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Biomedical subjects

R J Morgan

Publications and source records attributed to R J Morgan.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetics and toxicity of continuous infusion (6S)-folinic acid and bolus 5-fluorouracil in patients with advanced cancer.

Twenty-seven patients with advanced cancer were entered in a phase I study of bolus i.v. 5-fluorouracil at a dose of 370 mg/m2/day for 5 days combined with a continuous i.v. infusion of (6S)-folinic acid for 5.5 days, starting 24 h in advance of the first 5-fluorouracil dose. The dose of (6S)-folinic acid was escalated in cohorts of patients from 250 mg/m2/day to a maximum of 1000 mg/m2/day. The pharmacokinetics of (6S)-folinic acid were studied in the 3 patients given 250 mg/m2/day and in 6 patients given 1000 mg/m2/day. The mean steady-state plasma concentrations of (6S)-folinic acid and its principal metabolite (6S)-5-methyltetrahydrofolate at the 250 mg/m2/day dose were 2.7 and 5.1 microM, respectively. Both concentrations were comparable to the concentrations produced when (6S)-folinic acid was administered as half of a (6R,S)-folinic acid mixture (E. M. Newman et al., Cancer Res., 49:5755-5760, 1989). At the 1000 mg/m2/day dose of (6S)-folinic acid, the concentration of (6S)-folinic acid was 15.3 microM, more than the 4-fold increase predicted by linear pharmacokinetics, while the concentration of (6S)-5-methyltetrahydrofolate was only 16.5 microM. The change in the ratio of the parent compound to its metabolite was accounted for by a decrease in the nonrenal clearance of (6S)-folinic acid, probably indicating saturation of its metabolism. The toxicities observed in this phase I trial, including stomatitis, diarrhea, neutropenia, and anemia, did not differ in nature or severity from those produced by 5-fluorouracil and (6R,S)-folinic acid when administered on the same schedule. Finally, the degree of toxicity did not appear to depend on the dose of (6S)-folinic acid over the range of doses tested.

Adult↗
PubMed1992

Phase I trial of interleukin-2 plus gamma-interferon.

Interleukin-2 (IL-2) and gamma interferon (gamma-IFN) may be synergistic in inducing cell-mediated antitumor cytotoxicity. In order to determine the dose-limiting toxicities and define a maximum tolerated dose of these two agents in combination, we performed a Phase I clinical trial of intravenous IL-2 plus intramuscular gamma-IFN. Patients received both agents on a thrice-weekly schedule consisting of 4 weeks of treatment followed by 2 weeks of rest. Twenty-five patients were treated and received gamma-IFN doses between 0.05-0.25 mg/m2 (1-4 x 10(6) U/m2) with IL-2 doses from 0.33 mg/m2 to 2.33 mg/m2 (6-42 x 10(6) IU/m2). Two patients had partial responses of melanoma and adenocarcinoma of the lung lasting greater than 11 and 8 months, respectively. The toxicities of the combination were those expected from each agent, with no unusual effects, no irreversible organ toxicities, and no patient deaths. The doses recommended for outpatient administration on this schedule are IL-2, 2.0 mg/m2 plus gamma-IFN, 0.25 mg/m2, a dose combination that is unassociated with significant organ toxicity.

Adenocarcinoma↗
PubMed1992

Phase II trial of cisplatin and alpha-interferon in advanced malignant melanoma.

PURPOSE: To evaluate the antitumor activity of combination cisplatin (CDDP) and alpha-interferon (alpha-IFN) in advanced, measurable metastatic melanoma. PATIENTS AND METHODS: Adult patients with metastatic melanoma were required to have bidimensionally measurable lesions and a Karnofsky performance status > or = 60%. Serum creatinine < or = to 1.5 mg/dL, creatinine clearance > or = 60 mL/min, adequate organ and bone marrow function, and radiologic proof of the absence of brain metastases were required. CDDP 40 mg/m2 intravenously (IV) on day 1 and day 8, and alpha-IFN 3 million units/m2 subcutaneously on days 1 to 5 and 8 to 12 were administered every 3 to 4 weeks. RESULTS: Forty-two patients were entered onto this phase II trial and were assessable for response and toxicity. Three patients achieved complete responses (CRs) that lasted 31+, 5, and 8+ months. Seven patients had partial responses (PRs) and a median response duration of 4.4 months. The overall objective response rate was 24% (95% confidence interval, 12% to 39%). Toxicities were mild. Only 11% of the courses required dose reduction of alpha-IFN, and three of 128 courses required CDDP dose reduction for reversible nephrotoxicity. CONCLUSION: The combination of moderate-dose CDDP and alpha-IFN as administered in this schedule is well tolerated and possesses encouraging activity in metastatic melanoma.

