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Biomedical subjects

V Castillo

Publications and source records attributed to V Castillo.

At least 19 recordsLinked to original sources
PubMed2006

New aspects in the diagnosis and treatment of Cushing disease.

Cushing disease, which is caused by the excessive production of ACTH, is a rare and complex endocrine disorder that still represents a major challenge for the physician in terms of accurate diagnosis and efficient treatment. Diagnosing Cushing syndrome and its etiology is an elaborate procedure and no single test is sensitive and specific enough to provide sufficient accuracy. Therefore, an ordered cascade of tests is necessary recommended by a consensus statement in 2002. The proposed diagnostic algorithm will be summarized in the following section. In the absence of efficient drug therapy, transsphenoidal resection of the pituitary adenoma is the treatment of choice for the reduction of ACTH secretion. However, not all patients can be cured by surgery. In the present article, we examine recent studies that have investigated the therapeutic potential of new generations of drugs for the treatment of Cushing disease such as cabergoline and SOM230. The role of nuclear receptors: retinoic acid receptors and peroxisome proliferator-activated receptor-gamma as new approaches for treating pituitary tumors is also discussed.

Algorithms↗
PubMed2002

The Fanconi anaemia genome stability and tumour suppressor network.

Fanconi anaemia (FA) is a rare autosomal recessive disease characterized by increased spontaneous and DNA crosslinker-induced chromosome instability, progressive pancytopenia and cancer susceptibility. An increasing number of genes are involved in FA, including the breast cancer susceptibility gene BRCA2. Five of the FA proteins (FANCA, FANCC, FANCE, FANCF and FANCG) assemble in a complex that is required for FANCD2 activation in response to DNA crosslinks. Active FANCD2 then interacts with BRCA1 and forms discrete nuclear foci. FANCD2 is independently phosphorylated by ATM (the protein whose gene is mutated in ataxia telangiectasia) in response to ionizing radiation. In addition, the FA proteins are interconnected with other nuclear and cytoplasmic factors all related to cellular responses to carcinogenic stress and to caretaker and gatekeeper functions. In this review, the most recently published data on the molecular biology of the FA pathway and its molecular crosstalk with ATM, BRCA1 and BRCA2, proteins involved in xenobiotic and reactive oxygen species metabolism, apoptosis, cell cycle control and telomere stability, are summarized. The currently available data indicate that FA is a central node in a complex nuclear and cytoplasmic network of tumour suppressor and genome stability pathways fully committed to prevent cancer.

Apoptosis↗
PubMed1999

Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown.

In eukaryotes, the 20S proteasome contains two chymotrypsin-like, two trypsin-like, and two active sites shown here to have caspase-like specificity. We report that certain sites allosterically regulate each other's activities. Substrates of a chymotrypsin-like site stimulate dramatically the caspase-like activity and also activate the other chymotrypsin-like site. Moreover, substrates of the caspase-like sites inhibit allosterically the chymotrypsin-like activity (the rate-limiting one in protein breakdown) and thus can reduce the degradation of proteins by 26S proteasomes. These allosteric effects suggest an ordered, cyclical mechanism for protein degradation. We propose that the chymotrypsin-like site initially cleaves ("bites") the polypeptide, thereby stimulating the caspase-like sites. Their activation accelerates further cleavage ("chewing") of the fragments, while the chymotrypsin-like activity is temporarily inhibited. When further caspase-like cleavages are impossible, the chymotryptic site is reactivated and the cycle repeated.

Allosteric Regulation↗
PubMed1999

Presence of SSAO in human and bovine meninges and microvessels.

In spite that SSAO enzyme is widely distributed in almost all tissues, specially in vascularized ones, its presence in brain microvessels is still controversy. Our results resolve this question showing that both human and bovine cerebrovascular tissues do contain the SSAO enzyme. This was achieved biochemically, using benzylamine and methylamine as substrates, and by immunoblot analysis, using polyclonal antibodies anti-SSAO that recognized a 100 kDa single band in tissue homogenates.

Amine Oxidase (Copper-Containing)↗
PubMed1998

Semicarbazide-sensitive amine oxidase (SSAO) from human and bovine cerebrovascular tissues: biochemical and immunohistological characterization.

Semicarbazide-sensitive amine oxidase (SSAO) is widely distributed in almost all tissues, especially in vascularized ones. However, its presence in brain microvessels is still controversial. We have investigated the presence of SSAO in human and bovine brain microvessels by biochemical and immunohistological techniques, and we have compared it with SSAO present in meninges from the same species. SSAO metabolizes benzylamine and methylamine in all tissues tested and possibly dopamine and octopamine as well, as shown in competition studies. Kynuramine inhibited the metabolism of benzylamine by SSAO with high affinity in a non-competitive manner. Western-blot analysis rendered a positive staining of a 100 kDa band, in tissues from both species. These results were confirmed by immunohistological studies: the tunica media and intima of the meninges from both species were positively stained, and so was the endothelial layer of microvessels. SSAO was absent in brain parenchyma. These results definitively confirm the presence of SSAO in human and bovine cerebrovascular tissues and they demonstrate for the first time, the presence of this amine oxidase in endothelial cells from microvessels, through biochemical and immunological approaches.

