Long-term outcomes of liver transplant patients with human immunodeficiency virus infection and end-stage-liver-disease: single center experience

Objective

Orthotopic-liver-transplantation (OLT) in patients with Human-Immunodeficiency-Virus infection (HIV) and end-stage-liver-disease (ESDL) is rarely reported. The purpose of this study is to describe our institutional experience on OLT for HIV positive patients.

Material and methods

This is a retrospective study of all HIV-infected patients who underwent OLT at the University Hospital of Essen, from January 1996 to December 2009. Age, sex, HIV transmission-way, CDC-stage, etiology of ESDL, concomitant liver disease, last CD4cell count and HIV-viral load prior to OLT were collected and analysed. Standard calcineurin-inhibitors-based immunosuppression was applied. All patients received anti-fungal and anti-pneumocystis carinii pneumonia prophylaxis post-OLT.

Results

Eight transplanted HIV-infected patients with a median age of 46 years (range 35-61 years) were included. OLT indications were HCV (n = 5), HBV (n = 2), HCV/HBV/HDV-related cirrhosis (n = 1) and acute liver-failure (n = 1). At OLT, CD4 cell-counts ranged from 113-621 cells/μl, and HIV viral-loads from < 50-175,000 copies/ml. Seven of eight patients were exposed to HAART before OLT. Patients were followed-up between 1-145 months. Five died 1, 3, 10, 31 and 34 months after OLT due to sepsis and graftfailure respectively. Graft-failure causes were recurrent hepatic-artery thrombosis, HCV-associated hepatitis, and chemotherapy-induced liver damage due to Hodgkin-disease. One survivor is relisted for OLT due to recurrent chronic HCV-disease but non-progredient HIV-infection 145 months post-OLT. Two other survivors show stable liver function and non-progredient HIV-disease under HAART 21 and 58 months post-OLT.

Conclusions

OLT in HIV-infected patients and ESLD is an acceptable therapeutic option in selected patients. Long-term survival can be achieved without HIV disease-progression under antiretroviral therapy and management of the viral hepatitis co-infection.     

Large myelomeningocele repair

Background:

Wound closure is accomplished in most cases of myelomeningocele (MMC) by undermining of the skin edges surrounding the defect. However, large defects cannot be closed reliably by this simple technique. Due to the technical challenge associated with large MMC, surgeons have devised different methods for repairing large defects. In this paper, we report our experience of managing large defects, which we believe bears a direct relationship to decrease the incidence of wound complications.

Materials and Methods:

Forty children with large MMCs underwent surgical repair and represent our experience. We recommend using all hairy skin around the defect as a way to decrease the tension on the edges of the wound and the possible subsequent necrosis. It is our experience that vertical incision on one or two flanks parallel to the midline can decrease the tension of the wound. Moreover, ventriculo-peritoneal shunting for children who developed hydrocephalus was performed simultaneously, which constitutes another recommendation for preventing fluid collection and build up of pressure on the wound.

Results:

Patients in this study were in the age range of 2 days to 8 years. The most common location of MMC was in the thoracolumbar area. All but four patients had severe weakness in lower extremities. We used as much hairy skin around the MMC sac as possible in all cases. Vertical incisions on one or both flanks and simultaneous shunt procedure were performed in 36 patients. We treated children with large MMC defects with acceptable tension-free closure. Nonetheless, three patients developed superficial skin infection and partial wound dehiscence, and they were managed conservatively.

Conclusions:

We recommend using all hairy skin around the MMC defect for closure of large defects. In cases that were expected to be at a higher risk to develop dehiscence release incisions on one or two flanks towards the fascia were found to be useful. Simultaneous ventriculo-peritoneal shunting is also recommended in this cohort of patients, according to our experience. These recommendations neither prolong the time of surgery nor increase the cost, but facilitate a successful closure.     

