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Biomedical subjects

L Henderson

Publications and source records attributed to L Henderson.

At least 37 records · Page 2Linked to original sources

Cognitive-behavioral group therapy for social phobia in female adolescents: results of a pilot study.

OBJECTIVES: To examine the efficacy of cognitive-behavioral group therapy for adolescents (CBGT-A) in females with social phobia and the effect of this treatment on the risk for major depression. METHOD: Female adolescents with social phobia (N = 35) were randomly assigned to treatment (n = 12) or no treatment (n = 23) groups. Assessments were conducted at baseline, after treatment, and at a 1-year follow-up. RESULTS: Eleven subjects completed treatment. Sixteen weeks of treatment produced a significant improvement in interference and reduction in symptoms of social anxiety. There was a significant reduction in the number of subjects meeting DSM-IV criteria for social phobia in the CBGT-A versus the untreated group; however, at the 1-year follow-up there were no significant differences by treatment condition. There was also suggestive evidence that treatment of social phobia lowers the risk for relapse of major depression among those with a history of major depression. Combining social phobia and major depression as the outcome produced more robust treatment effects in the 1-year follow-up. CONCLUSIONS: This pilot study provides evidence for a moderate short-term effect of CBGT-A for treating female adolescents suffering from social phobia and indicates that treatment of social phobia may result in a reduction of major depression.

Adolescent↗

Fluorescent HPLC assay for 20-HETE and other P-450 metabolites of arachidonic acid.

This study describes a fluorescent HPLC assay for measuring 20-hydroxyeicosatetraenoic acid (20-HETE) and other cytochrome P-450 metabolites of arachidonic acid in urine, tissue, and interstitial fluid. An internal standard, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid, was added to samples, and the lipids were extracted and labeled with 2-(2,3-naphthalimino)ethyl trifluoromethanesulfonate. P-450 metabolites were separated on a C18 reverse-phase HPLC column. Coelution and gas chromatography-mass spectrometry studies confirmed the identity of the 20-HETE peak. The 20-HETE peak can be separated from those for dihydroxyeicosatrienoic acids, other HETEs, and epoxyeicosatrienoic acids. Known amounts of 20-HETE were used to generate a standard curve (range 1-10 ng, r(2) = 0.98). Recovery of 20-HETE from urine averaged 95%, and the intra-assay variation was <5%. Levels of 20-HETE were measured in 100 microliter of urine and renal interstitial fluid or 0.1 mg of renal tissue. The assay was evaluated by studying the effects of 1-aminobenzotriazole (ABT) on the excretion of 20-HETE in rats. ABT reduced excretion of 20-HETE by >65% and inhibited the formation of 20-HETE by renal microsomes. The availability of this assay should facilitate work in this field.

Animals↗

The knowledge and use of alternative therapeutic techniques by social work practitioners: a descriptive study.

A survey of use of alternative therapeutic methods was distributed to 1,000 clinical/direct service social work practitioners; a sample of 321 reported on their use of alternative techniques. Approximately three-quarters of the respondcnts used or referred mind-body techniques or community health alternatives. These two techniques accounted for about two-thirds of all alternative practices. Manual healing was used or referred by about one-third of all practitioners and professionalized alternative medicine was used by about 30%. Other methods, including botanical, pharmacological, and biological alternatives, diet and nutrition, and parapsychology were each used by fewer than 10% of the respondents. Social workers were most knowledgeable about mind-body techniques and community-based alternatives.

Adult↗

Remembered saccades with variable delay in Parkinson's disease.

The effect of increasing delay on the metrics of remembered saccades was studied in 10 subjects with mild Parkinson's disease, none of whom was receiving treatment with L-dopa, and nine age-matched control subjects. Delays of 1 msec, 250 msec, 1000 msec, 2500 msec, and 5000 msec were used, and reflexive saccades used as a control condition. Results were analyzed for the gain of the primary saccade and the accuracy of the final eye position (FEP gain). Reflexive saccades were normal in subjects with Parkinson's disease, but remembered saccades showed marked hypometria of primary saccade gain at all delays. FEP gain was unimpaired in Parkinson's disease, and primary saccade gain and FEP gain did not vary as a function of delay. Hypometria of primary saccades is compatible with dysfunction in striato-collicular inhibitory pathways in Parkinson's disease, arising as a functional consequence of dopamine deficiency in the basal ganglia. Maintenance of an accurate FEP gain suggests no deficit in oculomotor spatial working memory in Parkinson's disease, at least at delays of up to 5 sec.

