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P J Clements

Publications and source records attributed to P J Clements.

At least 37 records · Page 2Linked to original sources
PubMed1997

Choosing appropriate patients with systemic sclerosis for treatment by autologous stem cell transplantation.

Systemic sclerosis (SSc) with diffuse cutaneous scleroderma and visceral organ involvement is associated with considerable morbidity and mortality almost from its inception. Since the risk of accrual and progression of skin and organ complications is greatest in the first few years of SSc, the best opportunity for significantly modifying the course of SSc (prolonging survival and/or preventing or lessening the progressivity of organ involvement) is probably limited to the first 3 to 4 years. Transplantation of autologous stem cells (ASCT), after immune ablation of the host, has the potential to modify the disease course. Even though the mortality risk of ASCT is low (< 2% mortality in the first year), the mortality risk of the disease being treated must justify that risk. We suggest that patients with diffuse Sc of short duration (< 3 years from the first non-Raynaud sign/symptom) with evidence of at least mild involvement of heart, lung, or kidney, have sufficiently severe disease to warrant ASCT. In contrast, we suggest that patients with severe/end stage organ involvement have progressed to the point where ASCT will not be helpful in improving that degree of organ involvement.

Adult↗
PubMed1996

Recent advances in understanding the spectrum of canine generalised progressive retinal atrophy.

Canine generalised progressive retinal atrophy (gPRA) is a large and ever-increasing collection of naturally occurring, heterogeneous, progressive disorders. Most are inherited in an autosomal recessive manner and new, breed-specific forms continue to be described. The gPRAs cause photoreceptor cell death and subsequent retinal degeneration, culminating in blindness. In humans, similar inherited retinal dystrophies are recognised as retinitis pigmentosa and macular dystrophy. Molecular biological studies have revealed disease-causing mutations in several genes in humans and also in mice with retinal dystrophies. Recently, molecular genetic techniques have identified the cause of one form of gPRA in Irish setters while important candidate genes have been investigated in other breeds. Identification of mutations responsible for different forms of gPRA allows carrier and predegenerate animals to be detected using DNA-based tests. Such genetic tests will greatly facilitate the eradication of these diseases in different breeds.

Animals↗
PubMed1995

Genital tract abnormalities and female sexual function impairment in systemic sclerosis.

OBJECTIVE: Our purpose was to determine the involvement of the female genital tract and its functional consequences on menstrual and sexual aspects in systemic sclerosis. STUDY DESIGN: Sixty women with systemic sclerosis and 23 age- and disease duration-matched women with either rheumatoid arthritis or systemic lupus erythematosus were surveyed with a comprehensive questionnaire addressing problems before and after disease onset. Fourteen systemic sclerosis patients also had gynecologic evaluations. RESULTS: Vaginal dryness (71%), ulcerations (23%), and dyspareunia (56%) were significantly more frequent in patients with systemic sclerosis after disease onset than before and also in comparison with control subjects. Vaginal tightness and constricted introitus were present in 5 of 60 systemic sclerosis patients. More than half of systemic sclerosis patients reported a decrease in the number (p = 0.04) and intensity (p = 0.02) of orgasms, compared to < 20% of control subjects. The desire and frequency of coitus and the sexual satisfaction index were impaired equally in each group. Skin tightness, reflux-heartburn, and muscle weakness adversely affected sexual relations more in systemic sclerosis than in control subjects. On gynecologic examination 5 of 11 systemic sclerosis patients had small-sized uteri, and 3 of them had early menopause at 29, 38, and 43 years. Seven of 16 (44%) women with systemic sclerosis, compared with 6% of normal women in the United States, attained natural menopause before age 45. CONCLUSIONS: Although impairment in various indexes of sexual function occurs in a number of autoimmune diseases, decreased orgasmic function appears to be limited to systemic sclerosis. Vaginal involvement and other systemic sclerosis-related systemic symptoms adversely influence sexual relations. Menstrual abnormalities, including early menopause, affect many patients. Genital tract involvement occurs in a substantial proportion. Prospective longitudinal studies are warranted.

