bluuebunny/crossref_metadata_2025_split huggingface dataset:
C‐reactive protein and colorectal adenomas: Self Defense Forces Health Study
Authors: Otake Toshie , Uezono Kousaku , Takahashi Ryota , Fukumoto Jin , Tabata Shinji , Abe Hiroshi , Tajima Osamu , Mizoue Tetsuya , Ohnaka Keizo , Kono Suminori 
Published: February 2009

Chronic inflammation has been implicated in colorectal carcinogenesis. Several studies have investigated the relationship between C‐reactive protein (CRP), a biomarker of inflammation, and colorectal cancer and adenomas, resulting in inconsistent findings. The present study examined the relationship between circulating levels of high‐sensitivity CRP and colorectal adenomas. The study subjects comprised 646 cases of colorectal adenoma and 635 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces. Statistical adjustment was made for cigarette smoking, alcohol use, body mass index, physical activity, and other potential confounders. The multivariate‐adjusted geometric means showed no measurable differences between adenoma cases and controls, but were higher among cases with larger adenomas (trend P = 0.03). Likewise, although the prevalence odds of colorectal adenomas did not differ according to CRP levels as categorized at the 30th, 60th, and 90th percentiles in the controls, higher levels of CRP were associated with a statistically significant increase in the prevalence odds of large adenomas (≥5 mm), but not of small adenomas (<5 mm). The multivariate‐adjusted odds ratios of large adenomas for the lowest to highest categories of CRP were 1.00 (referent), 1.81 (95% confidence interval 1.17–2.80), 1.61 (95% confidence interval 1.03–2.52), and 2.21 (95% confidence interval 1.28–3.84), respectively (trend P = 0.01). A positive association between CRP and prevalence odds of large adenomas was not modified by either smoking or overweight. These findings suggest that inflammation is linked to the growth of colorectal adenomas. (Cancer Sci 2009; 100: 709–711)
Incidence of benign upper respiratory tract infections, HSV and HPV cutaneous infections in inflammatory bowel disease patients treated with azathioprine
Authors: SEKSIK P. , COSNES J. , SOKOL H. , NION‐LARMURIER I. , GENDRE J.‐P. , BEAUGERIE L. 
Published: February 2009

SummaryBackground  There are few data on the incidence of benign infections (upper respiratory tract infections, herpes lesions and viral warts) during exposure to azathioprine.Aims  To determine the incidence of benign infections in IBD out‐patients receiving azathioprine (AZA+) and to look at the influence of leucocyte counts in the onset of these events.Methods  A total of 230 patients were included in a prospective cohort and observed during 207 patient‐years. Episodes of benign infections were collected and incidences of benign infections were compared between the AZA+ group and patients without AZA (AZA−).Results  The incidence of upper respiratory tract infections in the cohort was 2.1 ± 2.2 per observation‐year. There was no difference between the AZA+ (n = 169) and AZA− (n = 61) groups (2.2 ± 2.3 vs. 2.1 ± 2.1, P = 0.77). The incidence of herpes flares was significantly increased in the AZA+ group compared to the AZA− group (1.0 ± 2.6 vs. 0.2 ± 0.8 per year, P = 0.04). Similarly, there were significantly more patients with appearance or worsening viral warts in the AZA+ group (17.2% (AZA+) vs. 3.3% (AZA−), P = 0.004).Conclusion  This study suggests that the incidence of herpes flares and the appearance or worsening of viral warts are increased in IBD patients receiving AZA.
Serum and monoclonal immunoglobulin E antibodies from NC/Nga mice with severe atopic‐like dermatitis recognize an auto‐antigen, histone H3
Authors: Matsubara T. , Aoki N. , Hino S. , Okajima T. , Nadano D. , Matsuda T. 
Published: February 2009

