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Biomedical subjects

L A Walker

Publications and source records attributed to L A Walker.

At least 19 recordsLinked to original sources
PubMed1995

Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.

Animals↗
PubMed1994

Urinary incontinence knowledge among community-dwelling people 65 years of age and older.

OBJECTIVES: We determined elderly persons' knowledge about the epidemiology and treatment of urinary incontinence (UI) as part of a preintervention survey for the Educational Demonstration of Urinary Continence Assessment and Treatment for the Elderly (EDUCATE). DESIGN: An intact-group pretest-posttest design was employed to measure the effects of multimethod educational interventions on the knowledge, attitudes, and practices of physicians and older people concerning UI. PARTICIPANTS: A random sample of community-dwelling people aged 65 years and older from two counties in Massachusetts was selected (n = 1,140). MEASUREMENT: A 14-item urinary incontinence quiz was developed from information presented in the AHCPR UI Guideline Panel's recommendations. Participants answers to the quiz were part of a 20-minute telephone interview. RESULTS: For nine of the fact items, the elderly respondents were more likely to give the correct answer than the incorrect answer. However, for only four of those nine did the percentage of correct responses exceed 50% (there were substantial proportions of "don't know" responses). For several fact items, those who were younger, female, or had more formal education were more likely to provide correct responses. CONCLUSIONS: There are substantial gaps in the knowledge of older persons about urinary incontinence, especially among men, those age 85 and older, and those with lower levels of education. These knowledge gaps may contribute to misinterpretation of symptoms and underreporting of symptoms to health care professionals. This pattern of findings indicates a greater need for community education on urinary incontinence.

Age Factors↗
PubMed1993

Identification of four biliary metabolites of the diterpene sclareol in the laboratory rat.

1. Ag.l.c. method was developed to determine sclareol (1) and its microbial metabolites: 3-keto-sclareol (2), 2 alpha-hydroxysclareol (3), 3 alpha-hydroxysclareol (4), 3 beta-hydroxysclareol (5), 18-hydroxysclareol (6), and 2 alpha, 18-dihydroxysclareol (7) in both microbial cultures and biological fluids of the laboratory rat. 2. Metabolism of the diterpene (1) was studied in the laboratory rat. This in vivo study was facilitated by the availability of microbial metabolites of sclareol as reference standards, and the g.l.c. assay for sclareol and its metabolites in biological fluids. 3. Following i.v. treatment (100 mg/kg), the disappearance of (1) from rat plasma was rapid and biphasic. No microbial metabolites of sclareol were detectable in plasma. 4. Sclareol (1) and its microbial metabolites were not detected in rat urine following either i.v. or oral treatments; unchanged (1) was excreted in rat faeces to the extent of 9% of an oral dose in 48 h. 5. Following i.v. treatment, 0.02% dose was recovered in bile as unchanged (1). Four biliary metabolites of (1) (0.4% dose) were identified as (2), and (4)-(6) based on g.l.c.-mass spectrometry and comparisons with reference standards. All four biliary metabolites of (1) in rat have been identified as microbial metabolites of (1).

Animals↗
PubMed1992

Hydrogen exchange in Pseudomonas cytochrome c-551.

Hydrogen exchange rates were measured or estimated for 75 amide protons in in ferrocytochrome c-551 from Pseudomonas aeruginosa (82 residues total) at neutral pH and 300 K. Rate constants span at least eight orders of magnitude. Rate constants or limiting estimates were determined by a combination of methods relying upon 1H-NMR spectroscopy, including the direct observation in one- or two-dimensional spectra of the decrease in proton intensity for samples dissolved in deuterium oxide, or, in a few favorable cases, saturation transfer from the solvent protic water. The heme ligand residues and the thioether bridge residues were slowly exchanging backbone amides, but the slowest exchanging backbone amides were found in two clusters. One was composed of Ile-48 and Lys-49 in the last turn of what is termed the 40's helix in the protein. The second was composed of Leu-74, Ala-75, Lys-76 and Val-78 in the C-terminal alpha helix.

Amino Acid Sequence↗
PubMed1992

Development and evaluation of a novel dissolution apparatus for medicated chewing gum products.

