bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of glomerular basement membrane (GBM) antibodies in HIV− patients with Pneumocystis carinii pneumonia
Authors: CALDERON E J , WICHMANN I , VARELA J M , RESPALDIZA N , REGORDAN C , FERNANDEZ-ALONSO J , MEDRANO F J , CANO S , CUELLO J A , NUÑEZ-ROLDAN A 
Published: November 2003

SUMMARY
Following the unexpected finding of antibodies to GBM in a patient with Pneumocystis carinii pneumonia in the absence of kidney abnormalities, the presence of anti-GBM antibodies was analysed in 14 patients with pulmonary P. carinii infection who did not have clinical evidence of autoimmune glomerulonephritis. Patients were divided into three groups: HIV− with P. carinii pneumonia (n = 4), HIV+ with P. carinii pneumonia (n = 5) and HIV− carriers of P. carinii without pneumonia (n = 5). As control groups, HIV− patients with community-acquired non-P. carinii pneumonia (n = 6) and healthy individuals (n = 16) were included. Anti-GBM antibodies, studied with a quantitative enzyme immunoassay (EIA) for anti-α3 chain of collagen IV antibodies, were detected in three out of the four HIV− patients with P. carinii pneumonia, but not in any individuals of the other categories. These results suggest that P. carinii alveolar injury or the host response to the organism could affect the basal membrane Goodpasture antigen or a similar antigen, and induces anti-GBM antibody production in HIV− patients, and support the hypothesis that, at least in some cases, Goodpasture's syndrome could be triggered by an alveolar lesion induced by a P. carinii pneumonia.
Comparative study of the complement-activating and specific IgE-binding properties of ragweed pollen allergen
Authors: HIDVÉGI T , BERRENS L , VARGA L , MARAÑON F , SCHMIDT B , KIRSCHFINK M , FÜST G 
Published: November 2003

SUMMARY
Previous reports have defined the capacity of ragweed pollen extract (RWA) to activate human complement (C) in fluid phase through the classical pathway and have ascertained a strong correlation between the extent of complement activation and the severity of symptoms of allergic rhinoconjunctivitis during the ragweed blooming season. In the present study the complement-activating and specific IgE-binding capacities of various ragweed allergen preparations were compared. Elimination of physically adsorbed (flavonoid) pigments from the allergenic proteins had no significant effect on their complement-consuming capacity, although the process strongly diminished specific IgE binding. Removal of an IgE-binding trypsin inhibitor from RWA significantly enhanced RWA-induced complement activation, whereas it did not change IgE binding. These findings indicate that neither the physically adsorbed pigments nor the trypsin inhibitor are involved in complement activation by ragweed pollen allergens, and suggest that complement activation and specific IgE binding are distinct molecular properties of ragweed pollen allergen.
Corticosteroids restore the balance between locally produced Th1 and Th2 cytokines and immunoglobulin isotypes to normal in sarcoid lung
Authors: MILBURN H J , POULTER L W , DILMEC A , COCHRANE G M , KEMENY D M 
Published: November 2003

