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Biomedical subjects

A Vilalta

Publications and source records attributed to A Vilalta.

At least 19 recordsLinked to original sources
PubMed2006

Lymphatic mapping and sentinel node biopsy in Merkel's cell carcinoma.

AIM: The purpose of this study was to determine the predictive value of lymphatic mapping with selective lymphadenectomy in patients with Merkel's cell carcinoma. METHODS: Eight patients with biopsy proven Merkel's cell carcinoma underwent sentinel node biopsy. Lymphoscintigraphy was performed the day before surgery following intradermal injection of 74-111MBq of 99mTc-nanocolloid divided into four doses around the biopsy scar. Dynamic and static images were obtained. RESULTS: At least one sentinel node was visualized in all patients. The sentinel node was intra-operatively identified with the aid of a hand-held gamma probe in all cases and patent blue dye in six out of eight cases. During surgery, all sentinel nodes were successfully harvested. Metastatic cell deposits were subsequently identified in three patients (37.5%) and they underwent regional lymphadenectomy. No additional involved lymph nodes were identified. No recurrence has been reported in a median follow-up of 4.6 years (range: 8 months-10 years). CONCLUSIONS: In conclusion, sentinel node biopsy in patients with Merkel's cell carcinoma appears to be a reliable staging technique.

Adult↗
PubMed2005

[Global systems for monitoring cerebral hemodynamics in the neurocritical patient: basic concepts, controversies and recent advances in measuring jugular bulb oxygenation].

Because of the importance of hypoxic/ischemic phenomena in head-injured patients, brain monitoring in these patients should be complemented by systems providing information on cerebral blood flow and metabolism. Indirect estimations of cerebral blood flow have been obtained from blood extracted from the jugular bulb, as a special bedside application of the Fick's principle to the brain. In the last few years, the use of jugular oximetry techniques has become routine in centers treating head-injured and other neurocritical patients such as those presenting subarachnoid hemorrhage or malignant middle cerebral artery infarction. The experience acquired in the use of these techniques, as well as the introduction of new neuromonitoring systems, have deepened our understanding of the information gained and have enabled more precise definition of their indications and limitations. This review describes the basic concepts underlying the use of jugular oximetry techniques in the neurocritical patient. We also explain the reasons why several variables derived from jugular blood such as arterio-jugular differences of lactate (AVDL) or the lactate-oxygen index (LOI) do not provide accurate information on brain metabolism.

Brain↗
PubMed2005

[Recent advances in regional cerebral monitoring in the neurocritical patient: brain tissue oxygen pressure monitoring, cerebral microdialysis and near-infrared spectroscopy].

The long term outcome of head-injured patients depends not only on the primary brain lesions but also to a large extent on the secondary lesions. The diagnosis of many secondary lesions, and specially that of brain ischemia, is based on simultaneous monitoring of several intracranial and systemic variables. Continuous intracranial pressure (ICP) monitoring is currently considered indispensable in the management of all patients with a severe head injury and intracranial lesions. However, the information provided by this technique is insufficient to diagnose some of the complex physiopathological processes that characterize traumatic brain lesions. Consequently, the use of methods to estimate cerebral blood flow such as transcranial Doppler and jugular oximetry to complement ICP monitoring is becoming increasingly widespread. Nevertheless, determining the effect of tissue lesions and therapeutic measures on cerebral metabolism currently requires direct access to the brain parenchyma at the bedside. In this review we focus on three methods of regional cerebral monitoring: oxygen tissue pressure (PtiO(2)) monitoring, microdialysis and near-infrared spectroscopy. The bases of each method and reference values for the variables analyzed will be discussed. We also make a series of recommendations on how results should be interpreted in light of current knowledge.

Brain↗
PubMed2004

Pilot study of treatment of biochemotherapy-refractory stage IV melanoma patients with autologous dendritic cells pulsed with a heterologous melanoma cell line lysate.

Eleven AJCC stage IV melanoma patients with progressive disease after treatment with biochemotherapy were treated with autologous dendritic cells pulsed with heterologous tumor cell lysates. The vaccine used mature DCs (CD1a+++, CD40++, CD80++, CD83+, and CD86+++) generated from peripheral blood monocytes in the presence of GM-CSF and IL-4. After 7 days, DCs were matured with a defined cocktail of cytokines (IL-1+IL-6+TNF-alpha+PGE2) and simultaneously pulsed with lysates of heterologous melanoma cell lines, for 2 days. A total of 4 x 10(6) DCs was injected monthly under ultrasound control in an inguinal lymph node of normal appearance. The study was closed when all patients died as a consequence of tumor progression. No sign of toxicity was observed during the study. One patient experienced a partial response lasting 5 months, and two patients showed a mixed response which lasted 3 months. The median survival of the whole group was 7.3 months (range 3-14 months). This vaccination program had specific antitumoral activity in highly pretreated and large tumor burden stage IV melanoma patients and was well tolerated. The clinical responses and the median survival of the group of patients, together with the low toxicity of our DC vaccine, suggest that this approach could be applied to earlier AJCC stage IV melanoma patients.

Adult↗
PubMed2004

Angiolymphoid hyperplasia with eosinophilia of the nail bed and bone: successful treatment with radiation therapy.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare entity characterized by the presence of one or several papules or nodules in the skin. Histopathology of ALHE shows a marked proliferation of blood vessels with distinctive large endothelial cells and variable inflammatory infiltrates with eosinophils. We report a 32-year-old Caucasian woman with multiple nodules involving the skin, subcutaneous tissue and bone of the distal phalanx of the fingers that were treated successfully with orthovoltage radiation therapy (40 Gy/20 fractions) and without any side-effects after 9 years of follow-up.

Adult↗
PubMed2004

Moderate hypothermia in the management of severe traumatic brain injury: a good idea proved ineffective?

Many drugs with proven efficacy in the preclinical stage have failed to show any benefit in improving the outcome of severe traumatic brain injury (TBI) when tested in controlled clinical trials. Hypothermia is still the most powerful neuroprotective method in experimental models of TBI. Its ability to influence the multiple biochemical cascades that are set in motion after TBI is quite unique. In experimental models hypothermia protects against mechanical neuronal and axonal injury and improves behavioral outcome. Encouraging results from phase II and III clinical trials of hypothermia in TBI reported in the 1990s generated great enthusiasm. However, enthusiasm faded in 2001 after the final report of the multicenter phase III trial in which the neuroprotective effects of moderate hypothermia in TBI were formally tested. This study found no significant effect on outcome in the hypothermia group, leading many clinicians to lose interest in this therapy. The present article reviews the historical background of the use of hypothermia, presents the rationale for using both immediate and deferred hypothermia, and summarizes both experimental and clinical evidence supporting its potential benefits in the management of severe TBI. New technologies using intravascular methods to induce fast hypothermia have recently become available. Cooling either through the intravenous or intra-arterial route is an exciting alternative with great potential. We argue that moderate hypothermia is still the most powerful neuroprotective candidate for severe TBI and that it merits further research and discussion. We also defend the need for further clinical trials to prove or refute its potential for treating high intracranial pressure refractory to first level therapeutic measures. The premature abandonment of hypothermia could close new avenues for improving the devastating effects of TBI.

Animals↗
PubMed2003

[Intraoperative detection of ischemic brain hypoxia using oxygen tissue pressure microprobes].

OBJECTIVE AND IMPORTANCE: Detection of intraoperative ischemic events could lead to the resolution of their cause and to the prevention of the definitive establishment of a postoperative infarct. We want to illustrate the possibilities that intraoperative monitoring of oxygen tissue pressure (PtiO2) in critical areas during a neurosurgical vascular procedure offers, enhancing its reliability and immediacy in obtaining information about tissue oxygenation status as a marker of ischemia in the vascular territory at risk. CLINICAL PRESENTATION: We report the case of a 32 year-old male with a deep arteriovenous malformation (AVM) localised in the insular region. The patient had been previously treated with radiosurgery without achieving a satisfactory result. INTERVENTION: AVM removal was performed through a transylvian transinsular approach. PtiO2 was monitorised at the temporal pole (reference area) and at the posterior temporal region (risk area). Both probes maintained close tissue oxygenation levels until the last stage of the AVM resection when, during the coagulation of a supposed afferent vessel, a brisk fall of the oxygen tissue pressure in the posterior temporal region was detected. An ischemic infarct in this area was observed postoperatively. CONCLUSIONS: PtiO2 monitoring has a high reliability in the detection of intraoperative tissue hypoxia. Data obtained could lead to early identification of these events and, whatever possible, to resolve this situation preventing the definitive establishment of an ischemic infarct.

