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Biomedical subjects

Beat Müller

Publications and source records attributed to Beat Müller.

54 records · Page 3Linked to original sources
PubMed2004

Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial.

BACKGROUND: Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay. METHODS: 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat. FINDINGS: Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%). INTERPRETATION: Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.

Acute Disease↗
PubMed2004

Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes.

OBJECTIVE: To explore the roles of peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages in sepsis-related increased procalcitonin and calcitonin gene-related peptide (CGRP) I production. DESIGN: Prospective, in vitro primary human cell culture study and human tissue samples gene expression analysis. SETTING: University hospital research laboratories. PATIENTS: Cells from healthy donors and septic patients. INTERVENTIONS: PBMCs were obtained from healthy donors. Isolation of pure monocyte cultures was performed by magnetic depletion of nonmonocyte cells from PBMCs. Adipose tissue biopsies and circulating leukocytes were collected from septic patients. Expressions of calcitonin messenger RNA and CGRP I messenger RNA were analyzed using reverse transcriptase-polymerase chain reaction and quantitative real-time polymerase chain reaction. Supernatant procalcitonin and CGRP protein content were determined by ultrasensitive chemiluminometric and radioimmunoassays, respectively. MEASUREMENTS AND MAIN RESULTS: PBMCs expressed and secreted procalcitonin and CGRP within 3-5 hrs after adherence to endothelial cells or plastic surfaces. This induction was transient, as it was not detectable after 18 hrs. No calcitonin or CGRP I messenger RNA was observed in leukocytes obtained from septic patients with markedly increased serum procalcitonin concentrations. Stimulation with cytokines, endotoxin, or Escherichia coli did not induce expression of calcitonin and CGRP I messenger RNA in PBMC-derived macrophages. However, inflammatory factors released from activated macrophages induced a marked expression of procalcitonin and CGRP in co-cultured human adipocytes. CONCLUSIONS: The adhesion-induced, transient expression and secretion of procalcitonin and CGRP in vitro may play an important role during monocyte adhesion and migration in vivo. PBMC-derived macrophages may contribute to the marked increase in circulating procalcitonin by recruiting parenchymal cells within the infected tissue, as exemplified with adipocytes.

Adipocytes↗
PubMed2004

Somatostatin is expressed and secreted by human adipose tissue upon infection and inflammation.

Somatostatin (SRIF) is a well-known neuroendocrine secretion product. SRIF expression and secretion are induced after inflammation in murine macrophages and in endotoxin-injected sheep and pigs. Because adipocytes have been demonstrated to produce numerous cytokines and peptide hormones, we investigated the expression of SRIF and its receptors (SSTR1-5) in human adipose tissue after inflammatory stimulation in vitro and in tissues from patients with septic disease.Preadipocyte-derived adipocytes, mesenchymal stem cell-derived adipocytes, and mature explanted adipocytes expressed SRIF-mRNA after endotoxin [lipopolysaccharide (LPS)] or IL-1beta treatments. LPS- and IL-1beta-mediated SRIF-mRNA induction was blocked by pretreatment with dexamethasone. Using cocultures and quantitative real-time PCR, we demonstrate adipocyte SRIF induction by secretion factors from activated peripheral blood mononuclear cell-derived macrophages. In contrast to basal adipocytes, SRIF protein was detected in culture supernatants of LPS-treated and of combined TNFalpha/IL-1beta/LPS-treated adipocytes. SRIF protein was visualized by immunohistochemistry in explanted minced adipose tissue after overnight incubation in culture medium supplemented with combined IL-1beta and LPS. In septic patients, expression of SRIF-mRNA and SRIF protein was found in visceral, but not in sc, adipose tissue. Adipocyte mRNA abundance of SSTR 1-5 was differentially regulated by inflammatory treatments.Thus, human visceral adipose tissue secretes SRIF during inflammation and sepsis and expresses several SSTRs. It is tempting to speculate that visceral adipose tissue-derived SRIF plays a modulatory role in the immunological and metabolic response to inflammation.