A novel dissolution apparatus was developed for medicated chewing gum products. A prototype gum product containing phenylpropanolamine hydrochloride (PPA) was used to evaluate the apparatus. The apparatus consists of a conical Teflon base and a rotating, ribbed Teflon plunger suspended in a dissolution vessel. Parameters evaluated were rotation speed, plunger frequency, medium volume, medium type, medium sampling location, number of plunger ribs, and number of gum pieces. Samples were taken over a 20-min period and samples were analyzed by HPLC. Cumulative percentage released-versus-time profiles were obtained for each parameter evaluated. Statistical analysis of the gum product indicated that the only significant differences occurred at the lowest rotation speed and lowest plunger frequencies. A Level A correlation was found between the in vitro release profile for the 20-rpm and 30-cycles/min plunger frequency and the in vivo chew-out study.

Chemistry, Pharmaceutical↗
PubMed1991

Rectal bioavailability of delta-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys.

Oral administration of delta-9-tetrahydrocannabinal (delta 9-THC) was shown to result in low and erratic bioavailability, while the drug showed no bioavailability from various suppository formulations. delta 9-THC-Hemisuccinate was formulated as a prodrug for delta 9-THC in suppositories using Witepsol H15 base. The bioavailability of delta 9-THC from this formulation was evaluated in monkeys. The plasma levels of delta 9-THC and its metabolite 11-nor-delta 9-THC-9-COOH were determined using GC/MS analysis. The calculated bioavailability of delta 9-THC from this formulation was found to be 13.5%. Non-compartmental analysis of the plasma concentration data using statistical moments showed the mean residence time (MRT) for delta 9-THC in the body to be 3 h following iv administration of delta 9-THC or its hemisuccinate ester (3.4 and 2.7 h, respectively), as compared with 5.8 h following rectal administration of the delta 9-THC hemisuccinate. The observed rectal bioavailability of delta 9-THC from suppositories containing the hemisuccinate ester as a prodrug is of significant importance in developing an alternative approach to oral administration of the drug.

Administration, Rectal↗
PubMed1991

Anticholinergic activity of bornaprine and its metabolites in the isolated rat atrium.

These studies evaluated the antimuscarinic activity of bornaprine hydrochloride, a synthetic anticholinergic drug utilized in the treatment of parkinsonism. Several of its metabolites were also evaluated. Biological activity was assessed by the ability of the compounds to inhibit the negative inotropic response to carbachol in the isolated left atrium of the rat. Bornaprine showed a pA2 value (concentration required to reduce the agonist response by 50%) of 7.27 +/- 0.21. The exo and endo epimers were approximately equipotent in this regard. One metabolite, the 5-hydroxyl, showed similar activity to the parent compound, whereas 2 other hydroxylated metabolites showed much less effect.

Animals↗
PubMed1990

Pharmacologic and toxicologic effects of di(beta-phenylisopropyl)amine (DPIA) in rats and mice.

1. Di(beta-phenylisopropyl)amine (DPIA) given i.p. to mice and rats in sublethal doses caused increased motility, mild stereotypic behavior and suppression of food intake. Repeated daily doses led to enhanced motor stimulation, and in one group, 40% lethality, indicating development of "reverse tolerance". Brain monoamine modifiers prevented DPIA-induced motor activity. 2. Treatment with toxic i.p. doses of DPIA enabled determination of the LD50, which was 106.8 mg/kg for isolated mice and 89.7 mg/kg for mice kept in aggregation after dosing. Possible antidotal agents given before a high DPIA dose (LD50) protected significantly against lethality. 3. Combinations of DPIA with (+)-amphetamine in mice at lethal doses showed a subadditive synergism. 4. Effects of DPIA on the cardiovascular system, both i.v. in anesthetized rats and in isolated atrial preparations, were mainly opposite to those of (+)-amphetamine, namely decreases in blood pressure, force of contraction and heart rate.

Amphetamine↗
PubMed1990

Renal function during onset of carbachol-induced hypertension in conscious rats.

