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Biomedical subjects

D Stewart

Publications and source records attributed to D Stewart.

At least 343 records · Page 19Linked to original sources
PubMed1980

Pharmacological disposition of N-(phosphonacetyl)-L-aspartate in humans.

The pharmacological disposition of N-(phosphonacetyl)-L-aspartate (PALA), an antitumor transition state analog currently in clinical trial, has been studied in 19 patients after i.v. administration of the agent at doses ranging from 800 to 5000 mg/sq m; PALA in biological specimens was assayed enzymatically, advantage being taken of its inhibition of L-aspartate carbamoyltransferase (EC 2.1.3.2) PALA disappeared from plasma biexponentially, with an average terminal t 1/2 of 5.3 hr. It was excreted in the urine unchanged; the 24-hr cumulative excretion was 85% of the administered dose. The average total clearance was 1.60 ml/kg/min and was linearly related to creatinine clearance, suggesting that in humans PALA is essentially cleared by glomerular filtration. The apparent volume of distribution of PALA was 309 ml/kg, approximately the sulfate space in humans. PALA penetrated into the central nervous system only to a limited extent. Tumor L-aspartate carbamoyltransferase activity was also measured before and 1.5 hr to 6 days after PALA administration; in all eight studies, a notable decrease in enzyme activity was observed.

Aspartate Carbamoyltransferase↗
PubMed1980

Clinical pharmacology of IMPY by radioimmunoassay.

A radioimmunoassay for IMPY has been developed using [3H]acetyl-IMPY and antibody induced by immunizing rabbits with succinyl-IMPY bovine serum albumin conjugates. The method was reproducible and sensitive at a dose of 0.2 microgram/ml. The cross-reactivities of IMPY and IMPY derivatives with the antibody were compared. Using this radioimmunoassay, clinical pharmacology was performed in cancer patients during phase I trials. Following 30-60-minute iv infusions of IMPY (450-1500 mg/m2/day for 5 days), the drug disappeared rapidly from plasma with an initial half-life of less than 10 minutes and second half-life of 4 hours. The half-lives are not affected by minimally abnormal hepatic function and are not dose-related. The apparent volume of distribution was approximately 125 ml/kg. The results obtained on Day 5 were essentially the same as those obtained on Day 1. IMPY was also detected in glioblastoma, brain, and temporalis muscle when the drug (500 mg/m2) was infused iv 4-5 hours before surgery. The tissue drug levels were comparable to or higher than those of plasma. The drug was also measurable in kidney and liver tissues obtained 4 hours after death in a patient who died 21 hours after iv infusion of IMPY at a dose of 1500 mg/m2/day for 3 days.

Antineoplastic Agents↗
PubMed1979

Kinetics of gallium nitrate, a new anticancer agent.

Pharmacokinetic studies were conducted in 8 patients with disseminated neoplasms refractory to conventional chemotherapy, who received gallium nitrate at doses of 300 to 600 mg/m2 intravenously in a phase I clinical trial. Gallium concentrations in biological fluids were determined colorimetrically. In patients with normal renal function, gallium showed a biphasic plasma disappearance with an initial half-life (t1/2) of 0.5 to 1.8 hr (mean 1.0) and a terminal t1/2 of 10.5 to 50.4 hr (mean 25.1). Gallium was distributed in total body water and often localized in some body compartment as evidenced by a volume of distribution ranging from 0.25 to 2.53 L/kg (mean 1.19). The total drug clearance from the plasma was 0.13 to 1.00 ml/kg/min (mean 0.65) in patients with normal renal function. Cumulative urinary excretion of gallium was 15% to 72% (mean 35%) of the administered dose in 24 hr (it fell to 23% in 8 days in a patient with acute oliguric renal failure). Gallium kinetics are altered in patients with acute renal dysfunction and in patients who have received multiple doses of gallium or other metal chemotherapy.

Adult↗
PubMed1979

Autologous bone marrow transplantation in relapsed adult acute leukemia.

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Adolescent↗
PubMed1978

Immunological, electrophoretic and kinetic properties of cardiac myosins from various species.

1. In a homologous radioimmunoassay for canine ventricular myosin light chains, the following percentages of cross-reactivities were obtained using the dog as a reference: human, 28%; sheep, 21%; cat, 8%; guinea-pig, 7%; rabbit, 5%; and rat, 4%. 2. In a homologous double diffusion immunoassay using specific gamma G to canine cardiac myosin heavy chains, dog cardiac myosin showed immunological identity with human and sheep cardiac myosin but partial identity with myosins of other species. 3. On a 5-20% polyacrylamide gradient, light chain C1 was electrophoretically distinct in some species; light chain C2 was electrophoretically identical in all species. 4. The K+-activated myosin ATPase of small animals was higher than that of larger animals at an alkaline pH; the same was true for Ca2+-activated myosin when assayed at pH 6.3.

Animals↗
PubMed1978

Hazards of calcium gluconate therapy in the newborn infant: intra-arterial injection producing intestinal necrosis in rabbit ileum.

