bluuebunny/crossref_metadata_2025 huggingface dataset:
T cell receptor VB repertoire diversity in patients with immune thrombocytopenia following splenectomy
Authors: FOGARTY P F , RICK M E , ZENG W , RISITANO A M , DUNBAR C E , BUSSEL J B
Published: December 2004

In recent years, a pathophysiological role for T cells in immune thrombocytopenia (ITP) has been established. We applied cDNA size distribution analysis of the T cell receptor (TCR) β-variable (VB) complementarity-determining region 3 (CDR3) in order to investigate T cell repertoire diversity among immune thrombocytopenia patients who had either responded or not responded to splenectomy, and compared them to normal controls. ITP patients who had had a durable platelet response to splenectomy showed a mean 2·8 ± 2·1 abnormal CDR3 size patterns per patient, similar to healthy volunteers (2·9 ± 2·0 abnormal CDR3 size patterns). In contrast, patients unresponsive to splenectomy demonstrated evidence of significantly more clonal T cell expansions than patients who had responded to splenectomy or controls (11·3 ± 3·3 abnormal CDR3 size patterns per patient; P < 0·001). Of the VB subfamilies analysed, VB3 and VB15 correlated with response or non-response to splenectomy, each demonstrating oligoclonality in non-responding patients (P < 0·05). These findings suggest that removal of the spleen may lead directly or indirectly to reductions in T cell clonal expansions in responders, or that the extent of T cell clonality impacts responsiveness to splenectomy in patients with ITP.
Influence of human T lymphotrophic virus type I on cryptogenic fibrosing alveolitis − HTLV-I associated fibrosing alveolitis: proposal of a new clinical entity
Authors: MATSUYAMA W , KAWABATA M , MIZOGUCHI A , IWAMI F , WAKIMOTO J , OSAME M
Published: December 2004

Human T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4+ lymphocytes and is thought to modify their function; a possible association with pulmonary diseases has also been suggested. However, little is known about the influence of HTLV-I on cryptogenic fibrosing alveolitis (CFA), a chronic inflammatory interstitial lung disease of unknown aetiology. In order to clarify the influence of HTLV-I infection on CFA, 72 CFA patients with and without HTLV-I infection were examined. HTLV-I positive CFA patients were likely to have larger affected areas and to show traction bronchiectasis with honeycombing change. An imbalance of matrix metalloproteinases and tissue inhibitor of metalloproteinases were also observed in the BALF of HTLV-I positive CFA patients. CD3+/CD25+ lymphocyte percentage was significantly higher in the BALF of HTLV-I positive patients compared to negative patients. MIP-1α, IP-10 and sICAM levels in BALF were also significantly higher in HTLV-I positive patients than in negative patients. The levels of MCP-1 and IL-8 were not significantly different. In HTLV-I positive patients, the MIP-1α and IP-10 levels showed a significant positive correlation with percentage of CD3+/CD25 lymphocytes. HTLV-I positive CFA patients showed a larger lesion than negative patients and exhibited increased levels of certain cytokines that correlated with activated T cells in the BALF. We suggest that HTLV-I infection may contribute to the development of CFA via activation of T cells. We also propose that these features should be taken into consideration in the treatment of CFA in HTLV-I infected individuals.
Plasmodium falciparuminfection of the placenta affects newborn immune responses
Authors: ISMAILI J , VAN DER SANDE M , HOLLAND M J , SAMBOU I , KEITA S , ALLSOPP C , OTA M O , MCADAM K P W J , PINDER M
Published: December 2004

The effects of exposure to placental malaria infection on newborn immunological responses, in particular Th1/Th2 cytokines and antigen-presenting cell (APC) function, were compared between cord blood mononuclear cells (CBMC) from parasitized and non-parasitized placentas of Gambian women. Cells were analysed in vitro for their ability to respond to mitogens [phorbol myristate acetate (PMA)/ionomycin, phytohaemagglutinin (PHA)], a malaria-unrelated test antigen [purified protein derivative of Mycobacterium tuberculin[purified protein derivative (PPD)] and Plasmodium falciparum schizont extracts. Mitogens induced strong proliferation and secretion of high concentrations of both IL-13 and sCD30 in CBMC from both groups. Conversely, significantly lower amounts of IFN-γ were induced in the parasitized group in response to low doses of PHA. Protein antigens induced very low amounts of all tested cytokines, in particular IFN-γ. However, a significantly higher release of sCD30 was observed in response to schizont extracts in the parasitized group. Addition of LPS to activate APC to low doses of PHA or schizont extracts increased the IFN-γ production in both groups but levels remained lower in CBMC from the parasitized group. This result correlates with the lower production of IL-12 found following lipopolysaccharide (LPS) stimulation in this group. Taken together, these data show that placental infection with P. falciparum affects Th1 differentiation and sCD30 priming of neonatal lymphocytes and that the probable mode of action is via APC.
Cancer immunotherapy using RNA-loaded dendritic cells
Authors: PONSAERTS P , VAN TENDELOO V F I , BERNEMAN Z N
Published: December 2004

