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Biomedical subjects

J M Esdaile

Publications and source records attributed to J M Esdaile.

At least 91 records · Page 5Linked to original sources

The pathogenesis and prognosis of lupus nephritis: information from repeat renal biopsy.

Of an inception cohort of 87 patients with lupus nephritis who underwent a renal biopsy, 42 underwent second biopsies a median of 25 months later. From first to second biopsy, focal and diffuse proliferative nephritis (World Health Organization classes III and IV) became less frequent, and mesangial hypercellularity (class II) and a membranous pattern (class V) increased. The National Institutes of Health activity index and mesangial and subendothelial deposits declined while the chronicity index, a tubulointerstitial index, and subepithelial deposits increased. The biopsy improvement in urinary protein excretion was best explained by decreases in the activity index score and the amount of subendothelial deposits. A decrease in the amount of subendothelial deposits tended to predict an improvement in the serum creatinine level from first to second biopsy. With follow-up from second biopsy in excess of 7 years, the best predictors of long-term outcome were the ultrastructural variables mesangial, subendothelial and subepithelial deposits. When the change in biopsy predictors from first to second biopsy was evaluated, a decrease in the amount of mesangial or subendothelial deposits was best at predicting a lower risk of renal impairment, renal insufficiency, and mortality. The results confirm the importance of immune complex deposition as measured by electron microscopy in the pathogenesis of lupus nephritis and suggest that control of this process may alter renal function and prognosis.

Biopsy↗

Aberrant cellular localization of rubella viral genome in patients with adult Still's disease--a pilot study.

The rubella virus (RV) genome was detected using polymerase chain amplification techniques in several peripheral blood cell populations in patients with adult Still's disease (ASD) and normal controls (NC), including mononuclear cells (PBMC), B-cells, T-cells, monocyte/macrophages, and polymorphonuclear leukocytes (PMN). Five of 6 ASD patients and 3 of 6 NC subjects had detectable RV genome. Viral genomic load was significantly higher in ASD than in NC subjects (4.4 fold higher, p = 0.03). Interestingly, a differential cellular distribution of viral genome was observed between ASD and NC individuals. RV genome was detected more frequently in the PBMCs of ASD (5 of 6) patients compared to 2 of 6 NC. The viral genome was more localized to the PMN compartment equally in ASD and in NC subjects. On further cellular analysis, RV genome was detected in B-cells and macrophages but not T-cells in one patient. Existence of a differential viral genomic reservoir between ASD and NC suggests that this may play a role in the pathogenesis of disease manifestations and may reflect the inability to clear latent virus.

Adolescent↗

Chest radiographs as a screening test for diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: To evaluate the sensitivity, specificity, predictive value, interrater reliability and intrarater reliability of using chest radiographs as a screening tool for the diagnosis of diffuse idiopathic skeletal hyperostosis (DISH). METHODS: After review of thoracic spine radiographs by 2 "gold standard" physicians, 45 patients with DISH meeting the criteria of Resnick and Niwayama were contrasted with 106 control patients consisting of 45 with thoracic spondylosis, 45 who lacked spondylosis and whose thoracic spine radiographs were otherwise normal for the age of the patient, and 16 with ankylosing spondylitis. The chest radiographs on the 151 subjects were placed in random order and read independently using an ordinal diagnostic certainty scale by 2 "test" radiologists, experienced in reading bone radiographs. Two months later the order of chest radiographs was rerandomized and the films reassessed by the same test radiologists. RESULTS: The averages for the diagnostic and population test characteristics were sensitivity = 77%; specificity = 97%; positive predictive value = 91%; and, negative predictive value = 91%. The area under the receiver operating characteristic curves was 0.975 and 0.976 for the radiologists, and kappa was 0.93, demonstrating that interrater reliability was high. On rereading the chest radiographs, intrarater reliability was exceptional (weighted kappa of 0.90 and 0.96 for the two test radiologists). DISH patients whose chest radiographs were read as not demonstrating DISH had significantly less extensive disease. CONCLUSIONS: We conclude that chest radiographs are a reliable and valid screening tool for the diagnosis of DISH.

