Biomedical subjects

R Bitton

Publications and source records attributed to R Bitton.

10 recordsLinked to original sources

PubMed1999

Immune modulation in autologous bone marrow transplantation: cyclosporine and gamma-interferon trial.

From March 1994 to November 1994, 16 patients with high risk hematological malignancies were entered in a phase I clinical trial, designed to confirm the toxicity of cyclosporine and gamma interferon given to induce autologous graft-versus-host disease (GVHD) after autologous bone marrow transplantation (ABMT). This trial was based on the results in a rodent model, in which cyclosporine given after ABMT induces an autoimmune syndrome (autologous GVHD) identical to allogeneic GVHD. Further, this autologous GVHD is associated with a graft-versus-tumor effect augmented by interferon that upregulates MHC class II expression on normal and tumor cells, the target of the cytolytic T cells in autologous GVHD. In this trial, cyclosporine 1 mg/kg/day was given from the day of bone marrow reinfusion until the completion of the interferon and gamma-interferon. Gamma-interferon at 0.025 mg/m2 every other day was started when the total white cell count was >200 cells/ml for 2 consecutive days and continued for a total of 10 doses after ABMT. The preparative regimens were busulfan and cyclophosphamide, or cyclophosphamide with total body irradiation. All patients received 4HC-purged marrow grafts. Median age was 45 years (range 19-68). The diagnoses included chemo-resistant non-Hodgkin's lymphoma (10), acute lymphoblastic leukemia (two), chemo-resistant Hodgkin's disease (two), acute myeloid leukemia (one), and multiple myeloma (one). Median absolute neutrophil count recovery was 25.5 days (range 19-46 days). Median platelet count recovery was 40.5 days (range 28-279 days). There were nine deaths, two were related to transplant toxicity (infection), while the other seven were due to relapse. Event-free survival with a median of 964 days (range 19-1441 days of follow-up was 44%. In conclusion, treatment with cyclosporine, and gamma-interferon after ABMT was well tolerated and did not impair engraftment. Further studies with a larger number of patients are required to document any beneficial anti-tumor effect of autologous GVHD induction after ABMT.

Adolescent↗

PubMed1998

Acute bleeding after bone marrow transplantation (BMT)- incidence and effect on survival. A quantitative analysis in 1,402 patients.

Acute bleeding after bone marrow transplantation (BMT) was investigated in 1,402 patients receiving transplants at Johns Hopkins Hospital between January 1, 1986 and June 30, 1995. Bleeding categorization was based on daily scores of intensity used by the blood transfusion service. Moderate and severe episodes were analyzed for bleeding sites. Analysis of the cause of death and the interval of the bleeding episode to outcome endpoints was recorded. Survival estimates were computed for 1,353 BMT patients. The overall incidence was 34%. Minor bleeding was seen in 10.6%, moderate bleeding was seen in 11.3%, and severe bleeding was seen in 12% of all patients. Fourteen percent of patients had moderate or severe gastrointestinal hemorrhage, 6.4% had moderate or severe hemorrhagic cystitis, 2.8% had pulmonary hemorrhage, and 2% had intracranial hemorrhage. Sixty-one percent had 1 bleeding site and 34.4% had more than 1 site. Moderate and severe bleeding was more prevalent in allogeneic (31%) and unrelated patients (62.5%) compared with autologous patients (18.5%). Significant distribution of incidence was found among the different diagnoses, but not by disease status in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma. Bleeding was associated with significantly reduced survival in allogeneic, autologous, and unrelated BMT and in each disease category except multiple myeloma. Survival was correlated with the bleeding intensity, bleeding site, and the number of sites. Although close temporal association was evident to mortality, bleeding was recorded as the cause of death in only the minority of cases compared with other toxicities after BMT (graft-versus-host disease, infections, and preparative regimen toxicity). Acute bleeding is a common complication after BMT that is profoundly associated with morbidity and mortality. Although bleeding was not a direct cause of death in the majority of cases, it has a potential prognostic implication as a predictor of poor outcome in clinical assessment of patients after BMT.

Acute Disease↗

PubMed1996

p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2.

Treatment of SKBr3 cells with benzoquinone ansamycins, such as geldanamycin (GA), depletes p185erbB2, the receptor tyrosine kinase encoded by the erbB2 gene. In the same cells, a biologically active benzoquinone photoaffinity label specifically binds a protein of about 100 kDa, and the ability of various GA derivatives to reduce the intracellular level of p185erbB2 correlates with their ability to compete with the photoaffinity label for binding to this protein. In this report, we present evidence that the approximately 100-kDa ansamycin-binding protein is GRP94. Membrane-associated p185erbB2 exists in a stable complex with GRP94. GA binding to GRP94 disrupts this complex, leading to degradation of pre-existing p185erbB2 protein, and resulting in an altered subcellular distribution of newly synthesized p185erbB2.

