bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic Analysis of Arabidopsis Mutants: Brassinosteroid Hormone Response
Authors: Wang Zhiyong
Published: June 2008

INTRODUCTION

Brassinosteroid (BR) is required for normal plant growth and development; most notably, BR promotes cell elongation. Thus, mutants with defects in BR biosynthesis or response have defects in cell elongation. They fail to undergo skotomorphogenesis (etiolation) in the dark and they are dwarves when grown in the light. Whether a cell elongation defect can be rescued, unaffected, or alleviated by BR treatment provides an important criterion for whether a mutant has a defect in BR biosynthesis or BR response or whether the mutant phenotype is unrelated to BR. On the other hand, mutants with increased BR signaling are less sensitive to the BR-biosynthesis inhibitor brassinazole (BRZ). The hypocotyl length of dark-grown seedlings and petiole length of light-grown plants are often measured to determine BR responsiveness; BRZ inhibition of BR biosynthesis can reduce hypocotyl and petiole elongation. Wild-type seedlings grown on 1 μM BRZ in the dark have hypocotyls approximately one-third the length of those on medium lacking BRZ. This protocol describes the measurement of BR responsiveness, with or without BRZ, in light- and dark-grown seedlings.
Immunogold Staining of Epoxy Resin Sections for Transmission Electron Microscopy (TEM): Figure 1.
Authors: Skepper Jeremy N. , Powell Janet M.
Published: June 2008

INTRODUCTION

In post-embedding methods of immunogold staining, the cells or tissues are fixed chemically or cryoimmobilized, dehydrated, and embedded in epoxy or acrylic resins. Thin sections (50-70 nm in thickness) are cut using an ultramicrotome with a diamond knife, using a water bath to collect the sections as they slide off the knife. The sections are stretched with solvent vapor or a heat source and collected onto either bare or plastic-coated nickel grids. The sections are then stained immunochemically with primary antibodies raised against antigens exposed on the surface of the sections. The primary antibodies are visualized by staining immunochemically with secondary antibodies raised against the species and isotype of the primary antibodies, conjugated to colloidal gold particles. The immunochemically stained sections are then contrast stained with salts of uranium (uranyl acetate) and lead (lead citrate) to reveal the ultrastructure of the cells, and are finally viewed by transmission electron microscopy (TEM). Chemical fixation and embedding in a highly cross-linked epoxy resin is the method of choice for optimal ultrastructure and stability of the thin section in the electron beam. Immunogold staining of thin epoxy resin sections, described here, is useful if the antigen of interest is very resistant to fixative, or if only archived material that was fixed primarily for ultrastructural studies is available.
Immunogold Staining of London Resin (LR) White Sections for Transmission Electron Microscopy (TEM): Figure 1.
Authors: Skepper Jeremy N. , Powell Janet M.
Published: June 2008

INTRODUCTION

In post-embedding methods of immunogold staining, the cells or tissues are fixed chemically or cryoimmobilized, dehydrated, and embedded in epoxy or acrylic resins. Thin sections (50-70 nm in thickness) are cut using an ultramicrotome with a diamond knife, using a water bath to collect the sections as they slide off the knife. The sections are stretched with solvent vapor or a heat source and collected onto either bare or plastic-coated nickel grids. The sections are then stained immunochemically with primary antibodies raised against antigens exposed on the surface of the sections. The primary antibodies are visualized by staining immunochemically with secondary antibodies raised against the species and isotype of the primary antibodies, conjugated to colloidal gold particles. The immunochemically stained sections are then contrast stained with salts of uranium (uranyl acetate) and lead (lead citrate) to reveal the ultrastructure of the cells, and are finally viewed by transmission electron microscopy (TEM). LR White was introduced as a low-toxicity alternative to epoxy resins, which frequently contained carcinogens. Unlike the simplest acrylic resins, in which monomers are polymerized to form long chains, the LR resins contain aromatic cross-linkers to improve the stability of the sections under the electron beam. LR White and Gold both have very low viscosity and readily penetrate, even into dense tissue. In this protocol, aldehyde-fixed tissue is dehydrated in ethanol, impregnated in LR White resin and polymerized under vacuum or in a nitrogen atmosphere before sectioning and immunogold staining.
Using BLOSUM in Sequence Alignments
Authors: Mount David W.
Published: June 2008

INTRODUCTION

The original Dayhoff percent accepted mutation (PAM) matrices were developed based on a small number of protein sequences and an evolutionary model of protein change. By extrapolating from the observed changes at small evolutionary distances to large ones, it was possible to establish a PAM250 scoring matrix for sequences that were highly divergent. Another approach to finding a scoring matrix for divergent sequences is to start with a more divergent set of sequences and produce a scoring matrix from the substitutions found in those less-related sequences. The blocks amino acid substitution matrices (BLOSUM) scoring matrices were prepared this way. This article explains how BLOSUM scoring matrices were created and how they can best be used.
Ultrastructural Immunochemistry
Authors: Skepper Jeremy N. , Powell Janet M.
Published: June 2008

