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Biomedical subjects

P Rubin

Publications and source records attributed to P Rubin.

At least 91 records · Page 5Linked to original sources
PubMed1996

An observer study for direct comparison of clinical efficacy of electronic to film portal images.

PURPOSE: To directly compare clinical efficacy of electronic to film portal images. METHODS AND MATERIALS: An observer study was designed to compare clinical efficacy of electronic to film portal images acquired using a liquid matrix ion-chamber electronic portal imaging device and a conventional metal screen/film system. Both images were acquired simultaneously for each treatment port and the electronic portal images were printed on gray-level thermal paper. Four radiation oncologists served as observers and evaluated a total of 44 sets of images for four different treatment sites: lung, pelvis, brain, and head/neck. Each set of images included a simulation image, a double-exposure portal film, and video paper prints of electronic portal images. Eight to nine anatomical landmarks were selected from each treatment site. Each observer was asked to rate each landmark in terms of its clinical visibility and to rate the ease of making the pertinent verification decision in the corresponding electronic and film portal images with the aid of the simulation image. RESULTS: Ratings for the visibility of landmarks and for the verification decision of treatment ports were similar for electronic and film images for most landmarks. However, vertebral bodies and several landmarks in the pelvis such as the acetabulum and public symphysis were more visible in the portal film images than in the electronic portal images. CONCLUSION: The visibility of landmarks in electronic portal images is comparable to that in film portal images. Verification of treatment ports based only on electronic portal images acquired using an electronic portal imaging device is generally achievable.

Observer Variation↗
PubMed1996

Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group.

PURPOSE: The objectives of this randomized trial were to determine if interstitial thermoradiotherapy (ITRT) improves tumor regression/control in accessible lesions in comparison with interstitial radiotherapy (IRT) alone and to assess the skin and soft tissue complications with either modality. METHODS AND MATERIALS: From January 1986 to June 1992, 184 patients with persistent or recurrent tumors after previous radiotherapy and/or surgery, which were amenable to interstitial radiotherapy, were accessioned to a protocol developed by the Radiation Therapy Oncology Group (RTOG). One hundred seventy-three cases were analyzed (87 patients in the IRT group and 86 in the ITRT arm). The two arms were well balanced regarding stratification criteria. Most tumors were in the head and neck (40% in the IRT group and 46% in the ITRT group), and pelvis (42% and 43%, respectively). Eighty-four percent of patients in both arms had prior radiation therapy (> or = 40 Gy); 50% and 40%, respectively, had prior surgery, and 34% in each arm had prior chemotherapy. The dose of radiation therapy administered was dependent on the previous radiation dose and did not exceed a total cumulative dose of 100 Gy. Hyperthermia was delivered in one or two sessions, either before or before and after interstitial implant. The intended goal of the hyperthermia was to maintain a minimal tumor temperature of 42.5 degrees C for 30 to 60 min. RESULTS: There was no difference in any of the study end points between the two arms. Complete response (CR) was 53% and 55% in both arms. Two-year survival was 34% and 35%, respectively. Complete response rate for persistent lesions was 69% and 63% in the two treatment arms as compared with 40% and 48% for recurrent lesions. A set of minimal adequacy criteria for the delivery of hyperthermia was developed. When these criteria were applied, only one patient had an adequate hyperthermia session. Acute Grade 3 and 4 toxicities were 12% for IRT and 22 % for ITRT. Late Grade 3 and 4 toxicities were 15% for IRT and 20% for ITRT. The difference was not significant. CONCLUSIONS: Interstitial hyperthermia, as applied in this randomized study, did not show any additional beneficial effects over interstitial radiotherapy alone. Delivery of hyperthermia remains a major obstacle (since only one patient met the basic minimum adequacy criteria as defined in this study). The benefit of hyperthermia in addition to radiation therapy still remains to be proven in properly randomized prospective clinical trials after substantial technical improvements in heat delivery and dosimetry are achieved.

