients had no evidence of liver dysfunction. In group B, six patients either had undergone or were awaiting OLDLT. In group C, all patients had undergone OLDLT. All patients had either adequate or impaired bile drainage in each liver segment. The segmental changes corresponded with the liver architecture at OLDLT. The changes could be evaluated on MRI at 1–2 years after surgery.

Conclusions:  Adequate and restricted areas of liver tissue with near‐normal structure were indicative of good and poor prognoses, respectively. Shortly after portoenterostomy, these segmental changes occurred and/or developed in each liver segment and could be detected on MRI. It is emphasized that patients with >40% area of near‐normal liver architecture at the initial stages did not require OLDLT, while those with <20% area did require OLDLT.
Management of an unusual pediatric difficult airway using ketamine as a sole agent
Authors: PATERSON NEIL A.
Published: July 2008

We present the case of a 9‐year‐old boy who suffered a fall while brushing his teeth. This resulted in impalement of the lateral pharyngeal wall by the toothbrush with its head becoming firmly lodged adjacent to the internal carotid artery as demonstrated by CT scan. The length of the toothbrush protruding from the mouth and the inability to adequately assess the airway prior to any intervention gave rise to a unique set of surgical and anesthetic airway management problems. These were compounded by the possibility of damage to the carotid artery and potential catastrophic hemorrhage with manipulation of the toothbrush at any point. We detail the problems and outline our management.
Dexmedetomidine disposition in children: a population analysis
Authors: POTTS AMANDA L. , WARMAN GUY R. , ANDERSON BRIAN J.
Published: July 2008

Background: There are few data describing dexmedetomidine population pharmacokinetics (PK) in children (0–15 years) despite increasing use.

Methods: An open‐label study was undertaken to examine the PK of i.v. dexmedetomidine 1–4 μg·kg−1bolus in children after cardiac surgery (n = 45). A population PK analysis of dexmedetomidine time–concentration profiles (148 observations) was undertaken using nonlinear mixed effects modeling. Estimates were standardized to a 70‐kg adult using allometric size models.

Results: Children had a mean age of 3.38 years (range 4 days to 14 years) and weight 15.1 kg (range 3.1–58.9 kg). A two‐compartment disposition model with first order elimination was superior to a one‐compartment model. Population parameter estimates (between subject variability) were clearance (CL) 39.2 (CV 30.36%) l·h−1per 70 kg, central volume of distribution (V1) 36.9 (69.49%) l per 70 kg, inter‐compartment clearance (Q) 68.2 (37.6%) l·h−1per 70 kg and peripheral volume of distribution (V2) 69.9 (48.6%) l per 70 kg. Clearance at birth was 15.55 l·h−1per 70 kg and matured with a half‐time of 46.5 weeks to reach 87% adult rate by 1 year of age. Simulation of an infusion of 1 μg·kg−1over 10 min followed by an infusion of 0.7 μg·kg−1·h−1for 50 min suggested that children arouse from sedation at a plasma concentration of 0.304 μg·l−1.

Conclusions: Clearance in neonates is approximately one‐third of that described in adults, consistent with immature elimination pathways. Maintenance dosing, which is a function of clearance, should be reduced in neonates and infants when using a target concentration approach.
The FLACC behavioral scale for procedural pain assessment in children aged 5–16 years
Authors: NILSSON STEFAN , FINNSTRÖM BERIT , KOKINSKY EVA
Published: July 2008

Objectives:  To evaluate the concurrent and construct validity and the interrater reliability of the Face, Legs, Activity, Cry and Consolability (FLACC) scale during procedural pain in children aged 5–16 years.

Background:  Self‐reporting of pain is considered to be the primary source of information on pain intensity for older children but a validated observational tool will provide augment information to self‐reports during painful procedures.

Methods:  Eighty children scheduled for peripheral venous cannulation or percutaneous puncture of a venous port were included. In 40 cases two nurses simultaneously and independently assessed pain by using the FLACC scale and in 40 cases one of these nurses assessed the child. All children scored the intensity of pain by using the Coloured Analogue Scale (CAS) and distress by the Facial Affective Scale (FAS).

Results:  Concurrent validity was supported by the correlation between FLACC scores and the children’s self‐reported CAS scores during the procedure (r = 0.59, P < 0.05). A weaker correlation was found between the FLACC scores and children’s self‐reported FAS (r = 0.35, P < 0.05). Construct validity was demonstrated by the increase in median FLACC score to 1 during the procedure compared with 0 before and after the procedure (P < 0.001). Interrater reliability during the procedure was supported by adequate kappa statistics for all items and for the total FLACC scores (κ = 0.85, P < 0.001).

