An update on assessment and treatment of complex attention-deficit hyperactivity disorder.
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Adolescent↗
Biomedical subjects
R D Hunt
Publications and source records attributed to R D Hunt.
The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder.
This article aims to review research in nonhuman primates demonstrating that norepinephrine can enhance the cognitive functioning of the prefrontal cortex through actions at alpha 2 A-adrenergic receptors postjunctional to noradrenergic terminals. As prefrontal cortex cognitive deficits are prominent in several psychiatric disorders, including attention-deficit hyperactivity disorder, these basic findings may have relevance for the development of novel pharmacotherapies.
Adrenergic alpha-Agonists↗
Effect of ketorolac on bleeding time and postoperative pain in children: a double-blind, placebo-controlled comparison with meperidine.
STUDY OBJECTIVE: To determine whether ketorolac 0.75 mg/kg would provide a comparable degree of analgesia to that of meperidine 1 mg/kg in terms of postoperative opioid requirements and pain scores in children undergoing surgeries associated with mild to moderate postsurgical discomfort. DESIGN: Randomized, prospective, placebo-controlled, double-blinded study of the initial 6 postsurgical hours. SETTING: University affiliated teaching hospital. PATIENTS: 90 healthy ASA status I and II children scheduled for elective general, orthopedic, or genitourinary procedures associated with mild to moderate postsurgical pain. Extensive surgical procedures associated with a significant risk of bleeding were excluded. INTERVENTIONS: Ketorolac 0.75 mg/kg, meperidine 1 mg/kg, or placebo (normal saline) was administered intramuscularly (IM) at the beginning of surgery. MEASUREMENTS AND MAIN RESULTS: Bleeding times were measured prior to and 180 minutes after study drug administration. Time to first rescue medication, total opioid requirement, pain scores, incidence of vomiting and length of stay were evaluated. Placebo-treated patients were rescued earlier (p < 0.0001) and required twice the rescue dosage (p = 0.013) when compared with either the ketorolac or meperidine groups. The ketorolac and meperidine groups did not differ with regard to time until first rescue, cumulative proportion requiring rescue, or the number of rescue doses required. A single dose of IM ketorolac prolonged bleeding time by 53 +/- 75 seconds (p = 0.006). CONCLUSIONS: Ketorolac provided analgesia comparable to that of meperidine and significantly reduced opioid requirements. Since ketorolac was not associated with a reduction in postoperative vomiting or length of stay, and in view of the uncertain risk of bleeding, it offers no advantage over meperidine in the management of mild to moderate acute postsurgical pain.
Analgesics, Non-Narcotic↗
An open trial of guanfacine in the treatment of attention-deficit hyperactivity disorder.
OBJECTIVE: Medications such as clonidine have been shown to facilitate calming, to enhance frustration tolerance, and to reduce aggression in hyperactive children. The use of guanfacine (Tenex), an alpha 2 noradrenergic agonist similar to clonidine, was studied as an alternative because of its longer excretion half-life, decreased sedative side effects, and more selective binding profile. METHOD: Thirteen psychiatric outpatients diagnosed with ADHD were rated at baseline and while taking guanfacine to determine its efficacy as a treatment for ADHD. Comparisons of Conners parent ratings within subject were used to measure behavioral changes in the subjects. RESULTS: During guanfacine treatment, patients' mean scores improved significantly overall (1.27 off, 0.85 on, t = 2.55, p < .015) and in Conners Hyperactivity (1.63 off, 0.94 on, t = 3.69, p < .01), Inattention (1.92 off, 1.21 on, t = 3.32, p < .01), and Immaturity (1.81 off, 0.92 on, t = 3.77, p < .01) factors. CONCLUSIONS: This preliminary study indicates that guanfacine is a beneficial and useful treatment of ADHD, reducing hyperactive behaviors and enabling greater attentional ability with minimal side effects. We are currently collecting data in a double-blind study measuring guanfacine's efficacy with and in comparison to methylphenidate.
Adolescent↗
Clinical patterns of ADHD: a treatment model based on brain functioning.
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Arousal↗
An immunohistologic study of granulomatous inflammation in SIV-infected rhesus monkeys.
We studied granulomatous inflammation in simian AIDS using histologic, immunohistologic, and in situ hybridization techniques. Complete Freund's adjuvant was used to induce granulomas in two control animals and two macaques infected with simian immunodeficiency virus (SIV) and having low peripheral CD4+ T cell counts. Control animals developed large (> 2 cm diameter) epithelioid granulomas containing CD68+ macrophages (m phi s), epithelioid m phi s and multinucleated giant cells (MNGCs), CD4+ and CD8+ T cells, and small perivascular collections of CD20+ B cells. Lymphocytes rarely expressed proliferating cell nuclear antigen (Ki-67), and only rare endothelial cells expressed vascular cell adhesion molecule 1 (VCAM-1). In contrast, SIV+ animals had smaller (< 0.5 cm diameter) epithelioid granulomas characterized by numerous large, dense CD8+, CD20+ lymphocyte aggregates with prominent local division (Ki-67+). Despite low blood CD4+ T cell numbers, there was a substantial CD4+ T cell infiltrate, accompanied by enhanced endothelial VCAM-1 expression. These granulomas contained no detectable SIV antigen or RNA. Thus, in simian AIDS, experimentally induced granulomatous responses are grossly attenuated, yet associated with increased local endothelial-leukocyte signaling and lymphocyte division.
