Biomedical subjects

B Zee

Publications and source records attributed to B Zee.

At least 73 records · Page 4Linked to original sources

PubMed1996

Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS: Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.

Adult↗

PubMed1996

Health-related quality-of-life studies of the National Cancer Institute of Canada Clinical Trials Group.

Since 1989, the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has been successful in implementing and completing health-related quality-of-life (HQL) assessments as part of phase III clinical trials. Compliance rates for completing HQL instruments remain high, with a minimal amount of missing data. It is believed that this success is attributable not only to the high degree of commitment to measuring HQL by clinical trials investigators, nurses, data managers, and central office administrative staff, but also to the educational process that was instituted after the development of a CTG policy for measuring HQL. From inception to May 1995, a total of 27 clinical trials with HQL assessment have been initiated or completed. In the majority of trials, the core HQL instrument is the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). In addition to answering specific questions about HQL in these clinical trials, the trials provide the opportunity to do research into the measurement of HQL. Thus, current clinical trials include research questions about the appropriate timing of assessments, the reliability and validity of the QLQ-C30 and other instruments, the role of HQL data in assessing toxicity, and the significance of the results of HQL assessments. It is anticipated that this activity not only will be a rich source of information about the effects of cancer and its treatment on HQL but also will lead to improvements in measuring HQL in oncology.

Canada↗

PubMed1995

Changes in mean trabecular orientation in the medial condyle of the proximal tibia in osteoarthritis.

In osteoarthritis of the knee, degenerative changes occur in the articular cartilage and underlying subchondral bone, particularly of the medial tibial condyle. Cancellous bone sclerosis that accompanies osteoarthritis is not only the result of an increase in bone volume fraction but also a change in trabecular structure. In a comparison with age-matched controls (n = 4), osteoarthritis (n = 11) demonstrated a significant (P < or = 0.05) increase in bone volume fraction and trabecular thickness. Overall trabecular orientation in the osteoarthritic group was more vertical or perpendicular to the articular surface than the control group (P < or = 0.05) especially in the trabeculae of the cancellous bone layer closest to the articular surface. These alterations in trabecular bone structure could have significant consequences for the mechanical properties of osteoarthritic bone.

Aged↗

PubMed1995

A proposal for a new approach to intergroup cancer trials.

Currently, North American intergroup trials are conducted according to the Intergroup Guidelines, which require that a lead group take responsibility for data management. Intergroup studies conducted in this manner have been very successful in rapidly accruing large numbers of patients to trials addressing significant questions, but it has been difficult for group statistical centres to cope with the resultant peaks in data flow. Our groups recently succeeded in combining the data from three independently designed and conducted trials to carry out a planned pooled analysis. This experience has led us to employ the same approach to data management in designing a forthcoming intergroup trial. We will use a common protocol and capture the same data elements on our forms, but each group will be responsible for the collection and quality control of its own data. A common data set will be created and updated periodically during the study, and will be used for the final analysis. We suggest that this model has advantages over the current approach to data management on intergroup trials, but still retains the features which distinguish an intergroup study from meta-analysis.

Clinical Trials as Topic↗

PubMed1995

Trabecular microstructure in the medial condyle of the proximal tibia of patients with knee osteoarthritis.

The microstructural characteristics of osteoarthritic subchondral bone in the medial tibial condyle are clearly different from normal age-matched bone. Subchondral sclerosis in osteoarthritis indicates not only an increase in bone volume fraction but also alteration in other microstructural characteristics. Eleven medial tibial condyles were collected from ten subjects during arthroplastic surgery for knee oseoarthritis. They were compared to four medial tibial condyles from four age-matched controls with no history of any bone or joint disorder. Six sections from anterior to posterior and three levels from proximal to distal were evaluated in each medial condyle. Five histomorphometric parameters were measured: bone volume fraction (BVf), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.S), and trabecular connectivity (Tb.C). In general, the osteoarthritic subchondral bone had a higher bone volume fraction than control bone but the microstructure was characterized by fewer, widely spaced, thicker than normal trabeculae. There were also highly localized regional differences by depth from the articular surface and from anterior to posterior across the medial condyle. These variations in OA subchondral bone microstructure may significantly affect biomechanical competence of bone in a way not predictable by bone volume fraction measurements alone.

Aged↗

PubMed1994

Patterns of failure following loco-regional radiotherapy in the treatment of limited stage small cell lung cancer.