INTRODUCTION

The use of colloidal gold technology was undoubtedly the most significant event in the development of immunochemistry. Gold particles are particularly useful for transmission electron microscopy (TEM) studies, because they scatter electrons strongly and even small particles are clearly visible under the electron microscope. Before proceeding to immunogold staining, it is important to gather as much information as possible about the antibody of interest and its respective antigen: Where is it likely to be located? Is the antigen extracellular, intracellular, membrane-associated, or a soluble component of the cytoplasm? Is it present in significant quantities? Is it sequestered at high concentration in any specific subcellular compartment, such as the mitochondria or the nucleus? How vulnerable to fixation and embedding is the antigen of interest? Information on the specificity of antibodies from Western blotting is valuable, but is not guaranteed to be useful for immunochemistry. Antibodies that “work well” on blots frequently have to be used at concentrations of up to three or more orders of magnitude greater for immunofluorescence and even more for immunogold staining studies, and some antibodies simply cannot be used for immunochemistry. This article describes methods and considerations for the use of immunogold staining, including fixation, controls, resolution, and quantification.
Day case general anaesthesia in a patient with narcolepsy
Authors: Doyle A. , Wilkinson D.
Published: June 2008

We report a patient suffering from narcolepsy who presented for day case gynaecological surgery under general anaesthesia. Her symptoms were normally well controlled using modafinil therapy which she had omitted on the day of surgery. Modafinil is a unique drug and has potential for many interactions with anaesthetic agents; these are discussed in this report. Her anaesthetic course was uneventful and we review previous reports of patients suffering with narcolepsy undergoing anaesthesia and suggest that narcolepsy should not be a contra‐indication to day case surgery.
Mantle cell lymphoma with aberrant expression of CD10
Authors: Zanetto U , Dong H , Huang Y , Zhang K , Narbaitz M , Sapia S , Kostopoulos I , Liu H , Du M‐Q , Bacon C M
Published: June 2008

Aims:  Morphological, immunophenotypic and genetic heterogeneity amongst mantle cell lymphomas (MCLs) can lead to difficulties in diagnosis and management. The aim was to describe the clinical and pathological features of MCLs with aberrant expression of CD10.

Methods and results:  Of 17 specimens from 13 patients, 14 expressed CD10 and three (presenting before or after a CD10+ specimen) did not. All expressed cyclin D1 and carried the t(11;14)(q13;q32)/CCND1‐IGH translocation. Similar to non‐selected MCL patients, most patients had disseminated disease and an adverse clinical course. Five specimens showed pleomorphic blastoid morphology and blastoid transformation was associated with a change in phenotype, including gain or loss of CD10. Additional phenotypic variations likely to cause diagnostic difficulty were present in eight specimens: five were CD5− and five (all CD10+) expressed Bcl‐6. One Bcl‐6+ case carried a BCL‐6 translocation and three others had extra copies of the BCL‐6 gene. Sequence analysis of the immunoglobulin heavy chain variable region in five cases showed only one to have low‐level somatic mutation, indicating that they did not arise from germinal centre B cells.

Conclusions:  Expression of CD10 by MCL is often associated with other variant morphological, immunophenotypic or genetic features, but does not reflect derivation from germinal centre B cells.
Women’s experiences of becoming a mother after prolonged labour
Authors: Nystedt Astrid , Högberg Ulf , Lundman Berit
Published: June 2008

Title.  Women’s experiences of becoming a mother after prolonged labour.

Aim.  This paper is a report of a study to explore women’s experiences of becoming a mother after prolonged labour.

Background.  The negativity associated with a complicated labour such as prolonged labour can lead to a struggle to become a healthy mother and could restrict the process of becoming a mother.

Methods.  Interviews were conducted in 2004 with 10 mothers who had been through a prolonged labour with assisted vaginal or caesarean delivery 1–3 months previously. Thematic content analysis was used.

Findings.  Three themes were formulated, describing women’s experiences as fumbling in the dark, struggling for motherhood and achieving confidence in being a mother. The difficulties and suffering involved in becoming a mother after a prolonged labour were interpreted to be like ‘fumbling in the dark’. Women experienced bodily fatigue, accompanied by feelings of illness and detachment from the child. Having the child when in this condition entailed a struggle to become a mother. In spite of these experiences and the desire to achieve confidence in being a mother, the reassurance of these women regarding their capacity for motherhood was crucial: it was central to their happiness as mothers, encouraged interaction and relationship with the child, and contributed to their adaptation to motherhood.

Conclusion.  Women experiencing prolonged labour may be comparable with the experience of and recovery from illness, which could contribute to difficulties transitioning to motherhood and limit a woman’s ability to be emotionally available for the child.
Hematopoietic stem cell transplantation in Langerhans cell histiocytosis: Case report and review of the literature
Authors: Kesik Vural , Citak Caglar , Kismet Erol , Koseoglu Vedat , Akyuz Canan
Published: June 2008

Abstract:  The prognosis in children with LCH who do not respond to the conventional therapies is very poor. SCT may be a new approach. However, there are limited data about the results of the transplantations. Herein we report a patient with refractory multisystem LCH who underwent allogeneic bone marrow transplantation and is disease and treatment free 54 months after transplantation. Further studies are required to establish the role of SCT in refractory LCH.
Phylogeny ofHystrixand related genera (Poaceae: Triticeae) based on nuclear rDNA ITS sequences
Authors: Zhang H.‐Q. , Fan X. , Sha L.‐N. , Zhang C. , Yang R.‐W. , Zhou Y.‐H.
Published: June 2008

