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Biomedical subjects

K D Davis

Publications and source records attributed to K D Davis.

At least 55 records · Page 3Linked to original sources
PubMed1995

fMRI of human somatosensory and cingulate cortex during painful electrical nerve stimulation.

Functional MRI (fMRI) can detect changes from resting levels of blood flow and oxygenation during task performance (i.e. activation). We used a simple electrical nerve stimulation technique together with fMRI to study pain process in the human cortex. Images of the primary somatosensory (SI) and cingulate cortex (Cg) were obtained from subjects during stimulation at painful and non-painful intensities. Stimuli that evoked non-painful tingling sensations activated the contralateral SI but not Cg. Stimuli that evoked painful sensations activated both the contralateral SI and Cg. These data indicate that fMRI can detect pain-related changes in SI and Cg evoked by electrical stimulation of peripheral nerves. These findings add to the evidence for a role of SI and Cg in human pain processes and provide a simple method of stimulus delivery for its study.

Adult↗
PubMed1995

Visceral pain evoked by thalamic microstimulation in humans.

Microstimulation within and below the ventrocaudal nucleus (Vc) in the human thalamus typically evokes non-painful, paraesthetic cutaneous sensations. We now describe cases in which thalamic microstimulation evoked visceral pains. Data were obtained during stereotactic thalamotomy procedures. Patient 211 had a history of essential tremor. At a site 0.5 mm ventroposterior to Vc, microstimulation elicited pain described as 'deep, internal, in a straight line like my appendix pain years ago'. Patient 153 had a history of post-stroke hemibody pain. In each of two trajectories, at sites approximately 2 mm ventroposterior to Vc, microstimulation evoked pain in the groin. At one of these sites, the pain was described as 'like having a baby'. These and additional observations suggest that stimulation ventroposterior to Vc can evoke visceral pain and may trigger pain 'memories'.

Adult↗
PubMed1995

Sleeping cells in the human thalamus.

Neurons in the lateral thalamus of a patient undergoing stereotactic surgery were found to fire in a characteristic bursting pattern only when the patient was asleep. These novel observations are consistent with animal studies in which the tonic firing pattern of thalamic neurons during wakefulness changes to a bursting pattern during slow-wave sleep.

Adult↗
PubMed1994

Differential neuronal activity in segments of globus pallidus in Parkinson's disease patients.

Microelectrode trajectories through the globus pallidus of 6 Parkinson's disease (PD) patients yielded neurophysiological 'landmarks' which enabled the identification of neurones located in the external segment (GPe) and internal segments, exterior (GPi,e) and interior (GPi,i) of globus pallidus and the surrounding borders (Bor). Firing rate histograms and inter-spike interval time histograms were constructed for neurones in each region. The neuronal activity in GPi,i was higher than in the other segments, and a high degree of bursting was found in GPe and GPi neurones. This profile of neuronal activity is similar to that observed in monkeys treated with MPTP, suggesting that the observed level of activity of neurones in GPi,i is excessive, and contributes to the bradykinesia and rigidity of PD patients.

Aged↗
PubMed1994

Hantavirus: emergency department response to a disaster from an emerging pathogen.

In May 1993, the appearance of critically ill patients with unexplained respiratory distress was noted in the Four Corners area formed by New Mexico, Arizona, and Colorado. This epidemic was ultimately linked to a hantavirus, an emerging pathogen. The impact on the emergency department of a new infectious disease with respiratory distress is described. A model is proposed to manage infectious disease disasters. Emerging infections that are important to emergency physicians are discussed. Recommendations that focus on disaster management and prevention of the spread of an unknown pathogen are developed.

Bunyaviridae Infections↗
PubMed1994

Physical therapy episodes of care for patients with low back pain.

BACKGROUND AND PURPOSE: Although individuals with low back pain frequently receive treatment from a physical therapist, few published studies exist that describe who sees a physical therapist for their low back pain nor is much known about physical therapy episodes of care for this condition. Secondary analysis of data from the American Physical Therapy Association's Survey of Physical Therapy Outpatient Practice provides new descriptive data on services provided to a national, representative sample of patients discharged from hospital-based and private outpatient practices. In addition, specific hypotheses were tested on clinical and background factors believed to influence low back pain episodes of care. SUBJECTS: Patients with low back pain represented over 25% of all outpatient discharges from physical therapy practices. METHODS: A mail survey was conducted with representatives of a national probability sample of facilities that provided outpatient physical therapy services. Data were provided on each facility and on a discharge sample of patients treated at each facility. RESULTS: On average, episodes of care extended over 5 weeks and consisted of 11 therapy visits, for an average charge of $766.70. Duration and charge for low back episodes of care did not differ, on average, in private versus hospital-based practices. Certain aspects of care, however, did vary across regions of the country. Episodes of care charged to workers' compensation were costlier than those charged to other insurance carriers, and whites were charged less, on average, than nonwhites. Duration of back symptoms was related to intensity, duration, and charges incurred for the episode of care. CONCLUSION AND DISCUSSION: Further research is needed to understand the reasons for the relationships observed in this study, as well as studies that relate care provided by physical therapists to specific patient outcomes. Further research is also needed to compare outcomes achieved across different health professions.

Adult↗
PubMed1994

Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.

Retinoids regulate gene transcription by interacting with both retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Since unliganded RXRs can act as heterodimerization partners for RARs and other nuclear hormone receptors, it is unclear whether ligand binding by RXRs actually regulates the expression of naturally occurring genes. To address this issue, we synthesized the RXR-selective retinoid SR11237 and confirmed its specificity in transient transfection and proteolytic susceptibility assays before using it to assess the contribution of ligand-activated RXRs to retinoid action. Unlike RAR ligands, SR11237 did not increase endogenous RAR beta mRNA levels in F9 embryonal carcinoma cells, even though it activated transcription of an RXR-responsive reporter gene in these cells. Thus, it is likely that RARs mediate the induction of RAR beta gene expression by RA. In contrast, the RXR-specific ligand induced rat growth hormone mRNA in GH3 pituitary cells, indicating that the effects of RA on growth hormone gene expression at least in part involve ligand binding to endogenous RXRs in vivo. Our results indicate that in addition to serving as cofactors for other nuclear hormone receptors, endogenous RXRs can function as ligand-dependent regulators of gene expression, i.e., classical nuclear hormone receptors.

Animals↗
PubMed1993

Chemosensitivity and sensitization of nociceptive afferents that innervate the hairy skin of monkey.

1. A large proportion of the cutaneous nociceptor population in monkey either does not respond to mechanical stimuli or has very high mechanical thresholds (> 6 bar). The goal of this study was to determine whether these mechanically insensitive nociceptive afferents (MIAs) differ from mechanically sensitive nociceptive afferents (MSAs) with regard to responses to chemical stimuli. 2. Teased-fiber techniques were used to record from 28 A delta-fiber (16 MIAs and 12 MSAs) and 23 C-fiber (10 MIAs and 13 MSAs) nociceptors in hairy skin of pentobarbital sodium-anesthetized monkeys. An electrocutaneous search technique was used to locate the putative receptive fields of the MIAs. The response to mechanical and heat stimuli was determined before and after intradermal injection of a standard mixture of algesic/inflammatory mediators (bradykinin, histamine, serotonin, and prostaglandin E1). 3. All 25 MSAs, but only 65% of the MIAs, responded to the chemical stimulus. The A delta-fibers, both MSAs and responsive MIAs, and the responsive C-fiber MIAs gave a robust discharge. In contrast, the C-fiber MSAs (the conventional polymodal C-fiber nociceptors) exhibited a significantly weaker response. Three MIAs responded only to the chemical mixture and not to mechanical or heat stimuli. 4. Before injection of the chemical mixture, a significantly smaller proportion of C-fiber MIAs (50%) than of C-fiber MSAs (92%) responded to heat stimuli, whereas a similar proportion (38%) of A delta-fiber MIAs and MSAs were heat sensitive. 5. Approximately one-half of the MIAs and MSAs were sensitized to mechanical stimuli after the chemical injection, as manifest by a decreased threshold and/or an enlarged receptive field. 6. The chemical injection sensitized 90% of A delta-fiber MSAs, but only 8% of A delta-fiber MIAs, to heat stimuli. In contrast, 38% of C-fibers were sensitized. 7. In 14 fibers, the chemical stimulus resulted in sensitization to mechanical stimuli without sensitization to heat stimuli, or vice versa. This dissociated sensitized state suggests that the molecular mechanisms of sensitization to heat and mechanical stimuli differ. 8. In conclusion, a large proportion of primate cutaneous nociceptors respond to intradermal injection of algesic/inflammatory mediators and may also become sensitized to mechanical and/or heat stimuli.

Animals↗
PubMed1993

Microinjection of lidocaine into human thalamus: a useful tool in stereotactic surgery.

A new method was developed to aid in the localization of the optimal site for a permanent lesion in movement disorder patients undergoing stereotactic thalamotomy. The method involved making small injections of a local anesthetic into the thalamus, which was also useful in assessing any possible side effects that could potentially arise from the lesion. Initial results indicate that 0.5 to 2-microliters injections of 2% lidocaine at appropriate sites in the thalamic ventrocaudal or ventrointermedius nucleus can produce a temporary marked suppression of tremor. In most cases the lidocaine induced effects mimicked those produced by high frequency electrical stimulation delivered to the same site. However, lidocaine had no effect at some sites where stimulation arrested tremor. This technique promises to be useful not only in the treatment of motor disorder patients but also in other cases where functional localization prior to lesioning is desirable.

