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Biomedical subjects

V Steen

Publications and source records attributed to V Steen.

15 recordsLinked to original sources
PubMed2005

Factors related to oral hygiene in persons with scleroderma.

OBJECTIVES: The purpose of this study was to assess potential risk factors for the development of poor oral hygiene and increased dental caries in individuals with scleroderma. METHODS: Twenty-two subjects with scleroderma participated in this study. All subjects were examined with the Patient Hygiene Performance (PHP) Index, which assesses the extent of plaque and debris over a tooth surface. In addition, oral aperature, xerostomia and dominant upper extremity strength, motion, skin thickness, and dexterity were measured. RESULTS: None of the subjects had good or excellent hygiene. Fifteen subjects had fair oral hygiene and seven subjects had poor oral hygiene as measured by the PHP Index. Significant differences were seen between these two groups for oral aperture, percentage of teeth with caries, skin thickness, dexterity and finger flexion. Dexterity and joint motion correlated significantly with the number of decayed surfaces and number of caries. Oral aperture correlated with the PHP Index and the number of dental caries. CONCLUSIONS: Subjects with poor oral hygiene required more time to complete manual dexterity task and had decreased hand strength and joint motion. Moreover, these same subjects had more contractures, scars, ulcers, and higher skin scores (more disease activity) than subjects in the fair hygiene group. In addition to frequent dental exam and routine cleaning, dental personnel may want to consider exercises to increase oral aperature and investigate toothbrush and dental floss selection used by persons with scleroderma.

Dental Caries↗
PubMed2001

The Disability Index of the Health Assessment Questionnaire is a predictor and correlate of outcome in the high-dose versus low-dose penicillamine in systemic sclerosis trial.

OBJECTIVE: To explore the clinical implications of a score of > or =1.0 on the Disability Index of the Health Assessment Questionnaire (HAQ DI) at the first patient visit, and to examine the implications of improvement in HAQ DI score over 2 years in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma. METHODS: SSc skin and visceral involvement was assessed in 134 SSc patients with diffuse scleroderma (mean +/- SD disease duration of 10 +/- 4 months) when they entered a multicenter drug trial and again 2 years later. Mortality and the occurrence of scleroderma renal crisis were assessed for a mean +/- SD of 4.0 +/- 1.1 years. Logistic and linear regression analyses were used to examine the relationship of the baseline HAQ DI score to morbidity, mortality, and visceral involvement, as well as the relationship of changes in the HAQ DI score to changes in physical examination, laboratory, and functional variables over 2 years. RESULTS: A baseline HAQ DI score of > or =1.0 was predictive of mortality (odds ratio 3.22, 95% confidence interval 1.097-9.468) over 4 years. Multivariate linear regression demonstrated that a model which included the erythrocyte sedimentation rate at baseline (P = 0.005) and changes at 2 years in the swollen joint count (P = 0.002), total skin score (P = 0.005), and white blood cell count (P = 0.005) best explained the change in HAQ DI score over 2 years (R2 = 0.528). The HAQ DI score and total skin score at baseline were highly correlated (correlation coefficient 0.368), as were changes in the HAQ DI score and the total skin score over 2 years (correlation coefficient 0.492). Although the HAQ DI score was heavily influenced by hand dysfunction at baseline and at 2 years, improvement (reduction) in the HAQ DI score over 2 years was related to factors other than hand dysfunction. CONCLUSION: A baseline HAQ DI score of > or =1.0 predicted mortality over 4 years. Improvement in the HAQ DI score in these patients with diffuse scleroderma was associated with improvement in skin thickening, hand function, oral aperture, lung function, signs of arthritis, serum creatinine level, and the investigator's global assessment of improvement. The HAQ DI is a self-administered questionnaire that SSc patients can complete easily and rapidly and that gives the practicing physician important information about prognosis, patient status, and changes in disease course over time.

