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Biomedical subjects

J L Klein

Publications and source records attributed to J L Klein.

At least 73 records · Page 4Linked to original sources
PubMed1993

Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2).

The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Preparation for marrow transplantation in Hodgkin's and non-Hodgkin's lymphoma using Bu/CY.

The results of autologous and allogeneic BMT in 44 patients with Hodgkin's or non-Hodgkin's lymphomas who received preparative therapy consisting of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg are presented. Sixteen patients are surviving free of disease between 8 months and 6 years after transplantation. Thirteen patients either did not attain complete remission or experienced a recurrence of their disease. Fifteen patients died from treatment-related complications. Karnofsky score < or = 70, lactate dehydrogenase greater than twice normal and the development of hepatic veno-occlusive disease were associated with failure to achieve lymphoma-free survival.

Adolescent↗
PubMed1992

Adrenocorticotropin hormone response to diazepam in healthy young men.

The effects of diazepam (DZ) infusions on changes in adrenocorticotropin hormone (ACTH) are a source of debate. In this study, 66 healthy young adult men were evaluated for changes in plasma ACTH after intravenous infusions with placebo, 0.12 mg/kg and 0.20 mg/kg of DZ. After the higher DZ dose, 85% of the subjects demonstrated a decrease in ACTH of 20% or more, with the nadir occurring between 30 and 60 min postinfusion and values returning to baseline levels by 180 min. These results support the conclusion that at the clinically relevant doses used here, DZ infusions are associated with a significant decrease in ACTH.

Adrenocorticotropic Hormone↗
PubMed1992

Radiolabeled antibody therapy for squamous cell carcinoma of the head and neck.

Immunohistochemical staining for ferritin was performed on 11 human head and neck squamous cell carcinomas transplanted in nude mouse xenografts. Seven tumors were found to be positive. Using ferritin as a tumor antigen target, escalating doses of yttrium-90-labeled antiferritin antibodies were injected intravascularly into nude mice that were transplanted with a ferritin-positive human squamous cell carcinoma. Forty-five days after injection, the mean treated tumor size was 25.6% of control in the 100-microCi group, and 20.6% of control in the 200-microCi group. Ninety days after injection the mean tumor size was 27.5% that of control in the 100-microCi group and 31.7% in the 200-microCi group. Higher doses of radiation (300 and 400 microCi per mouse) caused death of most of the animals due to radiation toxicity. Presensitization of the animal, before antibody injection, with a bolus intraperitoneal injection of 7.5 mg of cisplatin per kilogram of body weight, resulted in further reduction in tumor size when compared with antibody alone or cisplatin alone. This study demonstrates that radioimmunotherapy with selected doses of yttrium-90-labeled antiferritin antibodies is effective against human head and neck squamous cell carcinoma xenografts in nude mice.

Animals↗
PubMed1992

Selection of reagents for human radioimmunotherapy.

Promising response rates are noted in patients with refractory Hodgkin's disease after radioimmunoglobulin therapy (RIT) with Yttrium-90 labeled polyclonal antiferritin. To explore the most efficacious selection of RIT reagents for use in humans, experimental animal data are reviewed for radiolabeled antiferritin and B72.3. Nude mice with subcutaneously implanted human malignancies provide an excellent primary screen for radiolabeled antibodies under consideration for use in humans. They provide information on the potential of a new reagent to target a human malignancy in vivo. The other determinant of the therapeutic ratio of RIT reagents--normal tissue toxicity--is best analyzed in large animals, such as dogs. Hematologic toxicity is dose limiting in all species and best predicted by a prescription of radiolabeled antibodies in mCi per kilogram body weight and the presence or absence of bone marrow targeting. Per cGy, RIT is more effective in causing BM damage in dogs than in rats. In dogs, bone marrow transplantation with autologous cryopreserved bone marrow cells or G-CSF treatment can accelerate hemopoietic recovery and granulopoiesis, respectively, after RIT. When dose escalation beyond bone marrow toxicity is performed, the liver (dog) or the intestinal tract (rat) become the next dose limiting tissue in dose escalation studies. Significant improvement in RIT results will be achieved when the normal liver uptake of chelated monoclonal antibody in dogs and in human patients can be prevented. The described animal models and continued investigations of RIT in patients with endstage Hodgkin's disease will allow for further improvement in the therapeutic ratio of RIT and the applicability of RIT in humans.

Animals↗
PubMed1992

The anatomy of a follow-up.

