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Biomedical subjects

D Sampson

Publications and source records attributed to D Sampson.

At least 37 records · Page 2Linked to original sources

Phase I and pharmacokinetic study of tiazofurin (NSC 286193) administered by 5-day continuous infusion.

A phase I and pharmacokinetic study of tiazofurin (NSC 286193), a C-nucleoside that inhibits IMP dehydrogenase, has been completed. The drug was administered by continuous infusion over 5 days. The maximum tolerated dose was 1650 mg/m2 per day, neurological toxicity being the dose-limiting factor. Gastrointestinal and hematological toxicity were mild. A definite relationship exists between dosage and steady-state levels. The plasma clearance was 29.13 (+/- SD 4.05) ml/min per m2. No complete or partial remissions were demonstrated among the 18 patients treated at five dose levels between 550 mg/m2 and 2200 mg/m2 per day.

Adult↗

The value of magnesium in flush solutions for human cadaveric kidney preservation.

A cooperative clinical trial was conducted among 5 transplant centers in the western United States to determine the value of magnesium sulfate in intracellular electrolyte flush solutions for hypothermic, human kidney storage. Kidneys from alternate donors were flushed with either magnesium-free Euro-Collins' solution or magnesium-containing Collins' 2 solution. Donor and recipient ages, and mean preservation times were not significantly different between the 2 groups. There was a significantly lower dialysis requirement during the first week in the magnesium-containing Collins 2 group (33 per cent) versus the Euro-Collins group (54 per cent). Function rates and serum creatinine nadirs at 1 month were not significantly different. The beneficial effect of magnesium sulfate was more evident when preservation times exceeded 24 hours.

Adult↗

Changes in plasma biochemistry in horses competing in a 160 km endurance ride.

Plasma biochemical values were measured in 14 horses, before a 160 km endurance ride, immediately after 85 km, immediately after 160 km, after 30 min recovery period and the day after the ride. For statistical analysis, a group of 7 horses that completed the ride at a mean speed of 234 metres per min (m/min) (Fast Group) was compared with 7 horses that completed the ride at a mean speed of 144 m/min (Slow Group). Estimations were made of sodium, potassium, chloride, bicarbonate, glucose, creatinine, urea, bilirubin, iron, total protein, albumin, calcium, phosphate, cholesterol, alkaline phosphate, gammaglutamyl transferase, lactate dehydrogenase, alpha hydroxybutyrate dehydrogenase, asparate amino transferase, alanine amino transferase, cortisol and insulin. Disturbances in biochemical values associated with endurance exercise reflected dehydration, hepatic dysfunction, reduced renal function and muscle damage. The faster the speed of exercise, the greater was the stress as reflected by cortisol values. The Fast Group of horses also demonstrated lower glucose and higher CK and LD values than the Slow Group of horses. However, biochemical values the day after the ride were similar to values before the ride.

Animals↗

Effect of chest physiotherapy on the removal of mucus in patients with cystic fibrosis.

We studied the effectiveness of some of the components of a physiotherapy regimen on the removal of mucus from the lungs of 6 subjects with cystic fibrosis. On 5 randomized study days, after inhalation of a 99mTc-human serum albumin aerosol to label primarily the large airways, the removal of lung radioactivity was measured during 40 min of (a) spontaneous cough while at rest (control), (b) postural drainage, (c) postural drainage plus mechanical percussion, (d) combined maneuvers (postural drainage, deep breathing with vibrations, and percussion) administered by a physiotherapist, (e) directed vigorous cough. Measurements continued for an additional 2 h of quiet rest. Compared with the control day, all forms of intervention significantly improved the removal of mucus: cough (p less than 0.005), physiotherapy maneuvers (0.005 less than or equal to p less than 0.01), postural drainage (p less than 0.05), and postural drainage plus percussion (p less than 0.01). However, there was no significant difference between regimented cough alone and therapist-administered combined maneuvers, nor between postural drainage alone and with mechanical percussion. We conclude that in cystic fibrosis, vigorous, regimented cough sessions may be as effective as therapist-administered physiotherapy in removing pulmonary secretions. Postural drainage, although better than the control maneuver, was not as effective as cough and was not enhanced by mechanical percussion. Frequent, vigorous self-directed cough sessions are potentially as useful as more complex measures for effective bronchial toilet.

Adolescent↗

Changes in certain metabolic parameters in horses associated with food deprivation and endurance exercise.

Total and individual non-esterified fatty acids (NEFA), pyruvate, lactate, alpha ketoglutarate, acetoacetate, beta hydroxybutyrate, glucose and insulin were measured in horses during an 80 km endurance ride and during four days of food deprivation. In the latter group venous blood-gas and acid-base parameters, and plasma cortisol concentrations were also measured. During exercise and food deprivation the NEFA became considerably elevated, the predominant of which were oleic (35 per cent), palmitic (24 per cent), linoleic (19 per cent) and linolenic (10 per cent). By one hour after feeding total NEFA fell to approximately 20 per cent of 12 hour fasting concentrations. This was associated with a four fold rise in insulin. Small though significant increases occurred in lactate, acetoacetate and beta hydroxybutyrate after the 80 km endurance ride. It was concluded that a ketone pathway is relatively unimportant in the horse, probably due to the ability of the liver to maintain glycogenolysis.

Animals↗

Allopurinol modulation of fluorouracil toxicity.