Electric Stimulation↗
PubMed1993

Induction of retinoic acid receptor-beta by retinoic acid is cell specific.

The retinoic acid (RA) receptor-beta (RAR beta) gene is dramatically up-regulated by RA in F9 teratocarcinoma cells due to the presence of an RA-responsive element (RARE) in its promoter. Remarkably, however, RAR beta mRNA was essentially unaffected by RA in rat pituitary GH3 cells, even though the GH gene was induced by RA, and these cells express mRNAs specific for multiple RAR subtypes and for the potential RAR coactivators, retinoid X-receptors. The absence of RA induction of RAR beta was also observed in GH1 cells as well as in murine AtT-20 pituitary cells and rat H35 hepatocarcinoma cells. The RA unresponsiveness of the RAR beta gene in GH3 and AtT-20 cells was not due to a mutation in the RARE, which was identical to that in RA-responsive F9 cells. Furthermore, while AtT-20 and F9 cells both expressed multiple RAR beta isoforms, including RAR beta 2, which was profoundly induced by RA in F9 cells, none of these was highly regulated by RA in AtT-20 cells. The failure of RA to induce RAR beta mRNA in certain murine and rat pituitary and nonpituitary cell lines indicates that target gene responsiveness to RA is cell type specific in some cases.

Animals↗
PubMed1993

Immunocytochemical delineation of thyroid hormone receptor beta 2-like immunoreactivity in the rat central nervous system.

The thyroid hormone receptors (TR) are nuclear proteins that include TR alpha and TR beta subtypes, each encoded by a separate gene. Both TR alpha and TR beta give rise to several isoforms of which three, TR alpha 1, TR beta 1, and TR beta 2 bind T3 and mediate the action of thyroid hormone. Although TR beta 2 was initially thought to be confined to the anterior pituitary, we recently observed small quantities of TR beta 2 messenger RNA (mRNA) by polymerase chain reaction analysis of discrete hypothalamic regions. To further examine the distribution of TR beta 2 in the brain, we performed immunocytochemical studies using a highly specific antiserum to TR beta 2, raised against a unique amino acid sequence (TR beta 2[131-145]) that is not present in the other known TRs. This antiserum immunoprecipitated TR beta 2 but not TR alpha 1 or TR beta 1. Immunoreactive TR beta 2 was widely distributed throughout the brain and primarily localized to the cell nucleus. Particularly intense immunostaining was present in the cerebral cortex, cerebellum, and hypothalamus, including regions where TR beta 2 mRNA had not previously been identified. In addition, immunoprecipitation of nuclear extracts with anti-TR beta 2 reduced total T3 binding capacity by approximately 20%, suggesting that immunoreactive TR beta 2 comprises a substantial portion of the total content of nuclear thyroid hormone binding proteins. These studies demonstrate that immunoreactive TR beta 2 is more widely represented in the central nervous system than previously suspected and may play an important role in mediating the action of T3 in many different regions of the brain. The finding of TR beta 2-like material could be due to a disproportionately high ratio of the TR beta 2 translation product and its mRNA in certain regions of the brain, or could indicate the existence of a novel TR beta 2-related protein that is important for T3 binding.

Amino Acid Sequence↗
PubMed1992

Selective antagonism of thyroid hormone action by retinoic acid.

Thyroid hormone (T3) and retinoic acid (RA) regulate gene transcription by binding to similar nuclear receptors. We have investigated the effects of RA, alone and in combination with T3, on a number of T3-responsive genes expressed in rat pituitary adenoma cells. Like T3, RA increased growth hormone gene expression in GH3 as well as in GH1 cells, and the effects of the hormones were additive. In contrast, RA alone had little effect on the expression of the beta 2 form of T3 receptor (TR beta 2), which is markedly decreased by T3. Remarkably, however, RA completely inhibited the down-regulation of TR beta 2 mRNA by T3. RA alone also had little effect on TR beta 1 mRNA, but its presence did not prevent the up-regulation of TR beta 1 mRNA by T3. The target-gene-specific antagonism of T3 action by RA was observed in both GH cell lines. Nuclear run-on assays demonstrated that the effect occurred at the level of TR beta 2 gene transcription, and the half-life of the TR beta 2 mRNA was unchanged by RA in the presence or absence of T3. The half-maximal RA dose required for these effects suggested that they were mediated by one or more of the nuclear receptors for RA. Indeed, GH3 cells contain mRNAs encoding the three distinct RA receptor subtypes, alpha, beta, and gamma, as well as retinoid X receptors. These results demonstrate that the effects of RA and T3 on gene expression are dependent on the nature of the target gene as well as on hormonal interactions, probably at the level of the receptors.

