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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 271 records · Page 15Linked to original sources
PubMed1995

Rare diseases, drug development, and AIDS: the impact of the Orphan Drug Act.

The Orphan Drug Act provides public subsidies and incentives to spur the development of drugs for rare diseases--drugs that the private sector might otherwise consider unprofitable to produce. Although the act has achieved numerous successes, the high prices and extraordinary sales generated by some orphan drugs lead to a pivotal policy question: how can the act be used to meet the legislative goal of stimulating drug development for small patient populations without resulting in prices that make drugs inaccessible? This question is explored using the example of AIDS drugs, many of which received subsidies under the act, to illustrate central points. The history of the act, its weaknesses, and strategies for reform are described as well.

AIDS-Related Opportunistic Infections↗
PubMed1995

Carbohydrate absorption from fruit juice in young children.

OBJECTIVE: To compare carbohydrate absorption following ingestion of apple juice and white grape juice in 28 healthy children. DESIGN: Randomized, double-blind crossover study. SETTING: Outpatient pediatric clinic at Maimonides Medical Center. PARTICIPANTS: A total of 18 healthy infants (mean age 6.3 months) and 10 toddlers (mean age 18.0 months), representing those ages when juice is first introduced (6 months) and when juice comprises a large portion of the diet (18 months). METHODS: Breath hydrogen (H2) testing was performed after age-specific servings of white grape juice or apple juice, 4 and 8 ounces respectively, were consumed. These portions provided approximately 1 g of fructose per kg of body weight. Breath H2 responses of > 20 ppm were considered positive, indicating incomplete absorption of fruit juice carbohydrates. RESULTS: In the combined age groups, carbohydrate malabsorption occurred more frequently after apple juice consumption (54%) than after white grape juice (19%; P < .001). Significant differences in area under the breath H2 curve (AUC) were also found between the two juices in both age groups. Among toddlers, the differences between the mean peak breath H2 responses were significant (48 ppm after apple juice consumption compared with 12 ppm after white grape juice; P < .001). These differences were not significant in the infant group. Significant differences (P < .05) were seen between the two age groups after consumption of apple juice; the toddlers exhibited a greater number of positive breath H2 responses and higher peak responses compared with the infants. Data from the children who drank both juices showed significant differences in peak breath H2 responses after consumption of apple juice compared with white grape juice (P < .005). CONCLUSIONS: The study demonstrated less carbohydrate malabsorption following ingestion of white grape juice compared with apple juice in healthy 6- and 18-month-old children.

Beverages↗
PubMed1995

Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli.

The goal of this work was to test the involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning, using auditory and visual conditioned stimuli (CSs). The acoustic startle reflex in rats was used as the behavioral index of conditioning because startle is reliably enhanced in the presence of a conditioned stimulus (CS) previously paired with a footshock. Initially, differential conditioning procedures indicated reliable discrimination between a noise CS and a visual CS. Subsequently, the effects of amygdala lesions were evaluated when both modalities were paired with shocks in the same rats. Electrolytic or ibotenic acid lesions of the central nucleus of the amygdala blocked fear-potentiated startle to both auditory and visual CSs, consistent with the idea that the central nucleus serves as a response independent, final common relay for fear conditioning. Similarly, pre- or post-training electrolytic or NMDA-induced lesions of the basolateral complex of the amygdala, which damaged the lateral nucleus, and most of the basolateral nucleus, disrupted fear-potentiated startle to both CS modalities. This finding is consistent with the suggestion that, in fear conditioning, the basolateral complex of the amygdala serves as an obligatory relay of sensory information from subcortical and cortical sensory areas to the central nucleus of the amygdala.

Acoustic Stimulation↗
PubMed1995

Involvement of subcortical and cortical afferents to the lateral nucleus of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli.

