The face in marfan syndrome: A 3D quantitative approach for a better definition of dysmorphic features

Marfan syndrome (MFS) is a rare hereditable disorder of connective tissue caused by mutations in the fibrillin‐1 gene FBN1. Timely diagnosis of MFS is essential to prevent life‐threatening cardiovascular complications; nevertheless it can be difficult owing to the phenotypic variability of the syndrome. No clear quantitative definition of facial abnormalities associated with MFS is available. The aim of this study was to improve the definition of the facial phenotype associated with MFS and to verify the usefulness of a 3D noninvasive quantitative approach for its early recognition. 3D facial images of 61 Italian subjects with MFS, aged 16–64 years (21 males, 38 ± 15 years; 40 females, 41 ± 13 years) were obtained by stereophotogrammetry. From the coordinates of 17 soft‐tissue facial landmarks, linear distances and angles were computed; z score values were calculated to compare patients with healthy reference subjects (400 males, 379 females) matched for sex and age. Student's t test was used for statistical comparisons. All subjects with MFS showed greater facial divergence (P < 0.001; mean z score +1.9) and a lower facial height index (P < 0.001; mean z score ?1.9) than reference subjects, both values being influenced by a shorter mandibular ramus (P < 0.001; mean z score ?1.9) and a mild but significant increase in facial height (P < 0.001; mean z score +1.2). Palpebral down‐slanting was found in 85% of MFS subjects. There were no sex differences. Quantitative abnormalities identified in this study enrich information about the facial dysmorphism in MFS and confirm its usefulness for early recognition of the disease. Clin. Anat. 31:380–386, 2018. © 2017 Wiley Periodicals, Inc.     

Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials

Rationale: Several randomized, double‐blind, placebo‐controlled clinical trials have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the treatment of allergic rhinitis (AR) thus allowing for a meta‐analysis to determine the overall treatment effect. Methods: A comprehensive search of the MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October, 2007 was carried out. Randomized, double‐blind, placebo‐controlled, clinical trials evaluating the efficacy of MFNS in patients with AR compared to placebo were included. Total nasal symptom scores (TNSS), individual nasal symptoms, total non‐nasal symptom scores (TNNSS) and nasal airflow were analysed as the standardized mean difference (SMD). Meta‐analysis was performed with the random or the fixed effect models depending on heterogeneity, by using revman 5 software. Data synthesis: Sixteen of the 113 identified articles met the inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed: 1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was associated with a significant reduction in TNSS (SMD ?0.49, 95% CI: ?0.60 to ?0.38; P < 0.00001; I² = 50.1%). A significant effect on SMD for nasal stuffiness/congestion (?0.41; 95% CI: ?0.56 to ?0.27), rhinorrhoea (?0.44; 95% CI: ?0.66 to ?0.21), sneezing (?0.40; 95% CI: ?0.57 to ?0.23) and nasal itching (?0.39; 95% CI: ?0.53 to ?0.25) was also demonstrated. Mometasone furoate nasal spray treated subjects also showed a significant reduction in TNNSS (?0.30; 95% CI: ?0.43 to ?0.18). The proportion of patients with adverse events was similar for MFNS and placebo (0.99; 95% CI: 0.81–1.20; P = 0.91). Conclusions: This meta‐analysis provides a level Ia evidence for the efficacy of MFSN in the treatment of AR vs placebo. Adverse events frequency was similar in both groups.     

Relationship between body mass index and insulin measured during oral glucose tolerance testing in severely obese children and adolescents

Primary objective: The study evaluated the accuracy of body mass index (BMI) in detecting hyperinsulinaemia during oral glucose tolerance testing (OGTT) in severely obese children.

Research design: A cross-sectional study was carried out.

Materials and methods: A total of 118 obese children and adolescents (49 females and 69?males) aged 6–19 years were consecutively studied at an outpatient paediatric clinic. Hyperinsulinaemia was defined as a value of log-transformed fasting insulin ≥?80th percentile and OGTT hyperinsulinaemia as a value of the log-transformed area under the curve (AUC) of insulin ≥?80th percentile. The study hypothesis was tested using a logistic regression model with hyperinsulinaemia as the outcome variable and the z-score of BMI corrected for age (z-BMI_age) as the predictor variable. Receiver-operator characteristic (ROC) curves were used to evaluate accuracy.

