Faculty Bibliography
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126
Re: CT "invisible" lesion of the major salivary glands-a diagnostic pitfall of contrast-enhanced CT [Letter]
PMID: 19822250
ISSN: 0009-9260
CID: 1414662
A breathless woman with asthma [Case Report]
PMID: 19812143
ISSN: 0959-8146
CID: 1414672
Clinical and molecular phenotype of Aicardi-Goutieres syndrome
Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.
PMCID:2227922
PMID: 17846997
ISSN: 0002-9297
CID: 4372262
Intrapartum stillbirths in hospital unrelated to uteroplacental vascular insufficiency
The aim of this study was to investigate the causes of intrapartum asphyxia and its relationship to placental abnormalities. Twenty intrapartum fetal death autopsies carried out over a 10-year period in one hospital pathology department associated with a large obstetric unit were reviewed. All the intrapartum fetal deaths occurred in the hospital, while the mothers were being monitored during and after labor. On morphologic grounds, all the fetal deaths were thought to be caused by intrapartum asphyxia. Seven of the intrapartum fetal deaths were associated with intrauterine infection causing funisitis, and in 6 of these cases, chorioamnionitis was present as well. Two cases were caused by placental abruption, and 1 case was caused by cord compression. In 8 of the 10 remaining cases in which the placenta was examined, a minor placental abnormality was detected in only 1 case. Five of the 10 cases had a mild astrocytosis in the intracerebral periventricular white matter, suggestive of intrauterine ischemia at least 12 hours before death. Five of the 10 cases were thought by the delivering obstetrician to have umbilical cord abnormalities. The main conclusions from this study are that, except in cases of intrauterine infection, placental vascular abnormalities are unlikely to be associated with intrapartum asphyxia leading to fetal death during labor. The number of cases with umbilical cord abnormalities raises the possibility that cord accidents may be a significant cause of intrapartum stillbirth.
PMID: 17378621
ISSN: 1093-5266
CID: 4372252
Hip fractures in centenarians
The centenarian population is increasing yet there is little about their morbidity and mortality rates following hip fracture. The aim was to review centenarians treated for proximal femoral fractures in Edinburgh describing treatment outcomes in relation to mortality, walking ability and residential status comparing centenarians with a the more typical hip fracture population. In this retrospective review, 18 centenarians sustaining hip fractures in Edinburgh between 1998 and 2002 were compared to 18 randomly selected "normal" hip fracture patients aged 75-83 years. Centenarian in-hospital, 1 and 4 month mortality was 11.1, 33.3 and 50%, respectively, versus 0, 0 and 5.6% in the normal group. Centenarian 4 month mortality was significantly greater than that of the normal group (Fisher's Exact Test, P = 0.00723). A total of 22.2% of centenarians regained pre-fracture walking ability compared to 58.8% of the normal patients. A total 28.6% of centenarians could continue living independently post-fracture compared to 69.2% of the normal group.
PMID: 15351671
ISSN: 0020-1383
CID: 1414692
GABA(A) receptor sites in the developing human foetus
GABA(A) receptor sites were characterised in cerebral cortex tissue samples from deceased neurologically normal infants who had come to autopsy during the third trimester of pregnancy. Pharmacological parameters were obtained from homogenate binding studies which utilised the 'central-type' benzodiazepine ligands [3H]diazepam and [3H]flunitrazepam, and from the GABA activation of [3H]diazepam binding. It was found that the two radioligands behaved differently during development. The affinity of [3H]flunitrazepam for its binding site did not vary significantly between preparations, whereas the [3H]diazepam K(D) showed marked regional and developmental variations: infant tissues showed a distinctly lower affinity than adults for this ligand. The density of [3H]flunitrazepam binding sites increased approximately 35% during the third trimester to reach adult levels by term, whereas [3H]diazepam binding capacity declined slightly but steadily throughout development. The GABA activation of [3H]diazepam binding was less efficient early in the trimester, in that the affinity of the agonist was significantly lower, though it rose to adult levels by term. The strength of the enhancement response increased to adult levels over the same time-frame. The results strongly suggest that the subunit composition of cortical GABA(A) sites changes significantly during this important developmental stage.
PMID: 12480125
ISSN: 0165-3806
CID: 4372242
