Microparticle Enzyme Immunoassay Research Articles

Tacrolimus trough level and oxidative stress in Tunisian kidney transplanted patients

Background The effect of tacrolimus (TAC) on oxidative stress after kidney transplantation (KT) is unclear. This study aimed to evaluate the influence of TAC trough levels of oxidative stress status in Tunisian KT patients during the post-transplantation period (PTP). Methods A prospective study including 90 KT patients was performed. TAC whole-blood concentrations were measured by the microparticle enzyme immunoassay method and adjusted according to the target range. Plasma levels of oxidants (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)) and antioxidants (ascorbic acid, glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured using spectrophotometry. The subjects were subdivided according to PTP into three groups: patients with early, intermediate, and late PT. According to the TAC level, they were subdivided into LL-TAC, NL-TAC, and HL-TAC groups. Results A decrease in MDA levels, SOD activity, and an increase in GSH levels and GPx activity were observed in patients with late PT compared to those with early and intermediate PT (p < 0.05). Patients with LL-TAC had lower MDA levels and higher GSH levels and GPx activity compared with the NL-TAC and HL-TAC groups (p < 0.05). Conclusion Our results have shown that in KT patients, despite the recovery of kidney function, the TAC reduced but did not normalize oxidative stress levels in long-term therapy, and the TAC effect significantly depends on the concentration used.

LEVELS OF SERUM TSH AND ITS IMPLICATIONS IN DEVELOPMENT OF METABOLIC SYNDROME – TIP OF THE ICEBERG: IN YOUNG ADULTS OF GUWAHATI CITY.

Thyroid Stimulating Hormone (TSH) is a hormone secreted by the anterior pituitary that plays an important role in regulating the function of the thyroid gland. Levels of TSH in the blood - is a reliable index of the functional status of the thyroid gland. At present, TSH levels in serum are estimated by microparticle enzyme immuno assays (MEIA), which are very sensitive. In the current study, serum TSH levels were measured in 100 clinically euthyroid subjects, consisting of 50 males and 50 females. The study found that 12% of the subjects (5 males and 7 females) had TSH values above the normal, the normal range of the TSH assay being 0.35-4.50 m IU/ml. This nding is signicant in light of the recent focus on subclinical hypothyroidism being in limelight, particularly the risk of development of overt thyroid dysfunction in persons with high normal values of serum TSH. Furthermore, such kind of studies in general population among young population was done rarely previously, as a reection of their serum TSH levels in this part of the India who are considered euthyroid till the time they were tested. Moreover, detection of subclinical or overt hypothyroid state helps in the preventive aspects as well as to nd out other parameters of metabolic syndrome- which is considered now as just the tip of the iceberg. In the study, serum TSH levels were measured in 100 eut Materials and methods: hyroid subjects (50 males and 50 females) by microparticle enzyme immune assay. After analyzing the values of TSH i Results: t was detected that 12% of the subjects (5 males and 7 females) had TSH levels &gt;4.50 m IU/ml (Upper limit of the normal range). This nding is Conclusion: signicant in light of the recent focus on subclinical hypothyroidism being particularly at the risk of development of overt thyroid dysfunction in young age leading to a gamut of metabolic disorders and mortality &amp; morbidity occuring among such populace at a young age Further, it is of importance that such type of lifestyle modiable disorders can be prevented or reverted to normal if detected early.

Elevated B-type natriuretic peptide level expression associated with acute myocardial infarction patients in Jammu population (India)

B-type natriuretic peptide (BNP) is a highly sensitive and specific indicator of the size of myocardial infarction, which can help in assessing the degree of cardiovascular risk. Elevated BNP levels in patients hospitalized for acute myocardial infarction (AMI) are associated with heart failure and mortality, and the measurements of BNP in a short-term period could be helpful to predict the future events. The role of short-term follow-up BNP level has not been established in the patients with AMI. This retrospective study was conducted on the patients admitted to the Government Medical College, Jammu (India). The analysis of blood EDTA sample was analysed for BNP and this test was performed by using a fully automated random access immunoassay analyser whose principle is based on micro-particle enzyme immunoassay (MEIA). The reference range of BNP is 0-100 pg mL-1. The study revealed a 90% BNP increase in AMI patients in comparison to the 10% increase in normal healthy ones. However, BNP showed elevated levels in healthy individuals suffering from renal insufficiency. The BNP was > 100 pg mL-1 in the majority of AMI patients while in controls BNP is <100 pg mL-1.

