Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Mutation and protein expression of p53 in acquired immunodeficiency syndrome-related lymphomas

p53 mutations are found in a variety of neoplasia. B-immunoblastic lymphoma (BIBL) is a rapidly progressive, aggressive lymphoma. As patients with acquired immunodeficiency syndrome (AIDS) live longer, BIBL is becoming an increasing problem. We asked three questions in our study. What is the frequency of p53 mutations in BIBL? Is it more frequent in patients with AIDS? Can immunohistochemical staining of lymph nodes for expression of p53 substitute for mutational analysis of p53 to detect lymphomas with mutated p53? Exons 5, 6, 7, 8 of the p53 gene (hot-spots for mutations) were amplified and examined for mutations by single-strand conformation polymorphism (SSCP) analysis. Altered migration was observed in 7 of 52 BIBL samples. Of these, 4 of 25 were from individuals infected with human immunodeficiency virus (HIV) and 3 of 27 were not infected with HIV. Direct sequencing of amplified material confirmed the presence of mutations in exons 5, 7, 8 of p53. A total of 26 BIBL as well as other lymphoma/leukemia samples, stained strongly by immunohistochemistry with three antibodies directed against human p53. Five of 6 BIBL samples with p53 mutations stained strongly for p53, but 20 lymphoma samples with no detectable p53 mutations also stained strongly for p53. Of note, however, 10 hyperplastic, nonmalignant lymph nodes from individuals either infected or not infected with HIV had negligible staining for p53 protein. In conclusion, p53 mutations occur in about 14% BIBL samples; the frequency of p53 mutations in BIBL in individuals with and without AIDS was similar. Positive p53 immunohistochemistry did not correlate with detectable p53 mutations in the same tissue, but positive immunohistochemical staining for p53 was only found in neoplastic lymph nodes. This latter finding provides a strong warning that p53 immunochemistry with available reagents cannot be used to determine which tumors have mutations of p53.     

Clinical analysis of thoracic ossified ligamentum flavum without ventral compressive lesion

The aim of this study was to analyze the clinical characteristics of thoracic ossified ligamentum flavum (OLF) and to elucidate prognostic factors as well as effective surgical treatment modality. The authors analyzed 106 thoracic OLF cases retrospectively from January 1999 to December 2008. The operative (n = 40) and the non-operative group (n = 66) were diagnosed by magnetic resonance imaging (MRI) and/or computed tomography (CT) imaging. We excluded cases exhibiting ventral compressive lesions causing subarachnoid space effacement in thoracic vertebrae as well as those with a coexisting cervical compressive myelopathy. Those in the operative group were treated with decompressive laminectomy as well as resection of OLF. The preoperative neurologic status and postoperative outcomes of patients, as indicated by their modified Japanese Orthopedic Association (mJOA) scores and recovery rate (RR), Modic changes, the axial (fused or non-fused) and sagittal (omega or beak) configurations of OLF, and the ratios of the cross-sectional area (CSA) and anteroposterior diameter (APD) of the most compressed level were studied. The most commonly affected segment was the T10–11 vertebral body level (n = 49, 27.1%) and the least affected segment was the T7–8 level (n = 1, 0.6%). The ratios of the CSA in non-fused and fused types were 77.3 and 59.3% (p < 0.001). When Modic changes were present with OLF, initial mJOA score was found to be significantly lower than those without Modic change (7.62 vs. 9.09, p = 0.033). Neurological status improved after decompressive laminectomy without fusion (preoperative vs. last mJOA; 7.1 ± 2.01 vs. 8.57 ± 1.91, p < 0.001). However, one patient exhibited transient deterioration of her neurological status after surgery. In the axial configuration, fused-type OLF revealed a significant risk for a decreased postoperative mJOA score (0–7, severe and moderate) (Odds ratio: 5.54, χ² = 4.41, p = 0.036, 95% CI: 1.014–30.256). The results indicated that the new categorization of axial-type of OLF is a helpful predictor of postoperative patient outcome and fused type was related with poor prognosis. In OLF cases free from ventral lesions compressing the spinal cord, decompressive laminectomy is enough for successful surgical outcome. Therefore, early surgical treatment will be considered in cases with fused-type OLF compressing spinal cord even though they do not have myelopathic symptoms.     

CGA-7 and HHF, two monoclonal antibodies that recognize muscle actin and react with adherent cells in human long-term bone marrow cultures

The CGA-7, a monoclonal antibody that reacts with smooth muscle cell actin but not with endothelial cell or fibroblast actin, and HHF, a monoclonal antibody that reacts with smooth muscle, skeletal muscle, and cardiac muscle actin, both recognize microfilaments present within adherent cells from actively hematopoietic human long-term marrow cultures. Macrophages, monocytes, and cultured marrow fibroblasts do not react with either antibody. These data suggest that the anti-actin antibodies may serve as useful markers for in vitro microenvironmental cells and lend support to the hypothesis that stromal cells from long- term marrow cultures are different from marrow fibroblasts and may constitute a unique cell lineage.     

Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23)

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo- controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase- type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.     

体外膜肺氧合技术支持治疗期间患者血乳酸浓度及其预后

目的:探讨体外膜肺氧合支持治疗患者血乳酸浓度的变化和预后。方法:于2004-12/2006-09在中国医学科学院阜外心血管病医院因脱离体外循环困难的心脏外科术后患者、扩张性心肌病和冠状动脉粥样硬化性心脏病发生心源性休克的患者共40例进行了体外膜肺氧合支持治疗,按年龄和存活预后分为4组:成人存活组、成人死亡组、儿童存活组、儿童死亡组。分析4组的治疗效果,分别抽取各组患者体外膜肺氧合建立时、体外膜肺氧合运转6h、运转中间时点、停机前6h、停机时的血乳酸浓度。结果:①体外膜肺氧合支持治疗患者40例,成人组26例,20例脱机,16例生存,10例死亡,脱机率76.9%,生存率61.5%;儿童组14例,7例脱机,5例生存,9例死亡,脱机率50.0%,生存率35.0%。②成人或儿童存活组的乳酸浓度都与死亡组有明显差别,存活组血乳酸浓度明显低于死亡组,其中建立和运转6h、中间时点的差异有显著性意义(P<0.05),其余2个时点的差异有非常显著性意义(P<0.001)。组内与建立时比较,中间时点、停止前6h、停止时差异均有显著性意义(P<0.001),血乳酸浓度逐渐降低。结论:经体外膜肺氧合支持治疗的患者,血乳酸浓度明显下降,脱机时血乳酸仍高的患者预后不良。