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Survival in patients with chronic lower extremity ischemia: a risk factor analysis.

This is a prospective cohort comparison study aiming to determine the mortality of patients with peripheral arterial occlusive disease (PAOD) and identify the risk factors affecting their survival. Data regarding demographic and biochemical risk factors, and lower limb disease severity classified by vascular laboratory criteria were collected prospectively from 665 consecutive patients presenting with symptoms of peripheral arterial occlusive disease. The effect of patient and disease risk factors on survival was analyzed by the life-table method and independent significant variables examined by a multivariate Cox regression model. The cumulative survival for all patients at 1, 3, and 5 years were 86.1, 71.2, and 55.8%, respectively, with a median survival of 72.2 months. Female sex, age, smoking, heart disease, renal disease, respiratory disease, stroke, critical ischemia, lowest anklebrachial index, no vascular reconstruction, and major amputation were associated with higher mortality. Lipid and biochemical variables were not significant determinants. Using multivariate Cox regression, age (>70), disease severity, anklebrachial index (<0.5), no vascular reconstruction, diabetes mellitus, and renal and cardiorespiratory diseases were identified as independent risk factors affecting patient survival. The survival of patients with PAOD is poor compared with the general population. Significant patient-related variables were largely coexisting diseases and advanced age, whereas the other risk factors for atherosclerosis are less influential. Disease severity may bear a direct relationship to mortality, and patients with critical ischemia have the worst prognosis. Early disease detection and timely vascular reconstruction may lead to an improvement in overall survival.

Adult↗

Influence of coronary angioplasty on the progression of coronary atherosclerosis.

This study examines the effect of coronary angioplasty on the progression and appearance of new disease in sites of the coronary tree that were not dilated by the balloon. We examined 355 pairs of coronary angiograms from 252 patients. The study consisted of consecutive patients who were referred for catheterization > 1 month after successful angioplasty. Progression/regression and the appearance of new narrowings at sites not dilated by angioplasty were determined. The life-table method was used to determine outcome, and any event (progression, regression, and new narrowing) was analyzed according to the time of occurrence. The angioplasty artery was compared with the non-angioplasty artery and the effect of restenosis was determined by comparing arteries with and without restenosis. Progression/regression rates were not significantly different in angioplasty and non-angioplasty arteries. More new narrowings were identified in the angioplasty artery (p < 0.01). With regard to narrowings located in the angioplasty artery, progression was more common, regression less common, and the appearance of new narrowings more common in arteries with restenosis than in non-angioplasty arteries or arteries without restenosis. We believe that mechanical trauma to the artery during angioplasty could accelerate disease progression and the appearance of new narrowings in angioplasty arteries, whereas normalization of flow rate and pattern, especially in arteries without restenosis, attenuates the rate of progression and the appearance of new narrowings in these arteries. The final outcome depends on the balance between these factors.

Angioplasty, Balloon, Coronary↗

[Autologous peripheral blood stem cell transplantation in the treatment of patients with primary large mediastinal B-cell lymphoma].

OBJECTIVE: To evaluate the therapeutic effectiveness and safety of high dose chemoradiotherapy (HDC) combined with autologous peripheral blood stem cell transplantation (APBSCT) in the treatment of patients with primary large mediastinal B-cell lymphoma (PMLBL). METHODS: Among nine patients with PMLBL treated with APBSCT, high dose chemotherapy combined with total body irradiation (TBI) or total lymph node irradiation (TLI)/subtotal lymph node irradiation (STLI) were given to 7 patients and high dose chemotherapy only as pre-transplantation regimen in 2 patients. All patients received supplementary irradiation at the primary mediastinum after transplantation. RESULTS: After a median follow-up of 24 (10 - 84) months, 5 patients achieved complete remission (CR) and 3 patients partial remission (PR) after induction chemotherapy. One patient developed progressive disease before transplantation. All 5 patients who achieved CR after induction chemotherapy became disease-free survivors (DFS). One of 3 patients who achieved PR after induction chemotherapy was DFS, the other two died in the third and fifth month, respectively. The patient who relapsed before transplantation died in the sixth month carrying the disease all along. According to the life table method, the cumulative probability of 7-year DFS and overall survival (OS) were both 66.7%. No transplant-related mortality was found. CONCLUSION: High dose chemoradiotherapy combined with autologous peripheral blood stem cell transplantation is a highly potential therapeutic treatment for poor prognostic primary mediastinal large B-cell lymphoma.

