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1.
J Neonatal Perinatal Med ; 15(4): 753-758, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35811547

RESUMEN

BACKGROUND: Small for gestational age (SGA) infants are likely to have decreased placental transfer of opioids and other substances and lower amounts of fat deposition, hence less severe neonatal abstinence syndrome (NAS). The goal of this study is to correlate SGA status and severity of NAS in infants admitted to the neonatal intensive care unit (NICU). METHODS: This is a retrospective analysis of term and late-preterm infants (≥35 weeks gestation) exposed to in-utero substances, born between September 2006 and May 2021, and admitted to an inner-city NICU for medical therapy for NAS. Indicators of the severity of NAS (duration of medical treatment, duration of hospitalization, use of phenobarbital, and use of clonidine) were compared between infants characterized as SGA (birth weight <10th percentile for gestational age) to those not categorized as SGA (non-SGA). RESULTS: A total of 992 infants met the study criteria; 205 (20.7%) in the SGA group and 787 (79.3%) in the non-SGA group. The median duration of medical treatment was significantly lower in infants in the SGA group (22 days vs. 26 days, p = 0.04) and they were less likely to be treated with phenobarbital (19% vs. 26.8%, p = 0.02). CONCLUSION: SGA infants displayed less severe NAS symptoms as indicated by shorter a duration of medical treatment and decreased need for phenobarbital. Our findings may impact decisions around identifying the optimum treatment protocols catered to SGA infants with NAS.


Asunto(s)
Recien Nacido Prematuro , Síndrome de Abstinencia Neonatal , Recién Nacido , Humanos , Embarazo , Lactante , Femenino , Edad Gestacional , Estudios Retrospectivos , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Placenta , Fenobarbital/uso terapéutico
2.
J Neonatal Perinatal Med ; 14(3): 383-390, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33337392

RESUMEN

BACKGROUND: Based on the most recently published recommendations from the Committee on the Fetus and Newborn (COFN), three approaches currently exist for the use of risk factors to identify infants who are at increased risk of early-onset sepsis (EOS). Categorical risk factor assessments recommend laboratory testing and empiric antibiotic therapy for all infants born to mothers with a clinical diagnosis of chorioamnionitis. Risk assessments based on clinical condition recommend frequent examinations and close vital sign monitoring for infants born to mothers with chorioamnionitis. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, multivariate risk assessments. The aim of our study was to compare the three risk stratification approaches recommended by the COFN for management of chorioamnionitis-exposed infants. METHODS: Retrospective study of 1,521 infants born ≥35 weeks to mothers with chorioamnionitis. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition (CCA). RESULTS: Hypothetical application of SRC and CCA resulted in 79.6% and 76.8-85.1% respectively fewer infants allocated empiric antibiotic therapy. While CCA recommended enhanced observation for all chorioamnionitis-exposed infants, SRC recommended routine care without enhanced observation in 44.3% infants. For the six infants (0.39%) with EOS, SRC and CCA recommended empiric antibiotics only for three symptomatic infants. CONCLUSION: The SRC and CCA can reduce antibiotic use but potentially delay antibiotic treatment. The SRC does not recommend enhanced observation with frequent and prolonged vital signs for >44% of chorioamnionitis-exposed infants.


Asunto(s)
Corioamnionitis , Sepsis Neonatal , Sepsis , Antibacterianos/uso terapéutico , Corioamnionitis/diagnóstico , Corioamnionitis/tratamiento farmacológico , Corioamnionitis/epidemiología , Femenino , Feto , Humanos , Lactante , Recién Nacido , Madres , Sepsis Neonatal/tratamiento farmacológico , Embarazo , Estudios Retrospectivos , Sepsis/tratamiento farmacológico
3.
J Vet Intern Med ; 24(6): 1439-44, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20840314

