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Biomedical subjects

C Andrade

Publications and source records attributed to C Andrade.

At least 19 recordsLinked to original sources

In vivo co-ordinated interactions between inhibitory systems to control glutamate-mediated hippocampal excitability.

We present an overview of the long-term adaptation of hippocampal neurotransmission to cholinergic and GABAergic deafferentation caused by excitotoxic lesion of the medial septum. Two months after septal microinjection of 2.7 nmol alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), a 220% increase of GABA(A) receptor labelling in the hippocampal CA3 and the hilus was shown, and also changes in hippocampal neurotransmission characterised by in vivo microdialysis and HPLC. Basal amino acid and purine extracellular levels were studied in control and lesioned rats. In vivo effects of 100 mm KCl perfusion and adenosine A(1) receptor blockade with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) on their release were also investigated. In lesioned animals GABA, glutamate and glutamine basal levels were decreased and taurine, adenosine and uric acid levels increased. A similar response to KCl infusion occurred in both groups except for GABA and glutamate, which release decreased in lesioned rats. Only in lesioned rats, DPCPX increased GABA basal level and KCl-induced glutamate release, and decreased glutamate turnover. Our results evidence that an excitotoxic septal lesion leads to increased hippocampal GABA(A) receptors and decreased glutamate neurotransmission. In this situation, a co-ordinated response of hippocampal retaliatory systems takes place to control neuron excitability.

Adaptation, Physiological↗

Association between early detection of soluble TNF-receptors and mortality in burn patients.

OBJECTIVES: To describe early sequential profiling of circulating levels of tumor necrosis factor alpha (TNF-alpha), TNF-1 and TNF-2 soluble receptors (sTNFR1 and sTNFR2), and of endothelin (ET-1) in patients with severe burn injury, and its association with mortality. DESIGN: Prospective study. SETTING: Intensive Care Burn Unit at a community hospital. PATIENTS: Twenty patients with total burn surface area (TBSA)> or = 30%. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were enrolled within 6 h from the injury. Blood samples were drawn at zero, 6, 12, and 24 h for sequential ELISA measurement of plasma marker levels. Data are expressed as mean+/-SD. Age, TBSA, and inhalation injury were not significantly different between survivors ( n=9; 30+/-13 years, TBSA 40+/-12%) and nonsurvivors ( n=11, 38+/-15 years, TBSA 56+/-20%). sTNFR1 levels were increased in nonsurvivors (2937+/-1676 pg/ml; 4548+/-1436 pg/ml) as compared to survivors (1313+/-561 pg/ml; 2561+/-804 pg/ml) at 6 h and 24 h, respectively ( P=0.01 and 0.002). sTNFR2 levels were significantly increased in nonsurvivors (4617+/-1,876 pg/ml vs 2611+/-1,326 pg/ml) only at 6 h ( P=0.015). TNF-alpha and ET-1 levels were not different between nonsurvivors and survivors. After adjustment for TBSA, sTNFR1 and sTNFR2 remained significantly higher in nonsurvivors. CONCLUSION: Early and progressive increase in sTNFR1 and sTNFR2 levels is associated with higher risk for poor outcome in severely burned patients.

APACHE↗

Validation of the Spanish version of the geriatric depression scale (GDS) in primary care.

OBJECTIVE: To estimate the predictive value of the 30-question Geriatric Depression Scale (GDS) in Spanish and calculate the most adequate cut-point for its use in Primary Health Care consultations. METHOD: 218 patients over the age of 64 treated at three health centers of Area 10 in Madrid were selected. In the first phase, the subjects completed the GDS, the Mini-Mental State Examination (MMSE) and a questionnaire on health and socio-demographic variables. They were later interviewed using the Geriatric Mental Schedule (GMS), used as the gold standard by doctors who were unaware of the results of the GDS. Two categories were contemplated according to the results of the GMS: cases of depression (diagnosis of psychotic or neurotic depression) and non-psychiatric cases (no psychiatric diagnosis, although isolated symptoms could be present). RESULTS: 192 aged subjects were interviewed using the GDS and the GMS. Of these, 103 were considered "non-cases of depression" and 60 others made up the "cases of psychotic/neurotic depression" group. For the most effective cut-point (9/10), sensitivity was 86.7% and specificity 63.1%. Considering a prevalence of depression of 30%, the predictive value for positives was 50.2% and for negatives 91.7%. The Cronbach alpha coefficient was 0.82, and the area below the ROC curve obtained was 0.85. Those patients with cognitive deterioration had a mean GDS score similar to those that did not present deterioration (11.16 vs 10.52; p > 0.05). CONCLUSIONS: The Geriatric Depression Scale is valid as a screening test in Primary Care consultations due to its high sensitivity and negative predictive value. The most effective Spanish GDS cut-point (9/10) is lower than that obtained in the original English version (10/11).

