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Bisalbuminemia is characterized by two albumin peaks in the electrophoresis of serum. There are different forms of bisalbuminemia: inherited and acquired. The acquired form is mainly transitory, whereas the familial form is permanent. The frequency of bisalbuminemia in the general population has been reported to be between 0.0003 and 0.01%. This paper presents a case of familial bisalbuminemia as well as the family tree-to the extent obtainable. A married couple, in which the husband had bisalbuminemia, had seven children and 18 grandchildren. Bisalbuminemia was also found in two children and in two grandchildren., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The aim of the study was to investigate the role of complement factor 5 (C5) in reactions elicited by plasma separation using blood from a C5-deficient (C5D) individual, comparing it to C5-deficient blood reconstituted with C5 (C5DR) and blood from healthy donors. Blood was circulated through an ex vivo plasma separation model. Leukocyte CD11b expression and leukocyte-platelet conjugates were measured by flow cytometry during a 30-min period. Other markers were assessed during a 240-min period. Granulocyte and monocyte CD11b expression did not increase in C5D blood during plasma separation. In C5DR samples granulocytes CD11b expression, measured by mean fluorescence intensity (MFI), increased from 10481 ± 6022 (SD) to 62703 ± 4936, and monocytes CD11b expression changed from 13837 ± 7047 to 40063 ± 713. Granulocyte-platelet conjugates showed a 2.5-fold increase in the C5DR sample compared to the C5D sample. Monocyte-platelet conjugates increased independently of C5. In the C5D samples, platelet count decreased from 210 × 10 9 /L (201-219) (median and range) to 51 × 10 9 /L (50-51), and C3bc increased from 14 CAU/mL (21-7) to 198 CAU/mL (127-269), whereas TCC formation was blocked during plasma separation. In conclusion, up-regulation of granulocyte and monocyte CD11b during plasma separation was C5-dependent. The results also indicate C5 dependency in granulocyte-platelet conjugates formation., (© 2018 APMIS. Published by John Wiley & Sons Ltd.)

Introduction: Bisalbuminemia is a qualitative disorder of albumin and it is defined by the coexistence in the same individual of two types of serum albumin with different electrophoretic mobility. There are two forms: hereditary and permanent, or acquired and transient., Case Report: Girl, 17-years-old, referenced to the hospital consult after incidental finding of bisalbuminemia detected in plasma protein electrophoresis performed within the investigation of diminished muscular tone in the lower limbs. Physical examination was normal. Secondary causes of bisalbuminemia were excluded. Later, it was confirmed the same disorder in plasma protein electrophoresis performed to her 14-years-old brother and mother., Discussion: We describe a rare case of hereditary bisalbuminemia in a portuguese family. In general, this condition shows no pathological significance, however it is of interest to the clinicians the knowledge of this analytic change for better orientation of their patients.

Objectives: To define the underlying cause of bisalbuminaemia in an individual presenting with spontaneous venous thrombosis., Method: Plasma was examined by electrospray time-of-flight mass spectrometry (TOF MS) to assess albumin mutations and to quantify variant expression level. Tryptic peptide mapping and DNA sequencing were used to precisely define the mutation., Results: Whole protein MS indicated a 19Da increase in the mass of 50% of the albumin molecules suggesting a His→Arg substitution. A novel heterozygous 510His→Arg mutation was identified by peptide mass mapping and confirmed by DNA sequencing of exon 12 of the albumin gene., Conclusion: The nature and location of the mutation suggest it would have no direct influence on haemostasis through altered warfarin binding or increased fibrinogen attachment and it appears to be incidental to the thrombotic phenotype. However the highly conserved His510 residue is recognised as being of critical importance in albumin recycling through interaction with its savaging neonatal Fc receptor. The normal albumin level of 41.1g/l and the coequal expression of albumin Lyon demonstrate that the conservative 510His→Arg substitution does not interfere with the pH dependant capture and release of albumin by the receptor., (Copyright © 2016. Published by Elsevier Inc.)

