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Biomedical subjects

B Fulton

Publications and source records attributed to B Fulton.

At least 37 records · Page 2Linked to original sources
PubMed1995

Trimetrexate. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of Pneumocystis carinii pneumonia.

Trimetrexate is a folinic acid analogue structurally related to methotrexate, whose primary mechanism of action is believed to be inhibition of dihydrofolate reductase. This reduces the production of DNA and RNA precursors and leads to cell death. Trimetrexate is lipophilic and can passively diffuse across cell membranes including those of Pneumocystis carinii and its mammalian host. To minimise toxicity, trimetrexate must be coadministered with calcium folinate (leucovorin calcium), a reduced folate coenzyme, which is transported into, and protects, mammalian host cells but not P. carinii cells. In noncomparative trials trimetrexate was effective in the treatment of P. carinii pneumonia (PCP) in patients with AIDS who were intolerant of or refractory to cotrimoxazole (trimethoprim/sulfamethoxazole) and pentamidine treatment. In these patients, 2- to 4-week survival rates of 48 to 69% were reported. In a comparative trial in the initial therapy of PCP, trimetrexate was less effective than cotrimoxazole in moderate to severe disease as evidenced by a significantly higher failure rate. Trimetrexate was better tolerated than cotrimoxazole when used in this setting, however. Significantly fewer patients receiving trimetrexate plus calcium folinate discontinued treatment because of adverse events than did patients receiving cotrimoxazole. The most common adverse effect associated with trimetrexate is myelosuppression (neutropenia and thrombocytopenia); this is mitigated by coadministration of calcium folinate and is generally reversible upon dosage reduction or discontinuation. Other adverse effects include increases in serum aminotransferase levels, anaemia, fever, rash/pruritus, and increased alkaline phosphatase or serum creatinine levels. Further research into the use of trimetrexate, including its efficacy as prophylaxis, in combination with other agents and as an oral formulation, is needed to clearly define its role in the treatment of PCP and to identify patients most likely to benefit. Currently, trimetrexate should be considered as an alternative treatment option in immunocompromised patients with moderate to severe PCP who have not responded to or are intolerant of first-line therapy.

AIDS-Related Opportunistic Infections↗
PubMed1995

Propofol. An overview of its pharmacology and a review of its clinical efficacy in intensive care sedation.

Propofol is a phenolic derivative that is structurally unrelated to other sedative hypnotic agents. It has been used extensively as an anaesthetic agent, particularly in procedures of short duration. More recently it has been investigated as a sedative in the intensive care unit (ICU) where it produces sedation and hypnosis in a dose-dependent manner. Propofol also provides control of stress responses and has anticonvulsant and amnesic properties. Importantly, its pharmacokinetic properties are characterised by a rapid onset and short duration of action. Noncomparative and comparative trials have evaluated the use of propofol for the sedation of mechanically ventilated patients in the ICU (postsurgical, general medical, trauma). Overall, propofol provides satisfactory sedation and is associated with good haemodynamic stability. It produces results similar to or better than those seen with midazolam or other comparator agents when the quality of sedation and/or the amount of time that patients were at adequate levels of sedation are measured. Patients sedated with propofol also tend to have a faster recovery (time to spontaneous ventilation or extubation) than patients sedated with midazolam. Although most studies did not measure time to discharge from the ICU, propofol tended to be superior to midazolam in this respect. In a few small trials in patients with head trauma or following neurosurgery, propofol was associated with adequate sedation and control of cerebral haemodynamics. The rapid recovery of patients after stopping propofol makes it an attractive option in the ICU, particularly for patients requiring only short term sedation. In short term sedation, propofol, despite its generally higher acquisition costs, has the potential to reduce overall medical costs if patients are able to be extubated and discharged from the ICU sooner. Because of the potential for hyperlipidaemia and the development of tolerance to its sedative effects, and because of the reduced need for rapid reversal of drug effects in long term sedation, the usefulness of propofol in long term situations is less well established. While experience with propofol for the sedation of patients in the ICU is extensive, there are still areas requiring further investigation. These include studies in children, trials examining cerebral and haemodynamic outcomes following long term administration and in patients with head trauma and, importantly, pharmacoeconomic investigations to determine those situations where propofol is cost effective. In the meantime, propofol is a well established treatment native to benzodiazepines and/or other hypnotics or analgesics when sedation of patients in the ICU is required. In particular, propofol possesses unique advantages over these agents in patients requiring only short term sedation.

