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Biomedical subjects

R Benjamin

Publications and source records attributed to R Benjamin.

At least 55 records · Page 3Linked to original sources

Concomitant administration of recombinant human interleukin-2 and recombinant interferon alpha-2A in cancer patients: a phase I study.

Twenty-seven patients with metastatic cancer were treated with a daily continuous intravenous (IV) infusion of recombinant human interleukin-2 (rhIL-2) along with daily intramuscular recombinant interferon-alpha-2a (rIFN-alpha-2a) 4 days per week for 4 weeks with repeated treatment after 2 to 4 weeks of rest. The maximum-tolerated dose (MTD) was 3 million U/m2/d of rhIL-2 with 5 to 10 million U/m2/d of rIFN-alpha-2a. The dose-limiting toxicities are moderate hypotension requiring low doses of pressors and chronic fatigue associated with decreased performance status. Other common side effects included fever, chills, fluid retention, nausea/vomiting, erythrodermia, weight loss, elevated liver transminase levels, anemia, thrombocytopenia, and CNS toxic effects. There were seven objective responses among 25 evaluable patients. Four major responses (one complete response and three partial responses) were observed among 10 patients with melanoma treated with the MTD level. These data suggest that for cancer patients, concomitant rhIL-2 and rIFN-alpha-2a therapy is tolerable and has manageable side effects. Further phase II studies will be needed to define the antitumor activity of this combination.

Antineoplastic Combined Chemotherapy Protocols↗

Monoclonal antibodies for the depletion of specific subpopulations of lymphocytes.

A number of rat monoclonal antibodies of the IgG2b subclass have been used to deplete mice of T lymphocyte subsets. It has been possible to produce long-term depletion where antibodies are administered to mice thymectomized in their adult life, or short-term depletion in euthymic animals. It is therefore feasible to ablate a T lymphocyte subpopulation at any stage in the course of an immune response and to examine in detail the role of a particular subset in the induction or effector phases of that response. We have used such ablative procedures to define the T cell subsets which participate in graft rejection, graft-versus-host disease, antigenic competition and antiviral and anti-self immunity and have attempted to exploit such knowledge to establish immunological tolerance in an adult animal.

Animals↗

CD4 monoclonal antibody pairs for immunosuppression and tolerance induction.

A pair of rat anti-mouse CD4 monoclonal antibodies (mAb) have been selected which bind to different epitopes of the molecule. Both the mAb are rat IgG2b and show clear synergistic activity in complement lysis in vitro. When injected together in vivo, they exhibit an improved immunosuppressive effect, compared to each antibody alone, on allogeneic graft rejection, humoral responses and on tolerance induction. Limiting dilution analysis indicates that the in vivo depletion of interleukin 2-producing cells is improved using both mAb by 2-3-fold over that obtained with the individual antibodies. As little as 60 ng per mouse of the CD4 antibody pair was sufficient to allow the induction of tolerance to human gamma-globulin, even without elimination of the CD4+ cells. The results suggest that appropriate antibody pairs may be good candidates for effective immunosuppressive serotherapy in man.

Animals↗

Interrelationship between metabolism of tritiated water, 22sodium and dry matter intake by beef cattle consuming wheat straw and poultry litter in free choice.

1. Metabolism of tritiated water and 22sodium was studied in six beef cows under Mediterranean summer conditions in order to find whether the turnover of these tracers can be used to evaluate pasture intake. 2. The diet of the cows included ad libitum access to two components which were given separately in different troughs: one was poultry litter and the other was wheat straw, to simulate the dry pasture. 3. Voluntary daily dry matter intake (111 g/kg0.75) was unexpectedly high considering the low digestibility of the feed. 4. The assumptions of constant ratios of water intake to water turnover and of dry matter intake to water intake were confirmed. Consequently, dry matter intake was determined accurately from water turnover measurements. 5. Sodium intake was practically equal to sodium turnover and most of the sodium secreted in feces was of endogenous origin. 6. Pasture intake can be predicted from sodium turnover once the concentration in feed and water consumed is known.

Animal Feed↗

Radiation-induced sarcomas of the chest wall.