Adult↗

The longterm prognosis of lupus nephritis: the impact of disease activity.

An inception cohort of 87 patients with lupus nephritis was evaluated using a classification tree regression technique. Four relevant outcomes were studied: (1) renal insufficiency (serum creatinine > 5.0 mg/dl); (2) renal failure; (3) death due to renal involvement; and (4) any death due to systemic lupus erythematosus. All 4 outcomes could be predicted by one or more renal severity measures (serum creatinine, 24-h urinary protein excretion, nephrotic syndrome, or duration of prior renal disease), and among those with nonsevere renal disease, with a single disease activity measure (the National Institutes of Health or le Riche index). In general 3 prognostic groups (high, intermediate and low risk) could be identified for each outcome. Our results demonstrate the value of regression tree techniques in studies of prognosis and are compatible with a hypothesis of the interaction of disease activity with organ damage in lupus nephritis.

Adult↗

The efficacy of antimalarials in systemic lupus erythematosus.

The use of antimalarial drugs to treat systemic lupus erythematosus (SLE) is reviewed regarding their value in SLE of mild-to-moderate disease activity, as corticosteroid-sparing agents, and as an adjunctive therapy in severe SLE. A retrospective controlled study of a variety of antimalarials and a randomized discontinuation trial of hydroxychloroquine support the considerable clinical belief that antimalarials are of benefit in mild-to-moderate SLE. Anecdotal reports and the opinion of experienced clinicians suggest that antimalarials permit the use of lower doses of corticosteroids. No controlled study has confirmed a corticosteroid-sparing role for antimalarials, although no controlled study has been conducted specifically to address this hypothesis. The data on antimalarials in severe SLE are scant. Antimalarials are likely effective in at least a subgroup of SLE patients with mild-to-moderate disease activity. Whether these agents are corticosteroid sparing and prevent severe disease exacerbations is unproven. Given the low toxicity of antimalarials, further studies are clearly warranted.

Adrenal Cortex Hormones↗

Reactive fibromyalgia syndrome.

OBJECTIVE: To determine the frequency of a precipitating event occurring prior to the onset of fibromyalgia syndrome, in a consecutive series of patients. Outcome in patients in whom there was a causative factor was compared with that in patients with primary fibromyalgia. METHODS: Records of patients presenting over a 4-year period who fulfilled criteria for fibromyalgia were reviewed, and patients were classified as having reactive fibromyalgia if a specific event prior to the onset of illness could be identified. Outcome features, including employment status and disability compensation, were compared in patients with reactive fibromyalgia versus those with primary fibromyalgia. RESULTS: Twenty-nine of 127 patients (23%) with a primary rheumatologic diagnosis of fibromyalgia reported having trauma, surgery, or a medical illness before the onset of fibromyalgia, and were classified as having reactive fibromyalgia. Patients in this group were more disabled than those with primary fibromyalgia, resulting in loss of employment in 70%, disability compensation in 34%, and reduced physical activity in 45%. CONCLUSION: The development of fibromyalgia after a precipitating event may represent the onset of a prolonged and disabling pain syndrome with considerable social and economic implications.

Employment↗

Diagnosis and treatment of ossification of the posterior longitudinal ligament of the spine: report of eight cases and literature review.

