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.     

The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases.

Sera from 65 patients with spongiform virus encephalopathies (29 with kuru, 36 with Creutzfeldt-Jakob disease), 79 with other neurologic diseases, and 65 control subjects were examined for reactivity in immunoblots of preparations of myelinated axons and neurofilaments from mouse brain. The sera reacted most frequently with the 200-kDa and 150-kDa neurofilament proteins and less frequently with the 70-kDa neurofilament protein and a 62-kDa neurofilament-associated protein. The sera reacted with the same proteins as those which reacted with rabbit and mouse polyclonal antibodies and mouse monoclonal antibody to neurofilament proteins. Serum reactions were also seen with Trixon X-100 extracts of chimpanzee brain and bovine spinal cord but not with Triton extracts of liver, kidney, and muscle.     

RFLPs of the phenylalanine hydroxylase gene in the Italian population

Summary Different mutations of the phenylalanine hydroxylase (PAH) gene leading to phenylketonuria (PKU) have been described associated with specific haplotypes in several European countries. In order to investigate the distribution of DNA haplotypes in Italy, restriction fragment length polymorphism (RFLP) analysis of the PAH gene was performed in nine Italian PKU patients from eight unrelated families, and in the available relatives. The analysis of eight polymorphic sites revealed haplotypes 1 and 6 in association with PKU. This pattern appears to differ from those reported for other European populations.The majority of the 14 PKU subjects studied showed compound heterozygosity for different haplotypes, as observed for other European series.RFLP analysis at the PAH locus allowed us to offer the possibility of prenatal diagnosis to six of the studied families. One prenatal diagnosis was performed and a normal fetus was diagnosed.