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Biomedical subjects

R B Weiss

Publications and source records attributed to R B Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Hodgkin disease survivors at increased risk for problems in psychosocial adaptation. The Cancer and Leukemia Group B.

BACKGROUND: The long-term psychosocial adaptations of 273 survivors of advanced Hodgkin disease were assessed to determine the nature and extent of problems experienced and to identify those at high risk for maladaptation. METHODS: Hodgkin disease survivors were identified who initially had been treated in clinical trials within the Cancer and Leukemia Group B from 1966 to 1986, were currently disease free, and had completed treatment for a minimum of 1 year. All survivors had advanced Hodgkin disease (with disease diagnosed at a mean age of 28 years). Survivors were at a mean age of 37 years at the time of interview (6.3 years after treatment completion), and 60% were male. Survivors were interviewed over the telephone 7-10 days after questionnaires were mailed to them concerning their psychological, social, vocational, and sexual functioning. RESULTS: Psychological distress was found to be elevated by one standard deviation (SD) above that of healthy subjects on the Brief Symptom Inventory, and 22% met the criterion suggested for a psychiatric diagnosis. In addition, the following problems were reported by survivors to be a consequence of having had Hodgkin disease: denial of life (31%) and health (22%) insurance, sexual problems (37%), conditioned nausea in response to reminders of chemotherapy (39%), and a negative socioeconomic effect (36%). Survivors found to be at high risk for maladaptation were: men earning less than $15,000 per year or who were currently unemployed; unmarried individuals; those with serious illnesses since treatment completion; and those who were less educated. CONCLUSIONS: These findings suggest that including a routine assessment of these factors would help to target survivors in need of additional evaluation and treatment.

Adaptation, Psychological↗
PubMed1992

Pregnancy outcome in survivors of advanced Hodgkin disease.

BACKGROUND: Pregnancy outcome was reported by 139 survivors of advanced Hodgkin disease treated on nine protocols of Cancer and Leukemia Group B from 1966 to 1986. METHODS: These patients provided data on 302 singleton pregnancies of a duration of at least 20 weeks that occurred before, during, or after treatment for Hodgkin disease (252, 26, and 24 pregnancies, respectively). RESULTS: There were 4 perinatal deaths, as compared with 5.7 expected. Cancer subsequently developed in 2 offspring (expected, 1.2). However, 22 newborn infants had low a birth weight, exceeding the expected number of 13.7 (relative risk 1.6; 95% confidence interval, 1.0-2.4). The excess number of low weight births occurred primarily during the period of Hodgkin disease diagnosis and treatment but is based on small numbers. CONCLUSION: No increase in adverse outcome occurred in pregnancies that antedated the development of Hodgkin disease.

Adult↗
PubMed1992

A pilot trial of chemohormonal therapy for metastatic prostate carcinoma.

Fifteen patients with previously untreated metastatic prostate cancer were treated on a pilot trial with a combination of maximal androgen blockade plus intermittent cytotoxic therapy after androgen priming to stimulate cell division. Androgen blockage was carried out using a gonadotropin-releasing hormone analog (leuprolide) plus a nonsteroidal antiandrogen (flutamide). Carboplatin (CBDCA) (800 mg/m2) was given intravenously every 28 days, preceded for 3 days and followed for 3 days by androgen treatment with fluoxymesterone (5 mg orally twice a day), during which time flutamide was discontinued. Three patients (20%) achieved a complete response (CR), and eight patients (53.3%) achieved a partial response (PR). Four patients (26.7%) had stable disease (SD). The median progression-free survival (PFS) time was 31 months. Nine of 15 patients (60%) remain alive with a median follow-up time of 42+ months (range, 22 to 54 months). Grade 4 thrombocytopenia and Grades 3 or 4 leukopenia were experienced in 87% and 80% of patients, respectively, requiring dose reductions of CBDCA in 85% of the cycles. Six of 15 patients experienced a flare in bone pain with androgen priming. There were no associated spinal cord compressions; however, exclusion of impending spinal cord compression was required before entrance on study.

Adenocarcinoma↗
PubMed1992

Low fluorescence background electroblotting membrane for DNA sequencing.

A low fluorescence background polypropylene (PP) membrane has been developed for ultimate use as an electroblotting membrane in DNA sequencing based on fluorescence detection. The DNA binding capacity of this membrane is improved by a surface modification using radio frequency plasma discharge (RFPD) in ammonia gas. The RFPD operational parameters are evaluated both in terms of membrane nitrogen content and in terms of the product's capacity for binding radioisotope-labeled DNA fragments. The surface morphologies of the derivatized membranes are examined by scanning electron microscopy; their mechanical and electrical properties, which are important for the subsequent sequencing procedures, are likewise established. Due to the goal of developing a membrane suitable for multiplex processing, in which the electroblotted DNA must withstand dozens of hybridization/stripping cycles, special attention is given the covalent attachment of DNA to the membrane. The modified PP membrane is evaluated in a multiplex sequencing application using radioisotope-labeled DNA probes, and found to yield somewhat better binding of a given amount of electroblotted DNA than the commonly used GeneScreen membrane. A tenfold repetition of the probing indicates little loss of signal; the membrane-bound DNA is stable upon storage and shows no detectable loss in probing efficiency after one month.

Base Sequence↗
PubMed1992

Predicting genitourinary toxicity in patients receiving cisplatin-based combination chemotherapy: a Cancer and Leukemia Group B study.

Assessment of renal function prior to cisplatin chemotherapy has long been based on measurement of creatinine clearance by 24-hour urine collection (CrCmeas). Estimated creatinine clearance (CrCest) as calculated from the patient's age, weight, and serum creatinine level has been suggested as an adequate surrogate for CrCmeas, as it provides advantages of improved convenience, decreased cost, and possibly increased accuracy. We studied 847 patients receiving cisplatin-based chemotherapy on Cancer and Leukemia Group B (CALGB) protocols to determine whether the CrCmeas, CrCest, or serum creatinine value or the age of the patient would predict the subsequent genitourinary (GU) toxicity. Both CrCmeas (P = 0.001) and CrCest (P = 0.02) were predictive of subsequent grade 2+ GU toxicity, with CrCmeas being a slightly better predictor. Patient age also influenced subsequent GU toxicity, with the risk increasing with age (P = 0.0008). When patients were classified by age group and by CrCmeas, distinct subgroups were identified, with differences in the risk for grade 2+ GU toxicity ranging from 14% to 32%. Using a logistic model to assess the probability of grade 2+ GU toxicity, we found that an age of greater than or equal to 60 years (P = 0.005), a CrCmeas value of less than 75 ml/min (P = 0.004), and the risk characteristics of the individual cisplatin trial were important, whereas CrCest was not. Furthermore, CrCest proved to be a poor predictor of a CrCmeas value of less than 75 ml/min, "misclassifying" nearly half of the patients to a "lower-risk" subgroup. In summary, both CrCmeas and the patient's age independently provided predictive information concerning cisplatin GU toxicity. Our data support the continued clinical usefulness of determining the CrCmeas value prior to the administration of cisplatin-based chemotherapy to most patients.

Adult↗
PubMed1992

Prognosis and other clinical correlates of pathologic review in stage I and II testicular carcinoma: a report from the Testicular Cancer Intergroup Study.

PURPOSE: The Testicular Cancer Intergroup Study (TCIS) was undertaken to evaluate the pathologic findings in early-stage testicular cancer as determined by central pathology review, to compare these findings with the interpretation by the contributing pathologists, and to make correlations with various clinical parameters and outcomes. PATIENTS AND METHODS: The prospective study of non-seminomatous germ cell testicular cancer staged surgically involved 459 eligible patients with stage I (node-negative) or stage II (node-positive) disease. Pathologic materials from both the orchiectomy and lymphadenectomy specimens were submitted to a central laboratory for evaluation. RESULTS: Central and local pathologists differed significantly in their identification of certain cellular histologies (primarily yolk sac tumors [YST]) and recognition of invasion into vascular structures. In contrast to our prior findings with local pathologic assessment, venous/lymphatic invasion as determined by central review predicted relapse in both stages. In pathologic stage I disease, the relapse rate was 19.4% (12 of 62 cases) for those with invasion versus 6.0% (10 of 168 cases) for those without invasion. In pathologic stage II disease, the respective relapse rates were 63.5% (40 of 63 cases) and 24.0% (six of 25 cases). Vascular invasion was jointly predictive with nodal stage for risk of relapse. The percentage of embryonal carcinoma (EC) in the primary tumor was predictive of nodal stage and relapse in a univariate, but not a multivariate, analysis. In a large substudy, immunohistochemical staining identified a correlation between stain intensity in YST and serum alpha-fetoprotein (AFP) levels. In a similar fashion human chorionic gonadotropin (HCG) staining reactivity occurred exclusively in patients with syncytiotrophoblasts and correlated with serum levels of beta-HCG. CONCLUSIONS: A number of tumor histology correlates with clinical parameters have been identified or confirmed. Careful pathologic scrutiny of the primary testicular tumor, especially for vascular invasion, provides important prognostic information.

Adolescent↗
PubMed1992

No evidence of acute cardiovascular complications of chemotherapy for testicular cancer: an analysis of the Testicular Cancer Intergroup Study.

PURPOSE: The purpose of this study is to evaluate the risk of acute vascular events in patients receiving cisplatin-based chemotherapy for testicular cancer. PATIENTS AND METHODS: A questionnaire assessing cardiovascular toxicity was distributed to all participants in the Testicular Cancer Intergroup study and details of toxicity from the chemotherapy flow sheets were reviewed. Patients with pathologic stage I testicular cancer were registered on to the study and observed after retroperitoneal lymphadenectomy. Patients with pathologic stage II disease were randomized to receive two postoperative courses of adjuvant cisplatin-based chemotherapy or observation. Any patient who had disease recurrence after observation or adjuvant therapy was given four cycles of cisplatin-based chemotherapy. RESULTS: Review treatment-related toxicity for those patients receiving adjuvant chemotherapy (n = 97) or chemotherapy for recurrent disease (n = 83) showed no cases of acute cardiovascular toxicity. The median follow-up period after study enrollment was 5.1 years; 459 questionnaires were mailed and 270 were returned. The percent return was equal among the observed adjuvant and recurrent groups (59%, 54%, and 64%). There was a significant increase in the incidence of extremity paresthesias in the two groups receiving chemotherapy. Fatal myocardial infarction was reported in two patients in the observation group and one nonfatal infarction was reported in the adjuvant treatment group. No patient in any group reported an incidence of stroke. Three patients in the observation group and one patient in the recurrent group experienced a thromboembolic event. CONCLUSION: Despite sporadic case reports suggesting a causal association between chemotherapy for testicular cancer and acute vascular events, this retrospective analysis provides no evidence of an increased risk for subsequent cardiovascular disease in this patient population.

Acute Disease↗
PubMed1992

Hypersensitivity reactions.

All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells. It is possible to continue therapy with some drugs, despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken. An example of this is provided by taxol in which the lengthening of the infusion time and the administration of preventive medication allowed some patients to continue taxol therapy. The mechanisms of the HSRs have been carefully assessed in only a minority of patients who sustained such toxicity. Such evaluation would increase our understanding of this form of drug toxicity and perhaps lead to means of effectively reducing the risk and severity.

Antibiotics, Antineoplastic↗
PubMed1992

The anthracyclines: will we ever find a better doxorubicin?

The anthracyclines are the class of antitumor drugs with the widest spectrum of activity in human cancers, and only a few cancers (eg, colon cancer) are unresponsive to them. The first two anthracyclines were developed in the 1960s. Doxorubicin (DOX) differs from daunorubicin (DNR) only by a single hydroxyl group. This fact has spurred researchers worldwide to find analogs of DOX that have less acute toxicity, cause less cardiomyopathy, can be administered orally, and/or have different, or greater, antitumor efficacy. Five DOX/DNR analogs are marketed in other countries, and one (idarubicin) is available in the United States. None of these analogs have stronger antitumor efficacy than the original two anthracyclines, but there are some differences in toxicity. Methods have been fashioned to keep the peak plasma level of DOX muted to minimize cardiotoxicity, but the only apparently effective method available so far (prolonged drug infusion) is cumbersome. The bisoxopiperazine class of drugs (especially dexrazoxane) provides protection against anthracycline-induced cardiomyopathy and has much promise for helping mitigate this major obstacle to prolonged use of the anthracyclines. The DOX analogs being evaluated in the 1990s have been selected for their ability to overcome multidrug resistance in cancer cells. Thirty years after discovery of the anticancer activity of the first anthracycline, some means of reducing anthracycline toxicity have been devised. Current studies are evaluating increased doses of epirubicin to improve anthracycline cytotoxicity, while limiting cardiotoxicity, but at present DOX still reigns in this drug class as the one having the most proven cancerocidal effect.

Animals↗
PubMed1992

Suramin-induced skin reactions.

BACKGROUND AND DESIGN: Suramin sodium, a polysulfonated naphthylurea, has been used for more than 70 years as a chemotherapeutic agent for a variety of diseases. In a phase II trial of suramin, 20 patients with metastatic prostate carcinoma refractory to hormonal manipulation were evaluated retrospectively for evidence of skin toxicity. RESULTS: Three types of skin reaction were noted: generalized, erythematous, maculopapular eruption (10 patients); keratoacanthoma (two patients); and disseminated superficial actinic porokeratosis (one patient). A total of 15 episodes of some form of skin reaction occurred in 13 patients. The maculopapular eruptions resolved in 3 to 5 days despite continued treatment with suramin. CONCLUSIONS: Cutaneous toxicity was a frequent and, often, self-limited side effect of suramin therapy, occurring in 13 (65%) patients. Keratoacanthoma and disseminated superficial actinic porokeratosis have not previously been reported to occur with suramin therapy. The immunosuppressive effect of suramin may induce the keratoacanthoma and disseminated superficial actinic porokeratosis lesions.

Carcinoma↗
PubMed1991

A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B.

Between 1982 and 1986, 326 evaluable patients with acute myeloid leukemia (AML) were randomized to receive cytarabine (Ara-C) at 200 mg/m2 (A200) or 100 mg/m2 (A100) for induction and maintenance therapy. Cycle 1 of induction therapy consisted of 7 days of continuous intravenous (IV) Ara-C and 3 days of i.v. daunorubicin (DNR); cycle 2, if needed, consisted of 5 days of Ara-C and 2 days of DNR. Complete responders (CR) then received monthly subcutaneous (SC) Ara-C at the respective doses (A100 or A200) with 6-thioquanine (6TG) at months 1 and 5, with vincristine (VCR) and prednisone at months 2, 4, 6, and 8, and with DNR at months 3 and 7. Complete response rates were 58% (A100) and 64% (A200) (P = .29). Median survival was 46 weeks (A100) and 38 weeks (A200) (P = .64); 5-year survival was 10% (A200) and 8% (A100). Median time to remission was 6.7 weeks (A200) and 8.1 weeks (A100) (P = .18). Median disease-free survival was 41 weeks (A200) and 44 weeks (A100) (P = .86). Deaths were attributed to therapy-related toxicities in 21% (A200) and 13% (A100) (P = .05). The 5-year survival was 15% for patients with performance status (PS) 0, 8% for PS 1 to 2, and 2% for PS 3 to 4, 18% for patients less than 40 years, 8% for ages 40 to 59, and 3% for age 60 or greater. Stratification of data by age and PS suggested that A200 may improve survival in patients less than 60 years with a good PS 0 (P = .05). This trial does not support the superiority of A200 over A100 in the treatment of AML.

Acute Disease↗
PubMed1991

Phase I bioavailability and pharmacokinetic study of hexamethylene bisacetamide (NSC 95580) administered via nasogastric tube.

A Phase I clinical trial and pharmacological study of nasogastrically administered hexamethylene bisacetamide, a polar-planar compound with in vitro differentiating activity, was conducted in 14 adult patients with refractory cancer. Hexamethylene bisacetamide was administered as a 5% (w/v) solution via a nasogastric or gastrostomy tube every 4 h for 5 days, followed in 21 days by a 5-day continuous i.v. infusion at the same daily dose. Parenteral drug administration was then continued at the same interval in the absence of disease progression or unacceptable toxicity. Three patients each were treated at doses of 12 and 24 g/m2/day, while eight patients received a dose of 30 g/m2/day. Toxicity was comparable for both routes of drug administration at the above doses. Nasogastrically administered hexamethylene bisacetamide was well tolerated at the lower doses, whereas neurotoxicity and nausea and vomiting were the major, but manageable, toxicities at 30 g/m2/day. Metabolic acidosis, renal dysfunction, mucositis, and thrombocytopenia were the other commonly observed drug toxicities at this dose. No objective tumor responses were observed. Hexamethylene bisacetamide was rapidly absorbed from the gastrointestinal tract with a mean measured bioavailability of 99 +/- 15%. Pharmacokinetic parameters for hexamethylene bisacetamide and plasma concentrations of the two major metabolites, N-acetyl-1,6-diaminohexane and 6-acetamidohexanoic acid, were similar for either route of administration in individual patients. Hexamethylene bisacetamide exhibited apparent monoexponential plasma elimination after either nasogastric or parenteral administration with 27 to 60% of the administered dose being excreted in the urine as parent compound. Based on its demonstrated complete bioavailability and tolerability, nasogastric administration of hexamethylene bisacetamide can be directly and safely substituted for the comparable i.v. dose.

Acetamides↗
PubMed1991

cDNA sequence and genomic structure of EV12B, a gene lying within an intron of the neurofibromatosis type 1 gene.

The gene responsible for neurofibromatosis type 1 (NF1), one of the more common inherited human disorders, was identified recently, and segments of it were cloned. Two translocation breakpoints that interrupt the NF1 gene in NF1 patients flank a 60-kb segment of DNA that contains the EV12A locus (previously reported as the EV12 locus), the human homolog of a mouse gene, Evi-2A, implicated in retrovirus-induced murine myeloid tumors. EVI2A lies within an intron of the NF1 gene and is transcribed from telomere toward centromere, opposite to the direction of transcription of the NF1 gene. Here we describe a second locus, EVI2B, also located between the two NF1 translocation breakpoints. Full-length cDNAs from the EV12B locus detect a 2.1-kb transcript in bone marrow, peripheral blood mononuclear cells, and fibroblasts. Sequencing studies predict an EV12B protein of 448 amino acids that is proline-rich and contains an N-terminal signal peptide, an extracellular domain with four potential glycosylation sites, a single hydrophobic transmembrane domain, and a cytoplasmic hydrophilic domain. At the level of genomic DNA the EV12B locus lies within the same intron of the NF1 gene as EV12A and contains a 57-bp 5' exon that is noncoding, an 8-kb intron, and a 2078-bp 3' exon that includes the entire open reading frame. EV12B is transcribed in the same direction as EV12A; its 5' exon lies only 4 kb downstream from the 3' exon of the EV12A locus. In the mouse the 5' exon of the homologous gene, Evi-2B, lies approximately 2.8 kb from the 3' end of Evi-2A, in the midst of a cluster of viral integration sites identified in retrovirus-induced myeloid tumors; thus, Evi-2B may function as an oncogene in these tumors.

Amino Acid Sequence↗
PubMed1991

Ribosomal frameshifting, jumping and readthrough.

New examples of high-level ribosomal frameshift and readthrough events have been described over the past year and a half. These include -1 frameshifting at tandem codons and +1 frameshifting at neighboring slow codons. Several bizarre examples of ribosome jumping and multiple stop-codon readthrough continue to perplex investigators in this field.

Base Sequence↗
PubMed1991

Staging relationships and outcome in early stage testicular cancer: a report from the Testicular Cancer Intergroup Study.

The Testicular Cancer Center Intergroup Study entered surgically staged patients with nonseminomatous tumor and metastases limited to the regional lymph nodes into a previously reported cooperative trial of immediate versus delayed therapy for positive retroperitoneal node disease. Patients with negative nodes (stage I) were placed in an observation registry with specified treatment strategy upon relapse. Of 264 stage I cancer patients 27 (10.2%) had recurrence: 5 of these 27 patients died after recurrence of the testicular malignancies, while 4 other nontumor-related deaths have occurred. Pre-lymphadenectomy staging characteristics observed to predict significantly node positivity are the results of radiological examinations, presence of tumor invasion, vascular invasion and tumor histology. In a multiple logistic regression analysis with these variables, misclassification still occurs in more than a fourth of the patients. Future refinements in diagnosis may allow for better prediction of these patients at risk to have positive lymph nodes and ultimately recurrence. Presently, if assessment of nodal involvement is the objective, noninvasive procedures are not an adequate substitute for surgical staging with modified lymphadenectomy.

Adult↗
PubMed1991

Cytarabine and neurologic toxicity.

Cytarabine is an effective drug in the treatment of certain hematologic malignancies and its common toxicities are myelosuppression and gastrointestinal disturbance. In the past decade, neurotoxicity has been an increasingly recognized cytarabine effect. Intrathecal (IT) cytarabine may result in myelopathy that is incompletely reversible. Combined IT drug and cranial irradiation may lead to necrotizing leukoencephalopathy. Intravenous (IV) therapy may cause a peripheral neuropathy that varies greatly in its severity. The high IV cytarabine doses now commonly used can cause seizures, cerebral dysfunction, or an acute cerebellar syndrome with an incidence up to 14%. Patient age (greater than 60 years) appears to be the most important risk factor, but drug dose/schedule, cumulative drug dose, renal and hepatic dysfunction, and concomitant use of neurotropic antiemetic agents may also influence the risk of neurotoxicity. A better understanding of the pathophysiology and pharmacology of such cytarabine-induced neuronal injury will allow this drug to be used with greater efficacy and safety.

Central Nervous System Diseases↗