Adult↗
PubMed2001

Rabbit EPO gene and cDNA: expression of rabbit EPO after intramuscular injection of pDNA.

Erythropoietin (EPO) cDNA was cloned from kidney total RNA of a NZW rabbit. The cDNA comprises a 588-bp open reading frame encoding a 195 amino acid protein with distinguishable regions of high of homology to other mammalian EPOs. Intramuscular injection of mice with a rabbit EPO expression plasmid resulted in a significant hematocrit increase. A rabbit genomic DNA fragment was also cloned using the rabbit EPO cDNA. This 4312-bp genomic DNA fragment contains sequences homologous to the mouse EPO promoter and hypoxia-responsive enhancer. In addition, the genomic DNA also presents a high degree of conservation to other regions involved in hypoxia response. Sequence divergence in the 3' UTR may indicate differences in regulation of mRNA stability or response to low oxygen tension.

Amino Acid Sequence↗
PubMed2001

Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine.

MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.

Adjuvants, Immunologic↗
PubMed2000

An Alu element from the K18 gene confers position-independent expression in transgenic mice.

We have identified a 323-base pair fragment of the 5'-flanking sequence of the K18 gene, which confers position-independent and copy number-dependent expression on two heterologous transgenes. This fragment is composed primarily of an Alu repetitive element. Its activity in mice is correlated with its RNA polymerase III promoter activity and its orientation-dependent ability to inhibit potential transcriptional interference in a transfection assay. However, the activity of the Alu element is not correlated with its enhancer blocking activity, a characteristic of insulator elements. In addition, this Alu element did not block the suppressive effect of co-injecting mouse alpha satellite DNA with the transgene. This Alu element is likely responsible for at least part of the protective effects of the sequences flanking the K18. These results suggest that transcriptionally active Alu elements may eliminate transcriptional interference of neighboring genes. This Alu element is one component of the locus control region associated with the K18 gene. Other Alu repetitive elements may also function to define regulatory domains.

Alkaline Phosphatase↗
PubMed2000

Corrective photoepilation for improper hairline placement after hair transplantation.

BACKGROUND: Noncoherent filtered flashlamp pulsed light has not been used for correction of surgical problems after hair transplantation. OBJECTIVE: To evaluate the clinical results of photoepilation in a patient with improper hairline placement after hair transplantation. METHODS: A noncoherent filtered flashlamp pulsed light source was used to photoepilate the misplaced frontal hairline in a 37-year-old Caucasian man, skin phototype IV (Fitzpatrick scale), who suffered from common baldness grade IV (Ebling scale) and had undergone a hair transplant 6 years before. The frontal hairline received three treatment sessions at 2-month intervals with the following treatment parameters: 695 nm cutoff filter, fluence 38 J/cm2, 3.5-msec pulse duration, triple-pulse mode, and 30-msec delay. The gulfs received two treatment sessions with the same protocol. RESULTS: Final clinical aspect was good and no hair regrowth in the frontal hairline has been observed after 1.5 years of follow-up. CONCLUSION: Noncoherent filtered flashlamp pulsed light is a novel therapeutic choice that offers a nonsurgical solution to unnatural hairline after hair transplantation.

Adult↗
PubMed1997

An RNA polymerase III-defective mutation in TATA-binding protein disrupts its interaction with a transcription factor IIIB subunit in drosophila cells.