Aged↗

Effect of innate direction bias on T-maze learning in rats: implications for research.

Adult, male Wistar rats showed substantial left (22.2%) or right (52.8%) bias in spontaneous arm preference in the T-maze; this bias was consistent over 2 days of testing separated by a 30 day interval. Left and right biased rats learnt very rapidly when trained to enter the arm ipsilateral to the bias; learning was significantly poorer or did not occur in the contralateral arm. This contralateral learning difficulty was particularly evident when transfer of learning was assessed. Right-biased rats were more impaired in contralateral learning than left-biased rats. Unbiased rats (25%) also showed learning difficulties. This study has important implications for spatial tasks of learning and memory; with specific reference to the T maze, it is concluded that animals should be preselected for capacity to learn in both arms, randomization into experimental and control groups should be stratified for spontaneous arm bias, and original learning should be directed towards the contralateral arm while transfer of learning, if required, can be directed into the ipsilateral arm.

Animals↗

Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease.

We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 x 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3), acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear.

Adolescent↗

Nitroprusside and ECS-induced retrograde amnesia.

Previous research found that the administration of verapamil and felodipine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. This study examined whether sodium nitroprusside, an antihypertensive drug that does not affect calcium channels, has a similar action. Adult male Sprague-Dawley rats received nitroprusside (0.5 mg/kg ip) or saline 3 minutes before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after ECS using a passive avoidance task. Nitroprusside was associated with increased seizure duration in ECS-treated rats, and with enhanced recall in both true and sham ECS groups. The latter finding suggests that nitroprusside nonspecifically improves cognitive functions, and does not support the hypothesis that ECS-induced cognitive impairment is a result of blood-brain barrier breach. Nitric oxide mechanisms may underlie the benefits purveyed by nitroprusside.

Amnesia, Retrograde↗

Phenylephrine and ECS-induced retrograde amnesia.

Phenylephrine is a nonselective alpha-receptor agonist. This study examined whether the administration of phenylephrine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. Adult male Wistar rats received phenylephrine (0.25 mg/kg i.p.) or saline 3 min before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after the ECS course using a passive avoidance task. Phenylephrine increased seizure duration in ECS-treated rats, and also enhanced recall in both true and sham ECS groups. The latter finding suggests that phenylephrine nonspecifically improves cognitive functions, perhaps through adrenergic mechanisms that improve memory consolidation and storage. Since phenylephrine increases blood pressure, its cognitive effects also weaken the hypothesis that ECT-induced cognitive impairment results from the seizure-related hypertensive surge.

Adrenergic alpha-Agonists↗

A phase II trial of fractionated vinorelbine/doxorubicin as first-line therapy for advanced breast cancer.

