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Biomedical subjects

K Mueller

Publications and source records attributed to K Mueller.

At least 19 recordsLinked to original sources

Correlates of health insurance coverage: evidence from the Midwest.

The Midwest is often overlooked in national studies of health insurance status. We analyzed the economic and social characteristics of uninsured and underinsured individuals and households in a Midwestern state using both bivariate and multivariate techniques. As in much of the country, economic factors, particularly income and employment, were most significant in accounting for insurance coverage. Unexpectedly, rural and urban residents were equally likely to lack insurance. Results indicate that in rural areas, underinsurance may be a greater problem than uninsurance, and that income-based health insurance is more effective than employer-provided plans in reaching all Americans.

Adolescent

Functional characteristics of the rrnD promoters of Escherichia coli.

The function of the tandem rrnD promoters (P1, P2) of Escherichia coli, which are highly efficient in directing rRNA synthesis, was studied in vitro using the strong hybrid promoter PtacI as a reference. One of the characteristics of the rrnD promoters is a pronounced instability of binary and initiating complexes formed with RNA polymerase. The rate of productive complex formation and of chain initiation at these promoters was found to be limited by a step in binary complex transitions with an apparent first-order rate constant equal to 3.9 x 10(-2) s-1. A comparison of this rate with that determined previously by filter binding assays (Gourse, R. (1988) Nucleic Acids Res. 16, 9789-9809) suggests that the rate-limiting step is a conversion of an intermediate species of open complex to one that is efficient in productive initiation. The slow rate of this reaction and the instability of open complexes account for the relatively low competitive strengths of the rrnD promoters. However, this limitation of rrn promoter function changes with promoter occupancy because the rate of chain initiation increased after completion of the first round of initiation. Despite their poor competitive strength, the rrnD promoters are more productive than PtacI at nonlimiting RNA polymerase concentrations. This can be ascribed to the different rates with which RNA polymerases leave PtacI and the rrnD promoters. These functional differences of the promoters are consistent with a "stressed intermediate" model of chain initiation (Straney, D.C., and Crothers, D.M. (1987) J. Mol. Biol. 193, 267-278) which predicts that rapid clearance of the rrn promoters is mechanistically related to the instability of the binary complexes.

Chromosome Deletion

Effect of acupuncture-point stimulation on diastolic blood pressure in hypertensive subjects: a preliminary study.

Electrical stimulation of four specific acupuncture points (Liver 3, Stomach 36, Large Intestine 11, and the Groove for Lowering Blood Pressure) was examined in order to determine the effect of this stimulation on diastolic blood pressure in 10 subjects with diastolic hypertension. Subjects were randomly divided into two groups: (1) an Acu-ES group, which received electrical stimulation applied to the four antihypertensive acupuncture points, and (2) a Sham-ES group, which received electrical stimulation applied to non-acupuncture-point areas. A repeated-measures analysis of variance revealed a significant, immediate poststimulation reduction of diastolic blood pressure for the Acu-Es group versus the Sham-ES group. Further studies are needed to determine whether there are other acupuncture points, stimulation characteristics, or modalities that can enhance this treatment effect and whether the treatment effect can last for a clinically significant period of time.

Acupuncture Points

Enkephalin prevents CCK-induced enhancement of amphetamine-induced locomotor stereotypy.

Enkephalin (ENK) and/or cholecystokinin octapeptide (CCK-8) were infused into nucleus accumbens of rats prior to injection with saline or 1.0 mg/kg amphetamine. Behavior was observed in an open-field paradigm which allowed assessment of locomotor stereotypy (repetitive routes or patterns of locomotion) as well as assessment of lines crossed and rears. Neither CCK nor ENK nor the combination of the two affected the behavior of saline-injected rats in the open field. CCK enhanced the locomotor stereotypy produced by amphetamine without affecting any of the other behaviors recorded. ENK had no effect on the behavior of amphetamine-treated rats when given alone, but ENK prevented the effect of CCK. Thus, enkephalin and CCK interact to modulate amphetamine-induced locomotor stereotypy.

Amphetamines

The effects of haloperidol and amphetamine on ascorbic acid and uric acid in caudate and nucleus accumbens of rats as measured by voltammetry in vivo.

The ability of haloperidol (0.1 mg/kg) to reduce the amphetamine-induced (2 and 5 mg/kg) increase in ascorbic and uric acid in anterior caudate and in nucleus accumbens was tested using voltammetry in vivo. In both areas, haloperidol reduced the amphetamine-induced increase in uric acid. In both areas, haloperidol only marginally affected the amphetamine-induced increase in ascorbic acid. Amphetamine-induced increases in uric acid were more nearly dose-related than changes in ascorbic acid. Of the two compounds, uric acid seems more likely to be associated with dopamine.

Amphetamine

Scopolamine produces locomotor stereotypy in an open field but apomorphine does not.

