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Biomedical subjects

C A Carter

Publications and source records attributed to C A Carter.

At least 73 records · Page 4Linked to original sources
PubMed1989

Safety and acid-suppressant properties of histamine2-receptor antagonists for the prevention of stress-related mucosal damage in critical care patients.

Therapeutic intervention for the prevention of stress-related mucosal damage (SRMD) is currently directed at decreasing mucosal exposure to endogenous hydrochloric acid. We conducted a double-blind, parallel-group study in critically ill patients to investigate the comparative safety and acid-suppressant properties of the intravenously administered H2-receptor antagonists cimetidine and famotidine. This is a preliminary analysis. Study patients received either famotidine 20 mg q12h or cimetidine 300 mg q6h or q12h. Cimetidine dosing intervals were based upon the degree of renal and hepatic dysfunction due to pharmacokinetic considerations. In critically ill patients with severe renal impairment, a pH of greater than or equal to 4.0 was maintained more consistently with famotidine 20 mg q12h compared with treatment with cimetidine. In terms of safety, a greater number of patients receiving cimetidine reported adverse clinical experiences than those receiving famotidine and a greater number of cimetidine patients had to be withdrawn from the study when compared with famotidine patients. In conclusion, preliminary results of this study suggest that famotidine has superior acid-suppressant properties and a better safety profile when used intravenously for the prevention of SRMD in critically ill patients.

Adult↗
PubMed1988

Release of 7-alkylguanines from haloethylnitrosourea-treated DNA by E. coli 3-methyladenine-DNA glycosylase II.

Previous studies have related DNA modification by the haloethylnitrosoureas to their antitumor activity. Repair of this damage, particularly by O6-alkylguanine-DNA alkyltransferase, has been linked to tumor resistance by several previous investigations. We report here that E. coli 3-methyladenine-DNA glycosylase II can also remove several of the DNA modifications caused by the haloethylnitrosoureas. 7-Chloroethylguanine, 7-hydroxyethylguanine, and diguan-7-ylethane are all released into the supernatant from DNA modified by N-[2-chloroethyl-1,2-14C]-N'-cyclohexyl-N-nitrosourea. Release of diguan-7-ylethane is of particular interest since this entity evidently represents a DNA intrastrand cross-link. If a similar activity is present in mammalian cells, it might be an important source of resistance to the therapeutic action of the haloethylnitrosoureas.

Chromatography, High Pressure Liquid↗
PubMed1988

Phosphotriester formation by the haloethylnitrosoureas and repair of these lesions by E. coli BS21 extracts.

The alkylation of phosphates in DNA by therapeutically active haloethylnitrosoureas was studied by reacting N-chloroethyl-N-nitrosourea (CNU) with dTpdT, separating the products by HPLC, and identifying them by co-chromatography with authentic markers. Both hydroxyethyl and chloroethyl phosphotriesters of dTpdT were identified; a similar reaction between CNU and dTR yielded 3-hydroxyethyl and 3-chloroethyl dTR as the major products of ring alkylation. A DNA-like substrate for repair studies was synthesized by reacting 14C-labelled N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (14C-CCNU) with poly dT and annealing the product to poly dA. An extract of E. coli strain BS21 selectively transferred a chloroethyl group from one of the chloroethyl phosphotriester isomers in this substrate to the bacterial protein; chemical instability of the hydroxyethyl phosphotriesters precluded definite conclusions about the repair of this product.

Alkylation↗
PubMed1988

Pharmacokinetics of cetamolol in hypertensive patients with normal and compromised renal function.

The efficacy, safety, and pharmacokinetic parameters of a 30-mg oral dose of cetamolol hydrochloride (Betacor), a new synthetic cardioselective beta-adrenoceptor antagonist, with intrinsic sympathomimetic activity, were evaluated by studying 32 hypertensive patients with normal renal function or different degrees of renal impairment. After administration of cetamolol, serial blood and urine sample collections, as well as vital sign determinations for the next 48 hours, were performed in all patients (with the exception of urine collection, which was not possible in hemodialysis patients). Results indicate that cetamolol's pharmacokinetic parameters are significantly changed in patients who have moderate or severe renal impairment. Specifically, as the severity of renal impairment increased, the maximum serum concentration (Cmax) and the area under the serum concentration-time curve (AUC) increased, whereas the renal clearance (CLR), urinary excretion, and total body clearance (CL) decreased. Additionally, significant direct or inverse correlations for AUC, CL, CLR, and urinary excretion with creatinine clearance (CLCR) were demonstrated. In the subjects with mild renal impairment, the trends toward changes in the cetamolol pharmacokinetic parameters were evident, though small and not statistically significant. Although anuric, patients on hemodialysis still retained the ability metabolically to clear cetamolol at a rate of about one-third of that found in normal subjects. Reductions in blood pressure and heart rate also were found to be greater and more prolonged as the severity of renal impairment increased. There were no adverse drug or toxic effects noted in any of the study patients. Based on these findings, dosing recommendations are suggested for patients who have compromised renal function because of the effects of renal function on the pharmacokinetics of cetamolol.

