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T Pincus

Publications and source records attributed to T Pincus.

At least 181 records · Page 10Linked to original sources

Further evidence for the lack of association between acetylator phenotype and systemic lupus erythematosus.

An association between host acetylator phenotype and idiopathic systemic lupus erythematosus (SLE) has been sought for over a decade, without a definitive result. We have observed that the frequency of the slow acetylator phenotype was similar in 64 patients with idiopathic SLE (38%), 60 healthy volunteers (50%), and 52 non-SLE medical service patients (44%). The slow acetylator phenotype was not more frequent among subgroups of the SLE patients defined by demographic features or specific manifestations of disease. Our results, as well as a majority of previously published results, do not provide evidence for an association between acetylator phenotype and idiopathic SLE.

Acetylation↗

Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus.

Oxidative metabolism in patients with systemic lupus erythematosus (SLE) was studied using the antihypertensive drug, debrisoquine. The metabolism of this drug to its principal metabolite, 4-hydroxydebrisoquine, is catalyzed by a discrete isozyme of cytochrome P-450. The extent of this reaction exhibits genetic polymorphism, with 2 phenotypes, "poor metabolizers" and "extensive metabolizers," discernible in the normal population. We observed the poor metabolizer debrisoquine phenotype in 9 of 42 patients with idiopathic SLE (21%), in contrast with 12 of 147 healthy volunteers (8%), which is a significant difference in frequency (P less than 0.04). These data provide further evidence for altered oxidative metabolism in SLE and support the concept that genetic differences in oxidative metabolism of endogenous compounds, such as sex steroid hormones, or of xenobiotics might influence susceptibility to SLE.

Adult↗

Elevated MMPI scores for hypochondriasis, depression, and hysteria in patients with rheumatoid arthritis reflect disease rather than psychological status.

The Minnesota Multiphasic Personality Inventory (MMPI) scales for Hypochondriasis, Depression, and Hysteria were studied in patients with rheumatoid arthritis (RA). The RA patients showed elevated scores on these scales, and these results are similar to those reported in each of 6 published studies. The elevated MMPI scale scores can be explained largely by 5 "disease-related" MMPI statements which met 2 criteria: they were among 11 of the 117 MMPI statements that two-thirds of rheumatologists predicted would be RA-associated; and RA patients and normal subjects differed significantly in their responses to these statements. The responses of RA patients and normal subjects to most other statements in the MMPI Hypochondriasis, Depression, and Hysteria scales were quite similar. In RA patients, responses to "disease-related" statements were correlated with results of measures of disease activity, which indicates that responses to these MMPI items reflect the severity, as well as the presence, of RA. These findings suggest that new criteria are needed for validation of the MMPI as a clinical tool for the recognition of hypochondriasis, depression, and hysteria in a patient who has RA.

Arthritis, Rheumatoid↗

Left ventricular dysfunction induced by cold exposure in patients with systemic sclerosis.

Raynaud's phenomenon and cardiac abnormalities are frequent in patients with systemic sclerosis. Radionuclide ventriculograms were obtained in 16 patients with Raynaud's phenomenon and systemic sclerosis or the related CREST syndrome and in 11 normal volunteers in order to evaluate changes in left ventricular function that might be induced by exposure to cold. Left ventricular regional wall motion abnormalities developed in nine of 16 patients during cooling compared with only one of 11 control subjects, despite a comparable rise in mean arterial pressure (p less than 0.02). The abnormalities occurred in seven of 11 patients with systemic sclerosis, one of four with CREST syndrome, and one with Raynaud's disease. To test the potential protective effect of nifedipine, radionuclide ventriculograms were then obtained during cooling after sublingual nifedipine (20 mg). Only five of 13 patients had wall motion abnormalities, and the severity of the abnormalities was significantly less than during the first cooling period (p = 0.03). Five of eight patients who had cold-induced wall motion abnormalities during the first cooling period had none after nifedipine, whereas two other patients demonstrated small abnormalities only during the second cooling period after treatment with nifedipine. It is concluded that cold induces segmental myocardial dysfunction in patients with systemic sclerosis and that nifedipine may blunt the severity of this abnormal response.

Adult↗

Effects of arthritis on wage earnings.

Arthritis is the most frequently reported health condition in the working-age population, reported by nearly one quarter of the age 45 to 64 population in the 1978 Social Security Survey of disability and work. An economic model of earnings, which controls for differences in socioeconomic characteristics and other health conditions, indicates that arthritis is responsible for an annual loss of approximately $17 billion in wage earnings in the United States.

Adult↗

Observer variation in quantitative assessment of rheumatoid arthritis. Part I. Scoring erosions and joint space narrowing.