Benzoquinones↗

PubMed1996

A phase I study of pentosan polysulfate sodium in patients with advanced malignancies.

BACKGROUND: Pentosan polysulfate (xylanopolyhydrogensulfate) is a semi-synthetic sulfated heparinoid polysaccharide which has been used as an anticoagulant for nearly thirty years in Europe. It antagonizes the binding of bFGF to cell surface receptors and has thus been evaluated for antitumor activity in several animal models and human tumor cell lines. In two angiogenic models pentosan has been shown to inhibit bFGF stimulation of angiogenesis. Previous clinical studies have determined the coagulation effects of pentosan to be the dose-limiting toxicity. PATIENTS AND METHODS: We conducted a phase I study designed to define the duration-limiting toxicity associated with progressive prolongation of a continuous intravenous infusion (three, five, and eight weeks). This study was not designed to escalate the dose of pentosan beyond that required to maintain the activated partial thromboplastin time (aPTT) between 1.8 and 2.2 times the baseline value. RESULTS: Thirteen patients with advanced stage metastatic cancer were enrolled (median age 50 years, range 34 to 61 years). Four patients were treated in cohort #1 (three weeks of infusional therapy), five patients were treated in cohort #2 (five weeks of therapy), and four patients in cohort #3 (eight weeks of therapy). All patients experienced a progressive prolongation of their aPTT and PT. Furthermore, all patients experienced at least grade I thrombocytopenia. Other complications were, in general, mild. One patient developed grade III liver abnormalities while receiving the eight-week infusion and another patient developed grade IV thrombocytopenia while receiving the same regimen. One patient with colon cancer had stable disease for 24 weeks, while the remaining 12 patients had no objective evidence of response. CONCLUSION: Pentosan was well tolerated when doses were adjusted for aPTT prolongations and a five-week cycle appeared to be the maximum tolerated duration of infusion (initially 4 mg/kg/day). One patient had stable disease, but there was no objective tumor response noted in the remaining 12 patients.

Adult↗

PubMed1996

[Clinical imaging in psychiatry].

Brain imaging has made surprisingly remarkable progress since the early, and now historic days, of invasive radiology, which has now been replaced with a number of spectacularly precise techniques: structural (CT Scan, MRI) and functional (PET, SPECT) imaging, direct imaging during neurosurgery, EEG and its computer-assisted derivatives, and transcerebral ultrasonography. We present five cases with two alleged autisms, a cerebral malaria, a panic disorder and to Parkinson disease with a depressive component. Using modern imaging methods the following respective diagnoses were arrived at: a left temporal cyst, a Sanfilippo mucopolysaccharidosis, a septum lucidum agenesis, a right temporal cyst, and a pituitary adenoma. These cases illustrate the scientific, emotional and philosophical impact, on physicians, and patients alike, of modern imaging technology. Neuroradiology, biochemistry and surgical imaging require a multi disciplinary approach and a perfect knowledge of psychiatric semeiology. In addition, they stimulate us to carefully reassess our sociocultural understanding to mental illness.

Adenoma↗

PubMed1996

Paclitaxel dose intensity.

Paclitaxel is effective in the treatment of cancer of the ovary and cancer of the breast, as well as other malignancies. We have analyzed available phase II data in these two diseases, to assess the possibility that paclitaxel dose intensity may be important in the induction of disease response. When analyzed by the methods developed by Hrynuik and Levin, available data suggest that the relationship between objective disease response and paclitaxel dose intensity in recurrent cancer of the ovary is strongly statistically significant with a two-sided p value of 0.022. Available data suggest that the relationship in breast cancer is even stronger, with a two-sided p value of 0.004. In both diseases, optimal results have been observed at the dose schedule of 250 mg/m2/21 days, given as a 24 hour IV infusion. We have also performed an analysis comparing the only two prospective randomized studies that examined the potential role of dose intensity for this drug in cancer of the ovary. At 135 mg/m2/21 days, the objective response rate was 13.2%; and at 250 mg/m2/21 days, the objective response rate was 35.9%. The response rate seen at the intermediate dose of 175 were intermediate to 135 and 250; and linear regression analysis shows a correlation coefficient for these data of 0.946. Since flexible cytokine support may be essential in maintaining paclitaxel dose intensity, we have also discussed this approach as well as the paclitaxel dosing strategy that is associated with optimal clinical results in recurrent cancer of the ovary.

Antineoplastic Agents, Phytogenic↗

PubMed1995

A multicenter trial of low dose gallium nitrate in patients with advanced Paget's disease of bone.

