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Biomedical subjects

P Rubin

Publications and source records attributed to P Rubin.

At least 271 records · Page 15Linked to original sources
PubMed1983

Once-a-week irradiation for locally advanced lung cancer.

Twenty-eight patients with very advanced lung cancer were treated with 500 rad once weekly to a total dose of 6000 rad (2050 ret). Twenty-one of the 28 patients (75%) achieved at least a partial local response. There were 9 patients (32%) who achieved a complete response and 12 patients (43%) who achieved a partial response. The responses were 9/11 for squamous cell carcinoma, 5/10 for adenocarcinoma, 5/5 for large cell carcinoma, and 2/2 for small cell carcinoma patients. Treatment was very well tolerated and in fact, no acute radiation related complications were observed during the 10-12 week treatment duration. Radiation induced fibrosis of various degrees has occurred but it has been mostly asymptomatic and similar to what is normally seen using conventional continuous schedules. In this group of very advanced lung cancer patients, failures have mostly resulted from metastatic progression; only one patient progressed locally in the irradiated field without evidence of metastatic disease. A preliminary analysis indicates that this treatment yields results that are similar to those achieved with conventional fractionation regimens and should be explored further.

Adenocarcinoma↗
PubMed1983

Combined modality treatment of regional small cell undifferentiated carcinoma of the lung: a cooperative study of the RTOG and ECOG.

Between 1975 and 1979, 271 patients with regional small cell undifferentiated (including oat cell) carcinoma of the lung were entered into a study involving treatment by radiation therapy (4500 cGy (rad) in five weeks) to the primary tumor, mediastinum and supraclavicular lymph nodes, and a randomization to receive or not receive prophylactic treatment of the brain (3000 cGy in two weeks) and a randomization to prophylactic or delayed chemotherapy (cyclophosphamide and CCNU). Analysis of the data indicates that the median survival for responders (53 weeks) was significantly longer than that of the non-responders and partial responders (37 and 34 weeks). Median survival by treatment arm was 48 weeks for thoracic irradiation (TI), brain irradiation (BI), and early chemotherapy (CT), 44 weeks for TI alone, 41 weeks for TI and CT, 38 weeks for TI and BI. Regional complete and partial tumor responses were 52 and 25% for prophylactic chemotherapy and 44 and 35% for delayed chemotherapy. The site of first failure was regional in 12%, regional and distant simultaneously in 21%, and distant only in 46%. Elective brain irradiation significantly reduced the incidence of brain metastases from 21 and 5%, but did not improve survival.

Brain Neoplasms↗
PubMed1983

Surfactant release as an early measure of radiation pneumonitis.

The immediate release of surfactant into lung alveoli following irradiation has been studied as a potential indicator for the later development of radiation pneumonitis. Utilizing single dose radiation exposure to the whole thorax in male LAF1/J mice, steep dose response curves for lavaged alveolar surfactant were identified at 7 and 28 days after exposure. Seven days after irradiation there was no elevation with doses up to and including 12 Gy; above this dose a detectable increase occurred. At 28 days the surfactant recovered by lavage was elevated compared to the levels seen at day 7 for all doses; doses greater than 12 Gy produced surfactant values significantly greater than those found in mice treated with 12 Gy or less. The radiation pulmonary lethality dose response curve assessed four months later indicated an LD50 value of approximately 13 Gy. The early biochemical effect and the later radiation pneumonitis lethalities therefore closely coincided. The evidence strongly indicates that alveolar surfactant release uncovered hours to days after radiation exposure may be an early biochemical marker that predicts for subsequent pneumonitis radiation injury.

Animals↗
PubMed1983

Improved survival in cases of intracranial ependymoma after radiation therapy. Late report and recommendations.