Adolescent↗

Prognostic factors in renal cell carcinoma.

In order to evaluate the prognostic factors of renal cell carcinoma (RCC), a retrospective study was carried out on 215 patients (150 men, 65 women) who had undergone surgical treatment from March 1979 to December 1986. The average age of the patients was 58 years (ranging from 15 to 85 years). The ratios of survival to tumor stage and grade, as well as to nodal and venous involvement, distant metastases at the time of diagnosis (as TNM classification) were evaluated by means of the actuarial method (life table). Corrected 5-year survival rates for stage T1-T4 were 100, 81, 68.9 and 0%, respectively. Grade 1 and grade 2 tumors had a 5-year survival rate of 66.5 and 52.8%, respectively; grade 3 had a 3-year survival rate of 46.5%. Nodal involvement at the time of diagnosis had a prediction value for the 3- and 5-year survival rate of 39.8 and 34.5%, respectively. Metastases at time of diagnosis had a 14.1% prediction value for a 3-year survival rate. Tumor extension to the vena cava (21 patients) affected survival in a significant way (55.8% at 3 years). A definite tendency towards lower stage and grade was observed in incidentally diagnosed RCC (11%). In conclusion, stage, grade, nodal and venous involvement as well as metastases at the time of diagnosis have a significant prognostic value in RCC. These data and the lack of early diagnostic methods for RCC suggest the routine use of renal ultrasonography in clinically asymptomatic patients during examination for suspected abdominal diseases and in high-risk patients (Von Hippel-Lindau disease smokers).

Actuarial Analysis↗

An assessment of survival rates and within-patient clustering of failures for endosseous oral implants.

This study examined endosseous cylinder implant survival, defined as the unqualified presence of the implant in the mouth at the end of the observation period, in 598 consecutive VA patients, with a total of 2098 implants. Data were taken from the Department of Veterans Affairs (VA) Dental Implant Registry, which has maintained longitudinal data on the survival of individual dental implants in VA patients since 1987. The maximum time of observation in any one patient was 2040 days (5.6 yr). Survival analysis by use of life-table methods was carried out on both an implant- and a patient-specific basis. Implant cases were accrued randomly, and therefore a random censoring model was used. A correlated binomial model was used for assessment of the degree of within-patient clustering of implant removals. Results showed that the implant-specific survival rate during the longest time interval (5.6 yr) was 89.9%; the patient-specific implant survival rate during the same time was 78.2%. Among implants which were removed, the mean time to removal was 292 days. The hazard function, which describes the probability of implant loss as a function of time, decreased steadily throughout the observation period. The correlated binomial model suggested a clustering of removals within patients with multiple implants (rho = 0.11, p = 0.0001). The odds of having a second implant removed were 1.3 times greater if the patient had already had one implant removed. This study suggests that when implants fail, they do so soon after placement, and the likelihood of failure decreases steadily from implantation through the first five years post-surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cumulative pregnancy and live birth rates after gamete intra-Fallopian transfer.

To evaluate the efficacy of gamete intra-Fallopian transfer (GIFT) the Kaplan-Meier life table method was used to analyse a patient cohort treated with GIFT between 1991 and 1994. In a tertiary referral centre for reproductive medicine, 1628 women with a median age of 33 years and various causes of infertility were included to calculate cumulative pregnancy and live birth rates. Age and cause of infertility were main factor variables and the study was based on a total of 2941 consecutive GIFT cycles, leading to a first clinical pregnancy, and 3052 cycles, leading to a first live birth. The cumulative pregnancy and live birth rates were 49.6 and 38.8% respectively, after three initiated cycles and 64.1 and 52.0% respectively, after five initiated cycles. The multiple pregnancy rate was 22.6%. The implantation rate of 13.1% after GIFT demonstrates that the developing embryo benefits from a period of exposure within the environment of the Fallopian tube. The present results indicate that approximately 50% of couples will have at least one live baby after five initiated GIFT cycles. Advancing age was a major negative prognostic factor for the cumulative live birth rate because of higher cancellation rates, lower implantation rates and higher pregnancy failure rates.

Adult↗

Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma.

BACKGROUND: The aims of this study were to assess the incidence of micrometastases of lymph nodes in patients with early gastric cancer invading the submucosal layer and to investigate the correlation between nodal micrometastases and malignancy potential to determine whether micrometastases of lymph nodes have prognostic significance, by use of an anticytokeratin immunohistochemical technique. METHODS: A total of 2272 lymph nodes taken from 88 patients (25.8 per case) were assessed by immunohistochemical technique by use of monoclonal anti-human cytokeratin 8 antibodies. Clinicopathologic parameters and prognosis were compared between patients with and without micrometastases. RESULTS: The incidence of nodal involvement by tumor cells in 88 patients with submucosal gastric cancer increased from 19.3% (17 patients) by hematoxylin-eosin (H&E) staining to 31.8% (28 patients) by cytokeratin immunostaining. The rate of positive node in this study increased from 1.0% (23 of 2272 nodes) by H&E staining to 2.5% (57 of 2272 nodes) by immunostaining (P = .0002). No correlation was observed between the incidence of lymph node micrometastases and various clinicopathologic parameters, including tumor site and size, histological differentiation, Lauren classification, gross tumor type, vascular and lymphatic invasion, and perineural invasion. There was no difference in disease-free survival, estimated by the Kaplan-Meier life-table method, between the micrometastasis-negative and -positive groups (95% and 92.9%, respectively). Multivariate analyses showed that tumor size and diffuse subtype by the Lauren classification were significant factors for survival time (P = .0042 and .014, respectively). CONCLUSIONS: Immunohistochemical staining with an anticytokeratin antibody seems to be of little prognostic value in patients with submucosal gastric carcinoma. Thus, this immunostaining technique does not offer a significant benefit of different strategies for additional therapy or follow-up over conventional pathologic staging with H&E staining.

Adult↗

Mucosal melanoma of the head and neck.

Two hundred and fifty-nine patients with mucosal melanoma of the head and neck were reviewed. The data of these patients were obtained from the records of the Department of Head and Neck Oncology at the University of Liverpool and from the Merseyside and Cheshire Cancer Registry. Survival curves were constructed using the life table method and differences were investigated by the Log Rank Test. Prognostic factors were further analysed by Cox's proportional hazards model. Melanomas of the nasal cavities and sinuses accounted for 69%; 22% occurred in the oral cavity and 9% in the pharynx, larynx and upper oesophagus. In 49% treatment was by wide local resection and in 8% by irradiation. Thirty-six per cent had combined modalities of treatment. Primary site recurrence occurred in 52% and 36% developed nodal recurrence. The tumour specific survival at 5 years was 45% at 10 years 28%, at 20 years 17% and closely resembled the observed survival. Young male patients tended to have a favourable prognosis as did those treated surgically. Radiotherapy on its own was ineffective. Amelanotic melanoma had a particularly poor survival. Whereas site had no effect on survival. The study confirms the poor prognosis of mucosal melanoma of the head and neck. Young patients should be offered radical surgical treatment combined with radical radiotherapy if feasible as this offers the best chance of cure.

Adult↗

Molecular profile of advanced-stage transitional cell carcinoma of the ovary.

OBJECTIVES: Our purpose was to determine the molecular profile of advanced-stage transitional cell carcinoma in terms of immunostaining for p53, epidermal growth factor receptor and HER-2/neu, deoxyribonucleic acid index, and S-phase fraction and to analyze the prognostic significance of these markers. STUDY DESIGN: Archival paraffin-embedded tissue blocks from 29 advanced stage transitional cell carcinomas were obtained. Selected sections of the primary tumors were immunostained for p53, epidermal growth factor receptor, and HER-2/neu; deoxyribonucleic acid ploidy and S-phase fraction were determined with use of flow cytometry. Clinical information was abstracted from the medical records. Survival times were analyzed according to the life-table methods of Kaplan and Meier, and the statistical significance of the various factors was tested with the log-rank test. The proportional hazards model of Cox was used to identify prognostic factors. RESULTS: Positive immunostaining was observed for p53 in 13 cases (45%), for epidermal growth factor receptor in 14 cases (50%), and for HER-2/neu in 19 cases (65%). Tumors were diploid in 16 cases (55%) and aneuploid in 13 (45%). The S-phase fraction was < or = 15% (mean) in 13 cases (45%) and > 15% in 16 cases (55%). The median survival for the entire group was 52 months. None of the above variables had a significant effect on survival time. CONCLUSION: Neither immunostaining for p53, epidermal growth factor receptor, and HER-2/neu nor deoxyribonucleic acid ploidy nor S-phase fraction allowed us to distinguish transitional cell carcinoma from other more common epithelial ovarian cancers. In addition, no prognostic significance was associated with these biomarkers. A study of larger numbers of cases may be more elucidative.