Follicle-stimulating hormone and blood lead levels with bone mineral density and the risk of fractures in pre- and postmenopausal women.

The conclusions on the associations of serum follicle-stimulating hormone (FSH) and blood lead levels with bone mineral density (BMD) were controversial. Furthermore, little was known on the impacts of co-existence of serum FSH and blood lead levels on BMD and the risk of fractures in premenopausal and postmenopausal women. Therefore, the present study aimed to examine the associations of serum FSH and blood lead levels with BMD and the risk of fractures in premenopausal and postmenopausal women. Data were derived from the National Health and Nutrition Examination Survey. FSH is assayed using the Microparticle Enzyme Immunoassay technology. Blood lead levels were measured using atomic absorption spectrometry. BMD was measured using dual energy X-ray absorptiometry. Fractures were defined as subjects with fractures in any site of hip, wrist, and spine. This study included 3798 participants. Elevated blood lead levels were associated with increased serum FSH levels (β= 48.22, 95% CI: 40.21~ 56.22). Serum FSH levels were negatively associated with total femur BMD in pre- and postmenopausal women. However, elevated serum FSH levels were associated with a lower lumbar spine BMD and a higher risk of fractures only in postmenopausal women (β= -0.0010, 95% CI: -0.0015~ -0.0006; OR: 1.007, 95% CI: 1.000~1.014, respectively). Serum lead levels were associated with serum FSH levels. Serum FSH levels were associated with a lower BMD and a higher risk of fractures.

The non-linear associations of serum follicle-stimulating hormone levels with bone mineral density and the risk of osteoporosis during menopausal transition: an analysis of National Health and Nutrition Examination Survey data.

To explore the non-linear associations of serum FSH levels with BMD and the risk of osteoporosis in pre- and postmenopausal women. Data analyzed in this study were derived from the National Health and Nutrition Examination Survey (NHANES) III and the NHANES from 1999 to 2002. Women aged from 35 to 60 years with complete data of serum FSH levels and BMD were eligible. Serum FSH levels were assayed using the Microparticle Enzyme Immunoassay technology. Lumbar spine and femur neck BMD were measured using a dual energy X-ray absorptiometry. Osteoporosis was assessed according to BMD of lumbar spine, total femur, and femur neck. This study included 3743 women. A significant non-linear association of serum FSH levels with lumbar spine BMD was observed only in postmenopausal women (P for non-linear association = 0.013) but not in premenopausal women (P for non-linear association = 0.092). The results of femur neck BMD were comparable with those of lumbar spine BMD. Meanwhile, there was significant non-linear association of serum FSH levels with the risk of osteoporosis only in postmenopausal women (P for non-linear association = 0.050). Non-linear associations of serum FSH levels with BMD at lumbar spine and femur neck were observed only in postmenopausal women. Meanwhile, serum FSH levels were non-linearly associated with the risk of osteoporosis in postmenopausal women.

Associations of Serum Follicle-Stimulating Hormone and Luteinizing Hormone Levels with Fat and Lean Mass during Menopausal Transition