Amine Oxidase (Copper-Containing)↗
PubMed1997

[Changes in the concentrations of catecholamines and cortisol in balanced anesthesia and total intravenous anesthesia].

OBJECTIVE: To compare hormone response to stress caused by surgery performed under balanced general anesthesia and total intravenous anesthesia. PATIENTS AND METHOD: Two randomly formed groups of 24 patients each were studied. All patients were scheduled for lumbar laminectomy to correct disc hernias, with one group receiving balanced anesthesia with isoflurane (expiratory fraction between 0.5% and 0.6%), and the second group receiving total intravenous anesthesia (TIVA) (propofol infusion changed every 10 min from 12 to 6 mg/kg/h). Analgesics and relaxants were given by continuous infusion at preestablished doses (fentanyl 2 micrograms/kg/h; vecuronium 0.05 mg/kg/h). Cortisol and catecholamine (adrenalin, noradrenaline and dopamine) levels were determined at the following times: the morning of surgery (baseline), 5 min after intubation, 5 min after incision, 30 and 60 min after intubation; 5 min after tube removal and upon admission to the recovery unit. RESULTS: Cortisol levels decreased from baseline (14 +/- 3 pg/ml) until 30 min after intubation (4 +/- 2 pg/ml; p < 0.05) in the balanced anesthesia group. Adrenaline levels followed the same pattern (baseline 77 +/- 7 versus 57 +/- 10 pg/ml 30 min after intubation). Dopamine levels were statistically different (p < 0.05) at baseline (42 +/- 3 pg/ml), after intubation (38 +/- 2 pg/ml) and after incision (35 +/- 3 pg/ml), but the difference disappeared 30 minutes after intubation (38 +/- 8 pg/ml). Noradrenaline levels after incision (425 +/- 116 pg/ml) were significantly different from those at baseline (671 +/- 124 pg/ml), and the difference was evident until 60 min after incision. In the TIVA group we found significantly higher cortisol levels after intubation (21 +/- 0 pg/ml) than after baseline (14 +/- 2 pg/ml); this level decreased after extubation (7 +/- 0 pg/ml; p < 0.05). Adrenaline levels were significantly higher than at baseline (64 +/- 11 pg/ml) at times corresponding to intubation (76 +/- 5 pg/ml) and extubation (48 +/- 5 pg/ml). Noradrenaline increased significantly over baseline (497 +/- 99 pg/ml) after incision (597 +/- 90 pg/ml) and decreased significantly after 30 min. The increases in cortisol were significantly greater in the TIVA group than in the control group after intubation (21 +/- 0 versus 8 +/- 3 pg/ml, respectively) after intubation, after incision (18 +/- 2 versus 6 +/- 3 pg/ml) and 30 minutes after intubation (15 +/- 2 versus 4 +/- 2 pg/ml). Similar differences were found for dopamine after intubation (49 +/- 2 versus 38 +/- 2 pg/ml) and after incision (45 +/- 5 versus 35 +/- 3 pg/ml). CONCLUSIONS: Hormone levels are significantly higher during intravenous anesthesia than during balanced anesthesia, and the difference is evident from the earliest measurement performed.

Adult↗
PubMed1996

[Etiology and mechanism in cerebral infarction].

Cerebrovascular disease is the 3rd leading cause of death and an important cause of hospital admission and long-term disability in most industrialized populations. Many studies have shown that brain infarct is the most frequent form of cerebrovascular disease (83%). Brain infarct is a heterogeneous entity with several etiologies (mainly large-artery disease, small-artery disease, cardiac embolic disease). Different mechanisms are involved including arterial occlusion, thrombosis (atherosclerosis), embolism (from a cardiac or intraarterial source), and hemodynamic mechanisms (systemic hypoperfusion). Careful neurological assessment (cerebral computed tomogram, magnetic resonance imaging, Doppler ultrasound and angiography in selected cases) provides greater precision regarding these mechanisms and the choice of treatment.

Aortic Dissection↗
PubMed1996

[Preventive treatment of cerebrovascular accidents of arterial origin].

Inhibitors of platelet aggregation are in use for prevention of cerebrovascular insults (CVI). Aspirin at a dose of 250 +/- 100 mg/day is the most common regimen for patients at an elevated risk for vascular complications. Aspirin and ticlopidine (500 mg/day) are the best drugs for secondary prevention of arterio-arterial cerebrovascular incidents. Efficacy of inhibitors of platelet aggregation in prevention of primary cerebral infarcts has not been demonstrated. An analogue of ticlopidine, clopidogrel is presently under comparison with aspirin in the prevention of CVI. Endarterectomy of the carotid has been evaluated in several studies for prevention of CVI. In patients with symptomatic carotid stenosis (70 to 99%), endarterectomy decreases the risk for cerebral infarcts by 20 to 44%. The indication for endarterectomy in patients with asymptomatic stenosis has to be posed reluctantly because of controversial interpretations of recent study results.

Adult↗
PubMed1996

Stroke subtypes and hypertension. Primary hemorrhage vs infarction, large- vs small-artery disease.