Fever of unknown origin (FUO) may be due to infection, malignancy, collagen vascular/inflammatory disorders, or other causes. Cytomegalovirus (CMV) infection is a rare cause of FUO in immunocompetent adults. We present a case of FUO due to CMV in an immunocompetent adult with polyclonal gammopathy on serum protein electrophoresis (SPEP).

Background: A girl suffering from a rare syndrome of unknown aetiology, termed hypercalprotectinaemia, was evaluated for tissue zinc status, because calprotectin is a protein which chelates Zn at multiple binding-sites, which might have affected the distribution of Zn in her body., Methods: Measurement of serum, urine, hair and nail zinc (Zn) concentration, complemented with measurement of total Zn in ultrafiltrates of plasma., Results: Her serum Zn concentration was 105-133 μmol/L. Zn levels in her hair (102 μg/g), nail (90 μg/g) and urine (3-12 μmol/L; 20-80 μg/dL) were all at the lower end of the reference intervals described in the sparse literature. Zn concentrations in ultrafiltrates of plasma were below the detection limit (<100 nmol/L). Thus, the elevated serum Zn did not translate into a similarly increased level of Zn in any of the tissues tested, nor in free Zn concentrations. Instead it appeared to be a result of Zn being chelated to binder proteins, most probably calprotectin., Conclusion: Her grossly elevated serum calprotectin concentration is probably able to raise circulating total Zn concentrations without raising ionized concentrations, but this Zn remains confined to the circulating blood as well as to excreted body fluids, particularly faeces.

Some variant proteins cause diseases, and some diseases result in increases of proteins with abnormally modified structures. The detection, characterization, and estimation of the relative amounts of protein variants and abnormally modified proteins are important for clinical diagnosis and for elucidation of the mechanisms of the pathogenesis of diseases. Analysis of the covalent structures of proteins using matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography-electrospray ionization MS (LC-ESI-MS), which had been developed by the early 1990s, have largely replaced analyses by conventional protein chemistry. Here, we review the detection and characterization of hemoglobin variants, HbA1c measurement, detection of carbohydrate-deficient transferrin, and identification of variants of transthyretin (TTR) and Cu/Zn-superoxide dismutase (SOD-1) using soft ionization MS. We also propose the diagnostic application of the signals of modified forms of TTR, that is, S-sulfonated TTR and S-homocysteinyl TTR. The relative peak height ratio of the abnormal/normal components gives valuable information about the instability of variants and enables the detection of unstable Hb subunits or thalassemia heterozygotes. We found unique modified structures of TTR that suggested changes in amyloid fibrils.

Unlabelled: Serum ferritin levels may be increased in many conditions: renal diseases, liver diseases, human immunodeficiency virus infection. The purpose of this study was to assess the aetiological spectrum of high serum ferritin levels in a 1200-bed university hospital, to compare our results with the data already published and to assess a potential association between aetiology and ferritin levels., Patients and Methods: Patients with a serum ferritin level higher than 600 microg/l were retrospectively included between 15 November 2003 and 15 January 2004, and their medical records were reviewed., Results: Ninety-eight patients (38 women and 60 men; median age: 59,5 years [19-92]) were recruited in departments of hepatology and gastroenterology (22%), haematology (14%) and internal medicine (18%). Diagnosis performed were: non-HIV systemic infections (23,8%), haematological diseases (16,1%), alcoholism (11,2%) and malignancies (9,8%). Dialysed chronic renal failure, liver diseases, haemochromatosis and systemic inflammatory diseases counted for 4.2 to 5.2% of cases. Serum ferritin level lied between 600 and 1000 microg/l for 50 patients, between 1000 and 1500 microg/l for 24, and over 1500 microg/l for 24. There was no significant difference between the three groups as regards the etiological distribution., Discussion: In our study, chronic renal failure was not a major cause of high ferritin level: this is probably due to the current use of erythropoietin, which has decreased the use of blood transfusions. The two major aetiology of hyperferritinemia were non-HIV infections and malignancies.