Attention↗

Saccades and smooth pursuit in myotonic dystrophy.

Reflexive saccades, remembered saccades, antisaccades, fixation and smooth pursuit were recorded in seven subjects with myotonic dystrophy (MD) and seven age-matched controls using the magnetic scleral search coil technique. Neuropsychological performance was assessed using the Wisconsin Card Sort Test and measures of verbal fluency. Subjects with MD showed significantly elevated error rates in the antisaccade and remembered saccade paradigms, consistent with prefrontal dysfunction, and these two measures of distractibility were significantly correlated with each other. Saccadic latencies, square wave jerk frequency, and smooth pursuit peak velocity gain showed no significant difference between the two groups, although the peak velocity of all classes of saccades was significantly reduced in patients with MD. These results extend the findings of previous studies of oculomotor function in MD, and provide novel evidence for a central contribution to abnormalities of eye movements in this condition.

Adolescent↗

Eye movements and spatial working memory in Parkinson's disease.

Mechanisms of spatial working memory and eye movement control were investigated in eight mild to moderate Parkinson's disease patients (PDs). Subjects were presented with a sequence of four targets which had to be memorized and then recalled by moving their eyes to fixate the four locations in the correct order. Two variations on this procedure were used in which either a different sequence of lights was presented on each trial, or an identical sequence of lights was repeated on each trial. In both conditions subjects made memory-guided eye movements in the dark, without any visual cues to eye movement accuracy or the locations of the previously illuminated lights. Analysis of the amplitude of the primary eye movement and final eye position for each step in the sequence showed that PDs made several discrete saccadic eye movements of reduced amplitude before reaching the final eye position (multi-stepping). When a novel target sequence had to be memorized on each trial, the final eye position reached by PDs for each location was also found to undershoot relative to controls. In contrast, when an identical sequence of targets was repeated on each trial, PDs' final eye position was found to be normal, although primary movement amplitudes were still reduced. PDs showed no multi-stepping and normal final eye position gain under conditions for which the target lights in the sequence were illuminated during movement execution. PDs also made an increased proportion of overt errors in target sequence recall. Parallel neuropsychological testing in PDs and controls revealed that error rates in the sequential memory-guided saccade task were significantly correlated with performance in a task thought to be sensitive to spatial working memory dysfunction. The findings suggest that short-term spatial memory representations are disrupted in the early stages of PD.

Aged↗

Hypothalamic NPY status during positive energy balance and the effects of the NPY antagonist, BW 1229U91, on the consumption of highly palatable energy-rich diet.

We have studied the hypothalamic activity of the neuropeptide Y (NPY) system in dietary-induced obese male Wistar rats and examined whether the NPY antagonist, BW1229U91, can inhibit the hyperphagia during positive energy balance associated with feeding rats an energy-rich, highly palatable diet. Rats given a highly palatable, high-fat diet became obese after 8 weeks and exhibited hyperinsulinemia and hyperleptinemia, as compared to lean rats fed on standard pellet laboratory diet. Hypothalamic NPY mRNA concentrations were significantly reduced by approximately 70% in dietary-obese rats compared with lean controls, and the former were hypersensitive to intracerebroventricular injections of NPY, possibly as a result of NPY receptor up-regulation. Intracerebroventricular injections of BW 1229U91, that inhibits food intake in starved rats, did not alter food intake in either control or obese rats fed either standard pellet diet or the highly palatable diet, respectively. We conclude that dietary-obese rats have underactive hypothalamic NPYergic neurons compared to lean controls, possibly as a result of increased plasma concentrations of leptin and/or insulin that directly inhibit the NPY neuronal activity. The lack of effect of BW1229U91 on the increased caloric intake of dietary-obese rats suggests that the hyperphagia is not NPY-driven and supports the data indicating reduced synaptic activity of the hypothalamic NPY system.

