Faecal calprotectin and lactoferrin as markers of acute radiation proctitis: a pilot study of eight stool markers

BACKGROUND: Non-invasive diagnostic tools to evaluate the severity of acute, radiation-induced proctitis are not readily available. The faecal excretion of eight markers of gut inflammation was therefore examined. Five proteins and three lipid derivates were analysed in sequential stool samples taken before and during radiation therapy. METHODS: Stool samples from 15 patients with prostate cancer scheduled for radiation therapy were examined. Pretreatment and in-treatment samples (2nd and 6th weeks) were measured by enzyme-linked immunosorbent assay (ELISA) (calprotectin, lactoferrin, transferrin, leukotriene B4, prostaglandin E2, thromboxane B2 and TNF alpha) or nephelometry (alpha 1-antitrypsin). RESULTS: Calprotectin and lactoferrin concentrations increased significantly during radiation treatment (P = 0.0005 and P = 0.019). Transferrin was detected in only 9 out of 45 samples. There were no changes in tumour necrosis factor alpha (TNF alpha), leukotriene B4, prostaglandin E2 and thromboxane B2 during treatment. alpha 1-antitrypsin could not be detected in any sample. CONCLUSIONS: This study indicates that faecal calprotectin and lactoferrin concentrations could be markers of acute, radiation-induced proctitis. Patient compliance and stability of the markers make this a promising method for clinical research. Eicosanoids could be measured in stool samples, but the concentrations did not increase with increasing radiation dose.     

Increased turnover of Gc-globulin in patients with hepatic encephalopathy

BACKGROUND: A low serum level (< 100 mg/L) of the actin-scavenger Gc-globulin is a prognostic marker of non-survival in fulminant hepatic failure (FHF). It is unknown whether decreased production or increased consumption (or both) is responsible for the low Gc-globulin levels. METHODS: Ten patients with FHF and four patients with acute or chronic liver disease (AOCLD) with hepatic encephalopathy (HE) grades II-IV were included. Eight patients with cirrhosis (chronic liver disease, CLD) without HE served as controls. Total, free, and actin-bound Gc-globulin were measured in samples from an artery, a central vein, and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), concentrations were measured before and after high volume plasmapheresis (HVP). RESULTS: Total Gc-globulin was reduced to 21%, 40%, and 43% of the normal level in the FHF, AOCLD, and CLD groups, respectively, whereas bound Gc-globulin was within normal range in all patients. The Gc:actin complex ratio was increased 3.8, 2.5, and 1.9-fold compared with normal levels. Total, free, and bound serum Gc-globulin levels did not differ among arterial, systemic venous, or hepatic venous blood. Total Gc-globulin rose to >100 mg/L in all patients after HVP, whereas bound Gc-globulin remained unchanged. The Gc-globulin production rate in FHF and AOCLD patients was increased to 4.1 +/- 1.3 mg/min compared to literature values of 0.6 mg/min in healthy individuals. The estimated half-life of total Gc-globulin was shorter in the patients compared to healthy individuals (127 +/- 56 min and 870 min, respectively). CONCLUSIONS: Gc-globulin levels were reduced in patients with FHF and AOCLD because a 7-fold increase of Gc-globulin production rate could not compensate for the accelerated clearance. Bound Gc-globulin was maintained within normal levels in all circumstances studied, indicating a possible regulatory role of this parameter in the clearance of actin.     

Advances in pharmacotherapy for the treatment of allergic rhinitis; MP29-02 (a novel formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system) fills the gaps

Introduction: Effective pharmacologic treatment exists for most patients suffering from allergic rhinitis (AR). However, both in clinical trials and in real-life studies, many patients are dissatisfied with treatment. Physicians often use multiple therapies, in an attempt to improve symptom control, often with limited evidence of success. Novel treatment options are needed and must consider unmet medical needs.

Areas covered: This article reviews the clinical data for a new AR treatment. MP29-02 (Dymista®, Meda, Solna, Sweden) contains azelastine hydrochloride (AZE) and fluticasone propionate (FP), in a novel formulation and delivered in an improved device as a single nasal spray. It has shown superior efficacy in AR patients than either commercially available AZE or FP monotherapy for both nasal and ocular symptom relief, regardless of disease severity. MP29-02 also provided more effective and rapid symptom relief than either AZE or FP monotherapy delivered in the MP29-02 formulation and device. However, the effect was less than that observed versus commercial comparators, suggesting the impact of formulation and device on clinical efficacy.

Expert opinion: MP29-02 simplifies AR management, surpassing the efficacy of gold standard treatment, intranasal corticosteroids (INS), for the first time. It is indicated for the treatment of moderate-to-severe seasonal allergic rhinitis and perennial allergic rhinitis when monotherapy with either intranasal antihistamine or INS is NOT considered sufficient. Most patients present with moderate/severe disease, with evidence of current or previous treatment insufficiency. MP29-02 should be the treatment of choice for these patients.     

Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution

Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin γ-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.     

Insufficient tissue ablation by rotational atherectomy leads to worse long-term results in comparison with balloon angioplasty alone for the treatment of diffuse in-stent restenosis: insights from the intravascular ultrasound substudy of the ARTIST randomized multicenter trial.