Albumin is the major circulating protein. It plays a fundamental role maintaining intra-vascular oncotic pressure and carrying many endogenous and exogenous substances. Variations of plasma albumin levels can be physiologic or pathologic and both qualitative and quantitative (more frequent) disorders are regrouped under the name "dysalbuminemia". Although hypoalbuminemia are frequent, analbuminemia exists but is a rare disease. Qualitative disorders, mainly bisalbuminemia, are benign. Detected fortuitously on sera protein electrophoresis, bisalbuminemia could be genetically transmitted, it will then be permanent, or acquired and then be transient. This article proposes to review main kind of dysalbuminemia usually encountered in clinical biology laboratories.

Purpose: To report an association between retinal vein occlusion and increased plasma levels of histidine-rich glycoprotein., Design: Observational case report., Methods: A 56-year-old woman presented with sudden and painless decrease of visual acuity of her right eye. Indirect ophthalmoscopy revealed retinal vein occlusion. She had experienced central retinal vein occlusion in this eye 6 years earlier., Results: The patient's medical history was negative for cardiovascular risk factors. Further investigation into possible causes revealed increased values for histidine-rich glycoprotein., Conclusions: When ordering laboratory tests in patients with retinal vein occlusion to rule out coagulation disorders, increased plasma levels of histidine-rich glycoprotein should be considered in the differential diagnosis. Selective screening may be helpful in identifying retinal vein occlusion patients with thrombophilic defects, especially in young individuals with recurrent retinal vein occlusion in the absence of recognized cardiovascular risk factors.

We have coevaluated a combination of test processes for diagnosing von Willebrand disease (vWD) and monitoring deamino-delta-D-arginine vasopressin (DDAVP) therapy. Using normal controls (n = 23), closure time (CT) ranges measured by PFA-100(R) were (mean +/- 2SD): (i) collagen/ADP cartridge (C/ADP): 67-127 s (ii) collagen/epinephrine (C/Epi): 94-162 s. From a panel of 125 patients undergoing evaluation for clinical haemostatic defects, 29/30 samples from patients with vWD [17/18 type 1, 1/1 type 3, 3/3 type 2A, 7/7 type 2B and 1/1 pseudo-vWD] gave prolonged CTs using C/Epi. The C/ADP was less sensitive, being normal in 7/18 of the type 1 vWD individuals, with higher sensitivity to more severe vWD. Individuals with haemophilia (six factor VIII-deficient, one factor XI-deficient) gave normal CTs, while those with clinical thrombocytopenia (n=13) gave normal or prolonged CTs, somewhat dependent on platelet count. The PFA-100 was also evaluated as a part of the laboratory monitoring procedure in patients with either vWD or haemophilia undergoing a DDAVP trial as a therapeutic management process. For vWD, correction of an initially prolonged CT by DDAVP, accompanied by normalization of von Willebrand factor (vWF) measurable by von Willebrand factor antigen, vWF collagen binding activity and vWF ristocetin cofactor assays (vWF:Ag, vWF:CBA and vWF:RCof), was achieved in type 1 vWD (n=5). In an individual with type 2A vWD, DDAVP normalized vWF:Ag and vWF:RCof, but had no apparent effect on the baseline maximally prolonged CT. In an individual with type 2B vWD, factor VIII/vWF concentrate also normalized vWF:Ag and vWF:RCof, but similarly had no apparent effect on the baseline maximally prolonged CT. vWF:CBA did not normalize for either of these individuals, potentially suggesting that normalization of vWF:CBA might be required for normalization of CT. This concept is supported by correlation analysis undertaken between CT and various vWF parameters. Among these, vWF:CBA held the strongest relationship in our data set, which showed an inverse progressive rise in CT for falling vWF:CBA. Based on these results, we would conclude that the PFA-100 is highly sensitive to the presence of vWD, and may thus provide a valuable screening test for vWD. Furthermore, the combined utility of the PFA-100 and vWF:CBA as markers of DDAVP responsiveness may prove to be simple, quick but powerful, predictors for its clinical efficacy.