SUMMARY
In this study, we have investigated the balance between Th1- and Th2-like activity in the lungs in sarcoidosis and have determined the effect of corticosteroid treatment on this. Twenty-one patients with acute untreated sarcoidosis were investigated by bronchoalveolar lavage (BAL) and compared with 11 normal volunteers. Sixteen of the sarcoid patients required corticosteroid therapy and seven of these were reinvestigated after 2–3 months' treatment. In order to assess Th1- and Th2-like activity in the lungs, IgG subclasses and IgE were measured in BAL fluid and serum, and IL-2, IL-4 and interferon-gamma (IFN-γ) in BAL. In patients with untreated sarcoidosis, albumin-corrected BAL/serum ratios for IgG4 and IgE were significantly reduced (IgG4, 1·04±0·18 (mean±s.e.m.); IgE 9·58±3·11) compared with those in normal controls (IgG4 5·3±0·72, P&lt;0·001; IgE 67·7±28·9, P&lt;0·01). Estimates of actual levels of immunoglobulins produced in the lungs were also made and showed extremely high levels of total IgG in sarcoid patients (39·56±8·2 mg/l ) compared with controls (1·17±0·5 mg/l, P&lt;0·001). Although there was no difference between the groups in amount of IgG4 locally produced, the proportion of total IgG which was IgG4 was greatly reduced in those with sarcoidosis (1·6±0·4% compared with 38·5±3·2%; P&lt;0·001). Lavage levels of IL-4 were also reduced in sarcoid patients (IL-4 2·103±0·21 pg/ml) compared with those in normals (IL-4 6·8±1·05; P&lt;0·001). Levels of IL-2 were lower (7·63±0·51 pg/ml compared with 9·4±0·95 pg/ml), but this difference was not significant. IFN-γ, however, could not be detected above 0·4 pg/ml in any of the normal lavage fluid, but was detectable in 12/21 patients with sarcoidosis (χ2=7·74; P&lt;0·001). These changes reverted towards normal on treatment with oral corticosteroids. The mean albumin-corrected BAL/serum ratio for IgG4 before treatment was 0·88±0·33 compared with 5·5±2·1 (P&lt;0·05) on treatment, and for IgE before treatment 9·52±2·15 compared with 50·8±17·9 (P&lt;0·05) on treatment. Total IgG produced in the lung fell from 26·16±7·9 to 6·12±2·4 mg/l (P&lt;0·001) on treatment, and the proportion of IgG4 locally produced rose from 2·3±0·8% to 23·9±6·1% (P&lt;0·01). The mean level of IL-4 in lavage before treatment was 2·53±0·34 pg/ml compared with 4·7±0·34 (P&lt;0·001) on treatment. Levels of IL-2 also rose significantly on treatment from 8·74±0·95 pg/ml before to 14·44±1·38 pg/ml (P&lt;0·001) on treatment. Levels of IFN-γ fell from 1·65±0·43 pg/ml before treatment to undetectable levels in all patients (P&lt;0·001) on treatment. These results demonstrate an imbalance between Th1- and Th2-like activity in the lungs in sarcoidosis, with suppression of Th2 and increase in Th1. Corticosteroid therapy restores the normal balance between Th1 and Th2 cytokines and immunoglobulins in the lungs, suggesting an effect on local immune regulation.
Detection of T cells reactive to intestinal alkaline phosphatase, an autoantigen in acute bacterial infections, and discrimination between autoantigen-specific CD5+ and CD5− B cells
Authors: KOLBUS N , FLEISCHER U , MÄDER M , FELGENHAUER K , BEUCHE W 
Published: November 2003

SUMMARY
Autoantibodies of the IgG isotype, specifically directed against intestinal alkaline phosphatase (IAP), occur transiently in the majority of sera from patients with acute bacterial infections. Sometimes they are observed in autoimmune diseases. Using a T cell proliferation assay, it was found that isolated peripheral blood mononuclear cells (PBMC) from IAP autoantibody (IAPA)-positive patients (n=18) responded significantly to IAP, whereas proliferation could not be induced in PBMC from healthy donors (n=11). Significant stimulation of PBMC from patients (n=11) was not obtained by use of transferrin, a common autoantigen in humans, indicating the specificity of stimulation of IAP-reactive T cells. Furthermore, T cell proliferation was observed when a highly purified IAP fragment (CNBr 21) spanning amino acids 334–462 of the primary structure of IAP was used as antigen. Thus, it was shown that an immunodominant T cell epitope resides within the CNBr 21 fragment which also contains a discontinuous B cell epitope as evaluated previously. Double immunocytochemical staining of T cell-depleted PBMC with IAP and an anti-human CD5 antibody allowed the detection of CD5+ B lymphocytes, which probably produce natural IAPA (nIAPA). These nIAPA-specific CD5+ B cells occurred with approximately the same frequency among T cell-depleted PBMC from healthy donors and those from patients. In contrast, IAPA-producing CD5− B cells were found in B cell-enriched preparations from patients, but not in those from healthy individuals.
Analysis of T cell activation pathways in patients with liver cirrhosis, impaired delayed hypersensitivity and other T cell-dependent functions
Authors: SCHIRREN C A , JUNG M-C , ZACHOVAL R , DIEPOLDER H , HOFFMANN R , RIETHMÜLLER G , PAPE G R 
Published: November 2003

