Search

Background: The detection of monoclonal immunoglobulins (MIg) is a key element in the diagnosis of monoclonal gammopathies. Methods: Here we report two cases of high concentration serum IgM-kappa MIgs (6.4 g/L and 6.8 g/L) not detected with capillary electrophoresis (CE). A systematic literature search was conducted to assess the sensitivity of CE to detect MIgs. Results: The CE sensitivity to detect MIgs did not exceed 0.9 to 0.95 compared to immunofixation as standard. On the one hand, MIgs with blood concentrations below 1 g/L may be hidden by other serum proteins. On the other hand, some MIgs of high concentrations are not detected due to their insolubility in the electrophoresis buffer. Conclusions: Performing a second SPE with agarose gel electrophoresis method or modifying buffer properties may reveal some MIgs not detected by a first SPE alone. [ABSTRACT FROM AUTHOR]

Besides their many other functions, hair shafts (HS) also are a repository for potentially noxious compounds. These are neutralized by their deposition within terminally differentiated, avital epithelial cells (trichocytes) that also facilitate the interaction of potential toxins with melanin, a toxin‐adsorbent biopolymer. Trichocytes are completely extruded via HS shedding during exogen, an actively controlled process. This underappreciated functional property of the human hair follicle (HF) makes it a bona fide excretory (mini‐) organ. Here, we ask whether the ca. 2 million HFs of the human integument operate in part as primitive, spatially dispersed kidney‐like excretory organs. Despite the many obvious differences between kidneys and HFs, this provocative hypothesis is also supported by other underappreciated renal‐follicular similarities such as anatomical parallels between Bowman's capsule and the anagen hair bulb, renal podocytes and HF winged cells ["Fuegelzellen"], and hypoxia‐dependent production of erythropoietin and extensive prostaglandin synthesis by human scalp HFs—just as in the kidney. The proposed kidney‐like excretory function of HFs may have constituted a major selection advantage of mammals during evolution and could be clinically relevant. We explain how the many open questions (eg, how are molecules destined to be excreted by hair shaft entrapment recognized, taken up and deposited into hair matrix cells?) can be tested experimentally. Finally, we explore how the therapeutic targeting of kidney‐like excretory HF functions may usefully complement classical nephrological therapy (dialysis) and ask whether stimulation of intrafollicular erythropoietin synthesis might become exploitable for the benefit of patients with renal anaemia. [ABSTRACT FROM AUTHOR]

Background: Radioimmunoassays, which are often not automated and time-consuming, are gradually being replaced in medical laboratories by non-radioactive methods that need to be evaluated. The purpose was to compare the measurement of thyroid-stimulating hormone receptor antibodies (TRAb) by the new Brahms' kit using Kryptor TRACE technology and the Brahms' radioimmunoassay. Methods: We prospectively collected all samples from patients who received thyroid-stimulating hormone receptor antibodies testing in July 2018 at the University Hospital of Brest. The radioimmunoassay used was the Dynotest TRAK human by BRAHMS Diagnostica (Berlin, Germany). The Kryptor method used the BRAHMS TRAK human Kryptor kit performed with the Kryptor Compact Plus system. Results: The inter-assay coefficient variations for the radioimmunological and Kryptor methods were 11.07% and 8.36%, respectively, with the low level quality control and 8.36% and 4.38%, respectively, with the high level quality control. Forty-four patients were included in the study including thirty-two Graves' disease patients in follow-up. The sensitivity of the radioimmunological method for the detection of Graves' disease was 0.94 and the specificity was 0.73. The sensitivity of the Kryptor method was 0.91 and the specificity was 0.91. A non-proportional systematic bias in favor of higher values of TRAb concentrations with the radioimmunological method was observed: slope of 0.93 (0.74 - 1.07, 95% confidence interval) and an intercept of -0.69 IU/L (-1.58 to -0.30, 95% confidence interval). Compared to the Kryptor method, the radioimmunological method tends to overestimate TRAb concentrations by up to 120%. Conclusions: The fully automated Brahms Kryptor kit using TRACE technology to measure TRAb reduces sampling time and intra- as well as inter-assay variations. The Kryptor kit underestimates the results of TRAb leading to a lower sensitivity and higher specificity compared to the radioimmunoassay. Thus, the new Brahms Kryptor kit has good laboratory performances but the interpretation of the results must still be performed with caution. [ABSTRACT FROM AUTHOR]

The article offers information on the Vancomycin, a bactericidal glycopeptide antibiotic used to treat systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA), penicillin resistant streptococci or enterococci; and mentions that Vancomycin in the sample competes with acridinium ester-labelled vancomycin for a limited amount of anti-vancomycin monoclonal mouse antibody covalently bound to paramagnetic particles.