The capabilities of capillary electrophoresis (CE) for serum protein electrophoresis and immunotyping have been demonstrated. CE-based systems specifically designed for serum protein electrophoresis and immunotyping via immunosubtraction (IS) are now available and are being evaluated for efficiency, specificity and sensitivity by several groups. The use of CE for serum protein electrophoresis and immunotyping (IS) in the clinical laboratory compares well with agarose gel electrophoresis (AGE) and immunofixation (IF) for the detection and characterization of monoclonal proteins. In addition to routine use, this technology is useful for a subset of serum samples that are difficult to interpret with conventional technology. In this study, sera abnormalities difficult to detect/interpret by AGE-IF are subdivided into four categories: (i) patients with polyclonal increases in immunoglobulin, (ii) point of application artifacts, (iii) abnormalities in the beta region, and (iv) patients with free light chains. CE is superior to AGE for evaluating samples characterized by the above abnormalities. Sera containing monoclonal proteins within a polyclonal increase are easier to detect by CE as well as being easier to type by IS than by IF. Point-of-application artifacts, periodically observed with AGE, do not exist on CE since the point of detection is remote from the point of application. Enhanced resolution in the beta region allows for increased detection of monoclonal proteins migrating in this region. Some free light chains are undetected by CE as a result of no apparent abnormalities on the CE serum protein profile and, thus, still require IF for detection. CE detects more serum electrophoretic abnormalities than AGE in this clinically important group of patients with Bence Jones proteinemia.

It has been suggested that angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is closely related to peripheral T cell lymphoma (PTCL). However, the clinical course of AILD-like PTCL is notoriously unpredictable. A minor portion of patients enjoyed prolonged remission with steroid-only treatments (indolent AILD) while most others died rapidly despite the use of intensive chemotherapy (aggressive AILD). Recently, it has been suggested that histological features such as the presence or absence of clear cells and convoluted cells are of high prognostic value. The validity of this observation was addressed in this study. Eighteen patients who presented between 1977 and 1994 at the National Taiwan University Hospital were retrospectively studied. There were 11 men and 7 women, with a median age of 47 years. Twelve patients had received various regimens of systemic chemotherapy, and the other 3 patients had been treated with steroids alone. Eight patients had indolent AILD and 6 aggressive AILD. The follow-up period in 4 patients was too short to be analyzed. The histopathology of these cases was divided, according to the criteria of Aozasa et al., into group I (neither cells), 4 patients; group II (only convoluted cells), 1 patient, and group III (clear cells with or without convoluted cells), 13 patients. Contrary to others, our data revealed that group III patients were doing better than group I patients. Univariate analysis of other pertinent clinical features, including sex, age, lymphadenopathy, B symptoms, hepatosplenomegaly, hypergammaglobulinemia, elevated serum lactate dehydrogenase, and treatment regimens, revealed none of them to be prognostically relevant. However, patients who had achieved complete remission by steroids or other systemic chemotherapy had a significantly better prognosis than those who had not. Together, these preliminary data suggested that (1) the presence or absence of clear cells and convoluted cells failed to predict the clinical behavior, and (2) induction of complete remission by steroids or other chemotherapeutic agents is an important prognostic index.

The activated protein C resistance (APC-R) ratios in 50 patients with steady state homozygous sickle cell (SS) disease and 59 healthy AA controls was measured. There was a significant reduction in median APC-R ratio in sickle cell disease compared to controls. This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants. However, the raised levels of factor VIIIC in SS patients in this study may be contributing to increased resistance to APC, which in turn may contribute to the vaso-occlusive complications of SS disease.

