Biomedical subjects
Publications and source records attributed to J Singer.
Many different entities simulating colonic polyps on barium enema examination have been described. Of the extraluminal mimics, round bony structures such as vertebral pedicles are perhaps best known. We describe the cause of a previously undescribed artifact: bone marrow biopsy of the ilium.
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Definitions and classifications proposed for the neuropsychiatric complications of systemic lupus erythematosus (NP-SLE) indicate a wide range of approaches taken by different researchers and clinicians. A meeting of investigators was convened to begin a consensus process for standardizing its classification. We found that the level of agreement among raters on the importance of elements to the diagnosis of NP-SLE increased significantly as indicated by an intraclass correlation coefficient of 0.05 before the conference to 0.60 after the conference. The results of such studies can be used to generate and test the utility of diagnostic criteria for NP-SLE in multicenter trials.
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125I-Labeled recombinant human interleukin-3 (IL-3) was used to study the characteristics and distribution of receptors for IL-3 on human cells. Receptors were found on primary monocytes, on some strains of KG-1 cells, and on pre-B cell lines. Binding was rapid at 37 degrees C, while requiring several hours to reach equilibrium at 4 degrees C. Equilibrium binding studies indicated that IL-3 bound to a single class of high affinity receptor (less than 500 receptors/cell) with a Ka of approximately 1 x 10(10) M-1. Inhibition studies revealed that human granulocyte/macrophage colony stimulating factor partially inhibited the binding of 125I-IL-3 to human monocytes but not JM-1 cells. Additional analysis showed that on KG-1 cells, both IL-3 and GM-CSF partially competed specific binding of heterologous radiolabeled ligand, with approximately equivalent capacities. This competition occurred at both 37 and 4 degrees C. These results suggest heterogeneity in the binding sites for IL-3 and GM-CSF in which a subset of receptors binds only IL-3, a subset only GM-CSF, and another subset can bind both, all with high affinity. Additional heterogeneity was suggested by equilibrium binding of 125I-IL-3 to KG-1 cells which revealed a biphasic Scatchard plot containing a low affinity component not observed on monocytes and JM-1 cells.
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Paraesophageal hernias are relatively rare compared to the more commonly diagnosed sliding hiatus hernia. They tend to be asymptomatic initially, but may gradually enlarge and present with life-threatening complications. The treatment is surgical reduction, preferably as an elective procedure. Computed tomography (CT) clearly demonstrates a paraesophageal hernia through a widened esophageal hiatus, often as an incidental finding, and accurately documents the size, contents, and orientation of the herniated stomach within the lower thoracic cavity. In this report, the CT appearance of 4 patients with paraesophageal hernias is described along with a discussion of this uncommon but important surgical condition.
In recent years quality of life instruments have been featured as primary outcomes in many randomized trials. One of the challenges facing the investigator using such measures is determining the significance of any differences observed, and communicating that significance to clinicians who will be applying the trial results. We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change. Using this approach we have established a plausible range within which the minimal clinically important difference (MCID) falls. In three studies in which instruments measuring dyspnea, fatigue, and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item, when responses were presented on a seven point Likert scale. Furthermore, we have established ranges for changes in questionnaire scores that correspond to moderate and large changes in the domains of interest. This information will be useful in interpreting questionnaire scores, both in individuals and in groups of patients participating in controlled trials, and in the planning of new trials.
To test the relative merits of administering questionnaires with previous responses available (the informed condition) or unavailable (the blind condition), we administered blind and informed versions of a quality of life questionnaire (the Chronic Respiratory Disease Questionnaire, or CRQ) in a randomized, double-blind trial of bronchodilators in chronic airflow limitation. The responsiveness of the two methods, as reflected in the p-values associated with salbutamol and theophylline effects were comparable for three of the four dimensions of the CRQ. The data suggested possible increased responsiveness of the informed method for the emotional function dimension of the questionnaire. Changes in the informed CRQ dyspnea and fatigue dimensions showed stronger correlations with changes in spirometry, 6 minute walk distance, and rating of dyspnea after the walk test than did blind administration. Further, changes in all four CRQ dimensions showed stronger correlations with corresponding global ratings using the informed questionnaire. These results suggest that by letting study subjects see their previous responses the validity of subjective measures of health status in clinical trials can be improved.
The optimal method of assessing the effect of treatment on the day-to-day function of patients with chronic airflow limitation is not established. Therefore, we examined the performance of the Six Minute Walk test, a rating of dyspnea following the test and three different questionnaires measuring dyspnea in daily activities, in a controlled trial of inhaled salbutamol and oral theophylline in 24 patients with primarily fixed chronic airflow limitation. Clinically important and statistically significant effects of salbutamol and theophylline on dyspnea during day-to-day activities were detected by each measure, but the Chronic Respiratory Questionnaire (CRQ) appeared more powerful than either the Oxygen Cost Diagram or the Medical Research Council Dyspnea Questionnaire as modified by the Rand Corporation. Changes in the CRQ dyspnea score showed a higher correlation with changes in spirometry, walk test score, dyspnea following the walk test, and global ratings of dyspnea than did the other two measures. Results of the walk test demonstrated statistically significant salbutamol and theophylline effects, but suggested that no added benefit could be obtained with both drugs; the rating of dyspnea following the walk test, however, was consistent with an additive effect. We conclude that the CRQ is a responsive, valid measure of functional status for clinical trials in chronic lung disease, and that when the six minute walk is used as a measure of outcome, dyspnea following the walk test should be measured.
