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Biomedical subjects

R A Nash

Publications and source records attributed to R A Nash.

At least 19 recordsLinked to original sources
PubMed1992

Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate.

Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials.

Adult↗
PubMed1992

The development of a microwave fluid-bed processor. II. Drying performance and physical characteristics of typical pharmaceutical granulations.

Four typical pharmaceutical granulations were used to measure the enhanced drying performance of a laboratory-sized microwave fluid-bed processor, the design and construction of which were presented in Part I of this work (preceding paper). Results demonstrate improvements in observed drying rates by as much as sixfold depending upon the granulation type and drying conditions. At a low inlet temperature (30 degrees C), drying was achieved with microwave power inputs of 100-125 W/liter of working capacity, whereas similar targeted moisture levels were unattainable using conventional fluid-bed drying. Microwave energy available for heating and drying was 68 to 86% of the total microwave energy inputted.

Desiccation↗
PubMed1992

The development of a microwave fluid-bed processor. I. Construction and qualification of a prototype laboratory unit.

The static bed- and planetary-type microwave dryers currently available to process pharmaceutical materials are not designed to use hot-air fluidization for the purpose of maximizing microwave energy inputs and particle drying. To take advantage of the benefits offered by fluidization, a 1-kg Uni-Gatt laboratory fluid bed processor was modified to support microwave-assisted fluid bed drying of several representative pharmaceutical granulations. The construction, design features, and validation of this new microwave fluid bed processor are presented.

Calibration↗
PubMed1992

The possibility of lidocaine ion pair absorption through excised hairless mouse skin.

The purpose of the present research was to test the ion pair absorption hypothesis with respect to the topical route of drug delivery. The experiment consisted of preparing various lidocaine-n-alkanoate ion pairs, then characterizing them by proton magnetic resonance spectroscopy, elemental analysis and conductivity. Percutaneous absorption studies through excised hairless mouse skin were carried out using ethanolic solution of radiolabeled 14C-lidocaine-octanoate, 14C-lidocaine-decanoate and 14C-lidocaine-dodecanoate. Studies were conducted under steady-state conditions using Bronaugh's flow-through apparatus and normal saline as the receptor fluid. Ethanolic solution of a lidocaine base served as a control. The apparent differences in flux between lidocaine and the various ion pairs were statistically significant (p less than 0.05). The differences among the fluxes of the various ion pairs were not statistically significant (p greater than 0.05), nor were the differences in lag times (p greater than 0.05). The difference between the flux values of lidocaine-1-14C-dodecanoate and 14C-lidocaine-dodecanoate infers that lidocaine-dodecanoate did not cross the excised, full-thickness, hairless mouse skin as an intact 1:1 ion pair. The formation of weakly associated ion pairs was suggested by the apparent low-association constants (Ka = 15-17 liters/mol) obtained at 25 degrees C in methanol by conductometric analysis.

Animals↗
PubMed1991

Molecular cloning and in vivo evaluation of canine granulocyte-macrophage colony-stimulating factor.

Canine granulocyte-macrophage colony-stimulating factor (caGM-CSF) was cloned and expressed to allow further investigation of GM-CSF in a large animal model. The cDNA is 850 base pairs (bp) long and encodes a peptide of 144 amino acids. The nucleotide and amino acid sequence homology between caGM-CSF and human GM-CSF (hGM-CSF) is 80% and 70%, respectively. A mammalian expression vector pCMV/CAGM was constructed and used to transfect COS cells for expression of caGM-CSF. Supernatant from transfected COS cells enriched with caGM-CSF was shown to have significant stimulating activity in granulocyte-macrophage colony forming unit (CFU-GM) assays of canine marrow. caGM-CSF, expressed from bacteria, was used to treat seven dogs at varying doses twice daily subcutaneously (sc) for 14 to 16 days. Circulating blood neutrophils and monocytes increased significantly. The increase in circulating eosinophils was variable. Thrombocytopenia developed during administration of caGM-CSF but corrected rapidly after cessation of treatment. Evaluation of survival times of 51Cr-labeled autologous platelets suggested increased consumption as the primary reason for thrombocytopenia. A species-specific GM-CSF will be a useful tool for hematologic or immunologic studies in dogs.

Amino Acid Sequence↗
PubMed1989

Iontophoretic transport of a homologous series of ionized and nonionized model compounds: influence of hydrophobicity and mechanistic interpretation.

