Microinjection of Tetrahymena thermophila.
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Animals↗
Biomedical subjects
C Randolph
Publications and source records attributed to C Randolph.
Neuropsychological performance of monozygotic twins discordant for bipolar disorder.
BACKGROUND: A paradigm that involves cognitive assessment of monozygotic (MZ) twins discordant for a neuropsychiatric disorder (here bipolar illness) allows for the examination of both disease-specific impairments (in the comparison of affected to unaffected twins) and risk factors (in the comparison of unaffected twins to normal twins). METHODS: Neuropsychological functions were evaluated in seven MZ twin pairs discordant for bipolar illness and seven pairs of normal MZ twins in an attempt to highlight cognitive abilities associated with manifestations of disease and genetic risk factors. At the time of testing, 3 of the affected twins were euthymic, 2 had depressive symptoms, and 2 had manic symptoms; all were receiving medication. All twins receive neuropsychological tests to evaluate intelligence, attention, visuospatial skills, language, learning and memory, and problem solving. RESULTS: Statistical analyses revealed that the affected twins were significantly impaired as compared to the unaffected (and normal) twins on some measures of visuospatial functioning and some verbal memory measures. In contrast to a sample of MZ twins discordant for schizophrenia studied previously, the cognitive impairments we observed in bipolar twins were mild in nature and fairly circumscribed. The unaffected twins performed significantly worse than normal controls on a Brown-Petersen memory task, verbal list learning, and overall Wechsler Memory Quotient. CONCLUSIONS: These data suggest that while some visuospatial deficits and verbal memory deficits may be features of bipolar disorder related to disease parameters, mild attenuations in overall memory or retrieval function may be related to genetic factors associated with the illness.
Adult↗
Stressors and concerns in teen asthma.
Adolescents are uniquely susceptible to poor outcome with asthma because of their desire for autonomy, denial of disease, preference for immediate gain rather than prophylaxis, restricted ability to control their psychosocial and physical environment, and difficult transition to health care. Tobacco smoking as well as related drug abuse and passive exposure to tobacco is a major obstacle to managing adolescent asthma, together with atopy and psychosocial problems. Recent investigations indicate that adolescents are uniquely susceptible to tobacco industry promotions and logos because of these developmental characteristics. By understanding adolescent development, behavior and peer group impact, with its spectrum from early to late adolescence, clinicians can target their educational interventions more successfully in asthma. Health care provision for the adolescent with asthma requires a multidisciplinary team spearheaded by a primary care provider with the expert guidance of an allergist, outreach nurse, mental health worker, and social service representative. This care must be negotiated with an appropriate educational plan on the basis of NHLBI guidelines to be successful. Medications should be prescribed no more than twice a day, whenever possible, in conjunction with an action plan on the basis of peak flow readings to warn the adolescent when to use more medication and when to call the clinician. The plan should empower adolescents by recognizing their need for autonomy with self-management, enabling them to have a safe and comfortable lifestyle, and being physically and mentally at ease with their peers, family, school, and work environments.
Adolescent↗
The free running athletic screening test.
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Adolescent↗
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity.
Neuropsychological assessment of older individuals with dementing illnesses has suffered from a lack of appropriately designed test instruments. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was developed for the dual purposes of identifying and characterizing abnormal cognitive decline in the older adult and as a neuropsychological screening battery for younger patients. The entire battery takes less than 30 minutes to administer, and yields scaled scores for five cognitive domains. The current study reports preliminary clinical validity results with the RBANS, comparing very mildly demented patients with a diagnosis of probable Alzheimer's disease (n = 20) to patients with Huntington's disease (n = 20) and normal controls (n = 40). Although the patient groups had essentially identical total scores on the RBANS, they exhibited opposite profiles, differing significantly on four of the five subsections. The AD patients performed most poorly on Language, and Delayed Memory subsections, while the HD patients obtained their lowest scaled scores on the Attention and the Visuospatial/Constructional subsections. These results are consistent with the neuropsychological profiles of these dementing disorders derived from lengthier standardized tests and experimental investigations. In addition, even those patients who performed above the suggested cut-off points on the MMSE and the Dementia Rating Scale scored significantly below their controls on the RBANS. These data suggest that the RBANS is effective at both detecting and characterizing dementia of different etiologies.