PURPOSE: Ossification of the posterior longitudinal ligament (OPLL) is a common, well-recognized cause of spinal stenosis and myelopathy in Japan. Although also common in whites, especially among the elderly, it has received little scientific attention. We wish to increase awareness of this important cause of myelopathy, and to determine if the clinical characteristics of OPLL are similar in non-Japanese and Japanese patients. PATIENTS AND METHODS: The clinical and radiologic features of eight cases of OPLL are presented. These cases combined with 73 non-Japanese cases gathered from the English literature are contrasted with 2,125 Japanese cases of OPLL. RESULTS: Similarities among non-Japanese and Japanese cases included: (1) male predominance; (2) peak age at onset of symptoms in the sixth decade; (3) clinical presentation, which ranged from asymptomatic to quadriplegia, with progressive or acute onset of neurologic deterioration; (4) greater than 95% localization to the cervical spine, spastic quadriparesis being the most common neurologic presentation; (5) an association with several rheumatic conditions including diffuse idiopathic skeletal hyperostosis (DISH), spondylosis, and ankylosing spondylitis; and (6) neurologic improvement with either conservative or surgical treatment in a significant proportion of patients. Differences between the two groups were minimal and included a higher mean age at onset (although onset in both groups occurred within the sixth decade) and a greater proportion of patients with DISH and with the continuous type of OPLL in the non-Japanese group. CONCLUSION: The clinical characteristics of OPLL are similar in Japanese and non-Japanese patient populations. Increased awareness of this condition, which has potentially devastating neurologic complications, will favorably influence diagnosis, treatment, and outcome.

Adult↗

Steroid interactions affecting metabolic activities of a T-lymphocyte line.

A glucocorticoid sensitive T-lymphocyte cell line (CEM) was used to study in vitro interaction effects of steroidal compounds on their metabolic activity. Mixtures of steroidal hormones and related substances were added to the cells and assessed in short-term culture experiments by the incorporation of 3H dTr. Dose ranges were selected to include the linear portion of the dose-response curve of each of the potentially interactive substances. Evidence for synergy, additivism or antagonism was obtained for each of the various steroid combinations studied using algebraic and geometric calculations.

Androstanols↗

Can experienced clinicians predict the outcome of lupus nephritis?

The ability of four experienced clinicians to predict short-term outcome (serum creatinine level at 1 year) and long-term outcome (renal insufficiency) was evaluated in 87 patients with lupus nephritis. The correlational agreement and the accuracy of their predictions were contrasted with the actual outcomes observed and with statistically generated prognostic regression models. In contrast to previously published data, all four clinicians predicted both short-term outcomes (P < 0.001) and long-term outcomes (P < 0.02) well. The clinicians' predictions approximated that of a statistically generated computer model for both agreement and accuracy for renal function at 1 year. The four clinicians identified nearly identical clinical variables as important in determining prognosis. Provision of biopsy data to the clinicians improved short-term and long-term prediction slightly. The value of the statistical models was 'validated' by demonstrating that three of the four clinical variables identified by the models, but not by the clinicians, could enhance clinical prediction (P < 0.05). In addition, the extent of tubulo-interstitial involvement on biopsy, a predictor that has recently received increased attention, could improve the long-term clinical predictions of all four clinicians (P < 0.05).

Adolescent↗

Response to initial therapy and new onset as predictors of prognosis in patients hospitalized with congestive heart failure.

Clinical predictors of in-hospital fatality were assessed in 191 persons admitted to the Yale-New Haven Hospital Intensive Care Unit with a diagnosis of congestive heart failure. In the 17 (8.9%) patients who died, the most important individual predictors among the presenting clinical features were absence of dyspnea, presence of anterior chest pain or jugulovenous distension, and cardiac severity due to ischemia, valvular disease, or arrhythmia. Two important predictors, largely neglected in previous literature, were a prior history of congestive heart failure and a poor clinical response after 24 h of therapy. Multivariable analysis led to the identification of 6 features (age greater than 70 y, prior history of congestive heart failure, jugulovenous distension, chest pain, cardiac severity, and poor early response to therapy) that could be combined into a simple clinical predictive index. The new index identified 5 prognostic groups with fatality rates of 0, 3.5, 7.4, 19.2, and 85.7 percent. An advantage of the clinical index is the identification of a subgroup of patients, with low risk for fatality, who may not need prolonged treatment in an intensive care unit.