SUMMARY
Patients with cirrhosis of the liver frequently demonstrate anergy in intracutaneous tests and fail to respond to vaccination, suggesting impaired delayed hypersensitivity and other T cell-dependent functions in vivo. T cell activation through the coordinated interaction of different cells of the immune system (B cell, antigen-presenting cells (APC)) is an important step in the induction of cellular and humoral immune responses. Impaired T cell-dependent functions in patients with liver cirrhosis may thus be explained by defective T cell activation. We prospectively investigated T cell activation pathways in 12 patients (nine males, three females) with alcoholic liver cirrhosis (seven Child Pugh stage A and B (CP A+B), five Child Pugh stage C (CP C)) and five healthy controls and compared the in vitro results of T cell activation with data obtained in vivo, e.g. intracutaneous tests and vaccination against hepatitis B surface antigen (HBs-Ag). Five out of eight patients who completed vaccination against hepatitis B virus infection were non-responders; one of the three responders had a non-protective anti-HBs titre. Moreover, three of five patients with alcoholic liver cirrhosis CP A+B, and two out of three with CP C were anergic in intracutaneous tests to a set of diverse antigens. All parameters of T cell activation were normal, including proliferation mediated by CD2, CD3–T cell receptor (TCR) complex, and CD28; acquisition of responsiveness to exogenous IL-2 and IL-4; activation of proteinkinase C (PKC) by phorbol ester and calcium influx by addition of ionomycin. The ability of monocytes to deliver costimulatory signals was preserved in patients with alcoholic cirrhosis. In addition, serum of patients with alcoholic liver disease did not inhibit T cell proliferation. We conclude that, although in patients with alcoholic liver cirrhosis T cell-dependent functions are impaired in vivo, T cell activation pathways are not responsible for the observed immune defect.
Chloroquine self-treatment and clinical outcome of cerebral malaria in children
Authors: PICOT S , NKWELLE AKEDE A , CHAULET J-F , TETANYE E , RINGWALD P , PRÉVOSTO J-M , BOUDIN C , AMBROISE-THOMAS P 
Published: November 2003

SUMMARY
Chloroquine is widely used as self-medication for presumptive treatment of malaria despite the existence of parasite resistance to the drug. Recent studies suggest that tumour necrosis factor-alpha (TNF-α) overproduction probably has a causal association with poor outcome in cerebral malaria. In addition, chloroquine has been shown to have inhibitory action on TNF-α synthesis. The present study aimed at evaluating chloroquine/TNF-α interaction in 90 children hospitalized for severe malaria in a malaria-endemic zone. TNF-α and chloroquine varied in the same range on admission, but there was an inverse correlation between the two: the higher the chloroquine level, the lower the TNF-α level. Parasite resistance to chloroquine in vitro was high. The clinical course in the patients was uneventful, save for two fatal cases and one survivor with neurological sequela. The above data suggest beneficial effects of chloroquine self-medication with respect to anti-TNF-α action. Rational use of this tool should be encouraged.
Long‐term follow‐up of patients with hyperprolactinaemia
Authors: Jeffcoate W. J. , Pound N. , Sturrock N. D. C. , Lambourne J. 
Published: November 2003

AIM To determine the frequency with which hyperprolactinaemic illnes tends to resolve with time. STUDY DESIGN A retrospective case‐notes review from a specialist endocrine unit in a provincial teaching hospital and tertiary referral centre. PATIENTS Seventy women with hyperprolactinaemia referred to the unit in the 15 year period between May 1979 and May 1994. All those with a non‐pituitary cause or with macroadenoma had been excluded, as were those who did not have high‐resolution imaging, or who were on treatment at the time of referral. INTERVENTION Intermittent course of treatment with dopamine receptor agonists according to individual need. ENDPOINTS Latest serum PRL concentration in those who had discontinued treatment, and whether serum PRL tended to be lower in any particular group RESULTS There was a significant fall in median PRL concentration from 2000 (714–8000) to 1000 mU/l (220–5600) in the 31 women who had discontinued therapy (P<0.0005), and serum PRL was normal (<700 mU/l) in 11 of them. Serum PRL also fell to normal in three of ten women who had no treatment at all. Final PRL concentration was normal in 35% of women who had had at least one pregnancy during the period of follow‐up compared to 14% who had not (P<0.05). CONCLUSIONS These data confirm the findings of others that hyperprolactinaemia will prove self‐limiting in up to one‐third of women, and that pregnancy may be one factor which triggers a return to normal function
Androgens and the menopause; a study of 40–60‐year‐old women
Authors: Bancroft John , Cawood Elizabeth H. H. 
Published: November 2003

