Damage occurs early in systemic vasculitis and is an index of outcome.

Because death after acute systemic vasculitis is now uncommon, alternative measures of outcome are required. A significant component of patient morbidity is disease-related damage, which can be quantified by the Vasculitis Damage Index (64 items in 11 organ-based systems). We investigated serially the time-course of damage in 120 patients with systemic vasculitis, to determine the earliest indicators of outcome. High damage scores at 2 years after presentation were characteristic of fatal disease (OR 8.1-12.4). Significant damage occurred within 6 months of presentation, and was a feature of fatal disease. More damage occurred after presentation than after relapse. Lung and multi-system damage were early indicators of poor outcome in severe non-fatal disease. Damage occurs early in systemic vasculitis, and is an indicator of poor outcome. This novel observation, together with evidence of persistent subclinical disease activity and the high frequency of relapse, suggests a need for new treatment strategies. Analogy with the management of acute leukaemia suggests a strategy of early diagnosis and intensive induction of remission, with early escalation of treatment for resistant disease.

Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis.

The continuing morbidity of patients with vasculitis, despite the improved prognosis with aggressive therapy, underlines the need for accurate disease assessment. We have devised a clinical index of disease activity, and evaluated its use in several forms of necrotizing vasculitis. The weighted score is based on symptoms and signs in nine separate organ systems. Disease features are only scored if they are attributable to active vasculitis. The Birmingham Vasculitis Activity Score (BVAS) was compared with two other published vasculitis activity scores, with the physician's global assessment (PGA), with outcome, and with serological markers of disease activity. In a cross-sectional study of 213 consecutive patients with different forms of vasculitis, all 107 vasculitis patients who were judged completely well on clinical assessment had a BVAS score of 0. Twenty-two patients with active vasculitis prior to treatment had a median score of 7.5 (range 4-30) and 69 with active disease on treatment had a median score of 10 (1-29). Of the 12 who died, median score immediately prior to death was 20.5 (9-30). In a serial prospective study, 30 cases had documented episodes of active disease. During periods of disease activity, the median BVAS values were significantly higher than in remission (15 [range 3-32] vs. 0 [0-2], p < 0.001); the same was true for CRP values (80 [9-361] vs. 13.5 [5-68], p < 0.001). This was not true for erythrocyte sedimentation rate (ESR), haemoglobin (Hb) or von Willebrand factor (VWF).(ABSTRACT TRUNCATED AT 250 WORDS)

A single camera roentgen stereophotogrammetry method for static displacement analysis.

A new method to quantify motion or deformation of bony structures has been developed, since quantification is often difficult due to overlaying tissue, and the currently used roentgen stereophotogrammetry method requires significant investment. In our method, a single stationary roentgen source is used, as opposed to the usual two, which, in combination with a fixed radiogram cassette holder, forms a camera with constant interior orientation. By rotating the experimental object, it is possible to achieve a sufficient angle between the various viewing directions, enabling photogrammetric calculations. The photogrammetric procedure was performed on digitised radiograms and involved template matching to increase accuracy. Co-ordinates of spherical markers in the head of a bird (Rhea americana), were calculated with an accuracy of 0.12mm. When these co-ordinates were used in a deformation analysis, relocations of about 0.5mm could be accurately determined.

The role of motor evoked potentials in psychogenic paralysis.

STUDY DESIGN: This prospective clinical study identified patients in whom paralysis developed after lumbar surgery. OBJECTIVE: To determine whether patients with psychogenic paralysis could be identified using noninvasive techniques. SUMMARY OF BACKGROUND DATA: Before the advent of transcranial magnetic stimulation, no clinically applicable, noninvasive technique was available to confirm the integrity of the corticospinal tract. METHODS: Patients with suspected postoperative psychogenic paralysis were evaluated by clinical examination and neurophysiologic work-up, including transcranial magnetic stimulation. RESULTS: Six patients with psychogenic paralysis were identified in a 15-month period. In each case, motor evoked potentials could be demonstrated from the affected muscle(s), thus obviating the need for further invasive imaging or surgical exploration. CONCLUSIONS: Transcranial magnetic stimulation is a reliable, painless, and noninvasive technique for demonstrating structural integrity of the corticospinal tracts.

A study of the effects of replacing monensin ionophore with lasalocid ionophore in the field control of coccidiosis in broilers.