Animals↗

Correcting pretentious pronouns.

If pronouns following prepositions or verbs sound lofty or pretentious, they probably are. Without attention to grammar rules, nurse authors and editors can make common mistakes by selecting the wrong form of the pronoun. Pronouns following prepositions and transitive verbs should be the objective form of the pronoun, not the subjective form. These experienced editors describe the rule, suggest a quick-fix tip, and provide several practice items followed by answers.

Communication Barriers↗

Lack of UDS activity in the livers of rats exposed to allylisothiocyanate.

Allylisothiocyanate (AITC) has been evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the livers of male rats in vivo. Specific Pathogen Free outbred albino Hsd/Ola Sprague-Dawley rats were exposed by oral gavage to 37.5 or 125 mg/kg AITC in corn oil and hepatocytes assessed for UDS by autoradiography 2 and 14 h later. AITC did not induce UDS at either dose level at either time point. These data are consistent with all other evidence indicating that AITC does not act as a genotoxin in vivo, despite positive response in some in vitro screening assays. The reported occurrence of benign bladder papillomas in male rats but not female rats or mice of either sex is consistent with non-genotoxic action and may be attributed to chronic irritation of the bladder epithelium by AITC and its cysteine conjugate metabolite excreted by male rats in unusually concentrated form. It is concluded that the weight of evidence is insufficient to regard AITC as a genotoxin capable of human carcinogenicity.

Animals↗

Hyperphagia induced by hypoglycemia in rats is independent of leptin and hypothalamic neuropeptide Y (NPY).

Hypoglycemia causes hyperphagia and weight gain, through unknown peripheral and central signals. We investigated the effect of hypoglycemia on NPY and leptin expression and the ability of leptin to inhibit hypoglycemia-induced hyperphagia. Acute hypoglycemia (60 U/kg SC insulin; n = 8) increased food intake (p < 0.01) compared with controls (n = 8). Insulin- and leptin-treated rats (300 microg/kg IP leptin; n = 8) had reduced hyperphagia (p < 0.05 vs. controls; p < 0.05 vs. insulin alone) and a 15% fall in NPY mRNA levels compared with controls (p < 0.01). Chronic hypoglycemia, (20-60 U/kg/day insulin; n = 8) increased food intake compared with vehicle-treated controls (p < 0.01). Leptin and insulin administration (300 microg/kg/day IP leptin; n = 8) reduced hyperphagia (p < 0.01 vs. controls, p < 0.05 vs. insulin alone), and NPY mRNA fell by 18% vs. controls (p < 0.01). We conclude that hypoglycemia-induced hyperphagia is not mediated by either a fall in leptin or an increase in hypothalamic NPY mRNA. Leptin can inhibit feeding in hyperphagic hypoglycemic rats, and this may partly be attributable to its inhibition of the NPY neurons.

Acute Disease↗

The ability of the Comet assay to discriminate between genotoxins and cytotoxins.

The Comet assay has been used widely in genetic toxicology, radiation biology and medical and environmental research. This assay detects single-strand breaks and alkali-labile sites in DNA and DNA degradation due to necrosis or apoptosis. It may also be modified to detect DNA cross-linking. Although a considerable number of chemicals have been tested in the assay there are many aspects of validation to be considered before the method could be considered to provide definitive evidence of genotoxic potential. For example, very few non-genotoxins have been tested to assess specificity of the Comet assay and there has been only one reported study which investigated whether the in vitro Comet assay is prone to false positive responses due to cytotoxicity. We have investigated the response of the alkaline Comet assay in TK6 human lymphoblastoid cells to cytotoxic damage and genotoxic damage. Several compounds which are toxic by different mechanisms were tested in the assay. Cycloheximide and trypsin gave a negative comet response at a highest dose of 5 mg/ml and no toxicity was observed. Sodium lauryl sulphate and potassium cyanide produced a significant increase in DNA migration at cell survival levels of < or = 75%. The distribution of damaged cells indicated that cells at various stages of necrotic cell death were present. Hydrogen peroxide, 4-nitroquinoline oxide, 9-aminoacridine, ethyl methanesulphonate, N-nitroso-N-ethylurea and glyoxal gave a positive comet response. Mitomycin C was negative at survival levels of approximately 70%. These results indicate that the maximum concentration of test substance tested should produce viabilities > 75% in order to avoid false positive responses due to cytotoxicity. The assay was able to detect DNA damage induced by an alkylating agent, an intercalating agent and oxidative damage. The cross-linking agent mitomycin C was not detected if a cut-off point of 75% viability is used as the criterion of a positive response.

