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J Kahn

Publications and source records attributed to J Kahn.

At least 19 recordsLinked to original sources
PubMed1992

Radiation and thermal sensitivities of murine tumor (FSa-II) cells recurrent after a heavy irradiation.

Radiation and thermal sensitivities, and cell doubling times (Tds) of C3Hf/Sed mouse FSa-II cells recurring after a heavy irradiation were examined in vitro. Tumors in the leg were irradiated with gamma-rays and observed for late recurrence (in vivo clones), or removed immediately after irradiation and single cell suspensions were plated for colony formation (in vitro clones). Five subclones were selected from original cells in vitro. Survival curves were fitted to the multi-target and linear quadratic models. Surviving fractions at 2 (SF2) and 10 Gy (SF10) irradiations, and those at 30 and 60 min heatings at 44 degrees C (SF30 and SF60), were obtained for each clone. Although, Tds of subclones were slightly longer than those of the parental cells, those of recurrent clones were prolonged substantially with an exception of one cell line. Radiosensitivities of FSa-II parental cells tested in vitro and in vivo were equally radioresistant. Thermal sensitivities of parental cells tested in vitro and in vivo were also identical. All subclones were more radiosensitive compared to the parental cells. The in vitro recurrent clones showed smaller D0 (radiation dose to reduce survival from S to S/e in the exponential portion of survival curve) than the D0 of the parental cells. The SF2 values of four in vitro recurrent clones were greater than that of the parental cells whereas those of two lines were smaller. It was of interest that the in vivo recurrent tumor cells showed a wide variation in the radiation sensitivity. Among 9 tumor cell lines examined, 4 lines were more sensitive and 4 were more resistant compared to the original. FSa-II subclones as well as both in vitro and in vivo recurrent clones showed a wide variation in thermal sensitivity. No consistent changes in the shoulder or in the slope were found. The SF30 or SF60 showed that 5 out of 9 in vivo recurrent clones and 4 out of 9 in vitro clones were more resistant compared to the original cells. No correlation was observed between thermal and radiation sensitivities. The Td was not related with radiation or thermal sensitivity.

Adaptation, Physiological↗
PubMed1992

Anti-human immunodeficiency virus therapeutics: now and the future.

Knowledge of the HIV life cycle helps to plan rational modalities directed against the virus. The complex nature of the life cycle of HIV presents multiple unique targets. HIV binding to the cellular receptor CD4, viral enzymatic targets, HIV activation, viral protein synthesis, and protein packaging are examples of the types of targets available to inhibit the life cycle of HIV. Patients, community groups, regulatory agencies, national research groups, and the private pharmaceutical companies have joined forces to work to a common goal, effective HIV therapies. RT inhibitors have provided the best therapeutic options, but other drugs are being developed at a rapid pace. New drugs are entering clinical investigation and will be more widely available at early signs of clinical and laboratory effectiveness.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma. A prospective multi-institutional trial.

OBJECTIVE: --To ascertain if low-dose multiagent chemotherapy, with central nervous system prophylaxis and antiretroviral therapy, might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome (AIDS). DESIGN: --A phase II prospective clinical trial, with median follow-up of 33 months. SETTING: --Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National Institute of Allergy and Infectious Diseases. PATIENTS: --Forty-two patients with AIDS-related malignant lymphoma. All were evaluable for toxicity assessment, and 35 for response. INTERVENTION: --A low-dose modification of the M-BACOD regimen (day 1): cyclophosphamide, 300 mg/m2 intravenously (IV); doxorubicin, 25 mg/m2 IV; vincristine sulfate, 1.4 mg/m2 IV; bleomycin, 4 mg/m2 IV; dexamethasone, 3 mg/m2 orally on days 1 through 5; methotrexate, 500 mg/m2 IV on day 15, with leucovorin rescue. Intrathecal cytosine arabinoside (50 mg) to all on days 1, 8, 21, and 28, with radiation therapy to a helmet field to those with central nervous system involvement. Zidovudine for 12 months after completion of four to six cycles of chemotherapy. MAIN OUTCOME MEASURES: --Response rate and number of opportunistic infections. RESULTS: --Response rate was 51% with a complete response of 46%. Of 16 complete responses, relapse occurred in four, none isolated to the central nervous system. Opportunistic infections occurred in 21% of those receiving treatment. Median duration of survival among all 42 patients is 5.6 months, 6.5 months in 35 patients evaluable for response, and 15 months in patients with complete response. Lower concentration of CD4 cells, history of prior AIDS, bone marrow involvement, and stage IV disease were independently associated with decreased survival. CONCLUSIONS: --Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance may be associated with durable remissions in AIDS-related lymphoma with fewer opportunistic infections than noted in prior reports.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The accelerated repopulation of a murine fibrosarcoma, FSA-II, during the fractionated irradiation and the linear-quadratic model.