Adipocytes↗
PubMed2004

In vitro cultured islet-derived progenitor cells of human origin express human albumin in severe combined immunodeficiency mouse liver in vivo.

Studies in rodents suggest the presence of a hepatopancreatic stem cell in adult pancreas that may give rise to liver cells in vivo. The aim of the present study was to determine the ability of human islet-derived cells to adopt a hepatic phenotype in vivo. Cultured human islet-derived progenitor cells that did not express albumin in vitro were stained with the red fluorescent dye PKH26 and injected into the liver of severe combined immunodeficiency mice. After 3 or 12 weeks, red fluorescent cells were detected in 11 of 15 livers and were mostly single cells that were well integrated into the liver tissue. Human albumin was found in 8 of 11 animals by immunohistochemistry, and human albumin mRNA was detected in 4 of 10 host livers. The mechanism underlying this phenomenon seems to be transdifferentiation, because human and mouse albumin were found to be expressed in distinct cells in the host liver.

Albumins↗
PubMed2003

"Electromers" of the tetramethyleneethane radical cation and their nonexistence in the octamethyl derivative: interplay of experiment and theory.

Bicyclopropylidene 1a and its octamethyl derivative 1b are subjected to ionization by X-irradiation in solid argon. In accord with previous experiments, this treatment leads to the spontaneous opening of both cyclopropylidene rings, as does ionization of 1b by gamma-irradiation in CFCl(3) at 77 K. The resulting tetramethyleneethane (or bisallyl) radical cations 2a+* and 2b+* are distinguished by a broad band in the NIR. In the case of 2a+*, wavelength-selective photolyses reveal the presence of two interconvertible species with very similar yet distinct spectra. Based on DFT and CASSCF/CASPT2 calculations, these spectra are assigned to two "electromeric" forms of 2a+* which differ in the nature of the singly occupied MO. The NIR bands correspond to charge-resonance transitions between states with fully delocalized spin and charge. Calculations predict that similar electromers should also exist in 2b+* which shows a much weaker NIR band, but no corresponding experimental evidence could be found. On the other hand, the ESR spectrum of 2b+* indicates that, in contrast to 2a+*, the spin is largely localized in one of the two allylic moieties in 2b+*. Although no theoretical method is presently available that would permit an accurate modeling of the opposing factors favoring localized or delocalized structures in molecules such as 2a+* or 2b+*, the observed trends can be satisfactorily rationalized on the basis of semiquantitative considerations. In particular, the important role of vibronic coupling in shaping the potential surfaces for such systems is emphasized.

Journal Article↗
PubMed2003

In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue.

Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several thousand-fold in human sepsis, and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin I gene (CALC I) expression in human adipocyte primary cultures and in adipose tissue samples from infected and noninfected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, the expression of CT mRNA increased 24-fold (P < 0.05) after the administration of Escherichia coli endotoxin (lipopolysaccharide) and 37-fold (P < 0.05) after IL-1beta administration by 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with lipopolysaccharide treatment and 15.2-fold (P < 0.01) with IL-1beta after 48 h. In coculture experiments, adipocyte CT mRNA expression was evoked by E. coli-activated macrophages in which CT mRNA was undetectable. The marked IL-1beta-mediated ProCT release was inhibited by 89% during coadministration with interferon-gamma (IFNgamma). In patients with infection and markedly increased serum ProCT, CT mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFNgamma on IL-1beta-induced CT mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.

Adipocytes↗
PubMed2003

Diminished production of nitric oxide synthase cofactor tetrahydrobiopterin by rosiglitazone in adipocytes.

