Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 37 records · Page 2Linked to original sources

PubMed1992

Acidic fibroblast growth factor accelerates the healing of acetic-acid-induced gastric ulcers in rats.

Acidic fibroblast growth factor (aFGF) was evaluated for the healing of acetic-acid-induced gastric ulcers in rats. The effect of aFGF on angiogenesis in the gastric ulcer bed was determined by the carmine dye infusion method, while its effect on gastric acid secretion was assessed in chronic gastric fistula rats. Oral treatment with aFGF, in the presence of heparin, reduced (ED50 value = 30.2 micrograms/kg/day) the acetic-acid-induced gastric ulcer area, when assessed 1 week later. aFGF was about 1,333-fold more potent than famotidine for healing such ulcers. At a dose of 200 micrograms/kg/day, aFGF increased the carmine density 3-fold and correspondingly reduced (80%) the gastric ulcer area. Thus, the ulcer healing effect of this agent involves angiogenesis in the gastric ulcer bed. This effect of aFGF appears to be unrelated to an inhibition of gastric acid secretion, as it was ineffective in chronic gastric fistula rats. In summary, oral aFGF significantly accelerates the healing of experimental gastric ulcers in rats. It may be a potent and effective agent for the treatment of peptic ulcers in humans.

Acetates↗

PubMed1992

Maternal smoking and the risk of polyhydramnios.

BACKGROUND: Washington State birth certificates were used to conduct a population-based case-control study to assess the possible association of maternal smoking with polyhydramnios. METHODS: All singleton births complicated by polyhydramnios (n = 557) were identified from the vital records for the years 1984 to 1987. For comparison, 1671 records were randomly selected for the same years from singleton births uncomplicated by polyhydramnios. RESULTS: Women who reportedly smoked prenatally were found to be at increased risk for polyhydramnios (relative risk [RR] = 1.7, 95% confidence interval [CI] = 1.5-2.1, adjusted for marital status, maternal age, and parity). When women with conditions known to be associated with polyhydramnios were excluded, the risk for those who smoked prenatally remained elevated (RR = 1.8, 95% CI = 1.1-2.3). CONCLUSION: Overdistention of the uterus from polyhydramnios may cause a variety of pregnancy complications. The observed association of smoking with polyhydramnios may be a further indication for public health interventions aimed at preventing smoking during pregnancy.

Adult↗

PubMed1992

Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala.

Data derived from in vitro preparations indicate that NMDA receptors play a critical role in synaptic plasticity in the CNS. More recently, in vivo pharmacological manipulations have suggested that an NMDA-dependent process may be involved in specific forms of behavioral plasticity. All of the work thus far has focused on the possible role of NMDA receptors in the acquisition of responses. However, there are many examples in the behavioral literature of learning-induced changes that involve the reduction or elimination of a previously acquired response. Experimental extinction is a primary example of the elimination of a learned response. Experimental extinction is well described in the behavioral literature, but has not received the same attention in the neurobiological literature. As a result, the neural mechanisms that underlie this important form of learning are not at all understood. In the present experiments, the fear-potentiated startle paradigm was employed to begin to investigate neural mechanisms of extinction. The results show that infusion of the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure known to be important for fear conditioning, dose-dependently blocked extinction of conditioned fear. Control experiments showed that the blockade of extinction was neither the result of the permanent disruption of amygdaloid function nor the result of decreased sensitivity of the animals to the conditioned stimulus. Infusion of AP5 into the interpositus nucleus of the cerebellum, a control site, did not block extinction. Finally, intra-amygdala infusion of a selected dose of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione did not block extinction of conditioned fear. These results, together with a previous report from our laboratory (Miserendino et al., 1990), demonstrate the importance of the amygdala in the elaboration of conditioned fear and suggest that an NMDA-dependent process might underlie the extinction of conditioned fear.

2-Amino-5-phosphonovalerate↗

PubMed1992

Corticotropin-releasing factor: long-lasting facilitation of the acoustic startle reflex.

