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Biomedical subjects

K D Davis

Publications and source records attributed to K D Davis.

At least 19 recordsLinked to original sources
PubMed1998

Phantom sensations generated by thalamic microstimulation.

Many amputees have a sense of their missing 'phantom' limb. Amputation can alter the representation of the body's surface in the cerebral cortex and thalamus, but it is unclear how these changes relate to such phantom sensations. One possibility is that, in amputees who experience phantom sensations, the region of the thalamus that originally represented the missing limb remains functional and can give rise to phantom sensations even when some thalamic 'limb' neurons begin to respond to stimulation of other body regions. Here we use microelectrode recording and microstimulation during functional stereotactic mapping of the ventrocaudal thalamus in amputees to determine both the responses of the neurons to stimulation of the skin and the perceptual effects of electrical activation of these neurons. Thalamic mapping revealed an unusually large thalamic stump representation, consistent with the findings from animal experiments. We also found that thalamic stimulation in amputees with a phantom limb could evoke phantom sensations, including pain, even in regions containing neurons responsive to tactile stimulation of the stump. These findings support the hypothesis that the thalamic representation of the amputated limb remains functional in amputees with phantoms.

Adult↗
PubMed1997

Patterns of neuronal firing in the human lateral thalamus during sleep and wakefulness.

The firing patterns of thalamic neurons in mammals undergo a dramatic change as the animal's state changes between sleep and wakefulness. During sleep the normal tonic firing of thalamic neurons changes into a slower bursting mode characterized by repetitive activation of a low-threshold calcium (Ca2+) current. The present report describes the patterns of thalamic neuronal firing during sleep and wakefulness in one human patient. Extracellular single neuron activity was recorded during functional stereotactic surgery in the thalamus of a patient with chronic pain, who was observed to fall asleep during the recording. Evolutive power spectra of the thalamic slow wave were used in place of cortical encephalography to confirm the patient's states of sleep and wakefulness. Twenty-nine sites were observed in motor and somatosensory thalamus (Vop, Vim, and Vc) that were characterized by the presence of neurons with bursting activity when the patient was asleep. Such bursting was not observed in the patient when she was awakened. At 14 of these sites we were able to discriminate the bursting activity of single units. In each case the cell stopped firing or its bursting was replaced by a tonic firing pattern when the patient was awakened. In three cases the patient began to lapse back into sleep and the neuron resumed firing in a bursting pattern once again. None of these units had a peripheral receptive field (RF), while several other units recorded in nearby regions that did not fire in a bursting pattern during sleep had kinesthetic or cutaneous RFs. Analysis of the intraburst firing pattern revealed increasing interspike intervals (ISI) for successive action potentials in a burst and that the duration of the first ISI in the burst decreased as the number of ISIs increased. This pattern is similar to that reported to occur as a result of a calcium spike. These data have confirmed for the first time that state-dependent changes in thalamic firing exist in the human and that the physiological substrates at the thalamic level that are involved in human sleep are similar to those observed in animals.

Adult↗
PubMed1997

Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms.

Studies of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in monkeys suggest that excessive inhibitory outflow from the internal segment of the globus pallidus (GPi) suppresses the motor thalamus, which reduces activation of the cerebral cortex motor system, resulting in the slowness and poverty of movement of Parkinson's disease (PD). This hypothesis is supported by reports of high rates of spontaneous neuronal discharges and hypermetabolism in GPi (ref. 4-7) and impaired activation of the supplementary motor area (SMA) and dorsolateral prefrontal regions in PD patients. Furthermore, lesion or chronic high-frequency electrical (likely inactivating) stimulation of GPi (ref. 10-14) is associated with marked improvements in akinesia and rigidity, and the impaired activation of SMA is reversed when the akinesia is treated with dopamine agonists. To test whether improvement in motor function with pallidal surgery can be attributed to increased activity in premotor cortical regions, we assessed the changes in regional cerebral blood flow (rCBF) and parkinsonian symptoms during disruption of GPi activity with high-frequency stimulation delivered through implanted brain electrodes. Positron emission tomography (PET) revealed an increase in rCBF in ipsilateral premotor cortical areas during GPi stimulation, which improved rigidity and bradykinesia. These results suggest that disrupting the excessive inhibitory output of the basal ganglia reverses parkinsonism, via a thalamic relay, by activation of brain areas involved in the initiation of movement.

