bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in immune parameters and their correction in human cases of tick-borne encephalitis
Authors: ATRASHEUSKAYA A V , FREDEKING T M , IGNATYEV G M 
Published: March 2003

SUMMARY
Tick-Borne Encephalitis virus (TBEV) causes dangerous central nervous system diseases in humans. General infection leads to the development of meningitis or encephalitis, which is characterized by swelling of the brain due to inflammation. Tetracyclines may act locally to moderate inflammation in the CNS. In this study, we investigated the potential clinical benefits of administering tetracycline hydrochloride to patients hospitalized due to suspected TBEV infection presenting with fever and evidence of a recent tick bite. We also characterized an acute immune response to TBEV by profiling certain cytokines and soluble receptors in Tetracycline-treated and untreated patients. Increased serum levels of TNF-α, IL-1α and IL-6 were found in all patients at admission.
Soluble receptors presented in the serum of patients in a magnitude higher levels than the corresponding cytokines and were increasing during first weak of hospitalization. Levels of IL-10 were also rising during that period. In our study tetracycline hydrochloride acted as an immunomodulator, which was able to reduce manifestations of inflammation response during TBE course; this action led to quicker improvement of symptoms and, consequently, to a faster clinical recovery. The positive result of tetracycline hydrochloride treatment was accompanied by certain particularities in the dynamics of studyied cytokines and receptors: the concentrations of IL-6, IL-1β, TNF-α dropped quicker and reached lower levels, and the concentrations of sIL-6R, IL-1RA, sTNFR1 increased faster and reached higher maximum levels in the tetracycline-treated groups. Children had the highest levels of IL-6, which were not neurotoxic.
Endogenous glucocorticoids attenuate Shiga toxin-2-induced toxicity in a mouse model of haemolytic uraemic syndrome
Authors: GÓMEZ S A , FERNÁNDEZ G C , VANZULLI S , DRAN G , RUBEL C , BERKI T , ISTURIZ M A , PALERMO M S 
Published: March 2003

SUMMARYThe concept that during an immune challenge the release of glucocorticoids (GC) provides feedback inhibition on evolving immune responses has been drawn primarily from studies of autoimmune and/or inflammatory processes in animal models. The epidemic form of haemolytic uraemic syndrome (HUS) occurs secondary to infection with Gram-negative bacteria that produce Shiga toxin (Stx). Although Stx binding to the specific receptors present on renal tissue is the primary pathogenic mechanism, inflammatory or immune interactions are necessary for the development of the complete form of HUS. The aim of this study was to investigate the influence of endogenous GC on Stx-toxicity in a mouse model. Stx2 was injected into GC-deprived mice and survival rate, renal damage and serum urea levels were evaluated. Plasma corticosterone and cytosolic GC receptor (GR) concentration were also determined at multiple intervals post-Stx2 treatment. Higher sensitivity to Stx2 was observed in mice lacking endogenous GC, evidenced by an increase in mortality rates, circulating urea levels and renal histological damage. Moreover, Stx2 injection was associated with a transient but significant rise in corticosterone secretion. Interestingly, 24 h after Stx inoculation significant increases in total GR were detected in circulating neutrophils. These results indicate that interactions between the neuroendocrine and immune systems can modulate the level of damage significantly during a bacterial infection.
Local immune responses and systemic cytokine responses in zoster: relationship to the development of postherpetic neuralgia
Authors: ZAK-PRELICH M , MCKENZIE R C , SYSA-JEDRZEJOWSKA A , NORVAL M 
Published: March 2003

SUMMARY
Varicella zoster virus (VZV) causes varicella (chickenpox) as the primary infection and zoster (shingles) on reactivation from latency, often many years later. One of the most common and most severe sequela of zoster is postherpetic neuralgia (PHN). Apart from age, factors which predispose towards PHN are unknown. In the present study, the concentration of a variety of Th1 and Th2 cytokines in the serum of 30 zoster patients at the time of the acute disease were correlated with the subsequent development of PHN in nine of these patients, but no association was found. In addition, although some cytokines such as IFN-γ, IL-6 and IL-8 were slightly raised in the zoster group compared with a group of normal healthy subjects of a similar age distribution, these differences only verged on significance. Antibody titres to VZV were raised in the zoster group compared with the controls but these did not differ between the patients who developed PHN and those who did not. Biopsies of zoster lesions were collected from nine patients. There were significantly fewer infiltrating lymphocytes in the lesions of the three patients who subsequently developed PHN compared with the six who did not, although the expression of the neuropeptide, substance P, did not differ between the two groups. It is possible that the poor inflammatory response at the time of the acute zoster may result in less effective containment of the VZV and more damage in the dermatome, thus contributing to the persistence of the neuralgia.
Bright light exposure and pituitary hormone secretion
Authors: Kostoglou‐Athanassiou Ifigenia , Treacher David F. , Wheeler Michael J. , Forsling Mary L. 
Published: March 2003

