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A Schnabel

Publications and source records attributed to A Schnabel.

At least 73 records · Page 4Linked to original sources
PubMed1996

Long-term tolerability of methotrexate at doses exceeding 15 mg per week in rheumatoid arthritis.

The objective of this study was to examine longitudinally the tolerability of methotrexate (MTX) treatment at doses exceeding 15 mg/week in an open-label, prospective study. One hundred and eighty-five patients with rheumatoid arthritis were randomized to receive 15 mg or 25 mg MTX per week initially, and were followed over 30 months. Subsequent dose adjustments according to efficacy and tolerability resulted in levelling off of the mean dose at 18 mg/week, and the original treatment groups were combined for a longitudinal study comparing toxic events during months 1-12 and months 13-30. Withdrawals due to side-effects amounted to 17% during months 1-12 and 4% during months 13-30; dose reductions due to side-effects were 9% and 7%, respectively. The annual incidence of gastrointestinal side-effects increased from 26% to 39% (P = 0.05), that of liver enzyme elevation dropped from 43% to 10% (P < 0.001) and haemocytopenia remained stable at 5% and 7%. MTX pneumonitis was only observed during the first year, while airway complaints without evidence of parenchymal lung involvement increased to 10% beyond the first year. Fifty-six patients experienced 65 major infectious episodes over the 30-month period, with the respiratory tract being the most frequent site. This study showed that MTX treatment at doses exceeding 15 mg/week is tolerated over extended period of time. Major toxicity and withdrawals due to side-effects occurred predominantly during the first year of treatment and thus showed a decreasing trend over time, while minor toxic events continued throughout the study with a progressive rate of mucous membrane toxicity. MTX-treated RA appears to be a risk situation for major infection.

Aged↗
PubMed1996

Sustained cough in methotrexate therapy for rheumatoid arthritis.

Sustained cough is a frequent complaint in methotrexate (MTX) treatment for rheumatoid arthritis and can be a symptom of incipient MTX-induced pneumonitis. This study was performed to characterize MTX-associated cough clinically and to clarify by which means this condition can be distinguished from incipient MTX pneumonitis. Three patients with MTX-induced pneumonitis and 10 patients with sustained cough unassociated with pneumonitis were examined clinically, by pulmonary function testing, and bronchoalveolar lavage (BAL). In MTX pneumonitis, cough was associated with progressive dyspnoea, constitutional symptoms, impaired pulmonary function, and interstitial infiltration of variable degree by chest X-ray. BAL cytology invariably showed lymphocytic alveolitis while transbronchial biopsy revealed active interstitial inflammation in only one patient. Ten patients had sustained, nonprogressive cough in the absence of constitutional symptoms, progressive dyspnoea and impaired pulmonary function. Neither X-ray nor BAL nor transbronchial biopsy revealed any evidence of interstitial lung disease. In the majority of these patients, cough abated with symptomatic treatment with or without temporary discontinuation of MTX. It is concluded that MTX-associated cough can be a reflection of isolated airway disease. Clinically, absence of constitutional symptoms, impaired pulmonary function, and interstitial infiltration on X-ray distinguished this condition from incipient MTX pneumonitis. Cough without pulmonary parenchymal involvement appears to result from an irritant effect of MTX on the airways.

Aged↗
PubMed1996

Anti-neutrophil cytoplasmic antibodies in generalized autoimmune diseases.

