“Pulmonary tongue” a right ventricle phase abnormality in muga studies in patients with pulmonary hypertention

Pulmonary hypertension (PH) produces strain followed by hypertrophy and later dilatation of the right ventricle (RV) and pulmonary artery. The signs and symptoms are nonspecific. There is a need for a noninvasive sensitive way to diagnose PH. The purpose of this study is to evaluate phase abnormalities in radionuclide MUGA studies of patients with referred diagnosis of PH. In a retrospective analysis of 44 patients who had a radionuclide multigated study (MUGA) and contrast ventriculography (CV), 19 had high mean pulmonary pressure (over 20 mmHg) and a high pulmonary vascular resistance index (over 2.0). In 15 patients, a delayed phase segment in the RV corresponding to the pulmonary infundibulum and pulmonary conus was noted The Pulmonary Tongue sign (PT), 12 had PH (True positive) and 3 did not (false positive) on CV. No PT was seen in the remaining 29 patients, only 7 of them had PH (False negative). The sensitivity, specificity and accuracy of the PT sign in detecting PH was 80%, 72% and 77% respectively. The number of patients was too small to calculate the correlation of the grade of PT with the severity of PH. We conclude that The Pulmonary Tongue sign on a MUGA study is clinically useful in detecting PH.This project is supported by research project MLNO13 and funded by research Council, Kuwait University     

What is the appropriate aganglionic bowel length on contrast enema for attempting single stage transanal endorectal pull-through in Hirschsprung disease?

PurposeTo identify influence of different values of age and abnormal bowel length in HD patients selected for single stage TERPT which affects the technique of surgery.MethodsThis observational study was carried out for over 2.5 years. All children younger than 14 years old with clinical suspicion for HD, typical transitional zone (TZ) on contrast enema (CE) distal to splenic flexure, preoperative diagnosis approved by full thickness biopsy, no previous surgical history and no urgency were included. The distance between the anus and TZ was considered as aganglionic length on CE. Biopsy was taken from distal to proximal of resected bowel to reach circumferentially normal innervated bowel. Paired sample Student's t-test, Pearson correlation test, receiver operating characteristic (ROC) analysis were performed.ResultsForty-eight patients were enrolled in this study. Measured mean for aganglionic bowel length on CE and pathology were 33.5 ± 17.1 cm and 56.8 ± 33.5 cm, respectively (p < 0.01). Correlation coefficient (R) and coefficient of determination (R2) were 0.632 and 40%, respectively (p < 0.01). The difference between radiologic and pathologic measurements in females was higher than males (mean: 29.3 vs 21.9 cm) but was not statistically significant (p = 0.75). There was statistically significant difference between CE and pathologic results in the infants younger than 10 months (p = .004). Abnormal bowel length equal to 52 cm predicted requirement of laparoscopy assistance/laparotomy with 75% sensitivity and 85% specificity.ConclusionOur investigation showed it is safe to attempt for single stage TERPT when aganglionic length on CE is less than 52 cm and the child with HD is older than 10 months. Chance of requiring additional laparotomy or laparoscopy assistance is low in these patients.Type of studyStudy of diagnostic test.Level of evidenceLevel II.     

Induction of specific cell‐mediated immune responses and protection in BALB/c mice by vaccination with outer membrane vesicles from a Brucella melitensis human isolate

Brucellosis is a worldwide bacterial zoonosis caused by Brucella spp. No approved vaccine is available for human use against the disease. In this study, outer membrane vesicles (OMVs) from a Brucella melitensis biovar 1 human isolate obtained in Iran were used to immunize BALB/c mice (n = 12) by 2 intramuscular injections with a 2‐week interval. Another group of 12 mice was used as non‐vaccinated controls. Two weeks after the last vaccination, six mice of each group were sacrificed, and proliferation and interferon gamma (IFNγ) production responses of their splenocytes were evaluated following in vitro stimulation with killed Brucella cells. The other mice were challenged with the virulent B. melitensis isolate. Two weeks later, mice were killed and spleens were cultured to determine the number of the challenge strain. The results showed proliferative response and IFNγ production of splenocytes from vaccinated mice (stimulation index: 2.18 ± 0.57, and 1519.35 ± 10.70 pg/mL, respectively) were significantly higher than those of control mice (stimulation index: 1.02 ± 0.02, and 210.01 ± 17.58 pg/mL, respectively). Numbers of the challenge strain in spleens of vaccinated mice were also significantly less than those in the controls with 1.6 units of protection. Our study revealed vaccination with OMVs of the B. melitensis isolate could induce specific immune responses and protection against infection in the mouse model suggesting their potential application for active immunization against brucellosis.     

Novel Mutations in the DYNC1H1 Tail Domain Refine the Genetic and Clinical Spectrum of Dyneinopathies

The heavy chain 1 of cytoplasmic dynein (DYNC1H1) is responsible for movement of the motor complex along microtubules and recruitment of dynein components. Mutations in DYNC1H1 are associated with spinal muscular atrophy (SMA), hereditary motor and sensory neuropathy (HMSN), cortical malformations, or a combination of these. Combining linkage analysis and whole‐exome sequencing, we identified a novel dominant defect in the DYNC1H1 tail domain (c.1792C>T, p.Arg598Cys) causing axonal HMSN. Mutation analysis of the tail region in 355 patients identified a de novo mutation (c.791G>T, p.Arg264Leu) in an isolated SMA patient. Her phenotype was more severe than previously described, characterized by multiple congenital contractures and delayed motor milestones, without brain malformations. The mutations in DYNC1H1 increase the interaction with its adaptor BICD2. This relates to previous studies on BICD2 mutations causing a highly similar phenotype. Our findings broaden the genetic heterogeneity and refine the clinical spectrum of DYNC1H1, and have implications for molecular diagnostics of motor neuron diseases.