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John H Stone

Publications and source records attributed to John H Stone.

7 recordsLinked to original sources
PubMed2003

Limited versus severe Wegener's granulomatosis: baseline data on patients in the Wegener's granulomatosis etanercept trial.

OBJECTIVE: To report baseline data on 180 patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET), and to examine demographic and clinical differences between patients with limited disease and those with severe disease. METHODS: Definitions of limited and severe disease were agreed upon by consensus of the investigators at a pretrial meeting and were incorporated into the protocol as a stratification criterion. These data were applied prospectively to the WGET patient cohort, based on clinical features and the intention to treat patients according to disease activity. Data related to disease onset, date of diagnosis, clinical features, antineutrophil cytoplasmic antibody assays, tissue biopsy findings, and other medical history were collected on a baseline medical history form. Physician-investigators from each center participated in the development of this form, and all were certified in its use prior to the start of the trial. Selected data on patients who were screened for the trial but were not enrolled were also collected. RESULTS: Several significant differences between the limited and severe disease subsets were observed. Patients with limited disease were nearly a decade younger at disease onset compared with patients with severe disease. Thirty-three percent of patients with severe disease were women, compared with 58% of those with limited disease. Despite their younger age at symptom onset, patients with limited disease tended to have longer disease duration, a greater likelihood of experiencing exacerbation of previous disease following a period of remission, and a higher prevalence of destructive upper respiratory tract disorders at the time of enrollment (e.g., saddle-nose deformity). Patients with limited WG were less likely than those with severe disease to have antibodies to either proteinase 3 or myeloperoxidase. Patients with severe disease had a higher likelihood of previous thyroid disease, particularly either Graves' disease or Hashimoto thyroiditis, suggesting the possibility of different pathogenetic factors within these disease subsets. Other observed differences between these subsets, such as the greater frequency of alveolar hemorrhage in the severe disease group, were related to the a priori definitions of limited and severe disease. CONCLUSION: There are significant differences between patients with limited WG and those with severe WG with regard to sex, age, the likelihood of recurrent disease, the risk of damage in certain organ systems, and, possibly, etiologic factors. These differences (and perhaps other differences that are currently unrecognized) in patient subsets may have implications for mechanisms of pathogenesis, prognosis, response to treatment, and the design of future clinical investigations.

Adult↗
PubMed2002

Polyarteritis nodosa.

Polyarteritis nodosa (PAN) is regarded rightly as the grandfather of the vasculitides. In this Grand Rounds, the case of a 30-year-old man with a 12-year illness is described. The patient presented with daily fevers, tachycardia, and cutaneous ulcers on his distal extremities. He eventually developed mononeuritis multiplex. Because of the striking pattern of his fevers, he was diagnosed for many years as having adult-onset Still disease. Following the addition of daily cyclophosphamide to his long-standing regimen of prednisone, the patient's disease entered remission for the first time in more than a decade. He was ultimately able to discontinue all of his immunosuppressive medications. The case is discussed in the context of the first patient ever described with PAN, the classic report of Kussmaul and Maier.

Adult↗
PubMed2002

Gastrointestinal involvement in polyarteritis nodosa (1986-2000): presentation and outcomes in 24 patients.

PURPOSE: Gastrointestinal involvement in polyarteritis nodosa carries a poor prognosis. A 1982 review from our institution reported acute abdominal syndromes in 31% of patients with polyarteritis nodosa, and that all 5 patients with acute surgical abdomens died. We reviewed our more recent experience to determine if outcomes have changed since. SUBJECTS AND METHODS: We reviewed the records of all patients with polyarteritis nodosa in our vasculitis database between 1986 and 2000. Inclusion criteria were a diagnosis of polyarteritis nodosa, symptoms or signs of gastrointestinal involvement, and either a mesenteric angiogram consistent with polyarteritis nodosa or histopathologic proof of a medium-vessel vasculitis. We calculated a prognostic (5 factor) score for all patients. RESULTS: We identified 24 patients with polyarteritis nodosa who had gastrointestinal involvement during their illness. Thirteen (54%) of the patients developed acute surgical abdomens, 3 of whom died (P = 0.02 by comparison with the historical cohort). Mean (+/- SD) prognostic scores were higher among patients in the acute abdomen group compared with those who did not have acute abdominal syndromes (1.7 +/- 0.9 vs. 0.6 +/- 0.7, P = 0.002), corresponding with the observed mortality in these groups. CONCLUSION: Gastrointestinal involvement occurs commonly in polyarteritis nodosa and carries a poor prognosis. Compared with a historical cohort at our institution, mortality from this complication may have decreased, perhaps because of earlier diagnosis.

Abdomen, Acute↗
PubMed2002

A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis.

