A novel mutation in CDKN1C in sibs with Beckwith–Wiedemann syndrome and cleft palate,sensorineural hearing loss,and supernumerary flexion creases

We report on two daughters and a son of a Thai family who were affected with BWS. Their clinical findings consist of cleft palate, omphalocele, anterior ear creases, indented lesions on the posterior rim of the helix, macroglossia, posterior crossbite, and anterior open bite. The younger daughter and son had newly recognized findings of the BWS including sensorineural hearing loss and supernumerary flexion creases of the fingers. A novel mutation in CDKN1C (c.579delT; p.A193AfsX46) was found in all affected individuals and their mother. This mutation is located in the central highly polymorphic hexanucleotide repeat encoding a proline‐alanine series of repeats (PAPA‐domain). This domain is involved in MAP kinase phosphorylation. This is for the first time that sensorineural hearing loss and supernumerary flexion creases of the fingers are associated with mutation in CDKN1C. © 2012 Wiley Periodicals, Inc.     

Correlates of change in self-perceived oral health among older adults in Brazil: findings from the Health, Well-Being and Aging Study

BackgroundIdentifying changes in the oral health status of older populations, and their predictors and explanations, is necessary for public health planning. The authors assessed patterns of change in oral health–related quality of life in a large cohort of older adults in Brazil during a five-year period and evaluated associations between baseline characteristics and those changes.MethodsThe sample consisted of 747 older people enrolled in a Brazilian cohort study called the Health, Well-Being and Aging (Saúde, Bem-estar e Envelhecimento [SABE]) Study. Trained examiners measured participants' self-perceived oral health by using the General Oral Health Assessment Index (GOHAI). The authors calculated changes in the overall GOHAI score and in the scores for each of the GOHAI's three dimensions individually by subtracting the baseline score from the score at follow-up. A positive difference indicated improvement in oral health, a negative difference indicated a decline and a difference of zero indicated no change.ResultsThe authors found that 48.56 percent of the participants experienced a decline in oral health and 33.48 percent experienced an improvement. Participants with 16 or more missing teeth and eight or more years of education were more likely to have an improvement in total GOHAI score. Deterioration was more likely to occur among those with two or more diseases. Improvement and decline in GOHAI functional scores were related to the number of missing teeth. The authors found no significant model for the change in the psychosocial score, and self-rated general health was the only variable related to both improvement and decline in pain or discomfort scores.ConclusionsThe authors observed a bidirectional change in self-perceived oral health, with deterioration predominating. The strongest predictor of improvement in the total GOHAI score was the number of missing teeth, whereas the number of diseases was the strongest predictor of deterioration.Clinical ImplicationsDental professionals and policymakers need to know the directions of change in older adults' oral health to establish treatment priorities and evaluate the impact of services directed at this population.     

Chloroquine-induced hyperpigmentation of the hard palate

This article reports a rare case of extensive palatal pigmentation secondary to long-term chloroquine treatment. Chloroquine was originally used as an antimalarial agent, but it is now widely used as an adjunct in the treatment of autoimmune diseases. Adverse effects of chloroquine usually include skin changes such as bullous pemphigoid, exacerbation of psoriasis, and pigmentation of the skin and mucous membranes as well as retinopathy, gastrointestinal alterations, and neuromuscular disorders. Extensive oral pigmentation is an uncommon feature of an adverse drug effect, and diagnosis should be based on clinicopathological findings.     

Cervicofacial necrotizing fasciitis following periodontal abscess

Soft tissue infections are characterized by acute inflammation, diffuse edema, and suppuration, and are often associated with symptoms such as malaise, fever, tachycardia, and chills. Necrotizing fasciitis is a destructive bacterial infection affecting subcutaneous tissue and superficial fascia and is associated with high rates of mortality. It usually involves the abdomen and extremities, but it also can occur in the head and neck. Early diagnosis is critical and the most commonly accepted treatment includes radical surgical intervention and administration of broad-spectrum antibiotics. This article reports and discusses the case of a patient with odontogenic cervicofacial necrotizing fasciitis, and emphasizes the importance of early and effective treatment.     

Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder

Imaging studies indicate smaller orbitofrontal cortex (OFC) volume in mood disorder patients compared with healthy subjects. We sought to determine whether child and adolescent patients with bipolar disorder have smaller OFC volumes than healthy controls. Fourteen children and adolescents meeting DSM-IV criteria for bipolar disorder (six males and eight females with a mean age+/-S.D.=15.5+/-3.2 years) and 20 healthy controls (11 males and nine females with mean age+/-S.D.=16.9+/-3.8 years) were studied. Orbitofrontal cortex volume was measured using magnetic resonance imaging. Male bipolar patients had smaller gray matter volumes in medial (p=0.044), right medial (0.037) and right (p=0.032) lateral OFC subdivisions compared to male controls. In contrast, female patients had larger gray matter volumes in left (p=0.03), lateral (p=0.012), left lateral (p=0.007), and trends for larger volumes in right lateral and left medial OFC subdivisions compared with female controls. Male patients exhibit smaller gray matter volumes, while female patients exhibit larger volumes in some OFC sub-regions. Gender differences in OFC abnormalities may be involved in illness pathophysiology among young bipolar patients.     

Korotkoff sounds: development of the sphygmomanometry research at the Nursing School of the USP

This article pays homage to Sergei Nicolai Korotkoff, for the centenary of the auscultatory method discovery. It refers to his discover of blood pressure auscultatory method in Russia, in 1905; presents the evidence that resulted in the development of sphygmomanometry studies in Brasil; describes the important contribution of the Nursing School of the University of S?o Paulo to the development of blood pressure measurement research; and analyses the results of the research field of "Cuff width influence in blood pressure measurement", created at the Nursing School of The University of S?o Paulo, in 1974. The scientific results of doctoral studies are presented, identifying the research groups that are contributing to defying knowledge in this area. The article demonstrates the consolidation of the results related to the initial doctoral program studies developed in the area. Confirmation of hypothesis in longitudinal studies is emphasized.     

Differential induction of apoptosis in undifferentiated and differentiated HL-60 cells by DNA topoisomerase I and II inhibitors

The effects of monocytic/macrophage and granulocytic differentiation induced by phorbol myristate acetate (TPA) and all-trans retinoic acid, respectively, were tested on the induction of apoptosis in human promyelocytic leukemia HL-60 cells treated with topoisomerase I and II inhibitors. Using a filter-binding assay, we observed a strong inhibition of DNA fragmentation induced by 3- and 24-hour continuous exposure to camptothecin, VP-16, VM-26, and m-AMSA in TPA- differentiated cells. The inhibition of the typical internucleosomal DNA fragmentation was confirmed by agarose gel electrophoresis. By contrast, drug-induced DNA fragmentation was not inhibited in retinoic acid-differentiated cells, and apoptosis occurred in these cells after 4 to 5 days in the absence of drug treatment. The TPA inhibitory effect was maximal after 24 hours of treatment and was correlated with differentiation, because phorbol dibutyrate ester was active, whereas 4- alpha-TPA, a nontumor promoter that does not induce differentiation, was not active. Using alkaline elution, we observed that TPA and retinoic acid differentiation were associated with changes in topoisomerase-mediated DNA breaks that were not correlated with their differential effects on drug-induced DNA fragmentation. Moreover, TPA also inhibited DNA fragmentation induced by vinblastine, cycloheximide, calphostin C, and x-rays. Using a cell-free system, we observed that DNA fragmentation was not inhibited in nuclei from TPA-differentiated cells. Rather, inhibition of apoptosis seemed to take place in the cytoplasm. We conclude that phenotypic changes associated with TPA- induced differentiation include inactivation of a cytoplasmic activity that can induce DNA fragmentation associated with apoptosis.     

Expresividad variable de una mutación fundadora en el gen EIF2AK4 en pacientes con enfermedad venooclusiva pulmonar hereditaria. Impacto en la supervivencia

Introduction and objectives

Hereditary pulmonary veno-occlusive disease (PVOD) has been associated with biallelic mutations in EIF2AK4 with the recent discovery of a founder mutation in Iberian Romani patients with familial PVOD. The aims of this study were phenotypical characterization and survival analysis of Iberian Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial genetic screening was conducted, as well as assessment of sociocultural determinants with a potential influence on disease course.