Adult↗

[Endarterectomy versus vein bypass grafts in femoropopliteal occlusions (author's transl)].

On the basis of our experience with 1827 femoropopliteal arterial reconstructions performed from 1959 through 1974 we have worked up a system of strict guidelines for the choice of procedure. The vein bypass is the method of choice in all cases at stages III/IV (i.e. resting pain or gangrene), in lengthy occlusions of the femoral arteries continuing into the distal popliteal arteries or in stenotic lesions or occlusions of the tibial arteries, in all recurrent occlusions, and in cases with calcification or dilatation of the arterial wall. The indication for endarterectomy is restricted to stage II (i.e. intermittent claudication) and to segmental occlusions of the femoral or popliteal arteries as well as transitional or lengthy occlusions of the femoral artery continuing to the proximal popliteal artery. Under these guidelines a total group of 645 patients underwent 721 femoropopliteal reconstructions-307 endarterectomies and 414 vein grafts-from 1971 through 1974. The average age of the patients was 60 years. In 50% of all cases operations were carried out for advanced ischemia treatening the extremity. For all the series the patency rate of vein bypass was 79% and of endarterectomy 71%. Accumulative patency rates by the life table method according to the preoperative degree of arterial insufficiency and the postoperative follow up period of 4 years do not show statistically significant differences between both procedures under the given guidelines.

Adult↗

[Study on risk factors for progression of visual field damage in normal-tension glaucoma].

We investigated the risk factors for progression of visual field damage in normal-tension glaucoma (NTG), using multiple regression analysis with the proportional hazard model and the life-table method. Seventy-six eyes of 56 patients with untreated NTG showing minor visual-field defects, with a mean deviation (MD) of > - 5 dB by the Humphrey (30-2) STATPAC program at entry, were included in the study. Endpoints of study follow-up were defined as follows: in HFA STATPAC 2 Glaucoma Change Probability Analysis, more than 5 points which significantly deteriorated at p < 0.05 were found at 2 consequent examinations (Criterion 1) or a significant decrease in the MD value at p < 0.025 was encountered at one examination or that at p < 0.05 at 2 consecutive examinations (Criterion 2). During the follow-up period (37 months, mean), 33 eyes (42%) satisfied Criterion 1 and 23 eyes (29%) Criterion 2. When Criterion 1 was employed, peripapillary chorio-retinal atrophy/disc ratio (p = 0.023), intraocular pressure (IOP) (p = 0.03) and cup/disc ratio (p = 0.035) were identified as significant risk factors for progression of visual-field damage. When Criterion 2 was employed, Contribution of cup/disc ratio (p = 0.065) and IOP (p = 0.145) was relatively high, but not significant. These results suggested an association of IOP and local vascular risk factors with progression of visual-field damage in NTG.

Female↗

Recurrence rates of treated basal cell carcinomas. Part 4: X-ray therapy.

This is the fourth report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 862 primary (previously untreated) BCCs irradiated by a "standardized" x-ray therapy schedule. The overall 5-year recurrence rate for these lesions, as determined by the modified life-table method, was 7.4%. This rate was not significantly different from that experienced with 211 recurrent (previously treated) BCCs with a re-recurrence rate of 9.5% (P = .552). For the primary BCCs, multivariate analysis showed that increasing BCC diameter was the only independent risk factor for high recurrence rates (P = .003). The patient's age or sex, the duration of the BCC, the anatomic site of the BCC, or time-span treated (1955-1963, 1964-1972, 1973-1982) did not significantly affect the recurrence rate. Additional analysis showed that BCCs on the head less than 10 mm in diameter had a 5-year recurrence rate of 4.4% whereas those 10 mm or greater in diameter had a rate of 9.5%. Lastly, the proportion of recurrence-free treatment sites with a good or excellent long-term cosmetic outcome after x-ray therapy (63%) was lower than previous reports in this series with curettage-electrodesiccation (91%) and surgical excision (84%). Thus, if the long-term cosmetic outcome after treatment is not an overriding concern to the patient, x-ray therapy is an effective modality for many primary and recurrent BCCs.

