Department of Clinical Chemistry, Lund University Hospital, Lund, Sweden.
pal@dadlnet.dk
Date of birth: Born October 1st 1952 in Budapest.
Certification: 1980, MD, University of Copenhagen; 1983 Board certified Medicine (Denmark); 1992 Board certified Medicine (Sweden) 1992 Board certified Clinical Pathology (Sweden); 1992 Board certified Clinical Pathology (Denmark).
THESIS: Human progastricsin with special emphasis on the male reproductive system. Doctoral Dissertation LUMEDW/ (MECM-1012/1-128 1992. 1992 University of Lund, Sweden
Abstract: The prevalence of atopic disorders has increased in recent years. The pathogenesis is complex with genetic and environmental risk factors. Filaggrin loss-of-function mutations are common and associated with atopic disorders. We investigated whether the prevalence of filaggrin mutations increased in different birth cohorts in adults from the general population in Denmark.
Abstract: The mechanisms underlying the association between filaggrin (FLG) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development.
Abstract: â Psoriasis vulgaris could be associated with the filaggrin null genotype since certain known susceptibility loci for psoriasis are shared with susceptibility loci for atopic dermatitis. Furthermore, filaggrin expression is lowered in psoriatic skin lesions but normally expressed in uninvolved skin. So far five relatively small patient-based case-control studies have rejected a possible association between psoriasis and the two most prevalent filaggrin null mutations, 2282del4 and R501X.
Abstract: Filaggrin metabolites act as osmolytes and are important for skin hydration. Carriers of filaggrin loss-of-function mutations have a higher prevalence of atopic dermatitis and dry skin. There is also evidence to suggest that filaggrin mutations increase the risk of hand eczema in atopic individuals. In our clinic, we have observed a distinct phenotype of hand eczema in patients with filaggrin mutation carrier status, characterized by fissured dermatitis on the dorsal aspect of the hands and with only sparse involvement of the palms including fine scaling.
Abstract: The filaggrin protein is expressed as profilaggrin mainly in stratum granulosum cells of the epidermis. The profilaggrin gene codes for 10-12 filaggrin repeats. The filaggrin protein is important for skin barrier function. Filaggrin deficiency due to functional null-polymorphisms affects 8-10% of the people in Northern Europe and is a strong risk factor for several diseases. Here, we describe a novel method for efficient, multiplexed genotyping of variations in the profilaggrin gene.
Abstract: About 8-10% of the general population in Europe carry a null mutation in the filaggrin gene which is associated with early onset of atopic dermatitis as well as persistence into adulthood. No studies have investigated whether individuals with the homozygous filaggrin null genotype always develop dermatitis.
Abstract: Backgroundâ Studies have shown that filaggrin gene (FLG) mutations are positively associated with sensitization to aero allergens. We hypothesized that FLG mutations would also have an effect on the mean size of positive skin prick test (SPT) reactions as well as the number of positive reactions. Objectiveâ To investigate the effect of FLG mutations on the mean size and the number of positive SPT reactions, as well as the association with positive specific IgE. Methodsâ A random sample of 3335 adults from the general population in Denmark was genotyped for the R501X and 2282del4 mutations in the FLG. SPT and specific IgE measurements to common aeroallergens were also performed. Resultsâ FLG mutations did not influence the mean size and number of positive SPT reactions. Also, no association was found between FLG mutations and specific IgE measurements. Conclusionâ Our findings suggest that FLG mutations alone are insufficient to cause secondary sensitization to allergens. The positive association seen in patients must be explained by a combination of further barrier abnormality caused by dermatitis as well as increased allergen exposure.
Abstract: Seroma formation is the most prevalent postoperative sequela after breast cancer surgery. A total of 263 aspirations of seroma fluid in 42 patients were performed after mastectomy; cytokines were measured in 148 cases. The concentration of interleukin-1β (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12p70 (IL-12) and tumor necrosis factor α (TNF) were measured. The patients underwent 9.0 seroma aspirations on average (range 1-17) during an average of 30.7 days (range 7-72). The average cumulative seroma volume was 2056.1 mL (range 50-5130). In all samples, the maximal average concentrations of IL-6 (mean 10717 pg/mL, range 136-100000) and IL-8 (mean 7221 pg/mL, range 102-79828) were 55-200-fold above the serum/plasma levels of asymptomatic adults. In contrast, we observed levels similar to normal serum/plasma levels for IL-1 (mean 62.8 pg/mL, range 0-1226), IL-10 (mean 29.8 pg/mL, range 3.6-359), and lower-than-normal serum/plasma levels of TNF (mean 3.4 pg/mL, range 0-31.7) and IL-12 (mean 0.5 pg/mL, range 0-11.8). Patients with clinical infection had generally significant higher maximal IL-6 (p = 0.004) and IL-8 (0.019) than patients without clinical infection. However, most patients had no bacterial infection. None of the cytokines were associated with cumulative seroma volume, duration of seroma production or number of seroma aspirations. Seroma formation after mastectomy has a pro-inflammatory component, as indicated by the high levels of interleukin-6 and interleukin-8. However, these levels do not predict the course of seroma production.
Abstract: This study served the following three purposes: To evaluate the prophylactic effect against seroma of a single dose of steroid in the mastectomy cavity, to evaluate the thesis that there is a connection between subclinical bacterial colonization and seroma formation and to evaluate if a simple urine stix test can detect postmastectomy infection.
Abstract: Institut for Rationel Farmakoterapi (IRF) har i april 2011-udgivelsen bevæget sig uden for deres kerneområde (kompetence) ved at harcelere over referenceintervallet for kolesterol [1].
IFR's udsagn viser en manglende forståelse for, hvad referenceintervaller egentlig står for.