The goal of this work was to test the involvement, in fear conditioning, of afferents to the lateral nucleus of the amygdala originating from the auditory thalamus, auditory cortex, and perirhinal area. The acoustic startle reflex was used as the behavioral index of conditioning because it is reliably enhanced in the presence of a conditioned stimulus (CS) previously paired with a footshock. Auditory and visual CSs were used to assess the modality specificity of lesions to the above brain areas. Pre- or posttraining lesions of the entire auditory thalamus including the ventral, dorsal, and medial divisions of the medial geniculate body, the posterior intralaminar nucleus, and the suprageniculate nucleus, completely blocked fear-potentiated startle to the auditory CS, but had no effect on fear-potentiated startle to the visual CS. Posttraining lesions mostly restricted to the ventral and dorsal divisions of the medial geniculate body specifically disrupted fear-potentiated startle to the auditory CS. However, retraining in rats sustaining ventral and dorsal medial geniculate body lesions led to reliable fear-potentiated startle to the auditory CS. Posttraining lesions mostly restricted to the medial division of the medial geniculate body, posterior intralaminar, and suprageniculate nuclei did not disrupt fear-potentiated startle. These results indicate that the auditory thalamus is specifically involved, through either its direct or indirect amygdaloid afferents, in fear conditioning to auditory CSs. Pre- or posttraining lesions mostly restricted to the primary auditory cortex did not reliably attenuate fear-potentiated startle to the auditory or visual CSs. Extensive posttraining lesions of the perirhinal area (including secondary auditory cortices), but not its rostral aspect alone, blocked fear-potentiated startle to both CSs. However, reliable potentiated startle was observed to both CSs following similarly extensive pretraining lesions of the perirhinal area. Because post- but not pretraining lesions of the perirhinal area blocked fear-potentiated startle nonspecifically, at least with regard to auditory and visual CSs, the results are consistent with the involvement of the perirhinal area in general memory functions such as information storage or retrieval. Alternatively, the secondary auditory and/or perirhinal cortices might function as multimodal sensory relays to the amygdala.

Acoustic Stimulation↗
PubMed1994

Effect of corticosterone on the enhancement of the acoustic startle reflex by corticotropin releasing factor (CRF).

The present study evaluated the effects of adrenalectomy and chronic administration of corticosterone on the ability of CRF given intraventricularly to increase the amplitude of the acoustic startle reflex in rats. Experiment 1 showed that CRF-enhanced startle was not affected by adrenalectomy, indicating a central effect independent of the integrity of the hypothalamic-pituitary-adrenal axis. In Experiment 2, chronic injection of corticosterone augmented CRF-enhanced startle using a dose of CRF (0.25 micrograms) that normally is ineffective in increasing startle amplitude. Chronic injection of corticosterone by itself did not increase startle amplitude (Experiment 3). We suggest that the potentiation of CRF-enhanced startle by corticosterone may result from an activation of CRF in the central nucleus of the amygdala.

Acoustic Stimulation↗
PubMed1994

Stress-induced activation of prefrontal cortex dopamine turnover: blockade by lesions of the amygdala.

Stress consistently has been found to activate peripheral and central catecholamine systems. Dopamine (DA) turnover in the prefrontal cortex is especially sensitive to stress produced by relatively mild footshock, conditioned fear, or exposure to a novel cage. Because lesions of the central nucleus of the amygdala block the effects of both stress and fear in many experimental paradigms, the present study evaluated whether such lesions would block stress-induced increases in prefrontal dopamine turnover using either mild footshock or novelty as stressors. In Experiment 1 electrolytic lesions of the central nucleus of the amygdala attenuated the increase in the dopamine metabolite homovanillic acid (HVA) in the prefrontal cortex evaluated in post-mortem tissue normally produced by footshock. In Experiment 2 similar lesions attenuated the increase in dopamine turnover in the prefrontal cortex using a different stressor, novelty, and a different measure of dopamine turnover, DOPAC/DA ratios. These data provide further evidence for the critical role of the amygdala in stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Baseline and fear-potentiated startle in panic disorder patients.

The present study investigated whether patients with panic disorder had an increase in the startle response and whether this effect, if present, was specific to anticipatory anxiety. The eyeblink component of the acoustic startle reflex was measured in a paradigm involving the anticipation of electric shocks (fear-potentiated startle) in 34 patients with panic disorder and 49 healthy controls. Startle was also recorded in the absence of specific threat at the beginning and at the end of the testing. The testing consisted of three phases: adaptation, fear-potentiated startle, and recovery. In the adaptation and recovery phases, startle stimuli were delivered in the absence of threat. In the fear-potentiated startle phase, startle stimuli were delivered in threat conditions, when subjects anticipated shocks, and in safe conditions that predicted the absence of shocks. Startle was larger in the younger patients (age < 40 years old) compared to the younger controls throughout the testing. The difference reached significance only during the fear-potentiated startle phase, however. Startle was nonsignificantly reduced in the older patients (age > or = 39 years old), compared to the older controls. The results are discussed in terms of the contextual effects of the experimental setting.

Adolescent↗
PubMed1994

Plasma brain natriuretic peptide in assessment of acute dyspnoea.

Recognition of heart failure (HF) may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction. Since increased secretion of the cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) occurs early in the course of HF, we have assessed the value of measuring these hormones in plasma in the diagnosis of suspected HF in 52 elderly patients presenting with acute dyspnoea, and compared values with left-ventricular ejection fraction (LVEF), a standard measure of left-ventricular function, by radionuclide angiography. Patients were enrolled prospectively. On the basis of clinical findings, conventional tests, and response to specific treatment, 20 of the 52 patients were classified as having primary lung disorder (PLD), 12 as HF alone, and 20 as HF with underlying PLD (HF/PLD). Compared with findings in PLD patients, LVEF was significantly depressed in HF and HF/PLD patients (p < 0.001), whereas both plasma ANP and BNP were significantly increased (p < 0.001). Admission plasma BNP concentration more accurately reflected the final diagnosis of HF (93% sensitivity and 90% specificity when BNP > or = 22 pmol/L) than LVEF or plasma ANP concentration. When all patients were considered together, there were strong negative correlations between LVEF and log BNP (r = -0.7, p < 0.001) and log ANP (r = -0.59, p < 0.001). Our finding that plasma BNP is raised in dyspnoeic patients with HF but not in acutely breathless patients with PLD, suggests that rapid BNP assays may assist in the diagnosis of patients with acute dyspnoea.

Acute Disease↗
PubMed1994

Nonverbal aspects of therapist attunement.

In a follow-up to an earlier study (Davis & Hadiks, 1990) that reported positive and significant correlations between the patient's body positions during psychotherapy and Experiencing Scale (Klein, Mathieu, Gendlin, & Keisler, 1970) ratings, a similar analysis of her therapist's nonverbal behavior was completed. Results revealed positive and significant correlations among the therapist's body positions, the intensity and density of his gesticulations, and the Therapist Experiencing Scale. Data from the patient study also were included in the analysis, and these results revealed positive and significant correlations between the therapist's and patient's positions as well as the therapist's positions and the patient's Experiencing Scale scores. Results are discussed in terms of the significance of body movement as a measure of rapport and its role in therapist interventions.

Adult↗
PubMed1994

Safety signals and human anxiety: a fear-potentiated startle study.

The effect of a safety signal on the magnitude of anticipatory anxiety was investigated using the fear-potentiated startle reflex paradigm in humans. The amplitude of the acoustic startle reflex was measured during the anticipation of unpleasant electric shocks ("threat") and during "safe" conditions. Threat and safe conditions were signaled by three different colored lights. Two lights signaled safe conditions (safe 1, safe 2) and the other light signaled the threat condition (threat). In phase I, the lights alternated, each presentation consisting of one colored light. In phase II, the lights were presented alone or in the two combinations of safe 1 (or safe 2) + threat and safe 1 + safe 2. In both phases, the contingency between the lights and the shock was explained to the subjects. It was emphasized that no shock could be administered when the safe 1 and threat light were simultaneously presented in phase II. Subjects' belief and understanding of the instructions were verified. In Phase I, startle was increased in the threat-alone compared to the safe-alone condition, reflecting increased anticipatory anxiety in the threat-alone condition. In phase II, startle in the safe + threat condition was smaller than in the threat-alone condition, but was larger than in the safe + threat. These results were interpreted as suggesting that the threat signal was still able to elicit anticipatory anxiety despite the fact that it was no longer associated with a threat.

Acoustic Stimulation↗
PubMed1994

The effect of age on cerebral oedema, cerebral infarction and neuroprotective potential in experimental occlusive stroke.

A model of occlusive stroke in the aging brain has been developed and used to evaluate the effects of age upon cerebral infarction, cerebral oedema and neuroprotective potential. Focal ischaemia following left middle cerebral artery occlusion has been compared in aged (30 month) and adult (< 17 month) rats, with histological assessment of infarct volume and analysis of specific gravity as an index of cerebral oedema. Aging was associated with a significant increase in cerebral infarct size. The mean infarct volume in aged rats was 40.5% +/- 2.6% of the hemisphere volume, compared to 30.9% +/- 0.7% in adults (p < 0.01). Pre-treatment with the competitive N-Methyl-D-Aspartate (NMDA) receptor antagonist 3-(2-Carboxy Piperazin-4-yl)Propyl-l-Phosphonate (D-CPP-ene) reduced infarct volumes in both age groups to 33.0% +/- 1.8% and 20.7% +/- 3.2% in aged and adult animals, respectively (p < 0.05). There was significantly less oedema of the cerebral cortex in D-CPP-ene pre-treated rats; mean cortical specific gravity 4 hours post-infarction was 1.0381 +/- 0.0013 in untreated aged rats and 1.0391 +/- 0.0014 in untreated adults, compared to 1.0458 +/- 0.0031 in treated aged rats and 1.0442 +/- 0.0014 in treated adults (p < 0.05). At 24 hours post-infarction, D-CPP-ene pre-treated aged rats had a mean cortical specific gravity of 1.0403 +/- 0.0006 compared to 1.0361 +/- 0.0014 in untreated aged animals (p < 0.05). This study has demonstrated an age-related increase in cerebral infarct size, but has shown that the aging brain is amenable to neuroprotection by NMDA receptor antagonism.