论高等医学院校普及医院信息系统课程

在我国,医院信息系统已是现代化医院工作的支撑环境。高等医学院校的医院信息系统课程留白,可能削弱医学生临床工作能力和职业适应力。文章阐明了高等医学院校开设医院信息系统专业课的重要性,讨论了教学目标、教学内容;详细介绍了高校与医院合作建立HIS实验室、实地教学和针对专业掌握实际操作技能的教学方法。     

Ultrastructural characteristics of the sporogenesis of genus Myxobolus infecting some Nile fishes in Egypt

This study presents the ultrastructural characteristics of sporogenesis in the genus Myxobolus which infects four economically important Egyptian fishes: Oreochromis niloticus niloticus, Barbus bynni, Labeo niloticus and Hydrocynus forskalii, specimens of which were collected at Giza city. Although the cysts were observed in different organs, the pattern of sporogenesis was the same. Moreover, the sporogenesis found in the present study followed the usual pattern valid for most of the myxosporean genera studied.     

Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant

Missense mutations in the presenilin 2 (PS-2) gene on chromosome 1 were sought by direct nucleotide sequence analysis of the open reading frame of 60 pedigrees with familial Alzheimer's disease (FAD). In the majority of these pedigrees, PS-1 and beta-amyloid precursor protein (beta APP) gene mutations had been excluded. While no additional PS-2 pathogenic mutations were detected, four silent nucleotide substitutions and alternative splicing of nucleotides 1338-1340 (Glu325) were observed. Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years). This variability is not attributable to differences in ApoE genotypes. These results suggest (i) that, in contrast to mutations in PS-1, mutations in PS-2 are a relatively rare cause of FAD; (ii) that other genetic or environmental factor modify the AD phenotype associated with PS-2 mutations; and (iii) that still other FAD susceptibility genes remain to be identified.      

The Kallmann syndrome gene product expressed in COS cells is cleaved on the cell surface to yield a diffusible component

Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia and caused by a defect of migration and targeting of gonadotropin-releasing hormone-secreting neurons and olfactory axons during embryonic development. We previously cloned the gene responsible for the X-linked form of the disease encoding a 680 amino acid protein, KAL, which displays the unusual combination of a protease inhibitor domain with fibronectin type III repeats. Previous expression studies by northern blot and RNA in situ hybridization in human and chick indicated that the gene is expressed at very low levels in the olfactory bulb during development. Therefore, low abundance of the protein has hampered a detailed biochemical characterization. By overexpressing both the human and chick KAL cDNAs in eukaryotic cells, we now provide evidence that KAL is a glycosylated peripheral membrane protein with an apparent molecular weight of approximately 100 kDa. We show that this 100 kDa protein is proteolytically processed on the cell membrane to yield a 45 kDa diffusible component, which is detectable with an antisera against the C-terminal part of the protein and binds tightly to cell surfaces. These data provide a first step toward understanding KAL function in neuronal interactions and neurite extension in the olfactory bulb and suggest that KAL might be a diffusible chemoattractant molecule for olfactory axons.      

Serum luteinizing hormone,follicle-stimulating hormone and oestradiol pattern in women undergoing pituitary suppression with different gonadotrophin-releasing hormone analogue protocols for assisted reproduction

Gonadotrophin-releasing hormone analogues (GnRH-a) are used widely in controlled ovarian stimulation (COS) cycles for assisted reproduction. At present, there is great debate about the influence of exogenous hormone activity on the hypothalamus–pituitary axis following pituitary desensitization. The objective of this comparative study was to investigate the pattern of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestradiol in women undergoing ovarian stimulation with different GnRH-a preparations. We retrospectively analysed 201 women, aged between 27 and 43 years, who were referred consecutively to our infertility clinic between January 2002 and January 2003. All women had no endocrinopathies or occult ovarian failure as assessed by day-3 hormone profile. Women were enrolled in one of the following COS protocols: depot triptorelin long protocol (n?=?38), buserelin long protocol (n?=?101) or buserelin short protocol (n?=?62). Recombinant FSH was used to induce ovulation. Treatment was monitored by transvaginal ultrasound scan and serum measurement of FSH, LH and oestradiol. Among the women initially included, 30 had cancelled cycles due to poor ovarian response. Serum LH levels were significantly higher in the short-protocol group compared with the long-protocol groups (p?<?0.001). The number of follicles, oocyte yield, number of grade-I embryos and fertilization rate were significantly lower in the short-protocol group than in the long-protocol groups. These findings showed that LH concentrations are significantly higher in women undergoing reversible medical hypophysectomy with a GnRH-a short protocol than in women treated with a long protocol. The hypothesis of an LH ceiling is confirmed.     