Aged↗
PubMed1997

Functional MRI of pain- and attention-related activations in the human cingulate cortex.

The aims of the study were to use functional magnetic resonance imaging (fMRI) to 1) locate pain-related regions in the anterior cingulate cortex (ACC) of normal human subjects and 2) determine whether each subject's pain-related activation is congruent with ACC regions involved in attention-demanding cognitive processes. Ten normal subjects underwent fMRI with a 1.5-T standard commercial MRI scanner. A conventional gradient echo technique was used to obtain data from a single 4-mm sagittal slice of the left ACC, approximately 3.5 mm from midline. For each subject, interleaved sets of 6 images were obtained during a pain task, an attention-demanding task, and at rest, for a total of 36 images per task. Pain of different intensities was evoked via electrical stimulation of the right median nerve. The attention-demanding task consisted of silent word generation (verbal fluency). Additional experiments obtained data from the right ACC. A pixel-by-pixel statistical analysis of task versus rest images was used to determine task-related activated regions. The pain task resulted in a 1.6-4.0% increase in mean signal intensity within a small region of the ACC. The exact location of this activation varied from subject to subject, but was typically in the posterior part of area 24. The signal intensity changes within this region correlated with pain intensity reported by the subject. The attention-demanding tasks increased the mean signal intensity by 1.3-3.3% in a region anterior and/or superior to the pain-related activation in each subject. The activated region was typically larger than the pain-related activation. In some cases this activation was at or superior to the ACC border, near the supplementary motor area. These regions did not show any pain-intensity-related activation. In one subject both right and left ACC were imaged, revealing bilateral ACC activation during the attention task but only contralateral pain-related activation. These findings shed light on pain- and attention-related cognitive processes. The results provide evidence for a region in the posterior part of the ACC that is involved in pain and a more anterior region involved in other attention-demanding cognitive tasks.

Adult↗
PubMed1996

Triage: limitations in predicting need for emergent care and hospital admission.

STUDY OBJECTIVE: Little is known about the accuracy and reliability of current triage methods. We examined agreement among observers with regard to the need for ED care and the ability to predict at triage the need for admission to the hospital and compared these findings with admission rates after medical evaluation and management. METHODS: We used a crossover design in which each subject was subjected to nurse or computer-guided triage first, the other type of triage second, and physician triage last. Our null hypothesis: Triage methods will yield the same results. Our patients were a consecutive sample of patients at the ED of a university-affiliated county referral center. Critically ill patients were excluded. Triage categorization was examined for interobserver agreement (kappa-statistic) and prediction of admission (sensitivity, specificity, and predictive values). RESULTS: Of the 5,106 patients enrolled in the study, 289 (6.2%) were admitted. With regard to the agreement of triage categorizations, we found kappa-values of .452 and .185, respectively, for physician triage compared with nurse (SE +/- .012) and computer triage (SE +/- .012)(P = .001 for the difference between the kappa values). Sensitivity and specificity in predicting admission were 41.3 and 93.8, respectively, for nurses, 61.6 and 87.1, respectively, for physicians; and 68.2 and 73.6, respectively, for computer-aided triage. CONCLUSION: We found great variability among physicians, nurses, and a computer program with regard to triage decisions. Comparison of the three groups' triage decisions with actual data after medical evaluation and management showed that none of the three performed well in predicting which patients required admission. Until triage methods are standardized and validated, triage decisions should not be used to determine the timeliness of access to emergency care.

Adolescent↗
PubMed1996

Thalamic stimulation-evoked sensations in chronic pain patients and in nonpain (movement disorder) patients.