Results: The mean (SD) BMI for age of the children was 28.6 (4.0)?kg?m^?2, corresponding to 2.2 (0.5) standard deviation scores. The odds ratio (OR) of OGTT hyperinsulinaemia was 2.0 (95% CI 1.2–3.3; p = 0.007) for each unit increase of z-BMI_age and the corresponding ROC-AUC was 0.74 (95% CI 0.61–0.86; p = 0.0001). In comparison, the OR of fasting hyperinsulinaemia was 1.1 (95% CI 0.7–1.7; p = 0.716) for each unit increase of z-BMI_age and the corresponding ROC-AUC was 0.49 (95% CI 0.35–0.62; p = 0.863).

Conclusion: BMI is reasonably accurate in detecting OGTT hyperinsulinaemia in severely obese children.     

Growth and market integration in Amazonia: A comparison of growth indicators between Shuar,Shiwiar, and nonindigenous school children

We describe and compare the growth of three groups of juveniles, aged 0–18, who experience different degrees of market integration and acculturation in the Ecuadorian Amazon. These include 1,384 indigenous Shuar from the Upano Valley of Ecuador and surrounding areas, 570 nonindigenous colono (or colonist) children from the same area, and 42 Shiwiar from the interior of Ecuador. We use differences between these populations in National Health and Nutrition Examination Survey (NHANES) z‐scores to assess the effects of changing subsistence patterns on Shuar growth and nutrition. Although, for all three groups, mean height‐for‐age z‐scores were negative, Shuar z‐scores were significantly lower than either colono or Shiwiar z‐scores. Mean weight‐for‐age z‐scores were also negative for Shuar and colono juveniles, while mean BMI‐for‐age and weight‐for‐height z‐scores were greater than zero for all three groups. Using NHANES standards, 41% of male and 38% of female Shuar were classified as stunted, versus 16% of male and 20% of female colonos. Compared to Shuar, colonos were three times less likely to be stunted (OR = 0.33, P < 0.01) and Shiwiar were eight times less likely to be stunted (OR = 0.13, P = 0.01). These differences suggest that changes in diet have negatively affected Shuar growth and nutrition. Am. J. Hum. Biol, 2009. © 2008 Wiley‐Liss, Inc.     

United airways again: high prevalence of rhinosinusitis and nasal polyps in bronchiectasis

Background: Although various relationships between the lower and upper airways have been found, the association of bronchiectasis with chronic rhinosinusitis and nasal polyps has not been thoroughly evaluated. This study was undertaken to examine the association of idiopathic and postinfective bronchiectasis with chronic rhinosinusitis and nasal polyposis. Methods: In a prospective study, 56 patients with idiopathic and 32 with postinfective bronchiectasis were evaluated for chronic rhinosinusitis and nasal polyposis by using EP³OS criteria and assessing: symptoms score, nasal endoscopy, sinonasal and chest CT scan, nasal and lung function and nasal and exhaled NO. Results: Most bronchiectasis patients (77%) satisfied the EP³OS criteria for chronic rhinosinusitis, with anterior (98.5%) and posterior (91%) rhinorrhea and nasal congestion (90%) being the major symptoms. Patients presented maxillary, ethmoidal and ostiomeatal complex occupancy with a total CT score of 8.4 ± 0.4 (0–24). Using endoscopy, nasal polyps with a moderate score of 1.6 ± 0.1 (0–3) were found in 25% of patients. Nasal NO was significantly lower in patients with nasal polyposis (347 ± 62 ppb) than in those without them (683 ± 76 ppb; P < 0.001), and inversely correlated (R = ?0.36; P < 0.01) with the ostiomeatal complex occupancy. In the chest CT scan, patients with chronic rhinosinusitis showed a higher bronchiectasis severity score (7.2 ± 0.5; P < 0.001) than patients without (3.7 ± 0.7). The prevalence of chronic rhinosinusitis, nasal polyps and other outcomes were similar in idiopathic and postinfective bronchiectasis. Conclusions: The frequent association of chronic rhinosinusitis and nasal polyposis with idiopathic and postinfective BQ supports the united airways concept, and it suggests that the two type of bronchiectasis share common etiopathogenic mechanisms.     