RESUMEN

BACKGROUND: Identification of biomarkers that predict outcomes in dogs with osteosarcoma (OSA) would be valuable to veterinarians and owners. Leukocyte numbers in peripheral blood are associated with outcomes in some types of cancer in humans. HYPOTHESIS/OBJECTIVES: We hypothesized that increased numbers of monocytes would be associated with reduced disease-free interval (DFI) in dogs with OSA. ANIMALS: Medical data from 69 dogs with appendicular OSA treated with amputation and chemotherapy were selected for study. METHODS: Retrospective study. Statistical associations were assessed by univariate and multivariate analysis. Information about DFI and leukogram values, tumor location, and serum alkaline phosphatase was abstracted from the medical record. RESULTS: Higher numbers of circulating monocytes (>0.4×10(3) cells/µL) and lymphocytes (>1.0×10(3) cells/µL) before treatment were found to be significantly (P<.05) associated with shorter DFI in dogs with OSA. Other parameters associated with poor outcomes were increased alkaline phosphatase, primary tumor location, and age. CONCLUSION AND CLINICAL IMPORTANCE: These results indicated that pretreatment evaluation of monocyte and lymphocyte counts provided prognostic information for dogs with appendicular OSA. Notably, most animals in this study had monocyte counts within the normal reference range, indicating that variations within the reference range of leukocyte values might also have prognostic significance.


Asunto(s)
Enfermedades de los Perros/sangre , Recuento de Linfocitos/veterinaria , Osteosarcoma/veterinaria , Animales , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Perros , Femenino , Masculino , Monocitos/fisiología , Osteosarcoma/sangre , Osteosarcoma/tratamiento farmacológico
4.
Res Sports Med ; 16(4): 295-306, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19089750

RESUMEN

The aim of the present study was to explore whether there were any differences in the psychological content of practice between club-contracted and non-club-contracted physiotherapists when treating sports injuries. Eighty-seven certified physiotherapists (non-club contracted N = 42, club contracted N = 45) from the United Kingdom completed a modified version of the Athletic Training and Sport Psychology Questionnaire (ATSPQ). Results revealed significant between-group differences in psychological skills use and the importance of psychological skills knowledge. Non-club-contracted physiotherapists reported a higher use of improving social support and higher-order psychological skills (e.g., reducing depression, stress, and anxiety) and rated knowledge of these psychological skills to be more important whilst club-contracted physiotherapists reported a higher use of short-term goal settings. These findings suggest that non-club-based physiotherapists may approach the treatment of injured athletes in a different way to their club-based counterparts. Results suggest athletes treated outside of the club system may experience a different recovery process.


Asunto(s)
Traumatismos en Atletas/terapia , Actitud del Personal de Salud , Práctica Institucional , Modalidades de Fisioterapia/psicología , Especialidad de Fisioterapia , Práctica Privada , Adulto , Traumatismos en Atletas/psicología , Competencia Clínica , Estudios de Cohortes , Humanos , Pautas de la Práctica en Medicina
5.
Vet Comp Oncol ; 3(1): 1-7, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19379208

RESUMEN

Canine osteosarcoma is a common bone malignancy associated with aggressive local disease and rapid metastasis. Current local therapeutic modalities do not provide curative-intent options for dogs with significant orthopaedic or neurologic disease, dogs which are denied amputation or dogs with non-resectable lesions. The goals of this retrospective study included the evaluation of local control, survival, and time to the development of metastases in 14 dogs treated with curative-intent radiation therapy and chemotherapy. Median local disease control was 202 days (79-777). Median survival was 209 days (79-781). Median time to metastasis was 314 days (7-645). No significant correlation was found between the outcome and pre-treatment alkaline phosphatase levels, radiographic appearance, tumour site, radiation dose or chemotherapeutics administered. In these dogs, full-course radiation therapy in conjunction with chemotherapy was not found to yield equivalent results to the standard of care options.

6.
Vet Comp Oncol ; 3(2): 81-6, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19379216

RESUMEN

The purpose of this study was to evaluate one versus two doses of local delivery cisplatin in a biodegradable polymer (OPLA-Pt) for the treatment of osteosarcoma (OSA) after amputation in dogs. Medical records were reviewed retrospectively, and 105 dogs were included in the study; 39% of dogs received one treatment (surgical implantation) of OPLA-Pt and 61% of dogs received two treatments of OPLA-Pt after amputation. Administration of two doses of OPLA-Pt did not have a significant effect on disease-free interval or survival time compared to one dose. The anatomic site of the tumour was identified as a prognostic factor, and dogs with proximal humeral OSA had the shortest disease-free interval and survival times. There was no advantage to giving a second dose of local delivery cisplatin following amputation for the treatment of OSA in dogs.