Adult↗
PubMed1992

Effective initial therapy of advanced breast cancer with fluorouracil and high-dose, continuous infusion calcium leucovorin.

PURPOSE: The use of leucovorin (LV) to modulate fluorouracil (FU)-mediated inhibition of thymidylate synthase has been shown both in vitro and in vivo to improve the antitumor activity of this drug. Based on our previous demonstration that this combination was active in heavily pretreated patients with prior FU exposure, we performed a phase II study of FU and high-dose intravenous calcium LV in patients with advanced breast cancer who had been exposed to no more than one prior chemotherapy regimen. PATIENTS AND METHODS: Fifty-one female patients with metastatic breast cancer were entered onto this trial. Patients with metastatic disease limited to soft tissue, lymph nodes, skin, and pulmonary nodules were allowed no prior chemotherapy for advanced disease. Those with metastases in the liver or a lymphangitic pattern on chest x-ray were allowed either a single prior regimen for advanced disease or no therapy for metastatic disease if less than 1 year had elapsed since the completion of adjuvant chemotherapy. FU was given daily for 5 days at 400 mg/m2/d with calcium LV, 500 mg/m2/d, beginning 24 hours before and continuing 12 hours after the first and last FU doses, respectively. RESULTS: The overall objective response rate among 45 eligible patients was 36% (95% confidence interval, 22% to 51%). Fourteen of 31 patients in the soft tissue category responded (45%), and two of 14 in the visceral category experienced an objective response (14%). The median response duration was 5 months. Toxicities were moderate leukopenia and mucositis. CONCLUSIONS: FU plus LV is an active first-line regimen with antitumor efficacy comparable to that of the anthracyclines, which warrants further exploration in combination with other agents active in advanced breast cancer. FU plus LV in this schedule is also an excellent alternative for patients with medical contraindications to more intensive combination chemotherapy regimens.

Adult↗
PubMed1992

A programmable stimulator for electrophysiological studies.

We report on the design and construction of a programmable stimulator for use by neuroscientists. The stimulator is small, lightweight, and low powered. It generates positive, negative, or positive and negative pulses with widths and periods programmed by the user. The stimulator has ten parallel outputs to enable it to drive ten preparations at one time. It operates from 50-60 Hz, 115 v AC or 230 v AC and had a nominal peak-to-peak output of 30 volts. A liquid crystal display was used for the user interface and the timing was software-generated by a mincrocontroller.

Electric Stimulation↗
PubMed1991

Gastroduodenal mucosal surface and luminal pH in gastric ulcer.

Gastroduodenal mucosal surface pH was measured in situ by electrode in endoscopically normal and gastric ulcer patients. With the exception of the antrum, mucosal surface pH in the ulcer group (GU) resembled that of the endoscopically normal group. In contrast, the antral mucosal surface pH of the GU group of 7.06 +/- 0.11 (22) was significantly (P less than 0.001) higher than that of 5.46 +/- 0.36 (34) for the endoscopically normal group. This difference was also evident when comparison was restricted to subjects in both groups having a fundal luminal fluid pH of less than 3. When the fundal luminal pH was below pH 3, antral mucosal surface pH was 4.79 +/- 0.41 (24) in endoscopically normal subjects and significantly less (P less than 0.001) than the value of 6.98 +/- 0.18 (12) for gastric ulcer patients. Mucosal surface alkalinity of the GU antrum may be a response to damage but seems inappropriate in view of the likelihood of acid dependent inhibition of gastric acid secretion.

Adolescent↗
PubMed1991

Clinical aspects of pelvic inflammatory disease.

Pelvic inflammatory disease is caused by spread of organisms from the vagina and cervix to the upper genital tract. The patient may have a life-threatening illness or may remain asymptomatic. The disease may be caused by sexually or nonsexually transmitted organisms. Polymicrobial infections are the rule. Therapy requires antibiotic agents with broad coverage of aerobic and anaerobic organisms, including Chlamydia trachomatis and Neisseria gonorrhoeae.

Anti-Bacterial Agents↗
PubMed1991

Use of cytogenetic methods to determine mutagenic changes in the blood of pharmacy personnel and nurses who handle cytotoxic agents.