Adult↗
PubMed1996

A phase I/II study of high-dose cyclophosphamide, cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies.

The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colony-stimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m2 per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m2 per day as a 24-h continuous i.v infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300-900 mg/m2) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 microliter was 10 days (range, 9-12 days) for those who received PBPCs and 15 days (range, 15-34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2-17 months). The maximally tolerated dose of thioTEPA was 600 mg/m2 given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration, The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies.

Adult↗
PubMed1996

Retinopathy and optic neuropathy in bone marrow transplantation for breast cancer.

PURPOSE: To characterize the ocular toxicity of a bone marrow transplant regimen does not include total body or focal head irradiation. METHODS: Nine patients with advanced breast cancer were referred for visual symptoms after high-dose chemotherapy with cisplatin, cyclophosphamide, and carmustine and autologous bone marrow transplantation without total body irradiation or local head irradiation. RESULTS: Symptoms consistent with optic neuropathy and retinopathy developed in five patients. Retinopathy alone developed in three patients and optic neuropathy alone developed in one. Retinal abnormalities included cotton-wool spots, intraretinal hemorrhages, and macular exudate. Optic nerve findings included disk swelling and subsequent pallor. Symptoms and signs associated with retinopathy were generally reversible, whereas those associated with optic neuropathy often were permanent. Retinopathy and/or optic neuropathy developed in all of the patients from 1 to 5 months after bone marrow transplantation. Resolution or stabilization of findings was observed 2-4 months after presentation. Two patients with optic neuropathy showed progression of field and acuity loss after 4 months. When compared with control subjects, the exposure of patients to cyclophosphamide and carmustine was no different. However, cisplatin exposure was 1.2-fold higher in patients with ocular toxicity compared with control subjects. CONCLUSION: Optic neuropathy and retinopathy are presumed to arise from the administration of a high-dose chemotherapy regimen. As techniques in supportive care improve, long-term adverse effects of these therapies now are becoming apparent.

Adult↗
PubMed1996

Tumour bed biopsy detects the presence of multifocal disease in patients undergoing breast conservation therapy for primary breast carcinoma.

This study prospectively examined tumour bed biopsies in 135 consecutive patients undergoing conservative surgery for breast carcinoma. All had wide resection of the primary tumour and histologically clear margins. Twelve patients (9%) had positive tumour bed biopsies. Two subgroups of patients had positive bed biopsies; those with ductal carcinoma in situ, and a second group with more aggressive disease characterized by lymph node involvement, vascular invasion and a higher grade and mitotic count. As the majority of recurrences from breast carcinoma occur in the region of the primary tumour, bed biopsy may aid in the identification of a group of patients with multifocal or aggressive disease who are at increased risk of local recurrence.

Biopsy↗
PubMed1996

Accurate recovery of articulator positions from acoustics: new conclusions based on human data.

Vocal tract models are often used to study the problem of mapping from the acoustic transfer function to the vocal tract area function (inverse mapping). Unfortunately, results based on vocal tract models are strongly affected by the assumptions underlying the models. In this study, the mapping from acoustics (digitized speech samples) to articulation (measurements of the positions of receiver coils placed on the tongue, jaw, and lips) is examined using human data from a single speaker: Simultaneous acoustic and articulator measurements made for vowel-to-vowel transitions, /g/ closures, and transitions into and out of /g/ closures. Articulator positions were measured using an EMMA system to track coils placed on the lips, jaw, and tongue. Using these data, look-up tables were created that allow articulator positions to be estimated from acoustic signals. On a data set not used for making look-up tables, correlations between estimated and actual coil positions of around 94% and root-mean-squared errors around 2 mm are common for coils on the tongue. An error source evaluation shows that estimating articulator positions from quantized acoustics gives root-mean-squared errors that are typically less than 1 mm greater than the errors that would be obtained from quantizing the articulator positions themselves. This study agrees with and extends previous studies of human data by showing that for the data studied, speech acoustics can be used to accurately recover articulator positions.

