ABH gel is not absorbed from the skin of normal volunteers

BackgroundLorazepam (Ativan^®), diphenhydramine (Benadryl^®), haloperidol (Haldol^®) (ABH) topical gel is currently widely used for nausea in hospice because of perceived efficacy and low cost and has been suggested for cancer chemotherapy. However, there are no studies of absorption, a prerequisite for effectiveness. We completed this study to establish whether ABH gel drugs are absorbed, as a prerequisite to effectiveness.InterventionTen healthy volunteers, aged 25 to 58 years (mean 37 years), two African Americans and eight Caucasian Americans, applied the standard 1.0 mL dose (2 mg of lorazepam, 25 mg of diphenhydramine, and 2 mg of haloperidol in a pluronic lecithin organogel), rubbed on the volar surface of the wrists by the subject.MeasuresBlood samples were obtained at 0, 30, 60, 90, 120, 180, and 240 minutes. Plasma concentrations were analyzed by liquid chromatography-tandem mass spectrometry using deuterated internal standards for each drug.OutcomesNo lorazepam or haloperidol was detected in any sample from any of the 10 volunteers down to a level of 0.05 ng/mL. Diphenhydramine was found in multiple plasma samples at concentrations >0.05 ng/mL in three patients, with the highest concentration of 0.30 ng/mL in one person at 240 minutes. Overall, five of 10 patients exhibited detectable diphenhydramine in one or more samples, supporting limited absorption. No subject noted any side effects.Conclusions/Lessons LearnedAs commonly used, none of the lorazepam, haloperidol, or diphenhydramine in ABH gel is absorbed in sufficient quantities to be effective in the treatment of nausea and vomiting. Diphenhydramine is erratically absorbed at subtherapeutic levels. The efficacy of ABH gel should be confirmed in randomized trials before its use is recommended.     

Serum Fetuin-A and Pentraxin3 in hemodialysis and renal transplant patients

ObjectiveThe aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients.MethodSerum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods.ResultsIn the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p = 0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p = 0.003].ConclusionAlthough our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.     

Bone morphogenetic protein-2 will be a novel biochemical marker in urinary tract infections and stone formation

ObjectivesTo investigate the role of bone morphogenetic protein-2 (BMP-2) in patients with urinary tract infection (UTI) and renal stone in relation to Tamm–Horsfall protein (THP) and osteopontin (OPN).Design and methodsELISA kits were used to determine these markers in serum and urinary samples of 20 patients with UTI, 15 with renal stone and 10 controls.ResultsBMP-2 significantly increased in serum of patients who had UTI (P = 0.05) and renal stone (P = 0.01). In the case of UTI, serum BMP-2 at cutoff 44 pg/mL had sensitivity and specificity (92%, 80%), while cystatin C at cutoff 525 ng/mL showed sensitivity and specificity (85%, 91%). THP is a good predictor of renal diseases (P < 0.001) by regression analysis. It is also the most sensitive urinary marker for UTI with sensitivity and specificity (94%, 75%) at cutoff 305 ng/mL.ConclusionCombination of serum BMP-2 and cystatin C are more sensitive and accurate for early diagnosis of renal infection and damage.     

Drug interaction of (S)-warfarin, and not (R)-warfarin, with itraconazole in a hematopoietic stem cell transplant recipient

BackgroundItraconazole is a potent inhibitor of CYP3A4 and P-glycoprotein, but not CYP2C9. Herein, we report a case study in which the plasma concentration of the CYP2C9 substrate (S)-warfarin, and not the CYP3A4 substrate (R)-warfarin, increased with itraconazole coadministration.CaseA 67-y-old man received an allogenic bone marrow transplant for acute lymphoid leukemia. He was taking oral itraconazole (200 mg/day) and was started on a warfarin dose of 2.0 mg/day. The plasma concentrations of (S)- and (R)-warfarin 3 days after starting warfarin administration were 216 and 556 ng/mL, respectively (INR 0.98), and after 10 days, the concentrations were 763 and 545 ng/mL, respectively (INR 2.43). On day 11 after withdrawal of itraconazole, the concentrations of (S)- and (R)-warfarin were 341 and 605 ng/mL, respectively (INR 1.38). The concentration of (R)-warfarin was not affected by itraconazole; however, the final (S)-warfarin concentration had increased 7.3-fold. The (S)-warfarin/(S)-7-hydroxywarfarin ratio decreased to 2.45 from 8.40 after discontinuation of itraconazole. The permeability of warfarin enantiomers across Caco-2 cells was not influenced by itraconazole and showed no difference between enantiomers.ConclusionsCareful INR monitoring is necessary for warfarin co-administration with itraconazole. Further examination is necessary to elucidate mechanisms of the interaction between warfarin and itraconazole.     