The taxonomic status ofHystrixand phylogenetic relationships amongHystrixand its related genera ofPseudoroegneria(St),Hordeum(H),Psathyrostachys(Ns),Elymus(StH),Leymus(NsXm),Thinopyrum bessarabicum(Eb) andLophopyrum elongatum(Ee) were estimated from sequences of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. The type species ofHystrix,H. patula, clustered with species ofPseudoroegneria,Hordeum,Elymus,Th. bessarabicumandLo. elongatum, whileH. duthieissp.duthiei,H. duthieissp.longearistata,H. coreanaandH. komaroviiwere grouped withPsathyrostachysandLeymusspecies. The results indicate that: (i)H. patulais distantly related to other species ofHystrix, but is closely related toElymusspecies; (ii)H. duthieissp.duthiei,H. duthieissp.longearistata,H. coreanaandH. komaroviihave a close affinity withPsathyrostachysandLeymusspecies, andH. komaroviimight contain the NsXm genome ofLeymus; and (iii) the St, H and Ns genomes inHystrixoriginate fromPseudoroegneria,HordeumandPsathyrostachys, respectively, while the Xm inHystrixandLeymushas a complex relationship with the E or St genomes. According to the genomic system of classification in Tiritceae, it is reasonable to treatHystrix patulaasElymus hystrixL, and the other species ofHystrixas species of a section ofLeymus,LeymusSect.Hystrix.
Parental Distribution of Resources in Relation to Larval Hunger and Size Rank in the Burying BeetleNicrophorus vespilloides
Authors: Smiseth Per T. , Moore Allen J.
Published: June 2008

In altricial birds, the parents’ distribution of resources within the brood is influenced by variation in at least two components of nestling condition: hunger level and size rank. Here, we examine whether variation in larval hunger and size rank had similar influences on the parents’ distribution of resources in the burying beetleNicrophorus vespilloides. To this end, we analyzed hitherto unpublished data on parental resource distribution among individual larvae derived from three previous experiments. Our first experiment showed that resource distribution was biased towards hungry larvae at the expense of control larvae, but that actively begging hungry larvae were as likely to obtain resources from parents as actively begging control larvae. Thus, resource distribution was biased towards hungry larvae because hungry larvae spent more time begging than control larvae. Our second experiment showed that actively begging senior larvae (i.e. larvae that were older and larger) were more likely to obtain resources than actively begging junior larvae, suggesting that senior larvae had a competitive advantage or were treated preferentially by the parents. Our third experiment found no evidence that the interaction between larval hunger and size rank had an effect on parental resource distribution, suggesting that hunger level had a similar effect on resource distribution to seniors and juniors. We conclude that offspring hunger and size rank have remarkably similar effects in the burying beetleN. vespilloidesas reported in studies on altricial birds.
Male Head Secretion Triggers Copulation in the Dwarf SpiderDiplocephalus permixtus
Authors: Uhl Gabriele , Maelfait Jean‐Pierre
Published: June 2008

The term nuptial feeding is applied for any possible form of transfer of substances during the course of mating. However, the underlying functions can range from increased coupling efficiency or increased male survival to various levels of sexual selection. Males of many dwarf spider species (Erigoninae: Linyphiidae; Araneae) produce secretions from conspicuous grooves or elevations on their prosoma that seem to play a role during the mating episode. We asked if these structures represent a survival strategy, a mating effort in that they function as a mate attractant or as a mechanism to secure matings or if they simply facilitate successful genital coupling. InDiplocephalus permixtusmales possess a deep groove in the ocular area into which females sink their chelicerae before mating commences. Secretory glands in the area of the groove produce a substance, which is taken up by the female in the process of mating. We experimentally prevented females from taking up secretion by covering the head structures of one group of males and compared the behaviour with controls. We investigated effects in a single male setting as well as in a competitive two‐males setting. Under both experimental conditions the probability that copulation occurred was significantly reduced in head covered males: females bit into male head structures irrespective of male treatment but covered males did not commence pedipalp insertion despite optimal mating position. Our data suggest that in contrast to other gustatorial arthropod species investigated so far the head–mouth contact between the sexes primarily triggers the mating behaviour of the male and not that of the female. Clearly, the secretion does not function as a mate attractant as mating position was achieved with similar probability in covered and control males. A function as a survival strategy can be excluded as well, because sexual cannibalism never occurred. Potential stimulating or manipulative effects of the secretion during copulatory and post‐copulatory phases remain to be investigated.
ASSOCIATION BETWEEN µ‐OPIOID RECEPTOR‐1 102T>C POLYMORPHISM AND INTERMEDIATE TYPE 2 DIABETES PHENOTYPES: RESULTS FROM THE QUEBEC FAMILY STUDY (QFS)
Authors: Ruchat Stephanie‐May , Girard Martine , Weisnagel S John , Bouchard Claude , Vohl Marie‐Claude , Pérusse Louis
Published: June 2008

It has been suggested recently that molecules expressed both in the pancreas and hypothalamus, such as µ‐opioid receptor 1 (OPRM1), could form an integrated brain–liver system, which may sense glucose levels and therefore contribute to the development of type 2 diabetes mellitus (T2DM).

In the present study, we tested associations between OPRM1 gene polymorphisms (rs1799971, 102T/C and rs0648007G/A) and indices of glucose tolerance, insulin sensitivity (IS) and insulin secretion derived from plasma measures obtained in a fasting state and following a 75 g oral glucose tolerance test (OGTT) in 749 subjects from the Quebec Family Study (QFS). Polymorphisms were tested for association with glucose tolerance (normal vs IFG and T2DM combined) by calculating a χ2 statistic and corresponding P values, whereas associations with quantitative measures of glucose tolerance, IS and insulin secretion were tested using mixed linear models implemented in the MIXED procedure of sas (SAS Institute, Cary, NC, USA).

Associations were found between 102T/C OPRM1 and indices of glucose tolerance and IS. Compared with T/T homozygotes, carriers of the OPRM1 C‐102 variant exhibited a better glucose tolerance with a lower (P = 0.006) glucose area under the curve (AUC) following the OGTT and a better IS with a higher (P = 0.03) value of the Cederholm index, a numerical index of the curve relating glucose uptake to the log10 plasma insulin levels during the OGTT.