Dendritic cells (DC) are the most professional antigen-presenting cells of the immune system and are capable of initiating immune responses in vitro and in vivo. One of the great challenges in immunotherapy protocols is to introduce relevant antigens into DC for stimulation of major histocompatibility complex (MHC) class I- and class II-restricted anti-tumour or anti-viral immunity. This review will focus on the development of mRNA-loaded DC-based immunotherapy vaccines. First, several published results concerning mRNA transfection efficiency in DC are compared. Next, an overview is given for several published studies describing CD8+ and CD4+ T-cell clone activation using RNA-loaded DC. These data show that RNA-loaded DC efficiently process and present antigenic epitopes. Next, published data from in vitro T-cell activation studies using RNA-loaded DC are summarized and provide evidence that RNA-loaded DC can efficiently stimulate in vitro primary and secondary immune responses. Finally, the summarized data provide evidence that RNA-loaded DC are a promising strategy for the development of future cancer vaccination strategies.
Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy
Authors: Sakamoto Rie , Osada Hisao , Iitsuka Yoshinori , Masuda Kentarou , Kaku Kenshi , Seki Katsuyoshi , Sekiya Souei
Published: December 2004

objective Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it is also secreted in the placenta and is probably a cause of pre‐eclampsia. To provide a basis for elucidation of the relationship between pre‐eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood.

methods Fifty‐nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8–20 weeks’ gestation (early), 11 at 28–34 weeks (middle) and 24 at 35–40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method.

results The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood.

conclusion This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.
Long‐term follow‐up of bone mineral density in Addison's disease
Authors: Jódar Esteban , Valdepeñas María Pilar Ruiz , Martinez Guillermo , Jara Antonino , Hawkins Federico
Published: December 2004

background and aims There is conflicting evidence regarding the long‐term effects of long‐term glucocorticoid replacement therapy (GRT) on bone mineral density (BMD) in patients with chronic adrenal insufficiency. Our aim was to evaluate bone turnover and changes in BMD in patients on GRT.

patients and methods We have studied 25 subjects (six men, 19 women; aged 62·4 ± 11·3 years, duration of disease 21·7 ± 11·7 years, fasting cortisol 63 ± 36 nmol/l) on GRT (hydrocortisone 30 mg/day or prednisone 7·5 mg/day). BMD was assessed at the lumbar spine (LS; L2–L4), proximal femur (PF) and ultra distal radius (UR) by dual energy X‐ray absorptiometry (DXA). The rates of bone loss were calculated using previous DXA measurements at the LS (48 and 60 months earlier). Serum calcium, phosphate alkaline phosphatase (ALP), bone ALP, serum osteocalcin (BGP), intact parathyroid hormone (PTH) and 25(OH) vitamin D were also measured.

results BMD [Z‐score; 95% confidence interval (95% CI)] was normal at the LS: (−1·15–+0·07); PF: (−0·90–+0·22) and UDR (−0·77–+0·36). No significant differences were found according to the type of replacement therapy or sex. No significant bone loss (g/cm2; 95% CI) was detected at the LS: (−0·021–+0·023). Fifty‐six per cent of patients met osteoporotic criteria; a greater proportion of patients treated with prednisone had osteoporosis compared with those an hydrocortisone. All bone markers were in their normal ranges.

conclusions Patients on long‐term therapy do not show accelerated bone loss at the lumbar spine. Nevertheless, a considerable proportion of patients, mainly those treated with prednisone, showed densitometric osteoporosis.
Ultrasonography‐guided fine‐needle aspiration of thyroid incidentaloma: correlation with pathological findings
Authors: Nam‐Goong Il Seong , Kim Ha Young , Gong Gyungyub , Lee Ho Kyu , Hong Suck Joon , Kim Won Bae , Shong Young Kee
Published: December 2004

background  There are many reports that diagnostic accuracy of fine‐needle aspiration (FNA) of thyroid is improved with ultrasound guidance, especially for impalpable nodules. Despite its general acceptance, routine use of ultrasound‐guided fine‐needle aspiration (USGFNA) has been the source of much controversy due to the lack of large‐scale studies and lack of data on the natural course of well‐differentiated thyroid cancer of small size.

objective  The aim of our study was to define the rate of malignancy in relatively large numbers of patients with incidentally detected impalpable thyroid nodules and to assess the extent of disease in patients with suspicious or malignant cytology on USGFNA of thyroid nodules by surgery.

patients  We retrospectively reviewed the medical records of the 267 patients who underwent USGFNA of incidental thyroid nodules from January 2000 to December 2001.

results  Three hundred and seventeen nodules from 267 patients were aspirated. The average size of nodules was 0·9 ± 0·3 cm, a range of 0·2 cm to 1·5 cm. All 317 lesions were impalpable. Cytological diagnosis included 101 inadequate specimen (32%), 139 benign (44%), 29 indeterminate (9%), four suspicious of follicular or Hürthle cell neoplasm (1%), 42 papillary carcinoma (13%) and two others. The size of the nodule was not related to the probability of getting an adequate specimen for cytological diagnosis. Forty of 48 patients with suspicious or malignant cytology underwent surgery. All 35 patients with a cytological diagnosis of papillary carcinoma were confirmed to have papillary carcinoma on histological results. One of three patients with a cytological diagnosis of follicular neoplasm had a follicular carcinoma. In 36 patients with well‐differentiated thyroid cancer, extrathyroidal extension was observed in 44% (16/36), regional lymph node metastasis was found in 50% (18/36) and multifocal tumours were found in 39% (14/36).

conclusions  The rate of malignancy in incidentally detected impalpable thyroid nodules was 12% in retrospective analysis of our patients. In this subgroup, 69% (25/36) of patients had either extrathyroidal extension or regional node involvement and 39% had multifocal tumours at surgery. This suggests that the small size alone does not guarantee low risk in incidentally found thyroid cancers. USGFNA is a useful diagnostic method in these patients.
Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH‐independent macronodular adrenocortical hyperplasia
Authors: Tatsuno Ichiro , Uchida Daigaku , Tanaka Tomoaki , Koide Hisashi , Shigeta Azusa , Ichikawa Tomohiko , Sasano Hironobu , Saito Yasushi
Published: December 2004

objective  Vasopressin (AVP) is reported to be an important factor for regulating cortisol secretion in patients with Cushing's syndrome due to ACTH‐independent macronodular adrenocortical hyperplasia (AIMAH). Recently, there have been several case reports of subclinical Cushing's syndrome due to AIMAH, in which the pathophysiological role of AVP has been unknown. The aim was to conduct an extensive investigation of AVP in the autonomous secretion of cortisol in subclinical Cushing's syndrome due to AIMAH.