Et resultat behøver ikke at være unormalt, hvis det ligger uden for et referenceinterval (ikkenormalværdier), og skal ikke tolkes som sygdom, ligesom det ikke behøver at være normalt, hvis det ligger inden for. Ej heller er de angivne værdier nødvendigvis et klassisk 95 interpercentil-referenceinterval (95% RI). Nogle gange er det en diagnostisk grænse,
Abstract: It was recently shown that filaggrin null mutation carrier status was associated with nickel allergy and self-reported intolerance to costume jewellery. Because of the biochemical characteristics of filaggrin, it may show nickel barrier properties in the stratum corneum.
Abstract: The phenotypic traits of people with the filaggrin mutation (FLG) genotype and atopic dermatitis (AD) are still under elucidation, and the association with concomitant AD and contact allergy (CA) has not previously been examined.
Abstract: Consumption of industrially produced trans fatty acids (IP-TFA) has been positively associated with systemic markers of low-grade inflammation and endothelial dysfunction in cross-sectional studies, but results from intervention studies are inconclusive. Therefore, we conducted a 16 week double-blind parallel intervention study with the objective to examine the effect of IP-TFA intake on biomarkers of inflammation, oxidative stress, and endothelial dysfunction. Fifty-two healthy overweight postmenopausal women (49 completers) were randomly assigned to receive either partially hydrogenated soybean oil (15.7 g/day IP-TFA) or control oil without IP-TFA. After 16 weeks, IP-TFA intake increased baseline-adjusted serum tumor necrosis factor (TNF) α by 12% [95% confidence interval (CI): 5-20; P = 0.002] more in the IP-TFA group compared with controls. Plasma soluble TNF receptors 1 and 2 were also increased by IP-TFA [155 pg/ml (CI: 63-247); P < 0.001 and 480 pg/ml (CI: 72-887); P = 0.02, respectively]. Serum C-reactive protein, interleukin (IL) 6 and adiponectin and subcutaneous abdominal adipose tissue mRNA expression of IL6, IL8, TNFα, and adiponectin as well as ceramide content were not affected by IP-TFA, nor was urinary 8-iso-prostaglandin-F(2α). In conclusion, this dietary trial indicates that the mechanisms linking dietary IP-TFA to cardiovascular disease may involve activation of the TNFα system.
Abstract: Background Filaggrin proteins are located in the skin and prevent epidermal water loss and impede the entry of micro-organisms, allergens and chemicals. Filaggrin null mutations are strongly associated with ichthyosis vulgaris and atopic dermatitis. Objective The authors aimed to investigate the association between filaggrin null mutations, atopic dermatitis and diabetes. Design A random sample of 3335 adults from the general population in Denmark was filaggrin-genotyped for R501X and 2282del4 null-mutations and questioned about atopic dermatitis and diabetes. Furthermore, two independent study populations of patients with type 1 (n=104) or 2 (n=774) diabetes were genotyped. Results In a crude data analysis, a positive association was detected between the filaggrin null genotype and, respectively, subjects from the general population who reported diabetes (p=0.04) and patients with established type 2 diabetes (p=0.073). Adjustment for age and gender resulted in significant associations for patients with type 2 diabetes (p=0.048) and subjects with self-reported diabetes (p=0.032). Conclusions Adult Danes with a filaggrin null genotype had a significantly increased prevalence of self-reported diabetes. This finding was replicated when an independent sample of Danish patients with established type 2 diabetes was compared with control subjects from the general population.
Abstract: The administration of hydroxocobalamin (OHCob), alone or with sodium thiosulfate, is a standard therapy for cyanide poisoning. OHCob is a red chromophore, and its interference with co-oximetric and colorimetric laboratory measurements has been evaluated in a few conflicting reports. The interference of OHCob was investigated in samples spiked with 10 different concentrations of OHCob (0-1500 mg/L). The concentration of 73 different analytes was measured using nine different analysers (ABL 800 Flex, Advia 1800, Advia Centaur Xp, Architect ci8200, Immulite 2500, Konelab 30i, Modular Analytics SWA, Synchron LX 20 and Vitros 5.1). All instruments yielded some results that were affected by OHCob at concentrations equivalent to a single therapeutic dose. Of the 73 different analytes, 64% showed interference on at least one instrument. Of all 187 tests performed, 47% were biased with more than 10%. Interference was generally limited to photometric assays, whereas immunological and ion-selective electrode measurements were unaffected. OHCob present in the blood after treatment for cyanide poisoning interfered with many laboratory assays in an unpredictable way, making some results invalid. Some affected tests are important in the treatment of cyanide poisoning. The interference is not solely due to wavelength, but also to chemical interaction. Without delaying the administration of OHCob, blood should, preferably, be drawn in advance, or, at least, the laboratory should be informed about the OHCob treatment. If the laboratory receives OHCob-containing samples, methods and instruments should be selected to minimize bias, and the manufacturer of the OHCob should recommend relevant precautions to customers in the package insert.
Abstract: Summary Background It was recently shown that filaggrin gene (FLG) null mutations are positively associated with nickel sensitization. We have hypothesized that histidine-rich filaggrin proteins in the epidermis chelate nickel ions and prevent their skin penetration and exposure to Langerhans cells. Furthermore, we have proposed that the low degree of genetic predisposition to nickel sensitization found by a Danish twin study was explained by a high prevalence of ear piercing among participants resulting in 'bypassing' of the filaggrin proteins. Objectives To investigate the association between FLG null mutations and (nickel) contact sensitization. Methods A random sample of 3335 adults from the general population in Denmark was patch tested and genotyped for R501X and 2282del4 in the FLG gene. Results The combined carrier frequency of FLG null mutations was 8.1%. Nickel, fragrance and contact sensitization to at least one allergen were not associated with FLG null mutations. A crude analysis on women who did not have ear piercings revealed a positive association between FLG null mutations and nickel sensitization [8.3% vs. 2.4%; odds ratio (OR) 3.71, 95% confidence interval (CI) 0.73-18.96] as well as between FLG null mutations and allergic nickel dermatitis (8.3% vs. 1.3%; OR 6.75, 95% CI 1.17-38.91). FLG mutation status and atopic dermatitis were positively associated with neomycin or ethylenediamine sensitization. Conclusions This study suggests that FLG null mutations may be a risk factor for the development of nickel sensitization. However, ear piercing was a much stronger risk factor in our general population and we could therefore identify a positive association only in women without ear piercings. Contact sensitization to specific chemicals is related to treatment exposure.
