Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders.

INTRODUCTION: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. METHODS: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. RESULTS: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). CONCLUSION: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.

Sex-specific differences in trimethylamine N-oxide (TMAO) concentrations before and after cardiac rehabilitation in acute myocardial infarction patients.

Trimethylamine N-oxide (TMAO) is a biomarker of cardiovascular risk and may enhance the progression of atherosclerosis. The aim of the study was to determine whether there are sex-specific differences in TMAO concentrations before and after cardiac rehabilitation in acute myocardial infarction (AMI) patients. A total of 56 participants [45/56 (80.4 %) males, 11/56 (19.6 %) females] were drawn from AMI inpatients hospitalized at the Division of Cardiology, Medical University of Graz, Austria. For the assessment of TMAO, serum samples were collected within the first day after hospital admission due to AMI and at the start and end of cardiac rehabilitation. Shortly after hospital admission due to AMI, females had significantly higher TMAO blood concentrations than males. These initially high TMAO levels remained almost unchanged in the female AMI patients until the start of cardiac rehabilitation and only reached the lower TMAO concentrations observed in the male patients after rehabilitation [female patients: TMAO (acute myocardial infarction) = 5.93 µmol/L (SE = 1.835); TMAO (start of rehabilitation) = 5.68 µmol/L (SE = 1.217); TMAO (end of rehabilitation) = 3.89 µmol/L (SE = 0.554); male patients: TMAO (acute myocardial infarction) = 3.02 µmol/L (SE = 0.255), TMAO (start of rehabilitation) = 3.91 µmol/L (SE = 0.346), TMAO (end of rehabilitation) = 4.04 µmol/L (SE = 0.363)]. After AMI, women might be at higher cardiovascular risk due to persistently higher levels of TMAO. High TMAO levels in women might decrease after cardiac rehabilitation due to cardiac rehabilitation-associated lifestyle modifications. These lifestyle modifications after AMI might also prevent increases in TMAO concentrations in men.

Assessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction.

Background: Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective: Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method: A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients' TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results: Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions: An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.

Antecedentes: El trastorno de estrés postraumático (TEPT) es un trastorno relacionado con el estrés que se observa con frecuencia después de un infarto agudo de miocardio (IAM) y se caracteriza por numerosos síntomas, como flashbacks, intrusiones y ansiedad, así como pensamientos y sentimientos incontrolables relacionados con el trauma. Los correlatos biológicos del estrés severo podrían contribuir a identificar a los pacientes vulnerables al TEPT en una etapa temprana.Objetivo: Los objetivos del estudio fueron (1) determinar si los niveles sanguíneos de N-óxido de trimetilamina (TMAO, por sus siglas en ingles) varían inmediatamente después del IAM en pacientes con o sin sintomatología de TEPT inducida por IAM, (2) investigar si el TMAO es un biomarcador potencial que podría ser útil en la predicción de TEPT y los subgrupos de síntomas de TEPT que experimentan, evitación e hiperactivación, y (3) para investigar si el TMAO varía inmediatamente después del IAM en pacientes con o sin depresión 6 meses después del IAM.Método: Un total de 114 pacientes con IAM fueron evaluados con la Escala de Depresión de Hamilton tras su ingreso al hospital y 6 meses después. La Escala de TEPT para el DSM-5 administrada por el médico se utilizó para explorar los síntomas de TEPT en el momento del IAM y 6 meses después del IAM. Para evaluar el estado de TMAO de los pacientes, se recolectaron muestras de suero en la hospitalización y 6 meses después del IAM.Resultados: Los participantes con sintomatología de TEPT tenían niveles de TMAO significativamente más altos inmediatamente después del IAM que los pacientes sin síntomas de TEPT (ANCOVA: TMAO (TEPT x tiempo), F = 4.544, df = 1, p = 0.035). Con la inclusión de predictores clínicos adicionales en un modelo de regresión logística jerárquica, TMAO se convirtió en un predictor significativo de la sintomatología del TEPT. No se detectaron diferencias significativas en los niveles de TMAO inmediatamente después del IAM entre individuos con o sin depresión 6 meses después del IAM.Conclusiones: Un nivel elevado de TMAO inmediatamente después del IAM podría reflejar un estrés severo en pacientes vulnerables al TEPT, lo que también podría conducir a un aumento a corto plazo de la permeabilidad intestinal a la trimetilamina, el precursor de TMAO. Por lo tanto, un nivel elevado de TMAO podría ser un correlato biológico del estrés severo asociado con la vulnerabilidad al TEPT.