Many case reports have indicated the occurrence of monoclonal gammopathy of uncertain significance (MGUS) or multiple myeloma (MM) in patients with Ph-negative myeloproliferative neoplasms (MPN), but few cohorts of patients have been published. This study concerns 667 patients newly diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET) who were tested for monoclonal (M) protein at diagnosis (13.9% of patients). The overall survival of patients with M protein was dramatically lower than that of patients without M protein (12.7 versus 22.4 years; p = .0132). Univariate analysis identified the presence of M protein as a potential risk factor for the secondary occurrence of myelofibrosis (p = .02), myelodysplastic syndrome (p = .043), and MM/Waldenstrom macroglobulinemia (p < .0001). Our cohort shows that the presence of M proteins in patients with PV or ET leads to a poor prognosis. We believe that testing for M protein could help practicians to identify such patients. [ABSTRACT FROM AUTHOR]

Sensitive skin is a clinical syndrome characterized by the occurrence of unpleasant sensations, such as pruritus, burning or pain, in response to various factors, including skincare products, water, cold, heat, or other physical and/or chemical factors. Although these symptoms suggest inflammation and the activation of peripheral innervation, the pathophysiogeny of sensitive skin remains unknown. We systematically analysed cutaneous biopsies from 50 healthy women with non-sensitive or sensitive skin and demonstrated that the intraepidermal nerve fibre density, especially that of peptidergic C-fibres, was lower in the sensitive skin group. These fibres are involved in pain, itching and temperature perception, and their degeneration may promote allodynia and similar symptoms. These results suggest that the pathophysiology of skin sensitivity resembles that of neuropathic pruritus within the context of small fibre neuropathy, and that environmental factors may alter skin innervation. [ABSTRACT FROM AUTHOR]

Aim: Our aim was to evaluate the accuracy of aerobic exercise testing to diagnose metabolic myopathies. Methods: From December 2008 to September 2012, all the consecutive patients that underwent both metabolic exercise testing and a muscle biopsy were prospectively enrolled. Subjects performed an incremental and maximal exercise testing on a cycle ergometer. Lactate, pyruvate, and ammonia concentrations were determined from venous blood samples drawn at rest, during exercise (50% predicted maximal power, peak exercise), and recovery (2, 5, 10, and 15 min). Biopsies from vastus lateralis or deltoid muscles were analysed using standard techniques (reference test). Myoadenylate deaminase (MAD) activity was determined using p-nitro blue tetrazolium staining in muscle cryostat sections. Glycogen storage was assessed using periodic acid-Schiff staining. The diagnostic accuracy of plasma metabolite levels to identify absent and decreased MAD activity was assessed using Receiver Operating Characteristic (ROC) curve analysis. Results: The study involved 51 patients. Omitting patients with glycogenoses (n = 3), MAD staining was absent in 5, decreased in 6, and normal in 37 subjects. Lactate/pyruvate at the 10th minute of recovery provided the greatest area under the ROC curves (AUC, 0.893 ± 0.067) to differentiate Abnormal from Normal MAD activity. The lactate/rest ratio at the 10th minute of recovery from exercise displayed the best AUC (1.0) for discriminating between Decreased and Absent MAD activities. The resulting decision tree achieved a diagnostic accuracy of 86.3%. Conclusion: The present algorithm provides a non-invasive test to accurately predict absent and decreased MAD activity, facilitating the selection of patients for muscle biopsy and target appropriate histochemical analysis. [ABSTRACT FROM AUTHOR]

Due to the close interactions between the skin and peripheral nervous system, there is increasing evidence that the cutaneous innervation is an important modulator of the normal wound healing process. The communication between sensory neurons and skin cells involves a variety of molecules (neuropeptides, neurohormones, and neurotrophins) and their specific receptors expressed by both neuronal and nonneuronal skin cells. It is well established that neurotransmitters and nerve growth factors released in skin have immunoregulatory roles and can exert mitogenic actions; they could also influence the functions of the different skin cell types during the wound healing process. [ABSTRACT FROM AUTHOR]