Adolescent↗
PubMed1994

The temporal relationship between hepatic GSH loss, heme oxygenase induction, and cytochrome P450 loss following intraperitoneal aluminum administration to mice.

The time- and dose-dependent accumulation of aluminum (Al) in liver and its effect on several hepatic systems were investigated in female Swiss-Webster mice given intraperitoneal (ip) Al lactate. A single dose of 50, 75, or 100 mg Al/kg produced significant depletion of hepatic glutathione (GSH) and cytochrome P450 (P450) and an increase in heme oxygenase (HO) activity when measured at 6 hr. However, no increase in hepatic malondialdehyde (MDA) was seen at this time. Using a dose of 100 mg Al/kg, Al rapidly accumulated in liver (0.29 +/- 0.03 vs 0.12 +/- 0.04 micrograms Al/mg protein at 6 hr). Hepatic GSH was significantly depleted at 2, 4, and 6 hr postdosing, HO activity was significantly increased at 6, 12, 24, 48, and 96 hr postdosing, hepatic cytochrome P450 was decreased at 12, 18, 24, and 48 hr postdosing, while hepatic MDA was not significantly elevated until 24 hr postdosing. Twenty-four hours following three daily doses of 50 mg Al/kg, HO activity was increased, P450 levels were depleted, and hepatic Al content was significantly increased, although hepatic MDA was unaffected. We conclude that parenteral Al produces a course of hepatic damage that begins with GSH depletion and proceeds through a sustained increase in HO activity, with cytochrome P450 loss being an early event and production of hepatic MDA being a late event.

Aluminum↗
PubMed1994

Heme oxygenase induction. A possible factor in aluminum-associated anemia.

The effect of repeated parenteral administration of aluminum (Al) was investigated to determine if a relationship exists between the severity of anemia and increase in hepatic heme oxygenase activity. Female Swiss Webster mice were dosed for 11 d with 50 mg Al/kg, as Al lactate, and sodium lactate was given to control mice. On d 12, hematocrit, hemoglobin, blood smears, hepatic heme oxygenase activity, and cytochrome P450 levels were assessed. Significant decreases in hematocrit (39.1 +/- 0.7 vs 43.1 +/- 0.3% in controls) and hemoglobin (13.1 +/- 0.4 vs 14.2 +/- 0.2 g/dL in controls) were produced by Al administration. Blood smears from Al-treated mice consistently showed smaller, more irregular red cells. Cytochrome P450 content was significantly decreased (0.443 +/- 0.043 vs 0.665 +/- 0.055 nmol/mg) whereas hepatic heme oxygenase activity was significantly increased (2.75 +/- 0.34 vs 1.66 +/- 0.20 nmol/mg/h) in Al-treated animals. The production of mild anemia by parenteral aluminum correlated significantly with the increase in heme oxygenase activity, which, although only 66% greater than in control, preceded a significant loss of cytochrome P450. The increased heme oxygenase activity, with subsequent increased destruction of heme and/or heme proteins is discussed as a possible mechanism for the microcytic, hypochromic anemia associated with Al overload.

Aluminum↗
PubMed1990

Absorption and retention of aluminum from drinking water. 1. Effect of citric and ascorbic acids on aluminum tissue levels in rabbits.