A publication from the University of Rochester Cancer Center in 1975 suggested an improvement in the survival time of patients with intracranial ependymomas in whom an aggressive postoperative radiation therapy approach had been adopted. The regimen was tailored to the aggressiveness and spread patterns of these tumors and therefore considered the patient's age, tumor histopathology and location, and status of the subarachnoid space and cerebrospinal fluid (CSF). The authors proposed using whole brain (WB) fields for all patients with low-grade supratentorial tumors, and WB with cervical cord field extensions for low-grade infratentorial tumors if either group had no CSF or subarachnoid evidence of spinal metastases. They also proposed using craniospinal irradiation for all patients with high-grade ependymomas (regardless of location) or with low-grade infratentorial tumors with positive CSF or subarachnoid findings of spinal metastases. Recommended doses were as follows: 4500 rads to the whole brain, 5500 rads to the primary tumor volume, and 3000 to 4000 rads to the spine, depending on its subarachnoid status. Children aged 3 years or under were to receive 80% of these doses and more protracted daily treatments. Analysis of the updated experience indicates that in 51 patients treated with this approach these criteria have yielded a beneficial and consistent increase in the survival time. A 69% 10-year survival rate has been observed (75% for low-grade and 67% for high-grade ependymomas). A multifactorial analysis of survival by prognostic factors and by grouping of prognostic factors, analysis of failures, autopsy findings, and quality of survival is presented and discussed.

Adolescent↗
PubMed1983

Absence of the seventh component of complement in a patient with chronic meningococcemia presenting as vasculitis.

A previously healthy 40-year-old man presenting with fever, arthritis, and cutaneous vasculitis was found to have chronic meningococcemia. Evaluation of his complement system showed an absence of functional and antigenic C7, compatible with a complete deficiency of the seventh component of complement. Study of the patient's family spanning four generations showed heterozygous deficiency of C7 in five members. Chronic neisserial infection can be associated with C7 deficiency and must be distinguished from other causes of cutaneous vasculitis.

Adult↗
PubMed1983

The Chediak-Higashi gene in humans. III. Studies on the mechanisms of NK impairment.

Lymphocytes from six Chediak-Higashi (CH) patients were markedly depressed in their ability to lyse tumour cell targets in both 51Cr release and single cell cytotoxicity assays. The frequency of lymphocytes bearing the OKM1 marker and the frequency of T3+, T4+, T8+, Ia+, Mo1+, Mo2+ and B1+ cells was normal among sheep erythrocyte rosetting (E+) and non-rosetting (E-) peripheral blood leucocytes analysed by flow cytofluorography. Cells expressing the NK shared markers, OKM1, mac-1, FcR, and the characteristic large granular lymphocyte (LGL) morphology of NK cells were also present in normal numbers in the highly enriched NK fraction separated on Percoll density gradients. This fraction did not contain detectable numbers of cells expressing the Mo2 marker of human monocytes. Therefore most of the cells stained by monoclonal OKM1 and mac-1 in this fraction are likely NK cells, rather than monocytes, and we conclude that the size of the NK pool in CH patients is probably normal. The capacity of CH lymphocytes to recognize and bind to tumour cells was also normal as was the subsequent burst of oxygen intermediates produced by the NK cells in a chemiluminenscence assay. We have shown elsewhere that O2- generation is directly involved in activating subsequent steps in the NK cytolytic pathway. These results suggest that NK cells in CH patients are present in normal frequency but are blocked at some post-recognition, post-activation step in the cytolytic pathway subsequent to the burst of oxygen intermediates but preceding the lethal hit.

Adolescent↗
PubMed1982

Studies of human natural killer cells. III. Neutropenia associated with unusual characteristics of antibody-dependent and natural killer cell-mediated cytotoxicity.

A 52-year-old Caucasian man with chronic neutropenia and recurrent infections was found to have an increased proportion of peripheral T lymphocytes having Fc receptors for IgG (T gamma ). Although levels of antibody-dependent cell-mediated cytotoxicity (ADCC) and "natural" killing (NK) by unfractionated lymphocytes were similar to those of a control donor, the frequency of KN cells was markedly increased. Removal of E rosette-forming cells eliminated both NK and ADCC by the patient's peripheral blood, in marked contrast to the enhanced cytotoxicity seen with control lymphocytes. Both normal and patient ADCC and NK functions were removed by depletion of Fc receptor-bearing cells. These depletion experiments proved that all of the patient's killer cells were E rosette-forming T gamma cells, in contrast to the heterogeneous pattern of null gamma and T gamma killer cells seen in the blood of normal donors. The homogeneity of the T gamma proliferation suggested that ADCC and NK were mediated by the same cell type, albeit acting by different mechanisms. The addition of the patient's serum and lymphocytes to chromium-labelled normal granulocytes caused a low but significant level of cytotoxicity, indicating that the patient's neutropenia may have been caused by a similar mechanism in vivo. There was no evidence of complement-dependent serum antibody-mediated neutrophil lysis, but one serum sample taken over the course of the patient's disease agglutinated granulocytes from four of five donors tested.