The Long Evans shaker (les) rat is a myelin basic protein (MBP) mutant that exhibits severe central nervous system (CNS) dysmyelination. We used a combination of immunohistochemistry, immunoblot and Northern blot analyses to determine the effect of MBP deficits on the expression of other CNS myelin genes in this mutant. Immunohistochemistry revealed a marked reduction in all major myelin proteins and differences in their intracellular distribution. Immunoblots confirmed the decreased expression of these proteins and indicated that relative levels of proteolipid protein (PLP) and DM20 were altered in this mutant. Quantitation of mRNA levels indicated that decreases in PLP and DM20 were a result of changes in mRNA levels but detected no change in other myelin gene transcripts. [Copyright &y& Elsevier]

Skin-derived precursor cells (SKPs) are neural crest stem cells that persist in certain adult tissues, particularly in the skin. They can generate a large type of cell in vitro, including neurons. SKPs were induced to differentiate into sensory neurons (SNs) by molecules that were previously shown to be important for the generation of SNs: purmorphamine, CHIR99021, BMP4, GDNF, BDNF, and NGF. We showed that the differentiation of SKPs induced the upregulation of neurogenins. At the end of the differentiation protocol, transcriptional analysis was performed on BRN3A and a marker of pain-sensing nerve cell PRDM12 genes: 1000 times higher for PRDM12 and 2500 times higher for BRN3A in differentiated cells than they were in undifferentiated SKPs. Using immunostaining, we showed that 65% and 80% of cells expressed peripheral neuron markers BRN3A and PERIPHERIN, respectively. Furthermore, differentiated cells expressed TRPV1, PAR2, TRPA1, substance P, CGRP, HR1. Using calcium imaging, we observed that a proportion of cells responded to histamine, SLIGKV (a specific agonist of PAR2), polygodial (a specific agonist of TRPA1), and capsaicin (a specific agonist of TRPV1). In conclusion, SKPs are able to differentiate directly into functional SNs. These differentiated cells will be very useful for further in vitro studies. [ABSTRACT FROM AUTHOR]

The article discusses how learned immune function can optimize dermatological treatments through the placebo effect and nocebo effects. Topics discussed include placebo and nocebo effects being the positive or negative treatment effects that depends exclusively of the patient's expectations about a treatment outcome, its consequences for itch treatment, and meta-analysis of clinical trials of oral systemic medication showing substantial effects on itch of placebo medications.

The detection of monoclonal immunoglobulins is a key element in the diagnosis of monoclonal gammopathy. In clinical practice, screening and measurement of monoclonal proteins are commonly performed using capillary zone electrophoresis (CZE). Some exogenous substances, such as iodinated contrast agents, absorb incident UV light at the same wavelengths as the peptide bonds and may therefore interfere with the detection of proteins in CZE. We herein use the description of a case to illustrate that iodinated contrast agents can mask the presence of monoclonal immunoglobulins in CZE and we discuss the strategy needed to confirm this interference. Performing immunofixation, immunosubtraction, or a second CZE at a distance from the first blood sample is not only necessary to confirm the presence of an iodinated contrast media interference but also to ensure the absence of monoclonal proteins. [ABSTRACT FROM AUTHOR]

This is a case report of a challenging diagnosis of IgE monoclonal gammopathy of undetermined significance, which transformed into myeloma, then transformed into IgE-producing plasma cell leukaemia in a 71-year-old male who was followed in Brest, France, from 2015 to 2019. The IgEproducing variant is the rarest sub-type of multiple myeloma, and plasma cell leukaemia is considered to be the rarest and the most aggressive of human monoclonal gammopathies. In November 2015, hypogammaglobulinemia was detected during a systematic check-up. A kappa light chain monoclonal gammopathy was first diagnosed due to an increase of the free kappa/lambda light chains ratio. No monoclonal immunoglobulin was detected by either serum protein electrophoresis (Capillarys 2, Sebia, Issy-les-Moulineaux, France) or immunofixation (Hydrasys 2, Sebia, Issy-les-Moulineaux, France). In June 2018, a blood smear led to the diagnosis of plasma cell leukaemia. A monoclonal peak was detected and identified as IgE-kappa. Analysis of an archival sample taken three years earlier, revealed the presence of a monoclonal IgE, which had been missed at diagnosis. Chemotherapy with bortezomib and dexamethasone was introduced. The patient survived 10 months after the diagnosis of leukaemia. This case shows that an abnormal free light chain ratio should be considered as a possible marker of IgE monoclonal gammopathy even in the absence of a solitary light chain revealed by immunofixation. In addition, the use of an undiluted serum may increase the sensitivity of the immunofixation for the detection of IgE monoclonal gammopathies compared to the 1:3 dilution recommended by the manufacturer. [ABSTRACT FROM AUTHOR]

