Placental Transfer of Sulphasalazine and Sulphapyridine and Some of Its Metabolites

In eleven pregnant patients with ulcerative colitis or Crohn's disease who were treated with sulphasalazine (SASP) the scrum concentrations of SASP and sulphapyridine (SP) were measured at delivery. The concentrations of SASP and SP were almost identical in the cord serum and the maternal serum. In seven of the women the same concentrations were measured at a later occasion when they were not pregnant. The serum SASP concentration remained the same, but the SP concentration was higher in the non-pregnant women. This probably reflects the different degree of protein binding of SASP and SP, respectively, and the change of distribution volume that occurs in pregnancy. In the newborn the concentrations of SASP and SP were 4.6 ± 3.1 μg/ml and 18.2 ± 8.7 μg/ml, respectively. Current studies have shown that neither SASP nor SP in these concentrations causes significant displacement of bilirubin from albumin. Thus, SASP can be given to the pregnant patient up to delivery without risks for the newborn full-term infant.     

Estimation of Admission D-dimer Cut-off Value to Predict Venous Thrombotic Events in Hospitalized COVID-19 Patients: Analysis of the SEMI-COVID-19 Registry

BackgroundVenous thrombotic events (VTE) are frequent in COVID-19, and elevated plasma D-dimer (pDd) and dyspnea are common in both entities.ObjectiveTo determine the admission pDd cut-off value associated with in-hospital VTE in patients with COVID-19.MethodsMulticenter, retrospective study analyzing the at-admission pDd cut-off value to predict VTE and anticoagulation intensity along hospitalization due to COVID-19.ResultsAmong 9386 patients, 2.2% had VTE: 1.6% pulmonary embolism (PE), 0.4% deep vein thrombosis (DVT), and 0.2% both. Those with VTE had a higher prevalence of tachypnea (42.9% vs. 31.1%; p = 0.0005), basal O2 saturation <93% (45.4% vs. 33.1%; p = 0.0003), higher at admission pDd (median [IQR]: 1.4 [0.6–5.5] vs. 0.6 [0.4–1.2] μg/ml; p < 0.0001) and platelet count (median [IQR]: 208 [158–289] vs. 189 [148–245] platelets × 10⁹/L; p = 0.0013). A pDd cut-off of 1.1 μg/ml showed specificity 72%, sensitivity 49%, positive predictive value (PPV) 4%, and negative predictive value (NPV) 99% for in-hospital VTE. A cut-off value of 4.7 μg/ml showed specificity of 95%, sensitivity of 27%, PPV of 9%, and NPV of 98%. Overall mortality was proportional to pDd value, with the lowest incidence for each pDd category depending on anticoagulation intensity: 26.3% for those with pDd >1.0 μg/ml treated with prophylactic dose (p < 0.0001), 28.8% for pDd for patients with pDd >2.0 μg/ml treated with intermediate dose (p = 0.0001), and 31.3% for those with pDd >3.0 μg/ml and full anticoagulation (p = 0.0183).ConclusionsIn hospitalized patients with COVID-19, a pDd value greater than 3.0 μg/ml can be considered to screen VTE and to consider full-dose anticoagulation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07017-8.Key Words: COVID-19, SARS-CoV-2, venous thrombotic event, deep vein thrombosis, pulmonary embolism, D-dimer     

The metabolism of salicylazosulphapyridine in ulcerative colitis: I The relationship between metabolites and the response to treatment in inpatients

The metabolism of salicylazosulphapyridine was studied in 16 patients with ulcerative colitis admitted to hospital. The acetylator phenotype was determined on admission. The mean serum concentration (mug/ml) (at steady state eight +/- two days in patients responding to treatment) of SASP, total SP, and 5-ASA were 18.7 +/- 12.8; 53.7 +/- 23.1; and 1 +/- 0.9 for slow acetylators and 17.6 +/- 7.1; 31 +/- 9.0 and 1 +/- 0.9 for fast acetylators respectively. Twenty-four hour urinary excretion of SASP, total SP, and 5-ASA were 4.6% +/- 3.1; 52% +/- 9.6 and 22.3 +/- 6.7% of the administered dose respectively.Serum total SP concentration of 20 to 50 mug/ml appeared to coincide with clinical improvement in the absence of any side effects related to salicylazosulphapyridine. No such relationship could be shown with serum SASP, individual metabolites, or 5-aminosalicyclic acid.     

