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Results for “Stimulants, Historical”

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At least 19 recordsLinked to original sources

Interfacing T-cell effector and regulatory function through CD137 (4-1BB) co-stimulation.

Historically, co-stimulation has been regarded as a prerequisite for T-cell activation. A lack of co-stimulation results in peripheral T-cell tolerance, which manifests as unresponsiveness or death through apoptosis. Recent findings, however, suggest that eliciting co-stimulation can also induce tolerance. Reconciling these diametrically opposed results is certainly of academic importance but more importantly transcends basic immunology and impacts present and future clinical trials that are centered on modulating T-cell co-stimulation. This review will focus on CD137 (4-1BB) and propose a mechanism of action in which CD137-primed CD8 T cells express effector function and also inhibit CD4 T-cell activation. This model suggests that the same CD8 T cells possess antitumor effector function interfaced with regulatory capacity, which ultimately leads to concomitant inhibition of tumorigenesis and autoimmune disease.

Animals↗

Feasibility of controlled micturition through electric stimulation.

Historically, man has been aware of bioelectric phenomena for some 4,000 years. Yet it has only been during the last 20 years that technology has advanced to the stage where controlled bladder emptying has become feasible. A great deal of interest followed the introduction of transistor and bladder stimulation via the principle of radio frequency induction. Spinal cord, sacral, and pelvic nerve and direct bladder stimulation have all been attempted. Only direct bladder stimulation in lower motor neuron situations has shown any promise. The many difficulties associated with bladder stimulation include simultaneous sphincter contraction, pain, electrode and insulation difficulties, and fibroplasia due to movement of electrodes placed in pliable tissues. In addition, the role of the prostate, increased urethral length, and erection responses in the male have received little investigation. These problems are outlined and experimental observations of attempts to achieve controlled micturition in canines areresented. These studies were carried out over a 3-year period, and emphasize responses to stimulation of the spinal cord and sacral roots. It was concluded that the most efficient manner by which to effect simulated micturition is via stimulation of the ventral sacral root dominant for bladder responsiveness, and combine this with selective division of somatic fibers of only the root being stimulated.

Animals↗

Effects of preoperative electrical stimulability and historical factors on performance with multichannel cochlear implant.

We investigated the relationship between results of preoperative transtympanic electrical promontory stimulation, duration of deafness, postoperative implanted psychophysical results, and postoperative speech and speech sound recognition as indicated by a battery of five tests. Our subjects were 10 patients implanted with the Cochlear Corporation multielectrode implant, 1 year postimplantation, with a minimum of 17 active electrodes programmed in the bipolar + 1 mode. The results indicated that preoperative promontory thresholds, the slope of the threshold function, and the duration of auditory deprivation are excellent predictors of postoperative speech and speech sound recognition in the auditory (processor alone) mode. These results have significant implications for patient selection and counseling.

Adolescent↗

Ionic mechanisms mediating oscillatory membrane potentials in wide-field retinal amacrine cells.

Particular types of amacrine cells of the vertebrate retina show oscillatory membrane potentials (OMPs) in response to light stimulation. Historically it has been thought the oscillations arose as a result of circuit properties. In a previous study we found that in some amacrine cells, the ability to oscillate was an intrinsic property of the cell. Here we characterized the ionic mechanisms responsible for the oscillations in wide-field amacrine cells (WFACs) in an effort to better understand the functional properties of the cell. The OMPs were found to be calcium (Ca2+) dependent; blocking voltage-gated Ca2+ channels eliminated the oscillations, whereas elevating extracellular Ca2+ enhanced them. Strong intracellular Ca2+ buffering (10 mM EGTA or bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid) eliminated any attenuation in the OMPs as well as a Ca2+-dependent inactivation of the voltage-gated Ca2+ channels. Pharmacological and immunohistochemical characterization revealed that WFACs express L- and N-type voltage-sensitive Ca2+ channels. Block of the L-type channels eliminated the OMPs, but omega-conotoxin GVIA did not, suggesting a different function for the N-type channels. The L-type channels in WFACs are functionally coupled to a set of calcium-dependent potassium (K(Ca)) channels to mediate OMPs. The initiation of OMPs depended on penitrem-A-sensitive (BK) K(Ca) channels, whereas their duration is under apamin-sensitive (SK) K(Ca) channel control. The Ca2+ current is essential to evoke the OMPs and triggering the K(Ca) currents, which here act as resonant currents, enhances the resonance as an amplifying current, influences the filtering characteristics of the cell membrane, and attenuates the OMPs via CDI of the L-type Ca2+ channel.

