Hereditary spherocytosis and other hemolytic anomalies distort diabetic control by glycated hemoglobin.

Glycated hemoglobin (%HbA1c) has become a well established and reliable long term parameter indicative of the mean glucose load of the preceding 8 -10 weeks. A normal life span of approximately120 days of the red blood cells (RBC) is an essential condition. Hemolytic affections are characterized by a shorter life span, reducing the overall glucose uptake and %HbA1c. Measured %HbA1c is no longer correlated with mean blood glucose of the preceding period, simulating false low values. Underestimation of this kind is demonstrated for several hemolytic conditions, among them hereditary spherocytosis (HS). This latter, often harmless anomaly may lead to serious underestimation of glucose load. Recent investigations show not only a much higher incidence of HS than hitherto admitted (approximately 1 in 250 persons) but also an abnormally high incidence of diabetes in this hemolytic affection. In the presence of hemolysis %HbA1c is to be interpreted with caution. This justifies systematic detection of HS in routine hematology using--if available--the increase of the percentage of hyperchromic RBC.

Hereditary spherocytosis veiled by anemia and iron deficiency.

Permanent significant hyperchromia, equivalent to hyperspherocytosis, the leading symptom of hereditary spherocytosis (HS), has become accessible to routine screening by hematologic automats using double angle laser technology. This has resulted in the discovery of a much higher incidence of this anomaly. In previous investigations we suggested the permanence of significant hyperchromia as obligate criterion for the diagnosis HS. Intercurrent normal percentages of hyperchromic RBC rather pointed to secondary, non-hereditary spherocytosis. Describing 6 typical cases, we demonstrate that occasional normal percentages of hyperchromic red blood cells occurring during phases of anemia and/or iron deficiency are compatible with the diagnosis of HS.

HbSC hemoglobinopathy suspected by chest x-ray and red blood cell morphology.

Thorax scan was performed for elucidation of a pulmonary problem in a Nigerian immigrant. The aspect of the vertebrae suggested sickle cell disease, of course without specification of the genotype. Routine hematological tests seemed compatible with an HbSC disease, showing typical laboratory features, namely a significant proportion of hyperchromic RBC, corresponding to secondary, non hereditary spherocytosis, presence of numerous target cells and occasional HbC crystals on Pappenheim stained blood films. The diagnosis of HbSC disease was confirmed by HPLC, iso-electric focusing and citrate agar electrophoresis of hemoglobin and by reverse phase HPLC of globin-chains. This case illustrates the importance of screening for hemoglobin anomalies as it is performed in a multiethnic country such as the Grand Duchy of Luxembourg

[Economic assessment of iron deficiency. Replacement of ferritin and serum iron by other parameters]. / Mise en évidence économique d'une déficience en fer. Relève de la ferritine et du fer sérique par d'autres paramètres.

Economic assessment of iron deficiency. Replacement of serum iron and ferritin by other parameters. Serum iron and ferritin are still widely used parameters for the assessment of iron deficiency, in spite of their poor diagnostic performance. Compared to the combined use of ferritin, zinc protoporphyrin and soluble transferrin receptors an increase of the percentage of hypochromic erythrocytes (PEH) was found to be highly sensitive and specific for iron deficiency. We suggest to use it in a two phase strategy. Normal PEH excludes iron deficiency. Increased PEH may be confirmed by zinc protoporphyrin and/or soluble transferrin receptors.

Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit ?

A group of 100 totally or subtotally myeloperoxidase (MPO)-deficient individuals was compared to a reference population of 118 probands selected at random. Data for a protective effect of the deficiency against cardiovascular damage are presented. On the other hand, a significantly higher occurrence of severe infections and chronic inflammatory processes was noted among the deficient patients. An increased incidence of cancer among the MPO-deficient individuals was not demonstrated.

Screening for total and partial eosinoperoxidase deficiency by flow cytometry: prevalence in a general population, pathology and genetic implications.

The ADVIA (Bayer) haematological system differentiates leukocytes by their volume and their peroxidase (MPO and EPO) activity. It thus allows specific counting of the eosinophils and detection of totally EPO and MPO deficient individuals. EPO activity is determined by the coordinates of the eosinophil cluster on the outprint. A reliable method of quantitation by simple angle measure is suggested. It allows recognition of partial deficiencies. Among approximately 100,000 persons, 29 cases of total EPO deficiency were detected. No typical or specific pathology of the defect was noted. Family studies showed heterozygous parents and offspring to be partially deficient. The frequency of these partial deficiencies in the general population is studied. The results exclude a simple autosomal recessive monogenic transmission of the defect. A model for bigenic transmission is suggested.

The urine test strip of the future.

The aim of the classical multiple test strip is to perform routine chemical analysis in one single operation, yielding maximum diagnostic and prognostic information. A maximum of 10 test areas should not be exceeded. The efficiency of the currently marketed test strips is discussed and improvements within acceptable price limits are suggested.

Influence of urea on HbA1c-determinations by Menarini HA-8140 and on the difference between immunoturbidimetric and HPLC-HbA1c-results.

A secondary peak (#C) included in the HbA1c-calculation by the HA-8140 HPLC (Menarini) shows a fairly good correlation with serum urea. The correlation with HbA1c and with serum glucose is at first glance significant but reveals at a closer look being biased by some incorrect assumptions. The difference between immunoturbidimetric determination (Tinaquant HbA1c II Roche) and HPLC shows a similar behaviour to urea as does the #C-peak of the chromatographic separation. This peak as well as the difference between both determinations of HbA1c could be attributed to carbamylated haemoglobin. The definitive identity has to be proven. This peak could be a monitoring tool for long-time urea. The integration of this peak into total HbA1c by the HA-8140 (Menarini) can lead to a false diagnosis of diabetes in non-diabetic patients with elevated urea.

