bluuebunny/crossref_metadata_2025 huggingface dataset:
Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves
Authors: Srinivasan R. Sathish , Oliver Guillermo
Published: October 2011

Arteries, veins, and lymphatic vessels are functionally linked, and their physical interaction is tightly regulated. The lymphatic vessels communicate with the blood vessels only at the junction of the jugular and subclavian veins. Here, we characterize the embryonic lymphovenous valves controlling this vital communication and show that they are formed by the intercalation of lymphatic endothelial cells (LECs) with a subpopulation of venous endothelial cells (ECs) at the junction of the jugular and subclavian veins. We found that unlike LEC progenitors, which move out from the veins and differentiate into mature LECs, these Prox1-expressing ECs remain in the veins and do not acquire LEC features. We demonstrate that the development of this Prox1-expressing venous EC population, and therefore of lymphovenous valves, requires two functional copies ofProx1, as the valves are absent inProx1heterozygous mice. We show that this is due to a defect in the maintenance of Prox1 expression in venous ECs and LEC progenitors promoted by a reduction in Coup-TFII/Prox1 complex formation. This is the first report describing the molecular mechanism controlling lymphovenous communication.
Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells
Authors: Hollenhorst Peter C. , Ferris Mary W. , Hull Megan A. , Chae Heejoon , Kim Sun , Graves Barbara J.
Published: October 2011

The aberrant expression of an oncogenic ETS transcription factor is implicated in the progression of the majority of prostate cancers, 40% of melanomas, and most cases of gastrointestinal stromal tumor and Ewing's sarcoma. Chromosomal rearrangements in prostate cancer result in overexpression of any one of four ETS transcription factors. How these four oncogenic ETS genes differ from the numerous other ETS genes expressed in normal prostate and contribute to tumor progression is not understood. We report that these oncogenic ETS proteins, but not other ETS factors, enhance prostate cell migration. Genome-wide binding analysis matched this specific biological function to occupancy of a unique set of genomic sites highlighted by the presence of ETS- and AP-1-binding sequences. ETS/AP-1-binding sequences are prototypical RAS-responsive elements, but oncogenic ETS proteins activated a RAS/MAPK transcriptional program in the absence of MAPK activation. Thus, overexpression of oncogenic ETS proteins can replace RAS/MAPK pathway activation in prostate cells. The genomic description of this ETS/AP-1-regulated, RAS-responsive, gene expression program provides a resource for understanding the role of these ETS factors in both an oncogenic setting and the developmental processes where these genes normally function.
An Apoplastic H-Type Thioredoxin Is Involved in the Stress Response through Regulation of the Apoplastic Reactive Oxygen Species in Rice
Authors: Zhang Cui-Jun , Zhao Bing-Chun , Ge Wei-Na , Zhang Ya-Fang , Song Yun , Sun Da-Ye , Guo Yi
Published: October 2011

Thioredoxins (Trxs) are a multigenic family of proteins in plants that play a critical role in redox balance regulation through thiol-disulfide exchange reactions. There are 10 members of the h-type Trxs in rice (Oryza sativa), and none of them has been clearly characterized. Here, we demonstrate that OsTRXh1, a subgroup I h-type Trx in rice, possesses reduction activity in vitro and complements the hydrogen peroxide sensitivity of Trx-deficient yeast mutants. OsTRXh1 is ubiquitously expressed in rice, and its expression is induced by salt and abscisic acid treatments. Intriguingly, OsTRXh1 is secreted into the extracellular space, and salt stress in the apoplast of rice induces its expression at the protein level. The knockdown of OsTRXh1 results in dwarf plants with fewer tillers, whereas the overexpression of OsTRXh1 leads to a salt-sensitive phenotype in rice. In addition, both the knockdown and overexpression of OsTRXh1 decrease abscisic acid sensitivity during seed germination and seedling growth. We also analyzed the levels of hydrogen peroxide produced in transgenic plants, and the results show that more hydrogen peroxide is produced in the extracellular space of OsTRXh1 knockdown plants than in wild-type plants, whereas the OsTRXh1 overexpression plants produce less hydrogen peroxide under salt stress. These results show that OsTRXh1 regulates the redox state of the apoplast and influences plant development and stress responses.
Interplay Between N-Terminal Methionine Excision and FtsH Protease Is Essential for Normal Chloroplast Development and Function in Arabidopsis
Authors: Adam Zach , Frottin Frédéric , Espagne Christelle , Meinnel Thierry , Giglione Carmela
Published: October 2011

N-terminal methionine excision (NME) is the earliest modification affecting most proteins. All compartments in which protein synthesis occurs contain dedicated NME machinery. Developmental defects induced in Arabidopsis thaliana by NME inhibition are accompanied by increased proteolysis. Although increasing evidence supports a connection between NME and protein degradation, the identity of the proteases involved remains unknown. Here we report that chloroplastic NME (cNME) acts upstream of the FtsH protease complex. Developmental defects and higher sensitivity to photoinhibition associated with the ftsh2 mutation were abolished when cNME was inhibited. Moreover, the accumulation of D1 and D2 proteins of the photosystem II reaction center was always dependent on the prior action of cNME. Under standard light conditions, inhibition of chloroplast translation induced accumulation of correctly NME-processed D1 and D2 in a ftsh2 background, implying that the latter is involved in protein quality control, and that correctly NME-processed D1 and D2 are turned over primarily by the thylakoid FtsH protease complex. By contrast, inhibition of cNME compromises the specific N-terminal recognition of D1 and D2 by the FtsH complex, whereas the unprocessed forms are recognized by other proteases. Our results highlight the tight functional interplay between NME and the FtsH protease complex in the chloroplast.
Effect of an exon 1 mutation in the myostatin gene on the growth traits of the Bian chicken
Authors: Zhang G. X. , Zhao X. H. , Wang J. Y. , Ding F. X. , Zhang L.
Published: October 2011