PURPOSE: The probability of treatment resistant cells developing in a tumor, such as small cell lung cancer (SCLC) which has a rapid cell cycle time, is a function of the number of tumor cells present and of time. Theoretically, the development of resistance to chemotherapy and radiotherapy should be minimized by using all treatment modalities early in the treatment program. METHODS AND MATERIALS: The importance of the timing of loco-regional radiotherapy was assessed in a multi-institution randomized study. Three hundred and eight patients with limited small cell lung cancer (LSCLC) were given three cycles of cyclophosphamide, doxorubicin and vincristine alternating with three cycles of etoposide and cisplatin. In addition, patients were randomized to receive locoregional radiotherapy: 40 Gy in 15 fractions in 3 weeks with treatment planning techniques to limit the spinal cord dose to be < or = 35 Gy either with the first cycle (early) or with the sixth cycle of chemotherapy (late). Responding patients received prophylactic brain irradiation (25 Gy in 10 fractions in 2 weeks) after completion of locoregional radiotherapy and chemotherapy. RESULTS: 96% of the 155 eligible patients allocated to the "early" arm and 87% of the 153 allocated to the "late" arm received locoregional radiotherapy; 26 patients did not receive locoregional radiotherapy. The mean field sizes were similar in both arms. The mean radiation doses were significantly less in the "early" arm (p = 0.0319 Wilcoxon rank sum test). Any differences in the frequency of toxicities were minor. All patients have been followed for at least 2 years and the median follow up is 4 years. 64% had a complete response in the "early" arm compared with 56% in the "late" arm (p = 0.137). Survival was measured from the start of chemotherapy. There was a significant improvement in survival in the "early" arm; median survival was 21.2 months compared with 16.0 months in the "late" arm (p = .008 log rank test). Survival at 2, 3, and 4 years was 40%, 32%, and 25%, respectively, for the "early" arm and 33%, 22%, and 15% for the "late" arm. There were 232 (75%) recurrences among those patients whose disease recurred. The proportion who had local recurrence within the radiation field was 41% and 39% for "early" and "late" treatment arms respectively. The proportion of brain metastases in the "late" arm (28%) was significantly higher than in the "early" arm (18%) p = .0425 Fishers' exact test. CONCLUSION: We conclude that early administration of locoregional radiotherapy in a combined modality treatment is superior to late consolidative locoregional radiotherapy in limited small cell lung cancer.

Brain Neoplasms↗

PubMed1994

Inconsistency of prognostic factors for post-chemotherapy nausea and vomiting.

A number of prognostic factors have been reported to influence the probability of developing nausea and vomiting after cytotoxic chemotherapy. This study used data collected in four randomized anti-emetic trials conducted by the Clinical Trials Group of the National Cancer Institute of Canada (NCIC-CTG) to assess the consistency of the effects of these prognostic factors. A total of 582 patients, all of whom had received moderately emetogenic chemotherapy for the first time, but who were assigned to different anti-emetics, were included in the analysis. The major findings was that the probability of post-chemotherapy nausea and vomiting was much more strongly influenced by the type of chemotherapy given and the type of anti-emetic used than by patient (e.g., age, gender) or environmental (e.g., treatment location, time of administration) characteristics. Further, patient-related factors had different, and sometimes opposite, effects in different anti-emetic and chemotherapy subgroups. Finally, the relative potency of anti-emetics appeared to vary with chemotherapy regimens. Implications of these findings for future studies are discussed.

Antiemetics↗

PubMed1994

Psychometric properties and responsiveness of the EORTC quality of Life Questionnaire (QLQ-C30) in patients with breast, ovarian and lung cancer.

The QLQ-C30, a health-related quality of life questionnaire developed for use in patients with cancer, has been previously validated in patients with lung cancer and head and neck cancer. In this study, further validation was carried out for 535 patients, including patients with breast cancer (n = 143) and ovarian cancer (n = 111) for whom there is no previously published validation, as well as patients with lung cancer (n = 160) and a heterogeneous group of other cancers (n = 121). All patients were entered in one of two trials of anti-emetics to prevent chemotherapy-induced emesis. The QLQ-C30 was completed before chemotherapy and on day 8 after chemotherapy. The factor structure in patients with breast and ovarian cancer was similar to that previously described. Interdomain correlations, in the entire group, were strongest for the physical and role function domains and the fatigue, pain and global quality of life domains before and after chemotherapy. In addition, after chemotherapy, social function was also strongly correlated with fatigue and global quality of life. These correlations were not always of equal strength in the breast, ovarian and lung groups, suggesting that there may be differences between these groups. The responsiveness of the QLQ-C30 in the presence of widely metastatic, as compared with locoregional, disease showed changes in the expected directions (i.e., diminished function in physical and social role functions and in global quality of life, with greater fatigue and pain in patients with metastatic disease). Eight days after chemotherapy, decreases were seen in physical, role and social functioning and in global quality of life, and there was greater fatigue, nausea and vomiting compared with before chemotherapy. Patients with breast cancer had better physical, role and social functioning and less fatigue and pain than patients with ovarian cancer. This result is expected, since many of the patients with breast cancer had early stage disease, whereas those with ovarian cancer had advanced stage disease. Mean scores for patients with lung cancer were between the other two groups, in keeping with the mixture of early and advanced stage disease in these patients. There was a strong correlation between ECOG performance status scores and several domains of the QLQ-C30; these were all in the expected directions. The results of this study confirm those in earlier studies on patients with lung cancer, and provide new information on patients with breast and ovarian cancer. In addition, the QLQ-C30 is responsive to the effects of chemotherapy and of metastatic disease.

Breast Neoplasms↗

PubMed1994

Effect of schedule and maintenance on the antiemetic efficacy of ondansetron combined with dexamethasone in acute and delayed nausea and emesis in patients receiving moderately emetogenic chemotherapy: a phase III trial by the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: This study examines whether the schedule of ondansetron significantly influences its antiemetic efficacy in the first 24 hours after chemotherapy, whether the administration of oral ondansetron after 24 hours is effective in preventing delayed emesis, and whether the efficacy of ondansetron is preserved over multiple courses of moderately emetogenic chemotherapy. PATIENTS AND METHODS: A multicenter double-blind study randomized 302 cancer patients to one of three treatment arms. Arm A received dexamethasone 10 mg intravenously (i.v.) plus ondansetron (Zofran; Glaxo Canada Inc, Toronto, Canada) 8 mg i.v. prechemotherapy plus ondansetron 8 mg orally every 12 hours postchemotherapy for nine doses. Arm B received dexamethasone 10 mg i.v. plus ondansetron 16 mg i.v. prechemotherapy plus placebo orally postchemotherapy in the same schedule as arm A. Arm C received dexamethasone 10 mg i.v. plus ondansetron 8 mg prechemotherapy plus ondansetron 8 mg orally postchemotherapy for one dose followed by placebo orally every 12 hours for eight more doses. Response was assessed by the number of reported episodes of vomiting and by severity of nausea measured on a visual analog scale (VAS). RESULTS: The two schedules of ondansetron used in the first 24 hours were no different in their antiemetic efficacy, with similar rates for complete responses (76.7% v 72.0%, P = .472), complete plus major responses (90.2% v 82.0%, P = .135), and severity of nausea (P = .348). Oral ondansetron after 24 hours was more effective than placebo in preventing delayed nausea and emesis, with superior rates of complete responses (59.6% v 42.1%, P = .012 by one-sided test), complete plus major responses (80.9% v 66.3%, P = .018 by one-sided test), and less severe nausea (9.2 mm v 18.6 mm on a 100-mm VAS, P = .002). The efficacy of ondansetron was maintained over subsequent courses of chemotherapy. CONCLUSION: The schedule of ondansetron in the first 24 hours does not influence its efficacy. The use of oral maintenance ondansetron is effective in preventing delayed maintenance ondansetron is effective in preventing delayed nausea and emesis after moderately emetogenic chemotherapy.

Antineoplastic Agents↗

PubMed1993

Assessing the reliability of two toxicity scales: implications for interpreting toxicity data.