Trisomies 3, 5 and X in six Japanese patients with AILD were detected by fluorescence in situ hybridization (FISH). Trisomies 3 and X were detected using centromeric probes. Cosmid probes locating on 5q31.1, the commonly deleted region, was used to detect trisomy 5. FISH detected three patients with trisomy 3 alone, one with trisomy 5 alone and one with all the three trisomies analysed. The sample that showed all three aberrations was further analysed by dual color FISH. The three trisomies were present on different cells. The AILD cells with trisomy 5 tended to replicate slowly, whereas those with trisomy 3 seem to have a proliferative advantage. An increase in the histopathological stage was reflected in the increase in the percentage of trisomy 3 cells in one patient.

This is an original contribution on the first CZE in Austrian public and university hospitals. We are describing now the first results obtained with a new micro-method, namely CZE. Proteins are separated in microliter amounts by using 10,000 V and analyzed in a laser beam. 50 counts can be worked out per hour and immunoelectrophoresis replaced by subtraction CE. Dysproteinemias, double albuminemias, modifications of the haptoglobins, alpha-2 macroglobulin, transferin, complement system and the immunoglobulins can easily be detected and monoclonality revealed. No support except the capillary with buffer is necessary, no staining procedure required. The new system is rapid, reliable, cheap and reproducible, and allows us to replace more extensive forms of protein diagnosis such as the traditional electrophoresis and the immunoelectrophoresis or the immunoblotting.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is an atypical lympho-proliferative disorder with borderline features that often constitute a diagnostic challenge for the hematopathologist and a therapeutic dilemma for the treating clinician. Morphologically, the involved lymph nodes in this disorder are characterized by abnormal infilitration by immunoblasts and plasma cells, often in clusters or sheets. Regressed follicles may be seen; these are referred to as "burned out." Neovascularization is prominent, and a background of inflammatory cells is usually present. AILD was originally thought to represent an exaggerated autoimmune response. Because of the short median survival of the patients and the demonstration of T-cell clonality, AILD now is considered an aggressive lymphoma and is recognized as a subset of peripheral T-cell lymphoma by the REAL classification. In this article we present a patient with AILD who achieved durable partial remission after treatment with one cycle of 2-chlorodeoxyadenosine.

Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of two patients examined. Spontaneous production of IL-6 by LNMC was detected in all four patients studied. Immunosuppressive therapy with cyclosporin A (CsA) was attempted in a 68-year-old man, who was refractory to intensive combination chemotherapy. The increased level of IL-6 in this patient decreased to normal within 3 weeks of CsA administration and the patient became symptom-free. One and a half months later, the IL-6 level gradually increased along with clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4, IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but inhibited by CsA. These observations suggest that IL-6 is one of the important cytokines to be involved in the pathophysiology of AILD and CsA is a useful reagent for relieving symptoms.

Increased thyroxine (T4) binding to thyroid binding prealbumin (TBPA) or albumin causes a biochemical picture suggestive of thyrotoxicosis with increased total T4 (TT4). Previously described familial syndromes are characterized by increased binding of T4 to thyroid binding globulin (TBG), TBPA, or albumin. Increased T3 binding to TBG has been noted, but we are not aware of any kindreds reported with increased T3 binding to TBPA or albumin. We wish to report a family in which there is increased binding of T3 to TBG, TBPA and albumin. All family members were clinically euthyroid and tested negative for T3 antibodies. This family appears to demonstrate two abnormalities: first, elevated TBG, and second, normal levels of TBPA and albumin with increased binding of T3 and T4 to these proteins. We believe this may represent a new syndrome of familial dysproteinemia in which multiple proteins show enhanced binding of T3 and T4. This could reflect increased binding sites, increased binding affinity, or a combination of both.