Abstract: Background: Intake of industrially produced trans fatty acids (TFA)
is, according to observational studies, associated with an increased
risk of cardiovascular disease, but the causal mechanisms have not
been fully elucidated. TFA intake is suspected of promoting abdomi-
nal and liver fat deposition, but intervention studies on these end-
points are scarce.
Objective: We examined the effect of a high intake of TFA on
abdominal and hepatic fat deposition, blood lipids and plasma bio-
markers of inflammation.
Design: A 16-week double-blind parallel intervention study included
52 healthy overweight postmenopausal women, who were random-
ized to receive either partially hydrogenated soybean oil providing
15 g/d of TFA or a control oil with mainly oleic and palmitic acid.
Results: TFA intake decreased plasma HDL-cholesterol by 10% and
increased LDL-cholesterol by 18% resulting in an increased LDL/
HDL-cholesterol ratio compared with controls [baseline adjusted
mean (95%CI) difference between diet groups 0.41 (0.22; 0.60);
P < 0.001]. Plasma soluble tumor necrosis factor receptor 2
increased in the TFA group compared with controls [518 (174;
862) pg/ml; P = 0.004] whereas C-reactive protein and adiponectin
were not affected. TFA tended to increase waist circumference [1.1
()0.1; 2.4) cm; P = 0.08], whereas no differences in body weight or
ectopic fat were observed between diet groups.
Conclusions: This intervention study suggests that the mechanisms
linking dietary TFA to cardiovascular disease involve induction of
dyslipidemia and systemic inflammation but not abdominal or hepa-
tic fat.
Conflict of interest: A. Astrup is advisor or member of advisory
boards for Arla, European Almond Advisory Board, Communica-
tions and Scientific Advisory Board of The Global Dairy Platform.
Funding: This work was carried out as a part of the research pro-
gram of the Danish Obesity Research Centre (DanORC, see
www.danorc.dk). DanORC is supported by the Danish Council for
Strategic Research (Grant 2101-06-0005). This study was also sup-
ported by the Danish Council for Independent Research | Medical
Sciences (Grant 271-08-0715) and the Danish Diabetes Association.
cytes, whereas protein levels were similar in cell lysates. We next
addressed the question whether NAMPT protein is enzymatically
active in cell lysates and supernatants. We found a similar enzymatic
activity in cell lysates of monocytes, lymphocytes and granulocytes.
Contrary, supernatants of granulocytes exhibited significantly lower
enzymatic activity (P < 0.001) compared to monocytes and lympho-
cytes.
Conclusions: NAMPT levels are strongly related with obesity in chil-
dren. In addition to adipose tissue, granulocytes may represent a pre-
viously unrecognized source of circulating NAMPT.
Conflict of interest: There are no conflicts of interest.
Funding: Research was funded by German Research Council (DFG)
KFO 152 âAtherobesityâ and the German Diabetes Association.
Abstract: Hand eczema is prevalent in the general population. It remains unclear whether or not filaggrin gene (FLG) null mutations increase the overall risk of hand eczema or only increase the risk of hand eczema in subjects with atopic dermatitis.
Abstract: Physiological changes during pregnancy may affect laboratory parameters. Reference values based on samples from non-pregnant women are not necessarily useful for clinical decisions during pregnancy. There is a need to establish reference values during pregnancy in order to recognize pathological conditions.
Abstract: A case of Hb Canebière [β102(G4)AsnâHis] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques.
Abstract: It was recently shown that filaggrin gene (FLG) null mutations are positively associated with nickel sensitization. We have hypothesized that histidine-rich filaggrin proteins in the epidermis chelate nickel ions and prevent their skin penetration and exposure to Langerhans cells. Furthermore, we have proposed that the low degree of genetic predisposition to nickel sensitization found by a Danish twin study was explained by a high prevalence of ear piercing among participants resulting in 'bypassing' of the filaggrin proteins.
Abstract: Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. In this study, we establish gestational age-specific reference intervals for coagulation tests during normal pregnancy. Eight hundred one women with expected normal pregnancies were included in the study. Of these women, 391 had no complications during pregnancy, vaginal delivery, or postpartum period. Plasma samples were obtained at gestational weeks 13-20, 21-28, 29-34, 35-42, at active labor, and on postpartum days 1 and 2. Reference intervals for each gestational period using only the uncomplicated pregnancies were calculated in all 391 women for activated partial thromboplastin time (aPTT), fibrinogen, fibrin D-dimer, antithrombin, free protein S, and protein C and in a subgroup of 186 women in addition for prothrombin time (PT), Owren and Quick PT, protein S activity, and total protein S and coagulation factors II, V, VII, VIII, IX, X, XI, and XII. The level of coagulation factors II, V, X, XI, XII and antithrombin, protein C, aPTT, PT remained largely unchanged during pregnancy, delivery, and postpartum and were within non-pregnant reference intervals. However, levels of fibrinogen, D-dimer, and coagulation factors VII, VIII, and IX increased markedly. Protein S activity decreased substantially, while free protein S decreased slightly and total protein S was stable. Gestational age-specific reference values are essential for the accurate interpretation of a subset of haemostatic tests during pregnancy, delivery, and puerperium.
Abstract: Filaggrin null (FLG) mutations lead to skin barrier disruption with a reduced resistance towards exogenous agents and also influence the course of disease in atopic dermatitis.
Abstract: Objective: The changes during pregnancy may affect biochemical
tests. Reference values are based upon samples from non-pregnant,
not necessarily useful for decisions during pregnancy.
