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Biomedical subjects

H M Goldschmidt

Publications and source records attributed to H M Goldschmidt.

At least 19 recordsLinked to original sources
PubMed2001

Analytical performance of a direct assay for LDL-cholesterol.

We evaluated a direct assay for the determination of LDL-cholesterol (LDL-C) L-Type assay, Wako Pure Chemicals in two laboratories. This assay is applicable to most random access clinical chemistry analyzers, allowing full automation. Between-run coefficient of variation (NCCLS EP5) varied between 1.29% and 3.13% and thus met the National Cholesterol Education Program (NCEP) goal. The assay was considered linear over a physiologically relevant range of LDL-C, 2.22 to 7.04 mmol/l (NCCLS EP6). Method comparison yielded identical results at both evaluation sites for LDL-C when assayed with the direct method. LDL-C results obtained with the homogeneous method under investigation (y) differed significantly from values from density-gradient ultracentrifugation (x) according to Chung (y = 0.87x + 0.43 mmol/l, s(yx) = 0.38 mmol/l, r = 0.91). With the latter method as a reference method, mean bias was 3.16% meeting the NCEP criteria. Diagnostic performance was excellent at a clinically relevant cut-off level of 3.37 mmol/l. Results of the direct method (y) and the commonly used Friedewald formula (x) were highly correlated (s(yx) = 0.22 mmol/l, r = 0.97), but both slope and intercept differed significantly from one and zero respectively (y = 0.90x + 0.37 mmol/l). Bilirubin, hemolysis and ascorbate did not interfere; triglycerides did not cause clinically relevant interference below 11.3 mmol/l. The direct method we investigated is user-friendly and provides an improvement in the determination of LDL-C in routine laboratories.

Apolipoproteins B↗
PubMed2001

Infrared analysis of urinary calculi by a single reflection accessory and a neural network interpretation algorithm.

BACKGROUND: Preparation of KBr tablets, used for Fourier transform infrared (FT-IR) analysis of urinary calculus composition, is time-consuming and often hampered by pellet breakage. We developed a new FT-IR method for urinary calculus analysis. This method makes use of a Golden Gate Single Reflection Diamond Attenuated Total Reflection sample holder, a computer library, and an artificial neural network (ANN) for spectral interpretation. METHODS: The library was prepared from 25 pure components and 236 binary and ternary mixtures of the 8 most commonly occurring components. The ANN was trained and validated with 248 similar mixtures and tested with 92 patient samples, respectively. RESULTS: The optimum ANN model yielded root mean square errors of 1.5% and 2.3% for the training and validation sets, respectively. Fourteen simple expert rules were added to correct systematic network inaccuracies. Results of 92 consecutive patient samples were compared with those of a FT-IR method with KBr tablets, based on an initial computerized library search followed by visual inspection. The bias was significantly different from zero for brushite (-0.8%) and the concomitantly occurring whewellite (-2.8%) and weddellite (3.8%), but not for ammonium hydrogen urate (-0.1%), carbonate apatite (0.5%), cystine (0.0%), struvite (0.4%), and uric acid (-0.1%). The 95% level of agreement of all results was 9%. CONCLUSIONS: The new Golden Gate method is superior because of its smaller sample size, user-friendliness, robustness, and speed. Expert knowledge for spectral interpretation is minimized by the combination of a library search and ANN prediction, but visual inspection remains necessary.

Adolescent↗
PubMed2000

Evaluation of LabRespond, a new automated validation system for clinical laboratory test results.

BACKGROUND: Manual validation of laboratory test results is time-consuming, creating a demand for expert systems to automate this process. We have started to set up the program "LabRespond", which covers five validation levels: administrative, technical, sample, patient, and clinical validation. We present the evaluation of a prototype of an automated patient validation system based on statistical methods, in contrast to the commercially available program "VALAB", a rule-based automated validation system. METHODS: In the present study, 163 willfully altered, erroneous test results out of 5421 were submitted for validation to LabRespond, VALAB, and to a group of clinical chemists (n = 9) who validated these test results manually. The test results rejected by three or more clinical chemists (n = 281) served as a secondary reference standard. RESULTS: The error recovery rates of clinical chemists ranged from 23.9% to 71.2%. The recovery rates of LabRespond and VALAB were 77.9% and 71.8%, respectively (difference not significant). The false-positive rates were 82.7% for LabRespond, 83.6% for VALAB, and 27.8-86.7% for clinical chemists. Using the consensus of three or more clinical chemists as the secondary reference standard, we found error recovery rates of 64.8% for LabRespond and 72.2% for VALAB (P = 0.06). Compared with VALAB, LabRespond detected more (P = 0.003) erroneous test results of the type that were changed from abnormal to normal. CONCLUSIONS: The statistical plausibility check used by LabRespond offers a promising automated validation method with a higher error recovery rate than the clinical chemists participating in this study, and a performance comparable to VALAB.

