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Biomedical subjects

S Alonso

Publications and source records attributed to S Alonso.

At least 73 records · Page 4Linked to original sources

A conformal technique for a ring shaped conjunctive lymphoma treatment.

Radiotherapy is commonly utilised as standard treatment in the so called mucosa-associated lymphoid tissues (MALT), due to the low probability of distant relapse. The particularities of the lesion, make necessary both energy degradation and beam conformation. To keep homogeneity within acceptable limits, a lengthener attached to the electron applicator has been devised to closely fit the anatomy of the patient. Considering the small area of the outcoming field, film dosimetry is preferred, since the dimensions of an ionisation chamber and even of a semiconductor probe might be comparable to the field size.

Adult↗

Immunoreactivity in granular cell tumours of the larynx.

OBJECTIVE: To elucidate histogenesis and behaviour of laryngeal granular cell tumours (GCT) and to determine the role of p53 protein expression in these lesions. METHODS: The clinical, pathological and immunohistochemical findings of three cases of laryngeal GCTs are described. RESULTS: All tumours were surgically excised and appeared histologically benign. Pseudoepitheliomatous hyperplasia, mitosis and nuclear pleomorphism were not found in any of the three cases. All lesions were negative for keratin 8, desmin and actin. Only one case stained for collagen IV. Positive staining was found for S-100 protein and CD68 in all tumours. Ki-67 and Bcl-2 staining was confined to occasional cells. p53 reactivity was seen in all tumours; positivity ranged from 35 to 42%. The three patients have remained free of disease without complications up to 10 years after treatment. CONCLUSION: Immunohistochemical findings support benign behaviour and a Schwann cell origin for laryngeal GCT. The expression of p53 by granular cells is unclear but appears to be unrelated to behaviour.

Adult↗

Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type.

BACKGROUND: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT). PATIENTS AND METHODS: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20-72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria. TOXICITY: Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3-4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. RESPONSE: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months. CONCLUSION: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.

Adult↗

Dermatofibroma parasitized by Leishmania in HIV infection: a new morphologic expression of dermal Kala Azar in an immunodepressed patient.

Visceral leishmaniasis is a protozoan infection that may complicate the course of patients with human immunodeficiency virus (HIV). Dermatofibroma is a cutaneous fibrohistiocytic lesion considered neoplastic by some authors and inflammatory by others. Eruptive dermatofibromas have been described in patients with HIV infection or with other altered immunity situations. We present the case of a 32-year-old, HIV-positive man with visceral leishmaniasis who complained of the appearance of a cutaneous lesion in the leg formed by the coexistence of dermatofibroma and Leishmania parasitic colonization. As far as we know, this type of association has not been reported previously. We consider that the dermatofibroma could have developed as an unusual form of fibrohistiocytic reaction to leishmania. From a practical approach, we recommend the search of leishmaniasis in dermatofibroma in immunosuppressed patients.

Adult↗

Replication and packaging of transmissible gastroenteritis coronavirus-derived synthetic minigenomes.

The sequences involved in the replication and packaging of transmissible gastroenteritis virus (TGEV) RNA have been studied. The structure of a TGEV defective interfering RNA of 9.7 kb (DI-C) was described previously (A. Mendez, C. Smerdou, A. Izeta, F. Gebauer, and L. Enjuanes, Virology 217: 495-507, 1996), and a cDNA with the information to encode DI-C RNA was cloned under the control of the T7 promoter. The molecularly cloned DI-C RNA was replicated in trans upon transfection of helper virus-infected cells and inhibited 20-fold the replication of the parental genome. A collection of 14 DI-C RNA deletion mutants (TGEV minigenomes) was synthetically generated and tested for their ability to be replicated and packaged. The smallest minigenome (M33) that was replicated by the helper virus and efficiently packaged was 3.3 kb. A minigenome of 2.1 kb (M21) was also replicated, but it was packaged with much lower efficiency than the M33 minigenome, suggesting that it had lost either the sequences containing the main packaging signal or the required secondary structure in the packaging signal due to alteration of the flanking sequences. The low packaging efficiency of the M21 minigenome was not due to minimum size restrictions. The sequences essential for minigenome replication by the helper virus were reduced to 1,348 nt and 492 nt at the 5' and 3' ends, respectively. The TGEV-derived RNA minigenomes were successfully expressed following a two-step amplification system that couples pol II-driven transcription in the nucleus to replication supported by helper virus in the cytoplasm, without any obvious splicing. This system and the use of the reporter gene beta-glucuronidase (GUS) allowed minigenome detection at passage zero, making it possible to distinguish replication efficiency from packaging capability. The synthetic minigenomes have been used to design a helper-dependent expression system that produces around 1.0 microgram/10(6) cells of GUS.