OBJECTIVEExposure to bright light inhibits melatonin secretion in man. As the relationship between melatonin and pituitary function remains controversial, we investigated the effect of altering the melatonin rhythm by bright light during the early hours of darkness on pituitary hormone secretion in man.DESIGNThe investigation took the form of a randomized controlled clinical trial.SUBJECTSTen adult healthy male volunteers, who were non‐smokers and aged 21–33 years, were studied on two occasions: once during exposure to bright light from 2000 h to 0200 h and once during exposure to normal room lighting over the same period. On each day of the study, the subjects were allowed to sleep after lights were switched off at 0200 h. Observations were also performed when subjects were exposed to normal room lighting from 2000 h to 2400 h, thereafter being allowed to sleep. On each study day the subjects undertook their normal duties but refrained from taking heavy exercise and drinking alcohol.MEASUREMENTSSerum cortisol, GH and PRL, plasma vasopressin, oxytocin, melatonin, sodium, potassium and osmolality and packed cell volume were measured over 24 hours.RESULTSBright light delayed the nocturnal melatonin peak by 2 hours and resulted in a decrease in cortisol concentrations. Growth hormone levels decreased but subsequently there was a significantly greater nocturnal increase. The PRL peak was delayed and nocturnal vasopressin concentrations were lower in both the studies where subjects were exposed to a modified sleep schedule.CONCLUSIONExposure to bright light during the early hours of darkness delays the nocturnal melatonin peak and alters cortisol, GH, PRL and nocturnal vasopressin secretion, while modification of the sleep pattern decreases vasopressin concentrations and alters its nocturnal peak.
Radiotherapy for non‐functioning pituitary tumours
Authors: Gittoes  , Bates  , Tse  , Bullivant  , Sheppard  , Clayton  , Stewart  
Published: March 2003

OBJECTIVEPituitary radiotherapy (RT) is often used as adjuvant treatment in the post‐operative period for patients with clinically non‐functioning pituitary tumours (NFTs). There is a distinct lack of objective data, however, describing the efficacy of RT in preventing the regrowth of these tumours. We have therefore determined whether the recurrence rate for NFTs is significantly lower in patients treated with post‐operative RT compared with that observed in patients not treated with RT.PATIENTS AND METHODSA retrospective case notes review was performed on 126 patients with NFTs treated at two institutions in the UK. One hospital routinely administered RT within 12 months of initial pituitary surgery whereas the other used post‐operative RT only rarely. The main outcome measure was regrowth of pituitary tumours following surgery in patients who did or did not receive post‐operative RT.RESULTSThere was no significant difference between patients who received RT versus those who did not in terms of age, sex, initial tumour size or mode of operation. The actuarial progression‐free survival was 93% at both 10 years and at 15 years for the RT treated group, and was 68% and 33%, respectively, for the non‐RT‐treated group. Using Cox's model for proportional hazard analysis, we found the only prognostic factor for NFT regrowth was the administration of pituitary RT (P < 0.00005).CONCLUSIONSRadiotherapy administered within 12 months of initial pituitary surgery for non‐functioning pituitary tumours significantly reduces the risk of tumour regrowth. It remains to be determined whether sequential MRI scanning can help delineate those patients who should receive radiotherapy following pituitary surgery for non‐functioning pituitary tumours.
Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels
Authors: Greenman Yona , Tordjman Karen , Stern Naftali 
Published: March 2003

