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J S Andrews

Publications and source records attributed to J S Andrews.

At least 19 recordsLinked to original sources
PubMed1998

Synthesis, and in vitro and in vivo muscarinic pharmacological properties of a series of 1,6-dihydro-5-(4H)-pyrimidinone oximes.

A series of 1,6-dihydro-5-(4H)-pyrimidinone oxime derivatives I was synthesized (Scheme 1, Tables 1 and 2) and tested for muscarinic activity (Table 3) in receptor binding assays using [3H]-oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies that measured their potencies to inhibit the binding of Oxo-M and Pz. Preferential inhibition of Oxo-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. The series produced a wide range of active compounds with differing degrees of selectivity in M1, M2, and M3 functional models. Several compounds that have mixed agonist/antagonist profiles were able to reduce cholinergic-related cognitive impairments in models of mnemonic function. Substitutions (I, e.g. R2 or R3 = Me) at the 1,6-dihydro-5-(4H)pyrimidine ring disrupted binding and efficacy, whereas systematic variation of the oximes substituent R1 resulted in various degrees of potency and selectivity dependent on the nature of the substitution.

Animals↗
PubMed1998

Findings from the American College of Epidemiology's survey on Ethics guidelines. The American College of Epidemiology Ethics and Standards of Practice Committee.

PURPOSE: A survey to establish both the need and subject areas for a possible new set of ethics guidelines for epidemiologists was conducted among a random sample of 300 North American (Canada, Mexico, and United States) members of three major United States-based professional epidemiology organizations. METHODS: An 88% response rate revealed wide agreement on topics to be included in any new set of guidelines, but uncertainty prevailed about the need for new guidelines; 41% agreed that there was a need to develop a new set, 43% had no opinion, and 16% disagreed. RESULTS: There was almost no difference in preferences between men and women for topics to be included in a new set of guidelines, or between those aware or unaware of extant ethics guidelines in epidemiology. Fifty-four percent were aware of such guidelines and only 29% of these said they could describe the content of the guidelines. CONCLUSION: More needs to be done to evaluate the utility of ethics codes in epidemiology.

Data Collection↗
PubMed1998

5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential.

In vitro, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 exhibited high-affinity binding to the serotonin2C (5HT2C) receptors and stimulated turnover of inositol 1,4,5-triphosphate. Affinity to several of the other 5-HT receptor subtypes and to numerous nonserotonergic receptors was much lower. In rats, both compounds elicited behavioral signs of 5-HT2C receptor agonism but not 5-HT2A receptor agonism. Hypomotility induced in rats by high doses of these compounds was reversed by the 5-HT2C receptor antagonist N-(2-naphthyl)-N'-(3-pyridyl)-urea 1:1 HCI. In addition, these compounds were active in tests used to demonstrate anticompulsive effects: reducing schedule-induced polydipsia in rats (prevented by the 5-HT2C/2B receptor antagonist N-(1-methyl-5'-indolyl)-(3-pyridyl)urea 1:1 HCl, reversing increased scratching induced with 8-hydroxy-dipropylaminotetralin 1:1 HCl in squirrel monkeys (no tolerance developed), decreasing responding in the marble-burying task in mice, and decreasing excessive eating of palatable food in rats. In contrast to these compounds, fluoxetine was much less potent, and in some tasks less efficacious, in reducing excessive behavior in these models. These two 5-HT2C receptor agonists do not show anxiogenic effects in the plus-maze in rats. (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 reduced the olfactory bulbectomy-induced passive avoidance impairment in rats, a result that indicates antidepressant potential. Similarly, in the differential-reinforcement-of-low rate 72-s operant schedule task in rats, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 increased (and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 showed a tendency to increase) total reinforcements received, which is suggestive of antidepressant activity. The electroencephalography defined sleep-waking pattern in rats produced by these two 5-HT2C agonists, as well as fluoxetine, included increased quiet-waking and decreased rapid-eye-movement sleep, which is characteristic of antidepressant drugs. These results suggest that 5-HT2C receptor agonism is associated with therapeutic potential in obsessive compulsive disorder and depression.

