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P Clements

Publications and source records attributed to P Clements.

At least 19 recordsLinked to original sources
PubMed2001

Factors limiting the rate of living-related kidney donation to children in an inner city setting.

A recent review of our center experience revealed that only 38% of our pediatric renal transplants come from living-related donors (LRD), which is 11% lower than the national average. The present study was designed to identify factors that limit the availability of LRD in our population pool. Retrospective chart reviews and subsequent telephone interviews were conducted with parents of all children who received renal replacement therapy (RRT) at our institution from 1990 to 1999. The availability of parents and their willingness to donate a kidney were noted. Self-reported willingness was defined as the verbal expression of a desire to donate. Firm willingness was defined as the completion of the steps necessary for donation, unless excluded by the medical team. Factors that may impact the ability to donate, such as donor age, ethnicity, religion, educational attainment, employment, and presence of other siblings younger than 18 yr of age, were evaluated. Statistical analyses were performed using the Student's t-test and chi-square analysis. Significant results were entered into a single-step multiple regression analysis. Sixty children were identified with RRT, of whom 60% were Blacks, 30% Hispanics, 7% Caucasians, and 3% Asian. Fifty-five mothers were available for interview. Forty-four mothers reported a desire to donate, nine were unwilling to donate, and two were undecided. However, only 35 attended for screening. Only 30 fathers were available and, of these, 27 reported willingness to donate, yet only 20 attended for screening. Seventy-four per cent (26 out of 35) of mothers screened and 55% (11 out of 20) of fathers screened were medically unsuitable for kidney donation. Nineteen potential donors had hypertension, diabetes and/or obesity, seven had renal disease, four had anemia, two had hepatitis C, and five had other conditions. Expressed unwillingness to donate was associated with a greater number of children (3.1 compared to 1.5 children in addition to the child with end-stage renal disease [ESRD]) (odds ratio 2.91, p < 0.05) and employment (26.3% vs. 4.0%, p < 0.05) (odds ratio 31.2, p = 0.05). Comparing mothers who were firmly willing to donate with mothers who did not complete screening and evaluation, unwilling mothers had, likewise, a greater number of children (2.9 vs. 1.2 in addition to the child with ESRD) (odds ratio 3.23, p < 0.01) and a greater number of years of education (12.4 vs. 10.4) (odds ratio 2.14, p < 0.05). Hence, the availability of living kidney donors for our inner city children is severely limited by a high rate of single parenthood and a high rate of comorbid conditions in the parental donor pool. Furthermore, there is a diminished capacity of the available parent, particularly the mother, to donate as she tends to have numerous other dependents.

Black or African American↗
PubMed2001

Thrombotic thrombocytopenia purpura in a patient with systemic sclerosis.

Thrombotic thrombocytopenic purpura (TTP) has been associated with scleroderma renal crises (SRC) in the past. However such reports markedly diminished after the onset of ACE inhibitor use. Recently, reports again have surfaced that describe scleroderma patients presenting with clinical evidence of TTP. We describe a 50-year-old female with longstanding limited cutaneous scleroderma who presented with hematochezia and thrombocytopenia along with other findings suggesting TTP. A colon biopsy revealed thrombi within the lumen. Her course was complicated by renal failure and hypertension that did not respond to ACE inhibitor therapy alone. She improved after a course of plasma exchange. She was discharged home only to return 2 months later with grand mal seizures and hypertension. During her course she developed adult respiratory distress syndrome. She again responded to plasma exchange and she was discharged home. She has remained stable for 2 years. This report emphasizes the importance of fully evaluating patients with longstanding limited cutaneous scleroderma who present with renal failure, hypertension, and thrombocytopenia in association with multiorgan complications. All possible etiologies, including SRC, TTP, vasculitis, and sepsis should be considered. Tissue biopsies (in this case, a colon biopsy revealed thrombi within the vessel lumen) may prove beneficial in assisting with the diagnosis. For such patients who fail treatment with ACE inhibitors, plasma exchange may be considered.

Journal Article↗
PubMed2001

Early adolescent peer orientation and adjustment during high school.

The long-term consequences of early adolescents' orientation toward peers for their adjustment during high school were assessed. Approximately 1,200 adolescents completed questionnaires in the 7th grade and in the 10th or 12th grades; course grades were also obtained from the students' school records. Early adolescents who were willing to sacrifice their talents, school performance, and parents' rules engaged in greater problem behavior and evidenced lower academic achievement than did other adolescents during high school. The poorer adjustment of adolescents with this extreme orientation toward peers was mediated by their reported involvement in deviant peer groups. In contrast, a tendency to seek advice from peers more than from parents during early adolescence had little implication for later adjustment. Discussion focuses on the need to consider the role of peer dependence along with the effects of supportive friendships during adolescence.

