Cystic kidney dysplasia and polydactyly in 3 sibs with Bardet-Biedl syndrome

Two infants with cystic kidney dysplasia and polydactyly were born to consanguineous parents. One infant died at age 2 months, and the other is currently 3.5 years old. A third pregnancy was terminated following ultrasonographic visualization of large echodense fetal kidneys and polydactyly. Although none had apparent brain anomalies, they were considered to represent the Meckel syndrome. Extinguished responses on electroretinography in our 3.5-year-old patient has led to the diagnosis of Bardet-Biedl syndrome. This observation offers an opportunity to revisit the Bardet-Biedl syndrome and provides further evidence that structural renal abnormalities are characteristic of the syndrome. We wish to alert the clinician to the diagnosis of Bardet-Biedl syndrome in patients with infantile cystic kidney dysplasia. © Wiley-Liss, Inc.     

Emphysematous Gastritis Secondary to Ingestion of Large Amounts of Coca Cola

Acute emphysematous gastritis (AEG) is a life-threatening disease in which gas-forming bacteria invade the gastric wall and cause acute inflammation of it. The clinical presentation of the patient with AEG is stormy: severe sepsis which usually leads to an early death. Presented herein is a case of a 16-yr-old boy with AEG. There were no predisposing factors to the condition in this case. Gas invaded the stomach wall and portal venous system, as well as the duodenal wall, a finding that has not been reported previously. The clinical course was very severe but, in contrast to previously reported cases, recovery was very rapid and left no sequelae.     

Hematologic features and clinical course of an infant with Pearson syndrome caused by a novel deletion of mitochondrial DNA

OBJECTIVE: Pearson bone marrow-pancreas syndrome (PS) is a rare, usually fatal mitochondrial disorder involving the hematopoietic system in early infancy. Due to the diversity of clinical symptoms, the diagnosis can be difficult. The authors describe a boy with severe hypoplastic anemia in whom extensive clinical, biochemical, and morphologic findings led to the diagnosis of PS, and molecular analysis revealed a novel deletion of mitochondrial DNA from nucleotide position 10.371 to 14.607. METHODS: The patient is a 2-year-old boy who presented at age 5 months with hypoplastic macrocytic anemia. His first months of life and the family history were uneventful. Extensive pretransfusion evaluations did not reveal a metabolic, infectious, or hematologic-neoplastic etiology, and he had no evidence of exocrine pancreatic insufficiency. However, a second bone marrow aspirate at age 7 months showed a reduced cell number, vacuolated erythroblasts and myeloblasts, and ringed sideroblasts, so PS was suspected. RESULTS: Additional molecular analysis from the boy's blood leukocytes revealed a deletion of mitochondrial DNA from nucleotide position 10.371 to 14.607, which was absent in his mother's blood cells, consistent with a sporadic mutation as commonly seen in PS. The muscle histology and the respiratory chain enzymes were normal. CONCLUSIONS: Mitochondriopathies should be considered in children with persistent non-neuromuscular symptoms such as unexplained refractory anemia. Due to the often-fatal course of PS, the rapid detection of mitochondrial DNA deletions is imperative for diagnosis and family counseling.     

Expression of the recombination-activating genes in extrafollicular lymphocytes but no apparent reinduction in germinal center reactions in human tonsils.

V(D)J recombination in lymphocytes is mediated by 2 recombination-activating genes, RAG1 and RAG2, which are expressed during lymphocyte development in bone marrow and thymus. Prompted by studies reporting re-expression of the RAGs in germinal center B cells, the expression of RAGs and terminal deoxynucleotidyl transferase (TdT) in human lymphoid tissues was examined using in situ hybridization and immunohistochemistry, respectively. Here it is shown that RAGs and TdT are not reinduced in germinal center reactions. However, RAG(+)/TdT(+) cells are frequently present in extrafollicular areas of tonsils mainly at the boundary between lymphoid tissue and fibrous scaffold. Phenotypic analyses suggest that these cells are B cells. Finally, it is shown that RAG(+)/TdT(+) cells are found more frequently in tonsils than in other peripheral lymphoid tissues. This may reflect an increased influx of RAG(+)/TdT(+) cells as a result of higher antigenic stimulation at this site. Alternatively, this observation may indicate that the tonsils are an additional site of lymphocyte ontogeny.     

