bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of serum IL-13 and IL-5 levels with clinical response to Glatiramer acetate in patients with multiple sclerosis
Authors: WIESEMANN E , KLATT J , WENZEL C , HEIDENREICH F , WINDHAGEN A 
Published: December 2004

SUMMARY
Glatiramer acetate (GA) is effective in the treatment of Multiple Sclerosis (MS) presumably by the induction of an immunoregulatory T-cell response. We have previously shown that GA directly induces the Th2 cytokines IL-13 and IL-5 in T-cells in vitro. In the present study we compared the in vitro response to GA in healthy controls, untreated and GA-treated MS patients and tested whether the induction of IL-13 and IL-5 secretion is also detectable in the serum of 25 MS patients treated with GA. Patients were grouped into clinical responders and nonresponders in order to determine a possible correlation with the immunological response. As a result we found a significant increase of IL-13 in the serum of clinical GA-responders whereas IL-13 was not detectable in controls, untreated MS (P &lt; 0·001) and nonresponders (P = 0·015). Similarly, GA-treatment increased serum levels of IL-5 (P = 0·001). The correlation of serum IL-5 and clinical response was also significant (P = 0·039), however, there was an overlap between the different groups. The selective induction of IL-13 and IL-5 but not IL-4 by GA treatment suggests that the specific biological functions of these cytokines might be important for the therapeutic mechanism of GA. Measurement of serum IL-13 and IL-5 levels is a simple and inexpensive tool for monitoring the response to GA in MS patients.
Cell mediated immune responses against human prion protein
Authors: BAINBRIDGE J , WALKER B 
Published: December 2004

SUMMARY
Vaccination approaches that may provide protection against the abnormal form of prion protein (PrPSc) have recently focused on the ability of antibodies to prevent PrPSc propagation. Progress has been hampered due to the difficulty in generating antibody responses in wild type mice, which is believed to be a consequence of T cell tolerance to the normal form of prion protein (PrPC). The problem of tolerance can be avoided using transgenic mice unable to express PrPC. This study examines active PrP specific T cell responses that can be produced in PrP null (PrP 0/0) mice using simple peptide vaccination procedures. Spleenocytes recovered from vaccinated PrP 0/0 mice were tested in vitro for their specificity with T cell recognition demonstrated through a proliferative response to the peptide. Analysis of mRNA also indicates the stimulation of a heterogenous population of T cells with an increase in cytokines and cytotoxicity associated mRNA. Responsive T cells were expanded using a T cell cloning procedure and demonstrated an ability to recognize the mature human prion protein. These clones may potentially be used to negate the problem of T cell tolerance in wild type mice.
The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug‐treated patients with Graves’ disease
Authors: Fukao Atsushi , Takamatsu Junta , Murakami Yasuhiro , Sakane Sadaki , Miyauchi Akira , Kuma Kanji , Hayashi Shunichiro , Hanafusa Toshiaki 
Published: December 2004

Summaryobjective The relationship between emotional stress and the onset of hyperthyroidism has been well investigated, but the relationship between psychological factors and prognosis of antithyroid drug‐treated hyperthyroidism is not well known. This study has examined not only emotional stresses but also patients’ personality traits using specific tests.design A prospective cohort study.subjects Sixty‐nine patients with hyperthyroid Graves’ disease in the euthyroid state after 2–5 years of antithyroid drug therapy and 32 healthy subjects as the control group.measurements Patients responded to three types of questionnaires, including the Minnesota Multiphasic Personality Inventory for personality traits, the Natsume's Stress Inventory for major life events, and the Hayashi's Daily Life Stress Inventory for daily life stresses.results In the Graves’ disease patients, stress scores of life events correlated significantly with serum TSH receptor antibody activity (r = 0·424, P < 0·001) and thyroid volume (r = 0·480, P < 0·001). When the patients were divided according to prognosis (41 with relapse and 28 with remission), four personality traits including hypochondriasis, depression, paranoia and psychasthenia (mental fatigue) were significantly (P = 0·0146, 0·0052, 0·0125, and 0·0186, respectively) more common in the relapsed Graves’ disease group than those of the remitted group. Six personality traits of conversion hysteria, psychopathic deviation, masculinity and feminity, schizophrenia, hypomania, and social introversion were not significantly different between the two groups. The scores of daily hassles (problems of daily life) were also significantly (P = 0·0124) greater in the relapsed Graves’ disease group than in the remitted group. The scale scores of depression and psychasthenia showed a positive correlation with scores of daily hassles (r = 0·535, P < 0·0001; r = 0·580, P < 0·0001, respectively), while an inverse correlation with scores of daily uplifts (r = −0·373, P = 0·0332; r = −0·322, P = −0·0120, respectively).conclusions The results suggest that major life events, personality traits of hypochondriasis and depression, paranoia, mental fatigue, and daily problems aggravate the prognosis of antithyroid drug‐treated hyperthyroidism. Escape from life events is virtually impossible; thus coping strategies suggested by the physician may be useful in improving prognosis in Graves’ disease.
Pituitary apoplexy induced by corticotrophin‐releasing hormone in a patient with Cushing's disease
Authors: Rotman‐Pikielny Pnina , Patronas Nicholas , Papanicolaou Dimitris A. 
Published: December 2004

SummaryPituitary apoplexy can occur spontaneously or following anterior pituitary stimulation tests. Apoplexy is a rare complication of Cushing's disease. We report a 19‐year‐old woman who was admitted to the National Institutes of Health for evaluation of possible Cushing's syndrome. Her symptoms and initial laboratory work were suggestive of Cushing's disease. Magnetic resonance imaging (MRI) revealed a macroadenoma of the pituitary gland. As part of her evaluation she received corticotrophin‐releasing hormone (CRH). Two days later she developed severe headache, accompanied by nausea and vomiting, followed by meningismus, ptosis and diplopia. A diagnosis of pituitary apoplexy was made and she was treated conservatively with dexamethasone. Her neurological symptoms resolved shortly afterwards. By the time of discharge her anterior pituitary function was suppressed. All symptoms and signs of Cushing's syndrome resolved thereafter. This is the first case to demonstrate that CRH administration can induce pituitary apoplexy in a patient with Cushing's disease. Therapy with glucocorticoids was effective in our case, suggesting that conservative treatment can be successfully and safely applied in certain cases with pituitary apoplexy.
Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects
Authors: Elbers Jolanda M. H. , Giltay Erik J. , Teerlink Tom , Scheffer Peter G. , Asscheman Henk , Seidell Jacob C. , Gooren Louis J. G. 
Published: December 2004

Summaryobjective Sex differences are found in most components of the insulin resistance syndrome and the associated cardiovascular risk profile. These differences are attributed to sex‐specific sex steroid profiles, but the effects of sex steroids on the individual components of the insulin resistance syndrome remain incompletely understood.design Prospective, intervention study.subjects In 37 young (age range 16–36 years), nonobese [body mass index (BMI) < 29], transsexual subjects, effects of ethinyl oestradiol (100 µg/day) + cyproterone acetate (100 mg/day) administration were evaluated in 20 male‐to‐female transsexuals and of testosterone‐ester administration [250 mg intramuscularly (i.m.)/2 weeks] in 17 female‐to‐male transsexuals.measurements We studied lipid spectrum, postheparin hepatic lipase (HL) and lipoprotein lipase (LPL) activity, blood pressure, glucose utilization (by euglycaemic hyperinsulinaemic clamp), and fat areas (by magnetic resonance imaging) at baseline and during 1‐year cross‐sex hormone administration.results Oestrogens + antiandrogens increased high‐density lipoprotein (HDL)‐cholesterol and decreased LDL‐cholesterol, and HL activity, which are considered beneficial. But this combination also increased triglycerides, blood pressure, subcutaneous fat and visceral fat, and decreased the LDL‐particle size, LPL activity and insulin sensitivity, which are all considered detrimental. Testosterone reduced HDL‐cholesterol and the LDL‐particle size, and increased triglycerides and HL activity. An android fat distribution was induced (i.e. decreased subcutaneous and increased visceral fat). Blood pressure, total and LDL‐cholesterol, LPL activity and insulin sensitivity were mainly unaffected.conclusions The effects of cross‐sex hormone treatment – in the dosages used in this study – in healthy, nonobese, young transsexual subjects do not show unequivocally that female sex steroids, given in large amounts to male subjects, have beneficial effects on cardiovascular profile and that high dose testosterone administration to female subjects is detrimental with respect to cardiovascular risk.
Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency
Authors: Svensson J. , Monson J. P. , Vetter T. , Hansen T. K. , Savine R. , Kann P. , Bex M. , Reincke M. , Hagen C. , Beckers A. , Ilondo M. M. , Zdravkovic M. , Bengtsson B‐Å. , Korbonits M. ,   the NN703 Clinical Research Group
Published: December 2004

