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Biomedical subjects

C Lindley

Publications and source records attributed to C Lindley.

At least 19 recordsLinked to original sources
PubMed2000

Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis.

The theoretical basis for and clinical experience with using oral serotonin type 3 (5-HT3)-receptor antagonists for preventing chemotherapy-induced emesis are discussed. Evidence supports the idea that antineoplastic drugs and irradiation can initiate emesis by releasing serotonin from enterochromaffin cells in the gut mucosa, which activates peripheral vagal afferent nerves. In view of the GI site of serotonin release and vagal afferent activation, the proximity of neuronal 5-HT3 receptors, and the pharmacologic properties of 5-HT3-receptor antagonists, the oral use of these agents is rational. Oral granisetron 2 mg once daily or 1 mg twice daily has been evaluated in more than 4500 patients receiving highly or moderately emetogenic chemotherapy. Rates of total control of emesis ranged from 44% to 60%, and complete-response rates ranged from 70% to 94%. Oral ondansetron 8 mg three times daily has proven effective in patients receiving antineoplastics with moderate or moderately high emetogenic potential. Two double-blind studies demonstrated the efficacy of a single 24-mg oral dose of ondansetron administered approximately 30 minutes before cisplatin-based chemotherapy. Patients randomized to oral ondansetron had higher total-control and complete-response rates than patients receiving intravenous granisetron or ondansetron. Oral dolasetron 100 or 200 mg once daily also prevented emesis. Oral administration of 5-HT3-receptor antagonists for the prevention of acute emesis associated with chemotherapy is rational and appears to be effective.

Administration, Oral↗
PubMed2000

Clinical economics: calculating the cost of acute postoperative pain medication.

Few data are available that address the cost of postoperative pain management, although such knowledge would enhance our understanding of caregiver choices related to direct medical costs, such as type, frequency, and route of medication. This article describes the cost of postoperative pain medications before and after an educational program provided to nurses, pharmacists, and physicians in six community hospitals. Medication costs were calculated by averaging across all brands the average wholesale price of the most common dose administered in the sample for each medication. The median cost of postoperative pain medication across all days, all surgeries, was $9.46. Calculating the cost of acute postoperative pain medication suggested that cost over stay is highly influenced by the use of a few expensive medications. The relationship of medication cost to length of stay (LOS), function, and pain intensity is discussed.

Acute Disease↗
PubMed2000

In vivo and in vitro induction of human cytochrome P4503A4 by dexamethasone.

PURPOSE: The aims of these experiments were to determine the effect of a therapeutic regimen of dexamethasone on cytochrome P4503A4 (CYP3A4) activity in healthy volunteers; and the concentration-effect relationship between dexamethasone and CYP3A4 activity in primary human hepatocyte cultures. METHODS: The effect of dexamethasone (8 mg administered by mouth two times a day for 5 days) on CYP3A4 activity in 12 healthy volunteers was assessed with the erythromycin breath test and urinary ratio of dextromethorphan to 3-methoxymorphinan. Concentration-effect of dexamethasone on CYP3A4-dependent testosterone 6-beta-hydroxylation was determined in human hepatocytes treated with 2 to 250 micromol/L dexamethasone. RESULTS: The percent of erythromycin metabolized per hour increased from 2.20% +/- 0.60% (mean +/- SD) at baseline to 2.67% +/- 0.55% on day 5 of dexamethasone (mean increase in hepatic CYP3A4 activity 25.7% +/- 24.6%; P = .004). The mean urinary ratio of dextromethorphan to 3-methoxymorphinan was 28 (4.8 to 109) and 7 (1 to 23) at baseline and on day 5 of dexamethasone (mean decrease = 49%; P = .06). Substantial intersubject variability was observed in the extent of CYP3A4 induction. The extent of CYP3A4 induction was inversely correlated with baseline erythromycin breath test (r2 = 0.58). In hepatocytes, dexamethasone 2 to 250 micromol/L resulted in an average 1.7-fold to 6.9-fold increase in CYP3A4 activity, respectively. The extent of CYP3A4 induction with dexamethasone in hepatocyte preparations was inversely correlated with baseline activity (r2 = 0.59). CONCLUSIONS: These data demonstrate that dexamethasone at doses used clinically increased CYP3A4 activity with extensive intersubject variability and that the extent of CYP3A4 induction was, in part, predicted by the baseline activity of CYP3A4 in both healthy volunteers and human hepatocyte cultures.

