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Biomedical subjects

W Stein

Publications and source records attributed to W Stein.

At least 19 recordsLinked to original sources

Simple computer-assisted diagnosis of acute myocardial infarction in patients with acute thoracic pain.

In order to minimize the initial diagnostic uncertainty in patients suspected of having acute myocardial infarction, we prospectively extracted predictive variables from previous history, ECG, and clinical chemical parameters of 87 patients, who were admitted for acute thoracic pain. The variables thus extracted were: Thoracic pain in previous history, duration of pain, white blood cell count, blood glucose, creatine-kinase, and S-T elevation in the ECG. These parameters were used for formulating a mathematical model based upon univariate and multivariate statistical methods. The sensitivity of the model in the study population was 95% and the specificity 77%. Correct classification was achieved in 89% of cases. In a second phase, the prognostic index was prospectively evaluated in a second set of 122 consecutive patients. In this test population, the sensitivity was 89% and the specificity 86%. 87% of patients were classified correctly.

Adult

Infradian rhythms of alanine aminopeptidase excretion during gentamicin therapy.

Urinary excretion of alanine aminopeptidase (EC 3.4.11.2) was examined in 30 patients (22 women, 8 men, range 38-81 years; mean age 55.4) receiving gentamicin in a therapeutic dosage, which was based on the monitored blood creatinine concentration. In general, therapy lasted 10 days. The excretion of 24 individuals displayed significant infradian rhythms with periods between 2.2 and 8.1 days. In 10 of these 24 patients (42%) a circaseptan period was detected. The high portion of circaseptan rhythms might have been induced by the detrimental effects of gentamicin on the proximal tubule and the resulting processes of reconstitution.

Adult

Reference ranges for alpha-amylase in serum and urine with 4,6-ethylidene-(G7)-1-4-nitrophenyl-(G1)-alpha,D-maltoheptaoside as substrate.

Reference ranges for alpha-amylase in serum, spontaneously voided urine, and 24 h urine were determined, using 4,6-ethylidene-(G7)-1-4-nitrophenyl-(Gl)-alpha,D-maltoheptaoside as the substrate (EPS method), at 25, 30, and 37 degrees C. The measured values were evaluated with and without the use of a factor which converts the results of the alpha-amylase EPS method into values comparable to those obtained with the alpha-amylase PNP method (substrate: 4-nitrophenyl-alpha,D-maltoheptaoside); comparison with the established reference ranges of the PNP method was therefore possible. The values for urine sometimes deviated markedly from the PNP reference ranges, but the values for serum showed close agreement. With the use of the conversion factor, the following reference ranges are proposed for the new alpha-amylase method: Serum (186 males and 131 females): up to 120 U/l (25 degrees C), up to 160 U/l (30 degrees C), and up to 220 U/l (37 degrees C). Spontaneously voided urine: up to 600 U/l (n = 323, 25 degrees C), up to 800 U/l (n = 373, 30 degrees C), and up to 1000 U/l (n = 373, 37 degrees C). 24 h urine: up to 450 U/24 h (n = 90, 25 degrees C), up to 650 U/24 h (n = 129, 30 degrees C), and up to 900 U/24 h (n = 129, 37 degrees C).

Adolescent

Evaluation of a new alpha-amylase assay using 4.6-ethylidene-(G7)-1-4-nitrophenyl-(G1)-alpha-D-maltoheptaoside as substrate.

The determination of alpha-amylase activity using an ethylidene-blocked 4-nitrophenyl-maltoheptaoside (EPS) has been evaluated in five laboratories on eight different analysers at 25 degrees C, 30 degrees C and 37 degrees C. The protecting ethylidene group inhibits hydrolysis at the non-reducing end of the substrate molecule by the auxiliary enzyme, alpha-glucosidase. The combined reagent is therefore stable for at least 10 days at 2-8 degrees C. HEPES is used, because the molar absorbance of 4-nitrophenol is independent of temperature in the presence of this buffer. Compared with the method using unprotected substrate 4-nitrophenyl-alpha-D-maltoheptaoside (4NP-G7), the present method is equal or better with respect to the imprecision, linearity and interlaboratory transferability of results in human and control sera. Since the protected and unprotected substrates differ in their turnover rate, the new assay yields activities which differ from those of the 4-nitrophenyl-alpha-D-maltoheptaoside method. Based on the homogeneous results obtained in method comparisons between EPS and 4-nitrophenyl-alpha-D-maltoheptaoside, and in order to maintain the 4-nitrophenyl-alpha-D-maltoheptaoside reference values, a conversion factor was derived to eliminate the above differences: activityEPS x 2.50 = activity4NP-G7. The temperature and instrument independence of this relationship was demonstrated in a total of 720 human sera and plasmas.