OBJECTIVE: To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity. METHODS: This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day (<or=60 mg every day) prednisone, plus either 0.15 mg/kg/week MTX (increased to 0.25 mg/kg/week, for a maximum weekly dosage of 15 mg) or placebo. Two physicians, both blinded to treatment allocation, evaluated each patient at every trial visit. One physician was responsible for providing global medical care. The other assessed GCA status according to a standard protocol. Treatment failure was defined as 2 distinct relapses or persistence of disease activity after the first relapse, in spite of increased CS therapy. RESULTS: Ninety-eight patients were enrolled. No significant differences between treatment groups were noted with regard to age, frequency of positive findings on temporal artery biopsy (placebo 87%, MTX 79%), or comorbidities at the time of enrollment. The median dosage of MTX was 15 mg/week. The incidence of treatment failure was comparable between groups after 12 months: 57.5% in the MTX group failed treatment (95% confidence interval [95% CI] 41.6-73.4%) compared with 77.3% in the placebo group (95% CI 61.9-92.8%) (P = 0.26). In a Cox regression analysis, MTX was not associated with a reduced risk of treatment failure (relative risk 0.72; 95% CI 0.41-1.28). There were no significant differences between groups with regard to abnormal elevations of the erythrocyte sedimentation rate following initial remissions, serious morbidity due to GCA, cumulative CS dose, or treatment toxicity. In the MTX group, there were fewer cases of GCA relapse heralded by symptoms of isolated polymyalgia rheumatica (1 case versus 5 in the placebo group; P = 0.05). CONCLUSION: The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA.

Aged↗
PubMed2002

Temporal arteritis and Chlamydia pneumoniae: failure to detect the organism by polymerase chain reaction in ninety cases and ninety controls.

OBJECTIVE: To examine the reported correlation between the presence of Chlamydia pneumoniae in temporal artery biopsy specimens and the diagnosis of temporal arteritis (TA). METHODS: Among 90 possible cases of TA identified at our institution between 1968 and 2000, 79 of the positive biopsy specimens (88%) demonstrated giant cells and the other 11 cases (12%) had other histopathologic features compatible with TA; by chart review, all 90 patients were confirmed to have met the American College of Rheumatology classification criteria for TA. Controls had negative temporal artery biopsy specimens during the same 32-year time period and their postbiopsy disease courses were not compatible with TA. Controls were matched with each case by sex, year of biopsy, and age within 10 years. The biopsy specimens from all cases and controls were reevaluated and readings were confirmed in a masked manner by an experienced eye pathologist. Polymerase chain reaction (PCR) analyses for C pneumoniae were performed on the 180 samples using 2 different sets of PCR primers (which target 2 different genes). A primer set targeting the ompA gene (CP1-CP2/CPC-CPD) was used to perform a nested PCR, followed by confirmation of the findings with primers targeting the 16S ribosomal RNA (rRNA) gene (Cpn90/Cpn91) in a touchdown-enzyme time-release PCR. We used positive and negative controls, as well as controls made from infected and noninfected HEp-2 cells, suspended in a formalin-fixed, paraffin-embedded matrix. RESULTS: Seventy-six percent of the 180 cases and controls were women. The mean age of the cases was 72.0 years (range 53-90), and that of the controls was 70.4 years (range 51-86). Eighty percent of the control samples were obtained by temporal artery biopsy performed within 1 year of the biopsies performed on the matched cases. Using the CP1-CP2/CPC-CPD primer set, only 1 TA case sample (1% of all case samples) was positive for the ompA gene. One control sample was also positive using these primers. With the Cpn90/Cpn91 primers, none of the cases and none of the controls were positive for the 16S rRNA gene. CONCLUSION: The results of this study using sensitive and specific PCR analyses do not support a role for C pneumoniae in the pathogenesis of TA.

Aged↗
PubMedDate not supplied

Correlation of percentage of normal glomeruli with renal outcome in Wegener's granulomatosis.

BACKGROUND/AIMS: We examined the correlations between renal biopsy findings in Wegener's granulomatosis and renal function at baseline and 1 year in 22 patients who presented between 1988 and 1999. METHODS: Renal histology was independently reviewed by 2 pathologists who were masked to the clinical data. The primary outcome was the relationship of the percentage of normal glomeruli to reciprocal serum creatinine at baseline and 1 year. Other histologic data were collected using a series of ordinal rating scales. Acute and chronic sum scores were calculated. RESULTS: The median serum creatinine (SCr) at baseline was 3.9 mg/dl (0.8-14 mg/dl). Seven patients initially required hemodialysis, of whom 4 subsequently regained independent renal function. By 1 year of follow-up, the median (SCr) for patients with independent renal function was 1.9 mg/dl (0.9-6.8 mg/dl). Reciprocal SCr at baseline correlated with the percentage of normal glomeruli (r = 0.584, p = 0.005), crescent score (r = -0.595, p = 0.003), interstitial fibrosis as a percentage of cortical surface area (r = -0.669, p = 0.002), interstitial inflammation (r = -0.439, p = 0.041), eosinophil (r = -0.495, p = 0.019), neutrophil score (r = -0.557, p = 0.005), and acute sum score (r = -0.499, p = 0.018). However, only the percentage of normal glomeruli (r = 0.493, p = 0.023), the crescent score (r = -0.452, p = 0.035), and interstitial fibrosis as a percentage of cortical surface area (r = -0.466, p = 0.052) correlated with reciprocal SCr at 1 year of follow-up. CONCLUSION: In this relatively small data set, the percentage of normal glomeruli, the crescent score, and interstitial fibrosis as a percentage of cortical surface area correlated with renal function at both baseline and 1 year of follow-up.

Adult↗