Both dopaminergic and nondopaminergic drugs produce hyperlocomotion in rats. Dopaminergic drugs also produce focused stereotypy (absence of locomotion and intense sniffing or licking/biting of a restricted area of the environment). Some drugs produce repetitive routes of locomotion; this phenomenon might represent a combination of hyperlocomotion and stereotypy. Scopolamine (an acetylcholine antagonist) and apomorphine (a dopamine agonist) both produce hyperlocomotion in rats; apomorphine also produces focused stereotypy but scopolamine does not. This research determines whether these drugs also produce locomotor stereotypy as measured by gamma. Scopolamine (0.5 and 2.0 mg/kg) produced locomotor stereotypy at both doses. Apomorphine (1.0, 2.0, and 3.0 mg/kg) failed to reliably produce locomotor stereotypy. Thus, there is not necessarily a relationship between the ability of a drug to produce focused stereotypy and the ability of the drug to produce locomotor stereotypy.

Animals

The effects of amphetamine and pilocarpine on the release of ascorbic and uric acid in several rat brain areas.

Linear sweep voltammetry was used to investigate the effects of amphetamine (which enhances the release of dopamine) and/or pilocarpine (a cholinergic agonist) on the release of ascorbic acid and uric acid in brain areas differing in dopamine and acetylcholine concentrations. In caudate, nucleus accumbens, and hippocampus, the magnitude of the amphetamine-induced increase in ascorbic acid was roughly correlated with dopamine content of the brain area tested. Cingulate cortex was a notable exception; the increase in ascorbic acid was greater than that in nucleus accumbens. Pilocarpine produced the greatest increase in ascorbic acid in cingulate cortex, even though cingulate cortex has the lowest acetylcholine concentration of the brain areas tested. Except for cingulate cortex, the ascorbic acid data were consistent with the hypothesis that amphetamine and pilocarpine release different pools of ascorbic acid. The uric acid data were consistent with the hypothesis that amphetamine and pilocarpine release the same pool of uric acid. The unexpected findings in cingulate cortex may point to an important role of ascorbic acid in this brain area.

Amphetamine

Hypolipidemic activity of rifamycin derivatives.

Series of 3-piperidinyl- and 3-piperazinylrifamycins and to a certain extent 3-hydrazonorifamycins all bearing lipophilic side chains were found to exert potent hypolipidemic activity in lowering both serum cholesterol and LDL-cholesterol in rats. Starting from 3-[N'-(2,4,6-trimethylbenzyl)-N-piperazinyl]rifamycin SV (compound 25), a series of derivatives were synthesized with the aim of dissociating the hypolipidemic from the antibacterial activity, leading to the 8-O,N-dipivaloyl derivative of 25 (compound 48), which is devoid of any antibacterial activity but shows about 50-60% reduction of LDL-cholesterol and 20-30% reduction of serum cholesterol at a dose of 10 mg/kg. Compound 48 was selected for further pharmacological evaluation.

Animals

Repeated administration of high doses of amphetamine increases release of ascorbic acid in caudate but not nucleus accumbens.

Linear sweep voltammetry with carbon paste electrodes was used to monitor extracellular ascorbic acid (AA) in the caudate nucleus and nucleus accumbens of behaving rats. Amphetamine (2 or 5 mg/kg) was administered 4, 6 and 8 days after surgery. In general the amphetamine-induced increase in AA was greater in the caudate than in the nucleus accumbens. Furthermore, in the nucleus accumbens the amphetamine-induced increase in AA was very similar on all test days, but in the caudate the increase in AA produced by 5 mg/kg amphetamine was progressively larger on each test day. Thus AA seems to be regulated differently in the caudate and nucleus accumbens.

Amphetamines

Triazolam attenuates amphetamine but not morphine conditioned place preferences.

In a series of four experiments the benzodiazepine triazolam was tested for reinforcing effects and for effects on reinforcement induced by amphetamine and morphine. Reinforcement was assessed in a conditioned place preference paradigm. Triazolam did not produce reinforcing or aversive effects when administered in doses ranging from 0.0625 to 0.5 mg/kg. Triazolam did attenuate reinforcing effects produced by 0.75 and 1.25 mg/kg amphetamine. No effect of triazolam was observed on morphine-induced reinforcement. These results indicate that the administration of triazolam can affect the brain mechanisms that mediate the reinforcing effects of amphetamine but not morphine.

Amphetamine

Another look at amphetamine-induced stereotyped locomotor activity in rats using a new statistic to measure locomotor stereotypy.

Rat open field behavior is often used as a tool to study the behavioral effects of drugs. In this report, drug-induced patterns of locomotion in an open field were studied with the aid of a simple new statistic. Briefly, the animal's path through the open field is converted into a series of trips. Gamma (gamma) estimates the probability that the animal will repeat the trip that it has just exhibited; thus gamma quantifies "locomotor stereotypy". Trip lengths can also be compared across drug groups. Thus caffeine has no effect on gamma even though it produces a dose-related increase in locomotions. Caffeine does not produce amphetamine-like stereotypy. On the other hand, amphetamine produces a dose-related increase in gamma. Although gamma was designed to detect any pattern of locomotor behavior, rats treated with high doses of amphetamine almost always exhibited the same pattern of locomotor behavior - repetitive trips around the perimeter of the open field. Although further characterization of the statistic is necessary, these findings suggest that gamma has potential for quantifying "locomotor stereotypy" and for providing a more subtle description of locomotor behavior in general.