Summaryobjective Little is known of the usefulness of GH secretagogues (GHSs) in GH‐deficient (GHD) adults. The objective of this study was to determine the number of responders to treatment with NN703 in GHD adults.design A multicentre, randomized, double‐blind, and placebo‐controlled study.patients Ninety‐seven GHD adults were included.measurements The GH response before and after 1 week of oral treatment with NN703 (n = 83) or placebo (n = 14) was determined. The first and last dose of NN703 was 3 mg/kg, whereas the dose of NN703 was 1·5 mg/kg/day during the 6 days between the first and last doses. Furthermore, all 97 patients received 1 µg/kg GH‐releasing hormone (GHRH) 3 weeks after the last dose of NN703.results Serum GH peak and area under curve (AUC) values after the first NN703 administration were greater than those after placebo administration (P < 0·05). However, after correction for the lower body mass index (BMI) in the NN703 group, this difference lost statistical significance. After 1 week of therapy, GH peak and AUC values were similar following the final doses of NN703 and placebo. Serum peak and AUC values of other anterior pituitary hormones were similar between the NN703 and placebo groups both after the first and last administration of study drug. Nine of the 83 patients (11%) responded with a serum peak GH concentration ≥ 5 µg/l after the first and/or last NN703 administration, whereas no patient responded after placebo administration. Serum IGF‐I was unaffected by 1‐week NN703 treatment, whereas serum IGFBP‐3 was increased (P < 0·05 vs. placebo) also after correction for BMI. Mean serum peak GH concentration after GHRH administration was 2·1 µg/l (±0·3, SEM), which was higher than that after the first NN703 administration (1·32 ± 0·3, P < 0·05).conclusion NN703 administration was generally well tolerated. Eleven per cent of the GHD adult patients responded with a peak GH response ≥ 5 µg/l after the first and/or last administration of oral NN703. Although a majority of GHD adults will not respond to NN703, the present results suggest that oral NN703 treatment could be useful in some adult patients with moderately severe GHD. These patients may be identified by a test dose of GHS.
Iodine sufficiency and measurements of thyroid function in maternal hypothyroidism
Authors: Mitchell M. L. , Klein R. Z. , Sargent J. D. , Meter R. A. , Haddow J. E. , Waisbren S. E. , Faix J. D. 
Published: December 2004

Summaryobjectives To test the hypothesis that thyroglobulin (Tg) and free T4 (FT4) concentrations more than 2SD from the control mean are not increased in pregnancy in an iodine replete area in the absence of elevated TSH concentrations. The second hypothesis to be tested was that if such abnormalities in FT4 and Tg in the absence of elevated TSH concentrations were to exist they would not be associated with lowered IQs in the progeny.design Cross‐sectional study in New England comparing TSH, Tg, antibodies to Tg and FT4 in volunteer nonpregnant women 20–40 years old with those in hypothyroid mothers and matched euthyroid control mothers. The results are contrasted with those from similar studies reported from iodine deficient areas.subjects Sera obtained at 17 weeks gestation and stored at −20 °C for 8 years were retrieved and analysed from 62 mothers with subclinical hypothyroidism and 124 matched euthyroid mothers. The diagnosis of hypothyroidism was made by finding a TSH concentration > 97·7 percentiile for 25 000 consecutive pregnant women. Sera were also analysed from 53 healthy nonpregnant volunteer women aged 20–40 years.measurements TSH, Tg and Tg antibodies were measured in the sera of the nonpregnant volunteers, and Tg and Tg antibodies in the sera of the pregnant women who had previously been analysed for TSH and FT4. The incidence of FT4 concentrations below the 2·3 percentile of nonpregnant laboratory controls was compared for the euthyroid and hypothyroid mothers and the laboratory normal controls.results Thirty‐one per cent of the 62 hypothyroid mothers had FT4 concentrations below the 2·3 percentile compared with only one (0·8%) of the euthyroid mothers. Mean Tg concentrations did not differ between the nonpregnant controls and the euthyroid pregnant women, 14 ± 10 vs. 16 ± 10 µg/l. Tg concentration in the hypothyroid mothers was 44 ± 61, significantly greater than for either of the euthyroid control groups, P < 0·005. Positive antibodies to Tg were found in 9% and 10% of the control groups and 57% of the hypothyroid mothers, P < 0·0005. When TSH is included as an independent variable in multiple linear and logistic regressions, FT4 and Tg no longer correlate significantly with IQs.conclusions The incidences of FT4 concentrations more than 2SD below the control mean and of Tg > 2SD above the control mean are significantly increased in hypothyroid mothers in iodlne‐sufficient New England. However, in the absence of elevated TSH concentrations, the incidences of such abnormalities in FT4 and TG are negligible. Indeed, concentrations for FT4, Tg and Tg antibodies for nonpregnant and pregnant controls in our iodine‐replete area do not differ significantly from each other or from previously reported normative concentrations with the methods used. Thus, pregnancy in New England neither increases Tg nor lowers FT4 concentrations.
Serum concentrations of remnant‐like particles in hypothyroid patients before and after thyroxine replacement
Authors: Ito Mitsuru , Takamatsu Junta , Matsuo Takashi , Kameoka Keiichi , Kubota Sumihisa , Fukata Shuji , Tamai Hajime , Miyauchi Akira , Kuma Kanji , Hanafusa Toshiaki 
Published: December 2004