Myostatin (MSTN), or growth and differentiation factor 8 (GDF8), is a member of the transforming growth factor (TGF)‐β superfamily. This family functions as a negative regulator of skeletal muscle development and growth in mammals. Single‐nucleotide polymorphisms in exon 1 of the Bian chicken myostatin gene were detected by polymerase chain reaction‐restriction fragment length polymorphism. A mutation (c.234G>A) in exon 1 was found. Female Bian chickens of genotypes AA and GA had significantly higher body weights than those of genotype GG (P < 0.05 or P < 0.01) from 6 to 18 weeks of age. These results suggested that the mutation c.234G>A in exon 1 could be used as a genetic marker for Bian chicken growth traits.
Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema: randomized controlled trial with follow‐up until age 3 years
Authors: Gore C. , Custovic A. , Tannock G. W. , Munro K. , Kerry G. , Johnson K. , Peterson C. , Morris J. , Chaloner C. , Murray C. S. , Woodcock A.
Published: October 2011

Background

Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema.

Objective

We investigated whether dietary supplementation of infants with eczema at age 3–6 months with Lactobacillus paracasei CNCM I‐2116 or Bifidobacterium lactis CNCM I‐3446 had a treatment effect or altered allergic disease progression.

Methods

Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post‐randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen‐sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3–6 months with physician‐diagnosed eczema were recruited; 137/208 (SCORAD≥10, consuming ≥200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3‐month period, while receiving extensively hydrolysed whey‐formula (dairy‐free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula‐fed (n = 49). Trial number: ISRCTN41490500.

Results

Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12‐week treatment‐period (SCORAD‐score pre‐/post‐intervention: B. lactis 25.9 [95% CI: 22.8–29.2] to 12.8 [9.4–16.6]; L. paracasei 25.4 [22.1–29] to 12.5 [9.2–16.4]; placebo 26.9 [23.4–30.6] to 11.8 [9.6–14.3]; P = 0.7). Results were similar when analysis was controlled for allergen‐sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD‐score between randomized and observational groups.

Conclusion and Clinical Relevance

We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years.
Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency
Authors: Turton J.P. , Strom M. , Langham S. , Dattani M.T. , Le Tissier P.
Published: October 2011

Background  Mutations in the POU1F1 gene severely affect the development and function of the anterior pituitary gland and lead to combined pituitary hormone deficiency (CPHD).

Objective  The clinical and genetic analysis of a patient presenting with CPHD and functional characterization of identified mutations.

Patient  We describe a male patient with extreme short stature, learning difficulties, anterior pituitary hypoplasia, secondary hypothyroidism and undetectable prolactin, growth hormone (GH) and insulin‐like growth factor 1 (IGF1), with normal random cortisol.

Design  The POU1F1 coding region was amplified by PCR and sequenced; the functional consequence of the mutations was analysed by cell transfection and in vitro assays.

Results  Genetic analysis revealed compound heterozygosity for two novel putative loss of function mutations in POU1F1: a transition at position +3 of intron 1 [IVS1+3nt(A>G)] and a point mutation in exon 6 resulting in a substitution of arginine by tryptophan (R265W). Functional analysis revealed that IVS1+3nt(A>G) results in a reduction in the correctly spliced POU1F1 mRNA, which could be corrected by mutations of the +4, +5 and +6 nucleotides. Analysis of POU1F1R265W revealed complete loss of function resulting from severely reduced protein stability.

Conclusions  Combined pituitary hormone deficiency in this patient is caused by loss of POU1F1 function by two novel mechanisms, namely aberrant splicing (IVS1+3nt (A>G) and protein instability (R265W). Identification of the genetic basis of CPHD enabled the cessation of hydrocortisone therapy without the need for further assessment for evolving endocrinopathy.
Interobserver concordance in the assessment of features used for the diagnosis of cervical atypical squamous cells and squamous intraepithelial lesions (ASC‐US, ASC‐H, LSIL and HSIL)
Authors: Bigras G. , Wilson J. , Russell L. , Johnson G. , Morel D. , Saddik M.
Published: October 2011

G. Bigras, J. Wilson, L. Russell, G. Johnson, D. Morel and M. Saddik  Interobserver concordance in the assessment of features used for the diagnosis of cervical atypical squamous cells and squamous intraepithelial lesions (ASC‐US, ASC‐H, LSIL and HSIL)

Objectives:  Given the well‐known poor reproducibility of cervical cytology diagnosis, especially for atypical squamous cells of undetermined significance (ASC‐US) and low‐grade squamous intraepithelial lesion (LSIL), this study surveyed reproducibility in the assessment of individual cytomorphological features.