The following conclusions are made from an introductory investigation on the use of the coccidiostat lasalocid on 11 production farms of an integrated broiler production organisation. In terms of the incidence of sub-clinical coccidiosis, no significant difference was found between the previous use of monensin and the use of lasalocid during the investigation. However, the incidence of coccidiosis decreased with the introduction of lasalocid. Despite the fact that on some farms sub-clinical coccidiosis was diagnosed, the production performance clearly improved with lasalocid. EBI figures significantly increased from 163.6 to 172.5. During the investigation, in which approximately 220,000 broilers were involved, litter quality did not differ from that of previous crops in which monensin had been used. Feathering of the broilers in the trial crops in which lasalocid was used was similar to that of previous crops.

Close temporal and anatomic relationship between multicentric reticulohistiocytosis and carcinoma of the breast.

We describe a case of simultaneous development of a medullary carcinoma of the breast and multicentric reticulohistiocytosis (MRH) with identical characteristic histological lesions being found not only in the skin and synovium, but also in close proximity to the breast cancer as well as the connective tissue surrounding the tumor involved axillary lymph nodes. Successful treatment of the primary malignancy resulted in complete resolution of the MRH over 4 months. A close temporal relationship existed between the development and clinical remission of the malignancy and the course of the arthritis and skin lesions. Characteristics of this rare syndrome with particular reference to its association with malignancy are reviewed.

The effects of human skin fibroblast monolayers on human sperm motility and mouse zygote development.

A new system for co-culture in human in-vitro fertilization (IVF), using human skin fibroblasts, is described and tested pre-clinically. The first test involved the development of 1-cell mouse embryos which exhibit the 2-cell developmental block in vitro. Passage through this block (pb1-ratio) was determined by the ratio of compacted morula stages on day 4 of incubation. For nine human skin cell lines tested (fetal, neonatal and adult), the pb1-ratio was approximately 0.45 (0.07 in culture medium alone; P less than 0.0005). At the compacted morula stage, a second developmental block was observed. The ratio of passing this block (pb2-ratio) was 0.70 +/- 0.09 on skin fibroblasts obtained from fetal or neonatal tissue. On fibroblasts from adult patients the pb2-ratio was 0.30 +/- 0.04 (P less than 0.0005). The second test examined the influence of skin fibroblasts from fetal or neonatal tissue on human sperm motility. After 24 h of incubation, all skin cell lines had a positive influence (P less than 0.01) on the percentage motility compared to culture medium alone. The curvilinear velocity was not significantly increased. From the results we conclude that (i) human skin fibroblasts (especially from fetal tissue) have a positive influence on the development of mouse embryos in vitro, (ii) there is a positive influence of human skin fibroblasts on the percentage motility of human spermatozoa, and (iii) a clinical trial of co-culture with human skin fibroblasts can be justified.

Correlation of blood levels of soluble vascular cell adhesion molecule-1 with disease activity in systemic lupus erythematosus and vasculitis.

Levels of soluble adhesion molecules have been shown to reflect their cell surface expression in vitro, and thus may provide a useful surrogate marker of surface expression at inflammatory sites. In patients with SLE and vasculitis, serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selection were determined by ELISA during different stages of disease activity. Levels of soluble(s) VCAM-1 correlated with disease activity in patients with SLE, being significantly higher during active compared with inactive disease (P = 0.003), and normalizing with clinical remission. By contrast, in patients with vasculitis, although sVCAM-1 levels were elevated in active disease, they fell but did not normalize in inactive disease, suggesting that treatment may be suppressing the clinical manifestations rather than targeting the underlying pathogenic mechanism. Soluble ICAM-1 and E-Selectin levels did not relfect disease activity in either SLE or vasculitis.

An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation.

Through allele-segregation and loss-of-heterozygosity analyses, we demonstrated loss of the translocation-derivative chromosome 3 in five independent renal cell tumors of the clear-cell type, obtained from three members of a family in which a constitutional t(2;3)(q35;q21) was encountered. In addition, analysis of the von Hippel-Lindau gene, VHL, revealed distinct insertion, deletion, and substitution mutations in four of the five tumors tested. On the basis of these results, we conclude that, in this familial case, an alternative route for renal cell carcinoma development is implied. In contrast to the first hit in the generally accepted two-hit tumor-suppressor model proposed by Knudson, the familial translocation in this case may act as a primary oncogenic event leading to (nondisjunctional) loss of the der(3) chromosome harboring the VHL tumor-suppressor gene. The risk of developing renal cell cancer may be correlated directly with the extent of somatic (kidney) mosaicism resulting from this loss.