Two-dimensional gel electrophoresis in inclusion body myositis.

Inclusion body myositis (IBM) is an acquired inflammatory myopathy in which a wide range of proteins is deposited within the cytoplasm of muscle fibres. To explore the possibility that this deposition occurs due to uncontrolled protein production arising from a defect at the nuclear level, we studied muscle samples from IBM and control subjects using two-dimensional gel electrophoresis. Twenty-seven gels from five controls and 24 gels from six patients with IBM were exhaustively compared using image analysis software and visual inspection. We found significant intra- and inter-subject variability in the number of protein spots on the gels. From 2272 to 4522 spots were found in different control gels, and from 2821 to 4153 spots in the IBM gels. No unique spots were identified in the IBM gels. When viewed with other work, the results of this study suggest that widespread, uncontrolled activation of genes is unlikely to be a component of the pathogenesis in IBM.     

Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate ('Orange') in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a children's cancer group report.

Despite prolonged therapy (18 months), children with advanced non-lymphoblastic, non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG) trials achieved less than a 60% 5-year event-free survival (EFS). In this study we piloted a shorter but more intensive protocol ('Orange') to determine the feasibility, safety, and efficacy of this alternative treatment approach. Thirty-nine children received a CHOP-based induction, etoposide/ifosfamide consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside (Ara-C) and L-asparaginase) intensification, and either one or two similar but less intense maintenance courses. Patients were stratified to standard-risk (5 months) vs high-risk (7 months) treatment. High risk was defined as either bone marrow disease, CNS disease, mediastinal mass > or = one-third thoracic diameter at T5 and/or LDH > or =2 times institutional upper limits of normal. All other patients were considered to be standard risk. Results were compared with the previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered standard- vs. high-risk, respectively. The 5-year EFS and overall survival (OS) were 77 +/- 7% and 80 +/- 7%, respectively. The 5-year EFS and OS were significantly better in the standard- vs. high-risk subgroups (100% vs. 61 +/- 11%) (P < 0.003) and (100% vs. 65 +/- 11%) (P < 0.01), respectively. Lactate dehydrogenase (LDH) > or =2 x normal (NL) was associated with significantly poorer outcomes (LDH > or =2 x NL vs. <2 x NL) (5-year EFS: 55 +/- 12% vs. 100%) (P < 0.0004). This CCG hybrid regimen, 'Orange', of short and more intensive therapy resulted in a significant improvement in outcomes compared with the previous CCG trial of more prolonged but less intense therapy. This regimen that deletes high-dose methotrexate, if confirmed in a larger trial, could be considered as an alternative treatment approach in children without high tumor burdens (LDH <2 x NL) and Murphy stage III disease.     

Thioesterases and the premature termination of polyketide chain elongation in rifamycin B biosynthesis by Amycolatopsis mediterranei S699

The role of two thioesterase genes in the premature release of polyketide synthase intermediates during rifamycin biosynthesis in the Amycolatopsis mediterranei S699 strain was investigated. Creation of an in-frame deletion in the rifR gene led to a 30 approximately 60% decrease in the production of both rifamycin B by the S699 strain or a series of tetra- to decaketide shunt products of polyketide chain assembly by the rifF strain. Since a similar percentage decrease was seen in both genetic backgrounds, we conclude that the RifR thioesterase 2 is not involved in premature release of the carbon chain assembly intermediates. Similarly, fusion of the Saccharopolyspora erythraea DEBS3 thioesterase I domain to the C-terminus of the RifE PKS subunit did not result in a noticeable increase in the amount of the undecaketide intermediate formed nor in the amounts of the tetra- to decaketide shunt products. Hence, premature release of the carbon chain assembly intermediates is an unusual property of the Rif PKS itself.     

Electrophysiologic analysis of auditory,vestibular and brain stem function in chronic renal failure

Utilizing audiometry, acoustic reflex threshold and reflex decay testing, electronystagmography and the brain stem auditory evoked response, cochlear-vestibular and brain stem function in chronic renal failure has been investigated. After elimination of the etiologic factors known to affect — or possibly affect — such function, a clinically significant abnormality of auditory, vestibular and brain stem function was not noted.     