7.
Vet Comp Oncol ; 1(3): 152-8, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19379314

RESUMEN

The purpose of this retrospective analysis was to evaluate the use of nuclear scintigraphy in determining the rate of secondary sites of osseous malignancy at initial presentation in dogs with osteosarcoma. Radiographs of suspicious secondary lesions were reviewed and placed into four separate categories: benign lesions; no lesion seen on radiographs; subtle radiographic changes suggestive of, but not conclusive for, metastasis; and metastatic lesions highly suspected on radiographs. Three hundred and ninety-nine dogs were evaluated by technetium nuclear scanning for suspected osteosarcoma. Three hundred and twenty-six of 399 dogs (82%) had only one apparent site on the nuclear scan, whereas 72 dogs (18%) had more than one suspicious site on the nuclear scans. Highly suspected secondary metastatic lesions were detected by nuclear scans in 7.8% of cases. Although interpretation of nuclear scans is subjective, this study showed a 7.8% chance of detecting unsuspected osseous metastasis with nuclear scans in canine osteosarcoma patients on initial presentation.

8.
Kidney Int ; 60(6): 2399-405, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11737616

RESUMEN

BACKGROUND: Patients on long-term hemodialysis have a high mortality. Various clinical and biochemical markers are of prognostic value. Cardiac troponin T (cTnT) is a sensitive and specific marker for myocardial damage. Asymptomatic dialysis patients have a high prevalence of cTnT concentrations above the diagnostic threshold for myocardial damage. There is controversy over whether this represents a false positive cTnT or an underlying pathology with a poor outcome. It is not known whether cTnT reflects comorbidity in these patients. METHODS: A cohort of 73 long-term hospital hemodialysis patients had cTnT estimated once prior to a mid-week dialysis. Samples were analyzed using the second-generation cTnT assay from Boehringer Mannheim on an Elecsys 1010 analyzer. The standard diagnostic threshold for myocardial damage of 0.1 ng/mL was used. A commonly employed measure of comorbidity (Khan) was applied at the time cTnT was measured. Patients were followed for 15 months. Mortality was used as the clinical end point. Kaplan-Meier survival analysis was employed and differences between groups were assessed using the Cox-Mantel log-rank test. RESULTS: Of the 73 patients, 20 were positive for cTnT and 53 were negative, at the cut-off of 0.1 ng/mL. At fifteen months, 65% of the positive patients were dead, whereas only 15% of the negative patients were dead. Survival analysis confirmed that this difference was statistically significant (P < 0.00001), and that the effect of cTnT on survival was independent of comorbidity. CONCLUSIONS: There is a high prevalence of positive cTnT in stable hemodialysis patients. A single estimation of cTnT in this group has significant prognostic value, independent of comorbidity.


Asunto(s)
Diálisis Renal , Troponina T/sangre , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Pronóstico , Curva ROC , Análisis de Regresión , Diálisis Renal/mortalidad , Análisis de Supervivencia , Resultado del Tratamiento , Troponina T/metabolismo
9.
Mol Microbiol ; 35(4): 896-910, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10692166