SummaryBackground
NC/Nga mice are known to show a spontaneous outbreak of atopic‐like dermatitis accompanied by a marked elevation in serum IgE levels when reared in a conventional environment. The specific effects of such a strong serum IgE response on the development of the dermatitis and specific antigens recognized by the IgE antibodies are still uncertain.Objective and methods
To characterize the IgE of NC/Nga mice, we established IgE‐secreting hybridoma clones from spleen cells of NC/Nga mice spontaneously developing dermatitis and identified variable‐region genes and specific antigens of the IgE monoclonal antibodies (mAbs). Serum polyclonal IgE, as well as IgG1 and IgG2a, specific for the identified antigen were also analysed.Results
Four IgE‐producing hybridoma clones were established. Variable‐region nucleotide sequences of the IgE mAbs showed that these clones did not necessarily share common germline gene segments (V, D or J) for each variable region, and several somatic mutations had occured in the V gene segments. Through antigen screening, histone H3 was identified to be an auto‐antigen recognized by three of the four IgE mAbs. Serum IgE as well as IgG1 specific for histone H3 were almost undetectable in 6‐week‐old mice, but rapidly increased by 10–12 weeks of age. This age‐dependent increase in the serum anti‐histone H3 IgE was roughly in parallel with the onset of dermatitis, and slightly preceding total IgE elevation. The serum‐specific IgE level correlated well with a dermatitis‐severity score of each mouse at 12–16 weeks of age, and weakly with the severity of ear erosion of each mouse over 28 weeks of age. Furthermore, immunologically detectable histone‐H3 antigens were observed in skin tissue sections from the dermatitis sites.Conclusion
In NC/Nga mice, anti‐histone H3 auto‐antibodies may contribute, at least in part, to the considerably elevated serum IgE and might play some roles in the development and exacerbation of dermatitis.
Use of A‐type CpG oligodeoxynucleotides as an adjuvant in allergen‐specific immunotherapy in humans: a phase I/IIa clinical trial
Authors: Senti G. , Johansen P. , Haug S. , Bull C. , Gottschaller C. , Müller P. , Pfister T. , Maurer P. , Bachmann M. F. , Graf N. , Kündig T. M. 
Published: February 2009

SummaryBackgroundB‐type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half–life, which is due to its phosphorothioate backbone. A‐type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus‐like particles (VLP) consisting of the bacteriophage Qβ coat protein, A‐type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A‐type CpGs in humans.ObjectiveTo test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients.MethodsA single centre, open‐label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty‐one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end‐points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen‐specific IgG and IgE.ResultsQbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom‐free and this amelioration lasted for at least 38 weeks post‐treatment. Following injections of QbG10 and HDM allergen extract, allergen‐specific IgG increased, while there was a transient increase in allergen‐specific IgE titres. Skin reactivity to HDM was reduced.ConclusionThe subcutaneous application of HDM allergen, together with A‐type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo‐controlled phase II studies.
Safety and efficacy of treatment using interleukin-2 in a patient with idiopathic CD4+ lymphopenia andMycobacterium avium-intracellulare
Authors: Trojan T , Collins R , Khan D A 
Published: February 2009

SummaryWe present the case of a 39-year-old white man with a Myobacterium avium-intracellulare pulmonary infection found to have a CD4+ count of 172 cells/mm3 and diagnosed subsequently with idiopathic CD4+ lymphopenia (ICL). After receiving clathromycin for 4 months with minimal improvement, the patient was started on pegylated subcutaneous interleukin (IL)-2 at 600 000 units daily. Later, he received incrementally higher pegylated IL-2 doses until he reached a maintenance dose 3 months later of 11 million units weekly divided into three equal doses. After 5 months of therapy, the patient’s chronic cough resolved completely, sputum cultures became negative for Myobacterium avium-intracellulare and the CD4+ T cell count increased to 553 cells/mm3. After 35 months of well-tolerated IL-2 treatments and no recurrence of any opportunistic infections, IL-2 treatment was stopped. CD4+ counts 6 and 9 months after discontinuing IL-2 treatment were 596 and 378 cells/mm3 respectively, and he remains asymptomatic. This report supports IL-2 treatment for ICL-associated opportunistic infections as a safe and potentially efficacious treatment option, especially when combined with more traditional treatment regimens.
Decrease in phenotypic regulatory T cells in subsets of patients with common variable immunodeficiency
Authors: Horn J , Manguiat A , Berglund L J , Knerr V , Tahami F , Grimbacher B , Fulcher D A 
Published: February 2009