Methods:  One hundred and fifty cells or groups of cells, with a variety of morphological appearances, including normal cells, high‐grade squamous intraepithelial lesion (HSIL), LSIL, ASC‐US and ASC cannot exclude HSIL (ASC‐H), were precisely marked on 150 different liquid‐based cytological preparations. They were analysed by 17 observers who assessed 17 cytological features including nuclear features (chromatin texture, nuclear outline, nuclear shape, etc.), cytoplasmic features (cell shape, cytoplasmic staining, cytoplasmic clearing, etc.) and group characteristics (nuclear polarity, cellular density, etc.). A total of 43 350 data scores were collected in a database using a web‐based survey. Kendall’s W and relative entropy indexes were utilized to compute concordance indexes of respectively ordinal and nominal variables.

Results:  Nuclear features have significantly lower reproducibility (0.46) compared with other cytological features (0.59). The feature with least agreement is assessment of chromatin texture. A small but significant difference in concordance was found between two subsets of observers with different levels of experience.

Conclusion:  Most previous studies assessing reproducibility of cytological diagnoses show, at best, moderate reproducibility among observers. This study focused on agreement regarding the presence of constituent morphological features used to recognize dyskaryosis and various grades of squamous intraepithelial lesions. A map of reproducibility indexes is presented that highlights, for daily practice or teaching, the robustness of features used for cytological assessment, recognizing that diagnosis is always based on a combination of features.
The molecular pathogenesis of corticotroph tumours
Authors: Dworakowska Dorota , Grossman Ashley B.
Published: October 2011

Eur J Clin Invest 2012; 42 (6): 665–676

Background  The pathogenesis of tumour formation in the anterior pituitary including adrenocorticotropic hormone (ACTH)‐secreting tumours has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain unclear.

Materials and methods  We searched PubMed on any paper related with molecular pathology of pituitary corticotroph adenomas and have included to this review all relevant references published up to June 2011.

Results  Current studies increased our knowledge on the genetic basis of McCune–Albright syndrome (MAS), multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), pituitary adenoma predisposition syndromes and tuberous sclerosis, but they have performed little to elucidate the causes of sporadic pituitary tumours including Cushing disease.

Discussion  The aim of this review was to focus on the most recently published advances in the molecular pathology of corticotroph adenomas, which are presented in the context of changes seen in all types of pituitary adenomas, as well as in terms of corticotrophin‐releasing hormone/ACTH/cortisol‐specific pathways.

Conclusions  We would expect that over the next 5 years, more detailed analysis of inter‐cellular communication pathways between pituitary cells, including the cadherins and integrins, and their interactions with other signalling pathways such as the β‐catenin cascade will help elucidate what exactly goes awry in the formation of a benign corticotroph adenoma. This should in turn predict novel forms of pharmacological tumour control.
Plastic responses to four environmental stresses and cross‐resistance in a laboratory population of Drosophila melanogaster
Authors: Bubliy Oleg A. , Kristensen Torsten N. , Kellermann Vanessa , Loeschcke Volker
Published: October 2011

1. Acclimation or hardening to one stress in arthropods can lead to a plastic response, which confers increased resistance to other stresses. Such cross‐resistance may indicate shared physiological resistance mechanisms and a possibility of joint evolution for resistance traits.

2. In this study, we tested for cross‐resistance using Drosophila melanogaster as a model system. Adult females were assayed for resistance to cold, heat, desiccation and starvation following cold acclimation, heat hardening, desiccation hardening and starvation acclimation, resulting in 12 pretreatment‐by‐test combinations for estimating potential cross‐resistance effects. The acclimation/hardening regimes were chosen so that flies enhanced their resistance to the same type of stress as that used for the particular pretreatment.

3. Two cases of cross‐resistance were found, with desiccation‐hardened and starvation‐acclimated flies being more resistant than control ones in heat and desiccation resistance tests, respectively. In four cases, no acclimation/hardening effect was observed, and for six pretreatment‐by‐test combinations, the effect of acclimation/hardening was negative.

4. We also revealed that heat and desiccation hardening as well as acclimation to starvation had a cost under non‐stressful conditions leading to reduced longevity. Cold acclimation did not affect longevity, although its effect was difficult to estimate precisely: during pretreatment at a low temperature, biological ageing of the flies might be delayed.

5. The pattern of acclimation/hardening responses considered in the context of literature data on stress resistance indicates that expression of heat‐shock proteins is not likely to contribute to the observed cross‐resistance, but other probable general stress resistance mechanisms such as reduction of metabolic rate and accumulation of energy reserves might be involved.

6. The lack of cross‐resistance induced by acclimation/hardening treatments suggests that in an environment with multiple stresses, evolution of shared protective systems associated with plastic responses may be constrained.
Violence and under‐reporting: learning disability nursing and the impact of environment, experience and banding
Authors: Lovell Andrew , Skellern Joanne , Mason Tom
Published: October 2011

Aims and objectives.  The study explores the implications of a survey into the discrepancy between actual and reported incidents of violence, perpetrated by service users, within the learning disability division of one mental health NHS Trust.

Background.  Violence within the NHS continues to constitute a significant issue, especially within mental health and learning disability services where incidence remains disproportionately high despite the context of zero tolerance.

Design.  A whole‐population survey of 411 nurses working within a variety of settings within the learning disability division of one mental health NHS Trust.

Methods.  A questionnaire was administered to learning disability nursing staff working in community, respite, residential, assessment and treatment and medium secure settings, yielding a response rate of approximately 40%.