RESUMEN

The toxin-co-regulated pilus (TCP), a type 4 pilus that is expressed by epidemic strains of Vibrio cholerae O1 and O139, is required for colonization of the human intestine. The TCP structure is assembled as a polymer of repeating subunits of TcpA pilin that form long fibres, which laterally associate into bundles. Previous passive immunization studies have suggested that the C-terminal region of TcpA is exposed on the surface of the pilus fibre and has a critical role in mediating the colonization functions of TCP. In the present study, we have used site-directed mutagenesis to delineate two domains within the C-terminal region that contribute to TCP structure and function. Alterations in the first domain, termed the structural domain, result in altered pilus stability or morphology. Alterations in the second domain, termed the interaction domain, affect colonization and/or infection by CTX-bacteriophage without affecting pilus morphology. In vitro and in vivo analyses of the tcpA mutants revealed that a major function of TCP is to mediate bacterial interaction through direct pilus-pilus contact required for microcolony formation and productive intestinal colonization. The importance of this function is supported by the finding that intragenic suppressor mutations that restore colonization ability to colonization-deficient mutants simultaneously restore pilus-mediated bacterial interactions. The alterations resulting from the suppressor mutations also provide insight into the molecular interactions between pilin subunits within and between pilus fibres.


Asunto(s)
Adhesión Bacteriana/genética , Intestinos/microbiología , Proteínas de la Membrana/genética , Vibrio cholerae/genética , Alelos , Animales , Proteínas de la Membrana Bacteriana Externa/química , Proteínas de la Membrana Bacteriana Externa/genética , Bacteriófagos , Actividad Bactericida de la Sangre , Proteínas Fimbrias , Fimbrias Bacterianas/química , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/ultraestructura , Humanos , Proteínas de la Membrana/química , Ratones , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Mutación , Fenotipo , Mutación Puntual , Estructura Terciaria de Proteína , Relación Estructura-Actividad , Transducción Genética , Vibrio cholerae/citología , Vibrio cholerae/patogenicidad , Virulencia/genética
10.
Biochemistry ; 38(17): 5563-71, 1999 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-10220344

RESUMEN

The Azotobacter FeSII protein, also known as the Shethna protein, forms a protective complex with nitrogenase during periods when nitrogenase is exposed to oxygen. One possible mechanism for its action is an oxidation state-dependent conformational interaction with nitrogenase whereby the FeSII protein dissociates from the MoFe and Fe proteins of nitrogenase under reducing conditions. Herein we report the construction and characterization of five site-directed mutants of the FeSII protein (H12Q, H55Q, K14A, K15A, and the double mutant K14A/K15A) which were individually purified after being individually overexpressed in Escherichia coli. These mutant FeSII proteins maintain native-like assembly and orientation of the 2Fe-2S center on the basis of EPR and NMR spectroscopic characterization and their redox midpoint potentials, which are within 25 mV of that of the wild type protein. The abilities of the individual mutant proteins to protect nitrogenase were assessed by determining the remaining nitrogenase activities after adding each pure version back to extracts from an FeSII deletion strain, and then exposing the mixture to oxygen. In these assays, the H12Q mutant functioned as well as the wild type protein. However, mutation of His55, a few residues away from a cluster-liganding cysteine, results in much less efficient protection of nitrogenase. These results are consistent with pH titrations in both oxidation states, which show that His12 is insensitive to 2Fe-2S cluster oxidation state. His55's pK is weakly responsive to oxidation state, and the pK increase of 0. 16 pH unit upon 2Fe-2S cluster oxidation is indicative of ionization of another group between His55 and the 2Fe-2S cluster, which could modulate the FeSII protein's affinity for nitrogenase in a redox state-dependent manner. Both K14A and K15A mutant FeSII proteins partially lost their ability to protect nitrogenase, but the lysine double mutant lost almost all its protective ability. The nitrogenase component proteins in an Azotobacter strain bearing the double lysine mutation (in the chromosome) were degraded much more rapidly in vivo than those in the wild type strain under carbon substrate-limited conditions. These results indicate that the two lysines may have an important role in FeSII function, perhaps in the initial steps of recognizing the nitrogenase component proteins.