Anti-neutrophil cytoplasmic antibodies (ANCA) are a system of autoantibodies which are strongly associated with the primary systemic vasculitides (PSV). cANCA, as detected by indirect immunofluorescence, are mostly reactive to proteinase 3 (PR3) and bear high sensitivity and specificity for Wegener's granulomatosis. pANCA have varied subspecificities and clinical associations. The most important subspecificity of pANCA is anti-myeloperoxidase (MPO), which is strongly associated with microscopic polyaniitis and pauci-immune crescentic glomerulonephritis. pANCA also occur at low to moderate frequency in other PSV, collagen vascular disease, inflammatory bowel disease and autoimmune liver disease. In systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), pANCA of varied subspecificity have been found, including anti-MPO at low rate and low titer, while cANCA and anti-PR3 were generally absent. Consequently, anti-PR3 (PR3-ANCA) and anti-MPO (MPO-ANCA) at moderate and high titer are distinguishing features of the PSV and, in an appropriate clinical setting, argue strongly against the presence of SLE or RA. Since no significant clinical association has been found for other pANCA subspecificities, cANCA, PR3-ANCA and MPO-ANCA remain the critical elements of ANCA testing in the clinical diagnosis of generalized autoimmune diseases.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Pulmonary sarcoidosis coexisting with systemic lupus erythematosus.

A 23 year old female presented with fatigue, Raynaud's syndrome, symmetric polyarthritis, lymphocytopenia, hypocomplementemia, IgG elevation, and antinuclear antibodies with anti-U1RNP specificity. A diagnosis of systemic lupus erythematosus (SLE) was made. Disseminated micronodular infiltration in the chest X-ray, a pattern of lymphocytic alveolitis by bronchoalveolar lavage, histologic demonstration of non-caseating epitheloid microgranulomas, and rapid reversal of lung disease upon low-dose methylprednisolone treatment led to a diagnosis of concomitant sarcoidosis. Clues to the diagnosis of sarcoidosis coexisting with SLE are discussed.

Adult↗
PubMed1996

[Raynaud syndrome].

Explore the source record for details and available documents.

Collagen Diseases↗
PubMed1995

Bidirectional interlocus concerted evolution following allopolyploid speciation in cotton (Gossypium).

Polyploidy is a prominent process in plant evolution; yet few data address the question of whether homeologous sequences evolve independently subsequent to polyploidization. We report on ribosomal DNA (rDNA) evolution in five allopolyploid (AD genome) species of cotton (Gossypium) and species representing their diploid progenitors (A genome, D genome). Sequence data from the internal transcribed spacer regions (ITS1 and ITS2) and the 5.8S gene indicate that rDNA arrays are homogeneous, or nearly so, in all diploids and allopolyploids examined. Because these arrays occur at four chromosomal loci in allopolyploid cotton, two in each subgenome, repeats from different arrays must have become homogenized by interlocus concerted evolution. Southern hybridization analysis combined with copy-number estimation demonstrate that this process has gone to completion in the diploids and to completion or near-completion in all allopolyploid species and that it most likely involves the entire rDNA repeat. Phylogenetic analysis demonstrates that interlocus concerted evolution has been bidirectional in allopolyploid species--i.e., rDNA from four polyploid lineages has been homogenized to a D genome repeat type, whereas sequences from Gossypium mustelinum have concerted to an A genome repeat type. Although little is known regarding the functional significance of interlocus concerted evolution of homeologous sequences, this study demonstrates that the process occurs for tandemly repeated sequences in diploid and polyploid plants. That interlocus concerted evolution can occur bidirectionally subsequent to hybidization and polyploidization has significant implications for phylogeny reconstruction, especially when based on rDNA sequences.

Base Sequence↗
PubMed1995

Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus. Prevalence, specificities, and clinical significance.