patients and measurements  Five cases of AIMAH with subclinical Cushing's syndrome underwent prospective study including physical examination, imaging (MRI, CT and 131I‐adosterol scintigraphy) and endocrinological evaluation that comprised basal plasma cortisol levels and urinary excretions of steroid metabolites, a dexamethasone suppression test and an AVP stimulation test. In case 1, left adrenalectomy was performed and the pathological diagnosis of AIMAH was established. An in vitro experiment using the cultured AIMAH adrenal cells was conducted to investigate cortisol secretion and expression of the V1‐AVP receptor, mRNA by RT–PCR.

results  All five cases were discovered incidentally to have bilateral adrenal nodules. Imaging by MRI and CT revealed large multinodular lesions in both adrenal glands, which showed positive uptake on 131I‐adosterol scintigraphy. Although the basal values of plasma cortisol and urinary excretions of steroid metabolites were within normal limits, autonomous secretion of cortisol was assumed to occur because of lack of suppression during dexamethasone suppression. The five patients had no overt signs of Cushing's syndrome, and they were therefore diagnosed with subclinical Cushing's syndrome due to AIMAH. In all five patients, AVP stimulated cortisol secretion in vivo, whereas desmopressin acetate failed to affect cortisol secretion. In case 1, AVP stimulated cortisol secretion from cultured AIMAH adrenal cells, but this secretion had no relationship with cAMP production. In addition, over‐expression of V1‐AVP receptor mRNA in AIMAH tissue was determined by RT–PCR.

conclusion  Patients with subclinical Cushing's syndrome due to AIMAH commonly exhibit cortisol responsiveness to AVP, and this is probably mediated through activation of overexpressed V1‐AVP receptors.
Size at birth, the metabolic syndrome and 24‐h salivary cortisol profile
Authors: Kajantie Eero , Eriksson Johan , Osmond Clive , Wood Peter J. , Forsén Tom , Barker David J. P. , Phillips David I. W.
Published: December 2004

objective  Individual variation in hypothalamic–pituitary–adrenal axis (HPAA) function has been suggested to be important in linking small size at birth with adult cardiovascular disease and its risk factors, in particular the metabolic syndrome. Human studies have, however, so far only been performed in clinic settings, and their results have not been consistent. Our aim was to assess whether HPAA activity in everyday living circumstances is related to the metabolic syndrome and size at birth.

design  Clinical birth cohort study.

subjects  A total of 151 women born between 1924 and 1933 in Helsinki, Finland, with measurements at birth recorded. The subjects had previously undergone detailed clinical examinations including fasting cortisol measurement and 1 µg ACTH1−24 and overnight 0·25 mg dexamethasone tests.

measurements  Salivary cortisol concentration was measured during a normal 24‐h period: at awakening, 15 and 30 min thereafter, at 12·00 h, 17·00 h and 22·00 h and the following morning. In addition, the following summary variables were calculated: awakening response (mean of the three awakening measurements), mean of all individual measurements, and mean, SD and contrast (a measure of blunted diurnal variability, calculated as mean of morning minus mean of 1200, 1700 and 2200) of all individual z scores.

results  Salivary cortisol awakening response was correlated with serum fasting (r = 0·17; P = 0·04), ACTH1−24‐stimulated (r = 0·32; P < 0·0001), and dexamethasone‐suppressed (r = 0·29; P = 0·0004) cortisol concentrations. However, no salivary cortisol measurement was associated with any component of the metabolic syndrome (waist circumference, serum triglyceride, HDL cholesterol or glucose concentration, or blood pressure). Moreover, no correlation was observed between salivary cortisol and weight, length, ponderal index, or gestational age at birth.

conclusions  In elderly women, cortisol concentrations in an everyday environment do not appear to be associated with the metabolic syndrome or size at birth. We propose that detecting relationships between HPAA function, prenatal events and adult disease might require a test involving HPAA stimulation.
High leptin levels in women developing postpartum thyroiditis
Authors: Mazziotti G. , Parkes A. B. , Lage M. , Premawardhana L. D. K. E. , Casanueva F. F. , Lazarus J. H.
Published: December 2004

background  There is experimental evidence that leptin is required for the development of T helper 1 (Th1)‐mediated autoimmune diseases. However, to our knowledge, there are no studies demonstrating such a role in human autoimmune thyroid disease.

objective  In the present study we have retrospectively examined patients developing postpartum thyroiditis (PPT), as a model of autoimmune disease, for changes in serum leptin levels during the postpartum period.

materials and methods  The study group included 61 women in the first month postpartum who were positive for thyroid peroxidase antibodies (TPOAb+ve). Twenty TPOAb‐negative (–ve), age and body mass index (BMI)‐matched, postpartum women were enrolled as the control group. All subjects were evaluated for BMI, serum leptin values, thyroid function [serum free‐triiodiothyronine (FT3), free‐thyroxine (FT4), thyrotropin (TSH)] and autoimmunity [TPOAb levels and complement activity index (C3 index)] at 4, 12, 16, 20 and 24 weeks’ postpartum. During the postpartum period, 32 of 61 TPOAb+ve women (52·4%) showed one or more episodes of thyroid dysfunction (PPTD group), whereas the remaining 29 TPOAb+ve women remained euthyroid throughout the study period (PPTE group). None of the control group developed thyroid dysfunction.