Comparison of the in vitro Effects of One-day Exposure to Amodiaquine and Praziquantel on Schistosoma mansoni Adult Worm Pairs

It has been demonstrated that continuous exposure to amodiaquine (AQ) alone elicits in vitro antischistosomal activities at concentrations of 1–10 μg/ml. However, orally administered drugs reach a peak blood concentration within one or two hours and then gradually decrease. The blood concentration does not remain at a constant level over several days as in vitro concentration of continuous drug exposure. In vitro activities by one day exposure to AQ better reflect the actual antischistosomal activities after oral administration than those elicited by continuous exposure.The objective of the present study is to compare the antischistosomal potential of one-day exposure to AQ with that to praziquantel (PZQ), a current antischistosomal drug. Schistosoma mansoni adult worm pairs were incubated with 0 (control), 1, 2, 5 and 10 μg/ml AQ as well as 0.01, 0.02, 0.05 and 0.1 μg/ml PZQ for the first day, and were subsequently incubated in drug-free media for a period of 14 days. The one-day exposure to AQ significantly reduced the daily egg output of the worm pairs at 1–10 μg/ml. The inhibitory effect on egg production continued at 5 and 10 μg/ml but proved temporary at 1 and 2 μg/ml. Furthermore, AQ-induced specific morphological alterations (severe swelling and/or localization of hemozoin) were observed in the worms at 5 and 10 μg/ml. The AQ-specific appearance of the male worms gradually faded during subsequent incubation in drug-free media, although the female worms showed elongation. Meanwhile, PZQ inhibited the egg output of adult worm pairs at concentrations of 0.01–0.1 μg/ml during exposure. The inhibitory effect on egg production continued at 0.05 and 0.1 μg/ml but proved temporary at 0.01 and 0.02 μg/ml. Furthermore, PZQ induced a visible contraction and shortening of the male and female worms at 0.05 and 0.1 μg/ml during exposure, but the PZQ-specific alterations quickly disappeared during subsequent incubation in drug-free media. To our knowledge, this is the first report showing that one-day exposure to AQ inhibits the egg production of adult worm pairs at 1–10 μg/ml and induces specific morphological alterations in the worms at 5 and 10 μg/ml. The present findings have important implications for the evaluation of the therapeutic effects of both AQ monotherapy and combination therapy with artesunate on schistosomiasis in clinical field trials.     

Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites

In eleven pregnant patients with ulcerative colitis or Crohn's disease who were treated with sulphasalazine (SASP) the serum concentrations of SASP and sulphapyridine (SP) were measured at delivery. The concentrations of SASP and SP were almost identical in the cord serum and the maternal serum. In seven of the women the same concentrations were measured at a later occasion when they were not pregnant. The serum SASP concentration remained the same, but the SP concentration was higher in the non-pregnant women. This probably reflects the different degree of protein binding of SASP and SP, respectively, and the change of distribution volume that occurs in pregnancy. In the newborn the concentrations of SASP and SP were 4.6 +/- 3.1 microgram/ml and 18.2 +/- 8.7 microgram/ml, respectively. Current studies have shown that neither SASP nor SP in these concentrations causes significant displacement of bilirubin from albumin. Thus, SASP can be given to the pregnant patient up to delivery without risks for the newborn full-term infant.     

Effect of Zinc Supplementation on Serum Homocysteine in Type 2 Diabetic Patients with Microalbuminuria