Basophilia of the peripheral blood in patients with ulcerative colitis.

Background: Basophilia of the peripheral blood (PBB) has rarely been described in patients with ulcerative colitis (UC).Objective: This study aimed to determine the frequency of PBB in patients with UC and to examine a potential correlation of PBB with markers of inflammation.Methods: We compared retrospectively the basophil counts and the occurrence of basophilia (>200 basophils/µL) between 165 patients with UC and 35 controls, and analysed the correlation between the basophil count and the C-reactive protein (CRP).Results: Within the study period, data from 1750 leukocyte differential count determinations of UC patients and 158 results from control subjects were available in the medical records and were statistically analysed. The differences in the basophil counts between the UC and the control group were not statistically significant (60/µL (0-351) vs. 49/µL (0-184), p = .26). Basophilia was apparent in 23 measurements of 10 patients with UC, but was not observed in the controls (p = .30). The basophil count was not significantly correlated with the CRP (p = .065, r = 0.04).Conclusions: Our findings suggest that PBB represents an uncommon and not disease-specific laboratory feature of UC. It is not correlated with the CRP and may not represent a useful biomarker for disease monitoring in UC.

Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study.

BACKGROUND & AIMS: Anorexia nervosa (AN) is a severe psychosomatic disease that seriously affects nutritional status. Therapeutic approaches primarily aim for rapid weight restoration by high caloric diets and activity restriction. This often promotes abdominal body fat gain, which potentially negatively influences the patient's compliance and increases the risk of relapse. This study focused on the evaluation of body weight and subcutaneous adipose tissue (SAT) in AN patients by novel approaches. METHODS: The SAT of AN patients (n = 18, body mass index (BMI) 15.3 ± 1.3 kg/m2) was determined by a highly accurate and reliable ultrasound method. The sum of SAT thicknesses of eight sites (DINCL) was calculated. Individual metabolic profiles were analyzed. The mass index (MI), which considers body proportions, was used in addition to BMI. Additional to the standard laboratory diagnostics, dermal carotenoids measured by resonance Raman spectroscopy, leptin, and oxidative stress indicators were determined. RESULTS: The mean MI was 15.7 ± 1.4 kg/m2. The DINCL considerably differed between individuals with the same BMI. Half of the patients (Group 1) had low DINCL: 1.3-28.4 mm, and Group 2 showed values up to 58.2 mm (corresponding to approximately 6 kg SAT mass). The two group means differed by more than 300% (P < 0.001). Accordingly, leptin levels significantly differed (P < 0.001). Mean SAT thicknesses were significantly higher in Group 2 at all eight sites. The groups also significantly differed in two oxidative stress parameters: total antioxidative capacity, malondialdehyde-modified low density lipoprotein immunoglobulin M (MDA-LDL IgM), and in the carotenoid level. CONCLUSION: Half of the patients had sufficiently high fat mass, despite very low BMI. Consequently, their muscle (and other organ) masses must have been extremely low. Diagnostic criteria and treatment protocols for AN should consider each patient's body composition. In addition to dietary treatments, muscle training at low energy turnover rates may be essential for avoiding unnecessary body fat gain, better treatment results, and long-term recovery.

[Strangulation as scenic behavior. A case report of a pseudosuicide in the course of a NREM-parasomnia]. / Strangulation als szenische Handlung. Ein Fallbericht über einen Pseudosuizidversuch im Verlauf einer NREM-Parasomnie.