Adult, male New Zealand rabbits (three per group) were administered drinking water containing aluminum chloride (0, 100, or 500 mg Al/liter) together with citrate (0.11 M), ascorbate (0.11 M), or no added ligand ad libitum for 12 weeks. They were fed ad libitum regular rabbit chow analyzed to contain 297 mg Al/kg. Treatment had no effect upon food and water intake or weight gain during the experimental period. No effect of aluminum was observed on tissue levels of the essential metals zinc, copper, and iron, or on hemoglobin and hematocrit values. Aluminum levels were found to increase in a dose-dependent manner in stomach and intestinal mucosa, kidney, bone, urine, and feces. There was only a slight accumulation in liver, and no accumulation in brain (cerebral cortex or hippocampus). Although plasma aluminum was directly related to aluminum intake, whole blood aluminum bore no relation to aluminum dose. Citrate had no effect on aluminum accumulation in the stomach or intestine, but significantly enhanced plasma and bone aluminum levels. Ascorbate did not enhance aluminum accumulation in any tissue studied and even prevented accumulation in bone. Both citrate and ascorbate enhanced excretion of aluminum. Ascorbate therapy may be of potential clinical use to enhance aluminum excretion.

Absorption↗
PubMed1989

Bioavailability of aluminum from drinking water.

Aluminum, present in our drinking water as hydroxide or sulfate, is limited by solubility to 2.5 mg/liter at pH 7.0. This study was carried out to determine if aluminum at doses typically found in drinking water would accumulate in rat tissues if a ligand such as citrate at neutral or acid pH is coadministered, or in the absence of citrate at acid pH. Al(OH)3 or AlCl3 was given ad libitum in drinking water to male Sprague-Dawley rats at 0, 0.1, 2.0, or 100 mg/liter, in 4 mM acetate, pH 3.2 (A), 4 mM citrate, pH 2.6 (C), 4 mM citrate, pH 7.0 (7C), or distilled water, pH 7.0 (W). After 10 weeks, rats were killed and tissues were wet-ashed in nitric acid for determination of aluminum by flameless atomic absorption. Copper, iron, and zinc were determined by flame atomic absorption. Metal ion concentrations in tibia, brain, liver, blood, and kidney did not differ significantly between treatment groups. Aluminum accumulated in intestinal cells of all 100 mg Al/liter rats, with the C group accumulating more aluminum than the A or W groups. In the C group, intestinal aluminum content increased significantly in a dose-dependent manner. Intestinal iron was decreased significantly in all the 100 mg Al/liter groups. Intestinal copper was decreased in the W group at 100 mg Al/liter, with a trend toward a decrease in A and C groups. We conclude that at these low levels studied, aluminum accumulates in intestinal tissue, and that this accumulation is enhanced by citrate ligand. At 100 mg Al/liter, intestinal iron accumulation is decreased, and copper accumulation is marginally decreased.

Aluminum↗
PubMed1983

Hydrogen peroxide as a source of molecular oxygen for in vitro mammalian CNS preparations.

Using an isolated neonatal rat spinal cord preparation, we have studied the ability of hydrogen peroxide to act as a source of oxygen for mammalian central nervous system (CNS) maintained in vitro. We report here that hydrogen peroxide, in low concentrations (0.001-0.004%), can effectively provide the only source, or act as a supplementary source of oxygen. This is brought about via the intracellular enzyme catalase which catalyzes the conversion of H2O2 into molecular oxygen and water.

Animals↗
PubMedDate not supplied

A comparison of winged steel needles and Teflon cannulas in maintaining intravenous access during gastrointestinal endoscopy.

We have conducted a prospective study in 142 consecutive patients undergoing either gastroscopy or colonoscopy. The patients were randomized to have either a 23-gauge winged steel needle or a 23-gauge Teflon cannula inserted. The two groups were well matched, with 71 patients receiving each device. Intravenous access was achieved in every case. The steel needle was inserted at the first attempt in 65 of 71 cases (91.6%) compared with 67 of 71 cases (94.4%) for the Teflon cannula. Extravasation occurred in only 1 of 71 cases (1.4%) with Teflon cannulas compared with 18 of 71 cases (25.5%) of steel needle use (p < 0.01). Additionally, no Teflon cannula blocked completely, whereas 1 of 71 steel needles (1.4%) did so. Only 1 of 71 (1.4%) of the Teflon cannulas became difficult to flush compared with 12 of 71 steel needles (16.9%). The Teflon cannula was as easy to insert and provided significantly more reliable intravenous access than the steel needle.

Adult↗