Measurement of low serum methotrexate concentrations with the Syva Emit Methotrexate Assay.
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Biomedical subjects
Publications and source records attributed to H Neels.
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Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune-inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high-density lipoprotein cholesterol (HDL-C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL-C or by abnormal levels of serum total cholesterol, triglycerides, low-density lipoprotein-C (LDL-C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL-C and (iii) there are significant associations between serum HDL-C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T-helper/T-suppressor (CD4+/CD8+) T-cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL-C and total cholesterol, as well as the HDL-C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL-C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL-C or other lipid variables. Serum HDL-C levels were significantly and negatively correlated with the (CD4+/CD8+) T-cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL-C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL-C levels are probably induced by the immune/inflammatory response in depression and (iii) there is impairment of reverse cholesterol transport from the body tissues to the liver.
We investigated the components of biological variation in serum soluble transferrin receptor (TfR) in relation to serum iron, transferrin (Tf), ferritin, soluble interleukin-2 receptor (sIL-2R), sIL-6R, and number of erythrocytes, haemoglobin (Hb), haematocrit (Ht), mean corpuscular volume (MCV), mean cell haemoglobin (MCH), and erythrocyte distribution width (RDW). We took monthly blood samples during 1 calendar year from 26 healthy subjects for assay of the above variables. The estimated CVs for TfR were interindividual CVg = 20.8%, and intra-individual CVi = 13.6%; for Tf, CVg = 14.4% and CVi = 6.7%; for iron, CVg = 16.8% and CVi = 29.2%; and for ferritin, CVg = 71.1% and CVi = 26.5%. There was a statistically significant seasonal pattern in the four variables with significant annual, biannual and/or trimonthly rhythms, which were expressed as a group phenomenon. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were: for TfR, 11.7%; for iron, 39.2%; for Tf, 11.7%; and for ferritin, 29.3%. Up to 34.2% of the within-subject variability in TfR (which reflects changes over time) could be explained by the regression on iron, ferritin, Tf, sIL-2R, sIL-6R and MCH values. Up to 67.2% of the between-subject variability in TfR (which reflects differences in the homeostatic setpoint during the study year) could be explained by the regression on gender, iron, Tf, and ferritin values.
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Strong evidence has recently been reported that major depression is accompanied by an acute phase response (APR), characterized by elevated levels of positive acute phase proteins (APPs) and decreased levels of negative APPs. The APR is also reflected in lowered total serum protein (TSP) and specific changes in the major electrophoretically separated protein fractions. The present study examined pretreatment and posttreatment serum TSP and the concentrations and percentages of the major electrophoretically separated serum protein fractions in 37 major depressed subjects, of whom 29 had treatment-resistant depression (TRD), and in 29 normal controls. We found that TSP and the percentage and concentration of serum albumin (Alb) and gamma-globulin fraction were significantly lower in major depression and TRD than in normal controls. Serum beta-globulin concentrations were significantly lower in major depressed and TRD subjects than in normal controls. The percentages of the alpha 1- and alpha 2-globulin fractions were significantly higher in major depressed subjects than in normal controls. There were no significant effects of subchronic treatment with antidepressants on TSP, the percentage or concentration of the major electrophoretically separated protein fractions, i.e. alpha 1-, alpha 2- and beta-globulin. There was a significant increase in percentage of the gamma-globulin fraction after subchronic treatment with antidepressants. The results support the hypothesis that major depression and TRD are accompanied by a chronic APR.