The results of the present study reveal that the 102T/C OPRM1 gene polymorphism is associated with a better glucose tolerance and improved IS, both of which suggest a potential protective effect of this variant on T2DM risk.
COMPARATIVE EFFECTS OF TRAMADOL ON VASCULAR REACTIVITY IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Raimundo Juliana M , Pontes Luana B , Antunes Fernanda , Sudo Roberto T , Trachez Margarete M , Zapata‐Sudo Gisele
Published: June 2008

The aim of the present study was to determine the effects of tramadol on vascular reactivity in aortic rings from Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).

Aortic rings, with or without endothelium, were obtained from male WKY rats and SHR (15–20 weeks old) and prepared for isometric tension recording. Aortic rings were precontracted with phenylephrine (10 µmol/L) or 40 mmol/L KCl and then exposed to cumulative concentrations of tramadol (0.1–1 mmol/L).

Tramadol produced a concentration‐dependent relaxation of precontracted aortic rings from WKY rats and SHR, which was not dependent on functional endothelium. Vascular relaxation was significantly greater in rings from SHR than WKY rats.

The concentration of tramadol necessary to produce a 50% reduction of the maximal contraction to phenylephrine (IC50) in rings with and without endothelium from SHR was 0.47 ± 0.08 and 0.44 ± 0.03 mmol/L, respectively (P = 0.76).

Tramadol attenuated the contracture elicited by Ca2+in depolarized tissue, suggesting that it may inhibit L‐type Ca2+channels. However, pretreatment with nicardipine (1 µmol/L) prevented the relaxation induced by tramadol in aortic rings from WKY rats and partially reduced its inhibitory effect in aortic rings from SHR.

Pretreatment of endothelium‐denuded aorta with glybenclamide (3 µmol/L), 4‐aminopyridine (3 mmol/L), tetraethylammonium (3 mmol/L) and naloxone (100 µmol/L) did not affect tramadol‐induced vasodilation of aortic rings from either WKY rats or SHR.

Intravenous administration of tramadol (10 mg/kg) to conscious SHR significantly reduced both systolic and diastolic blood pressure from 171.4 ± 5.3 to 129.3 ± 5.3 (P = 0.002) and from 125.0 ± 6.5 to 57.8 ± 8.9 mmHg (P = 0.003), respectively.
Washout of water‐soluble vitamins and of homocysteine during haemodialysis: Effect of high‐flux and low‐flux dialyser membranes
Authors: HEINZ JUDITH , DOMRÖSE UTE , WESTPHAL SABINE , LULEY CLAUS , NEUMANN KLAUS H , DIERKES JUTTA
Published: June 2008

Aim:  Vitamin deficiencies are common in patients with end‐stage renal disease (ESRD) owing to dietary restrictions, drug–nutrient interactions, changes in metabolism, and vitamin losses during dialysis. The present study investigated the levels of serum and red blood cell (RBC) folate, plasma pyridoxal‐5′‐phosphate (PLP), serum cobalamin, blood thiamine, blood riboflavin, and plasma homocysteine (tHcy) before and after haemodialysis treatment.

Methods:  Vitamin and tHcy blood concentrations were measured in 30 patients with ESRD before and after dialysis session either with low‐flux (n = 15) or high‐flux (n = 15) dialysers.

Results:  After the dialysis procedure, significantly lower concentrations of serum folate (37%), plasma PLP (35%), blood thiamine (6%) and blood riboflavin (7%) were observed. No significant changes were found for serum cobalamin or for RBC folate. There were no differences in the washout of water‐soluble vitamins between treatments with low‐flux and high‐flux membranes. Furthermore, a 41% lower concentration in tHcy was observed. The percentage decrease in tHcy was significantly greater in the patients treated with high‐flux dialysers (48% vs 37%; P < 0.01). The percentage change during dialysis was significantly inversely related to the molecular weight of the vitamins measured (r =−0.867, P < 0.01).

Conclusion:  This study showed significantly lower blood or serum levels of various water‐soluble vitamins after dialysis, independently of the dialyser membrane. The monitoring of the vitamin status is essential in patients treated with high‐flux dialysers as well as in patients treated with low‐flux dialysers.
Carbamylated low‐density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells
Authors: ASCI GULAY , BASCI ALI , SHAH SUDHIR V , BASNAKIAN ALEXEI , TOZ HUSEYIN , OZKAHYA MEHMET , DUMAN SONER , OK ERCAN
Published: June 2008

Aim:  Presence of accelerated atherosclerosis in dialysis patients cannot be entirely explained by conventional risk factors. Exposure to urea, which is elevated in patients with kidney disease, leads to the carbamylation of proteins. We investigated the effects of carbamylated low‐density lipoprotein (cLDL) on human coronary artery vascular smooth muscle cells (VSMC).

Methods:  Native LDL (nLDL) was carbamylated with potassium cyanate. Cells were incubated with different concentrations of cLDL carbamylated at different time points. Cytotoxicity, apoptosis, proliferation (bromodeoxyuridine incorporation), expression of adhesion molecules and extracellular matrix protein synthesis were studied.

Results:  Carbamylated low‐density lipoprotein exposure leads to morphological alterations and presence of cellular debris. Neither nLDL nor cLDL caused apoptosis. Lactate dehydrogenase (LDH) release was not different between groups. Carbamylated low‐density lipoprotein led to a striking proliferation in VSMC compared to nLDL. Carbamylated low‐density lipoprotein significantly increased intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 expression compared to the control. The effects of cLDL on proliferation and adhesion molecule expression were dose‐dependent and correlated with the degree of low‐density lipoprotein carbamylation. cLDL had no effect on extracellular matrix protein synthesis.

