Search PubMed⌕ Search

Biomedical subjects

T D Walsh

Publications and source records attributed to T D Walsh.

At least 19 recordsLinked to original sources
PubMed1992

A controlled study of sustained-release morphine sulfate tablets in chronic pain from advanced cancer.

The purpose of this double-blind crossover study was to determine whether a sustained-release morphine sulfate (SRMS) tablet given orally every 12 hours could adequately replace immediate-release morphine sulfate solution (IRMS) given orally every 4 hours in hospitalized patients with chronic pain from advanced cancer. Of 33 patients entered, 27 completed the study and were included in the efficacy and safety analysis. Patients were initially randomized to receive either 30-mg SRMS tablets every 12 hours or IRMS at the same mg/24 hours dose, every 4 hours. After 2 days, a crossover was performed, and patients received the alternate treatment for 3 days. Pain and side effects were assessed using a standard 100 mm visual analogue scale (VAS). There were no statistically significant differences between the two treatment groups for mean VAS pain scores or scores for sleepiness, nausea, depression, and anxiety. The incidence of breakthrough pain was similar for both treatment groups, as was the incidence of confusion and constipation. The results demonstrated that SRMS is a safe, effective analgesic preparation for patients who require oral opioids for cancer pain. The data also support the conclusion that sustained-release morphine tablets administered every 12 hours can replace an immediate-release morphine solution administered every 4 hours.

Chronic Disease↗
PubMed1991

Psychosocial aspects of palliative care in advanced cancer.

One hundred patients with advanced cancer referred to a palliative care service were evaluated for psychosocial distress using a standard questionnaire. A high incidence of emotional upset, financial distress, and home-care problems was found. Psychosocial distress is common among patients (and their families) with advanced cancer and may have a significant impact on provision of optimal care. Community services are often inadequate. A dedicated palliative care service employing a multidisciplinary approach can best provide care. We make specific recommendations about how to combat psychosocial distress using specific administrative and management techniques.

Adult↗
PubMed1991

Clinical pharmacokinetics of morphine.

Morphine (M) is recommended by the World Health Organization as the treatment of choice for moderate-to-severe cancer pain. Development of sensitive radioimmunoassays (RIA) and high-performance liquid chromatography in the past 20 years has allowed study of the pharmacokinetics of M, which remain incompletely understood. Data derived by RIA must be interpreted with caution due to cross-reactivity with anti-sera by metabolites, impairing assay specificity. The pharmacokinetics of M have been determined for various clinical situations, but there is large interpatient variability for most parameters. M is readily absorbed from all routes of administration, except transdermal, and it can be injected spinally. Peak plasma levels are achieved within 15-20 min of intramuscular and subcutaneous administration, and within 30-90 min after oral. Peak levels after oral administration are much lower than after parenteral routes, since oral M undergoes extensive first-pass metabolism in the liver. With repeated administration, the oral-parenteral relative potency ratio is 1:3 M can be administered epidurally or intrathecally and has also been given intracerebroventricularly. Epidural M enters the subarachnoid space, but is also absorbed into the systemic circulation. Only 5% of a dose crosses the dura. M administered in the lumbar region is quickly redistributed in the cerebrospinal fluid in a rostral direction, explaining the high incidence of systemic side effects following spinal administration. After absorption, M is rapidly and widely distributed and crosses the blood-brain barrier. With therapeutic doses, plasma protein binding is only 20-35%, and the volume of distribution is 1-6 L/kg. The primary site of M metabolism is the liver, and the dose should be reduced in patients with liver disease. Glucuronidation is the main metabolic pathway, but the principal metabolite, morphine-3-glucuronide (M3G), is inactive. Morphine-6-glucuronide (M6G) is produced in smaller amounts than M3G, but is pharmacologically active and many times more potent than M. The ratio of M6G to M in plasma, after a dose of M, is approximately 10:1, and the ratio does not change with increasing doses or prolonged treatment. Normorphine (NM) is also active, and is formed to a greater extent after oral administration; it is not, however, usually found in plasma. NM may be neurotoxic. M and its metabolites are excreted by the kidney, but urinary free M accounts for less than 10% of an administered dose. In patients with renal insufficiency, the metabolites accumulate, though M itself is still excreted.(ABSTRACT TRUNCATED AT 400 WORDS)

Biotransformation↗
PubMed1991

A simple, rapid method for the simultaneous determination of morphine and its principal metabolites in plasma using high-performance liquid chromatography and fluorometric detection.