There is now some evidence that major depression is accompanied by biochemical and immune changes pointing to the presence of a chronic inflammatory response. The latter condition is reportedly characterized by changes in iron (Fe) metabolism and the erythron, such as decreased serum Fe and transferrin (Tf) and increased serum ferritin, lower number of red blood cells (RBC), lower hematocrit (Htc) and hemoglobin (Hb). The aim of the present study was to examine Fe metabolism and the erythron in 38 major depressed subjects versus 15 normal volunteers, as well as the effects of antidepressant treatments on these variables. Major depressed subjects had significantly lower serum Fe and Tf, a lower number of RBC, lower Htc and Hb, and a significantly increased number of reticulocytes than normal controls. Serum ferritin was significantly higher in major depressed patients with melancholia than in those with simple major depression and normal controls. Mean corpuscular volume (MCV), MC Hb (MCH), MC Hb concentration (MCHC) and RBC distribution width (RDW) were not significantly different between major depressed subjects and normal controls. Treatment with antidepressants during 5 weeks had no significant effect on the alterations in number of RBC and reticulocytes, Htc, Hb, Fe and Tf. There were significant relationships between the above Fe and erythron variables and established immune-inflammatory markers of major depression, e.g., lowered serum albumin and zinc and the increased electrophoretically-separated alpha 1-globulin fraction. The results suggest that the disorders in Fe metabolism and the erythron during major depression may be induced by the immune-inflammatory response in that illness.
Recently, it has been reported that major and melancholic depression are accompanied by a lower availability of total L-tryptophan (L-TRP) to the brain and by significant changes in electrophoretically separated protein fractions, such as albumin and alpha 2-globulin. The aim of this study was to examine the relationships between serum L-TRP availability and total serum protein, albumin, and alpha 2-globulin in 42 depressed and 24 normal subjects. In depressed and normal subjects, alone and together, there were significant and positive correlations between serum L-TRP and total serum protein or albumin concentrations. In the depressed subjects, but not in normal controls, there were significant inverse relationships between the L-TRP/competing amino acid ratio and the alpha 2-globulin fraction. Serum L-TRP and albumin were significantly lower in melancholic subjects than in normal and minor depressed subjects. Depressed subjects had a significantly lower L-TRP/competing amino acid ratio and significantly higher serum alpha 2-globulin than normal controls. Total serum protein was significantly lower in major depressed subjects than in normal controls. The results suggest that lower L-TRP availability to the brain in depression is related to lower serum albumin and to increased alpha 2-globulin fraction, which are both hallmarks of the acute phase response in depression. the results further corroborate the hypothesis that lowered L-TRP availability in depression is related to the acute phase response in that illness.
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The components of biological variation in serum vitamin E in relation to serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), apolipoprotein A-I (apo A-I), and apo B were examined in 26 healthy volunteers who had monthly blood samplings during one calendar year. The estimated CVs for vitamin E were: interindividual, 19.9%, and intraindividual, 11.9%; the index of individuality (I-index) was 0.59. The I-indices for all lipid variables were < 0.51. Serum concentrations of vitamin E, cholesterol, triglycerides, HDL-C, LDL-C, and apo B were lower in spring than in the other seasons. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were for vitamin E 14.5%, cholesterol 16.2%, triglycerides 14.5%, and LDL-C 24.3%. A significant common annual rhythm was expressed in vitamin E or lipid variables and in the changes in ambient temperature the weeks before blood sampling (inverse relations). There were highly significant positive time relations between serum vitamin E and cholesterol, triglycerides, and apo B. Subjects with higher homeostatic setpoints of cholesterol showed higher homeostatic setpoints of vitamin E, triglycerides, LDL-C, and apo B.
