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We wanted to have a more substantiated idea about the extreme values which are possible in patients not dying or being moribund. for nine regular analytes the five most extreme results registered between 2014 and 2018 in our database were searched. Results had to have been confirmed by multiple analyses in different samples. Patients should have lived at least 28 days after the extreme analyte value was observed. Patient diagnoses and symptoms were checked to understand the pathology and apparent consequences of the extreme values. most extreme values (lowest and highest; mmol/L): sodium 100/178, potassium 1.2/9.8, chloride 58/138, total calcium 1.02/4.98, ionized calcium 0.37/2.44, magnesium 0.07/3.31, phosphate <0.1/7.3, pH <6.8/7.81, hemoglobin 1.3/14.9 in non-newborns; not determined/16.4 in newborns. All extreme values deviated 7 s.d. or more from the means. Patients obviously can survive rather deviant analyte values. [ABSTRACT FROM AUTHOR]

Background: Laboratory test ordering under time pressure may impact test-ordering behavior. Methods: To investigate the test-ordering behavior of doctors working under such pressure, we designed a questionnaire for trainees and staff in the Emergency Department (ED). This questionnaire addressed topics such as necessity of requested tests, time spent on ordering, costs and availability of tests, and the time of the day. We hypothesized that ordering behavior would be guided predominantly by the medical need of tests and aimed at identifying practical motives that also have an effect. Results: Remarkably, two-third of the respondents (67%) admitted that tests were ordered that would not influence treatment policy directly and 48% of the doctors stated that tests were ordered that do not impact treatment at all. The frequency of such orders was "sometimes" and "frequent" in a 50 : 50 ratio. Interestingly, tests that could prove relevant at a later stage are often ordered simultaneously to reduce burden on the patient. None of the respondents spent more than 3 min on the ordering process and very few (8%) desired more time for ordering. Most respondents (81%) declared to have limited knowledge of the costs of laboratory tests. A random survey covering four tests confirmed this. Generally, turnaround time did influence ordering behavior while time of the day did not. Conclusions: In conclusion, doctors in an ED - besides first of all medical motives - heavily exploit practical (non-medical) reasoning for laboratory test ordering, e.g. taking availability of tests into account and ordering non-immediate tests. [ABSTRACT FROM AUTHOR]

To investigate why men offer sperm donation via the internet, a questionnaire was disseminated via 39 Dutch-language websites thought to be visited by potential sperm donors. Nine internet donors completed the survey, men who typically knew the women they were donating to. Their responses were compared with those of a control group of 35 general sperm bank donors who were recruited using flyers in Dutch sperm banks, and who were typically unaware of the identity of the eventual recipients. The findings shed light on the motives and attitudes of internet donors. Both groups of donors indicated that their primary motivation for donating was altruism (>80% of all respondents). However, internet donors had a more pronounced desire to procreate than sperm bank donors (6 out of 9, i.e. 66 vs. 22%, respectively) and more often felt that they had good genes they wished to pass on (5 out of 9, i.e. 55 vs. 31%, respectively). The main reason internet donors gave for donating via the internet was that they wanted to know the prospective parents and be kept up to date on the progress of the offspring conceived from their donations. This distinguishes them significantly from sperm bank donors. A further finding was that they were not prompted to avoid the formal donation circuit for which, by law in the Netherlands, pregnancies resulting from donations have to be registered in a central database. This study is subject to several, in some cases inevitable, limitations, but it provides an interesting starting point that future studies can seek to confirm and extend. [ABSTRACT FROM AUTHOR]

The introduction of legislation in the Netherlands in 2004 enabling donor offspring to identify and make contact with their donors has led to a need to reconsider the number of offspring that an individual semen donor may produce. To this end, we made a survey on the limits for offspring per donor in 29 different countries, distinguishing between systems with anonymous and open-identity sperm donation. We counted donations as individual offspring conceived, or as the number of women/families helped, by a single donor. The interests of the various participants in gamete donation in open-identity and anonymous systems are considered with some of the basic assumptions and interactions between the different parties that might be used to formulate reasonable guidelines. A number of recommendations are made. [ABSTRACT FROM AUTHOR]

