bluuebunny/crossref_metadata_2025 huggingface dataset:
Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tc1 mouse model of Down syndrome
Authors: Morice Elise , Andreae Laura C. , Cooke Sam F. , Vanes Lesley , Fisher Elizabeth M.C. , Tybulewicz Victor L.J. , Bliss Timothy V.P.
Published: July 2008

Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of the human chromosome 21 (Hsa21). Recently, O’Doherty and colleagues in an earlier study generated a new genetic mouse model of DS (Tc1) that carries an almost complete Hsa21. Since DS is the most common genetic cause of mental retardation, we have undertaken a detailed analysis of cognitive function and synaptic plasticity in Tc1 mice. Here we show that Tc1 mice have impaired spatial working memory (WM) but spared long-term spatial reference memory (RM) in the Morris watermaze. Similarly, Tc1 mice are selectively impaired in short-term memory (STM) but have intact long-term memory (LTM) in the novel object recognition task. The pattern of impaired STM and normal LTM is paralleled by a corresponding phenotype in long-term potentiation (LTP). Freely-moving Tc1 mice exhibit reduced LTP 1 h after induction but normal maintenance over days in the dentate gyrus of the hippocampal formation. Biochemical analysis revealed a reduction in membrane surface expression of the AMPAR (α-amino-3-hydroxy-5-methyl-4-propionic acid receptor) subunit GluR1 in the hippocampus of Tc1 mice, suggesting a potential mechanism for the impairment in early LTP. Our observations also provide further evidence that STM and LTM for hippocampus-dependent tasks are subserved by parallel processing streams.
Dopamine D1 and D2 receptors in the nucleus accumbens core and shell mediate Pavlovian-instrumental transfer
Authors: Lex Anja , Hauber Wolfgang
Published: July 2008

Pavlovian stimuli previously paired with food can markedly elevate the rate of food-reinforced instrumental responding. This effect, termed Pavlovian-instrumental transfer (PIT), depends both on general activating and specific cueing properties of Pavlovian stimuli. Recent evidence suggests that the general activating properties of Pavlovian stimuli are mediated by mesoaccumbens dopamine systems; however, the role of NAC dopamine D1 and D2 receptors is still unknown. Here we examined the effects of a selective dopamine D1 and D2 receptor blockade in the shell and core subregion of the NAC on general PIT. Rats were trained to press a single lever for food, and the effect of a single Pavlovian stimulus previously associated with the same food on performance of that lever was measured in extinction. Results reveal that PIT, that is, the increase in instrumental responding during presentation of the Pavlovian stimulus, was reduced by microinjections of the dopamine D1 receptor antagonist SCH-23390 and, less pronounced, by microinjections of the dopamine D2 receptor antagonist raclopride into the NAC core or shell, respectively. Our data suggest that dopamine D1 and D2 receptors in the NAC core and shell mediate the general activating effects of Pavlovian stimuli on instrumental behavior.
Facilitation of taste memory acquisition by experiencing previous novel taste is protein-synthesis dependent
Authors: Merhav Maayan , Rosenblum Kobi
Published: July 2008

Very little is known about the biological and molecular mechanisms that determine the effect of previous experience on implicit learning tasks. In the present study, we first defined weak and strong taste inputs according to measurements in the behavioral paradigm known as latent inhibition of conditioned taste aversion. We then demonstrated that a strong novel taste input facilitated acquisition of the memory of subsequent weak taste input in inverse correlation with the time interval between the inputs. However, not only was a strong taste input unable to rescue an immediately subsequent strong taste input when the gustatory cortex was under the influence of the protein-synthesis inhibitor, anisomycin, but the effect of the interaction was to reduce the variation among individual taste memories. Taken together, these results demonstrate that taste memory facilitation, induced by previously experiencing a different unimodal taste input, depended on time, novelty, and directionality. Moreover, the results imply that learning is enhanced on the level of acquisition but not of molecular consolidation.
Positioning errors during stepped scans in X-ray crystallography
Authors: Shayduk Roman , Braun Wolfgang
Published: July 2008

It is demonstrated that many X-ray measurements, especially at grazing incidence, allow continuous data acquisition during stepped scans without deadtime for diffractometer motor motions. Analyzing the deviation from the ideal trajectory during independent motor movements, it is found that the deviation from the direct line connecting two data points in reciprocal space is very small for large volumes of reciprocal space. A synchronization algorithm to determine coordinated motor movements that follow the direct line connecting the data points is presented. Verification experiments on a six-circle diffractometer demonstrate the validity of the approach.
The local post-perovskite structure and its temperature dependence: atom-pair distances in CaIrO3revealed through analysis of the total X-ray scattering at high temperatures
Authors: Martin C. David
Published: July 2008

The temperature-dependent post-perovskite structure model of MgSiO3is reinvestigated through analysis of the atom-pair distances observed experimentallyviaFourier transformation of X-ray diffraction and diffuse scattering, the total X-ray scattering, from CaIrO3. In contrast to the results of a previous Rietveld structure refinement, which shows a negative or null thermal expansion of Ir—O and Ca—O bond lengths within the average long-range structure, visual inspection of these atom-pair distances in the pair-distribution function, in addition to structure models fitted through least-squares refinement to this local-structure data, strongly suggests that these distances between atom pairs increase with temperature. The average long-range structure of CaIrO3, visible from Rietveld structure refinement, is distinct from the short-range structure (≤ 18 Å) at all of the temperatures examined in this study (325–1114 K) and is reproduced in structure models fitted to the pair-distribution function extending to sufficiently long atom-pair distances (≥ 50 Å). While previous data obtained with Rietveld structure refinement show the iridium coordination octahedra to distort with increasing temperature, models of the short-range structure demonstrate that these polyhedra instead reduce distortion and rotate in a manner similar to that occurring in the perovskite structure.
Finding crystal structures from few diffraction data by a combination of a random search with genetic algorithms
Authors: Immirzi Attilio , Erra Loredana , Tedesco Consiglia
Published: July 2008