Age Factors↗

Cricotracheal anastomosis for assisted ventilation-induced stenosis.

OBJECTIVE: To review the long-term results and our experience with cricotracheal anastomosis via a cervical approach for assisted ventilation-induced stenosis. DESIGN: A case series of 41 patients consecutively treated with cricotracheal anastomosis. SETTING: A tertiary care center and university teaching hospital. PATIENTS: Group 1 consisted of 22 patients with stenosis reaching the lower border of the cricoid cartilage that did not require resection of the cricoid cartilage. Group 2 consisted of 19 patients in whom correction of the stenosis required cricoid resection. MAIN OUTCOME MEASURES: Statistical analysis of airway patency was based on the Kaplan-Meier actuarial life table method. Incidence for the various postoperative complications was presented. Univariate analysis was performed to analyze the relationships between various factors, airway patency, and the incidence for the various complications encountered. RESULTS: The Kaplan-Meier 5-year airway patency estimate was 100% in group 1 patients and 82.5% in group 2 patients. In group 2 patients, complementary treatment with dilatations in 2 patients resulted in an overall 94.8% airway patency rate. In the last patient, the airway patency was not reestablished after cricotracheal anastomosis, and a Montgomery T tube was inserted. Postoperative complications included unilateral inferior laryngeal nerve paralysis (3 patients), cervical neck abscess (2 patients), pneumothorax (1 patient), and major subcutaneous emphysema (1 patient). None of the following variables was statistically related to the airway patency or to the various complications encountered: sex, age, cause for stenosis, delay from initial injury, prior treatment, presence of a tracheotomy, number of tracheal rings resected, type of sutures used, and type of anastomosis performed. CONCLUSIONS: The data reported reemphasized that cricotracheal anastomosis with or without cricoid resection is a safe and reliable procedure for assisted ventilation-induced upper tracheal stenosis reaching and/or involving the subglottis and/or cricoid cartilage.

Adolescent↗

Effective hemodynamic diameter: an intrinsic property of vein grafts with predictive value for patency.

INTRODUCTION: Conduit size and quality are major determinants of the long-term success of infrainguinal autologous vein grafting. However, accurate measurement of the internal diameter of vein grafts is difficult given their variable wall thickness and taper. The purpose of this study was to define the "effective" internal diameter of a vein graft according to its hemodynamic properties and to determine its significance for graft patency. METHODS: Sixty infrainguinal bypass grafts performed on 57 patients were evaluated intraoperatively. Proximal and distal graft pressure and blood flow (Q(meas)) were measured with fluid-filled catheter transduction and ultrasonic transit-time flowimetry, respectively, after unclamping. Waveforms were recorded digitally at 200 Hz under baseline conditions and after stimulation with 60 mg of papaverine. According to Fourier transformation of the measured pressure gradient (DeltaP), the Womersley solution for fluid flow in a straight rigid tube was used to calculate theoretical flow waveforms (Q(calc)) for a range of graft diameters. The theoretical waveforms were then compared with the measured flow waveforms and the best-fit diameter chosen as the "effective hemodynamic diameter" (EHD). Only grafts in which the correlation coefficient of Q(calc) versus Q(meas) was more than 0.90 were accepted (n = 47) to assure validity of the hemodynamic model. After a mean follow-up of 12.5 months (range, 0.1-43.9 months), patency was determined by the life table method. Hemodynamic and clinical variables were tabulated, and their effect on patency determined the use of univariate and multivariate Cox regression. RESULTS: Mean EHD was 4.1 +/- 0.1 mm with a range of 2.5 to 5.7 mm. Administration of papaverine caused profound changes in DeltaP (+78% +/- 17%) and Q(meas) (+71% +/- 12%) as expected, but had no effect on EHD (+0.05% +/- 0.1%). Univariate regression identified five variables associated with decreased secondary patency (P <.10): low EHD, conduit source other than the greater saphenous vein, high baseline DeltaP(mean), female sex, and redo operation. Of these, only low EHD was significant after multivariate analysis (P =.03). Patency of small diameter grafts (EHD < 3.6 mm; n = 11) was compared with patency of larger grafts (EHD > 3.6 mm; n = 36) to test a frequently espoused clinical guideline. Grafts with an EHD less than 3.6 mm exhibited significantly lower secondary patency compared with larger grafts (P =.0001). The positive and negative predictive values for an EHD less than 3.6 mm for secondary graft failure for grafts with at least 1 year follow-up were 86% and 88%, respectively. CONCLUSION: An EHD is a unique parameter that quantifies conduit size and has a significant impact on vein graft patency. An EHD less than 3.6 mm portends graft failure.