Humans↗
PubMed1996

Intrauterine growth retardation and premature delivery: the influence of maternal smoking and psychosocial factors.

OBJECTIVES: This study investigated the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol, and smoking on intrauterine growth retardation and premature delivery. METHODS: At a Copenhagen university hospital, 2432 pregnant women completed a questionnaire on general health, psychosocial stressors, and sociodemographic characteristics. RESULTS: In 212 cases (8.7%) the women delivered prematurely. Preterm delivery as associated with psychosocial stress (adjusted odds ratio [OR]=1.14 for each 1-point increase on the psychosocial stressor 5-point scale and 1.92 for the whole scale) and poor school education (adjusted OR=2.62 for 7-9 years of schooling, 1.91 for 10 years, and 1.0 for 11-13 years). In 152 cases (6.3%), infants had a birthweight below the 10th percentile. Intrauterine growth retardation was associated with smoking, daily drinking, school education, and social network variables. In a multiple logistic regression model, intrauterine growth retardation was associated with smoking habits (adjusted OR=2.40 for 0-9 cigarettes daily, 2.68 for 10-15 daily, and 2.88 for more than 15 daily). CONCLUSIONS: Psychosocial stressors and limited duration of schooling appeared to influence preterm delivery. Smoking habits influenced intrauterine growth retardation.

Adult↗
PubMed1996

Early and persistent alterations in the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor alpha mRNA levels in fibrosis-resistant and sensitive mice after thoracic irradiation.

Fibrosis, characterized by the accumulation of collagen, is a consequence of a chronic inflammatory response. The purpose of this study was to determine if tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta mRNA expression are altered acutely after irradiation, during the so-called "latent" phase of pulmonary injury, and to examine if these alterations persist through the development of pneumonitis and fibrosis. Further, we wished to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by slot blotting and hybridized with radiolabeled cDNA probes encoding for TNF-alpha, IL-1 alpha and IL-1 beta. Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceraldehyde-3-phosphate dehydrogenase. It was found that TNF-alpha mRNA levels were increased in C57BL/6 mice at days 1 and 7 postirradiation after 5 Gy and day 14 postirradiation after both 5 and 12.5 Gy, and IL-1 alpha mRNA levels were increased in C57BL/6 mice at days 56, 112 and 182 postirradiation after both 5 and 12.5 Gy, and IL-1 beta mRNA levels in the C3H/HeJ mice were increased at days 56 and 182 postirradiation after 12.5 Gy. In summary, these studies demonstrated early and persistent alterations in TNF-alpha, IL-1 alpha and IL-1 beta mRNA levels even at the lower dose (5 Gy). The temporal relationship between the elevation of these cytokines and the strain-dependent variation in fibrosis response suggests that IL-1 alpha and TNF-alpha contribute to the radiation-induced component of pulmonary fibrosis, whereas IL-1 beta may have a protective function.

Animals↗
PubMed1996

A comparison of mesalamine suspension enema and oral sulfasalazine for treatment of active distal ulcerative colitis in adults.

OBJECTIVES: To compare the efficacy and safety of mesalamine (5-ASA) suspension enema versus oral sulfasalazine (SAS) in patients with active mild to moderate distal ulcerative colitis. METHODS: Thirty-seven patients were randomly assigned to treatment with either rectal mesalamine, 4 g at night, (n = 19) or oral sulfasalazine, 1 g four times a day, (n = 18) in a 6-wk, double-blind, double-dummy, parallel-group, multicenter study. Patients known to be refractory to SAS or 5-ASA preparations were excluded. Efficacy was assessed by a physician-rated Disease Activity Index (DAI), which included symptom evaluations and sigmoidoscopic findings, by physician-rated Clinical Global Improvement (CGI) scores, and by Patient Global Improvement (PGI) scores. Safety was assessed by adverse event reports, clinical laboratory tests, and physical examination. Results. Mean DAI scores indicated significant improvement from baseline in both treatment groups. CGI scores indicated that 94% of the 5-ASA patients were either "Very Much Improved" or "Much Improved" at wk 6 versus 77% of the SAS patients. PGI ratings showed more improvement in the 5-ASA treatment group than in the SAS group at wk 2 (p = 0.02) and at wk 4 (p = 0.04). Adverse events, primarily headache and nausea, occurred significantly more frequently (p = 0.02) in the SAS than in the 5-ASA group (83 vs 42%). Three patients were withdrawn from SAS treatment because of adverse events. CONCLUSIONS: Rectally administered 5-ASA is as effective as oral SAS in treatment of active distal ulcerative colitis but is associated with fewer and milder adverse events. Patients treated with 5-ASA reported improvement earlier than those treated with SAS.