Cluster immunotherapy with a glutaraldehyde-modified mixture of grasses results in an improvement in specific nasal provocation tests in less than 2.5 months of treatment

Background Cluster immunotherapy is becoming increasingly used. It allows for a rapid build up phase and the administration of higher doses of allergen in a shorter period of time. Objectives To evaluate the effect of short‐term pre‐seasonal immunotherapy using a glutaraldeyde‐modified allergen vaccine in reducing specific nasal hyperreactivity in nasal challenge tests. Materials and Methods Thirty‐three patients were selected. All patients had a positive history of allergic rhinitis and skin tests to grass pollen, although most of them (72.7%) were sensitized to other allergens as well. The study was conducted outside of the pollen season and the patients did not receive any pharmacological treatment during this period of time. Two randomized groups of patients were established; Group A: 22 patients (13 females and nine males) and Group B, 11 control patients (seven females and four males). Patients in Group A received immunotherapy with a vaccine containing 50% of the wild grasses Trisetum paniceum and Dactylis glomerata. All patients underwent titrated nasal provocation tests (NPT) before and after completion of the study (2.3 and 2.8 months for Groups A and B, respectively). The administration schedule consisted of 0.1 and 0.2 mL at day 1, followed by 0.3 and 0.5 mL at day 7, 0.5 mL after 2 weeks followed by 0.5 mL monthly. A single vial was used containing an allergen concentration of 10 000 TU/mL (105 μg of total protein and 24.6 μg of Group 1 plus 5 allergens/mL). A mean of 6.5 injections were administered to Group A patients between NPTs. Results There were no significant differences between both groups at the beginning of the study (P=0.48). At the end, only Group A patients needed significant greater threshold concentrations for a positive NPT than at the beginning (P=0.002). Conclusions A short‐term cluster pre‐seasonal inmunotherapy with a modified vaccine containing a mixture of grass pollen is effective as determined by an objective measure after only a mean 2.3 months of treatment.     

Omalizumab is more effective than suplatast tosilate in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis

Background Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a major problem in Japan. Omalizumab, a humanized monoclonal anti‐IgE antibody, improves symptoms associated with SAR, but a comparative study with an anti‐allergy drug has not yet been conducted. Objective To compare the efficacy and safety of omalizumab with suplatast tosilate, a selective T‐helper type 2 (Th2) cytokine inhibitor, in patients with Japanese cedar pollen‐induced SAR. Methods A randomized, double‐blind, double‐dummy study was conducted in 308 Japanese patients with a history of moderate‐to‐severe SAR who showed a CAP‐RAST value (2+) specifically to Japanese cedar pollens. Patients were treated for 12 weeks with omalizumab plus placebo of suplatast tosilate or suplatast tosilate plus placebo of omalizumab. Results The mean daily nasal symptom medication scores (sum of the daily nasal symptom severity score and daily nasal rescue medication score) were significantly lower in the omalizumab group than in the suplatast tosilate group during three evaluation periods (P<0.001). The omalizumab group also had significantly lower mean daily nasal severity scores, each of the mean daily nasal and ocular symptom severity scores (sneezing, runny nose, stuffy nose, itchy nose, itchy eyes, watery eyes, and red eyes). Omalizumab reduced rescue medication requirements, and the proportion of days with any rescue medication use in the omalizumab group was significantly lower. Serum‐free IgE levels markedly decreased in the omalizumab group and it was associated with clinical efficacy. The adverse reaction profiles were similar between the two groups. The overall incidence of injection site reactions was higher in the omalizumab group than in the suplatast tosilate group, but all these events were of mild degree. No anti‐omalizumab antibodies were detected. Conclusion Omalizumab showed significantly greater improvements than suplatast tosilate in the treatment of SAR induced by Japanese cedar pollens.     

Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo for the symptomatic treatment of seasonal allergic rhinitis: a randomized, double-blind, parallel-group study

Background Bilastine is a new non‐sedative H₁ receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial). Objective To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR). Methods Overall, 683 SAR patients, aged 12–70 years, were randomized to a double‐blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non‐nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre‐determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS‐AUC_{0?14 days}). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms. Results The mean TSS‐AUC_{0?14 days} (score × day) was reduced in bilastine‐ and cetirizine‐treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P<0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine‐treated group experienced somnolence (1.8%; P<0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine‐treated group (7.5% and 4.8%, respectively). Conclusions Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.     

United airways: the impact of chronic rhinosinusitis and nasal polyps in bronchiectasic patient's quality of life

Background: The nose and the bronchi belong, in anatomical and physiopathological terms, to the concept of united airways. Associations between upper and lower airways diseases have been demonstrated in allergic rhinitis and asthma, nasal polyposis (NP) and asthma, chronic rhinosinusitis (CRS) and chronic obstructive pulmonary disease, and more recently CRS/NP and bronchiectasis (BQ). Objective: To evaluate the impact of CRS on quality of life (QoL) of patients with BQ, and to correlate these findings with the pulmonary status, nasal symptoms, and general health status. Methods: In a prospective study, patients with BQ (n = 80) were evaluated for CRS and NP using EP³OS criteria, and severity of BQ using chest high resolution computed tomography (HRCT)‐scan. Quality of life was assessed in all patients by using specific [Sinonasal Outcome Test‐20 (SNOT‐20), St George Respiratory Questionnaire (SGRQ)], and generic (Short Form‐36; SF‐36) questionnaires. Results: Using SNOT‐20, patients with CRS had worse QoL (2.1 ± 0.1; P < 0.001) than patients without CRS (0.4 ± 0.06). Using SGRQ total score, patients with CRS had worse QoL (43.7 ± 2.2; P < 0.001) than patients without CRS (24.7 ± 2.5). Using SF‐36, patients with CRS had worse QoL, both in the physical summary (64 ± 3.4; P < 0.05) and the mental summary (65.5 ± 4.7; P < 0.05), than patients without CRS (physical summary [PS]: 76.2 ± 3.3; mental summary [MS]: 78.3 ± 5.3, respectively). Sinonasal Outcome Test‐20 was correlated with SGRQ total score (r = 0.72; P < 0.01), and SF‐36 physical summary (r = ?0.63; P < 0.01). St George Respiratory Questionnaire was correlated with SF‐36 on physical summary (r = ?0.58; P < 0.05) and with forced expiratory volume in 1 s (r = ?0.41; P < 0.05). Conclusion: These results suggested that CRS, measured by both specific and generic questionnaires, has a considerable impact on the QoL of patients with BQ.     

Utility of hepatocyte nuclear factor‐1β as a diagnostic marker in ovarian carcinomas with clear cells

Kao Y‐C, Lin M‐C, Lin W‐C, Jeng Y‐M & Mao T‐L
(2012) Histopathology  61, 760–768 Utility of hepatocyte nuclear factor‐1β as a diagnostic marker in ovarian carcinomas with clear cells Aims: Overexpression of hepatocyte nuclear factor‐1β (HNF‐1β) has been found in ovarian clear cell carcinoma (OCCC) but not in other types of ovarian carcinoma. The aim of this study was to clarify whether the overexpression of HNF‐1β is specific for OCCC, and does not occur in ovarian carcinoma with clear cell change. Methods and results: Immunohistochemistry was performed on 178 ovarian carcinomas with clear cells (80 OCCCs, 60 high‐grade serous, 25 endometrioid, and 13 mixed endometrioid and clear cell), 22 ovarian high‐grade serous carcinomas without clear cells, 41 renal cell carcinomas (RCCs) and 20 hepatocellular carcinomas (HCCs) with clear cytoplasm. Results were evaluated using an H‐score (percentage × intensity). Most OCCCs were diffusely and strongly positive (mean H‐score 15.1). High‐grade serous carcinoma and endometrioid carcinoma with clear cells were usually negative or focally and weakly positive (mean H‐scores 1.5 and 1.7, respectively). High‐grade serous carcinoma without clear cells had a mean H‐score of 0.77. The mean H‐scores of the endometrioid and clear cell components in mixed endometrioid and clear cell carcinoma were 6.2 and 15.7, respectively. HNF‐1β was expressed in 95.1% of RCCs and in 30% of HCCs. Conclusions: The diagnosis of ovarian carcinomas with clear cells can be made with greater accuracy by using the intensity and extent of immunoreactivity for HNF‐1β.     