This article describes the methods that were used to maximize subject retention in an 8-12 year follow-up study of 454 men. Guidelines and suggestions are given regarding follow-up structure, strategies to relocate lost subjects, and efforts to maintain contact and ensure subject cooperation. Through these methods all 454 subjects have been located, and at the present time an estimated 98% or greater will be completely evaluated at follow-up. Hopefully these suggestions will be helpful to researchers and clinicians interested in longitudinal studies.

Alcoholism↗
PubMed1992

Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients.

Hypertension is a risk factor for coronary atherosclerosis possibly via an adverse effect on the vascular endothelium. Endothelium-mediated relaxation is impaired in animal models of hypertension. However, the effects of hypertension on human coronary artery endothelial cell function are unknown. To test whether endothelium-mediated relaxation is impaired in the coronary arteries of patients with hypertension, we studied 14 patients with essential hypertension requiring therapy and 15 nonhypertensive control patients undergoing cardiac catheterization. All had angiographically normal, smooth-appearing coronary arteries. Patients were matched for age and other coronary atherosclerosis risk factors. To assess endothelial cell function, the endothelium-dependent vasodilator acetylcholine (ACh, 0.01, 0.1, and 1.0 microM) and the endothelium-independent vasodilator nitroglycerin (40 micrograms) were selectively infused into the left anterior descending or circumflex coronary artery. Diameter change (expressed as percent) was assessed using quantitative angiography. There was a marked vasoconstrictor response to serial doses of ACh in hypertensive patients (-7%, -21%, and -27%) compared with control patients (-4%, -5%, and -7%) (p less than 0.02). The vasodilator response to nitroglycerin was preserved in hypertensive patients (+29%) and control patients (+25%) (p = NS), suggesting that endothelial cell dysfunction accounted for the differences in response to ACh. Thus, patients with hypertension have an accentuated coronary vasoconstrictor response to ACh, suggesting that endothelium-mediated regulation of coronary vascular tone is impaired by essential hypertension. This may reflect more generalized coronary endothelial changes contributing to the pathogenesis of atherosclerosis as well as hypertension.

Acetylcholine↗
PubMed1992

Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.

PURPOSE: The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS: Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION: LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.

Actuarial Analysis↗
PubMed1991

Growth suppression of transformed cells by a human placental extract not related to transforming growth factor beta.

We have examined whether human placental extracts contain tumour-growth-inhibitory factors. One fraction (EAP) from such extracts inhibited growth, in soft agar, of Ha-ras-transformed BALB/c 3T3 cells and human squamous lung carcinoma A-2182 cells. However, this fraction had no effect on the anchorage-dependent growth of these cells, although there was a slight mitogenic activity on nontransformed cells. These data together with those on plating efficiency indicated no significant cytotoxicity of EAP on transformed cell lines. Although this fraction contained transforming growth factor beta (TGF beta), this cannot account for its inhibitory activity, since (a) pure TGF beta does not inhibit anchorage-dependent growth of Ha-ras-transformed BALB/c 3T3 cells, (b) EAP retains its inhibitory activity in the presence of antibodies against TGF beta and (c) the inhibitory activity did not copurify with TGF beta. Partial characterization of our inhibitory factor suggests that the inhibitory factor is a new tumour-growth-inhibitory factor.

Animals↗
PubMed1991

Prognostic factors in unresectable hepatocellular cancer: Radiation Therapy Oncology Group Study 83-01.

The Radiation Therapy Oncology Group (RTOG) conducted a Phase I/II study in hepatocellular cancer that closed on September 9, 1987 and some results presented previously. Here, 17 patient characteristics are evaluated to identify any of prognostic significance. Two hundred sixteen patients were entered and 198 (74% with metastases and/or previous chemotherapy) were evaluable. Treatment began with an induction regimen of external beam radiotherapy to the liver (21.0 Gy, 3.0 Gy/Fx, 10 MV photons, 4 days per week) with low-dose chemotherapy (5-Fluorouracil (FU), 500 mg, i.v.; Doxorubicin, 15 mg, i.v.) on treatment Days 1, 3, 5 and 7. In the later stages of these studies, 56 patients received external beam radiotherapy as hyperfractionated treatment (1.2 Gy twice daily, 4 hours separation, 5 days per week, 24.0 Gy total) with similar chemotherapy. One month following induction therapy, cycles of radiolabeled antibody therapy were given every 2 months. Each cycle was derived from a different species of animal and consisted of 30 mCi I-131 antiferritin, Day 0, and 20 mCi, Day 5. On Day -1, 5-FU, 500 mg, and Adriamycin, 15 mg, were administered. The overall median survival for the entire group, including previously treated patients, was 4.9 months. The median survival for alpha-fetoprotein (AFP) - patients not previously treated was 10.5 months. Median survival for all AFP - patients was 8.5 months and for all AFP + patients was 4.6 months (p = 0.006). Of the 17 pretreatment characteristics investigated for prognostic value Karnofsky Performance Score (KPS) (80-100 vs. less than 80) (p = 0.0001), presence/absence of ascites (p = 0.0002), bilirubin level (less than 1.5 vs. greater than or equal to 1.5) (p = 0.018), SGOT (less than or equal to 35 vs. greater than 35) (p = 0.001); alkaline phosphatase (less than or equal to 95 vs. greater than 95) (p = 0.008) were found to be significant independently using a multivariant regression model. The relative risk of dying for the unfavorable component of each of these characteristics was 2.2, 2.0, 1.5, 1.9 and 1.7, respectively. Good and poor prognostic groups were then defined and compared to a similar patient population (RTOG study 83-19) with confirmation of the validity of the model. When stratification for these overpowering clinical factors was incorporated, AFP status was again significant with a relative death rate 1.80 times higher for AFP+ patients. Our recommendations for structuring future prospective randomized trials are discussed and include stratification by AFP status.