Low back pain in elite rhythmic gymnasts

BACKGROUND: Rhythmic gymnastics is a sport that blends the athleticism of a gymnast with the grace of a ballerina. The sport demands both the coordination of handling various apparatus and the flexibility to attain positions not seen in any other sport. To attain perfection and reproducibility of their routines, the athletes must practice and repeat the basic elements of their routines thousands of times. In so doing, the athlete places herself at risk of a myriad of overuse injuries, the most common being low back pain. METHODS: To document the presence and severity of low back pain in elite rhythmic gymnasts, a prospective study of seven national team members was undertaken that documented injuries and complaints with daily medical reports over a 7-wk period. These findings were correlated with a retrospective review of 11 elite level gymnasts followed over a 10-month period whose complaints ultimately required evaluation by a physician. RESULTS: Eighty-six percent of the gymnasts in the prospective study complained of back pain at some point over the course of the study. The only injury recorded that required a time loss from sport was a low back injury. The most common complaint requiring a physician's evaluation was low back pain with the diagnoses varying from muscle strains to bony stress reaction or complete fracture of the pars inter-articularis (spondylolysis). No athlete had a spondylolisthesis or ruptured disk. Two had mild scolioses which did not appear to be associated with their low back pain. CONCLUSIONS: It would appear that rhythmic gymnasts are at relative increased risk of suffering low back complaints secondary to their sport.     

Life events, ethnicity and perceptions of discrimination in patients with severe mental illness

  Background: Whilst it is commonly believed that black and ethnic minority (B&EM) people living in the UK experience social disadvantage compared with the white British (WB) population, no study has specifically addressed this issue in patients with severe mental illness. We sought to test the hypothesis that B&EM patients experience more negative life events than their WB counterparts, and to examine the extent to which they attribute these events to discrimination. Method: Thirty-four WB, 78 African Caribbean (AC) and 35 other ethnic minority patients with psychotic illnesses, defined using Research Diagnostic Criteria, were asked to complete a Racial Life Event Questionnaire examining life events and perceptions of discrimination at baseline and 12 and 24 months later. Results: African Caribbean patients experienced more `Financial' life events across the study period, otherwise there were no significant differences between patient groups in number of life events experienced. The B&EM group collectively (n = 113), however, were significantly more likely than the WB group (n = 34) to attribute `Assault', and `Legal' life events to discrimination. The AC patient group were significantly more likely than the other two ethnic groups to attribute the `Financial' and `Health' life events they experienced to discrimination. The B&EM group was also significantly more likely, and particularly the AC patient group, to report that members of their own ethnic group are adversely affected by discrimination. Further analyses showed skin colour rather than ethnicity or nationality to be the major contributing factor to perception of discrimination; thus, the Irish (n = 11) had similar scores to the WB while Africans (n = 16) scored like the ACs. Conclusion: Our study shows that B&EM patients do not experience significantly more life events than WB patients; however, their perception of these events is clearly different, and significantly more often attributed to racism. It is reasonable to suppose that patients may be disinclined to utilise services they believe to be prejudiced against them on the basis of their skin colour, and service providers need to be aware of this in order to create health care services that B&EM patients feel confident to use. Accepted: 3 September 1999     

IMMUNOLOGICAL STUDIES IN TWO CHILDREN WITH RECURRENT PAROTITIS

ABSTRACT. In two children with recurrent parotitis, labial salivary gland biopsies showed chronic sialoadenitis. Immunofluorescence studies disclosed deposits of immunoglobulins and complement in juxta-acinar small vessels. Case 1 had gluten enteropathy, IgA deficiency and high titres of antinuclear antibodies (ANA), and in vivo fixation of ANA to nuclei of different cells in lip, skin and jejunum was present. Case 2 showed deposition of IgM in the dermo-epidermal junction of the skin. These findings suggest that autoimmune reactivity and immune complexes may play a role in the pathogenesis of this disorder.