Some unsolved problems--late onset of anemia and growth retardation (at age 7 years), healthy siblings showing very low transferrin (TF) level, and unexplained mode of inheritance--were found in family members of a congenital atransferrinemia already reported in 1972. The long-term clinical, laboratory, and developmental observations revealed that after 5 years of apo-TF supplementary therapy the patient's anemia gradually disappeared, and he started to grow again without further therapy. Immunoelectrophoretic study disclosed a severe deficiency of both TF and haptoglobin in the patient. The recovery from his anemia and the resumption of his physical development were dependent only on his TF level: that is, from a negligible level it increased to 10-20 mg/dl (normal, 205-370 mg/dl), a level similar to that of his TF-deficient siblings, who had been in good health since birth. The TF analysis of the patient and his family suggests that the minimum TF requisite in this family may be close to 10-20 mg/dl; subjects with more than 20 mg/dl are apparently healthy; with less than 10 mg/dl they may develop severe growth retardation and anemia, and extreme deficiency may be lethal. Also, coexisting haptoglobin deficiency might alleviate hemosiderosis. Further, the isoelectric focusing study disclosed that there was only a small amount of TF variant in these siblings including the patient. The study of the family confirmed that this variant was produced by an allelic gene derived from their father. So, the original diagnosis of congenital atransferrinemia should be revised as familial hypotransferrinemia transmitted with autosomal recessive mode, and the subjects with a recessive character may be compound heterozygotes of the "variant" allele and the "null" allele.

Dyslipoproteinemia is prevalent in women as well as in men. In both, its consequences--premature atherosclerosis and CAD morbidity and mortality--are more common. Although clinical evidence of the benefits of cholesterol lowering is less abundant in women, it is not entirely absent. As in men, cholesterol lowering in women is associated with a decline in CAD risk and with regression of coronary atherosclerosis. Lipoprotein risk factors have some special characteristics in women. Low-density lipoprotein cholesterol may be a less important risk factor in women, perhaps because estrogen protects the arterial wall against LDL deposition. High-density lipoprotein cholesterol is a better predictor of risk in women than in men. Triglycerides are an independent predictor of CAD risk in postmenopausal women. The effects of endogenous gonadal hormones in life-cycle changes in women is evident. As girls pass through puberty, HDL-C levels do not fall as they do in boys of the same age. In pregnancy, LDL-C, HDL-C, and triglyceride levels all rise. However, LDL-C stays elevated until well after delivery, whereas triglycerides fall to baseline at about the time of delivery, and HDL-C levels begin to fall at about 24 weeks. Interestingly, this fall in HDL-C is not accompanied by a fall in apoA-I levels, implying a change in HDL composition during the latter portion of pregnancy. After menopause, LDL-C levels rise sharply, whereas HDL-C levels decline modestly. Again, this decline in HDL-C is accompanied by a rise in apoA-I levels, implying a change in HDL composition. Diet, weight loss, and exercise are less effective in altering lipoprotein levels in women than in men. The reasons for this are not clear, although it is reasonable to speculate that endogenous gonadal hormones play a role. Genetic dyslipoproteinemia occurs in women, although the effect on CAD rates may be mitigated by the generally higher levels of HDL-C enjoyed by women. Exogenous hormones in the form of OCs and postmenopausal HRT affect circulating lipoprotein levels according to their composition. Generally, estrogens have favorable effects, raising HDL-C and lowering LDL-C levels. Progestins are either neutral or oppose estrogen effects, depending on their dose and androgenicity. Use of modern OCs probably does not adversely affect CAD risk except in combination with cigarette smoking. However, HRT has a strong favorable effect on CAD risk when unopposed estrogen is used, probably due to increases in HDL-C levels.(ABSTRACT TRUNCATED AT 400 WORDS)

A four-year-old Polynesian girl with a two-year history of severe microcytic, hypochromic anemia (which was refractory to iron therapy) had a decreased beta-globulin fraction on serum protein electrophoresis, resulting from the absence of the transferrin (TRF) band. Subsequent assays for TRF showed a level below the detectable range. Liver biopsy revealed significant deposition of hemosiderin within hepatocytes and Kupffer cells, in addition to early fibrosis. Two bone marrow aspirates were hypercellular, with decreased myeloid-erythroid ratios. This case represents the eighth reported example of congenital atransferrinemia, a rare, apparently autosomal recessive disease.