Clinical Laboratory Techniques↗
PubMed2000

Impact of insurance coverage type on laboratory test ordering behaviour of general practitioners.

BACKGROUND: There exists much variation between GP's in the use of laboratory tests. Although the requesting pattern of GPs has been extensively described in the literature, little is still known of the factors which influence the GP's test ordering behaviour. AIM: This study aimed to determine whether the payment scheme according to which general practitioners are reimbursed influences the laboratory test ordering behaviour. METHOD: The laboratory test ordering behaviour of the general practitioners of Tilburg, a town with 180,000 citizens in the south of The Netherlands, was studied during a four month period, in relation to the type of insurance coverage of the patients. Two types of insurance were considered: voluntary and compulsory. The data were collected from the laboratory administration and coupled with information obtained from two, interview rounds. RESULTS: Two findings support the hypothesis that the type of insurance coverage of the patient, has an impact on the test ordering behaviour of the physician: The ratio between laboratory requests for sickness fund patients and patients with a private health insurance was found to depend on the fraction of persons with a private health insurance within the family practice. This was tested with multiple linear regression analysis. General practices were divided into two subgroups, those with many > 29%) and few (< 29%), voluntarily insured patients. Where a patient was privately insured it was found that relatively more tests were ordered. In case of general practices with many voluntarily insured patients this distinction disappears. The relative proportion of voluntarily insured patients was found to be an important variable in explaining the test ordering behaviour of general practice physicians in Tilburg.

Aged↗
PubMed1999

Postanalytical factors and their influence on analytical quality specifications.

Quality thinking in medical laboratories is placed within the framework of the European Foundation for Quality Management Model which suggests the use of medical outcome indicators such as those developed by the Joint Commission on Accreditation of Healthcare Organizations. From here concepts were illustrated to improve the quality of the medical laboratory towards the data produced but moreover towards the information given, the knowledge acquired and the decision taken. Postanalytical factors were used to define analytical quality specifications.

Clinical Laboratory Techniques↗
PubMed1998

A re-appraisal of the tri-axial chart for monitoring arterial acid-base values.

OBJECTIVE: To demonstrate the practicability of a tri-axial chart for the graphical and quantitative monitoring of arterial pH, arterial carbon dioxide partial pressure (PaCO2) and actual arterial bicarbonate-ion concentration (a[HCO3-]) in intensive care patients. DESIGN: Case report. SETTING: A general intensive care unit (ICU). METHODS: Using a standard mathematical transformation, a data set of pH, log PaCO2 and log a[HCO3-] values can be transformed in such a way that a graphical display of all three variables is possible while being faithful to their linear relationship. Remarkably, the graphical display closely resembles the tri-axial chart that Hastings and Steinhaus described in 1931 for studying displacements of the acid-base balance. Two new monitoring parameters based on the chart and the transformation are described. One monitors the abnormality of the acid-base status while the other monitors the rate of acid-base changes. CONCLUSIONS: With the tri-axial acid-base chart, the complete acid-base status can be faithfully monitored. Moreover, the proposed monitoring parameters provide extra information about the arterial acid-base status that, otherwise, would remain hidden.

Acid-Base Imbalance↗
PubMed1997

Vascular complications in relation to ethnicity in non-insulin-dependent diabetes mellitus.

