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Biomedical subjects

C W Ryan

Publications and source records attributed to C W Ryan.

At least 19 recordsLinked to original sources
PubMed2002

A phase II trial of oral temozolomide in patients with metastatic renal cell cancer.

PURPOSE: To determine the activity of temozolomide, an oral imidazotetrazine alkylating agent that has exhibited broad antitumor activity in preclinical studies, in renal cell cancer (RCC) patients. METHODS. Metastatic RCC patients were treated with temozolomide, 200 mg/m(2) per day orally, and traditional radiologic response endpoints were assessed. O(6)-Alkylguanine-DNA alkyltransferase (AGT) activity was measured in four pretreatment biopsies. RESULTS: Among 12 patients, there were no responses. High AGT activity was observed in all four biopsies analyzed. CONCLUSIONS: Temozolomide is not active against RCC and this clinical observation may be due to high levels of AGT in this tumor.

Aged↗
PubMed2001

Docetaxel and exisulind in hormone-refractory prostate cancer.

Single-agent docetaxel has been shown to produce a significant decrease in prostate-specific antigen (PSA) levels among patients with hormone-refractory prostate cancer (HRPC). A recent study also showed that exisulind, a sulfone metabolite of the nonsteroidal anti-inflammatory drug sulindac, lengthens the median PSA doubling time in men who had increasing PSA levels after radical prostatectomy. Furthermore, exisulind has shown significant antineoplastic activity in prostate cancer cell lines in vitro and in nude mouse xenograft models. Because preclinical studies have suggested synergistic interactions between docetaxel and exisulind, a phase I/II clinical trial combining these agents has been initiated in patients with HRPC. The primary objective of this study is to determine PSA response and measurable disease response rate of the combination therapy; secondary objectives include toxicity assessment and determination of time to disease progression, duration of response, and overall survival. Accrual is ongoing.

Aged↗
PubMed2000

Granulocyte-macrophage-colony stimulating factor in combination immunotherapy for patients with metastatic renal cell carcinoma: results of two phase II clinical trials.

BACKGROUND: The aim of this study was to determine the response rates and toxicity of two regimens containing granulocyte-macrophage-colony stimulating factor (GM-CSF) in combination with interleukin-2 (IL-2) in the treatment of patients with metastatic renal cell carcinoma. METHODS: Therapy given in the first trial (Trial 1) consisted of irradiation to the primary tumor or metastatic site, followed by GM-CSF 100 microg/day administered subcutaneously (sc) for 2 weeks and IL-2 11x10(6) IU sc 4 days per week for 4 weeks. In the second trial (Trial 2), the therapy consisted of GM-CSF 125 microg/day sc for 2 weeks, followed by IL-2 11x10(6) IU sc 4 days per week and interferon-alpha 10x10(6) IU sc 2 days per week for 4 weeks, plus oral 13-cis-retinoic acid 1 mg/kg daily for 4 weeks. RESULTS: There were no responses among 20 patients in Trial 1, but 3 patients had stable disease. There was 1 partial responder (5%) of 20 evaluable patients in Trial 2 who achieved a complete response with surgical resection. An additional 3 patients maintained stable disease, 2 of whom were rendered disease free by resection of the renal primary and a single metastatic site. The 1-year survival rate was 75% (95% confidence interval [CI], 50-89) in Trial 1 and 48% (95% CI, 20-71) in Trial 2. In Trial 1, Grade 3 toxicities included fever, fatigue, anorexia, nausea/vomiting, hyperbilirubinemia, and mental status change. Toxicity was more frequent in Trial 2 and included Grade 3 fever, fatigue, anorexia, mucositis, and dermatitis. One on-study death may have been therapy-related. CONCLUSIONS: GM-CSF does not enhance the low response rate of IL-2-based immunotherapy for patients with metastatic renal cell carcinoma. New active agents are needed to treat patients with this disease.

Administration, Oral↗
PubMed2000

CI-980 in advanced melanoma and hormone refractory prostate cancer.