Intracerebroventricular infusion of corticotropin-releasing factor (CRF) (0.1-1.0 micrograms) produced a pronounced, dose-dependent enhancement of the acoustic startle reflex in rats. This excitatory effect began about 20-30 min after infusion, grew steadily over the 2 hr test period, and lasted at least 6 hr. Higher doses of CRF (10 micrograms) often produced marked facilitation and then inhibition of startle that oscillated repeatedly with a period of 10-20 min. CRF-enhanced startle did not result from an increase in sensitization produced by repetition of the startle stimulus or from a blockade of habituation. Peripheral injections of the autonomic ganglionic blockers hexamethonium (10 mg/kg) or chlorisondamine (3 mg/kg) slightly attenuated the magnitude of CRF-enhanced startle, suggesting a partial role of peripheral sympathetic activation. Intracerebroventricular infusion of the CRF antagonist alpha-helical CRF9-41 (alpha hCRF; 25 or 50 micrograms) blocked CRF-enhanced startle when infused 5 min prior to CRF, indicating a central site of action. CRF-enhanced startle also was reversed when alpha hCRF was given 90 min after infusion of CRF. This suggests that exogenously applied CRF remains in the brain for a very long time after administration or that CRF given exogenously initiates a process that results in a long-lasting activation of endogenous CRF. Because the startle reflex is elevated by both conditioned and unconditioned fear, these data lend further support to the idea that CRF infusion produces a behavioral state that resembles fear or anxiety. Because startle is mediated by a well-defined neural pathway, CRF-enhanced startle may provide a useful behavioral assay to analyze the neural systems upon which exogenous CRF acts to produce its behavioral effects.

Acoustic Stimulation↗

PubMed1992

A comparison between two forms of aerobic dance and treadmill running.

Aerobic dance has been reported to result in a disproportionately higher heart rate than running at a similar percent of VO2max. It has been suggested that the extensive use of the arms overhead during aerobic dance results in an increase in sympathetic outflow thereby disproportionately increasing the heart rate. To compare the hemodynamic and sympathetic nervous system activity responses during aerobic dance and treadmill running, nine healthy females exercised at approximately 50% of their VO2max during each of the following three exercise trials: aerobic dance where the arms were used extensively overhead (ABOVE), aerobic dance where the arms were kept below the shoulders (BELOW), and treadmill running (TR). Mean heart rate values during the ABOVE, BELOW, and TR trials were 136 beats.min-1 for all three trials. Mean VO2 values during the ABOVE, BELOW, and TR trials were 1.48, 1.51, and 1.47 l.min-1, respectively, and were not significantly different. Mean cardiac output for the ABOVE, BELOW, and TR trials were 13.5, 14.0, and 13.0 1. min-1, respectively, and were not significantly different. Postexercise blood lactate and norepinephrine values were not significantly different among the three trials. These results suggest a similar relationship between heart rate and VO2 during low intensity aerobic dance and running and do not support the contention that the use of the arms overhead during aerobic dance exercise elicits a disproportionately greater increase in heart rate as compared with running. Additionally these results demonstrate similar cardiovascular and sympathetic nervous system responses between aerobic dance exercise and running.

Adult↗

PubMed1992

Lesions of the perirhinal cortex but not of the frontal, medial prefrontal, visual, or insular cortex block fear-potentiated startle using a visual conditioned stimulus.

The present study is part of an ongoing series of experiments aimed at delineation of the neural pathways that mediate fear-potentiated startle, a model of conditioned fear in which the acoustic startle reflex is enhanced when elicited in the presence of a light previously paired with shock. A number of cortical areas that might be involved in relaying information about the visual conditioned stimulus (the light) in fear-potentiated startle were investigated. One hundred thirty-five rats were given 10 light-shock pairings on each of 2 consecutive days, and 1-2 d later electrolytic or aspiration lesions in various cortical areas were performed. One week later, the magnitude of fear-potentiated startle was measured. Complete removal of the visual cortex, medial prefrontal cortex, insular cortex, or posterior perirhinal cortex had no significant effect on the magnitude of fear-potentiated startle. Lesions of the frontal cortex attenuated fear-potentiated startle by approximately 50%. However, lesions of the anterior perirhinal cortex completely eliminated fear-potentiated startle. The effective lesions included parts of the cortex both dorsal and ventral to the rhinal sulcus and extended from approximately 1.8 to 3.8 mm posterior to bregma. Lesions slightly more posterior (2.3-4.8 mm posterior to bregma) or lesions that included only the perirhinal cortex dorsal to the rhinal sulcus had no effect. The region of the perirhinal cortex in which lesions blocked fear-potentiated startle projects to the amygdala, and thus may be part of the pathway that relays the visual conditioned stimulus information to the amygdala, a structure that is also critical for fear-potentiated startle. In addition, the present findings are in agreement with numerous studies in primates suggesting that the perirhinal cortex may play a more general role in memory.