Materials and Methods: We included 801 women with expected
normal pregnancy at Gentofte University Hospital, Denmark. Of
those 391 proved to have a totally uncomplicated pregnancy,
vaginal delivery and early postpartum period.
Plasma was obtained at gestational week 13â20, 21â28, 29â34,
35â42, at active labor and at one and two days postpartum. Analysis
was performed on ADVIA 2120, Immulite 2500, VITROS 950, COBAS
INTEGRA 400 plus and STA-R Evolution. Reference intervals (2.5
and 97.5 percentiles) were calculated for each gestational period as
recommended by IFCC.
Results: Many tests differed already at week 13â20 from nonpregnant
reference intervals and many showed minor change
during pregnancy. Some test (like uric acid, alkaline phosphatase,
protein S, D-dimer) showed so large differences that gestational
age specific reference intervals are needed. Even among these
uncomplicated pregnancies was D-dimer >0.5 mg/l at nearly all women from week 20 with a reference interval at 0.7â13 mg/l
at labor. We only observed a minor decrease in albumin. This
canât be due to hemodilution as other components with same
particle/molecular size didnât show a similar decrease. Many tests
showed a broad distribution around labor.
Conclusion: Gestational age-specific parameters are necessary for
some test.
Notes: XIX FIGO World Congress of Gynecology & Obstetrics
Cape Town, South Africa from 4th to 9th October 2009.
Abstract: Objective: Asymptomatic ovarian cysts in pregnant women
compose a diagnostic and therapeutic dilemma. Surgical treatment
is not tempting, yet we fear overlooking malignancy. Physiological
changes occurring during pregnancy may affect biochemical
parameters including CA125. Most reference values are based
upon samples from non-pregnant women not necessarily useful
for clinical decision during pregnancy.
Materials and Methods: We included 801 women with expected
normal pregnancy at Gentofte Hospital, University of Copenhagen,
Denmark. Of those 391 proved to have a totally uncomplicated
pregnancy, vaginal delivery and early postpartum period.
Plasma was obtained at gestational week 13â20, 21â28, 29â34,
35â42, at active labor and at one and two days postpartum. Analysis
was performed on Immulite 2500. Reference intervals (2.5 and
97.5 percentiles) were calculated for each gestational period as
recommended by IFCC.
Results: During pregnancy CA 125 increased slightly (3â36 U/ml).
At delivery a drastic rise was seen (3â264 U/ml); the first and
second day postpartum a slow decrease was found: 10â137 U/ml,
7â70 U/ml, respectively.
Conclusion: The CA 125 cut-off value (<35 U/ml) for non-pregnant
women can be used during pregnancy as a supplement to
ultra sound in evaluation of ovarian cysts. However CA 125
concentrations fluctuate so highly during delivery and postpartum
that it is impossible to use as a marker for malignancy.
Notes: XIX FIGO World Congress of Gynecology & Obstetrics
Cape Town, South Africa from 4th to 9th October 2009.
Abstract: The physiological changes occurring during pregnancy may affect biochemical parameters. Most reference values are based upon samples from non-pregnant women not necessarily useful for clinical decision in pregnant women.
Eight hundred and one women were recruited among 2147 women attending first trimester screening. Among these, 391 women with a totally uncomplicated pregnancy, delivery and puerperium were identified.
Plasma were obtained at gestational week 13â20, 21â28, 29â34, 35â42, at active labor and 1 and 2âdays postpartum.
All tests were assayed on the STA-R Evolution coagulation analyzer with reagents from Stago.
Reference ranges (2.5th and 97.5th percentiles) were calculated for each test and gestational period using RefVal ver. 4.11 as recommended by IFCC.
Free protein S decreased slightly (approximately 20%) while protein S activity decreased substantially (approximately 50%). In contrast, Factor VII (approximately 50%), VIII (approximately 100%), IX (approximately 50%), D-dimer (approximately 400%) and fibrinogen (approximately 50%) increased during pregnancy. Quick prothrombin time, aPTT, antithrombin, protein C, coagulation factors II, V, X, XI, & XII did not change significantly.
Protein S deficiency during pregnancy is not easily revealed, however measurement of free protein S antigen might be indicative. If protein S activity is measured, gestational specific reference intervals is mandatory, however, the lower reference limit is as low as 20%. Gestational age specific reference values are also recommended to be used for fibrinogen, factor VII, VIII & IX, while the usefulness of measuring D-dimer during pregnancy is doubtful.
Notes: Abstract/Poster on XXII IST Congress Boston july 2009
Abstract: The physiological changes occurring during pregnancy may affect biochemical
parameters. Most reference values are based upon samples from non-pregnant women
not necessarily useful for clinical decision in pregnant women.
Eight hundred and one women were recruited among 2147 women attending first
trimester screening. Among these, 391 women with a totally uncomplicated
pregnancy, delivery/caesarians and puerperium were identified.
Plasma were obtained at gestational week 13-20, 21-28, 29-34, 35-42, at active labor
and one and two days postpartum.
All tests were assayed on the STA-R Evolution coagulation analyzer with reagents
from Stago.
Reference ranges (2.5th and 97.5th percentiles) were calculated for each test and
gestational period using RefVal ver. 4.11 as recommended by IFCC.
Free protein S decreased slightly (â20%) while protein S activity decreased
substantially (â50%). In contrast, Factor VII (â50%), VIII (â100%), IX (â50%), Ddimer
(â400%) and fibrinogen (â50%) increased during pregnancy. Quick
prothrombin time, aPTT, antithrombin, protein C, coagulation factors II, V, X, XI, &
XII did not change significantly.
Protein S deficiency during pregnancy is not easily revealed, however measurement
of free protein S antigen might be indicative. If protein S activity is measured,
gestational specific reference intervals is mandatory, however, the lower reference limit is as low as 20%. Gestational age specific reference values are also
recommended to be use for fibrinogen, factor VII, VIII & IX, while the usefulness of
measuring D-dimer during pregnancy is doubtful. Nearly all women from gestation
week 20 had D-dimer values above the conventional cut-off point of 0.5 mg/l with
increasing levels peaking at delivery. We had too few cases with thromboembolism,
but it is unlikely that D-dimer levels can differentiate between normal and
pathological cases.Most values fluctuated somewhat more around the delivery, and
were similar independent of delivery method.