Ascending single-dose study of the safety profile, tolerability, and pharmacokinetics of bosutinib coadministered with ketoconazole to healthy adult subjects

BackgroundBosutinib (SKI-606) is an orally bioavailable, competitive tyrosine kinase inhibitor that selectively targets both Src and Abl tyrosine kinases. Bosutinib is metabolized primarily through the cytochrome P450 3A4 pathway. Inhibition of bosutinib metabolism by coadministration with the potent cytochrome P450 3A4 inhibitor ketoconazole could potentially increase plasma concentrations of bosutinib, allowing for the study of bosutinib tolerability at supratherapeutic concentrations in a healthy subject population.ObjectiveThis study assessed the safety profile, tolerability, and pharmacokinetics of different dose combinations of bosutinib coadministered with ketoconazole in healthy adults, and determined whether supratherapeutic concentrations of bosutinib can be achieved with ketoconazole.MethodsThis was a randomized, Phase I, double-blind, placebo-controlled, sequential-group study conducted in healthy adults. Single oral doses of bosutinib 100, 200, 300, 400, 500, and 600 mg or placebo were administered with ketoconazole and food on day 1; daily single oral doses of ketoconazole 400 mg were administered on days –1 and 1 through 4.ResultsForty-eight subjects were enrolled. Their mean (SD) age was 32.0 (10.7) years (range, 18–50 years). The majority of the subjects (n = 44 [92%]) were white, 2 (4%) were black or African American, and 2 (4%) were of other races. Bosutinib was associated with acceptable tolerability at doses from 100 to 600 mg, with adverse events either mild (n = 30 [63%]) or moderate (n = 12 [25%]) in severity; no subject discontinued treatment due to adverse events, and no serious events were reported. Mean (SD) values for bosutinib 100 to 600 mg ranged from 58.4 (13.3) to 426 (100) ng/mL for C_max and 2980 (802) to 23,000 (4020) ng · h/mL for AUC_0–∞; mean AUC_0–24 and AUC_0–last ranged from 876 (234) to 7080 (1640) ng ·  h/mL and from 2740 (854) to 22,200 (3630) ng  ·  h/mL, respectively. C_max and AUC were linear and dose proportional. Mean C_max at 600 mg was 2.1-fold higher than the steady-state C_max previously observed for patients with chronic myelogenous leukemia who received bosutinib 500 mg once daily with food.ConclusionsSingle doses of bosutinib up to 600 mg coadministered with multiple doses of ketoconazole were acceptably well tolerated in this small, selected group of healthy male volunteers. In addition, supratherapeutic exposure was achieved within this range for bosutinib when coadministered with ketoconazole. ClinicalTrials.gov identifier: NCT00777530.     

Lipoprotein(a)-cholesterol: a significant component of serum cholesterol

BackgroundLipoprotein(a) [Lp(a)] is known to be a cholesterol-rich lipoprotein, however, the contribution of Lp(a)-cholesterol [Lp(a)-C] to the serum cholesterol and LDL-C levels has not yet been fully evaluated.MethodsWe determined the serum Lp(a)-C in 55 subjects with serum Lp(a) concentrations ranging from 9 to 129 mg/dl. To measure the serum Lp(a)-C concentrations, we developed an immunoaffinity gel assay; serum was incubated with Sepharose 4B gel coupled with immunoglobulin G (IgG) prepared from a polyclonal anti-Lp(a) goat antiserum. After separating Lp(a) from other lipoproteins, we determined the serum Lp(a)-C concentrations. Validation of the assay showed satisfactory results in terms of the specificity and reproducibility.ResultsThe mean cholesterol content of Lp(a), determined as Lp(a)-C/Lp(a), was 29.5 ± 10.4%. The serum Lp(a)-C values were found to be highly correlated with the serum Lp(a) mass (r = 0.923, p < 0.001). At serum Lp(a) levels of over 50 mg/dl, the contribution of Lp(a)-C to the serum total cholesterol was 10.2%. Further, the Friedewald formula overestimated the serum LDL-C by 20.4%.ConclusionsLp(a) contains approximately 30% cholesterol in each molecule. In subjects with markedly elevated serum Lp(a) concentrations, the Lp(a)-C values should be taken into account when evaluating the serum LDL-C.     