Asunto(s)
Azotobacter vinelandii/genética , Proteínas Bacterianas/genética , Proteínas Portadoras , Histidina/genética , Proteínas Hierro-Azufre , Lisina/genética , Mutagénesis Sitio-Dirigida , Nitrogenasa/metabolismo , Oxígeno/toxicidad , Azotobacter vinelandii/efectos de los fármacos , Azotobacter vinelandii/enzimología , Proteínas Bacterianas/metabolismo , Activación Enzimática/efectos de los fármacos , Activación Enzimática/genética , Escherichia coli/genética , Histidina/metabolismo , Lisina/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación
11.
Int J Dev Biol ; 43(1): 69-73, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10213084

RESUMEN

The activity of two X-linked genes, Pgk1 and Hprt, that are localized on X-chromosomes of different parental origins in the XX mouse embryo was analyzed by the quantification of allele-specific transcripts. For the Pgk1 gene, the maternal allele-specific transcripts were consistently more abundant than the paternal transcripts in the blastocyst and the late gastrula. For the Hprt gene, the Hprt(b) allele was preferentially expressed in the blastocysts when it is present on the maternal X-chromosome. However, this skewed expression of the maternal allele was not observed in the reciprocal situation when the Hprt(a) allele was on the maternal X-chromosome. Like the Pgk1 locus, significantly more maternal Hprt transcripts were found in the gastrula-stage embryos irrespective of their genotypes. One possible interpretation of these results is that, in the XX mouse embryos, the genetic loci on maternal X-chromosome may be transcriptionally more active than their paternal counterparts during peri-implantation development.


Asunto(s)
Impresión Genómica , Hipoxantina Fosforribosiltransferasa/genética , Fosfoglicerato Quinasa/genética , Cromosoma X , Alelos , Animales , Blastocisto/metabolismo , Compensación de Dosificación (Genética) , Femenino , Gástrula/metabolismo , Regulación del Desarrollo de la Expresión Génica , Ligamiento Genético , Masculino , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo
12.
Biochemistry ; 37(45): 15974-80, 1998 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-9843404

RESUMEN

The primary structure of Clostridium pasteurianum hydrogenase I appears to be composed of modules suggesting that the various iron-sulfur clusters present in this enzyme might be segregated in structurally distinct domains. On the basis of this observation, a gene fragment encoding the 76 N-terminal residues of this enzyme has been expressed in Escherichia coli. The polypeptide thus produced contains a [2Fe-2S]n+ cluster of which the oxidized level (n = 2) has been monitored by UV-visible absorption, circular dichroism, and resonance Raman spectroscopy. This cluster can be reduced by dithionite or electrochemically to the n = 1 level which has been investigated by EPR and by low-temperature magnetic circular dichroism. The redox potential of the +2 to +1 transition is -400 mV (vs the normal hydrogen electrode). The spectroscopic and redox results indicate a [2Fe-2S]2+/+ chromophore coordinated by four cysteine ligands in a protein fold similar to that found in plant- and mammalian-type ferredoxins. Among the five cysteines present in the N-terminal hydrogenase fragment, four (in positions 34, 46, 49, and 62) are conserved in other sequences and are therefore the most likely ligands of the [2Fe-2S] site. The fifth cysteine, in position 39, can be dismissed on the grounds that the Cys39Ala mutation does not alter any of the properties of the iron-sulfur cluster. The spectroscopic signatures of this chromophore are practically identical with some of those reported for full-size hydrogenase. This confirms that C. pasteurianum hydrogenase I contains a [2Fe-2S] cluster and indicates that the polypeptide fold around the metal site of the N-terminal fragment is very similar, if not identical, to that occurring in the full-size protein. The N-terminal sequence of this hydrogenase is homologous to sequences of a number of proteins or protein domains, including a subunit of NADH-ubiquinone oxidoreductase of respiratory chains. From that, it can be anticipated that the structural domain isolated and described here is a building block of electron transfer complexes involved in various bioenergetic processes.


Asunto(s)
Clostridium/enzimología , Ferredoxinas/biosíntesis , Hidrogenasas/biosíntesis , Fragmentos de Péptidos/biosíntesis , Secuencia de Aminoácidos , Espectroscopía de Resonancia por Spin del Electrón , Escherichia coli/genética , Ferredoxinas/química , Ferredoxinas/genética , Hidrogenasas/química , Hidrogenasas/genética , Datos de Secuencia Molecular , Oxidación-Reducción , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Estructura Terciaria de Proteína , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Espectrofotometría Ultravioleta , Espectrometría Raman
13.
Vet Radiol Ultrasound ; 38(6): 474-8, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9402717

