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Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

At least 145 records · Page 8Linked to original sources
PubMed1985

Stability of ranitidine hydrochloride in total parenteral nutrient solution.

The stability of ranitidine hydrochloride was studied in a standard total parenteral nutrition (TPN) solution. The Canadian formulation of ranitidine hydrochloride (25 mg/mL) was added in 100-, 200-, and 300-mg doses to approximately 1200 mL of a TPN solution and allowed to stand at room temperature (23 degrees C) for seven days. During this time, samples were drawn at least once a day, and the ranitidine concentration was determined by high-performance liquid chromatography. The ranitidine concentration declined at roughly the same rate regardless of the initial concentration. During the study period, each of the three different concentrations declined to less than 70% of the initial concentration. Approximately 10% of the initial concentration was lost in 48 hours. Ranitidine hydrochloride admixtures were stable for up to 48 hours at room temperature in this standard TPN solution.

Chromatography, High Pressure Liquid↗
PubMed1984

Sjögren's syndrome in MRL/l and MRL/n mice.

Six autoimmune murine models (MRL/l, MRL/n, NZB, NZB/NZW, PN, C57BL/6J-lpr/lpr) were compared with normal control C57BL/6J and DBA/2 mice to determine if spontaneous autoimmune disease was associated with evidence of Sjögren's syndrome. Schirmer tests documented dry eyes in NZB/NZW and PN mice; other autoimmune strains and controls had normal tear formation. All autoimmune mice had conjunctivitis, but this abnormality was most severe in the PN strain. Ninety-eight percent of MRL/l and MRL/n mice had mononuclear cell infiltrates in lacrimal glands, and salivary glands were involved to a lesser degree. New Zealand mice and PN mice had smaller gland lesions. The extensive gland destruction in MRL/l and MRL/n mice suggested that these substrains merit further studies as animal models of Sjögren's syndrome.

Animals↗
PubMed1984

Responses to T-cell and B-cell mitogens in autoimmune Palmerston North and NZB/NZW mice.

Palmerston North (PN) mice, a newly recognized model of systemic lupus erythematosus, were compared with autoimmune hybrid NZB/NZW mice in a study designed to examine spleen cell responsiveness to T-cell and B-cell mitogens. Modest reductions of responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were noted in PN females after 24 weeks of age; these responses were reduced significantly in NZB/NZW females. In contrast, male PN and NZB/NZW mice responded actively to PHA and Con A throughout the first year of life. Responses to lipopolysaccharide were not affected by age or sex. Anti-DNA antibody levels, blood urea nitrogen, and glomerular histology were analyzed to determine if autoantibody production or renal failure correlated with suppressed mitogenic responsiveness. These factors, examined singly and together, were not as important as age. In this system, age and sex did not influence spleen cell responses to mitogens in normal CD-1 mice. Age and sex were of minimal importance in determining responses to T-cell mitogens in the recently defined PN model of autoimmunity. In contrast, age and sex exerted strong influences upon responses to PHA and Con A in the NZB/NZW model of lupus.

Age Factors↗
PubMed1984

The goldfish nervus terminalis: a luteinizing hormone-releasing hormone and molluscan cardioexcitatory peptide immunoreactive olfactoretinal pathway.

Antisera to two putative neurotransmitters, luteinizing hormone-releasing hormone (LHRH) and molluscan cardioexcitatory tetrapeptide (H-Phe-Met-Arg-Phe-NH2; FMRF-amide), bind specifically to neurites in the inner nuclear and inner plexiform layers of the goldfish retina. Retrograde labeling showed that intraocular axon terminals originate from the nervus terminalis, whose cell bodies are located in the olfactory nerves. Double immunocytochemical and retrograde labeling showed that some terminalis neurons project to the retina; others may project only within the brain. All terminalis neurons having proven retinal projections were both LHRH- and FMRF-amide-immunoreactive. The activity of retinal ganglion cells was recorded with microelectrodes in isolated superfused goldfish retinas. In ON- and OFF-center double-color-opponent cells, micromolar FMRF-amide and salmon brain gonadotropin-releasing factor ( [Trp7, Leu8] LHRH) caused increased spontaneous activity in the dark, loss of light-induced inhibition, and increased incidence of light-entrained pulsatile response. The nervus terminalis is therefore a putatively peptidergic retinopetal projection. Sex-related olfactory stimuli may act through it, thereby modulating the output of ganglion cells responsive to color contrast.

Animals↗
PubMed1984

The evaluation of an automatic system for filling liquids into hard gelatin capsules.

