Mediastinal and hilar fibrosis

A case is described of mediastinal and hilar fibrosis in a woman aged 22 years. The fibrotic mass compressed the lobar arteries as well as the veins of various lobes of both lungs. These large vessels as well as numerous smaller arteries and veins were to a large extent obstructed by organized thrombi. It seems likely that 3 years after the beginning of symptoms the fibrosing process was still active. The case provides some support for an immunopathological aetiology of this condition.     

Validation of two survey diagnostic interviews among primary care attendees: a comparison of CIS-R and CIDI with SCAN ICD-10 diagnostic categories

BACKGROUND: The most widely used survey measures in psychiatry, the Composite International Diagnostic Interview (CIDI) and the Clinical Interview Schedule-Revised (CIS-R) have generated estimates of psychiatric morbidity that show considerable variation. Doubts have been raised regarding the validity of these structured lay interviewer assessments. There have been no direct comparisons of the performances of these instruments against a common, established criterion. METHOD: A total of 105 unselected primary care attendees were each interviewed with CIDI, CIS-R and SCAN in a single sitting with random order of administration. SCAN was administered by a SCAN trained psychiatrist, and CIDI and CIS-R by a public health doctor. Concordance was estimated for all ICD-10 neurotic disorders. We assessed the overall discriminability of the CIS-R morbidity scale using a receiver operating characteristic (ROC) analysis. RESULTS: The concordance for CIDI for ICD-10 diagnoses was moderate to excellent (kappa= 0.58-0.97). Concordance for CIS-R ranged between poor and moderate (kappa = 0.10-0.65). The area under the ROC curve for the CIS-R morbidity scale with respect to any ICD-10 disorder [0.87 (95% CI 0.79-0-95)] indicated good overall discriminability, but poor sensitivity (44%) and high specificity (97%) at the usual CIS-R cut-point of 11/12. CONCLUSION: Among primary care attendees the CIDI is a highly valid assessment of common mental disorders, and the CIS-R is moderately valid. Previous studies may have underestimated validity. Against the criteria of all ICD-10 diagnoses (including less severe depressive and anxiety disorders) a much lower CIS-R cut-point is required than that which is usually advocated.     

Is there a contradiction between telemedicine and business?

Is there a contradiction between telemedicine and business? The driving forces in the telemedicine market are: competition within the health-care industry, newly developed cheap information technology (especially the Internet) and 21st-century health-care consumers, with their expectations of free choice and a high level of health-care. The market has four segments (citizens, patients, professionals and employees) and the boundaries between these segments are blurred. The telemedicine market is obviously growing, but it is still unstructured, fractured and disorganized. The telemedicine market needs a meeting place where the status of telemedicine and telecare can be reviewed. This would be a place in which to explore new ways to improve the efficiency of health-care services and a forum in which to draw a roadmap for future developments. One such place is the International Trade Event and Conference for eHealth, Telemedicine and Health ICT, Med-e-Tel. At the 2004 event, there were 32 exhibitors from 23 countries and over 400 industry and medical participants. A survey of participants showed that the event was judged to be a success. There is no conflict between telemedicine and business. On the contrary, telemedicine is a promising area of business development.     

Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families

Germline mutations in succinate dehydrogenase subunits B, C and D (SDHB, SDHC and SDHD), genes encoding subunits of mitochondrial complex II, cause hereditary paragangliomas and phaeochromocytomas. In SDHB (1p36)- and SDHC (1q21)-linked families, disease inheritance is autosomal dominant. In SDHD (11q23)-linked families, the disease phenotype is expressed only upon paternal transmission of the mutation, consistent with maternal imprinting. However, SDHD shows biallelic expression in brain, kidney and lymphoid tissues (Baysal et al., 2000). Moreover, consistent loss of the wild-type (wt) maternal allele in SDHD-linked tumours suggests expression of the maternal SDHD allele in normal paraganglia. Here we demonstrate exclusive loss of the entire maternal chromosome 11 in SDHD-linked paragangliomas and phaeochromocytomas, suggesting that combined loss of the wt SDHD allele and maternal 11p region is essential for tumorigenesis. We hypothesize that this is driven by selective loss of one or more imprinted genes in the 11p15 region. In paternally, but not in maternally derived SDHD mutation carriers, this can be achieved by a single event, that is, non-disjunctional loss of the maternal chromosome 11. Thus, the exclusive paternal transmission of the disease can be explained by a somatic genetic mechanism targeting both the SDHD gene on 11q23 and a paternally imprinted gene on 11p15.5, rather than imprinting of SDHD.     

A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with increased bilirubin and HDL levels but not with coronary artery disease

Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous anti-oxidant bilirubin which exerts beneficial effects against arteriosclerosis. A (GT) repeat polymorphism in the HO-1 promoter region modulates HO-1 expression in response to oxidative stress. Recently, this polymorphism has been reported to protect from coronary artery disease in Orientals. We intended to confirm this observation in Caucasians. We studied 649 individuals with myocardial infarction (n=258), stable coronary artery disease (n=180) and controls without coronary artery disease (n=211). Carriers of short alleles (<25 repeats) had higher bilirubin levels (median 0.66 mg/dL, IQR 0.49 to 0.91) compared to non-carriers (median 0.61 mg/dL, IQR 0.45 to 0.82; p=0.03) and a more favourable lipid profile (HDL median 47 mg/dL, IQR 40 to 50 vs. median 45, IQR 37 to 55, p=0.01; triglycerides median 118 mg/dL, IQR 87 to 174 vs. median 132, IQR 97 to 191, p=0.03). However, no significant differences of the genotype distribution were observed between the three groups in this Caucasian study population (p=0.94). Although potentially beneficial effects of the short HO-1 allele on lipid profile and serum bilirubin were observed, in contrast to Orientals, the HO-1 genotype was not associated with coronary artery disease in Caucasians.     

Beta2-microglobulin aberrations in diffuse large B-cell lymphoma of the testis and the central nervous system

Human leukocyte antigen (HLA) class I molecules are expressed on the surface of all nucleated cells and present antigenic peptides to cytotoxic T cells, thereby playing an important role in initiating the cellular anti-tumor immune response. We previously reported that loss of HLA class I expression in diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) and the testis is a common event. Loss of expression and mutations of the light chain of the HLA class I molecule, beta(2)-microglobulin (beta(2)m) have been described in a variety of human tumors and cell lines. In our study, we screened 15 DLBCL cases with a combined loss of HLA class I and beta(2)m expression for mutations in the latter gene by direct sequencing. Frame shift mutations in repetitive sequences within the beta(2)m gene leading to loss of functional beta(2)m were detected in 2 cases. Loss of heterozygosity (LOH) and fluorescent in situ hybridization (FISH) analysis for chromosome 15 exhibited loss of the remaining copy of the beta(2)m gene in both cases but also hemizygous deletions and monosomies in 6 additional cases. Since similar mutations in the beta(2)m gene have been associated with microsatellite instability (MSI), we used 8 markers to study MSI involvement in DLBCL. Low MSI was more frequent (33%) as compared to nodal DLBCL (n=15) but did not correlate with the beta(2)m mutations. Our data indicate that multiple mechanisms lead to downregulation of beta(2)m and concomitant loss of HLA class I expression in DLBCL.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.