Detection of extended-spectrum beta-lactamases among Enterobacteriaceae by use of semiautomated microbiology systems and manual detection procedures

Three commercially available microbiology identification and susceptibility testing systems were compared with regard to their ability to detect extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae, i.e., the Phoenix Automated Microbiology System (BD Diagnostic Systems, Sparks, MD), the VITEK 2 System (bioMérieux, Marcy l'Etoile, France), and the MicroScan WalkAway-96 System (Dade Behring, Inc., West Sacramento, CA), using routine testing panels. One hundred fifty putative ESBL producers were distributed blindly to three participating laboratories. Conventional phenotypic confirmatory tests such as the disk approximation method, the CLSI double-disk synergy test, and the Etest ESBL were also evaluated. Biochemical and molecular characterization of beta-lactamases performed at an independent laboratory was used as the reference method. One hundred forty-seven isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Serratia marcescens, Proteus mirabilis, Proteus vulgaris, and Morganella morganii were investigated. Of these isolates, 85 were identified as ESBL producers by the reference method. The remaining isolates were identified as non-ESBL producers; they were either hyperproducers of their chromosomal AmpC, Koxy, or SHV enzymes or lacked any detectable beta-lactamase activity. The system with the highest sensitivity for the detection of ESBLs was the Phoenix (99%), followed by the VITEK 2 (86%) and the MicroScan (84%); however, specificity was more variable, ranging from 52% (Phoenix) to 78% (VITEK 2). The performance of the semiautomated systems differed widely with the species investigated. The sensitivities of the conventional test methods ranged from 93 to 94%. The double-disk synergy test showed the highest specificity and positive predictive value among all test methods, i.e., 97% and 98%, respectively.     

Gaucher Disease

Objective. Our large tertiary clinic for patients with Gaucher disease has used sonography as the preferred modality to monitor hepatosplenomegaly in hundreds of patients for more than 18 years. With the advent of specific enzyme replacement therapy (ERT), sonographic monitoring of changes in both hepatomegaly and the echogenicity of the hepatic tissue may highlight features that are amenable to ERT. Methods. All patients (500) seen at presentation and at annual or semiannual routine visits have undergone sonographic examinations by a single senior radiologist (I.H.‐H.). Results. Thirty‐nine patients (7.8%) had sonographic evidence of hepatic disease (21 male and 18 female; age range, 18–90 years); 26 (66.7%) of these received ERT, and 10 (25.6%) were splenectomized. Conclusions. Liver findings are relatively rare. Among 500 patients, there was no instance of computed tomographic findings that had not been previously shown by sonography. Radiologists should be acquainted with the variable sonographic spectrum of the Gaucher liver. If hepatic lesions are small, hyperechoic, and slowly evolving, one may surmise that they are due to Gaucher cell accumulation. However, special attention should be paid to progressive deterioration and irregularities in liver texture because other metabolic processes and cancers must be ruled out.     

Genetic Determinants Involved in the Susceptibility of Pseudomonas aeruginosa to β-Lactam Antibiotics