Administration, Oral↗
PubMed1996

Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer.

Five hundred and eighty-one patients with stage II-IV breast cancer were treated at Duke University Medical Center with high-dose chemotherapy, followed by hematopoietic support. All patients received a conditioning regimen of cyclophosphamide, cisplatin and carmustine. Of these patients, 15 (2.6%) developed symptoms similar to the hemolytic-uremic syndrome with evidence of thrombotic microangiopathy (TMA). The time of onset ranged from 75 days to 281 days post-transplant, with a median of 143 days. Hemolytic anemia and thrombocytopenia, without alternative cause, were required for diagnosis. All patients were treated with steroid therapy. In addition, 12 patients were treated primarily with plasmapheresis, and received a median of 46 treatments. Additional therapy included staphylococcal protein A column apheresis (eight patients), vincristine (three patients) and danazol (one patient). The mortality rate was 11 of 15 patients (73%). These patients had a median survival of 41 days from diagnosis of TMA (range 2-76 days). The four survivors are alive at 76, 186, 1837 and 2387 days from diagnosis of TMA. Three of these patients received twice daily plasmapheresis and protein A column apheresis therapy. One patient recovered without specific therapy. TMA is an infrequent complication of high-dose chemotherapy, but is associated with a high mortality. It frequently follows significant pulmonary drug toxicity. Survival may be improved with early diagnosis and aggressive plasmapheresis therapy.

Anemia, Hemolytic↗
PubMed1996

Ocular toxicity following high dose chemotherapy and autologous transplant.

A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Radiation palliation of cervical cancer.

Radiation is a useful modality for palliation of local-regional disease in patients with cervical cancer who require palliation because of distant metastases, extensive local-regional disease, medical consideration, or patient concerns. Two radiation schedules have been reported on for the treatment of advanced pelvic disease including cervical cancer. The large single-dose schedule consisted of 10-Gy fractions repeated at monthly intervals to a maximum of 30 Gy. This schedule has produced good palliative results with symptomatic improvement in approximately 50% of patients and objective response in 35%-80%. However, severe late toxicity was shown to be as high as 42% (actuarial). The second schedule tested by the Radiation Therapy Oncology Group consisted of 3.7-Gy fractions given twice a day for 2 days (14.8 Gy) repeated after 2-4 weeks for a maximum of 44.4 Gy. There were 284 patients accrued, and the subgroup of 61 cervical cancer patients is analyzed in this article. The subjective response (50%-100% complete response) and objective response (53%) were similar to those observed with the large single-fraction schedule. The late toxicity was significantly lower (7%-actuarial). For patients who may survive 6 months or longer, this second schedule is preferable.

Female↗
PubMed1995

Correlation of survival with quantitative tissue staining of prostate specific acid phosphatase in patients with prostate carcinoma by using microscopic image analysis: a preliminary report of correlative studies on RTOG protocols 75-06, 77-06, and 83-07.