Disability Evaluation↗
PubMed2001

Effects of the American College of Rheumatology systemic sclerosis trial guidelines on the nature of systemic sclerosis patients entering a clinical trial.

OBJECTIVES: To compare the systemic sclerosis (SSc) patients entered into the d-penicillamine trial with SSc patients entered into previous controlled SSc trials. It was hypothesized that the d-penicillamine trial patients, who conformed to the American College of Rheumatology (ACR) guidelines for clinical trials in SSc were different from patients entered into previous trials. METHODS: Patients entering a double-blind, randomized trial of low- vs high-dose d-penicillamine were described carefully and completely. Their characteristics were then compared with previously published data on SSc and its treatment. RESULTS: One hundred and thirty-four patients had early [mean duration 9.5 (s.d. 4.2) months], diffuse [skin score 21 (8)] disease. Organ involvement in the patients was as follows: pulmonary 54%, cardiac 20%, joints 38%, muscular 20%. Thirty-three per cent had mild proteinuria and 13% were hypertensive when first seen. Compared with patients in most previous studies, these SSc patients had earlier disease and uniformly had diffuse disease. They had less muscular involvement, less dyspnoea, less abnormal pulmonary function and less cardiac and less renal involvement than patients in earlier studies. CONCLUSIONS: The use of the new ACR guidelines for SSc trials may change the nature of patient populations entering future studies.

Adult↗
PubMed2000

Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Systemic sclerosis (scleroderma) is characterized by fibrosis of the skin, vasculature, and internal organs. OBJECTIVE: To assess the efficacy, safety, and dose-response effect of recombinant human relaxin in patients with scleroderma. DESIGN: Multicenter, parallel-group, randomized, double-blind, placebo-controlled trial. SETTING: Academic referral centers. PATIENTS: 68 patients who had had stable, diffuse scleroderma (moderate to severe) for less than 5 years. INTERVENTION: Recombinant human relaxin, 25 or 100 microg/kg of body weight per day, or placebo administered by continuous subcutaneous infusion over 24 weeks. MEASUREMENTS: Modified Rodnan skin score was the primary efficacy measure. Secondary measurements were pulmonary function, the Health Assessment Questionnaire, and other measures of scleroderma that reflected fibrosis. RESULTS: Patients who received 25 microg/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (mean change, -3.6 at 4 weeks [P = 0.021], -7.5 at 12 weeks [P < 0.001], and -8.7 at 24 weeks [P = 0.040]). Similar trends were noted in other outcome measures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 microg/kg of relaxin per day did not differ from those who received placebo. Drug-related adverse events included menometrorrhagia, reversible anemia, and complications of the subcutaneous drug administration system (site irritation and local infection). CONCLUSIONS: Twenty-four weeks of recombinant human relaxin, 25 microg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma.

Adolescent↗
PubMed1999

High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial.

OBJECTIVE: To test the hypothesis that systemic sclerosis (SSc) patients taking high-dose D-penicillamine (D-Pen) would have greater softening of skin, lower frequency of renal crisis, and better survival than patients taking low-dose D-Pen. METHODS: Seventeen centers enrolled 134 SSc patients with early (< or =18 months) diffuse cutaneous scleroderma into a 2-year, double-blind, randomized comparison of high-dose D-Pen (750-1,000 mg/day) versus low-dose D-Pen (125 mg every other day). All 134 patients were followed up for a mean+/-SD of 4.0+/-1.1 years to assess the frequencies of new-onset scleroderma renal crisis (SRC) and mortality. RESULTS: Sixty-eight patients completed 24 months of drug treatment. The course of the modified Rodnan skin thickness score in the 32 high-dose and the 36 low-dose D-Pen completers was not different at 24 months: the skin score dropped 4.8+/-10.3 (mean+/-SD) units in the high-dose group and 6.9+/-8.4 units in the low-dose group (P = 0.384 by t-test; favoring low-dose D-Pen) from 20.4+/-10.3 in the high-dose and 19.9+/-6.6 in the low-dose D-Pen group at study entry. The incidences of SRC and mortality were not different (P > 0.38 by Cox proportional hazards and by chi-square test) in the 66 high-dose patients (8 developed SRC and 8 died) compared with the 68 low-dose patients (10 developed SRC and 12 died). Of the 20 adverse event-related withdrawals, 80% occurred in the high-dose D-Pen group. CONCLUSION: The course of the skin score and the frequencies of SRC and mortality in the high-dose D-Pen group were not different from those in the low-dose D-Pen group. Eighty percent of the adverse event-related withdrawals occurred in the high-dose D-Pen patients. Although this study cannot answer the question of whether low-dose D-Pen is effective, it does suggest that there is no advantage to using D-Pen in doses higher than 125 every other day.