Considerable interest has developed in the modulation of fluorouracil activity by nucleosides. The toxicity of fluorouracil in mice is known to be reduced by concurrent administration of allopurinol, presumably because biochemical pathways activating fluorouracil in normal tissues are blocked. We have given allopurinol (300 mg t.d.s. PO) concurrently with continuous infusions of fluorouracil (2.0--2.25 g/m2/day X 5) to 34 patients with colorectal cancer and 11 patients with various adenocarcinomas. There were 41 patients assessable for toxicity. Stomatitis was the predominant dose-limiting toxicity (22% grade 1, 19% grade 2, and 27% grade 3 toxicity). Neutropenia (Less Than 1,000/mu l) occurred in 17% patients. Among 26 colorectal cancer patients assessable for response there was a 15.4% response rate. We conclude that allopurinol modulates fluorouracil toxicity in man, allowing a two-fold increase in dose. However, at least in colorectal cancer no greater frequency of tumour response is seen than with lower doses of fluorouracil given by standard schedules of administration without allopurinol.

Allopurinol↗

Stability of renal transplant function with alternate-day corticosteroid therapy.

Fifty-three renal transplant recipients with good to excellent renal function, while receiving daily maintenance or near-maintenance doses of azathioprine and methylprednisolone, were gradually converted to alternate-day corticosteroid therapy. Stability of allograft glomerular filtration rate (GFR) in each patient was assessed by calculating the slope of a plot of the reciprocal of the serum creatinine concentration vs time. After conversion to alternate-day therapy, GFR was stable in 80% but deteriorated in 20% of patients. However, most of the patients who experienced deteriorating GFR during alternate-day therapy regained stable renal function when given the same total corticosteroid dose but on a daily basis. This suggests but does not prove that maintenance-level daily corticosteroid therapy is better than maintenance-level alternate-day therapy in stabilizing allograft function. We conclude that maintenance-level alternate-day corticosteroid therapy should be used cautiously until a long-term prospective study determines whether there is an increased risk of losing renal function with this schedule and whether this potential risk is offset by reduced corticosteroid toxicity.

Adrenal Cortex Hormones↗

Plasma biochemistry in the horse during 3-day event competition.

Blood samples were collected from 16 Thoroughbred horses before, during and after the second day of a 3-day event. Plasma osmolality, concentrations of sodium, potassium, chloride, urea, creatinine, glucose, bilirubin, iron, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, creatine kinase, calcium, inorganic phosphate, uric acid, cholesterol, triglycerides and non-esterified fatty acids were measured. Significant differences from pre-event values were found in all parameters with the greatest changes being found after the cross-country phase. Most parameters showed significant rises following exercise, except calcium and chloride, which decreased. It was deduced from the changes in biochemistry that dehydration, reduced glomerular filtration rate, increased glycogenolysis and increased lipid metabolism, were a result of this form of competitive exercise.

Animals↗

Plasma cyclic AMP levels in response to exercise and terbutaline sulphate aerosol in normal and asthmatic subjects.

A study was performed to investigate changes in plasma cyclic adenosine monophosphate (cyclic AMP), peak expiratory flow and arterial blood gas tensions in response to running exercise and terbutaline sulphate aerosol in asthmatic patients regularly receiving sympathomimetic bronchodilator aerosols. Seven normal subjects were controls. Placebo aerosol was administered 20 min before the first exercise study and 1.0-1.25 mg terbutaline sulphate substituted 20 min after the first test and again 20 min before the second test. Blood gas tensions, expiratory flow and cyclic AMP were measured at rest, during and after exercise. Exercise induced a significant increase in cyclic AMP in both asthmatic and normal subjects. The change in plasma levels was not significantly different between groups. Cyclic AMP values were higher at rest and during exercise with terbutaline sulphate compared with placebo for both groups. Terbutaline sulphate blocked the marked fall in peak expiratory flow and arterial oxygen tension observed in the asthmatic subjects following the first test. Values for cyclic AMP following exercise were not significantly different between asthmatic and normal subjects. In contrast to other reports our asthmatics have a marked increase in cyclic AMP in response to exercise and to a beta-sympathomimetic aerosol.

Adult↗

Changes in blood gas, acid-base and metabolic parameters in horses during three-day event competition.

Sixteen horses competing in a three-day event had venous blood samples collected during the speed and endurance test (day 2) to examine changes in blood gas ands acid-base balance, and the concentrations of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, alpha-ketoglutarate and cortisol. Following the roads and tracks and steeplechase phases there was a significant metabolic and respiratory alkalosis despite a rise in lactate. After completion of the cross country section, although there was a significant decrease in total base, there was no significant change in pH from pre-event values. This was because the decrease in total base was accompanied by a concomitant fall in carbon dioxide levels.

Animals↗

Posttransplant hypersplenism.

Posttransplant hypersplenism, manifested by leukopenia and azathioprine intolerance, can be diagnosed with a high degree of accuracy and promptly reversed by emergency splenectomy. Functioning cadaver kidney homograft survival rates in patients undergoing posttransplant splenectomy are equal to that of patients undergoing pretransplant splenectomy and are statistically superior (p less than 0.01) to recipients who have never had their spleens removed. However, mortality (21%) for posttransplant splenectomy is excessively high when compared to our mortality (1.3%) for pretransplant splenectomy.

Azathioprine↗

Flow and function in machine-preserved kidneys.

One hundred machine-preserved cadaver kidneys were transplanted irrespective of their flow rates on the preservation machine. Twenty-five per cent had flows of below 100 ml/min and 11 per cent had flows of below 80 ml/min. There was no correlation between the flow rate and function at 1, 3 or 12 months. There was no difference in the flow rate between those kidneys which functioned immediately and those which never functioned. A fall in flow rate was associated with acute tubular necrosis of longer duration but eventual function was not impaired. There was a higher incidence of early aggressive rejection in kidneys which functioned immediately. Preservation failure per se is a rare cause of primary non-function. Adherence to a policy of ignoring the flow characteristics of machine-preserved kidneys could make up to 25 per cent more kidneys available for transplantation.

Cadaver↗