SummaryCommon variable immunodeficiencies (CVID) are a heterogeneous group of antibody deficiency disorders complicated by autoimmune, lymphoproliferative and/or granulomatous manifestations, suggesting variations in immunoregulation. We sought to quantify regulatory CD4 T cells (Treg cells) in the blood of CVID patients and to correlate the frequency with clinical manifestations and classification subgroups. Blood samples from 99 CVID patients in Freiburg, London and Sydney, who had been phenotyped clinically and stratified according to their memory B cell phenotype (Freiburg and Paris classification schemes), were analysed for the proportion of Treg cells, defined either as CD25+/forkhead box P3 (FoxP3)+, CD25+/CD127low/FoxP3+ or CD25+/CD127low CD4+ T cells, and results compared with 49 healthy controls. Irrespective of the phenotype used to define them, there was a significant decrease in the Treg cell proportion in patients with granulomatous disease and immune cytopenias. This allowed the definition of a subgroup of CVID patients with abnormally low Treg cells, which had a higher rate of these two manifestations as well as autoimmune disease in general. There was also a significant reduction in the proportion of Treg cells in the Freiburg group Ia compared with other CVID patients and controls, but there were no differences between the Paris groups. The reduction in Treg cells in subsets of CVID patients may be relevant to their clinical manifestations, and may contribute to our understanding of the pathogenesis of CVID complications.
An inhibitor of interleukin-6 trans-signalling, sgp130, contributes to impaired acute phase response in human chronic liver disease
Authors: Lemmers A , Gustot T , Durnez A , Evrard S , Moreno C , Quertinmont E , Vercruysse V , Demetter P , Franchimont D , Le Moine O , Geerts A , Devière J 
Published: February 2009

Summary
In chronic liver disease, high circulating interleukin (IL)-6 contrasts with a poor acute phase response. We evaluated the impact of liver and circulating IL-6-receptor (IL-6R) forms on IL-6 bioactivity in chronic liver disease. IL-6, soluble IL-6-receptor and sgp130 levels were assayed in plasma from 45 patients with alcoholic liver disease, 84 with hepatitis C virus (HCV) infection undergoing transjugular liver biopsies and 15 healthy subjects. IL-6R mRNA was quantified on liver extracts from 54 patients with alcoholic liver disease with or without cirrhosis and 18 HCV-infected patients. The effect of gp130–Fc on fibrinogen secretion induced by IL-6 trans-signalling was evaluated on hepatocyte cultures. Levels of plasma IL-6 and sgp130, but not soluble IL-6R, increased with the stage of chronic liver disease, and correlated significantly with disease severity. Alcoholic liver disease patients had higher plasma IL-6 levels than hepatitis C, but lower liver IL-6R expression. In alcoholic and HCV-related liver diseases, liver IL-6R expression decreased with advanced fibrosis stage. In vitro, on hepatocytes, gp130–Fc blunted the acute phase response while soluble IL-6R enhanced IL-6 stimulation. In advanced chronic liver disease, high plasma IL-6 is associated with low liver IL-6R expression. This situation enables high plasma sgp130 to act as a major negative regulator of liver IL-6 trans-signalling, as demonstrated functionally here on hepatocytes. This might explain the poor acute phase response induced by IL-6 in chronic liver disease.
Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli–Seip congenital generalized lipodystrophy syndrome
Authors: Miranda Debora M. , Wajchenberg Bernardo L. , Calsolari Maria R. , Aguiar Marcos J. , Silva José M. C. L. , Ribeiro Marcia G. , Fonseca Cristina , Amaral Daniela , Boson Wolfanga L. , Resende Bruna A. , De Marco Luiz 
Published: February 2009