Abstract Background The capillary zone electrophoresis method of albumin measurement is frequently used in monoclonal gammopathy patients but some studies suggest poor performances of the method in this population. The aim of this study was to analyse the impact of serum monoclonal immunoglobulins on human serum albumin determination by capillary zone electrophoresis method compared to other available methods. Method We prospectively measured albumin in 100 freshly collected non-frozen serum samples in a monoclonal gammopathy patients population, by using four different methods: the capillary zone electrophoresis method, the bromocresol purple dye method, the nephelometric method and the turbidimetric method. Differences in albumin values between the different methods were analysed with respect to serum monoclonal immunoglobulin concentration. These differences were further investigated by measuring albumin levels in human serum samples spiked with exogenous monoclonal immunoglobulins. Results Human serum albumin difference values between capillary zone electrophoresis compared to immunonephelometry method are significantly correlated with increasing monoclonal immunoglobulins concentrations: regression analyses revealed a correlation coefficient r2 = 0.60 and a slope of 0.14 (0.12–0.17, 95% confidence interval). The capillary zone electrophoresis method overestimated serum albumin levels by up to 67% (12 g/L) when monoclonal immunoglobulin level was 63 g/L. The determination of albumin levels in human serum samples spiked with exogenous monoclonal immunoglobulins showed an overestimation of human serum albumin measurement by the capillary zone electrophoresis method proportional to the amount of monoclonal immunoglobulin added in the serum with a slope of 0.19 (0.18–0.20, 95% confidence interval). Conclusion Monoclonal immunoglobulins directly interfere with serum albumin measurement by the capillary zone electrophoresis method leading to a systematic overestimation of serum albumin concentrations proportional to the serum monoclonal immunoglobulin level. Highlights • Monoclonal immunoglobulins systematically interfere with capillary zone electrophoresis serum albumin measurement method. • Serum monoclonal immunoglobulins lead to an overestimation of serum albumin by capillary zone electrophoresis method. • The capillary zone electrophoresis method overestimates human serum albumin concentrations by up to 67% (12 g/L). • The capillary zone electrophoresis method tends to overestimate human serum albumin concentrations for albumin levels below 30 g/L. [ABSTRACT FROM AUTHOR]

Abstract Background The capillary zone electrophoresis method of albumin measurement is frequently used for oncologic and haematologic patients but few data exist about the agreement between the albumin measurements performed by capillary zone electrophoresis and other methods. The aim of this study was to analyse the agreement between human serum albumin measurements by capillary zone electrophoresis and by the nephelometry, bromocresol purple and turbidimetry methods. Method We prospectively measured 100 freshly collected non-frozen patient serum samples, by using four different methods: the capillary zone electrophoresis method performed with a CAPILLARYS 2 instrument, the bromocresol purple dye method performed with an Advia XPT analyser, the nephelometric method performed with a BN ProSpec analyser and the turbidimetric method with reagents from DiAgam and performed with the Advia XPT analyser. Results A bias towards higher values in the lower range of albumin concentrations was observed with capillary zone electrophoresis compared to immunonephelometry: correlation coefficient r2 = 0.925; slope of 0.86 (0.82–0.89, 95% confidence interval), which is significantly different from 1; and an intercept of 4.94 g/L (3.67–6.16, 95% confidence interval). Similar results were observed when comparing capillary zone electrophoresis to the bromocresol purple and immunoturbidimetry methods. The capillary electrophoresis method overestimated low albumin levels by up to 25% (5 g/L). Conclusion Compared to the nephelometry, turbidimetry and bromocresol purple methods, the capillary zone electrophoresis method tends to overestimate human serum albumin concentrations for levels below 30 g/L. This discrepancy could lead to an overestimation of the nutritional status, an inappropriate scoring of the disease and a delay in nutritional treatment. Highlights • The agreement between capillary zone electrophoresis and nephelometry measurements of human serum albumin concentrations is low. • Human serum albumin measurements by capillary zone electrophoresis are not consistent with bromocresol purple and turbidimetry measurements. • The capillary zone electrophoresis method tends to overestimate human serum albumin concentrations for levels below 30 g/L. • The capillary zone electrophoresis method overestimates human serum albumin concentrations by up to 25% (5 g/L) in patients with hypoalbuminaemia. [ABSTRACT FROM AUTHOR]

