S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing

Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.     

Prevalence of mitochondrial DNA mutations in childhood/congenital onset non-syndromal sensorineural hearing impairment

Genetic factors are the major causes of childhood hearing impairment. Whereas autosomal recessive mutations account for the majority of prelingual non-syndromic sensorineural hearing impairment (NSSHI), the relative contribution of mitochondrial DNA (mtDNA) mutations to childhood onset NSSHI has not been established.
We screened 202 subjects with congenital/childhood onset NSSHI, consisting of 110 sporadic cases, 75 sib pairs, and 17 families with affected subjects in more than one generation, in order to determine the prevalence of mtDNA mutations associated with NSSHI.
mtDNA mutations were found in three of 10 families (30%) in whom the affected members were related through the maternal lineage. One sporadic case (0.9%) was also found to have a known mtDNA mutation but none was found in the sib pairs.
Although the prevalence of mtDNA mutations was low in the group as a whole (2%), we suggest that screening should be considered in cases of childhood hearing impairment when it is progressive and particularly in families where transmission is compatible with maternal inheritance.


Keywords: mitochondrial DNA; point mutation; hearing impairment     

双能量X线骨质密度测量仪监测小儿下肢骨延长骨矿物质的变化

目的　在儿童骨延长的患儿中 ,为了能够有效地控制骨延长的速率 ,达到骨延长的目的 ,采用双能量X线骨质密度测量仪 (dualenergyX Rayabsorptiometry ,DEXA)监测延长断端骨矿含量 (bonemineralcontent,BMC)的变化。方法　 30例患儿中有 5 0处下肢作了骨延长术 ,平均年龄10 .9岁 (5～ 17岁 ) ,引起短肢的病因不同。术后 7～ 10d开始行骨延长 ,每次延长 0 .2 5mm ,每天 4次。牵引延长期间每周扫描一次 ,拆除外固定器后每 2周扫描一次到术后 2年。DEXA扫描的分辨率是 1mm× 1mm ,扫描速度 30mm/s。比较不同延长时期中骨矿含量的变化。分析不同病因和不同外固定器之间骨矿含量变化的差别。结果　不同固定器之间骨矿含量的差别无著性意义。根据骨延长区BMC增加速率 ,将患儿分为快速组、一般组和慢速组。快速组每日BMC增加速率为 0 .3%～ 0 .6 % ,新骨生长快速 ;一般组每日BMC增加 0 .1%～ 0 .3% ,新骨中速生长 ;慢速组每日增加 <0 .1% ,新骨生成缓慢。骨矿化速率与原发病因相关。结论　DEXA能动态监测骨延长中新生骨的骨矿含量的变化 ,根据骨矿含量变化的程度 ,能够调整骨延长的速率 ,从而达到预期骨延长的目的。     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Little girl who conquered the "ALPPS’’

An insufficient future liver remnant(FLR)is associated with post-hepatectomy liver failure.Associating liver partition and portal vein ligation for stage hepatectomy(ALPPS)has been shown to be effective for the induction of rapid FLR hypertrophy so as to improve the resectability in patients with insufficient FLR.We hereby report our experience of this novel approach for a 6-year-old patient with hepatoblastoma.Computed tomography showed a hepatoblastoma measuring12.5 cm×9.9 cm×11.7 cm in the right liver(Couinaud segmentⅣ,ⅤandⅧ).Volumetric assessment of the FLR i.e.,left lateral section was 112.6 mL i.e.,21.2%of the estimated total liver volume.In view of the small-for-size FLR,ALPPS was contemplated.An anterior approach was adopted for the in-situ parenchymal split without mobilisation of the right liver.FLR volumetry on the seventh postoperative day was 160.7 mL,which represented a 46.1%gain in volume,and a FLR/ESLV ratio of 30.2%.A right trisectionectomy was performed on the eighth postoperative day.Postoperative recovery was uneventful.Patient was discharged on day 16 after the first operation.To our knowledge,this was the first report that showed the applicability of ALPPS to a paediatric patient.     

Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma

Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites.