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Biomedical subjects

R Andrade

Publications and source records attributed to R Andrade.

At least 19 recordsLinked to original sources

The clinical, neuroradiographic, and endocrinologic profile of patients with bilateral optic nerve hypoplasia.

PURPOSE: The purpose of the study was to expand on ophthalmologic and endocrinologic data and report the neuroimaging findings of 35 patients with bilateral optic nerve hypoplasia (BONH). METHODS: A retrospective chart review of 35 children with BONH was conducted. Data on visual acuity, refractive error, and presence of nystagmus and strabismus were collected. Twenty-six children underwent full-endocrinologic evaluation and magnetic resonance imaging or computed tomography scanning. RESULTS: The male:female ratio was 2:1. Ten percent of eyes had visual acuity of 20/60 or better, whereas 34% had no light perception. Eighty-six percent of eyes had acuity less than 20/200, and 80% of patients were legally blind. Most patients (86%) had nystagmus or strabismus or both. Forty-six percent had absence of the septum pellucidum and corpus callosum on neuroimaging. Twenty-seven percent of patients had endocrinologic abnormalities, with growth hormone deficiency being the most common. Panhypopituitarism occurred in 11.5% of children. CONCLUSIONS: Although the visual prognosis of children with BONH generally is poor, 10% of such patients have excellent acuity. In contrast to previous reports, endocrine abnormalities were seen in only one quarter of patients, and the full-blown deMorsier syndrome (septo-optic dysplasia with panhypopituitarism) was seen in only 11.5% of patients with BONH.

Abnormalities, Multiple

Acute renal failure in open heart surgery.

A case-control study was performed to establish possible risk factors for acute renal failure (ARF) and mortality in patients undergoing cardiac surgery. A consecutive series of 704 patients were included in the study. A randomized sample of 255 patients was taken to analyze risk factors for ARF and mortality. Incidence of acute renal failure was 3.8% (27/704). Low cardiac output (LCO) was observed in all patients who developed ARF and in 72/255 without ARF (p < 0.0005). When LCO was isolated, no difference was found between groups. Association to prolonged perfusion time and sepsis increased the probability of developing ARF: 5/27 versus 0/255, p < 0.001; and 9/27 versus 0/255, p < 0.001, respectively. Overall mortality was 7.2% (51/704). Significant difference was found between ARF (55.6%, 15/27) and non-ARF patients (5.4%, 36/704), p < 0.005. Neither age nor sex was associated to outcome. Nonsurvivor patients were more oliguric (11/15 vs. 0/12, p < 0.005), required dialysis more frequently (7/15 vs. 0/12, p < 0.005), and were complicated with sepsis more often (9/15 vs. 0/12, p < 0.005), compared to survivors. We concluded that ARF was an uncommon complication in this group of patients, but mortality rate was dramatically high. This study identified LCO associated to prolonged perfusion time and sepsis as risk factors for ARF. Severity of ARF (oliguric forms and dialysis requirement) and postoperative events (sepsis) were associated with mortality.

Acute Kidney Injury

[Retrospective multicenter study of the efficacy of interferon alpha in chronic hepatitis C].

BACKGROUND: Until very recently, interferon (INF) in Spain was authorized in chronic hepatitis C (C-HCV) at a dosis of 3 megaunits (mu) for 6 months. Nonetheless, the rate of maintained complete response is lower than that obtained with more prolonged treatments. The first aim of this study was to retrospectively know the effectiveness of alpha INF in patients treated for 6 or 12 months with a dosis of 3 or 5-6 MU. The second was to analyze the characteristics of the patients who achieved a maintained complete response. PATIENTS AND METHODS: Patients with C-HCV treated in 9 hospitals in Andalucía, Spain who fulfilled the following conditions were retrospectively analyzed: liver biopsy prior to treatment, positive test for anti HCV and a follow up of at least 6 months after alpha INF treatment. A total of 344 patients were studied: 267 treated with alpha INF-2b, 51 with alpha INF-2a and 26 with lymphoblastoid INF. One hundred ninety-five patients were treated for 6 months and 149 for 12 months. RESULTS: Seventy-seven (22%) of the patients presented maintained complete response, 170 (50%) did not respond and 97 (28%) relapsed. On comparing the three types of interferon used over 6 months, no significant differences were observed. Neither were differences found on comparing the dosis of 3 mu versus 5 or 6 mu. On analyzing the treatments of 6 and 12 months, the following was observed, respectively: maintained complete response 15% vs 32%, relapse 29% vs 30% and non responders 57% vs 38% (p < 0.001). Multivariate analysis demonstrated that the patients who responded the best to INF were those who presented the following characteristics: female sex, age under 40 years last, history of transfusion or IVDA, basal GPT level higher than 145 IU/I, GGT less than 55 IU/I, less evolved histologic lesions and duration of treatment over 12 months. CONCLUSIONS: Of the different treatments analyzed with alpha interferon in chronic hepatitis C, the best was found to be that with 3 mu during 12 months.

Adult

Muscarinic activation of a voltage-dependent cation nonselective current in rat association cortex.

The ionic mechanism underlying the acetylcholine-induced depolarization of layer V pyramidal neurons of rat prefrontal cortex was examined using whole-cell recording in in vitro rat brain slices. Consistent with previous results, pressure application of acetylcholine to layer V pyramidal neurons elicited a strong depolarization. Pharmacological analysis of this response indicated that it was mediated by the stimulation of muscarinic receptors as it was mimicked by muscarinic agonists, but not by nicotine, and was blocked by atropine. The inward current responsible for the depolarization resulted from the activation of a voltage-dependent, cation nonselective current. Thus, the amplitude of the current was critically dependent on extracellular sodium concentration but not on extracellular potassium or chloride concentration. Examination of the I-V relationship for the muscarinic current using voltage clamp revealed that the current reversed near -15 mV and exhibited a strong voltage dependence, turning off rapidly in the subthreshold range. The voltage dependence of the current led to the appearance of a current associated with a conductance decrease when examined using steady-state voltage- or current-clamp measurements. This might have led to earlier misidentification of this response as mediated by a decrease in potassium conductance. These results question the traditional interpretation that muscarinic depolarization in cortex is mediated by a decrease in potassium conductance. They indicate that the fundamental mechanism responsible for muscarinic depolarization in prefrontal cortex involves the activation of a voltage-dependent, cation nonselective current. This current might represent a previously unsuspected mechanism capable of mediating slow depolarization in the central nervous system.

Acetylcholine

5-Hydroxytryptamine4 receptors reduce afterhyperpolarization in hippocampus by inhibiting calcium-induced calcium release.

Serotonin acting on 5-hydroxytryptamine4 receptors increases membrane excitability in CA1 hippocampal pyramidal cells by reducing the slow calcium-activated afterhyperpolarization. This effect is mediated through an increase in cAMP and activation of protein kinase A, although subsequent steps have not been elucidated. We now report that a significant portion of the calcium responsible for the generation of the afterhyperpolarization originates from the release of intracellular calcium through a calcium-induced calcium-release mechanism. Thus, the afterhyperpolarization is enhanced by caffeine, whereas it is inhibited by dantrolene and ruthenium red, two blockers of calcium-induced calcium release. The afterhyperpolarization is also inhibited by thapsigargin, which depletes intracellular calcium stores. These observations raised the possibility that serotonin might reduce the afterhyperpolarization by regulating calcium-induced calcium release. Consistent with this possibility, administration of calcium-induced calcium-release blockers, as well as of thapsigargin, occluded the ability of serotonin to inhibit the afterhyperpolarization. Similarly, administration of caffeine, which enhances the contribution of calcium-induced calcium release to the afterhyperpolarization, enhanced the effect of serotonin. These results indicate that serotonin inhibits the afterhyperpolarization in the CA1 region of hippocampus by reducing the ability of extracellular calcium to trigger calcium release from intracellular stores. As such, they identify a physiological role for the calcium-induced calcium release in hippocampus and provide evidence for its regulation by G protein-coupled receptors and, more specifically, 5-hydroxytryptamine4 receptors.