Conclusion:  The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.
Serine/threonine kinase, Cot/Tpl2, regulates renal cell apoptosis in ischaemia/reperfusion injury
Authors: YAOMURA TAKAAKI , TSUBOI NAOTAKE , URAHAMA YOSHINORI , HOBO AKINORI , SUGIMOTO KENJI , MIYOSHI JUN , MATSUGUCHI TETSUYA , REIJI KANNAGI , MATSUO SEIICHI , YUZAWA YUKIO
Published: June 2008

Aim:  Cot/Tpl2, a serine/threonine (Ser/Thr) protein kinase, has been classified as a member of the mitogen‐activated protein kinase (MAPK) family, and is known to have a pleiotropic role. Many studies have reported the involvement of Cot/Tpl2, mainly as a member of the Toll‐like receptor (TLR) 4 signalling pathway in lipopolysaccharide (LPS)‐induced tumor necrosis factor‐α (TNF‐α) production. At the same time, it is also related to the caspase‐dependent apoptotic pathway. Thus, the role of Cot/Tpl2 in ischaemia/reperfusion injury (IRI) in which TNF‐α and apoptosis are the major pathogenetic factors was studied.

Methods:  IRI was induced in wild type (Cot/Tpl2+/+) mice and in Cot/Tpl2‐deficient (Cot/Tpl2−/−) mice. The extent of tubular injury and renal function were studied. TNF‐α production, neutrophil infiltration and apoptosis were also compared between the two groups.

Results:  Cot/Tpl2−/− mice had preserved renal function compared with wild type mice in IRI. Although Cot/Tpl2 was phosphorylated in IRI and in the cultured tubular epithelial cells (TEC) after stimulation with LPS and hydrogen peroxide, there were no significant differences in terms of TNF‐α production, neutrophil infiltration or MAPK activation between Cot/Tpl2+/+ and Cot/Tpl2−/− mice. In contrast, Cot/Tpl2−/− mice showed obviously reduced terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling positive cells and cleaved caspase‐3 positive cells. Furthermore, Cot/Tpl2‐deficient TECs demonstrated significantly less caspase‐3 activation after hydrogen peroxide stimulation with comparable caspase‐9 activation to wild type TEC.

Conclusion:  Cot/Tpl2 did not function as a member of MAPK family, but as a promoter of apoptosis in IRI. These results suggest that Cot/Tpl2 could be a possible therapeutic target in IRI.
Cost‐effectiveness of the oral adsorbent AST‐120 versus placebo for chronic kidney disease
Authors: TAKAHASHI TOMOHIKO , REED SHELBY D , SCHULMAN KEVIN A
Published: June 2008

Aim:  This study was designed to evaluate the cost‐effectiveness of AST‐120, an oral adsorbent that attenuates the progression of chronic kidney disease.

Methods:  We developed a Markov model with six health states, including four levels of serum creatinine, haemodialysis and death, using data from a randomized clinical trial conducted in Japan. Direct costs relevant to chronic kidney disease were calculated from a Japanese reimbursement perspective. Projected quality‐adjusted life years (QALY) and costs were compared between the AST‐120 and placebo groups. The target population was nondiabetic patients with serum creatinine levels from 5.0 to 8.0 mg/dL (442–707 µmol/L) at baseline. Probabilistic sensitivity analysis was performed to evaluate the stability of the results.

Results:  At 3 years, mean total costs per patient were estimated at ¥6.67 million (US$56 982) in the AST‐120 group and ¥9.38 million (US$80 196) in the placebo group. Mean total costs were ¥2.72 million (US$23 205) lower among patients receiving AST‐120. QALY per patient were 0.295 (approximately 3.5 months) greater for patients receiving AST‐120 than for those receiving placebo over 3 years. The finding that treatment with AST‐120 dominated placebo (i.e. was less costly and resulted in more QALY) was upheld in sensitivity analyses.

Conclusion:  The use of AST‐120 in patients with advanced chronic kidney disease may help to slow the rate of growth in expenditures for kidney disease.
A systematic review of continuous renal replacement therapy and intermittent haemodialysis in management of patients with acute renal failure
Authors: GHAHRAMANI NASROLLAH , SHADROU SHAHROUZ , HOLLENBEAK CHRISTOPHER
Published: June 2008

Background:  Acute renal failure (ARF) still bears a poor prognosis with mortality rates up to 70% and the ideal form of renal replacement therapy (RRT) remains controversial. The purpose of this study was to conduct a systematic review and meta‐analysis of all randomized controlled trials (RCT) to examine the effect of dialysis modality (IHD: Intermittent haemodialysis; CRRT: continuous renal replacement therapy) on survival of patients with ARF and to also study the effect of each modality on dialysis dependence (DD).

Methods:  Using and combining two comprehensive search themes (ARF and RRT), we searched electronic databases from 1969 through September of 2007, supplemented by a manual review of abstracts from nephrology meetings and reference lists of review articles. All RCT comparing IHD with CRRT in adult patients with ARF and with explicit reporting of mortality were included. The primary outcome was the pooled estimate of the odds ratio (OR) of mortality for patients with ARF treated with CRRT versus IHD. The secondary outcome was OR of DD at time of discharge for surviving patients.