Adult↗
PubMed1999

Correlates of the disability index of the health assessment questionnaire: a measure of functional impairment in systemic sclerosis.

OBJECTIVE: To evaluate functional impairment in systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma at the time of entry into a trial of a therapeutic intervention (D-penicillamine). METHODS: The 20-item Disability Index of the Health Assessment Questionnaire (HAQ-DI) was administered to 134 patients as they entered a multicenter trial of high-dose versus low-dose D-penicillamine. All patients had diffuse SSc of < 18 months' duration. SSc patients who had severe organ system involvement and recent renal crisis and who were receiving prednisone > 10 mg/day were excluded from entry. Logistic regression modeling was used to examine the relationship of HAQ-DI scores to SSc skin and organ system involvement. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to estimate effects. RESULTS: The mean (+/-SD) HAQ-DI score at entry was 1.04 +/- 0.67. Fifty-three percent of patients had HAQ-DI scores > or = 1.0 (signifying moderate-to-severe functional impairment). Multivariate logistic regression demonstrated that impaired fist closure > or = 23 mm (OR 4.24, 95% CI 1.68-10.70), reduced handspread < or = 175 mm (OR 4.5, 95% CI 1.80-11.24), joint tenderness count > or = 1.0 (OR 2.93, 95% CI 1.16-7.40), age > or = 43 years (OR 2.44, 95% CI 1.01-5.95), platelet count > or = 330,000/mm3 (OR 2.30, 95% CI 0.96-5.57), and female sex (OR 2.43, 95% CI 0.77-7.73) were the most important correlates of HAQ-DI scores > or = 1.0. CONCLUSION: Increased HAQ-DI scores at baseline were correlated with reduced fist closure, reduced hand-spread, elevated platelet count, presence of tender joints, older age, and female sex. The most important contributor to functional impairment was hand dysfunction. Even within the first 18 months after SSc onset, moderate-severe functional impairment (HAQ-DI scores > or = 1.0) was frequent (53%) in this group of diffuse SSc patients. In early diffuse SSc, the self-administered HAQ-DI is therefore a valuable assessment of function that correlates with objective physical and laboratory measures of SSc disease involvement. Abnormal HAQ-DI scores may support patient claims of functional impairment, help to focus physician attention on implementing measures to reduce functional impairment, and be useful in reflecting the disease course over time.

Adolescent↗
PubMed1998

Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer.