It is generally accepted, that sleepwalkers show complex behaviors leading to non-intended consequences. It is not unusual that these persons are thereby injured. However, sporadically a bizarre endangering of themselves or others is reported also, which ranges from homicide of the life partner to accidental (pseudo-)suicide.In this article, we report on a 28year-old man who unexpectedly attempted to hang himself by a whip at night. We discuss the reasons, why this bizarre act should actually be taken as a scenic behavior in the course of a NREM-parasomnia, and the difficulty to proof this claim.

Metabolomics approach in the investigation of depression biomarkers in pharmacologically induced immune-related depression.

BACKGROUND: The aim of this study was to identify previously unrecognised biological pathways and biomarkers that might expand the inflammatory hypothesis of depression. METHODS: Broad metabolomics analyses in plasma samples from 31 chronic hepatitis C-infected patients with and without immune-related depression were carried out using the Absolute IDQ p180 kit-a targeted metabolomics approach of combined direct flow injection and liquid chromatography that measures acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. RESULTS: The measurements showed that the average concentration of the branched-chain amino acid isoleucine was significantly lower in depressive HCV patients in comparison to non-depressive HCV patients [depression group: Median 51.35 (43.4-60.2 µmol/L) vs. Median 62.10 (38.4-81.7 µmol/L); U = -2.958; p = 0.002]. All other amino acids, acylcarnitines, biogenic amines, glycerophospholipids, sphingolipids, sugars, liver enzymes and thyroid levels showed no statistically significant differences. CONCLUSIONS: The results of the present study suggest that the branched-chain amino acid isoleucine might play a role in the pathophysiology of immune-related major depression, which expands existing knowledge about inflammatory hypothesis of depression.

The clinical significance of borderline results of the Elia CTD Screen assay.

Background Data on the clinical relevance of borderline results of solid-phase assays in the screening for antinuclear antibodies (ANA) are sparse. This study aimed to determine the clinical significance of borderline results of the Elia CTD Screen (ECS; Phadia/Thermo Fisher Scientific, Freiburg, Germany), a fluoroenzymeimmunoassay incorporating 17 recombinant human nuclear antigens. Methods We retrospectively examined the medical records of 143 subjects with borderline ECS results for ANA-associated autoimmune disorders (AASARD) and the association with the results of indirect immunofluorescence (IIF) and confirmatory assays for ANA. Results AASARD were diagnosed in 10 patients (7%) with systemic lupus erythematosus (n=5; four patients were prediagnosed and in clinical remission), polymyositis overlap syndromes (n=2), scleroderma, Raynaud's syndrome and undetermined connective tissue disease (each n=1). Most frequently, homogeneous and nucleolar IIF patterns were found. Positive ANA subsets were observed in three patients. Furthermore, four patients were diagnosed with autoimmune liver diseases and yielded positive IIF in three and positive confirmatory assays in all cases. Taken together, 129 subjects had no AASARD. Within this group, 43 patients were IIF positive and most frequently showed speckled, unspecific nucleolar and only rarely homogeneous patterns. Positive ANA subsets were found in low concentrations near to the upper reference range in 18 subjects. Conclusions AASARD were observed in 7% of the subjects with borderline ECS and showed homogeneous or nucleolar IIF patterns in the majority of these cases. Our findings suggest that borderline results of the ECS can be clinically relevant and support the concept of a parallel or sequential screening for ANA by both ECS and IIF.

Revisiting the tryptophan-serotonin deficiency and the inflammatory hypotheses of major depression in a biopsychosocial approach.

