胎儿和新生儿同种异体免疫性血小板减少症:进展与持续性争议

胎儿和新生儿同种异体免疫性血小板减少症(AIT)是引起胎儿和新生儿严重血小板减少的最常见原因.母亲针对源自父亲的胎儿血小板抗原的IgG抗体,在妊娠早期就可通过胎盘,通常导致胎儿严重血小板减少.由于一些血小板减少症临界值(50、100或150×109/L)的不同,他们的发生率亦各不相同.但在多数未经选择的人群中,AIT影响1/1 000到1/2 000活产数.在新生儿病房,临床确诊的重症AIT很罕见,可能只有1:10 000分娩数.     

Diversity and repertoire of IgW and IgM <Emphasis Type="Italic">VH</Emphasis> families in the newborn nurse shark

Background

Adult cartilaginous fish express three immunoglobulin (Ig) isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric) IgM and monomeric/dimeric IgM_1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric) IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3) with non-templated nucleotide (N-region) addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT) expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families.

Results

IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1) and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge) within a species.

Conclusion

As in ratfish, sandbar and horn sharks, most nurse shark IgM VH genes are from one family with multiple, heterogeneous loci. Their IgW VH genes have diversified, forming at least three families. The neonatal shark Ig VH CDR3 repertoire, diversified via N-region addition, is shorter than the adult VDJ junction, suggesting one means of postnatal repertoire diversification is expression of longer CDR3 junctions.

     

Efficacy and safety of imidacloprid 10 %/moxidectin 1 % spot-on formulation in the treatment of feline infection by Capillaria aerophila

The nematode Capillaria aerophila (Trichuroidea, Trichuridae) affects the respiratory system of cats and other animals and occasionally of human beings. Infected cats may show bronchovesicular sounds, inflammation, sneezing, wheezing and, chronic cough and, sometimes, bronchopneumonia and respiratory failure. The present study evaluated the efficacy and safety of the antiparasitic spot-on formulation containing imidacloprid 10?%/moxidectin 1?% (Advocate?, Bayer Animal Health) in the treatment of natural feline infection with the lungworm C. aerophila. The efficacy of Advocate? administered once was tested on days 7?±?1 and 11?±?1 following treatment at day 0 and compared to faecal egg counts on days -6?±?1 and -2?±?1. Overall, 36 cats treated either with Advocate? (treatment group, n?=?17 cats) or left untreated (control group, n?=?19 cats) were included in the study. Geometric means of faecal egg counts values in eggs per gram of faeces were 124.03 prior to treatment and 0.26 posttreatment in treatment group, while 107.03 and 123.94 pre- and posttreatment in the untreated cats. Post-baseline egg counts showed a 99.79?% reduction in Advocate?-treated animals in comparison with cats which were left untreated. Also, treated cats showed no adverse events. This trial demonstrated that Advocate? spot-on formulation is safe and effective in the treatment of feline lung capillariosis caused by C. aerophila.     

Metabolic and monogenic causes of seizures in neonates and young infants

Seizures in neonates or young infants present a frequent diagnostic challenge. After exclusion of acquired causes, disturbances of the internal homeostasis and brain malformations, the physician must evaluate for inborn errors of metabolism and for other non-malformative genetic disorders as the cause of seizures. The metabolic causes can be categorized into disorders of neurotransmitter metabolism, disorders of energy production, and synthetic or catabolic disorders associated with brain malformation, dysfunction and degeneration. Other genetic conditions involve channelopathies, and disorders resulting in abnormal growth, differentiation and formation of neuronal populations. These conditions are important given their potential for treatment and the risk for recurrence in the family. In this paper, we will succinctly review the metabolic and genetic non-malformative causes of seizures in neonates and infants less than 6 months of age. We will then provide differential diagnostic clues and a practical paradigm for their evaluation.     

Mapping of three novel loci for non‐syndromic autosomal recessive mental retardation (NS‐ARMR) in consanguineous families from Pakistan

Rafiq MA, Ansar M, Marshall CR, Noor A, Shaheen N, Mowjoodi A, Khan MA, Ali G, Amin‐ud‐Din M, Feuk L, Vincent JB, Scherer SW. Mapping of three novel loci for non‐syndromic autosomal recessive mental retardation (NS‐ARMR) in consanguineous families from Pakistan. To date, of 13 loci with linkage to non‐syndromic autosomal recessive mental retardation (NS‐ARMR), only six genes have been established with associated mutations. Here we present our study on NS‐ARMR among the Pakistani population, where people are traditionally bound to marry within the family or the wider clan. In an exceptional, far‐reaching genetic survey we have collected more than 50 consanguineous families exhibiting clinical symptoms/phenotypes of NS‐ARMR. In the first step, nine families (MR2‐9 and MR11) with multiple affected individuals were selected for molecular genetic studies. Two families (MR3, MR4) showed linkage to already know NS‐ARMR loci. Fifteen affected and 10 unaffected individuals from six (MR2, MR6, MR7, MR8, MR9 and MR11) families were genotyped by using Affymetrix 5.0 or 6.0 single‐nucleotide polymorphism (SNP) microarrays. SNP microarray data was visually inspected by dChip and genome‐wide homozygosity analysis was performed by HomozygosityMapper. Additional mapping was performed (to exclude false‐positive regions of homozygosity called by HomozygosityMapper and dChip) on all available affected and unaffected members in seven NS‐ARMR families, using microsatellite markers. In this manner we were able to map three novel loci in seven different families originating from different areas of Pakistan. Two families (MR2, MR5) showed linkage on chromosome 2p25.3‐p25.2. Three families (MR7, MR8, and MR9) that have been collected from the same village and belong to the same clan were mapped on chromosome 9q34.3. MR11 maps to a locus on 9p23‐p13.3. Analysis of MR6 showed two positive loci, on chromosome 1q23.2‐q23.3 and 8q24.21‐q24.23. Genotyping in additional family members has so far narrowed, but not excluded the 1q locus. In summary, through this study we have identified three new loci for NS‐ARMR, namely MRT14, 15 and 16.     

18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience

¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.     

Hospital-acquired urinary tract infection

From 16,534 admissions, 60 patients, 4 days to 15 years of age, with one or more hospital-acquired urinary tract infections were identified during a 5-year period by a prospective surveillance system. The patient charts were subsequently reviewed to characterize the population at risk for such infections and to describe the course and consequences of these infections. Infections in individual patients ranged from one to greater than 50. The hospital-acquired urinary tract infection rate for the study period was 14.2 infections per 1,000 admissions. In the patients in whom all urinary tract infections were well documented, the following characteristics were defined: (1) 92% (97 of 105) of the infections occurred in catheterized patients; (2) almost half (49 of 105) of the infections occurred in patients exposed to only intermittent catheterization; (3) 28% (29 of 105) of the infections were asymptomatic; (4) fever was the most frequent finding in the symptomatic patients and occurred in 66% (60 of 105); (5) pyuria was found in only 51% (35 of 69) of the urinalyses performed at diagnosis; (6) 85% (89 of 105) of the infections were single-organism infections; (7) 82% (101 of 123) of the causative organisms were Escherichia coli, Pseudomonas sp, coagulase-negative staphylococci, Enterococcus spp, Klebsiella spp, or Enterobacter sp. The urinary tract infections in the 60 patients were not complicated by bacteremia, and no direct relationship between the infections and the minimal mortality in our patients could be established.