Advantages of prostate-specific antigen (PSA) clearance model over simple PSA half-life computation to describe PSA decrease after prostate adenomectomy

ObjectivesA population kinetic approach based on PSA clearance (CL_PSA) may be a more rational strategy to characterize prostate-specific antigen (PSA) decrease profile after prostate surgery than the commonly used method (half-life from mono/bi-exponential models).MethodsWe used 182 post-adenomectomy PSA concentrations from 56 benign prostatic hyperplasia patients to build, with NONMEM software, a multi-exponential and a CL_PSA model for comparison.ResultsThe best multi-exponential model was PSA(t) = 4.96e^? 0.269t + 3.10e^? 0.16t + 0.746e^+ 0.0002t with a stable median residual PSA at 0.64 ng/mL. The best model parametrized with clearance was CL_PSA = 0.0229 ^? (AGE/69)^3.78. Akaike information criteria and standard errors favored the CL_PSA model. Median peripheral zone and transitional zone productions were 0.034 ng/mL/cm³ and 0.136 ng/mL/g. A threshold at 2 ng/mL on day 90 allowed for a diagnostic of biochemical relapse diagnostic.ConclusionsThe population CL_PSA model was superior to the multi-exponential approach for investigating individual post-adenomectomy PSA decreases.     

Serum procalcitonin at the time of admission to the ICU as a predictor of short-term mortality

ObjectiveThis purpose of this study was to determine if serum procalcitonin (PCT) concentration at the time of admission to the ICU is a predictor of all-cause short-term mortality.Design and methodsThis prospective cross-sectional study was conducted over a 16-month period with 86 consecutive critically ill patients. The semi-quantitative PCT-Q test was performed and APACHE II scores and C-reactive protein (CRP) concentrations were determined within 24 h of admission.ResultsPCT-Q test value was a better predictor of all-cause short-term mortality than CRP value or APACHE II score. PCT ≥ 10 ng/mL was highly and independently correlated with mortality. Use of PCT-Q ≥ 10 ng/mL was superior to use of APACHE II ≥ 25 or CRP ≥ 10 mg/dL as a predictor of poor outcome.ConclusionsA PCT-Q value ≥ 10 ng/mL obtained at the time of admission to the ICU is a strong predictor of short-term mortality.     

Analytical evaluation of the new Abbott Architect 25-OH vitamin D assay

ObjectivesValidation of the Architect 25-OH vitamin D assay.Design and methodsDetermination of repeatability, reproducibility, accuracy profile and 25(OH)-vitamin D2 recovery on native samples. Comparison with DiaSorin Liaison and RIA.Results and conclusionCoefficients of variation: < 6% (13.6 ng/mL) and 2.2% (78.1 ng/mL). Functional sensitivity: 5 ng/mL. Accuracy profile shows that the method is validated between 13.6 and 78.1 ng/mL. Recovery of 25(OH)D2: 75,8%( 95% CI: 61.9–89.7%). Good correlation with DiaSorin RIA and Liaison < 50 ng/mL; above this threshold a systematic positive bias was observed.     

No correlation between pretreatment serum CEA levels and tumor volume in locally advanced rectal cancer patients

BackgroundAlthough serum carcinoembryonic antigen (CEA) levels reflect tumor volume in rectal cancer patients intrapersonally, it is unclear interpersonally. We determined the correlation between pretreatment serum CEA levels and tumor volume.MethodsA total of 489 patients with locally advanced primary rectal cancer who underwent preoperative chemoradiotherapy followed by surgery between October 2001 and April 2007 were retrospectively evaluated. CEA levels were measured by chemiluminescent microparticle immunoassay, and magnetic resonance (MR) volumetry was performed using MR data. The correlation between CEA levels and tumor volume was assessed using linear regression analysis and one-way analysis of variance. The prognostic values of CEA levels and tumor volume for survival were evaluated.ResultsThere was no significant correlation between CEA levels and tumor volume. The five-year overall survival and disease-free survival were 89.0%, 80.6% and 82.9%, and 72.0%, 70.0% and 60.3% in patients with CEA levels of ≤ 3 ng/ml, > 3–10 ng/ml, and > 10 ng/ml, respectively. Tumor volume had no prognostic value for either overall survival or disease-free survivalConclusionsPretreatment serum CEA levels were not correlated with tumor volume. While there was no correlation between tumor volume and survival, there was a positive correlation between CEA levels and survival.     

Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease

ObjectivesWe sought to determine whether serum concentrations of fibroblast growth factor 19 (FGF19) – an ileum-derived enterokine which plays a role in the control of glucose and lipid homeostasis – are altered in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).Design and methodsSerum levels of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 74 controls.ResultsFGF19 levels were significantly lower in patients with biopsy-proven NAFLD (median: 130 pg/mL) than in controls (median: 210 pg/mL, P < 0.001). Serum FGF19 levels were significantly but modestly associated with hepatocyte ballooning scores in univariate analysis (r = ? 0.25, P < 0.05) but not after adjustment for potential confounders (β = ? 0.18; t = 1.78, P = 0.08).ConclusionsThis pilot study suggests that serum FGF19 levels are decreased in patients with NAFLD but are not independently associated with liver histology findings.     

A spicamycin derivative (KRN5500) provides neuropathic pain relief in patients with advanced cancer: a placebo-controlled, proof-of-concept trial

ContextNeuropathic pain in patients with cancer can be difficult to treat effectively.ObjectivesThe purpose of the study was to determine safety and efficacy of KRN5500, a novel, spicamycin-derived, nonopioid analgesic agent, in patients with advanced cancer and neuropathic pain of any etiology.MethodsThe study was a Phase 2a, multicenter, double-blind, placebo-controlled, dose escalation clinical trial. Patients with refractory neuropathic pain and advanced cancer were randomly assigned 2:1 to receive a maximum of eight single escalating doses of KRN5500 or placebo, ranging from 0.6 to 2.2 mg/m². The primary objective was safety and tolerability. The secondary objective was efficacy, measured by change in average pain intensity on a 0–10 numeric rating scale administered one week after the patient’s final dose.ResultsNineteen patients received treatment (KRN5500 n = 12; placebo n = 7). The most frequently reported adverse events were gastrointestinal symptoms, which were more frequent and severe with KRN5500 than placebo; two (17%) KRN5500 patients discontinued the study because of nausea and vomiting. At study endpoint, KRN5500 exhibited a significant median decrease in pain intensity from baseline of 24% compared with 0% for placebo (P = 0.03). The median for largest weekly reduction in target pain intensity was 29.5% for KRN5500 and 0% for placebo patients (P = 0.02).ConclusionThis proof-of-concept study for KRN5500 in patients with advanced cancer and any type of neuropathic pain found gastrointestinal adverse events to be the predominant safety concern. The results also provided the first indication of clinical and statistical efficacy in reducing pain intensity.     

Correlation of haloperidol levels between saliva and plasma of acutely ill schizophrenic patients

ObjectiveClinical usefulness of monitoring haloperidol in salivary samples based on plasma:saliva correlation.Design and MethodsPlasma and saliva samples of schizophrenic patients [N = 105] were analyzed by highly sensitive reverse phase liquid chromatographic method to measure haloperidol at 240 nm using UV-PDA detector. Mobile phase consist of acetonitrile and water [50:50], pH 2.5 (0.1% acetic acid and 0.05 M KHPO₄) at flow rate 1.4 mL/min. Method was linear over 3–200 ng/mL.ResultsObserved therapeutic range was 5–19 ng/mL [11.66 ± 3.97] and 17–54 ng/mL [27.52 ± 11.51] for plasma and saliva respectively. Mean S:P was found to be 2.36.ConclusionCurrent study showed significantly high correlation [r = 0.93, p < 0.0001] between haloperidol levels in saliva and plasma with linear relationship. It is therefore concluded that monitoring of salivary concentration can be a clinically beneficial substitute. Patients showing clinical improvement [N = 90] were within salivary concentration range of 17–54 ng/mL, which can be an appropriate steady state monitoring range for haloperidol in saliva.     