We investigated the components of biological variation, including seasonality, in plasma haptoglobin (Hp) levels and the relationships between plasma Hp and interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6), sIL-2R, fibrinogen (Fb) and absolute number of peripheral blood mononuclear cells, such as leukocytes, neutrophils, monocytes, lymphocytes, CD4+, CD8+, CD25+ T cells and CD20+ B cells. Monthly blood samples were taken from 26 normal volunteers during one calendar year. The estimated inter- and intra-individual C.V. values for plasma Hp were 27.9% and 20.0%, respectively; the index of individuality was 0.72. No significant seasonal rhythms could be detected in plasma Hp levels. The yearly mean values in plasma Hp were significantly and positively related to those in plasma Fb, absolute number of leukocytes, neutrophils, CD4+ T cells and the CD4+/CD8+ T cell ratio. 49.0% of the variance in the yearly mean values of plasma Hp could be explained by variances in serum IL-6 and number of CD4+ (positively related) and CD8+ (negatively related) T cells. There were significant and positive time relationships between plasma Hp, on the one hand, and plasma Fb, sIL-6R, sIL-2R and number of leukocytes, neutrophils and monocytes, on the other. A smaller part of the within-subject variability in plasma Hp (i.e. 6.0%) could be explained by serum sIL-6R and sIL-2R. It is concluded that there are (1) important between-subject differences in the homeostatic setpoints of plasma Hp, which are related to those in plasma Fb and in immune status and (2) significant within-subject, time relationships between plasma Hp and indicators of immune activation and plasma Fb.
Recently, it has been reported that major depression is accompanied by changes in plasma protein concentrations indicative of an acute-phase protein (APP) response. The purpose of the present study was to examine total serum protein (TSP) and the electrophoretically separated major fractions of serum proteins (SP), i.e., albumin (Alb), alpha 1, alpha 2, beta and gamma globulin, in depression. Highly significant differences were found in TSP and the separated SP fractions between major depressed patients and normal controls and between melancholic and minor depressed patients. Major depressed subjects showed significantly lower TSP and Alb concentrations and a higher percentage of the alpha 1 globulin fraction than normal controls and minor depressed subjects. Major depressed subjects had significantly higher and lower percentages, respectively, of alpha 2 and gamma globulin fractions than normal controls. In depressed subjects, there were significant negative correlations between TSP or Alb concentrations and severity of illness. Psychomotor retardation and anorexia were psychopathological correlates of lower TSP and Alb concentrations while middle insomnia and psychomotor retardation were related to changes in the alpha 2 globulin fractions. Basal plasma cortisol values were significantly and positively related to serum alpha 2 globulin. The results support the view that major depression is accompanied by an APP response.
This study has been carried out in order to examine the components of biological and, in particular, seasonal variation in hematologic measurements in normal humans. Toward this end, 26 normal volunteers had monthly blood samplings during one calendar year for determination of number of red blood cells (RBC) and platelets, hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), MC Hb (MCH), MC Hb concentration (MCHC), RBC distribution width (RDW), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), and plasma fibrinogen concentrations. The data were analyzed by means of spectral analyses of a group of time series or a single time series, and by means of repeated measures analyses of variance. Most of the hematologic variables show seasonal rhythms, such as annual rhythms or harmonics, which are expressed as a group phenomenon. An important part of the variance ( > 15%) in Ht, MCV, MCH, MCHC, RDW, number of platelets, MPV and plasma fibrinogen was explained by a yearly variation. The peak-trough differences (expressed as a percentage of the mean) in the yearly variations in number of RBC, Ht, MCV, MCH, MCHC and RDW were very low (all < 8.5%). Number of platelets (14.4%) and plasma fibrinogen values (28%) showed a high-amplitude yearly variation. All hematological variables, except MCHC, show a high interindividual variability which exceeds by far the intraindividual variability.