Antibodies↗
PubMed1991

Variable low dose rate irradiation (131I-anti-CEA) and integrated low dose chemotherapy in the treatment of nonresectable primary intrahepatic cholangiocarcinoma.

Previous experience using 131I anti-CEA antibody, which irradiates at a variable low dose rate in combination with a multimodality treatment program, has demonstrated acceptable toxicity and response in primary intrahepatic cholangiocarcinoma. In attempting to improve therapy, Cis-platin was added to the prior regimen. Induction therapy was unchanged. One month later, chemotherapy was given (doxorubicin, 15 mg, 5-fluorouracil, 500 mg, plus Cis-platin, 20 mg/M2) followed the next day by outpatient administration of 20 mCi 131I anti-CEA by i.v. bolus. Five days later, 10 mCi was administered. The latter regimen (chemotherapy plus 20 + 10 mCi 131I anti-CEA) was repeated every 2 months using polyclonal antibodies derived from different species (rabbit, pig, baboon, and horse). Twenty-four patients (29% with prior chemotherapy and/or metastases) were prospectively treated according to this regimen. Toxicity was limited to hematologic toxicity and was manifested by thrombocytopenia and leukopenia (17% and 4% grade 4, respectively, according to RTOG toxicity criteria). Tumor remission was evaluated by CT volumetric analysis and demonstrated a 14% response rate for the induction portion of therapy, 24% for the radioimmunoglobulin portion of treatment, and 50% remission rate when all subsequent tumor volumes were compared to the pre-treatment volume (entire program). The median survival for the entire group of patients was 10.1 months. This result is superior to previously reported trials and, in comparison to our previous study (10.1 vs 6.5 months median survival), further advancement in protocol design appears to have been made. In view of the rarity of this disorder, a randomized trial is not possible and strict statistical analyses cannot be made. The mechanism of 131I-anti-CEA variable low dose irradiation and chemotherapy interaction is discussed as well as further potential modifications for treatment improvement.

Adenoma, Bile Duct↗
PubMed1991

Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin's disease, including Radiation Therapy Oncology Group 87-01.

Radiolabeled antiferritin immunoglobulin (Ig) preparations were tested in patients with advanced, end-stage Hodgkin's disease. Four patients received indium-111 (111In)-labeled monoclonal antiferritin (QCI). Targeting was not observed in tumor-bearing areas. Instead, scans showed rapid accumulation of QCI in normal liver. Forty-five patients were injected with 111In-labeled polyclonal antiferritin (rabbit, pig, or baboon). Forty (89%) patients showed tumor uptake, with dosimetric estimates ranging from 300 to 3,000 cGy in 1 week for the subsequently administered yttrium-90 (90Y)-labeled antiferritin. Yttrium-labeled antibody caused hematologic toxicity. Treatment-induced toxicity was not observed in any other organ system. Intravenous autologous bone marrow cells, 18 days after the yttrium infusion, accelerated hematopoietic recovery in eight patients receiving 30 mCi or 40 mCi. Hematopoietic recovery after a 20 mCi 90Y-labeled antiferritin infusion was not influenced by an autologous bone marrow transplant. Two patients receiving 20 mCi and one patient receiving 50 mCi remained aplastic after transplantation for unknown reasons. In 29 assessable patients, a 62% response rate was observed; nine of the 18 responses were complete. Responses ranging from 2 to 26 months were more commonly noted in patients with small tumors and long disease histories. Dosimetric calculations did not predict for responses. Recurrences frequently occurred in new areas instead of areas exhibiting bulky disease at the start of the treatment. Complete responses after 90Y antiferritin were significantly (P less than .02) more frequent than in a previous study with iodine-131 (131I) antiferritin. Further improvements are needed to make this new treatment modality curative.

Adolescent↗
PubMed1991

High levels of sensitivity to alcohol in young adult Jewish men: a pilot study.

This article compares the intensity of response to ethanol in 15 men who reported having Jewish mothers and fathers with the responses of 15 non-Jews who have a close alcoholic relative (FHP) and 15 non-Jews who have no such family history (FHN). After matching the three groups on demography and drinking history, there were no differences on their expectations of the effects of alcohol, nor on the blood alcohol concentrations following the consumption of 0.75 ml/kg of ethanol. However, the men who considered themselves as having a Jewish heritage evidenced significantly more intense subjective feelings after the alcohol challenge, with a similar but nonsignificant trend observed for their level of postdrinking body sway.

Adolescent↗
PubMed1991

The role of chronic viral hepatitis in hepatocellular carcinoma in the United States.

Although hepatocellular carcinoma is a relatively uncommon tumor in the United States, it is quite common in sub-Saharan Africa and the Far East, where most cases are associated with infection with the hepatitis B virus. We have studied 99 American patients with hepatocellular carcinoma for evidence of hepatitis B or hepatitis C viral infection and compared these findings to those in a group of matched controls with other cancers. The two groups differed in proportion, with hepatitis B surface antigen in serum being significantly higher in patients with hepatocellular carcinoma (7% vs. 0%, p = 0.009). Antibody to hepatitis C virus was also found more frequently in patients with hepatocellular carcinoma (13% vs. 2%, p = 0.002). The relative risk for hepatocellular carcinoma in hepatitis B surface antigen-positive patients was calculated to be 17.3 and for antibody to hepatitis C virus to be 7.3. The attributable fraction of cases related to the hepatitis B surface antigen carrier state was 6.7% and for patients infected with the hepatitis C virus was 11.4%. Approximately three quarters of cases of hepatocellular carcinoma did not have evidence of either hepatitis C or hepatitis B virus infection. These findings provide strong evidence that hepatitis C virus infection is associated with the development of hepatocellular carcinoma, and in the United States may even play a more important role than the hepatitis B virus.

Adolescent↗
PubMed1991

Correlations between drinking intensity and reactions to ethanol and diazepam in healthy young men.

This article presents data on the relationship between the recent drinking histories of 80 healthy men aged 18 to 25 years and their intensities of reaction to challenges with 0.75 ml/kg of ethanol, 0.12 mg/kg of diazepam, and 0.20 mg/kg of diazepam. Significant and consistent negative correlations between the usual quantity x frequency of alcohol intake and scores on all 13 items of the Subjective High Assessment Scale were demonstrated. Expectation of the effects of alcohol appears to be an important mediator of these relationships, although other factors may be involved as well. Although few significant relationships were observed for more objective measures of reactions to the challenges, these data underscore the potential effect of drinking history on evaluations of subjective feelings following challenges with these drugs.

Adolescent↗
PubMed1991

Quantitative SPECT for indium-111-labeled antibodies in the livers of beagle dogs.

Results are presented for SPECT computations of liver volumes and 111In-labeled antibody activities in the livers of eight normal beagle dogs. Administered activities ranged from 1 to 2 mCi. SPECT studies were acquired 1 day postinjection using a rotating gamma camera system with elliptical orbits in a 360-degree rotation (128 views, 15 sec/view, 64 x 64 matrices). Uniformity-corrected images were reconstructed by use of the circular harmonic transform algorithm with computer software developed in-house. Liver volumes and activities were computed from transverse slices, 1 pixel (6.25 mm) in thickness. Comparison of SPECT and autopsy data demonstrated that absolute values of percent differences between measured and computed liver volumes ranged from 1.0% to 7.2%. Absolute values of percent differences between autopsy data and computed 111In activities in the liver ranged from 2.3% to 7.5%. These results suggest that quantitative SPECT has the potential of becoming an important tool in clinical trials for determining activities and localization volumes of radiolabeled antibodies directly from radionuclide images.

Animals↗
PubMed1990

Radiolabeled antibodies: results and potential in cancer therapy.

Radiolabeled antibodies are analyzed from the classical approach in radiation oncology being compared to geometric isotopic implants, external radiation, and tumor-dose response and energy of the isotope used for cytotoxicity. In addition, physiological factors that limit antibody uptake, varied routes of administration, toxicity of treatment, as well as present clinical progress are reviewed.

Antibodies, Neoplasm↗