PURPOSE: We have previously shown that the intensity (graded semiquantitatively as 1-4+) of tissue prostate-specific acid phosphatase (PSAP) staining determined immunocytochemically in a cohort of prostate carcinoma patients from Radiation Therapy Oncology Group Protocols (RTOG) protocols 75-06 and 77-06 correlated with survival. The extent of this staining was heterogeneous and was estimated. The extent of staining was not found to be significantly associated with survival. We undertook the present quantitative study to see if the improved precision and reliability of measurement of the intensity and extent of prostate specific acid phosphatase staining would confirm and extend our previous observations. METHODS AND MATERIALS: Patient cohorts representative of the entire group were obtained from RTOG 75-06 plus 77-06 and 83-07. The RTOG 77-06 plus 75-06 patients (No-Hormone population) did not receive preradiation hormonal therapy. RTOG 83-07 patients (Prehormone population) received one of two types of preradiation chemical androgen ablation. In this study, histologic slides of tumors were immunocytochemically stained for PSAP by the peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as a substrate and hematoxylin as a nuclear counterstain. The intensity and extent of immunocytochemical PSAP staining (IPSAP stain) was quantified using our dual wavelength and batch mode image process technique. RESULTS: Our study of 151 cases confirmed that overall survival of patients in both populations was positively correlated with the intensity and extent of IPSAP stain. Results of the two studies were similar. The statistical significance of the relationship of both extent and intensity was greater in the cohort from protocol 83-07, which was the patient group receiving pretreatment with hormones. In a Cox multiple regression analysis including clinical stage, Gleason and M. D. Anderson grades, and the cohort of patients (Prehormone or No-Hormone group) as covariables, both the intensity and extent of the IPSAP stain significantly correlated with survival along with M. D. Anderson grade of the tumor. CONCLUSION: Quantitative image analysis of the IPSAP stain predicts survival in patients treated with external beam radiotherapy with and without prior hormonal therapy.

Acid Phosphatase↗
PubMed1995

A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis.

PURPOSE: Radiation-induced pulmonary reactions have classically been viewed as distinct phases--acute pneumonitis and, later, fibrosis--occurring at different times after irradiation and attributed to different target cell populations. We prefer to view these events as a continuum, with no clear distinction between the temporal sequence of the different pulmonary reactions; the progression is the result of an early activation of an inflammatory reaction, leading to the expression and maintenance of a cytokine cascade. In the current study, we have examined the temporal and spatial expression of cytokine and extracellular matrix messenger ribonucleic acid (mRNA) abundance in fibrosis-sensitive mice after thoracic irradiation. METHODS AND MATERIALS: Radiation fibrosis-prone (C57BL/6) mice received thoracic irradiation of 5 and 12.5 Gy. At Day 1, and 1, 2, 8, 16, and 24 weeks after treatment, animals were killed and lung tissue processed for light microscopy and isolation of RNA. Expression of cytokine and extracellular matrix mRNA abundance was evaluated by slot-blot analysis and cellular localization by in situ hybridization and immunochemistry. RESULTS: One of the cytokines responsible for the inflammatory phase (IL-1 alpha) is elevated at 2 weeks, returns to normal baseline values, then increases at 8 weeks, remaining elevated until 26 weeks when lung fibrosis appears. Transforming growth factor-beta (TGF beta), a proliferative cytokine, is elevated at 2 weeks, persists until 8 weeks, and then returns to baseline values. In parallel with the cytokine cascade, the fibrogenic markers for CI/CIII/IV (collagen genes) correlate by showing a similar early and then later elevation of activity. For instance, the collagen gene expression of CI/CIII is a biphasic response with an initial increase at 1-2 weeks that remits at 8 weeks, remains inactive from 8 to 16 weeks, and then becomes elevated at 6 months when collagen deposition is recognized histopathologically. CONCLUSION: These studies clearly demonstrate the early and persistent elevation of cytokine production following pulmonary irradiation. The temporal relationship between the elevation of specific cytokines and the histological and biochemical evidence of fibrosis serves to illustrate the continuum of response, which, we believe, underlies pulmonary radiation reactions and supports the concept of a perpetual cascade of cytokines produced immediately after irradiation, prompting collagen genes to turn on, and persisting until the expression of late effects becomes apparent pathologically and clinically.

Animals↗