Notes: Abstract/Poster 2009 AACC/CSCC Annual Meeting Chicago Julyl 2009
D-56
Abstract: The objective was to design a method by which any electronic ordering result system
(ORS) in combination with any laboratory information system (LIS) can present
appropriate gestational age-specific reference values known to differ from the usual
reference values in non-pregnant individuals.
In ORS/LIS the appropriate test is given a period suffix and defined in both systems as a separate test with the correct gestational age-specific reference values. The test with
its period suffix appears on the ordering screen or sheet as other tests, although the
analysis performed is exactly the same as usual.
In this way âD-dimerâ may in addition appear as âD-dimer 2. trimesterâ etc. Also
packages with a period suffix may be defined, for instance âPreeclampsia 2. trimesterâ
containing a number of tests, some with the period suffix (if the reference values
change during pregnancy) and some without period suffix (if the reference values do
not change), all ordered simultaneously by only one click or tick on the name of the
package with its appropriate suffix.
The clinicians should select the relevant âpackageâperiod suffixâ or âtest-period
suffixâ in the ordering system. Subsequently, test results will appear on the final lab
report with relevant gestational age-specific reference values. If the ORS/LIS allows a
special typography for results outside reference values, this will also be the case for
the test results in the pregnant woman, but only if they are outside the gestational agespecific
reference interval. In our hospital, with 2000 deliveries yearly, such
gestational age- specific ordering has been established in the ORS/LIS (Web-ICE and
Flexilab, Sunquest Arizona, US) for 40 different commonly used biochemical tests.
For some tests with a profound change during pregnancy such as albumin, uric acid,
D-dimer and others, separate tests for 2. and for 3. trimester and for day-1-post partum
have been established.
This has immediately eliminated the traditional need of pocket folders for reference
values during pregnancy. Furthermore, the general lab report is now the source for
information whether a test result from a pregnant woman is outside the reference
range for women with uncomplicated pregnancies at a similar gestational age.
Notes: Abstract/Poster 2009 AACC/CSCC Annual Meeting Chicago Julyl 2009
A-33
Abstract: BACKGROUND: We report our results for the systematic recording of all errors in a standard clinical laboratory over a 1-year period. METHODS: Recording was performed using a commercial database program. All individuals in the laboratory were allowed to report errors. The testing processes were classified according to function, and errors were classified as pre-analytical, analytical, post-analytical, or service-related, and then further divided into descriptive subgroups. Samples were taken from hospital wards (38.6%), outpatient clinics (25.7%), general practitioners (29.4%), and other hospitals. RESULTS: A total of 1189 errors were reported in 1151 reports during the first year, corresponding to an error rate of 1 error for every 142 patients, or 1 per 1223 tests. The majority of events were due to human errors (82.6%), and only a few (4.3%) were the result of technical errors. Most of the errors (81%) were pre-analytical. Of the remainder, 10% were analytical, 8% were post-analytical, and 1% was service-related. Nearly half of the errors (n=550) occurred with samples received from general practitioners or clinical hospital wards. Identification errors were relatively common when non-technicians collected blood samples. CONCLUSIONS: Each clinical laboratory should record errors in a structured manner. A relation database is a useful tool for the recording and extraction of data, as the database can be structured to reflect the workflow at each individual laboratory.
Abstract: Objective: To design a method by which any laboratory information
system (LIS) can present gestational age-specific reference values
known to differ from reference values in non-pregnant individuals.
Methods: In LIS the usual test name is given a period suffix and
defined as a separate test with the correct gestational age-specific
reference values. The test with its period suffix appears on the
ordering screen or sheet as a new test, although the analysis
performed is exactly the same as usual. In this way âD-dimerâ
may in addition appear as âD-dimer gestation week 35â42â etc.
Also packages with a period suffix may be defined, for instance
âPreeclampsia gestation week 35â42â containing a number of tests
all with the same period suffix ordered simultaneously by only one
click or tick on the name of the package with its suffix.
Results: Test results will appear on the final lab report with relevant
gestational age-specific reference values. If the LIS allows a special
typography for results outside reference values, this will also be
the case for test results in the pregnant woman, but only if they
are outside the gestational age-specific reference interval. In our
hospital, with 2000 deliveries yearly, such gestational age-specific
ordering has been established for 30 different commonly used
chemical tests each with a period suffix for relevant gestation
weeks and for day-1-postpartum.
Conclusion: The lab report now shows test results and appropriate
reference values not only for non pregnant but also for pregnant
women.
The traditional need of pocket folders for reference values during
pregnancy has been eliminated.
Notes: XIX FIGO World Congress of Gynecology & Obstetrics
Cape Town, South Africa from 4th to 9th October 2009.
Abstract: The introduction of a new test is often slow and obsolete tests are hard to get rid of. After nearly 20 years, the cardiac proteins troponin I and T have not yet replaced the old creatinin kinase myocardial band (CK-MB). International guidelines now recommend the use of troponin as marker for myocardial necrosis and only CK-MB when troponin is not available. However, 23 of 46 Danish laboratories still use CK-MB. The additional cost thus incurred could be used for other beneficial purposes. It is recommended to follow the international guidelines.