Action Potentials

Cyclic AMP and protein kinase A mediate 5-hydroxytryptamine type 4 receptor regulation of calcium-activated potassium current in adult hippocampal neurons.

In the CA1 region of the hippocampus, activation of serotonin receptors of the 5-hydroxytryptamine (5-HT)4 subtype increases membrane excitability by reducing the calcium-activated potassium current responsible for the slow afterhyperpolarization observed in these cells. In the present study, the signaling mechanism by which 5-HT4 receptors reduce the afterhyperpolarization in the CA1 region was examined using intracellular recording in brain slices. Administration of the membrane-permeable cAMP analog 8-bromo-cAMP mimicked the effect of serotonin on the afterhyperpolarization, whereas administration of the protein kinase inhibitor staurosporine inhibited the effects of serotonin. These observations suggested a role for protein kinase A in this response. This was confirmed by intracellular injection of the selective protein kinase A inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate ((Rp)-cAMPS), which noncompetitively inhibited the ability of serotonin to reduce the after-hyperpolarization. Additional evidence for the involvement of cAMP in the signaling by 5-HT4 receptors was obtained using the general phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. When this compound was bath administered at concentrations sufficient to enhance a known cAMP-mediated response, a significant enhancement of the ability of 5-HT4 receptors to reduce the afterhyperpolarization was observed. Together, these results indicate that serotonin reduces the afterhyperpolarization in the CA1 region by acting on 5-HT4 receptors that increase intracellular cAMP levels and activate protein kinase A.

Alkaloids

S-100-positive T-cell lymphoproliferative disorder. A case report and review of the literature.

The authors describe a patient with a S-100-positive T-cell lymphoproliferative disorder, characterized by clinically aggressive behavior, with leukemic dissemination and death within 1 year of the onset of symptoms. The neoplastic cells had abundant amphophilic cytoplasm, suggestive of plasmacytoid differentiation, but demonstrated a mature T-cell immunophenotype characteristic of the suppressor-cytotoxic subset. In addition, the cells expressed the S-100 protein within the cytoplasm. Genotypic studies were performed by Southern blot analysis, which demonstrated beta-chain T-cell receptor gene rearrangement, further confirming the T-cell nature of this disorder. This case had features very similar to those of the seven cases previously reported. It has been proposed that the S-100-positive T-cell lymphoproliferative disorder is a distinctive clinicopathologic entity.

Adult

[Intracranial cavernous angioma].

Clinical, radiological and histopathological features of eight cases of symptomatic cavernous angioma are presented. Five patients were being evaluated for seizure, two for mass lesions and one for intracranial hemorrhage. CT and/or MRI detected the lesion in all cases, but there is not a characteristic image for cavernous angioma. Good results were obtained by microsurgical approach to these malformations in seven patients with only one patient suffering a worsening of neurological status after surgery.

Adolescent

Antagonists of 5-HT4 receptor-mediated responses in adult hippocampal neurons.