Age Factors↗
PubMed1994

The HIV mental health spectrum.

The growing mental health needs that are related to HIV are immense and diverse. The HIV mental health spectrum is a model that identifies and characterizes populations in need of HIV-related services which can be offered by Community Mental Health Centers. The spectrum describes the specialized service requirements for each of these populations, the challenges in providing these services, and staff training needs. The authors propose this as a useful model for clinicians, researchers, educators, and administrators in planning to meet the needs of this expanding epidemic.

Community Mental Health Centers↗
PubMed1994

Recovery of epinephrine response but not hypoglycemic symptom threshold after intensive therapy in type 1 diabetes.

PURPOSE: Patients with intensively treated insulin-dependent diabetes mellitus (IDDM) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients. In this prospective study in patients with preexisting defects in counterregulation, we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM (diabetes duration of 2 to 16 years; aged 19 to 36 years; 3 women, 2 men) who were receiving intensive therapy. METHODS: Counterregulatory responses were assessed by using a single-step (approximately 2.8 mmol/L plasma glucose) and multiple-step (from approximately 5 mmol/L to 2.2 mmol/L plasma glucose) clamped hypoglycemia procedure. Patients were first studied after a stable period of conventional insulin therapy (glycosylated hemoglobin [HbA1c] 9.5 +/- 1.2%), then after 3 to 5 months of intensive therapy (HbA1c 6.6 +/- 0.2%), and a third time after resuming conventional therapy (HbA1c 8.7 +/- 0.9%). RESULTS: Intensive therapy was associated with a 44% decline (P < 0.01) in the average plasma epinephrine increase during hypoglycemia, and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 +/- 0.2 to 3.0 +/- 0.1 mmol/L (P < 0.01). The threshold, but not the magnitude, of the plasma norepinephrine response was similarly altered. Hypoglycemic symptoms also decreased in intensity (by 67%, P < 0.01), and the glucose level required for symptom activation fell from 3.4 +/- 0.3 to 2.7 +/- 0.2 mmol/L, P < 0.01). When conventional therapy was resumed, the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed. However, the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed. CONCLUSIONS: There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM, and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy.

Adult↗
PubMed1994

Instructional conditions and stereotyped behavior: the function of prompts.

The relationship of instructional prompts to rate of task completion and stereotypy was studied in one adolescent student with autism and high-frequency stereotypic behavior. Using an ABAB design, one experiment was conducted which systematically examined the role of prompts on (a) task completion and (b) time engaged in stereotyped behavior. Results suggested that prompts had little effect on the rate of task completion across sessions but did reduce time spent in stereotypies. These results are discussed in relation to stereotypies and implications for intervention and instruction.

Adolescent↗
PubMed1994

Effects of small angle discrepancies on interpretations of subtraction images.

The present study examines interpretations of subtraction images of pairs of radiographs taken at 0 degrees, 1 degree, or 2 degrees of angle discrepancy. The radiographs were taken at each of 48 alveolar crestal sites on 15 dried human skulls. Computer-simulated lesions were induced at the sites on three fourths of the radiographs. Ten instructed dentists were asked to interpret the subtraction images as to the presence or absence of crestal change. A 2-degree angle discrepancy between radiographs resulted in a significant difference in sensitivity from that of radiographic pairs with a 0-degree discrepancy. However, we found no significant difference in sensitivity between 1-degree and 0-degree pairs of radiographs. In conclusion, a 1-degree geometric difference between pairs of radiographs does not significantly contribute to errors in interpretation of subsequent subtraction images.

Alveolar Bone Loss↗
PubMed1994

Neurotransmission in the rat amygdala related to fear and anxiety.

An impressive amount of evidence from many different laboratories using a variety of experimental techniques indicates that the amygdala plays a crucial role in the acquisition, consolidation and retention or expression of conditioned fear. Electrophysiological data are beginning to detail the transmitters and inter-amygdala connections that transmit information to, within, and out of the amygdala. In general, treatments that increase the excitability of amygdala output neurons in the basolateral nucleus (for example, by decreasing opiate and GABA transmission, and increasing noradrenergic transmission) improve aversive conditioning, whereas treatments that decrease excitability of these neurons (by increasing opiate and GABA transmission, and decreasing NMDA and noradrenergic transmission) retard aversive conditioning as well as producing anxiolytic effects in appropriate animal tests. A better understanding of brain systems that inhibit the amygdala, as well as the role of its very high levels of peptides, might eventually lead to the development of more effective pharmacological strategies for treating clinical anxiety and memory disorders.

Amino Acids↗