Adolescent↗
PubMed2000

Mutation of a BRCT domain selectively disrupts DNA single-strand break repair in noncycling Chinese hamster ovary cells.

The DNA single-strand break repair protein XRCC1 contains a BRCT domain that binds and stabilizes intracellular DNA ligase III protein. We recently demonstrated that this domain is largely dispensable for single-strand break repair and cellular resistance to DNA base damage in cycling cells. Here, we report that the BRCT domain is required for single-strand break repair in noncycling cells. Mutations that disrupt the BRCT domain and prevent DNA ligase III interaction abolished XRCC1-dependent repair in serum-starved Chinese hamster ovary cells, and reentry into cell cycle induced by readdition of serum restored repair. Elevating DNA ligase III levels in XRCC1 mutant cells using proteosome inhibitors or by expressing XRCC1 protein in which the BRCT domain is disrupted but can still bind DNA ligase III failed to restore repair in noncycling cells. The requirement for the BRCT domain for DNA strand break repair is thus for more than simply binding and stabilizing DNA ligase III. These data provide evidence in support of a selective role for a DNA repair protein or protein domain in noncycling cells. We propose that the XRCC1 C-terminal BRCT domain may be important for genetic stability in postmitotic cells in vivo.

Animals↗
PubMed2000

The mitotic spindle and DNA damage-induced apoptosis.

EM9 Chinese hamster ovary cells cannot rejoin DNA strand breaks induced by alkylating agents. Ethyl methanesulphonate (EMS)-treated EM9cells underwent G2 arrest for a prolonged period followed by entry into mitosis and apoptosis. EM9 cells treated with EMS in G1 entered mitosis 24-36 h after release from synchrony, approximately 12 h after untreated control cells, but the mitoses were morphologically abnormal. The spindle-poison nocodazole reduced apoptosis by greater than 60%, and allowed some cells to complete a second round of DNA replication. We conclude that the assembly of a mitotic spindle, or progression beyond the mitotic checkpoint, is important for apoptosis following DNA strand breakage.

Animals↗
PubMed2000

Direct and indirect costs associated with the onset of seropositive rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: To examine the direct and indirect costs of rheumatoid arthritis (RA) during the first year of disease. METHODS: As part of a longitudinal observational study, 150 patients with seropositive RA of 5.9 +/- 2.9 mo duration were recruited through the Western Consortium of Practicing Rheumatologists. Subjects completed questionnaires about health care services and resources utilized and about the number of days of usual activity lost as a result of RA during the 6 month period prior to enrolment. RESULTS: Study participants had active RA as evidenced by mean tender and swollen joint counts of 24.9 +/- 13.5 and 20.6 +/- 11.6, respectively, and moderate functional impairment reflected by a mean Health Assessment Questionnaire (HAQ) score of 1.24 +/- 0.7. The average total direct cost of RA was $200/month. Health care visits, medications, and radiographs accounted for 78% of the total direct cost, while expenditures for hospitalizations accounted for only 3.5% of the total. The average number of days of usual activity lost per month because of RA was 3.8 +/- 7.7, translating into an average indirect cost of $281/month. Of the 95 subjects who were gainfully employed prior to disease onset, 12 were disabled and 5 were on sick leave as a result of RA, corresponding to a work disability rate of 18%. Work disabled subjects reported significantly lower total household incomes and higher HAQ disability and global disease activity scores than subjects who continued working. CONCLUSION: In this group of patients with seropositive RA substantial costs, both direct and indirect, were incurred during the first year of disease.

Arthritis, Rheumatoid↗
PubMed1999

A mitotic spindle requirement for DNA damage-induced apoptosis in Chinese hamster ovary cells.

Promiscuously reactive electrophilic agents induce DNA and other cellular damage. DNA repair-defective cells, when compared with genetically matched, repair-proficient parental cells, provide a means to distinguish cellular responses triggered by individual genetic lesions from other macromolecular damage. The Chinese hamster ovary (CHO) cell line EM9 is hypersensitive to the alkylating agent ethyl methanesulfonate (EMS) and is unable efficiently to repair DNA single strand breaks in contrast to parental AA8 cells. EM9 was used to examine how CHO cells couple unrepaired DNA strand breaks to loss of viability. Flow cytometry revealed that EMS-treated EM9 cells underwent prolonged cell cycle arrest in G2, followed by entry into mitosis, micronucleation, and apoptosis. EM9 cells synchronized in G1 prior to EMS treatment entered mitosis 24-36 h after release from synchrony, approximately 12 h after untreated control cells. Mitoses in EMS-treated cells were abnormal, involving multipolar mitotic spindles and elongated and/or incompletely condensed chromosomes. The mitotic spindle poison nocodazole reduced DNA damage-induced apoptosis by >60%, whereas the frequency of micronucleation was similar in the presence or absence of nocodazole. Flow cytometry revealed that nocodazole-treated cells sustained a second round of DNA replication without intervening mitosis. These results demonstrate that nuclear fragmentation and inappropriate DNA replication are insufficient to trigger apoptosis following DNA strand breakage and demonstrate a requirement for mitotic spindle assembly for this process in CHO cells.