Animals↗
PubMed1992

The adrenergic pharmacology of sympathetically-maintained pain.

The authors seek to highlight some of the recent advances in understanding the pharmacology and pathophysiology of sympathetically-maintained pain, and to develop alternate, and possibly more specific, diagnostic tests for this phenomenon. Mechanical hyperalgesia in sympathetically-maintained pain can be explained by central sensitization so that the activation of A-beta mechanoreceptors now causes pain. The sensitization of central pain-signaling neurons is dynamic and reversible. The authors propose that an ongoing input from peripheral nociceptive afferents is necessary to maintain central sensitization. This nociceptive input may be due to an alpha-adrenoceptor mediated excitatory action of sympathetic efferents on sensory nerves that is independent of neurovascular transmission.

Adrenergic alpha-Agonists↗
PubMed1992

The plasticity of cutaneous hyperalgesia during sympathetic ganglion blockade in patients with neuropathic pain.

In order to investigate the plasticity of cutaneous sensory abnormalities in neuropathic pain, we monitored sensory and vasomotor effects of diagnostic sympathetic ganglion blocks in 24 patients, who suffered from chronic pain and cutaneous hyperalgesia following peripheral nerve or tissue injury. Ongoing pain was rated on a visual analogue scale, and pain evoked by innocuous tactile and cooling stimuli (hyperalgesia) on a verbal rating scale. Skin temperatures were determined at symmetric sites. In two patients, cutaneous blood flow was measured with a laser Doppler device. The sympathetic blocks led to a significant reduction of the group mean ongoing pain (40%) and cutaneous hyperalgesia (50%). Between patients, however, there was a large variability that could not be related merely to adequacy of sympathetic blockade. Neither the magnitude of change in skin temperature nor the final skin temperature after the block correlated with the amount of pain relief. The relief of hyperalgesia, however, correlated with the relief of ongoing pain. Nine patients experienced pain relief of greater than 50%. In these patients, the time course of hyperalgesia relief was similar to the time course of relief of ongoing pain. Pain relief occurred simultaneously with or a few minutes before cutaneous vasodilatation. During the block, even vigorous mechanical or cold stimuli did not rekindle hyperalgesia. In all patients, pain and hyperalgesia returned within a day after the block. In three patients tested, passive warming of the limb to the temperature achieved by the sympathetic block had negligible effects on pain and hyperalgesia. The hyperalgesia of sympathetically maintained pain is thought to be due to sensitization of central pain-signalling neurons to mechanoreceptor input. The present data indicate that this sensitization is highly plastic even when the disease has persisted for months or years. It could be reversed within minutes by a sympathetic blockade, but returned when sympathetic block subsided. Mechanoreceptor input by itself was not sufficient to maintain or rekindle the central sensitization. This supports the hypothesis that low-grade activity of nociceptors, possibly due to development of alpha-adrenergic sensitivity after injury, is involved in the maintenance of central sensitization.

Adult↗
PubMed1991

Mechanically insensitive afferents (MIAs) in cutaneous nerves of monkey.

A problem in the study of nociceptors is that intense stimuli are used to locate the receptive field (RF), and thus the receptor may be damaged before the first responses are recorded. In addition, some nociceptors do not respond to the mechanical stimuli often used to search for the RF. To overcome these problems, an electrical search technique was developed to locate the RF of cutaneous nociceptors. In the hairy skin of anesthetized monkey, we used this technique to locate the RF of 63 A delta-fibers and 22 C-fibers that had extremely high thresholds or were unresponsive to mechanical stimuli. We refer to these afferents as mechanically insensitive afferents (MIAs). Ten A delta-fiber MIAs had a short latency response to stepped heat stimuli and could be responsible for first pain sensation. Five A delta-fiber MIAs and one C-fiber MIA did not respond to mechanical or heat stimuli but did respond to injection into the electrical RF of an artificial inflammatory soup containing histamine, bradykinin, prostaglandin E1, and serotonin. These chemoreceptors might be responsible for the pain and itch sensations that result from chemical stimuli. Some MIAs became more responsive to mechanical stimuli after injection into the RF of the inflammatory soup and, thus, may contribute to the hyperalgesia to mechanical stimuli associated with cutaneous injury. A large proportion of the A delta-fiber (48%) and C-fiber (30%) afferents in this study were insensitive to mechanical stimuli. The role of these MIAs in sensation needs to be studied further. The electrical search technique enables a systematic study of these afferents to be performed. This technique may also be of use to identify and characterize dorsal horn neurons that have inputs from MIAs.

Action Potentials↗