[Febrile syndrome without focus. Prevalence, etiology, and predictive factors of bacteremia].
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Adult↗
Biomedical subjects
M Sánchez
Publications and source records attributed to M Sánchez.
[Study of mortality in a medical unit of emergency department: incidence, causes and consequences].
OBJECTIVES: To define the mortality pattern in a medical unit of emergency department (ED) and to know the satisfaction of relatives with ED provided care. PATIENTS AND METHODS: We computed the number of patients visited and dead from 1989 to 1996. From all patients dying during 1996, we recorded clinical and epidemiological data and we interviewed the patients' family to know their satisfaction with ED provided care. RESULTS: Whole mortality rate was 0.71 (0.15)% X (SD) with an annual increase of 10.4% (r = 0.78, p < 0.05). The clinical profile of patient dying at ED is an individual of advanced age, with a poor quality of life, and in whom the death was expected when arrived to ED. From the family interview, 61% of cases preferred that their relative was dying in the hospital, and 88% were satisfied with ED provided care. CONCLUSIONS: Although the annual mortality rate has progressively increased in ED, family satisfaction with the received care is good.
Age Factors↗
[Unscheduled revisits in medical emergency units at the hospital: incidence and related factors].
BACKGROUND: To known the revisit rate in an emergency department (ED), to define the clinical and epidemiological profile of revisited patients, and to identify influencing factors for revisits. PATIENTS AND METHODS: During one year period, we included all revisited patients returning to ED before 72 h of a previous discharge from medical unit of ED. As controls we included the next patient seen after every case being discharged. We compiled clinical and epidemiological data from both groups. For revisited patients, we identify the cause of the revisit, changes in diagnosis and/or treatment, diagnosis mistakes and final destination of the patient. RESULTS: We identified 406 revisits (revisit rate: 1.42%). Multivariate analysis disclosed, as positive predictive factors for revisit, and age over 60 years (p = 0.006), male sex (p = 0.02), visit performed at level 2 (severe diseases) (p = 0.02), initial assessment by junior resident (p = 0.01), number of complementary procedures higher than 2 (p = 0.01) and gastrointestinal disease as diagnosis after the first visit (p = 0.03). On the other hand, dermatologic symptoms as initial complaint and unspecific symptoms (p = 0.01) were negative predictors for revisit. In only 16% of cases, the revisit did not imply changes in the diagnosis or treatment. Revisits were due to disease-related factors in 34% of cases, physician-related factors in 33%, patients-related factors in 10%, system-related factors in 3% and there were no relationship with the previous visit in 15% (in 5% of cases the cause was unassessable). The diagnosis error most frequently seen was "nonspecific abdominal syndrome". Seventy six percent of revisited patients were admitted. CONCLUSIONS: The revisit rate in our ED is relatively low. Patients being revisited have well-defined clinical and epidemiological profile. The majority of revisited patients require to be admitted.
Appointments and Schedules↗
DNA sequencing and analysis of a 40 kb region from the right arm of chromosome II from Schizosaccharomyces pombe.
We have determined the complete nucleotide sequence of a 39,648 bp segment, contained in cosmid c32F12, derived from the right arm of chromosome II from the fission yeast Schizosaccharomyces pombe. Computer analysis of the sequence revealed the presence of 15 non-overlapping open reading-frames (ORFs) longer than 300 bp and one tRNA-Thr gene. Six ORFs correspond to the previously known rec14+, tug1+, rum1+, pch1+, gpd1+ and cyr1+ genes. Five ORFs code for putative proteins with significant homology to proteins from other organisms. SPBC32F12.01c shows considerable similarity to human neutral sphingomyelinase, whereas SPBC32F12.03c, SPBC32F12.10 and SPBC32F12.14 exhibit strong homology to glutathione peroxidase, phosphoglucomutase and ubiquitin protein ligase E-3 components from various organisms, respectively. The four remaining ORFs identified show weak or non-significant homology to previously sequenced genes. The nucleotide sequence has been submitted to the EMBL database under Accession Number AL023796.
Amino Acid Sequence↗
The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces cerevisiae.