Animals↗
PubMed1999

Equivalence of the acute phase reactants C-reactive protein, plasma viscosity, and Westergren erythrocyte sedimentation rate when used to calculate American College of Rheumatology 20% improvement criteria or the Disease Activity Score in patients with early rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: In an additive cohort of patients with early rheumatoid arthritis (RA), to determine the effect of substituting one acute phase reactant for another on the number of patients satisfying the American College of Rheumatology (ACR) 20% preliminary criteria for improvement, and on calculated Disease Activity Scores (DAS). METHODS: A total of 251 patients with 6.4 months average disease duration had detailed clinical assessments at entry and 6, 12, and 24 months in a multicenter prospective longterm observational study. Matched erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma viscosity (PV) assays were done at 366 time points. Disease modifying antirheumatic drugs were not started until after the baseline evaluation. RESULTS: After 6, 12, and 24 months, 50%, 53%, and 57% of patients were responders, as defined by the ACR 20% improvement criteria. The difference in response rates when ESR, CRP, or PV was used as the acute phase reactant ranged from 0.4% at 12 months to 3% at 24 months. Percentile distributions of the 366 matched CRP, ESR, and PV values were used to prepare a nomogram that can be used to calculate the other acute phase reactant values if the value of one is known. When the nomogram was used to impute ESR values from observed PV or CRP values, average DAS scores calculated with the actual ESR values were not different from average DAS scores calculated from the imputed ESR values. CONCLUSION: ESR, CRP, and PV are equally useful in calculating ACR 20% response rates in patients with active early RA. A nomogram can be used to impute ESR values from CRP or PV values; use of the imputed ESR values is as accurate as use of the actual ESR values to calculate average DAS.

Acute-Phase Reaction↗
PubMed1999

Patient self-report tender and swollen joint counts in early rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: To determine the correlation between patient self-report joint counts and standard physician joint counts, and to compare pictorial (Mannequin) and text (Rapid Assessment of Disease Activity in Rheumatology, RADAR) formats for obtaining patient self-reports. METHODS: Baseline patient self-report joint counts were mailed and completed by 60 patients with early rheumatoid arthritis (RA) one day before and one day after being examined by a physician. Twenty-seven were randomized to the Mannequin tender and Mannequin swollen joint counts; 33 were randomized to the RADAR tender and swollen joint counts. Agreement between patient and physician self-report joint counts, diagnostic characteristics, and test-retest reliability of patient self-report joint counts was computed. Stepwise regression analyses were performed to identify predictors of patient-physician differences in total joint count. RESULTS: Means and standard deviations of paired patient and physician total joint counts were not different for Mannequin or RADAR forms. Spearman correlations were moderate (0.58 to 0.69 for Mannequin, 0.37 to 0.58 for RADAR). Agreement (intraclass correlations) was 0.65 for the Mannequin and 0.56 for the RADAR forms. Patient test-retest reproducibility was moderate for RADAR tenderness (0.58) and high (r>0.90) for RADAR swollen and both Mannequin forms. Level of patient education predicted patient-physician differences on the RADAR swollen joint counts (p = 0.003), but was not significant in Mannequin forms, suggesting that education was not a factor in accurate completion of Mannequin forms. CONCLUSION: Both pictorial and text format patient self-report joint counts are significantly correlated with physician joint counts. In addition to moderately high patient test-retest reproducibility, this suggests that patient self-reports in both formats may yield accurate measures of improvement in disease activity.

Adult↗
PubMed1998

Allogeneic CD34 selected peripheral stem cell transplant for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): rapid haemopoietic and biochemical reconstitution.

