The nephronophthisis complex

Summary The clinical and morphological findings are described in 27 children with nephronophthisis. Seventeen children were considered as sporadic cases. In 10 familial cases the presumed mode of inheritance was autosomal recessive. The clinical picture was rather uniform: polyuria-polydipsia, hyposthenuria, anemia, growth retardation, and azotemia with progressive renal failure. Six patients presented with tapeto-retinal degeneration. In a further seven children other ocular changes were detected. Two female siblings showed additional non-renal manifestations: mental retardation, pulmonary emphysema, skeletal anomalies, and congenital hepatic fibrosis.Renal histology displayed a chronic sclerosing tubulo-interstitial nephropathy with extensive tubular atrophy and dedifferentiation. Medullary cysts were frequently found in end-stage kidneys. Immunofluorescence was either non-specific or completely negative. On electron microscopy, the tubular basement membrane changes predominated: thickening, lamellation, splitting, and deposition of microfibrils within the increased basement membrane substance. Detailed light- and electron microscopic findings were non-specific but the overall morphologic picture was characteristic and even diagnostic in conjunction with the clinical presentation.A recurrence of nephronophthisis in transplanted kidneys has not been observed.The pathogenesis of nephronophthisis is obscure but with respect to the morphologic findings a primary or secondary tubular basement membrane defect seems very likely.Our experience suggests that nephronophthisis is a frequent cause of chronic renal failure in children and commonly associated with non-renal abnormalities. To avoid the separation of different syndromes presenting with a uniform renal disease but various non-renal manifestations, we suggest that the term nephronopthisis complex be used.Presented in part at the 63th Annual Meeting of the German Society of Pathology, Stuttgart 1979     

The risk for congenital heart defects in offspring of individuals with congenital heart defects

BACKGROUND: Congenital heart defects (CHDs) occur in approximately 1% of all live births. Although most CHDs are of unknown etiology, a family history of CHDs is a known risk factor, and offspring of individuals with CHDs are at a higher risk of having CHDs. The aim of this study was to investigate the relative risk for CHDs to offspring of individuals with CHDs. METHODS: The prevalence rates of CHDs in offspring of 203 individuals with CHDs and 282 individuals without CHDs were investigated. The study participants completed a questionnaire that included information on medical and reproductive history, lifestyle indicators, and family history of CHDs and other congenital malformations. The prevalence rates of CHDs in offspring were calculated. RESULTS: The prevalence of CHDs was 3.1% (18/575) in offspring of individuals with CHDs and 1.3% (8/589) in offspring of individuals without CHDs. The adjusted odds ratio for CHDs to offspring of parents with CHDs was 1.73 (95% confidence interval [95% CI] 0.89-2.44, p=0.02). The estimated relative risk for offspring to females with CHD was higher than for males [2.3 (95% CI 1.1-4.7, p=0.03) versus 1.31 (95% CI 0.48-4.30, p=0.66), respectively]. There was no suggestion of association between CHDs and maternal smoking, alcohol consumption, and use of medication during pregnancy. CONCLUSIONS: Offspring of parents with CHDs are at a higher risk for CHDs compared with the general population. Couples where one member is affected with CHD should receive pre-conceptional or pre-natal genetic counseling and should be informed about the magnitude of the potential risk of CHDs to the offspring.     

Travel vision in infant monkeys: Maturation rate and abnormal stereotyped behaviors

Three monkeys with travel vision and 5 controls were observed with their mothers during the first 6 months of age and then for another 3 months after they had been placed in social isolation. In the home cage, the experimental animals did not differ from controls except that two held a hand before their eyes in a stereotyped fashion not previously reported for animals. In an unfamiliar environment the blind animals did not look at an observer, threatened less than normal, and were awkward in moving around. Animals who held hands before eyes tended to approach a flickering visual stimulus.     

Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head injury

Previous studies suggest that traumatic brain injury is associated with increased risk factor for developing Alzheimer's disease. Furthermore, the extent of the risk seems to be most pronounced in Alzheimer's disease patients who carry the ε4 allele of apolipoprotein E, suggesting a connection between susceptibility to head trauma and the apolipoprotein E genotype. Apolipoprotein E-deficient mice provide a useful model for investigating the role of this lipoprotein in neuronal maintenance and repair. In the present study apolipoprotein E-deficient mice and a closed head injury experimental paradigm were used to examine the role of apolipoprotein E in brain susceptibility to head trauma and in neuronal repair. Apolipoprotein E-deficient mice were assessed up to 40 days after closed head injury for neurological and cognitive functions, as well as for histopathological changes in the hippocampus. A neurological severity score used for clinical assessment revealed more severe motor and behavioural deficits in the apolipoprotein E-deficient mice than in the controls, the impairment persisting for at least 40 days after injury. Performance in the Morris water maze, which tests spatial memory, showed a marked learning deficit of the apolipoprotein E-deficient mice when compared with injured controls, which was apparent for at least 40 days. At this time, histopathological examination revealed overt neuronal cell death bilaterally in the hippocampus of the injured apolipoprotein E-deficient mice.

The finding that apolipoprotein E-deficient mice exhibit an impaired ability to recover from closed head injury suggests that apolipoprotein E plays an important role in neuronal repair following injury and highlights the applicability of this mouse model to the study of the cellular and molecular mechanisms involved.     

3D-printed prostheses for large bone defect reconstruction following bone tumor surgery北大核心

BACKGROUND: Tumor segment resection is one of the standard methods for the treatment of bone tumors. However, the reconstruction of bone defects atumor resection faces many challenges. A growing number of researchers are focusing on 3D-printed prostheses for bone defect repair and reconstruction following bone tumor surgery. OBJECTIVE: To explore the feasibility of 3D-printed prostheses in the reconstruction of large bone defect following bone tumor surgery and to evaluate the postoperative outcomes. METHODS: Retrospective analysis of clinical data of 24 patients [19 males and 5 females, age 23.8 (6-61) years] who underwent bone tumor resection and 3D-printed prosthesis implantation in the Department of Bone Oncology, the First Affiliated Hospital of Xinjiang Medical University from December 2020 to September 2021 was conducted. There were 7 cases with distal femur tumor, 5 with pelvis tumor, 4 with proximal tibia tumor, 3 with middle femur tumor, 1 with distal tibia tumor, 1 with proximal humerus tumor, 1 with middle humerus tumor, 1 with scapula tumor, 1 with ulna tumor, and 22 cases with primary tumors (13 osteosarcoma, 4 Ewing sarcoma, 2 giant cell tumor of bone, 1 chondroblastoma, 1 chondrosarcoma, and 1 osteoblastoma), 2 metastatic carcinoma. Preoperative and postoperative imaging data were recorded and neoadjuvant chemotherapy was administered in 17 cases before surgery. The Musculoskeletal Tumour Society score was used to assess limb function before surgery and 6 months after surgery, and pain was assessed by the Visual Analog Scale, as well as the complications were recorded. RESULTS AND CONCLUSION: (1) All patients undergoing resection of the tumor segment and 3D-printed prosthesis implantation for the reconstruction of the bone defect were followed for 6-49 months, and the results showed that the length of osteotomy was (18.2 ± 7.3) cm and an average intraoperative bleeding volume was 740 (100-3 000) mL. (2) Two patients died of systemic metastasis, the remaining 22 had no pulmonary metastasis or recurrence during the follow-up period, and 1 patient developed aseptic loosening of the prosthesis at 25 months postoperatively. (3) The Musculoskeletal Tumour Society scores were significantly increased, while Visual Analog Scale scores were significantly decreased (P < 0.05) at 6 months postoperatively. (4) The Musculoskeletal Tumor Society score was rated excellent in all 22 patients at the final follow-up. (5) These results suggest that 3D-printed prosthesis is suitable for the reconstruction of large bone defects caused by bone tumor resection. Patients have good postoperative function and few complications. However, further investigations are needed to explore long-term follow-up results. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Steinfeld syndrome: Report of a second family and further delineation of a rare autosomal dominant disorder