A new procedure for performing structural analysis of crystalline materials from diffraction data, using internal coordinates, is described. For starting information only unit-cell content, space group, chemical formula, molecular connectivity and a limited amount of diffraction data are required. After first selecting a number of solutions using a Monte Carlo approach with severe filters, which reject the most unrealistic solutions, genetic algorithms (crossover and mutations) are applied. In fact, the initial selection step alone is, frequently, a powerful tool for discovering structures, without recourse to the genetic algorithms. The procedure, while suffering from the limitation that connectivity must be known, is effective in cases where direct methods are not applicable because the diffraction data are scarce, are limited to low diffraction angles or are missing in specific portions of the reciprocal space. The main features of the algorithm are described and examples of validation given. The routines are now available as part of the freely distributed general-purpose programTRY. The program is available on the Web at http://www.theochem.unisa.it/try.html.
A versatile sample-environment cell for non-ambient X-ray scattering experiments
Authors: Chupas Peter J. , Chapman Karena W. , Kurtz Charles , Hanson Jonathan C. , Lee Peter L. , Grey Clare P.
Published: July 2008

A compact reaction cell is described forin-situexperiments requiring control of both the temperature of the sample and the atmosphere over the sample. The cell incorporates an optional furnace capable of temperatures of up to ∼1273 K. The compact design and ability of the cell to mount directly on a standard goniometer head allows portability to a large number of diffraction instruments at synchrotron sources.
Temporal patch occupancy dynamics of the Siberian flying squirrel in a boreal forest landscape
Authors: Hurme Eija , Mönkkönen Mikko , Reunanen Pasi , Nikula Ari , Nivala Vesa
Published: July 2008

Ability to predict species distribution in a landscape is of crucial importance for natural resource management and species conservation. Therefore, the understanding of species habitat requirements and spatio‐temporal dynamics in occurrence is needed. We examined patch occupancy patterns of the Siberian flying squirrel Pteromys volans in northern Finland across a seven year study period. Forest patches dominated by mature spruce (Picea abies) in a study area (375 km2) were surveyed to monitor the presence or absence of the flying squirrel. The patch occupancy pattern was dynamic: about half of the habitat patches were occupied at least once during the study period and more patches were colonised than were abandoned. Patches that were continuously occupied (i.e. occupied during all sample periods) were typically of high quality (based on habitat and landscape characteristics), continuously unoccupied patches were usually of low quality, and intermediate quality patches were occupied intermittently. The variables explaining patch occupancy were similar each year, and a statistical model based on data from the year 2000 also predicted occupancy in 2004 with similar accuracy. However, data from a single survey were inadequate for identifying patches used intermittently by flying squirrels. Despite inconsistent occupancy, these patches may be important for the local persistence of flying squirrels. The dynamic occupancy pattern may thus affect estimates of suitable habitat area and identification of functional patch networks for landscape planning. These results emphasise the need for follow‐up studies to better understand population patterns and processes in time.
Association of an insulin‐like growth factor 1 gene microsatellite with phenotypic variation and estimated breeding values of growth traits in Canchim cattle
Authors: Andrade P. C. , Grossi D. A. , Paz C. C. P. , Alencar M. M. , Regitano L. C. A. , Munari D. P.
Published: July 2008

A population of 1398 Canchim (CA) cattle was genotyped to assess the association of an insulin‐like growth factor 1 (IGF1) gene microsatellite with phenotypic variation and estimated breeding values of pre‐weaning, weaning and post‐weaning growth traits. After an initial analysis, the IGF1 genotype only had a significant effect (P < 0.05) on birth weight (BW) and weaning weight adjusted to 240 days (WW240). For these two traits, direct and maternal breeding values were estimated using the restricted maximum likelihood (reml). Two analyses were carried out. In the first (Model I), all fixed effects were fitted. In the second (Model II), the fixed effect of the IGF1 genotype was omitted. The estimated genetic and phenotypic components of variance were similar for every trait in both models. For Model I, estimated direct and maternal heritabilities were 0.26 and 0.16 for BW and 0.23 and 0.14 for WW240 respectively. The genetic and phenotypic correlations between BW and WW240 were 0.38 and 0.38 (Model I) and 0.19 and 0.38 (Model II) respectively. Fifty animals were classified according to their direct and maternal breeding values for both traits. Spearman rank‐order correlation between animal rankings in the two models was used to assess the effect of including the IGF1 genotype in the model. Non‐significant values from this correlation were indicative of a difference in breeding value rankings between the two approaches. The IGF1 gene was found to be associated with phenotypic variation and breeding values in the early phase of growth.
A rapid and robust sequence‐based genotyping method for BoLA‐DRB3 alleles in large numbers of heterozygous cattle
Authors: Baxter R. , Hastings N. , Law A. , Glass E. J.
Published: July 2008