Consistency of efficacy, patient acceptability, and nasal tolerability of fentanyl pectin nasal spray compared with immediate-release morphine sulfate in breakthrough cancer pain

ContextWe recently reported that fentanyl pectin nasal spray (FPNS) provides superior pain relief from breakthrough cancer pain (BTCP) compared with immediate-release morphine sulfate (IRMS), with significant effects by five minutes and clinically meaningful pain relief from 10 minutes postdose.ObjectivesTo report the consistency of efficacy, tolerability, and patient acceptability of FPNS vs. IRMS.MethodsPatients (n = 110) experiencing one to four BTCP episodes/day while taking ≥60 mg/day oral morphine (or equivalent) for background pain entered a double-blind, double-dummy (DB/DD), multiple-crossover study. Those who completed an open-label titration phase (n = 84) continued to a DB/DD phase; 10 episodes were randomly treated with FPNS and overencapsulated placebo or IRMS and nasal spray placebo (five episodes each). Pain intensity (PI) and pain relief scores were assessed. Patient acceptability scores were assessed at 30 and 60 minutes. Safety and tolerability were assessed by adverse events (AEs) and nasal assessments.ResultsPer-episode analysis revealed that FPNS consistently provided relief from pain more rapidly than IRMS; by 10 minutes, there were significant differences in PI difference scores and in the percentages of episodes showing clinically meaningful pain relief (P < 0.05). Overall acceptability scores were significantly greater for FPNS than for IRMS at 30 (P < 0.01) and 60 (P < 0.05) minutes. Patients were “satisfied/very satisfied” with the convenience (79.8%) and ease of use (77.2%) of FPNS. Only 4.7% of patients withdrew from titration because of AEs; no significant nasal effects were reported.ConclusionThis study demonstrates that FPNS is efficacious, well accepted, and well tolerated by patients with BTCP.     

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

ObjectivesThe aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance.Design and methodsWe studied 112 patients with T2DM and 80 age- and gender-matched control subjects.ResultsSerum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5 ± 5.2 ng/mL vs. 20.0 ± 7.3 ng/mL, P < 0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P < 0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (ρ = 0.458, P < 0.05) and HOMA-R (ρ = 0.444, P < 0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F = 5.294, P < 0.05) in female patients with diabetes.ConclusionsThese findings suggest that BDNF may contribute to glucose metabolism.     

Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus

ObjectivesMatrix metalloproteinases (MMPs) are suggested to play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study is to examine the MMPs expressions and activities in Taiwanese RA and SLE patients.Design and methodsLevels and activities of plasma MMP-2 and MMP-9 were investigated by enzyme-linked immunosorbent assay and zymography, respectively.ResultsMMP-2 levels in control subjects, RA and SLE patients were 146.1 ± 34.2, 194.0 ± 24.2 and 208.9 ± 75.9 ng/mL respectively, and for MMP-9 were 51.4 ± 57.1, 567.7 ± 313.1 and 208.7 ± 105.5 ng/mL respectively. Both MMP-2 and MMP-9 levels and activities from all patients were significantly higher than that from control subjects.ConclusionsMMP-2 levels in both patients groups were approximately 1.3–1.4 folds higher than that in control subjects, notably, MMP-9 levels were 11- and 4-folds significantly higher, respectively, in RA and SLE patients. The results which MMP-2 and MMP-9 levels and activities are significantly elevated support the involvement of MMPs proteins in these autoimmune disorders.     

Soluble serum Klotho in diabetic nephropathy: Relationship to VEGF-A

ObjectivesBoth kidney expression and soluble serum Klotho are influenced by chronic kidney disease (CKD) and diabetes. Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A).Design and methodsWe included 43 controls and 146 diabetic patients with different stages of CKD. Laboratory evaluation, urinary albumin/creatinine ratio (UACR), Klotho (ELISA), VEGF-A (ELISA) were performed.ResultsKlotho was 0.40(0.10–1.30) ng/mL in diabetic patients without CKD and 0.80(0.30–1.30) ng/mL in controls, p = 0.20; VEGF-A was higher in diabetic patients 73.85(57.32–119.00) pg/mL than in controls 43.20(30.1–65.9) pg/mL, p < 0.0001. Klotho increased with CKD stage: 0.2(0.10–0.40) ng/mL in CKD 1/2, 0.60(0.20–1.1) ng/mL in CKD 3/4 and 1.45(0.425–2.90) ng/mL in dialysis patients, p < 0.0001; it also increased with decreasing glomerular filtration rate (GFR). Klotho was lower in albuminuric (UACR > 30 mg/g) patients 0.20(0.10–0.70) ng/mL than in normoalbuminuric (UACR < 30 mg/g) ones 0.50(0.20–1.30) ng/mL, p = 0.03; lowest Klotho was found in microalbuminuric (UACR 30–300 mg/g) patients, p = 0.07. VEGF was lower in microalbuminuric patients but was not influenced by GFR. In diabetic patients but not in controls, Klotho correlated to VEGF-A (r = 0.29, p = 0.0003); in multiple regression VEGF-A was the only significant predictor of Klotho: b = 0.27, 95%CI (0.01–0.04), p = 0.001.ConclusionsIn diabetic patients, Klotho is decreased in early CKD and increases thereafter, paralleling reduced GFR. VEGF-A is higher in diabetic patients than in controls. Both Klotho and VEGF-A are decreased in the presence of microalbuminuria. In diabetes, Klotho strongly correlates to VEGF-A.     