In western countries breast cancer is still the leading cause of death of women. Very promising results have been obtained by combining vinorelbine and doxorubicin, two of the most active drugs in metastatic breast cancer. However, despite the activity reported, this combination has shown a 10% rate of grade 2-4 cardiac toxicity, mainly due to the total cumulative doses of anthracycline delivered. The aim of this study was to divide the total dose of doxorubicin into two administrations on days 1 and 8, in order to cut down its toxicity while maintaining the same activity. Fifty-two chemotherapy naïve patients with metastatic breast cancer entered into the study and were treated with vinorelbine 25 mg/m2 plus doxorubicin 25 mg/m2 both on days 1 and 8 every three weeks. Fifty-one patients were eligible and evaluable for toxicity while 47 of them were evaluable for activity. Haematological toxicity was predominantly related to neutropenia, with grade 3/4 in 16% of cycles. Non-haematological toxicity was represented by alopecia grade 3 (which affected 65% of the patients), local phlebitis and severe constipation. No clinically significant cases of neuropathy or cardiac dysfunction were seen. With regard to activity, 38 out of 47 patients (80%) responded to therapy, nine of them achieving complete responses (19%). Median response duration was 16 months and the median overall survival was 22.7 months. We conclude that the fractionated administration of vinorelbine and doxorubicin is associated with excellent haematological and non-haematological tolerability (especially as regards cardiac toxicity), coupled with high levels of activity comparable to those observed using regimens based on unfractionated administration of treatment.

Alopecia↗

Prevalence and intensity of soil-transmitted helminthiasis in the city of Portoviejo (Ecuador).

We studied the stool samples of 151 school children in a district of the city of Portoviejo (Ecuador) in order to determine the prevalence and intensity of soil-transmitted helminthiasis (STH) and their relationships with anthropometric indices. The samples were analyzed with the semiquantitative Kato-Katz technique and the intensity of infections was categorized as light, moderate or high according to the thresholds set by the World Health Organization. Prevalence of soil transmitted helmintiasis was 65% (92 out of 141 collected samples), Ascaris lumbricoides was the most common STH (63%) followed by Trichuris trichiura (10%) and hookworm (1.4%). Heavy intensity infections were found in 8.5% of the stool samples, with T. trichiura showing higher worm burdens than A. lumbricoides. Sixteen percent of the children were below the third percentile for weight (wasted), while 27% were below the third percentile for height (stunted). A significant relationship was found between the worm burden and the degree of stunting. This study suggests that the periodic administration of an antihelminthic drug should be targeted to preschool and school children to allow a normal growth spurt and prevent stunting.

Anthropometry↗

Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study.

BACKGROUND: It has been suggested that melatonin improves sleep functioning, but this possibility has not been studied in medical populations. METHOD: 33 medically ill persons with initial insomnia were randomly assigned to receive either melatonin (N = 18) or placebo (N = 15) in a flexible-dose regimen. Double-blind assessments of aspects of sleep functioning were obtained daily across the next 8 to 16 days. RESULTS: The mean stable dose of melatonin was found to be 5.4 mg. Relative to placebo, melatonin significantly hastened sleep onset, improved quality and depth of sleep, and increased sleep duration without producing drowsiness, early-morning "hangover" symptoms, or daytime adverse effects (p < .05). Melatonin also contributed to freshness in the morning and during the day and improved overall daytime functioning. Benefits were most apparent during the first week of treatment. CONCLUSION: Melatonin may be a useful hypnotic for medically ill patients with initial insomnia, particularly those for whom conventional hypnotic drug therapy may be problematic.

Adult↗

A preliminary survey of rhinotillexomania in an adolescent sample.

BACKGROUND: Rhinotillexomania is a recent term coined to describe compulsive nose picking. There is little world literature on nose-picking behavior in the general population. METHOD: We studied nose-picking behavior in a sample of 200 adolescents from 4 urban schools. RESULTS: Almost the entire sample admitted to nose picking, with a median frequency of 4 times per day; the frequency was > 20 times per day in 7.6% of the sample. Nearly 17% of subjects considered that they had a serious nose-picking problem. Other somatic habits such as nail biting, scratching in a specific spot, or pulling out of hair were also common; 3 or more such behaviors were simultaneously present in 14.2% of the sample, only in males. Occasional nose bleeds complicating nose picking occurred in 25% of subjects. Several interesting findings in specific categories of nose pickers were identified. CONCLUSION: Nose picking is common in adolescents. It is often associated with other habitual behaviors. Nose picking may merit closer epidemiologic and nosologic scrutiny.

Adolescent↗

Confusion and dysphoria with low-dose topiramate in a patient with bipolar disorder.