4-Nitroquinoline-1-oxide↗

Preparing to react in the absence of uncertainty: I. New perspectives on simple reaction time.

Almost from the inception of psychological enquiry into reaction time (RT), a broad distinction has been drawn between two types of process-serving performance in RT tasks, namely, the on-line processes initiated by the arrival of the imperative signal and preparatory processes, which precede the imperative signal and may contribute to performance efficiency. Restriction of attention to on-line processing fosters the conclusion that the processes serving simple RT are no more than a subset of those involved in choice reactions. If, however, latencies can be reduced by specific preparation then the certitudes of the simple reaction task may invest it with distinctive properties. The possibility of preparation being sensory as well as motor needs to be considered. Until recently, attempts to study preparedness have failed to make controlled comparisons across simple and choice RT. However, recent work has shown that simple reactions have distinctive characteristics that set them apart from minimal choice reactions. The optimization of simple RT seems to depend upon attention-demanding processes which are probably preparatory in nature. When attention has to be shared with a concurrent task, much of the normal advantage of the simple reaction is lost. Neuropsychological studies suggest that patients may be found with abnormally extended simple RT but spared choice reactions. In these patients, the simple reactions are prolonged relative to those of controls but less vulnerable to imposition of a secondary task. Evidence is beginning to accrue to the effect that some distinctive processing features of simple reactions may be mediated by activity in the frontal lobes.

Attention↗

The clinical benefit of in-hospital observation in 'low-risk' pneumonia patients after conversion from parenteral to oral antimicrobial therapy.

OBJECTIVE: To assess the benefit of in-hospital observation in "low-risk" patients with community-acquired pneumonia. DESIGN: Retrospective review of data from a prospective study. SETTING: Teaching community hospital. PATIENTS: We studied 717 consecutive, adult patients admitted to the hospital for pneumonia. MEASUREMENTS AND RESULTS: One hundred forty-five patients were classified at low-risk for complications using previously studied criteria; 144 (99%) charts were available for review. Two patients had "obvious reasons for continued hospitalization" on the day of antibiotic conversion and were excluded. One hundred two patients were observed, and 40 were not observed in-hospital after switch to oral antibiotics. No patient from either group required medical intervention within 24 h after hospital discharge. Five "observed" patients (5%, 95% confidence interval [CI], 2 to 11%) returned to the emergency department, three (3%; 95% CI, 0 to 9%) with respiratory complaints. Two (2%; 95% CI, 0 to 7%) "observed" patients were admitted to the hospital with recurrent pneumonia. One (3%; 95% CI, 0 to 13%) "not observed" patient returned to the emergency department with a nonrespiratory complaint and was not admitted. No patient from either group died within 30-day clinical follow-up. The length of stay for the "observed" and "not observed" groups was 98+/-33 h and 83+/-49 h, respectively. The difference in length of stay was 15 h (95% CI, 3 to 27). CONCLUSIONS: In-hospital observation for low-risk patients admitted with community-acquired pneumonia after switch from parenteral to oral antibiotics is of limited benefit, and elimination of this practice could potentially reduce length of stay by almost 1 day per patient. This could translate into a cost savings of $57,200 for the 22-month study period. These results require prospective validation in a larger study.

Administration, Oral↗

A comparison of training approaches for support assistants using the Hanen philosophy.