A homoallelic FECH mutation in a patient with both erythropoietic protoporphyria and palmar keratoderma

Background Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by the deficiency of ferrochelatase (FECH) in the haem biosynthetic pathway. In the majority of families, EPP is transmitted as a pseudodominant trait. Autosomal recessive form of EPP is found in only about 3% of the families. Objectives In this study, we describe a 6‐year‐old boy who suffered from both EPP and palmar keratoderma. Methods and Results A novel homoallelic missense mutation (p.Ser318Tyr) was identified in the FECH gene. In addition, a region of homozygosity of approximately 6.8 Mb was observed in chromosome 18 of the patient by both microsatellite and SNP array. The parents of the patient, both of Palestinian (Jordanian) origin, were heterozygous for the S318Y mutation, although no history of consanguinity was known. Microsatellite genotyping identified a partial haplotype from each parent that corresponds to the region of homozygosity in the patient. Assuming S318Y is a founder mutation, the number of generations separating the two parents from their common ancestor from whom they inherited S318Y was estimated as 21.7 (95% CI 3.42–69.7). Conclusion EPP was therefore inherited as an autosomal recessive trait in the family. This study confirms the association between palmar keratoderma and autosomal recessive EPP.     

Bacteria etiological agents causing respiratory tract infections in children and their resistance patterns to a panel of ten antibiotics

ObjectiveTo study the bacteria etiological agents of respiratory tract infection among 280 school children in South East Nigeria, and to determine their antimicrobial resistance patterns to a panel of ten antibiotics.MethodsThroat swabs (280) were collected from students in four boarding schools located in Enugu and Onitsha metropolis. Standard microbiological procedures were used to screen these swabs to determine the prevalence of respiratory pathogens while the disc diffusion test was used to determine the antimicrobial resistance patterns of the recovered isolates.ResultsOf the 280 samples screened, 57.1% were positive. Haemophilus influenzae was the most prevalent (16.1%), followed by Streptococcus pyogenes (13.9%), Klebsiella pneumoniae (12.5%), Streptococcus pneumoniae (6.8%), Staphylococcus aureus (5.4%) and Corynebacterium diphtheriae (2.5%). More isolates were recovered in the two male schools investigated. However, there was no significant difference in the overall prevalence of isolates according to sex or school location of the subjects. Greater number of isolates (56%) was recovered from those aged 11–14 years. This was statistically significant (P<0.05), compared to the other two age groups (15–18 years and 19–23 years). The pattern of resistance varied according to the bacteria species. There were multi-resistant isolates. Since these students stand the risk of contracting respiratory tract infection particularly from reservoirs among them, there is need to increase surveillance and develop better strategies to curb the increasing prevalence of respiratory tract infection in this and other similar regions of Africa.ConclusionsThe spectrum of bacteria causing respiratory tract infection is still wide in Nigeria. Many isolates showed appreciable levels of antibiotic resistance apparently due to antibiotic abuse. Development of new strategies to curb this increasing prevalence of respiratory tract infection is warranted.     

Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients

Aspartyglucosaminuria (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases. An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation. These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine. Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation. Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermates. However, in the Morris water maze test, a slow worsening of performance could be seen with age. The phenotype mimics well AGU in humans, the patients characteristically showing only slowly progressive mental retardation and relatively mild skeletal abnormalities.