Evaluation of desloratadine on conjunctival allergen challenge-induced ocular symptoms

Background Allergic conjunctivitis (AC) is frequently associated with allergic rhinitis (AR) and affects up to 91% of patients with AR. Desloratadine, an orally administered, non‐sedating second‐generation antihistamine, has proven efficacy and safety in the control of nasal and non‐nasal – including ocular – symptoms of AR. This randomized‐controlled trial is the first to evaluate the effects of continuous oral desloratadine treatment on ocular symptoms after conjunctival allergen challenge. Objective To evaluate the impact of administering oral desloratadine 5 mg daily for 7 days on ocular symptoms in conjunctival allergen‐challenged subjects. Methods In this crossover study, adults with a history of seasonal AC and a minimal threshold response to allergen challenge were randomized to receive desloratadine 5 mg daily (n=20) or placebo (n=21) for 7 days after which they underwent a second ocular allergen challenge. After a 2‐week washout period, subjects crossed over to the other treatment. The primary efficacy parameter was the intra‐subject difference from baseline at end‐point in the post‐challenge mean composite ocular redness score (the sum of redness scores in ciliary, conjunctival, or episcleral vessel beds). Secondary efficacy parameters included the intra‐subject and inter‐subject differences in individual symptom scores for ciliary, conjunctival, or episcleral redness; pruritus; chemosis; eyelid swelling; and tearing. Results The mean composite ocular redness score was reduced at 10, 15, and 20 min post‐challenge with desloratadine treatment compared with placebo, though these differences were not statistically significant (P=NS). Desloratadine was significantly more effective than placebo in preventing post‐challenge ocular pruritus (P<0.001). Significant improvements post‐challenge were also seen in ciliary and episcleral redness, chemosis, eyelid swelling, and tearing (P<0.05 vs. placebo for all comparisons). Desloratadine was well tolerated. Conclusion Treatment with desloratadine 5 mg daily for 7 days reduced allergic ocular symptoms following allergen challenge.     

Desloratadine relieves nasal congestion and improves quality-of-life in persistent allergic rhinitis

Background:  Symptoms of allergic rhinitis (AR), particularly nasal congestion, can impair quality-of-life (QoL). However, only a modest correlation exists between these symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, suggesting that both be evaluated for a complete assessment of health.
Methods:  Subjects with a ≥2-year history of moderate-to-severe AR to dust mite or cat dander were randomized to desloratadine 5 mg/day ( n  =   293) or placebo/day ( n  =   291) for 28 days. Primary endpoint was change from baseline in a.m./p.m. nasal congestion score. Secondary outcomes included change from baseline in total nasal symptom score, individual symptom scores and RQLQ scores (completed on days 1, 7, and 28).
Results:  The Allergic Rhinitis and its Impact on Asthma criteria for persistent allergic rhinitis (PER) were fulfilled by 99% of subjects in the placebo arm. Between-treatment difference in a.m./p.m. nasal congestion score, observed from day 8 onward, significantly favored desloratadine ( P  =   0.0003). Desloratadine significantly improved a.m./p.m. nasal congestion and RQLQ scores after 1 week and at treatment end ( P  <   0.05). Improvements in 5 of 7 RQLQ domain scores exceeded the minimal important difference. On days 7 and 28, desloratadine was also significantly superior to placebo in mean change from baseline in a.m./p.m. total nasal symptom score and rhinorrhea score (both P  ≤   0.01). Symptomatic benefit was primarily driven by improvement in nasal congestion and rhinorrhea.
Conclusions:  Desloratadine 5 mg/day significantly improved symptoms associated with PER, including nasal congestion, and provided significant improvement in QoL after 1 week of treatment.     