The Saccharomyces cerevisiae Cdc6 protein is necessary for the formation of pre-replicative complexes that are required for firing DNA replication at origins at the beginning of S phase. Cdc6p protein levels oscillate during the cell cycle. In a normal cell cycle the presence of this protein is restricted to G1, partly because the CDC6 gene is transcribed only during G1 and partly because the Cdc6p protein is rapidly degraded at late G1/early S phase. We report here that the Cdc6p protein is degraded in a Cdc4-dependent manner, suggesting that phosphorylated Cdc6 is specifically recognized by the ubiquitin-mediated proteolysis machinery. Indeed, we have found that Cdc6 is ubiquitinated in vivo and degraded by a Cdc4-dependent mechanism. Our data, together with previous observations regarding Cdc6 stability, suggest that under physiological conditions budding yeast cells degrade ubiquitinated Cdc6 every cell cycle at the beginning of S phase.
Cell Cycle Proteins↗
Two-dimensional analysis of proteins secreted by Saccharomyces cerevisiae regenerating protoplasts: a novel approach to study the cell wall.
Protoplasts of Saccharomyces cerevisiae incubated in regenerating conditions secrete cell wall components in order to allow the biosynthesis of this structure. During the first hours of incubation, many of these are not retained in the forming cell wall but remain in the medium. We have developed a method for collecting the secreted proteins and have analysed these by two-dimensional electrophoresis to obtain a reference map of putative cell wall proteins. Several proteins were identified by microsequencing or immunoblotting; namely, cell wall hydrolytic enzymes, heat shock proteins, glycolytic enzymes and others. Some beta-1,3- and beta-1, 6-glucosylation was detected in the proteins secreted by regenerating protoplasts.
Amino Acid Sequence↗
Influence of skeletal site of origin and donor age on osteoblastic cell growth and differentiation.
Bone loss with aging may be due, at least in part, to inadequate bone formation. Moreover, the process of bone aging is known to follow a different pattern throughout the skeleton. In this study, we examined the cell proliferation rate (area under the cell growth curve, AUC) and the secretion of C-terminal type I procollagen (PICP), alkaline phosphatase (ALP), and osteocalcin (OC) in primary cultures of osteoblastic cells from human trabecular bone. Osteoblastic cells were obtained for 168 donors (100 women and 68 men). Ninety-eight bone samples were obtained from subjects undergoing knee arthroplastia, 52 aged 50-70 years (64 +/- 5) and 46 over age 70 (73 +/- 2). Another 70 bone samples were obtained from subjects undergoing hip arthroplastia; 51 were 50-70 years old (64 +/- 4) and 19 were over 70 (75 +/- 5). Osteoblastic cells from the older donors had a lower proliferation rate and OC secretion than those from younger subjects. However, ALP secretion was higher in the former subjects, whereas PICP secretion was unchanged. Osteoblastic cells from hip had a lower proliferation rate than those from knee. PICP secretion was also lower and ALP secretion was higher in the former cells. In age-matched cell cultures, osteoblastic cells from the knee had higher proliferation rate and PICP secretion than osteoblastic cells from the hip. However, ALP secretion was lower in knee osteoblastic cells than those from hip only in the younger group. With aging, ALP secretion was found to increase in knee osteoblactic cells, whereas OC secretion decreased in osteoblastic cell cultures from the hip. Our findings suggest that bone loss with aging may be accounted for, at least in part, by a decreased osteoblastic cell proliferation and an increased osteoblastic maturation. In addition, our data indicate that these changes with aging do not occur similarly at different skeletal sites.
Aged↗
Influence of skeletal site of origin and donor age on 1,25(OH)2D3-induced response of various osteoblastic markers in human osteoblastic cells.