The BoLA‐DRB3 gene is a highly polymorphic major histocompatibility complex class II gene of cattle with over one hundred alleles reported. Most of the polymorphisms are located in exon 2, which encodes the peptide‐binding cleft, and these sequence differences play a role in variability of immune responsiveness and disease resistance. However, the high degree of polymorphism in exon 2 leads to difficulty in accurately genotyping cattle, especially heterozygous animals. In this study, we have improved and simplified an earlier sequence‐based typing method to easily and reliably genotype cattle for BoLA‐DRB3. In contrast to the earlier method, which used a nested primer set to amplify exon 2 followed by sequencing with internal primers, the new method uses only internal primers for both amplification and sequencing, which results in high‐quality sequence across the entire exon. The haplofinder software, which assigns alleles from the heterozygous sequence, now has a pre‐processing step that uses a consensus of all known alleles and checks for errors in base calling, thus improving the ability to process large numbers of samples. In addition, advances in sequencing technology have reduced the requirement for manual editing and improved the clarity of heterozygous base calls, resulting in longer and clearer sequence reads. Taken together, this has resulted in a rapid and robust method for genotyping large numbers of heterozygous samples for BoLA‐DRB3 polymorphisms. Over 400 Holstein–Charolais cattle have now been genotyped for BoLA‐DRB3 using this approach.
Effect of atorvastatin on hs‐CRP in acute coronary syndrome
Authors: Gupta Ankur , Badyal Dinesh K. , Khosla Prem P. , Uppal Bharti , Jaison Thannikot M. , Chopra Sandeep
Published: July 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Markers of inflammation are being investigated as predictors of coronary ischaemic events. All major statins have shown almost similar and significant efficacy in reducing C‐reactive protein (CRP) concentrations in acute coronary syndrome (ACS), but atorvastatin was used in a high dose (80 mg).

• This study was designed to evaluate the effect of a lower dose (20 mg) of atorvastatin on hs‐CRP concentrations in patients with ACS.

WHAT THIS STUDY ADDS

• A lower dose of atorvastatin (20 mg) was effective in decreasing hs‐CRP and LDL concentrations in as short a duration as 4 weeks. The use of a lower dose of atorvastatin in patients of ACS can offer an attractive approach for early treatment of ACS patients.

AIMS

To evaluate the effect of a lower dose (20 mg) of atorvastatin on hs‐CRP concentrations in patients with ACS.

METHODS

Group A (n = 50) patients received atorvastatin 20 mg day−1 for 4 weeks in addition to standard anti‐anginal treatment. Group B (n = 50) patients received standard anti‐anginal treatment without atorvastatin.

RESULTS

hs‐CRP concentrations decreased in both groups, but the decrease was greater in group A. The decrease in hs‐CRP was also significantly greater in the subgroups of smoking, hypertension and past history of cardiovascular disease with atorvastatin.

CONCLUSIONS

The use of a lower dose (20 mg) of atorvastatin can offer an attractive approach for early treatment of patients with ACS.
Serum retinol‐binding protein 4 is not increased in obesity or obesity‐associated type 2 diabetes mellitus, but is reduced after relevant reductions in body fat following gastric bypass
Authors: Gómez‐Ambrosi J. , Rodríguez A. , Catalán V. , Ramírez B. , Silva C. , Rotellar F. , Gil M. J. , Salvador J. , Frühbeck G.
Published: July 2008

Objective  Controversy exists regarding the elevation of serum retinol‐binding protein 4 (RBP4) in human obesity and type 2 diabetes mellitus (T2DM). In the present study, we have compared serum RBP4 in lean and obese patients with or without T2DM, and analysed the effect of weight loss on serum RBP4.

Design  Forty‐two Caucasian subjects were included in the study. Serum RBP4 was measured by ELISA and Western blot. In addition, serum RBP4 was measured in 21 morbidly obese patients before and after 4, 8 and 15 months of weight loss following Roux‐en‐Y gastric bypass (RYGBP).

Results  No significant effect of either obesity or diabetes on serum RBP4 was observed. Serum RBP4 concentrations (measured by either ELISA or Western blot) did not correlate with body mass index (BMI), body fat or any indicator of glucose metabolism or insulin resistance. Weight loss following RYGBP did not modify serum RBP4 at 15 months (P = 0·472). However, the variations in serum RBP4 were significantly associated with the reduction in body fat (r = 0·48; P = 0·026). Patients loosing over 20% of fat mass (n = 11) showed significantly different RBP4 concentrations compared to those individuals exhibiting smaller adiposity reductions (n = 10) (–11·0 ± 6·4 vs.+5·8 ± 3·6 mg/l; P = 0·036). Furthermore, RBP4 levels were significantly reduced at 4 (P = 0·006) and 8 (P = 0·015) months only in those patients loosing over 20% of fat mass.