Introduction: The association of serum follicle-stimulating hormone (FSH) levels with body fat mass remains inconclusive. Furthermore, little was known about the association of luteinizing hormone (LH) with body fat. This study aimed to investigate the associations of serum FSH and LH levels with fat and lean mass in women during menopausal transition. Methods: The data analyzed in this study were derived from the National Health and Nutrition Examination Survey from 1999 to 2002. Women aged from 35 to 60 years were eligible. Serum FSH and LH levels were assayed using the microparticle enzyme immunoassay technology. A dual energy X-ray absorptiometry was used to measure body fat mass and lean mass. Fat mass index (FMI) and fat-free mass index (FFMI) were respectively used to assess fat and lean mass. General linear regression was employed to examine the associations of serum FSH and LH levels with FMI and FFMI. Results: This study included 1,329 women. For the total participants, elevated serum FSH and LH levels were associated with an increased FMI (β = 0.004 and 0.007; 95% CI: 0.002, 0.006 and 0.004, 0.010, respectively) and a decreased FFMI (β = −0.004 and −0.007; 95% CI: −0.006, −0.002 and −0.010, −0.004, respectively). Furthermore, the significant associations of serum FSH and LH levels with FMI and FFMI were fully observed in postmenopausal women, especially in a certain range of higher serum FSH and LH quartiles. Conclusion: Elevated serum FSH and LH levels were associated with increased body fat mass but decreased lean mass in postmenopausal women but not in premenopausal women. Furthermore, only higher serum FSH and LH percentiles were associated with fat and lean mass in postmenopausal women.

Impact of genetic polymorphisms at the promoter area of IL-10 gene on tacrolimus level in Jordanian renal transplantation recipients.

BackgroundTacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients.MethodsBlood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients.ResultsGenotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 .ConclusionsOur current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.

The optimal interval for post-vaccination serological test in infants born to mothers with positive hepatitis B surface antigen

ABSTRACT Postvaccination serologic testing (PVST) is utilized to monitor the success or failure of vaccination against hepatitis B virus (HBV) infection in infants of hepatitis B surface antigen (HBsAg) positive mothers. This secondary analysis of 1255 infants of HBsAg-positive mothers at 7–14 months age included in two prospective studies aimed to determine the optimal interval for PVST after three hepatitis B vaccine doses. HBsAg and anti-HBs were quantitatively tested with microparticle enzyme immunoassay. The average PVST interval was 3.8 ± 2.2 months. Overall, 1.7% (21/1255) infants had anti-HBs <10 mIU/mL. The non-response rates were 1.6%, 1.1%, 0.9%, 0.7%, 1.1%, 0.7%, and 5.7% when PVST was performed at an interval of 1, 2, 3, 4, 5, 6, and 7–8 months after the third vaccine dose, respectively. Compared with 1 month of PVST interval, the non-response rate in infants who underwent PVST 7–8 months was significantly higher (χ2 = 4.616, P = .032). Anti-HBs titers were significantly declined in infants with medium responses when PVST was performed with longer intervals (χ2 = 27.592, P < .001), actually declined from interval of 6, and 7–8 months (Z = −3.177, P = .001 and Z = −3.715, P < .001), respectively. These results indicate that PVST may be performed at the age of 7–12 months for infants vaccinated on 0, 1, and 6-month schedule. To identify non-responders as early as possible, we suggest that PVST is performed at 7 months age or 1 month after the final vaccine dose.

Hepatitis B Viral Markers in the Human Milk of HBsAg-Positive Mothers: An Observational Study

Quantification of viral antigens and viral loads in human milk samples from mothers infected with hepatitis B virus is largely unknown. The aim of the study was to quantitatively measure the levels of viral antigens and deoxyribonucleic acid of hepatitis B virus in human milk from mothers infected with hepatitis B virus. Fifty-five pairs of milk and serum samples from mothers with positive hepatitis B surface antigen, including 11 hepatitis B e antigen positive, were quantitatively tested to measure viral antigens by microparticle enzyme immunoassay and viral loads by real-time polymerase chain reaction assay. The median level of hepatitis B surface antigen in the human milk samples of mothers with positive or negative hepatitis B e antigen was each lower than that in the sera, respectively (1.10 vs. 4.32 log10 IU/ml, t = 10.693, p < .001; -0.77 vs. 2.53 log10 IU/ml, t = -25.135, p < .001). The titers of hepatitis B surface antigen or hepatitis B e antigen in the human milk samples were each correlated with that in maternal serum. The detectable level of deoxyribonucleic acid of hepatitis B virus in human milk ranged from 1.42-5.27 log10 IU/ml, whereas that in maternal sera was 1.44-8.66 log10 IU/ml. The viral level in human milk was not correlated with that in maternal circulation. The present study data illustrate the relatively low titers of viral markers in the milk of mothers with positive hepatitis B surface antigen.

