Biomedical subjects

G Donaldson

Publications and source records attributed to G Donaldson.

At least 37 records · Page 2Linked to original sources

PubMed1995

Antiemetic efficacy and pharmacokinetics of intravenous ondansetron infusion during chemotherapy conditioning for bone marrow transplant.

We investigated the antiemetic efficacy and safety of intravenous ondansetron infusion in the BMT setting. We conducted prospective randomized comparison trials between ondansetron at 2 dose levels and metoclopramide (MCP) plus droperidol for the prevention of chemotherapy-induced nausea and vomiting in 2 patient populations scheduled to undergo BMT. One patient population (n = 30) received CY alone, the other population (n = 30) received combination chemotherapy of Bu and CY. The CY alone group received ondansetron for 3 days, and the Bu/CY group received ondansetron for 7 days. The primary endpoints were emesis control and nausea. Secondary endpoints included acute (headache, diarrhea and sedation) and delayed (engraftment and regimen-related) side-effects. In both trials, ondansetron provided better emesis control than did MCP plus droperidol during CY administration (P = 0.009, 3-day trial; P = 0.0022, 7-day trial). There was a wide interpatient variation in serum ondansetron levels, although group averages were proportional to the dose administered. Intrapatient day-to-day variation was 10-30% and did not change significantly with concurrent CY administration. Antiemetic efficacy did not correlate with ondansetron serum levels at the doses tested. Headache incidence was similar in all groups. Sedation was highest in the MCP plus droperidol group (P = 0.048, 3-day trial; P = 0.016, 7-day trial). No statistically significant differences in engraftment or regimen-related toxicities were observed between groups in either trial. Ondansetron appears to be a safe and efficacious antiemetic during conditioning for BMT.

Aged↗

PubMed1995

Quality of life analyses from vinorelbine (Navelbine) clinical trials of women with metastatic breast cancer.

The effect of therapy on a patient's quality of life (QOL) is an important factor in choosing a treatment, especially when the primary intent of therapy is palliation of symptoms. An increasing recognition of the importance of QOL prompted inclusion of QOL assessments in a number of clinical trials of women with breast cancer. This report describes two clinical trials in which women with metastatic breast cancer were treated with intravenous (IV) vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France). In a randomized trial, IV vinorelbine was compared with IV melphalan (Alkeran; Burroughs Wellcome Co) as second- or third-line treatment in patients with anthracycline-refractory breast cancer. In a second, nonrandomized study, vinorelbine was used as first- or second-line treatment in patients who had not received doxorubicin previously. Both studies assessed the QOL dimensions of physical functioning, symptom status, role functioning, and global QOL. In the randomized trial, analyses of linear time trends indicated that patients treated with vinorelbine compared with patients receiving IV melphalan had better physical functioning throughout most of the study. Differences between the two treatment groups in other QOL dimensions were not significant. In the nonrandomized study, patients who received vinorelbine as first-line therapy had worse role functioning and somewhat worse physical functioning than those who received the drug as second-line treatment. Overall, these studies suggest that patients who receive IV vinorelbine treatment maintain a reasonable QOL and that this agent is comparable to or better in some respects than IV melphalan.

Antineoplastic Agents↗

PubMed1994

Mechanisms of cold intolerance in patients with angina.

OBJECTIVES: Patients with angina often report that symptoms are worse in cold weather. This study was designed to determine differences between cold-tolerant and cold-intolerant patients in the hemodynamic and ischemic response to exercise at cold temperatures and to assess the role of catecholamines and baroreceptor function. BACKGROUND: Studies have suggested that the heart rate response may differ at cold temperatures, but the mechanism and role of this variation have not been examined. METHODS: Seven cold-intolerant and seven cold-tolerant patients with angina underwent exercise treadmill testing at 6 and 25 degrees C with measurement of catecholamines. Baroreceptor function was assessed by the decrease in systolic blood pressure after patients stood up from the supine position. RESULTS: Norepinephrine levels increased by 139% in the cold environment, but there were no differences between cold-intolerant and cold-tolerant patients. Consequently, blood pressure was higher in the cold environment in all patients, but the heart rate response was similar. However, cold-intolerant patients had a steeper heart rate response in the cold and developed ischemia (mean [+/- SEM] 201 +/- 58 vs. 242 +/- 50 s, p = 0.05) and angina (348 +/- 87 vs. 449 +/- 60 s, p = 0.04) earlier in the cold environment, a difference not seen in the cold-tolerant patients. Baroreceptor function was impaired in cold-intolerant patients (decrease in systolic blood pressure after patients stood up from the supine position 19 +/- 7 vs. 0 +/- 4 mm Hg, p = 0.04). CONCLUSIONS: Exposure to cold causes an increase in blood pressure with an associated increase in myocardial oxygen demand in all patients. In cold-tolerant patients, this increase may be offset by a reduction in heart rate if baroreceptor function is normal. If baroreceptor function is abnormal, heart rate may not decrease in response to a cold-induced increase in blood pressure. This mechanism may account for some of the variability in tolerance to cold exposure that affects patients with exertional angina.