PURPOSE: This phase I study was performed to evaluate the safety and pharmacokinetics of escalating doses of Marimastat (British Biotech, Inc, Oxford, United Kingdom) in patients with advanced malignancies and to determine the phase II recommended dose to be used in subsequent studies. PATIENTS AND METHODS: A standard phase I design was used in this study, in which consecutive groups of three patients were treated with escalating doses of the study drug. Marimastat was administered orally at 25, 50, or 100 mg twice daily to consecutive groups of patients with advanced lung cancer. An additional three patients were added at the highest dose studied (100 mg orally twice daily) to assess whether the inflammatory polyarthitis observed at that dose level can be prevented by a concurrent administration of nonsteroidal antiinflammatory drugs (NSAIDS) and/or low-dose corticosteroids. Blood was drawn for safety monitoring, pharmacokinetic analysis, and plasma levels of metalloproteinase (MMP)-2 and MMP-9 (determined by zymography). A total of 12 patients were studied. RESULTS: The most significant toxicity at the highest dose studied (100 mg orally twice daily) was a symptomatic inflammatory polyarthritis that persisted for up to 8 weeks after discontinuation of the study drug and was dose-limiting. The estimated plasma elimination half-life of Marimastat was 4 to 5 hours. The mean maximum concentration (Cmax) at a reasonably well-tolerated dose (50 mg orally twice daily) was 196 ng/mL and was reached within 1 to 2 hours (Tmax) after administration. Areas under the curve (AUC) tended to correlate with the dose of Marimastat. Zymographic analysis of peripheral-blood ratios of activated proenzymatic forms of MMP-2 and -9 did not show any consistent patterns of change in MMP levels or in a degree of their activation during the course of treatment. CONCLUSION: Marimastat was well absorbed from the gastrointestinal tract, with high levels of the study drug detected in plasma within hours after drug administration. Plasma concentrations of Marimastat achieved at dose levels 2 and 3 (50 mg and 100 mg orally twice daily) were substantially higher than those required for MMP inhibition in vitro. The dose-limiting toxicity (DLT) was severe inflammatory polyarthritis, which seemed to be a cumulative toxicity.

Administration, Oral↗
PubMed1997

Small fiber neuropathy and vasculitis.

Vasculitis-associated neuropathy usually presents as multiple mononeuropathies or sensorimotor polyneuropathies that affect large nerve fibers; painful small fiber sensory neuropathy has not previously been described in association with vasculitis. This report describes 2 patients with small fiber neuropathy in whom vasculitis was found to be present. Patients with small fiber neuropathy for which no other cause has been identified should be evaluated for the presence of vasculitis.

Aged↗
PubMed1996

Lack of association between augmentation mammoplasty and systemic sclerosis (scleroderma).

OBJECTIVE: To examine the possible association between augmentation mammoplasty and systemic sclerosis (SSc; scleroderma). METHODS: Eight hundred thirty-seven women with a clinical diagnosis of SSc, recruited as a volunteer sample from 3 university-based, tertiary care scleroderma clinical research centers, and 2,507 race-matched local control women, recruited by the technique of random-digit-dialing and frequency-matched on age, completed a questionnaire providing data on history of augmentation mammoplasty, including possible complications of the procedure. The odds ratio (OR) and 95 percent confidence interval (95% CI) for the association of augmentation mammoplasty with SSc were estimated by multivariate logistic regression analysis with adjustment for age, race and center, and by conditional logistic regression analysis with adjustment for age. RESULTS: Eleven (1.31%) of the 837 cases reported a history of augmentation mammoplasty prior to diagnosis of SSc, compared with 31 (1.24%) of the 2,507 controls. The adjusted OR from the unmatched analysis was 1.07 (95% CI 0.53-2.13), while that from the matched analysis was 1.11 (95% CI 0.55-2.24). CONCLUSION: These results fail to demonstrate a significant association between augmentation mammoplasty and SSc, and are consistent with those reported from other epidemiologic studies.

Adult↗
PubMed1995

Prevalence of self-reported physician-diagnosed systemic lupus erythematosus in the USA.

The objective of this study was to estimate the prevalence of self-reported physician-diagnosed systemic lupus erythematosus (SLE) in the USA. During the conduct of an epidemiologic study of systemic sclerosis (scleroderma), 16 607 randomly selected telephone numbers in the continental USA were called to recruit controls. All potentially eligible women were asked 'Have you ever been told by a doctor that you have lupus or SLE'? Of 4034 women aged 18 and above who completed telephone screening, 15 stated they had a physician diagnosis of SLE, corresponding to a prevalence of 372 cases per 100 000 (95% confidence intervals: 208, 614). After review of available medical records in six cases, however, the prevalence of 'validated' SLE was revised to 124 cases per 100 000 (95% confidence intervals: 40, 289). In conclusion, these data suggest that the prevalence of SLE in the USA may be up to three to 10-fold greater than previously estimated. Based on 1990 census data, we would project that over 275 000 women aged 18 and above have SLE in the USA.