OBJECTIVES: Elevated homocysteine levels are considered to be an independent risk factor for cardiovascular complications in diabetic patients. The aim of this study was to find out if zinc supplementation improves homocysteine levels, which may exert vascular-protective effects in type 2 diabetes subjects with microalbuminuria. METHODS: In a randomized, double-blind, controlled, crossover study, 50 type 2 diabetic patients with microalbuminuria were subdivided into two groups and supplemented with 30 mg/d of zinc (group 1) or placebo (group 2) for three months with a four-week wash out period. Serum creatinine, vitamin B₁₂, folate, fasting plasma glucose, HbA1c, lipid profiles, zinc, homocysteine levels and random urine albumin were measured before and after the first and second phase of the study in all participants. RESULTS: Mean serum zinc was significantly increased after zinc supplementation (from 76 ± 16 μg/dl to 93 ± 20 µg/dl; p < 0.05), while there was no change in the placebo group (75 ± 16 µg/dl to 75 ± 15 µg/dl). With zinc supplementation, homocysteine levels reduced significantly (from 13.71 ± 3.84 μmol/l to 11.79 ± 3.06 μmol/l; p < 0.05), which did not occur on placebo (from 12.59 ± 2.13 μmol/l to 13.36 ± 2.03 μmol/l). Simple regression was used to show a positive correlation between urine albumin excretion and serum homocysteine (r = 0.37, p = 0.023). Vitamin B₁₂ and folate levels increased significantly in patients who received zinc in comparison to those who received placebo. A negative correlation was observed between homocysteine and vitamin B₁₂ concentration (r = -0.36, p = 0.025). CONCLUSION: Zinc supplementation reduced serum homocysteine and increased vitamin B₁₂ and folate concentrations in type 2 diabetic patients with microalbuminuria.     

Lipid levels in serum and cancerous tissues of colorectal cancer patients

AIM: To investigate the correlations between lipid metabolism disorder and the occurrence and development of colorectal cancer by monitoring the alterations in lipid levels in cancerous tissue and serum in patients with colorectal cancer.METHODS: The levels of total and free cholesterol (TCH and FCH), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), apolipoprotein A1 (ApoA-1) and ApoB in serum of 206 patients with colorectal cancer, 70 patients with benign colorectal disease and 300 healthy participants, and in the cancerous tissue and paracancerous tissue of 152 patients with colorectal cancer were measured with an Olympus 600 auto-biochemical analyzer. The obtained data were statistically analyzed.RESULTS: Serum FCH level was significantly higher (1.9 ± 0.4 mmol/L vs 1.3 ± 0.3 mmol/L, 1.9 ± 0.4 mmol/L vs 1.2 ± 0.4 mmol/L, P < 0.05), whereas serum levels of TCH, LDL-C, ApoA-I and ApoB were significantly lower in patients with colorectal cancer than in patients with benign colorectal disease and healthy controls. The levels of FCH and TG in cancerous tissue were significantly lower (14.5 ± 9.6 μmol/g vs 19.3 ± 13.9 μmol/g, P < 0.05; 16.3 ± 19.8 μmol/g vs 44.1 ± 38.1 μmol/g, P < 0.05), whereas HDL-C level was significantly higher (7.9 ± 4.5 μmol/g vs 5.7 ± 3.9 μmol/g, P < 0.01) in cancerous tissue than in paracancerous tissue. The levels of TCH and TG in serum and the levels of TCH and HDL-C in cancerous tissue in patients with colorectal cancer were significantly correlated with TNM stage. The levels of TCH and LDL-C in serum were significantly lower, whereas HDL-C level in cancerous tissue was significantly higher in patients with lymph node metastasis than in patients without lymph node metastasis. The levels of TCH, FCH, TG, HDL-C and LDL-C in cancerous tissue were not significantly different from those in paracancerous tissue. The serum levels of FCH and TG were significantly higher, whereas serum HDL-C levels were significantly lower in patients with rectum cancer than in patients with colon cancer.CONCLUSION: The disordered and abnormally altered levels of lipids in cancerous tissue and serum of patients with colorectal cancer may be correlated with the occurrence and development of colorectal cancer.     

Expression of lipocalin-type prostaglandin D synthase (β-trace) in human heart and its accumulation in the coronary circulation of angina patients

Lipocalin-type prostaglandin D synthase (L-PGDS) is localized in the central nervous system and male genital organs of various mammals and is secreted as β-trace into the closed compartment of these tissues separated from the systemic circulation. In this study, we found that the mRNA for the human enzyme was expressed most intensely in the heart among various tissues examined. In human autopsy specimens, the enzyme was localized immunocytochemically in myocardial cells, atrial endocardial cells, and a synthetic phenotype of smooth muscle cells in the arteriosclerotic intima, and accumulated in the atherosclerotic plaque of coronary arteries with severe stenosis. In patients with stable angina (75–99% stenosis), the plasma level of L-PGDS was significantly (P < 0.05) higher in the great cardiac vein (0.694 ± 0.054 μg/ml, n = 7) than in the coronary artery (0.545 ± 0.034 μg/ml), as determined by a sandwich enzyme immunoassay. However, the veno-arterial difference in the plasma L-PGDS concentration was not observed in normal subjects without stenosis. After a percutaneous transluminal coronary angioplasty was performed to compress the stenotic atherosclerotic plaques, the L-PGDS concentration in the cardiac vein decreased significantly (P < 0.05) to 0.610 ± 0.051 μg/ml at 20 min and reached the arterial level within 1 h. These findings suggest that L-PGDS is present in both endocardium and myocardium of normal subjects and the stenotic site of patients with stable angina and is secreted into the coronary circulation.     