The resistome of P. aeruginosa for three β-lactam antibiotics, namely, ceftazidime, imipenem, and meropenem, was deciphered by screening a comprehensive PA14 mutant library for mutants with increased or reduced susceptibility to these antimicrobials. Confirmation of the phenotypes of all selected mutants was performed by Etest. Of the total of 78 confirmed mutants, 41 demonstrated a reduced susceptibility phenotype and 37 a supersusceptibility (i.e., altered intrinsic resistance) phenotype, with 6 mutants demonstrating a mixed phenotype, depending on the antibiotic. Only three mutants demonstrated reduced (PA0908) or increased (glnK and ftsK) susceptibility to all three antibiotics. Overall, the mutant profiles of susceptibility suggested distinct mechanisms of action and resistance for the three antibiotics despite their similar structures. More detailed analysis indicated important roles for novel and known β-lactamase regulatory genes, for genes with likely involvement in barrier function, and for a range of regulators of alginate biosynthesis.Pseudomonas aeruginosa is an important opportunistic pathogen and a leading cause of nosocomial infections (32, 41) and is the major cause of morbidity and mortality among individuals affected by cystic fibrosis (CF) (33). Infections caused by this opportunistic pathogen are difficult to eradicate due to its high intrinsic resistance to different classes of antibiotics. Treatment of patients is further complicated by the emergence of multidrug resistance arising principally from mutations, but also through acquisition of plasmids with antibiotic resistance determinants (32, 41).β-Lactam antibiotics are among the main antibiotics currently used in anti-pseudomonal therapy (18, 56). The killing mechanism of β-lactams is initiated by binding to cell wall transpeptidases (penicillin-binding proteins [PBPs]), thus blocking an important step in peptidoglycan biosynthesis (59). This family of antibiotics includes penicillins, cephalosporins, monobactams, and carbapenems. Resistance to β-lactams commonly results from drug inactivation by β-lactamases, drug extrusion through efflux pumps, changes in outer membrane permeability, and modification of PBPs (46). However, recent publications have demonstrated that a myriad of genetic determinants modulate susceptibility to antibiotics, aside from those responsible for typical antibiotic resistance mechanisms, like the ones described above (8, 16, 19, 52), especially when one considers mutations causing modest changes in the MIC (e.g., 2-fold). Furthermore, β-lactam antibiotics are known to affect global gene expression, suggesting that the response to these drugs entails many different genes (1, 6).To identify novel genetic determinants involved in susceptibility to β-lactams, we screened a comprehensive P. aeruginosa mutant library (31) for changes in the MICs of imipenem and meropenem (carbapenems) and ceftazidime (a cephalosporin). Our findings demonstrated that mutations in a broad array of genes belonging to different functional families can modulate the susceptibility of P. aeruginosa to these antibiotics. This study contributes to our understanding of how pathogens respond and become resistant to β-lactam antibiotics, revealing certain mutations that, because they cause modest changes in the MIC, may be missed in examination of clinical strains but likely contribute to the stepwise development of resistance in the clinic.     

Systemic depletion of macrophages by liposomal bisphosphonates reduces neointimal formation following balloon-injury in the rat carotid artery

OBJECTIVES: Macrophage depletion by liposomal clodronate inhibits neointimal formation after balloon-injury. The present study examined bisphosphonates (BPs) potency-effect relationship and the role of systemic versus local monocytes in vascular repair. METHODS AND RESULTS: Liposomal preparations of clodronate, pamidronate, alendronate, and ISA-13-1 inhibited RAW-264 macrophages growth in a dose-response manner. Administration to balloon-injured rats suppressed neointimal growth. Neointima to media ratio (N/M) at 14 days was reduced from 1.35 +/- 0.22 (control) to 0.4 +/- 0.1 and 0.9 +/- 0.17 by liposomal alendronate (1.5 mg/kg, i.v.) and liposomal ISA-13-1 (15 mg/kg), respectively (n = 8-10, P < 0.05). Suppression of neointimal formation was preserved at 30 days. Subcutaneous administration of liposomal BP (LBP) was also effective in suppressing neointimal formation, while short local intraluminal application had no effect. Immunostaining for ED-1 and ED-2 revealed no resident macrophages in the arterial wall, and reduced macrophage infiltration in LBP-treated animals. Arterial PDGF-B chain and PDGF-beta receptor activation were reduced in LBP-treated animals and up-regulation of the PDGF receptor was noted. CONCLUSIONS: Systemic transient inactivation of monocytes and macrophages by LBPs reduced macrophage infiltration and neointimal formation in the rat carotid injury model. The findings demonstrate a BP potency-effect relationship, and highlight the role of circulating monocytes in vascular injury and repair.     

Young Children's Food-Related Knowledge: Kindergartners’ Free Categorization of Food Items

ObjectiveStudies concerning young children's food-related knowledge have dealt mostly with specific types of knowledge or with researchers’ predetermined categories. This approach may neglect certain aspects of children's knowledge and may limit the understanding of its general structure. The present study aimed to examine and analyze a wide scope of young children's constructed food-related knowledge.MethodsQualitative thematic analysis of 40 kindergartners’ free categorizations of food items.ResultsChildren's food-related knowledge was broad and derived from 3 primary sources: personal experience, environmental experience, and perceived messages. Novel aspects of knowledge were found, such as different treatments of food and partial familiarity with nutrients.Conclusions and ImplicationsThe findings demonstrated the existence of various types of young children's food-related knowledge. Attention to the broad spectrum of their knowledge and its possible sources may contribute to the design of relevant and effective nutrition education interventions aimed at young children.