The purpose of this study was to investigate the effect of ethnicity on the development of diabetic retinopathy and nephropathy as markers for microvascular complications and of angina pectoris as a marker for macrovascular complications. We evaluated data from 1124 patients with non-insulin-dependent diabetes mellitus (NIDDM) of Caucasian, Mongoloid, Asian, Armenian, Northern African and Negroid origin who were referred between January 1993 and December 1994. Logistic regression analyses showed that the occurrence of microvascular complications was significantly associated with duration of NIDDM. In addition, retinopathy was significantly associated with glycated haemoglobin A1c (HbA1c) and nephropathy with triglycerides (P < 0.05 and P < < 0.001 respectively). Northern African origin was associated with retinopathy (P < 0.05) and Asian origin with nephropathy (P < 0.005). Macrovascular complication was associated with age and triglyceride level (P < 0.001 and P < 0.05 respectively). Northern African and Negroid ethnicity exclusively did not show a gradual increase in the risk for angina pectoris with increasing age. Moreover, a negative association between Northern African as well as Negroid ethnicity and macrovascular complication was observed (P = 0.05 and P < 0.05 respectively). In support of these observations, we found a favourable lipid profile in both mentioned groups. In summary, we have shown that, in patients with NIDDM, ethnicity is associated with macrovascular complications and duration of the disease with microvascular complications.

Adult↗
PubMed1996

Nocturnal blood glucose profiles in patients with type 1 diabetes mellitus on multiple (> or = 4) daily insulin injection regimens.

The aim of the study was to examine nocturnal blood glucose profiles in Type 1 diabetic patients on multiple (> or = 4) daily insulin injections. Nocturnal blood glucose profiles were evaluated in 31 patients collecting blood samples half-hourly from 23.00 till 07.30 h, while they were asleep. Nocturnal episodes of hypoglycaemia (blood glucose < 3.0 mmol l-1 occurred in 29% of these nights; 67% of episodes were asymptomatic. In the early night (23.00-01.00 h), five episodes occurred with a median duration of 1 h. In the early morning (04.00-07.30 h) seven episodes occurred with a median duration of 3 h. No hypoglycaemia was noted from 01.00 to 04.00 h. Bedtime glucose levels appeared to predict 'early night' hypoglycaemia but not 'early morning' hypoglycaemia. Fasting glucose levels < 5.5 mmol l-1 were indicative of preceding 'early morning' hypoglycaemia. There was a large intra-individual variation in nocturnal blood glucose profiles. It is concluded that daily monitoring of bedtime and fasting blood glucose levels may be both more reliable and convenient for the prevention of nocturnal hypoglycaemia than periodic testing of blood glucose at 03.00h as is often advised. Setting a target of > 5.5 mmol l-1 for fasting blood glucose may decrease the frequency of nocturnal hypoglycaemia.

Activity Cycles↗
PubMed1996

Advanced management facilities for clinical laboratories.

As part of the OpenLabs (AIM 2028) programme a decision support system (DSS) for laboratory capacity management has been developed. This DSS contains a simulation module for determining the performance of planning rules given the equipment and staffing of the clinical laboratory and the demand for laboratory services. User requirements are discussed and a method is developed to (re-)define rules concerning various planning decisions. To show the functionality of the simulation module some simulation experiments are described.

Clinical Laboratory Information Systems↗
PubMed1995

Decision support for clinical laboratory capacity planning.

The design of a decision support system for capacity planning in clinical laboratories is discussed. The DSS supports decisions concerning the following questions: how should the laboratory be divided into job shops (departments/sections), how should staff be assigned to workstations and how should samples be assigned to workstations for testing. The decision support system contains modules for supporting decisions at the overall laboratory level (concerning the division of the laboratory into job shops) and for supporting decisions at the job shop level (assignment of staff to workstations and sample scheduling). Experiments with these modules are described showing both the functionality and the validity.

Clinical Laboratory Information Systems↗
PubMed1993

The relationship between serum triiodothyronine and thyroxine concentrations in hyperthyroidism.

