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Biomedical subjects

W Craig

Publications and source records attributed to W Craig.

35 records · Page 2Linked to original sources
PubMed1993

Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens.

Pharmacodynamic parameters, such as the rate of bactericidal activity with increasing drug concentrations, post-antibiotic effect, sub-MIC effects, post-antibiotic leukocyte enhancement and first-exposure effect, more accurately describe the time course of antimicrobial activity than the MIC and MBC. Aminoglycosides and quinolones exhibit concentration-dependent killing and induce prolonged post-antibiotic effects. The amount of drug rather than the dosing frequency determines the efficacy of these drugs. However, high peak levels can reduce the emergence of resistance, and once-daily dosing of aminoglycosides can also reduce nephrotoxicity and ototoxicity. On the other hand, beta-lactam antibiotics show time-dependent killing and produce prolonged post-antibiotic effects only with staphylococci. The frequency of drug administration is an important determinant of outcome for these drugs, as the duration of time serum levels exceed the MIC is the major determinant of efficacy.

Animals↗
PubMed1993

Relevance of animal models for clinical treatment.

The use of animal models has become an integral part of the evaluation of drugs for antimicrobial chemotherapy. Animal models can be used to define the penetration of antimicrobial agents at foci of infections, the time course of in vivo antimicrobial therapy, dose-response relationships, and the influence of therapy on the pathophysiologic consequences of infection. Animal models have been useful in the delineation of many of the basic principles currently used in clinical practice and in the selection of new agents and new therapeutic approaches for clinical trials in humans. In spite of the many positive aspects of animal models, several problems, such as altered pharmacokinetics in animals, can preclude direct application of results to clinical practice. Studies in animal models cannot replace the need for human clinical trials.

Animals↗
PubMed1993

A novel integrin specificity exemplified by binding of the alpha v beta 5 integrin to the basic domain of the HIV Tat protein and vitronectin.

Several studies have addressed the interaction of the HIV Tat protein with the cell surface. Our analysis of the cell attachment-promoting activity of Tat and peptides derived from it revealed that the basic domain of Tat, not the arg-gly-asp (RGD) sequence, is required for cell attachment to Tat. Affinity chromatography with Tat peptides and immunoprecipitation with various anti-integrin antibodies suggest that the vitronectin-binding integrin, alpha v beta 5, is the cell surface protein that binds to the basic domain of Tat. The Tat basic domain contains the sequence RKKRRQRRR. A related sequence, KKQRFRHRNRKG, present in the heparin-binding domain of an alpha v beta 5 ligand, vitronectin, also bound alpha v beta 5 in affinity chromatography and, in combination with an RGD peptide, was an inhibitor of cell attachment to vitronectin. The alpha v beta 5 interaction with these peptides was not solely due to high content of basic amino acids in the ligand sequences; alpha v beta 5 did not bind substantially to peptides consisting entirely of arginine or lysine, whereas a beta 1 integrin did bind to these peptides. The interaction of alpha v beta 5 with Tat is atypical for integrins in that the binding to Tat is divalent cation independent, whereas the binding of the same integrin to an RGD-containing peptide or to vitronectin requires divalent cations. These data define an auxiliary integrin binding specificity for basic amino acid sequences. These basic domain binding sites may function synergistically with the binding sites that recognize RGD or equivalent sequences.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Trimethoprim-sulfamethoxazole prophylaxis in granulocytopenic patients with acute leukemia: evaluation of serum antibiotic levels in a randomized, double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study.

Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (< 100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purported activity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.

Acute Disease↗
PubMed1991

Randomized controlled trial of prophylactic rifampin for peritoneal dialysis-related infections.

Staphylococcal infections are a major cause of catheter infections and peritonitis in peritoneal dialysis patients. Since catheter-related infections are associated with nasal carriage of Staphylococcus aureus in this population, we studied the effect of intermittent rifampin, an antibiotic known to decrease S aureus nasal carriage, on catheter-related infections and peritonitis. We randomly assigned 64 patients to receive either rifampin 300 mg twice daily for 5 days every 3 months or no treatment. The rifampin-treated patients had a significant delay in time to first catheter-related infection (P less than 0.015) and significantly fewer catheter-related infections overall (P less than 0.001). The catheter-related infection rate in rifampin-treated patients was .26 per patient-year versus .93 per patient-year in untreated patients. Multivariate analysis defined baseline colonization of nares or catheter exit-site and prior renal transplant as risk factors for catheter-related infections. There was no significant difference in peritonitis rates between groups, although the trend was for a delayed time to first episodes and fewer episodes in rifampin-treated patients. Adverse effects necessitated withdrawal of rifampin in four patients. We conclude that intermittent rifampin administration is effective in decreasing catheter-related infections in a peritoneal dialysis population.