Animals↗
PubMed1997

Pediatric carve outs. The use of disease-specific conditions as risk adjusters in capitated payment systems.

OBJECTIVE: To address the issue of adverse selection in capitated payment systems by developing a list of disease-specific pediatric conditions (i.e., "carve outs") to be considered for separate reimbursement. DESIGN: A descriptive study using a large Medicaid database. INTERVENTION: With the use of fiscal year 1993 Washington State Medicaid cost data for 302,240 pediatric patients, a list of disease-specific carve outs was developed to meet the following criteria: high cost, low variability in cost, and association with a large proportion of medical spending. RESULTS: Six-hundred seventy-three patients (0.2%) in the database had annual costs totaling $25,000 or more. Ten percent of the cases accounted for approximately two thirds of spending, while the least expensive 70% of cases made up only 15% of the expenditures. Prematurity and complications of prematurity, neoplasms, congenital heart disease, organ transplantations, congenital anomalies, and respiratory problems were general categories of disease that met our criteria for a carve out. The association of a major surgical procedure with a diagnosis increased the predictive accuracy for high cost. CONCLUSION: Lists of disease-specific carve outs such as this one can be used by Medicaid plans and other insurers who are concerned about risk selection to identify conditions for separate reimbursement in capitated payment systems.

Adolescent↗
PubMed1997

The father's role during infancy. Factors that influence maternal expectations.

OBJECTIVE: To describe factors that influence maternal expectations of the father's role during infancy. RESEARCH DESIGN: Cross-sectional survey. SETTING: Postpartum obstetric ward of an inner-city teaching hospital. SUBJECTS: Mothers who were residents in the inner-city communities that surround the hospital and who were recently delivered of a newborn. SELECTION PROCEDURE: Consecutive sampling from March to May 1992. MEASUREMENTS: Through structured maternal interviews, the father's expected role was measured in terms of accessibility, engagement in child care tasks, and decision-making responsibility. Influences included demographics, the mother's desire for the father's involvement, and her perceptions of his motivation, prenatal support, and ability to parent. RESULTS: Of 226 eligible mothers, 197 (87%) were interviewed. Expectations varied widely. Concerning accessibility, 48% and 18% of the mothers expected to see the father daily and less than weekly, respectively. Concerning engagement, 81% of the mothers expected some paternal involvement; the average mother assumed that the father would participate in one third of child care tasks. Concerning decision-making responsibility, 34% of the mothers expected to share all decisions; 30% expected to share none. In all areas, expectations were positively associated with the mother's desires, the strength of the parents' relationship, and the mother's perceptions of the father's motivation and ability to parent and the father's prenatal involvement (all, P < .001). Expected accessibility and engagement were greater for fathers who worked; expected engagement and decision-making responsibility were greater for fathers without children from other relationships (all, P < .03). CONCLUSIONS: The maternal desire for the father's participation, the strength of the parents' relationship, the mother's perception of the father as a parent, and the father's prenatal involvement are all consistently associated with the maternal expectations of the father's role. The demographic characteristics of either parent are not as strongly or consistently associated with the maternal expectations.

Adult↗
PubMed1996

Possible confounding influence of strain, age and gender on cognitive performance in rats.

There are substantial differences in the performance of various rat strains in tasks of learning, memory and attention. Strain, age and sex differences are not consistent over procedures: poor performance in one paradigm does not predict poor performance in a different paradigm. Some strain differences are not readily apparent until a direct comparison is made between one or more strains. Moreover, large differences in nominally the same strain but obtained from different suppliers have been observed in behavioural, pharmacological and physiological parameters and can have important consequences for interpretation of drug effects. Longevity, and the effects of ageing can differ dramatically from one strain to another; drug effects can alter radically with increasing age and show strain (and individual) differences in their action. Sex can further complicate interpretation of results. Thus, non-cognitive factors may exert a major effect on results in cognitive testing, and strain-dependent effects may account for many conflicting results in the literature concerning mnemonic performance. Strain differences in particular must be identified and used to help identify fundamental effects on memory, rather than continue to be ignored and allowed to obscure interpretation of drug effects on cognitive processes.