Lymphocytes of subjects from throughout the United Kingdom were studied over a two-year period beginning in January 1985 to determine the level of chromosomal damage produced by environmental exposure to cytotoxic agents. A small pilot study was conducted to determine the expected background level of chromosomal aberrations. Four groups of subjects were then recruited: pharmacy personnel who reconstituted the drugs under recommended conditions, nurses who did not reconstitute the drugs but worked on units where patients received cytotoxic chemotherapy, unexposed office workers from the same geographic location as the pharmacy personnel and nurses (negative control), and patients receiving cytotoxic drugs (positive control). Subjects completed questionnaires about smoking, viral illnesses, radiation exposure, and medication use in the past 12 months; pharmacy personnel were asked the numbers of times (1) they had handled specific drugs and (2) spills had occurred with these drugs. Lymphocytes from subjects were incubated for 48 hours, and first-division metaphases were examined for chromosome and chromatid aberrations; damage was measured as the number of aberrations per 100 cells. For a blood sample to be included in the analysis, at least 100 metaphase divisions had to be examined. Data were analyzed for 50 pharmacy staff members, 11 nurses, 12 controls, and 6 patients. Metaphase divisions in cells of the pharmacy personnel and nurses indicated no significant difference in chromosomal damage compared with the unexposed office workers. When the pharmacy, nurse, and control groups were pooled into a nonpatient group and compared with the patient group, significantly greater damage was observed in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1990

Introducing patient-controlled analgesia for postoperative pain control into a district general hospital.

Patient-controlled analgesia was introduced in a district general hospital in order to improve postoperative pain control. Techniques of management were developed with effectiveness, safety and practicality as the main objectives. An analysis of the first 1000 patients to use the system is presented. Problems were encountered with slow respiratory rate, monitoring, equipment function and ward management. Identification of specific hazards and management problems led to improvements in system safety. Patient-controlled analgesia has become the standard technique for postoperative pain control after major surgery in this hospital.

Adult↗
PubMed1990

Efficacy of betaxolol in the treatment of stable exertional angina pectoris: a dose-ranging study.

To assess the efficacy of oral betaxolol in the treatment of stable exertional angina pectoris and to determine the relationship between betaxolol doses/serum concentrations and clinical/hemodynamic responses the authors studied 24 patients prior to and following stepwise administration of 5, 10, 20, 40, and 80 mg doses. The major endpoint for the study was the achievement of clinical beta blockade (heart rate 50-60 beats/min and less than or equal to 20% rise in treadmill stage I heart rate). Betaxolol produced a decrease in mean angina pectoris frequency from 6.6 +/- 1.9 episodes/week with placebo to 0.2 +/- 0.5 episode/week during clinical beta blockade (p less than 0.00005). Mean treadmill exercise time increased from 3.1 +/- 1.7 min with placebo to 7.3 +/- 2.3 min with doses sufficient to reduce angina pectoris frequency greater than or equal to 75% (p less than 0.00005) and to 8.0 +/- 2.3 min during clinical beta blockade (p less than 0.00005). The mean doses of betaxolol required to produce a greater than or equal to 75% decrease in angina pectoris frequency and clinical beta blockade were 12 +/- 5 mg (range 5-40 mg) and 28 +/- 29 mg (range 5-80 mg) respectively. Mean serum concentrations associated with these clinical endpoints were 23.8 +/- 9.7 ng/mL and 59.7 +/- 54.0 ng/mL respectively. The results indicate that betaxolol, in widely ranging doses, is highly effective in reducing angina pectoris frequency and improving exercise capacity in patients with stable exertional angina pectoris.

Angina Pectoris↗
PubMed1989

Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma.

We analyzed 49 patients with multiple myeloma (MM) using propidium iodide (PI) staining and flow cytometry to assess DNA content of MM cells in bone marrow. In 12 patients the presence or absence of DNA content aneuploidy could not be determined by analysis of single-parameter DNA histograms alone. Using forward light scatter measurement, resolution of ploidy was readily obtained in all but three cases. Assuming the DNA content of the low light scatter population to be diploid, we were able to classify 7 cases as hypodiploid and 39 as hyperdiploid or diploid. Hyperdiploid or diploid patients survived a median of 24 months and hypodiploid patients only 2.5 months. We conclude that multiparameter analysis of DNA content and light scatter provides easier analysis for the presence or absence of aneuploidy. Patients with DNA content hypodiploidy have a short survival.

Bone Marrow↗
PubMed1989

An analog data acquisition board for the Macintosh II.

The Macintosh II has the hardware to make a good scientific data acquisition and data processing machine. The data acquisition boards currently available do not sample multiple channels simultaneously. They are also relatively slow. We have designed a fast Analog-to-Digital Board for the Macintosh II that samples eight channels at once. This board acquires data with sampling periods from 1 microsecond to 1.6777215 seconds in increments of 100 nanoseconds. Any jitter is due to the stability of the clock which is about one part per billion. The actual analog-to-digital conversion time is 500 nanoseconds with another 500 nanoseconds taken up by the track-and-hold amplifier acquisition time and the multiplexer setting time. The board samples as many as eight channels, giving 12-bit resolution for signals between plus and minus 2.5 volts. For eight channels the maximum Nyquist frequency is 62.5 KHz. The board will acquire single-channel data that has frequencies up to 500 KHz. Simultaneous comparisons of two channels can be made for signals that have a highest frequency component of 250 KHz. Thirty-eight integrated circuits were used on a single-slot board that connects to the Macintosh II's 32-bit NuBus.