1. Little is known about the effect of central and peripheral nervous system injury on the processing of somatosensory information at the thalamic level in humans. The role of the human thalamic ventrocaudal nucleus (Vc) in nociception is not well understood because reports of nociceptive neuronal responses and stimulation-evoked pain are rare. In this study, we have characterized effects of microstimulation in the tactile region of Vc. Specifically, we investigated the incidence of painful sensations evoked by thalamic microstimulation in patients with and without chronic pain. 2. Data were obtained during stereotactic thalamic procedures for relief of pain or motor disorders. Patients were divided into three groups, those with 1) central poststroke pain (PSP, n = 13); 2) nonstroke pain (NSP, n = 23); and 3) movement disorders (controls, n = 24). Most (15 of 23) of the NSP patients had peripheral nerve damage. Tungsten microelectrodes were used to record neuronal responses in the thalamus and to deliver stimuli. Localization of tactile Vc was determined according to stereotactic coordinates and neuronal responses to innocuous somatic stimuli. At selected sites, microstimulation (1-s trains, 300 Hz, 0.1-0.2 ms pulses, < 100 microA) was performed and the patient was requested to describe the quality of the sensation and its peripheral location (projected field, PF). 3. Microstimulation in tactile Vc commonly evoked paresthesia-type sensations. Threshold stimulation never evoked pain in the NSP patients and evoked pain at only 2% of Vc sites in the movement disorder patients. In these latter 2 groups of patients, stimulation at > 98% of Vc sites evoked paresthesia. By contrast, in the PSP patients, 28% of Vc sites stimulated evoked painful sensations at threshold. Suprathreshold stimuli evoked painful sensations at 46% of Vc sites in the PSP patients but at only 8% of Vc sites in NSP patients and 12% of Vc sites in the movement disorder patients. 4. The thresholds to evoke paresthesia in the NSP and movement disorder patients were significantly lower than the thresholds in the PSP patients. However, stimulation thresholds to elicit pain were similar in all patient groups. 5. All patients were capable of differentiating stimulation-evoked paresthesia from pain. Stimulation-evoked painful sensations in the PSP patients were often described as burning and sometimes as "sharp," "shocking," or "unpleasant." By contrast, the quality of pain evoked in the other patient groups was typically described as unpleasant or shocking. Pain could be evoked at sites throughout tactile Vc, although most sites were located in the ventral 2/3 of the nucleus. 6. In the movement disorder patients, the location of the projected sensation usually corresponded to the location of the receptive fields of the tactile neurons recorded at the same site. By contrast, in both groups of pain patients there was a high incidence of mismatches between the projected and receptive fields. 7. These results suggest that the effective thalamic output from Vc to the cortex is affected by somatosensory deafferentation in pain patients. In addition, in the PSP patients there are also changes in the thalamocortical processing of noxious information. The increased incidence of thalamic-evoked pain in PSP patients may be due to 1) loss of low-threshold mechanoreceptive thalamic neurons such that nociceptive neuronal output is now prominent, 2) reduced tonic inhibition of thalamic or cortical nociceptive neurons, and/or 3) unmasking or strengthening of nociceptive pathways.

Cerebrovascular Disorders↗
PubMed1996

Decreased follistatin gene expression in gonadotroph adenomas.

What growth factors are involved in the pathogenesis of gonadotroph adenomas is not yet known. Activin is one possible candidate because it stimulates growth and differentiation in many cells, including the gonadotroph cell, and it stimulates FSH secretion, characteristic of gonadotroph adenomas. As activin beta B-subunit is expressed in gonadotroph adenomas, we sought to determine whether activin receptor II and follistatin are also expressed. Total ribonucleic acid (RNA) was extracted from 10 gonadotroph adenomas that did not express pit-1 and was reverse transcribed. The resulting complementary DNAs for human activin receptor II and follistatin were amplified by PCR. All 10 adenomas expressed activin receptor II messenger RNA (mRNA), as did nonadenomatous pituitary tissue. Only 2 of the 10 gonadotroph adenomas expressed detectable follistatin mRNA, although all 4 nonadenomatous pituitaries did. Quantitation of follistatin mRNA by competitive reverse transcription-PCR showed that none of the 10 gonadotroph adenomas expressed as much follistatin mRNA as did the 4 nonadenomatous pituitaries, and 8 of the 10 expressed less than 10% as much. Immunospecific staining showed follistatin in the cytoplasm of the gonadotroph cells of all 5 nonadenomatous pituitaries studied, but only faintly in 1 gonadotroph adenoma and not at all in the other 9. These results suggest that pit-1-negative gonadotroph adenomas express less follistatin mRNA and follistatin peptide than do nonadenomatous gonadotroph cells. A consequence could be less binding, and thereby enhanced effectiveness, of activin, contributing to adenoma growth.

Activin Receptors↗
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↗