Summaryobjectives  Remnant‐like particles (RLPs) reflect chylomicron remnants and very‐low‐density lipoprotein remnants, which are most likely to be atherogenic particles. To investigate the effect of thyroxine replacement on the metabolism of RLPs in hypothyroidism, we measured serum concentrations of RLPs during an oral fat‐loading test in patients with hypothyroidism before and after thyroxine replacement.patients and methods  Thirteen patients with hypothyroidism, having serum‐free thyroxine (FT4) of 4·25 ± 2·23 pmol/l (mean ± SD) and TSH of 72·5 ± 27·7 mU/l, participated in the study. Two‐hundred grams of cream containing 32·9% of fat were given to each patient followed by blood draws every 2 h for 8 h. The patients became euthyroid after 3 months of T4 replacement, and the fat‐loading tests were then repeated.results  Fasting levels of serum total cholesterol and low‐density lipoprotein cholesterol were remarkably decreased after T4 therapy (P < 0·0005). Serum high‐density lipoprotein cholesterol and triglyceride were also decreased by T4 therapy, not so remarkably but significantly (P < 0·05). Activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) increased 52% and 85%, respectively, from the pretreatment values. Serum concentrations of remnant‐like particle cholesterol (RLP‐C) and remnant‐like particle triglyceride (RLP‐TG), measured by immunoseparation assays, significantly decreased from 0·14 ± 0·03 to 0·09 ± 0·03 mmol/l (P < 0·0005) and from 0·19 ± 0·11–0·11 ± 0·07 mmol/l (P < 0·01), respectively. In the fat‐loading test, serum low‐density lipoprotein cholesterol concentrations were not changed, while serum RLPs concentrations were increased and remained high throughout the test, with the peak value at 6 h in a hypothyroid condition. In an euthyroid condition after T4 therapy, the peak values of RLPs were obtained at 4 h, and the concentrations were decreased rapidly. As the result, areas under the curve of serum RLPs were decreased remarkably after T4 therapy.conclusions  Hypothyroidism seems to be associated with a decrease in metabolism of serum RLPs. Such altered metabolism of RLPs may be related to the decreased activities of LPL and HTGL and can be corrected by T4 replacement therapy.
Molecular analysis of 5α‐reductase type 2 gene in eight unrelated egyptian children with suspected 5α‐reductase deficiency: prevalence of the G34R mutation
Authors: Mazen Inas , Gad Yehia Z. , Hafez Mona , Sultan Charles , Lumbroso Serge 
Published: December 2004

Summaryobjective Analysis of the 5α‐reductase type 2 (SRD5A2) gene in Egyptian patients with suspected 5α‐reductase (5αR) deficiency.patients and methods Eight unrelated patients, originating from different geographical areas of Egypt, were referred to the Department of Pediatrics. Six prepubertal and two postpubertal patients presented with ambiguous genitalia. Four were being reared as females while the others were being reared as males. Six patients were products of consanguineous marriages. All patients had 46,XY karyotype. Basal and post‐human chorionic gonadotrophin (hCG) stimulation plasma levels of testosterone and dihydrotestosterone were determined. Sequencing of five exons of the SRD5A2 gene was carried out.results All patients had normal male testosterone levels, both basal and post‐hCG stimulation. The T/DHT ratio was available for six patients and showed values that ranged from normal to high. Three different homozygous mutations were identified. One patient carried a Y235F substitution and two had a N160D substitution. Interestingly, all five of the other patients had the G34R mutation. The parents were heterozygous for the mutations, although the mother of one patient was homozygous for the G34R mutation.conclusion Among eight unrelated Egyptian children with 5α‐reductase deficiency, the G34R mutation was identified in five patients. The high consanguinity rate in Egypt suggests a common ancestor with a founder gene effect in cases of G34R mutation.
Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction
Authors: Aversa Antonio , Isidori Andrea M. , Spera Giovanni , Lenzi Andrea , Fabbri Andrea 
Published: December 2004