An in vitro study was carried out to elucidate the mechanisms controlling iontophoretic transport. The investigation focused on three areas, including the nature of the permeant (state of ionization and hydrophobicity), skin structures (hair follicle distribution and stratum corneum), and various parameters influencing iontophoresis (current, permeant concentration, and competitive ion effects). The data indicate that iontophoretic-facilitated transport is essentially pore mediated and that the transport of ionized and nonionized molecules may be enhanced through the pore-type pathway. The data presented show that iontophoresis has a detrimental effect on the lipoidal transport pathway and that the transport of more hydrophobic nonionized molecules is decreased compared with passive diffusion. The iontophoretic enhancement values decreased linearly with increasing alkyl chain length of n-alkanols. The iontophoretic permeability coefficients of ionized n-alkanoic acids was shown to decrease with increasing permeant hydrophobicity.

Administration, Cutaneous↗
PubMed1989

Studies on the efficacy of methyl esters of n-alkyl fatty acids as penetration enhancers.

The efficacy of the methyl esters of medium chain n-alkyl fatty acids as penetration enhancers was evaluated in vitro using various animal and human skins with minoxidil as the test drug. Both methyl nonanoate and methyl caprate at a 10% concentration were found to be effective penetration enhancers for a 2% solution of minoxidil in alcohol USP. The percent of the applied radioactive dose of minoxidil penetrated after 17 h was 5-8 times greater for methyl non-anoate and methyl caprate enhanced solutions than for a 2% solution of minoxidil in alcohol USP alone or with the addition of 10% Azone, dimethylsulfoxide (DMSO) or N,N-diethyl-m-toluamide (DEET). The penetration enhancing activity of methyl caprate was effective for human, mouse, and hamster skins. Methyl caprate also enhanced the penetration of vitamin D3, erythromycin, triamcinolone acetonide, testosterone, and hydrocortisone.

Absorption↗
PubMed1988

Preformed enzyme profiles of reference strains of gram-positive anaerobic cocci.

The preformed (constitutive) enzyme profiles of 30 type strains and reference strains of gram-positive anaerobic cocci were determined with two commercial systems, RapID ANA and a prototype system from API. Both systems identified Peptostreptococcus anaerobius, Ps. asaccharolyticus, Ps. indolicus, Ps. magnus and Ps. micros accurately, except for one strain of Ps. magnus misidentified as Ps. micros by the RapID ANA system. The indole-negative, butyrate-producing cocci (classified at present as Ps. prevotii and Ps. tetradius) produced several different, unique patterns with the prototype API system, but the results with RapID ANA were often misleading. Eight strains of Hare group cocci produced previously described profiles. Four strains of streptococci produced profiles easily distinguished from those of the gram-positive anaerobic cocci. We conclude that most gram-positive anaerobic cocci can be identified rapidly and reliably to the species level by their preformed enzyme profiles, providing that their underlying classification is sound. Problems were encountered with the butyrate-producing cocci, which appear to be a more heterogeneous group of organisms than is currently acknowledged; further taxonomic studies on these organisms are required.

Animals↗
PubMed1986

Clinical evaluation of rosoxacin for the treatment of chancroid.

One hundred seven men with Haemophilus ducreyi-positive chancroid were assigned to receive 300 mg of rosoxacin as a single dose or 150 mg twice daily for 3 days. Ulcers and buboes were followed clinically and bacteriologically for 1 month. Of 40 evaluable males on the 3-day regimen, 38 (95%) were cured, while only 14 of 23 (61%) males on the single-dose regimen were cured; this regimen was discontinued. There was one ulcer relapse at day 21 in both groups; the one relapse in the single-dose group had a persistent culture-positive bubo. Eight of nine (89%) buboes followed to the endpoint on the 3-day rosoxacin regimen were cured, versus three of six (50%) on the single-dose regimen. Adverse effects were mainly related to the central nervous system but were minor and did not require intervention. None of the treatment failures was due to organisms resistant to rosoxacin, and failure of the single-dose regimen presumably was related to duration of tissue levels rather than to drug resistance. Administration of 150 mg of rosoxacin twice daily for 3 days is an effective regimen for the therapy of chancroid and is a reasonable alternative to other short-course regimens.

4-Quinolones↗
PubMedDate not supplied

Single-dose ceftriaxone therapy of gonococcal ophthalmia neonatorum.

Ceftriaxone (125 mg) given as a single intramuscular dose without topical therapy was evaluated in seven infants with smear-positive gonococcal ophthalmia neonatorum. Neisseria gonorrhoeae was isolated from the eyes of six infants, and four of these isolates were penicillinase-producing N. gonorrhoeae. Two infants had concomitant ocular infection with Chlamydia trachomatis. All seven infants, when seen at follow-up, showed marked clinical improvement. Conjunctivitis resolved completely in four infants. One infant was lost to subsequent follow-up, while two infants had persistent ophthalmia due to C. trachomatis. Follow-up eye cultures for N. gonorrhoeae were all negative.

Ceftriaxone↗