Abstract: Background: Epidemiological studies have established that a low serum concentration of carotenoids was associated with risk of Age-Related Macular Degeneration (ARMD). The aim of this study was to determine carotenoid levels in serum and in different lipoprotein fractions in patients diagnosed for ARMD and in matched control group. Method: Thirty-four ARMD patients and 21 control subjects from Brest area (France) have been included to this study. Lipoproteins have been separated from serum by gradient density ultracentrifugation. We measured concentration of carotenoids and tocopherols in serum and in different lipoprotein fractions by HPLC. Results: No difference was observed between ARMD patients and control subjects in total serum carotenoids. Individual carotenoid levels showed that only lycopene was decreased significantly in serum, LDL and HDL fractions in patients (P &#60;0.05). Concentrations in serum and lipoparticle fractions of lutein and zeaxanthin, the major pigments present in macula were not modified between both groups. Conclusions: Lycopene, as liposoluble antioxidant nutrient, is the only carotenoid altered in ARMD patients. It cannot be excluded that this effect is related to different dietary habits, but we hypothesise that lower lycopene status could result also from specific antioxidant protection of lutein and zeaxanthin by lycopene. [Copyright &y& Elsevier]

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

In recent years, studying the central mechanism of itch has gained momentum. However, a proper meta-analysis has not been conducted in this domain. In this study, we tried to respond to this need. A systematic search and a meta-analysis were carried out to estimate the central mechanism of itch. The itch matrix comprises the thalamus and the parietal, secondary somatosensory, insular and cingulate cortices. We have shown that the basal ganglia (BG) play an important role in itch reduction. Finally, we explored itch processing in AD patients and observed that the itch matrix in these patients was different. In conclusion, this is the first meta-analysis on the central mechanisms of itch perception and processing. Our study demonstrated that different modalities of itch induction can produce a common pattern of activity in the brain and provided further insights into understanding the underlying nature of itch central perception., (Copyright © 2019. Published by Elsevier Masson SAS.)

Pheochromocytoma and paraganglioma are neuroendocrine tumors characterized by a catecholamine production potential. The biochemical diagnosis for this type of tumor is carried out through the metanephrine titration on 24-hours urines. Some authors have suggested that the sensitivity of the test could be improved by sampling and analyzing urines 3 days in a row (cycle) versus a unique measurement but this method has never been fully evaluated. The goal of this study was to establish a comparison of diagnosis performances between urinary metanephrines measurement for 3 consecutive days, and metanephrines measurement on a unique 24-hour sample. Patients of Brest Regional University Hospital whose 3-consecutive day 24-hour urine samples had been analyzed from January 2011 to May 2017 were included in this study. The primary endpoint was the comparison of diagnostic performances of urinary metanephrine titration over a single day versus 3 consecutive days. Eighty-two patients for a total of 103 cycles among which 7 revealed a pheochromocytoma were analyzed. ROC curve analysis shows that the metanephrine cycle titration method is more efficient than the metanephrine single titration method (metanephrine: AUC=0.881 against 0.826 respectively; normetanephrine: AUC=0.946 against 0.901 respectively). Urinary titration over 3 days allows the diagnosis of 100% (7/7) of pheochromocytomas against 85.7% (6/7) for the the single urinary titration. In conclusion, metanephrine titration over 3 consecutive days of 24-hours urine samples shows a better sensitivity and better diagnosis performances for detecting pheochromocytoma and paraganglioma than the single titration method.

Paraprotein interferences assays are known but rather unusual in clinical chemistry.we here report a paraprotein interference with a bicarbonate assay in a IgA kappa-type myeloma patient. Serum bicarbonate level was assessed by the enzymatic method of a multiparametric chemistry analyzer (Advia 1800, Siemens) as well as a specific electrode assay on a blood gas analyzer (GEM 4000, IL). Paraprotein interference with the enzymatic assay was evidenced by an abnomally low bicarbonate level measured by the enzymatic method in contrast with usual levels obtained by using the gas analyzer and with the clinical status of the patient. Therefore, gammapathy has to be taken into consideration when interpreting biological data.