Aged↗

Alpha-1 antitrypsin deficiency and systemic necrotizing vasculitis.

We describe a 42-year-old woman with polyarteritis nodosa characterized by polyarthritis, purpuric rash, mononeuritis multiplex, focal segmental glomerulonephritis and necrotizing arteritis. alpha-1 antitrypsin deficiency was diagnosed incidentally on a liver biopsy. This is the third reported case of systemic necrotizing vasculitis in association with alpha-1 antitrypsin deficiency of the PI ZZ type, and the first to show significant response to cyclophosphamide and steroids.

Adult↗

Ankylosing spondylitis antirheumatic drug trials. I. Effects of standardization procedures on observer dependent outcome measures.

We designed a study to assess the effects of standardization procedures on reducing interobserver variability for outcome measures given in the current Food Drug Administration and European League Against Rheumatism guidelines and others selected from the rheumatology literature. Over 2 days, 6 rheumatologists independently examined 7 patients with ankylosing spondylitis (AS) in predetermined order before and after standardizing their examination techniques. An important and beneficial effect of the standardization procedure was observed on the majority of outcome variables. Such reductions in observer variability have the potential to diminish sample size requirements for AS antirheumatic drug studies.

Adult↗

Ankylosing spondylitis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials.

The calculation of sample size requires knowledge of the standard deviation (SD) of index variables. Unfortunately, there are no published lists of standard deviations and it is exceedingly difficult to locate variance estimates based on relevant populations. We used standardized procedures to determine in 60 patients with ankylosing spondylitis (AS) the SD of key outcome measures recommended in current Food Drug Administration and European League Against Rheumatism guidelines for AS clinical trials. We anticipate that these tables will be useful to clinical researchers in selecting outcome measures as well as for calculating sample size requirements for future clinical studies in AS.

Analysis of Variance↗

Ankylosing spondylitis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--results of a consensus development (Delphi) exercise.

Defining the minimum clinically important difference or delta to be detected in a clinical trial depends on a number of factors including the research hypothesis, patient characteristics, the nature of the intervention and the trial design. In 2 previous studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for clinical trials in ankylosing spondylitis, and thereafter, determined the standard deviation for these outcome measures. In the final component of this series of studies, we have employed a Delphi technique to establish estimates for delta, and calculated the sample size requirements under 2 different conditions of Type I and Type II error probabilities.

Anti-Inflammatory Agents↗

Predictors of one year outcome in lupus nephritis: the importance of renal biopsy.

The short-term prognosis of lupus nephritis was evaluated by assessing serum creatinine 12 months after renal biopsy in 87 patients with lupus nephritis. On univariate analysis, significant clinical and laboratory predictors of this outcome included clinical signs of renal injury (serum creatinine, 24-hour urinary protein, prolonged renal disease, nephrotic syndrome, serum albumin), as well as thrombocytopenia, older age, and coexisting illness or hypertension at the time of biopsy. On renal biopsy, diffuse proliferative nephritis, higher activity, chronicity, or tubulointerstitial scores, or subendothelial or subepithelial electron dense deposits predicted a higher serum creatinine 12 months after biopsy. A clinical predictive model was developed which included as independent predictors serum creatinine, age, platelet count and 24-hour urinary protein. Any one of three biopsy variables added information to the clinical prediction model: a marked quantity of subendothelial deposits (p = 0.02), a higher activity index score (p = 0.02), or the presence of diffuse proliferative lupus nephritis (p = 0.05). However, the relative predictive accuracy of the clinical model did not improve with the addition of any of the biopsy variables. The value of renal biopsy in lupus nephritis is discussed based on the ability of biopsy information to confirm the prognosis, to add new predictive information for a group of subjects, and to improve predictive accuracy for individual patients.

Adolescent↗

Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis.

144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2.5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3.8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15.6 mumols/l and mean arterial blood pressure by 6.27 mmHg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study.

Activities of Daily Living↗