A system is described in which an intermittent motion powder filling capsule machine is modified to fill liquids into hard gelatin capsules suitable for pilot scale or small production batches. The system is shown to be suitable for filling materials covering a wide range of viscosities and to give excellent fill weight uniformity which is largely independent of operating conditions. The process is clean and trouble-free.

Automation↗
PubMed1984

Educating patients with rheumatoid arthritis: a prospective analysis.

Twenty-two men with rheumatoid arthritis were randomly assigned to either a patient education group, receiving standard inpatient medical care in addition to a formal education program, or a control group receiving only the inpatient medical care. Members of the groups were not significantly different in terms of age, degree of life stress, socioeconomic status, educational level, or years since onset of rheumatoid arthritis. Dependent measures included the Arthritis Knowledge Inventory (AKI), the Arthritis Impact Measurement Scales (AIMS), and the Beck Depression Inventory (BDI), and they were collected preeducation, posteducation, and at a three-month followup. Results from the AIMS revealed improvement in dexterity, social role, depression, and overall health status for both groups. The BDI also revealed significantly less depression for both groups, reflecting a general improvement following medical intervention. Although the patient education group revealed significantly higher scores on the knowledge measure, they also revealed significantly more impairment of activity levels and significantly higher pain scores. Education was effective for increasing rheumatoid arthritis knowledge, but such topics as joint protection and disease process may adversely affect how patients view their physical capacities and interpret their pain.

Adaptation, Psychological↗
PubMed1983

Band keratopathy in MRL/l and MRL/n mice.

To define ocular abnormalities in mice with autoimmune disease, we performed biomicroscopic examinations and examined ocular tissue in MRL/l, MRL/n, NZB, NZB/NZW, and Palmerston North mice. Results were compared with MRL/Mp--lpr/lpr, C57BL/6J--lpr/lpr, and normal control strains. Eighty-seven percent of MRL/l and MRL/n mice had typical band keratopathy; this was confirmed by histologic examination. Posterior uveitis was found in 35% of adult MRL/l mice. MRL substrains are potentially important models of ocular disease.

Animals↗
PubMed1983

High incidence of neoplasms in female NZB/NZW mice treated with pulse doses of cyclophosphamide.

The immunosuppressive properties of cyclophosphamide prevent formation of anti-DNA antibodies and prolong lifespans in autoimmune NZB/NZW mice, an animal model of systemic lupus erythematosus. In the current study, NZB/NZW mice were treated with weekly doses of cyclophosphamide to determine if intermittent pulses of the drug were effective therapy. Life-long treatment with cyclophosphamide, 56 mg/kg/week, was started at the mean age of 6 weeks; results were compared with saline-injected control mice. Pulse therapy with cyclophosphamide suppressed anti-DNA antibody levels, prevented severe glomerulonephritis and prolonged longevity. Seventeen of 19 treated mice developed neoplasms; 7 of these immunosuppressed animals had 2 to 4 separate neoplasms. Examination of earlier studies in this laboratory in which NZB/NZW mice were treated each day with cyclophosphamide showed that daily and weekly therapeutic regimens had similar immunosuppressive and oncogenic effects.

Animals↗
PubMed1983

Dose-dependent effect of cimetidine on phenytoin kinetics.

Eight normal subjects were given 250 mg intravenous phenytoin alone and with 3-day regimens of oral cimetidine, 400 mg at bedtime, 1200 mg a day, and 2400 mg a day in a randomized crossover fashion. Plasma samples for phenytoin and cimetidine, and urinary concentrations for phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) were measured by HPLC. All cimetidine regimens decreased phenytoin clearance, and there was no difference between the 400-mg bedtime dose and the 1200-mg a day regimens. There was, however, a difference between the 400-mg and 1200-mg and the 2400-mg regimens. There was no linear correlation between steady state cimetidine plasma concentrations and the decrease in phenytoin clearance. Urinary HPPH/phenytoin ratios decreased with all cimetidine treatments, but the differences were not significant. Phenytoin toxicity may result when cimetidine is added to existing regimens of this anticonvulsant.

Adult↗
PubMed1982

Prolonged lifespans in female NZB/NZW mice treated with the experimental immunoregulatory drug frentizole.

Autoimmune female New Zealand Black/New Zealand White mice were treated with frentizole, an experimental immunosuppressive drug. Three groups of "young," 8-week-old mice received high-dose frentizole (80-84 mg/kg/day), low-dose frentizole (8 mg/kg/day), or no drug (controls); these mice were followed until spontaneous death. Three groups of "old," 24-week-old mice with established lupus-like disease were treated with high or low doses of frentizole. Old control mice received no drug. After 12 weeks of therapy, surviving old mice were killed. Beneficial therapeutic response was achieved when high-dose treatment was started at an early age; antiDNA values were suppressed, and longevity was prolonged significantly. Frentizole did not arrest the progression of renal disease in old mice. Glomerulonephritis and vasculitis were the most common causes of death in young and old animals. Twenty-nine percent of young, high-dose-treated mice died with neoplasms. Large glomerular deposits of IgG, IgM, and C3 were present in renal tissue from treated and control mice. Peripheral lymphocyte counts and mitogenic responses of spleen cells were not changed by treatment. The efficacy of frentizole in a murine model of lupus supports its usefulness as an immunoregulatory drug.