Proguanylin and prouroguanylin--assay evaluation and clinical analyte characterization

BackgroundThe biomarkers proguanylin and prouroguanylin are members of the natriuretic peptide family. The aim of this study was to evaluate two commercially available assays for proguanylin and prouroguanylin and to further characterize both analytes in terms of important clinical features.MethodsWe evaluated precision and linearity of the BioVendor human proguanylin and prouroguanylin ELISAs. In order to characterize both analytes, we tested in vitro analyte stabilities at ? 80 °C, and determined biological variability and reference values for proguanylin and prouroguanylin.ResultsWithin-run and total coefficients of variation were < 10% for the BioVendor proguanylin and prouroguanylin assays. Both methods were linear across the tested measurement ranges. The analytes proguanylin and prouroguanylin were stable for at least 2 months at ? 80 °C. With respect to biological variability, the reference change values (RCV) were 27% and 59% for proguanylin and prouroguanylin, respectively. For proguanylin, age-independent reference values were 4.0–13.4 ng/mL in males and 4.6–16.3 ng/mL in females. For prouroguanylin, age- and sex-independent reference values were 2.1–11.2 ng/mL.ConclusionThe BioVendor human proguanylin ELISA and the BioVendor human prouroguanylin ELISA meet the needs of quality specifications of laboratory medicine. The results of the characterization of both analytes provide essential information for further clinical studies.     

Palliative sedation in advanced cancer patients followed at home: a retrospective analysis

ContextData regarding palliative sedation at home in dying patients are lacking.ObjectivesTo describe the frequency, indication, and modality of palliative sedation (PS) in patients followed at home.MethodsA retrospective analysis of home care cancer patients was performed. Patients who received PS before dying were selected and information about epidemiologic characteristics, indications, duration, drugs, and outcomes was collected.ResultsOf 370 medical charts of patients who died at home, 49 patients received PS before dying. PS was proposed by the team, relatives, or both in 63.3%, 4.1%, and 32.6% of cases, respectively. Delirium alone or in combination with other symptoms was the most frequent indication to begin PS. Midazolam was the most frequently used drug to initiate PS (98%), at a mean dose of 28.1 mg/day, in combination with parenteral morphine (84.7%) at a mean dose of 25.4 mg/day. At the time of death, midazolam was administered in 98% of patients (mean dose 22.3 mg/day), combined with parenteral morphine in 87.8% of patients (mean dose 28.1 mg/day). Satisfaction for physicians and principal caregivers after PS was good in 46 and 48 cases, respectively.ConclusionPS at home seems to be a feasible treatment option among selected patients and makes a potentially important contribution to improving care for those who choose to die at home.     

Is serum transthyretin a reliable marker of nutritional status in patients with end-stage renal disease?

ObjectiveTo test the value of serum transthyretin (TTR) concentration as a nutritional marker in renal patients.MethodsThe study included 115 renal patients, out of which 35 are on conservative treatment, 50 on hemodialysis and 30 renal transplant recipients, and 31 healthy control subjects. Serum TTR, albumin, transferrin, C-reactive protein (CRP) and α1 anti trypsine (AAT) were assessed by immunoturbidimetry, and vitamin A by HPLC. Linear regression models were applied to test the association between serum TTR and body mass index (BMI).ResultsSerum TTR concentrations were normal, but serum vitamin A, CRP and AAT concentrations were significantly higher in patients. In renal patients, serum TTR was positively and independently related to BMI and was significantly lower in malnourished than well-nourished patients (367 ± 91 vs. 417 ± 130 mg/L; p = 0.05). The risk of serum TTR < 300 mg/L was higher in malnourished patients [OR, 4.82 (1.78–13.2); p = 0.001].ConclusionSerum TTR concentrations were at normal range in renal patients despite evidence of malnutrition and inflammation. However, they were related to BMI and were significantly lowered in malnourished patients. Thus, serum TTR would reflect nutritional status in renal patients. However, the cutoff of malnutrition should be raised to 300 mg/L.