Results:  A total of 587 studies were identified, 554 of which were excluded on initial screening. Analysis of the nine RCT (1635 patients) showed an OR of 0.89 (0.63–1.24) for survival in patients on CRRT. Limiting the analysis to the seven RCT published after the year 2000, revealed an OR of 0.72 (0.58–0.90). The OR of all the studies before 2000 was 1.06 (95% CI 0.67–1.68), as compared with OR of 0.61 (95% CI 0.50–0.74) for studies post‐2000. Four studies showed a significantly lower risk of DD among the CRRT group and none showed higher OR for DD. When analysis was limited to the RCT, the OR for DD was 1.07 (0.47–2.39), suggesting no difference in DD between the modalities.

Conclusions:  Similar to previously reported meta‐analyses, we did not find a significant effect of CRRT on the OR of survival. The progressive reduction in the OR of survival with CRRT relative to IHD might reflect progressive improvements in IHD. The OR of DD was not affected by mode of RRT. In conclusion, compared with IHD, CRRT does not offer an advantage with regards to survival or DD in ARF. Considering its cost and potential disadvantages, it is imperative to identify the subset of patients with ARF that would potentially derive maximum benefit from CRRT. This will require large, adequately powered studies with sufficient follow‐up.
Estimation of glomerular filtration rate in South Asian healthy adult kidney donors
Authors: SRINIVAS SANJAY , ANNIGERI RAJEEV A , MANI MUTHU KRISHNA , RAO BUDITHI SUBBA , KOWDLE PRAKASH C , SESHADRI RAJAGOPALAN
Published: June 2008

Aim:  We evaluated the performance of serum creatinine based equations to estimate glomerular filtration rate (GFR) in South Asian healthy renal donors.

Methods:  GFR by 99mTc‐diethylenetriamine pentaacetic acid (DTPA) renogram (mGFR) in 599 renal donors was measured. GFR was estimated using a six variable modification of diet in renal disease formula (MDRD1), a four variable MDRD formula (MDRD2), Cockcroft‐Gault creatinine clearance (CG CrCl), Cockcroft‐Gault glomerular filtration rate (CG GFR) and the Mayo Clinic formula (Mayo GFR). The performance of various prediction equations was compared for global bias, precision (R2) and accuracy (percentage of estimated GFR (eGFR) falling within 15% and 30% of mGFR).

Results:  The mean age was 37.4 ± 11 years and 48.2% were male. The mGFR was 95.5 ± 11.6 mL/min per 1.73 m2. The bias (mL/min per 1.73 m2) was 7.5 ± 0.9, −9.0 ± 0.75, 13.1 ± 0.9, 7.5 ± 0.9 and 23.4 ± 0.76 for CG CrCl, CG GFR, MDRD1, MDRD2 and Mayo GFR, respectively. R2 was 0.082 for CG CrCl and MDRD1, 0.081 for CG GFR and MDRD2 and 0.045 for Mayo GFR. The percentages of eGFR falling within 15% and 30% of mGFR were 50.5 and 80.1 for CG CrCl, 65.8 and 84 for CG GFR, 50 and 74 for MDRD1, 54.3 and 80.1 for MDRD2 and 32 and 63.4 for Mayo GFR. Overall CG GFR performed better in estimating GFR in all subjects.

Conclusion:  The CG GFR equation was better than other equations to estimate GFR in South Asian healthy renal donors. We propose a new equation derived from the regression model in our study population to estimate GFR in a South Asian healthy adult population.
Experiences with acute kidney injury complicating non‐fulminant hepatitis A
Authors: KIM HYUN W , YU MI H , LEE JANG H , CHANG JAI W , YANG WON S , KIM SOON B , LEE SANG K , PARK JUNG S , PARK SU‐KIL
Published: June 2008

Aim:  To describe the clinical features and to identify factors related to development of acute kidney injury in acute hepatitis A patients.

Methods:  The study and control groups consisted of 21 and 425 patients who did or did not develop acute kidney injury, respectively, after acute hepatitis A from January 1997 to May 2007.

Results:  There were 13 men and eight women; their mean age at diagnosis was 28.8 ± 8.2 years in the study group. Peak values for renal and liver function impairment consisted of a median serum creatinine of 4.6 mg/dL (range, 1.5–15.3 mg/dL) on day 6 (range, days 1–20) and a median total bilirubin of 10.7 mg/dL (range, 2.6–57.5 mg/dL) on day 8 (range, day 1–19). Serum creatinine concentrations returned to baseline level by a median of 16 days and total bilirubin levels returned to normal by a median of 62 days. Six of 21 (29%) patient underwent haemodialysis. Renal biopsies performed in two patients showed acute tubular necrosis and interstitial nephritis, respectively. Logistic regression analysis showed that a lower haematocrit, the presence of coagulopathy and high C‐reactive protein concentration on admission, and higher peak bilirubin value during the illness were associated with development of acute kidney injury.