Sixteen patients are presented who had sarcomas of the chest wall at a site where a prior malignancy had been irradiated. The first malignancies included breast cancer (ten cases), Hodgkin's disease (four cases), and others (two cases). Radiation doses varied from 4200 to 5500 R (mean, 4900 R). The latency period ranged from 5 to 28 years (mean, 13 years). The histologic types of the radiation-induced sarcomas were as follows: malignant fibrous histiocytoma, nine cases; osteosarcoma, six cases; and malignant mesenchymoma, one case. The only long-term survivor is alive and well 12 years after resection of a clavicular chondroblastic osteosarcoma. Three cases were recently diagnosed. Despite aggressive multimodality treatment, the remaining 13 patients have all died from their sarcomas (mean survival, 13.5 months). All patients have apparently been cured of their first malignancies. Chemotherapy was ineffective. No treatment, including forequarter amputation, appeared to palliate the patients with supraclavicular soft tissue sarcomas. Major chest wall resection offered good palliation for seven of eight patients with sarcomas arising in the sternum or lateral chest wall. Close follow-up is needed to detect signs of these sarcomas in the ever-increasing number of patients receiving therapeutic irradiation.

Adolescent↗

Difluoromethylornithine and leukocyte interferon: a phase I study in cancer patients.

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and human leukocyte interferon (IFN-alpha) have synergistic anti-tumor activities in vivo in B 16 melanoma and in vitro against several human cancer cell lines. We have, therefore, carried out a phase I combination study with DFMO plus alpha interferon in the following manner: DFMO was maintained at a steady dose for the first four levels, 1.5 g/m2 every 6 hr. IFN-alpha was given in 100% increments ranging from 0.4 X 10(6)U/m2 to 3.2 X 10(6)U/m2 i.m. daily. At the fifth dose level both IFN-alpha and DFMO were raised by 100 and 50% respectively. From levels one through four the combination was well tolerated with no dose interruptions required because of G.I. toxicity or myelosuppression. However, at dose level 5, one-third of the patients required dose cessation and decrease due to nausea, vomiting and diarrhea. We conclude that for phase II studies the maximal tolerated dose is 3.2 million units of IFN-alpha/m2 and 1.5 g/m2 of DFMO every 6 hr. Of 12 patients with metastatic melanoma, 2 had partial remissions lasting 58+ and 36+ weeks. Two additional patients had minor responses lasting 29 and 32+ weeks. Minor responses were observed in a patient with colon carcinoma and a patient with renal carcinoma. The clinical activity of the combination is currently being pursued in a phase II study among patients with metastatic malignant melanoma.

Adult↗

Benign methylmalonic aciduria.

Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency is usually considered to be a serious, often life-threatening disease. However, through routine screening of urine in neonates or screening of siblings of clinically affected neonates, we have identified eight children who have a benign clinical variant of this disorder. Their urinary methylmalonic acid levels have ranged from 1.0 to 3.4 mg per milligram of creatinine, with serum values ranging from an undetectable level to 1.7 mg per deciliter (130 nmol per liter). The children have not received dietary or vitamin therapy, have had normal growth and development (age range, 18 months to 13 years), and have performed as well as their unaffected siblings on psychometric testing. These children have no evidence of a deficiency of vitamin B12, which acts as a cofactor with methylmalonyl-CoA mutase, and they did not respond to the administration of vitamin B12. Two siblings were found by complementation analysis to have a defect in the methylmalonyl-CoA mutase apoenzyme; complementation analysis was not performed on the other patients. We conclude that the clinical spectrum of methylmalonyl-CoA mutase deficiency is wider than indicated by previously reported cases.

Adolescent↗

Massachusetts Metabolic Disorders Screening Program: III. Sarcosinemia.