results  Four weeks postpartum, TPOAb+ve women showed higher serum leptin values than TPOAb–ve women, despite comparable BMI. At this time, PPTE and PPTD patients showed no significant differences in leptin levels or leptin/BMI ratio. Throughout the postpartum period, PPTD patients maintained significantly higher leptin values and leptin/BMI ratio compared to the healthy women. In PPTE women, however, a significant reduction in leptin levels and leptin/BMI ratio was seen at 12 weeks’ postpartum. This decrease was transient and correlated negatively with the variation in C3 index at the same time. No significant correlation was found between serum leptin variations and FT4 or TSH levels.

conclusions  This study has demonstrated that women developing postpartum thyroiditis have higher leptin values compared to the healthy women. The higher levels were maintained for 6 months postpartum. This result would suggest an involvement of leptin in the pathogenesis of postpartum thyroid disease, although further studies are needed to characterize the reciprocal effects of leptin, immune system and thyroid hormones during the course of this disease.
Standard and low‐dose IGF‐I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature
Authors: Blair J. C. , Camacho‐Hübner C. , Miraki Moud F. , Rosberg S. , Burren C. , Lim S. , Clayton P. E. , Bjarnason R. , Albertsson‐Wikland K. , Savage M. O.
Published: December 2004

objective  Abnormalities in the GH–IGF‐I axis, consistent with GH insensitivity (GHI), have been reported in some patients with idiopathic short stature (ISS). The standard IGF‐I generation test (IGFGT) has not demonstrated mild GHI in subjects with ISS. The aim of this study was to investigate the GH–IGF‐I axis in ISS by performing standard and novel low‐dose IGFGTs together with determination of spontaneous GH secretion.

patients and methods  Twenty‐one (17 male) prepubertal children with ISS, mean age 8·3 years (4·5–12·2), mean height −3·48 SD (−5·40 to −1·79), mean peak GH to provocation with glucagon/clonidine 32·3 mU/l (14·1–66·0) were studied. Serum IGF‐I and IGFBP‐3 levels were measured during standard (GH 0·033 mg/kg/day × 4) and low (GH 0·011 mg/kg/day × 4) dose IGFGTs at 0, 12, 36 and 84 h. The low‐dose IGFGT was performed in seven naive GH‐deficient patients (4 male), mean age 8·5 years (range 4·1–11·1). Determination of spontaneous 24‐h GH secretion was performed in the 21 ISS patients.

results  Basal IGF‐I and IGFBP‐3 standard deviation scores (SDS) in ISS patients were −1·39 (−2·4–1·16) and −0·45 (−1·13–0·38), respectively, IGF‐I being lower than IGFBP‐3 (P < 0·0001). IGF‐I increased in the standard IGFGT at 12 h (P < 0·005), 36 h (P < 0·001) and 84 h (P < 0·001); maximal increment 1·54 (−0·32–3·48), and in the low‐dose test at 12 h (P < 0·005), 36 h (P < 0·001) and 84 h (P < 0·005); maximal increment 0·53 (0·08 to −1·23). IGFBP‐3 SDS increased in the standard IGFGT at 36 h (P < 0·01) and 84 h (P < 0·001); maximal increment 0·72 (−0·44–1·96), and in the low‐dose test at 84 h (P < 0·005); maximal increment 0·33 (−0·08–0·87). Five/19 patients with an IGF‐I response > 2 × coefficient of variation (CV) of assay in the standard test failed to respond in the low‐dose test, suggestive of mild GHI. In GH‐deficient patients, IGF‐I increased at each time point (P < 0·05) and IGFBP‐3 at 36 h (P < 0·05). Mean GH secretion, expressed in SDS, compared with 66 normal stature controls was: basal GH −0·48 (−0·84–0·93), height of GH peaks compared with zero −0·36 (−1·26–1·51) (both P < 0·05), total GH secretion −0·76 (−1·22–0·42), total GH secretion above baseline −0·67 (−1·21–0·94) (both P < 0·01).

conclusions  In children with ISS, basal IGF‐I and IGFBP‐3 SDS values were below the mean, IGF‐I showing a greater response in both IGFGTs. In the standard IGFGT, the IGF‐I increase at 36 h was equal to that at 84 h. The low‐dose IGFGT, in combination with the standard test, may identify patients with mild GHI.
Predictors of intellectual outcome in a cohort of brazilian children with congenital hypothyroidism
Authors: Kreisner E. , Schermann L. , Camargo‐Neto E. , Gross J. L.
Published: December 2004

objective  To identify predictors of intellectual development in a cohort of children with permanent primary congenital hypothyroidism.

design  Cohort study with intellectual development as the outcome.

patients and measurements  Thirty‐one consecutive newborns with permanent primary congenital hypothyroidism diagnosed by a screening programme were recruited from the outpatient clinic of a district hospital and underwent psychometric evaluation with the Wechsler Intelligence Scales after a minimum follow‐up of 4 years.

results  Eight of the 31 patients (25·8%) presented impaired intellectual development (full‐scale intellectual quotient < 85), and one of them presented mental deficiency (full‐scale intellectual quotient ≤ 69). The following were associated with worse prognosis: initial serum T4 levels ≤ 32·18 nmol/l, treatment beginning after 30 days of age, fewer than seven clinic visits during the first year of life, living in rural areas, nonintellectual parental occupation and little parental schooling. In a multiple regression analysis, only maternal schooling (B = 0·401; β coefficient = 13·053, P = 0·063), number of clinic visits during the first year of life (B = 0·382; β coefficient = 4·145, P = 0·047) and initial serum T4 (B = 0·287; β coefficient = 1·336, P = 0·089) remained significantly associated with full‐scale intelligence quotient scores.