Adult↗
PubMed1995

Incidence of the gene mutation causal for rod-cone dysplasia type 1 in Irish setters in the UK.

A survey to establish the UK prevalence of the gene mutation causing the rod-cone dysplasia type one (rcd1) form of generalised progressive retinal atrophy (gPRA) in Irish setters was carried out. The dogs were selected by members of two Irish setter breed societies to provide examples from most of the main breeding lines in the UK. A total of 210 Irish setters were tested and one bitch was found to be a carrier of the rcd1 mutation. These results show that although a confirmed case of rcd1 has not been reported in Irish setters in the UK for over a decade the gene is still present in the gene pool.

Animals↗
PubMed1995

Measuring disease activity and severity in scleroderma.

Now that guidelines for conducting trials of disease-modifying treatments in systemic sclerosis (SSc) have been published and guidelines for evaluating SSc organ-specific treatments are in preparation, our attention should focus on how to measure disease activity and severity in SSc. Several proposals for measuring disease severity have been forwarded and are discussed. In this editorial, what we know of SSc natural history and pathophysiology is reviewed, and several candidate variables that may reflect disease activity are proposed for evaluation in longitudinal studies and/or drug trials.

Humans↗
PubMed1994

Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis. DESIGN: Multicenter, randomized, parallel placebo-controlled, double-blind study. SETTING: University medical centers. PATIENTS: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years. INTERVENTION: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo. MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing. RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo. CONCLUSION: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

Adult↗
PubMed1994

Abnormalities of renal physiology in systemic sclerosis. A prospective study with 10-year followup.

OBJECTIVE: To evaluate the prognostic value of measurements of renal plasma flow and circulating vasoactive hormones in patients with systemic sclerosis (SSc). METHODS: Renal plasma flow (para-aminohippurate [PAH] clearance) and levels of selected circulating hormones (plasma renin activity [PRA] and serum aldosterone and catecholamines) were assessed in 57 SSc patients under the following conditions: at rest, in response to cold, while in upright position, and in response to sodium depletion. Survival was assessed 10.7 years after testing (20 patients had died). RESULTS: Both unstimulated and stimulated PRA clearance rates were frequently elevated. Resting PAH clearances were usually abnormally low. PAH clearances and levels of aldosterone and catecholamines did not change during cold stimulation. Supine PRA levels following acute sodium depletion correlated with survival (P < 0.008). CONCLUSION: The frequent finding of elevated PRA and reduced PAH values reflects clinically the high frequency of renovascular disease noted histopathologically in SSc. Isolated decreases in PAH and elevations in PRA, however, did not predict renal crisis. Changes in PAH clearances were not demonstrable during cold stimulation. An abnormally high supine PRA after sodium depletion correlated with improved survival.

Adolescent↗
PubMed1994

Interrelationships between pulmonary and extrapulmonary involvement in systemic sclerosis. A longitudinal analysis.