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

AIM:To explore the relationship between α-fetoprotein(AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma(HCC) thoroughly.METHODS:A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study.The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis,such as status of hepatitis B virus(HBV) infection,tumor size,tumor number,vascular invasion and degree of tumor differentiation.Also,patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP(≤ 20 μg/L,21-400 μg/L,401-800 μg/L,and ≥ 801 μg/L),to compare the positive rate of patient among four groups stratified by various clinicopathological variables.And the correlation of different kinds of tumor staging systems,such as TNM,Barcelona Clinic Liver Cancer(BCLC) staging classification and China staging,were compared with the serum concentration of AFP.RESULTS:A total of 2304 HCC patients were enrolled in this study totally;the mean serum level of AFP was 555.3 ± 546.6 μg/L.AFP levels were within the normal range(< 20 μg/L) in 27.4%(n = 631) of all the cases.81.4%(n = 1875) patients were infected with HBV,and those patients had much higher serum AFP level compared with non-HBV infection ones(573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L,P < 0.001).The AFP level in tumors ≥ 10 cm(808.4 ± 529.2 μg/L) was significantly higher(P < 0.001) than those with tumor size 5-10 cm(499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm(444.9 ± 514.2 μg/L).AFP levels increased significantly in patients with vascular invasion(694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L,P < 0.001).Patients with low tumor cell differentiation(559.2 ± 545.7 μg/L) had the significantly(P = 0.007) highest AFP level compared with high differentiation(207.3 ± 420.8 μg/L) and intermediate differe     

Development of a Chemiluminescence Immunoassay for Serum YB-1 and its Clinical Application as a Potential Diagnostic Marker for Hepatocellular Carcinoma

Background

Y-box binding protein 1 (YB-1) overexpression has been shown in various tumor cells including hepatocellular carcinoma (HCC); moreover, this protein can be actively secreted.

Objectives

The aim of this study was to establish a method to quantify serum YB-1 and evaluate its clinical application in the clinical diagnosis of HCC.

Patients and Methods

Recombinant YB-1 and two populations of its antibodies were prepared. A monoclonal antibody was specific to the N-terminus of YB-1 amino acids 134-160; and another was a polyclonal antibody. A sandwich-type chemiluminescence immunoassay (CLIA) was developed and evaluated. Levels of YB-1 and alpha fetoprotein (AFP) in serum samples from 105 HCC patients, 25 hepatitis B virus patients, 25 cirrhosis patients, and 50 healthy donors were detected using the established method and an AFP electrochemiluminescence kit.

Results

The developed method was linear to 150 μg/L of YB-1 with a minimum detection limit of 0.01 μg/L. The average recoveries were between 93.9% and 109.0%. The mean intra- and inter-assay coefficients of variation (CVs) were 4.0-4.8% and 8.2-10.2%, respectively. The relationship between the concentration of diluted YB-1 and the dilution ratios gave a good linear correlation coefficient of 0.9986. The YB-1 concentration was increased in serum of HCC patients (33.0 ± 23.39 μg/L) compared to healthy individuals (13.2 ± 5.29 μg/L, P < 0.0001), patients with HBV (17.9 ± 7.49 μg/L, P = 0.0003), and patients with HBV cirrhosis (20.7 ± 8.75 μg/L, P < 0.05). Moreover, the combination of YB-1 and alpha-fetoprotein had a high sensitivity (89.5%) and reasonable specificity (62.0%) in identifying HCC.

Conclusions

The established method has an acceptable performance in quantifying YB-1. In addition, serum YB-1 may aid in the diagnosis of HCC.     