Aged↗
Standardized assessment of concussion (SAC): on-site mental status evaluation of the athlete.
OBJECTIVE: This study investigated the clinical utility of the Standardized Assessment of Concussion (SAC) in detecting concussion in athletes. METHOD: Athletic trainers administered the SAC to 568 nonconcussed high school and college football players prior to the 1995 and 1996 football seasons. Thirty-three of these players experienced concussion and were tested immediately following injury; 28 of the 33 underwent additional follow-up testing 48 hours after the injury. RESULTS: Concussed players scored significantly below nonconcussed controls on all SAC measures and significantly below their own pre-injury baseline performance. Follow-up testing documented return to preinjury baseline. CONCLUSION: These findings support the SAC's effectiveness in detecting concussion and tracking recovery in order to determine a player's fitness to return to play.
Adolescent↗
Pyrogenicity of etiocholanolone and interleukin-1 in New and Old World Monkeys.
Etiocholanolone (5beta-androstan-3alpha-ol-17-one; designated E) is one of the major products of metabolism of testosterone and androstenedione (androst-4-ene-3,17-dione) in many mammalian species, including humans. E and several other 5beta-reduced steroids have been found to induce fever in humans. The pyrogenic effect of these steroids has been shown to be due to the release of interleukin-1 (IL-1) from the leukocytes that are mobilized in response to the steroid injections. Old World Monkeys such as Rhesus monkeys (Macaca mu/atta), metabolize androgens similarly to humans, and E is a normal metabolite. However, New World Monkeys such as Squirrel monkeys (Saimiri sciureus), lack hepatic 5alpha- and 5beta-steroid reductases and excrete androgens primarily in an unaltered state; E is not produced. Therefore, we postulate that Squirrel monkeys likewise may have lost the ability to respond to 17-ketosteroids such as E. To test this hypothesis, adult male Rhesus and Squirrel monkeys were treated with E, and their rectal temperatures were recorded over a 24-hr period. Rhesus monkeys exhibited a rise of up to 3 degrees F following E injection. Squirrel monkeys, on the other hand, did not exhibit any increase in rectal temperature over the 24-hr period, even when doses up to 250 times the effective human dose were used. However, both species responded to injected IL-1alpha with a robust increase in rectal temperature. The data show that E is pyrogenic in Rhesus, but not Squirrel monkeys. The findings support the notion that injected E may induce release of IL-1 in Rhesus monkeys, but not in Squirrel monkeys.
Androsterone↗
In response to Dr. Richard Evans's Update on childhood asthma.
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Asthma↗
Visuospatial working memory in patients with schizophrenia.
Recent investigations have documented abnormalities in working memory related processes in schizophrenics on tasks assessing the central executive component of this cognitive model. This preliminary study investigated the function of another component of the working memory system, the visuospatial scratch pad in schizophrenia. The "scratch pad's" passive visual store--responsible for the temporary retention of visual material--was assessed via a computerized spatial delayed response task, whereas its active spatial rehearsal subsystem--specialized for retaining the temporal properties--was explored through visual block span. To assess elemental visual spatial abilities we used the Judgment of Line Orientation test. Thirty-two schizophrenics and 27 controls were tested. Although we discovered the basic perceptual abilities of patients to be intact, we determined that whenever memory was necessitated on spatial tasks, patients demonstrated marked deficits. This pattern of cognitive dysfunction is consistent with impairments in a neural network involving prefrontal and/or posterior brain regions in schizophrenia.
Adult↗
Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia.