Extracellular cAMP induces the activation of adenylate cyclase in Dictyostelium discoideum cells. Conditions for both stimulation and inhibition of adenylate cyclase by guanine nucleotides in membranes are reported. Stimulation and inhibition were induced by GTP and non-hydrolysable guanosine triphosphates. GDP and non-hydrolysable guanosine diphosphates were antagonists. Stimulation was maximally twofold, required a cytosolic factor and was observed only at temperatures below 10°C. An agonist of the cAMP-receptor-activated basal and GTP-stimulated adenylate cyclase 1.3-fold. Adenylate cyclase in mutant N7 could not be activated by cAMP in vivo; in vitro adenylate cyclase was activated by guanine nucleotides in the presence of the cytosolic factor of wild-type but of not mutant cells. Preincubation of membranes under phosphorylation conditions has been shown to alter the interaction between cAMP receptor and G protein [Van Haastert (1986) J. Biol. Chem. in the press]. These phosphorylation conditions converted stimulation to inhibition of adenylate cyclase by guanine nucleotides. Inhibition was maximally 30% and was not affected by the cytosolic factor involved in stimulation. In membranes obtained from cells that were treated with pertussis toxin, adenylate cyclase stimulation by guanine nucleotides was as in control cells, whereas inhibition by guanine nucleotides was lost. When cells were desensitized by exposure to cAMP agonists for 15 min, and adenylate cyclase was measured in isolated membranes, stimulation by guanine nucleotides was lost while inhibition was retained. These results suggest that Dictyostelium discoideum adenylate cyclase may be regulated by Gs-like and Gi-like activities, and that the action of Gs but not Gi is lost during desensitization in vivo and by phosphorylation conditions in vitro. [ABSTRACT FROM AUTHOR]

The article presents information on the antidiuretic hormone antagonist for the treatment of reducing cystine stone formation. It mentions the cystine as the principle reason for the disease due the absorption of the biochemical at the proximal renal tubule. It highlights the treatment of dilution process of decreasing the concentration of cystine below 1000 micro mole per liter with the increase in the urine volume.

Background: Practical application of prospective risk analysis (PRA) in clinical laboratories should reflect processes as they are carried out, while making the PRA results obtained from different processes comparable. This means that not only STAT and standard testing and testing for critical and less critical parameters should be distinguished (as published), but also that the throughput in processes and process steps should be taken into account., Methods: Building on our previously published PRA, a method was developed to compensate for the throughput in processes and process steps. A factor T, related to the actually observed throughput, was introduced in the risk score calculation. Introduction of this compensation factor leads to different overall risk scores. The criteria by which the risk scores are evaluated were modified accordingly., Results: Introduction of a factor in the PRA to compensate for throughput leads to a change in the risk score for various conceivable failures in process steps. As compared to the PRA in which no compensation for throughput is made, in a process with low throughput the risk score for various conceivable failures in process steps comes out higher after introduction of the compensation factor, while in a process with high throughput various risk scores come out lower., Conclusions: Introduction of a factor to account for the throughput in a process (and process steps) leads to an improved, more realistic PRA, the results of which makes the risk scores of different processes (and process steps) better comparable to each other.

Clinical laboratories are regularly requested to inspect uncommon body fluids obtained from patients because clinicians are uncertain as to the origin of the collected material. They may need this information for the actual diagnosis, to confirm a supposition, or for guiding treatment and invasive operations like draining and puncturing. Often there is also a need to know more precisely what is going on in the cavity that gave rise to the fluid, for instance a local infection or metastasis, or whether the cavity is connected to organs or fluid compartments nearby etcetera. The results of the laboratory investigations often have () direct consequences. As the investigation of uncommon body fluids is distinct from routine laboratory analyses it requires special attention. This paper presents an overview of the characteristics of uncommon human body fluids, constituents useful as markers for recognizing and differentiating fluids and considerations that have to be taken into account when interpreting the results of analyses. In addition a number of practical recommendations for approaching the task of identifying uncommon body fluids are given., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Prospective risk analysis (PRA) is a valuable instrument in quality assurance. The practical application of PRA in clinical laboratories according to the method we have described elsewhere leaves room for a number of adaptations to make it more applicable to and consistent with actual laboratory processes., Methods: We distinguished between more and less critical tests and products in the laboratory processes and scored the consequences of failures at different steps in line with the previously described failure type and effect analysis (FMEA) method. PRA was carried out for two typical laboratory processes: standard clinical laboratory testing and the cryopreservation of semen., Results: Tests in standard clinical laboratory in processes were labeled critical, semi-critical or non-critical. Consequence scoring (C) and assessed risk (R) were significantly higher for processes containing tests considered to be critical (C=6.6±1.5, R=19.3±13.5) as compared to processes containing tests considered semi- or non-critical (C=3.0±1.4, R=8.2±5.3 and C=3.2±1.8, R=8.6±5.9, respectively). There were no differences in the C and R scores for processes with tests considered semi- or non-critical. In the semen cryopreservation process, a distinction between the processes involving private semen and generally accessible semen was made. The C scores for these were significantly different (C=5.9±2.2 and 5.0±2.0, respectively), the R scores did not differ., Conclusions: Introduction of a test criticality classification for the purpose of consequence scoring led to an improved PRA methodology, better reflecting the reality of clinical laboratory practice. We found that two levels of criticality, critical and less critical, were sufficient to achieve this improvement.