Severe Maroteaux-Lamy syndrome is usually fatal in teenage or early adult life. Until recently, allogeneic bone marrow transplantation was the only form of enzyme replacement. We report the first successful transplant using CD34 selected, mobilised allogeneic blood cells for an inborn error of metabolism. A busulphan, cyclophosphamide, melphalan and antithymocyte globulin conditioning regimen was used as myeloablative therapy. Allogeneic CD34 selected granulocyte colony-stimulating factor (G-CSF)-mobilised blood cells from a HLA-identical sibling were used for the transplant. Haemopoietic reconstitution occurred on day 10 post-transplant with normal N-acetylgalactosamine-4-sulphatase levels. Infectious and graft-versus-host disease (GVHD) complications were minimal. We suggest that CD34 selected, mobilised allogeneic blood cells are a safe form of enzyme replacement therapy in Maroteaux-Lamy syndrome and should be considered in other metabolic diseases where the benefits of haemopoietic transplantation are proven.

Adolescent↗
PubMed1998

Issues related to caring for infants to adults on an integrated epilepsy unit.

We integrated the care of patients of all ages (ranging thus far from 4 weeks to 73 years) in our dedicated 8-bed Epilepsy Unit. Administrative issues pertaining to admission and discharge criteria, unit policies and procedures and an interdisciplinary quality assurance plan were examined in relation to the impact of combining both pediatric and adult patients. Clinical considerations included the diversified abilities needed to care for pediatric and adult patients both in relation to the technical skills as well as psychosocial skills required. The advantages of integrating patients of all ages on one unit include having a staff highly trained in assessment and intervention skills for a particular disorder. The psychosocial issues that arise in these patients, regardless of age, tend to encompass the entire family; therefore a holistic approach is appropriate for both children and adults. An autonomous nursing practice was established with the development of critical pathways and patient care protocols. Our experience suggests that integrated specialized units can enhance the care of patients with intractable seizures.

Adolescent↗
PubMed1996

The relationship between socioeconomic status and recently diagnosed rheumatoid arthritis.

OBJECTIVE: To examine the role of socioeconomic status (SES) in physical functioning, pain, and depressive symptoms among newly diagnosed rheumatoid arthritis (RA) patients with severe disease. METHODS: Data are from 118 non-Hispanic patients of European origin at baseline of a longitudinal study of early, severe RA. Outcome measures with the Health Assessment Questionnaire (HAQ) functional disability index, the HAQ visual analog pain scale, and the Center for Epidemiologic Studies Depression Scale. Hierarchical regression analyses were conducted using a health status block (disease activity and comorbidities), a non-SES related social structure block (age, sex and Lubben Social Network Scale), and indicators of SES (income and education). RESULTS: Non-SES related social structure and SES were important independent determinants of functional disability and depressive symptoms, but both they and the health status variables were unrelated to pain. Further, neither income nor education was related to disease activity or comorbidities. CONCLUSION: It cannot be argued from these data that poorer health status explains the link between SES and disability and depressive symptoms. Although, at baseline, the psychosocial effects of early RA are more severe for those with SES, the disease does not appear to be more severe. It may be that the biologic impact of status differentials will become clearer as the effects of treatment and the course of the disease unfold over time.

Activities of Daily Living↗
PubMed1995

Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis.

OBJECTIVE: Assessment of the inter and intraobserver variability of the modified Rodnan (m-Rodnan) total skin thickness score by clinical palpation [a commonly used outcome measure in trials of systemic sclerosis (SSc)]. METHODS: Skin thickness was assessed by clinical palpation of 17 body areas on 0 to 3 scale (normal, mild, moderate, severe). The m-Rodnan total skin thickness score was derived by summation of the scores from all 17 body areas. Using the m-Rodnan, 6-7 investigators assessed skin thickness in 5-6 patients with SSc (22 patients and 23 examiners total) at each of 4 sessions for the determination of interobserver variability (accuracy). In addition 21 of the investigators then assessed m-Rodnan in 2-3 patients each (60 patients total) 3 times over a 2-8 week period to quantitate intraobserver variability (reliability). RESULTS: Interobserver and intraobserver mean +/- within patient standard deviations (SD) for the m-Rodnan were found to be 17.7 +/- 4.6 and 20.7 +/- 2.45, respectively. CONCLUSION: The m-Rodnan total skin thickness score is at least as reliable for measuring skin thickness in SSc as are the ARA and Ritchie joint tenderness counts for assessing joint disease in rheumatoid arthritis. These data are useful for the determination of sample size and for the definitions of clinically meaningful response. Assessment of skin score is sufficiently reproducible to include as a measure of disease outcome, especially if patients are serially evaluated by the same investigator.

Humans↗
PubMed1993

The course of skin involvement in systemic sclerosis over three years in a trial of chlorambucil versus placebo.