BACKGROUND: Hypertension is the major risk factor for stroke associated with small-artery disease and large-artery disease, but the factors behind the development of a particular stroke subtype in individual patients are not known. METHODS: We determined risk factors potentially predictive of stroke subtype in 822 of 2760 patients consecutively admitted to a primary care stroke center with (1) first-ever stroke, (2) hypertension (blood pressure >160/90 mm Hg at least twice before the stroke), and (3) no cardioembolic source. We used logistic regression analysis to delineate factors associated with ischemic (brain infarct) vs hemorrhagic (primary hemorrhage) stroke and with large- vs small-artery disease. A scoring system was elaborated on the basis of the estimated regression coefficients. Observed proportions and calculated risks were determined. RESULTS: Age greater than 67 years, cigarette smoking, hypercholesterolemia, and a family history of stroke or ischemic heart disease were independent predictors of ischemic vs hemorrhagic stroke. In women, diabetes mellitus was an additional risk factor for ischemic vs hemorrhagic stroke. Only one of 144 patients with primary hemorrhage had an ipsilateral carotid stenosis. In men with brain infarct, cigarette smoking, cardiac ischemia, and a family history of stroke or ischemic heart disease were significantly and independently associated with large- vs small-artery disease. In women with brain infarct, smoking was the only predictive factor for large- vs small-artery disease. CONCLUSION: In patients with stroke and hypertension, associated risk factors influence the subtype of stroke (hemorrhage vs brain ischemia, large- vs small-artery disease).

Adolescent↗
PubMed1996

Prognosis after stroke followed by surgical closure of patent foramen ovale: a prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler ultrasound.

BACKGROUND: The risk of stroke and the long-term prognosis of recurrent strokes in young patients with patent foramen ovale (PFO) are not well known. For this reason, the treatment of these patients remains empirical. An alternative treatment to prolonged antithrombotic therapy may be surgical closure of the PFO. METHODS: Thirty patients (20 men and 10 women) with stroke and PFO were prospectively selected among 138 patients with stroke and PFO for a study of surgical closure of PFO at our center. Eligible patients were < 60 years old, had negative results of a systematic search for another cause of stroke (first criterion), and met two of the four following criteria: (1) recurrent clinical cerebrovascular events or multiple ischemic lesions on brain MR, (2) PFO associated with an atrial septal aneurysm, (3) > 50 microbubbles counted in the left atrium on contrast transesophageal echocardiography (TEE), and (4) Valsalva maneuver or cough preceding the stroke. Patients selected in this manner for surgery were considered to be a subgroup with a higher risk of stroke recurrence. RESULTS: All patients had a direct suture of PFO while under cardiopulmonary bypass without recorded early or delayed significant complication. All patients underwent a new brain MRI and TEE simultaneous with transcranial Doppler ultrasonography after contrast injection at 8 +/- 3 months after surgery. After a mean follow-up of 2 years without antithrombotic treatment, no recurrent cerebrovascular event (stroke or transient ischemic attack [TIA]) and no new lesion on MRI had developed. Postoperative contrast TEE and transcranial Doppler ultrasonography showed that two patients had residual interatrial right-to-left shunting, although much smaller than before surgery, associated with single versus double continuous suture. CONCLUSIONS: Our study of 30 selected stroke patients with surgical suture of PFO showed a stroke recurrence rate of 0% and no significant complication. Residual right-to-left shunting may be avoided by double continuous suture of the PFO. In the absence of controlled studies to guide individual therapeutic decisions, our findings show that PFO closure can be done safely and may be considered to avoid recurrence in selected patients with long life expectancy and presumed paradoxic embolism.

Adult↗
PubMed1976

[Hydroa vacciniforme, a well defined photodermatosis (clinical, histopathological and photobiological aspects, apropos of 3 personal cases].

Three cases of "hydroa vacciniforme" are reported. The clinicopathological findings are emphasized. In two cases the patients presented keloids on the blister scars and in one of them there was association with focal epilepsia. The occular complications in the "hydroa vacciniforme" are uncommon but severe. The studies of cellular photobiology ("in vitro" irradiation of lymphocytes with U.V. rays) showed an imapirement of the ADN dark1repair, as demonstrated by other authors.

Adolescent↗
PubMedDate not supplied

"Tumor-mimicking" multiple sclerosis.

The spectrum of clinical manifestations of multiple sclerosis (MS) may include rare cases where cerebral lesions simulate brain tumors or abscesses on neuroimaging. We report here on a 43-year-old woman with numerous ring-enhancing cystic lesions in the white matter of cerebral hemispheres, brainstem and cerebellum. The radiological picture was overwhelmingly in favor of a metastatic or infectious etiology, but brain biopsy showed subacute demyelination with central necrosis.

Adult↗
PubMedDate not supplied

[Nursing care for the diabetic child].

Nursing care is reviewed in six patients hospitalized with diagnosis of insulin-dependent diabetes mellitus (type I), three of them with poor metabolic control of disease (hospitalized in miscellaneous ward) and three with diagnosis of diabetic ketoacidosis (hospitalized in intensive care ward). Importance of nurse's work in the hospital assistance staff is pointed out.

Adolescent↗