Abstract: The screening test used for evaluation of antinuclear antibodies (ANA) has
traditionally been the immunofluorescence method on Hep-2 cells,
in spite of a cumbersome and biased technique. Quantitative ANA
immunoassays have replaced the Hep-2 cells in many laboratories, but
some doubt still exists if the non-biased results are equivalent to the
subjective morphological information. We studied 400 consecutive
patients routinely tested for ANA. Immunofluorescence on Hep-2 cells
(Immunoconcept, Sacramento, CA, USA) at two independent sites were
compared with ANA immunoassays measurements of antibodies toward
EliA double-stranded DNA and Symphony (Phadia, Freiburg,
Germany). If the ANA screening (Symphony) result was above 1.0,
were the 7 differentiation antigens analysed (Sm, U1RNP, RNP70, Ro,
La, Scl-70, Centromer, Jo-1) Using the manufactures cut-off for the
immunoassays, we found agreement with the results from the Hep-2
method in 90% of the cases (19 positive, 341 negative). Of the remaining
cases were the two approaches differed, were 29 patients Hep-2
NEG/ANA POS and 12 patients Hep-2 POS /ANA NEG. The diagnosis
and antibody response for all these 40 patients are presented.
Notes: THE 32ND SCANDINAVIAN CONGRESS OF RHEUMATOLOGY
Levi, Lapland, Finland, 30 January â 3 February 2008
FP8-13
Abstract: With the aim of producing unique targets for malignant cells we have identified peptide ligands for the clonal surface immunoglobulin isolated from the B cells of a chronic lymphocytic leukaemia (CLL) patient. The peptides were identified from random-peptide phage-display libraries. The obtained ligands bound specifically to the surface of the target lymphocytes as well as to clonal immunoglobulin in lysate from the same cells. Peptide-based antigen mimotopes may have a future use in targeted therapy of CLL and other B-cell-derived malignancies displaying surface immunoglobulin.
Abstract: We have taken advantage of the selection power of phage display technology to define specific peptide mimotopes that recognize individual M-proteins, isolated from patients with multiple myeloma. Preferred amino acid motifs of phages binding to M-proteins were identified in 6/9 patients investigated. Chemically synthesized peptides, corresponding to the phage-displayed peptide inserts, were used to verify the specificity of binding in competition assays. The peptides were able to bind to the M-proteins, as well as the myeloma cells, with high sensitivity and specificity. Employing simple immunological techniques, < 0.01 g/l of M-protein could be quantified, suggesting a novel way for monitoring minimal residual disease in the production of guidelines for adjusting or reintroducing conventional chemotherapy. The peptide mimotopes defined by this technology may be useful as tumour-specific targeting agents and as a tool for purging cells in autologous bone marrow transplantation.
Abstract: The aspartic protease progastricsin (EC 3.4.23.3) is found in all parts of the mammalian stomach and has also been found extragastrically. In humans and monkeys, seminal fluid usually contains high concentrations of progastricsin. Using immunohistochemistry and in situ hybridization, we determined in this investigation the origin of seminal progastricsin to be the epithelia of both the prostatic gland and the seminal vesicles. In addition, Northern (RNA) blotting showed the presence of a 1.8-kb transcript in both tissues. Seminal progastricsin clones from two human prostatic gland cDNA libraries were isolated and sequenced. The combined sequence manifested only six nucleotide differences from the published genomic and gastric cDNA sequence. One conservative base substitution was present in both libraries. N-Terminal amino acid sequencing of all 43 residues of the seminal proenzyme and the first 34 residues of the mature enzyme yielded sequences identical to those deduced from cDNAs derived from both gastric and prostatic origin. The results obtained indicate that gastric and seminal progastricsin are products of the same gene and that the observed molecular differences between the zymogen from the two sources are probably due to posttranslational modifications.
Abstract: The proteolytic degradation of human seminal fluid proteins at acidic conditions has been investigated. Upon acidification to the pH level of the human vagina, autoproteolysis of most seminal fluid proteins occurred after 30 minute of incubation at 37 degrees C. The degradation was unaffected by inhibitors of serine, thiol, or metallo proteases, whereas pepstatin prevented any proteolysis. The proteins in seminal fluid depleted of the aspartic protease progastricsin did not degrade upon acidification. Readdition of the progastricsin restored the autoproteolytic ability of seminal fluid. Prostate-specific antigen, prostatic acid phosphatase, and Zn-alpha 2-glycoprotein are quickly degraded; albumin, transferrin, and lactoferrin are degraded more slowly. The low molecular weight fragments of semenogelin I and II and especially beta-microseminoprotein are somewhat resistant to proteolysis. These observations strongly suggest that the aspartic protease progastricsin is responsible for the autoproteolysis of seminal fluid proteins under acidic conditions. This suggests that the function of the enzyme is to degrade seminal fluid proteins deposited in the vagina; this in turn may decrease the antigenic load in the vagina and prevent immuno-infertility.
Abstract: Serum pepsinogen has been suggested as a risk marker for the development of gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs). The relation between serum levels of pepsinogen A (PGA) and pepsinogen C (PGC) and endoscopic findings in association with short-term NSAID use was investigated in two double-blind, crossover studies in healthy volunteers. Thirty-two male subjects with a median age of 23 years were given naproxen, oxindanac, or piroxicam for 2 weeks. Upper endoscopy was performed by the same investigator before and after each treatment period, scoring mucosal injection and erosive and hemorrhagic lesions separately on 150-mm visual analogue scales. Blood samples for pepsinogen analyses were drawn before each endoscopy. PGA and PGC were analyzed by means of solid-phase radioimmunoassays. Significant amounts of gastroduodenal mucosal lesions were found in all treatment periods, whereas neither PGA nor PGC changed during treatment. Moreover, the initial levels of serum pepsinogen also failed to predict the subsequent development of gastroduodenal lesions. The risk of a type-II error was small in this study, and our results therefore do not support the use of PGA or PGC as a risk marker in this context.
Abstract: A flow-through microsampling device that can be inserted in the column elution flow line of a chromatographic system has been developed. A sample drop (volume 2.2 nl) is ejected when a voltage pulse is applied to a piezo-electric transducer. The drops can be ejected with up to 70 Hz frequency, giving a sample flow range of 0-9 microliters/min. Samples were collected on a moving agarose surface during elution of freshly prepared human serum. The precipitate pattern obtained after immunoelectrophoresis is similar to what would be obtained in a fused rocket electrophoresis of multiple samples from a fraction collector.