Summaryobjectives We have recently shown that, in men with erectile dysfunction (ED), free testosterone (FT) directly correlates with penile arterial inflow. This led us to further investigate the effect(s) of androgen administration on cavernous arteries in patients failing sildenafil treatment.design Prospective randomized placebo‐controlled pilot study.patients Twenty patients with arteriogenic ED as evaluated by dynamic colour duplex ultrasound (D‐CDU) studies, normal sexual desire but testosterone (T) and FT in the lower quartile of normal range (low‐normal), not responding to sildenafil treatment (100 mg) on six consecutive attempts.measurements All patients had D‐CDU, hormonal [LH, prostate‐specific antigen (PSA), total and free testosterone, sex hormone‐binding protein (SHBG), oestradiol], biochemical [haematocrit, low‐density lipoprotein (LDL) and HDL cholesterol, triglycerides], and sexual evaluations [International Index of Erectile Function (IIEF)] before and after 1 month of therapy with transdermal testosterone (5 mg/day, n = 10) or placebo along with sildenafil treatment on demand. Measurement of flow parameters by D‐CDU on cavernous arteries was the primary endpoint of the study. Improvement of erectile function was assessed using the IIEF questionnaire and the Global Assessment Question (GAQ).results One month treatment with transdermal testosterone led to a significant increase in T and FT levels (23·7 ± 3·3 SD vs. 12·8 ± 2·1 nmol/l and 473 ± 40·2 vs. 260 ± 18·1 pmol/l, P < 0·01, respectively). In addition testosterone administration induced a significant increase in arterial inflow to cavernous arteries measured by D‐CDU (32 ± 3·6 vs. 25·2 ± 4 cm/s, P < 0·05), with no adverse effects. Also, a significant improvement in erectile function domain score at IIEF was found in the androgen but not in the placebo‐treated patients (21·8 ± 2·1 vs. 14·4 ± 1·4, P < 0·05) which was associated with significant changes in the GAQ score (80%vs. 10%, P < 0·01).conclusions In patients with arteriogenic ED and low‐normal androgen levels, short‐term testosterone administration increases T and FT levels and improves the erectile response to sildenafil likely by increasing arterial inflow to the penis during sexual stimulation.
Growth hormone treatment improves body composition in adults with Prader–Willi syndrome
Authors: Höybye Charlotte , Hilding Agneta , Jacobsson Hans , Thorén Marja 
Published: December 2004

Summaryobjective Low growth hormone (GH) secretion and hypogonadism are common in patients with Prader–Willi syndrome (PWS). In this study we present the effects of GH treatment on body composition and metabolism in adults with PWS.patients and measurements Nineteen patients with clinical PWS were recruited, 13 had PWS genotype. They were randomised to treatment with placebo or GH (Genotropin®, Pharmacia Corporation, Sweden) 0·8 IU (0·2 mg) daily for 1 month and then 1·6 IU (0·5 mg) daily for 5 months. Thereafter patients recieved open label treatment so that all had 12 months of active GH treatment. Doses were individually titrated to keep serum IGF‐I within the normal range for age. Body composition using dual energy X‐ray absorptiometry (DXA), metabolic and endocrinological parameters, including oral glucose tolerance test (OGTT), were studied every 6 months. Seventeen patients, nine men and eight women, 17–32 years of age, with a mean body mass index (BMI) of 35 ± 3·2 kg/m2 completed the study.results Compared to placebo, GH treatment increased IGF‐I (P < 0·01) levels and decreased body fat (P = 0·04). When all patients recieved GH treatment a mean reduction in body fat of 2·5% (P < 0·01) concomitant with a mean increase in lean body mass of 2·2 kg (P < 0·05) was seen. Significant changes in body composition were only seen in the patients with the PWS genotype. Lipid profiles were normal in most patients before treatment and did not change. OGTT was impaired in five patients at 12 months, but two of these patients increased in fat mass. Insulin levels were unchanged. According to homeostasis model assessment (HOMA), insulin resistance did not change. Side‐effects attributed to water retention occurred in three patients, one of whom had to be given increased diuretic therapy.conclusion This study shows beneficial effects of GH treatment on body composition in adult PWS patients without significant side‐effects. Consequently, further studies are encouraged.