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Biomedical subjects

D Schoenfeld

Publications and source records attributed to D Schoenfeld.

At least 73 records · Page 4Linked to original sources
PubMed1988

Evidence of differential control of FSH and LH secretion by gonadotropin-releasing hormone (GnRH) from the use of a GnRH antagonist.

The differential regulation of immunoactive FSH and LH secretion by endogenous GnRH was studied using a GnRH antagonist, [Ac-D2Nal1,D4FPhe2,DTrp3,DArg6]GnRH (the NAL-ARG antagonist), in normal women in the early follicular phase of the menstrual cycle, and their responses were compared to those in two groups of control women. Pulsatile LH secretion was examined as an index of the completeness of blockade of endogenous GnRH secretion. There was a dose-dependent decrease in both the frequency and amplitude of LH pulses. At the highest dose, LH pulses were completely abolished within 20 min after sc administration of the GnRH antagonist and for a minimum of 8 h in all women. The mean plasma LH levels were reduced within the first 4 h after antagonist administration at all doses (P less than 0.001). The duration of LH suppression was influenced by antagonist dose, with a continued effect 24 h after administration of the 500 micrograms/kg dose only. The maximum degree of LH suppression was 40% after 50 micrograms/kg (n = 6), 60% after 150 micrograms/kg (n = 6), and 59% after 500 micrograms/kg (n = 5). In contrast, plasma immunoreactive FSH levels did not change after these doses of the NAL-ARG GnRH antagonist. The maximum degree of FSH suppression was 16%, and the changes in plasma FSH concentrations were not dose dependent. Serum antagonist concentrations rose within 30 min after its administration to mean peak levels of 7.5 +/- 2.1 (+/- SE), 20.4 +/- 6.1, and 151 +/- 21 ng/mL after the 50, 150, and 500 micrograms/kg doses, respectively. The half-time of the disappearance of the NAL-ARG GnRH antagonist from plasma was 8.8 +/- 1.5 h. While there were no effects of antagonist administration on hematological, hepatic, or renal function, three women developed urticaria distant from the site of injection when administered the highest dose. We conclude that blockade of GnRH receptors by a GnRH antagonist 1) effectively antagonizes the action of GnRH, as assessed by its ability to block pulsatile LH secretion and reduce mean plasma LH levels; and 2) inhibits LH release to a considerably greater degree than FSH release, providing further evidence of possible GnRH-independent FSH secretion.

Adult↗
PubMed1988

Combined modality approach to treatment of malignant gliomas--re-evaluation of RTOG 7401/ECOG 1374 with long-term follow-up: a joint study of the Radiation Therapy Oncology Group and the Eastern Cooperative Oncology Group.

The Radiation Therapy Oncology Group (RTOG) and the Eastern Cooperative Oncology Group (ECOG) conducted a phase III trial in patients with malignant gliomas to evaluate 4 treatment arms: 1) 60 Gy to the whole brain; 2) 60 Gy plus 10-Gy boost; 3) 60 Gy plus carmustine (BCNU); and 4) 60 Gy plus semustine plus dacarbazine. Between September 1974 and March 1979, 626 patients with malignant gliomas were treated on protocol RTOG 7401/ECOG 1374. Each institution chose a subset of the treatments to which the patients would be randomized. Patients were stratified according to subset and randomized to the 4 treatment arms. There were no differences in survival among treatment arms. For patients greater than 60 years of age, the addition of chemotherapy to radiation therapy did not improve survival. For patients aged 40-60 years, there was a statistically significant increase in overall survival when BCNU was added to 60 Gy (P less than .01), with an increase in 2-year survival from 8% to 23%. This beneficial effect of BCNU is apparent in both histological groups (astrocytoma with atypical or anaplastic foci and glioblastoma multiforme). Although few confirmatory autopsies are available, long-term survival in patients with astrocytomas with atypical and anaplastic foci who were treated with 60 Gy plus BCNU (5-yr survival, 22%) suggests no significant late CNS toxicity, compared to 60 Gy alone (5-yr survival, 15%). This is confirmed by comparable neurological function in long-term survivors.