Conclusions:  The findings of this study support the use of FLACC as a valid and reliable tool for assessing procedural pain in children aged 5–16 years.
Anaesthetic management of gastrochisis – a review of our practice over the past 5 years
Authors: RAGHAVAN MURALI , MONTGOMERIE JAMES
Published: July 2008

Background:  Surgical closure of gastrochisis has traditionally been performed under general anesthesia followed by admission to intensive care and postoperative ventilation. We reviewed the management of these neonates in our hospital over the past 5 years to identify the changes in practice and possible factors which affect the peri‐operative course.

Methods:  We retrospectively identified cases of gastrochisis undergoing repair from June 2002 to May 2007. Details of the demographic data, preoperative factors, intra‐operative anesthetic and surgical management, and postoperative care were collected from the anesthetic chart, operative record, and patient notes.

Results:  Forty‐eight self‐ventilating neonates underwent operative repair in theatre. A neuraxial local anesthetic block was performed as part of the anesthetic technique in 22 patients. There was a significant difference in the need for postoperative ventilation in this group (23%) when compared with a traditional opioid‐based method of providing analgesia (88%, P < 0.05). This difference was seen in both term and preterm babies.

Conclusion:  Conclusions are difficult to make when analyzing retrospective data in patients with a heterogeneous variety of factors. The results suggest that anesthesia which includes a regional technique is a valid method in these cases. Traditional opioid analgesia when compared with regional techniques may be associated with increased need for postoperative ventilation.
Diversity and disease: community structure drives parasite transmission and host fitness
Authors: Johnson Pieter T. J. , Hartson Richard B. , Larson Donald J. , Sutherland Daniel R.
Published: July 2008

Changes in host diversity and community structure have been linked to disease, but the mechanisms underlying such relationships and their applicability to non‐vector‐borne disease systems remain conjectural. Here we experimentally investigated how changes in host community structure affected the transmission and pathology of the multi‐host parasite Ribeiroia ondatrae, which is a widespread cause of amphibian limb deformities. We exposed larval amphibians to parasites in monospecific or heterospecific communities, and varied host number to differentiate between density‐ and diversity‐mediated effects on transmission. In monospecific communities, exposure to Ribeiroia significantly increased mortality (15%), malformations (40%) and time‐to‐metamorphosis in toads. However, the presence of tree frogs significantly reduced infection in toads, leading to fewer malformations and higher survival than observed in monospecific communities, providing evidence of parasite‐mediated facilitation. Our results suggest that interspecific variation in parasite resistance can inhibit parasite transmission in multi‐species communities, reducing infection and pathology in sensitive hosts.
Nonrandom extinction leads to elevated loss of angiosperm evolutionary history
Authors: Vamosi Jana C. , Wilson John R. U.
Published: July 2008

The phylogenetic clustering of extinction may jeopardize the existence of entire families and genera, which can result in elevated reductions of evolutionary history (EH), trait diversity, and ecosystem functioning. Analyses of globally threatened birds and mammals suggest current extinction threats will result in a much higher loss of EH than random extinction scenarios, while the analyses of the taxonomical distribution of regionally rare plants find the opposite pattern. The disproportionately high number of rare plant species within species‐rich families potentially suggests that lower losses of plant EH will be sustained than expected under random extinction. We show that at a global scale, this is not the case. Species‐poor (especially monotypic) angiosperm families are more often at risk of extinction than expected. Because these high‐risk species‐poor families are as evolutionarily distinct as other families, the expected family‐level EH plausibly lost in the next 100 years exceeds that predicted from random extinction by up to ∼1165 million years.
Challenging urban species diversity: contrasting phylogenetic patterns across plant functional groups in Germany
Authors: Knapp Sonja , Kühn Ingolf , Schweiger Oliver , Klotz Stefan
Published: July 2008

Cities are hotspots of plant species richness, harboring more species than their rural surroundings, at least over large enough scales. However, species richness does not necessarily cover all aspects of biodiversity such as phylogenetic relationships. Ignoring these relationships, our understanding of how species assemblages develop and change in a changing environment remains incomplete. Given the high vascular plant species richness of urbanized areas in Germany, we asked whether these also have a higher phylogenetic diversity than rural areas, and whether phylogenetic diversity patterns differ systematically between species groups characterized by specific functional traits. Calculating the average phylogenetic distinctness of the total German flora and accounting for spatial autocorrelation, we show that phylogenetic diversity of urban areas does not reflect their high species richness. Hence, high urban species richness is mainly due to more closely related species that are functionally similar and able to deal with urbanization. This diminished phylogenetic information might decrease the flora’s capacity to respond to environmental changes.
Soil microbial respiration in arctic soil does not acclimate to temperature
Authors: Hartley Iain P. , Hopkins David W. , Garnett Mark H. , Sommerkorn Martin , Wookey Philip A.
Published: July 2008