Age-related bone loss may be a consequence of a lack of osteoblastic formation and/or function. In vitro, the osteoblastic response to 1,25(OH)2D3, an important regulator of osteoblastic function, appears to depend on the stage of osteoblastic maturation. In this study, we examined the response to 1,25(OH)2D3 of C-terminal type I procollagen (PICP), alkaline phosphatase (ALP), and osteocalcin (OC) secretion in primary cultures of osteoblastic cells from human trabecular bone (hOB). Forty-four bone samples were obtained from subjects undergoing knee arthroplastia, 20 aged 50-70 (64 +/- 5), and 24 >70 (73 +/- 2) years. Another 33 bone samples were obtained from subjects undergoing hip arthroplastia, 21 were aged 50-70 (64 +/- 4) and 12 >70 (75 +/- 5) years. Pooling knee and hip hOB cell cultures, we found that PICP secretion decreased after 1,25(OH)2D3 in hOB cells from the older group (>70 years). Treatment with 1,25(OH)2D3 increased ALP secretion in these cells only in the younger group (50-70 years), whereas it increased OC secretion in hOB cells in both age groups. By pooling hOB cell cultures from both age groups we found that knee hOB cells increased OC secretion, and decreased PICP secretion, after 1,25(OH)2D3. This metabolite also increased OC secretion in hip hOB cells. Considering the influence of donor age at the same skeletal site, 1,25(OH)2D3 was found to stimulate ALP secretion only in knee hOB cells in the younger group. In contrast, this metabolite decreased ALP secretion in hip hOB cells in the older group. PICP secretion decreased after 1,25(OH)2D3 only in hOB cells in the older group, at both skeletal sites. In age-matched cultures, OC secretion was lower in hip hOB cells compared with those from the knee in the older group, but was similar in these cell cultures from both skeletal sites in the younger group. OC secretion after 1,25(OH)2D3 stimulation did not show age differences in knee hOB cells, but was lower in hip hOB in the older group. In summary, our results demonstrate that the response of various osteoblastic markers to 1,25(OH)2D3 in primary cultures of hOB cells depends on the donor age and skeletal site of origin.
Aged↗
BOMP/EPI intensive alternating chemotherapy for IGCCC poor-prognosis germ-cell tumors: the Spanish Germ-Cell Cancer Group experience (GG)
BACKGROUND: Patients with poor-prognosis germ-cell tumors according to the IGCCC have a poor long-term survival. This study evaluates the efficacy and toxicity of the intensive alternating chemotherapy regimen BOMP/EPI in these patients. PATIENTS AND METHODS: Patients with IGCCC poor-prognosis germ-cell tumors treated at 13 centres were studied. Treatment consisted of bleomycin 30 mg, vincristine 2 mg, methotrexate 300 mg/m2 and cisplatin 100 mg/m2 (BOMP), alternating after a 14-day interval with etoposide 120 mg/m2 day 1-4, ifosfamide 1.3 g/m2 day 1-4 and cisplatin 25 mg/m2 day 1-4 (EPI). BOMP was administered 21 days after the EPI. Bleomycin was administered weekly per 12 weeks. RESULTS: Thirty-eight patients were treated. The median number of cycles administered was 7 (1-10 cycles). Eighteen patients achieved complete responses with chemotherapy alone (12 had necrosis and 2 mature teratoma at postchemotherapy resection), and four achieved complete responses with chemotherapy and surgical resection of viable cancer. Thus, an overall favorable response was achieved in 22 patients (60%). Four additional patients had marker-negative non-resected residual masses. Eleven patients were considered treatment failures, including one who died early and another who succumbed to granulocytopenic sepsis and renal failure. Hematologic toxicity was the most common, with 26 patients (70%) having grade 4 granulocytopenia. After a median follow-up of 41 months, the actuarial two-year overall survival and progression-free survival were 64% and 58%, respectively. CONCLUSION: BOMP/EPI is active in poor-prognosis germ-cell tumors according to the IGCCC criteria. The results obtained compare favorably with those expected with conventional chemotherapy, and justify further studies.
Adolescent↗
Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase.
We compared antihypertensive efficacy and safety of a single administration of equipotent doses of lacidipine versus nifedipine in the hypertensive urgencies. Twenty-nine asymptomatic essential hypertensive patients (nine men, 20 women) with a mean age of 55.03+/-11.19 years and baseline diastolic blood pressure (DBP) of > or =120 mm Hg after resting 30 min, not taking antihypertensive drugs for the last 24 h, were randomized in a single-blind fashion to receive lacidipine, 4 mg (LCD, 15 patients) or short-acting nifedipine, 20 mg (NFD, 14 patients) in a single dose. Blood pressure (BP) and heart rate (HR) were taken every 30 min during the first 8 h and every 2 h until 24 h of follow-up. Baseline BP values were similar in the two groups (LCD, 222.5+/-32.8/124.6+/-8.4 mm Hg vs. NFD, 215.9+/-20.6/128+/-7.7 mm Hg; p = NS). Both drugs promoted a significant reduction of systolic blood pressure (SBP; 169.6+/-27.8 vs. 170.6+/-25.3 mm Hg) and diastolic blood pressure (DBP; 104.1+/-16 vs. 102.9+/-12.4 mm Hg) after 8 h. However, either SBP (165+/-27.3 vs. 190.6+/-18.2 mm Hg; p = 0.008) and DBP (99.9+/-12.3 vs. 117.2+/-11.4 mm Hg; p = 0.001) were significantly higher in the NFD group after 24-h dosing. Eleven patients in the LCD group had a decrease in BP >25% of the baseline value both 8 and 24 h after the dose. Although 10 patients showed the same response in the NFD group 8 h after the dose, only four patients maintained these values at 24 h. One patient treated with NFD had a transient cerebrovascular ischemic attack. No adverse effects were observed in the LCD group. We conclude that the long-acting calcium antagonist lacidipine was more effective than the short-acting nifedipine in both controlling BP and maintaining this BP reduction over 8 h in essential hypertensive patients with acute asymptomatic BP increase.