INTRODUCTION: CI-980 is a novel chemotherapeutic agent that inhibits polymerization of tubulin. Preclinical studies have indicated a high level activity of this agent against various tumor cell lines. METHODS: 13 malignant melanoma patients who had failed prior chemotherapy and/or immunotherapy and 13 hormone refractory prostate cancer patients, including 4 who had received prior chemotherapy, were treated in 2 separate NCI-supported clinical trials. Subjects received a recommended phase II dose of CI-980 of 4.5 mg/m2/day by continuous infusion for 72 hours every 3 weeks. RESULTS: No activity was seen in either study. Toxicity was tolerable with neutropenia being the most common, significant toxicity. Among the melanoma patients, 15% and 31% developed grade 3 and grade 4 neutropenia, while 7% and 38% of the prostate patients developed grade 3 and grade 4 neutropenia, respectively. CONCLUSIONS: CI-980 at this dose and schedule is ineffective against malignant melanoma and hormone refractory prostate cancer.

Adult↗
PubMed2000

A phase I study of liposomal doxorubicin (Doxil) with topotecan.

New therapies are needed for patients with advanced ovarian cancer who relapse after initial treatment with platinum and/or paclitaxel-based regimens. This study sought to determine the toxicities of combined liposomal doxorubicin (Doxil) and topotecan, and to determine a regimen for future phase II testing in ovarian cancer. Nine patients with advanced malignancies were treated with topotecan 1.0 mg/m2/day X 5 days followed by liposomal doxorubicin at a starting dose of 30 mg/m2 on day 5. Cycles were repeated every 28 days. A total of 13 cycles of therapy were administered. Grade IV neutropenia and grade IV thrombocytopenia developed in both of the two patients treated at the first dose level. Subsequent patients received only 20 mg/m2 liposomal doxorubicin. At that dose level, three patients experienced dose-limiting toxicity (one grade IV neutropenia, two grade IV neutropenia and thrombocytopenia). No responses were observed. These data indicate that the described regimen of liposomal doxorubicin and topotecan is not feasible because of excessive hematologic toxicity. Escalation to doses of liposomal doxorubicin or topotecan that have previously demonstrated antitumor activity was not possible. Future strategies to minimize such toxicity may include limiting eligibility to patients with minimal prior therapy, reducing the number of days of topotecan administration, or use of oral topotecan.

Adult↗
PubMed2000

Gemcitabine in the treatment of bladder cancer.

New agents are available for the treatment of metastatic transitional cell carcinoma of the bladder. In the US, the combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) remains the standard chemotherapy regimen for advanced bladder cancer. Gemcitabine (2',2'-difluorodeoxycytidine [dFdC]) is a relatively new agent with a favourable toxicity profile that has demonstrated activity against a number of solid tumours in both preclinical and clinical studies. Single-agent gemcitabine has shown activity in bladder cancer in both pretreated and chemotherapy-naïve patients. The combination of gemcitabine plus cisplatin is a regimen with significant activity and moderate toxicity in bladder cancer patients. A randomised trial of gemcitabine plus cisplatin versus M-VAC has completed accrual but has not yet been reported. New combination studies of gemcitabine with other chemotherapy agents, including the taxanes, are ongoing.

Antimetabolites, Antineoplastic↗
PubMed2000

Association between administrative and ownership characteristics of hospices and their proportion of inpatient deaths.

Hospice patients are more likely to die at home than patients involved in conventional medical care, but the proportion of home deaths varies between programs. A study of the effect of hospice administrative characteristics on inpatient death rates is presented. Data from hospice programs that operated in New York State between 1993 and 1995 were obtained from the State Health Department and from publications of the National Hospice Organization. Inpatient death rates varied significantly between different operating structures: 11% for hospices that were divisions of home health care agencies; 34% for hospices that were divisions of hospital corporations; and 20% for hospices that were independent hospice corporations. This difference was explained by the presence of dedicated inpatient hospice units: Programs with such units demonstrated higher inpatient death rates than those without (42% versus 11%; P < .00001). Though not necessarily causal, these associations should be of interest to patients, physicians, families, and policy-makers.

Hospices↗
PubMed1998

A review of chemotherapy trials for malignant mesothelioma.

Treatment of malignant pleural mesothelioma continues to be frustrating regardless of the modality employed. Numerous trials of chemotherapeutic agents have been performed, but until recently, these studies were small and subject to inaccuracies of disease measurement. To our knowledge, no chemotherapeutic regimen has emerged as a standard of care. A review of the literature reveals that small activity against this disease has been shown by the anthracyclines, platinum compounds, and alkylating agents, whereas higher activity has been reported with the antimetabolites. The plant alkaloids have not demonstrated any activity against mesothelioma. Dose-escalated chemotherapeutic regimens may offer an advantage, whereas combination chemotherapy has not shown any benefit over single-agent therapy. Favorable responses have been reported with the administration of intrapleural biological response modifiers. Further trials and the investigation of new agents in the treatment of this disease are necessary.