Age Factors↗
PubMed1996

Synthesis and muscarinic activities of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives.

A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of 3H-OXO-M and 3H-PZ. Preferential inhibition of 3H-OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. All compounds with agonistic properties showed 3H-PZ/3H-OXO-M potency ratios in excess of 20. In contrast, for antagonists this ratio was found to be close to unity. Mono-halogenation resulted in compounds (4b and 4d) with M3 agonistic properties as shown by their atropine sensitive stimulant properties in the guinea pig ileum, but with very little or no M1 activity. Some minor in vivo effects were observed for both these compounds, with the iodinated compound 4d inducing salivation. Compound 4d also showed some positive mnemonic properties in rats where spatial short-term memory had been compromised by temporary cholinergic depletion. These data indicate that some M3 agonism may be desired in therapeutic agents aimed at the treatment of the cognitive deficits of Alzheimer's disease patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Synthesis and muscarinic M3 pharmacological activities of 1-azabicyclo[2.2.2]octan-3-one oxime derivatives.

A series of 1-azabicyclo[2.2.2]octan-3-one oximes and related 1-azabicyclo-[2.2.2]-octan-3-one hydroxylamines were synthesized and tested for muscarinic M3 activity. All compounds showed at least some muscarinic binding properties, however, only one member of the series demonstrated mucarinic M3 agonistic properties in vitro (contraction of guinea pig ileum) and in vivo (mydriasis, salivation). In addition, this compound partially reversed the cognitive deficit induced by central cholinergic depletion in two procedures testing memory in the rat, namely the delayed matching to position and swim maze tasks of spatial memory in the rat.

Animals↗
PubMed1995

Pediatrics.

Children of mothers who smoked during pregnancy had IQ scores that were lower than the scores of children born to mothers who did not smoke. Routine use of nebulized steroids for croup can potentially reduce the need for hospitalization.

Humans↗
PubMed1995

Synthesis of a thio analogue of n-propyl kojibioside, a potential glucosidase inhibitor.

The disaccharide alpha-D-Glc p-(1-S-2)-beta-D-Glc p-(1-OPr) 1, a thio analogue of alpha-D-Glc p-(1 --> 2)-alpha-D-Glc p-(1-OPr)(n-propyl kojibioside) in which the inter-glycosidic oxygen atom is replaced by sulfur, has been synthesized for evaluation as a potential glucosidase inhibitor. Glycosylation of the 2-thiol glucopyranosyl acceptor 4 with the trichloroacetimidate of 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranose 5 gave the alpha-linked disaccharide 6 stereoselectively. Deprotection was performed by hydrogenolysis in the presence of Pd/C to give 1 as the beta-n-propyl glycoside. Glycosylation of the thiol 4 with the trichloroacetimidate of 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranose 8 gave a 1:2.3 mixture if the alpha and beta disaccharides (9 and 10); evidence is presented for the occurrence of the orthoester 11, as an intermediate in the formation of the beta-disaccharide.

Carbohydrate Sequence↗
PubMed1995

Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory.