Adult↗
PubMed1988

Blinded comparison of cefuroxime to cefaclor for lower respiratory tract infections.

Cefuroxime axetil was compared with cefaclor for the therapy for lower respiratory tract infections. Sixty-one patients were randomized to receive the following drug dosages: (1) cefuroxime axetil, 250 mg orally every 12 hours (21 patients); (2) cefuroxime axetil, 500 mg orally every 12 hours (21 patients); and (3) cefaclor, 500 mg orally every eight hours (19 patients). Of these 61 patients, 80% were male, with a mean age of 59.5 years; 56% had acute pneumonia, and the remainder had an acute bronchitis. Causative pathogens included typical respiratory tract pathogens. Overall, 23 of 27 patients with bronchitis were clinically cured at the end of therapy. Thirty-one of 34 pneumonias were clinically cured or improved at the end of therapy; the three pneumonia treatment failures occurred in the lower dose cefuroxime (n = 2) and cefaclor (n = 1) treatment groups. Overall, bacteriologic cure occurred in 86% of patients treated with 500 mg of cefuroxime axetil compared with 60% of cefaclor-treated patients. Adverse clinical effects were uncommon. From this study, it was concluded that cefuroxime given every 12 hours is at least as clinically efficacious as cefaclor; it is a new oral cephalosporin with pharmacologic and bacterial spectrum advantages over many older agents.

Acute Disease↗
PubMed1984

Pharmacokinetic and experimental data on beta-lactam antibiotics in the treatment of patients.

The in vitro and animal model studies on optimal dosage of the newer beta-lactams are summarized and put into historical perspective. They provide a rationale for dosage schedules that continuously maintain inhibitory serum and tissue concentrations throughout the dosage interval. In vitro studies on the post-antibiotic effect (PAE) with beta-lactams revealed only short time periods of post-antibiotic growth suppression with gram-positive cocci and no post-antibiotic effect with gram-negative bacilli. A similar lack of persistent growth suppression was observed with beta-lactams in a neutropenic mouse thigh infection model for both gram-positive and gram-negative bacteria. In the same animal model, dosing regimens of beta-lactams which continuously provided serum concentrations above the MIC were more efficacious than those that did not. The newer third-generation cephalosporins have prolonged half-lives and can maintain serum levels above the MIC for most pathogens, even when dosed at widely spaced intervals.

Animals↗
PubMed1983

Functional orthopedics: the "four pieces" and Class II treatment.

The authors describe a new functional appliance called the Chateau four pieces, which is designed for the orthopedic treatment of Class II problems during growth. The versatility of the use of the four pieces simultaneously or separately, enables the practitioner to control treatment in three dimensions. The indications and the prescription are discussed, and the results are shown.

Activator Appliances↗
PubMed1979

Prostatic mucinous carcinoma.

Four criteria are proposed for establishing the pathologic diagnosis of prostatic mucinous carcinoma. Twenty-one reported cases of this rare tumor are reviewed, and a new case is presented. The clinical and pathologic features of 16 authentic features of 16 authentic cases are analyzed.

Adenocarcinoma, Mucinous↗
PubMed1978

Cetocycline, tetracycline analog: in vitro studies of antimicrobial activity, serum binding, lipid solubility, and uptake by bacteria.

Cetocycline (formerly chelocardin or cetotetrine) is structurally related to the tetracyclines. It was found to be more active than tetracycline against many clinical isolates of aerobic gram-negative bacilli, but is less active against staphylococci, and has no activity against Pseudomonas. It is bactericidal against susceptible enteric gram-negative bacteria at concentrations two to four times higher than the minimal inhibiting concentrations. The drug is highly lipid soluble; more than 80% is bound to serum, and it is more avidly taken up by susceptible bacteria than tetracycline. A direct correlation between drug uptake and susceptibility of bacteria was not noted, except with a strain of Proteus vulgaris.

Bacteria↗