Conclusion  Serum RBP4 concentrations are not increased in obese patients with or without T2DM. A decrease in RBP4 levels was only observed after surgically induced weight loss accompanied by relevant reductions in body fat. RBP4 might be considered as a dynamic marker of negative energy balance being reduced during weight loss when a negative energy balance threshold is reached. Furthermore, RBP4 variation in the first month after RYGBP may be a predictor of weight loss success.
Changes in gut hormones after bariatric surgery
Authors: Vincent R. P. , Le Roux C. W.
Published: July 2008

Bariatric surgery is one of the most effective treatments for achieving long‐term weight loss in morbidly obese patients. Bariatric surgery causes weight loss through substantial decline of hunger and increased satiety. Recently our understanding of neuroendocrine regulation of food intake and weight gain, especially regarding the role of gut hormones, has significantly increased. The changes in these hormones following bariatric surgery can partly explain the mechanism behind weight loss achieved through these procedures. In this paper, we review the effect bariatric procedures have on different gut hormone levels and how they in turn can alter the complex neuroendocrine regulation of energy homeostasis.
Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta‐cell function in former gestational diabetes
Authors: Tura A. , Mari A. , Prikoszovich T. , Pacini G. , Kautzky‐Willer A.
Published: July 2008

Objective  Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta‐cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta‐cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance.

Design and patients  A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT).

Measurements  Insulin sensitivity and beta‐cell function were assessed by both the IVGTT and the OGTT.

Results  Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4·2 ± 0·3 vs. 5·4 ± 0·4 10−4 min−1 (µU/ml)−1; OGTT: 440 ± 7 vs. 472 ± 9 ml min−1 m−2). Conversely, no difference was found in beta‐cell function from the IVGTT. However, some parameters of beta‐cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 ± 5 vs. 124 ± 7 pmol min−1 m−2 mm−1, P = 0·0407) and insulin secretion at 5 mm glucose (168 ± 9 vs. 206 ± 10 pmol min−1 m−2, P = 0·003).

Conclusions  Both insulin sensitivity and beta‐cell function are impaired in normotolerant fGDM but the subtle defect in beta‐cell function is disclosed only by OGTT modelling analysis.
Immunotherapeutic agents in type 1 diabetes: a systematic review and meta‐analysis of randomized trials
Authors: Gandhi Gunjan Y. , Murad M. Hassan , Flynn David N. , Elamin Mohamed B. , Erwin Patricia J. , Montori Victor M. , Kudva Yogish C.
Published: July 2008

Objective  Although recent trial results of anti‐CD3 therapy are promising, there have been conflicting results of various immunotherapeutic agents used in patients with type 1 diabetes. We conducted a systematic review and meta‐analysis to determine the efficacy of nonantigen‐based immunotherapeutic approaches for preservation of beta‐cell function in patients with type 1 diabetes.

Methods  We searched MEDLINE, EMBASE, Cochrane CENTRAL, reference lists, and content expert files up to September 2006. Eligible studies were randomized controlled trials (RCTs) of antiproliferative agents (methotrexate, azathioprine), monoclonal antibodies (CD3, CD4), T‐cell inhibitors (cyclosporin) and other immunotherapeutic agents (photopheresis, linomide, fusidin, buffy coat, intravenous immunoglobulin, BCG, nicotinamide) in patients with newly diagnosed type 1 diabetes followed for ≥ 6 months. Pairs of reviewers working independently and with adequate reliability assessed the trials’ methodological quality, collected data, and conducted random‐effects meta‐analyses on measures of preservation of beta‐cell function (e.g. C‐peptide secretion, insulin independence).

Results  Of the 299 potentially relevant articles identified after an initial search, 20 trials met selection criteria. Meta‐analysis of 20 trials (n = 1187 patients) found a small to moderate improvement in beta‐cell function with immunotherapy [vs. placebo, effect size 0·37, 95% confidence interval (CI) 0·14–0·6] but there was moderate inconsistency in results across trials (I2 65%, 95% CI 39–77%). Subgroup analysis suggested a greater effect of cyclosporin and antiproliferative agents on beta‐cell function when used for ≥ 6 months (pooled effect size 0·77 vs.–0·11, respectively; Pinteraction = 0·002).

Conclusions  Long‐term immunotherapy may preserve beta‐cell function in newly diagnosed patients with type 1 diabetes. Patients and clinicians must await the conduct of rigorous trials reporting on diabetes resolution, adverse events, and other patient‐important outcomes.
Primary hyperparathyroidism is associated with marked impairment of GH response to acylated ghrelin
Authors: Cecconi E. , Bogazzi F. , Morselli L. L. , Gasperi M. , Procopio M. , Gramaglia E. , Broglio F. , Giovannetti C. , Ghigo E. , Martino E.
Published: July 2008

Background  Impaired GH secretion is a common finding in patients with primary hyperparathyroidism (PHP). Ghrelin displays strong GH‐releasing action, mainly at the hypothalamic level.

Objective  To evaluate secretory response of GH to ghrelin in PHP patients.

Patients  Fifteen patients [11 women/4 men, mean age 54 years, range 32–70 years, body mass index (BMI) 25·0 ± 0·7 kg/m2] affected with PHP due to single parathyroid adenoma and 35 normal age‐matched subjects (23 women/12 men, mean age 58 years, range 35–68 years, BMI 24·1 ± 1·1 kg/m2).

Methods  A measure of 1 µg/kg body weight i.v. acylated ghrelin or 1 µg/kg body weight i.v. GH releasing hormone (GHRH) followed by 0·5 g/kg body weight i.v. arginine (ARG) hydrochloride were administered to all subjects on alternate days in order to evaluate GH response.