SummaryContext  Congenital generalized lipodystrophy, or Berardinelli–Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present.Design  We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly.Results  Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518–519insA, IVS5‐2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3‐1G>C and c.299G>A).Conclusions  We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli–Seip syndrome and Brunzell syndrome (AGPAT2‐related syndrome).
Markers of insulin sensitivity in placentas and cord serum of intrauterine growth‐restricted newborns
Authors: Street Maria E. , Volta Cecilia , Ziveri Maria A. , Viani Isabella , Bernasconi Sergio 
Published: February 2009

SummaryObjective  Intrauterine growth restriction (IUGR) has been related to a higher incidence of insulin resistance in adult life, which is associated with low adiponectin and high resistin, insulin and interleukin (IL)‐6 serum concentrations. This study assessed cortisol, insulin, total insulin receptor, resistin, adiponectin and IL‐6 concentrations, as markers of insulin sensitivity, in placental lysates and cord serum of IUGR and appropriate for gestational age (AGA) newborns, to establish relationships among peptides and with growth parameters at birth.Design and patients  Whole villous tissue and cord serum at birth were collected from 24 AGA and 18 IUGR newborns of comparable gestational age.Measurements  Hormonal and peptide concentrations were assayed in placental lysates and cord serum using specific commercial kits. Concentrations in lysates were adjusted per mg of total protein content.Results  Cortisol, insulin and resistin concentrations and the total amount of insulin receptor were similar in both groups. IL‐6 concentration in lysates was significantly higher in IUGR compared with AGA newborns. Adiponectin was significantly lower in lysates from IUGR compared with AGA newborns. Placental insulin and resistin concentrations were positively correlated. Placental adiponectin concentration was positively correlated with the weight of the placenta, birthweight and head circumference. IL‐6 concentration in lysates was negatively correlated with birth length, birthweight and head circumference.Conclusions  This study evaluated the markers of insulin sensitivity in the placentas of subjects born IUGR, showing new potential roles for adiponectin and IL‐6 in particular, and suggesting a role for the placenta in the programming of these hormones.
The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index
Authors: Jostel Andreas , Ryder W. David J. , Shalet Stephen M. 
Published: February 2009

SummaryBackground  TSH secretion in hypopituitary patients may be decreased due to TSH deficiency but it also remains under feedback inhibition by free thyroxine (fT4). We propose a TSH index (TSHI), as ‘fT4‐adjusted TSH’, that corrects for any physiological TSH suppression, to provide a true estimate of pituitary thyrotroph function and any pathological pituitary suppression.Methods  A total of 9519 thyroid function tests (TFTs) (Bayer Immuno‐1®) in 4064 patients of our institution were examined, including 444 patients investigated for hypopituitarism. Based on the physiological log‐linear relationship between fT4 and TSH, we estimated the amount of feedback‐induced change in log TSH per change in fT4, which allowed the extrapolation of log TSH to a fixed fT4 of 0, defining the TSHI. TSHIs were compared with other measures of pituitary function.Results  Feedback inhibition was estimated to cause a 0·1345 decrease in log TSH (mU/l) for 1 pmol/l increase in fT4 concentration, therefore TSHI = log TSH + 0·1345 × fT4. Patients with lower peak‐stimulated GH and cortisol concentrations had a significantly lower TSHI (P < 0·0001). TSHIs measured before pituitary stimulation tests predicted highly significantly the risk of test failure (P = 0·0002). Of all potential fT4–TSH combinations within the current reference ranges, 21·9% were identified as abnormal on the basis of the TSHI.Conclusion  The TSHI provides an accurate estimate of the severity of pituitary dysfunction in hypopituitary patients based on simple TFTs. It predicts the probability of pituitary stimulation test failure and extends the diagnosis of TSH deficiency into areas of the normal TFT reference ranges.
Parathyroidectomy is safe and improves symptoms in elderly patients with primary hyperparathyroidism (PHPT)
Authors: Stechman Michael J. , Weisters Mary , Gleeson Fergus V. , Sadler Gregory P. , Mihai Radu 
Published: February 2009