This study evaluated the changes in renal function that occur during the early phases of chronic infusion of carbachol into the lateral ventricle in conscious rats. Infusion of 1.0 micrograms/h of carbachol i.c.v. resulted in a prompt pressor response with mean arterial pressure rising 20 mm Hg within 15 min. The pressure remained elevated for the duration of a 2-hour infusion. Carbachol infusion at 0.5 micrograms/h induced a similar elevation in blood pressure, but the onset was delayed, reaching significance only after 30-60 min. The higher dose of carbachol was associated with a marked and sustained natriuresis, with sodium excretion increasing from 2.1 +/- 0.3 to 5.3 +/- 1.0 microEq/100 g min after 2 h, compared to 2.0 +/- 0.5 and 1.8 +/- 0.3 microEq/100 g min in vehicle-infused control animals. Sodium excretion did not change significantly in animals infused with carbachol at 0.5 microgram/h. There were no significant changes in glomerular filtration rate in any of the groups. Plasma levels of atrial natriuretic peptide (ANP) were not altered significantly by ventricular infusion of carbachol (188 +/- 99 before vs. 83 +/- 17 pg/ml after infusion). It is concluded that the pressor response to central carbachol infusion is not dependent on retention of sodium and water. The natriuresis observed with carbachol infusion can be dissociated from the pressor response, and is not mediated by ANP.

Animals↗
PubMed1990

Effects of morphine on the renal handling of sodium and lithium in conscious rats.

The present study was carried out in order to assess the renal response to i.v. morphine in the rat, particularly the effects on tubular handling of sodium and lithium. Rats were prepared surgically with arterial and venous catheters and bladder cannulas. Clearance experiments and measurements of blood pressure and heart rate were carried out at least 4 days after surgery in unanesthetized animals. Intravenous administration of morphine (4 mg/kg b.wt.) caused a decrease in fractional sodium excretion, (at 90 min after injection, vehicle, 2.49 +/- 0.30% vs. morphine, 1.12 +/- 0.17%, P less than .05), in the absence of significant changes in systemic hemodynamics or glomerular filtration rate. This effect was prevented by pretreatment with naloxone. Enhanced proximal tubular reabsorption of sodium was considered as a possible explanation for the decrease in sodium excretion which followed morphine administration. Proximal tubular fluid reabsorption was estimated utilizing the lithium clearance method. Results indicated a reduction in fractional excretion of lithium by morphine administration (at 90 min, vehicle, 34.2 +/- 3.3% vs. morphine, 18.8 +/- 2.3%, P less than .05), which was also prevented by naloxone pretreatment. It is concluded that, under the present experimental conditions, morphine enhances tubular reabsorption of sodium by an opiate receptor-dependent mechanism and that this effect is, at least in part, localized in the proximal tubule.

Animals↗
PubMed1988

MAST application in the treatment of paroxysmal supraventricular tachycardia in a child.

A case of paroxysmal supraventricular tachycardia (PSVT) in a child with successful termination of the arrhythmia by military antishock trouser (MAST) application is described. The use of MAST application in terminating PSVT in adults has been previously reported. Ours is the first such case reported using this method in the therapy of PSVT in children. Our report suggests that MAST application may be another maneuver to add to those vagal maneuvers known to be of benefit in the termination of PSVT in children as well as in adults.

Child↗
PubMed1988

Urinary concentrations of ovarian steroid hormone metabolites and bioactive follicle-stimulating hormone in killer whales (Orcinus orchus) during ovarian cycles and pregnancy.

Reproductive hormone profiles of six captive killer whales (Orcinu orcus) from three Sea World aquaria were studied for intervals up to 2 yr. Daily urine samples and bimonthly blood samples were collected and analyzed for hormone concentration. Immunoreactive estrone conjugates, pregnanediol-3-glucoruonide, 20-alpha-hydroxyprogesterone as well as bioactive follicle-stimulating hormone (FSH) were measured in urine samples and indexed by creatinine concentrations of the same sample. In selected cases, serum progesterone concentrations were also measured. Three of the animals in the study became pregnant during the study period and two of these animals were evaluated during the time of conception and throughout most of gestation. From the data of the three animals that conceived, hormone profiles of the complete ovarian cycle, early pregnancy, and mid- to late gestation are described. The remaining three animals did not conceive and only one of these demonstrated hormone changes that indicated regular ovarian activity. The female reproductive pattern of the killer whale is characterized by a gestation of 17 mo and an ovarian cycle of 6-7 wk in duration. The hormone changes associated with the ovarian cycle of the killer whale are similar to those of most other mammalian species. A bimodal pattern of bioactive FSH with a pronounced rise of estrogen predominates the preovulatory hormone profile. After ovulation, increased progesterone production is observed for approximately 4 wk in the nonconceptive ovarian cycle. During the luteal phase and early pregnancy, when progesterone metabolites are elevated, estrogen metabolite excretion remains low. These data extend the application of urine collections for longitudinal studies involving hormone changes, particularly those involving nondomesticated species.(ABSTRACT TRUNCATED AT 250 WORDS)

20-alpha-Dihydroprogesterone↗
PubMed1988

Iron-regulated outer membrane proteins of Escherichia coli K-12 and mechanism of action of catechol-substituted cephalosporins.