Adolescent↗
Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans.
The relevance of the mitogen-activated protein (MAP) kinase Hog1p in Candida albicans was addressed through the characterization of C. albicans strains without a functional HOG1 gene. Analysis of the phenotype of hog1 mutants under osmostressing conditions revealed that this mutant displays a set of morphological alterations as the result of a failure to complete the final stages of cytokinesis, with parallel defects in the budding pattern. Even under permissive conditions, hog1 mutants displayed a different susceptibility to some compounds such as nikkomycin Z or Congo red, which interfere with cell wall functionality. In addition, the hog1 mutant displayed a colony morphology different from that of the wild-type strain on some media which promote morphological transitions in C. albicans. We show that C. albicans hog1 mutants are derepressed in the serum-induced hyphal formation and, consistently with this behavior, that HOG1 overexpression in Saccharomyces cerevisiae represses the pseudodimorphic transition. Most interestingly, deletion of HOG1 resulted in a drastic increase in the mean survival time of systemically infected mice, supporting a role for this MAP kinase pathway in virulence of pathogenic fungi. This finding has potential implications in antifungal therapy.
Animals↗
Functionally homologous DNA replication genes in fission and budding yeast.
The cdc18(+) gene of the fission yeast Schizosaccharomyces pombe is involved in the initiation of DNA replication as well as in coupling the S phase to mitosis. In this work, we show that the Saccharomyces cerevisiae CDC6 gene complements cdc18-K46 ts and cdc18 deletion mutant S. pombe strains. The budding yeast gene suppresses both the initiation and the checkpoint defects associated with the lack of cdc18(+). The Cdc6 protein interacts in vivo with Cdc2 kinase complexes. Interestingly, Cdc6 is an in vitro substrate for Cdc13/Cdc2 and Cig1/Cdc2, but not for Cig2/Cdc2-associated kinases. Overexpression of Cdc6 in fission yeast induces multiple rounds of S-phase in the absence of mitosis and cell division. This CDC6-dependent continuous DNA synthesis phenotype is independent of the presence of a functional cdc18(+) gene product and, significantly, requires only Cig2/Cdc2-associated kinase activity. Finally, these S. pombe over-replicating cells do not require any protein synthesis other than that of Cdc6. Our data strongly suggest that CDC6 and cdc18(+) are functional homologues and also support the idea that controls restricting genome duplication diverge in fission and budding yeast.
Base Sequence↗
[Efficacy of intralesional treatment with antimonials in four cases of cutaneous leishmaniasis].
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Aged↗
[Early appearance of myelodysplastic syndrome secondary to therapy for Burkitt-type acute lymphoblastic leukemia (ALL3)].
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Aged↗
Cloning, sequencing and characterization of the rat hereditary hemochromatosis promoter: comparison of the human, mouse and rat HFE promoter regions.
We have cloned and sequenced 1398bp of the rat HFE gene promoter region. The alignment of the rat promoter HFE sequence with the HFE promoter sequence from human and mouse detected several highly conserved sequences present at orthologous or heterologous positions in the three species. Subsequent analysis of the conserved promoter sequences identified the presence of 10 novel transcription elements present in the promoter regions of the human, mouse and rat HFE genes (GATA, NF-IL6, AP1, AP2, CREB, PEA3, gamma-IRE, GFI1, HNF-3beta, HFH2). Different gel retardation analyses performed with rat-liver nuclear extracts have confirmed the presence of factors binding to some of these transcription elements. This represents the first data concerning the identification of potential transcriptional elements of the HFE promoter in these three species. The expression pattern of the transcription factors corresponding to the novel elements identified in the HFE promoter is consistent with the potential role of the HFE promoter in the transcription regulation and function of the HFE gene. Knowledge of the identified conserved elements in the HFE promoter from human, mouse and rat provides the basis for subsequent in-vitro or in-vivo studies leading to identification of the detailed mechanisms involved in the regulation of the iron metabolism and the design of potential future alternative therapies.