Conclusions.  There were distinct differences in the levels of violence reported within specific specialist services along with variation between these areas according to clinical environment, years of experience and nursing band. The study does not support previous findings whereby unqualified nurses experienced more incidents of violence than qualified nurses. The situation was less clear, complicated by the interrelationship between years of nursing experience, nursing band and clinical environment. The conclusions suggest that the increased emphasis on reducing violent incidents has been fairly successful with staff reporting adequate preparation for responding to specific incidents and being well supported by colleagues, managers and the organisation. The differences between specific clinical environments, however, constituted a worrying finding with implications for skill mix and staff education.

Relevance to clinical practice.  The study raises questions about the relationship between the qualified nurse and the individual with a learning disability in the context of violence and according to specific circumstances of care delivery. The relationship is clearly not a simple one, and this group of nurses’ understanding and expectations of tolerance requires further research; violence is clearly never acceptable, but these nurses appear reluctant to condemn and attribute culpability.
Self‐care competence in the case of Brazilian patients with diabetes mellitus in a multiprofessional educational programme
Authors: Landim Camila AP , Zanetti Maria L , Santos Manoel A , Andrade Thiago AM , Teixeira Carla RS
Published: October 2011

Aim.  To compare self‐care competencies in the physical, cognitive and emotional and motivational dimensions of patients with diabetes mellitus before and after participation in an educational programme.

Background.  Diabetes mellitus is mainly characterised by a dysfunction of glucose metabolism. The growth of diabetes mellitus as a chronic condition requires continuous management and requires health services to implement care strategies. Diabetes education and self‐care competence have been recognised over the last few decades as essential for patients with diabetes mellitus to achieve positive treatment results.

Design.  A prospective, comparative study was used.

Methods.  A total of patients with 43 diabetes mellitus participated in this study, before and after a four‐month educational programme on diabetes held in Ribeirão Preto, SP, Brazil in 2009. Data were collected through the Scale to Identify diabetes mellitus Patients’ Self‐Care Competence [Escala para Identificação da Competência do Portador de diabetes mellitus para o Autocuidado] at two points in time: at the beginning (T1) and at the end (T2) of the programme. Linear mixed effects models were used (p < 0·05) in the analysis.

Results.  Statistically significant differences were not found in relation to physical competence in the comparison between T1 and T2. Statistically significant differences were found in the comparison of cognitive and emotional and motivational competencies, respectively, between T1 and T2.

Conclusion.  The scores related to cognitive and emotional and motivational competencies for self‐care presented statistically significant differences between T1 and T2.

Relevance to clinical practice.  The educational activities implemented in the educational programme favoured improved cognitive, emotional and motivational competence for the incorporation of positive self‐care actions.
Studies on mechanisms for enhanced clearance of low‐density lipoproteins in patients with primary hypertriglyceridaemia
Authors: VEGA G. L. , GRUNDY S. M.
Published: October 2011

Abstract Vega GL, Grundy SM (Center for Human Nutrition and Departments of Clinical Nutrition, Internal Medicine and Biochemistry. University of Texas Southwestern Medical Center at Dallas, and Veterans Administration Medical Center, Dallas, Texas, USA). Studies on mechanisms for enhanced clearance of low‐density lipoproteins in patients with primary hypertriglyceridaemia.

Patients with primary hypertriglyceridaemia usually have increased clearance rates for plasma low‐density lipoproteins (LDL). To evaluate the mechanisms for this effect, simultaneous turnover rates for autologous and normal homologous LDL were determined in 12 patients with primary hypertriglyceridaemia. On average, the autologous LDL was cleared more rapidly than the normal homologous LDL. Fractional catabolic rates (FCRs) for autologous LDL averaged 0.61 ± 0.06(SEM) pools d−1, whereas FCRs for homologous LDL averaged 0.49 ± 0.04 pools d−1. In eight of the 12 patients the FCRs for ‘hypertriglyceridaemic’ LDL were found to be significantly higher than for normal LDL; in four others both forms of LDL were cleared at essentially the same rate. In all cases, however, both for the normal and ‘hypertriglyceridaemic’ LDL, clearance rates were higher than normal. Thus, besides the variability in LDL affinity for removal pathways, hypertriglyceridaemic patients appear to have an increased availability of LDL receptors for removal of circulating LDL.
Addition of non‐pharmacological methods of treatment in patients on antihypertensive drugs: results of previous medication, laboratory tests and life quality
Authors: ÅBERG H. , TIBBLIN G.
Published: October 2011

AbstractÅberg H, Tibblin G (Department of Family Medicine. University Hospital, University of Uppsala, Uppsala, Sweden). Addition of non‐pharmacological methods of treatment in patients on antihypertensive drugs: results of previous medication, laboratory tests and life quality.

Four hundred patients from eight health centres were recruited for this 2‐year study on the possible replacement of antihypertensive drugs by non‐pharmacological therapy. All the patients were given a device to measure their blood pressure at home and had monthly checks at a health centre. Two hundred patients on antihypertensive drugs (G1) started additional non‐pharmacological therapy after 1 year in the study, while the rest (G2) had used it from the beginning. Antihypertensive drugs were withdrawn according to predetermined criteria.