Radiation response of a spontaneous mouse fibrosarcoma, FSa-II, to various fractionated doses was studied in vivo together with single dose cell survival curves. Early generation isotransplants were used. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Lung colony and TD50 assays were used to determine cell survival. Surviving fractions were determined following fractionated irradiations of 1.0 to 5.0 Gy each per fraction with interfractional time intervals of 4 hr. The alpha/beta ratio based on fractionated irradiations was 8.8 Gy for aerobic FSa-II tumor cells and flexure dose was less than 1.3 Gy. Multiple fractions of 5.0 Gy each given with 4, 12, and 24 hr intervals showed an increase in survival with increasing interfractional time interval, suggesting a rapid repopulation of tumor cells between fractions; namely, cell doubling time was shortened between fractions after the first 5.0 Gy doses. These results indicated that tumor cell repopulation is a critical factor in the fractionated radiotherapy. Linear-quadratic model was fitted to single dose survival data. Single dose survival curve of aerobic FSa-II tumor cells following lung colony assays which allowed determination of minimal survival of approximately 3.0 x 10(-3) showed that alpha, beta, and alpha/beta ratios were 0.25 Gy-1, 0.048 Gy-2, and 8.47 Gy, respectively. Single dose survival curve of the same aerobic cells determined by both lung colony and TD50 assays to a survival level of approximately 3.0 x 10(-6) demonstrated that alpha, beta, and alpha/beta ratios were 0.375, 0.0127, and 29.5, respectively. Similar determination for hypoxic FSa-II tumor cells showed that alpha, beta values were smaller whereas the alpha/beta ratio was much larger than for aerobic cells. The oxygen enhancement ratio calculated by the alpha/beta ratios was greater than 3.0.

Animals↗
PubMed1991

MRI of cardiac pseudoaneurysm and other complications of myocardial infarction.

The purpose of this paper is to review the spectrum of pathology revealed by cardiac magnetic resonance (MR) in the evaluation of myocardial infarction. In addition, the paper is intended to provide a concise introduction to the capabilities and limitations of MR in the evaluation of myocardial infarction and its complications. To provide this introductory guide, three cases of infarction are reviewed in detail, including one unusual case of infarction with both true and false ventricular aneurysm formation. A selected review of the literature is included to demonstrate the current role of MR in the work-up and follow-up of acute infarction.

Aged↗
PubMed1991

The effect of 5-fluorouracil at elevated temperatures on a spontaneous mouse tumour: Arrhenius analysis and tumour response.

In a series of studies to investigate activation energies and thermal enhancements of various chemotherapeutic agents the effect of 5-fluoruracil (5FU), an antimetabolite, on murine tumour cells was studied at elevated temperatures. Animal tumours were early generation isotransplants of a spontaneous fibrosarcoma, FSa-II tumours, and C3Hf/Sed mice were used throughout. Cell survival curves for 5FU were obtained as a function of treatment time by in vitro treatment-in vivo lung colony assay at temperatures between 37.0 and 43.5 degrees C. The D0, or the treatment time to reduce surviving fraction from S to S/e in the exponential portion of the survival curve, decreased slightly from 37 degrees C treatment to 41.5 degrees C treatment. The D0 decreased substantially from 41.5 degrees C to 43.5 degrees C. Arrhenius-plot analysis indicated that the activation energies were 92.9 and 731 kJ/M at temperatures between 37 and 41.5 degrees C, and between 41.5 and 43.5 degrees C, respectively. The activation energy of 92.9 kJ/M for the temperature range from 37 to 41.5 degrees C was the lowest of the other agents, bleomycin, cis-diamminedichloroplatinum and 1,3-bis(2-chloroethyl)-N-nitrosourea, which have been investigated in our laboratory. This indicated that the thermal enhancement was smallest among these agents. In vivo experiments failed to demonstrate thermal enhancement of the anti-tumour effect of 5FU. Namely, combined 5FU and heat treatments at 41.5 and 43.5 degrees C did not prolong the tumour growth time compared with 5FU given at room temperature. No pH effect was found in an in vitro experiment and glucose administration did not enhance the anti-tumour effect of 5FU.