OBJECTIVE: To describe the course of cutaneous involvement in systemic sclerosis (SSc; scleroderma) over 3 years, in the context of a placebo-controlled drug trial. METHODS: The course of skin tethering (assessed by a semiquantitative skin scoring technique) was documented annually for 3 years in 64 SSc patients with early (< 3 years duration at entry), intermediate (3-8 years duration), or late (> 8 years duration) diffuse or limited SSc. RESULTS: Mean +/- SD entry skin scores were significantly greater in the 33 diffuse SSc patients (13.1 +/- 5.0) than in the 31 limited SSc patients (4.3 +/- 2.1) (P < 0.001). In patients with diffuse SSc, the skin score remained stable for the first 12 months, but had decreased significantly by 24 months (P < 0.022) and 36 months (P < 0.004). In those with limited SSc, the skin score did not change significantly over 3 years. CONCLUSION: Trials of treatments designed to affect skin thickening/tethering should be conducted in patients who have diffuse SSc (of short, intermediate, or long duration) at entry. The best time to study therapies designed to affect skin thickening may be in the first year after entry.

Adult↗
PubMed1992

Clinical aspects of localized and systemic sclerosis.

Now that renal disease is no longer the leading cause of death in patients with systemic sclerosis, attention has shifted to cardiopulmonary involvement. Several reports addressed the issue of whether the pulmonary vasculature in patients with systemic sclerosis is vasoactive or fixed, and one report addressed the use of high-resolution computed tomographic lung scan to diagnose active alveolitis. The issue of whether the clinical syndrome of thrombotic thrombocytopenic purpura in systemic sclerosis is part of, or is distinct from, scleroderma renal crisis has again been raised. Worsening of cutaneous and visceral systemic sclerosis following radiotherapy was noted in several reports.

Gastrointestinal Diseases↗
PubMed1987

Pharmacokinetics and pharmacodynamics of thiazinamium in asthmatic patients.

The pharmacokinetics and pharmacodynamics of thiazinamium (Multergan) were studied after intravenous and intramuscular administration to 7 males with chronic reversible airways obstruction. Disposition after i.v. administration was described by a clearance of 0.54 l.min-1, central compartment volume of 14.8 l, distribution rate constant 0.092 min-1, and an elimination rate constant of 0.0044 min-1. The corresponding estimates after i.m. administration were 0.324 l.min-1, 34.1 l, 0.035 min-1, and 0.0018 min-1. The bronchodilator response (expressed as % predicted FEV1) after i.v. administration was characterized by maximum increase in FEV1 of 33.9%, with an EC50 of 12.8 ng.ml-1 and an equilibration half-time of 11 min. Corresponding parameter estimates after i.m. administration were 32.2%, 18.8 ng.ml-1, and 9 min. Anticholinergic activity, measured by the change in heart rate after i.v. administration, showed maximum increase of 76 beats.min-1, with an EC50 of 176 ng.ml-1 and an equilibration half-time of 1.3 min. After i.m. administration the corresponding values were 120 beats.min-1, 250 ng.ml-1, and 3 min. The optimal plasma concentration of thiazinamium was about 100 ng.ml-1, which should give a near maximal bronchodilator response (over 80% of predicted normal) and a heart rate of about 100 beats.min-1.

Adult↗
PubMed1987

Longitudinal changes in lung function and respiratory symptoms in progressive systemic sclerosis. Prospective study.

Most patients with progressive systemic sclerosis (PSS) exhibit lung involvement. However, the natural history of lung disease in PSS remains poorly defined. To evaluate lung function over time in PSS, a battery of lung function tests were prospectively performed serially between 1973 and 1982 in 61 patients with PSS. Functional indexes of restriction (vital capacity and total lung capacity) and diffusion impairment (diffusing capacity) showed greater-than-expected annual rates of change. Male subjects showed a trend toward faster declines in forced vital capacity, forced expired volume in one second, total lung capacity, and functional residual capacity and a more rapid increase in static recoil pressure at 90 percent of total lung capacity than did female subjects. Nonsmokers had greater rates of decline in total lung capacity and static lung compliance (but not in forced vital capacity or diffusing capacity) and a greater rate of increase in static recoil pressure than did current and former smokers. Level of lung function at initial study visit, age, race, and chlorambucil therapy had no significant effect on the annual rates of change in lung function, whereas longer duration of disease prior to study entry was associated with a slower annual decrease in lung volumes. Between the first and last visits (mean interval 3.1 years, maximum nine years), the frequency of abnormality in pulmonary function test results showed significant change only in the diffusing capacity (60 percent increasing to 82 percent) and static lung compliance (40 percent increasing to 54 percent), whereas the frequency of respiratory symptoms showed little change. These findings indicate an overall indolent progression of PSS-related lung disease, with substantial individual variability.

Adult↗