Analysis of epidemiological serosurvey of hepatitis B virus among people under 29 years of age in Jiangsu Province, China

ABSTRACT Background: The purpose of this paper was to analyze the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc)in1-29 years old living in the most populous eastern province of China,22 years after introduction of hepatitis B vaccine (HepB) vaccination of infants and provide provincial baseline data for developping a better prevention and control plan for hepatitis B virus (HBV)in Jiangsu Province, China Methods: The incidence rates of HBV in Jiangsu province from 2004 to 2014 were obtained from the National Notifiable Disease Reporting System (NNDRS). A stratified cluster random sampling method was used to select 3,002 participants aged 1–29 years across 13 HBV monitoring points throughout the province, which had been classified as either urban or rural. HBV serological markers were measured by Abbott microparticle enzyme immunoassay (MEIA) kits (Abbott Laboratories, Chicago, Illinois). Results: The incidence of hepatitis B decreased by approximately 71.44% in Jiangsu province between 2004 and 2014. Serological assessments showed that the prevalence of the HBsAg, anti-HBc, and anti-HBsin the 1–29 age group were 1.20%, 5.33%,and 66.89%, respectively. There was a significantly lower prevalence of HepB who were vaccinated than in unvaccinated subjects (0.46% vs 14.93%, p < .0001). Among these the ages of 1–29, the coverage rate drops from 97.7% to 56.6% with age,andthe timely rate among people aged 1–14 years was 90.93%. Conclusions: Since the HepB was integrated into the immunization programme in Jiangsu province,the rate of hepatitis B reported and the prevalence of HBsAg decreased significantly, and the coverage of HepB and the vaccination rate within 24 hours after birth have played an important role in reducing HBV infection.

Lysosomal or brush border enzymuria in kidney enzyme activities in seronegative rheumatoid arthritis

Introduction: To determine the effects of non-treated seronegative rheumatoid arthritis (RA) on proximal renal tubule, sensitivity of Alanine aminopeptidase (AAP), g-glutamyltransferase (g--GT), β2 microglobulin in urine β2M), as well as relation with rheumatoid factor (RF) and C-Reactive protein (CRP), DAS 28 disease activity index. Methods: RF was determined by agglutination test (Latex RF test, while kinetic methods were used for determination of Alanine aminopeptidase (AAP) and g-glutamyltransferase (g-GT), as well as MEIA (Micro particle Enzyme Immunoassay) to determine β2 microglobulin in urine. Samples (serum and urine) of 70 participants were examined (35 RA not treated, 35 health control group). Results: In 35 RF negative RA, AAP enzymuria was present in 12 (34.28%) patients, g-GT was present in 7 patients (20%), while β2 microglobulin was present in 3 patients (8.57%). In the healthy control group, 4 patients showed AAP positivity (11.42%), 2 patients g-GT positivity (5.71%) and 1 patient showed presence of β2 microglobulin in urine (2.85). RF was not present in any patient (0%). Conclusion: AAP has a higher sensitivity of g-GT and b2 microglobulin in the detection of asymptomatic renal lesions in non treated seronegative RA.

The Genetic Polymorphism of CYP3A4 rs2242480 is Associated with Sirolimus Trough Concentrations Among Adult Renal Transplant Recipients.

The large interindividual variability in the genetic polymorphisms of sirolimus (SIR)- metabolizing enzymes, transporters, and receptors can lead to qualitatively and quantitatively distinct therapeutic responses. We examined the impact of numerous candidate single-nucleotide polymorphisms (SNPs) involved in the trough concentration of SIR-based immunosuppressant regimen. This is a retrospective, long-term cohort study involving 69 renal allograft recipients. Total DNA was isolated from recipient blood samples and trough SIR concentrations were measured by microparticle enzyme immunoassay. Genome sequence reading was targeted based on next-generation sequencing. The association of tagger SNPs to SIR trough concentrations with non-genetic covariate adjusting was analyzed using logistic regression. A total of 300 SNPs were genotyped in the recipient DNA samples using target sequencing analysis. Only the SNP of CYP3A4 (Ch7: 99361466 C>T, rs2242480) had a significantly higher association with SIR trough concentration as compared to the other 36 tagger SNPs. The mean trough SIR concentration of patients in the CYP3A4 rs2242480-CC group was more significant compared to that of the CYP3A4 rs2242480-TC and TT group, respectively 533.3; 157.4 and 142.5 (ng/ml)/mg/kg, P<0.0001. After adjusting the SNPs, there was no significant association between clinical factors such as age, follow-up period, the incidence of delayed graft function, immunosuppression protocol, and sex with SIR trough concentration. These findings indicated a significant association of polymorphism in the CYP3A4 (Ch7: 99361466 C>T, rs2242480) with SIR trough concentration after 1-year administration in patients who have undergone kidney transplantation.