Agglutination↗
PubMed1982

Sequential effects of irradiation on the pulmonary surfactant system.

This study examines the effect of irradiation on lung surfactant synthesis and secretion in mice. Animals were irradiated with 650, 1300, or 1950 rad and morphological and biochemical indices of surfactant system function were followed for 18 weeks. No changes were seen at 650 rad; the results at 1300 and 1950 rad were virtually identical. Increased amounts of alveolar surfactant phospholipid were measureable by 24-hours. This persisted for four weeks and returned to normal by 18 weeks. Tissue surfactant phospholipid was initially reduced, returned to normal by four weeks and was increased at 18 weeks. At 18 weeks there was increased incorporation of surfactant precursor and increased production of alveolar surfactant. These biochemical changes were reflected in morphologic alterations showing release of lamellar body contents into alveoli in the first week and an increase in lamellar bodies in type II pneumocytes by 18 weeks. Elevated tissue protein levels and morphologic evidence of increased collagen formation were also found at 18 weeks. These findings indicate effects of irradiation on the pulmonary surfactant system and have important implications for the pathogenesis and potential therapy of radiation pneumonitis.

Animals↗
PubMed1982

High-dose radiation therapy with low-dose (pulsed) BCNU in malignant gliomas: an Eastern Cooperative Oncology Group (ECOG) report.

Based on preliminary favorable results with the use of postoperative high-dose radiation therapy for malignant gliomas and encouraging experimental studies which indicated that fractionated does of BCNU given 16 hours before irradiation significantly enhanced the effect of radiation both in vitro and in vivo, the Eastern Cooperative Oncology Group (ECOG) decided to explore the use of high-dose radiation therapy in combination with pulsed low doses of Group (ECOG) decided to explore the use of high-dose radiation therapy in combination with pulsed low doses of BCNU in a high-risk Phase I-II pilot study. The radiation therapy consisted of delivering 6000 rad to the whole brain plus a boost of 1000 rad to the tumor. BCNU was given i.v. 16 hours before the next radiation fraction with doses of 20 mg/M2 twice weekly for six weeks beginning on the second day of irradiation. Twelve patients were treated (5 with Grade III and 7 with Grade IV Astrocytomas). The median survival for the entire group was 80 weeks (30 weeks for Grade IV and 210 weeks for Grade III tumors). These results are not difficult from what was achieved by high-dose radiation alone. Subsequent experimental data seem to indicate that probably the smallest dose of BCNU that should be used in pulsed BCNU combined modality therapy is 80 mg/M2. In general, the treatment as offered in this study was well tolerated. There were no fatal or life-threatening hematologic toxicities and only one patient exhibited a transitory leukopenia of 1600.

Adult↗
PubMed1982

Further studies of natural killer cell function in Chediak-Higashi patients.

Spontaneous natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of blood lymphocytes against five human tumour cell lines (K562, Molt-4, HL-60, Chang, Daudi) and three mouse tumour lines (YAC, P815, RBL-5) were ten- to 100-fold lower than normal in six patients with Chediak-Higashi (CH) disease. NK and ADCC were defective at 4 hr, and less so at 18 hr. The NK activity in normals and CH patients was mediated in part by FcR+, E- effector cells. ADCC against human erythrocytes was normal in CH patients, as were lectin-dependent cytolysis and mixed lymphocyte proliferative responses. Phagocytosis of antibody-coated ox erythrocytes was normal in CH patients as well. These observations confirm that the CH syndrome is associated with a profound and selective defect in NK and ADCC activity against tumour cells, whereas other mononuclear cell-mediated functions are normal.

Adult↗
PubMed1982

Diurnal pattern of insulin requirements in insulin-dependent diabetics.

A total of 35 experiments in which insulin-dependent diabetics were connected to an artificial beta cell (Biostator) for feedback control of blood glucose during at least 24 h, were evaluated. Only 14 experiments, however, were available for analysis, since interruptions of more than 45 min/24 h in feedback control due to clots in analyser tubing occurred in those remaining. In these 14 experiments the 24-h insulin-infusion pattern was analysed. Basal insulin requirements (BIR), (between 01.00 and 04.00 hours) was found to be 0.178 +/- 0.044 (SD) mU/kg X min. Insulin requirements increased in the early morning (04.00-07.00 hours) to 0.231 +/- 0.084 mU/kg X min (P less than 0.01). A significant correlation between BIR and 24-h insulin requirement was found (r = 0.53, P less than 0.05). Insulin requirements per kJ following breakfast were higher than after lunch, 0.57 +/- 0.20 muU/kg X min X kJ versus 0.41 +/- 0.29 muU/kg X min X kJ (P less than 0.05).