Increased nitric oxide (NO) synthesis has been proposed to participate in the generation of insulin resistance in adipose and muscle tissues. Therefore, we examined the potential rate-limiting role of tetrahydrobiopterin (BH4) in cytokine-induced NO synthesis, and the effect of peroxisome proliferator activated receptor-gamma (PPARgamma) activation using the insulin-sensitizer rosiglitazone on cytokine-induced BH4 synthesis in 3T3-L1 adipocytes. Our data indicate that modulated availability of the mandatory nitric oxide synthase (NOS) cofactor BH4 affected cytokine-induced NO generation. Semiquantitative linear range reverse transcription polymerase chain reaction (RT-PCR) analysis demonstrated that rosiglitazone not only reduced inducible nitric oxide synthase (iNOS) mRNA transcription, but also guanosine triphosphate cyclohydrolase (GTPCH), the rate-limiting and controlling step of BH4 synthesis. Accordingly, intracellular BH4 concentration was reduced by 45% following rosiglitazone treatment. Furthermore, we observed a transient inhibitory effect of natural PPARgamma ligand 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PJ2) on cytokine-mediated iNOS and GTPCH induction. Thus, the inhibition of cytokine-induced NO synthesis by rosiglitazone is at least in part attributable to reduced availability of BH4, the synthesis of which might represent a potential new target in the treatment of type 2 diabetes and insulin resistance.

3T3 Cells↗
PubMed2003

Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial.

Hypothyroidism is associated with premature atherosclerosis and cardiovascular disease. Recently, total homocysteine (tHcy) and C-reactive protein (CRP) emerged as additional cardiovascular risk factors. We first investigated CRP and tHcy in different severities of primary hypothyroidism and in a second study we evaluated the effect of L-thyroxine treatment in patients with subclinical hypothyroidism (SCH) in a double-blind, placebo-controlled trial. One hundred and twenty-four hypothyroid patients (63 with subclinical, 61 with overt hypothyroidism, OH) and 40 euthyroid controls were evaluated. CRP was measured using a latex-based high sensitivity immunoassay; tHcy was determined by a fluorescence polarization immunoassay. tHcy values were significantly elevated in OH (P=0.01). In SCH tHcy levels were not augmented as compared to controls. CRP values were significantly increased in OH (P=0.016) and SCH (P=0.022) as compared to controls. In a univariate analysis tHcy correlated significantly with fT4, vitamin B12, folic acid and creatinine levels. In multiple regression analysis only fT4 (beta=0.33) had a significant effect on tHcy. CRP did not correlate with thyroid hormones. In SCH, L-T4 replacement had no significant effect on either tHcy or CRP levels. This is the first paper to show that CRP values increase with progressive thyroid failure and may count as an additional risk factor for the development of coronary heart disease in hypothyroid patients. In contrast to overt disease, only CRP, but not tHcy values, are affected in SCH, yet without significant improvement after L-thyroxine therapy.

Aged↗
PubMed2003

Influence of organic carbon decomposition on calcite dissolution in surficial sediments of a freshwater lake.

A multi-sensor approach was used to determine high-resolution porewater gradients of Ca(2+), CO(3)(2-), H(+) and O(2) in sediment cores along a depth transect from eutrophic Lake Sempach (Switzerland). We quantified the reproducibility of measurements and analyzed concentration profiles with a one-dimensional diffusion-reaction model to quantify benthic fluxes. Calculation of oxic respiration in the sediment showed that almost all settled organic carbon was degraded with O(2) at shallow depths while only 28% was decomposed aerobically at the deepest location. Fluxes were highest at 8 m depth (24.4 mM m(-2) d(-1)) and lowest at the deepest site of 85 m (7.1 mM m(-2) d(-1)). Dissolution of calcite from the sediment was also depth dependent. A total of 1.1 mM m(-2) d(-1) was found for the shallowest site, and values decreased with depth to 0.6 mM m(-2) d(-1) at the deepest site.

Calcium Carbonate↗
PubMed2003

Permeation, metabolism and site of action concentration of nicotinic acid derivatives in human skin. Correlation with topical pharmacological effect.