Five infants received 10% calcium gluconate via umbilical artery catheters, which resulted in intestinal bleeding and lesions of the buttock, anus, groin, and thigh. The effects of intra-arterial calcium gluconate in two animal models were investigated. Injection of calcium into the aorta in the region of the posterior mesenteric artery resulted in immediate hyperperfusion of the descending colon; this may be an early hemodynamic response to injury in the area of colon supplied by this vessel. Injections into the arterial arcade of the rabbit ileum resulted in intestinal necrosis and villous atrophy. The use of umbilical artery catheters for administration of calcium gluconate is potentially hazardous.

Animals↗
PubMed1978

Autologous bone marrow transplantation in patients with adult acute leukemia in relapse.

Nine patients with adult acute leukemia were treated in relapse with piperazinedione plus supralethal total body irradiation in conjunction with autologous marrow infusion. Bone marrow cells were collected and stored in first remission. Storage time varied from 3 to 23 months. Before storage, marrow cells were separated using density albumin gradients in order to reduce the number of leukemic cells in the graft. Three patients died before day 14 after transplantation because of complications already present at the time of transplantation. In six patients, hemopoietic recovery started to occur within 14 days after transplantation. In four patients leukemia-free periods were obtained, lasting 60+ days. The three patients with the longest leukemia-free period after transplantation (range 75 to 220+ days) are reported in more detail. One patient is still alive without evidence of leukemia, with full hematological recovery 220+ days after transplantation.

Acute Disease↗
PubMed1978

Supporting lactation when mothers and infants are separated: a clinical guideline for perinatal nurses.

It has been our intention to describe the vital role a nurse may play in assisting a woman to establish lactation successfully. Stitt indicates that the two most common reasons why women decline to breast-feed are (1) embarassment about their lack of knowledge of techniques and (2) fear of failure. Nurses are in a unique position to intervene constructively in both instances. It is essential for nurses to explore their own feelings about breast-feeding and sexuality and to help each other recognize how attitudes and values affect care. Only through understanding ourselves can we become sensitive to the desires of those who need our care.

Adaptation, Psychological↗
PubMed1977

Acupuncture analgesia: an experimental investigation.

A study was designed to establish whether acupuncture has any analgesic properties beyond those of suggestion. In three one-hour experimental sessions the increases in detection thresholds and tolerances for thermal pain at six body locations on 12 subjects were compared. A control session (without needles) was followed by one session in which electrically stimulated needles were inserted in accord with Chinese practice, and another in which the needles were inserted to avoid all recognised acupuncture "points." Acupuncture was significantly more effective than suggestion in raising overall body pain thresholds but just below significance for tolerances. A significant disproportionate effect on the epigastrium, predicted by the choice of acupuncture points, was found for tolerances but not thresholds.

Abdomen↗
PubMed1977

Azlocillin: in vitro studies of a new semisynthetic penicillin.

The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of Pseudomonas aeruginosa were inhibited at a concentration of 12.5 mug or less per ml. Azlocillin is also active against indole-negative and -positive Proteus spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 mug or less per ml. Isolates of Klebsiella spp. and Enterobacter spp. showed less susceptibility than isolates of Escherichia coli and Serratia spp. Gram-positive cocci except penicillin G-resistant Staphylococcus aureus were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of P. aeruginosa. It was not as active as mezlocillin against the majority of the other gram-negative bacilli.

Bacteria↗
PubMed1977

In vitro studies on netilmicin, a new aminoglycoside antibiotic.

Netilmicin, a semisynthetic derivative of sisomicin, was tested in vitro against 600 clinical bacterial isolates. At a concentration of 1.56 mug/ml, over 90% of gram-negative bacilli were inhibited. Netilmicin was substantially more active against isolates of Serratia marcescens and Enterobacter spp. than gentamicin, sisomicin, tobramycin, or amikacin. Isolates of Staphylococcus aureus (both penicillin G susceptible and resistant) were quite susceptible to netilmicin. Most isolates of Klebsiella spp. and Serratia spp. and some of the isolates of Pseudomonas aeruginosa that were resistant to gentamicin proved to be susceptible to netilmicin.

Anti-Bacterial Agents↗
PubMed1977

Clinical pharmacology of netilmicin.

Pharmacological studies of netilmicin were conducted in 30 cancer patients. After intravenous administration of 50 mg of netilmicin or gentamicin per m(2) over a 1-h period in 10 patients, the mean peak serum concentrations occurred at the end of the infusion and were 7.6 and 7.3 mug/ml, respectively. At 6 h, the mean serum concentrations of both drugs was 1.1 mug/ml. After intramuscular injection of 50 mg of netilmicin per m(2) to each of the same 10 patients, the mean peak serum concentration was 5.5 mug/ml and occurred at 1 h, and, at 6 h, the mean serum concentration was 1.4 mug/ml. The mean proportion of netilmicin excreted in urine during 6 h after intramuscular injection was 55%, and after intravenous injection it was 40.9%. Results were similar with gentamicin sulfate. After administering 60 mg of netilmicin per m(2) intravenously over 30 min every 6 h in 9 patients, the mean peak serum concentration (7.9 mug/ml) occurred at the end of the infusion. The concentration gradually decreased to below 2.0 mug/ml after 4 h. Continuous infusion of 60 mg of netilmicin per m(2) every 6 h after a 60-mg/m(2) loading dose in 11 patients produced levels consistently above 2.9 mug/ml, during the initial 6-h infusion, and levels above 2.0 mug/ml for at least 1 week.

Adult↗