Abstract: The Aspartic proteases (EC 3.4.23) are a group of proteolytic enzymes that share the same catalytic apparatus. Members of the aspartic protease family can be found in different organisms, ranging from humans to plants and retroviruses. The best known sources of aspartic proteases are the stomach of mammals, yeast and fungi, with porcine pepsin as the proto type. The aim of this review is to summarize some of the characteristics of the aspartic protease family.
Abstract: The prevalence and development of antibodies to H+,K+-ATPase were investigated with a sensitive enzyme-linked immunosorbent assay in 86 patients with autoimmune atrophic gastritis (type A). Sixty-nine of the patients had pernicious anemia, and 17 had simple atrophic gastritis. Elevated titers were found in 93% of pernicious anemia probands. Women had higher levels than men: 3.24 versus 1.58 U/l (p = 0.002) (upper reference limit, 0.55 U/l). The antibody levels did not change over 1-4 years, but a gradual decrease in titers over decades was observed. All patients with pernicious anemia had low levels of pepsinogen A, a product of the gastric chief and mucous neck cells (median, 8.5 micrograms/l; reference range, 10-90 percentile, 64.4-195.5 micrograms/l), and elevated serum gastrin values (greater than 55 pmol/l) were found in 87%. Serum pepsinogen A, but not serum gastrin, correlated with H+,K(+)-ATPase antibody titers (r = 0.35, p = 0.01). In the 17 cases with simple atrophic gastritis, H+,K(+)-ATPase antibodies correlated inversely with fundic mucosal gland destruction. The data indicate that H+,K(+)-ATPase antibody titers reflect the immune responsiveness of a given patient as well as the antigenic amount, dependent on the degree of mucosal destruction and the duration of the disease.
Abstract: The relationship between male infertility and the pepsinogen C content in semen has been investigated. The activation of the seminal pepsinogen C in the vagina has been studied under physiological conditions. Samples of semen from 48 vasectomized males and from 46 males of infertile couples were analyzed for pepsinogen C by radioimmunoassay. No correlation was found between the level of pepsinogen C and seminal characteristics, including sperm concentration, motility, and morphologic features. The mean concentration of pepsinogen C was 42.2 micrograms/ml; the first, second, and third quartile were 18.4, 29.6, and 57.6 micrograms/ml, respectively. No significant difference in the level of pepsinogen C was observed between semen of normal quality, semen of reduced quality, and semen with aspermia. Activation of pepsinogen C occurred within 3 h when semen was incubated at pH below 5.0 at 37 degrees C. Intravaginal activation was investigated in six experiments in which semen from two males was instilled in three females. In four experiments with two couples, post-coital activation was investigated. Pepsin C activity in vaginal fluid was detected an average of 3 h (range 2-5 h) and 5 h (4-7 h) after instillation or ejaculation, respectively. Vaginal pH had then been below 4.5 for approximately 1 h. Pepsin C activity was present in the vagina for more than 24 h thereafter. It is most likely that seminal pepsin C is without influence on the fertilizing spermatozoon. However, pepsin C may exert a local effect in the vagina by degrading seminal proteins, thus preventing an immunogenic response in females.
Abstract: To diagnose fundic atrophic (type A) gastritis as part of the clinical investigation of various diseases or for epidemiologic purposes, a simple and reliable diagnostic test would be of great value. We studied circulating levels of pepsinogen A (PGA) and pepsinogen C (PGC) in 179 patients with fundic atrophic gastritis, 29 unselected patients with gastric adenocarcinoma, 15 totally gastrectomized patients, and 50 gastroscopically examined normal controls. Of 147 patients with severe atrophic gastritis, 42 (29%) had serum PGA and 22 (15%) serum PGC values within the range of those in totally gastrectomized patients. The most sensitive test for fundic atrophic gastritis was the PGA/PGC ratio in serum, the sensitivity and specificity being 99% and 94%, respectively (discrimination limit, 5.5). Correspondingly, the positive predictive value was 98%, and the negative predictive value 98%. Of 29 unselected patients with gastric adenocarcinoma 22 (76%) had serum PGA/PGC values lower than the discrimination limit for atrophic gastritis. We conclude that the relatively simple analysis of PGA and PGC in serum is a powerful test for fundic atrophic gastritis with several potential areas of application.
Abstract: Human seminal pepsinogen C has been purified and compared with gastric pepsinogen C. The two zymogens cannot be distinguished by amino acid compositions and sequences of the first 28 N-terminal amino acid residues are identical. Apparent immunological identity is observed with polyclonal antisera. Monoclonal antibodies toward seminal pepsinogen C have been produced. One is able to recognize a non-carbohydrate antigenic determinant only present in seminal pepsinogen C.
Abstract: Pancreatic tissue from 16 post mortem kidney donors have been examined for the content of pepsinogens. A zymogen with electrophoretic mobility, isoelectric point and molecular weight equal to that of pepsinogen C of gastric origin was found in all specimens. A comparison between pepsinogen C extracted from pancreatic tissue and gastric mucosa demonstrated immunological identity. Quantitative measurements with a radioimmunoassay showed pepsinogen C concentrations in pancreatic tissue three to 80 times higher than those of blood serum. Immunohistochemical staining gave positive reaction for pepsinogen C only in the alpha cells of the pancreatic islets.
Abstract: Antiserum raised against an erythrocyte membrane-attached aspartic proteinase precipitates a non-pepsin gastric proteinase. With a monospecific antiserum raised against the non-pepsin gastric proteinase the two enzymes show immunochemical identity. The isoelectric points of both are between 4.5 and 4.6. By SDS-polyacrylamide gel electrophoresis the two proteinases behave the same way. Under non-reducing conditions the main components show molecular weights around 90 000 and after reduction about 58 000. The proteinase may tentatively be classified as cathepsin E.