BACKGROUND: Impaired Wisconsin Card Sorting Test (WCST) performance has been one critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia. However, the specific cognitive processes underlying impaired performance have not been identified. Impaired WCST performance in schizophrenia might in part reflect a fundamental working memory deficit. METHODS: We examined the performance of 30 normal subjects and 36 patients with schizophrenia on a neuropsychological battery including a novel measure of working memory-letter-number (LN) span. RESULTS: Patients with schizophrenia were impaired on LN span performance, which was also highly correlated with WCST performance (r = 0.74). Between-group WCST differences were eliminated when we covaried LN span. Regression analyses suggested that LN span performance predicted the WCST category achieved score, whereas measures of set shifting, verbal fluency, and attention were predictive of perseveration. CONCLUSION: Working memory may be a critical determinant of one aspect of WCST performance in schizophrenia.
Adult↗
Exercise-induced asthma: update on pathophysiology, clinical diagnosis, and treatment.
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Adolescent↗
Pattern and source of secretion of relaxin in the reproductive cycle of the spotted hyena (Crocuta crocuta).
Female spotted hyenas are highly masculinized at birth and have no external vagina. Copulation with males and birth of young are accomplished through the central urogenital canal of the clitoris. This unusual adaptation requires remarkable changes in the elasticity of the connective tissues of the clitoris, without which neither copulation nor birth would be possible. We hypothesized that relaxin, a hormone that increases the extensibility of the connective tissues of the uterus and cervix of many other mammalian species, plays a role in the clitoral changes observed in hyenas. Serum relaxin was determined by specific RIA. Relaxin was not detected in serum of males, pubertal or nonpregnant adult females, or ovariectomized females. Immunoactive relaxin was detected in serum of juveniles at the time of initial growth of the urogenital meatus. High concentrations of immunoactive relaxin appeared in the serum of pregnant hyenas in the 2 wk preceding parturition. Immunoassays of extracts of hyena tissues and serum obtained from uterine and ovarian veins indicated that the placenta was the predominant source of relaxin, with possible ovarian contributions. Circulating relaxin decreased promptly following cesarean section near term. We conclude that relaxin secretion coincides with changes in extensibility of clitoral connective tissues 1) during growth of the clitoris in juveniles and 2) near the time of parturition in adults.
Animals↗
Regulatory sequences for the amplification and replication of the ribosomal DNA minichromosome in Tetrahymena thermophila.
We have analyzed the cis-acting sequences that regulate rRNA gene (rDNA) replication in Tetrahymena thermophila. The macronucleus of this ciliated protozoan contains 9,000 copies of a 21-kbp minichromosome in the form of a palindrome comprising two copies of the rDNA. These are derived from a single chromosomally integrated copy during conjugation through selective amplification and are maintained by replicating once per cell cycle during vegetative growth. We have developed a transformation vector and carried out a deletion analysis to determine the minimal sequences required for replication, amplification, and/or stable maintenance of the rDNA molecule. Using constructs containing progressively longer deletions, we show that only a small portion (approximately 900 bp) of the rDNA is needed for extrachromosomal replication and stable maintenance of this molecule. This core region is very near but does not include the rRNA transcription initiation site or its putative promoter, indicating that replication is not dependent on normal rRNA transcription. It includes two nearly identical nuclease-sensitive domains (D1 and D2), one of which (D1) corresponds to the physical origin of replication determined previously. Deletion of both domains abolishes replication, whereas deletion of either domain allows the molecules to replicate, indicating that only one domain is required. In addition to this core region, we have found several DNA segments, including a tandem array of a 21-nucleotide repeat (type II repeats) and sequences within the rRNA coding region, that play distinctive and important roles in maintaining the rDNA at a high copy number.
Animals↗
Standardized assessment of concussion in football players.
The recent formulation of guidelines for the management of concussion in sports adopted by the American Academy of Neurology specifically calls for the development of a standardized, systematic sideline evaluation for the immediate assessment of concussion in athletes. The present study involved the preliminary investigation of the feasibility and clinical validity of a standardized version of a brief sideline examination complied in accordance with these guidelines. This examination, intended for use by athletic trainers, was administered by three trainers to 141 nonconcussed high school football players at three separate schools. All players suspected of suffering a concussion (N = 6) during the fall 1995 season were also tested immediately following their injury. The examination was easily administered and scored. The concussed players as a group scored significantly below the nonconcussed controls and below their own baseline (pre-injury) performance, despite their all having been considered by the trainers to have suffered mild, grade 1 concussions. Although preliminary, these data suggest that a standardized sideline examination of this type can be useful in detecting concussion and determining fitness to return to play.