This article describes a high-performance liquid chromatography (HPLC) method for the simultaneous determination of morphine (M) and its principal metabolites morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), and normorphine (NM) in plasma. All four compounds are extracted from plasma using a C8 solid-phase extraction column, separated by reverse-phase HPLC on a C18 analytical column, and detected by spectrofluorometry at 210 nm excitation wavelength. The method takes advantage of the compounds' native fluorescence, so that derivitization is not required. Samples have been quantified over a concentration range of 25-100 ng/ml M and NM, 50-200 ng/ml M3G, and 100-300 ng/ml M6G, using nalorphine (500 ng/ml) as internal standard. Within-run and between-run errors were less than 10% for morphine and less than 13% for all the metabolites. The lower limit of quantitation for morphine is 10 ng/ml. The accuracy of the method was confirmed by including quality controls fitted to the standard curves of each compound. The assay described in this article represents a simplification of previous versions of the method, which included cumbersome extraction procedures and multiple detectors. For the first time, an internal standard has been employed. The assay is reliable and easy to use and can be performed in any therapeutic drug monitoring laboratory.

Chromatography, High Pressure Liquid↗
PubMed1991

An overview of palliative care in cancer and AIDS.

Many patients with cancer or AIDS present with pain and multiple other physical and psychological symptoms. For patients with advanced cancer or AIDS, the symptoms are truly the disease and should be the basis for the therapeutic plan. This requires maintaining an active problemsolving approach, giving particular attention to major clinical problems (eg, pain control), and instituting early treatment of other symptoms. These problems need management throughout the course of disease, not just in the terminal stages. In incurable disease, management priorities must focus on controlling symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Common symptoms in patients with advanced cancer.

The goal of this study was to identify the symptoms of patients with advanced cancer. One hundred consecutive patients referred to the Palliative Care Service at the Cleveland Clinic Foundation were studied using a standard tool that included questions on 38 specific symptoms. The most common symptoms were pain, weight loss, and anorexia. Significant findings also included that women had more frequent and severe gastrointestinal complaints than men. These do not appear to be related to specific cancer primary sites.

Adult↗
PubMed1990

Phase I clinical and pharmacological study of merbarone.

Merbarone, a nonsedating derivative of thiobarbituric acid, has demonstrated excellent activity against certain murine tumors, including L1210 and P388 leukemias, B16 melanoma, and M5076 sarcoma. Preclinical studies suggested that the antitumor effects of this drug were schedule dependent, since repeated dosing increased killing of tumor cells when compared to intermittent injections. We have completed a Phase I clinical and pharmacological study of merbarone in which the drug was administered both as a 2-h infusion and as a continuous i.v. infusion over 24 h. In view of the increased toxicity observed in animals following bolus injections and the possibility of schedule-dependent anticancer activity, a schedule of drug administration daily for 5 days was selected. Fifty patients with advanced cancer were treated at dose levels that ranged from 100 to 1500 mg/m2/day. When the drug was administered by peripheral vein, phlebitis was observed at the infusion site at daily doses greater than or equal to 150 mg/m2. Therefore, all patients who received drug doses greater than or equal to 200 mg/m2 were treated by continuous i.v. infusion using central venous catheters. Renal insufficiency, initially observed at a dose of 1000 mg/m2/day, was the dose-limiting toxic reaction at 1500 mg/m2/day. Three of five patients treated at the highest dose level were unable to complete the infusion due to this effect. Marked hypouricemia was observed in all patients. Other toxic effects were mild and included nausea, fatigue, leukopenia, thrombocytopenia, and anorexia. Alopecia was noted in several patients who received doses greater than or equal to 1000 mg/m2/day. No major antitumor effects were observed. Dose-dependent, steady-state plasma concentrations of merbarone were reached within 24-48 h after beginning the continuous i.v. infusion. Elimination of drug from plasma followed a two-compartment model, with a t1/2 alpha of 4.2 h and a t1/2 beta of 15.3 h. Renal excretion of merbarone and its major metabolites accounted for less than 30% of the administered dose. We conclude that merbarone is relatively well tolerated with few constitutional symptoms. The current formulation of the drug causes phlebitis when administered by peripheral vein, and renal insufficiency is commonly observed at daily doses which exceed 1250 mg/m2. The recommended dose for extended Phase II evaluation is 1000 mg/m2/day daily for 5 days administered by central venous catheter.

Adult↗
PubMed1990

Prevention of opioid side effects.