OBJECTIVE The impact of the menopause on androgen production is poorly understood. We have investigated the impact of the menopause, as well as other factors such as age, body mass index (BMI) and cigarette smoking, on ovarian and adrenal androgen levels in women aged 40–60 years. DESIGN Cross‐sectional study of blood hormones sampled weekly over one month in volunteer 40–60‐year‐old women. SUBJECTS One hundred and forty‐one women, aged between 40 and 60, recruited from community sources (non‐clinical), not using hormone replacement or steroidal contraceptives, and with a current sexual partner. Fifty were categorized as premenopausal (ovulating), 37 as perimenopausal and 54 as post‐menopausal. MEASUREMENTS The following variables were assessed; menopausal status (based on menstrual history and pattern and plasma progesterone), age, BMI, smoking, oestradiol (E2), oestrone (E1), LH, FSH, total testosterone (TT), androstenedione (A), SHBG, free androgen index (FAI), dihydroepiandrosterone (DHEA), dihydroepiandrosterone sulphate (DHEAS) and cortisol. RESULTS are based on multiple regression analysis. TT was positively related to A, BMI and LH. A was negatively related to age and FSH, and positively to DHEA, DHEAS and premenopausal status. SHBG was negatively related to BMI and positively to E1 and non‐smoking. DHEA and DHEAS were negatively related to age and were higher in smokers. Both E1 and E2 were related to menopausal status and to FSH. Surprisingly, E2 was negatively related to BMI. CONCLUSIONS A variety of factors influence androgen production in this age group. Whereas it is difficult to predict the effect of menopause on androgen levels, LH stimulation of post‐menopausal interstitial cells, modulated by a variety of factors including nutrition, and smoking, are likely to be relevant.
The assessment of growth hormone status in normal young adult males using a variety of provocative agents
Authors: Rahim A. , Toogood A. A. , Shalet S. M. 
Published: November 2003

OBJECTIVE In adults, there are few data regarding GH responses to provocative stimuli other than insulin‐induced hypoglycaemia. We have compared the GH response to four different growth hormone secretagogues and placebo in normal healthy adult males. DESIGN This was a prospective, randomized, placebo‐controlled study in 18 normal male subjects. After an overnight fast, an intravenous cannula was inserted into the arm of each subject and a blood sample was taken for GH at −30, −15, and 0 minutes. Four provocative agents (intravenous insulin 0.2 IU/kg; intravenous arginine 20 g/m2 as an infusion over 30 minutes; oral clonidine, either 100 or 200 μg; intramuscular glucagon 1 mg) and placebo were administered to each subject in a randomized manner on different days. Further blood samples were taken at 15‐minute intervals for 180 minutes for GH estimation. RESULTS The median (range) GH peak response for each agent was insulin 107.7 (28.1–200) mU/l; arginine 22.3 (3.1–72.9) mU/l; glucagon 42 (11.8–200) mU/l; 100 μg clonidine 7.2 (<1–22.2) mU/l; 200 μg clonidine 8.2 (1.1–88) mU/l and placebo 2.4 (<1–30.2) mU/l. The peak GH response to insulin‐induced hypoglycaemia (ITT) was significantly greater than for any other agent (P<0.0001). The peak GH response to glucagon was significantly greater than for arginine (P<0.05), clonidine at 100 and 200 μg (P<0.01) and placebo (P<0.01). The peak GH response following administration of arginine was significantly greater than for clonidine 100 and 200 μg (P<0.05), and placebo (P<0.01). The peak GH response following clonidine 200 μg was not significantly greater than following clonidine 100 μg (P=0.38) or placebo.  On an individual basis two, six and 15 of 18 subjects failed to achieve a peak GH level of >20 mU/l to glucagon, arginine and clonidine respectively. In complete contrast only one subject achieved a peak response of less than 40 mU/l (28.1 mU/l) to ITT. CONCLUSIONS The most profound GH release is seen after insulin‐induced hypoglycaemia. Glucagon appears to be more effective at inducing GH release than arginine. Clonidine at a dose of 100 or 200 μg is no more effective than placebo.
The short Synacthen and insulin stress tests in the assessment of the hypothalamic–pituitary–adrenal axis
Authors: Hurel S. J. , Thompson C. J. , Watson M. J. , Harris M. M. , Baylis P. H. , Kendall‐Taylor P. 
Published: November 2003