BACKGROUND: The aim of this cross-sectional study was to identify important biopsychosocial correlates of major depression. Biological mechanisms, including the inflammatory and the tryptophan-serotonin deficiency hypotheses of major depression, were investigated alongside health-related quality of life, life satisfaction, and social support. METHODS: The concentrations of plasma tryptophan, plasma kynurenine, plasma kynurenic acid, serum quinolinic acid, and the tryptophan breakdown to kynurenine were determined alongside health-related quality of life (Medical Outcome Study Form, SF-36), life satisfaction (Life Satisfaction Questionnaire, FLZ), and social support (Social Support Survey, SSS) in 71 depressive patients at the time of their in-patient admittance and 48 healthy controls. RESULTS: Corresponding with the inflammatory hypothesis of major depression, our study results suggest a tryptophan breakdown to kynurenine in patients with major depression, and depressive patients had a lower concentration of neuroprotective kynurenic acid in comparison to the healthy controls (Mann-Whitney-U: 1315.0; p = 0.046). Contradicting the inflammatory theory, the concentrations of kynurenine (t: -0.945; df = 116; p = 0.347) and quinolinic acid (Mann-Whitney-U: 1376.5; p = 0.076) in depressive patients were not significantly different between depressed and healthy controls. Our findings tend to support the tryptophan-serotonin deficiency hypothesis of major depression, as the deficiency of the serotonin precursor tryptophan in depressive patients (t: -3.931; df = 116; p < 0.001) suggests dysfunction of serotonin neurotransmission. A two-step hierarchical linear regression model showed that low tryptophan concentrations, low social support (SSS), occupational requirements (FLZ), personality traits (FLZ), impaired physical role (SF-36), and impaired vitality (SF-36) predict higher Beck Depression Inventory (BDI-II) scores. DISCUSSION: Our study results argue for the validity of a biopsychosocial model of major depression with multiple pathophysiological mechanisms involved.

Beta-trace Protein as a new non-invasive immunological Marker for Quinolinic Acid-induced impaired Blood-Brain Barrier Integrity.

Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity. The research hypotheses were tested in three subsamples with different states of immune activation (patients with HCV-infection and interferon-α, patients with major depression, and healthy controls). BTP has also been described as a sensitive marker in detecting impaired renal function. Thus, the renal function has been considered. Our study results revealed highest quinolinic acid and highest BTP- levels in the subsample of patients with HCV in comparison with the other subsamples with lower or no immune activation (quinolinic acid: F = 21.027, p < 0.001 [ANOVA]; BTP: F = 6.792, p < 0.01 [ANOVA]). In addition, a two-step hierarchical linear regression model showed that significant predictors of BTP levels are quinolinic acid, glomerular filtration rate and age. The neurotoxin quinolinic acid may impair blood-brain barrier integrity. BTP might be a new non-invasive biomarker to indicate quinolinic acid-induced impaired blood-brain barrier integrity.

Branched-Chain Amino Acids as New Biomarkers of Major Depression - A Novel Neurobiology of Mood Disorder.

BACKGROUND: The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are altered in patients with major depression and might thus be appropriate biomarkers for major depression. METHODS: The concentrations of valine, leucine and isoleucine were determined in 71 in-patients with major depression and 48 healthy controls by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at the time of in-patient admittance. RESULTS: The BCAAs are significantly decreased in patients with major depression in comparison with healthy subjects (valine: Mann-Whitney-U: 968.0; p <0.0001, leucine: Mann-Whitney-U: 1246.5; p = 0.013, isoleucine: Mann-Whitney-U: 1252.5; p = 0.014). Furthermore, as shown by Spearman's rank correlation coefficients, there is a significant negative correlation between valine, leucine and isoleucine concentrations and the Hamilton Depression Rating Scale (HAMD-17) as well as Beck Depression Inventory (BDI-II) scores. CONCLUSIONS: Our study results are strong evidence that in patients with major depression, BCAAs might be appropriate biomarkers for depression. Reduced activation of the mammalian target of rapamycin (mTor) due to a reduction of BCAAs might play a crucial unrecognised factor in the etiology of depression and may evoke depressive symptomatology and lower energy metabolism in patients with major depression. In the future, mTor and its up- and downstream signalling partners might be important targets for the development of novel antidepressants.

Comparison of the clinical utility of the Elia CTD Screen to indirect immunofluorescence on Hep-2 cells.