Quality specifications for ordinal scale measurements with multiproperty (multiple) urine test strips.

Analytical quality specifications for ordinal scale measurements have not been presented so far. Criteria are suggested for multiproperty (multiple) urine test strips based on upper limits of healthy reference intervals, analytical performance and statistical tests applicable to ordinal scales. Trueness (accuracy) can be evaluated against an acceptable comparison method by applying sensitivity and specificity concepts, and defining a grey zone with a lower detection limit and an upper confirmation limit. Concordance (agreement) of two or more ordinal scale categories should be evaluated by subtracting random agreement, using Kappa statistics. Repeatability (precision) can be calculated for categorized results using binomial statistics.

Prevalence of myeloperoxidase deficiency: population studies using Bayer-Technicon automated hematology.

The Bayer-Technicon hematological devices differentiate leukocytes by their peroxidase activity and their volume, displaying them as separate clusters. Peroxidase deficiencies are manifested by the irregular location of these clusters. This makes it possible to identify persons totally or partially lacking myeloperoxidase. The deficiency is quantified by the myeloperoxidase index, which is expressed for every routine analysis and for which normal values were determined. Values of the myeloperoxidase index confirm varying degrees of deficiency and prevalence. Family studies using these degrees show that the hereditary pattern must be more complicated than the classical autosomal-recessive mode. A bigenic mode is suggested. While about half of the totally deficient individuals detected were free of typical symptoms, in the other half we found infectious complications that were sometimes life-threatening. The hematological devices allow the identification of persons suffering from eosinoperoxidase deficiency and from MPO deficiency of the monocytes. The latter symptom seems to indicate immaturity of these cells and may lead to unexpected diagnosis of malignancy.

Dry chemistry urinalysis of pathological proteinuria.

The paper presents a review of the characteristics and analytical performance of the most current dry chemistry methods for detection and estimation of the different urinary proteins. Description of the classical "protein error" dipsticks for macroalbuminuria is supplemented by data on more sensitive alternatives based on the same principle, reaching into the zone of microalbuminuria. Immunological test strips are available for detection of low concentrations of albumin. Application of the same principle is attempted for detection of other specific proteins. Highly sensitive enzymatic reactions allow detection of "lysis proteins": haemoglobin, leukocyte esterase and beta-N-acetyl-glucosaminidase. An efficient strategy for screening for all types of pathological proteinuria based on detection of low albumin levels is presented.

Multicentre evaluation of the urine analyser Miditron Junior.

A multicentre evaluation of the urine analyser Miditron Junior was performed at four laboratories. The Miditron Junior analyser provides semi-quantitative results for erythrocytes, bilirubin, urobilinogen, ketone bodies, glucose, protein, nitrite, leukocytes, pH and relative density. Accuracy of the Miditron Junior analyser was evaluated by comparison to quantitative analytical chemistry methods (glucose, total protein), physical methods (pH, relative density), and microscopic methods (erythrocytes, leukocytes). Agreement was defined as identical or neighbouring concentration block. The level of agreement found with chemical, physical or microscopic methods for the six analytes tested varied from 79 to 99%. The within-run precision was determined as repeatability by using 31 native urines. The results of repeated measurements (n = 10) fell in the same concentration block, or in case of borderline concentration were spaced between two adjacent colour blocks. Day-to-day precision covering a minimum of 20 days using commercially available control solutions yielded results within +/- one colour block from the mean.

Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria.

OBJECTIVE: To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS: Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS: For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of < 10 degrees C led to lower readings. In the case of samples with massive leucocyturia and erythrocyturia that may delete the chromatographic process, waiting an additional 1-2 min is needed before reading. CONCLUSIONS: The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.

A simple and inexpensive screening test for low protein levels in urine.

Nigrosin binds to proteins yielding a dark blue complex. This reaction is used for detecting low protein concentrations in urine by applying spots of urine to cellulose acetate strips which are coloured by nigrosin. The intensity of coloured spots remaining after washing of the strips indicates protein concentration. With a cut-off at 50 mg protein/l, the test offers an excellent possibility for first line screening for microalbuminuria at lowest cost.

A case of total peripheral aneosinophilia associated with complete deficiency of myeloperoxidase.

Complete and permanent absence of peripheral eosinophilic granulocytes was observed in a patient also presenting with total myeloperoxidase deficiency. The anomaly was suspected because of complete absence of the eosinophilic cluster in the display of a H*3 Technicon hematological automate and was confirmed by traditional staining of more than 100,000 leukocytes. A severe infectious problem during adolescence could be related to MPO deficiency in this patient. No specific disorder attributable to aneosinophilia was however observed subsequently.

A case of eosinophil peroxidase deficiency.

A case of eosinophil peroxidase deficiency is described after fortuitous detection by the H*3 Technicon hematological analyzer. From the cytochemical aspect total deficiency is admitted. The abnormality is thought to be extremely rare in a well-mixed population as exists in the Grand-Duchy of Luxembourg.

[Urine analysis in the physician's laboratory]. / Urinanalytik im Arztlabor.

The practitioner who wants to perform urinalysis by means of rapid tests either in his office or at the bedside is informed of the available possibilities. Directives for the choice of appropriate reagents and for their interpretation are presented.