A novel methodology for establishing a pharmacological dose-effect relationship of methyl nicotinate, hexyl nicotinate and nicotinic acid acting as peripheral vasodilators in the skin following topical application is investigated. This methodology involves the estimation of the unbound drug concentration in the aqueous compartment at the site of action in tissue, termed C(*), which was evaluated as the pertinent concentration responsible for the pharmacological effect. Blood capillaries next to the epidermis-dermis boundary were postulated to be the relevant site of action. C(*) was estimated from drug transport parameters for different layers of human cadaver skin determined in vitro. Immunohistochemical studies showed that the plane of separation of skin achieved by heat treatment was between the basal cells of the epidermis and the lamina lucida, confirming the integrity of the epidermis and the dermis used in the experiments. The permeation rate for epidermis increased drastically with increasing lipophilicity of the drug. Dermis permeability was roughly the same for all three compounds. The epidermis represented the major transport barrier in vitro for methyl nicotinate and nicotinic acid but not for hexyl nicotinate. The esters were metabolised to nicotinic acid during tissue permeation to an extent that was rather limited for the epidermis but very pronounced for the dermis. Nonspecific alpha-naphthylacetate-esterase activity was predominantly located in the dermis, which was in agreement with the metabolism results. The drugs were applied each at three different concentrations in vivo to the ventral forearm of healthy human volunteers and vasodilation was evaluated based on skin erythema which was quantified by measuring colour change of reflected light. Area under the curve of the change of colour co-ordinates as a function of time was used as a measure of pharmacological effect. The pharmacological effect of all three drugs was comparable when similar C(*) values were considered, even though the concentrations applied to the skin differed by orders of magnitude. The effect showed a strong positive dependence on C(*). Methyl and hexyl nicotinate showed identical, nearly sigmoidal effect/C(*)-profiles, while the profile for nicotinic acid was linear, suggesting a possible difference in the intrinsic pharmacological potency between the esters and the acid. These results demonstrate the validity of C(*) as the relevant drug concentration for the cutaneous pharmacological effect of the topically applied drugs and underline the usefulness of the presented methodology for establishing dose-response relationships in dermal therapy and expressing bioavailability.

Administration, Topical↗
PubMed2003

Antiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis?

We describe a rare case of bilateral hemorrhagic infarction of the adrenal glands diagnosed in the context of positive antiphospholipid antibodies (aPL). The patient presented atypical clinical symptoms of adrenal insufficiency. Laboratory investigation showed complete adrenal failure and increased aPL, both manifestations persisted 1 yr after the initial event. MR imaging at baseline was compatible with bilateral hemorrhagic infarction and showed almost complete loss of viable adrenal tissue 1 yr later. Although no direct causal effect can be proved, the sequence of events and the exclusion of other common causes of bilateral adrenal hemorrhage (e.g. tuberculosis, severe coagulation disorder) support an association between aPL and adrenal hemorrhagic infarction. A unique link between particular anatomical characteristics of the adrenal fascicular zone and a novel, previously described, explanation model of aPL-thrombosis is hypothesized. It is based on the properties of late endosomes, which are important organelles participating in cholesterol trafficking and protein sorting within cells and express epitopes recognized by aPL. It would be interesting to investigate adrenal tissue for presence of late endosomes and their aPL relevant epitopes for proof of this tempting hypothesis. Focal accumulation of aPL and isolated, simultaneous, bilateral adrenal infarctions could thus be explained.

Adrenal Glands↗
PubMed2003

High temporal resolution monitoring of inorganic nitrogen load in drainage waters.

Nitrate (NO3-), ammonium (NH4+) and pH were monitored with a novel flow cell equipped with ion-selective electrodes (ISEs) in a drainage pipe during one year. The high temporal resolution of the measurements (six measurements per hour) allowed the detection of diurnal oscillations in pH, NO3- and NH4+ concentrations, the relation of variations in concentrations to discharge rates changing during rain events, understanding of the processes resulting in such variations and tracing of unpredictable manure spills. Annual loads estimated from random samples collected every second day tended to underestimate the "true" loads calculated from quasi-continuous electrode measurements by 550% for NH4+ and 22% for NO3-.

Environmental Monitoring↗
PubMed2003

Prolactin dysregulation in women with subclinical hypothyroidism: effect of levothyroxine replacement therapy.