BACKGROUND: We compared the Elia CTD Screen (ECS), a fluoroenzymeimmunoassay incorporating 17 human antinuclear antigens (ANA), with indirect immunofluorescence (IIF) on Hep-2 cells in order to determine the clinical utility of the ECS in additon to or without IIF. METHODS: We examined 1708 consecutive serum samples submitted for ANA testing using the ECS and IIF in parallel. Positive screen results were further examined by quantitative fluoroenzymeimmunoassays and/or immunoblots for antibody identification. The medical records were evaluated for systemic rheumatic disorders. RESULTS: Concordance between ECS and IIF was observed in 1344 (78.8%) samples. ECS had a better detection rate for anti-dsDNA, -SSA/Ro, -SSB/La, -U1RNP and -Jo-1 antibodies, whereas IIF was superior in the detection of anti-CENP-B antibodies as well as anti-histone, -nucleosome and -Pl-12 antibodies, which are not included in the ECS antigen panel. ECS had a 100% sensitivity for Sjögren's syndrome, systemic sclerosis and Sharp syndrome. The sensitivity for Sjögren's syndrome was slightly higher for ESC than for IIF (94%). IIF had a higher diagnostic sensitivity for systemic lupus erythematosus, indeterminated connective tissue disease, Raynaud's syndrome and limited scleroderma, compared to ESC (100% vs. 80%, 100 vs. 75%, 89 vs. 57%, 100 vs. 88.9%). CONCLUSIONS: Our results suggest that the ECS represents an appropriate diagnostic tool for ANA screening. However, since some antigens are not incorporated in the ECS panel, and some ANA can also be missed by IIF, sequential or parallel screening with ECS and IIF may be reasonable when the clinical suspicion for connective tissue disease is high.

Nitric Oxide-Related Biological Pathways in Patients with Major Depression.

BACKGROUND: Major depression is a well-known risk factor for cardiovascular diseases and increased mortality following myocardial infarction. However, biomarkers of depression and increased cardiovascular risk are still missing. The aim of this prospective study was to evaluate, whether nitric-oxide (NO) related factors for endothelial dysfunction, such as global arginine bioavailability, arginase activity, L-arginine/ADMA ratio and the arginine metabolites asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) might be biomarkers for depression-induced cardiovascular risk. METHODS: In 71 in-patients with major depression and 48 healthy controls the Global Arginine Bioavailability Ratio (GABR), arginase activity (arginine/ornithine ratio), the L-arginine/ADMA ratio, ADMA, and SDMA were determined by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at baseline at the time of in-patient admittance and at the time of hospital discharge. RESULTS: The ADMA concentrations in patients with major depression were significantly elevated and the SDMA concentrations were significantly decreased in comparison with the healthy controls. Even after a first improvement of depression, ADMA and SDMA levels remained nearly unchanged. In addition, after a first improvement of depression at the time of hospital discharge, a significant decrease in arginase activity, an increased L-arginine/ADMA ratio and a trend for increased global arginine bioavailability were observed. CONCLUSIONS: Our study results are evidence that in patients with major depression ADMA and SDMA might be biomarkers to indicate an increased cardiovascular threat due to depression-triggered NO reduction. GABR, the L-arginine/ADMA ratio and arginase activity might be indicators of therapy success and increased NO production after remission.

Quinolinic Acid Responses during Interferon-α-Induced Depressive Symptomatology in Patients with Chronic Hepatitis C Infection - A Novel Aspect for Depression and Inflammatory Hypothesis.