OBJECTIVEHyperprolactinaemia in humans may be associated with a high prevalence of obesity but the nature of this link is poorly defined. The aim of this study was to establish the relationship between hyperprolactinaemia and body weight in patients with prolactin‐secreting pituitary tumours.DESIGNWe conducted a retrospective study of prolactinoma patients treated at the Endocrine Institute of the Tel Aviv Medical Center, Israel, during the period 1989–1996. Patients with clinically nonfunctioning pituitary macroadenomas (NFA) served as the control group. Data on demographic parameters, body weight before and during treatment, clinical presentation including history of weight fluctuations, tumour size as measured by computed tomography or magnetic resonance imaging, modalities and response to treatment, and pituitary function before and during treatment were recorded from medical files.PATIENTSForty‐two patients with prolactinomas (PR) and 36 patients with clinically non‐functioning macroadenomas (NFA) comprised the study population.RESULTSMean weight was 93 ± 3.4 kg and 78 ± 2.7 kg in male patients with PR and NFA respectively (P = 0.0007). Recent weight gain (8 to 22 kg) was a presenting symptom in 13 PR patients, whereas only one NFA patient had this clinical presentation (P = 0.001). Seventeen PR patients lost weight (mean change −8.3 ± 1.5 kg, range −2–28 kg), during prolactin lowering therapy, 11 of whom had entirely normalized prolactin levels. Fourteen of the 18 patients who did not lose weight still had elevated prolactin levels (P = 0.01). Weight loss in patients with PR could not be attributed to altered pituitary function nor to compression of the third ventricle. In contrast to PR, no significant weight loss was observed in NFA patients.CONCLUSIONWeight gain and elevated body weight are frequently associated with prolactinomas regardless of a mass effect on the hypothalamus or pituitary function. In this series, weight loss was recorded in 70% of prolactinomas patients and in 90% of male patients who normalized their prolactin levels. We propose the inclusion of hyperprolactinaemia in the differential diagnosis of endocrine obesity and weight gain.
Diurnal variation of the serum leptin concen_tration in patients with anorexia nervosa
Authors: Støving  , Vinten  , Handberg  , Ebbesen  , Hangaard  , Hansen‐Nord  , Kristiansen  , Hagen  
Published: March 2003

OBJECTIVEIn rodents, leptin is involved in regulating eating behaviour, fat storage, and reproductive function. In humans, the serum leptin concen_tration in obese and normal weight subjects correlates with body mass index, reflecting the body fat store. The serum leptin exhibit diurnal variation, however, this has been reported to be absent in normal weighted amenorrheic athletes. Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic amenorrhoea often precedes the weight loss and may persist after weight recovery. We hypothesized that leptin could be involved in the regulation of eating behaviour and gonadal function in anorexia nervosa.DESIGNWe measured the concen_tration of leptin in serum samples taken after an overnight fast in 18 female anorexia nervosa patients and 11 controls. To study diurnal variation, eight patients and 11 controls were hospitalized for 24 h and had a standardized diet at regular times. Seven blood samples were obtained at 4 h intervals from each subject.PATIENTSThe patients fulfilled the DSM‐IV criteria for anorexia nervosa. The mean body mass index for the patients was 14.2 ± 2.3 kg/m2 and for controls 20.3 ± 1.7 kg/m2.RESULTSThe mean fasting leptin concen_tration as well as the 24 h mean concen_tration were significantly lower in the anorectic group than in the control group (2.5 ± 0.9 vs 10.1 ± 6.1 μg/l, P < 0.01 and 2.7 ± 1.5 vs 10.6 ± 7.1 μg/l, P < 0.01 respectively). In the whole group of subjects (n = 28) a significant positive correlation between the leptin level and body mass index was found (r = 0.63, P < 0.001). In the anorectic group it was found that the leptin level correlated better with body fat percen_tage than with body mass index. In normalized data the time course of the mean leptin levels showed a monophasic variation with nadir and zenith at about 0900 and 0100 h respectively. However, the individual coefficients of variance were significantly lower in the anorectic group compared to the group of healthy women.CONCLUSIONIn patients with anorexia nervosa the leptin level is low, reflecting the low body fat mass, and the relative diurnal variation is strikingly reduced. The similarity to that of normal weighted women with hypothalamic amenorrhoea suggest that altered leptin oscillations may be of particular significance in the hypothalamic regulation of reproductive function.
Leptin is involved in gender‐related differences in insulin sensitivity
Authors: Fernández‐Real Jośe‐Manuel , Casamitjana Roser , Ricart‐Engel Wifredo 
Published: March 2003

