Magnetic resonance studies on brain dysfunction induced by organic solvents.

A 38-year-old layer of parquet flooring was referred because of memory impairment, tiredness and diffuse headaches. His work involved using several neurotoxic organic solvents. Extensive laboratory, neuropsychological, clinical neurophysiological, neuroadiological, magnetic resonance (MR) imaging and spectroscopy studies were performed. The neuropsychological and behavioural assessments showed an organic brain syndrome. MR imaging and CT scanning of the brain revealed enlarged ventricles and generalized atrophy. 31P and 1H MR spectroscopic measurements did not show any abnormalities. Owing to recent improvements regarding sensitivity and facilitated assignment, MR spectroscopy may provide in the near future significant additional information on brain metabolism in patients with brain dysfunction presumably induced by organic solvents.     

Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer

AIM: To investigate whether multiparameter flow cytometry (MP-FCM) can be used for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast cancer. METHODS: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n = 238) from 98 patients were analysed. For each lymph node, sections for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for cytokeratin (MNF116) were cut at three levels with a distance of 500 microm. The intervening material was used for MP-FCM. Cells were immunostained with MNF116, followed by an incubation with fluorescein isothiocyanate (FITC) labelled goat antimouse immunoglobulin. DNA was stained using propidium iodide. From each lymph node 100,000 cells were analysed on the flow cytometer. RESULTS: Thirty eight of the 98 patients with breast carcinoma showed evidence of metastatic disease in the SLN by one ore more of the three methods. In 37 of 38 cases where metastatic cells were seen in the routine H&E and/or IHC, more than 1% cytokeratin positive cells were detected by MP-FCM. In 24 patients, metastatic foci were more than 2 mm (macrometastasis) and in 14 these foci were smaller than 2 mm (micrometastasis). In three of these 14 cases, MP-FCM revealed positive SLNs, although this was not seen at first glance in the H&E or IHC sections. After revision of the slides, one of these three remained negative. However, MP-FCM analysis of the cytokeratin positive cells showed an aneuploid DNA peak, which was almost identical to that of the primary breast tumour. Duplicate measurements, done in 41 cases, showed a 99% reproducibility. In five of 14 patients with micrometastasis, one or two metastatic foci were found in the non-SLN. However, in 15 of 24 macrometastases multiple non-SLNs were found to have metastatic tumour. All micrometastases except for the remaining negative one mentioned above showed only diploid tumour cells, despite the fact that their primary tumours contained both diploid and aneuploid tumour cells. In primary tumours with more than 60% aneuploid cells, predominantly aneuploid macrometastasis were found, whereas diploid primary tumours only showed diploid micrometastases or macrometastases in their SLN. Aneuploid SLN macrometastases were associated with non-SLN metastases in five of seven patients, whereas diploid cases showed additional non-SLN metastases in only seven of 16 patients. CONCLUSION: In all cases, MP-FCM was sufficient to detect micrometastatic tumour cells in a large volume of lymph node tissue from SLNs. In some cases it was superior to H&E and IHC staining. Approximately 30% of SLN micrometastases are accompanied by additional non-SLN metastases. The size of the aneuploid fraction (> 60%) in the primary tumour may influence the risk of having both SLN and non-SLN metastases.     

Renal expression of endothelial and inducible nitric oxide synthase, and formation of peroxynitrite-modified proteins and reactive oxygen species in Wegener's granulomatosis

To investigate the role of nitric oxide (NO) in glomerular inflammation, the expression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was studied in conjunction with inflammatory cell influx, H2O2 production, and the formation of nitrotyrosines in renal biopsies from patients with Wegener's granulomatosis (WG). Renal cryostat sections from patients with WG (n=15) were stained by immunohistochemistry for eNOS, iNOS, endothelial cells (CD31), nitrotyrosines, polymorphonuclear cells (PMNs, CD15), and monocytes/macrophages (CD14, CD68). Production of H2O2 was identified by enzyme cytochemistry using diaminobenzidine. In control tissues, strong staining for eNOS was found in glomerular and interstitial tubular capillaries and cortical vessels. A significant reduction in eNOS expression was found in WG biopsies, which was associated with a reduction in CD31 expression. Expression of iNOS was found in infiltrating inflammatory cells, mainly located in the interstitium. H2O2-producing cells were detected in glomeruli and were abundantly present in the interstitium. Nitrotyrosine-positive cells, however, were almost exclusively found in the interstitium. It is concluded that renal inflammation in WG is associated with the induction of iNOS in inflammatory cells and the formation of nitrotyrosines. Expression of eNOS in glomerular capillaries is lost, most likely due to endothelial cell damage. These results suggest that decreased NO production by endothelial cells, in conjunction with increased NO production by iNOS-positive inflammatory cells, is involved in renal tissue injury in WG.     

Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation

In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere.     

Income differences in persons seeking outpatient treatment for mental disorders: a comparison of the United States with Ontario and The Netherlands

BACKGROUND: Variations in the relationships among income, use of mental health services, and sector of care are examined by comparing data from 3 countries that differ in the organization and financing of mental health services. METHODS: Data come from the 1990-1992 National Comorbidity Survey (n = 5,384), the 1990-1991 Mental Health Supplement to the Ontario Health Survey (n = 6,321), and the 1996 Netherlands Mental Health Survey and Incidence Study (n = 6031). Analysis of the association between income and use of mental health services was carried out for the population that was between ages 18 and 54 years. Differential use of mental health treatment was examined in 3 sectors: the general medical sector, the specialty sector, and the human services sector. RESULTS: No significant association between income and probability of any mental health treatment was observed for persons with psychiatric disorders in any of the 3 countries. However, there were significant differences among countries in the association between income and sector of mental health care treatment. In the United States, income is positively related to treatment being received in the specialty sector and negatively related to treatment being received in the human services sector. In the Netherlands, patients in the middle-income bracket are less likely to receive specialty care, while those in the high-income bracket are less likely to be seen in the human service sector. Income is unrelated to the sector of care for patients in Ontario. CONCLUSIONS: Future research should examine whether differential access to the specialty sector for low-income people in the United States is associated with worse mental health outcomes.     

Presence of active MRI lesions in patients suspected of non-radiographic axial spondyloarthritis with high disease activity and chance at conversion after a 6-month follow-up period

Clinical Rheumatology - The primary aim is to evaluate signs of inflammation on MRI of sacroiliac joints (SIJ)/spine in inflammatory back pain (IBP) patients suspected of nr-axSpA with high disease...     

Systemic bevacizumab to facilitate anticoagulation in antiphospholipid syndrome and bleeding gastrointestinal angiodysplasia

Journal of Thrombosis and Thrombolysis - Bleeding gastrointestinal angiodysplasia may occur in patients with vasculitis and can be challenging to treat. We describe the novel use of bevacizumab...