Results  Mean serum GH peak after GHRH + ARG was 32·6 ± 7·8 and 17·4 ± 4·0 µg/l, in controls and PHP patients, respectively (P < 0·05). Mean serum GH peak after ghrelin was 70·4 ± 31·5 and 16·8 ± 1·9 µg/l, in controls and PHP patients, respectively, (P < 0·001). Using ROC curves, a serum GH peak > 22 µg/l after ghrelin stimulation might be considered as a cut‐off value for identifying normal subjects. Ten (67%) PHP patients have impaired GH response to GHRH + ARG and 13 (87%) to ghrelin. Serum GH peak after ghrelin or GHRH + ARG was unrelated to serum IGF‐1, PTH or ionized calcium concentrations.

Conclusions  The present data confirm that GH secretion is impaired in PHP patients using the potent GH secretagogue ghrelin and suggest that impaired GH secretion is likely due to a deleterious effect of hypercalcaemia at the hypothalamic level in PHP patients.
Bone demineralization in adult thalassaemic patients: contribution of GH and IGF‐I at different skeletal sites
Authors: Scacchi Massimo , Danesi Leila , Cattaneo Agnese , Valassi Elena , Giraldi Francesca Pecori , Argento Crocetta , D’Angelo Emanuela , Mirra Nadia , Carnelli Vittorio , Zanaboni Laura , Tampieri Benedetta , Cappellini Maria Domenica , Cavagnini Francesco
Published: July 2008

Background and objective  GH and IGF‐I exert an important role in the control of bone formation, as shown by decreased bone mineral density and increased fracture risk in adult hypopituitary patients untreated for GH deficiency (GHD). Different degrees of bone demineralization are frequently reported in patients affected by β‐thalassaemia. Considering the high prevalence of GHD recently observed by our group among adult thalassaemic patients, we elected to study the possible role of GH–IGF‐I abnormalities in the pathogenesis of the osteopenia/osteoporosis of this disease.

Design  Sixty‐four adult thalassaemic patients (49 with thalassaemia major and 15 with thalassaemia intermedia, 23 men and 41 women, aged 31·4 ± 6·8 years) were studied.

Methods  Bone mineral density was assessed by dual energy X‐ray absorptiometry at lumbar spine in 62 patients and at proximal femur in 58. All patients underwent GHRH (1 µg/kg as an i.v. bolus) plus arginine (0·5 g/kg as a 30‐min i.v. infusion) testing. Severe GHD was defined by GH peaks < 9 µg/l, whereas partial GHD was defined by GH peaks ranging from 9 to 16·5 µg/l. Blood samples for IGF‐I measurement were collected.

Results  Lumbar osteoporosis and osteopenia were demonstrated in 46/62 (74·1%) and 14/62 (22·5%) patients, respectively. Femoral osteoporosis and osteopenia were documented in 22/58 (37·9%) and 32/58 (55·1%) patients, respectively. Severe GHD was demonstrated in 16/64 patients (25%), while 11 additional patients (17·1%) displayed partial GHD. IGF‐I standard deviation score (SDS) was low, that is, below –1·88, in the majority (54·6%) of patients. Lumbar T‐score values were not correlated with either GH peaks or IGF‐I SDS values. Femoral T‐score values were positively correlated with GH peaks (r = 0·38, P < 0·005) and IGF‐I SDS values (r = 0·39, P < 0·005). Multiple regression analysis pointed to both GH peak and IGF‐I SDS as predictors of femoral T‐score. Furthermore, mean femoral T‐score was significantly lower in patients with severe GHD than in those with normal GH secretion (–2·94 ± 0·25 vs.–2·15 ± 0·12, P < 0·01).

Conclusion  This study, while confirming the high prevalence of both osteopenia/osteoporosis and somatotropin–somatomedin deficiency in adult thalassaemic patients, indicates that defective GH secretion and diminished serum IGF‐I levels may contribute to femoral demineralization in these patients. Further studies are worth carrying out to evaluate the efficacy of biosynthetic GH administration on bone abnormalities of GH‐deficient thalassaemic adults.
Severe hypomagnesaemia in long‐term users of proton‐pump inhibitors
Authors: Cundy T. , Dissanayake A.
Published: July 2008

Objective  To explore the mechanism underlying severe hypomagnesaemia in long‐term users of proton‐pump inhibitors (PPIs).

Patients  Two cases of severe hypomagnesaemia in adult long‐term users of the PPI omeprazole, presenting with hypocalcaemic seizures.

Measurements  We studied renal magnesium handling during an incremental intravenous magnesium infusion, and assessed total body magnesium status by the 24‐h retention of the parenteral load. We also observed the effects of oral magnesium supplements whilst continuing the PPI, and the effect of withdrawal of the PPI.

Results  Both patients were severely magnesium‐depleted and had avid renal magnesium retention, implicating a failure of intestinal magnesium absorption. There was no evidence of generalized malabsorption. The hypomagnesaemia could be partially corrected by high dose oral magnesium supplementation, and resolved on withdrawal of PPIs.

Conclusions  PPI use can inhibit active magnesium transport in the intestine, though it is not clear if this is an idiosyncratic effect. Long‐term PPI users who are highly adherent to treatment can eventually deplete total body magnesium stores and present with severe complications of hypomagnesaemia.
Thyroid function in short children born small‐for‐gestational age (SGA) before and during GH treatment
Authors: De Kort S. W. K. , Willemsen R. H. , Van Der Kaay D. C. M. , Van Dijk M. , Visser T. J. , Hokken‐Koelega A. C. S.
Published: July 2008

Context  Disturbances in thyroid function have been described in small‐for‐gestational age (SGA) children but the influence of prematurity is unclear. In addition, the effect of GH treatment on thyroid function has not been studied in short SGA children.