Assessment of Maximum Voluntary Ventilation (MVV) in Female Hypothyroids and Its Relationships with Serum TSH and FT4 Levels

Background: Hypothyroidism is a common hormonal disorder affecting various organs including lungs and pulmonary dysfunction in hypothyroid patients has been noted.&#x0D; Objective: To observe maximum voluntary ventilation (MVV) in hypothyroid female patients.&#x0D; Materials and method: This cross-sectional study was carried out in the Department of Physiology, BSMMU, Dhaka, Bangladesh, from 1st July 2008 to 30th June 2009 on 60 hypothyroid female patients of 30-50 years old. Based on treatment, hypothyroid patients were divided into B1 (untreated patients on their 1st day of diagnosis) and B2 (patients treated for at least 12-18 months). For comparison, 30 age and BMI matched apparently healthy subjects (Group A) were also studied. The study group was selected from the Out Patient Department of Endocrinology, BSMMU, Dhaka, Bangladesh, and the control group was selected by personal contact. Serum TSH and serum FT4 levels were measured by Microparticle Enzyme Immunoassay (MEIA) principle in AxSYM system. Maximum voluntary ventilation (MVV), which is a lung function parameter, was measured by a digital MicroDL spirometer. Data were analyzed by one way ANOVA test, independent sample t-test and Pearson’s correlation coefficient test.&#x0D; Results: The mean percentage of predicted values of lung function parameter of MVV in control subjects and treated hypothyroids were within normal ranges. However, this value was significantly lower in untreated hypothyroid subjects in comparison to those of control and treated hypothyroid subjects. In addition, MVV showed negative correlation with serum TSH level and positive correlation with serum FT4 level and these relationships were statistically significant in control group and treated hypothyroid subjects.&#x0D; Conclusion: This study reveals that MVV may be lower in untreated hypothyroid female patients compared to control and treated hypothyroids and the deterioration may be positively correlated with serum FT4 level and negatively correlated with serum TSH level. Treatment of hypothyroids may reverse these changes.&#x0D; Delta Med Col J. Jul 2020;8(2): 55-60

EFEK FORTIFIKASI VITAMIN B12 TERHADAP KADAR VITAMIN B12 SERUM DAN HOMOSISTEIN SERUM PADA VEGETARIAN

Introduction: Vegetarians consume plant-based foods with or without eggs and milk. Vegetarians are at risk of vitamin B12 deficiency, as natural sources of vitamin B12 are limited to animal-based foods. Vitamin B12 deficiency can lead to megaloblastic anemia, nerve damage and increase homocysteine level. Higher homocysteine level can increase the risk of coronary heart disease and stroke. The objective of this study was to investigate the effect of vitamin B12 fortification on the level of serum vitamin B12 and homocysteine in vegetarian. Method: The research design was an experimental study, community trial. The samples were 42 vegetarians with vitamin B12 deficiency (&lt; 156 pmol/L) selected from 118 vegetarians as members of Indonesia Vegetarian Society (IVS) Pekanbaru, treated by vitamin B12 fortified oatmeal for three months from March to June 2010. Serum vitamin B12 and homocysteine were measured by electrochemiluminescent immunoassay and microparticle enzyme immunoassay method respectively.&#x0D; Result: Prevalence of vitamin B12 deficiency in vegetarian was 35.6%. Statistical analysis showed a significant increase of serum vitamin B12 from 124.6 to 284.6 pmol/L (p=0.001) and significant decrease of serum homocysteine from 20.1 to 15.1 µmol/L (p=0.001).&#x0D; Conclusion: Consumption of vitamin B12 fortified oatmeal increases the level of serum vitamin B12 and decreases the level of serum homocysteine significantly in vegetarian with vitamin B12 deficiency.