Glucosides

A comparison of the actions of noradrenaline and UK-14,304 in the longitudinal smooth muscle of the rat isolated portal vein--no evidence for a population of post-junctional alpha 2-adrenoceptors.

The pharmacological characteristics of post-junctional alpha-adrenoceptors mediating contractions of the longitudinal smooth muscle of the rat isolated portal vein have been examined. Responses to the noncumulative addition of either noradrenaline, or the selective alpha 2-adrenoceptor agonist UK-14,304, were equally sensitive to a low concentration (0.005 mumol/l) of prazosin. Idazoxan (0.1 mumol/l-0.5 mumol/l), a selective alpha 2-adrenoceptor antagonist, was less potent than prazosin against both agonists. The combination of 0.1 mumol/l idazoxan and 0.125 mumol/l prazosin failed to produce a greater inhibition of responses to UK-14,304 than 0.125 mumol/l prazosin alone. A study involving the effect of various antagonists against a single concentration producing a submaximal response to UK-14,304, provided evidence for a prazosin-resistant component of responses which was sensitive to phentolamine. This component could, therefore, be attributed to an alpha-adrenoceptor. However, this particular response could not be ascribed to stimulation of an alpha 2-subtype since the selective alpha 1-adrenoceptor antagonist, corynanthine, produced greater inhibition than the selective alpha 2-adrenoceptor diastereoisomer rauwolscine.

Animals

Multicenter evaluation of a specific pancreatic isoamylase assay based on a double monoclonal-antibody technique.

Eleven evaluators from nine laboratories in five countries evaluated a new immunoinhibition method for pancreatic isoamylase determination that is as simple to perform as that for total amylase. The precision at low and intermediate activity concentrations was superior, and at high concentrations it equalled that of the wheat-germ inhibitor method. The test was linear to approximately 2000 U/L, depending on the instrumentation used. The percentage salivary isoamylase activities remaining in specimens after reaction with two monoclonal antibodies ranged from 2 to 4.4%. Comparative studies showed good correlation with the wheat-germ inhibitor (r greater than 0.978) and electrophoresis methods (r = 0.920). Hemolysis, lipemia, and bilirubinemia have no effect on results. Interlaboratory studies demonstrated excellent transferability of the method, if instruments are calibrated with the same calibrator. Reference intervals for pancreatic isoamylase are 13 to 64 U/L (25 degrees C), 13 to 83 U/L (30 degrees C), and 17 to 115 U/L (37 degrees C). A clinical evaluation of patients with acute pancreatitis showed that pancreatic isoamylase has a greater clinical sensitivity than total amylase.

Acute Disease

The fetal phenotype of the 18p-syndrome. Report of a male fetus at twenty-one weeks.

Morphological and cytogenetic findings in a male fetus at 21 weeks gestation after prenatally detected monosomy 18p are reported. The fetus displayed dysmorphic features resembling the 18p-syndrome, such as decreased head circumference, slightly receding forehead, hypertelorism, epicanthus, horizontal palpebral fissures, depressed nasal bridge, long philtrum, carp mouth, irregular crenated maxillar alveolar ridge, retrognathia, lowset dysplastic ears with posterior rotation, edema of neck, hands and feet respectively, fingers with drop-shaped tips, short first toes with dysplastic nails, hypoplastic male external genitalia. After termination of the pregnancy, biopsies from different fetal organs as well as from the placenta were taken and set up for long term cell cultures. The metaphases of fetal organs all showed the karyotype 46,XY,18p-. A fetal blood culture failed to grow. Unexpectedly, the metaphases of the placenta showed the mosaic karyotype 46,XY/46,XY,18p-/46,XY,18p+.