Soluble P-selectin and matrix metalloproteinase 2 levels are elevated in patients with diastolic dysfunction independent of glucose metabolism disorder or coronary artery disease

OBJECTIVE:

The development of diastolic dysfunction (DDF) is multifactorial. Possible mechanisms include metabolic disturbances, myocardial fibrosis, chronic inflammation and endothelial dysfunction. Recognizing early stages of DDF may help to identify patients at risk of developing symptomatic DDF. Therefore, biomarkers reflecting pathophysiological changes within the myocardium were investigated in patients with DDF.

METHODS:

Seventy-seven patients submitted for coronary angiography with stable or suspected coronary artery disease (CAD) were consecutively enrolled. Those without known diabetes mellitus (DM) underwent a standardized oral glucose tolerance test. Echocardiography for the diagnosis of DDF was performed according to the European Society of Cardiology. Matrix metalloproteinase 2 (MMP-2) and soluble P-selectin (sP-selectin) serum concentrations were analyzed using the ELISA technique.

RESULTS:

A total of 36% of patients had DM and 74% had CAD. The prevalence of DDF was higher in patients with DM (89% versus 74%) and CAD (84% versus 53%) (P<0.05). DDF in patients with DM was more severe with a significantly lower mitral annulus velocity of 6.5 cm/s versus 7.8 cm/s (P<0.01). Patients with DDF showed significantly higher sP-selectin (140.3 μg/L versus 107.6 μg/L, P<0.05) and MMP-2 (270.5 μg/L versus 224.7 μg/L, P<0.05) levels compared with those without DDF. There was a significant correlation between sP-selectin and MMP-2 (P=0.01), independent of the diagnosis of DM or CAD.

CONCLUSION:

sP-selectin as a marker for platelet hyperactivity, inflammation and endothelial dysfunction, and MMP-2 as a marker for extracellular matrix turnover were significantly elevated in patients with DDF. This elevation was independent of coexisting DM or CAD. This observation may help to identify and monitor patients with DDF.     

Effect of Intraoperative and Postoperative Infusion of Dexmedetomidine on the Quality of Postoperative Analgesia in Highly Nicotine-Dependent Patients After Thoracic Surgery: A CONSORT-Prospective,Randomized, Controlled Trial

Smoking is one of the most common addictions in the world. Nicotine inhalation could increase the risk of cardiorespiratory diseases. However, the solution that improved postoperative analgesia for highly nicotine-dependent patients undergoing thoracic surgery has not been specifically addressed.This CONSORT-prospective, randomized, double-blinded, controlled trial investigated the efficacy of combination of dexmedetomidine and sufentanil for highly nicotine (Fagerstrom test of nicotine dependence ≥6)-dependent patients after thoracic surgery.One hundred seventy-four male patients who underwent thoracic surgery were screened between February 2014 and November 2014, and a total of forty-nine were excluded. One hundred thirty-two highly nicotine-dependent male patients who underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia were divided into 3 groups after surgery in this double-blind, randomized study: sufentanil (0.02 μg/kg/h, Group S), sufentanil plus dexmedetomidine (0.02 μg/kg/h each, Group D1), or sufentanil (0.02 μg/kg/h) plus dexmedetomidine (0.04 μg/kg/h) (Group D2). The patient-controlled analgesia (PCA) program was programmed to deliver a bolus dose of 2 ml, with background infusion of 2 ml/h and a lockout of 5 min, 4-hour limit of 40 ml, as our retrospective study. The primary outcome measure was the cumulative amount of self-administered sufentanil; the secondary outcome measures were pain intensity (numerical rating scale, NRS), level of sedation (LOS), Bruggrmann comfort scale (BCS), functional activity score (FAS), and concerning adverse effects.The amount of self-administered sufentanil were lower in group D2 compared with S and D1 groups during the 72 hours after surgery (P < 0.05), whereas the total dosage and dosage per body weight of sufentanil were significantly lower in D1 group than that of S group only at 4, 8, and 16 hours after surgery (P < 0.05). Compared with S group, the NRS scores at rest at 1, 4, and 8 hours after surgery and with coughing at 4, 8, 16, and 24 hours after surgery were significantly lower in D2 group (P < 0.05). However, compared with D1 group, the NRS scores both at rest and with coughing at 4 and 8 hours after surgery were significantly lower in D2 group (P < 0.05). The NRS scores both at rest and with coughing show that there were no significant differences between D1 group and S group at each time point after surgery (P > 0.05). LOS of group D2 was higher than S and D1 groups at 1 hour after surgery (P < 0.05), BCS of group D2 was higher than S and D1 groups at 4, 8, and 16 hours after surgery (P < 0.05), and FAS of group D2 was higher than S and D1 groups at 48 and 72 hours after surgery (P < 0.05). The number of rescue analgesia during 72 hours after surgery in D2 group was lower than S and D1 groups (P < 0.05). There were no significant differences among the 3 groups in terms of baseline clinical characteristics and postoperative adverse effects except for itching (P > 0.05).Among the tested patient-controlled analgesia options, the addition of dexmedetomidine (0.04 μg/kg/h) and sufentanil (0.02 μg/kg/h) showed better analgesic effect and greater patient satisfaction without other clinically relevant side effects for highly nicotine-dependent patients during the initial 72 hours after thoracic surgery.Trial Registration: chictr.org (ChiCTR-TRC-14004191).     