The drop‐out rate was 1.5% each year. Medication was withdrawn completely from 42.7% of G1, and in 21.5% it was withheld for at least 18 months. The corresponding figures for G2 were 46.4% and 25.5% respectively. Most of the medication withdrawal in G1 occurred during the first year, when the group's management consisted solely of blood pressure measurements at home and frequent visits to the health centre. Serum triglycerides decreased on non‐pharmacological treatment in both sexes in both groups. Life quality improved, particularly for the group (n= 173) that had the drugs withdrawn.
Fulminant severe retinopathy in a newly diagnosed diabetic without risk factors
Authors: O'MAHONY D. , FERRISS J. B. , PERRY I.
Published: October 2011

Abstract O'Mahony D, Ferriss JB, Perry I (Department of Medicine, Regional Hospital. Wilton, Cork, Ireland). Fulminant severe retinopathy in a newly diagnosed diabetic without risk factors.

The authors describe a 26‐year‐old female developing severe proliferative retinopathy within 2 weeks of diagnosis of insulin‐dependent diabetes mellitus. The patient presented with profound diabetic ketoacidosis, but had no other risk factors for retinopathy. She had marked bilateral myopia which did not protect her from retinopathy. Nine months after diagnosis of diabetes, she has profound visual impairment despite correction for myopia, and has also developed marked autonomic neuropathy and diabetic nephropathy.
Nephropathy is delayed by intensified insulin treatment in patients with insulin‐dependent diabetes mellitus and retinopathy*
Authors: REICHARD P. , ROSENQVIST U.
Published: October 2011

Abstract Reichard P, Rosenqvist U (Department of Internal Medicine II, The Southern Hospital, and Stockholm County Council Teaching Centre for Diabetes (LUCD). Stockholm, Sweden). Nephropathy is delayed by intensified insulin treatment in patients with insulin‐dependent diabetes mellitus and retinopathy.

Patients with insulin‐dependent diabetes mellitus (IDDM) and non‐proliferative retinopathy were randomized to intensified conventional insulin treatment (ICT, n = 44) or regular treatment (RT, n = 51).

During a 3‐year period the glycosylated haemoglobin (HbA1c) levels were reduced to a greater extent (P = 0.00001) in the ICT group (from 9.5 ± 0.2 to 7.4%, P = 0.0001) than in the RT group (9.4 ± 0.2 to 9.0 ± 0.2. P = 0.004).

The urinary albumin excretion rate (UAER) increased significantly (P = 0.033) in the RT group but not in the ICT group, and the UAER differed significantly (P = 0.031) between the groups after 3 years.

The mean HbA1c values during the study period independently influenced the deterioration of UAER levels (P = 0.029). Initial diastolic blood pressure (P = 0.112). the HbA1c value at entry (P = 0.480) and the smoking habits (P = 0.959) were not related to change of UAER levels.

Manifest nephropathy after 3 years was seen almost exclusively in patients with HbA1c levels above 9%. Improved blood glucose control, without ‘near normoglycaemia’, delayed the progression of nephropathy in patients with IDDM and retinopathy.
Response to erythropoietin in anaemic haemodialysis patients
Authors: NIELSEN O. J. , THAYSEN J. H.
Published: October 2011

Abstract Nielsen OJ, Thaysen JH (Medical Department P, Division of Nephrology, Rigshospitalet, Copenhagen, Denmark). Response to erythropoietin in anaemic haemodialysis patients.

An open non‐randomized clinical trial with recombinant human erythropoietin (rhEpo) was conducted in 10 chronic haemodialysis patients with considerable iron overload. Pretreatment serum erythropoietin levels were significantly decreased for the degree of anaemia (22.0 ± 7.6 mUnits (U) ml−1).

Initially all patients received 120 U kg−1 of rhEpo intravenously three times a week and after a period of 45 days the haematocrit rose from 25 ± 3 to 36 ± 5. A reduced dose of 30 U kg−1 was then instituted which stabilized the haematocrit at this level.

The development of anti‐erythropoietin antibodies to rhEpo could not be demonstrated. Endogenous serum erythropoietin levels remained unchanged during therapy with rhEpo. The serum ferritin concentration, which was initially 3118 ± 1556 μg l−1. was significantly reduced to 2203 ± 1299 μg l −1 after an 80‐d treatment period.

The side‐effects in three patients included the occasional sensation of increased body heat without fever. In one previously hypertensive patient the antihypertensive therapy had to be temporarily increased, but otherwise both the mean diastolic and systolic blood pressure remained constant during the observation period. No clotting of arteriovenous fistulas occurred.
Clinical relevance of pedal pulse palpation in patients suspected of peripheral arterial insufficiency
Authors: CHRISTENSEN J. H. , FREUNDLICH M. , JACOBSEN B. A. , FALSTIE‐JENSEN N.
Published: October 2011

Abstract Christensen JH, Freundlich M, Jacobsen BA, Falstie‐Jensen N (Department of Clinical Physiology, Aalborg Hospital, Aalborg, Denmark). Clinical relevance of pedal pulse palpation in patients suspected of peripheral arterial insufficiency.