Abstract: Clotting of casein provides a sensitive method for detection of proteases after gel electrophoresis. The method is here designated "caseogram." After electrophoresis the gel was equilibrated with 0.15-0.3 M sodium acetate, pH 5.3, and an 1% agarose gel containing 1% skim-milk powder in 0.1 M sodium acetate, pH 5.3, was placed on top of the electrophoresis gel. By incubation at 37 degrees C for 2 h the protease-containing zones produced distinct precipitates in the skim-milk gel. For permanent documentation the skim-milk gel was stained with amido black. The detection limit for pepsin A is 5 ng in the caseogram against 25 ng by hemoglobin digestion at pH 2.5. For calf chymosin it is 1 ng against 100 ng by digestion of hemoglobin at pH 3.5. Caseograms work well after agar gel electrophoresis, after different types of immunoelectrophoresis, and after isoelectric focusing or disc electrophoresis in polyacrylamide gels. Since inert proteins do not interfere with the detection, the method is especially suitable for analysis of crude samples. Samples containing pepsinogen or pepsinogen-like zymogens may be activated at pH 2 before equilibration at pH 5.3.
Abstract: The concentration of group I pepsinogens (PG I) in serum was determined in 235 healthy persons and hospital controls. The concentration was significantly higher in males. Correction of PG I with regard to body weight or lean body mass eliminated the sex difference but not the weak correlation with age. The normal range was 0.60-3.3 ng PG I/ml serum/kg body weight. For comparison with other PG I studies another normal range, 46-211 ng PG I/ml serum, was calculated as the 95% interpercentile range of the present PG I concentrations. In a study of diurnal rhythm and in a 6-month study of seasonal variation, no significant variation of PG I in serum was found. Serious non-gastric surgical disease did not influence the PG I level in serum. The PG I levels in blood groups O, A, and B did not differ significantly.
Abstract: Antisera were raised in rabbits against chromatographically purified preparations of pepsin and gastricsin. With these antisera the contents of pepsin and gastricsin in gastric juice were determined by rocket immunoelectrophoresis. The potential content of pepsin and gastricsin of a secondary standard of gastric mucosal extract was calibrated against the chromatographically purified enzymes. This secondary standard was used for routine analyses. The intra-assay and between-assay precision was 3-4% and 6-9%, respectively. Ten healthy volunteers underwent a standard pentagastrin test. The amounts of pepsin and gastricsin determined by rocket immunoelectrophoresis corresponded to the amounts observed by ion exchange chromatography of gastric juice. After stimulation with pentagastrin the secretion of both pepsin and gastricsin was increased about 10 times.
Abstract: SUMMARY
The Aspartic proteases (EC 3.4.23) are a group of proteolytic enzymes that share the same catalytic apparatus. Members of the aspartic protease family can be found in different organisms, ranging from humans to plants and retroviruses. The best known sources of aspartic proteases are the stomach of mammals, with porcine pepsin as the proto type.
This thesis provides a general review of the aspartic proteases and especially on human progastricsin EC 3.4.23.3). Our results on extra-gastric localization of progastricsin are presented with focus on human seminal enzyme. The major findings of these investigations are as follows:
* Employing a developed specific detection method, we have determined progastricsin activity in tissue extracts from duodenal and jejunal mucosa, pancreas, striated muscle, seminal vesicles, prostatic gland and testes, serum and seminal fluid. The electrophoretic mobility of progastricsin from seminal fluid was faster than that observed from extract of gastric mucosa, indicating a structural difference.
* Human pancreatic islets contained progastricsin in a concentration of 32-816 ng/g. The zymogen had the same molecular weight and isoelectric point and immunochemical properties as the gastric progastricsin. The progastricsin was localized to the glucagon producing α- cell.
* Purified seminal progastricsin had the same amino acid composition and the same sequence of the 28 N-terminal residues as gastric progastricsin. However, isolated monoclonal antibodies were able to distinguish between progastricsin from the two sources.
* The concentration of progastricsin in seminal fluid is 42.2 μg/ml (mean of 94 samples) with only few individuals with trace amounts. The concentration of progastricsin was not related to the conventional fertility parameters. Progastricsin activates in the vagina 2-7 h after deposition in the vagina and progastricsin can be determined 24 h after intercourse.
* Seminal gastricsin degrades most seminal fluid proteins at pH levels found in the human vagina. The function of seminal gastricsin might be to prevent immunoinfetility.
* Seminal progastricsin cDNA was cloned and the sequence was very alike the published gastric and the genomic sequences. Only one conservative base substitution was found. Further N-terminal sequencing of the protein revealed no difference between gastric and seminal progastricsin in the first 77 residues. The observed differences in antigenecity and mobility are most likely due to posttranslational modification and gastric and seminal progastricsin originates from the same gene.
* The progastricsin in semnal fluid originates from the epithelium of both the prostatic gland and the seminal vesicles as judged by immunohistochemistry and in situ hybridization.
Abstract: REAGENT DATA SHEET
Reagent:
Antiserum to HTLV-I
Catalog Number:
1189
Release Category:
B
Lot Number:
4 96187
Provided:
1 ml various polyclonal, immunoglobulin fraction. Contains sodium azide.
Biohazardous:
Not Bio
Contributor:
Drs. Pal Szecsi, H. Halgreen, and Jordan Tang.
Datasheet Note:
Acknowledgment for publications should read "The following reagent was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: Antiserum to HTLV-I from Drs. P. Szecsi, H. Halgreen, and J. Tang."
Host Site:
Goat.
Recommended Storage:
4-8°C.
References:
Personal communication.
Release Category:
B
Special Characteristics:
This antiserum was raised against virions isolated from medium of MT-2 cells (Catalog #237). Reacts mainly with p19 and gp46Env. Also detects p36Tax, p24Gag, p21Envr.
status:
Active
Titer:
1:100 - 1:400 by Western blot. Immunoprecipitates HTLV-I Tax at 1:1000.
Last Updated:
August 11, 2007