A subunit of the Drosophila RNA polymerase III transcription factor IIIB (TFIIIB) complex has been identified using antibodies directed against the analogous human protein, hIIIB90. This protein has an apparent molecular mass of 105 kDa and has been designated dTAFIII105. Drosophila S-2 cell extracts that were immunodepleted of dTAFIII105 were substantially reduced in their capacity to support tRNA gene transcription. A protein (far Western) blot analysis revealed that dTAFIII105, present in a TFIIIB fraction, directly interacts with TATA-binding protein (TBP). Coimmunoprecipitation assays demonstrated that this protein associates with TBP in S-2 cell extracts. Our previous studies have identified a mutation at position 332 within Drosophila TBP that changes a highly conserved arginine residue to a histidine residue, which renders it specifically defective in its ability to support RNA polymerase III transcription in S-2 cells (Trivedi, A., Vilalta, A., Gopalan, S., and Johnson, D. L. (1996) Mol. Cell. Biol. 16, 6909-6916). We further demonstrate that extracts prepared from a stable cell line expressing epitope-tagged wild-type TBP exhibit an increase in tRNA gene transcription, whereas extracts derived from cells expressing the mutant TBP protein do not. Coimmunoprecipitation assays and far Western blot analysis demonstrate that this mutation in TBP abolishes its ability to stably interact with dTAFIII105. Thus, we have identified both a Drosophila protein that is directly associated with TBP in the TFIIIB complex, dTAFIII105, and an amino acid residue within the highly conserved carboxyl-terminal region of TBP that is critical for dTAFIII105-TBP interactions.

Animals↗
PubMed1996

Neoadjuvant and adjuvant chemotherapy in the multidisciplinary treatment of oral cancer stage III or IV.

We performed a retrospective analysis on the effect of initial induction chemotherapy with two courses of cisplatin (each course 120 mg/m2 cisplatin on day 1, then 20 mg/m2 bleomycin (alone) per day for 5 days with 4 weeks between courses) in 75 consecutive patients with advanced cancer of the oral cavity or lip. Further local therapy consisted of surgery or radiation, depending on tumour location. In 18 resected patients adjuvant chemotherapy was added. This consisted of carboplatin, 400 mg/m2 on day 1 then ftorafur alone, 500 mg/m2/day for 30 consecutive days, repeated every month for 4 consecutive months. Among the patients treated in the neoadjuvant setting, complete response was observed in 10 out of 75 patients (13%), and partial response in a further 50 patients (67%) (partial plus complete rate 80%). Of all the patients, 43% in stage III and 26% in stage IV were long-term survivors. Improved survival was observed in surgical patients where adjuvant postoperative chemotherapy was added (P < 0.025). The main toxic effect was vomiting, observed in 71 patients. We noted a low rate of stomatitis (4%) and an important hearing loss (12%). Neoadjuvant and adjuvant cisplatin-based chemotherapy as part of a multidisciplinary approach have a high overall response rate and low toxicity, and should increase survival in cancer of the oral cavity or lip.

Adult↗
PubMed1996

TATA-binding protein is limiting for both TATA-containing and TATA-lacking RNA polymerase III promoters in Drosophila cells.

We have investigated the role of the TATA-binding protein (TBP) in modulating RNA polymerase (Pol) III gene activity. Epitope-tagged TBP (e-TBP) was both transiently and stably transfected in Drosophila Schneider S-2 cells to increase the total cellular level of TBP. Analysis of the transcripts synthesized from cotransfected tRNA and U6 RNA genes revealed that both types of RNA Pol III promoters were substantially stimulated by an increase in e-TBP in a dose-dependent manner. Furthermore, a TBP-dependent increase in the levels of endogenous tRNA transcripts was produced in the stable line induced to express the e-TBP. We further determined whether the ability of increased TBP to induce RNA Pol III gene expression was due to a direct effect of increased TBP complexes on RNA Pol III gene promoters or an indirect consequence of enhanced expression of RNA Pol II genes. A TBP expression plasmid (e-TBP332), containing a mutation within the highly conserved carboxy-terminal domain, was both transiently and stably transfected into S-2 cells. e-TBP332 augmented the transcription from two RNA Pol II gene promoters indistinguishably from that observed when e-TBP was expressed. In contrast, e-TBP332 was completely defective in its ability to stimulate either the tRNA or U6 RNA gene promoters. In addition, increasing levels of a truncated TBP protein containing only the carboxy-terminal region failed to induce either the tRNA or U6 RNA gene promoter, whereas it retained its ability to stimulate an RNA Pol II promoter. Thus, the TBP-dependent increase in RNA Pol II gene activity is not sufficient for enhanced RNA Pol III gene transcription; rather, a direct effect on RNA Pol III promoters is required. Furthermore, these results provide the first direct evidence that the amino-terminal region of TBP is important for the formation or function of TBP-containing complexes utilized by TATA-less and TATA-containing RNA Pol III promoters. Together, these studies demonstrate that TBP is limiting for the expression of both classes of RNA Pol III promoters in Drosophila cells and implicate an important role for TBP in regulating RNA Pol III gene expression.