Animals↗

Targeted recombination demonstrates that the spike gene of transmissible gastroenteritis coronavirus is a determinant of its enteric tropism and virulence.

Targeted recombination within the S (spike) gene of transmissible gastroenteritis coronavirus (TGEV) was promoted by passage of helper respiratory virus isolates in cells transfected with a TGEV-derived defective minigenome carrying the S gene from an enteric isolate. The minigenome was efficiently replicated in trans and packaged by the helper virus, leading to the formation of true recombinant and pseudorecombinant viruses containing the S proteins of both enteric and respiratory TGEV strains in their envelopes. The recombinants acquired an enteric tropism, and their analysis showed that they were generated by homologous recombination that implied a double crossover in the S gene resulting in replacement of most of the respiratory, attenuated strain S gene (nucleotides 96 to 3700) by the S gene of the enteric, virulent isolate. The recombinant virus was virulent and rapidly evolved in swine testis cells by the introduction of point mutations and in-phase codon deletions in a domain of the S gene (nucleotides 217 to 665) previously implicated in the tropism of TGEV. The helper virus, with an original respiratory tropism, was also found in the enteric tract, probably because pseudorecombinant viruses carrying the spike proteins from the respiratory strain and the enteric virus in their envelopes were formed. These results demonstrated that a change in the tropism and virulence of TGEV can be engineered by sequence changes in the S gene.

Animals↗

Phase I-II study of gemcitabine and fluorouracil as a continuous infusion in patients with pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and efficacy of gemcitabine combined with fluorouracil (5-FU) in patients with pancreatic cancer. PATIENTS AND METHODS: Patients with measurable, locally advanced, nonresectable or metastatic pancreatic cancer were candidates for the study. 5-FU was given via protracted venous infusion (PVI) at a fixed dosage of 200 mg/m2/d, and gemcitabine was administered weekly for 3 consecutive weeks every 4 weeks. The initial dose of gemcitabine was 700 mg/m2 and was escalated in increments of 100 mg/m2/wk until the appearance of severe toxicity. Measurements of efficacy included the following: response rate; clinical benefit response, which is a composite measurement of pain, performance status, and weight loss; time to disease progression; and survival. RESULTS: Twenty-six patients received a total of 109 courses. Dose-limiting toxicity, which consisted of grade 4 neutropenia with fever (one patient) and grade 4 thrombocytopenia (one patient), was observed in two of three patients treated with 1,100 mg/m2/wk of gemcitabine. On the basis of these results, the MTD of gemcitabine with 5-FU via PVI on this schedule was 1,000 mg/m2. Sixteen patients developed grade 3-4 neutropenia, and three patients developed grade 3-4 thrombocytopenia. Grade 3-4 nonhematologic toxicity consisted of diarrhea (two patients) and cutaneous toxicity, asthenia, edema, mucositis, and nausea and vomiting (one patient each). The delivered dose-intensity of gemcitabine was similar at the 1,000 mg/m2 dose level (599 mg/m2/wk) as at the 900 mg/m2 (601 mg/m2/wk) dose level. For this reason, the recommended dose of gemcitabine for phase II evaluation on this schedule was 900 mg/m2. Five patients had objective responses (one complete response and four partial responses; response rate, 19.2%; 95% confidence interval [CI], 6.5 to 39.3), and 10 patients had improvement of disease-related symptoms (45%; 95% CI, 24 to 67). After a median follow-up of 17.7 months (range, 7.8 to 24.8 months), the median progression-free survival and overall survival times were 7.4 months (95% CI, 3.3 to 11.4) and 10.3 months (95% CI, 8.1 to 12.5), respectively. CONCLUSION: The MTD of gemcitabine when combined with 5-FU via PVI on this schedule was 1,000 mg/m2/ wk; however, on the basis of administered dose-intensity, the recommended dose for additional investigation is 900 mg/m2. This combination chemotherapy regimen was well tolerated and showed promising antitumor activity in the treatment of pancreatic cancer.

Adult↗

[Levels of evidence in the prevention and control of nosocomial infection].

BACKGROUND: Sanitary, economic and social importance of nosocomial infections justifies the introduction and development of control and surveillance systems in hospitals. The practice of a rational medicine needs the scientific evidence evaluation of the control measures employed, in terms of efficacy, efficiency and effectivity. METHODS: Critical appraisal of medical literature with special emphasis in recommendations provided by Centers for Disease Control and Prevention (CDC). RESULTS: A minimum proportion of prevention and control recommendations provided by Centers for Disease Control and Prevention (CDC) are included in the Category IA (demonstrated evidence in well-designed epidemiological or experimental studies), while sanitary impact (reduction of the nosocomial infection incidence or prevalence) or economic impact (the benefit derived of this nosocomial infection frequency reduction) of numerous interventions keeps being a motive for study and discussion because its evidence level is not demonstrated due to internal or external validity problems. CONCLUSIONS: An appropriate strategy to be adopted by sanitary professionals in charge of nosocomial infection control is the application of the evidence-based medicine methodology and principles.