Gallium nitrate is a potent antiresorptive drug that has been extensively tested in patients with accelerated bone turnover. We have evaluated the effects of this new agent in a pilot multicenter trial of 49 patients with advanced Paget's disease of bone. Patients were randomized to receive 0.05, 0.25, or 0.5 mg/kg.day gallium nitrate administered by sc injection in two 14-day cycles. Serum alkaline phosphatase, fasting 2-h urinary hydroxyproline and N- telopeptide collagen cross-links excretion, and quality of life were assessed every 2 weeks for 12 weeks. The group mean alkaline phosphatase activity at baseline was 854 +/- 100 (+/- SEM) IU/L. The mean changes from baseline to week 12 in serum alkaline phosphatase were +0.5%, -24%, and -31%, respectively, for the three doses tested. The differences for each of the higher dose levels (0.25 and 0.5 mg/kg.day) was statistically significant (P < or = 0.05), and nearly half of the patients treated with the 0.5 mg/kg.day dose achieved a 50% or more reduction in enzyme activity. The nadir value in hydroxyproline excretion occurred at 10 weeks, with mean changes of +9%, -10%, and -17% for the 0.05, 0.25, and 0.5 mg/kg.day doses, respectively; the difference was significant only at the 0.5 mg/kg.day level (P < 0.01). Urinary collagen cross-link excretion showed a significant decrease at the 0.25 and 0.5 mg/kg.day doses. We also observed a definite, but nonsignificant, trend for improved quality of life in patients treated at the highest drug dose. Minor discomfort at the injection site was frequently reported, but did not lead to interruption of therapy. Our results in these patients who had received moderate to extensive prior therapies with other drugs show that cyclical, low dose, sc administration of gallium nitrate is safe and effective for treating patients with advanced Paget's disease of bone.

Adult↗

PubMed1993

Leukemia after a small dose of radioiodine for metastatic thyroid cancer.

Radioiodine is widely used in the treatment of thyroid cancer. It is one of the most benign forms of therapy for malignancy. Leukemia is a rare complication of 131I therapy, usually occurring after cumulative dosages of more than 800 mCi and with intervals between doses of less than 12 months. We report the occurrence of acute myelogenous leukemia in a 28-yr-old woman 14 months after receiving a total dose of 300 mCi 131I for metastatic follicular thyroid cancer. We also review the published literature of the incidence of leukemia after low dose 131I.

Adult↗

PubMedDate not supplied

Role of thyroid-stimulating immunoglobulin in aggressiveness of well-differentiated thyroid cancer.

OBJECTIVE: To assess whether a relationship exists between thyroid-stimulating antibodies and increased aggressiveness of thyroid cancer. METHODS: We analyzed clinical, histologic, and biochemical data, including thyroid-stimulating antibodies, from 26 patients (24 women and 2 men) who had had well-differentiated thyroid carcinoma for 1 to 5 years and had undergone total thyroidectomy and radioactive iodine ablative therapy. For analysis, the overall study cohort was divided into two groups: group 1 (N = 16), with stable disease and no evidence of metastatic activity, and group 2 (N = 10), with aggressive disease and substantiated metastatic involvement. RESULTS: The thyroid-stimulating antibodies ranged from 92 to 129% in group 1 and from 95 to 118% in group 2. Thus, both study groups had thyroid-stimulating antibody levels within the normal range (normal, <130%). CONCLUSIONS: Apparently, thyroid-stimulating antibodies had no contributory role in the growth of the metastatic lesions in the 10 patients with aggressive disease. Further studies should be undertaken to investigate other potential factors involved in stimulating the progression of thyroid cancer.

Adult↗

PubMedDate not supplied

[Panic attacks and 24-hour ambulatory EEG monitoring].

A 24 hour ambulatory EEG study performed in a population of 300 non epileptic outpatients with an anxious and depressive pathology revealed a high prevalence of abnormalities in subjects referred with panic disorder. Two groups of 150 medication-free patients each have been selected on the base of DSM-III-R = one with panic attacks (PA), the other with depressive patients without paroxystic anxiety (DS). The results showed respectively = in the PA group 63.2% abnormal, 19.7% normal and 17.1% dubious records. In the DS group = 74.5% normal, 18.3% abnormal and 7.2% dubious records. Epileptiform abnormalities were 4 times more frequent in the PA group (80%) than in the DS group (20%). Two nycthemeral peaks were found (5-8 pm and 3 hours after awakening). MRI has permitted the discovery of abnormal cerebral images in 3 patients of the PA group (cyst of the insula, temporal and parietal cryptic angiomas, sequelae of a parietal vasculo-cerebral stroke) frequency appearing to be clearly superior to the one resulting from recent epidemiologic data. The subclinical character of 2/3 of these abnormalities refers beyond epilepsy to their signification in the field of emotive and intellectual disturbances. The paradoxal efficiency of tricyclic drugs in panic disorder, sets the problem of their eventual antiepileptic action at low doses. If recent data on standard EEG in panic disorder is available, we did not find any similar study to ours in order to confront our results.

Adult↗