In toxic nodular goitre relapses of hyperthyroidism after medical therapy probably are more common than in toxic diffuse goitre. It has also been reported that in patients with toxic diffuse goitre a high ratio of triiodothyronine (T3) and thyroxine (T4), initially or during medical treatment, predicts a relapse of the hyperthyroidism after cessation of therapy. We therefore studied the relationship between T3 and T4 in untreated patients with toxic diffuse goitres (n = 46, mean ratio T3/T4 29.6 nmol/mumol +/- 10.7 SD) and toxic nodular goitres (n = 12, ratio 29.3 +/- 17.1), and found no significant difference. Both groups differ significantly from normal controls (n = 16, ratio 14.6 +/- 1.5, P < 0.01). From the patients with toxic diffuse goitres we compared two groups. Patients in the first group remained in remission after short-term medical treatment (n = 10); the second group contains patients with a relapse of hyperthyroidism (n = 10). Differences between both groups in the median ratio of T3 and T4 were assessed before the start of treatment, at 4 and at 8 weeks. No significant differences were found between the two groups. The ratio of T3 and T4 is not helpful in distinguishing diffuse and multinodular toxic goitre or in determining the prognosis after medical treatment of hyperthyroidism caused by a hyperfunctioning thyroid gland. However, recurrence of hyperthyroidism was found in 3 patients with a T3/T4 ratio > 60 nmol/mumol after 8 weeks of treatment.

Adult↗
PubMed1992

Accessibility and function of human thyroid epithelial cells in monolayer culture.

Measurement of thyroid stimulating immunoglobulins (TSI) has not yet found widespread application in the diagnosis and management of Graves' disease. One of the problems is the poor and variable sensitivity of the different assays. We therefore studied the influence of the accessibility of the basal part of human thyroid epithelial cells in monolayer culture on their cAMP response to thyroid stimulating hormone (TSH) and TSI. Test media containing either ammoniumsulphate-precipitated globulin fractions of sera from normal controls and treated or untreated patients with Graves' disease or TSH were used to stimulate cAMP production by cryopreserved human thyroid epithelial cells in monolayer culture. Incubations with and without the use of porous membrane inserts as culture surface were compared by univariate parametric and non-parametric testing. It appears that more TSH-receptors, probably on the basal part of the thyrocyte, can be exposed to the medium by using a porous membrane as culture surface as demonstrated by the increased analytical sensitivity of the semi-bioassay of TSH and TSI.

Autoantibodies↗
PubMed1991

Evaluation of a bench-top nephelometric immunoassay analyzer.

We evaluated the Technicon DPA-1 immunoassay analyzer on its analytical characteristics. Therefore we studied three assays: albumin in cerebrospinal fluid and IgG and transferrin in serum. When tested with the Cusum test for linearity albumin, IgG, and transferrin measurements showed no deviation from linearity. Closer examination revealed an abrupt difference of recovery (from 99 to 87%) in the albumin assay when the automatic dilution changed over from the primary analytical to the high analytical concentration range. One calibration was found sufficient for at least 14 days of measurement. Imprecision was well below the critical limits for reproducibility. We found reasonable agreement between the results from the DPA-1 and the results from comparison methods. However, the correlation plot of IgG showed lack of fit at a distinct segment of the regression line. This appeared to be caused by the poor recovery of the DPA-1 at the lower limit of the high analytical concentration range. The assays of IgG and transferrin were found insensitive for interference by hemoglobin, triglycerides, urea, and bilirubin. The albumin assay was found sensitive for bilirubin and triglycerides. No reagent- and sample-to-sample carry-over could be detected in the assays evaluated.

Albumins↗
PubMed1991

Short-term in vitro drug testing of mamma tumors: relation to estrogen and progesterone receptor levels, age, and proliferation rate.

The correlation between age, proliferation rate of tumors, estrogen and progesterone receptors, and in vitro chemosensitivity to Adriamycin was studied on 43 primary mamma tumors. From an univariate statistical analysis of the results, it appeared that sensitive tumors, unlike resistant tumors, have fewer estrogen receptors and show a higher proliferation rate. And in addition, they are blocked to a greater extent by Adriamycin. In both groups age and progesterone receptors were not significantly different. A multivariate statistical analysis showed that in the classification into sensitive and resistant tumors, the percentage remaining incorporation after addition of Adriamycin and the proliferation rate contributed 94 and 5%, respectively. The first variable was the best measure for in vitro chemosensitivity. The classification of the tumors with the aid of a discriminant function proved to be successful in 91% of all the cases. No significant difference was observed between the in vitro sensitivity to Adriamycin when patients were divided into two groups according to age (less than or equal to 50 and greater than 50 years; 64 and 45% sensitive, respectively). This indicates that all patients benefit from the treatment. It also appeared that 85% of the estrogen negative tumors were sensitive to Adriamycin. So a chemotherapeutic instead of a hormonal therapy has to be considered for all ages, particularly in the case of estrogen negative receptors.