Animals↗
PubMed1995

Chromosome 9p deletions in cutaneous malignant melanoma tumors: the minimal deleted region involves markers outside the p16 (CDKN2) gene.

We have analyzed 12 microsatellite markers on chromosome 9p in 54 paired cutaneous malignant melanoma (CMM) tumors and normal tissues. Forty-six percent of the tumors, including two in situ CMMs, showed loss of heterozygosity (LOH) at 9p. Only one tumor was homozygously deleted for 9p markers. The smallest deleted region was defined by five tumors and included markers D9S126 to D9S259. Loss of eight or more markers correlated significantly with worse prognosis (P < .002). Among the primary tumors, 87.5% of those with large deletions have a high risk of metastasis, as compared with only 18% of those without deletions or with loss of fewer than 8 markers (P < .001). It was not possible to demonstrate homozygous deletions of p16 in any of the CMM tumors. In four tumors, the LOH for 9p markers did not involve p16. The reported data suggest the existence of several tumor suppressor genes at 9p that are involved in the predisposition to and/or progression of CMM and exclude p16 from involvement in the early development of some melanoma tumors.

Base Sequence↗
PubMed1994

The rat vault RNA gene contains a unique RNA polymerase III promoter composed of both external and internal elements that function synergistically.

A novel gene transcribed by RNA polymerase (pol) III has been recently identified that produces an RNA component of a large cytoplasmic ribonucleoprotein complex (Kickhoefer, V. A., Searles, R. P., Kedersha, N. L., Garber, M. E., Johnson, D. L., and Rome, L. H. (1993) J. Biol. Chem. 268, 7868-7873). Since sequence analysis revealed that this gene contains promoter elements from two different classes of RNA pol III gene promoters, we examined the function of the 5'-flanking type-3 and internal type-2 sequences on transcription activity and the production of stable transcription complexes. We find that the vRNA gene contains a novel RNA pol III promoter, where both the external and internal sequences are essential for template activity and for the productive interaction of TFIIIC with the internal elements. Thus, the vRNA gene represents the first example of a template that requires both type-2 and type-3 promoter elements that appear to function synergistically in the formation of productive transcription complexes. We have further examined the function of the unique arrangement of an internal A box and two B box elements. We find that at least one B element is required for template activity. In the absence of the 5'-flanking sequence the presence of both B elements inhibits transcription and the binding of TFIIIC. The formation of active complexes is restored when either the B2 element is inactivated or the distance separating the two B elements is increased. Therefore, the B2 element appears to negatively regulate template activity in the absence of the upstream sequences. This unique RNA pol III promoter arrangement may provide a novel mechanism for the regulation of vRNA gene activity.

Animals↗
PubMed1994

Carboplatin plus ftorafur as a palliative treatment in locally advanced cancer of the oral cavity and lip.

Forty consecutive patients with local advanced cancer of the oral cavity and lip, heavily pretreated, were palliated with two courses of carboplatin, 400 mg/m2 intravenously once a month plus ftorafur, 500 mg/m2 daily per os for 30 days. Previous treatment consisted of surgery (17 patients), radiation therapy (23 patients), and chemotherapy with cisplatin plus bleomycin (15 patients). The main sites of primary tumor were the tongue (12 patients), hard palate (6 patients), retromolar area (6 patients), tonsils (6 patients), perioral skin and lip (5 patients), and floor of the mouth (5 patients). Complete response was observed in 3 patients, and partial response in 7. Symptomatic improvement was observed in 56% of the cases. Median duration of response was 9 months. Median survival was 7 months. The main toxic effects were nausea (39 cases), vomiting (35 cases), and thrombocytopenia (4 cases). We conclude that carboplatin plus ftorafur has a role as palliative chemotherapy in cancer of the oral cavity and lip in heavily pretreated patients when local therapies are not suitable.

Adult↗