conclusion  Maternal schooling, number of visits during the first year of life and baseline T4 levels were the main predictors of cognitive outcome in this cohort of patients.
Adiponectin, hepatocellular dysfunction and insulin sensitivity
Authors: López‐Bermejo Abel , Botas Patricia , Funahashi Tohru , Delgado Elías , Kihara Shinji , Ricart Wifredo , Fernández‐Real José Manuel
Published: December 2004

objective  Insulin resistance plays a major aetiological role in the development of fatty liver disease. Because adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumour necrosis factor, a cytokine known to induce insulin resistance and liver damage, we wished to study whether low circulating adiponectin would be associated with higher serum concentrations of liver enzymes in healthy subjects.

design  Cross‐sectional, population‐based study dealing with diabetes prevalence in northern Spain.

patients  Two hundred and fifty‐seven apparently healthy Caucasian subjects consecutively enrolled in the study.

measurements  Adiponectin serum levels were measured by enzyme‐linked immunosorbent assay (ELISA), liver function tests (LFTs) by colourimetry and insulin resistance by the homeostasis model of assessment (HOMA value).

results  Adiponectin levels were negatively correlated with alanine aminotransferase (ALT) and γ‐glutamyltranspeptidase (GGT), before and after adjustment for sex, age, body mass index (BMI) and insulin resistance (ALT; r = −0·32, P < 0·001; adjusted: r = −0·13, P = 0·033; GGT; r = −0·31, P < 0·001; adjusted: r = −0·16, P = 0·011). Additionally, adiponectin correlated with alkaline phosphate (ALKP) only after adjusting for the same confounding variables (r =−0·10, P = 0·098; adjusted: r = −0·14, P = 0·031). A general linear model, adjusting for age, sex and BMI, was constructed to predict the decrease in circulating adiponectin for each LFT value (i.e. ALT, GGT and ALKP) above the median. Beyond one LFT value above the median, serum adiponectin decreased by –0·97 mg/l (95% CI −1·46 to −0·48). In multiple regression analysis, sex, BMI and adiponectin, but not insulin resistance, predicted serum concentrations of both ALT and GGT, explaining 19% and 14% of their variance, respectively. Age, BMI and adiponectin, but not sex or insulin resistance, explained 20% of ALKP variance.

conclusions  Adiponectin levels are associated in healthy humans with plasma concentrations of various liver function tests. The contributions of adiponectin to maintaining liver integrity through the regulation of both insulin sensitivity and/or the inflammatory response merit further studies.
Influences of mandatory breathing on rhythmical components of electrodermal activity
Authors: Rittweger J. , Lambertz M. , Langhorst P.
Published: December 2004

We investigated whether rhythmical components of electrodermal activity (EDA) can be influenced by voluntary modification of the respiratory frequency. Fifty‐five volunteers participated in an experiment with nine mandatory sections of cycle times between 3·1 s and 12·2 s. The cycle time of the rhythmical EDA components often differed considerably from respiratory cycle time. ANOVA yielded that both cycle time and position within the section had an effect on the EDA power of the mandatory cycles (P<0·05). No significant interaction between effects of section and of position was discovered (P>0·1). A separate analysis of the cycle times of the rhythmical EDA components revealed integer relationship with the respiratory cycle times. Thus, voluntary changes in the respiratory frequency can influence occurrence and cycle time of rhythmical EDA components in a way similar to sliding coordination in the sense of E. von Holst.
A methodological study of arterial wall function using ultrasound technique
Authors: Jensen‐Urstad K. , Rosfors S.
Published: December 2004

We aimed to establish reference values for three important properties of the arterial wall using a conventional ultrasound scanner. We measured: (1) intima–media thickness (IMT) of the carotid arteries with the internal trace function of the ultrasound system; (2) wall stiffness by pulsatile diameter changes in the right common carotid artery assessed by M‐mode; and (3) endothelial function expressed as flow‐mediated dilatation (FMD) of the brachial artery. IMT and wall stiffness measurements and reproducibility were compared with those obtained by external analysing systems. All variables were obtained in healthy subjects (n = 20), 29–53 years old. IMT increased with age (P<0·01). There was no difference in IMT between men and women. The inter‐operator variability for measuring IMT was 6–9%. The same order of reproducibility was obtained with an external PC‐based analysing system. Regarding wall stiffness, no correlation was found with age, nor any difference between men and women. A low intra‐operator variability (CV < 10%) was found for measurements of wall stiffness with both M‐mode and an external wall tracking system. FMD of the brachial artery diminished with age (P<0·01). There was a relation between FMD and brachial artery size (P<0·01) and, therefore, as men have larger arterial diameters (P<0·01), smaller FMD in men. We conclude that it is possible to characterize arterial wall function non‐invasively in an adequately reproducible manner using a conventional ultrasound system in healthy middle‐aged men and women.
Einflußfaktoren auf die Mikromorphologie von melanozytären Nävi
Authors: Tronnier Michael
Published: December 2004

Die zahlreichen Faktoren, die das morphologische Erscheinungsbild von melanozytären Nävi beeinflussen können, müssen gleichermaßen den klinisch‐praktisch tätigen Dermatologen zur Indikationsstellung und Befundinterpretation wie auch dem Histopathologen bekannt sein, um eine Fehlinterpretation der Dignität von melanozytären Nävi zu vermeiden.
Lebensqualität und Berufsdermatosen – Entwicklung und Überprüfung eines Fragebogens zur Lebensqualität bei Berufsdermatosen (LIOD – Life Quality Index Occupational Dermatoses)
Authors: Batzdorfer Ludger , Klippel Ulrike , Sörensen Tanja , † Hans Joachim Schwanitz
Published: December 2004

Hintergrund: Die Berücksichtigung der Lebensqualität ist in der Dermatologie langjährig etabliert und es konnten Einschränkungen durch Hauterkrankungen nachgewiesen werden. Spezifische Instrumente, die zur Selektion den auslösenden Sachverhalt, wie z. B. die Berufsbedingtheit nutzen, existieren bislang nicht, obwohl ein solches spezifisches Inventar den Vorteil besitzen kann, die Lebensqualität gezielt mit der beruflichen Situation in Verbindung zu bringen.