Adolescent↗
PubMed1992

Lower extremity amputation in scleroderma.

Scleroderma or Systemic Sclerosis (SSC) is a disorder characterized by fibrosis of the skin and multiple internal organs. The pathological lesion is a triad of small artery intimal proliferation, medial thinning and adventitial scarring. Autoamputation of fingers and toes is often seen, but only a few cases of limb amputation in scleroderma patients have been reported. The Pittsburgh Scleroderma databank includes 1,030 patients with SSC. Among these were seven patients who sustained lower limb amputation. There were four patients with the CREST variant of SSC, two with diffuse scleroderma, and one who had SSC/rheumatoid arthritis/polymyositis overlap who sustained limb amputation. Of the seven, three were male and five had a significant smoking history. Ages ranged from 46 to 71 years. All patients underwent amputation for nonhealing ulcerations. No problems with postoperative wound healing were seen. Pathologic changes typical of SSC in addition to atherosclerotic peripheral vascular disease were described in one case. Three patients were successfully fitted with prostheses and became independent ambulators. Four patients could not be fitted with prostheses. No skin problems were reported related to prosthetic use. Our review demonstrates that SSC patients who undergo amputation can become successful prosthetic users and should be considered for prosthetic prescription.

Aged↗
PubMed1991

Treatment of systemic sclerosis.

The last few years have brought a resurgence in interest in managing systemic sclerosis. In the past year, there have been reports of small series of patients and several well-designed, double-blind, controlled trials. Treatment has been directed at a variety of potential pathogenic mechanisms. Stanazol, iloprost, plasmapheresis, thyroxine, and calcitonin were felt to have positive effects on vascular aspects of disease, ie, Raynaud's phenomenon. Immune-mediated treatment using antithymocyte and antilymphocyte globulin, cyclosporine, and methotrexate were encouraging in a small number of patients, but controlled studies of plasma exchange, extracorporeal phototherapy, and 5-fluorouracil were not very exciting. Changing fibroblast function was used with some success in some patients with D-penicillamine and interferon gamma, but not ketotifen. A very dramatic improvement in the survival of renal crisis occurred with the use of angiotensin-converting enzyme inhibitor. Hopefully, this improvement in survival will also occur in the other visceral abnormalities. All this activity in the therapy of systemic sclerosis will certainly lead to improvement in the overall management of disease.

Calcitonin↗
PubMed1990

Functional and phenotypic analysis of T lymphocytes cloned from the skin of patients with systemic sclerosis.

Activated T lymphocytes often accumulate in the lower dermis of patients with systemic sclerosis (scleroderma) and may play a role in the development of dermal fibrosis. We propagated and cloned these cells directly from skin biopsies in four of eight cases of early, untreated systemic sclerosis with diffuse scleroderma. The cloning frequency estimates were f = 0.20 and f = 0.48 for T cells derived from the skin of two patients versus f = 0.68 and f = 0.96 for autologous blood T lymphocytes. All but one of 24 skin-derived scleroderma clones were CD4+. Clonal analyses performed with CD4+ clones from patients and normal controls showed that all but one skin-derived clones synthesized either interferon-gamma (60%), glycosaminoglycan-stimulatory factor (26%) or both (9%) when induced in vitro by a mitogen, concanavalin A, but not by autologous dermal fibroblasts. In contrast, blood-derived clones had a different functional phenotype. All skin-derived clones produced tumour necrosis factor-alpha. Our results demonstrate that T lymphocytes obtained from the skin of patients with systemic sclerosis synthesized cytokines which could modulate functions of human dermal fibroblasts.

Adult↗