Aged↗

Leukaemia complicating treatment for Hodgkin's disease: the experience of the British National Lymphoma Investigation.

OBJECTIVE: To determine the incidence of and risk factors for the development of secondary acute leukaemia and myelodysplasia in patients treated in British National Lymphoma Investigation's studies of Hodgkin's disease since 1970. PATIENTS: 2676 Patients entered into Hodgkin's disease studies between February 1970 and November 1986. Data accrued up to November 1988 were analysed, ensuring a minimum follow up period of two years. DESIGN: Retrospective analysis of multicentre trial data by case-control and life table methods. RESULTS: 17 Cases of secondary leukaemia were recorded in this group of 2676 patients, giving an overall risk at 15 years of 1.7%. The risks of leukaemia after chemotherapy alone and chemotherapy with radiotherapy were not significantly different. The risk of leukaemia increased sharply with the amount of treatment given as measured by the number of attempts at treatment. The 15 year risks of leukaemia were 0.2%, 2.3%, and 8.1% for patients receiving one, two, or three or more attempts at treatment. The highest risk, 22.8% at 15 years, was observed in patients treated with lomustine (CCNU), and a case-control study suggested that this was an independent risk factor. The risk of secondary leukaemia was largely related to the overall quantity of treatment, although exposure to lomustine seemed to be an important risk factor. Treatment with both drugs and radiation was not more leukaemogenic than treatment with drugs alone. The greatest risk of secondary leukaemia was seen in multiply treated patients who were unlikely to be cured of Hodgkin's disease. CONCLUSIONS: Avoidance of secondary leukaemia should be a minor factor in the choice of treatment for Hodgkin's disease.

Acute Disease↗

[14C]Aminopyrine breath analysis and conventional biochemical tests as predictors of survival in cirrhosis.

Twenty-eight patients with histologically confirmed cirrhosis were followed for up to 3.8 years after [14C]aminopyrine breath analysis. Survival rates were calculated by life-table method and outcome analyzed by log rank test. A normal breath test score was associated with a higher probability of survival than a low score, although the difference was not statistically significant. A normal serum albumin was a better predictor of outcome. Survival curves constructed according to the results of breath analysis and serum albumin differed in that the former appeared to predict early survival and the latter late survival. For this reason, data were reanalyzed by subjects' results for both tests. A normal breath test score and a normal serum albumin was associated with a significantly higher probability of survival than an abnormal result for either test.

Adult↗

Methotrexate use in systemic lupus erythematosus.

Low dose pulse oral methotrexate (MTX) is a well established treatment for rheumatoid arthritis, and short term open studies have suggested beneficial effects of MTX in SLE. This study was designed to investigate MTX treatment maintenance rates in SLE using life table analysis, and to determine whether MTX use was associated with a dose reduction of concomitant steroid therapy. All SLE patients managed by physicians affiliated with a single centre were studied cross-sectionally. Information regarding disease variables and drug use were ascertained by interview and chart review. Drug therapy data including dates of treatment and indications for treatment were analysed using Kaplan-Keier life table methods. Among 101 subjects with SLE, 25 MTX treatment episodes were observed in 24 subjects. The period studied totalled 19766 patient-days, with a median (range) duration of observed MTX treatment of 14.4 (5.1-41.6) months. The median (range) initial and peak MTX doses with 7.5 (2.5-10)mg/wk and 10 (7.5-15) mg/week respectively. The principal indication for commencing methotrexate therapy was arthritis. Only two subjects terminated treatment for toxicity, with the most common reason for termination being remission. The cumulative probability of continuing treatment was 68% at 12 months and 61% at 24 months, or 75% and 71% respectively if cessations for remission were excluded. The median (interquartile range) monthly steroid intake during MTX therapy [279.4 (193.4-492.9)mg] was somewhat lower than during the 6 months prior to [298.1 (237.9-531.4)428.8)mg] MTX therapy, but this difference was not significant. A total of 36% of subjects reduced their steroid dose during MTX therapy, but this reduction was not significant. Treatment of SLE with MTX, predominantly for arthritis, was well tolerated over prolonged periods of observation. Toxicity of sufficient severity to lead to treatment termination was uncommon. A subset of subjects were able to reduce steroid intake during MTX therapy, but no overall reduction in steroid dose was observed.