Adult↗
PubMed1982

Morphologic changes reflecting early and late effects of irradiation of the distal lung of the mouse: a review.

In radiation of the thorax, the lung has been shown to be a major dose-limiting organ. The early and late responses of the lung to radiation has been reviewed, with primary emphasis on the following cell types: type II pneumocyte, type I pneumocyte, pulmonary endothelial cell and macrophage. The earliest observable and quantifiable cellular response to radiation is exhibited by the type II pneumocytes as a decrease in lamellar bodies and a corresponding increase in surfactant content of the alveolar lavage. By 18-63 weeks following exposure, several type II cells, restored in their lamellar body population, undergo degeneration and sloughing into alveolar spaces. Type I pneumocytes generally exhibit little change, although some investigators describe alveolar denudation due to degenerating type I cells. Macrophages decrease in numbers following irradiation, returning to normal populations by 4 weeks. These changes correspond closely to the changes in alveolar lavage phospholipid phosphorus. Descriptions of radiation-induced damage to endothelial cells are variable. However, blebbing and vacuolation appear to be late developing responses, although altered permeability may be earlier in its expression. Radiation pneumonitis and fibrosis are the two major clinical and experimental responses of the lung to radiation following exposures of greater than 12 Gy. The former appears to involve type II cells, macrophages and pulmonary endothelial cells, and for the latter macrophages, fibroblasts, type II pneumocytes and the pulmonary endothelial cells are involved. The two events are not interdependent, and may not necessarily be interrelated.

Animals↗
PubMed1981

Second malignant neoplasms in patients treated for Hodgkin's disease with radiotherapy or radiotherapy and chemotherapy.

The incidence of second malignant neoplasms (SMN) was assessed in 248 patient with Hodgkin's disease (HD) treated by radiotherapy alone (XRT) or in combination with chemotherapy (XRT + C) between January/1960 and June/1977. Radiation therapy was categorized as less than extended field (less than EF), extended field (EF) or total nodal irradiation (TNI). Chemotherapy was scored as single agent (SAC) or multiagent (MAC). MAC consisted primarily of either nitrogen mustard, vincristine, prednisone and procarbazine (MOPP) or cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP). Ten metachronous malignancies occurred 1-21 years (median 10 years) after the diagnosis of HD. With a median follow-up of 6 years the observed-to-expected ratio (O/E) was 4.2 for XRT alone and 7.6 for XRT + MAC. For 46 patients with greater than or equal to 10 years follow-up (median 13 years) the O/E ratio was 16.1 for XRT and 26.5 for XRT + MAC. All SMN occurred in patients who had not had a splenectomy at or prior to the time of HD diagnosis. Only four of nine solid SMN were within treatment portals or near portal margins. The diagnosis of another malignant neoplasm was made prior to or simultaneous with the diagnosis of HD in four additional patients. This observation, and the occurrence of five of six SMN outside of the treatment field in the XRT alone group, suggest that there may be factor(s) associated with the incidence of SMN in HD in addition to treatment itself.

Adolescent↗
PubMed1981

Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity.

On analysis of in vitro assays of human natural killer (NK) cell function the inadequacy of commonly used methods of expressing lytic activity was apparent. A comparison was made of the data obtained using modifications of two equations-the simple exponential fit and the von Krogh equations. Both of these equations were found to satisfy the following essential criteria for use in these assays. First, the majority of the results obtained in the chromium-release assay could be used in data reduction; second, the resultant "dose-response" curve was reduced to linearity; and third, a single numerical expression was obtained which was directly proportional to the cytotoxic activity. Of the two methods the more conventional exponential fit was found to be the simpler to use. The closeness of fit of the experimentally derived data to the ideal curves did not support the possibility that normal lymphocyte preparations contain suppressor cells capable of inhibiting NK activity. Data have also been presented showing that NK-sensitive targets could be categorized with respect to their susceptibility by comparing the slopes of the target cell survival curves obtained using the exponential fit equation. These observations are relevant to the accurate assessment of NK activity in patient populations and to the determination of the effects of disease and its treatment on this activity.

Animals↗