Acoustic Stimulation↗

PubMed1992

Fluids, electrolytes, and nutrition in the low-birth-weight infant.

The management of fluids, electrolytes, and nutrition in the low-birth-weight and premature infant is an essential component of nursing care. The discussion of this crucial aspect of care includes the implications of physiologic immaturity and current recommendations for intervention as infants progress from intravenous fluids and electrolytes to parenteral nutrition, gavage feeding, and bottle feeding. It is hoped that breastfeeding is achieved.

Enteral Nutrition↗

PubMed1992

Lesions of the central nucleus of the amygdala, but not the paraventricular nucleus of the hypothalamus, block the excitatory effects of corticotropin-releasing factor on the acoustic startle reflex.

Intracerebroventricular (icv) infusion of corticotropin-releasing factor (CRF) was previously found to produce a long-lasting, dose-dependent (0.1-1.0 microgram) increase in the amplitude of the acoustic startle reflex. The present study sought to determine where in the CNS CRF acts to increase startle. Intracisternal infusion of CRF (0.1-1.0 microgram) increased startle with a time course and magnitude similar to that produced by icv CRF, unlike intrathecal infusion, which produced a small, more rapid enhancement of startle. While lesions of the paraventricular nucleus of the hypothalamus had no effect on icv CRF-enhanced startle, bilateral lesions of the central nucleus of the amygdala significantly attenuated the excitatory effect of icv CRF but had no effect on intrathecal CRF-enhanced startle. Even though lesions of the amygdala blocked icv CRF-enhanced startle, local infusion of CRF into the amygdala did not significantly elevate startle. The present data indicate that the amygdala is part of the neural circuitry required for icv CRF to elevate startle, but does not appear to be the primary receptor area where CRF acts. The involvement of the amygdala in icv CRF-enhanced startle is consistent with the hypothesis that both the amygdala and CRF are critically involved in fear and stress.

Acoustic Stimulation↗

PubMed1991

Induction of the c-fos proto-oncogene in rat amygdala during unconditioned and conditioned fear.

Induction of the nuclear proto-oncogene c-fos in rat amygdala was investigated 30-40 min following the presentation of mild footshocks (unconditioned fear) or of contextual cues associated with similar footshocks 24 h earlier (conditioned fear). Initially, it was found that handling rats for the first time elevated c-fos mRNA levels, but this response could be blocked completely by repeated handling. Unconditioned and conditioned fear both elevated amygdala c-fos mRNA dramatically above control levels.

Amygdala↗

PubMed1991

A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS.

OBJECTIVE: To evaluate foscarnet sodium in treating cytomegalovirus retinitis in patients with AIDS. PATIENTS: Twenty-four previously untreated persons with AIDS and cytomegalovirus retinitis who were at low risk for loss of their visual acuity. INTERVENTION: PATIENTS were randomly assigned to receive either no therapy (delayed treatment, control group) or immediate treatment with intravenous foscarnet at a dose of 60 mg/kg body weight three times a day for 3 weeks (induction regimen) followed by a maintenance regimen of 90 mg/kg once a day. MEASUREMENTS: PATIENTS were examined weekly until they reached the primary clinical end point, defined as progression of their retinitis border by 750 microns or the development of a new retinal lesion due to cytomegalovirus. Progression was evaluated using retinal photographs by masked readers. Secondary evaluations included changes in visual acuity, cytomegalovirus shedding in the blood and urine, serum levels of human immunodeficiency virus type 1 (HIV-1) p24 antigen, and total CD4 T lymphocyte counts. RESULTS: The mean time to progression of retinitis was 3.2 weeks in the control group (n = 11) compared with 13.3 weeks in the treatment group (n = 13) (P less than 0.001). Nine of 13 patients in the treatment group had positive blood cultures for cytomegalovirus at entry and all nine cleared their blood of cytomegalovirus by the end of the induction period (P = 0.004) compared with one of six patients in the control group. No reductions in p24 levels were seen in the control patients compared with a reduction of more than 50% in p24 levels for all four patients on treatment for whom follow-up levels were available. The main adverse effects of foscarnet treatment were seizures (2 of 13 patients), hypomagnesemia (9 of 13), hypocalcemia (11 of 13), and elevations in serum creatinine above 176.8 mumol/L (2.0 mg/dL) (3 of 13). The control patients received an average of 0.2 units of blood per week compared with an average of 0.6 units of blood per week for the patients on treatment. CONCLUSIONS: The administration of foscarnet decreases the rate of progression of cytomegalovirus retinitis in persons with AIDS. Its judicious use is likely to prevent loss of vision in these patients. In this study, however, there was little change in visual acuity in patients in either the immediate or delayed treatment group because only patients with non-sight-threatening disease were selected.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Heterogeneity of the molecular basis of hereditary pyropoikilocytosis and hereditary elliptocytosis associated with increased levels of the spectrin alpha I/74-kilodalton tryptic peptide.