Animals↗
Plasma adenosine changes during cardiac surgery.
Changes in plasma adenosine and inosine were measured during high-dose narcotic anesthesia and surgery for coronary artery bypass grafting (CABG), and mitral or aortic valve replacement (V). Arterial and mixed venous blood samples were obtained for measurement of adenosine and inosine at eight sampling intervals ranging from preanesthesia induction to discontinuation of cardiopulmonary bypass (CPB). Arterial but not mixed venous adenosine was markedly elevated in blood samples 10 minutes after intubation, but the fourfold elevation was significant only in the CABG patient group. Mixed venous inosine and adenosine were most consistently elevated in post-CPB samples. In a separate study of arterial adenosine changes during induction, a uniform drug administration protocol was used, and again adenosine was significantly increased immediately after intubation. It is possible that adenosine and perhaps inosine may contribute to cardiovascular responses following induction-intubation and also after discontinuing CPB.
Adenosine↗
Opposite alterations in cerebrospinal fluid uridine after severe cerebral ischemia or intrathecal blood injection.
1. Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. 2. Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. 3. It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells.
Animals↗
Comparative biology of natural and experimental SIVmac infection in macaque monkeys: a review.
Epidemiologic and clinicopathologic data from 11 macaques with naturally acquired SIV infection--10 of which have died--were compared with those from 34 rhesus monkeys that have died of experimental SIVmac infection. Several differences, including gender affected, age at time of death, and the occurrence of certain opportunistic infections, could be explained by the experimental design; others remained unexplained. The most striking difference was the 41% incidence of meningoencephalomyelitis in the experimental group and its absence in naturally SIV-infected animals.
Age Factors↗
Infrared spectroscopic investigations of pulmonary surfactant. Surface film transitions at the air-water interface and bulk phase thermotropism.
The molecular structure of the phospholipid component of intact pulmonary surfactant isolated from bovine lung lavage has been examined by Fourier transform infrared spectroscopy. Two different physical states of the surfactant were examined by means of different infrared spectroscopic sampling techniques. Transmission infrared experiments were used to study the surfactant in the bulk phase. In these experiments, the thermotropic behavior of the bulk surfactant was monitored by temperature-induced variations in the phospholipid acyl chain CH2 stretching frequencies. A broad phase transition (confirmed by differential scanning calorimetry) was noted with an onset temperature near 15 degrees C and a completion temperature near 42 degrees C. In addition to the bulk transmission experiments, external reflection infrared spectroscopy was used to examine surfactant films in situ at the air-water interface. As surface pressure was increased from 0 to 43 dyn/cm, a gradual and continuous decrease in the CH2 stretching frequency was noted for the surfactant. Thus, under surface pressures which correspond to large lung volumes in vivo, the surfactant acyl chains exist mostly in the ordered (trans) configuration. The frequency shift in the CH2 stretching mode is consistent with a continuous ordering of the acyl chains upon compression over the pressure range 0-43 dyn/cm, and implies that a weakly cooperative phase transition occurs in the hydrocarbon region of the surface film. The surface film transition is especially noted in the pressure-area curve of the surfactant and approximates in two dimensions the broad thermotropic phase transition of the bulk phase surfactant. Substantial differences were observed between the response to surface pressure changes of intact surfactant compared with the main surfactant phospholipid, 1,2-dipalmitoyl-sn--glycero-3-phosphocholine. The changes in response are attributed to the presence of additional surfactant components. The current work demonstrates the ability of infrared spectroscopy to obtain structural information on the surfactant in physical states that directly relate to those in vivo.
1,2-Dipalmitoylphosphatidylcholine↗
Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.
The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme-linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero-positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease.
Animals↗
Simian immunodeficiency virus-induced meningoencephalitis: natural history and retrospective study.