The study of serotonin-4 (5-HT4) receptors in the central nervous system has been hindered by the lack of effective, selective antagonists. However, recently, several novel compounds have been synthesized and shown to act as antagonists at 5-HT4 receptors in smooth muscle and embryonic neurons in culture. In the present study, intracellular electrophysiological recordings were used to test the effects of three of these compounds: endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl-2,3-dihydro-6-methoxy- 2-oxo-1H-benzimidazole-1-carboxylate (DAU 6285), [1-[2-(methylsulfonylamino)ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate (GR 113808) and 2-diethylaminoethyl-(2-methoxy-4-amino-5-chloro) benzoate (SDZ 205-557) on the 5-HT4 reduction of the afterhyperpolarization seen in adult CA1 hippocampal neurons in brain slices. GR 113808, SDZ 205-557 and DAU 6285 all functioned as competitive antagonists at these 5-HT4 receptors. Although all three compounds tested acted as effective antagonists, they differed considerably in potency. When the potency of these antagonists at the 5-HT4 receptor that mediates the reduction of the afterhyperpolarization was compared with that observed for 5-HT4 receptors in biochemical and binding assays, an excellent correlation was observed. Among the antagonists tested, GR 113808 was the most potent (pA2 = GR 113808 > SDZ 205-507 > DAU 6285). It exhibited an apparent affinity for the 5-HT4 receptors in the low nanomolar range but did not antagonize 5-HT1A, beta-adrenergic or muscarinic receptor-mediated responses when applied at concentrations two orders of magnitude higher.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobenzoic Acid

Unilateral pterional approach to bilateral cerebral aneurysms.

Between 1976 and 1991, we determined that 19 patients harboring bilateral supratentorial aneurysms should be approached in a single sitting through a unilateral pterional craniotomy. Using microsurgical techniques, the Sylvian cistern was opened widely to expose the aneurysms located ipsilateral to the craniotomy. These aneurysms were clipped in the usual fashion. Following clipping, a tunnel was developed over the contralateral anterior cerebral artery and over or under the contralateral optic nerve allowing access to the opposite carotid and middle cerebral arteries. The contralateral nonruptured aneurysms were clipped in a routine fashion. We were able to clip or wrap with muscle all bilateral aneurysms in 15 cases, and we have concluded that this approach can be safely employed in selected patients with bilateral supratentorial aneurysms, and thus a second craniotomy can be avoided.

Adult

Enhancement of beta-adrenergic responses by Gi-linked receptors in rat hippocampus.

Many excitable cells express a class of neurotransmitter receptors functionally defined by their ability to increase potassium conductance through G proteins of the Gi/G(o) class that directly activate the potassium channels. Biochemical studies have shown that these same receptors can also inhibit forskolin-stimulated adenylyl cyclase, although the functional significance of this effect remains unclear. In this study electrophysiological techniques were used to examine how activation of serotonin and gamma-aminobutyric acid receptors belonging to this class affect beta-adrenergic responses signaled through adenylyl cyclase. Surprisingly, activation of these receptors not only failed to inhibit but actually enhanced beta-adrenergic responses. These observations are consistent with evidence indicating that Gi-linked receptors can enhance the ability of Gs to stimulate certain adenylyl cyclases.

Adenylyl Cyclases

Pulmonary perfusion during lung transplant rejection and experimental pneumonia.

Six left lung allotransplants were performed in healthy mongrel dogs. Immunosuppression was established with cyclosporine (15 mg/kg/day p.o.) from the day of transplantation for 30 days. Another group of animals (n = 3) was used to produce acute experimental pneumonia by instilling 4-6 ml of a 10(8) CFU suspension of Pseudomonas aeruginosa into the right lower lobe. Dynamic perfusory lung scintigraphy (DPLS) was performed before transplant/pneumonia (control), during acute rejection/pneumonia as detected radiologically, and after treatment with methylprednisolone (1 g/day for 3 days i.v.) (transplant group) or antibiotics (pneumonia group). Seroalbumin macroaggregates (5-8 McI) marked with 99-mTc were injected into the cephalic vein and the percentage of perfusion to each lung was determined. Eight acute rejection episodes were detected. DPLS showed similar perfusion to each lung, whereas during acute rejection perfusion was significantly reduced by almost 30%. Perfusion was reestablished to control levels after treatment with methylprednisolone. Reduction in perfusion correlated with radiological rejection grading. No reduction in left lung perfusion was detected in pneumonia animals. In conclusion, acute rejection reduces perfusion to the transplanted lung as measured by DPLS. Treatment restores normal perfusion.

Animals