Acetamides↗
PubMed1988

Processing of in vitro-synthesized gag precursor proteins of human immunodeficiency virus (HIV) type 1 by HIV proteinase generated in Escherichia coli.

We expressed the gag and proteinase regions of human immunodeficiency virus (HIV) type 1 by transcription and translation in vitro. A synthetic RNA spanning the gag and pro domains gave primarily the unprocessed capsid precursor pr53. Efficient cleavage of this precursor was observed when the gag and pro domains were placed in the same translational reading frame, yielding equimolar amounts of the gag protein and of proteinase (PR). Expression of HIV type 1 PR in Escherichia coli as a fusion protein gave rapid autocatalytic processing to an HIV-specific protein of approximately 11 kilodaltons. HIV PR generated in E. coli specifically induced cleavage of the HIV capsid precursor, whereas deletion of the carboxy-terminal 17 amino acids of the proteinase rendered it inactive. Inhibitor studies showed that the enzyme was insensitive to inhibitors of serine and cysteine proteinases and metalloproteinases and was inhibited only by a very high concentration (1 mM) of pepstatin A.

Cloning, Molecular↗
PubMed1988

Review of diclofenac and evaluation of its place in therapy as a nonsteroidal antiinflammatory agent.

Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Therapeutic assessment of Slow-K and K-tab potassium chloride formulations in hypertensive patients treated with thiazide diuretics.

Therapeutic equivalency among different drug products is one of the major issues confronting many clinicians today who are functioning as members of pharmacy and therapeutic committees and state Medicaid programs (SMP). Selection of one of the available slow-release potassium chloride formulations for inclusion in a hospital formulary or SMP exemplifies one of these therapeutic equivalency issues. To evaluate this issue, we studied 20 hypertensive adult patients receiving hydrochlorothiazide 50 mg/d to determine if there are significant differences between the administration of 24 mEq of Slow-K given as 8 mEq/tablet tid, and 30 mEq of K-Tab given as a 10 mEq/tablet tid. The study was conducted in a randomized, open-label, crossover design in which the two drug formulations of potassium chloride were compared over two four-week treatment periods. Results from this study indicate that 24 mEq of Slow-K and 30 mEq of K-Tab were equally effective in maintaining serum electrolyte concentrations, blood pressure measurements, and electrocardiogram evaluations within normal limits in all 20 hypertensive patients studied. Furthermore, no adverse effects were noted with either potassium chloride formulation, and patient acceptance, tolerability, and compliance to prescribed dosing regimens were similar for both products. Based on our findings, therefore, we conclude that 24 mEq of Slow-K and 30 mEq of K-Tab given three times daily as 8 mEq and 10 mEq tablets, respectively, are therapeutically equivalent.

Adult↗
PubMed1987

Drug Information Center network: need, effectiveness, and cost justification.

During the past 15 years, the pharmacy profession has experienced much change. Certain pharmacy roles are being challenged and others are coming into existence. Today, health-care practitioners and health-care providers are seeking services not sought before from pharmacists in the area of rational therapeutics. This need for information extends to all pharmacy practice settings: institutional, independent pharmacies, chain stores, governmental agencies, and the pharmaceutical industry. In order to meet this demand for drug and toxicology information, however, the pharmacist must use resources outside the immediate area of his practice. The Drug Information Center (DIC) can be used as such a resource by pharmacists in their daily practice to provide the best possible care with regard to the rational use of drugs for their patients/clients. Specifically, our data indicate that in Tennessee, there is a need for providing drug and toxicology information; pharmacists perceive their role to be providers of drug information as well as drugs; the DIC plays an integral and necessary role as a back-up information resource and in teaching, service, research, and continuing education programs; and the programs provided by the DIC are cost effective and cost justifiable.

Cost-Benefit Analysis↗
PubMed1986

Leuprolide: a gonadotropin-releasing hormone analog for the palliative treatment of prostatic cancer.