Sarcosinemia has been detected by routine screening of urine for metabolic and transport disorders in Massachusetts. Three infants who had sarcosinemia were detected through the neonatal urine specimen, an observed incidence of 1:350,000. A fourth child had sarcosinemia detected through family screening after his brother was found to have Hartnup disease by neonatal urine screening. These four children with sarcosinemia have plasma sarcosine concentrations ranging from 80 to 603 mumol/L and urine sarcosine from 2.1 to 9.4 mumol/mg of creatinine, findings similar to those reported for persons with sarcosinemia. No treatment has been given. At 3.8 to 15 years of age, the children had normal findings on physical examination and had no specific illnesses. Their full-scale IQ scores ranged from 89 to 111. The oldest child had a learning and emotional disorder, and one other child was emotionally unstable. It was concluded that sarcosinemia as a specific disorder is probably benign and that the mental retardation and dysmorphic features described in some affected persons are likely coincidental with the biochemical defect. The emotional disturbances that were encountered in two children are also probably coincidental but need further attention in this disorder.

Adolescent↗

Rubidazone in combination with Ara-C, vincristine and prednisone (ROAP) in the treatment of adult acute leukemia. A Southwest Oncology Group Study.

In an 18-month period, 340 consecutive adult patients with acute leukemia were treated using a 7-day continuous infusion of Ara-C in combination with rubidazone, vincristine and prednisone (ROAP). Of 334 (96%) evaluable cases, 77% were 50 years of age or older. The complete remission (CR) rate was 51% with a standard error of 3%. After adjustment for known prognostic factors this overall CR rate is 10% higher than the predicted CR rate when compared to the last completed SWOG study which used adriamycin in combination with a similar regimen of Ara-C, vincristine, and prednisone. The CR rate in patients over 50 years of age was particularly noteworthy. Using rubidazone, the CR rate was 46.1% (116/256) compared to 37.4% (91/243) for the adriamycin study in this poorly responding age group. The median survival time achieved was 27 weeks. However, in the age groups 40-49 years and 50-59 years the median survival was 70 and 44 weeks, respectively.

Acute Disease↗

Radiographic and angiographic changes in osteosarcoma after intraarterial chemotherapy.

Transcatheter arterial infusion has improved the preoperative control of osteosarcoma. The conventional radiographs and angiograms of osteosarcoma were evaluated in 53 patients before and after treatment. In the responders, two types of calcifications representing healing are observed: peripheral and central. The calcification is readily differentiated from that of tumor new bone. Angiography revealed a decrease in tumor vascularity and stain in responding tumors. Excellent angiographic and pathologic correlation of these changes is presented.

Angiography↗

Intraarterial cis-platinum for patients with inoperable skeletal tumors.

Twenty-three patients with inoperable skeletal tumors were treated with intraarterial cis-platinum prior to attempted surgery. The antitumor effect of intraarterial cis-platinum was monitored clinically by radiologic imaging techniques, and whenever possible, evaluated histopathologically by examinatin of surgical or biopsy tumor specimens. Objective responses were noted in 12 patients (52%) and included 2 complete, 7 partial and 3 less-than-partial remissions lasting from 14 to 70 weeks. Limb-saving surgery or hemipelvectomy became subsequently feasible in four and one patients respectively. Preoperative intraarterial cis-platinum is a safe procedure which might be used effectively in combination with other, more conventioal postoperative adjuvant chemotherapy against skeletal tumors.

Bone Neoplasms↗

Low molecular weight RNA species from chromatin.

Several methods of preparing low molecular weight RNA from chick embryo chromatin have been examined. Traditional methods for dissociating chromatin utilizing high concentrations of salt (greater than 2 M) followed by high-speed centrifugation resulted in very low yields of RNA. Increased yields of RNA were obtained by treating chromatin at lower salt concentration (0.2-0.5 M). By using low salt extraction and sodium dodecyl sulfate-phenol deproteinization, six to eight low molecular weight homogeneous RNA species were isolated from chick embryo chromatin and mouse myeloma chromatin. In the myeloma system, all these RNAs are metabolically stable. Each component is homogeneous as examined by gel electrophoresis and hybridizes with mouse DNA at a rate consistent with a single species. There are multiple gene copies for these RNA species in the mouse genome, varying from 100 to 2000 copies for the different species. One of these RNAs is identical with 5S rRNA. In addition, the redundancy of genes for 18S, 28S, and 5S rRNA and tRNA was determined. Approximately 300 copies for 18 and 28S rTRNA and 500 copies for 5S rRNA were found. tRNAs were on an average 110-fold redundant with about 55 different species measured.

Animals↗