An international working group was established with the aim of making recommendations on the number of offspring for a sperm donor that should be allowable in cases of international use of his sperm. Considerations from genetic, psychosocial, operational and ethical points of view were debated. For these considerations, it was assumed that current developments in genetic testing and Internet possibilities mean that, now, all donors are potentially identifiable by their offspring, so no distinction was made between anonymous and non-anonymous donation. Genetic considerations did not lead to restrictive limits (indicating that up to 200 offspring or more per donor may be acceptable except in isolated social-minority situations). Psychosocial considerations on the other hand led to proposals of rather restrictive limits (10 families per donor or less). Operational and ethical considerations did not lead to more or less concrete limits per donor, but seemed to lie in-between those resulting from the aforementioned ways of viewing the issue. In the end, no unifying agreed figure could be reached; however the consensus was that the number should never exceed 100 families. The conclusions of the group are summarized in three recommendations., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Ordering laboratory tests by means of test panels is a convenient way of requesting tests, preventing necessary tests from being forgotten. However, it also leads to redundant test ordering, as not all tests in a given panel are required for each patient. As test panels proposed by doctors may contain redundant, overlapping or infrequently used tests, the active involvement of knowledgeable laboratory staff in the organisation of test panels is advisable to promote efficient test use., Methods: Laboratory staff initiated an intervention in the organisation of test panels at our hospital in 2009. After a review of the existing panels and the proposals for new panels, we established a total of 60 panels (down from 171 previously). We also stipulated that the laboratory is to be involved with all proposals for new test panels in the future., Results: The reorganisation reduced the number of tests in the test panels by 17.7% (n=60), which theoretically should have resulted in 4.5% fewer tests being ordered. However, as an estimated 14% of the tests removed were then ordered individually in addition to the panels, 3.9% fewer tests were ordered, yielding an annual saving of about €58,000 (4.5% of the costs of all tests ordered in test panels). The savings amount to 7-8% if the frequently ordered metabolic panel (which was left unchanged) was excluded from the survey., Conclusions: Active intervention by the laboratory in the organisation of test panels results in a reduction in the use of tests and in interesting savings.

Background: Laboratory tests in hospitals are among the most important diagnostic tools for medical decision making at the Emergency Department. They are often ordered as part of extended test panels, which, although helpful and convenient for doctors, may lead to overuse of tests and overdiagnosis. To improve the ordering process, we investigated which laboratory tests are essential for optimal decision making at the Emergency Department of our hospital., Methods: Forty-nine doctors regularly involved with the Emergency Department filled in a questionnaire asking for their opinions on laboratory test ordering and use., Results: A limited number of laboratory tests are considered indispensable for the Emergency Department: CRP and leukocytes, urea and creatinin, sodium and potassium, and haemoglobin. Glucose and troponin should probably also be included in this list, but were not mentioned as glucose is measured using portable point-of-care devices in our hospital, while cardiac patients are referred directly to the cardiac care unit., Conclusions: Only a limited number of laboratory tests are essential for early medical decision making at the Emergency Department. Ordering facilities should be arranged such that these tests are permanently available, easy to order, and performed with short turnaround times. Test panels for the ED should incorporate these essential tests, with additional other tests so as to prevent essential tests from being forgotten, maintain convenience for doctors and promote sensible and effective use of diagnostic testing. The outcome of these conflicting aims is a compromise, as is discussed.