Animals↗
PubMed1991

Chemotherapy for AIDS-associated Kaposi's sarcoma.

Clinical staging and response criteria for AIDS-associated Kaposi's sarcoma (AIDS-KS) are not well-developed, but classifying patients into limited or extensive disease categories allows a clinician to select appropriate local or systemic therapy. A prospective staging system has been proposed to uniformly evaluate pretreatment patient characteristics and subsequent clinical responses. Combination chemotherapy is effective, but its use is often limited by toxicities. Antiretroviral medications, if clinically tolerated, should be continued during combination chemotherapy. Future therapies will evaluate the utility of ddI or ddC with combination chemotherapy. A second area of research involves combination therapy using chemotherapy and antiretroviral agents along with growth factors to limit myelotoxicity.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Lack of efficacy of water-suppressed proton nuclear magnetic resonance spectroscopy of plasma for the detection of malignant tumors.

Water-suppressed proton nuclear magnetic resonance (NMR) spectroscopy of plasma has been proposed by Fossel et al. (N Engl J Med 1986; 315:1369-76) as a technique for detecting malignant tumors. In their analysis, plasma samples from patients with cancer were clearly distinguished from those of normal subjects by measuring and averaging the methyl and methylene line widths of plasma lipoproteins in NMR spectrums. To evaluate this diagnostic procedure further, we collected and analyzed by NMR spectroscopy 145 samples of plasma from patients who served as controls, most of whom were undergoing orthopedic or cardiac surgery (n = 66); patients with a variety of untreated malignant tumors (n = 25) or treated malignant tumors (n = 18); and patients with hyperplastic or "premalignant" diseases, such as benign prostatic hyperplasia and ulcerative colitis (n = 36). All the samples were coded, and NMR spectroscopy was performed without knowledge of the patients' clinical status. There were no significant differences in the NMR line widths among the four study groups (P greater than 0.05 for all pairwise comparisons). The specificity and sensitivity of this method for distinguishing the control patients (mean line width [+/- SD], 44.0 +/- 7.4 Hz) from those with untreated cancer (43.8 +/- 6.9 Hz) were poor, with a false positive rate of 52 percent (34 of 66) and a false negative rate of 56 percent (14 of 25). Inverse correlations of line widths with age (P less than 0.01) and with the plasma triglyceride level (P less than 0.001) were detected. We conclude that NMR spectroscopy of plasma is not an accurate test for the detection of malignant tumors.

False Negative Reactions↗
PubMed1990

Failure of 1H nuclear magnetic resonance spectroscopy of blood plasma to detect malignancy.

Water-suppressed proton nuclear magnetic resonance (NMR) of plasma was proposed as a technique for detecting malignant tumors. In that analysis, bloods drawn from cancer patients at the Beth Israel Hospital (BIH; Boston, MA), were easily distinguished from normal subjects by measuring and averaging the proton NMR methyl and methylene line widths of plasma lipoproteins. We collected blood at the Massachusetts General Hospital (MGH), including from normal controls, patients with untreated and treated malignant tumors, and patients with nontumor diseases. The plasma NMR analyses were carried out blind. The code was not broken until all patient charts and pathology records were reviewed, plasma analyses were completed, and patients had been divided into appropriate clinical groups. Analysis of these data showed no differences between the means of the study groups (false-positive and false-negative frequencies 46% and 57%, respectively). An inverse correlation of methyl/methylene line widths with age (P less than .01), and a correlation with nitrate-requiring cardiovascular disease (P less than .05) was, however, evident. This test cannot be validly used to detect malignancy.

Adult↗
PubMed1990

Current approach to the treatment of human immunodeficiency virus-associated weight loss: pathophysiologic considerations and emerging management strategies.

Relationships between nutrition and infection are generally complex, bidirectional, and not perfectly worked out. Healthy people can adapt to simple decreases in intake or increases in expenditure. However, the imposition of infection with associated cytokines may impair such adaptations, resulting in wasting of lean tissue. In human immunodeficiency virus (HIV) infection, nutritional abnormalities are common. Lean body mass depletion is associated temporally with death in a subset of acquired immune deficiency syndrome (AIDS) patients. Weakness, fatigue, and anorexia are important symptomatic complaints affecting quality of life. Pathophysiologic mechanisms remain speculative, although there is reason to suspect four theoretic factors: decreased intake, malabsorption, hypermetabolism, and altered metabolism. More than one disturbance may be necessary for clinical wasting to develop; ie, a primary abnormality plus a failure of homeostatic adaptation. Excess cytokine production also may be involved, but this is uncertain. Therapeutics remain empiric in the absence of known mechanisms. Current options are restricted to diet adjustments or supplements, treatment of underlying diseases (where possible), and rarely, parenteral alimentation. Promising investigational possibilities include an appetite stimulant (megestrol acetate) and therapies to oppose cytokine production or actions, but definitive beneficial effects on nutritional status, subjective performance, disease activity, or survival have not yet been demonstrated. Advances in clinical therapeutics await an improved understanding of pathophysiologic mechanisms and carefully designed clinical trials testing proposed interventions.