The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis.

During the past ten years we have identified in five girls a previously unreported hereditary metabolic disease with severe neurologic involvement. A common defect in the carbohydrate structure of serum glycoproteins could be demonstrated. This disease illustrates the great challenge that metabolic diseases are for pediatrics. Their number is very large and increases steadily; most of them can not yet be treated efficiently, and nearly all these disorders are hereditary. These and other features make a national and international approach necessary.

To evaluate a new ultrafiltration-fluorescence polarization immunoassay (FPIA) for monitoring blood levels of unbound phenytoin, the drug, with or without a 14C label, was added to three serum pools obtained from normal, uremic, and hypoalbuminemic patients and to 10 individual patient sera that varied greatly in phenytoin binding (11-50%). Protein-unbound phenytoin fractions were obtained from the sera by ultrafiltration using the Amicon Micropartition System and by a classic equilibrium dialysis method. The percent unbound phenytoin in each serum was determined by a radioassay and an automated FPIA (TDx System). An analysis of variance revealed no significant difference in the percent unbound phenytoin obtained at 37 degrees C by the FPIA and radioassay methods (alpha = 0.05). The data indicate that the ultrafiltration system can be combined with FPIA to produce a convenient laboratory method for routine therapeutic drug monitoring that gives results comparable to the equilibrium dialysis, radioassay reference method.

The measurement of body/venous haematocrit ratio has been assessed in 329 cases, in order to study the degree of error if the total blood volume were calculated from the red cell or plasma volume, using a pre-established correction factor. Three facts are clear from this study: (1) the ratio (correction factor f) is slightly lower than in the previous published data; (2) in polycythaemic and normal subjects, a low dispersion of the results around the mean value makes the potential error very low in all the cases; (3) in patients with an enlarged spleen, with anaemia and with dysproteinaemia, the large variation from case to case of the body/venous haematocrit ratio could cause large errors in determining total blood volume when using such a simplified method.

An aqueous solution of 66 per cent ethanol and 6.6 per cent ammonium acetate has been used in the development of a relatively simpler and rapid as well as highly reproducible method of separation of antibody-bound and free hormones in the radioimmunoassay of human growth hormone (HGH). The present assay is sensitive to detect 20 pg. of hormone with a precision of plus or minus 5 per cent, hence, as little as 20 mul of plasma is required to perform the radioimmunoassay. Serum levels of HGH have been found to be approximately 70 per cent of the plasma concentrations in the same subjects.

The distribution of tetracycline into human red blood cells was studied in vitro at 37 degrees. The drug was taken up rapidly by the cells, and its distribution equilibrium was reached after approximately 10 min of incubation. The steady-state distribution ratio of the drug between the red cells and extracellular fluid of 0.9% NaCl solution was 2.84, while the distribution ratio between the cells and the plasma solution was 0.9. The reduced cellular uptake in plasma was due to binding of the drug to plasma components. Calcium ions in plasma appeared to reduce tetracycline uptake by the red cells. The red cell distribution of tetracycline in dogs was in close agreement with the in vitro data using the washed human red cells. A dog suffering from severe hypoalbuminemia showed greater uptake of the drug by the erythrocytes, while a normal healthy dog exhibited the red cell-plasma distribution ratio of 0.98. The release rate of tetracycline from the preloaded cells into normal saline solution indicated that the release was directly proportional to the cellular concentration of the drug; the first-order release rate was approximately 1.38 hr-1.