Previous studies in patients with peripheral arterial disease (PAD) have shown that the prognosis is relatively good when the distal systolic ankle index (ankle systolic pressure/arm systolic pressure) is above 50% and the distal toe systolic pressure is above 40 mmHg. In 132 patients suspected of PAD in the legs we investigated the relationship between the presence of pedal pulse and the distal systolic pressure in order to discover what diagnostic and prognostic information could be found from pulse palpation alone. The prospective study consisted of three consecutive series (A, 51 patients: B, 42 patients: and C, 39 patients); three of the authors palpated the arteries of the patients’ feet: one author in each series. The palpatory findings were related to the distal systolic pressures. When pedal pulses were present we found: (a) ankle indices above 50%: and (b) toe systolic pressures above 40 mmHg. These minimal pressure values were reproducible in the three series. Furthermore, patients lacking palpable pulses in both feet had ankle indices below 90%. We conclude: (a) if pulses are palpable on both feet of a patient the prognosis for progression is relatively good regarding the patient's PAD; (b) if pedal pulse is palpable an arteriosclerotic ulcer on the foot will heal; and (c) patients lacking palpable pulses in both feet actually suffer from PAD.
Coffee and tea consumption, dietary fat intake and serum cholesterol concentration of Finnish men and women
Authors: ARO A. , PIETINEN P. , UUSITALO U. , TUOMILEHTO J.
Published: October 2011

Abstract Aro A. Pietinen P, Uusitalo U, Tuomilehto J (Departments of Biochemistry and Epidemiology. National Public Health Institute. Helsinki, Finland). Coffee and tea consumption, dietary fat intake and serum cholesterol concentration in Finnish men and women.

The association between the consumption of coffee and tea and serum cholesterol concentration was studied in a population sample of 653 men and 695 women from east and south‐west Finland. Cholesterol and high density lipoprotein (HDL) cholesterol were determined from fresh serum samples. Smoking and the intake of coffee, tea and alcohol were assessed by a questionnaire, and nutrient intake was determined from 3‐day food records. Serum cholesterol and non‐HDL cholesterol showed a positive and linear association with coffee consumption in men. In women, no such significant linear association was evident, although the highest mean serum cholesterol levels were found in subjects consuming seven to nine cups of coffee daily. Both in men and in women coffee consumption was positively associated with smoking and the intake of saturated and monounsaturated fatty acids and cholesterol. Serum cholesterol values, adjusted for age, body mass index, smoking, dietary cholesterol, fatty acids, alcohol and physical activity, showed a significant linear association with coffee consumption in men but not in women. Although coffee consumption and high intake of saturated fatty acids and cholesterol were related both in men and in women, adjustment for dietary and other confounding factors did not remove the association between coffee consumption and serum cholesterol concentration in men.
Can villous atrophy be induced by chronic alcohol consumption?
Authors: SJÖLUND K. , PERSSON J. , BERGMAN L.
Published: October 2011

Abstract Sjölund K, Persson J, Bergman L (Departments of Internal Medicine and Surgery, Central Hospital, Karlstad, Sweden). Can villous atrophy be induced by chronic alcohol consumption?

A 43‐year‐old man presented with loose stools, abdominal pain and a weight loss of 15 kg. Investigations revealed a pancreatic insufficiency and an enteropathy with villous atrophy. Coeliaki was suspected. In spite of treatment with a gluten‐free diet in hospital the patient did not improve and the villous atrophy remained unchanged. Other causes than coeliaki to villous atrophy were ruled out. The patient had a heavy consumption of alcohol and after prolonged abstinence the patient gained weight, the pain disappeared and the stools were normalized. The jejunal biopsy was now normal. This case report raises the possibility that enteropathy and villous atrophy may be causally related to alcohol overconsumption.
Abrupt change from a β‐adrenoceptor blocking drug to enalapril in hypertension*
Authors: LILJA M. , IKÄHEIMO M. , JUUSTILA H. , PIRTTIAHO H. , PAKARINEN A. , LEPPÄLUOTO J. , JOUNELA A.J. , RUSKOAHO H.
Published: October 2011

Abstract Lilja M, Ikäheimo M, Juustila H, Pirttiaho H, Pakarinen A, Leppäluoto J, Jounela AJ, Ruskoaho H (Departments of Medicine, Clinical Chemistry. Physiology and Pharmacology. University of Oulu, Oulu. Finland). Abrupt change from a β‐adrenoceptor blocking drug to enalapril in hypertension.

The haemodynamic and hormonal effects of an elective change of antihypertensive therapy from a β‐adrenoceptor blocking drug to a converting enzyme inhibitor, enalapril, were monitored in 12 hypertensive in‐patients (WHO I). Blood pressure and heart rate were determined every 2–4 h using an automatic sphygmomanometer during an abrupt cessation of the previous β‐adrenoceptor blocking drug and commencement of treatment with enalapril 20 mg o.d. 12 h later. Mean blood pressure values at rest and during the hand grip test were lower when on enalapril, but heart rate was significantly higher, and three patients suffered from palpitations during the change. The change resulted in an improvement in cardiac function both at rest and during isometric work, as shown by echocardiography. A rapid decrease in plasma angiotensin converting enzyme (ACE) activity and an increase in renin activity were also seen after the change, while plasma levels of atrial natriuretic peptide (ANP) decreased towards normal values. The results suggest that an abrupt change from a chronic β‐adrenoceptor blocking drug to enalapril is safe, feasible and is likely to produce favourable haemodynamic and hormonal effects in hypertensive patients.
Serum and urinary phosphate during and after prolonged muscular ischaemia in non‐exercising men and women
Authors: ANDERSEN P. T. , NIELSEN L. K. , HANSEN A. K. , TOFT E. , JENSEN B. V.
Published: October 2011

Abstract Andersen PT, Nielsen LK, Hansen AK, Toft E. Jensen BV (Departments of Thoracic and Vascular Surgery, Medicine C. and Cardiology. Aalborg Sygehus, Aalborg. Denmark). Serum and urinary phosphate during and after prolonged muscular ischaemia in non‐exercising men and women.