Lymphocytopenia as a marker for pandemic influenza A/H1N1 2009 virus infection in children

Lymphocytopenia has been reported in adults with pandemic influenza A/H1N1 2009 infection, but data in children are inconclusive. Data from 76 children presented with flu‐like symptoms between July and November 2009 and tested for pandemic influenza A/H1N1 2009 virus and white blood cell (WBC) counts were analyzed. Samples from 37 (48.7%) children resulted in a positive PCR assay for pandemic influenza A/H1N1 2009 virus. When comparing data from these children with data from 39 (51.3%) children with uncomplicated flu‐like illness and negative PCR assay for pandemic influenza A/H1N1 2009 virus, no difference in disease duration, median age, red blood cell count, hemoglobin concentration, C reactive protein concentration, and absolute neutrophil count was observed, whereas significant differences were apparent when considering WBC count, relative and absolute lymphocyte count, absolute lymphocyte count z‐score, and platelet count. Receiver operating characteristic curve analysis revealed that the best absolute lymphocyte count and absolute lymphocyte count z‐score cut‐points that simultaneously maximized sensitivity and specificity were 2,256 cells/µl and ?0.89, respectively, sensitivity being 0.81 (95% CI: 0.68–0.94), specificity 0.87 (95% CI: 0.77–0.98), positive predictive value 0.85 (95% CI: 0.74–0.97), and negative predictive value 0.83 (95% CI: 0.71–0.94). In conclusion, lymphocytopenia is a marker for influenza A/H1N1 2009 virus infection in children. Absolute lymphocyte count <2,556 cells/µl or absolute lymphocyte count z‐score < ?0.89 may be useful cut‐offs to discriminate against children at higher risk of infection during epidemics. Considering that the pandemic virus is highly likely to continue to circulate in the coming winter season, these findings provide direct and practical implications for the near future. J. Med. Virol. 83:1–4, 2011. © 2010 Wiley‐Liss, Inc.     

Nasal Septal and Premaxillary Developmental Integration: Implications for Facial Reduction in Homo

The influence of the chondrocranium in craniofacial development and its role in the reduction of facial size and projection in the genus Homo is incompletely understood. As one component of the chondrocranium, the nasal septum has been argued to play a significant role in human midfacial growth, particularly with respect to its interaction with the premaxilla during prenatal and early postnatal development. Thus, understanding the precise role of nasal septal growth on the facial skeleton is potentially informative with respect to the evolutionary change in craniofacial form. In this study, we assessed the integrative effects of the nasal septum and premaxilla by experimentally reducing facial length in Sus scrofa via circummaxillary suture fixation. Following from the nasal septal‐traction model, we tested the following hypotheses: (1) facial growth restriction produces no change in nasal septum length; and (2) restriction of facial length produces compensatory premaxillary growth due to continued nasal septal growth. With respect to hypothesis 1, we found no significant differences in septum length (using the vomer as a proxy) in our experimental (n = 10), control (n = 9) and surgical sham (n = 9) trial groups. With respect to hypothesis 2, the experimental group exhibited a significant increase in premaxilla length. Our hypotheses were further supported by multivariate geometric morphometric analysis and support an integrative relationship between the nasal septum and premaxilla. Thus, continued assessment of the growth and integration of the nasal septum and premaxilla is potentially informative regarding the complex developmental mechanisms that underlie facial reduction in genus Homo evolution. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients

Background: Nonsedating H₁‐antihistamines are recommended for the treatment of urticaria by the recent EAACI/GA²LEN/EDF guidelines. The aim of this study was to compare the efficacy, after 4 weeks of treatment, with levocetirizine 5 mg and desloratadine 5 mg, both once daily in the morning, in symptomatic chronic idiopathic urticaria (CIU) patients. Methods: This multi‐center, randomized, double‐blind study involved 886 patients (438 on levocetirizine and 448 on desloratadine). The primary objective was to compare their efficacy on the mean pruritus severity score after 1 week of treatment. Mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient’s and investigator’s global satisfaction with treatment, were secondary efficacy measures. Results: Levocetirizine led to a significantly greater decrease in pruritus severity than desloratadine over the first treatment week; mean pruritus severity scores of 1.02 and 1.18 for levocetirizine and desloratadine, respectively (P < 0.001). The result was similar for the entire 4‐week treatment period (P = 0.004). In addition, levocetirizine decreased pruritus duration and the mean CIU composite scores to a significantly greater extent than desloratadine during the first week (P = 0.002 and 0.005, respectively) and over the entire study (P = 0.009 and P < 0.05, respectively). Similarly, levocetirizine increased the patients’ global satisfaction after one and 4 weeks (P = 0.012 and 0.021, respectively), compared with desloratadine. Safety and tolerability were similar in both groups. Conclusions: Levocetirizine 5 mg was significantly more efficacious than desloratadine 5 mg in the treatment of CIU symptoms.     

High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome

Klinefelter syndrome (KS) occurs in 1:600 males and is associated with high morbidity and mortality due to diabetes and cardiovascular disease. Up to 50% of men with KS have metabolic syndrome, a cluster of features conferring increased risk for diabetes and cardiovascular disease. These cardiometabolic (CM) risk features have not been studied in adolescents with KS. The objective of this cohort study was to compare CM risk features in adolescents with KS to controls matched for sex, age, and BMI z score. Fifty males with KS (age 10–17 years) were well‐matched to male controls (n = 50) for age (14.0 ± 1.7 vs. 14.0 ± 1.5 years) and BMI z score (0.3 ± 1.3 vs. 0.4 ± 1.2). Three CM risk features were present in 30% of adolescents with KS compared to 12% of controls (RR 2.5, 95% CI 1.1–5.9, p = .048). The KS group had significantly lower HDL cholesterol (p = .006), higher triglycerides (p < .001), and greater waist circumference percentile (p < .001). Despite a normal BMI, the prevalence of CM risk features was very high in adolescents with KS, particularly for central adiposity and dyslipidemia. The pathophysiology of this metabolic profile independent of obesity needs further investigation to facilitate prevention of the high morbidity of cardiovascular disease and diabetes in this population. ClinicalTrials.gov identifiers: NCT01585831 and NCT02723305.     

Bilateral cleft lip and palate: A morphometric analysis of facial skeletal form using cone beam computed tomography

Bilateral cleft lip and palate (BCLP) is caused by a lack of merging of maxillary and nasal facial prominences during development and morphogenesis. BCLP is associated with congenital defects of the oronasal facial region that can impair ingestion, mastication, speech, and dentofacial development. Using cone beam computed tomography (CBCT) images, 7‐ to 18‐year old individuals born with BCLP (n = 15) and age‐ and sex‐matched controls (n = 15) were retrospectively assessed. Coordinate values of three‐dimensional facial skeletal anatomical landmarks (n = 32) were measured from each CBCT image. Data were evaluated using principal coordinates analysis (PCOORD) and Euclidean Distance Matrix Analysis (EDMA). PCOORD axes 1–3 explain approximately 45% of the morphological variation between samples, and specific patterns of morphological differences were associated with each axis. Approximately, 30% of facial skeletal measures significantly differ by confidence interval testing (α = 0.10) between samples. While significant form differences occur across the facial skeleton, strong patterns of differences are localized to the lateral and superioinferior aspects of the nasal aperture. In conclusion, the BCLP deformity significantly alters facial skeletal morphology of the midface and oronasal regions of the face, but morphological differences were also found in the upper facial skeleton and to a lesser extent, the lower facial skeleton. This pattern of strong differences in the oronasal region of the facial skeleton combined with differences across the rest of the facial complex underscores the idea that bones of the craniofacial skeleton are integrated. Clin. Anat. 28:584–592, 2015. © 2015 Wiley Periodicals, Inc.     

Development and Validation of a Predictive Equation for Lean Body Mass in Children and Adolescents

Background: Lean body mass (LBM) is not easy to measure directly in the field or clinical setting. Equations to predict LBM from simple anthropometric measures, which account for the differing contributions of fat and lean to body weight at different ages and levels of adiposity, would be useful to both human biologists and clinicians.

