Does Meningitis Stop CSF Rhinorrhea following Lateral Skull Base Surgery?

In cases of cerebrospinal fluid (CSF) rhinorrhea following lateral skull base surgery, fibrosis and fibrin formation resulting from meningitis has been postulated as a mechanism of spontaneously resolving the CSF leak. This study was undertaken to explore any possible relationship between the cessation of CSF leak and meningitis. A retrospective study at a tertiary referral center of 232 consecutive patients was performed. Out of a total of 232 procedures, 29 patients developed CSF rhinorrhea, of whom 7 subsequently developed meningitis. Bacteria were isolated in CSF obtained at lumbar puncture in 5 cases, with the CSF analysis in the remaining 2 cases suggesting aseptic meningitis. Conservative treatment failed to stop the CSF rhinorrhea in 6 of 7 cases. In this study, the development of meningitis did not appear to aid in the resolution of the CSF rhinorrhea. We conclude that surgical intervention should not be delayed in the expectation that meningitis and conservative interventions may promote CSF leak resolution.     

Inhibition of human benzylamine oxidase (BzAO) by analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

A sensitive assay for human plasma BzAO, involving the conversion of 14C-benzylamine to 14C-benzaldehyde, was developed. MPTP and several of its analogues were found to be competitive inhibitors of the enzyme. Ki values for the MPTP analogues in the presence of human plasma BzAO were determined. The analogues had a different rank order of inhibition of human plasma BzAO compared with the rank order of inhibition of bovine plasma BzAO found previously. MPTP and 1-methyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP), which are potent nigrostriatal toxins, were weak inhibitors of human plasma BzAO.     

Otogenic Fusobacterium necrophorum meningitis

A case of meningitis secondary to acute suppurative otitis media in a previously healthy child is reported. The only organism isolated from blood after aerobic and prolonged anaerobic culture was identified as Fusobacterium necrophorum. Complete recovery followed treatment with surgery and prolonged antibiotic therapy. The role of anaerobes in the development of meningitis, the isolation and identification of Fusobacterium necrophorum, the clinical presentations of F. necrophorum infection and the choice of antibiotics in the treatment of these infections are discussed.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Membrane transferrin receptor (TfR) and nuclear proliferation-associated Ki-67 expression in hemopoietic malignancies

The expression of membrane transferrin receptors (TfRs), as defined by monoclonal antibody OKT9, and the nuclear proliferation-associated antigen Ki-67 were examined in 159 cases of hematological malignancy. Of the "chronic" B and T cell leukemias studied (n = 85), 61% showed less than 5% OKT9-positive cells and only 7% of cases were TfR+ (defined as greater than 20% positive cells). For comparison, the acute leukemias (n = 62) showed higher (p less than 0.001) TfR expression with 39% TfR+ cases, although there was considerable variation within diagnostic subgroups. Nuclear Ki-67 expression was generally insignificant (less than 1%) in chronic leukemias (78 of 88 cases), although two of eight B cell-type prolymphocytic leukemia and four of four cases of plasma cell leukemia showed greater than 10% Ki-67+ components. In contrast, 47% (31 of 66) acute leukemias had greater than 10% Ki-67+ cells, although there appeared to be no relationship between Ki-67 expression and leukemic type. Combined assessments of TfR and Ki-67 expression revealed a Ki-67- TfR- phenotype in 82% of chronic leukemias, compared with 28% of acute type, and a Ki-67+ TfR+ pattern was found in 27% of acute proliferations but not in any case of chronic leukemia. The determination of membrane TfR expression appears to have little value in the diagnostic differentiation of leukemias, whereas Ki-67 is considered to be a useful supplementary investigation in defining high grade tumors, in the recognition of prognostically poor cases of otherwise well defined low grade malignancy, and of potential value in resolving discrepancies between morphological and immunophenotypic features in leukemias of "intermediate" type.     

The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2

Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.     

Counselling dilemmas associated with the molecular characterisation of two Angelman syndrome families.

We report the molecular characterisation of two families with Angelman syndrome referred for prenatal diagnosis, in which atypical molecular findings resulted in counselling dilemmas. The first is a familial case of Angelman syndrome in which the two affected children have mutations which affect the imprinting mechanism, as shown by the presence of paternal DNA methylation patterns at D15S63 and SNRPN and biparental inheritance of 15q11-q13 markers. DNA prepared from a 21 week fetal blood sample detected a fetus with normal maternal and paternal DNA methylation patterns at D15S63, but inheritance of the same maternal chromosome 15q11-q13 as the two affected sibs. This is probably a result of germline mosaicism in the mother. The second is a case of Angelman syndrome with an atypical deletion of 15q11-q13, which involves both unusual proximal and distal breakpoints. The deletion was characterised in order to assess the risk of Angelman syndrome in a second pregnancy in the mother of this child.     

Diagnostic issues in a family with late onset type 2 neurofibromatosis.

We report a family with type 2 neurofibromatosis and late onset tumours. Five members of this family have developed hearing loss late in life, two of whom have only been shown to have the diagnosis in their seventies, and three other obligate gene carriers died undiagnosed at 64, 72, and 78 years of age. A missense mutation at the C-terminal end of the NF2 protein has been identified in this family and segregates with disease. The use of highly polymorphic markers for predictive testing is also shown. There appears to be an autosomal dominant form of spinocerebellar degeneration which is segregating separately to NF2 in this family, which created a diagnostic dilemma.