OBJECTIVE: To investigate the seasonal variation in levels of plasma L-tryptophan and competing amino acids (CAAs) in healthy humans in relation to climatic variables, total serum protein levels, and violent suicide occurrence. METHODS: Twenty-six healthy volunteers (13 men and 13 women; mean [+/- SD] age, 38.7 +/- 13.4 years) had monthly blood samplings for assays of L-tryptophan, valine, leucine, isoleucine, tyrosine, and phenylalanine during 1 calendar year. RESULTS: Significant annual rhythms were detected in L-tryptophan, the L-tryptophan/CAA ratio, phenylalanine, valine, and leucine, and semiannual rhythms in L-tryptophan values and in L-tryptophan/CAA ratios. Plasma L-tryptophan and the L-tryptophan/CAA ratio were significantly lower in the spring than in the other seasons. The peak-trough differences in the yearly variation expressed as a percentage of the mean were 17.1% and 16.1% for L-tryptophan values and L-tryptophan/CAA ratios, respectively. The amplitude of the yearly variation in all CAAs was low, ie, less than 7%. An important part of the variance in L-tryptophan availability (ie, 12% to 14%) could be explained by the composite effects of present and past climatic factors; higher ambient temperature and relative humidity in the face of lower air pressure are the most important predictors of low L-tryptophan availability. Important and positive time relationships were noted between total serum protein level and all amino acid concentrations, and a significant time relationship was also noted between the seasonal variation in L-tryptophan availability and the occurrence of violent suicide in Belgium. CONCLUSION: Our results show a bimodal seasonal pattern in the availability of plasma L-tryptophan that matches seasonal patterns in the prevalence of violent suicide in the local population and depression in other studies.
The last decade an increase has been seen in drug smuggling. Body-packing and body-stuffing are the terms used for intracorporeal concealment of illicit drugs (mainly cocaine and heroine, but sometimes also amphetamines and cannabinoids). These body-packets are especially prone to rupture. In order to avoid systemic cocaine toxicity, which can involve nearly every organ and therefore nearly every subspecialty of medicine urgent diagnosis is necessary. Obtaining a detailed history remains crucial. Further clues to diagnosis are given by the urinary drug concentrations and the benzoylecgonine/cocaine ratio in urine. Plain abdominal films, CT and contrast studies of the bowel can be helpful in identifying the package but are of limited value. In addition to activated charcoal, polyethylene glycol-electrolyte lavage solution, enteral feeding and laxatives (not paraffin) can be used to eliminate the body-package by enhancing bowel transit. Alkalinisation of gastric fluids enhances hydrolysis to cocaine's major inactive metabolite benzoylecgonine. If the package fails to progress through the gut or if mechanical obstruction occurs surgical removal is indicated. In no way endoscopic removal of the package should be attempted. Systemic symptoms should be treated by blocking the sympathetic overreactivity; this can be done with diazepam (Valium), labetalol (Trandate) or esmolol. Flumazenil (Anexate), lidocaine (Xylocaine) and pure beta-blockers like propranolol (Inderal) are to be avoided.
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We investigated the components of biological variation in plasma prolyl endopeptidase (PEP; EC 3.4.21.26) and dipeptidyl-peptidase IV (DPP IV; EC 3.4..14.5) activity in healthy individuals. We took monthly blood samples from 26 healthy volunteers for determination of plasma PEP and DPP IV activity during one calendar year. The estimated CVs for PEP activity were: total (CVt) = 25.0%, interindividual (CVg) = 13.9%, and intraindividual (CVi) = 16.8%. There was a statistically significant (P < 0.0001) seasonal pattern in plasma PEP activity, with significantly higher values in the fall than in the other seasons. The peak-trough difference in the yearly variation in PEP activity, expressed as a percentage of the mean, was as high as 56.8%. The estimated CVs for DPP IV activity were: CVt = 17.1%, CVg = 14.5%, and CVi = 8.2%. DPP IV activity was significantly (P < 0.0001) higher in summer than in the other seasons but the amplitude of the yearly variation was small.
A patient intentionally ingested an unknown amount of methanol and was admitted to the hospital 6 h later. On admission, the methanol concentration in blood was estimated as approximately of 134 mmol/L, based on the calculation of the osmolal gap. Intravenous ethanol administration and hemodialysis were promptly started. During hemodialysis, several blood samples were collected for determination of methanol and ethanol concentrations. Initially, we used gas chromatography with split-mode injection of pretreated serum samples; however, methanol concentrations turned out to be significantly lower than expected, based on calculated osmolal gap values. Because no explanation for the excess serum osmolal gap was apparent, we reanalyzed samples, using head-space gas chromatography. The methanol concentrations measured were significantly higher and osmolal gap values were no longer excessive.