Bacterial Infections↗

Synchronous glottic granular cell tumor and subglottic spindle cell carcinoma.

We report the clinicopathologic findings in a case of coexistent glottic granular cell tumor and subglottic spindle cell carcinoma. There is no evidence in this case that suggests malignant transition of the granular cell tumor to malignant tumor. To our knowledge, this is the first report of synchronous granular cell tumor and subglottic spindle cell carcinoma.

Carcinoma↗

The spike protein of transmissible gastroenteritis coronavirus controls the tropism of pseudorecombinant virions engineered using synthetic minigenomes.

The minimum sequence required for the replication and packaging of transmissible gastroenteritis virus (TGEV)-derived minigenomes has been determined. To this end, cDNAs encoding defective RNAs have been cloned and used to express heterologous spike proteins, to determine the influence of the peplomer protein in the control of TGEV tropism. A TGEV defective interfering RNA of 9.7 kb (DI-C) was isolated, and a cDNA complementary to DI-C RNA was cloned under the control of T7 promoter. In vitro transcribed DI-C RNA was replicated in trans upon transfection of helper virus-infected cells. A collection of DI-C deletion mutants (TGEV minigenomes) was generated and tested for their ability to be replicated and packaged. The size of the smallest minigenome replicated in trans was 3.3 kb. The rescue system was used to express the spike protein of an enteric TGEV isolate (C11) using as helper virus a TGEV strain (C8) that replicates very little in the gut. A mixture of two pseudorecombinant viruses containing either the helper virus genome or the minigenome was obtained. These pseudorecombinants display in the surface the S proteins from the enteric and the attenuated virus, and showed 10(4)-fold increase in their gut replication levels as compared to the helper isolate (C8). In addition, the pseudorecombinant virus increased its enteric pathogenicity as compared to the C8 isolate.

Animals↗

Left main coronary artery patch angioplasty: midterm experience and follow-up with spiral computed tomography.

BACKGROUND: Patch angioplasty is an alternative surgical technique in cases of left main coronary artery stenosis. We report our experience with this technique, with particular mention of the use of spiral computed tomography for the follow-up of our patients. METHODS: In this retrospective study we analyzed the results obtained in all 7 patients (3 women and 4 men) who were operated on with this technique in our institution between July 1992 and August 1994. Five consenting patients also underwent graft patency assessment with spiral computed tomographic imaging. RESULTS: The operation was uneventful in all patients and there were no hospital deaths. Two patients required reoperation (1 of them dying at reoperation), 1 because of restenosis of the graft and 1 because of the presence of a new stenosis in the proximal anterior descending coronary artery. The remaining 5 patients were asymptomatic after 51 +/- 2 months. Spiral computed tomographic images were artifacted and of poor quality. CONCLUSIONS: Patch angioplasty of the left main coronary artery can be a valuable therapeutic method in selected cases. Conventional spiral computed tomography is not an optimal noninvasive method for the assessment of graft patency.

Adult↗

Neurons derived in vitro from ES cells express homeoproteins characteristic of motoneurons and interneurons.

We have characterized different neuronal subpopulations derived from in vitro differentiation of embryonic stem (ES) cells using as markers the expression of several homeodomain transcription factors. Following treatment of embryo-like aggregates with retinoic acid (RA), Pax-6, a protein expressed by ventral central nervous system (CNS) progenitors is induced. In contrast, Pax-7 expressed in vivo by dorsal CNS progenitors, and erbB3, a gene expressed by neural crest cells and its derivatives, are almost undetectable. CNS neuronal subpopulations generated expressed combinations of markers characteristic of somatic motoneurons (Islet-1/2, Lim-3, and HB-9), cranial motoneurons (Islet-1/2 and Phox2b) and interneurons (Lim-1/2 or EN1). Molecular characterization of neuron subtypes generated from ES cells should considerably facilitate the identification of new genes expressed by restricted neuronal cell lineages.

Animals↗

Meat intake, 'mate' drinking and renal cell cancer in Uruguay: a case-control study.