Prevalence of Non-Responsiveness to an Indigenous Recombinant Hepatitis B Vaccine: A Study among Health Care Workers in A Tertiary Hospital

Background and Aim: Health care workers (HCW) are at higher risk of contracting HBV infection. Non-response to HBV vaccine is one of the major impediments to prevent healthcare associated HBV infection (HAHI). We estimated the prevalence of non-responsiveness to initial 3-dose regimen of an indigenous recombinant HBV vaccine (GeneVac-B) among South Indian HCWs and typed the HLA in non-responders. Study Design and Method: Of the 778 subjects screened over 1 year, 454 completed all three doses of the hepatitis B vaccination. Anti-HBs titers were estimated by microparticle enzyme immunoassay Automated ELISA. HLA typing was done using AllSet+™ Gold SSP. Conclusion: Our findings suggest that non-response to HBV vaccine is not a major impediment to prevent HAHI. Robust seroprotection rates can be achieved using this indigenous HBV vaccine. However, gender and BMI might influence the level of anti-HBs titers. We recommend the use of this cost effective HBV vaccine as well as post vaccination anti-HBs testing to prevent HAHI among HCWs.

CYP3A5 polymorphisms and their effects on tacrolimus exposure in an ethnically diverse South African renal transplant population.

Tacrolimus forms the cornerstone for immunosuppression in solid-organ transplantation. It has a narrow therapeutic window with wide inter- and intra-patient variability (IPV). Cytochrome P-450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A&gt;G is the most frequently studied polymorphism in the CYP3A5 gene. The rs776746A&gt;G (i.e. CYP3A5*3) single-nucleotide polymorphism in CYP3A5 alters tacrolimus predose trough concentration (C0) and may also affect IPV, which may lead to immune- and/or drug-mediated allograft injury. CYP3A5*3 may result in absent (*3/*3), partial (*1/*3) or normal (*1/*1) CYP3A5 expression. The effect of CYP3A5*3 on tacrolimus exposure and variability has not been examined in South African (SA) transplant recipients. To determine the frequencies and effect of CYP3A5 and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms on tacrolimus C0/dose ratios in different ethnic groups attending a tertiary renal transplant clinic in SA, and other factors that may explain inter- and IPV in tacrolimus C0. All consenting stable renal transplant recipients on tacrolimus at the Livingstone Hospital Renal Unit in Port Elizabeth, SA, were included. Tacrolimus concentrations were obtained using a microparticle enzyme immunoassay method (ARCHITECT analyser, Abbott Laboratories). Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 and *6 allelic variants. There were 43 participants (35% black African, 44% mixed ancestry and 21% white), with a mean age of 44.5 years, median duration post-transplant of 47 months and median (interquartile range) creatinine and estimated glomerular filtration rate levels of 118(92- 140) µmol/L and 62 (49 - 76) mL/min at study inclusion. The mean tacrolimus C0 in the study was 6.7 ng/mL, with no difference across the different ethnic groups. However, the mean total daily dose of tacrolimus required was 9.1 mg (0.12 mg/kg), 7.2 mg (0.09 mg/kg) and 4.3 mg (0.06 mg/kg) in black, mixed-ancestry and white patients, respectively (p=0.017). The frequencies for CYP3A5 expressors (i.e. CYP3A5*1/*1 + CYP3A5*1/*3 genotypes) were 72%, 100%, 76% and 12% for all patients combined and black, mixed-ancestry and white patients, respectively. The frequencies for CYP3A5 non-expressors (i.e. CYP3A5*3/*3 genotypes) were 0%, 24% and 88% among the black, mixed-ancestry and white patients, respectively. None of the patients carried the CYP3A5*6 allele. CYP3A5*1/*1 and CYP3A5*1/*3 genotype carriers required a two-fold increase in dose compared with the non-expressor genotype carriers, CYP3A5*3/*3 (p&lt;0.05). CYP3A5*3/*3 carriers also demonstrated higher IPV than CYP3A5*1/*1 and *1/*3 carriers (18.1% v. 14.2%; p=0.125). Compared with global transplant populations, SA renal transplant recipients demonstrated a very high rate of CYP3A5 expression, with a significant impact on tacrolimus pharmacokinetics. Genetic variation in CYP3A5 expression affects tacrolimus dosing requirements, and knowing the CYP3A5 genotype of transplant patients may allow better dose prediction compared with current standard dosing recommendations in a multi-ethnic population. Overall, black African patients required higher doses of tacrolimus than their white counterparts. While further prospective studies are needed to better evaluate dosing algorithms, it would appear that the starting dose of tacrolimus should be higher in black and mixed-race patients.