BACKGROUNDAlthough the effects of insulin on leptin levels are relatively well characterized, the possible actions of leptin on insulin sensitivity are not so well studied. This study was undertaken to examine whether gender‐related differences in insulin sensitivity could be explained partially by leptin levels.SUBJECTSThe study involved 22 women (13 obese) and 20 (11 obese) fat mass‐ and age‐matched men. All participants were healthy.MEASUREMENTSSeveral anthropometric measures of body fatness were quantified and the percentage of body fat was determined through bioelectric impedance. Oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test was performed in all subjects. Serum leptin was measured by radioimmunoassay.RESULTSNine lean women (BMI 20.4±2 kg m2 mean±SD) showed increased leptin levels (7.8±2.7 vs. 4.3±1.3 μg/l, P=0.003), increased insulin sensitivity (5.2±1.3 vs. 2.9±0.9 min−1/mU/l, P=0.001) and similar fat mass (11.1±3.7 vs. 13.2±7.8 kg, P=NS) in comparison with 9 age‐matched lean men (33.6±6 vs. 34.5±6.3 years, P=NS). Thirteen obese women (BMI 32.5±2.7) kg m2 also showed increased leptin levels (29.6±8.4 vs. 11.7±4.8 μg/l, P < 0.0001), increased insulin sensitivity (1.7±0.7 vs. 0.95±0.9 min−1 mU/l, P = 0.04) and similar fat mass (34.4±8.0 vs. 30.9±9.6 kg, P = NS) in comparison with 11 age‐matched obese men (34.5±7.8 vs. 38.7±8.2 years, P = NS). A strong linear association between leptin levels and insulin sensitivity (SI) was found (r = −0.67, P = 0.001, in men; r = −0.82, P<0.0001, in women). After controlling for percentage of body fat, this association remained significant only in men (r = −0.56, P = 0.01, in men; r = −0.30, P = NS in women). In stepwise regression analysis models, both gender (P = 0.00001) and leptin (P = 0.00001) contributed to 67% of the variance in SI independently of body fat.CONCLUSIONSLeptin levels and gender contribute to the variance of insulin sensitivity, independently of body fat. These results suggest that leptin could affect insulin sensitivity.
Growth hormone replacement inhibits renal and hepatic 11β–hydroxysteroid dehydrogenases in ACTH‐deficient patients
Authors: Walker Brian R , Andrew Ruth , MacLeod Kenneth M , Padfield Paul L 
Published: March 2003

OBJECTIVESThe commonest side‐effects of GH replacement therapy relate to sodium retention but its mechanism is unclear. In rats, GH inhibits renal and hepatic 11β–hydroxysteroid dehydrogenase (11β–HSD) activities. In man, this action might impair inactivation of cortisol to cortisone in the distal nephron thereby allowing cortisol to activate mineralocorticoid receptors. In this study, we examined the effects of GH replacement on cortisol metabolism.DESIGNA randomized double‐blind study comparing 6 months GH replacement with placebo in adults with GH deficiency due to pituitary or hypothalamic disease.PATIENTS6 men and 8 women received placebo and 8 men and 9 women received GH.MEASUREMENTSCortisol and its metabolites were measured in overnight urine samples and in a fasting morning plasma sample at baseline and at 6 months.RESULTSFive patients withdrew from the study, 4 because of adverse effects of GH. Amongst those who completed the study, the effects of GH on cortisol metabolism differed between patients with and without ACTH deficiency. Amongst those receiving hydrocortisone replacement (n = 18), GH had no effect on plasma cortisol/cortisone ratio, or urine tetrahydrocortisols/tetrahydrocortisone ratio, but produced a substantial reduction in total urinary cortisol metabolites (from 1326±191 to 777±229 μg/mmol creatinine; P < 0.01) and an increase in urinary free cortisol/cortisone ratio (from 0.88±0.10 to 2.57±0.74; P < 0.02). By contrast, GH had none of these effects in patients with normal ACTH secretion. There were no changes in blood pressure or plasma electrolytes, aldosterone, or renin activity with GH, and no changes in any variables with placebo.CONCLUSIONSThe increase in cortisol/cortisone ratio in urine but not in plasma, and the lack of effect on hepatic cortisol metabolites, suggests that GH inhibits both the conversion of cortisol to cortisone by renal 11β–HSD2 and the conversion of cortisone to cortisol by hepatic 11β–HSD1. It is unclear why this action of GH only affects patients with ACTH deficiency. The reduction in total cortisol metabolite excretion suggests that GH also affects bioavailability of hydrocortisone tablets. These observations suggest that glucocorticoid replacement therapy may need to be adjusted in hypopituitary patients who are commenced on GH replacement.
The effect of chronic hexarelin administration on the pituitary–adrenal axis and prolactin
Authors: Rahim A. , O'Neill P. A. , Shalet S. M. 
Published: March 2003