RESUMEN

Thirteen dogs with malignant tumors of the nasal cavity were treated with a combination of slow release cisplatin and megavoltage radiation. Radiation was delivered on a Monday through Friday schedule using a 6 MV linear accelerator. The median total dose was 49.5 Gy (range 49.5-56 Gy). Cisplatin was given using an open-cell polylactic acid polymer, impregnated with the drug and implanted intramuscularly at a distant site, as a slow release delivery system (OPLA-Pt [THM Biomedical, Inc]). The median dose used was 60 mg/m2 (range 60-100 mg/m2). When combined with radiation, this delivery system caused no systemic drug toxicity, and a local tissue reaction was seen in only two dogs. Acute side effects to normal tissue from radiation were not enhanced, as measured by subjective assessment. When compared to a group of historical controls that received radiation without OPLA-Pt, the dogs that received combined radiation and cisplatin had longer overall survival times, with a median of 580 days. The control group had a median survival of 325 days. Previously reported median survival times for comparable megavoltage radiation treatment range from 6 to 13 months. Some dogs in both groups also received adjubant chemotherapy but this did not influence survival time. By multivariate analysis, only the use of OPLA-Pt was found to significantly influence survival, with a p value of p = 0.023. Mega-voltage radiation and slow release cisplatin appears to be a well tolerated combination that may favorably affect survival of dogs with nasal tumors.


Asunto(s)
Cisplatino/administración & dosificación , Enfermedades de los Perros/terapia , Neoplasias Nasofaríngeas/veterinaria , Animales , Biopsia , Cisplatino/efectos adversos , Terapia Combinada/veterinaria , Preparaciones de Acción Retardada , Perros , Femenino , Masculino , Análisis Multivariante , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia , Tasa de Supervivencia
14.
Biochemistry ; 36(39): 11811-20, 1997 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-9305972

RESUMEN

The type and properties of the Fe-S cluster in recombinant Escherichia coli biotin synthase have been investigated in as-prepared and dithionite-reduced samples using the combination of UV-visible absorption and variable-temperature magnetic circular dichroism (VTMCD), EPR, and resonance Raman spectroscopies. The results confirm the presence of one S = 0 [2Fe-2S]2+ cluster in each subunit of the homodimer in aerobically purified samples, and the Fe-S stretching frequencies suggest incomplete cysteinyl-S coordination. However, absorption and resonance Raman studies show that anaerobic reduction with dithionite in the presence of 60% (v/v) ethylene glycol or glycerol results in near-stoichiometric conversion of two [2Fe-2S]2+ clusters to form one S = 0 [4Fe-4S]2+ cluster with complete cysteinyl-S coordination. The stoichiometry and ability to effect reductive cluster conversion without the addition of iron or sulfide suggest that the [4Fe-4S]2+ cluster is formed at the subunit interface via reductive dimerization of [2Fe-2S]2+ clusters. EPR and VTMCD studies indicate that more than 50% of the Fe is present as [4Fe-4S]+ clusters in samples treated with 60% (v/v) glycerol after prolonged dithionite reduction. The [4Fe-4S]+ cluster exists as a mixed spin system with S = 1/2 (g = 2. 044, 1.944, 1.914) and S = 3/2 (g = 5.6 resonance) ground states. Subunit-bridging [4Fe-4S]2+,+ clusters, that can undergo oxidative degradation to [2Fe-2S]2+ clusters during purification, are proposed to be a common feature of Fe-S enzymes that require S-adenosylmethionine and function by radical mechanisms involving the homolytic cleavage of C-H or C-C bonds, i.e., biotin synthase, anaerobic ribonucleotide reductase, pyruvate formate lyase, lysine 2, 3-aminomutase, and lipoic acid synthase. The most likely role for the [4Fe-4S]2+,+ cluster lies in initiating the radical mechanism by directly or indirectly facilitating reductive one-electron cleavage of S-adenosylmethionine to form methionine and the 5'-deoxyadenosyl radical. It is further suggested that oxidative cluster conversion to [2Fe-2S]2+ clusters may play a physiological role in these radical enzymes, by providing a method of regulating enzyme activity in response to oxidative stress, without irreversible cluster degradation.