BACKGROUND: The toxicity of a given cancer therapy is an important end point in clinical trials examining the potential costs and benefits of that therapy. Treatment-related toxicity is conventionally measured with one of several toxicity criteria grading scales, even though the reliability and validity of these scales have not been established. PURPOSE: We determined the reliability of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) expanded toxicity scale and the World Health Organization (WHO) standard toxicity scale by use of a clinical simulation of actual patients. METHODS: Seven experienced data managers each interviewed 12 simulated patients and scored their respective acute toxic effects. Inter-rater agreement (agreement between multiple raters of the same case) was calculated using the kappa (kappa) statistic across all seven randomly assigned raters for each of 18 toxicity categories (13 NCIC-CTG and five WHO categories). Intra-rater agreement (agreement within the same rater on one case rated on separate occasions) was calculated using kappa over repeated cases (where raters were blinded to the repeated nature of the subjects). Proportions of agreement (estimate of the probability of two randomly selected raters assigning the same toxicity grade to a given case) were also calculated for inter-rater agreement. Since minor lack of agreement might have adversely affected these statistics of agreement, both kappa and proportion of agreement analyses were repeated for the following condensed grading categories: none (0) versus low-grade (1 or 2) versus high-grade (3 or 4) toxicity present. RESULTS: Modest levels of inter-rater reliability were demonstrated in this study with kappa values that ranged from 0.50 to 1.00 in laboratory-based categories and from -0.04 to 0.82 for clinically based categories. Proportions of agreement for clinical categories ranged from 0.52 to 0.98. Condensing the toxicity grades improved statistics of agreement, but substantial lack of agreement remained (kappa range, -0.04-0.82; proportions of agreement range, 0.67-0.98). CONCLUSIONS: Experienced data managers, when interviewing patients, draw varying conclusions regarding toxic effects experienced by such patients. Neither the NCIC-CTG expanded toxicity scale nor the WHO standard toxicity scale demonstrated a clear superiority in reliability, although the breadth of toxic effects recorded differed.

Canada↗

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↗

PubMed1992

Immunohistochemical reaction to human milk fat globule antibodies and breast cancer differentiation.

Immunohistochemical studies of human breast cancers using human milk fat globule (HMFG) antibodies are divergent regarding the association with histologic differentiation. To clarify this association 392 tumors were assessed using two antibodies, HMFG-1 and HMFG-2. In half the tumors studied the tissue reaction to both antibodies was the same and in 63% the site of reaction was identical. Using both univariate and multivariate statistics, a highly significant association was recorded between membrane staining and well differentiated cancers and cytoplasmic staining and poor differentiation. Well differentiated tumors contained significantly more reactive cells. Complementing these findings was the association between age at diagnosis, tumor stage, and estrogen receptor status and differentiation. It is possible that immunohistochemical analysis with HMFG antibodies will provide better characterization of tumor differentiation than morphologic interpretation.

Antibodies↗

PubMed1992

Prognostic significance of the immunohistochemical reaction to human milk fat globule antibodies in node-negative and node-positive breast cancer.

The status of axillary lymph nodes in patients with breast cancer is important prognostically but does not identify all patients who will have long or short survival. To determine if the immunohistochemical reaction of tumor cells to human milk fat globule (HMFG) antibodies will define prognosis more specifically, we examined patients with node-negative disease and patients with more than three positive nodes, the extremes of the prognostic spectrum. In both node-negative and node-positive groups, patients who relapsed were matched by age at diagnosis, tumor size, histologic type, and receptor status, with patients who remained disease-free for a minimum of 48 months. Patients with poor survival had a higher proportion of poorly differentiated cancers. The ability to generate antigens recognized by HMFG antibodies was decreased in patients with recurrent disease, but this was significant only in patients with node-positive tumors. Tumors of patients who remained disease-free were more likely to have a pattern of membrane staining, while cytoplasmic staining was more frequent in those who relapsed. The results suggest that immunohistologic response to HMFG antibodies may assist in identifying cancers with poor prognosis, supplementing the prediction derived from node status.

Adult↗

PubMed1992

Immunohistochemical characteristics of human milk-fat globule antibodies in predicting chest wall and distant metastasis after mastectomy for localized cancer of the breast.

Because postoperative radiation reduces chest wall metastasis after mastectomy, it is important to identify patients in whom it might develop. Pathologic and immunohistochemical features in 59 patients with chest wall metastasis were compared with characteristics in disease-free patients and patients with systemic metastases without chest wall metastasis. Immunohistochemical studies with human milk-fat globule (HMFG)-2 were not predictive, but a membrane reaction with HMFG-1 was associated with fewer systemic metastases and tumors, in which most of the cells reacted with the antibody had significantly decreased likelihood of chest wall metastasis. Antigenic concordance between the primary breast cancer and the chest wall metastasis was demonstrated. Neither tumor size nor axillary node metastasis predicted development of chest wall metastasis, but systemic metastases were less common when fewer than four nodes were involved, the primary tumor was well differentiated, and estrogen receptors were positive.