Adolescent↗
Neuropsychological characterization and detection of subclinical hepatic encephalopathy.
OBJECTIVE: To elucidate the nature of the neuropsychological deficits associated with subclinical hepatic encephalopathy. DESIGN: Prospective study comparing the performance of patients with liver disease and carefully matched normal controls on a short but comprehensive neuropsychological test battery. SETTING: A university medical center. PARTICIPANTS: Twenty patients with cirrhosis (10 alcoholic and 10 nonalcoholic) and 20 controls carefully matched on the basis of age, sex, education, and alcohol history. RESULTS: The cirrhotic patients exhibited relatively selective deficits in complex attentional and fine motor skills, with preservation of general intellectual ability, memory, language and visuospatial perception. CONCLUSIONS: This pattern of neuropsychological deficits suggests a subcortical pathophysiology, possibly reflecting involvement of the basal ganglia. These neuropsychological findings are consistent with recent neuroradiological, electrophysiological, and neurophysiological research implicating basal ganglia involvement in cirrhosis.
Female↗
Isolating the mnemonic component in spatial delayed response: a controlled PET 15O-labeled water regional cerebral blood flow study in normal humans.
In this study we attempted to elucidate the neural network involved in maintaining spatial information over short delays by means of the PET 15O-labeled water method for measuring regional cerebral blood flow. To isolate the mnemonic component of delayed response processing we designed a control task isomorphic to the experimental task (in which the subject remembered the location of four targets in an array over a 7 s delay) and controlled for spatial encoding. Fourteen normal subjects participated in the study. Regional cerebral blood flow (rCBF) data were analyzed using statistical parametric mapping, a data-driven approach which canvasses the whole brain for significantly activated pixels in the experimental vis-à-vis the control task, and a hypothesis driven region of interest approach involving comparisons of control and experimental conditions using normalized rCBF data. We found convergent evidence for a spatially distinct but functionally related network in which dorsolateral prefrontal cortex and extrastriate occipital cortex were activated by the experimental task vis-à-vis the control task, as well as evidence for superior parietal and supplementary motor area cortical activation. These findings suggest that anterior components of the network may be involved in mnemonic rehearsal functions, while posterior components may store critical perceptual attributes of the memoranda.
Adult↗
Utility of clinical trial batteries in the measurement of Alzheimer's and Huntington's dementia.
Tests used as outcome measures in clinical trials of antidementia agents are not typically employed as part of diagnostic evaluations, and little information exists as to the sensitivity of these tests in terms of either differentiating demented patients from normal individuals or in distinguishing dementias of various types and etiologies. Sensitivity to mild dementia and sensitivity to impairment of various neuropsychological domains are, however, prerequisites for valid use of an instrument as an outcome measure in this context. The present study was undertaken to directly compare six different tests (three traditional psychometric tests and three clinical trial batteries) in terms of their sensitivity to detect and distinguish between mild dementia in patients with either Alzheimer's disease (n = 15) or Huntington's disease (n = 15), when compared to normal controls (n = 15). Tests included the Mattis Dementia Rating Scale, the Mini-Mental State Examination, the Wechsler Memory Scale-Revised, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the Computerized Drug Research (CDR) Cognitive Assessment System, and the Repeatable Battery for the Assessment of Dementia (RBAD). All of the tests were roughly equivalent in terms of their ability to discriminate normal subjects from mildly demented patients. Only the CDR and RBAD, however, were able to reliably discriminate between the two patient groups. The results are discussed in terms of the applicability of these tests as outcome measures for clinical trials in dementing disorders.
Adult↗