Serum inorganic phosphate (Pi) concentrations and urinary Pi excretions were measured in nine patients undergoing abdominal aortic bypass grafting (group I) and in nine patients undergoing lower limb arterial embolectomy (group II). In group I, serum Pi concentrations were normal until 24 h after reperfusion. when they decreased, reaching their nadir at 48 h (median Pt 0.45 mmol l−1). The urinary phosphate clearance relative to the creatinine clearance (Cp/Cc) increased 5 min after reperfusion reaching a maximal median value (0.454) in the 2–24‐h collection period. In group II. eight patients had a normal and one had a subnormal serum Pi before reperfusion. None developed hypo‐ or hyperphosphataemia and the Cp/Cc. remained unchanged. Daily urinary Pi excretion was higher in group I than in group II (P < 0.03).

The authors concluded that the regional muscular ischaemia in non‐exercising men and women was not associated with hyperphosphataemia. The possible influence of major surgery and anaesthesia on phosphate homeostasis should be considered.
Plasma concentrations of calcitonin gene‐related peptide increase during haemodialysis: relation to blood pressure*
Authors: ODAR‐CEDERLÖF I. , THEODORSSON E. , ERIKSSON C.‐G. , KJELLSTRAND C. M.
Published: October 2011

Abstract Odar‐Cederlöf I, Theodorsson E, Eriksson C‐G, Kjellstrand CM (Division of Nephrology, Department of Medicine and Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden). Plasma concentrations of calcitonin gene‐related peptide increase during haemodialysis: relation to blood pressure.

The authors measured the plasma levels of calcitonin gene‐related peptide (CGRP), the most potent vasodilatator known, during sequential ultrafiltration and haemodialysis in 12 patients using a radio‐immunoassay method. Mean plasma levels of CGRP were 70.3 ± 16.5 (mean ± SE) pmol l−1 at the start of treatment, it increased to 85.3 ± 17.6 pmol l−1 during ultrafiltration and to 114.5 ± 25.3 pmol l−1 during dialysis. Systolic blood pressure decreased during haemodialysis. Plasma levels of CGRP were negatively correlated to systolic blood pressure before and at the end of dialysis, and changes in plasma levels of CGRP were strongly correlated to changes in systolic blood pressure. The increase in CGRP levels was not correlated to the fluid removal, toxin removal or changes in osmolality.

The increase in plasma levels of CGRP observed during dialysis may be an important cause of dialysis induced vasodilatation and fall in blood pressure.
Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid
Authors: CARLSON L. A. , HAMSTEN A. , ASPLUND A.
Published: October 2011

Abstract Carlson LA, Hamsten A, Asplund A (King Gustaf V Research Institute and Department of Internal Medicine, Karolinska Institute and Karolinska Hospital, Stockholm, Sweden). Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid.

Thirty‐one consecutive unselected hyperlipidaemic patients were treated daily with 4 g of nicotinic acid for 6 weeks. The concentrations in serum of lipoprotein Lp(a), and the major lipoprotein classes, were determined before and after the treatment. Nicotinic acid significantly reduced the serum levels of Lp(a) in the whole patient group. Linear regression analysis showed a strong negative relationship between the percentage reduction of Lp(a) and the serum triglyceride level before treatment (r = −0.78), which implied that for patients with a serum triglyceride concentration above 7.5 mmol l−1 there was a rise of Lp(a). The average individual percentage decrease of the concentration of Lp(a) was calculated after the exclusion of four patients who had serum triglyceride levels above 10 mmol l−1. The decrease was 38% with a 95% confidence interval of 28–47%. The absolute decrease of Lp(a) was correlated with the pretreatment levels of Lp(a) (r = 0.91). Within the whole group of patients there was a linear relationship between the percentage decrease of Lp(a) and that of LDL cholesterol (r = 0.88). This latter strong relationship might be due to an inhibition of the synthesis of the protein common to the two lipoproteins, apolipoprotein B.
Peripheral neuropathy, coagulopathy and nodular regenerative hyperplasia of the liver in a patient with multiple serologic auto‐antibody activities and IgM B‐cell lymphoma
Authors: ZUBER M. , GHERARDI R. , DEFER G. , GAULARD P. , DIVINE M. , ZAFRANI E. S.
Published: October 2011

Abstract Zuber M, Gherardi R, Defer G, Gaulard P, Divine M, Zafrani ES (Service de Neurologie, Département de Pathologie Tissulaire et Cellulaire and Départment d'Hématologie Clinique, Hôpital Henri Mondor. Créteil. France). Peripheral neuropathy, coagulopathy and nodular regenerative hyperplasia of the liver in a patient with multiple serologic auto‐antibody activities and IgM B‐cell lymphoma.

