Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

Indoor nitrogen dioxide and childhood respiratory illness

Abstract: Nitrogen dioxide is produced from the combustion of fossil fuels and as an emission from gas-fired appliances, and is also a component of tobacco smoke. Nitrogen dioxide has been shown in experimental animals to be toxic to the respiratory tract. A number of recent studies have suggested that children exposed to significant levels of nitrogen dioxide in the home may be more susceptible to respiratory illness than children exposed to normal ambient levels. Respiratory illness is a major cause of morbidity in children everywhere. Here, we review the available evidence of this association and explore methodological issues in measurement of nitrogen dioxide exposure— misclassification of subjects, symptom bias and confounding. It has recently been shown that some New South Wales school rooms, where unflued gas heaters are often used as a source of warmth, have nitrogen dioxide levels which are above recommended ambient levels for outside air. This has underlined the need for setting standards for indoor levels of various pollutants, and cohort studies are suggested, to include personal monitoring and prospective data collection techniques.     

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.     

Presence of the cfxA gene in Bacteroides distasonis

In this study we investigated the presence of the cfxA gene (encoding a class A beta-lactamase) in 73 strains of the Bacteroides fragilis group belonging to the species B. distasonis (34), B. vulgatus (14), B. thetaiotaomicron (8), B. merdae (6), B. caccae (9) and B. ovatus (2) isolated from human intestinal microflora of healthy children and adults. Employing specific primers to the cfxA gene, a 312-bp amplified fragment was obtained in 2 strains of B. vulgatus and 9 strains, the majority from children, of B. distasonis. The expression of this enzyme was analysed by determining the MICs to cefoxitin and cefotaxime and values varied from 2 to >256 microg/ml of both cefoxitin and cefotaxime. Sequence analysis of the amplicons corresponding to the cfxA gene from B. distasonis and B. vulgatus revealed identical sequences between these isolates and high similarity with other beta-lactamase genes of anaerobes such as cfxA of B. vulgatus (99%) and cfxA2 of Prevotella intermedia (99%), both sequences of which deposited in Genbank under accession numbers U38243 and AF118110, respectively. However, a fragment obtained from a B. distasonis strain (EC17-4) showed a unique RFLP profile and 87% nucleotide similarity with cfxA and cfxA2 genes. These results seem to suggest a dissemination of these resistance determinants among Bacteroides species.     

Loss of lamin A/C expression revealed by immuno-electron microscopy in dilated cardiomyopathy with atrioventricular block caused by<Emphasis Type="Italic"> LMNA</Emphasis> gene defects

Mutations of the LMNA gene encoding the lamin A and C nuclear envelope proteins cause an autosomal dominant form of dilated cardiomyopathy (DCM) with atrioventricular block (AVB). The aim of this study was to investigate ultrastructural nuclear membrane changes by conventional electron microscopy and protein expression by immuno-electron microscopy in the heart of patients with DCM and AVB due to LMNA gene mutations. Four immunohistochemical techniques were used: pre-embedding and post-embedding in Epon-Araldite resin and London Resin White (LRW), with and without silver enhancement. Parallel light microscopy immunohistochemistry studies were performed. Conventional electron microscopy showed a loss of integrity of the myocyte nuclei with blebs of the nuclear membrane, herniations and delamination of the nuclear lamina and nuclear pore clustering. Post-embedding LRW was the most informative technique for morphology and immuno-labelling. Immuno-labelling was almost absent in the nuclear envelope of patients with LMNA gene mutations, but intensely present in controls. The loss of labelling selectively affected myocyte nuclei; the endothelial cell nuclei were immunostained in patients and controls. Light immunohistochemistry confirmed the results. These findings confirm the hypothesis that LMNA gene defects are associated with a loss of protein expression in the selective compartment of non-cycling myocyte nuclei.     

Industry, air quality, cigarette smoke and rates of respiratory illness in Port Adelaide

OBJECTIVES: To examine the prevalence of self-reported asthma, bronchitis/emphysema, wheezing, night cough and smoking in Port Adelaide; to explore the relationship of the disorders to the presence of industry, tobacco smoke, indoor appliances and air quality. METHODS: Prevalence data from a 1995 survey of Port Adelaide residents were compared with data from the 1995 National Health Survey and the 1995 South Australian Health Omnibus Survey. These data were then compared across three geographic areas in Port Adelaide, one being highly industrialised. Their relation to tobacco smoke and the presence of unflued gas appliances were examined. Finally, outdoor gaseous air pollutants were examined across the three areas. RESULTS: Males in Port Adelaide had higher rates of asthma and bronchitis/emphysema than nationally. Asthma was significantly higher for children aged 5-14 years and for adults aged 25-44 years. Bronchitis/emphysema was significantly higher for males aged 25-64. The highly industrial area had a higher rate of asthma (OR 1.85, 95% CI 1.07-3.22) in males that appeared unrelated to smoking or ambient gaseous pollutants. Smoking in Port Adelaide was significantly higher than in the general population, and was significantly associated with wheeze, night cough and bronchitis/emphysema. The presence of unflued gas heaters at home was significantly associated with asthma prevalence in males (OR 3.27, 95% CI 1.40-7.64). CONCLUSIONS: Respiratory disease appeared to be independently related to an area of high industry, smoking and presence of unflued gas appliances in Port Adelaide.     

The effect of antibiotic resistance on the outcome of three 1-week triple therapies against Helicobacter pylori

BACKGROUND: Resistance of Helicobacter pylori to antibiotics may be a major reason for treatment failure. AIM: To evaluate the effect of primary H. pylori resistance to antibiotics on the cure rates of three anti-H. pylori 1-week triple therapies. METHODS: One hundred and sixteen consecutive patients diagnosed H. pylori-positive by gastric histology, rapid urease test and culture were enrolled. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for 7 days with: (i) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and metronidazole 250 mg q.d.s. (PAM); (ii) pantoprazole 40 mg o.d. plus clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s. (PCM); or (iii) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (PAC). Two months after completion of therapy, endoscopy and gastric biopsies were repeated. RESULTS: Primary resistance rates to metronidazole, clarithromycin and amoxycillin were 17.2, 6.9 and 0%, respectively. Overall H. pylori cure rates expressed as intention-to-treat and per protocol analyses were, respectively, 79% and 86% with PAM, 82% and 89% with PCM, and 85% and 85% with PAC. Significantly lower cure rates were observed in metronidazole-resistant patients treated with PAM (56% vs. 96%, P = 0.01) or PCM (50% vs. 97%, P = 0.01). A trend towards lower H. pylori cure rates was observed in clarithromycin-resistant patients treated with PCM (67% vs. 91%, P = 0.74) or PAC (50% vs. 87%, P = 0.68). CONCLUSION: Primary resistance to metronidazole influences the H. pylori cure rate of anti-H. pylori proton pump inhibitor-based triple therapies which include this antibiotic. A similar trend exists for primary clarithromycin resistance.