Amacrine Cells↗

The Tulane Electrical Brain Stimulation Program a historical case study in medical ethics.

In 1950 physicians at Tulane University School of Medicine began a program of research on the use of electrical brain stimulation that would span three decades and involve approximately 100 patients. Initially, electrical brain stimulation was used to treat of schizophrenia, but later it was applied to a variety of other conditions. Throughout its history the Tulane research was well publicized in both the professional and lay literature, and for almost twenty years, with rare exception, these accounts were laudatory. However, in the early 1970s this work began to draw sharp public criticism. Despite its public and controversial nature, the Tulane electrical brain stimulation program has received relatively little attention from historians. This review recounts the history of the Tulane program with particular emphasis on the ethical propriety of the work. Factors that shaped the historical context in which the Tulane experiments were conducted are discussed.

Brain↗

Clinical applications of colony-stimulating factors: a historical perspective.

The development of the therapeutic roles of filgrastim and sargramostim over the past decade is reviewed. Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), and sargramostim, a recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), have been available in the United States for over a decade to treat various types of neutropenia. In addition, data are available to support their use in a variety of clinical settings. Because of the high cost of these agents, clinical guidelines for their appropriate use have been developed. With respect to the comparability of filgrastim and sargramostim, the American Society of Clinical Oncology recommends that additional data be generated since current data are insufficient to adequately address this question in each clinical setting. A limited number of randomized, comparative trials have directly compared filgrastim with sargramostim. Outcomes data from these trials are reviewed. Further, there is evidence to suggest that, at least for GM-CSF, tolerability is dependent on the degree of protein glycosylation. A nonglycosylated protein, molgramostim, available in Europe appears to be associated with greater toxicity in clinical trials, although randomized comparative trials are lacking. The therapeutic equivalence of CSFs requires further study. While data show that the efficacy and tolerability of CSFs are similar in certain settings, there has been no definitive, randomized, large-scale clinical trial conducted to address this issue. Pharmacists should continue to evaluate clinical data to determine not only which CSF to use but also when a CSF should be used.

Antineoplastic Agents↗

Injectable electronic identification, monitoring, and stimulation systems.

Historically, electronic devices such as pacemakers and neuromuscular stimulators have been surgically implanted into animals and humans. A new class of implants made possible by advances in monolithic electronic design and implant packaging is small enough to be implanted by percutaneous injection through large-gauge hypodermic needles and does not require surgical implantation. Among these, commercially available implants, known as radio frequency identification (RFID) tags, are used for livestock, pet, laboratory animal, and endangered-species identification. The RFID tag is a subminiature glass capsule containing a solenoidal coil and an integrated circuit. Acting as the implanted half of a transcutaneous magnetic link, the RFID tag is powered by and communicates with an extracorporeal magnetic reader. The tag transmits a unique identification code that serves the function of identifying the animal. Millions of RFID tags have been sold since the early 1980s. Based on the success of the RFID tags, research laboratories have developed injectable medical implants, known as micromodules. One type of micromodule, the microstimulator, is designed for use in functional-neuromuscular stimulation. Each microstimulator is uniquely addressable and could comprise one channel of a multichannel functional-neuromuscular stimulation system. Using bidirectional telemetry and commands, from a single extracorporeal transmitter, as many as 256 microstimulators could form the hardware basis for a complex functional-neuromuscular stimulation feedback-control system. Uses include stimulation of paralyzed muscle, therapeutic functional-neuromuscular stimulation, and neuromodulatory functions such as laryngeal stimulation and sleep apnea.

Animal Identification Systems↗

Mechanism of ethanol-induced adrenal stimulation.

A historical review of studies addressing the adrenal cortical response to ethanol and the mechanisms thought to contribute to such responses is presented. Studies reviewed range from the earliest based upon crude bioassay techniques to more modern papers which have utilized highly specific radioimmunoassay techniques and isolated perfused rat adrenal glands. Evidence for both hypothalamic-pituitary as well as direct adrenal stimulation is presented. Available evidence, however, would suggest that acetaldehyde rather than ethanol per se, is responsible for direct adrenal stimulation when it occurs.

Adrenal Cortex Hormones↗

The role of LH in ovarian stimulation: exogenous LH: let's design the future.