Conclusion:  Acute hepatitis A should be considered in the differential diagnosis of patients with acute kidney injury, even without fulminant hepatic failure. A lower haematocrit, the presence of coagulopathy and high C‐reactive protein level at presentation, and higher peak bilirubin level during the illness were associated with development of acute kidney injury in acute hepatitis A patients.
Chloroplast DNA content in Dinophysis (Dinophyceae) from different cell cycle stages is consistent with kleptoplasty
Authors: Minnhagen Susanna , Carvalho Wanderson F. , Salomon Paulo S. , Janson Sven
Published: June 2008

Kleptoplasty is the retention of plastids obtained from ingested algal prey, which can remain temporarily functional and be used for photosynthesis by the predator. With a new approach based on cell cycle analysis, we have addressed the question of whether the toxic, bloom‐forming dinoflagellate Dinophysis norvegica practice kleptoplasty or if they replicate their own plastid DNA. Dividing (G2) and non‐dividing (G1) D. norvegica cells from a natural population were physically separated with a flow cytometer based on their DNA content. Average numbers of nuclear and plastid rDNA copies were quantified with real‐time PCR both in the G1 and G2 group. Cells from the G1 group contained 5800 ± 340 copies of nuclear rDNA and 1300 ± 200 copies of plastid rDNA; cells from the G2 group contained 9700 ± 58 copies of nuclear rDNA and 1400 ± 220 copies of plastid rDNA (mean ± SD, n = 3). The ratio G2/G1 in average rDNA copies per cell was 1.67 for nuclear DNA and 1.07 for plastid DNA. These ratios show that plastid acquisition in D. norvegica is either uncoupled with the cell cycle, or plastids accumulate rapidly in the beginning of the cell cycle owing to feeding, as would be expected in a protist with kleptoplastic behaviour but not in a protist with own plastid replication. In addition, flow cytometry measurements on cells from the same population used for real‐time PCR showed that when kept without plastidic prey, live Dinophysis cells lost on average 36% of their plastid phycoerythrin fluorescence in 24 h. Together these findings strongly suggest that D. norvegica does not possess the ability for plastid replication.
Endoscopic haemostasis of staple‐line haemorrhage following colorectal resection
Authors: Malik A. H. , East J. E. , Buchanan G. N. , Kennedy R. H.
Published: June 2008

Objective  Bleeding from stapled colonic stapled anastomoses is rare, but occasionally may be severe enough to require re‐operation, with associated morbidity. Endoscopic therapy is a potential alternative.

Method  We examined a large 15‐year prospective series of patients who had undergone colorectal resection with stapled anastomosis. We reviewed the management of cases where severe postoperative rectal bleeding had occurred.

Results  In six of 777 (0.8%) patients, bleeding occurred that was severe enough to require intervention. In the first three cases, conventional re‐operation was performed. In the latter three cases, endoscopic therapy (adrenaline injection, diathermy or endoscopic clipping) was used to control the bleeding. No complications occurred as a result of endoscopic therapy, either patient or anastomosis related.

Conclusion  Endoscopic management using standard endoscopic techniques appears safe and effective for haemostasis in colorectal stapled anastomotic bleeding. Endoscopic therapy should probably be attempted before re‐operation is considered.
Family history of diabetes impacts on interactions between minimal model estimates of insulin sensitivity and glucose effectiveness
Authors: Lopez X. , Bouché C. , Tatro E. , Goldfine A. B.
Published: June 2008

Aims/hypothesis:  Insulin resistance and glucose effectiveness (SG) are major determinants of glucose tolerance and independently predict the development of type 2 diabetes in individuals with a family history of disease. We examined the inter‐relationship between insulin sensitivity (SI) and SG in offspring of two parents with type 2 diabetes and in individuals with no family history of diabetes.

Methods:  Fifty non‐diabetic individuals, including 26 offspring of two type 2 diabetic parents (family history, FH+) and 24 with no family history of diabetes (FH−) similar in gender, age, ethnicity and body mass index (BMI) were studied. Each subject underwent a 100‐g oral glucose tolerance test (OGTT) and insulin modified frequently sampled intravenous glucose tolerance, analysed using the Bergman’s minimal model (MINMOD).

Results:  Thirteen subjects of the FH+ group and nine of the FH− group had impaired glucose tolerance (IGT). SI and SG were independent variables in the FH+ group, while they correlated highly with each other in the FH− group (r = 0.69, p = 0.0002). The relationship between SI and SG persisted when analysing the IGT and normal glucose tolerance subgroups separately, demonstrating that these associations were not because of differences in glycaemia. Consistently, SG strongly correlated with additional measures of insulin resistance only in the FH− group, including fasting insulin (r = 0.56, p = 0.004), homeostasis model assessment of insulin resistance (r = 0.57 p = 0.003) and BMI (r = 0.66, p = 0.0004).

Conclusions:  These results demonstrate that familial factors impart important physiological differences in the inter‐relationship between insulin‐dependent and insulin‐independent glucose disposal, which may be important in modulating risk for development of disease.
Expenditure on diabetes treatments and achievement of glycaemic control: retrospective analysis
Authors: Eaton S. , Brent S. , Shah N. , Masters G.
Published: June 2008

Aims  To establish if a relationship exists between the prescribing costs of diabetes treatments and the achievement of Quality and Outcome Framework DM6 standards of glycaemic control.

Methods  A retrospective cross‐sectional study of all 92 primary care organizations in the north of England comparing net ingredient cost of diabetes treatments, corrected for diabetic population, with the percentage of patients achieving HbA1c < 7.4% (Quality and Outcome Framework DM6 indicator).

Results  The overall net ingredient cost for diabetes treatments varies from £225 to £382 per person per year. On regression analysis, expenditure on all diabetes treatments, on glitazones or on blood glucose test strips have no significant impact upon the percentage of people achieving an HbA1c < 7.4%. There is an inverse relationship between spending on analogue insulins and target achievement (r = −0.08, P = 0.001).

Conclusions  At primary care organization level, there is no association between weighted expenditure on diabetes treatments and achievement of glycaemic control targets. Although there are limitations to what can be inferred from analyses of this type, these data support a judicious and carefully directed approach to the use of newer, more expensive treatments until clear evidence of added benefit is forthcoming.
Outcomes of pregnancies in women with pre‐gestational diabetes mellitus and gestational diabetes mellitus; a population‐based study in New South Wales, Australia, 1998–2002
Authors: Shand A. W. , Bell J. C. , McElduff A. , Morris J. , Roberts C. L.
Published: June 2008

Aim  To determine population‐based rates and outcomes of pre‐gestational diabetes mellitus (pre‐GDM) and gestational diabetes mellitus (GDM) in pregnancy.