Age Factors↗
PubMed1991

Logistic multiple regression analysis of factors predicting recurrence of hyperthyroidism after medical treatment of toxic diffuse goitre.

In order to determine which factors predict the outcome of short term antithyroid drug treatment we studied 42 patients with diffuse goitre in whom 43 instances of thyrotoxicosis were treated. Treatment duration ranged from 24 to 61 wk (median 30 wk). All patients received high-dose carbimazole and thyroid hormone substitution. Patients in remission were followed for 39 to 134 wk (median 73 wk). The relapse rate at 1 yr and at 2 yr after cessation of antithyroid drug treatment was 51%. Of the parameters studied presence or absence of eye signs and initial serum levels of thyroxine, triiodothyronine and immunoglobulin-G in the relapse group and in the remission group showed significant differences in univariate analysis. No significant differences were found for age, sex, family history of thyroid disease, thyroid gland volume or TSH-receptor stimulating autoantibodies. Linear discriminant analysis shows that of the four remaining factors thyroxine is not important in separating both groups. Cox analysis yields only initial serum triiodothyronine and eye signs as significant prognostic factors. With these two factors 18 out of 23 predictions of remission and 16 out of 18 predictions of relapse in the 41 patients with known initial serum triiodothyronine concentrations are correct. Such predictions can be used in the choice of therapy, short-term medical treatment for patients with a low risk and long-term medical treatment or, at the appropriate time, a destructive form of therapy for patients with a high risk of relapse.

Analysis of Variance↗
PubMed1989

Rapid assay for the in vitro chemosensitivity testing of human breast tumours. Control of assay conditions and quality assurance.

This study has been initiated by the definite need of a rapid, in vitro and patient-specific test to examine oncolytic drug effects on tumour cells. Therefore, we applied a test in which we monitored the incorporation of labelled nucleosides in isolated tumour cells, as a measure of nucleus activity (i.e. the Volm assay). A novel technique of erythrocytes co-precipitation has been developed and this enabled us to use a small number of tumour cells per test (200,000 cells/tube). During the assay, a strict pH control and a high starting viability have been introduced. A cytotoxic control and a t-test at two levels deal with the technical errors and the imprecision. For the evaluation of a specific drug a number of 1.8 million cells proved to be sufficient. Time-course studies of the incorporation of labelled nucleosides into isolated tumour cells have shown the optimal incubation time to be 2 h. The entire assay is completed within one day. HeLa cell cultures were employed as quality control material and criteria for interpretation have been developed. Preliminary results, based upon the evaluation of 43 human breast tumours with doxorubicin, indicate the correctness of the proposed procedures. In conclusion we can state that this assay not only provides useful information but above all that the results are made available in such a short time that they can be used directly in the medical management of the individual patient.

Antineoplastic Agents↗
PubMed1986

A comparison of porcine and human thyroid tissue in the assay of thyroid stimulating immunoglobulins.

The central role of Thyroid Stimulating Immunoglobulins (TSI) in the pathogenesis of the hyperthyroidism of Graves' disease has become generally accepted and a wide variety of assays for the detection of these antibodies has been developed. The dependence on the availability of human thyroid tissue makes most of these assays unsuitable for routine clinical use, a problem circumvented by the use of nonhuman thyroid tissue in some TSI assays. We therefore compared porcine and human thyroid tissue in a TSI assay based on in vitro cAMP generation. No major differences in within and between run variation were found and, with some notable exceptions, a reasonable correlation could be demonstrated between the results in both assays (R = 0.89, P less than 0.001). However, the sensitivity of the porcine TSI assay is only 60% of the estimated sensitivity of the human TSI assay. In spite of the practical advantages this porcine TSI assay, and possibly also other TSI assays using non-human thyroid tissue, cannot totally replace human TSI assays. The value of these assays in predicting the outcome of medical treatment of Graves' disease remains to be established.

Animals↗