Warming‐induced release of CO2 from the large carbon (C) stores in arctic soils could accelerate climate change. However, declines in the response of soil respiration to warming in long‐term experiments suggest that microbial activity acclimates to temperature, greatly reducing the potential for enhanced C losses. As reduced respiration rates with time could be equally caused by substrate depletion, evidence for thermal acclimation remains controversial. To overcome this problem, we carried out a cooling experiment with soils from arctic Sweden. If acclimation causes the reduction in soil respiration observed after experimental warming, then it should subsequently lead to an increase in respiration rates after cooling. We demonstrate that thermal acclimation did not occur following cooling. Rather, during the 90 days after cooling, a further reduction in the soil respiration rate was observed, which was only reversed by extended re‐exposure to warmer temperatures. We conclude that over the time scale of a few weeks to months, warming‐induced changes in the microbial community in arctic soils will amplify the instantaneous increase in the rates of CO2 production and thus enhance C losses potentially accelerating the rate of 21st century climate change.
A cohort study of results following elective colonic and rectal resection within an enhanced recovery programme
Authors: Faiz O. , Brown T. , Colucci G. , Kennedy R. H.
Published: July 2008

Objective  The use of laparoscopic surgery coupled with an enhanced recovery programme (ERP) has resulted in hospital stays of 4 or less days for colonic and 6 days following rectal resection, in previously reported small selected groups of patients. This report analyses an unselected cohort to determine if such benefits are reproducible.

Method   Consecutive patients undergoing elective colonic or rectal surgery at a single centre between January 2002 and January 2006 were followed. All were included in the ERP and underwent either laparoscopic or open surgery.

Results   The study group comprised 241 patients (mean age of 67 ± standard deviation 14 years and 49% male sex distribution) who underwent elective colorectal resection within the context of an ERP. One hundred and fifty‐one (62.7%) patients had malignant disease. Overall, 191 (79.3%) patients underwent a laparoscopic procedure and the remaining underwent an open operation. Postoperative stay was shorter in patients undergoing laparoscopic vs open, colonic surgery (4 days vs 6 days, P = 0.002). A nonsignificant trend towards reduced postoperative stay was observed for patients undergoing laparoscopic vs open, rectal surgery (6 days vs 9 days, P = 0.088). Patients undergoing laparoscopic colectomy demonstrated significantly lower 30‐day mortality rates than those undergoing traditional colectomy (3/131 vs 3/39, P = 0.049).

Conclusion  Laparoscopic colonic surgery in the context of an ERP offers reduced hospital stay and may confer a survival advantage over traditional techniques. These results confirm that previously reported benefits of laparoscopic surgery are reproducible within an unselected population.
Systematic review of economic evaluations of laparoscopic surgery for colorectal cancer
Authors: Hernández R. A. , De Verteuil R. M. , Fraser C. M. , Vale L. D. ,   on behalf of the Aberdeen Health Technology Assessment Group
Published: July 2008

Objective Colorectal cancer is one of the most common cancers and the standard surgical treatment for this cancer is open resection (OS), but laparoscopic surgery (LS) may be an alternative treatment. In 2000, a Health Technology Assessment (HTA) review found little evidence on costs and cost‐effectiveness in comparing the two methods. The evidence base has since expanded and this study systematically reviews the economic evaluations on the subject published since 2000.

Method Systematic review of studies reporting costs and outcomes of LSvsOS for colorectal cancer. National Health Service Economic Evaluation Database (NHS EED) methods for abstract writing were followed. Studies were summarized and incremental cost‐effectiveness ratios (ICER) for common outcomes were calculated.

Results Five studies met the inclusion criteria. LS generally had higher healthcare costs. Most studies reported longer operational time and shorter length of stay and similar long‐term outcomes with LSvsOS. Only one outcome, complications, was common across all studies but results lacked consistency (e.g. in two studies, OS was less costly but more effective; in another study, LS was less costly but more effective; and in the further two studies, LS could potentially be cost effective depending on the decision‐makers’ willingness to pay for the health gain).

Conclusion The evidence on cost‐effectiveness is not consistent. LS was generally more costly than OS. However, the effectiveness data used in individual economic evaluation were imprecise and unreliable when compared with data from systematic reviews of effectiveness. Nevertheless, short‐term benefits of LS (e.g. shorter recovery) may make LS appear less costly when productivity gains are considered.