Methods  This was a cross‐sectional study, using linked population databases, of all women, and their infants, discharged from hospital following birth in New South Wales (NSW) between 1 July 1998 and 31 December 2002. Women with, and infants exposed to pre‐GDM or GDM were compared with those without diabetes mellitus for pregnancy characteristics and outcomes.

Results  Women with a singleton pregnancy (n = 370 703) and their infants were included: 1248 women (0.3%) had pre‐GDM and 17 128 (4.5%) had GDM. Of those women with pre‐GDM, 57% had Type 1 diabetes, 20% had Type 2 diabetes and for 23% the type of diabetes was unknown. Major maternal morbidity or mortality was more common in women with pre‐GDM (7.9%) [odds ratio (OR) 3.2, 95% confidence interval (CI) 2.6, 3.9] and in women with GDM (3.1%) (OR 1.2, 95% CI 1.1, 1.4) when compared with women without diabetes (2.6%). Major infant morbidity or mortality occurred more frequently in infants exposed to pre‐GDM compared with no diabetes (13.6% vs. 3.1%) (OR 5.0, 95% CI 4.2, 5.8) and in infants exposed to GDM compared with no diabetes (3.2% vs. 2.3%) (OR 1.4, 95% CI 1.3, 1.5).

Conclusions  Pre‐GDM and GDM continue to be associated with an increased risk of adverse maternal and neonatal outcomes; however, women with GDM have adverse outcomes less frequently. Rates of GDM and pre‐GDM appear to be increasing over time. Clinicians should consider the potential for adverse outcomes, and arrange referral to appropriate services.
Delivery of care to diabetic patients with foot ulcers in daily practice: results of the Eurodiale Study, a prospective cohort study
Authors: Prompers L. , Huijberts M. , Apelqvist J. , Jude E. , Piaggesi A. , Bakker K. , Edmonds M. , Holstein P. , Jirkovska A. , Mauricio D. , Tennvall G. R. , Reike H. , Spraul M. , Uccioli L. , Urbancic V. , Van Acker K. , Van Baal J. , Van Merode F. , Schaper N.
Published: June 2008

Aims  To determine current management and to identify patient‐related factors and barriers that influence management strategies in diabetic foot disease.

Methods  The Eurodiale Study is a prospective cohort study of 1232 consecutive individuals presenting with a new diabetic foot ulcer in 14 centres across Europe. We determined the use of management strategies: referral, use of offloading, vascular imaging and revascularization.

Results  Twenty‐seven percent of the patients had been treated for > 3 months before referral to a foot clinic. This varied considerably between countries (6–55%). At study entry, 77% of the patients had no or inadequate offloading. During follow‐up, casting was used in 35% (0–68%) of the plantar fore‐ or midfoot ulcers. Predictors of use of casting were male gender, large ulcer size and being employed. Vascular imaging was performed in 56% (14–86%) of patients with severe limb ischaemia; revascularization was performed in 43%. Predictors of use of vascular imaging were the presence of infection and ischaemic rest pain.

Conclusion  Treatment of many patients is not in line with current guidelines and there are large differences between countries and centres. Our data suggest that current guidelines are too general and that healthcare organizational barriers and personal beliefs result in underuse of recommended therapies. Action should be undertaken to overcome these barriers and to guarantee the delivery of optimal care for the many individuals with diabetic foot disease.
Small‐fibre involvement in diabetic patients with neuropathic foot pain
Authors: Vlckova‐Moravcova E. , Bednarik J. , Belobradkova J. , Sommer C.
Published: June 2008

Aims  To assess small‐fibre involvement in diabetic patients with neuropathic pain.

Methods  Peripheral nerve function was assessed in 30 patients with Type 2 diabetes mellitus (T2DM, n = 24) or impaired glucose tolerance (IGT, n = 6), and clinical symptoms of neuropathic pain in the feet, using nerve conduction studies, autonomic tests, thermal quantitative sensory testing (T‐QST) and quantification of intra‐ and subepidermal nerve fibre densities in skin punch biopsies.

Results  Clinical signs of isolated small‐fibre sensory involvement were present in 13 patients [pure small‐fibre neuropathy (pSFN)], seven patients had isolated positive sensory symptoms without neurological deficits (pSFN–). Ten patients had concomitant electrophysiological and/or clinical signs of large‐fibre sensory involvement [mixed‐fibre neuropathy (MFN)]. Twenty‐seven patients (90%) had both reduced skin innervation and abnormalities of the T‐QST parameters. Two other patients displayed either abnormal skin innervation or T‐QST, and only one patient had normal findings on both tests. The criteria of small‐fibre neuropathy (SFN) were met in all 20 patients without large‐fibre involvement. Small‐fibre involvement was also present in the 10 MFN patients. Both T‐QST and skin biopsy parameters revealed significant differences between these clinical subgroups, with increased severity of small‐fibre involvement in the MFN group. Autonomic dysfunction was found in 43% of patients and did not correlate with either clinical, T‐QST or skin biopsy data.

Conclusions  Although the exact mechanism of neuropathic pain in diabetic patients is not known, pain is almost invariably accompanied by small‐fibre dysfunction and pathology irrespective of autonomic or large‐fibre involvement.