Development of a simple method for measuring tedizolid concentration in human serum using HPLC with a fluorescent detector

The objective of the present study was to develop a method to measure tedizolid (TZD) concentration for studying target concentration intervention, pharmacokinetics, and pharmacodynamics of TZD. We established a high-performance liquid chromatography-fluorescence detector assay to measure the TZD concentration in serum for clinical application. Chromatographic separation was carried out on a 5 μm octadecyl silane hypersil column 150 mm × 4.6 mm. The mobile phase consisted of 0.1 M phosphoric acid and methanol (60:40, pH 7.0). Detection was performed at 300 nm and 340 nm for the excitation and emission wavelengths, respectively. The average retention times of TZD and the internal standard were 12.9 and 8.8 min, respectively. High linearity was exhibited over a concentration range of 0.025 to 10.0 μg/mL for TZD (R² > 0.999). The intra- and inter-assay accuracies of TZD were 99.2% to 107.0% and 99.2% to 107.7%, respectively. The lower limit of quantitation and the lower limit of detection for TZD measurement were 0.025 and 0.01 μg/mL, respectively. The extraction recoveries of TZD were 100.4% to 114.1%.The high-performance liquid chromatography method developed in this study could separate the analytes with a single eluent (isocratic system), within a total run time of 15 min. Both TZD and IS were well separated, without interference from the peaks. Sharp peaks were observed in the chromatograms; problems such as double peaks, shoulder peaks, and broadened peaks were not observed. The proposed method showed acceptable analytical performance and could be used to evaluate serum TZD concentrations in patients.     

Observational study of the clinical utility of sulfamethoxazole serum level monitoring in the treatment of brain abscesses due to Nocardia species

Although there is a lack of data in trimethoprim-sulfamethoxazole (TMP-SMX) serum monitoring utility for invasive nocardial infections, therapeutic drug monitoring is widely used to optimize dosing and avoid adverse reactions that may cause treatment interruption.We retrospectively reviewed all adults who received TMP-SMX to treat nocardial brain abscess and had SMX serum level testing from 2010 to 2020.Twenty-two patients received treatment with TMP-SMX for Nocardia species brain abscess and 16 (72.7%) had a reported SMX level, with a median patient age of 65.5 years (interquartile range, IQR 59.5–72.5). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a shorter median course of TMP-SMX treatment (322 days [IQR 188–365] vs. 365 [IQR 224–365]; P = .31) and higher therapeutic induction dose (10 [62.5%] vs. 3 [50%]; P = .92). Similarly, they were more frequently on hemodialysis (3 [13.6%] vs. 1 [4.5%]; P = > .99). The median peak level was 158.5 (IQR 120–218) μg/mL, collected at 2 hours (75%) post-administration in the induction phase (81.3%). Patients with documented SMX levels had fewer reported drug toxicity (5 [31.3%] vs. 4 [66.7%]; P = .1) than those without SMX levels. Among the five patients who reported TMP-SMX-related toxicity, 4 (80%) had an SMX peak level >150 μg/mL. There was no difference in the cure, relapse, and death rates among the two groups.While SMX level was not associated with Nocardia species brain abscess cure rates and mortality, most patients with SMX peak >150 μg/mL experienced drug toxicity.     