Patienten und Methodik: Mit dem Fragebogen zur Lebensqualität bei Berufsdermatosen (LIOD – Life Quality Index Occupational Dermatoses) wurde nach einer Literaturrecherche und der Analyse bestehender Erhebungsinstrumente sowie einer Itemreduktion ein standardisierter, valider Fragebogen entwickelt, der vier unterschiedlichen Personengruppen (N = 228) vorgelegt wurde.

Ergebnisse: In Orientierung an der Leitlinie zur Erfassung von Lebensqualität in dermatologischen Studien ergab sich im Paralleltest ein Reliabilitätswert von 0,804. Cronbachs‐Alpha betrug 0,898. Die logische und diskriminante Validität wurden überprüft und führten zu signifikanten Ergebnissen. Die im Zuge der Entwicklung formulierten Hypothesen konnten bestätigt werden.

Schlußfolgerung: Mit dem validierten LIOD steht ein Instrument zur Verfügung, mit dem ergänzend zu bereits existierenden Instrumenten Ergebnisse gewonnen werden können, die sich u. U. wie medizinische Daten zur Beurteilung eines Behandlungsergebnisses eignen.
Photodynamische Therapie mit Methylaminooxopentanoat (Metvix®) und einer Breitbandlichtquelle (PhotoDyn 501): Praktische Erfahrungen bei Problem‐Patienten mit Aktinischen Keratosen und Basalzellkarzinomen
Authors: Kreutzer Katharina , Bonnekoh Bernd , Franke Ingolf , Gollnick Harald
Published: December 2004

Hintergrund: Aktinische Keratosen (AK) und Basalzellkarzinome (BCC) können aufgrund von Besonderheiten des Typs, der Lokalisation und therapeutischen Vorgeschichte wie auch von Begleiterkrankungen eine Herausforderung darstellen. Die photodynamische Therapie (PDT) bietet für ausgewählte Indikationen eine wichtige semi‐konservative Therapieoption.

Patienten und Methode: n = 28 Patienten unserer dermatoonkologischen Spezialambulanz mit entsprechender Problemfall‐Zuweisung wurden wegen AK (n = 22) oder BCC mit Methylaminooxopentanoat (MAOP, Methyl‐Ala, Metvix®) und einer Breitbandlichtquelle (PhotoDyn 501) behandelt. Der Therapieerfolg und die subjektive Verträglichkeit (Schmerzempfinden unter PDT) wurden evaluiert.

Ergebnisse: Bei AK und BCC konnte in 11/22 (50 %) bzw. 4/6 (67 %) Fällen eine Vollremission (VR) erzielt werden, wobei eine solche in allen 3 Fällen eines superfiziellen BCC‐Subtyps zu verzeichnen war. Eine gute Verträglichkeit zeigte sich bei diesen Respondern in 12/15 Fällen (80 %), hingegen nur in 4/13 Fällen (31 %) bei den Non‐Respondern. Bei Betrachtung der insgesamt 16/28 Patienten mit guter Verträglichkeit (57 %) kam es in 12 Fällen zu einer VR (75 % Rate), während bei den 12/28 Patienten mit mäßiger bzw. schlechter Verträglichkeit nur in 3 Fällen eine VR (25 %) zu beobachten war. Bei einem Subkollektiv von n = 8 Patienten mit einer teilweise durch Zweitkrankheiten bedingten, begleitenden Retinoid‐ oder immunsuppressiv‐zytostatischen Systemmedikation zeigte sich eine VR in 3/8 (38 %) und eine gute Verträglichkeit in lediglich 1/8 Fällen (13 %).

Schlußfolgerung: Diese Beobachtungen bestätigen eine gute Wirksamkeit und Verträglichkeit der PDT bei ≥ 50 % in einem AK/BCC Problempatienten‐Kollektiv. Dabei ergeben sich Hinweise für 1) eine positive Korrelation zwischen Wirksamkeit und subjektiver Verträglichkeit sowie 2) die präsumptive Existenz einer Retinoid‐abhängigen kutanen PDT‐Hyperalgesie. Insgesamt scheint eine optimale Schmerztherapie während der PDT für einen Behandlungserfolg mitentscheidend zu sein.
Role of the sarcoplasmic reticulum in altered action potential and contraction of myopathic human and hamster ventricle
Authors: Wei Jeng , Liu Hsiang‐Cheng , Lee Fan‐Yen , Lee Meei‐Shyuan , Huang Chan‐Yao , Pan Hsin‐Pao , Lin Cheng‐I
Published: December 2004

1. The present experiments were performed in order to study the role of the sarcoplasmic reticulum (SR) in the altered action potential and contraction of ventricular myocardium obtained from myopathic Syrian hamster and explanted human hearts (n = 8). The hamsters included age‐matched healthy hamsters (F1B; n = 18), young myopathic hamsters (Bio 14.6; n = 8; aged 17–27 weeks) and older myopathic hamsters (n = 10; aged 39–43 weeks).

2. Action potentials were recorded by means of a microelectrode technique and force was recorded using a transducer. Post‐rest potentiation of contraction (PRPC), a measure of the SR Ca2+‐pumping activity, was determined after different rest intervals (2–60 s). Furthermore, cyclopiazonic acid (10 µmol/L), a specific blocker of SR Ca2+‐ATPase, was used to unmask abnormalities in the function of the SR.