SummaryObjective  Parathyroidectomy for primary hyperparathyroidism (PHPT) is curative in over 95% of cases. Although PHPT affects up to 2% of the elderly population, whose life expectancy may be a decade or more, such patients may be denied surgery because of perceived risk. This study investigates the outcomes of surgery for PHPT in the elderly.Design and patients  Consecutive patients with PHPT treated at a tertiary referral centre over 5 years.Measurements  A prospective database recorded clinical, biochemical and pathological information. Pasieka’s parathyroid symptom scores were obtained pre‐operatively and post‐operatively, from a recent subgroup of 70 consecutive patients. Deaths during follow‐up were identified using the NHS Strategic Tracing Service. Statistical analysis was performed with spss v12.0.Results  Between November 2002 and October 2007, 224 patients (17–89 years) underwent surgery for PHPT. In the subgroup comprising patients aged >75 years there was a significantly greater proportion of women (47/56 vs. 52/81, P < 0·05). Pre‐operative indices of these patients were similar to younger patients, as were proportions undergoing minimally invasive parathyroidectomy (n = 134) or bilateral neck exploration (n = 90). Patients >75 years had a longer hospital stay (1·6 vs. 0·8 days, P = 0·003). Pasieka’s symptom scores improved significantly at 3–6 months postoperatively in all age groups. During a minimum median follow‐up of 22 months, there were seven patients with persistent/recurrent disease. Median 2‐year survival of those aged 60–74 and those over 75 ranged from 85–90%.Conclusion  Parathyroidectomy is safe in the elderly and is associated with a significant improvement in symptoms. As survival after operation is similar to younger patients, surgery should be considered in all elderly patients with PHPT.
New and emerging treatments for osteoporosis
Authors: Clarke Bart L. 
Published: February 2009

SummaryA variety of new treatments for osteoporosis have become available within the last several years, and a number of emerging treatments remain in late clinical stage development. New and emerging treatments include more potent members, or more convenient formulations, of existing classes of therapy, but a number of the emerging treatments are first‐generation compounds addressing specific therapeutic targets based on recent advances in understanding of basic bone biology. These new and emerging treatments include agents with anticatabolic effects, compounds with anabolic effects, and one agent possibly containing both anticatabolic and anabolic effects. The increasing variety of new and emerging treatments increases the possibility that effective therapy will be targeted to the specific needs of the individual patient.
Relationships between cortisol level, mortality and chronic diseases in older persons
Authors: Schoorlemmer R. M. M. , Peeters G. M. E. E. , Van Schoor N. M. , Lips P. 
Published: February 2009

SummaryContext  High cortisol level is known to be associated with osteoporosis, hypertension, diabetes mellitus (DM), susceptibility to infections and depression and may protect against chronic obstructive pulmonary disease.Objective  This study assesses the association between cortisol level, 6‐ to 7·5‐year mortality risk and prevalence of chronic diseases.Design/setting/participants  Subjects were selected from the Longitudinal Aging Study Amsterdam, an ongoing multidisciplinary cohort study in a general population of older persons (≥65 years). Serum cortisol was measured in 1181 men and women in 1995/1996 (second cycle) and salivary cortisol in 998 men and women in 2001/2002 (fourth cycle).Main outcome measures  Six to seven and a half year mortality and prevalence of chronic diseases.Results  Men with high salivary morning cortisol had a higher mortality risk than men with low levels [hazard ratio (HR) = 1·63, P = 0·04 for the third vs. the lowest tertile]. Women with high salivary evening cortisol had a higher mortality risk than women with low levels (HR = 1·82, P = 0·04 for the third vs. the lowest tertile). In men, high serum cortisol was independently associated with chronic nonspecific lung disease (CNSLD): odds ratio (OR) = 0·72, P < 0·01; hypertension: OR = 1·38, P < 0·01; DM: OR = 1·38, P = 0·02. In women, high salivary evening cortisol was independently associated with DM: OR = 1·33, P = 0·01 and CNSLD: OR = 0·58, P = 0·02. No independent association between cortisol and number of chronic diseases was found.Conclusion  High salivary cortisol levels are associated with increased mortality risk in a general older population. High cortisol levels are associated with higher risks of hypertension and DM and lower risk of CNSLD.