Animals↗
Morphogenesis beyond cytokinetic arrest in Saccharomyces cerevisiae.
The budding yeast lyt1 mutation causes cell lysis. We report here that lyt1 is an allele of cdc15, a gene which encodes a protein kinase that functions late in the cell cycle. Neither cdc15-1 nor cdc15-lyt1 strains are able to septate at 37 degreesC, even though they may manage to rebud. Cells lyse after a shmoo-like projection appears at the distal pole of the daughter cell. Actin polarizes towards the distal pole but the septins remain at the mother-daughter neck. This morphogenetic response reflects entry into a new round of the cell cycle: the preference for polarization from the distal pole was lost in bud1 cdc15 double mutants; double cdc15-lyt1 cdc28-4 mutants, defective for START, did not develop apical projections and apical polarization was accompanied by DNA replication. The same phenomena were caused by mutations in the genes CDC14, DBF2, and TEM1, which are functionally related to CDC15. Apical polarization was delayed in cdc15 mutants as compared with budding in control cells and this delay was abolished in a septin mutant. Our results suggest that the delayed M/G1 transition in cdc15 mutants is due to a septin-dependent checkpoint that couples initiation of the cell cycle to the completion of cytokinesis.
Cell Cycle↗
Disruption of six Saccharomyces cerevisiae genes from chromosome IV and basic phenotypic analysis of deletion mutants.
We report here the construction of six deletion mutants and the analysis of their basic phenotype. Deletion cassettes containing the KanMX4 marker module and long flanking regions homologous to the target locus were constructed for each of the six open reading-frames (ORFs YDL088c, YDL087c, YDL086w, YDL085w, YDL084w and YDL082w) located on chromosome IV. Sporulation and tetrad analysis of heterozygous deletant strains revealed that, in the FY1679 genetic background, ORFs YDL088c, YDL087c and YDL084w are essential genes for vegetative growth whereas YDL086w, YDL085w and YDL082w are non-essential. ydl088c delta and ydl084w delta haploid strains are viable in the CEN. PK2 genetic background although ydl084w delta grows at a slower rate than the wild type. Complementation tests by corresponding cognate genes confirmed that gene inactivation was responsible for these growth defects.
Cloning, Molecular↗
Pharmacological evidence for a receptor mediating sustained nucleotide-evoked contractions of rat aorta in the presence of UTP.
The contractile effect of ATP given alone or in the presence of other nucleotides was studied in rat aortic strips. A sustained contraction in response to ATP (30 microM to 10 mM) was observed during UTP exposure instead of the fast transient contraction produced via P2x purinoceptor activation in the absence of UTP, and contrary to the relaxation elicited when the tone had been raised by noradrenaline and KCl. This sustained ATP effect was produced in the smooth muscle and not via the same mechanism through which UTP elicited contraction, since the contractions in response to UTP and ATP were additive. They were also coupled to different transduction pathways: the effect of UTP but not that of ATP was pertussis toxin-sensitive. In contrast to the fast transient ATP contraction during basal tone, the sustained response was not desensitized by alpha,beta-methylene ATP exposure (30 microM), but was inhibited by reactive blue 2 (10 and 30 microM). Among the nucleotides assayed, UDP and ATPgammaS also enabled ATP to elicit a sustained contraction. ADP, AMP, dATP, 2-methylthio ATP, alpha,beta-methylene ATP, GTP, GDP, GMP, CTP and ITP also induced a sustained contraction in the presence of UTP. However, adenosine (1 mM) and adenine (0.3 to 3 mM) induced relaxation when the tone had been raised by UTP. According to these results a non-selective nucleotide receptor, different from the P2 purinoceptors functionally characterized so far, seems to mediate sustained contractions in rat aortic strips in the presence of UTP, UDP or ATPgammaS.
Adenosine Triphosphate↗