Hereditary pyropoikilocytosis (HPP) and hereditary elliptocytosis are closely related, congenital disorders of the red blood cell usually associated with defective spectrin self-association and abnormal limited tryptic digestion of the N-terminal of domain of spectrin. Enhanced cleavage by trypsin of spectrin from affected individuals at arginyl residue 45* and lysyl residue 48* frequently yields increased amounts of an alpha 1/74-Kd fragment at the expense of the normal alpha 1/80-Kd parent fragment. Limited tryptic digestion of three unrelated individuals with HPP showed the alpha 1/74 defect. To ascertain the molecular defect responsible for the abnormality, the structure of exon 2 of the alpha-spectrin gene was examined. Genomic DNA from the subjects was amplified by the polymerase chain reaction using primers flanking exon 2. Restriction endonuclease digestion of amplified products showed the loss of the HindIII site at codons 47 and 48 in one allele of subject 1 and abolished the AhaII site at codons 27 and 28 in one allele of subjects 2 and 3. Nucleotide sequence analysis of subcloned amplified DNA from the HPP subjects showed three novel amino acid substitutions. In subject 1 (a black individual), a single base substitution (AAG----AGG) at codon position 48 changes amino acid residue lysine to arginine. In subject 2 (a white individual), a single base substitution (CGT----AGT) at codon 28 changes arginine to serine. In subject 3 (a black individual), a different base substitution at position 28 (CGT----CTT) changes arginine to leucine. These mutations occur at positions of the alpha l domain where other mutations have also been described, indicating that the normal residues at these positions play an important role in spectrin dimer self-association and thus, in membrane stability.

Adolescent↗

PubMed1991

Comparison of Oculab Tono-Pen readings obtained from various corneal and scleral locations.

When estimating intraocular pressure in patients who are uncooperative or who have central corneal disturbances, the physician may find it either impractical or undesirable to place the small tip of a portable electronic applanation tonometer (Tono-Pen) over the central cornea. To gauge better the usefulness of Tono-Pen readings obtained from various locations, we compared such readings measured through the central cornea, midperipheral cornea, limbal cornea, and sclera of 15 cannulated eye bank eyes. Mean Tono-Pen readings from the midperipheral and clear limbal cornea did not differ significantly from central corneal readings over a 10- to 35-mm Hg range of intraocular pressures and were within +/- 2.4 mm Hg of mean central corneal readings. Mean readings taken from the sclera, however, were 8.8 to 17.0 mm Hg higher than mean central corneal readings over the 10- to 40-mm Hg range. We concluded that multiple noncentral corneal readings with the Tono-Pen provided a useful approximation of intraocular pressure, whereas scleral readings did not.

Cornea↗

PubMed1991

Public-academic linkages in western States.

The role of the Western Interstate Commission for Higher Education (WICHE) in facilitating collaboration between higher education and state mental health agencies in the western states is presented in this paper. Unique service and training problems posed by sparsely populated states with limited numbers of professionally trained personnel and few clinical training programs make collaboration an important human resource issue in the West. WICHE's efforts over the past ten years to strengthen collaboration and the recent development of a regional coalition of educators, providers, and consumers to solve chronic treatment and research problems in the western states are described.