Asunto(s)
Escherichia coli/enzimología , Proteínas Hierro-Azufre/química , Sulfurtransferasas/química , Ditionita/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Proteínas Hierro-Azufre/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Espectrofotometría Ultravioleta , Espectrometría Raman , Sulfurtransferasas/metabolismo
15.
In Vivo ; 11(4): 345-50, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9292302

RESUMEN

BACKGROUND-MATERIALS: Based on previous polymer release experience, this study was conducted to evaluate the toxicity, efficacy and systemic absorption of cisplatin administered subcutaneously in dogs. METHODS-RESULTS-CONCLUSIONS: Fifty to 70 mg/m2 cisplatin was suspended in saline and injected subcutaneously in 6 dogs as an adjunct to their primary treatment for sarcoma. Gastrointestinal, bone marrow, renal or local tissue toxicity occurred following the first (dogs 1-3,5,6) and second (dogs 1 and 2) treatments. Low, yet measurable levels of platinum were present in serum through day 14 following injection in all dogs. Due to the toxicity seen, all further planned treatments were discontinued and adjuvant regimes were completed with intravenous carboplatin. Although slow systemic absorption of platinum can occur following subcutaneous administration, the degree of toxicity seen following this treatment would indicate that a drug delivery vehicle may be necessary if cisplatin is to be administered for sustained release and adsorption.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Cisplatino/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Enfermedades de la Médula Ósea/inducido químicamente , Neoplasias Óseas/cirugía , Carboplatino/uso terapéutico , Quimioterapia Adyuvante , Cisplatino/farmacocinética , Cisplatino/toxicidad , Perros , Enfermedades Gastrointestinales/inducido químicamente , Inyecciones Subcutáneas , Enfermedades Renales/inducido químicamente , Osteosarcoma/secundario , Osteosarcoma/cirugía
16.
Gene ; 192(1): 79-85, 1997 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-9224877

RESUMEN

Several experimental approaches have provided evidence suggesting that a domain within the C-terminal region of the TcpA pilin, delineated by the single disulfide loop, is directly responsible for the colonization function mediated by the toxin coregulated pilus (TCP) of Vibrio cholerae. This evidence includes the mapping of domains recognized by protective monoclonal antibodies to this region, the ability of peptides from within this region to elicit cholera protective antibody, the construction of tcpA missense mutations that abolish TCP function, and the requirement of a periplasmic disulfide isomerase to produce functional TCP.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa/química , Fimbrias Bacterianas/fisiología , Vibrio cholerae/química , Vibrio cholerae/patogenicidad , Animales , Anticuerpos Monoclonales/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/fisiología , Proteínas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Cólera/prevención & control , Disulfuros/química , Disulfuros/metabolismo , Proteínas Fimbrias , Fimbrias Bacterianas/metabolismo , Inmunización Pasiva , Isomerasas/metabolismo , Ratones , Mutagénesis Sitio-Dirigida , Fenotipo , Conformación Proteica , Proteína Disulfuro Isomerasas , Vibrio cholerae/ultraestructura
17.
Scott Med J ; 42(3): 79-80, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9351121

RESUMEN

A case of a highly sensitised haemodialysis patient who developed severe vascular rejection in her third renal allograft is presented. This severe rejection episode responded to mycophenolate mofetil (MMF) and high dose steroids.


Asunto(s)
Antiinflamatorios/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Prednisolona/uso terapéutico , Adulto , Ciclosporina/uso terapéutico , Femenino , Rechazo de Injerto/inmunología , Humanos , Ácido Micofenólico/uso terapéutico
18.
Anticancer Res ; 17(6D): 4499-505, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9494558