BACKGROUND: Topiramate, a newer antiepileptic agent, may benefit several neurological and psychiatric states, including bipolar disorder. CASE REPORT: A physically healthy, stockily built, 47-year-old, hypomanic Asian male with a >20-year history of uneventful use of psychotropic agents received topiramate in a dose that was stepped up to 100 mg/day across 10 days. He developed dysphoria, confusion, word-finding difficulties, and difficulties in maintaining a train of thought; the symptoms vanished within a week of drug discontinuation, and reappeared 1-2 days after rechallenge at a dose of 25 mg/day. CONCLUSION: It appears that, while confusion is usually a dose-dependent adverse effect of topiramate, certain patients may idiosyncratically develop this adverse effect at very low doses.

Anticonvulsants↗

Increase in AMPA receptors in aged memory-impaired rats is not associated with increase in monoamine oxidase B levels.

Aged rats may be behaviorally classified as either cognitively impaired or unimpaired based upon their performance in the Morris water maze task. In aged Long-Evans rats, emergence of functional deficits has been related to the increase in the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subtype in most hippocampal subfields, not observed in other brain structures. As AMPA receptors expressed in astrocytes may participate in the delayed and long-term glial response to injury, we investigated whether astrocytes participate in the increase of AMPA receptor observed in these aged rats. To this end, distribution of monoamine oxidase B, used as an astroglial marker, was characterized by quantitative autoradiography in the hippocampus and septum of young adults (six months) and aged (24-25 months) rats using [3H]lazabemide. Specific binding to brain sections of young, aged unimpaired, and aged impaired animals were calculated densitometrically. Compared to young animals, all hippocampal subfields in the aged unimpaired group showed a significant age-related increased labeling, which was not present in the aged impaired group. This contrasts with the increased glial transcription described in this last group. We propose that increase in AMPA receptors in the aged memory-impaired animals may be related to an atypic astrocytic reactivity.

Aging↗

Herbal treatments for ECS-induced memory deficits: a review of research and a discussion on animal models.

During the last decade the use of herbal medicinal substances in the attenuation of anterograde and retrograde amnesia induced by electroconvulsive shock (ECS) has been studied using animal research. We will discuss the background of herbal medicine in India, review the research findings on herbal medicines for ECS-induced amnestic deficits, and examine the applications and limitations of animal models in this context. We will focus on our own research and insights, with particular emphasis on practical issues.

Amnesia↗

Electroconvulsive therapy and the alpha-2 noradrenergic receptor: implications of treatment schedule effects.

Six factorially designed studies evaluated the effects of different schedules of electroconvulsive shocks (ECSs) on alpha-2 adrenoceptor function in the rat brain. Attenuation of the hypomotility response to a clonidine challenge was taken to indicate alpha-2 adrenoceptor downregulation, a putative mediator of antidepressant action. Six daily and six alternate-day ECSs were shown separately to produce this receptor change. Three alternate-day ECSs produced comparable downregulation for a comparable period as six daily ECSs; this suggests that ECS produces time-dependent effects. No changes were elicited with a single ECS, which indicates that a single ECS may not influence alpha-2 receptor function. Three daily ECSs produced brief downregulation, which has implications for receptor dynamics as a function of the ECS schedule. Finally, maintenance ECSs sustained alpha-2 adrenoceptor downregulation over 6 weeks, which suggests a possible neurochemical basis for maintenance electroconvulsive therapy. The clinical relevance and scope for further research are discussed.

Adrenergic alpha-Agonists↗

[Recommendations for the diagnosis and treatment of unstable angina and non-Q-wave myocardial infarction (proposed revision)].

The optimal diagnostic and treatment strategies for unstable angina/non-Q-wave myocardial infarction patients will continue to be redefined as rapid progress is made in the understanding, and treatment of this syndrome. The recommendations presented here reflect, in part, discussions at the International Cardiology Forum in September 1998. Although areas of controversy remain, we have summarized major points on which a consensus could be reached and for which the weight of the clinical evidence supports a change in practice.

Angina, Unstable↗