Six observers, including two bone and joint radiologists, two general radiologists, and two senior radiology residents, compared scores to quantitate radiographic findings in the hands and wrists of patients with rheumatoid arthritis. In the scoring system used, erosions and joint-space narrowing are graded separately. This scoring system differs from other methods in that equivocal findings are not scored, while ankylosis, subluxation, and dislocation are scored, and data from postoperative joints are included. Total radiographic scores were highly significantly correlated for all observers (R = .908-.958, P less than .001), as were subtotal scores for erosions (R = .723-.931, P less than .001) and joint-space narrowing (R = 0.843-0.966, P less than .001). Analysis of proximal interphalangeal, metacarpophalangeal, and wrist-joint scores showed highly significant correlations for all observers in each location. Highly significant correlations were found among three separate readings of two bone and joint radiologists (R = .950-.961, P less than .001). This scoring system provides highly consistent and reproducible results, even in the hands of less experienced observers.

Analysis of Variance↗

Formal education as a marker for increased mortality and morbidity in rheumatoid arthritis.

Increased mortality and morbidity was seen in association with lower formal educational levels in 75 rheumatoid arthritis (RA) patients over 9 years. Nine of the 20 patients with 8 or fewer years of education had died, compared to 10 of 34 with 9-12 years of education, and only one of 21 with more than 12 years of education. Among survivors with functional capacity data available from baseline and 9 year review, declines greater than 20% were seen in 8 of 10, 13 of 21, and 9 of 19 patients in the three education categories. Overall, 79% of grade-school educated, 43% of high-school educated, and 20% of college-educated patients had either died or declined more than 50% in functional capacity. Patients of different formal educational levels were similar at baseline in age, duration of disease, measures of functional capacity, number of involved hand joints, number of severe radiographic changes, use of gold, oral corticosteroids or other therapies, and associations between formal educational level and disease course are not explained by these variables. Formal educational level appears a simple quantitative marker which identifies a surrogate or composite variable associated with increased mortality and morbidity in RA.

Activities of Daily Living↗

The measurement of helplessness in rheumatoid arthritis. The development of the arthritis helplessness index.

We describe the development of the Arthritis Helplessness Index (AHI), a self-report instrument designed to measure patients' perceptions of loss of control with arthritis. The participants in this research were 219 patients with rheumatoid arthritis (RA) who completed a quantity of mailed materials, including the AHI, functional measures and other psychological scales. Significant evidence of reliability and validity of the AHI was found. Greater helplessness correlated with greater age, lesser education, lower self-esteem, lower internal health locus of control, higher anxiety, and depression, and impairment in performing activities of daily living using a health assessment questionnaire. Over one year, changes in helplessness correlated with changes in difficulty in performing activities of daily living. The AHI appears to be a useful measure for further studies in RA and a valuable clinical tool in monitoring the psychological status of patients with RA.

Adolescent↗

Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years.

Seventy-five patients with rheumatoid arthritis (RA) were reviewed 9 years after an extensive evaluation which included quantitative measures of functional capacity. These patients had received multiple intraarticular injections of thiotepa with corticosteroids early in their course, but appear demographically and functionally similar to other RA patients who had not received this therapy. Severe morbidity was seen over the 9-year period in the 55 surviving patients, including significantly lower overall functional capacity in 92% of patients studied, lower grip strength in 93%, and longer button test results in 84%. Work disability occurred in 85% of patients under age 65 who had been working full-time at disease onset. There was increased mortality at the 9-year review, similar to most reported series of RA patients from referral centers; however, a significant increase in neoplasia, which was of concern because of the use of intraarticular thiotepa, was not seen. In terms of functional capacity, including responses to questions about ability to perform activities, walking time, and the button test, those patients who had died prior to review had significantly lower baseline values than did those who survived. Of the 75 patients, 20 had died and 51 had lost significant functional capacity over a 9-year period, documented by quantitative measures of functional capacity.

Activities of Daily Living↗

Occult systemic lupus erythematosus in elderly men.

Systemic lupus erythematosus (SLE) is often not suspected in elderly men with a debilitating illness, particularly when pleuropericarditis is not prominent. Five elderly men with SLE were initially seen with a systemic illness, marked by fever, weight loss, and arthritis. The diagnosis of SLE was established after considerable delay with extensive diagnostic evaluations and was supported by the presence of DNA antibodies in four patients. Treatment with corticosteroids was effective in three patients. Early testing for DNA antibodies may be cost effective in the evaluation of the elderly patient with a debilitating illness.

Age Factors↗

Assessment of patient satisfaction in activities of daily living using a modified Stanford Health Assessment Questionnaire.