Acquired Immunodeficiency Syndrome↗
PubMed1989

AIDS-associated non-Hodgkin's lymphoma in San Francisco.

The characteristics of acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma in 84 patients diagnosed and treated at San Francisco General Hospital are presented herein. While the majority were high-grade B-cell lymphomas, one cutaneous T-cell and one peripheral T-cell lymphoma were observed. In addition, three other tumors were suspicious for T-cell lymphoma. Sixty-seven percent of patients had stage IV disease, often at unusual sites. Epstein-Barr virus DNA sequences were identified in only five of 15 tumors by dot-blot analysis. Patients were treated with a variety of standard chemotherapeutic regimens, with radiation therapy alone, or with a novel chemotherapy protocol (COMET-A). No significant differences in complete response rates were observed. The most important predictor of survival was the total number of CD4-positive lymphocytes. Other predictors of survival included history of a diagnosis of acquired immunodeficiency syndrome, Karnofsky performance score, and the presence of extranodal disease. Survival was shorter among patients who received higher doses of cyclophosphamide (greater than 1 g/m2), including those treated with the COMET-A regimen. Implications for therapeutic decision making are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The effect of hyperthermia on the early- and late-appearing mouse foot reactions and on radiation carcinogenesis: Part II. Effect on radiation carcinogenesis (thermal enhancement and oxygen enhancement).

The effect of hyperthermia on radiation carcinogenesis was investigated in the C3Hf/Sed mouse foot. The foot was irradiated under hypoxic conditions, in air, or under hyperbaric oxygen conditions to evaluate the oxygen effect. Hyperthermia at 43.5 degrees C for 45 min was given by immersing the animal foot into a constant temperature water bath. A malignant tumor in the irradiated foot was first observed congruent to 250 days after irradiation. Tumors developed in the irradiated area until day 850. RCD50, or 50% radiation carcinogenesis dose was the endpoint and was calculated based on the tumor incidence 650 days after irradiation. RCD50 following radiation given alone under hypoxic conditions was 66.3 (60.0-73.2) Gy, and the oxygen enhancement ratio (hypoxic/hyperbaric oxygen) was 3.0 (2.5-3.5). Radiation carcinogenesis was enhanced by hyperthermia given with a 20 min treatment interval with no significant alteration in the oxygen effect. Thermal enhancement was greatest when hyperthermia was given 20 min prior to irradiation (2.5 [2.2-2.9] under hypoxia). No thermal enhancement was observed when two treatments were given with a treatment interval of 2 days. The median time to develop a malignant tumor decreased with increasing radiation dose. This median time was shorter following combined hyperthermia and irradiation (423 days) than following radiation alone (504 days). Histological studies revealed that more than 80% of tumors were soft tissue sarcomas, and the most common tumor was fibrosarcoma. Squamous cell carcinoma was found in 7% of all tumors.

Animals↗
PubMed1989

Relationship between energy status, hypoxic cell fraction, and hyperthermic sensitivity in a murine fibrosarcoma.

The energy status, radiobiological hypoxic cell fraction, and hyperthermic sensitivity of a spontaneous murine fibrosarcoma, FSa-II, have been evaluated as a function of tumor size. Tumors were evaluated over the size range of 70 to 800 mm3. The concentration of the high-energy phosphate reservoir creatine phosphate progressively decreased by a factor of 5 with increasing tumor volume, and was matched by an increase in creatine. The concentration of ATP also decreased with increasing tumor size, although this decrease was substantially less pronounced. The sum of ATP, ADP, and AMP did not vary with tumor size, suggesting that the necrotic fraction remained constant. The decrease in energy status occurred in parallel with an increase in the size of the hypoxic cell fraction and with increasing thermal sensitivity. The results suggest that energy status may be an important modifier of hyperthermic sensitivity in vivo and reflect tissue oxygen concentration.

Adaptation, Physiological↗