Antigens, Neoplasm↗

PubMed1991

Phase I pharmacokinetic and pharmacodynamic study of a new anthrapyrazole, CI-937 (DUP937).

We performed a phase I trial of CI-937 (DUP937), an anthrapyrazole, with the following objectives: (a) to determine the maximally tolerated dose in humans; (b) to define the toxicity spectrum of this agent; (c) to describe the pharmacokinetics of the drug; (d) to test a pharmacokinetics based hypothesis of dose escalation; and (e) to relate drug pharmacokinetics to pharmacodynamics. CI-937 was administered as a single bolus injection every 3-4 weeks at doses ranging from 3.6 to 25.2 mg/m2. Thirty-two patients and 57 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 30 patients on the first course using a sensitive and selective radioimmunoassay. The maximally tolerated dose in patients with no prior therapy was 25.2 mg/m2 and dose-limiting toxicity was neutropenia. Thrombocytopenia, nausea, vomiting, stomatitis, and alopecia were mild. A partial response was recorded in a patient with mesothelioma. The area under the curve increased linearly with dose, and total body clearance of CI-937 was independent of dose. The mean total body clearance was 107 +/- 55.8 ml/min/m2, mean steady state volume of distribution was 492 +/- 469 liters/m2, and terminal half-life was 3.78 +/- 2.86 days. The extended factors of 2 methods of pharmacologically guided dose escalation were intended for use but ultimately were equivalent to that of the modified Fibonacci dose escalation method. Dose and the area under the curve were significant predictors of a percentage change in WBC and neutrophil count in a univariate analysis. Only dose and baseline neutrophil count predicted a percentage change in WBCs in a multifactor analysis. Dose and prior chemotherapy predicted percentage change in neutrophil count in a multifactor analysis. We conclude that the dose-limiting toxicity of CI-937 is neutropenia and that the recommended phase II starting dose is 22 mg/m2.

Adult↗

PubMed1991

Thermography as a predictor of prognosis in cancer of the breast.

Although thermography is generally considered to lack sufficient sensitivity to be a useful in diagnosis of cancer of the breast, the association of a thermal abnormality with some breast cancers cannot be discounted. Breast cancers demonstrating such a thermographic abnormality have been reported to be associated with decreased survival when compared with patients with no such change. In a study of 214 patients confirmed to have breast cancer without distant metastases, 121 were found to have a thermographic abnormality. Patients whose tumors were thermographically abnormal had significantly larger primary lesions and a higher proportion of metastatic axillary lymph nodes. However, both the 5-year survival and the 5-year disease-free survival were not significantly different from patients who had no thermographic abnormality.

Breast Neoplasms↗

PubMed1991

Effect of daily etidronate on the osteolysis of multiple myeloma.

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.

Aged↗

PubMed1988

Renal vascular histology and morphometry in systemic sclerosis. A case-control autopsy study.

An autopsy case-control study of renal vascular histology and morphometry in systemic sclerosis (scleroderma) was performed. Thirty-five of 70 systemic sclerosis cases had renal tissue available for study: 26 had diffuse cutaneous involvement (9 with "renal crisis" and 17 without) and 9 had limited cutaneous disease (CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias]). Age-matched (within 10 years) and sex-matched controls with renal specimens were obtained. New sections were cut from tissue blocks, and morphometry was completed using a Zeiss Image Analyzer. Using analysis of variance, the intimal area (Ai) was significantly increased (intimal thickening) in small and medium-sized arteries of patients with diffuse scleroderma and in small arteries of CREST patients, compared with those in controls, while a decreased medial area (Am) was seen consistently in all groups. The proportion of the vessel wall occupied by intima (Ai:[Ai + Am]) was significantly greater in all vessel size groups in patients with diffuse scleroderma compared with that in controls. The percentage of luminal occlusion was greatest in patients with diffuse disease with renal crisis. These same patients had severe edematous and mucinous intimal thickening in small and medium vessels, often in association with fibrinoid necrosis. We conclude that renal vascular structural changes are an integral part of systemic sclerosis. However, the significant differences between diffuse scleroderma patients and CREST syndrome patients, for both intimal thickening and percentage of luminal occlusion, suggest that the arterial disease in these 2 patient subsets is distinctive.

Calcinosis↗