Endoscopy within 7 days after detecting high calprotectin levels can be useful for therapeutic decision-making in ulcerative colitis

The aim of this study was to assess the appropriate time interval to identify the association between the fecal calprotectin (FC) test and endoscopic activity, and to evaluate whether the time interval affects the therapeutic plan adjustment in patients with ulcerative colitis (UC).This study included 103 patients who underwent FC tests and endoscopic examinations within the past three months. The FC test results classified cases into three groups as follows: moderate to severe (>200, >250, or >300 μg/g), mild (100–200, 100–250, or 100–300 μg/g), and inactive (<100 μg/g) activity. The Mayo endoscopic subscore was used to determine endoscopic activity. Therapeutic plan adjustment included the addition or increased dosage of anti-inflammatory drugs, steroids, immunomodulators, and biologics.Using the cutoff value for FC of 200 μg/g, the appropriate time interval for dividing the association and non-association between Mayo endoscopic subscore and FC was 7 days (sensitivity, 74.4%; specificity, 50.0%; area under the curve [AUC], 0.6032). When using FC 250 or 300 μg/g, the appropriate time interval was 5.5 days, with a sensitivity of 71.7% and specificity of 49.1 (AUC 0.5862) in FC 250 μg/g, a sensitivity of 69.6%, and a specificity of 47.4 (AUC 0.5549) for FC 300 μg/g. Therapeutic plans changed in 29.1% of patients. In patients with shorter intervals (≤7 days) between the FC test and endoscopy, significant therapeutic plan adjustments were observed in patients with UC (36.5% vs. 17.5%, P = .047).Although the need for endoscopy within 7 days after detecting high FC (≥ 200 μg/g) was not statistically supported, endoscopy within a shorter interval (≤7 days) in UC patients with high FC can help determine the therapeutic plan.     

The influence of fasting insulin level in post-gestational diabetes mellitus women receiving low-glycaemic-index diets

Post-gestational diabetes mellitus (GDM) women are recommended weight loss to manage increased cardio-metabolic risks. We investigated the effects of lowering diet glycaemic index (GI) on fasting blood glucose (FBG), serum lipids, body weight and composition of post-GDM women with varying fasting insulin levels (INS). Seventy-seven Asian, non-diabetic women with previous GDM (aged 20–40 years, mean BMI: 26.4±4.6 kg m⁻²) were recruited. At baseline, 20 subjects with INS <2 μIU ml⁻¹ and 18 with INS ⩾2 μIU ml⁻¹ received conventional dietary recommendations (CHDR) only. CHDR emphasised energy and fat intake restriction and encouraged increase in dietary fibre intakes. Twenty-four subjects with INS <2 μIU ml⁻¹ and 15 with INS ⩾2 μIU ml⁻¹, in addition to CHDR, received low-GI education (LGI). Changes in FBG, serum lipids, body weight and body composition were evaluated. Subjects with INS <2 μIU ml⁻¹ had similar outcomes with both diets. After 1 year, subjects with INS ⩾2 μIU ml⁻¹ who received LGI education had reductions in FBG and triglycerides. Subjects who received CHDR observed increase in both FBG and triglycerides (P<0.05). Among all subjects, diet GI was lower and dietary fibre intakes were higher in LGI compared with CHDR subjects (all P<0.05). Thus, in Asian post-GDM women with normal/higher INS, adding low-GI education to CHDR improved management of FBG and triglycerides.     

Linking soluble vascular adhesion molecule-1 level to calcific aortic stenosis in patients with coronary artery disease

BACKGROUND:

Calcific aortic stenosis (AS) is an atherosclerosis-related process and the most common cause of valve disease requiring surgery.

OBJECTIVE:

To assess the association of inflammatory markers with AS in advanced atherosclerosis.

METHODS:

Consecutive patients with coronary artery disease (CAD) associated with AS were prospectively identified (mean transvalvular aortic gradient of 30 mmHg or greater). Subjects with aortic sclerosis (mean transvalvular aortic gradient of 10 mmHg or less) served as controls. All patients underwent clinical evaluation, echocardiography and coronary angiography.