Academies and Institutes↗

PubMed1991

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats.

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05-10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (-) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 micrograms) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methyl-para-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, to an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.

Acoustic Stimulation↗

PubMed1991

Effects of septal lesions on fear-potentiated startle, and on the anxiolytic effects of buspirone and diazepam.

The present study evaluated the effect of septal lesions on baseline startle amplitude, potentiated startle (a measure of conditioned fear), and the ability of either buspirone or diazepam to block potentiated startle. Baseline responding to an acoustic stimulus was obtained for all rats, followed by potentiated startle training (ten light-shock pairings on each of two days). Rats were then given bilateral electrolytic lesions of the septum or sham surgery. Four and seven days following surgery all rats were tested again for baseline startle amplitude. Ten days postsurgery, rats were injected with either 5.0 mg/kg buspirone or vehicle and tested for potentiated startle (increased acoustic startle in the presence of a light previously paired with shock). Five days later septal-lesioned animals were injected with either 5.0 mg/kg of diazepam or vehicle and again tested for potentiated startle. Septal lesions increased baseline startle amplitude significantly, but did not alter the magnitude of potentiated startle or impair the ability of buspirone or diazepam to block potentiated startle. In Experiment 2 rats were trained using the above procedures, and were subsequently given discrete bilateral lesions of the lateral septum or sham surgery. Lateral septal lesions again had no effect on the magnitude of potentiated startle. These findings do not support an involvement of the septum in the inhibition of fear, or in the mediation of the anxiolytic effects of buspirone or diazepam.

Animals↗

PubMed1991

Topical mechlorethamine in the treatment of mycosis fungoides. Uniformity of application and potential for environmental contamination.

Topical mechlorethamine hydrochloride is commonly used in the treatment of mycosis fungoides and has been formulated in both aqueous and ointment vehicles. Two concerns regarding the topical application of mechlorethamine hydrochloride relate to the adequacy of skin coverage that can be attained by the patient and the extent to which others in the patient's household might be exposed to the drug. In this study six patients applied either aqueous or ointment vehicles containing a fluorescent dye. Subsequent examination of the skin under a Wood's lamp revealed a significant percentage of body surface area to be missed during application; several areas were noted to be missed most commonly. These observations have led to specific alterations in instructions given to patients regarding drug application. Examination of the surrounding environment showed minimal evidence of contamination.

Administration, Cutaneous↗

PubMed1991

Efferent pathway of the amygdala involved in conditioned fear as measured with the fear-potentiated startle paradigm.

Fear-potentiated startle in the rat is a measure of conditioned fear that is blocked by lesions of the central nucleus of the amygdala. In a companion study, Rosen, Hitchcock, Sananes, Miserendino, and Davis (1991) demonstrated a direct anatomical projection from the central nucleus to the brainstem startle reflex circuit. In the present study, fear-potentiated startle was blocked by lesions that interrupted this pathway at 3 different levels or by a crossed lesion that interrupted the pathway at its source on one side and at a more caudal level on the other side. Although synaptic relays have not been ruled out entirely, the data suggest that the direct projection from the central nucleus of the amygdala to the startle circuit mediates the expression of fear-potentiated startle. These findings are consistent with the literature indicating that efferent projections from the central nucleus to various brainstem structures are involved in the expression of several conditioned fear responses.

Amygdala↗

PubMed1991

A direct projection from the central nucleus of the amygdala to the acoustic startle pathway: anterograde and retrograde tracing studies.

Previous work has shown that lesions of the central nucleus of the amygdala block fear-potentiated acoustic startle and that electrical simulation of the central nucleus enhances acoustic startle in rats. In the present study, the anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to identify and delineate the course of a direct projection from the central nucleus of the amygdala to the nucleus reticularis pontis caudalis, a nucleus in the acoustic startle circuit. Experiments using the retrograde tracer Fluoro-Gold confirmed this and indicated that the rostral part of the medial subdivision of the central nucleus of the amygdala contains the cells that project to the startle circuit. With this information, lesion studies (see companion article Hitchcock & Davis, 1991) may be used to determine whether this projection plays a role in fear-potentiated startle.

Amygdala↗