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Biomedical subjects

S L George

Publications and source records attributed to S L George.

At least 19 recordsLinked to original sources
PubMed1992

A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines.

In previous studies, combinations of immunotoxins reactive with different cell-surface antigens have exerted additive cytotoxicity against tumor cells in culture. In this report we describe a combination of 2 immunotoxins that produce synergistic cytotoxic activity. Recombinantly derived ricin A chain (RTA) was conjugated with murine monoclonal antibodies (MAbs) 317G5, 260F9, 454A12 and 741F8 that bound to cell-surface determinants of 42, 55, 180 (transferrin receptor) and 185 kDa (HER-2/neu) expressed by the SKBr3 human breast-cancer cell line. When inhibition of clonogenic growth was measured in a limiting dilution assay, the combination of 260F9-RTA and 454A12-RTA produced synergistic cytotoxic activity against SKBr3 and 2 other breast-cancer cell lines. All other combinations produced only additive inhibition of clonogenic growth. Simultaneous binding of 260F9 and 454A12 was not supra-additive, but sub-populations of cells which lacked one or the other antigen could be detected. Kinetic studies of internalization, using antibodies conjugated with gold particles, indicated that 454A12 remained within peripheral endosomes for a longer interval in the presence of 260F9. This change in the traffic of the transferrin receptor may contribute to synergy between 260F9-RTA and 454A12-RTA.

Antibodies, Monoclonal↗
PubMed1992

Ha-ras polymorphisms in epithelial ovarian cancer.

Unusual restriction fragment length polymorphisms (RFLPs) of the Ha-ras locus have been found in DNA from leukocytes and tumor tissue of cancer patients. To determine whether rare alleles would be observed frequently in patients with ovarian cancer, Ha-ras RFLPs were studied in DNA from 42 different ovarian epithelial tumors and from the peripheral blood leukocytes of 76 normal individuals. Four common, seven intermediate, and seven rare alleles were detected overall. Similar fractions of rare alleles were found in DNA from ovarian cancers and from the peripheral blood of normal individuals. Thus, the frequency of unusual Ha-ras RFLPs did not distinguish patients with ovarian cancers from apparently healthy individuals.

Alleles↗
PubMed1992

Relationships among tumor temperature, treatment time, and histopathological outcome using preoperative hyperthermia with radiation in soft tissue sarcomas.

The lack of an unambiguous thermal dosimetry continues to impede progress in clinical hyperthermia. In an attempt to define better this dosimetry, a model based on the cumulative minutes during which arbitrary percentages of measured tumor temperature points exceeded an index temperature was tested in patients with soft tissue sarcomas treated with preoperative hyperthermia and conventional radiation therapy. Patients received 5000-5040 cGy at 180-200 cGy per fraction. Hyperthermia was delivered 30-60 minutes after radiation therapy and given for 60 minutes. Patients were randomized between one and two hyperthermia treatments per week for a total of five or 10 treatments, respectively. Lesions were excised 4-6 weeks after completion of hyperthermia/radiation therapy. Successful treatment outcome was considered to be the finding of greater than 80% necrosis of the sarcoma upon histopathologic examination of the resected specimen. Forty-five patients were eligible with thermometry data available in 44 patients. An average of 19 interstitial sites were monitored each treatment per tumor. Sixty percent of tumors had a successful histopathologic outcome. Univariate analysis demonstrated that several descriptors of the temperature distribution were strongly related to treatment outcome; more strongly than nonthermometric factors, such as the number of treatments per week, tumor volume and patient age and more strongly than the commonly used temperature descriptors Tmin and Tmax. Descriptors that incorporated both temperature and time were also superior to the more commonly used descriptors Tmin and Tmax. Multivariate stepwise logistic regression analysis revealed that a descriptor of both the hyperthermia treatment time and the frequency distribution of intratumoral temperatures was the strongest predictor of histopathologic outcome and that the best predictive model combined this time/temperature descriptor and one versus two treatment per week grouping. The more conventional temperature descriptor, minimum measured tumor temperature, did not significantly enhance the predictive power of treatment group. Based on these results, we recommend that descriptors based on both the frequency distribution of intratumoral temperatures and hyperthermia treatment time be tested for relationships with treatment outcome in other clinical data bases. Furthermore, we recommend that temperature descriptors that are less sensitive to catheter placement and tumor boundary identification than Tmin and Tmax (such as T90, T50, and T10) be tested prospectively along with other important thermal variables in Phase II trials in further efforts to define a thermal dosimetry for spatially nonuniform temperature distributions.

Combined Modality Therapy↗
PubMed1992

Therapeutic and prognostic considerations of head and neck melanoma.

Therapeutic considerations are discussed based on recurrence and survival statistics of 900 patients treated at Duke University Medical Center (Durham, NC). Approximately one-third of all patients developed recurrence. Factors affecting recurrence include tumor thickness, presence of positive regional nodes at diagnosis, and advanced Clark level. Patients with more than one adverse index had even higher rates of recurrence than with one alone. The 5-year survival of all patients after recurrence was 32%. Therapeutic decisions should include considerations that relate to patients' recurrence patterns and survival curves.

Academic Medical Centers↗
PubMed1992

Multiple authorship in two English-language journals in radiation oncology.

Multiple authorship is the listing of more than one person as author of an article in the scholarly literature. Editors, researchers, and others in science publishing have raised concerns about the increasing number of authors being listed per article, the practice of "honorary authorship" (listing as an author someone who made little or no contribution to the work being reported), and the danger of the dilution of responsibility when many authors are involved. The authors studied multiauthorship in the two most popular English-language journals on radiation oncology, examining 1,908 papers and letters published in the International Journal of Radiation Oncology, Biology, and Physics (IJROBP) and Radiotherapy and Oncology (RO) from 1983 through 1987. There was no increase in the number of authors per article during this period, when the median number for IJROBP was four and that for RO was three. The number of authors varied by type of article, by country (France had the largest median number, six for IJROBP and five for RO), and by the authors' institution. The first author's gender was unrelated to the number of subsequent authors for an article. The proportion of men first authors varied widely between countries and institutions. Possible explanations for these variations include the multidisciplinary nature and complexity of some forms of research, institutional policies concerning the use of authorship as a commodity of exchange, and social-cultural factors.

Authorship↗
PubMed1992

Comparison of a novel assay for breast cancer mucin to CA15-3 and carcinoembryonic antigen.

PURPOSE: To compare the sensitivity and specificity of an automated microparticle enzyme immunoassay (MEIA) for breast cancer mucin (IMx BCM; Abbott Laboratories, North Chicago, IL) to that of CA15-3 and carcinoembryonic antigen (CEA) for detecting and monitoring breast cancer. MATERIALS AND METHODS: IMxBCM was compared to assays of CA15-3 and CEA in 630 serum specimens from healthy women, and from women with breast cancer, other malignancies, benign breast conditions, or other benign diseases. RESULTS: Analysis of the log-transforms for the three markers in all specimens showed a high correlation of IMxBCM with CA15-3 (r = .78), but not with CEA (r = .25). Based on a receiver-operating-characteristics (ROC)-curve analysis for any given specificity, IMxBCM was found to be a more sensitive marker than either CA15-3 or CEA for distinguishing 105 women with advanced or metastatic breast cancer from 89 healthy women (P = .003 and P = .04, respectively), from 98 women with benign breast conditions (P = .02 and P = .002), or from 191 women with benign diseases (P = .03 and P less than .0001). At 95% specificity, the sensitivities of IMxBCM, CA15-3, and CEA for detecting advanced or metastatic breast cancer were 69%, 51%, and 30%, respectively. Serial serum samples (n = 177) were analyzed in 20 additional metastatic breast cancer patients with measurable disease. Serial IMxBCM levels corresponded with the clinical course of disease in 80%, CA15-3 in 65%, and CEA in 60% of the 20 patients. CONCLUSIONS: Increased sensitivity of IMxBCM, despite a high correlation with CA15-3, suggests that IMxBCM and CA15-3 may recognize distinct epitopes on the same molecule. Although further research is indicated, IMxBCM may provide a promising marker in the clinical management of breast cancer patients.

Adult↗
PubMed1992

Analysis of 945 cases of pulmonary metastatic melanoma.

From 1970 to 1990, 7564 patients with melanoma were seen at Duke University Cancer Center. Complete follow-up data were available in all patients. The estimated probability of a pulmonary metastasis developing 5, 10, or 20 years after initial diagnosis was 0.13, 0.19, and 0.30, respectively. Pulmonary metastases were documented in 945 patients (12%), these having 1-, 3-, and 5-year survival rates of 30%, 9%, and 4%, respectively. The methods of diagnosis were chest radiograph (n = 544), computed tomography (n = 157), transthoracic needle biopsy (n = 121), bronchoscopy (n = 14), thoracotomy (n = 112), and autopsy (n = 7). Evidence of advanced pulmonic spread included bilateral disease in 543 and more than two nodules in 595. Univariate predictors for early formation of pulmonary metastases (p less than 0.001) were male sex, black race, increased primary thickness (millimeters), higher Clark's level, nodular or acral lentiginous histology, location on trunk or head and neck, and regional lymph nodes positive for metastasis. Multivariate predictors of improved survival (p less than 0.001) in order of importance were complete resection of pulmonary disease, longer time for formation of metastases, treatment with chemotherapy, one or two pulmonary nodules, lymph nodes negative for metastasis lymph nodes (p less than 0.005), and histologic type (p less than 0.04). Additionally, survival in patients with one nodule and resection (n = 84) was better than in those with similar disease and no resection (n = 142 months, p less than 0.001). These data comprise the largest series to date and emphasize the importance of long-term follow-up, as well as supporting the selective use of resection for isolated pulmonary metastases, increasing the 5-year survival rate from 4% to 20%.

Adult↗
PubMed1991

Census of single homeless people in Sheffield.

OBJECTIVE: To determine the number of single homeless people in Sheffield and to examine their demography and social and medical details. DESIGN: Census carried out between 8 am and 8 pm on one day. Participants completed a questionnaire designed to provide data relating to employment history, contact with welfare and health services, social state, prison history, medical history, and health state. SETTING: Sites in Sheffield identified by local workers as being places of residence of homeless people. SUBJECTS: 340 single homeless people. MAIN OUTCOME MEASURES: Self reported history of alcohol or drug misuse, existence of a chronic medical condition, and use of general practitioner and hospital services. RESULTS: The mean age of the population was 42.5 years and a quarter of the population were aged less than 30; there were 48 women. Significant differences were noted between men and women with respect to self reported psychiatric illness (77/266 men v 27/42 women), self reported alcoholism (83/273 v 4/44), prison history (152/255 v 8/41), and registration with a general practitioner (73/275 v 38/46). Various chronic medical conditions were reported, and the perceived health state of the population was low; 129 claimed to have been admitted to a psychiatric hospital. 220 people were registered with a general practitioner, and 179 claimed to see their doctor. Sixty five had attended or been admitted to a general hospital in the month preceding the study, 45 for accident and emergency services. CONCLUSIONS: The homeless in this population were younger than those found in previous studies. The prevalence of psychiatric illness was high in the population, and the overall health state was poor. Most subjects obtained health services from general practitioners.

Adolescent↗
PubMed1991

An exploratory study of environmental and medical factors potentially related to childhood cancer.

To determine whether a general-purpose epidemiologic questionnaire can be used in childhood cancer hospitals to identify associations between environmental factors and the major types of childhood cancer, we report the results of the analysis of the data obtained from such a questionnaire. On admission to St. Jude Children's Research Hospital in Memphis, Tennessee, between 1979 and 1986 a questionnaire was administered to 1,270 mothers of patients diagnosed with childhood cancer. Approximately one-half of the children had acute leukemias (n = 629); the remainder had lymphomas (n = 237) or solid tumors (n = 404). Responses to questions regarding the patients' and parents' environmental and medical histories were compared across nine diagnostic categories. Only 5 of 232 variables remained nominally statistically significant (P less than 0.05) after adjusting for confounding by patient or maternal age, year of birth or diagnosis, patient's race, and social class. The variables identified were length of time the patient was breast-fed (chi 2 = 16.1, P = 0.04); having a garden with fertilizers, herbicides, and pesticides (chi 2 = 17.2, P = 0.03); maternal use of sex hormones during the year before the patient's birth (chi 2 = 18.2, P = 0.02); maternal cigarette consumption (chi 2 = 18.0, P = 0.02); and patient contact with persons with cancer (chi 2 = 20.7, P = 0.01). Despite the large number of patients studied, we identified fewer significant variables than would be expected, on the average, under the null hypothesis. We conclude that the data obtained from a general-purpose epidemiologic questionnaire do not provide a useful overview of the association between exposure to environmental factors and several types of childhood cancer.

Breast Feeding↗
PubMed1991

Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X.

We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure.

Adolescent↗
PubMed1990

Use of immunotoxins in combination to inhibit clonogenic growth of human breast carcinoma cells.

Substantial heterogeneity has been observed in the expression of individual antigens within tumor cell populations. Immunotoxins which bind to different cell surface antigens might exert additive or synergistic cytotoxicity when used in combination to eliminate all clonogenic cells within a tumor. Immunotoxins have been prepared by conjugating recombinantly derived toxin A chain to different monoclonal reagents which recognize cell surface determinants of Mr 42,000 (317G5), 55,000 (260F9), and 200,000 (741F8). Each immunotoxin was evaluated for binding, internalization, and cytotoxicity with four breast cancer cell lines. Each of the three immunotoxins bound to the SKBr3 cell line and exerted antitumor activity in a limiting dilution clonogenic assay. Simultaneous treatment with two immunotoxins produced additive antitumor activity with each of the possible combinations. Additive binding could be demonstrated by immunofluorescent techniques, however, with only one of three combinations. With two of the three combinations, subpopulations of tumor cells could be identified which lacked one or the other antigenic determinant but not both. Consequently, log-additive antitumor activity was produced by immunotoxins in combination, and heterogeneity of antigenic targets may have contributed to the combined cytotoxicity in some but not all cases.

Antibodies, Monoclonal↗
PubMed1989

Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia.

We studied the risk of the development of acute myeloid leukemia (AML) during initial remission in 733 consecutive children with acute lymphoid leukemia (ALL) who were treated with intensive chemotherapy. This complication was identified according to standard morphologic and cytochemical criteria in 13 patients 1.2 to 6 years (median, 3.0) after the diagnosis of ALL. At three years of follow-up, the cumulative risk of secondary AML during the first bone marrow remission was 1.6 percent (95 percent confidence limits, 0.7 and 3.5 percent); at six years, it was 4.7 percent (2 and 10 percent). The development of secondary AML was much more likely among patients with a T-cell than a non-T-cell immunophenotype (cumulative risk, 19.1 percent [6 and 47 percent] at six years). Sequential cytogenetic studies in 10 patients revealed entirely different karyotypes in 9, suggesting the induction of a second neoplasm. In eight of these patients, the blast cells had abnormalities of the 11q23 chromosomal region, which has been associated with malignant transformation of a pluripotential stem cell. There was no evidence of loss of DNA from chromosome 5 or 7, a karyotypic change commonly observed in cases of AML secondary to treatment with alkylating agents, irradiation, or both. We conclude that there is a substantial risk of AML in patients who receive intensive treatment for ALL, especially in those with a T-cell immunophenotype, and that 11q23 chromosomal abnormalities may be important in the pathogenesis of this complication.

Adolescent↗
PubMed1989

Complications of therapy for testicular cancer.

Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 months) 88 (36.1%) experienced 1 or more early complications (within 1 year), while 16 (6.6%) had a late (greater than 1 year) complication. Chemotherapy-related complications occurred in 55 of 141 patients (39%), including 6 (4.3%) treatment-related deaths. Chemotherapy-related complications were correlated to the initial extent of disease (p equals 0.021) and to more than 4 cycles of cisplatin-based therapy (p equals 0.001). Retroperitoneal lymphadenectomy-related complications occurred in 48 of 148 patients (32.4%) without surgical mortality and were not statistically increased in those performed after chemotherapy. Kidney loss occurred in 6 patients (4.1%) after retroperitoneal lymphadenectomy. Nine of 110 patients (8.2%) treated with radiotherapy experienced an early therapy-related complication, while late complications included 3 gastrointestinal strictures requiring surgical intervention 8 to 10 years after radiotherapy. Only 1 secondary malignancy (other than contralateral testis cancer) was discovered in this review. Initial extent of disease was the best predictor for over-all complication rate and higher over-all complications were noted in the cisplatin era (1979 to 1987) but these associations were not necessarily present for complication rates of individual therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Carcinomas in children. Clinical and demographic characteristics.

Carcinomas occur rarely in children and adolescents. Despite their rarity, these tumors present a unique opportunity to assess theories of origin because the interval from birth to tumor onset is relatively short compared with that seen in adults. We describe the clinical and demographic characteristics of 151 patients younger than 20 years of age with carcinomas who were treated at a pediatric cancer center having a large referral area. Incidence data for the major types of carcinomas in children, based on unpublished data provided by the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER), also are reported.

Adolescent↗
PubMed1988

Efficacy of oral sucralfate suspension in prevention and treatment of chemotherapy-induced mucositis.

The efficacy of orally administered sucralfate suspension in preventing and treating chemotherapy-induced mucositis was evaluated in a double-blind trial. Forty-eight children and adolescents with newly diagnosed acute nonlymphocytic leukemia were randomized to receive suspensions of either sucralfate or placebo orally every 6 hours during the first 10 weeks of intensive remission-induction chemotherapy. Patients given sucralfate suspension were less likely than subjects receiving placebo to acquire colonization with potentially pathogenic microorganisms: 14 (58%) of 24 versus 22 (92%) of 24, respectively (p = 0.008). However, no effect on preexisting colonization was noted. Subjective reporting of discomfort, objective scoring of the severity of mucositis, and the maximal percent of body weight lost during therapy were similar; 58% of patients receiving sucralfate reported no oral pain compared with 25% receiving placebo (p = 0.06). Ten episodes of gastrointestinal bleeding, 25 documented infections, and 886 days with fever were also equally distributed between sucralfate and placebo groups. We conclude that sucralfate suspension is of limited, if any efficacy, in the prevention and treatment of chemotherapy-induced mucositis. Sucralfate administration can, however, reduce acquisition of alimentary colonization with potential pathogens, perhaps by interfering with adherence to mucosal membranes.

Administration, Oral↗
PubMed1988

Transcutaneous electrical nerve stimulation treatment of sickle cell pain crises.

Transcutaneous electrical nerve stimulation (TENS) has been used in a variety of acute and chronic painful conditions, but has not been studied in sickle cell pain crises. We compared TENS versus placebo in a randomized, double-blind, cross-over study involving 60 trials in 4 crisis severity categories. TENS electrodes were applied to the area of severest pain and patients' pain ratings and medication usage were evaluated over a 4-hour period. Pain ratings and analgesic requirements at 1 and 4 h from onset of study were similar in the TENS and placebo groups. Patients assessments of overall treatment efficacy indicated that TENS was more frequently helpful, but there was a substantial placebo effect. Although the value of TENS in this condition was not established in this study, further trials, using varied stimulation parameters, are warranted.

Acute Disease↗