OBJECTIVEWith the development of growth hormone (GH) releasing agents and their use in human subjects, it is clear that these agents are not specific for GH release. More recent studies in humans have demonstrated acute increases in adrenocorticotrophic hormone (ACTH), cortisol and prolactin (PRL) after boluses of intravenous or subcutaneous GHRPs. The potential adverse effects of repeated episodes of transient hyperprolactinaemia and hypercortisolaemia during long‐term therapy with growth hormone releasing peptides (GHRPs) and similar agents have raised concern. We have therefore assessed the impact of chronic hexarelin administration on the pituitary‐adrenal axis and serum prolactin levels.DESIGNEach subject received twice‐daily subcutaneous hexarelin therapy (1.5 μg/kg body weight) for 16 weeks. The ACTH, cortisol and PRL responses to the morning subcutaneous injection of hexarelin were assessed. Hexarelin was administered at time 0 and blood samples were taken at −10, 0, 10, 20, 30, 40, 50, 60, 90, 120, 170 and 180 min. The ACTH and PRL responses were assessed at baseline and after 16 weeks of therapy. The cortisol response was assessed at baseline, 16 weeks and also 4 weeks after completion of hexarelin therapy. Basal levels of cortisol binding globulin (CBG), 24‐h urinary free cortisol (UFC) estimations, thyroid stimulating hormone (TSH) and total thyroxine (TT4) were performed at baseline, weeks 16 and 20.RESULTSThe mean (±SEM) area under the cortisol curve (AUCCORT) at baseline, week 16 and week 20 were 1506 (±77) nmol/l/h, 1222 (±92) nmol/l/h and 1586 (±58) nmol/l/h, respectively. There was a significant change in AUCCORT over the study period (P = 0.008). Compared with baseline, AUCCOPRT had decreased significantly (P < 0.05) after 16 weeks of hexarelin therapy. Four weeks after completion of hexarelin therapy, the AUCCORT increased significantly compared with AUCCORT at week 16 (P < 0.01) and was no longer significantly different from baseline values. There were no significant changes in UFC (P = 0.3), basal cortisol measurements (P = 0.19), area under the ACTH curve (AUCACTH) (P = 0.24) or CBG (P = 0.6) over the study period. The mean (±SEM) area under the PRL curve (AUCPRL) at the baseline and week 16 were 624 (±82) mU/l/h and 641 (±83) mU/l/h, respectively. There was no significant change in AUCPRL over the study period (P = 0.35).CONCLUSIONThe present study demonstrates clearly that in this hexarelin dosage regimen, overstimulation of the pituitary adrenal axis and prolactin secretion do not occur. In fact the impact of chronic hexarelin therapy on the pituitary–adrenal axis, i.e. decreased AUCCORT, contradict the findings reported after acute hexarelin administration and cannot be explained by changes in CBG. The lack of change in UFC, however, suggests that these changes are unlikely to be of clinical significance although the underlying mechanism requires further study.
Salivary cortisol for screening of Cushing's syndrome in children
Authors: Martinelli Carlos E. , Sader Soraya L. , Oliveira Eduardo B. , Daneluzzi Júlio C. , Moreira Ayrton C. 
Published: March 2003

OBJECTIVECushing's syndrome (CS) is characterized by changes in diurnal cortisol variation and total or partial resistance to cortisol suppression by dexamethasone (DEX). Diagnosing CS is a challenge especially in childhood and requires differentiation from primary obesity. The aim was verify the efficacy of salivary cortisol in differentiating primary obesity from CS in children.SUBJECTS AND METHODSWe studied 11 patients with CS confirmed by standard laboratory investigation and surgical findings aged 1–16 years, and 21 age‐matched primary obese controls. Salivary samples were collected at 0900 h, 2300 h, and after an overnight DEX suppression test (20 μg/kg up to 1 mg). Salivary cortisol was measured by RIA.RESULTSDiurnal variation of salivary cortisol levels was observed in all controls, as opposed to only 5 of 11 patients with CS. Suppression of salivary cortisol was detected in all controls but in no CS patient after the overnight DEX test. Mean salivary cortisol levels were higher in the CS than in the control group both at 2300 hours and at 0900 hours after DEX but no difference was observed at 0900 hours of the first day. The sensitivity and specificity of salivary cortisol at 0900 h, 2300 hours and after‐DEX in diagnosing CS were 27% and 95.2%, 100% and 95.2%, and 100% and 95.2%, respectively. Sensitivity and specificity of 100% were obtained by combining the data for 2300 hours and after‐DEX.CONCLUSIONThe combination of salivary cortisol determination at 2300 hours and after‐Dexamethasone is an easily performed and noninvasive method with high specificity and sensitivity for diagnosing Cushing's syndrome in children.