Therapeutic drug monitoring of tacrolimus in kidney transplantation

Calcineurin inhibitors (CNI) are the backbone of present-day immunosuppressive regimen in kidney transplant recipients. Tacrolimus (TAC) has gradually replaced cyclosporine as CNI of choice due to its better potency and side effect profile. One of the key challenges in using TAC is therapeutic drug monitoring (TDM) of TAC, as it is a drug of narrow therapeutic index. Various methods of TDM are available; there are older immunoassay (IA)-based methods and recent liquid chromatogram (LC) based. The problems with older IAs like microparticle enzyme IA (Abbott Diagnostics, Chicago, IL, USA), and enzyme multiplied IA (EMIT, Dade Behring, Glasgow, DE, USA) are; they are not so accurate, there is interference with other substances, they measure inactive metabolite, and their limit of detection is not wide. The LC-based methods such as liquid chromatogram mass spectroscopy or LC-tandem mass spectroscopy overcome these issues; however, they are costly, labor intensive, and require good technical support. Newer IAs, such as chemiluminescent microparticle IA (Abbott Diagnostics) and Quantitative Microsphere System (QMS™, Thermo-Fisher), have functional sensitivity

Yield of screening blood work and MRI of the brain and orbits in the work-up of unilateral chronic optic neuropathy.

No guidelines exist for the investigation of treatable causes of chronic optic neuropathy, including sarcoidosis, lupus, and syphilis. The purpose of this study was to determine the diagnostic yield of screening blood work (ACE (Angiotensin Converting Enzyme)for sarcoidosis, Antinuclear Antibodies (ANA) for lupus, CMIA(chemiluminescence microparticle enzyme immunoassay) for syphilis) and contrast-enhanced MRI brain and orbits in atypical unilateral chronic optic neuropathy. Retrospective review from February 2012 to June 2018 at a neuro-ophthalmology practice. Six hundred and eighty-three consecutive charts with optic neuropathy were reviewed. Inclusion criteria were unilateral chronic optic neuropathy and a work-up including contrast-enhanced MRI brain and orbits, CBC, ESR, CRP, ANA, CMIA, and ACE. Exclusion criteria were optic nerve swelling in either eye on initial assessment or an established cause of optic neuropathy. The main outcome measure was diagnostic yield. Fifty-seven patients were included. One patient had elevated ACE, seven had positive ANA titers, and three had positive CMIA. Zero patients were diagnosed with sarcoidosis, one patient was diagnosed with lupus-related optic neuropathy, and one patient was diagnosed with syphilitic optic neuropathy. The diagnostic yield of ACE was 0%, ANA was 1.75%, and CMIA was 1.75%. MRI revealed planum sphenoidale meningioma causing compressive optic neuropathy in one patient, giving it a diagnostic yield of 1.82%. Routine screening blood work (ACE, ANA, CMIA) and MRI brain and orbits for chronic idiopathic unilateral optic neuropathy has low diagnostic yield, especially if clinical suspicion for syphilis, lupus, and sarcoidosis is low. MRI should still be performed in all cases in order to rule out compressive lesions.