The results are reported from a multicentered, randomized clinical trial of a physician-delivered smoking cessation intervention package. All physicians attended a four-hour training session during which the rationales for the different aspects of the intervention were discussed, including a detailed description of the proper use of nicotine-bearing chewing gum. Patients were randomized to receive an offer of a prescription of 2 mg of nicotine chewing gum in addition to the basic intervention (n = 111) or the basic intervention alone (n = 112). The basic intervention included advice, setting a date for quitting, self-help materials, and the offer of supportive follow-up visits. Receptionists were instructed to recruit the first two smokers attending the practice each day. One-year smoking cessation was validated by cotinine saliva analysis. The validated three-month sustained abstinence rates at one year were 8.1 percent and 9.8 percent in the gum and no-gum groups, respectively. The 95 percent confidence interval about this difference was -9.3 percent to 6.4 percent. There is no evidence from this study that the offer of 2 mg of nicotine-bearing gum enhances smoking cessation rates when added to a comprehensive intervention offered to all smokers in primary care. Until larger trials are completed, however, the possibility that this dose of nicotine gum may produce small beneficial effects cannot be excluded.
We have developed a measure of subjective health status (quality of life) for patients with inflammatory bowel disease (IBD). Ninety-seven patients with IBD described problems they had experienced as a result of the disease; the 32 most frequent and important items were included in the Inflammatory Bowel Disease Questionnaire (IBDQ). Sixty-one IBD patients were evaluated twice. One month separated the evaluations, at which disease activity indices, the IBDQ, and a number of other questionnaires were administered. Reproducibility studies in 19 stable patients showed improvement in scores, but also a small within-person standard deviation. Responsiveness studies revealed large changes in scores in patients who had improved or deteriorated and suggested that the IBDQ was more responsive than a general health status measure. Responsiveness appeared greater in patients with ulcerative colitis than in those with Crohn's disease. Predicted and observed correlations between changes in IBDQ score and changes in other measures were similar. We conclude that although further testing is required, particularly in examining the relation between changes in the IBDQ and changes in the activity of Crohn's disease, the IBDQ shows promise as a measure of health status for clinical trials in IBD.
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A new technique to evaluate methods for the synthesis of peptides was developed. It is based on the identification and quantitation of peptide by-products by mass spectrometry. Model oligopeptides containing 10 or 20 alanine residues were synthesized by automated solid phase methods using a variety of protocols, and the levels of deletion and insertion peptides were measured by the 252Cf fission fragment ionization time-of-flight spectrometric technique in which the total, unfractionated, synthetic product was deposited on a film of nitrocellulose and analyzed. The introduction of D-alanine at every third residue of the model eliminated peptide conformation problems that led to incomplete reactions in the all L model. Couplings with preformed symmetrical anhydrides in dimethylformamide gave rise to significant levels of both deletion peptides and insertion peptides. The best of the protocols examined was a double coupling of tert-butyloxycarbonyl-alanine by in situ activation with dicyclohexylcarbodiimide in dichloromethane. [D-Ala3,6,9,12,15,18]Ala20-Val was synthesized with an average deletion of only 0.036% per step and an average insertion of only 0.029% per step, which is equivalent to a stepwise yield of 99.93% for the target peptide.
We assessed the impact of three conditions on one-year smoking cessation rates. Physicians in 70 community general practices were randomly allocated by practice to one of three groups: In the usual care group, smoking patients were to receive the care they normally would receive. In the gum only group, physicians were asked to speak to patients about smoking cessation and offer nicotine gum. In the gum plus group, physicians were trained in the experimental intervention. This intervention involved advice to stop smoking, the setting of a quit date, the offer of nicotine gum, and four follow-up visits. Smoking cessation was measured by self-report after one year and validated using saliva cotinine measures. Using a criterion of at least three months of abstinence, 8.8% of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4% and 6.1% of the patients in the usual care and gum only groups, respectively.
The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge. Clozapine, an atypical antipsychotic drug, has long been of scientific interest, but its clinical development has been delayed because of an associated risk of agranulocytosis. This report describes a multicenter clinical trial to assess clozapine's efficacy in the treatment of patients who are refractory to neuroleptics. DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospective, single-blind trial of haloperidol (mean dosage, 61 +/- 14 mg/d) for six weeks. Patients whose condition remained unimproved were then randomly assigned, in a double-blind manner, to clozapine (up to 900 mg/d) or chlorpromazine (up to 1800 mg/d) for six weeks. Two hundred sixty-eight patients were entered in the double-blind comparison. When a priori criteria were used, 30% of the clozapine-treated patients were categorized as responders compared with 4% of chlorpromazine-treated patients. Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale, Clinical Global Impression Scale, and Nurses' Observation Scale for Inpatient Evaluation; this improvement included "negative" as well as positive symptom areas. Although no cases of agranulocytosis occurred during this relatively brief study, in our view, the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients.