Biomedical subjects
R Vance
Publications and source records attributed to R Vance.
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Another look at nonverbal rule induction in children with SLI: testing a flexible reconceptualization hypothesis.
This study focuses on the ability of preschool children with specific language impairment (SLI) to extract target regularities from recurring nonverbal stimuli. As a step beyond previous methodologies, we also assessed their ability to shift and extract other regularities after feedback indicated that their choices were no longer correct. This step was motivated by Connell and Stone's (1994) hypothesis that difficulties manifested by children with SLI in extracting nonverbal "rules" from multiple problem sets may reflect difficulties in "flexible reconceptualization," that is, in the ability to flexibility shift across regularities. Thirty 4- and 5-year-olds with SLI and 30 age-matched children developing language normally participated in a discrimination learning-shift paradigm. Findings indicated that both language groups were successful in extracting regularities and making shifts. In fact, language groups did not differ in number of regularities extracted, number of shifts completed, or trials to criterion. As a consequence, findings failed to provide evidence that children with SLI are limited in either the ability to extract nonverbal regularities or to flexibly reconceptualize them. From a larger theoretical perspective, the findings fail to support theories positing that generalized "rule-induction" deficits underlie the verbal and nonverbal impairments of SLI.
The role of chemotherapy in the management of celomic epithelial carcinoma of the ovary.
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The role of paclitaxel in the management of patients with carcinoma of the cervix.
The major role for systemic therapy in the management of carcinoma of the cervix is to treat those patients with advanced or recurrent disease. While 19 single agents have activity, defined as a response rate > or = 15%, the agents that have attracted the greatest attention are the platinum compounds and ifosfamide. Combinations of these two drugs have produced high response rates in phase II trials. A recent randomized trial found that a combination of ifosfamide/cisplatin yielded a superior response rate to cisplatin alone (33% v 19%), although no differences in progression-free or overall survival were observed. While ongoing randomized trials continue to explore platinum/ifosfamide combinations, current attention also is directed to paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), which has demonstrated activity in a phase II trial (18% response rate). The Gynecologic Oncology Group plans to conduct a phase II trial of a platinum/paclitaxel combination and may follow it with a phase III trial of the same combination if the phase II results suggest enhanced therapeutic benefit. Randomized trials in patients with less advanced (stages IIB to IVA) disease have demonstrated superior response rates and overall survival with concomitant chemoradiation. Regimens of demonstrated efficacy in this setting include hydroxyurea plus radiation and cisplatin/5-fluorouracil plus radiation. The Gynecologic Oncology Group currently is conducting a phase I trial of concomitant paclitaxel plus radiation and may consider a paclitaxel-based regimen in future phase III trials of concomitant chemoradiation or possibly neoadjuvant chemotherapy in patients with limited disease (stages IIB to IVA).
The role of ifosfamide and systemic therapy in the management of carcinoma of the cervix.
Nineteen single agents have activity in patients with advanced or recurrent carcinoma of the cervix. The agents that have attracted the greatest attention, however, are the platinum compounds and ifosfamide. Although most phase II trials combining these agents demonstrate activity but not relative merit, a recent phase III randomized trial shows that ifosfamide/cisplatin yields a superior response rate than cisplatin alone (33% v 19%, respectively). An ongoing randomized study is evaluating cisplatin/ifosfamide with or without bleomycin on the basis of a number of phase II reports suggesting a high order of activity for the three-drug combination. Randomized trials in less advanced disease demonstrate superior response rate, progression-free interval, and overall survival for concomitant chemoradiation in patients with stage IIIB to IVA disease. Regimens with demonstrated efficacy in this setting include hydroxyurea plus radiation and cisplatin/5-fluorouracil plus radiation. Of two randomized trials of cisplatin/ifosfamide/bleomycin followed by radiation versus radiation alone, the one completed study shows no overall advantage for the combined approach but does suggest an improved 32-month survival in patients with stage IIIB disease. The other trial is ongoing, with an early observation of a superior response rate with the combined approach. Current recommendations are to use ifosfamide/cisplatin as the treatment of choice for advanced or recurrent disease and concomitant chemoradiation with either hydroxyurea or cisplatin/5-fluorouracil for stage IIIB to IVA disease.
Developing an interdisciplinary approach to enhanced clinical resource utilization.
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Chemotherapy as a palliative treatment in carcinoma of the uterine cervix.
The vast majority of patients with cervix carcinoma present with either preinvasive or minimally invasive (stage IA) disease and are cured with surgery alone. The remaining patients can be classified into two groups: those with disseminated (extrapelvic) disease at the time of presentation or recurrence after initial treatment and those with advanced pelvic disease. In the first group, the goal of therapy is palliative and the principal modality is chemotherapy. A number of single agents have significant activity (> or = 15% response rate): the platinum compounds, certain alkylating agents, the anthracyclines, bleomycin, the vinca alkaloids, certain antifols, 5-fluorouracil, 5'-floxuridine, ICRF-159, hexamethylmelamine, and CPT-11. Although uncontrolled trials report high response rates with combination regimens, no such regimen has been shown to be superior to single-agent therapy. The current standard of care for initial treatment is single-agent cisplatin 50 to 100 mg/m2 every 3 weeks, with an expected 23% response rate. In the second group, palliation takes the form of prevention of recurrence. Patients who have stage IIIB or IVA disease benefit from the addition of concomitant chemotherapy to radiation. The current standard of care is hydroxyurea 80 mg/kg orally twice weekly during radiotherapy. For patients with stage IB or II disease, surgery and/or radiotherapy remains the standard of care. Although concomitant or neoadjuvant chemotherapy followed by either surgery or radiotherapy has been evaluated, no conclusive evidence proves the value of the addition of chemotherapy to the management of these patients. Ongoing phase III trials are evaluating both approaches.
Chemotherapy in advanced ovarian carcinoma: current standards of care based on randomized trials.
The mainstay of the treatment of advanced (stage III or IV) ovarian carcinoma is systemic therapy. The following review bases conclusions regarding standards of care on large, randomized trials of chemotherapy in advanced ovarian carcinoma. As of 1976, "standard" chemotherapy was single alkylating agent usually with melphalan. Studies of combination chemotherapy failed to show superiority over single alkylating agent until the introduction of cisplatin. The Gynecologic Oncology Group conducted a series of two trials in patients with large-volume disease, the first randomizing patients to either single-agent melphalan or a combination of doxorubicin and cyclophosphamide and the second to doxorubicin plus cyclophosphamide with or without cisplatin. These studies demonstrated superiority for the cisplatin-based combination in terms of overall response rate, clinical complete response rate, progression-free survival, and overall survival. Subsequent randomized trials demonstrated several important facts. First, platinum-based combinations yielded results superior to single-agent cisplatin. Second, a two-drug combination of cisplatin plus cyclophosphamide provides benefit equivalent to the three-drug combination of the same two drugs plus doxorubicin. Third, substitution of carboplatin for cisplatin yields similar results. Finally, dose escalation of chemotherapy by a factor of 2 does not offer a therapeutic advantage. The next major advance after the introduction of the platinum compounds was the demonstration of the activity of taxol, a new agent with a unique mechanism of action and apparent clinical non-cross-resistance with the platinum compounds. A recently completed GOG trial of cisplatin plus cyclophosphamide versus cisplatin plus taxol in patients with large-volume disease shows that the taxol-based combination has a superior overall response rate, clinical complete response rate, rate of achieving a state of no gross residual disease at second-look laparotomy, and progression-free survival. Survival analysis awaits maturation of the data, but the control arm has already been shown to have a median survival of 23.2 months with the median not yet reached for the taxol-based arm. These data suggest that a combination of taxol plus cisplatin should be considered the standard of care for patients with advanced ovarian carcinoma. Ongoing trials seek to define further the role of taxol in frontline chemotherapy for ovarian carcinoma. In conclusion, the standard chemotherapy for advanced ovarian carcinoma should be considered a combination of taxol plus a platinum compound.
Effect of intra-arterial cisplatin and 1,3-bis(2chloroethyl)-1-nitrosourea (BCNU) dosage on radiographic response and regional toxicity in malignant glioma patients: proposal of a new method of intra-arterial dosage calculation.
The frequency of both neurologic toxicity and therapeutic response due to intra-arterial (IA) chemotherapy is decreased by dose reduction. A method to individualize IA drug dosage is needed to provide each patient with the safest, most effective dose. Most trials of IA chemotherapy for malignant glioma have used body surface area (BSA) to calculate dosage; but brain size and arterial distribution do not correlate well with BSA. Fixed doses of cisplatin and BCNU were used in combination to perform 35 IA infusions in 20 malignant gliomas patients. Doses modified by the number of major intracranial vessels supplied by the infused artery were used in 34 infusions in 19 patients. Patients receiving 150 to 200 mg CP and 300 mg BCNU had an incidence of neurologic deficit of 5.6% if greater than or equal to 3 vessels were supplied by the infused artery compared to 42% for those with only 2 vessels. This crude dose modification maintained efficacy while reducing neurologic toxicity. Further refinement is possible using well established intra-arterial pharmacokinetic principles. Intra-arterial dosing based on volume flow at the site of infusion would yield a more reproducible exposure of the infused capillary bed to a drug than methods currently in use. More consistent drug exposure should reduce toxicity due to over dosing and treatment failure due to under dosing.
Relations among verbal and nonverbal cognitive skills in normal language and specifically language-impaired children.
This study tested the hypothesis that specifically language-impaired (SLI) children have a qualitatively different cognitive system from that of normal language (NL) children. Twenty NL and 20 SLI children between the ages of 4:2 (years:months) and 5:11 were presented with experimental language-learning measures, experimental nonverbal measures, and verbal and nonverbal norm-referenced tests. A confirmatory analysis of the covariance matrix structures of the two subject groups indicated that relations among cognitive skills differed between NL and SLI children. In addition, a planned comparison indicated that the relation between nonverbal rule-induction and novel bound-morpheme learning differed significantly between groups. The findings indicate that a "qualitative-differences" model of specific language impairment better accounts for the co-occurrence of poor verbal and poor nonverbal cognitive skills in SLI children than a "low-normal" model.
1987 to 1991 cost and utilization of Class IV HIV patients.
The 1987 to 1991 direct medical costs and service utilization of Class IV Human Immunodeficiency Virus (HIV) patients cared for at a Group Health Cooperative of Puget Sound (GHC) are described and compared across four time periods: 1987-'88, 1989, 1990, and 1991. Cost and utilization information for an age- and sex-matched control group of GHC enrollees not having Class IV HIV conditions are also compared to those of the Class IV HIV group. Data are presented on pharmacy, inpatient care, outpatient visits by physician specialty, laboratory, radiology, home health/hospice and other costs. The costs of the Class IV HIV population are, on average, 20 times those of the control group. The percent distribution of the control group's costs did not experience much change from 1989 to 1991. Conversely, the Class IV HIV group experienced a shift in costs from the inpatient to outpatient setting from 1987-'88 to 1989. This shift was temporary, as the locus of care shifted back to the inpatient setting over the following 2 years. Anecdotal evidence suggests that antiretroviral treatment may have led to a period in which patients required less intensive settings to manage their illness. Inpatient costs may have increased as the initial benefit of zidovudine treatment began to wane. The Class IV HIV population had greater percent of total expenses in pharmacy, laboratory, radiology, and home health/hospice services, and lower percent of total expenses in outpatient primary and specialty care than the control group.
MRI findings in boys with specific language impairment.
Magnetic resonance imaging scans of specifically language-impaired (SLI) boys were examined to determine whether atypical cerebral findings could be documented in children whose primary deficits were in language skills. Clinical examination of the scans failed to reveal any visually obvious lesions or abnormalities. In contrast, measurement of the scans revealed atypical perisylvian asymmetries in most of these subjects. The distribution of perisylvian asymmetries in SLI subjects was significantly different from the distribution in controls (p less than .01). Measurement of other brain regions revealed that extraperisylvian areas were occasionally deviant in individual SLI subjects; but no one region was consistently deviant across the SLI group. Thus, only atypical perisylvian asymmetries were linked to the language disorder. These neuroanatomical findings suggest that a prenatal alteration of brain development underlies specific language impairment.
Anatomical correlates of normal and impaired language in a set of dizygotic twins.
This report presents findings for a set of dizygotic twins at age 4 years 9 months. The male was diagnosed as specifically language impaired. For both children, the left-right perisylvian configuration was atypical. Only the male's configuration was symmetrical, a finding in line with autopsy data reported for subjects with "developmental dyslexia" who also may have had a form of language impairment. In addition, the male had an atypical (L greater than R) configuration of the cerebral hemispheres, a finding not seen in his twin, or in a series of volunteers without a history of developmental language impairment. The in utero effects of gonadal hormones that may account for these findings are discussed.
Preoperative evaluation with radionuclide brain scanning and computerized axial tomography of the brain in patients with breast cancer.
To determine the roles of radionuclide brain scanning and computerized tomography of brain in the pretreatment evaluation of patients with primary and locoregional recurrence of breast cancer, we reviewed the clinical and radiologic findings in 226 patients with breast cancer who underwent one of these scans either preoperatively or within 6 weeks of operation and in 34 patients presenting with locoregional recurrence. Four of 131 radionuclide brain scans in primary breast cancer suggested calvarial metastasis, and the findings were confirmed with bone scans and skull radiographs. One of 95 computerized tomographic scans of the brain showed brain metastasis, and this patient had profound neurologic deficits. With respect to locoregional recurrence, the results of 2 of 23 radionuclide scans and 1 of 11 computerized tomographic scans were positive. All three patients had clinical evidence for brain metastasis. We conclude that in the absence of signs and symptoms, routine evaluation for brain metastasis is not justified in primary and locoregional recurrence of breast cancer.
Chemotherapy for advanced or recurrent gynecologic cancer.
Studies of chemotherapy in advanced or recurrent gynecologic cancer have focussed on ovarian, cervical, and endometrial carcinoma. For celomic epithelial carcinomas of the ovary, a large number of cytotoxic agents have been shown to be active. Dramatic improvement in frequency of response with lesser improvement in survival has been noted with the use of cisplatin-based combination chemotherapy as compared to single alkylating agents. More recent studies have evaluated alternative ways to employ cisplatin: higher dose schedules, intraperitoneal administration, and platinum compounds with a potentially better therapeutic index. None has yet been shown superior to a combination of relatively low-dose cisplatin plus an alkylating agent with or without doxorubicin. Cisplatin remains the best studied and most active single agent in patients with squamous cell carcinoma of the cervix. While a number of other agents have demonstrated moderate activity, no combination of drugs has as yet proved superior to single-agent cisplatin. In endometrial carcinoma, progestins and doxorubicin are the most active agents. Tamoxifen, cisplatin, and hexamethylmelamine appear to have moderate activity. No combination has yet been shown to be superior to single agents. Information on chemotherapy for less common gynecologic malignancies is largely anecdotal. Two observations are of note. Cisplatin-based combination chemotherapy is highly active against germ-cell neoplasms of the ovary. Cisplatin also has definite activity against mixed mesodermal sarcoma of the uterus.
Evaluation of bone scan as a screening work-up in primary and local-regional recurrence of breast cancer.
To evaluate the use of radionuclide bone scan in staging patients with primary and local-regional recurrence of breast cancer, we reviewed the results in 265 patients with primary breast cancer who had the scan either preoperatively or within 6 weeks of surgery, and in 39 patients presenting with their first local-regional recurrence. All patients were clinically staged according to the revised 1983 criteria of the American Joint Committee for Cancer Staging and End-Results Reporting. None of the 92 with stage I and four of 95 patients with stage II had a positive scan. Eleven of 41 with stage IIIA and 13 of 37 with stage IIIB had a positive bone scan. In patients with their first local-regional recurrence, 12 of 39 had a positive scan. Follow-up scans were available in 61 patients with clinical stage I and II breast cancer who had adjuvant chemotherapy for pathological involvement of axillary node. There were six conversions observed in 61 scans obtained during the first year. Seven converted in follow-up scans in 47 patients in the second year. We conclude that although bone scans have a low positive yield in stage I and II breast cancer, their use in the preoperative setting and in the follow-up of patients with axillary node involvement detects early converters. Bone scans are justified in stage IIIA and IIIB breast cancer and in patients being evaluated for local-regional recurrence.
Combined therapies for squamous-cell carcinoma of the esophagus, a Southwest Oncology Group Study (SWOG-8037).
Conservative treatment of esophageal cancer with radiation therapy has afforded few long-term survivors. In order to improve outcome, patients with locoregional disease were treated using a combined modality approach. Patients were treated with chemotherapy consisting of a 96-hour continuous infusion of 5-fluorouracil (5-FU), 1,000 mg/m2/d, days 1 to 4 and days 29 to 32; cisplatin 75 mg/m2, day 1 and 29; and radiation 3,000 rad, days 1 to 19. In the absence of progressive disease, patients underwent esophagectomy. One hundred twenty-eight patients were registered of whom 113 were eligible and 106 were evaluable. Toxicity included gastrointestinal (GI) symptoms, mucositis, and myelosuppression. One hundred two patients completed chemoradiotherapy. Following its completion, 11 patients refused surgery, six were considered poor surgical risks, and 14 had progressive disease. Of the remaining 71 patients, 16 had unresectable disease, 13 had residual disease which was incompletely resected, 24 had disease which could be completely resected, and 18 were without disease on pathologic examination. The overall operability rate was 63% and the overall resectability rate, 49%. Surgical mortality was 11%. Eighty-nine of 113 eligible patients have died, with a median survival of 12 months and a 2-year survival of 28%. The median postsurgical survival for all 71 patients was 14 months and was 32 months for those patients attaining complete remission (CR). Combined modality therapy remains an investigational approach. Attempts should be directed at increasing response rate to initial therapy. A randomized comparison between combined modality treatment and radiation therapy is necessary to definitively determine the usefulness of this more aggressive approach.