A patient with IgM‐secreting B‐cell lymphoma developed demyelinating peripheral neuropathy, nodular regenerative hyperplasia of the liver, coagulopathy, and terminal miliary lymphomatous spreading. Serologic auto‐antibody activities directed against myelin associated glycoprotein, prothrombinase complex (i.e. lupus anticoagulant) and smooth muscle cells were detected. It is suggested that there is a link between the IgM gammopathy, the immunological abnormalities and the various clinico‐pathological conditions.
Pulsatile insulin infusion and glucose‐homeostasis in well‐controlled Type 1 (insulin‐dependent) diabetic patients
Authors: HEINEMANN L. , SONNENBERG G. E. , HOHMANN A. , RITZENHOFF A. , BERGER M. , BENN J. , SÖNKSEN P. , KELLEY D. , GERICH J. , AOKI T. , SORENSEN J.
Published: October 2011

Abstract Heinemann L, Sonnenberg GE, Hohmann A, Ritzenhoff A, Berger M, Benn J, Sönksen P, Kelley D, Gerich J, Aoki T, Sorensen J. (Department of Nutrition and Metabolic Diseases, Heinrich‐Heine University of Düsseldorf, Düsseldorf, West Germany, Department of Medicine, United Medical and Dental Schools of Guys and St. Thomas's Hospital, London, UK, Diabetes Section, Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, University of Pittsburgh. Pittsburgh, Division of Endocrinology, Department of Internal Medicine, University of California, Davis, Sacramento, American Technology and Ventures, Division of Baxter Travenol, Irvine, USA). Pulsatile insulin infusion and glucose‐homeostasis in well‐controlled Type 1 (insulin‐dependent) diabetic patients.

Pulsatile, intravenous insulin infusion designed to mimic the portal insulin concentrations that emerge physiologically after a meal, has been postulated to improve glucose tolerance in Type 1 (insulin‐dependent) diabetic patients. We studied the effects of insulin pulsing (10 i.v. pulses of human insulin of 0.035 U kg−1 idealised body weight were given, each of 20 s duration, with intervals of 6 min, three times per day covered with adequate administration of glucose) on 2 successive days on glucose‐tolerance in nine well‐controlled Type 1 diabetic patients on continuous subcutaneous insulin infusion therapy (age 26 (7) years, mean (SD): duration of diabetes 10(7) years: body mass index 23.4 (2.3) kg m−2; HbA1c. 6.0 (0.6)%). On the days before and after the insulin pulsing, the patients were subjected to metabolic assessments by an oral glucose tolerance test (1 g glucose kg−1 body weight) 30 min after the subcutaneous injection of 0.15 U kg−1 body weight regular human insulin and a subsequent bicycle‐ergometer test.

During these metabolic assessments, plasma free insulin concentrations, plasma glucagon and the non‐protein respiratory quotient remained unaffected by the insulin pulsing. However, glucose tolerance deteriorated significantly (maximal glucose concentration 120 min after glucose load was 10.0 mmol l−1 before and 13.9 mmol l−1 after insulin pulsing. P < 0.01).

In conclusion, the pattern of insulin pulsing used in this study did not ameliorate oral glucose homeostasis in well‐controlled Type 1 (insulin dependent) diabetic patients.
Effect of xamoterol on exercise capacity and left ventricular function in angina pectoris and in dilated cardiomyopathy
Authors: BOSTRÖM P.‐A. , JOHANSSON B. W. , LECEROF H. , LILJA B. , TORP A.
Published: October 2011

Abstract Boström P‐Å, Johansson BW, Lecerof H, Lilja B, Torp A. (Department of Medicine, Section of Cardiology and Department of Clinical Physiology, Lund University, Malmö General Hospital, Malmö, Sweden.) Effect of xamoterol on exercise capacity and left ventricular function in angina pectoris and in dilated cardiomyopathy.

The present study evaluates the effect of the β1 partial agonist xamoterol in patients with coronary artery disease compared to the effect in patients with dilated cardiomyopathy. Nineteen patients with angina pectoris and nine patients with dilated cardiomyopathy received xamoterol 200 mg b.i.d. for 4 weeks in a placebo‐controlled double‐blind study. The effect was evaluated with a standardized exercise test and radionuclide angiocardiography with determination of global and regional ejection fraction. At rest xamoterol caused no significant changes among the angina patients while global and regional ejection fraction increased among the cardiomyopathy patients. During exercise, when the drug exerts a β1‐antagonist effect, xamoterol increased the exercise performance among the angina pectoris patients. Fourteen out of 19 patients with angina pectoris were unable to increase their ejection fraction from rest to work due to coronary ischaemia. These 14 patients improved their global ejection fraction during work after xamoterol treatment.
Relationships between serum triglycerides and γ‐glutamyltransferase among shift and day workers
Authors: KNUTSSON A.
Published: October 2011

AbstractKnutsson A (National Institute for Psychosocial Factors and Health, Stockholm. Sweden). Relationships between serum triglycerides and γ‐glutamyltransferase among shift and day workers.

Increased levels of serum triglycerides in shift workers have been reported in two population‐based studies. In order to examine this relationship and to take some common confounding factors into account this cross‐sectional study of 562 shift and day workers was carried out. The shift workers had significantly higher levels of serum triglycerides. γ‐glutamyltransferase and total cholesterol, and Body Mass Index did not differ between the groups.

The cause of increased serum concentrations of triglycerides is unclear. The present study provides no evidence to support the assumption that alcohol drinking or obesity accounts for increased levels of serum triglycerides in shift workers.