Analog-Digital Conversion↗
PubMed1988

Induction and exacerbation of hyaline droplet formation in the proximal tubular cells of the kidneys from male rats receiving a variety of pharmacological agents.

Kidneys from male and female Wistar rats dosed with 1 of 3 chemically unrelated pharmacological agents, a pyrazoline BW540C, a naphthoquinone BW58C and the levoisomer of tetramisole, levamisole or the light hydrocarbon Decalin, were examined by light and electron microscopy. Paraffin histology showed that all 4 agents induced and exacerbated hyaline droplet accumulation in the renal proximal tubular cells of the male rats. Resin histology at both the light and electron microscope level, along with cytochemical procedures for acid phosphatase and the protein 'alpha 2U globulin', helped further in the characterisation of these cytoplasmic inclusions. These techniques confirmed that the accumulation of hyaline droplets seen by paraffin histology represented an increase in the size and number of secondary lysosomes which have been shown to be involved in protein uptake and metabolism. Time course studies showed that increased numbers of small dense lysosomes appear first, which then increase in size, presumably by fusion. Crystalloid bodies form in these large lysosomes eventually giving rise to rectilinear bodies. The accumulation of these protein laden secondary lysosomes took place primarily in the cells of the S1 and S2 segments of the proximal tubules. In extreme cases of lysosomal accumulation however, loading of the S3 segments was noted. In tubules where cellular inclusion loading was heavy, there was evidence of increased cell turnover. The kidneys of female rats dosed with any one of the 4 agents appeared normal.

Administration, Oral↗
PubMed1988

Effect of increasing intraabdominal pressure and volume on left ventricular function in continuous ambulatory peritoneal dialysis (CAPD).

To determine the effect of increasing intraabdominal pressure on left ventricular (LV) systolic function in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), we studied 15 patients who had been on CAPD for at least 2 months. The study protocol included measurement of echocardiographic LV internal dimensions in diastole and systole, LV wall thickness and mass, LV ejection time, the mean velocity of circumferential fiber shortening (mean Vcf), heart rate, BP, and intraabdominal pressure. Measurements were obtained at baseline (OL) and following intraperitoneal infusion of 1-L increments of dialysate solution (up to 4 L) in both the recumbent and standing positions. Significant differences in LV systolic function resulting from intraperitoneal infusion of dialysate were confined to the subgroup with increased LV wall thickness (n = 8). In this subgroup, mean Vcf decreased progressively from 0.99 +/- 0.18 circumferences/second at baseline to 0.88 +/- 0.16 circumferences/second at 1 L (P = NS), to 0.86 +/- 0.16 circumferences/second at 2 L (P = NS), to 0.66 +/- 0.18 circumferences/second at 3 L (P less than 0.005), and to 0.60 +/- 0.14 circumferences/second at 4 L (P less than 0.005) in recumbent position. Measurements obtained in the standing position paralleled those observed during recumbency. These changes were accompanied by a significant decrease in the mean LV internal dimension in diastole and a significant increase in intraabdominal pressure, but no significant change in the mean LV internal dimensions in systole, mean heart rate, or mean systolic or diastolic BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1987

Comparative survival following permanent ventricular and dual-chamber pacing for patients with chronic symptomatic sinus node dysfunction with and without congestive heart failure.

To determine whether survival following permanent ventricular demand pacing differs from survival following permanent dual-chamber pacing in patients with symptomatic sinus node dysfunction (unexplained sinus bradycardia, subsidiary rhythms, sinus arrest, sinoatrial block, or the bradycardia/tachycardia syndrome), we followed 79 patients who received a VVI pacemaker (group 1) and 49 patients who received a DVI or DDD pacemaker (group 2) for 1 to 5 years. There was no significant difference in sex distribution, mean age, or the incidence of coronary heart disease, hypertension, valvular heart disease, diabetes mellitus, stroke, or renal failure between groups 1 and 2. Overall, the predicted cumulative survival rates at 1, 3, and 5 years were 89%, 82%, and 74%, respectively, for group 1 and 94%, 86%, and 78%, respectively, for group 2. In patients with preexistent congestive heart failure (CHF), predicted cumulative survival rates at 1, 3, and 5 years were 78%, 69%, and 57%, respectively, for group 1 (n = 23) and 90%, 83%, and 75%, respectively, for group 2 (n = 16). Five-year predicted cumulative survival was significantly lower in group 1 patients with CHF than in group 2 patients with CHF (p less than 0.03). There was no significant difference in 5-year cumulative survival rates between groups 1 and 2 in patients without CHF. The results suggest that permanent dual-chamber pacing enhances survival to a greater extent than permanent ventricular demand pacing in patients with chronic symptomatic sinus node dysfunction and CHF.

Aged↗