Adult↗

Wheat bran and psyllium diets: effects on N-methylnitrosourea-induced mammary tumorigenesis in F344 rats.

BACKGROUND: Experimental and epidemiologic evidence suggests that increased dietary fiber is associated with decreased breast cancer risk. Little is known about the role played by different types of fiber and, particularly, mixtures of soluble and insoluble fibers similar to those consumed by human populations in reducing breast cancer risk. High intake of fiber may suppress bacterial hydrolysis of biliary estrogen conjugates to free (absorbable) estrogens in the colon and thus may decrease the availability of circulating estrogens necessary for the development and growth of breast cancers. PURPOSE: The purpose of this study was to evaluate the effect of wheat bran (an insoluble fiber) and psyllium (a soluble fiber) alone and in combination on overall estrogen status, on fecal bacterial beta-D-glucuronidase (a key diet-responsive estrogen-deconjugating enzyme) activity, and on the induction of mammary tumors in rats treated with N-methylnitrosourea (MNU). METHODS: One hundred fifty virgin female F344 rats were fed the NIH-07 diet from 28 days of age until 50 days of age; they were then given a single dose (40 mg/kg of body weight) of MNU by tail vein injection. Three days later, they were randomly assigned to one of five experimental dietary groups (30 animals per group). Soft, white wheat bran (45% dietary fiber content) and psyllium (80% dietary fiber content) were added to a modified (high-fat) American Institute of Nutrition (AIN)-76A diet at the following percents, respectively: 12% + 0% (group 1), 8% + 2% (group 2), 6% + 3% (group 3), 4% + 4% (group 4), and 0% + 6% (group 5). Blood, urine, and feces were collected and analyzed by radioimmunoassay techniques for estrogens. Cecal contents were analyzed for bacterial beta-D-glucuronidase activity. After 19 weeks on the experimental diets, the rats were killed, and mammary tumors were counted and classified by histologic type. Cumulative tumor incidence was evaluated by the Kaplan-Meier life-table method and the logrank test. Tumor number was evaluated by the chi-squared test of association, and tumor multiplicity was evaluated by the Mantel-Haenszel chi-squared test. All statistical tests were two-tailed. RESULTS: As the level of psyllium relative to that of wheat bran increased, the total tumor number and multiplicity of mammary adenocarcinomas in rats decreased as a statistically significant linear trend across groups 1-5 (P < .05). Compared with the group given wheat bran alone, the group given the 1:1 (wheat bran:psyllium) combination had maximum protection against mammary tumorigenesis, while the groups given the 4:1 or 2:1 (wheat bran:psyllium) combination or psyllium alone had intermediate protection. No statistically significant differences in circulating estrogens or urinary estrogen excretion patterns were observed among the five experimental groups. Fecal estrogen excretion, however, decreased with increasing levels of psyllium (P < .01), and cecal beta-D-glucuronidase activity exhibited a decreasing trend with respect to the increasing psyllium content of the diet across groups 1-5 (P < .01). CONCLUSIONS: The addition of a 4%:4% mixture of an insoluble (wheat bran) fiber and a soluble (psyllium) fiber to a high-fat diet provided the maximum tumor-inhibiting effects in this mammary tumor model. Although increasing levels of dietary psyllium were associated with decreased cecal bacterial beta-D-glucuronidase activity, these changes were not reflected in decreased circulating levels of tumor-promoting estrogens. Therefore, the mechanism(s) by which mixtures of soluble and insoluble dietary fibers protect against mammary tumorigenesis remains to be clarified.

Animals↗