Objectives  To determine whether short SGA children have higher TSH levels compared to age‐matched controls and evaluate the influence of gestational age. To investigate whether GH treatment alters thyroid function.

Patients  A total of 264 short SGA children (116 preterm), prepubertal and non‐GH deficient.

Measurements  Serum FT4 and TSH at baseline and after 6, 12 and 24 months of GH treatment.

Results  Baseline mean TSH was higher in preterm short SGA children than in age‐matched controls (P < 0·05). Mean FT4 was not significantly different between short SGA children and controls. Baseline FT4 or TSH did not correlate with gestational age, or SDS for birth weight, birth length, height, body mass index, IGF‐I or IGFBP‐3. Mean FT4 decreased significantly during the first 6 months of GH treatment, but remained within the normal range. TSH did not change during treatment. The change in FT4 did not correlate with the change in height SDS during 24 months of GH treatment.

Conclusion  Preterm short SGA children have higher, although within the normal range, TSH levels than controls. The level of TSH does not correlate with gestational age, birth weight SDS or birth length SDS. FT4 decreases during GH treatment, but is neither associated with an increase in TSH nor does it affect the response to GH treatment. As these mild alterations in thyroid function do not appear clinically relevant, frequent monitoring of thyroid function during GH therapy is not warranted in short SGA children.
Intracranial haemorrhage in patients with congenital haemostatic defects
Authors: MISHRA P. , NAITHANI R. , DOLAI T. , BHARGAVA R. , MAHAPATRA M. , DIXIT A. , SETH T. , KUMAR R. , SAXENA R.
Published: July 2008

Summary.  We investigated 52 of 457 patients with congenital factor deficiencies with 57 episodes of intracranial haemorrhage (ICH) between 1998 and 2007. There were 38 severe haemophiliacs, 6 with factor XIII deficiency, 5 with factor X deficiency, 2 factor V‐deficient patients, and 1 with type 3 von Willebrand disease (VWD). The median age was 8 years (range 1 month–22 years). Most patients were below 15 years of age (86.5%). All patients with factor X deficiency were between 1 and 5 months of age. ICH was the primary bleeding episode leading to detection of factor deficiency in 19.2% (five patients with severe haemophilia and all patients with factor X deficiency). Trauma caused bleeding in 66%. None of the patients with factor X deficiency had history of prior trauma. Surgery was performed in five patients with subdural haematomas, all of whom survived. Conservative factor replacement with 100% correction for 3 days followed by 50–60% correction for 7 days was possible in 60% patients. Seizures requiring prolonged therapy were noted in eight patients. Death was recorded in 15 patients (29%). Inadequate therapy in the form of delay or insufficient replacement was noted in 7/15 deaths. ICH was seen in 11.3% of all patients with coagulation factor deficiencies. Factor X deficiency presented with ICH at an earlier age. Inadequate replacement therapy including delayed treatment caused nearly 50% of all deaths. Most patients can be managed satisfactorily with adequate replacement therapy alone, with surgery being reserved for those with worsening neurological conditions.
Haemophilia care in China: achievements of a decade of World Federation of Hemophilia treatment centre twinning activities
Authors: POON M.‐C. , LUKE K.‐H.
Published: July 2008

Summary.  The World Federation of Hemophilia (WFH) began its involvement in China in 1993, supporting Chinese haemophilia centre twinning programmes in 1997. Although only three Chinese centres were in a twinning relationship (Tianjin/Calgary 1997–2004, Guangzhou/Ottawa 2000–2006, Shanghai/Ottawa, Calgary 2002–2007), WFH helped establish a collaborative network of six Chinese centres (Tianjin, Guangzhou, Shanghai, Beijing, Hefei, Jinan) in 2004. These network centres, in collaboration with haemophilia patients, shared and coordinated several successful ongoing priority projects (Registry, Nursing, Laboratory Diagnosis, Physiotherapy and Prophylaxis). A number of physicians, nurses and technologists have received WFH fellowships for training internationally. They are becoming haemophilia‐care leaders and are key personnel working towards comprehensive care in China. National and regional workshops/conferences in addition to educational material development have been successful in reaching out to healthcare professionals and persons with haemophilia across the country. Key elements of success include the enthusiasm and commitment of the Chinese professionals and patient leaders in their desire to advance haemophilia care and their commitment to work collaboratively in a coordinated manner. They are beginning to gain national and international recognition and are launching outreach education and care programmes to cover other parts of China. WFH is now transitioning support in China from a twinning program to country programme (Global Alliance for Progress). Haemophilia work in China is still in the beginning, but there is now a solid foundation for future progress.
Endometrial intraepithelial neoplasia is associated with polyps and frequently has metaplastic change
Authors: Carlson J W , Mutter G L
Published: July 2008

Aims:  Endometrial intraepithelial neoplasia (EIN) is a monoclonal precursor to endometrioid endometrial adenocarcinoma characterized by a geographic cluster of crowded glands with epithelial cytology altered relative to the background. It may demonstrate epithelial metaplastic changes, or arise within polyps, but the frequencies of these features as encountered in practice is unknown. The aim was to report the epithelial differentiation state and polyp context of 83 sequential EIN lesions diagnosed over a 2‐year period.