Chromosome Aberrations

Clinical chemistry.

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Chemistry, Clinical

Macro lipase--a new member of the family of immunoglobulin-linked enzymes.

This first report describes a variant form of lipase in the serum of a woman suffering from a malignant non-Hodgkin lymphoma. Activity measurements of serum lipase and amylase showed persistently elevated activities of lipase with simultaneously normal activities of amylase. Results of exclusion chromatography and immunological investigations clearly demonstrate that the atypical time-course of lipase activity is not due to injury of the pancreas or alterations of the patient's lipase, but rather due to the presence of lipase-binding autoantibodies, resulting in the formation of immune complexes with high molecular mass (Mr greater than 200,000) between lipase and immunoglobulin G lambda. A clinical significance, if any, of this macro lipase has yet to be determined.

Antigen-Antibody Complex

Indices for the age of the creatine kinase M-chain in the blood.

The apparent activation energy of the CK reaction as well as the Michaelis-Menten constants and the isoelectric point of CK MM can be used as indices for the mean age of the CK M-chain in the blood in vivo and in vitro. Modifications in the CK M-chain take place in vivo in the blood and in vitro in a serum matrix. Gradual increases in the apparent activation energy are also observed both in vivo and in vitro. It is confirmed that the modification in the CK M-chain causes a rise in the apparent activation energy, mu. A gradual increase in apparent activation energy, due to the ageing process of the CK M-chain, was observed after myocardial infarction. A significantly increased value for u was observed at the time that total CK activity already had returned to reference values. In spite of the normal CK value, the apparent activation energy still indicated that there had been myocardial damage. The Michaelis-Menten constants for creatine phosphate and ADP are also influenced significantly by the modification in the M-chain. While the apparent activation energy increases, the Michaelis constants decrease in the order MM3, MM2, MM1. The Michaelis-Menten constants for both ADP and CrP can be used as an index for the mean age of the enzyme in the blood. The Michaelis-Menten constants for CrP and ADP show significant variations with the measuring temperature for virtually all CK MM forms.

Creatine Kinase

Influence of autoantibodies to creatine kinase-BB on assays for MB isoenzyme.

We describe the influence of autoantibodies that bind creatine kinase BB (CK-BB) on the methods for MB isoenzyme. If these autoantibodies are present in patients' sera, they cause the formation of macro CK type 1 (immunoglobulin-linked CK-BB). In some of these cases they can bind not only endogenous CK-BB but also CK-MB without significantly affecting enzyme activity. Although these antibodies show distinctly less affinity for CK-MB than for CK-BB, they nevertheless bind CK-MB in these particular sera, because their concentration exceeds that of CK-BB isoenzyme. If a person with such autoantibodies has an acute myocardial infarction, the immunoinhibition method for CK-MB, which does not discriminate between CK-MB and CK-BB, will recognize the increase and peak of CK-MB with time, although persistent macro CK activity will be superimposed on the typical isoenzyme pattern. However, isoenzyme electrophoresis and recently introduced immunoenzymometric assays for CK-MB in these cases may be less sensitive for detecting myocardial infarctions, because the typical increase in CK-MB activity may be identified later in the progression of symptoms, or even be missed.

Autoantibodies

Analytical patterns and biochemical properties of macro creatine kinase type 2.

Here we describe our findings for 105 patients' sera containing macro creatine kinase (CK) type 2, as confirmed by exclusion chromatography. Depending on the technique used for determining isoenzyme CKs (electrophoresis, ion-exchange chromatography, immunoinhibition), this variant CK shows characteristic patterns and interferes in CK-MB assays by different mechanisms and to various degrees, thus complicating test interpretation. Macro CK type 2 evidently is not of cytoplasmic origin; rather it is a separate CK activity of human serum, characterized by its heat stability and, especially, by its increased molecular mass and high energy of activation. These latter characteristics have never been associated with the normal-size, dimeric cytoplasmic CK isoenzymes, but are typical for mitochondrial CK isolated from human tissues. We conclude that mitochondrial CK released after severe cell damage usually appears in blood in macromolecular forms (macro CK type 2), not in a dimeric form.

Chromatography, Gel