Angina Pectoris↗

PubMed1994

Pharmacology of epidural fentanyl, alfentanil, and sufentanil in volunteers.

BACKGROUND: Despite a large number of clinical investigations in postoperative patients, the pharmacology of epidural fentanyl, alfentanil, and sufentanil has not been well characterized in a human laboratory setting. In this double-blind, placebo-controlled crossover study, we evaluated analgesia and side effects produced by epidural fentanyl (30 and 100 micrograms), alfentanil (300 and 1,000 micrograms), and sufentanil (3 and 10 micrograms) in volunteers. METHODS: Each of 12 volunteers participated in four separate study sessions. The pain model was cutaneous electrical stimulation of intensity sufficient to produce a pain report of 5 on a 0-5 scale, delivered alternately to the finger and tow. Ventilatory drive, pupil size, and subjective ratings of alertness, nausea, and pruritus were measured using visual analog scales. On each study day, after baseline measurements, an epidural catheter was placed at the L2-L3 or L3-L4 interspace. Subjects received the small dose of study drug, and the tests were repeated at 2, 55, and 95 min after drug administration. Subjects then received the large dose of the same study drug, and the series of tests was repeated at 2, 55, and 95 min later. Plasma opioid concentrations were measured using gas chromatography-mass spectrometry. RESULTS: Dose-dependent analgesia was found for all study opioids. For both doses of all opioids, toe analgesia was significantly greater than finger analgesia. Epidural fentanyl and alfentanil provided greater analgesia than sufentanil at the doses investigated. Sedation, increased end-tidal carbon dioxide, and pupillary constriction occurred only after the large epidural doses of all opioids. Overall, the incidence of subjective side effects was low, but four subjects experienced pruritus after 100 micrograms fentanyl, and four were nauseated after 1,000 micrograms alfentanil. Plasma opioid concentrations were near minimum effective analgesic plasma concentrations only after larger epidural doses. CONCLUSIONS: Lumbar epidural fentanyl, alfentanil, and sufentanil produce selective lower-extremity analgesia. Low plasma opioid concentrations measured after small epidural opioid doses suggest a spinal mechanism for analgesia. Larger doses of epidural opioids result in systemic absorption and are likely to produce supraspinal analgesia and other side effects.

Adult↗

PubMed1994

Antenatal fetal magnetocardiography: a new method for fetal surveillance?

OBJECTIVE: To establish the reliability of fetal magnetocardiography as a method of measuring the time intervals of the fetal heart during the antenatal period. DESIGN: A prospective study. SETTING: Wellcome Biomagnetism Unit, Southern General Hospital. SUBJECTS: One hundred and six low risk pregnant women at 20 to 42 weeks gestation. MAIN OUTCOME MEASURES: Success in obtaining QRS complexes, P waves and T waves. Correlation of time intervals with fetal outcome. RESULTS: The technique was acceptable to pregnant women. A QRS complex was successfully demonstrated in 68 (67%) of the unaveraged traces. Using off-line averaging techniques on these 68 cases, P waves were obtained in 75% and T waves in 72%. Although good quality traces were obtained throughout the range of gestational ages, in general it was more difficult below 28 weeks. QRS duration (R2 = 7%, P = 0.02) demonstrated a positive linear correlation with increasing gestation. Of the 35 (51%) cases with umbilical vein pH analysis available, only one result was less than 7.2. No significant relation was found between measurements of the fetal waveforms and the pH results. CONCLUSION: The technique of fetal magnetocardiography provides a significant advance in the technological field for the demonstration of QRS complexes and the full PQRST waveforms in gestations from 20 weeks onwards. With further technical improvements the clinical impact of this technique can be assessed more fully.

Adolescent↗

PubMed1993

Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial.