Evaluation of ovarian reserve function in patients with systemic lupus erythematosus by anti-Mueller hormone

Objective To evaluate the effect of anti-Mueller hormone on ovarian reserve in female patients with systemic lupus erythematosus(SLE). Methods The clinical data of 80 women with SLE in the Department of Rheumatism of Zaozhuang Municipal Hospital from June 2015 to June 2018 were collected.The patients used cyclophosphamide before entering the group were selected as A group(35 cases), and patients who didn't use cyclophosphamide were selected as B group(45 cases), and 30 healthy female volunteers were selected as the control group at the same time.All of them were normal menstrual cycle.At the third day of the menstrual cycle, the levels of anti-Mueller hormones were detected by enzyme linked immunosorbent assay.The serum levels of estrogen and alveolar hormone were detected by microparticle enzyme immunoassay, and the number of ovarian sinus follicles in each group was recorded by transvaginal ultrasound. Results The incidence rate of thrombocytopenia, nephritis, hemolytic anemia and neuropsychiatric manifestations in A group were 54.29%(19/35), 85.71%(30/35), 37.14%(13/35) and 22.86%(8/35), respectively, which were significantly higher than those in B group[48.89%(22/45), 53.33%(24/45), 13.33%(6/45), 0.00%(0/45)](χ2=6.33, 9.41, 6.16, 9.03, all P 0.05). The level of anti-Mueller hormone in patients with SLE aged>30 years[(0.98±0.31)g/L]was significantly lower than patients ≤30 years old[(1.86±0.60)g/L], and the level of anti-Mueller hormone in patients with cyclophosphamide accumulation>10 g[(0.36±0.11)g/L]was significantly lower than that of 10 g[(1.76±0.52)g/L](t=7.54, 11.30, both P<0.01). The results of Pearson correlation analysis showed that the anti-Mueller hormone showed negative correlation with the age of SLE and the accumulation of cyclophosphamide(r=-0.56, -0.45, both P<0.01). Conclusion The use of anti-Mueller hormone has good evaluation value for ovarian reserve function in female patients with SLE, and the level of anti-Mueller hormone is closely related to the age and the accumulation of cyclophosphamide.Therefore, cyclophosphamide should be used carefully in patients who are over 30 years old and the cumulative amount of cyclophosphamide over 10 g. Key words: Anti-mueller hormone; Lupus erythematosus, systemic; Ovarian function tests; Cyclophosphamide; Estrogens; Follicle stimulating hormone; Ovarian sinusoidal follicles; Age groups; Female

Soluble intercellular adhesion molecule-1 is a prognostic marker in colorectal carcinoma

PurposeSerological tumor markers are routinely used to monitor tumor onset and progression. In colorectal carcinoma (CRC), the carcinoembryonic antigen (CEA) is roughly elevated in 50% of patients at initial diagnosis. Soluble ICAM-1 (sICAM-1) is elevated in different cancers. The aim of this study was to evaluate the prognostic relevance of sICAM-1 combined with CEA in patients with CRC.MethodsIn blood samples of 297 CRC patients, sICAM-1 was determined by ELISA and CEA by microparticle enzyme immunoassay the day before oncologic resection. Separation in patients with sICAM-1high and sICAM-1low was performed by minimum p value approach; separation in CEA normal and elevated was performed according to the established diagnostic cutoff. Clinical data were obtained from the prospective collected data from the Erlangen Registry for Colorectal Carcinomas.ResultsCancer-related 5-year survival rate of patients with sICAM-1low (< 290 ng/ml, n = 208) was significantly increased (83.4%) as compared to that of patients with sICAM-1high (≥ 290 ng/ml, n = 89) (66.2%; p < 0.001). Patients with normal CEA concentrations (n = 199; 90.8%) showed a significantly (p < 0.001) improved cancer-related 5-year survival rate compared to patients with elevated CEA concentrations (n = 98; 52.1%). Moreover, high sICAM-1 was an independent risk factor (hazard ratio 1.6) in multivariate analysis. Of note, increased sICAM-1 levels, either within normal or within elevated CEA, allowed to identify high-risk subgroups, both for overall (p < 0.001) and cancer-related survival (p < 0.001).ConclusionApplication of a novel risk score combining CEA/sICAM-1 serum concentrations allows the identification of high-risk groups for poor survival in CRC patients.