Unlabelled: The hook effect, which has long been detected and documented for immunoradiometric assays (IRMA) such as those measuring prolactin or thyroglobulin, occurs when the serum antigen level is extremely high, thus inducing a bias in the methodology of measurement., Results: We report the case of an 80-year-old man with confirmed medullary thyroid carcinoma (MTC). In the case reported here, the clinical status of the patient contrasts with his tumor antigen, serum calcitonin (CT), concentrations. The measured increased CT concentrations revealed the presence of a hook effect. This phenomenon occurs due to an excess of antigen during the one-step IRMA where the signal antibodies, bound to the non-captured antigens, are washed out during the measurement, inducing the loss of signal. Aiming to prevent the "hook effect", successive dilutions of the same sample of serum were done., Conclusions: Previous studies have shown when one-step IRMA reveals high concentrations of a tumor serum antigen (i.e. prolactin or thyroglobulin), a two-step IRMA or a systematic 1:10 dilution of the serum sample prevents the formation of the "hook effect". In our case report, the CT "hook effect" formation was prevented by performing serial dilutions of the serum sample., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to highlight the link between induced hypothermia and increased survival duration as observed in the septic model developed by the laboratory. To reach this objective, survival duration and blood oxygen transport capacity were measured at two temperatures-38 °C (induced normothermia) and 34 °C (induced hypothermia)-in septic rats., Design: A prospective, randomized, experimental animal study., Setting: University laboratory., Subjects: Forty-four male Sprague-Dawley rats (median weight, 232 g; range, 200-303 g)., Interventions: After anesthesia and obtention of the temperature goal, sepsis was induced by cecal ligation and perforation., Measurements and Main Results: Sepsis induction led to death 5 hrs 11 mins ± 0 hr 36 mins after cecal ligation and perforation at 38 °C. At this temperature, significant changes in blood oxygen transport capacity were observed in septic rats; Hill number decreased from 2.36 ± 0.10 (baseline group) to 1.99 ± 0.17 (septic group) (p = .008) and oxygen-hemoglobin affinity decreased and P50 increased from 41.40 ± 2.4 Torr (baseline group) to 51.17 ± 14.07 Torr (septic group). Furthermore, in normothermia, a significant increase of creatinine and albumin plasmatic concentrations was observed 4 hrs after sepsis induction. Survival duration was significantly higher in induced hypothermia (7 hrs 22 mins ± 0 hr 12 mins at 34 °C) compared with induced normothermia. At 34 °C, no significant change in blood oxygen transport capacity was observed. In the same way, exposure to 34 °C induced no change in measured plasmatic parameters except an increase in albumin concentration in septic rats compared with the baseline group., Conclusions: Sepsis led to a decrease of both oxygen hemoglobin cooperativity and affinity at 38 °C. By contrast, no change in these parameters was observed when sepsis was induced during hypothermia. Taken together, these results could be interpreted in normothermia septic rats as an adaptive mechanism that could enhance the release of oxygen at the tissue level. Hypothermia by slowing down sepsis evolution could increase survival duration.

Measurement of catecholamines derivatives is used to diagnose tumors such as pheochromocytomas and paragangliomas. Despite the low incidence of these diseases, their diagnosis is essential because of potentially lethal episodes of malignant hypertension related to an inappropriate secretion of catecholamines by these tumors. The catecholamines derivatives include 3-methoxytyramine, normetanephrine and metanephrine, assayed in urine or plasma. The significance of the measurement of urinary 3-methoxytyramine was addressed by analysing the records of 28 patients aged 25 to 84 years with isolated elevation of this derivative, with non-pathological urinary rates of metanephrine and normetanephrine, that might help suspect a catecholamine inappropriate secretion. In these situations, no pheochromocytoma or paraganglioma was diagnosed. This study, after discussing possible biases in the clinical care and diagnosis approach of these patients, raises the question of the relevance of this assay in the diagnostic management of these diseases.

Double and triple immunocytochemistry with stage-specific markers and specific antireceptor antibodies was used to study expression of nuclear thyroid hormone receptor (TR) isoforms in cultured mouse oligodendrocytes. To evaluate the coexpression of each TR isoform, antibodies were raised in rabbits and mice against specific regions of alpha1-TR and alpha2-TR common to both alpha isoforms and beta1-TR. Their specificities were assessed by Western blotting and by immunocytochemistry on rat hepatocytes. Oligodendrocyte subpopulations were found to coexpress the alpha- and beta1-TR epitopes at defined developmental stages. Both alpha- and beta1-TR isoforms are colocalized in oligodendrocytes during an early stage identified by the marker OL-1, before 2',3'-cyclic nucleotide 3'-phosphohydrolase is expressed. Expression of beta1-TR varies during maturation, and that of alpha-TR decreases during terminal maturation., (Copyright 2002 Wiley-Liss, Inc.)