In recent years much has changed in care for artificial insemination with donor sperm (AID). Since new laws and regulations were implemented, a large number of sperm banks have closed and the total number of sperm donors and their availability have decreased. Long waiting times and the use of sperm donors recruited by foreign commercial sperm banks can indicate a shortage of sperm donors. The fact that the internet offers women the possibility of ordering donor sperm and starting treatment without the intervention of a sperm bank means that future donor-conceived children may be prevented from obtaining the identity of their sperm donor as stipulated in the Dutch law on donor information in the context of artificial insemination. In order to comply with this law, an active recruitment policy is needed for Dutch sperm donors, to prevent waiting lists and treatments outside Dutch sperm banks. Only then can current AID care be guaranteed in the Netherlands in the future.

Objective: Various reasons may guide the decision of men to become a sperm donor. Our aim was to identify a comprehensive set of possible reasons for and against sperm donation., Design: Concept mapping., Setting: Assisted reproduction clinics., Sample: Nine sperm donors and seven non-sperm donors., Methods: Interviews to obtain statements for and against sperm donation, card-sorting tasks to categorize these statements according to similarity, and hierarchical cluster analysis to structure these categorizations., Main Outcome Measures: Hierarchical structure with reasons for and against sperm donation., Results: The hierarchical structure with 91 reasons comprised selfishness (including narcissism and procreation), psychosocial drives (including altruism, detached procreation, and sexual/financial satisfaction), and psychosocial barriers (including normative and moral barriers related to oneself, one's spouse, the donor child, and society)., Conclusions: The identified hierarchical overview of reasons for and against sperm donation may help potential sperm donors when considering becoming a sperm donor, enable more systematic counseling of potential sperm donors, and guide further research on reasons for and against sperm donation., (© 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Modern computer systems allow limits to be set on the periods allowed for repetitive testing. We investigated a computerised system for managing potentially overtly frequent laboratory testing, calculating the financial savings obtained., Methods: In consultation with hospital physicians, tests were selected for which 'spare periods' (periods during which tests are barred) might be set to control repetitive testing. The tests were selected and spare periods determined based on known analyte variations in health and disease, variety of tissues or cells giving rise to analytes, clinical conditions and rate of change determining analyte levels, frequency with which doctors need information about the analytes and the logistical needs of the clinic., Results: The operation and acceptance of the system was explored with 23 analytes. Frequency filtering was subsequently introduced for 44 tests, each with their own spare periods. The proportion of tests barred was 0.56%, the most frequent of these being for total cholesterol, uric acid and HDL-cholesterol. The financial savings were 0.33% of the costs of all testing, with HbA1c, HDL-cholesterol and vitamin B12 yielding the largest savings. Following the introduction of the system the number of barred tests ultimately decreased, suggesting accommodation by the test requestors., Conclusions: Managing laboratory testing through computerised limits to prevent overtly frequent testing is feasible. The savings were relatively low, but sustaining the system takes little effort, giving little reason not to apply it. The findings will serve as a basis for improving the system and may guide others in introducing similar systems.

Background: To manage the costs and performance of diagnostic services involving laboratory testing permanent evaluation is required. Among these, the ever increasing use of stat ordering, involving labour intensive phlebotomy,warrants explanation, especially for a phlebotomy service organised by the laboratory, not by those responsible for and/or carrying out the requests, such as doctors and nurses., Methods: To explore the possibilities to reduce the number of stat phlebotomy requests, we conducted a survey among nurses and doctors of their motives in requesting 109 randomly selected stat orders., Results: Fifty-fi ve percent of all stat phlebotomy orders were requested for immediate decision-making with respect to urgently required diagnosis and patient care, defined by us as medical reasons. The other 45 % of the stat orders were made for logistical reasons relating to the patient care or the hospital organisation. In total, 19 phlebotomy requests(17 % ) were unnecessary and could have been avoided.For most of the stat phlebotomy orders alternatives were not possible, as only 2 % of the requests could have been replaced by analysis in material that had been withdrawn earlier., Conclusions: The majority of the stat orders for phlebotomy were requested for good reasons, about equally distributed among the medical and logistical needs. This sets limits to the measures being feasible to further improve stat phlebotomy ordering efficiency, taking into account the way of functioning of modern hospital care.