PURPOSE: (1) To evaluate the relationship between the degree of pulmonary involvement by systemic sclerosis (SSc) and the degree of involvement of other organ systems by SSc at baseline. (2) To assess the degree of impairment in lung function at presentation and the annual rate of change in lung function to predict the rate of progression of involvement of extrapulmonary organ systems by SSc over time. (3) To determine whether survival in patients with SSc can be predicted from the degree of lung function impairment at baseline or from the annual rate of change in lung function. METHODS: Semiquantitative indices of pulmonary and extrapulmonary involvement and pulmonary function tests (PFTs) were analyzed and compared in 62 nonsmoking scleroderma patients enrolled in a 3-year prospective drug trial, vs 47 in a "study group" who underwent serial evaluation. The other 16 "early withdrawals" withdrew prior to the second evaluation. The indices of organ system involvement were based on clinical, physiologic, and biochemical findings as previously published. The PFTs included total lung capacity (TLC), forced vital capacity (FVC), FEV1, and single-breath diffusing capacity for carbon monoxide (Dsb). Annualized rates of change in PFTs and indices of extrapulmonary involvement were calculated for each subject from data collected on at least 2 separate occasions at least 6 months apart. Spearman rank correlations were performed between individual baseline PFTs (expressed as percent predicted) and (a) indices of extrapulmonary involvement at baseline, (b) annualized rates of change in PFTs, and (c) annualized rates of change in indices of extrapulmonary involvement. Correlations also were performed between the rate of change in each lung function measure and rates of change in indices of extrapulmonary involvement. The ability of PFTs at baseline and their rates of change to predict cumulative survival was assessed by Cox stepwise regression. RESULTS: The degree of impairment in baseline PFTs was related to involvement of the right side of the heart but not to other extrapulmonary system involvement. Baseline PFTs were not related to the rate of subsequent decline of lung function or worsening of extrapulmonary organ system involvement. Subsequent annual rates of decline in lung function were related to worsening skin and upper gastrointestinal involvement. Cumulative survival may be related to the rate of decline in DCO, TLC, and FVC, but was not predicted by impairment in any measure of lung function. CONCLUSION: With the exception of involvement of the right side of the heart consistent with cor pulmonale, the degree of pulmonary involvement by SSc was not correlated with the extent of extrapulmonary involvement. The degree of pulmonary involvement by SSc did not predict subsequent worsening of either pulmonary or extrapulmonary involvement. Worsening pulmonary involvement by SSc, in general, does not correlate with worsening involvement of extrapulmonary organ systems, except for the skin and upper gastrointestinal tract. A rapid decline in DCO or lung volumes may predict poor survival.

Bone Diseases↗
PubMed1994

Progressive retinal atrophy: a model for retinitis pigmentosa in companion animals.

The generalised progressive atrophies (PRA's) are a heterogeneous group of inherited retinopathies in dogs and cats. They show marked similarities to the retinitis pigmentosas (RP) in man, as well as to a number of inherited retinal degenerations of laboratory rodents. Of the various recessively inherited forms of PRA in the dog, that in the Irish setter is due to a nonsense mutation in the gene encoding cGMP-PDE-beta subunit. Mutations at this locus are also known to cause a proportion of human RP cases. We are interested in applying gene therapy to these diseases.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1993

Early undifferentiated connective tissue disease: III. Outcome and prognostic indicators in early scleroderma (systemic sclerosis).

OBJECTIVE: To characterize the course of early scleroderma and to delineate prognostic factors present within 1 year of disease onset that might identify patients at high risk. DESIGN: Inception cohort study. SETTING: Ten university-based rheumatology clinics participating in the Cooperative Systematic Studies of Rheumatic Diseases Program. PATIENTS: Forty-eight patients who had had scleroderma for less than 1 year. MEASUREMENTS: Fifteen patients with early scleroderma who died were compared with those still living during the initial study period (1982 to 1992). Kaplan-Meier survival estimation and Cox proportional hazards analysis were used to analyze baseline variables for their ability to predict survival duration. RESULTS: Eight of 15 deaths were due to cardiac or pulmonary system failure. The estimated 5-year survival rate was 68%. Baseline factors that were the most predictive of a poor outcome included the presence of abnormal cardiopulmonary signs and abnormal urine sediment (pyuria, hematuria). CONCLUSION: Evidence of early cardiopulmonary disease, renal disease, inflammation, or immune activation may identify a subset of patients with scleroderma who will experience rapidly progressive disease and early death.

Adult↗
PubMed1993

Cyclosporine in systemic sclerosis. Results of a forty-eight-week open safety study in ten patients.

OBJECTIVE: To evaluate safety and efficacy of cyclosporin A (CSA) treatment in systemic sclerosis (SSc). METHODS: Ten patients with < or = 60 months of SSc were entered into a 48-week open study of CSA. Patients with hypertension or azotemia were excluded. Concurrent use of nonsteroidal antiinflammatory agents or diuretics was not permitted. The extent of cutaneous and visceral involvement at 48 weeks and at study entry were compared. RESULTS: Adverse reactions (especially nephrotoxicity) were frequent, usually transient, often dose-limiting, and usually associated with CSA doses > or = 3-4 mg/kg/day. Skin thickening decreased significantly (P < 0.001), while pulmonary and cardiac involvement remained unchanged. CONCLUSION: CSA should undergo blinded controlled study in patients with SSc.