Adult↗
PubMed1986

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery: final report of an RTOG study.

This randomized RTOG study evaluated misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. One hundred and forty-six evaluable patients were treated with conventional radiation therapy to 60.00 Gy in 6-7 weeks plus BCNU 80 mg/m2/d for 3 days every 8 weeks (XRT + BCNU). One hundred and forty-seven evaluable patients were treated with misonidazole 2.5 gm/m2 once a week for 6 weeks, radiation therapy to 60 Gy and BCNU (MISO + XRT + BCNU). Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics was comparable among the treatment groups. The median survival for XRT + BCNU was 55.0 weeks, and for MISO + XRT + BCNU 46.0 weeks (p = 0.35). With patients on a minimum dose of dexamethasone of 3 mg/d, misonidazole neurotoxicity included 8.8% peripheral neuropathy, 2.7% CNS toxicity, and a 0.68% ototoxicity. BCNU pulmonary toxicity occurred in 9.3% of patients who received 902-2062 mg/m2 of BCNU.

Adult↗
PubMed1986

High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial.

Twenty-nine patients were treated with 31 courses of high-dose combination cyclophosphamide, cisplatin, and carmustine (BCNU) with and without melphalan with autologous bone marrow support. Toxicity was dose related. The maximum tolerated dose for cyclophosphamide, cisplatin, and BCNU in this combination in mg/m2 was 5,625, 165, and 600, respectively. Further dose escalation was precluded by the development of multiple organ toxicity, including venoocclusive disease, refractory thrombocytopenia, and hypertension. Melphalan added to the three-drug combination produced excessive renal and gastrointestinal toxicity. Objective tumor regression occurred in 21 of 25 evaluable cases. The results suggest that selected alkylating agents can be combined in full or nearly full doses before nonmyelosuppressive dose-limiting toxicity precludes further escalation.

Adult↗
PubMed1986

Pulsatile secretion of thyrotropin in man.

To examine pulsatile TSH secretion, serum TSH was determined every 10 min for 24 h in 6 normal subjects and every 15 min in 10 euthyroid patients with underlying thyroid disease. Serum T4, T3, and PRL were simultaneously measured in the 10 patients. Pulsatile TSH secretion was identified in all individuals. There was a highly significant correlation between the mean 24-h TSH concentration and pulse amplitude (P less than 0.001). There was a highly significant inverse correlation between the mean 24-h TSH concentration and pulse frequency (P = 0.002) and between the pulse amplitude and frequency (P = 0.002). The mean serum TSH level at night (1800-0600 h) was significantly higher than that during the day (P less than 0.001) and was associated with increases in pulse amplitude (P = 0.008) and frequency (P = 0.007). TSH pulses did not correlate with serum T4 or T3, but did correlate with serum PRL (P = 0.03) in patients with thyroid disease. We conclude that TSH pulsations can be identified in normal subjects and patients with thyroid disease; elevations in serum TSH levels correlate with an increase in pulse amplitude and a decrease in pulse frequency; the nocturnal rise in serum TSH is associated with increases in both pulse amplitude and frequency; and peripheral serum T4 or T3 concentrations are not closely associated with pulsatile TSH secretion.

Adult↗
PubMed1986

Single-chamber and dual-chamber cardiac pacemakers. A formal cost comparison.

Dual-chamber pacemakers, more sophisticated and costly than single-chamber pacemakers, are being used with increasing frequency, often with unclear indications. Proponents of dual-chamber devices have focused on initial differences in cost without considering additional induced costs. We examined the incremental cost of dual-versus single-chamber pacemakers over the expected lifetime of a pacemaker recipient. In addition to initial costs, we included the costs of pacemaker malfunction, reimplantation, generator replacement, and follow-up. Expected differences in cumulative costs per patient were calculated over a 12-year period. Dual-chamber pacing is $2500 more costly at implantation. The difference in cumulative cost increases to $5100 by year 12, reflecting shorter functional life for dual-chamber pacemaker generators and increased cost of follow-up. The incremental cost of dual-chamber pacemaking is neither short-term nor trivial. Dual-chamber pacemakers should be reserved for those who clearly benefit from its advanced technology.

Costs and Cost Analysis↗
PubMed1983

Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study.

Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty-seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6-7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1-2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl-CCNU (125 mg/m2/day orally X 1 and repeat methyl-CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18-month survival of 64%, patients who were age 40-60 years had an 18-month survival of 20%, and patients who were older than age 60 had an 18-month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40-60-year-old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one-sided). Similarly, methyl-CCNU + DTIC was suggestively better than the control (P = 0.08, one-sided). The higher radiation dose, 7000 rad/8-9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl-CCNU + DTIC produced some toxicity. The combination of methyl-CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.

Adult↗
PubMed1983

Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas.

Surgical specimens of malignant, supratentorial, astrocytic gliomas from 503 patients randomized on an RTOG-ECOG treatment protocol were examined by central pathologic review. The diagnosis of glioblastoma multiforme (GBM) was made only when one or more foci of coagulation necrosis involving astrocytic tumor cells were identified histologically. Malignant astrocytic neoplasms without necrosis were classified as astrocytoma with atypical or anaplastic features (AAF). The median survival stratifying for treatment for patients with GBM was eight months compared to 28 months for patients with AAF. In most cases the specimens were received with a Kernohan grade. On the basis of these grades, patients with astrocytoma Grade 3 had a median survival of ten months as compared to a median survival of nine months for those with astrocytoma Grade 4. Observations demonstrate that necrosis is a reliable, decisive prognostic factor associated with malignant, supratentorial, astrocytic gliomas. The Kernohan system is of limited value in assessing prognosis for this group of tumors.

Aged↗
PubMed1983

Second malignancies diagnosed in patients receiving chemotherapy at the Pennsylvania Hospital.

During the past 15 years, the records of 2,020 patients who received chemotherapy on the surgical oncology, chemotherapy service at the Pennsylvania Hospital were reviewed. Thirty-five patients had pathologically confirmed second independent malignant tumors (not recurrences). The second cancers that developed were varied. The patients who developed these second malignancies ranged in age from 35 to 77 years (24 females, 11 males). The time interval involved was two to 102 months. Nine patients in this group of second malignancies received prior radiation therapy. The following is a list of the second cancers. There were 8 colons, 5 ovaries, 5 lungs, 6 acute myelogenous leukemias, 1 esophagus, 2 bladders, 2 epidermoid carcinomas of the skin, 2 melanomas, 1 chronic lymphatic leukemia, 1 breast cancer, 1 non-Hodgkin's malignant lymphoma, and 1 stomach cancer. The majority of second malignant tumors were amenable to some form of therapy, ie, surgery, radiation or chemotherapy. However, all of the acute myelogenous leukemias were totally refractory to any therapeutic modalities and rapidly expired. The majority of second cancers developed in patients receiving adjuvant chemotherapy. This is a patient population with a much longer expected survival time, particularly when compared to patients receiving chemotherapy for advanced disease. Twenty-five of the 34 second cancers developed in patients who received adjuvant chemotherapy for breast (14) or colorectal (11) cancers. The etiology of the second malignancies is very difficult to determine. However, alkylating agents appeared to be the possible etiologic agent involved in the development of acute myelogenous leukemia.

Adult↗
PubMed1983

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery; preliminary results of an RTOG study.

A randomized prospective study was performed to evaluate misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. The control arm, Group A, consisted of conventional radiation therapy (6000 cGy/6-7 weeks) to the whole brain plus BCNU (80 mg/m2 on day 3, 4, 5, and then repeated q 8 weeks for 2 years). The BCNU schedule was identical in both arms. In the experimental arm, Group B, misonidazole 2.5 gm/m2 was given once a week for six weeks, to a total dose of 15 gm/m2. It was given orally four hours prior to 400 cGy on Mondays. On Tuesdays, Thursdays and Fridays, 150 cGy was delivered to a total of 5100 cGy/6 weeks. An additional 900 cGy/5F/1 week was given without misonidazole. Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics among the treatment groups was comparable. As of March 1, 1982, 245 patients were randomized with follow-up information available on 202 patients. The median follow-up is 12 months (range 3-39 months). There is no significant difference in the survival of the two groups. The median survival for Group A was 12.6, and for Group B, 10.7 months. Misonidazole toxicity included an 11% peripheral neuropathy and a 3% central nervous system toxicity. BCNU toxicity included severe hematologic toxicity in 25%, including one death, and significant pulmonary toxicity in 6 out of 55 patients who received a minimum total dose of 960 mg/m2 of BCNU.

Adolescent↗
PubMed1982

Mitomycin-C, methotrexate, bleomycin and cis-diamminedichloroplatinum II in the chemotherapy of advanced squamous cancer of the head and neck.

Thirty-four patients with advanced squamous cancer of the head and neck were treated with an outpatient regimen combining mitomycin-C, cis-diamminedichloroplatinum (II), methotrexate and bleomycin. Five had complete remissions and 15 partial remissions, for an overall response rate of 59%. Responses were noted on 11 of 13 patients (85%) with disease above the clavicles without prior irradiation. Median duration of partial remission was four months. Response rate was independent of age, performance status, presence of distant metastases and primary site. Hematologic toxicity was substantially more severe with this program than had been observed in a prior study using the same regimen without mitomycin-C. Since neither complete nor partial response rates, nor response durations improved with the addition of mitomycin, we conclude that it adds little to the efficacy of the other three agents.

Adult↗
PubMed1981

A randomized prospective comparison of intermittent methotrexate, methotrexate with leucovorin, and a methotrexate combination in head and neck cancer.

A randomized prospective clinical trial involved 259 cases of advanced recurrent Stage III and IV epidermoid cancers of the head and neck. The cases were randomized among three treatment programs evaluating two dose schedules and a combination treatment of methotrexate. The treatments consisted of: weekly methotrexate, biweekly methotrexate with leucovorin rescue (ML), and biweekly ML combined with cyclophosphamide and cytosine arabinoside (MLCC). Equivalent overall drug-related toxicity was produced with a 5% drug-related fatality rate. Methotrexate alone produced significantly more skin and mucosal toxicity, and the combination (MLCC) resulted in more hematologic toxicity than other treatments. Complete and partial objective responses were achieved in 26%, 24%, and 18% by each treatment. Methotrexate alone produced a median duration of response and 105 days compared with 42 and 49 days from the other treatments. Duration of response was significantly longer and survival was better in the methotrexate-alone group. Response was markedly stage dependent; 40% of Stage III patients achieved response, whereas only 17% of Stage IV patients responded. Presence of visceral metastases decreased response rates and the likelihood of response was particularly compromised by pulmonary metastatic spread; only seven of 54 such patients responded. Decreased survival was related to non-ambulatory performance status, disease-free intervals of less than one year and weight loss. Survival differences between Stage III and IV patients could not be shown. This study demonstrates the therapeutic superiority of weekly i.v. treatment with methotrexate but failed to support claims of an improved therapeutic index for high-dose methotrexate with leucovorin rescue. As the only randomized prospective clinical trial of chemotherapy in advanced head and neck cancer, this study reinforces the weekly i.v. schedule of methotrexate as the standard against which other drug schedules and drug combinations should be compared.

Adult↗
PubMed1980

Determining the labeling index in autoradiography.

A method is proposed for estimating the labeling index in autoradiographs. It is based on a model for the frequency distribution of grain counts for those cells which have few grains. The method does not require extensive grain counting and provides reasonable estimates even when the background level is high. It is particularly suited for experiments where tumnor cells, labeled in vivo, are autoradiographed after being cultured in vitro.

Autoradiography↗
PubMed1980

The uterotrophic effect of delta 9 THC in ovariectomized rats and mice.

We have reanalyzed the statistics on uterine weights used by Virgo in his article, The Estrogenicity of Delta-9-Tetrahydrocannabinol (THC): THC Neither Blocks nor Induces Ovum Implantation, nor does it Effect Uterine Growth, which appeared in Res. Comm. Chem. Path. and Pharmacol. 25:65-77 (1979). The reanalysis shows that administration of 3 and 6 mg/kg delta 9 THC to ovariectomized mice results in highly significant (P < .002; P < .0001 respectively) increases in uterine weights. These data are in accord with the uterotrophic effect of delta 9 THC observed in ovariectomized rats.

Animals↗
PubMed1980

Randomized trial of chlorpromazine, caffeine, and methyl-CCNU in disseminated melanoma.

One hundred and fifty-seven evaluable patients with advanced metastatic malignant melanoma were randomly assigned to receive either methyl-CCNU (MeCCNU) (200 mg/m2 orally every 6 weeks) (82 patients) or a combination of MeCCNU, chlorpromazine (50 mg/m2 im), and caffeine (600 mg/m2 sc) in the periumbilical area (75 patients). The response rate was 12% for the combination (three complete responses and six partial responses) and 11% for MeCCNU alone (two complete responses and seven partial responses). The median survival was 20 weeks and was the same for both treatments. The data support the hypothesis that caffeine and chlorpromazine do not enhance MeCCNU activity in malignant melanoma, unlike the marked enhancement seen for this drug combination in L1210 leukemia in mice.

Caffeine↗
PubMed1979

Prospective comparison of intralesional and multipuncture BCG in recurrent intradermal melanoma.

Fifty-nine patients with metastatic melanoma predominantly localized in the skin were randomly assigned to treatment with BCG given either intralesionally (IL-BCG) or by multiple puncture vaccination at a nontumor bearing site in the skin (MPV-BCG). Half the patients with IL-BCG experienced moderate fever, chills and malaise, suggesting systemic exposure to this live organism. However, only three of these patients required systemic antituberculous chemotherapy and all responded to it. MPV-BCG treated patients experienced significantly less systemic toxicity. Among fully evaluable patients 45% objective response rate was seen in the IL-BCG group and a 9% response rate in the MPV-BCG group, a significant difference. The only complete responses were seen in the IL-BCG group. Among fully evaluable patients, median survival was 21.1 months in the IL-BCG group and 13.3 months in the MPV-BCG groups (NSD). No patients with pretreatment anergy to all skin tests utilized, experienced objective response to BCG.

Adult↗
PubMed1977

Results with methyl-CCNU and DTIC in metastatic melanoma.

This report is the result of an Eastern Cooperative Oncology Group (ECOG) study. Four hundred and 15 patients with inoperable metastatic malignant melanoma, excluding those with cutaneous metastases only, were randomized to one of three drug treatments: DTIC alone, methyl-CCNU alone, or the combination DTIC plus methyl-CCNU. Responses were seen in 14% of DTIC patients (19/127), 15% of methyl-CCNU patients (18/119) and 14% of DTIC plus methyl-CCNU patients (18/122). Duration of response was the same (14 weeks) for all three treatment groups. There was no difference among the treatments in achieving complete responses. Survival was improved significantly for responders (50 weeks) compared with nonresponders (15 weeks) regardless of treatment regimen. Toxicities were generally tolerable. DTIC caused significantly more gastrointestinal toxicity than methyl-CCNU. Methyl-CCNU caused significantly more bone marrow toxicity than DTIC. There were three drug-related deaths. All occurred in patients on combination DTIC plus methyl-CCNU. Important pretreatment characteristics that favor response are ambulatory status, female, less than 50 years old, no prior chemotherapy and no liver or brain metastases. Patients with favorable characteristics combinations had a 30% response rate, while those with unfavorable characteristic combinations had only a 9% response rate.

Brain Neoplasms↗