Amphetamine

Infusions of cholecystokinin octapeptide into the ventral tegmental area potentiate amphetamine conditioned place preferences.

Cholecystokinin (CCK) and dopamine (DA) coexist in both cell body and terminal areas of a mesolimbic pathway that projects from the ventral tegmental area (VTA) to the nucleus accumbens (N ACC). Autoradiography reveals extensive CCK binding sites in the N ACC, but not in the VTA. However, iontophoresis of CCK into the VTA results in activation or deactivation of DA neuronal firing rates, and bursting activity (depending on the dose of CCK administered). CCK could have neuromodulatory effects on mesolimbic DA neurons. In two studies, behavioral effects of infusions of CCK into the VTA were examined in the conditioned place preference (CPP) paradigm. The CPP paradigm is a behavioral test used to assess reinforcement induced by drug administration. Drugs with reinforcing properties can condition preferences for novel environments. CCK infusions into VTA (0.0, 0.04, 0.4, and 4.0 ng/cannula) potentiated amphetamine CPPs in a dose-dependent linear manner. CCK infusions by themselves did not have significant effects in the CPP paradigm. Results indicate a neuromodulatory role for CCK on the neuronal mechanisms that mediate the reinforcing effects of amphetamine. Results also implicate sites of action for CCK in the VTA.

Amphetamine

Time course of amphetamine-induced locomotor stereotypy in an open field.

Gamma (gamma) is a recently proposed statistic that quantifies and describes the repetitive patterns of locomotion (locomotor stereotypy) exhibited by amphetamine-treated rats in an open field. The time-course of locomotor stereotypy after 1, 2, 3, and 4 mg/kg amphetamine was investigated in this research. Locomotor stereotypy was often evident during the first observation period after amphetamine. Lower doses of amphetamine produced qualitatively different locomotor stereotypy than higher doses. Rats given higher doses of amphetamine exhibited locomotor stereotypy during the "hyperactivity" phase of the three-phase response produced by higher doses of amphetamine (hyperactivity; absence of locomotions, increased sniffing, biting etc.; hyperactivity). Contrary to expectations, rats injected with 2 mg/kg amphetamine exhibited the highest and most sustained increase in gamma. We conclude that locomotor stereotypy is an important component of the behavioral effects of amphetamine in rats. Whether locomotor stereotypy and focused stereotypy are similar phenomena is still unclear.

Amphetamine

Effects of caerulein + haloperidol on amphetamine-induced locomotor stereotypy in rats.

The combination of haloperidol + caerulein has been reported to produce a long-lasting reduction of amphetamine-induced hyperlocomotions in rats. This study was designed to replicate those findings and to determine whether haloperidol + caerulein produce any unique effect on amphetamine-induced locomotor stereotypy. In two experiments, haloperidol + caerulein failed to produce a long-lasting reduction in amphetamine-induced hyperlocomotions. Although haloperidol reduced the locomotor stereotypy produced by higher doses of amphetamine, caerulein had no effect, either alone or combined with haloperidol.

Amphetamine

Illness behavior and personality changes in patients with chronic prostatitis during a two-year follow-up period.

Illness behavior and personality changes during a 2-year follow-up period were studied in 40 patients with chronic prostatitis. In the first study, the existence of psychic problems among the subjects was high. Sexual problems were striking. During the follow-up period the personality of the patients did not change, but subjective well-being, both psychosocial and somatic, was impaired. Sexual problems and homosexual behavior also increased. In addition, the cooperation of the patients markedly decreased and their illness behavior became problematic. The results indicate a strong need for psychic support of these patients.

Adult

The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.

CGP 28238 (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ) exhibits very potent anti-inflammatory activity in rat adjuvant arthritis (ED40 = 0.05 mg/kg, p.o.) and pronounced analgesic and antipyretic activity in acute models in mice and rats (ED50 2-5 mg/kg, p.o.), but has clear advantages over reference NSAIDs with respect to gastro-intestinal tolerability. Threshold doses for gastro-intestinal ulcerogenicity in rats after single and repeated (10x) doses were found to be 30 mg/kg, p.o., and prostaglandin (PGE2) production in rat gastric and ileal mucosa was only marginally inhibited (ED50 greater than 30 mg/kg, p.o.). On the other hand, PGE2 production in rat inflammatory exudate and thromboxane synthesis in rat blood were inhibited with ED50 values of less than or equal to 2 mg/kg, p.o. Although CGP28238 does not inhibit cyclooxygenase in bovine seminal vesicle microsomal preparations (IC50 greater than 10(-3) mol/l), potent inhibition of prostaglandin synthesis was shown in various in vitro systems using human and animal cells with IC50 values of less than 10(-6) mol/l. IL-1-stimulated bone resorption and PGE2 production in murine calvarial cultures were inhibited with IC50 values of 3 x 10(-7) and 2 x 10(-8) mol/l, respectively. 5-Lipoxygenase (murine macrophages), phospholipase A2 (human PMN) and phospholipase C (human platelets) were not inhibited. CGP 28238 may represent a novel highly potent anti-inflammatory compound with improved gastro-intestinal safety.

Analgesics