Samarium-153-ethylenediaminetetramethylene phosphoric acid (EDTMP), a bone-seeking radiopharmaceutical, was given to prostate cancer patients in a dose escalation protocol for pain palliation to determine the maximally tolerated dose. Fifty-two patients with hormone refractory prostate cancer with bony metastases were treated with doses beginning at 0.5 mCi/kg (18.5 MBq/kg), escalating in 0.5-mCi (18.5 MBq) increments to 3.0 mCi/kg (111 MBq/kg). Pain response after treatment was assessed as well as hematologic and serum chemistry parameters. Pain palliation with a mean duration of 2.6 mo was present in 74% of the patients. Toxicity was exclusively hematologic at the highest dose levels. No infectious or bleeding complications occurred, with 45 of the 52 (86%) patients demonstrating complete hematologic recovery. Patients receiving higher doses had significantly greater reductions in serum prostate specific antigen and serum prostatic acid phosphatase levels. The patients receiving greater doses also showed a trend toward improved survival.

Aged↗

PubMed1992

Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index.

Oral complications can be serious and disabling problems for patients undergoing cancer therapy. Therefore, the authors wanted to develop a sensitive and specific instrument to measure oral mucosal changes during therapy. The Oral Mucosa Rating Scale (OMRS) has an examination rating scale to quantify the type and severity of clinically evident oral mucosal changes (atrophy, erythema, ulceration, and pseudomembranous, hyperkeratotic, lichenoid, and edematous changes), with a scale ranging from 0 to 3 (normal to severe). Separate visual analogue scales are obtained for oral pain and dryness. One hundred eighty-eight bone marrow transplant recipients were studied from before transplant through day 42 after transplant. The OMRS then was used to develop a specific index for assessing acute oral mucositis after bone marrow transplant--the Oral Mucositis Index (OMI). The OMI internal consistency measures (Chronbach alpha and Guttman split-half coefficients) were strong (range, 0.84 to 0.93). Support for the validity of the OMI is presented. These scales should help improve the study of oral complications of cancer therapy.

Adult↗

PubMed1990

Steady-state infusions of opioids in human volunteers. I. Pharmacokinetic tailoring.

We report a method for controlling and adjusting plasma opioid concentration to preselected target values in individual human subjects in order to study analgesic and other effects of opioids at steady state. The method employs a computer-controlled infusion pump and an algorithm that utilizes individual subject pharmacokinetic parameters predetermined with tailoring bolus opioid doses. We used this approach to produce 3-step increases in plasma concentrations of alfentanil, fentanyl and morphine in each of 15 subjects. We maintained each plasma concentration plateau for 70 min, measured plasma opioid concentrations achieved during the infusions and analyzed the results for bias and precision of the individually tailored infusions. Our results show that pharmacokinetically tailored opioid infusions produce stable plasma opioid concentrations within 10 min for alfentanil and morphine; with each drug overall prediction error was 20% or less. Fentanyl was somewhat more difficult to control by this method than were the other 2 opioids. We conclude that individual tailoring of opioid infusions minimizes the impact of individual pharmacokinetic differences on achieving preselected plasma opioid concentrations and provides an accurate means of controlling steady-state drug concentrations for studies of concentration-effect relationships and comparisons of side-effect intensities produced by equianalgesic plasma opioid concentrations.

Adult↗

PubMed1989

A randomized clinical trial of home nursing care for lung cancer patients.

A randomized clinical trial was conducted to assess the effects of home nursing care for patients with progressive lung cancer. One hundred sixty-six patients were assigned to either an oncology home care group (OHC) that received care from oncology home care nurses, a standard home care group (SHC) that received care from regular home care nurses, or an office care group (OC) that received whatever care they needed except for home care. Patients were entered into the study 2 months after diagnosis and followed for 6 months. Patients were interviewed at 6-week intervals across five occasions. At the end of the study, there were no differences in pain, mood disturbance, and concerns among the three groups. There were significant differences in symptom distress, enforced social dependency, and health perceptions. The two home nursing care groups had less distress and greater independence 6 weeks longer than the office care group. In addition, the two home nursing care groups steadily reported worse health perceptions over time. Thus, it was remarkable that the office care group, which indicated more symptom distress and social dependency with time, also indicated perceptions of improved health with time. These results suggest that home nursing care assists patients with forestalling distress from symptoms and maintaining their independence longer in comparison to no home nursing care. Home care may also include assisting patients in acknowledging the reality of their situation.

Adult↗

PubMed1985

Adjuvant postoperative radiotherapy in carcinoma of the rectum and rectosigmoid.