Selected aminothiazolyl-oxime cephalosporin congeners substituted at C-3' with a catechol moiety were used to probe the basis of the enhanced antibacterial activity against Escherichia coli K-12 often associated with chemical modifications of this type. Evidence is presented for a tonB-dependent illicit transport of the compounds across the outer membrane of E. coli K-12, the process involving jointly and specifically the Fiu and Cir iron-regulated outer membrane proteins. Thus, both tonB and fiu cir mutants showed a comparably reduced susceptibility to the probe compounds, whereas mutants singularly lacking any one of the six iron-regulated outer membrane proteins (Fiu, FepA, FecA, FhuA, FhuE, and Cir) or lacking any combination of any two of these proteins (except Fiu plus Cir) did not show this resistance. Mutants devoid of all six iron-regulated outer membrane proteins were no more resistant to the probe compounds than fiu cir or tonB strains. In addition to the latter genes, the products of the exbB and possibly the exbC loci were necessary for maximal antibacterial potency. A dependence of antibacterial activity on the level of expression of the uptake system components was noted. Comparison of penicillin-binding protein target affinity with antibacterial activity suggested a possible periplasmic accumulation of active compounds by E. coli K-12. Free vicinal hydroxyl groups of the catechol residue were a primary chemical requirement for recognition by the uptake pathway and thus for high antibacterial activity.

Bacterial Outer Membrane Proteins↗
PubMed1988

AIDS encephalopathy with response to treatment.

A 3 year old boy who had acquired HIV infection transplacentally developed the classical features of AIDS encephalopathy, spastic diplegia and expressive aphasia. His computed tomogram showed cerebral atrophy. Treatment with zidovudine and weekly infusions of gammaglobulin led to considerable clinical improvement and an almost normal computed tomogram nine weeks later.

Antiviral Agents↗
PubMed1988

Selective induction of light chain synthesis in cultures of blood lymphocytes from patients with IgG myelomatosis.

In the present study evidence is provided that neoplastic B cells from the blood from four of 24 patients with myelomatosis were activated selectively with polyclonal B cell mitogens. In three of these patients the activated cells produced light chains without heavy chains; of these, two patients had IgGK paraproteins and one had free lambda light chain disease. The ratio of kappa-expressing to lambda-expressing B cells in the initial blood B cell preparations was within the range for healthy controls for all four patients where neoplastic B cells were selectively activated. It is concluded that in some patients with myelomatosis the neoplastic clone is a mosaic of: (1) cells capable of synthesizing both light and heavy chains with (2) cells producing light chains only.

Adult↗
PubMed1988

Effects of central administration of morphine on renal function in conscious rats.

Systemic administration of morphine in rats produces an anti-natriuretic effect that is at least partially dependent on renal nerves. The present studies were carried out in order to assess the renal response to central administration of morphine. Male Sprague-Dawley rats were surgically prepared with arterial, venous and bladder cannulas. In addition, a guide cannula was placed into the lateral ventrical and secured to the surface of the skull. Experiments were carried out at least 3 days after surgery. Renal clearance measurements were 30 min each. After a basal period, morphine sulfate (4 micrograms/4 microliters) or vehicle was injected into the lateral cerebral ventricle. Two clearance measurements were obtained, followed by central administration of naloxone HCl (4 micrograms/4 microliters) or vehicle and two more clearance periods. Morphine administration had no effect on blood pressure or heart rate but caused a sharp reduction in sodium excretion (3200 +/- 958 vs 970 +/- 158 nEq/100 g/min in period 5; P less than .05). This response was reversed by the addition of naloxone (3280 +/- 583 nEq/100 g/min in period 5; P less than .05). Furthermore, morphine had no effect on renal plasma flow and glomerular filtration rate. Naloxone increased the renal plasma flow and glomerular filtration rate in morphine-treated rats, whereas it had no effect in controls. It is concluded that central administration of morphine in conscious rats enhances renal tubular sodium reabsorption by an opiate receptor-dependent mechanism.

Animals↗