OBJECTIVE: To examine the prevalence, subspecificities, and clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with systemic lupus erythematosus (SLE). METHODS: One hundred fifty-seven sera from 120 patients with SLE were examined for classic (c) and perinuclear (p) pattern ANCA by indirect immunofluorescence. Antibody subspecificities were determined by enzyme-linked immunosorbent assay (ELISA). Serologic results were correlated with clinical manifestations as categorized by the BILAG (British Isles Lupus Assessment Group) index. RESULTS: ANCA were found in 40 of the 157 sera (25%). Only a pANCA, not a cANCA, pattern of fluorescence was seen. By ELISA testing, 16 sera reacted to lactoferrin, 8 to elastase, and 4 to lysozyme. There was no reactivity to proteinase 3 (PR3) or myeloperoxidase (MPO). No correlation of pANCA, or any of the ANCA subspecificities, with organ system involvement, as categorized by the BILAG index, was found. Notably, there was no correlation of ANCA results with lupus vasculitis. CONCLUSION: The absence of cANCA, anti-PR3, and anti-MPO shows that with appropriate assay conditions, ANCA testing assists in the differentiation between SLE and the ANCA-associated vasculitides. The lack of a correlation between pANCA or any ANCA subspecificity and clinical manifestations suggests that ANCA do not identify particular clinical subsets among SLE patients, including those with lupus vasculitis.

Adult↗
PubMed1995

An unusual ribosomal DNA sequence from Gossypium gossypioides reveals ancient, cryptic, intergenomic introgression.

The New World allopolyploid (AD-genome) cottons (Gossypium) originated through hybridization of ancestral diploid species that presently have allopatric ranges in Africa-Asia (the A-genome) and the American tropics and subtropics (the D-genome). Phylogenetic analysis of sequence data from the ribosomal DNA internal transcribed spacer region (ITS1, 5.8S rRNA, ITS2) reveals two strongly supported clades, one corresponding to African species and the other containing all American D-genome species except Gossypium gossypioides, which occupies a basal position within the African clade. This placement conflicts with evidence from fertility relationships, morphology, cytogenetics allozymes, and cpDNA restriction site analysis, which specify a sister-species relationship for G. gossypioides and Gossypium raimondii, deeply embedded within the American D-genome clade. Several alternative explanations for this striking incongruence are considered. The most probable involves: (1) an ancient hybridization event, whereby G. gossypioides experienced contact with an A-genome, either at the diploid level or at the triploid level as a consequence of hybridization with a New World allopolyploid and (2) repeated backcrossing of the hybrid into the G. gossypioides lineage, thereby restoring a nearly pure D-genome, but in the process generating a recombinant ribosomal DNA. We suggest that this process may implicate G. gossypioides, rather than G. raimondii, as the closest living descendant of the ancestral D-genome parent of the allopolyploids. In addition, this example of cryptic, intergenomic introgression between species groups now occupying different hemispheres illustrates how ITS data may provide insights into genome composition and evolutionary history, especially when used in the context of a holistic view that encompasses information from a variety of sources.

Africa↗
PubMed1995

Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

Adult↗
PubMed1994

Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with Wegener's granulomatosis.

OBJECTIVE: To assess the effectiveness of pulse cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG) and to identify the patients who are responsive to the treatment. METHODS: The prospective study included 43 patients with biopsy-proven WG. Clinical, radiographic, laboratory, and immunologic data were evaluated for predictive values regarding the outcome of pulse CYC therapy. RESULTS: Only 42% of the patients showed complete or partial remission that lasted at least 6 months after cessation of pulse CYC therapy. These responders had a higher frequency of disease activity limited to the upper and lower respiratory tract (39%, versus 8% in the nonresponder group; P < 0.05) and had lower titers of classic antineutrophil cytoplasmic antibody (cANCA) prior to treatment (< 1:64 42%, versus 6% in the nonresponder group; P < 0.05). In the 58% of patients who did not respond to pulse CYC treatment, there was both systemic disease involving more than 4 organ systems (mainly, the heart, nervous system, eye, and skin) and constitutional symptoms. Serious side effects induced by pulse CYC occurred in only 1 patient. CONCLUSION: Based on these findings, pulse CYC therapy appears to be effective in WG patients with moderate disease activity and low titers of cANCA, but of little benefit in patients with severe WG. Pulse CYC should therefore not be used as first-line therapy in patients with severe and rapidly progressing forms of WG associated with high titers of cANCA.

Adolescent↗