Local recurrence occurs in 30% to 50% of rectal cancer patients treated with surgery alone if there is tumor extension beyond the bowel wall alone or in conjunction with nodal involvement. This analysis is of 97 such patients who received postoperative irradiation (XRT) in prospective and standardized fashion at Massachusetts General Hospital (MGH) (4500 rad in 25 fractions to large fields and minimum dose of 5040 rad in 28 fractions within a boost field). Results were compared with a group of 103 previously analyzed patients treated with surgery alone at MGH. A statistically significant decrease in local recurrence was seen in four of the six irradiated subgroups (modified Astler-Coller Stages B2g, B3, C1 + C2m, and C2g) at an interval 3 years from resection. This improvement was achieved with no increase in small bowel complications (4% with XRT versus 5% with surgery alone) in view of efforts at surgical reconstruction and use of multiple-field XRT techniques, bladder distension, etc.

Adenocarcinoma↗

PubMed1984

Local failure following curative resection of colonic adenocarcinoma.

A retrospective review of the medical records of 533 patients undergoing resection with curative intent of large bowel above the peritoneal reflection was undertaken to identify subsets of patients at high risk for local failure. The overall local failure rate was 102/533 (19%) with 32/102 patients having local failure only and 70/102 patients having concurrent local failure and distant metastases. Pathological confirmation of local failure was obtained in 79% of the cases and by surgical exploration in 75%. Overall local failure rates increased with advancing stage of disease. Tumors staged B3, C2 and C3 all had local failure rates in excess of 30%, whereas for Stage A, B1, B2 and C1 lesions, the incidence of local failure was less than 4%. Stage B2 tumors arising in high and low sigmoid and splenic and hepatic flexure had a moderate incidence of local failure (21%) compared to low incidence (5%) at all other sites. The majority of local and regional failures 84/102 (82%) occurred in tumor bed and adjacent soft tissues whereas only 18/102 (18%) local failures occurred in regional nodal groups. The overall local failure rate increased from 27% with one lymph node involved to 50% with greater than 5 lymph nodes involved. Patients with Stage B3, C2 and C3 colon tumors at all sites and selected B2 tumors have a high rate of local failure after surgical resection. The value of postoperative radiotherapy should be formally studied in these patients.

Adenocarcinoma↗

PubMed1983

Patterns of recurrence of rectal cancer after potentially curative surgery.

The results of surgical treatment alone for 142 cases of carcinoma of the rectum and rectosigmoid from the Massachusetts General Hospital were reviewed. The incidence of local failure as any component of failure was found to be strongly dependent on the pathologic stage, and for Dukes' A was 8.0% (3/39); Dukes' B, 31% (18/59), and Dukes' C, 50% (22/44). The incidence of local failure for tumors without lymph node metastasis was 17% with only microscopic extension through the wall (modified Astler-Coller Stage MAC-B2m), but increased to 54% in tumors that were adherent to or invading adjacent organs and structures (MAC-B3). Similarly, in tumors with positive lymph nodes, there was a 36% incidence of local failure for tumors confined to the wall or with only microscopic extension through the wall (MAC-C1/C2m), compared to a 67% incidence for tumors with adherence or involvement of adjacent organs (MAC-C3). Other predictors of local recurrence were the tumor location, grade, number of lymph nodes, and blood vessel invasion. The pathologic factors predicting distant metastasis are also presented. Five-year survival for Dukes' A was 77% (30/39); Dukes' B, 44% (26/59); and Dukes' C, 23% (10/44). The implications for future adjuvant therapy based on the identification of patients with the highest risk for local and distant failure are discussed.

Follow-Up Studies↗

PubMed1983

Clinical experience with prostaglandin E1 in the treatment of arteriosclerosis obliterans. A preliminary report.

Eleven patients with severe arteriosclerotic disease of the lower extremities who were unsuitable for surgical bypass procedures or who had surgical bypass failure have been treated with prostaglandin E1. The patients all responded well to the prostaglandin treatment, except for one patient who required an above the knee amputation. Subjective evidence of pain and swelling disappeared and the patients' narcotic requirements were reduced. In those patients who had ulcers of the lower extremities, healing was promoted spontaneously or together with skin grafting. Side effects experienced by some patients, such as diarrhea, joint pain and swelling of the extremities, did not warrant discontinuation of drug therapy. There were no changes in blood chemistry. There was marked inhibition of platelet aggregation, and moderate inhibition of red cell deformability.

Aged↗

PubMed1981