Administration, Oral↗
PubMed1999

Changing acute pain management to improve patient outcomes: an educational approach.

The United States Agency for Health Care Policy and Research (AHCPR) Acute Pain Management Guidelines were written to provide a scientific basis for practice. Educational programs designed to promote use of the guidelines may change practice in community hospitals. This article describes the development and implementation of an education program for nurses, physicians, and pharmacists in six community hospitals. Program content addressing the use of continuous quality improvement (CQI) teams, detailed pain histories, application of algorithms and dose calculation is described; direct and indirect outcome measures are reviewed. Six months after the program, all three experimental sites reported use of the AHCPR Guidelines in practice. Nurses reported that assessment and documentation of patients' duration of pain were perceived to be the most important caregiver behaviors providing benefit to patients: Across all respondents' reports of regularly performed activities, the activity performed by the largest proportion was assessing and documenting pain using a 0-10 rating scale.

Acute Disease↗
PubMed1999

Organization of hospital-based acute pain management programs.

BACKGROUND: The management of acute pain is an aspect of hospital-based practice that has been neglected. Control of pain is important for ethical reasons, for compliance with new guidelines and standards, and for optimizing patient satisfaction and outcomes. METHODS: Be review the rationale for establishing priority to the control of acute pain, the importance of an institutional approach to improve pain management, and specific steps in the establishment and conduct of an acute pain program. RESULTS: Improvement in pain control depends on an institutional approach to facilitate changes in attitude and prioritization. Pain management programs should provide for patient and staff education, adequate documentation of care, institutional standards for pain control, quality assurance/continuous quality improvement (CQI) activities, and periodic review of practice and policy. CONCLUSIONS: Effective pain management can set the stage for a rehabilitational approach to postoperative care, which should lead to earlier recovery and improved outcomes.

Acute Disease↗
PubMed1999

Cyclic AMP can decrease expression of genes subject to catabolite repression in Saccharomyces cerevisiae.

External cyclic AMP (cAMP) hindered the derepression of gluconeogenic enzymes in a pde2 mutant of Saccharomyces cerevisiae, but it did not prevent invertase derepression. cAMP reduced nearly 20-fold the transcription driven by upstream activation sequence (UAS1FBP1) from FBP1, encoding fructose-1,6-bisphosphatase; it decreased 2-fold the activation of transcription by UAS2FBP1. Nuclear extracts from cells derepressed in the presence of cAMP were impaired in the formation of specific UASFBP1-protein complexes in band shift experiments. cAMP does not appear to act through the repressing protein Mig1. Control of FBP1 transcription through cAMP is redundant with other regulatory mechanisms.

Carboxy-Lyases↗
PubMed1999

American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants.

PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Adult↗
PubMed1998

Quality of life and preferences for treatment following systemic adjuvant therapy for early-stage breast cancer.

PURPOSE: To evaluate the quality of life (QOL) of breast cancer patients who survived 2 to 5 years following initiation of adjuvant cytotoxic and/or hormonal therapy and to characterize relationships between QOL and patient physical symptoms, sexual function, and preferences regarding adjuvant treatment. PATIENTS AND METHODS: Eighty-six patients who had completed systemic adjuvant therapy for early-stage breast cancer between 1988 and 1991 were surveyed by written questionnaire and telephone interview. Sociodemographic information was obtained for each patient, and patients were asked to complete the Functional Living Index-Cancer (FLIC), the Symptom Distress Scale (SDS), the Medical Outcomes Study (MOS) Short Form 36 (SF-36), a series of questions regarding sexual function, and a survey about preferences for adjuvant therapy in relation to possible benefit. RESULTS: The mean FLIC score among all patients was 138.3 (+/- 12.2), which suggests a high level of QOL. The reported frequency of moderate to severe symptoms was generally low (ie, < 15%), with fatigue (31.4%), insomnia (23.3%), and local numbness at the site of surgery (22.1%) occurring with greatest frequency. Patients reported a wide range of sexual difficulties. Preference assessment showed that more than 65% of patients were willing to undergo 6 months of chemotherapy for a 5% increase in likelihood of cancer cure. CONCLUSION: Self-rated QOL in breast cancer patients 2 to 5 years following adjuvant therapy was generally favorable. Less than one third of patients reported moderate to severe symptoms. Selected aspects of sexual function appeared to be compromised. The majority of patients indicated a willingness to accept 6 months of chemotherapy for small to modest potential benefit.

Adult↗
PubMed1996

Antiemetic therapy in managed care oncology: roundtable discussion.

Few diagnoses are feared more by patients than cancer. In addition to the life-threatening nature of many cancers, the spectre of very difficult the treatment provides patients with little or no level of comfort. However, recent advances in the treatment of the side effects of cancer chemotherapy are helping to change these attitudes. On April 4, 1996, a panel of experts was convened to discuss these issues and how they affect MCOs.

Antiemetics↗
PubMed1995

Vinorelbine: a novel vinca alkaloid.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of vinorelbine are reviewed. Vinorelbine is a semisynthetic vinca alkaloid with a broader spectrum of antitumor activity in vitro than naturally occurring vinca alkaloids have. Vinorelbine shows selective activity against mitotic microtubules. Higher concentrations of vinorelbine relative to vinblastine and vincristine are required to affect axonal microtubules; presumably this accounts for the decreased neurotoxicity of vinorelbine. Vinorelbine is lipophilic and is rapidly distributed into peripheral tissues. It is highly bound to blood components. Vinorelbine is excreted slowly by the fecal route and rapidly by the urinary route. Disposition is characterized by a three-compartment model, high systemic clearance, and a long terminal-phase elimination half-life. In clinical studies, vinorelbine has shown antitumor activity both as a single agent and in combination with cisplatin in patients with non-small-cell lung cancer (NSCLC). Vinorelbine plus cisplatin produces a higher response rate and longer survival than vindesine plus cisplatin, a combination previously found to be superior to best supportive care. Encouraging results for vinorelbine in the treatment of advanced breast cancer, advanced ovarian epithelial cancer, and other tumors have also been observed. The dose-limiting adverse effect of vinorelbine is myelosuppression. Vinorelbine has FDA-approved labeling for use alone or in combination with cisplatin for the first-line treatment of unresectable, advanced NSCLC. The recommended dosage is 30 mg/sq m i.v. weekly administered by either slow i.v. push or i.v. infusion. Vinorelbine alone or in combination with other antineoplastics has shown activity against NSCLC, advanced breast cancer, and other malignancies. More study is needed to determine whether vinorelbine is superior to best supportive care in patients with NSCLC.

Antineoplastic Agents↗
PubMed1994

Overview of current development in patient-controlled analgesia.