Methods and results:  EIN is a rare lesion, seen in only 1.4% of endometrial biopsy specimens in a busy hospital‐based practice. Of 83 EIN cases, 39 contained metaplastic changes (18% squamous morular, 14% tubal secretory and 5% each of secretory, mucinous or ciliated change). Endometrial polyps were more likely (odds ratio 5.2, P < 0.001) to occur in the endometrial biopsy specimens of women with EIN lesions (43.3%), compared with the background polyp rate (12.9%) of comparable specimens from the same patient population.

Conclusions:  Non‐endometrioid differentiation and occurrence within polyps are frequent presentations of EIN lesions. Possible mechanisms of polyp association with EIN include: non‐shedding of polyp tissue creating a shelter for persistence of pre‐existing neoplastic glands, or promotion of premalignant glandular clones by unique polyp stroma.
Unexpectedly high 20th century floristic losses in a rural landscape in northern France
Authors: Van Calster H. , Vandenberghe R. , Ruysen M. , Verheyen K. , Hermy M. , Decocq G.
Published: July 2008

Resurveys of regional floras allow assessment of long‐term floristic change and to pinpoint driving forces behind these changes. Causes of floristic decline derived from such resurveys depend on the considered landscape, but are often associated with human activities especially in urbanized areas. Much could be learned from comparisons of contrasting landscapes.

Vascular plant abundance categories from a detailed, late 19th century flora were matched with distribution data from a late 20th century plant database in a rural area (Thiérache; 1673 km2) in northern France. Floristic change was characterized both in absolute numbers of extinct and extant species and by a measure for relative change in range size. Knowledge of land use changes and ecological correlates of floristic change permitted the causes for species change to be inferred and to identify which traits are associated with species vulnerability. Extinction rates were compared with similar studies from contrasting landscapes, taking into account the negative relationship between standardized extinction rates and log‐transformed size of the study area.

Of the 959 species from the historical list, 186 (19.4%) may be considered regionally extinct. Most extinct species were already rare historically. Differences among habitats indicated strong declines for aquatic species and arable weeds and least change for forest species. Percentage species loss per year in Thiérache equalled 0.22, which was higher than two other similar sized predominantly rural landscapes.

Across the main habitat groups, relative species decline was always associated with relatively higher stress tolerance and lower competitiveness and biased towards therophytes. The main causes of species decline were management intensification, eutrophication, secondary succession in semi‐natural open habitats and land use change.

Synthesis. Rural landscapes with no population density increase, no urbanization and a stable landscape configuration are believed to be less vulnerable; yet, on a relatively short time scale, without nature conservation measures, these landscapes may suffer strong species loss comparable to that in urbanized landscapes. Effective management of landscapes for biodiversity conservation whether they are urbanized or rural requires the development of a network of nature reserves.
Attitudes of patients and nurses towards diarrhoea during enteral tube feeding
Authors: Majid H.A. , Emery P.W. , Whelan K.
Published: July 2008

Background:  Diarrhoea is a common complication during enteral tube feeding (ETF) and, despite little empirical evidence, is said to be unpleasant for both patients and nurses (Whelan et al., 2007). The aspects of diarrhoea considered to be unpleasant among patients receiving ETF or among nurses caring for these patients has not previously been investigated. Therefore, the aim of the study was to investigate patients’ and nurses’ attitudes towards diarrhoea during ETF.

Methods:  A questionnaire was developed following an extensive literature review and was pre‐tested for clarity. An interviewer‐administered questionnaire survey was then conducted by the same interviewer, in patients receiving ETF and in nurses caring for patients receiving ETF. Seven different characteristics of diarrhoea (faecal colour, consistency, frequency, quantity, incontinence, odour, need to change underwear) were rated for their unpleasantness using a four‐point Likert scale. Ratings were then ranked and a mean rank calculated for each group to determine the most and least unpleasant characteristic. Ranks were then compared within patients and within nurses using a Friedman test. Ethical approval was obtained from an NHS Research Ethics Committee.

Results:  In total, 22 patients (16 male, six female; mean age 58.5 ± 15.2 years) receiving ETF due to dysphagia, post‐surgery, tracheostomy and inadequate nutritional intake and 57 nurses (16 male, 41 female) from respiratory, intensive therapy, elderly care and renal units were interviewed. There were differences in the rankings of the seven characteristics among patients (P < 0.001) and among nurses (P < 0.001). Patients rated incontinence and frequency as the most unpleasant characteristic of diarrhoea, whereas nurses rated odour and changing underwear as the most unpleasant characteristic of caring for patients with diarrhoea during ETF (Table 1).

 Mean ranking of attitude towards diarrhoea during ETF within nurses and patients (Rank 1 = least unpleasant, 7 = most unpleasant)

Characteristics
Patient (n = 22)
Nurses (n = 57)

Incontinence
5.5
4.0

Frequency
4.8
4.0

Consistency
4.4
4.1

Odour
4.2
5.3

Quantity
3.8
3.7

Colour
2.8
2.4

Changing underwear
2.5
4.5

P‐value (Friedman test)
<0.001
<0.001

Discussion:  The characteristics of diarrhoea considered to be unpleasant by patients are not the same as for nurses. The importance of understanding the patient perspective of symptoms is increasingly recognised in practice and research.