We report on a fetus with alobar holoprosencephaly, microphthalmia, midline cleft lip and palate, absent nose, dysplastic ears, radial defects, pentalogy of Fallot, unilateral renal aplasia, absent gallbladder, vertebral anomalies, and absence of ribs. The father had a cleft palate, bilateral colobomas of the iris and retina, a bifid uvula, vertebral anomalies, and unilateral congential hearing loss. His sister had a cleft lip. On the basis of this family and the family reported by Steinfeld [1982], this malformation syndrome can be defined as a rare autosomal dominant syndrome whose main component manifestations are holoprosencephaly, predominantly radial limb deficiency, heart defects, kidney malformations, absence of gallbladder, and vertebral anomalies. © 1993 Wiley-Liss, Inc.     

Screening for coeliac disease as a possible maternal risk factor for neural tube defect

Coeliac disease is an important cause of malabsorption, particularly of folic acid, in adults. We investigated the possibility that it might be a maternal risk factor for neural tube defect (NTD)-associated pregnancy by screening affected mothers using serum endomysial antibody (EmA) which has high sensitivity and specificity for coeliac disease. One (1.6%) of 60 patients was EmA positive and had a diagnosis of coeliac disease confirmed by the finding of villous atrophy on jejunal biopsy. In conclusion, the majority of NTD-associated pregnancies are not associated with maternal coeliac disease and our study is additional evidence that abnormalities of folic acid metabolism rather than absorption are the most important risk factors for NTD. Further studies are needed to determine whether the coeliac disease prevalence among women with NTD-affected pregnancy is higher than that of the general population.     

BMP4 is required in the anterior heart field and its derivatives for endocardial cushion remodeling, outflow tract septation, and semilunar valve development

The endocardial cushions play a critical role in septation of the four-chambered mammalian heart and in the formation of the valve leaflets that control blood flow through the heart. Within the outflow tract (OFT), both cardiac neural crest and endocardial-derived mesenchymal cells contribute to the endocardial cushions. Bone morphogenetic protein 4 (BMP4) is required for endocardial cushion development and for normal septation of the OFT. In the present study, we show that anterior heart field (AHF)-derived myocardium is an essential source of BMP4 required for normal endocardial cushion expansion and remodeling. Loss of BMP4 from the AHF in mice results in an insufficient number of cells in the developing OFT endocardial cushions, defective cushion remodeling, ventricular septal defects, persistent truncus arteriosus, and abnormal semilunar valve formation.     

成人室间隔缺损的外科治疗

目的：报告成人室间隔缺损的外科治疗经验。方法：对26例成人室间隔缺损的手术治疗进行回顾性分析。其中行室缺直接缝合3例,单纯补片修补19例,单向活瓣补片修补4例。同时行主动脉瓣折叠悬吊2例,双瓣置换l例,二尖瓣成成形l例,三尖瓣成形4例．结果：无手术死亡。术后并发症：切口感染、术后出血二次开胸止血、呼吸道感染和片周漏各l例,心动过速4例．术后随访24例(92．3％),随访时间1月～92月,晚期死亡l例,死因为片周漏并感染性心内膜炎．结论：成人室间隔缺损的临床表现虽较为复杂,手术效果令人满意．选择正确的手术方法及注意围术期处理是手术治疗成功的关键。     

自体骨膜游离移植修复关节软骨缺损进展

探讨自体骨膜游离移植修复关节软骨缺损的研究进展。从骨膜的解剖生理功能和骨膜再生软骨能力两方面进行分析,并阐述了关节内营养环境、关节活动、骨膜生发层不同朝向、年龄及手术技巧等因素对移植修复的影响。同时总结了该方法的临床应用状况、效果及存在的问题。实验及临床的研究证明自体骨膜游离移植是修复关节软骨缺损的重要手段,局部环境因素影响骨膜成软骨。