Aim: To develop and validate equations to predict LBM in children and adolescents across the entire range of the adiposity spectrum.

Subjects and methods: Dual energy X-ray absorptiometry was used to measure LBM in 836 healthy children (437 females) and linear regression was used to develop sex-specific equations to estimate LBM from height, weight, age, body mass index (BMI) for age z-score and population ancestry. Equations were validated using bootstrapping methods and in a local independent sample of 332 children and in national data collected by NHANES.

Results: The mean difference between measured and predicted LBM was ? 0.12% (95% limits of agreement ? 11.3% to 8.5%) for males and ? 0.14% ( ? 11.9% to 10.9%) for females. Equations performed equally well across the entire adiposity spectrum, as estimated by BMI z-score. Validation indicated no over-fitting. LBM was predicted within 5% of measured LBM in the validation sample.

Conclusion: The equations estimate LBM accurately from simple anthropometric measures.     

Intergenerational gains in relative knee height as compared to gains in relative leg length within Taiwanese families

Evidence indicates that variation in relative leg length (RLL) is a sensitive indicator of early childhood circumstances, but research presents conflicting evidence of how lower leg growth contributes to variability. This study investigates the extent of intergenerational changes in subischial leg length and knee height relative to stature among father–son, mother–daughter, and midparent–offspring pairs. These changes and differences in the extent of mean change in the two indices within like‐sex parent–offspring pairs were assessed using repeated measures ANOVA. Results indicate that within all categories, mean generational differences in both indices were substantial [Δ RLL z: 0.64–0.73; Δ relative knee height (RKH) z: 0.46–0.64] and statistically significant (P ≤ 0.010). Mean increases in RLL and RKH across parent–offspring categories were consistently greater in Taipei than Auckland, though only the midparent–offspring generation by location contrast for RLL was statistically significant (P = 0.037). Father–son and mother–daughter average differences were virtually identical for RLL (0.73 z vs. 0.72 z). When differences within pairs in the extent of change in RLL and RKH were assessed directly, mother–daughter mean differences approached significance at an α level of 0.05 (Δ = 0.26 z; F = 3.42, df = 1, 42, P = 0.071). Father–son differences were smaller (Δ = 0.09 z) and statistically insignificant suggesting very similar amounts of change in the two indices. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Modulation of neurotrophin and neurotrophin receptor expression in nasal mucosa after nasal allergen provocation in allergic rhinitis

Background: Patients with allergic rhinitis (AR) feature both allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. Still, it is unclear whether or not neurotrophins are involved in airway pathophysiology of AR and in nasobronchial interaction. Methods: Nine AR patients with mono‐allergy to grass pollen and nine healthy controls underwent nasal allergen provocation (NP). Serum samples, nasal and bronchial biopsies were taken before (T₀) and 24 h after (T₂₄) NP. Pan‐neurotrophin receptor p75^NTR, tyrosine kinase A (trkA), trkB, nerve growth factor (NGF), and brain‐derived neurotrophic factor (BDNF) were assessed with immunohistochemistry, and NGF and BDNF levels with ELISA. Results: At T₂₄, BDNF and NGF were upregulated in nasal mucosa (P < 0.05) and increased in the peripheral blood of AR compared with T₀. The increase in nasal BDNF expression correlated positively with the maximum increase in total nasal symptom score in AR (P = 0.02). p75^NTR was expressed on peripheral nerves and epithelial layer, trkA on endothelial cells, and trkB on mast cells. trkB + mast cells significantly decreased after NP in AR (P < 0.01). NP did not modulate p75^NTR and trkA expression in nasal mucosa and had no effect on the expression of neurotrophins and receptors in bronchial mucosa. Conclusion: This study shows that neurotrophins and their receptors are expressed in human airways. Allergic rhinitis was characterized by a modulation of BDNF, NGF, and trkB in nasal mucosa after NP and a correlation of nasal BDNF with the maximal increase of total nasal symptom score. Therefore, our data suggest that neurotrophins participate in upper‐airway pathophysiology in AR, whereas their role in nasobronchial interaction remains unclear.