This study investigated the effect of levothyroxine treatment on serum prolactin (PRL) levels in women with subclinical hypothyroidism. Sixty-six women (mean age, 58.5 +/- 1.3 years) with confirmed subclinical hypothyroidism (mean thyrotropin [TSH], 11.7 +/- 0.8 mIU/L) were randomly assigned to receive levothyroxine or placebo for 48 weeks. Based on blinded TSH monitoring, physiologic levothyroxine replacement (85.5 +/- 4.3 microg/d; TSH, 3.1 +/- 0.3 mIU/L) was ascertained throughout the study. PRL levels were measured before and after administration of thyrotropin-releasing hormone (TRH) at baseline, after 24 and 48 weeks. Sixty-three of the 66 women completed the study. At baseline, basal PRL levels were elevated in 19% of the patients. None of the patients reported menstrual disturbances, infertility, or galactorrhea. In the levothyroxine group (n = 31) basal and peak PRL levels were significantly reduced after 24 and 48 weeks (p = 0.03 and p = 0.001). Mean changes in PRL levels differed significantly between the two treatment groups after 24 weeks (p = 0.03 and p = 0.01). The treatment effect was more pronounced in patients with PRL and TSH levels above the median at baseline (i.e., PRL > 16 ng/mL; TSH > 11 mIU/L). Based on this double-blinded, placebo-controlled study we demonstrate that in subclinical hypothyroidism PRL regulation is altered with elevated basal and stimulated PRL levels, and that physiologic levothyroxine treatment restores PRL concentrations.

Double-Blind Method↗
PubMed2002

P, As, Sb, Mo, and other elements in sedimentary Fe/Mn layers of Lake Baikal.

Distinct layers with accumulated iron and manganese oxyhydroxides are found in the recent sediments of Lake Baikal (Siberia). In the South and Central Basins, these concretions accumulate close to the sediment-water interface. In northern Lake Baikal and the area of Academician Ridge, however, massive Fe/Mn crusts are formed within several thousand years at redox fronts 10 to 15 cm below the sediment surface. In some places, precipitated iron and manganese oxyhydroxides are spatially separated. The patterns are a result of secondary iron and manganese oxide precipitation. This natural long-term experiment allows the analysis of competitive adsorption and coprecipitation of trace elements with iron and manganese oxides in sediments. Background concentrations in the sediment of oxoanions (P, As, Sb, Mo); of trace metals (Cr, V, Cu, Zn, Cd, Pb); and of Mg, Ca, Sr, La, Ce, Pr, Nd, and Sm were analyzed by inductively coupled plasma mass spectrometry. Despite the differences in catchment geology of the many tributaries, they are remarkably uniform in sediment cores from different basins of Lake Baikal. Enrichment factors of P and As within Fe crusts revealed concentrations up to 14 and 58 times higher than the background, respectively. No enrichment of P and As was found in the Mn layers. By contrast, Mo accumulated exclusively in the Mn layer with up to 35-fold enrichment. Sb was only slightly enriched in both the Fe and the Mn layers. Among the trace metals studied, only Cd was found at elevated concentrations with a preference for the Mn layer. Ca and Sr were correlated with both Fe and Mn accumulations. The study quantifies the well-known specific adsorption and coprecipitation of P and As at authigenic iron oxides and of Mo on manganese oxides. In addition, the enrichment of Cd at manganese oxides in contrast to the conservative behavior of Zn and Pb reveals highly selective accumulation processes.

Environmental Monitoring↗
PubMed2002

Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs.