The possibilities for ordering laboratory testing in hospitals inevitably need to be managed, given physicians' knowledge on the use of laboratory testing, their attitudes towards test ordering, the constant increase in testing and the limited resources available. On the assumption that some tests may not be strictly necessary or are even redundant, this paper reviews various methods to manage the demand for laboratory tests, evaluating the extent to which these methods are applicable and effective in daily practice. The most promising new management tools seem to be computerised laboratory management systems (CDSS), a reimbursement system based on the diagnosis-treatment combination (as in The Netherlands), and the allocation of laboratory budget to those requesting laboratory services., (2010 Elsevier B.V. All rights reserved.)

Background: At least 20 inborn errors of metabolism may cause hydrops fetalis. Most of these are lysosomal storage diseases. The study proposes a diagnostic flowchart for prenatal diagnosis of non-immune hydrops fetalis., Methods: This study contains a series of 75 non-immune hydrops fetalis pregnancies. Mucopolysaccharides, oligosaccharides, neuraminic acid and 21 lysosomal enzymes were measured in amniotic fluid and cultured amniotic cells., Results: The study gives reference values for mucopolysaccharides and neuraminic acid at various stages of gestation. Four definite and two probable lysosomal diagnoses were found among the 75 investigated cases (=5.3-8%). Fetal death was found to cause false positive values for mucopolysaccharides in amniotic fluid. In the galactosialidosis case, two novel mutations were found in the cathepsin A gene., Conclusions: Reference values for mucopolysaccharides and neuraminic acid depend on gestational age. In a relatively high percentage of the hydrops foetalis pregnancies, a lysosomal aetiology is found. This study provides a strategy to diagnose lysosomal diseases in hydrops fetalis pregnancies. Awareness of lysosomal storage diseases causing hydrops fetalis is useful as it gives an opportunity for risk evaluation, genetic counseling to parents and targeted prenatal diagnostics for ensuing pregnancies.

Aims: The analytical performance of the new Tina-quant % carbohydrate-deficient transferrin (%CDT) was assessed in a multicentre study on Roche/Hitachi analysers., Methods: Intra-assay/total precision studies revealed median coefficients of variation (CVs) of 4.7/7.4% within the sites. Precision between the sites was proven using a serum panel., Results: Inter-laboratory CVs from 6.3 to 10.7% were obtained. The results of the participating laboratories compared well with high-performance liquid chromatography-UV technique fulfilling the criteria of a reference method for %CDT determination (slope 1.03, intercept -0.09% CDT, correlation 0.984). Good agreement was also found with the Axis-Shield %CDT microtitre test., Conclusions: Data from this study indicate that reliable, well standardized %CDT results are obtained using the new assay.

A limit of 25 offspring per sperm donor has been imposed in The Netherlands since 1992, in order to prevent children from donors having a greater risk of consanguineous relationships than would occur in random individuals. An incident with a donor who developed a serious hereditary brain disease raised the question whether the limit of 25 should be reduced. Here I consider this suggestion from a genetic, psychological and legal standpoint. There appears to be no valid population genetics argument for limiting the number of donor offspring to below the figure that would prevent an increased chance of inbreeding. Reduction of the number of children per donor theoretically only results in transmission of greater diversity to donor offspring. Moreover, as within the general population, the total number of children conceived from sperm donors is negligible, the impact of donor offspring on the population genetics is anyhow insignificant. From a psychological standpoint, it should be noted that individuals making use of a donor, or their offspring, have no knowledge of other offspring conceived with their particular donor. This implies that the number of offspring per donor is of no relevance to them (provided of course there is an acceptably low chance of inbreeding). The new Dutch law on disclosure of donor identity to donor-insemination children, also produces no compelling reasons for a general reduction in the number of offspring per donor. Reduction desired by individual donors can be obtained by means of mutual agreements between sperm banks and donors. In conclusion neither the possible transmission of late-onset autosomal dominant diseases, nor other considerations necessitate a reduction in the offspring limit calculated to prevent increased risks of inbreeding among donor offspring.