3. The relationship between PRPC and rest interval was similar in younger healthy and myopathic hamsters, but the curve of the older myopathic muscle was obviously shifted downwards. Cyclopiazonic acid decreased predominantly the ascending part of the curve in both the healthy and myopathic hamster myocardium and could induce spontaneous action potentials during drug exposure or after washout.

4. In human myopathic myocardium, the curve of the PRPC–rest interval peaked at longer intervals (40–60 s) compared with that of the hamsters (10–20 s). Cyclopiazonic acid markedly depressed the relationship and increased the diastolic force (contracture) at high driving frequency, but did not induce action potentials during the rest interval.

5. We conclude that an impaired function of the SR contributes to the progressive deterioration of ventricular function in dilated cardiomyopathy and that the electromechanical behaviour of the ventricular myocardium of patients affected by dilated cardiomyopathy shows similarity and differences with the myopathic Syrian hamster model.
Long‐term measurement of cerebral blood flow and metabolism in a rat chronic hypoperfusion model
Authors: Otori Tatsuo , Katsumata Toshiya , Muramatsu Hiromi , Kashiwagi Fumihiko , Katayama Yasuo , Terashi Akiro
Published: December 2004

1. Rat bilateral common carotid artery occlusion (BCAO) was used as a chronic cerebral hypoperfusion model. We observed autoradiographically the long‐term changes in regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCGU) after 2 days and 1, 4 and 8 weeks of BCAO and in controls. Regions evaluated included the cerebral cortex, white matter and basal ganglia. Pathological changes were also observed with Klüver–Barrera and haematoxylin–eosin staining.

2. After 2 days, rCBF was significantly reduced to 33–58% in the cortex, white matter and amygdala and similar reductions were observed after 1 week.

3. After 4 weeks, rCBF recovered; however, rCBF remained significantly reduced in the occipital cortex, white matter, globus pallidus and substantia nigra.

4. After 2 days, rCGU was mostly maintained but, after 1 week, rCGU was reduced significantly to 40–70% in the cortex, white matter, basal ganglia and thalamus. Four weeks later, these reductions were no longer seen.

5. Rarefaction of the white matter was observed from 1 week.

6. These results showed that the BCAO in rats is an appropriate model for chronic cerebral hypoperfusion and that uncoupling of rCBF and rCGU was observed from 2 days until 4 weeks in the white matter.
Effects of taurine on serum cholesterol levels and development of atherosclerosis in spontaneously hyperlipidaemic mice
Authors: Matsushima Yoshibumi , Sekine Takumi , Kondo Yukiko , Sakurai Takanobu , Kameo Kazuya , Tachibana Masayoshi , Murakami Shigeru
Published: December 2004

1. The effects of two naturally occurring substances, namely taurine and catechins, on serum cholesterol levels and on the progression of atherosclerotic lesions were evaluated using spontaneously hyperlipidaemic (SHL) mice as an animal model of atherogenesis.

2. Twelve weeks treatment of SHL mice with taurine (1% in drinking water) significantly elevated serum high‐density lipoprotein–cholesterol (HDL‐C) levels without affecting levels of low‐density lipoprotein– and very low‐density lipoprotein–cholesterol. In addition, taurine suppressed the development of atherosclerotic lesions by 29%, as determined by oil red O‐stained areas in cross‐sections of the aorta.

3. In contrast, 12 weeks treatment with a catechin mixture had no apparent effect on serum cholesterol levels and on the progression of atherosclerosis.

4. Serum levels of thiobarbituric acid‐reactive substances, an index of oxidized substances, significantly decreased from 9.6 to 6.7 nmol/mL following taurine treatment.

5. We suggest that retardation of atherosclerosis by taurine in SHL mice may be related to decreases in oxidized substances and increases in serum HDL‐C levels.
Endothelin ETA receptor antagonism does not attenuate angiotensin II‐induced cardiac hypertrophy in vivo in rats
Authors: De Smet HR , Menadue MF , Oliver JR , Phillips PA
Published: December 2004

1. Angiotensin (Ang) II causes cardiac hypertrophy in vitro and in vivo. It also stimulates the release of endothelin (ET)‐1. Endothelin‐1 induces hypertrophy of cardiomyocytes in vitro.

2. In the present study, we examined whether the cardiac hypertrophic action of AngII in vivo was mediated by ET‐1 via ETA receptors. We also determined whether arginine vasopressin (AVP), another ET‐1 stimulator, could cause cardiac hypertrophy in vivo through an ET‐1‐dependent pathway.

3. In Sprague‐Dawley rats (n = 8 per group), we determined whether the orally administered ETA receptor antagonist BMS 193884 could attenuate the cardiac hypertrophic effect of: (i) i.v. AngII infusion at either 100 or 200 ng/kg per min, i.v., for 1 week; (ii) AngII infusion at 100 ng/kg per min, i.v., for 2 weeks; and (iii) AVP infusion at either 2 or 10 ng/kg per min, i.v., for 1 week. Mean arterial pressure and heart rate were also measured.

4. Infusion with AngII for both 1 and 2 weeks increased left ventricular weight. Only AngII infusion at 200 ng/kg per min for 1 week increased blood pressure. Endothelin ETA receptor blockade did not attenuate the left ventricular hypertrophy, even though it reduced the hypertensive effect of AngII. Arginine vasopressin increased blood pressure, but did not cause cardiac hypertrophy.