The performance of four strains of rats commonly used in behavioural research was assessed in three different tests of learning and memory. The four strains included three outbred lines (Long-Evans, Sprague-Dawley, Wistar) and one inbred strain (S3). Learning and memory were tested using three different paradigms: autoshaping of a lever press, a two-object discrimination test, and performance in a two-island swim maze task. The pigmented strains showed better performance in the autoshaping procedure: the majority of the Long-Evans and the S3 rats acquired the response, and the majority of the Wistar and Sprague-Dawley failed to acquire the response in the set time. The albino strains were slightly better in the swim maze than the pigmented strains. There appeared to be a speed/accuracy trade-off in the strategy used to solve the task. This was also evident following treatment with the cholinergic-depleting agent hemicholinium-3. The performance of the Long-Evans rats was most affected by the treatment in terms of accuracy and the Wistar and Sprague-Dawleys in terms of speed. In the two-object discrimination test only the Long-Evans showed satisfactory performance and were able to discriminate a novel from a known object a short interval after initial exposure. These results show large task- and strain-dependent differences in performance in tests of learning and memory. Some of the performance variation may be due to emotional differences between the strains and may be alleviated by extra training. However, the response to pharmacological manipulation may require more careful evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Discriminative stimulus properties of the stereoisomers of the phosphodiesterase inhibitor rolipram.

The discriminative stimulus properties of the specific type IV phosphodiesterase inhibitor, rolipram, and its two stereoisomers were assessed using standard two-lever drug discrimination procedures in which responding on the appropriate lever was reinforced on a FR10 schedule. In three separate drug cues based on training rats to discriminate the racemate (0.2 mg/kg, IP), the (-)-isomer (0.1 mg/kg), or the (+)-isomer (2 mg/kg) from vehicle, all forms substituted for one another, differing only in potency. In keeping with published reports, the (-)-isomer was the more potent form, the (+)-isomer being approximately 10 times less potent. Several phosphodiesterase (PDE) inhibitors were found to substitute for the racemate cue, their potencies in the behavioural measure correlating with their potency in displacing [3H]rolipram from its forebrain binding sites in vivo (r = 0.95), suggesting that the discriminative stimulus depends on an action of the drug upon this site. Because rolipram has been reported to possess antidepressant activity, the ability of the tricyclic antidepressant imipramine to substitute for rolipram was investigated; doses of 10 and 20 mg/kg did not substitute. Amphetamine (0.156-1.25 mg/kg) also was inactive. Lisuride gave rise to drug-appropriate responding in 50% of rats only at a dose of 0.078 mg/kg, which severely disrupted responding. It is concluded that the rolipram discriminative stimulus is dependent on the selective PDE inhibitory activity of the drug, and that it does not constitute a cue based on the antidepressant property of rolipram.

Animals↗
PubMed1995

Tissue distribution and influence of selenium status on levels of selenoprotein W.

Rabbits were immunized with two synthetic peptides based on hydrophilic regions of selenoprotein W from rat muscle. The resulting polyclonal antibodies were used in Western blots to determine the compartmentation and tissue distribution of selenoprotein W, and to determine the influence of selenium on the levels of this selenoprotein in rat muscle. Selenoprotein W exists mainly in cytosol, but very small amounts were associated with membranes. Western blots revealed selenoprotein W in muscle, spleen, testis, and brain of rats. Rats were fed diets of either no addition of selenium (0 ppm Se) or additions of 0.1 and 4.0 mg selenium/g (0.1 ppm Se and 4.0 ppm Se) diet for 6 wk. Selenoprotein W was undetectable in skeletal muscle of rats fed the basal diet, detectable in those fed 0.1 ppm selenium in the diet, and much higher in muscle from rats fed 4 ppm selenium diet. In a species comparison, Western blots indicated the presence of selenoprotein W in muscle of rabbits, sheep, and cattle.

Amino Acid Sequence↗
PubMed1995

Conscious sedation in the pediatric emergency department.

Anxiety-provoking and painful emergency department procedures such as laceration repair are made more tolerable to the pediatric patient and easier for the practitioner through the judicious use of pharmacologic agents for conscious sedation and analgesia. Both the American Academy of Pediatrics and the American College of Emergency Physicians have published documents that guide the physician in the use of these agents in the care of children. Most new information concerns the evaluation of new drugs for use in the pediatric emergency department, adverse effects of familiar products, and evaluation of sedative and analgesic antagonist medications that may increase a practitioner's control when conscious sedation is used. Large controlled trials of protocols and drugs are necessary to establish safe, appropriate standards for conscious sedation in the pediatric emergency department.