OBJECTIVE The best dynamic test for the assessment of the hypothalamic–pituitary–adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic–pituitary–adrenal axis.DESIGN Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed.SETTING Programmed Investigation Unit.SUBJECTS Fifty‐seven healthy volunteers and 166 patients.MAIN OUTCOME MEASURES Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycaemia (plasma glucose < 2mmol/l) during an IST.RESULTS From normal data the mean‐2SD 30‐minute value during the SST was 392 nmol/l and 60‐minute value was 497 nmol/l. The maximal cortisol response (mean − 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30‐minute cortisol value > 600 nmol/l. The 30‐minute value provided a better index than the 60‐minute value. The basal, 30 and 60‐minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post‐adenomectomy evaluation, and in those patients who had received long‐term steroids provided that the medication had been reduced and stopped two days prior to admission.CONCLUSIONS Using a 30‐minute cortisol value > 600 nmol/l as a cut‐off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one‐quarter and thus provide a substantial saving without detriment to patient care.
Relation between serum interleukin‐6 and thyroid hormone concentrations in 270 hospital in‐patients with non‐thyroidal illness
Authors: Davies Peter H. , Black Elizabeth G. , Sheppard Michael C. , Franklyn Jayne A. 
Published: November 2003

OBJECTIVES Non‐thyroidal illness (NTI) is frequently accompanied by alterations in circulating thyroid hormone concentrations, despite patients remaining clinically euthyroid. The mechanisms accounting for these changes in circulating thyroid hormone concentrations remain unknown. Much attention has focussed on the role of inflammatory cytokines which are known to be important mediators of disease. The aim of this study was to investigate the role of the cytokine interleukin‐6 (IL‐6) in alterations of thyroid hormone metabolism seen in NTI.DESIGN Longitudinal study of hospital in‐patients, correlating serum IL‐6 concentrations with circulating thyroid hormone concentrations.PATIENTS Two hundred and seventy in‐patients recruited consecutively, excluding those with known or suspected thyroid disorder. The patients were divided into 5 subgroups reflecting the nature of their NTI and comprised 41 patients with liver disease, 99 with renal disease, 19 intensive care (ITU) patients, 22 with cardiac disease and 89 patients with general medical, or surgical conditions.MEASUREMENTS Serum IL‐6 concentrations were determined using a commercially obtained immunoassay (IL‐6 Quantikine assay, R&D Systems, Abingdon, UK). Serum total T4 and total T3 were measured using chemiluminescent immunometric assays (Kodak Clinical Diagnostics Ltd, Amersham, UK) and serum TSH was measured using a third‐generation chemiluminescent immunometric assay (Amerlite TSH 30, Kodak Clinical Diagnostics Ltd, Amersham, UK).RESULTS Ninety‐three patients studied (35%) had a serum T3 below the normal range (<1.0 nmol/l), 89 patients (33%) had a serum T4 below the normal range (<65 nmol/l) and in 58 patients (21%) both serum T3 and T4 were below the normal range. There was a significant negative correlation between serum total T3 and IL‐6 (r = −0.219; P<0.001) and total T4 and IL‐6 (r = −0.132; P = 0.032), but not between TSH and IL‐6 (r = −0.075; P = 0.22). The ITU patient subgroup had the highest IL‐6 concentrations (229.3 ± 48.1 ng/l, mean ± standard error), whilst also having the lowest T3 (0.93 ± 0.08 nmol/l), TSH (0.79 ± 0.25 mU/l) and T4 concentrations (66.6 ± 7.3 nmol/l). The subgroup of patients under general medical or surgical care had least disturbance of their T3 (low in 19%) and T4 (low in 8%) concentrations, whilst also having the lowest mean IL‐6 concentration (39.0 ± 5.3 ng/l). The renal patient subgroup, whilst including a high proportion of patients with low T3 (39%) and T4 (45%) concentration, demonstrated only modest elevation of IL‐6 concentrations (mean 41.4 ± 8.5 ng/l).CONCLUSIONS Our data revealed a statistical relation between elevated serum IL‐6 concentrations and alterations in circulating thyroid hormone concentrations seen in NTI; however, the findings in patients with renal disease suggest that circulating IL‐6 is not the only factor responsible for alteration in thyroid hormone metabolism in NTI.