Historically, follicular stimulation protocols have included both FSH and LH in an attempt to mimic the physiology of normal human folliculogenesis. However, many recent gonadotrophin administration regimens have completely eliminated LH bioactivity. The importance and the amount of LH necessary for optimal follicular stimulation has been a topic of debate. Several recent studies have added to our understanding of the actions of androgens, oestrogens, gonadotrophins, and insulin on the follicle-oocyte unit, allowing a less speculative approach. Moreover, the availability of human gonadotrophins synthesized by recombinant DNA technology and gonadotrophin-releasing hormone (GnRH) antagonists, should soon permit a precise in-vivo assessment and re-evaluation of the historical 2-cell, two-gonadotrophin hypothesis. These pharmacological tools may also provide essential insights into the physiological roles of FSH and LH in human follicular development and oocyte maturation. The recombinant gonadotrophins give clinicians the unique opportunity to tailor ovarian stimulation regimens according to the patient's medical history, in an effort both to maximize oocyte yield and to improve oocyte quality.

Androgens↗

Historical vignette: cerebral cortical stimulation and surgery for epilepsy.

In 1909, in an isolated community hospital, on the northern tip of the Province of Newfoundland and Labrador, Canada, Dr. John Mason Little, Jr. performed electrical stimulation of the cerebral cortex, prior to cortical excision, as treatment of recurrent cerebral seizures in three patients. Extracts from Dr. Little's written records of the clinical features, the neurosurgical procedures and cerebral cortical stimulation are summarised. A brief review of the contemporaneous history of neurosurgical procedures for epilepsy provides a prospective of Dr. Little's remarkable surgical virtuosity.

Canada↗

Selective posterior rhizotomy for children with cerebral palsy: a 7-year experience.

Although selective posterior rhizotomy (SPR) was pioneered as early as 1913, only over the past decade has the procedure gained popular use for the treatment of spasticity in cerebral palsy. The medical knowledge base regarding this procedure is expanding, and surgical techniques continue to be revised. We present our 7 years of experience in treating spastic cerebral palsy using SPR. The aspects of preoperative evaluation used by the multidisciplinary team to determine candidacy are outlined. The surgical procedure is detailed with a particular emphasis on the role of intraoperative nerve root stimulation to aid in selection for rootlet sectioning. Historical nerve stimulation protocols are reviewed and compared to our findings over the years. The functional goals are discussed in the context of the postoperative evaluation and therapies. Specific outcome in relation to joint range of motion, self care tasks, and ambulation is reported. The paper outlines a concise overview of our experiences and will assist the clinician in defining a protocol and expectations for SPR.

Activities of Daily Living↗

Alternatives to growth hormone stimulation testing in children.

Despite more than 40 years of pediatric growth hormone (GH) replacement, we are still limited in our ability to make a definitive diagnosis of GH deficiency (GHD) in children. Historically, GH stimulation tests (GHSTs) have been used to discriminate between GHD and idiopathic short stature. Over the years, increases in the peak diagnostic GH cutoffs and the proliferation of GH assays have fundamentally changed the nature of the GHST. In our opinion, today's GHSTs lack reproducibility and accuracy, are expensive, and can be dangerous. Moreover, newer diagnostic tools, such as high-resolution neuroimaging, measurements of serum insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, and an increasing number of genetic tests, have emerged. We believe that it is no longer appropriate to use GHSTs to diagnose childhood GHD. Instead, diagnosis should be based on a combination of auxological, biochemical, neuroradiological and genetic considerations. Here, we examine the alternatives to the GHST that are currently available and literature that supports their use. We believe that these alternative methods should replace the GHST.

Adolescent↗

Cerebral evoked potentials: a historical review of the marseilles contributions and a preliminary report on a study of the effects of various stimulus parameters on the P90 component of the pattern visual evoked potential.

A preliminary report is given of a study in 10 normal subjects comparing the laterality of the P90 component of the PVEP as elicited by pattern reversal and pattern appearance stimuli delivered monocularly and binocularly in the central and peripheral portions of one-life field. P90 was shown often to appear maximally over the hemisphere ipsilateral to the stimulus field with pattern reversal stimuli in central targets viewed monocularly. Pattern appearance, peripheral targets and binocular stimulation provoked less consistently lateralized and sometimes differently configured responses. It is concluded that while all combinations provoked responses consistent with a dipole generator model similar to that proposed by Blumhardt et al. (1978), these different modes of stimulation cannot be considered to be equivalent.

Cerebral Cortex↗