Conclusion:  Faecal incontinence and frequency are considered to be the most unpleasant characteristics of diarrhoea by patients. These characteristics should be monitored by healthcare professionals and strategies developed to minimize their occurrence in hospitalised patients receiving ETF.

Reference  Whelan, K. (2007) Enteral‐tube‐feeding diarrhoea: manipulating the colonic microbiota with probiotics and prebiotics. Proc. Nutr Soc. 66, 299–306.
Dietary management of orofacial granulomatosis: quantification of benzoates in foods and cosmetics
Authors: Nagarajah R. , Campbell H. , Sanderson J.D. , Lomer M.C.E.
Published: July 2008

Background:  Orofacial granulomatosis (OFG) is a chronic inflammatory disorder of unknown aetiology that typically presents with lip swelling, although a number of intra‐oral sites may also be affected. Management is challenging but recent evidence implicates dietary antigens. Benzoates are used as preservatives and occur naturally in some foods, particularly spices, some fruit and vegetables. A strict cinnamon and benzoate free diet is used as first line treatment with a clinical response in 68% patients (White et al., 2006). The benzoate free dietary treatment was recently extended to avoid cosmetics and toiletries containing benzoates. The aim of the current study is to quantify the level of added benzoates in food, cosmetics and toiletries for the development of education material to minimise benzoate exposure in long term management of OFG.

Methods:  Food, drink, cosmetic and toiletry manufacturers (n = 174) were identified by visiting local supermarkets and chemists. They were contacted by letter for information about whether benzoates were used in their products and, if so, at what levels. Companies that did not respond within 4 weeks were then contacted by telephone for information. An updateable database of benzoates in food, drinks, cosmetics and toiletries was developed for analysis of data and development of patient information.

Results:  Ninety manufacturers (51%) responded to the request for information on benzoates in their products. Sixteen manufacturers confirmed that some of their products (2–534) contained added benzoates. Of these, two food/drink and seven cosmetic/toiletry manufacturers provided quantitative data relating to the levels of benzoates in their products. A total of 136 products contained benzoates (foods 0.54–0.8 mg kg−1, non alcoholic drinks 140 mg L−, cosmetics 5.2–11 511 mg kg−1, pharmaceuticals 0.001–0.25 mg/100 mL), while all other products were free from added benzoates.

Discussion:  Obtaining quantitative data on the level of benzoates in the diet, cosmetics and toiletries is difficult due to manufacturers’ unwillingness to disclose information. Further research using an analytical technique may be the way forward to further quantify benzoates added to food, drinks, cosmetics and toiletries. It would also help to establish the levels at which benzoates occur naturally in some foods.

Conclusions:  Identification of the amount of benzoates in the diet, cosmetics and toiletries is not easy and using an analytical method to measure benzoates in products directly may help to increase quantitative information.

Reference  White, A., Nunes, C., Escudier, M., Lomer, M.C.E., Barnard, K., Shirlaw, P., Challacombe, S.J. & Sanderson, J.D. (2006) Improvement in oro‐facial granulomatosis on a cinnamon and benzoate free diet. Inflamm. Bowel Dis.12, 508–514.
A nutritional screening audit of new adult out‐patients with HIV
Authors: Pribram V. , Childs K. , Poulton M.
Published: July 2008

Background:  National guidelines state nutrition screening should be done on all out‐patients at first appointment as malnutrition is known to contribute to morbidity and mortality (NICE, 2006). Implementation of nutritional screening for adult out‐patients newly diagnosed with HIV was audited at the Caldecot Centre, King's College Hospital.

Methods:  Sixty patients were included by selecting every third patient from list of 142 patients attending new patient clinic between 1 April 2006 and 28 February 2007. A doctor and dietitian collected all data from integrated care pathway (ICP) forms and descriptive statistical analyses were performed.

Results:  Information was available for 50 patients with a mean age of 35. Of these, height and weight were recorded in 49 (SD 8.0) but body mass index (BMI) calculated in only 28. The number of patients reporting symptoms to nurses were; weight loss = 34%, appetite loss = 38%, diarrhoea = 12%, vomiting = 10%. Amount and duration of weight loss were recorded for only eight patients (range 2–12.7 kg) and seven patients, respectively. Referral to dietitian was indicated for 23 patients but only 10 patients had evidence of a planned appointment. Patients were seen within the following time period: 1 week = 3; 2 weeks = 2; 3 weeks = 5. Median BMI was 24.5 kg m−2 (range 17.7–36.4). Seven patients had BMI of 20 or less, 15 were in over‐weight range of which four were obese. One‐third of patients had a low CD4 (<200 cells mm−3) indicating increased risk of opportunistic infection. Symptoms related to HIV and malnutrition (e.g. diarrhoea, candidiasis, TB, pneumonia) were recorded by physician for 22% of patients.

Discussion:  Essential data were not collected or calculated in the majority of cases perhaps because patients newly diagnosed with HIV often have other urgent social and medical problems. There is clearly a need for nutritional screening in this population as large numbers (33%) presented with advanced infection and HIV and malnutrition related symptoms were widely reported.

Conclusion:  Nutritional screening of new HIV positive patients is inadequate. Training and education, repeat screening, redesign of screening form, and/or improved care pathways may help improve the implementation of nutritional screening for adult out‐patients with HIV.

Reference  National Institute for Health and Clinical Excellence (NICE). (2006) Nutritional Support in Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition. Clinical Guideline 32. London: National Institute for Health and Clinical Excellence.