Patient satisfaction in performing activities of daily living (ADL) was assessed by using a self-administered questionnaire modified from the Stanford Health Assessment Questionnaire (HAQ). The HAQ includes questions to determine a patient's degree of difficulty and need for help and assistive devices in ADL. A modification of the HAQ (MHAQ) was developed to include questions concerning perceived patient satisfaction regarding the same ADL, along with perceived change in degree of difficulty. In order to add additional questions while maintaining the length of the questionnaire in a format suitable in routine care, the number of ADL included in the MHAQ was reduced from 20 to 8. Information regarding degree of difficulty derived from 8 questions in the MHAQ is comparable with that derived from 20 questions in the HAQ. The response of a patient that a specific activity is associated with difficulty in functional capacity was not inevitably associated with the absence of patient satisfaction; 43.7% of patients responding "with some difficulty" and 19.1% of patients responding "with much difficulty" expressed satisfaction with their functional capacity. A major determinant of expression of patient satisfaction was perceived change in difficulty: 81.4% of patients noting that their function was "less difficult now," in contrast to 16.9% of patients responding "more difficult now," expressed satisfaction. These studies suggest that data regarding patient satisfaction and perceived change in difficulty can be assessed to more completely characterize patients' functional status in ADL.

Activities of Daily Living↗

Evidence that retrovirus expression in mouse spleen cells results from B cell differentiation.

Induction of endogenous retroviral proteins from spleen cells exposed to lipopolysaccharide (LPS) was studied in individual cells in relation to polyclonal B cell differentiation. After 4 days of culture with LPS, 30 to 40% of cells in many mouse strains stained for cytoplasmic mu heavy chains. A smaller number of lymphoid cells stained for cytoplasmic viral proteins, with a characteristic proportion for each strain, including 21% of lymphoid cells of AKR mice, 125 of DBA/2 cells, 7% of C57BL/6 cells, and 2% of BALB/c cells. More than 75% of retrovirus-positive cells were also mu-chain-positive in all strains. Cells from young (3- to 8-week-old) and old (43- to 46-week-old) mice of several strains showed similar proportions of retrovirus-positive cells typical for each strain, without differences at different ages. The induction of retrovirus proteins, as well as mu-chains, by LPS was markedly inhibited by goat anti-mu-chain antibody added to the culture medium (10 to 100 micrograms/ml). These data suggest that retrovirus induction may result from B cell differentiation.

Animals↗

Plasmapheresis in systemic lupus erythematosus: a cautionary note.

Plasmapheresis was used as the sole treatment modality in 4 patients with systemic lupus erythematosus. The presence of circulating immune complexes in this group of patients was not predictive of response to plasmapheresis. Lymphocytotoxic antibody levels fell in 3 of the 4 patients, and no consistent changes in T lymphocytes, T lymphocyte subsets, complement, or immunoglobulin levels were observed. Followup during the subsequent 6 months showed deterioration in clinical and laboratory parameters in all 4 patients, and the protocol was discontinued. Plasmapheresis without concomitant therapy may be detrimental to certain patients with systemic lupus erythematosus.

Adult↗

Heterogeneity of polyclonal B-cell activity in systemic lupus erythematosus.

We have examined the abnormal in vitro polyclonal B-cell activity observed in patients with systemic lupus erythematosus (SLE) using a staphylococcal protein A reverse hemolytic plaque assay. We have found the mean level of circulating immunoglobulin secreting cells (IgSC) in 30 SLE patients to be significantly elevated compared to that of normal subjects, although half of the SLE patients fell within the normal range. Cultures of SLE peripheral blood mononuclear cells (MC) stimulated with optimal or suboptimal doses of pokeweek mitogen (PWM) showed depressed IgSC responses as a group, compared to cultures of normal MC (p less than 0.005), although a fraction of patients had normal responses. In 11 of 30 SLE patients, IgSC were less numerous in stimulated than in unstimulated cultures, whereas all normal subjects showed augmented IgSC response in stimulated cultures (p less than 0.005). Impaired in vitro response was not due to (1) altered PWM induced activation, (2) aberrant kinetic response or (3) decreased survival in culture of SLE MC. Of note, altered IgSC responses did not appear to reflect antecedent in vivo B-cell activation. Numbers of circulating IgSC and PWM-induced IgSC were not correlated with clinical and serological indices of disease activity or status of corticosteroid therapy. These data indicate considerable heterogeneity with respect to polyclonal B-cell activity in SLE, and provide further insight into the relationships of in vivo and in vitro B-cell activation in patients with this disease.

Antibody-Producing Cells↗

Evidence that endogenous ecotropic virus is not expressed in AKR thymic lymphoid cells of chimeric hosts.

AKR/J thymocytes derived from fetal liver cells do not produce virus when they differentiate in lethally irradiated B10.K mice, whereas spleen and bone marrow cells are virus producers. In contrast, B10.K thymocytes that differentiate in lethally irradiated AKR mice become virus producers. These results suggest that infection of the thymus in AKR mice is initiated in thymic stromal cells.

Animals↗