In the period January 1988-December 1995, a case-control study of diet and renal cell carcinoma (RCC) risk involving 121 cases and 243 hospitalized controls was carried out in Montevideo, Uruguay. After adjusting for major covariates, red meat intake was associated with a 3.4 increase in risk for the highest category of intake, with a significant dose-response pattern. Also, barbecued meat, protein and heterocyclic amine intakes were associated with significant increases in risk of RCC. The consumption of the beverage known as 'mate' (a ocal tea derived from the herb Ilex paraguariensis) was associated with an increased risk of 3.0 for heavy drinkers.

Adult↗

MS205 minisatellite diversity in Basques: evidence for a pre-Neolithic component.

A number of studies have suggested that Basques might be a relic of Mesolithic Europeans who escaped much of the homogenization brought about by the Neolithic expansion. In an attempt to add new insights into this hypothesis, MS205 minisatellite diversity has been investigated by Minisatellite Variant Repeat (MVR) analysis in a sample of >100 autochthonous individuals from the Basque Country, along with 24 Castilian (N. Spain) and 23 individuals from the United Kingdom. These populations were examined in the context of the available world database for MS205 alleles. To deduce the similarities among populations, we have applied a phylogenetic approach that takes into account similarity between alleles. The variability of these populations seems to be a subset of the greater and presumably older African diversity, as has been suggested previously for non-Africans. Within non-Africans, Basques seem to cluster with other Northern European populations; however, some apparently Basque-specific alleles can be dated back to post-Aurignacian times, supporting the continuity of some lineages of this population since the Upper Paleolithic period.

Anthropology, Physical↗

Genetic and functional analysis of the styrene catabolic cluster of Pseudomonas sp. strain Y2.

The chromosomal region of Pseudomonas sp. strain Y2 involved in the conversion of styrene to phenylacetate (upper catabolic pathway) has been cloned and sequenced. Four catabolic genes, styABCD, and two regulatory genes, stySR, were identified. This gene cluster when transferred to Escherichia coli W confers to this phenylacetate-degrading host the ability to grow on styrene as the sole carbon and energy source. Genes styABCD are homologous to those encoding the styrene upper catabolic pathway in Pseudomonas fluorescens ST. Northern blot analyses have confirmed that genes styABCD constitute a transcription unit. The transcription start site of the sty operon was mapped 33 nucleotides upstream of the styA translational start codon. The styS and styR genes, which form an independent transcriptional unit, are located upstream of the styABCD operon, and their gene products show high similarity to members of the superfamily of two-component signal transduction systems. The styS gene product is homologous to histidine kinase proteins, whereas the styR gene product exhibits similarity at its N-terminal domain with cluster 1 of receiver modules and at its C terminus with the LuxR/FixJ family 3 of DNA-binding domains. Expression of the catabolic operon decreased significantly in the absence of the stySR genes and was restored when the stySR genes were provided in trans in the presence of styrene, suggesting that the stySR system behaves as a styrene-inducible positive regulator of the styABCD operon. Finally, a gene encoding a phenylacetyl-coenzyme A ligase that catalyzes the first step in the phenylacetate catabolism (styrene lower catabolic pathway) has been identified upstream of the styS gene. This activity was found to be induced in Pseudomonas sp. strain Y2 cells grown on styrene but not present in cells grown on glycerol. These results strongly suggest that the genes responsible for the complete mineralization of styrene are clustered in the chromosome of Pseudomonas sp. strain Y2.

Amino Acid Sequence↗

Genetic characterization of APOB and D17S5 AFLP loci in a sample from the Basque Country (northern Spain).

VNTR polymorphism of AFLP loci D17S5 and APOB was analyzed in 100 unrelated individuals residing in the Basque Country by PCR amplification and polyacrylamide gel electrophoresis. Population parameters were estimated to validate these loci as routine markers in human identification. Thus, although both loci showed extensive polymorphism (with gene diversities of approximately 80% for both systems) and although concordance with Hardy-Weinberg equilibrium and linkage equilibrium was observed, comparisons with other populations displayed significant differences. Moreover, further analysis of neutral parameters limits this validation to D17S5 because APOB displays excesses of both the total number of alleles and the number of rare alleles; possible reasons for this discrepancy (presence of deleterious alleles, bottleneck effect, admixture, complexity of APOB polymorphism) are discussed.

Alleles↗

Sialic acid measurement by a modified Aminoff method: a time-saving reduction in 2-thiobarbituric acid concentration.

Our results show that if the 2-thiobarbituric acid concentration is decreased, its co-precipitation with the chromophore is diminished. Subsequent running of this reaction mixture by high-performance liquid chromatography still allows measurement of Neu-5-Ac in the picomole order, with a substantial time and reactive saving, as compared with the original assay.

Chemical Precipitation↗