OBJECTIVE: The 116 amino acid prohormone procalcitonin and some of its component peptides (collectively termed calcitonin precursors) are important markers and mediators of sepsis. In this study, we sought to evaluate the effect of immunoneutralization of calcitonin precursors on metabolic and physiologic variables of sepsis in a porcine model. DESIGN: A prospective, controlled animal study. SETTING: A university research laboratory. SUBJECTS: 30-kg Yorkshire pigs. INTERVENTIONS: Sepsis was induced in 15 pigs by intraperitoneal instillation of a suspension of cecal content (1 g/kg animal body weight) and a toxinogenic Escherichia coli solution (2 x 10(11) colony-forming units). During induction of sepsis, seven pigs received an intravenous infusion of purified rabbit antiserum, reactive to the aminoterminal portion of porcine prohormone procalcitonin. Another eight control pigs received an intravenous infusion of purified nonreactive rabbit antiserum. For all 15 animals, physiologic data (urine output, core temperature, arterial pressure, heart rate, cardiac index, and stroke volume index) and metabolic data (serum blood urea nitrogen and creatinine, arterial lactate, and pH) were collected or recorded hourly until death at 15 hrs. MEASUREMENTS AND MAIN RESULTS: In this large-animal model of rapidly lethal peritonitis, serum calcitonin precursors were significantly elevated. Amino-prohormone procalcitonin-reactive antiserum administration resulted in a significant improvement or a beneficial trend in a majority of the measured physiologic and metabolic derangements induced by sepsis. Specifically, arterial pressure, cardiac index, stroke volume index, pH, and creatinine were all significantly improved, while urine output and serum lactate had beneficial trends. Treated animals also experienced a statistically significant increase of short-term survival. CONCLUSIONS: These data from a large-animal model with polymicrobial sepsis demonstrate the salutary effect of early immunoneutralization of calcitonin precursors on physiologic and metabolic variables. Immunologic blockade of calcitonin precursors may offer a novel therapeutic approach to human sepsis.

Animals↗
PubMed2002

High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration.

The objective of this study was to evaluate whether the interleukin (IL)-1 decoy receptor (R), a negative pathway of regulation of IL-1, is correlated with severity of infection in critically ill patients and reflects the activation of anti-inflammatory pathways by glucocorticoid hormones. Plasma samples were obtained from 101 consecutive, critically ill patients admitted to the intensive care unit with different severities of microbial infection, as defined by standardized criteria. Here, we report that the IL-1 type II decoy R(II) is elevated in critically ill patients, especially in severe, systemic infection and culture-positive infections. In patients with a marked systemic inflammatory response syndrome 4, a pronounced, sepsis-induced further increase of circulating IL-1 decoy RII levels was evident. Thirty-six patients treated with glucocorticoid hormones had significantly higher levels of IL-1 decoy RII, but lower IL-6 and C-reactive protein, than 67 untreated subjects. The usefulness of IL-1RII, in particular as a potential marker for the activation of anti-inflammatory pathways or for responsiveness to anti-inflammatory agents such as glucocorticoid hormones, deserves further analysis.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Effect of restoration of euthyroidism on peripheral blood cells and erythropoietin in women with subclinical hypothyroidism.

BACKGROUND: In overt hypothyroidism (OH) anemia is common, while less frequently basophilia has been described. In subclinical hypothyroidism (SCH), however, data on the distribution of peripheral blood cells are lacking. Therefore, we evaluated the effects of L-T4 replacement therapy on peripheral blood elements in female patients with SCH before and after restoration of euthyroidism in a randomized, double-blind and placebo-controlled study. PATIENTS AND METHODS: Sixty-six women with SCH (TSH 12.9 +/- 8.2 mU/L) were randomly assigned to receive L-thyroxine or placebo for 48 weeks. 63 of the 66 women completed the study. Peripheral blood cells were measured at baseline and 48 weeks after L-thyroxine or placebo treatment, respectively. RESULTS: The percentage of lymphocytes decreased (p<0.05), whereas percent of monocytes (p<0.05) and eosinophiles (p<0.05) increased significantly upon restoration of euthyroidism after 48 weeks. Hemoglobin and hematocrit remained unchanged throughout the study period. However, erythropoietin levels increased significantly (p<0.01) during L-T4 treatment. In the placebo group all parameters remained unchanged throughout the study. CONCLUSIONS: Overall, we observed subtle alterations of the leuco-lympho-monocytic distribution of the peripheral blood cells upon restoration of euthyroidism in patients with SCH. Hemoglobin and Hematocrit remained unchanged; however, the increasing level of erythropoietin during L-T4 treatment suggests an already stimulated, yet compensated erythropoietic system in mild thyroid failure.

Journal Article↗