The introduction of the Hanen Programme (Watson, 1993) for parents of children who will in the future attend special schools can have training implications for their school's staff. These factors have led to a speech and language therapy service working in collaboration with its local schools to offer courses for special needs support assistants. The design, planning and delivery of the courses were based on Hanen philosophy. Some courses were exclusively for support assistants and others offered the opportunities for them to work in differing degrees of partnership with children's parents. The successes and the limitations of support assistants attending parents Hanen courses were evaluated.

Education, Continuing↗

Reciprocal regional changes in brain NPY receptor density during dietary restriction and dietary-induced obesity in the rat.

Neuropeptide Y (NPY) potently induces feeding, reduces thermogenesis and induces obesity in rats when injected into the cerebral ventricles. Groups of male Wistar rats were either restricted to 60% of their normal daily food intake over 10 days or made obese by presenting them with a high-calorie diet rich in sugars and fat over 6 weeks. Food restricted rats lost up to 20% of their body weight, compared with control rats and had large reductions in their body fat mass. By contrast, rats with dietary-induced obesity weighed 26% more than controls due mainly to increased body fat mass. Quantitative receptor autoradiography demonstrated reduced [(125)I]PYY binding in the hypothalamic lateral (perifornical) and dorsal areas, hypothalamic ventromedial, arcuate and dorsomedial nuclei, hippocampal CA3 region, centromedial amygdaloid nucleus and thalamic paraventricular and reuniens nuclei in dietary restricted rats compared with controls. By contrast, regional [(125)I]PYY binding was significantly increased in hypothalamic lateral and dorsal areas, hypothalamic arcuate and dorsomedial nuclei, amygdaloid medial and centromedial nuclei, thalamic centromedial and paraventricular nuclei of dietary obese rats versus controls. Masking NPY Y1 receptors with 1 microM BIBP3226, a selective Y1 receptor antagonist, revealed that the changes in [(125)I]PYY binding in brains of food-restricted and dietary-obese rats were due to changes in BIBP3226-insensitive binding sites, presumably Y2 or Y5 NPY receptors. These data suggest that dietary-restriction stimulates NPY release resulting in down-regulation of NPY Y5 'feeding' and/or Y2 receptors and reduced BAT thermogenesis thereby providing an increased drive to eat to restore normal caloric intake whilst reducing thermogenesis in order to conserve fat reserves. By contrast, the up-regulation of NPY Y5 and/or Y2 receptors in dietary-induced obesity is consistent with inhibition of NPY release in the hypothalamus, amygdala and thalamus. Overall, we suggest that there is a regional increase in NPY release during negative energy balance, such as during food-restriction and a reduced regional release of NPY in positive energy balance, such as during hyperphagia associated with the development of obesity.

Amygdala↗

Abnormalities of predictive saccades in Parkinson's disease.

Saccades of patients with mild Parkinson's disease (PD) are said to be abnormal in the absence of a concurrently visible target or when they are part of a rapid sequence of eye movements. We tested this hypothesis using a predictive saccade paradigm in which target visibility is withdrawn for a period. Three rates of target alternation were used (0.25 Hz, 0.5 Hz and 1.0 Hz). Withdrawal of target visibility brought out the extremes of primary saccade gain for both the controls and the patients with PD, most undershoot being displayed at the lowest frequency, whereas the gain was greatest at the highest frequency, actually overshooting the target location. These results demonstrate that the spatial error of parkinsonian saccades does not invariably take the form of hypometria when part of a rapid sequence of eye movements.

Adult↗

Safety evaluation of tannase enzyme preparation derived from Aspergillus oryzae.

Tannase is an acylhydrolase enzyme preparation from Aspergillus oryzae that can be used as a processing aid for the manufacture of cold water-soluble tea beverages. A 91-day oral toxicity study in the rat and a gene mutation study in Salmonella typhimurium were performed to establish the safety of the enzyme preparation for the consumer. General toxicity was low, with no adverse effects observed at the highest dose tested, 1% in the diet. There was no evidence of mutagenic potential with or without metabolic activation. These results, together with knowledge of the production organism and the chemical and microbiological characterization of the enzyme preparation, indicate that tannase can be regarded as safe for its intended use in processing tea.

Administration, Oral↗