Simian immunodeficiency virus (SIV) is a lentivirus with morphological and antigenic similarities to human immunodeficiency virus, the causative agent of acquired immunodeficiency syndrome (AIDS) of humans. Macaque monkeys infected with SIV show profound immunological impairment, clinically characterized by multiple opportunistic infections and neoplasms. Retrospective examination of autopsy tissue from 27 SIV-infected animals demonstrated that approximately 60% of the experimentally inoculated animals had a meningoencephalitis characterized by perivascular infiltrates of macrophages and multinucleate giant cells in the white and gray matter and leptomeninges. Ultrastructurally, these macrophages contained typical lentiviral particles within membrane-bound intracytoplasmic vacuoles. Other findings in the central nervous system included discrete randomly located neuroglial nodules, endothelial hypertrophy, and leptomeningeal thickening. The results indicate tha the meningoencephalitis induced by SIV in monkeys is similar to the lesions of the central nervous system in patients with AIDS and that SIV infection in the macaque is a useful animal model to study the pathogenesis of human immunodeficiency virus--related subacute encephalitis or AIDS encephalopathy.
Animals↗
Alterations in cerebrospinal fluid uridine, hypoxanthine, and xanthine in head-injured patients.
1. Examination of the cerebrospinal fluid (CSF) of head-injured patients reveals that the concentration of intraventricular xanthine is elevated and that of uridine is decreased relative to those of adult lumbar CSF. 2. No correlations were observed between CSF lactate and CSF hypoxanthine, xanthine, or uridine, suggesting that changes in purine metabolites and the pyrimidine nucleoside do not index similar cellular events as does lactic acid production. 3. Ventricular CSF from hydrocephalic infants had uridine and hypoxanthine concentrations not significantly different from those of normal adult lumbar CSF, but xanthine was significantly elevated. 4. Since uridine has anticonvulsant properties and is a crucial substrate for cerebral metabolism, it may be useful to evaluate this pyrimidine for use in the management of patients with head injury.
Adult↗
Immunophenotypic characterization of mononuclear phagocytes and dendritic cells in lymphoid organs of the rhesus monkey.
Mononuclear phagocytes and dendritic cells are potent antigen-presenting cells that localize to distinct microenvironmental compartments in many different organs. These cells are particularly plentiful in spleen and lymph node. Recently, these cells have been identified and immunophenotypically characterized in human tissue sections using monoclonal antibodies. However, similar studies in animal species, particularly those representing models of human diseases, have yet to be completely performed. We have evaluated 18 monoclonal reagents raised against human determinants for their reactivity with macrophages and dendritic cells in lymphoid organs of rhesus monkeys. Six of the 18 (EBM11, 25F9, Mol, R4/23, To5, and SK9) produced labeling patterns in rhesus monkey lymphoid tissue that paralleled the staining patterns described for human tissues. Seven others (KB90, FMC17, Mo3, PHM3, PHM2, G16/1, and 27E10) stained varying subsets of specific cells types in these simian tissues. These reagents are requisite for the future study in an experimental animal of the afferent immune response in both normal and disease states.
Animals↗
Parotid gland salivary secretion in Tourette's syndrome and attention deficit disorder: a model system for the study of neurochemical regulation.
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Adolescent↗
Simian models for AIDS.
The macaque immunodeficiency syndrome has many parallels to AIDS in humans. Affected monkeys develop profound, prolonged T lymphocyte dysfunction and die of lymphomas or opportunistic infections. We recently isolated a virus that we call SIV from four sick macaque monkeys. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of human AIDS. The pathogenicity of this newly isolated virus was tested in macaque monkeys. Five of six died between 127 and 352 days following inoculation. The animals developed a wasting syndrome and died with adenovirus pancreatitis and/or pneumonia and primary retroviral encephalitis. Immunological abnormalities in these animals included a decrease in circulating T4+ lymphocytes and depressed peripheral blood lymphocyte proliferative response to pokeweed mitogen. The SIV monkey model holds great promise for testing antiviral agents and for the development of vaccines against AIDS.
Acquired Immunodeficiency Syndrome↗
Treatment effects of oral and transdermal clonidine in relation to methylphenidate: an open pilot study in ADD-H.
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Administration, Cutaneous↗
Lymphoproliferative syndrome in an immunodeficient rhesus monkey naturally infected with an HTLV-III-like virus (STLV-III).
A rhesus monkey with a naturally acquired STLV-III infection developed immunosuppression and a lymphoproliferative syndrome characterized by progressive lymphadenopathy and widespread visceral mononuclear cell infiltration. On microscopic examination, diffuse sheets of plasmacytoid lymphoblasts obliterated the sinuses and follicles of the nodes, replaced normal cellular elements of the spleen, bone marrow, and thymus, and infiltrated the lung, liver, kidney, salivary gland, pancreas, thyroid, stomach, and tongue. Immunohistologic studies indicated that the predominant cell in these infiltrates was a B lymphocyte, of oligo- or polyclonal origin. Similar but less extreme lymphoproliferative abnormalities were seen at necropsy in a substantial number of other animals with naturally occurring macaque immunodeficiency syndrome. The present case represents the first prospectively studied monkey with a naturally acquired simian T lymphotropic virus type III infection and illustrates an important manifestation of disease associated with such an infection.
Acquired Immunodeficiency Syndrome↗