Age Factors↗
PubMed1982

Active groups of saxitoxin and tetrodotoxin as deduced from actions of saxitoxin analogues on frog muscle and squid axon.

1. The actions of three saxitoxin (STX) analogues have been studied on the frog sartorius muscle fibre and the squid giant axon. One--neosaxitoxin--is a natural analogue, and two--decarbamylsaxitoxin and reduced saxitoxin--are synthetic. 2. The maximum dV/dt of the action potential in paired-muscle protocol is reduced by the analogues with relative potencies: STX (1), tetrodotoxin (1), neo-STX (1), decarbamyl-STX (0.2) and reduced-STX (0.01). 3. In constant-current studies on frog muscle fibres and in voltage-clamp studies on squid axons, all three analogues block only the sodium channel without affecting the potassium channel. 4. All three analogues bind to the same site as does STX in a competitive manner. 5. The experimental results suggest that the active groups in STX are the 7,8,9 guanidinium and the C-12 hydroxy groups. The carbamyl group contributes to, but is not essential for activity. 6. Stereospecific groups in the tetrodotoxin (TTX) molecule are the 1,2,3 guanidinium and the C-9, C-10 hydroxy groups. C-4 and C-8 groups are also important. 7. As new view is proposed in which STX and TTX can bind to a receptor located in the outside surface of the membrane very close to the orifice of the sodium channel.

Action Potentials↗
PubMed1982

Stability of sodium hypochlorite solutions.

The stability of diluted solutions of sodium hypochlorite was studied. Sodium hypochlorite 1% solutions were diluted (1:8, 1:12, and 1:20) and stored at room temperature in a window exposed to sunlight in amber-glass, two-liter bottles that were two-thirds full. Samples were taken 25 times throughout a six-month study period; bottles were opened only on sampling days. An iodometric titration was used to determine the percent available chlorine in each sample. Least-squares regression analyses of the percent available chlorine yielded lines with negative slopes for each dilution (-7.7 X 10(-6), -8.1 X 10(-6), and -1.5 X 10(-6) for the 1:8, 1:12, and 1:20 dilutions, respectively). Using the fastest degradation rate (from the 1:12 dilution), 5.24% of available chlorine would be lost per year. The concentration of sodium hypochlorite would therefore remain above 90% of the initial concentration for 22.9 months. It is concluded that sodium hypochlorite solution stored in amber-glass bottles should carry a 23-month expiry date on chemical stability.

Drug Stability↗
PubMed1981

High-performance liquid chromatographic methods for determination of gentamicin in biological fluids.

A selective and sensitive methods for the determination of gentamicin in plasma and urine by high-performance liquid chromatography has been developed. Following deproteinization, the gentamicin is reacted with fluorescamine to produce a fluorescent derivative. This reaction mixture is directly chromatographed on a cation exchange column using as mobile phase acetonitrile-phosphoric acid (7:3). The gentamicin compounds elute as a single peak. Using 0.1 ml of plasma, quantitation of gentamicin concentration as low as 1 mg/l are possible. Possible interference from other aminoglycosides and antibiotics is discussed.

Animals↗
PubMed1981

Cold dependent activation of complement in systemic lupus erythematosus. A unique cause for a discrepancy between clinical and laboratory parameters.

A 31-year-old woman with systemic lupus erythematosus (SLE) was studied because she developed markedly reduced total hemolytic complement activity at a time when her disease was clinically inactive. Functional assays demonstrated reduced activities of C1, C4, and C2, but normal concentrations of C3 and the terminal (C5-9) components were present. Antigenic concentrations of C1, C4, and C2 were normal. Plasma or serum obtained from blood allowed to clot at 37 degrees C had normal complement activity. Complement activity was depleted when the patient's serum was incubated in the cold. At reduced temperatures, the patient's serum (or purified IgG) depleted complement activity of normal human sera. A second patient with SLE was also demonstrated to have this same phenomenon. Cryoglobulins were not detectable in these patients. These data indicate that in vivo the patients' complement was normal and that the observed in vitro reduction was caused by cold dependent activation of the classical pathway.

Adolescent↗