Leuprolide is the first member of the class of gonadotropin-releasing hormone (GnRH) agonist analog to be released in the U.S. The pharmacology of leuprolide is complex and not yet completely defined. This agonist analog is more potent than natural GnRH and appears to be capable of occupying pituitary GnRH receptors. This results in a "down regulation" of the receptors' activity and gonadotropin release, ultimately decreasing serum testosterone levels to those seen following castration. Leuprolide has been found effective in the palliative treatment of advanced cases of prostatic cancer and is not associated with the cardiovascular and thromboembolic toxicity seen with conventional diethylstilbestrol therapy. Leuprolide is administered by daily subcutaneous injections and has been generally well tolerated. The most common adverse effects are hot flashes and a possible flare-up of prostatic carcinoma symptoms on initial dosing. As clinical experience grows in the use of GnRH agonist analog, GnRH will assume a greater role in the treatment of metastatic prostatic cancer.

Animals↗
PubMed1986

Dialyzability and pharmacokinetics of indomethacin in adult patients with end-stage renal disease.

Indomethacin, a nonsteroidal antiinflammatory drug, has been shown to be effective for the treatment of pericarditis in chronic hemodialysis patients. Data regarding the dialyzability of indomethacin in these patients, however, is lacking. The aim of this study, therefore, was to evaluate (1) the dialyzability, and (2) the absorption and elimination kinetics of indomethacin, using six stable anephric adult patients who were maintained on chronic hemodialysis and were receiving indomethacin for the management of their uremic pericarditis. The results from this study demonstrate that indomethacin is dialyzable, but not to an appreciable extent. The mean predialysis and postdialysis indomethacin plasma levels were 3.4 and 1.6 micrograms/ml, respectively. The mean total amount of indomethacin removed by five hours of hemodialysis was 19.6 percent of the single dose of indomethacin 100 mg po. However, mean Cpmax, tmax, t1/2, and AUC0-infinity during and in the absence of hemodialysis were 5.4 and 5.4 micrograms/ml (not statistically significant [NS]), 1.9 and 2.0 h (NS), 6.1 and 5.3 h (NS), and 30.9 and 35.7 micrograms h ml-1 (NS), respectively. Based on these findings, it can be concluded that although indomethacin is dialyzable, no dosage adjustment is required in patients receiving indomethacin for the management of their uremic pericarditis when undergoing maintenance hemodialysis.

Adult↗
PubMed1986

Corneal cell culture and organ storage.

This paper presents methods for corneal cell cultures and examples of investigations that have been performed using these cultures. The techniques and benefits of corneal storage systems, which have arisen from knowledge gained from biologists are outlined. It is likely that both the use of cell culture and organ storage will become of increasing value in the future, and that advances in the understanding of biological processes at a cellular level will improve knowledge of corneal disease and corneal preservation.

Animals↗
PubMed1985

Terfenadine, a nonsedating antihistamine.

Terfenadine is an antihistamine recently approved for use in the U.S. Terfenadine possesses a unique chemical structure when compared with other antihistamines. It is a selective inhibitor of H1-receptors with little or no anticholinergic, antiserotoninergic, or antiadrenergic effects. Comparative studies have shown that terfenadine is as effective as other antihistamines in the treatment of allergic rhinitis and other hypersensitivity conditions. This drug produces a minimal amount of central nervous system (CNS) depression, which is documented by studies demonstrating that terfenadine and its metabolites do not readily pass into the CNS and have little affinity for central H1-receptors. The lack of CNS depression and anticholinergic effects, and the long duration of action that allows twice-a-day dosing make terfenadine an attractive alternative to other antihistamines.

Benzhydryl Compounds↗
PubMed1985

Requirement of essential fatty acid for mammary tumorigenesis in the rat.

In an attempt to determine the requirement of essential fatty acid for dimethylbenz(a)anthracene-induced mammary tumorigenesis, rats were fed diets containing different levels of linoleate: 0.5, 1.1, 1.7, 2.2, 3.5, 4.4, 8.5, or 11.5%. Each diet contained 20% of fat by weight, with varying amounts of coconut oil and corn oil added to achieve the desired levels of linoleate. Mammary tumorigenesis was very sensitive to linoleate intake and increased proportionately in the range of 0.5 to 4.4% of dietary linoleate. Regression analysis indicated that a breakpoint occurred at 4.4%, beyond which there was a very poor linear relationship, suggesting the possibility of a plateau. From the intersection of the regression lines in both the upper and lower ranges, the level of linoleate required to elicit the maximal tumorigenic response was estimated to be around 4%. The differences in tumor yield could not be correlated with changes in prostaglandin E concentration in the mammary fat pads of normal animals maintained on similar diets, suggesting that linoleate may act by some other mechanism to stimulate mammary tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