Physician education in cancer pain management is seriously deficient. Many problems occur with opioids simply because of therapeutic ignorance. Opioid side effects are best prevented by using morphine as the drug of first choice for severe pain. Anticipation and prevention of opioid side effects avoids most problems. Physicians need to be aware of how to transfer patients from one opioid to another or from one route of administration to another. Side effects common in clinical practice are constipation, nausea/vomiting, dry mouth, and sedation. The importance of the issues of tolerance, dependence, and respiratory depression have been exaggerated.

Analgesics↗
PubMed1990

Continuing care in a medical center: the Cleveland Clinic Foundation Palliative Care Service.

Approximately 500,000 people die of cancer in the United States each year. Most attention has focused on curative approaches to cancer management. Despite the fact that 80% of persons with advanced cancer suffer from chronic pain and an equal number have a major problem with anorexia and weight loss, little systematic evaluation of these problems has been conducted, although they have a high medical, psychological, and socioeconomic impact. The need for a palliative care service (PCS) at the Cleveland Clinic Foundation was originally identified by physicians within the Department of Hematology and Medical Oncology. During 1987, a pilot study was conducted to evaluate the service, define its potential patient base, and assess its impact on patient care. It is astonishing that so little attention has been paid to this area by the major institutions and organizations involved in care of patients with advanced cancer, despite the hundreds of thousands dying of the disease each year. A dedicated palliative care service would therefore seem appropriate in any major medical institution dealing with significant numbers of cancer patients. It also seems appropriate that the provision of a PCS should be part of the requirements for a comprehensive cancer center, if a center is to claim to provide the entire spectrum of services, from diagnosis until death.

Cancer Care Facilities↗
PubMed1990

Pseudohypoproteinemia and multiple myeloma.

Paraproteinemia is an important diagnostic feature of multiple myeloma. The M-protein level reflects tumor burden and helps to determine the response to chemotherapy. A case is described that illustrates the phenomenon of reversible in vitro gelification of an M-protein. Paraprotein IgG1-kappa formed a concentration- and temperature-dependent gel, which was reversed by agitation. Measurement of paraprotein without previous vortexing of the specimen can erroneously lower the apparent M-protein level as well as reduce serum viscosity levels. This phenomenon can downstage the disease at diagnosis, produce inappropriate assessment of treatment response, or lead to premature withdrawal of chemotherapy. In addition, misdiagnosis of hyperviscosity syndrome can occur with serious clinical consequences.

Aged↗
PubMed1990

Metastatic carcinoma of the prostate with hypercalcemia.

A patient presented with advanced cancer of the prostate and underwent bilateral orchiectomy. After 2 years, hypercalcemia developed and was managed successfully with saline diuresis, furosemide, and oral glucocorticoid therapy. It is believed that the patient's hypercalcemia was caused by a metabolic complication of progressive, advanced disease.

Adenocarcinoma↗
PubMed1987

Phase I and clinical pharmacology study of trimetrexate administered weekly for three weeks.

Trimetrexate, a new antifolate compound, was administered by 30-min infusions weekly for 3 weeks to 29 patients with solid tumors in a Phase I study. Thrombocytopenia was dose limiting, but highly variable among patients at a given dose level; other toxicity was mild and uncommon. Twenty-three patients participated in pharmacokinetic studies and five patients participated in a study of the effects of trimetrexate on [6-3H]-deoxyuridine incorporation into hematopoietic cell DNA. The median total body clearance of trimetrexate for each dose level was independent of dose but the total body clearance varied widely among patients at a given dose level. The magnitude of the fall in platelet count in individual patients correlated well with the amount of exposure to trimetrexate, but not with the extent of prior therapy. The amount of [6-3H]deoxyuridine incorporation into hematopoietic cell DNA at 72 h after drug administration correlated with the total body clearance of trimetrexate. The total body clearance of trimetrexate was reduced in patients with impaired hepatic synthetic function, as judged by low pretreatment serum albumin concentrations. The recommended Phase II starting dose on this schedule is 130 mg/m2 weekly for 3 weeks; patients with hypoalbuminemia should be treated at lower doses.

Adenocarcinoma↗
PubMed1987

Control of pain and other symptoms in advanced cancer.

In the patient with advanced cancer, effective symptom control requires a multidisciplinary, multimodal approach. Considerations involved in the control of pain can serve as a model for management of other symptoms, such as anorexia and dyspnea, as well.

Analgesics↗