BACKGROUND: The aim of this exploratory study is to gain for the first time a more comprehensive picture of the impact of changes of quinolinic acid concentrations on depressive symptomatology during and after IFN-α therapy. METHODS: The quinolinic acid concentrations of 35 HCV patients are examined in a prospective survey over the entire period of IFN-α treatment as well as three months later at six different times (baseline, one, three, six and nine months after the beginning of IFN-α treatment, and after the end of treatment). RESULTS: During IFN-α treatment Hamilton Depression Rating Scale scores rise significantly. At the same time there is greater activity of indoleamine 2,3-dioxygenase, with a resulting increase in plasma kynurenine concentrations. Compared to baseline values quinolinic acid concentrations increase significantly during therapy, reflecting an increased neurotoxic challenge. In addition, patients with higher scores in the Hamilton Depression Rating Scale at six and nine months after starting therapy show significantly higher levels of quinolinic acid concentration. CONCLUSIONS: The increase of quinolinic acid during IFN-α therapy might contribute to depressive symptomatology through the neurotoxic challenge caused by quinolinic acid. Subsequently, our exploratory study results support the inflammatory hypothesis of depression. The awareness of relevant risk factors of IFN-α treatment-induced depression is essential to develop preventative treatment strategies.

Dacryocytes are a common morphologic feature of autoimmune and microangiopathic haemolytic anaemia.

BACKGROUND: Dacryocytes are teardrop-shaped erythrocytes which are most frequently observed in peripheral blood smears of patients with primary or secondary myelofibrosis as well as malignant infiltrative disorders of the bone marrow. Dacryocytes have rarely been described in blood smears of patients with autoimmune (AIHA) and microangiopathic haemolytic anaemia (MAHA). The clear prevalence of dacryocytes in AIHA and MAHA is unknown. METHODS: We compared the dacryocyte counts in blood smears stained according to the May-Grünwald-Giemsa technique between 20 subjects with AIHA and MAHA with those from 21 controls. The dacryocytes, defined as erythrocytes tapered to a point at one end, were counted as cells per 20 high power fields (HPF) at 630-fold magnification. RESULTS: In AIHA, MAHA and controls, dacryocytes were found in 89%, 91% and 19% of the slides, respectively. The rate of dacryocyte positivity and the dacryocyte counts between haemolytic anaemias and controls differed statistically highly significant (p<0.0001). CONCLUSIONS: The results of this study indicate that dacryocytes are commonly apparent in blood smears of patients with AIHA and MAHA. Knowledge of this frequent feature may be beneficial in clinical routine diagnosis.

The anti-VLA-4 antibody natalizumab induces erythroblastaemia in the majority of the treated patients with multiple sclerosis.

The presence of erythroblasts in the peripheral blood is generally associated with severe underlying disorders. The anti-very late antigen-4 (anti-VLA-4) antibody natalizumab, which is approved for treatment of multiple sclerosis, mediates an increase in circulating haematopoietic stem cells and may also trigger erythroblastaemia. We investigated the prevalence of erythroblastaemia in sequential blood smears of 14 natalizumab-treated and 14 interferon-treated patients with multiple sclerosis. Erythroblastaemia was found in 13 natalizumab-treated subjects (93%), whereas all controls were negative (p<0.0001). Knowledge of this frequent side effect is crucial for the correct interpretation of blood smears in natalizumab-treated patients and to avoid unnecessary diagnostic procedures.

A critical analysis of whole body bioimpedance spectroscopy (BIS) for the estimation of body compartments in health and disease.

Aim of the study was to assess the accuracy and precision of a BIS device and the relative contribution of BIS beyond the anthropometric parameters. The output of the Impedimed device (SFB7) and the relative contribution of height, weight, age, sex and resistance values at zero and infinite frequency (Rzero and Rinf respectively) to the prediction of total body water (TBWd, deuterium space), of extracellular fluid (ECFbr, sodium bromide space) and of fat mass (FMDXA) were assessed in 116 subjects (32 healthy subjects and 84 patients with disorders of body composition). Using a repeated randomization procedure, new equations for TBW, ECF and FM were derived. The SFB7 gave measures of determination similar to those obtained with equations that included only anthropometric data. The SFB7, but not the newly derived regression equations, underestimated TBW and ECF by 3.82±3.37 (mean±SD) and by 0.93±2.62l and overestimated FM by 6.55±3.86kg. Nine of 16 patients with ECF overload as detected by ECFbr were also detected by BIS. BIS measurements contribute marginally but not significantly beyond anthropometric data to the prediction of TBW, ECF and FM, either in healthy subjects or in patients with disturbed body composition.