Over the past two decades, numerous trials have assessed the safety and efficacy of patient-controlled analgesia (PCA). Advantages over conventional parenteral narcotics reported from these trials include equivalent to superior pain relief, superior patient satisfaction, decreased sedation and anxiety, faster return to normal functional status, and reduction in nursing time and hospitalization. The majority of these trials have been conducted in the postoperative patient population. In the mid to late 1980s, interest arose in applying PCA technology to the management of cancer pain. Factors that served as an impetus for the use of PCA in cancer pain included favorable reports from the postoperative setting and the often-cited statistics regarding the magnitude of the cancer pain problem. Advances in PCA technology coupled with advances in vascular access technology that allow the placement of long-term ports and catheters to facilitate intravenous, epidural, or intrathecal administration of opioid analgesics have made the applicability of PCA in ambulatory cancer patients an attractive option. The greatest breakthrough in PCA technology came with the introduction of devices making it possible to choose between intermittent (demand bolus) and continuous administration (continuous infusion) or both intermittent and continuous modes. A comparison of these types of PCA devices is described. The limitations of the literature involving PCA therapy in cancer patients make it difficult to identify optimal patient selection criteria, PCA administration schedules, drug selection and dosing, and optimal route of administration. The current status and pertinent issues related to these topics are addressed.

Analgesia, Patient-Controlled↗
PubMed1992

Treatment of gastrointestinal and renal adenocarcinomas with interferon-alpha.

Treatment of adenocarcinomas with interferon-alpha as a single agent has been disappointing. Recent efforts have focused on the combination of interferon with cytotoxic drugs such as 5-fluorouracil. A number of postulated mechanisms can explain synergistic interactions between 5-fluorouracil and interferon-alpha, including interaction with pyrimidine pathways, and alteration of drug metabolism. Previous studies in colorectal cancer, using 5-fluorouracil and interferon-alpha are reviewed, suggesting that the combination is more active than 5-fluorouracil alone. In renal cell carcinoma, the literature is reviewed, suggesting that daily interferon is the most efficacious schedule; preliminary data suggest that addition of 5-fluorouracil to interferon-alpha can double the expected response rate of 16% achieved by interferon-alpha alone.

Adenocarcinoma↗
PubMed1992

Quality of life measurements in oncology.

Quality of life (QOL) has transcended from an implicit concern to an explicit measurement in oncology. In contemporary clinical research, QOL can now often be identified and objectively measured in health as well as in illness. The major domains which comprise QOL in patients with cancer include symptoms and side effects, social function, physical function, and psychological status. One of the preferred methods for measuring QOL consists of self-administered questionnaires. A number of instruments have been developed which vary in features such as type of domains included, number of items, response options, specificity for disease type, and psychometric assessments. The role of QOL assessment is becoming increasingly important in clinical oncology.

Activities of Daily Living↗
PubMed1991

The lymphomas: Hodgkin's disease and non-Hodgkin's lymphomas.

This review presents an overview of a heterogeneous group of disorders that fall under the general heading of lymphomas. Many specific subtypes and presentations exist; their presentations, treatments, and prognoses vary greatly. Patients with lymphomas are generally treated with external beam radiation therapy, chemotherapy, or a combination of these two modalities. The community pharmacist may play an important role in management of patients by recognizing and alleviating the distressing side effects of treatment. Unfortunately, prevention and early detection play little role in the management of lymphomas. The improvement in survival rates of patients with all but indolent NHL is a direct result of advances in chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Outcome assessment: functional status measures and quality of life as therapeutic endpoints in oncology.

There is now agreement among most authorities regarding the need for a global measure of outcome in cancer clinical trials and guarded enthusiasm for incorporation of these. The next step--selection of existing instruments or development of new ones--appears to represent the current state of affairs. There is an urgent need for additional research into the meaning of life and health that the diagnosis of cancer generates. There are obvious dangers in relying on scales that do not reflect the patient's perception of quality of life. A number of instruments are available, and some of these are adequate in selected contexts. Poor psychometric testing and absence of evidence of predictive validity of existing or newly developed instruments may be expected to lead to false negative findings, however, when the impact of treatments on quality of life are compared. Following instrument development will be the incorporation of questionnaires into study design, which will represent a large task for many individuals. And last, but probably most important, we will have to determine how the results of QOL trials will be interpreted. The first important step towards incorporation of QOL/functional status as outcome measures in cancer clinical trials has occurred. To reach this goal will undoubtedly require a positive commitment from both medical and research staffs.

Clinical Trials as Topic↗