5. We showed that AngII can cause cardiac hypertrophy through a direct, blood pressure‐independent effect on the heart. Endothelin‐1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors. This may indicate the involvement of ETB receptors in this model of cardiac hypertrophy. Arginine vasopressin did not cause cardiac hypertrophy in vivo.
Pilot study examining the effect of cholesterol lowering on platelet nitric oxide responsiveness and arterial stiffness in subjects with isolated mild hypercholesterolaemia
Authors: Stepien Jacqueline M , Prideaux Rhonda M , Willoughby Scott R , Chirkov Yuliy Y , Horowitz John D
Published: December 2004

1. Hypercholesterolaemia has been associated with impaired endothelial function. However, there are no available data as to whether hypercholesterolaemia is also associated with platelet dysfunction.

2. In a group of asymptomatic adults with (n = 16) and without (n = 13) mild hypercholesterolaemia, we evaluated inhibition of platelet aggregation in response to the nitric oxide (NO) donor sodium nitroprusside (SNP), as well as the augmentation index (AIx), a parameter of arterial stiffness that is impaired in the presence of endothelial dysfunction.

3. Neither SNP response nor AIx varied significantly between normocholesterolaemic (NC) and hypercholesterolaemic (HC) subjects.

4. Three months treatment with pravastatin (40 mg/day) in HC subjects lowered mean (±SEM) total cholesterol levels from 6.6 ± 0.2 to 5.5 ± 0.2 mmol/L. Platelet response to SNP increased in platelet‐rich plasma and tended to increase in whole blood. The AIx did not change significantly. However, falls in low‐density lipoprotein (P = 0.03) and total cholesterol (P = 0.08) correlated with reductions in AIx in individual subjects.

5. These data provide evidence that moderate reduction of cholesterol levels may improve platelet responses to NO, whereas improvement in arterial stiffness may be detectable only with more extensive and/or a prolonged reduction in cholesterol levels.
Extra‐adrenal production of corticosteroids
Authors: Davies Eleanor , MacKenzie Scott M
Published: December 2004

1. The major corticosteroids aldosterone and cortisol (corticosterone in rodents) are secreted from the adrenal cortex under the regulation of the renin–angiotensin system and the hypothalamic–pituitary–adrenal axis.

2. In addition to their accepted roles in such processes as blood pressure regulation, glycogenesis, hepatic glyconeogenesis and immunosuppression, the corticosteroids have been implicated in the development of cardiac fibrosis, modulation of hippocampal neuron excitability, memory formation and neurodegeneration.

3. The advent of sensitive molecular biological techniques has produced a wealth of evidence to support the existence of extra‐adrenal corticosteroidogenic systems. Most attention has been paid to the cardiovascular system and the central nervous system, where the full array of enzymes required for the de novo synthesis of corticosteroids from cholesterol has been identified.

4. Although the evidence for local corticosteroid production is strong, the quantities of steroid would be small compared with adrenal production. Therefore, it is still a matter of debate as to whether extra‐adrenal corticosteroids are of any physiological significance. This will depend on factors such as local concentration, proximity to target cells and, possibly, to tissue‐specific control mechanisms.
Comparison of the Zeiss IOLMaster and applanation A‐scan ultrasound: biometry for intraocular lens calculation
Authors: Rose Loreto T , Moshegov Con N
Published: December 2004

Purpose: A comparison of axial length estimates using applanation A‐scan ultrasound and the Zeiss IOLMaster was conducted. The accuracy in predicting postoperative refraction determined by each method was also compared.

Methods: A cross‐sectional study was performed on 51 eyes in 46 patients presenting to clinical practice for cataract surgery assessment. Preoperative measurement of axial length was performed with applanation ultrasound and the IOLMaster. The IOLMaster measurements were used to determine the intraocular lens power based on the SRK/T formula. Postoperative refractive outcomes were obtained and spherical equivalent calculated and compared to the predicted refractive error with each biometric method.

Results: On average the axial lengths measured by the IOLMaster were longer by 0.15 mm compared to ultrasound biometry (P < 0.01). Using the IOLMaster over applanation ultrasound biometry significantly improved the postoperative refractive outcome from 0.65 D to 0.42 D (P = 0.011).

Conclusions: The IOLMaster provides an accurate axial length measurement and results in accurate intraocular lens power calculation based on the SRK/T formula. It is quick and easy to use and provides a non‐contact technique with no risk of infection or corneal abrasion.
Topical anaesthesia: a risk factor for post‐cataract‐extraction endophthalmitis?
Authors: Ellis Mark F
Published: December 2004

Purpose: To investigate if the incidence of postoperative endophthalmitis in temporal clear corneal cataract surgery is influenced by the use of topical anaesthesia compared to retrobulbar anaesthesia.

Methods: A retrospective study was conducted of one surgeon's cataract surgery between October 1997 and October 2001.

Results: Between October 1997 and May 2000, there were 633 cataract extractions performed with 219 patients operated under topical anaesthesia and 414 under retro­bulbar injection. The selection criteria were that surgically easier cases underwent topical anaesthesia. There were five patients who suffered postoperative endophthalmitis in their first week, of which four cases were under topical anaesthesia. This was shown to be borderline significance of P = 0.05 using the Fischer exact 2‐tailed test. There was a complicated case, operated under retrobulbar anaesthesia, who had a low‐grade endophthalmitis in the second postoperative week. The four topical cases and the case from the second week all grew Staphylococcus epidermidis. The retrobulbar case developing endophthalmitis in the first week grew alpha haemolytic Streptococcus. After May 2000, there was a change to performing all cataract surgery under retrobulbar anaesthesia and the next 453 cases had no incidence of endophthalmitis.

Conclusion: Topical anaesthesia techniques in temporal clear corneal cataract extraction may be a factor in endophthalmitis.