Uniparental disomy 7 in Silver--Russell syndrome and primordial growth retardation

Maternal uniparental disomy for the entire chromosome 7 hasso far been reported in three patients with intrauterine andpostnatal growth retardation. Two were detected because theywere homozygous for a cystic fibrosis mutation for which onlythe mother was heterozygous, and one because he was homozygousfor a rare COL1A2 mutation. We investigated 35 patients witheither the Silver-Russell syndrome or primordial growth retardationand their parents with PCR markers to search for uniparentaldisomy 7. Four of 35 patients were found to have maternal disomy,including three with isodisomy and one with heterodisomy. Thedata confirm the hypothetical localization of a maternally imprintedgene (or more than one such gene) on chromosome 7. It is suggestedto search for UPD 7 in families with an offspring with sporadicSilver-Russell syndrome or primordial growth retardation.     

Autosomal imbalance syndromes: Genetic interactions and the origin of congenital malformations in aneuploidy syndromes

In some autosomal imbalance syndromes an additional imbalance interferes with the occurrence of the anomalies typical of the syndrome itself. For example, polydactyly was found in patients with “pure” del(3p) more frequently (11/23) than in patients where these deletions were associated with different partial trisomies (2/28). The opposite situation was shown in del(7q) syndrome where various defects of the holoprosencephalic group were found to be rarer in patients with “pure” deletions, than in cases with simultaneous occurrence of various partial trisomies. It suggests the importance of gene interaction in determining the phenotypic picture of autosomal imbalance syndromes. © 1993 Wiley-Liss, Inc.     

Further delineation of the Beemer–Langer syndrome using concordance rates in affected sibs

Six familial cases of the Beemer–Langer syndrome (BLS) were analyzed to further elucidate the spectrum and frequency of anomalies observed in this disorder. Preaxial polydactyly was found in 3/6 affected sibs, and, therefore, its frequency previously may have been underestimated. Some patients, described as infants affected with the Majewski syndrome (MS) or “atypical” short rib-poly-dactyly conditions, may indeed have BLS. A high frequency of brain defects (16/26) and cleft tongue, oral frenula, and/or natal teeth (13/29) widens the list of typical findings in this syndrome. The specific type of tibial defect seems to be the most important discrimination of the MS and the BLS. © 1994 Wiley-Liss, Inc.     

Leptin and Its Emerging Role in Children and Adolescents

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Recent “proof of concept” studies involving leptin administration to humans support its critical role in regulating energy homeostasis, neuroendocrine and immune function as well as insulin resistance in states of energy/ caloric deprivation. Moreover, interventional studies in leptin deficient children and observational studies in normal girls and boys support a role for leptin as a permissive factor for the initiation of puberty in children. The potential clinical usefulness of leptin in several disease states in children and adolescents, including hypothalamic amenorrhea, eating disorders and syndromes of insulin resistance is still under investigation.     

Frequency of Susceptibility Testing for Patients with Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

Currently, no standards exist for determining the optimal frequency of repeat antimicrobial susceptibility testing (AST) when an organism is recurrently isolated from the same specimen source. Although testing every 2 to 5 days is thought sufficient, we present three cases of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia where current laboratory protocol for repeating AST every 5 days was inadequate to identify resistant organisms.     

Empyema due to ventriculopleural shunt

Empyema developing seven weeks after craniotomy in a 62-year-old black woman with an ipsilateral ventriculopleural (V-PL) shunt is described. Infection of the pleural space presumably resulted from transfer of organisms from a proximal V-PL shunt infection to the thorax. Empyema resulting from V-PL shunt infection has not previously been reported. Pleural effusions in patients with V-PL shunts must be considered as a potential site of infection with possible development of empyema.     

In Vitro Activity of Daptomycin in Combination with β-Lactams,Gentamicin, Rifampin,and Tigecycline against Daptomycin-Nonsusceptible Enterococci

Enterococci that are nonsusceptible (NS; MIC > 4 μg/ml) to daptomycin are an emerging clinical concern. The synergistic combination of daptomycin plus beta-lactams has been shown to be effective against vancomycin-resistant Enterococcus (VRE) species in vitro. This study systematically evaluated by in vitro time-kill studies the effect of daptomycin in combination with ampicillin, cefazolin, ceftriaxone, ceftaroline, ertapenem, gentamicin, tigecycline, and rifampin, for a collection of 9 daptomycin-NS enterococci that exhibited a broad range of MICs and different resistance-conferring mutations. We found that ampicillin plus daptomycin yielded the most consistent synergy but did so only for isolates with mutations to the liaFSR system. Daptomycin binding was found to be enhanced by ampicillin in a representative isolate with such mutations but not for an isolate with mutation to the yycFGHIJ system. In contrast, ampicillin enhanced the killing of the LL-37 human antimicrobial peptide against daptomycin-NS E. faecium with either the liaFSR or yycFGHIJ mutation. Antagonism was noted only for rifampin and tigecycline and only for 2 or 3 isolates. These data add support to the growing body of evidence indicating that therapy combining daptomycin and ampicillin may be helpful in eradicating refractory VRE infections.