Administration, Oral↗
PubMed1995

A quantitative system to evaluate diabetic retinopathy from fundus photographs.

PURPOSE: To evaluate a quantitative system to measure the early lesions of diabetic retinopathy seen in stereoscopic fundus photographs. METHODS: Using a quantitative classification system, photographs of 4657 eyes (7 stereo pairs of 35-mm slides per eye) were scored for 16 diabetic lesions. A single severity level (identical to the ETDRS Interim Scale) was calculated for each eye. The reliability of this technique, and its reproducibility by independent examiners, was evaluated for individual lesions and severity levels using percent agreement, kappa, and weighted kappa statistics. RESULTS: This quantitative technique demonstrated an "almost perfect" agreement (weighted kappa > or = 0.810) on all but one lesion by independent observers. For the severity levels, there was a 95.7% perfect agreement (kappa = 0.9428). The reproducibility of agreement over time was "almost perfect" on all but four lesions; with 88% perfect agreement (kappa = 0.8394) for severity levels. CONCLUSIONS: When used to evaluate the early lesions of diabetic retinopathy, the Vanderbilt Classification System is highly reliable between graders and over time. This system can gather quantitative data and evaluate incremental changes in an accurate, reproducible manner.

Diabetic Retinopathy↗
PubMed1994

Effects of disrupting the cholinergic system on short-term spatial memory in rats.

The effects of disrupting the muscarinic or nicotinic systems on short-term spatial memory were investigated using a delayed matching to position (DMTP) procedure. Rats were trained on the DMTP until stability and then divided into two groups: one group was implanted with an indwelling cannula aimed at the lateral ventricle. The cannulated group received injections of selective muscarinic antagonists (pirenzepine, M1; AFDX 116, M2; UH-AH 37, M1/M3) or hemicholinium-3 (a choline uptake inhibitor). The remaining animals were treated with conventional muscarinic antagonists (scopolamine, methyl scopolamine) or nicotinic channel blockers (mecamylamine, hexamethonium). Scopolamine, methyl scopolamine and UH-AH 37 disrupted all performance parameters in a non-specific but dose related manner. Pirenzepine disrupted accuracy in a delay, but not dose dependent manner, and exerted no other negative effects on performance. Hemicholinium-3-induced performance deficits showed some elements of effects seen following pirenzepine and scopolamine (delay dependent effects on accuracy, some negative effects on other motoric aspects of performance). AFDX 116 and hexamethonium had no significant effects on performance with respect to control. Mecamylamine reduced accuracy and increased response latencies at the highest dose tested. These data indicate that muscarinic antagonists are more effective at disrupting mnemonic performance than nicotinic blockers, and moreover, that distinct muscarinic receptors may have differential effects on cognitive performance.

Animals↗
PubMed1994

The effects of ibotenic acid lesions of the basal forebrain on visual discrimination performance in rats.

Rats were trained to stable performance in a conditional brightness discrimination task and then received infusions of ibotenic acid or vehicle into the basal forebrain. Following 2 weeks of recovery, animals were retested in the original discrimination. Lesioned rats tended to performed badly on the first day of testing as measured by all parameters (percent correct responding, latency to respond, and missed trials) but thereafter, most rats recovered quickly to prelesion levels. In keeping with previous reports, an approximately 30% reduction in choline acetyltransferase activity was observed in the lesioned animals. Four rats showed no recovery over a period of several months; however, an analysis of the choline acetyltransferase in several brain regions revealed no obvious differences to those animals in which performance recovered. Postlesion testing with the putative nootropic beta-carboline ZK 93426 showed no major differences to the effects observed in control animals. Scopolamine had similar negative effects in both groups tested. These data indicate that deficits induced by lesions of the basal forebrain do not correlate with reductions in cholinergic activity.

Animals↗