Adult↗
PubMed1993

Predictors of psychosocial adjustment in systemic sclerosis. The influence of formal education level, functional ability, hardiness, uncertainty, and social support.

OBJECTIVE: To determine predictors of psychosocial adjustment in patients with systemic sclerosis (SSc). METHODS: We surveyed 94 patients with SSc. Age, sex, education level, marital status, work status, income, support group attendance, length of time since diagnosis, functional status, social support, illness-related uncertainty, and hardiness were examined as potential predictors of psychosocial adjustment. The reliability and validity of the instruments used to measure these variables have been established. RESULTS: Only education level, functional ability, illness-related uncertainty, hardiness, and social support were predictive of psychosocial adjustment. Education level and functional ability explained 14% of the variance in psychosocial adjustment, while illness-related uncertainty, hardiness, and social support increased the explained variance to 38%. CONCLUSION: Although patients with relatively poorer psychosocial adjustment to illness have lower formal education levels and more functional disability, the majority of the explained variance in psychosocial adjustment is ascribable to illness-related uncertainty, low level of hardiness, and less satisfaction with social support.

Adaptation, Psychological↗
PubMed1993

Confirmation of the rod cGMP phosphodiesterase beta subunit (PDE beta) nonsense mutation in affected rcd-1 Irish setters in the UK and development of a diagnostic test.

Rod/cone dysplasia type one (rcd-1) is an early onset inherited retinal dystrophy segregating in the Irish setter breed. It is classed as one of the autosomal recessive canine generalised Progressive Retinal Atrophies (PRA). The disease results in complete loss of photoreceptors by approximately one year of age. Levels of retinal cGMP are markedly elevated and of abnormal distribution in rod photoreceptors. Rod phosphodiesterase activity is absent and mRNA encoding the beta subunit (PDE beta) of the holoenzyme is uniquely reduced in predegenerate retinae. Using retinae from normal, unrelated adult dogs we have PCR-amplified and sequenced the cDNA for PDE beta. The cDNA is almost identical to that recently described for the Irish setter in the USA apart from two translationally silent single nucleotide changes. Using carrier and affected setters from a UK breeding colony we have screened genomic DNA and can confirm the G to A transition in rcd-1 affected dogs at position 2420, creating an amber mutation in codon 807. However, PRA-affected Tibetan terriers and miniature longhaired dachshunds are normal at this locus, underlining the genetic heterogeneity of this disease group. In addition we have developed a rapid, PCR-based diagnostic test for this mutation that will differentiate normal dogs from asymptomatic carriers.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1993

Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies.

OBJECTIVE: Using data from 3 independent studies, to quantify the interobserver reliability of semi-quantitative skin scoring methods (the original and the modified Rodnan skin thickness scores) used to assess the degree and extent of cutaneous thickening in systemic sclerosis (SSc). METHOD: Interobserver variability of the original Rodnan skin thickness score method (cutaneous thickness assessed in 26 body surface areas using a 0-4 scale) was evaluated in one study. The modified Rodnan method (cutaneous thickness assessed in 17 body surface areas using a 0-3 scale) was evaluated in 2 studies. In all 3 studies, each patient's skin thickness was assessed by 6 or 7 observers in a blinded fashion. RESULTS: The overall within patient standard deviations were not statistically different in all 3 studies (5.4, 4.6 and 4.6) irrespective of the overall mean skin thickness scores (26.6, 18.3 and 17.7). With the original Rodnan technique, the within patient standard deviation tended to be higher in patients with higher skin thickness scores. In the 2 studies which used the modified technique, no significant differences in within patient standard deviation were noted between high and low skin thickness scores. CONCLUSIONS: Three independent studies demonstrate that the Rodnan skin thickness scoring techniques are reproducible among different observers (the within patient standard deviation being consistently about 5 units). Our data provide valuable information needed for sample size calculations for SSc trials in which skin thickness score is an outcome variable.

Humans↗