Clinical features and genetic analysis of a new form of spinocerebellar ataxia

BACKGROUND: The autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of disorders. The mutations for SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA-12 are identified and caused by an expansion of a CAG or a CTG repeat sequence of these genes. Six additional loci for SCA4, SCA5, SCA-10, SCA-11, SCA-13, and SCA-14 are mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic etiologies of at least 20% of ADCA have yet to be elucidated. METHODS: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant phenotype for SCA. Direct mutation analysis, repeat expansion detection analysis, and linkage analysis for all known SCA loci were performed. RESULTS: Direct mutational analysis excluded SCA1, 2, 3, 6, 7, 8, and 12; genetic linkage analysis excluded SCA4, 5,10, 11, 13, and 14, giving significant negative lod scores. Examination of the family showed that all affected members had gait ataxia and akinesia with variable features of dysarthria, hyporeflexia, and mild intellectual impairment. Eye movements were normal. Head MRI showed atrophy of the cerebellum without involvement of the brainstem. In 10 parent-child pairs, median onset occurred 10.5 years earlier in offspring than in their parents, suggesting anticipation. CONCLUSION: This family is distinct from other families with SCA and is characterized by cerebellar ataxia and extrapyramidal signs.     

Cytogenetic and molecular genetic analysis of tumorigenic human bronchial epithelial cells induced by radon alpha particles

To establish a cell culture model for lung carcinogenesis, independent populations of the human papillomavirus 18-immortalized human bronchial epithelial cell line BEP2D were treated with high linear energy transfer radon-simulated alpha-particles, expanded and xenotransplanted into Nu/Nu mice. Six independent cell lines were established from tumors that developed from three separate radiation treatments as follows: treatment (Tx) 1 (30 cGy--two doses), H2BT, Tx 2 (30 cGy-- single dose), R30T1L, R30T2 and R30T3L, Tx 3 (30 cGy--single dose), H1ATN and H1ATBA1. Cytogenetic analysis revealed common changes in all tumor lines: loss of the Y chromosome (ch), one of three copies of ch8, one of three copies of ch14, and one of two copies of ch4p16-pter and ch11p15-pter. Analysis of polymerase chain reaction-amplified short tandem repeats of informative loci confirmed the loss of chY in all lines and loss of heterozygosity (LOH) at eight loci spanning the length of ch8 in all lines from Tx's 1 and 2. Our data support previous studies indicating the presence of tumor suppressor genes on ch8. LOH also was confirmed on ch14 at locus D14S306 in all cell lines from Tx 2 and in one of two lines from Tx 3. This region, 14q12-q13, may contain changes in one of the five known somatostatin receptor genes (SSTR1). No LOH was detected at any of the informative loci tested for on ch4 or ch11.      

Mycobacterial infection in an inner city children's hospital

Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition.     

Les polyamines : intérêt clinique, diagnostique et pronostique

Polyamines (putrescine, spermidine, spermine) are organic cations which are omnipresent in the living world and intimately involved in the phenomena of cell kinetics. Putrescine primarily reflects tissue growth while spermidine concentrations correlate with lysis. Several techniques exist for polyamine measurement in serum, urine and other biological fluids. At present, use of an automatic ion exchanger represents the most satisfactory method, with urine being the ideal physiological fluid.Neoplasias without residual disease present concentrations identical to those of the control group, whereas excessive values are specific to tumors in evolution. While high concentrations of these kinetic markers are also associated with certain benign affections, the latter are rare or easily diagnosed, and the value of these markers in oncology remains unaffected.Combined measurement of putrescine and spermidine levels allows evaluation of the tumor growth/lysis ratio at any given moment. The most important feature of this analysis of kinetics is the possibility of short term evaluation of the efficacy of a therapy program.     

MR imaging of blood vessels using three-dimensional reconstruction: methodology

Multisection, dual-echo magnetic resonance (MR) transaxial images of blood vessels contain both anatomic and qualitative information about flow. Even so, the images are produced as a series of two-dimensional tomographic sections from which full visualization of connected structures is difficult. A computer algorithm was developed that automatically detects flowing blood based on pixel intensity and calculated T2 and provides reconstructed views of vessels while analyzing and displaying flow characteristics. Images of abdominal vessels, aortic aneurysms, and the heart were encoded by flow and color to demonstrate depth. In addition, these data were reconstructed to derive a more accurate assessment of patency. With this technique, transaxial images can be used to analyze flow patterns, determine patent areas, and visualize all levels of vessels in a single image.     

A new PCR-ELISA for diagnosis of visceral leishmaniasis in blood of HIV-negative subjects

The PCR-ELISA represents a promising advance for diagnosis of visceral leishmaniasis (VL) in blood samples. However, the method has been validated mostly with HIV-positive patients who are known to have high levels of parasitaemia. We developed a new PCR-ELISA assay for specific detection of Leishmania in patients' blood and validated it in Nepalese subjects with clinically suspected VL, almost all of whom were HIV-negative. For blood samples, PCR-ELISA was more sensitive (83.9%) than conventional PCR (73.2%), and demonstrated 100% and 87.2% specificity when using healthy controls who had never travelled to a VL-endemic area and controls from a VL-endemic area as references, respectively. We have demonstrated the ability of PCR-ELISA to detect parasites in blood of HIV-negative patients. The method could be used for epidemiological as well as clinical purposes, as it reduces the need for traumatic bone marrow sampling and risky spleen aspiration.     

An exploration of the social stigma of tuberculosis in five "municipios" of Nicaragua to reflect on local interventions

OBJECTIVE: The social stigma of tuberculosis is much less studied than those of other diseases such as AIDS or mental problems. However, it has important implications on the affected person's well being and on the epidemic's control. Our study aims at exploring this social stigma in five local health systems of Nicaragua, prior to implementing interventions to reduce it. METHODS: Through in-depth interviews and focus groups involving stakeholders in the care of people affected by tuberculosis (PATBs), we analysed interactions between PATBs and family members, first line government health services' personnel, and community members. RESULTS: According to our results, the interaction between stakeholders and PATBs can be described as the intersection between two sets of contradictory feelings and attitudes: (a) feelings of affection and supportive attitudes toward PATBs opposed to the fear of being infected or that PATBs will infect others and, (b) confidence in PATBs considered to be unlucky opposed to mistrust of PATBs considered to be negligent. PATBs react against this mainly by hiding their condition which leads them to a, loss of confidence and depression. This intricate group of feelings and attitudes is influenced by two sets of determinants related to domination and power between stakeholders and issues of knowledge and information. CONCLUSION: Analysing tuberculosis-related social stigma as a social process enabled us to better understand some key social structural factors of health care system's organisation and identify locally acceptable interventions to reduce such stigma. The fact of analysing, in a more thorough study, some interventions in the currently changing social structural context of health care systems in Nicaragua will give us a better insight into the relevance of our analysis and the interventions' effectiveness in reducing the social stigma of tuberculosis.