Antineoplastic Agents↗
PubMed1997

Alcohol and minor trauma.

A prospective study of breath alcohol levels among mildly injured adult patients was conducted over a 7-month period in the emergency department of a 15-bed hospital on a U.S. Air Force base in rural upstate New York. Severely injured patients were systematically excluded from the analysis. Three hundred twenty-seven patients were invited to participate. Two hundred sixty-seven submitted both a demographic questionnaire and a breath alcohol test (BAT). Forty-six submitted just a questionnaire. Fourteen declined to participate. Eight patients had positive BATs, representing 2.4% of the study population, or 3% of those who submitted a BAT. Thus, the prevalence of alcohol intoxication among patients presenting to a small military hospital with minor injuries is much lower than that among patients with major trauma. Minor injury may not be the marker for alcoholism that major trauma is thought to be.

Adult↗
PubMed1996

Evaluation of patients with chronic headache.

Most chronic headache syndromes can be identified by conducting a careful interview that yields a thorough understanding of the patient's headache experience. The interview should explore the PQRST of the pain: provocation, quality, region, strength and time course, with the last element being the most helpful. Associated symptoms, such as nausea and vomiting in migraine, can be clues to the etiology. A list of all current medicines and the frequency of use should be obtained, since overuse of various analgesics can convert paroxysmal migraine into chronic daily headache. Psychosocial issues should be addressed, since depression can manifest as chronic headache. Changes in mood, energy, appetite, sleep, libido, enjoyments and suicidal ideation (represented by the acronym MEASLES) can indicate depression. A neurologic examination is important, and any focal findings warrant tomographic imaging of the brain. Findings on physical examination, however, are usually normal in patients with chronic headache. Laboratory and imaging studies are of most value when targeted to elucidate potential diagnoses raised by the detailed interview.

Aged↗
PubMed1995

More pearls.

Explore the source record for details and available documents.

Alcoholism↗
PubMed1994

Epilepsy brain surgery: a Pittsburgh perspective.

The views of the authors are presented about the past history and recent situation of epilepsy brain surgery in the United States. Issues of efficacy and quality of life are reviewed, and little empirical evidence is found supporting epilepsy brain surgery as a cost-effective treatment modality. Prospective randomized clinical trials have not been run to address these issues and various problems with patient recruitment and funding seem destined to preclude them.

Cost-Benefit Analysis↗
PubMed1991

Characterization of Lrp, and Escherichia coli regulatory protein that mediates a global response to leucine.

Exogenous leucine affects the expression of a number of different operons in Escherichia coli. For at least some of these operons, the leucine-related effect is mediated by a protein called Lrp (Leucine-responsive regulatory protein). The purification of Lrp to near homogeneity is described. Lrp is a moderately abundant, basic protein composed of two subunits of molecular mass 18.8 kDa each. In addition, the corresponding protein was purified from a strain having a mutation within the gene that encodes Lrp (lrp). This mutation (lrp-1) causes high constitutive expression of ilvIH, one of the operons controlled by Lrp (Platko, J. V., Willins, D.A., and Calvo, J.M. (1990) J. Bacteriol. 172, 4563-4570). The Lrp-1 and Lrp proteins have similar physical properties, but they show some differences in the characteristics with which they bind DNA upstream of the ilvIH promoter. The nucleotide sequences of the lrp and lrp-1 genes differ by only a single nucleotide, a C to G change that would substitute a Glu for an Asp at amino acid 114. Lrp has some amino acid sequence similarity to AsnC, a protein that regulates asnA expression (Kolling, R., and Lother, H. (1985) J. Bacteriol. 164, 310-315).

Amino Acid Sequence↗
PubMed1983

Law and science policy in federal regulation of formaldehyde.

An examination of the way in which the Environmental Protection Agency, Occupational Safety and Health Administration, and Consumer Product Safety Commission each responded to evidence of formaldehyde's carcinogenicity in animal systems reveals the interplay between politics and science policy in regulatory determinations. In some cases there were significant and unjustified departures from reasoned decision-making. Agency decisions not to take action deserve special attention by citizens, the Congress, and the judiciary to ensure that federal regulatory agencies take the necessary steps to protect the public from significant health, safety, and environmental risks.

Carcinogens↗