RESULTS:

One hundred twenty-two patients with AS (85 men) and 101 with aortic sclerosis (76 men) of similar CAD severity were enrolled. The AS patients were older (mean [± SD] 71±7 years versus 66±7 years; P<0.001), had higher soluble vascular adhesion molecule-1 (s-VCAM-1) levels (1533±650 μg/L versus 1157±507 μg/L; P<0.001), but lower soluble intercellular adhesion molecule-1 (s-ICAM-1) (254±81 μg/L versus 293±84 μg/L; P<0.01) and soluble E-selectin (53±28 μg/L versus 62±29 μg/L; P<0.05) levels. The two groups did not differ with respect to C-reactive protein level (3±2.9 mg/L versus 3.4±2.6 mg/L; P not significant). Higher s-VCAM-1 (OR 1.09, 95% CI 1.04 to 1.14; P<0.001) and lower s-ICAM-1 (OR 0.82, 95% CI 0.72 to 0.94; P<0.001) levels were associated with AS after adjustment for age.

CONCLUSION:

Increased s-VCAM-1 levels were associated with calcific AS in patients with significant CAD.     

EFFECT OF SULPHASALAZINE AND ITS METABOLITES ON MITOGEN INDUCED TRANSFORMATION OF LYMPHOCYTES--CLUES TO ITS CLINICAL ACTION?

The effects of sulphasalazine (SASP), sulphapyridinc (SP), and5-aminosalicylic acid (5-ASA) have been studied on mouse spleencells cultured in the presence of phytohaemagglutmin (PHA),concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide(LPS). SASP exhibited a significant degree of suppression, at dosesin the range 25–100 .µg/ml (p < 0.01), this suppressionbeing >50% at 50 µg/ml. SP exhibited only a minor degreeof suppression (10% at 75 µg/ml. p < 0.01). Coadministrationof a non-steroidal anti-inflammatory drug (NSAID), indomethacin,produced no evidence of further suppression in the presenceof SASP or SP. Administration of SP plus 5-ASA to parallel culturesthat were profoundly suppressed by the molecular equivalentamount of SASP resulted in no suppression. This implied requirementof the intact parent molecule (SASP) to produce this effect,at these concentrations. The concentration of SASP required to produce more than 50%suppression was higher than that ever attained in the peripheralblood of humans receiving therapeutic doses of the drug. Humanlymphocytes are similarly suppressed by SASP, but only at higherconcentrations than are required for murine cells. Thus, ifthe parent drug is the active moiety and requires these concentrationsto be effective in vivo, it follows that the site where theseeffects may be mediated is likely to be the intestinal tract.The effects described would suggest the gut associated lymphoidtissue as a likely target. KEY WORDS: 5-Aminosalicylic acid, Small intestine, Rheumatoid arthritis, Reactive arthritis, Ankylosing spondylitis     

The Microvasculature in Chronic Kidney Disease

Summary

Background and objectives

Individuals with chronic kidney disease (CKD) stages 3 to 5 have an increased risk of cardiac and other vascular disease. Here we examined the association of CKD 3 to 5 with small vessel caliber.

Design, setting, participants, & measurements

This was a cross-sectional observational study of 126 patients with CKD stages 3 to 5 (estimated GFR [eGFR] <60 ml/min per 1.73 m²) and 126 age- and gender-matched hospital patients with CKD 1 or 2. Retinal vessel diameters were measured from digital fundus images by a trained grader using a computer-assisted method and summarized as the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE).

Results

Patients with CKD 3 to 5 had a smaller mean CRAE and CRVE than hospital controls (139.4 ± 17.8 μm versus 148.5 ± 16.0 μm, P < 0.001; and 205.0 ± 30.7 μm versus 217.4 ± 25.8 μm, respectively; P = 0.001). CRAE and CRVE decreased progressively with each stage of renal failure CKD1–2 to 5 (P for trend = 0.08 and 0.04, respectively). CKD and hypertension were independent determinants of arteriolar narrowing after adjusting for age, gender, diabetes, dyslipidemia, and smoking history. Patients with CKD 5 and diabetes had a larger mean CRAE and CRVE than nondiabetics (141.4 ± 14.9 μm versus 132.9 ± 14.2 μm; 211.1 ± 34.4 μm versus 194.8 ± 23.8 μm).

Conclusions

The microvasculature is narrowed in patients with reduced eGFR.