The ARTIST trial demonstrated a worse outcome for patients with in-stent restenosis (ISR) treated with rotational atherectomy (RA) and adjunctive balloon angioplasty (PTCA) as compared to PTCA alone. This intravascular ultrasound (IVUS) substudy compares effects of lumen enlargement and examines reasons for failure of RA in this setting. IVUS (n = 56) was performed after each interventional step and at follow-up. Volumetric lumen gain measured 79 +/- 68 mm(3) after PTCA (13 +/- 4 atm) as compared to 44 +/- 26 mm(3) after RA and adjunctive PTCA (7 +/- 3 atm; P < 0.0001). RA itself enlarged lumen by only 19 +/- 17 mm(3) and stent volume was 47% smaller as compared to high-pressure PTCA. Low-pressure strategy after RA did not prevent tissue growth during follow-up (19 +/- 25 vs. 36 +/- 38 mm(3); RA vs. PTCA; P = 0.09). Consequently, net lumen gain after PTCA was 82% higher compared to RA (46 +/- 54 vs. 25 +/- 24 mm(3); P = 0.09). Further stent expansion is the key mechanism to achieve luminal gain by PTCA of ISR. Neointimal ablation by RA has only minor effects. Low-pressure PTCA does not prevent recurrent tissue growth and failed for treatment of ISR due to insufficient stent expansion.     

Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis: a review of randomized, controlled trials

For several years there has been discussion of whether first-line pharmacological treatment of allergic rhinitis should be antihistamines or intranasal corticosteroids. No well documented, clinically relevant differences seem to exist for individual nonsedating antihistamines in the treatment of allergic rhinitis. Likewise, the current body of literature does not seem to favor any specific intranasal corticosteroid. When comparing efficacy of antihistamines and intranasal corticosteroids in allergic rhinitis, present data favor intranasal corticosteroids. Interestingly, data do not support antihistamines as superior in treating conjunctivitis associated with allergic rhinitis. Safety data from comparative studies in allergic rhinitis do not indicate differences between antihistamines and intranasal corticosteroids. Combining antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis does not provide additional beneficial effects to intranasal corticosteroids alone. Considering present data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis, when compared with antihistamines.     

Hormonal responses to a potent gonadotropin hormone-releasing hormone antagonist in normal elderly men

GnRH analogs, both agonists and antagonists, have potential use in androgen-dependent diseases of older men, such as prostatic cancer and benign prostatic hyperplasia. Previous experience with agonists of GnRH has suggested that GnRH analogs may be more effective in aged men than in young men, but little is known about GnRH antagonists in older men. Therefore, we evaluated the hormonal effects of a single dose and a short course of a GnRH antagonist (Nal-Glu) in normal elderly men. Six young men (25-34 yr old) and six older men (66-76 yr) each received single morning injections of Nal-Glu (25, 75, and 250 micrograms/kg), separated by 2 weeks. Serum levels of testosterone (T), immunoreactive LH (LH RIA) and FSH (FSH RIA), and bioactive LH (LH BIO) were evaluated periodically for 7 days after each injection. In addition, six elderly men received 25 and 75 micrograms/kg.day Nal-Glu for 10 consecutive mornings each, and serum levels of T, inhibin, LH RIA, LH BIO, FSH RIA, and bioactive FSH were evaluated. Nal-Glu in all three single doses caused a significant (P less than 0.01) decline in serum levels of T and gonadotropins that was similar in extent in the elderly and young men. For example, T declined to a level of 19% of baseline after the 250 micrograms/kg dose of Nal-Glu in both age groups. For both the young and elderly men, the major effect of increasing the Nal-Glu dose was a prolongation of the period of suppression. Multiple Nal-Glu injections in the elderly men also resulted in a rapid decline in T, inhibin, and bioactive and immunoreactive gonadotropins. For both LH and FSH, bioactivity decreased to a greater extent than immunoreactivity. Local side-effects of Nal-Glu tended to be fewer and of less intensity in the elderly men compared to those in the young men. These results demonstrate that the response to Nal-Glu in healthy elderly men is similar to that in younger men, and extended administration of Nal-Glu in elderly men effectively suppresses gonadal and pituitary function. These results suggest that the role of GnRH antagonists in the effective treatment of androgen-dependent disease in the aging male needs to be explored further.     

Novel Z Scores to Correct Biases Due to Ventricular Volume Indexing to Body Surface Area in Adolescents and Young Adults

BackgroundReference values for cardiac magnetic resonance imaging (cMRI) in children and young adults are scarce. This leads to risk stratification of patients with congenital heart diseases being based on volumes indexed to body surface area (BSA). We aimed to produce cMRI Z score equations for ventricular volumes in children and young adults and to test whether indexing to BSA resulted in an incorrect assessment of ventricular dilation according to sex, body composition, and growth.MethodsWe retrospectively included 372 subjects aged < 26 years with either normal hearts or conditions with no impact on ventricular volumes (reference group), and 205 subjects with repaired tetralogy of Fallot (TOF) aged < 26 years. We generated Z score equations by means of multivariable regression modelling. Right ventricular dilation was assessed with the use of Z scores and compared with indexing to BSA in TOF subjects.ResultsVentricular volume Z scores were independent from age, sex, and anthropometric measurements, although volumes indexed to BSA showed significant residual association with sex and body size. In TOF subjects, indexing overestimated dilation in growing children and underestimated dilation in female compared with male subjects, and in overweight compared with lean subjects.ConclusionsIndexed ventricular volumes measured with cMRI did not completely adjust for body size and resulted in a differential error in the assessment of ventricular dilation according to sex and body size. Our proposed Z score equations solved this problem. Future studies should evaluate if ventricular volumes expressed as Z scores have a better prognostic value than volumes indexed to BSA.