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the toxicity and efficacy against local disease recurrence of soft tissue sarcomas (STS) in dogs using intracavitary cisplatin released from a polymer device (OPLA-Pt). MATERIALS AND METHODS: OPLA-Pt was placed into the wound following marginal (histologically incomplete) resection of STS in 30 dogs (32 tumors) with a median tumor diameter of 3 cm (range = 1-14 cm). Median cisplatin dose was 35.5 mg/m2 (body surface area) with a range of 5.3-133.3 mg/m2. RESULTS: The OPLA-Pt was removed from 9/32 (28%) sites due to local wound complication. Local recurrence occurred in 10/32 (31%) tumors. Higher tumor grade had a significant negative influence on local tumor recurrence (p = 0.031). CONCLUSIONS: The rate of recurrence appeared to be similar using intracavitary cisplatin compared to previous reports of STS treated by marginal surgery followed by radiotherapy. The complication rate indicates the need for further refinement of the polymer/cisplatin system.


Asunto(s)
Antineoplásicos/uso terapéutico , Biopolímeros , Cisplatino/uso terapéutico , Enfermedades de los Perros , Sarcoma/veterinaria , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Perros , Índice Mitótico , Necrosis , Recurrencia , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Sarcoma/cirugía , Factores de Tiempo
19.
Nephrol Dial Transplant ; 11(10): 2031-6, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8918718

RESUMEN

BACKGROUND: Dry skin is frequently observed in uraemic patients and a link with the common complaint of pruritus has been suggested. Objective data on skin dryness in haemodialysed patients is sparse and equivocal. No such information exists for the many patients now receiving peritoneal dialysis. We assessed the prevalence and severity of both pruritus and skin dryness in a uraemic population receiving maintenance dialysis. METHODS: Forty-eight haemodialysis and 24 peritoneal dialysis patients were examined and skin dryness assessed by clinical grading and measurement of stratum corneum hydration using a corneometer. Forty age- and sex-matched controls were also assessed. Several biochemical parameters with possible relevance to pruritus were measured. Regular emollient therapy was prescribed to pruritic dialysis patients and efficacy assessed. RESULTS: Dialysis patients overall had clinically drier skin than controls, especially the peritoneal dialysis group. Stratum corneum hydration levels were significantly reduced in the peritoneal dialysis (P < 0.004), but not the haemodialysis, population. Twenty-seven per cent of haemodialysed and 54% of peritoneal dialysis patients complained of pruritus. Pruritic patients in each dialysis group had significantly lower hydration than non-pruritic patients (P < 0.05). Regular emollient use in pruritic patients produced a marked reduction in severity of pruritus, abolishing the symptom in nine of 21 patients treated. CONCLUSION: Reduced stratum corneum hydration correlates with pruritus in patients on maintenance haemodialysis and peritoneal dialysis, and may be alleviated by simple emollient therapy.


Asunto(s)
Diálisis Peritoneal/efectos adversos , Prurito/etiología , Diálisis Renal/efectos adversos , Piel/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Emolientes/uso terapéutico , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Prurito/tratamiento farmacológico , Prurito/metabolismo , Piel/efectos de los fármacos , Agua/metabolismo
20.
Oncol Nurs Forum ; 21(9): 1539-44, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7816679

RESUMEN

PURPOSE/OBJECTIVES: To describe immune status in patients prior to colorectal surgery for cancer, to establish values to serve as a baseline for subsequent analyses, and to describe a procedure for studying phenotypes of the immune system, elucidating its advantages. DESIGN: One component of a larger longitudinal survey. SETTING: Two large, inner-city university hospitals and two of their affiliated hospitals in the northeastern United States. SAMPLE: Patients undergoing surgery for colorectal cancer (N = 94). Subjects were primarily male (n = 57) and Caucasian (n = 85) and ranged in age from 26-88 years (mean = 63). Seventy-seven percent (n = 73) had cancer, 23% (n = 21) had benign diseases or conditions. METHODS: Flow cytometry analysis of lymphocyte phenotypes was performed on blood samples drawn from patients before they underwent surgery for colorectal cancer. MAIN OUTCOME MEASURES: The average absolute lymphocyte subset levels and the average relative lymphocyte subset levels of blood samples taken from patients undergoing surgery for colorectal cancer were compared (using t-tests) with the subset levels of two normal reference samples. FINDINGS: The average absolute lymphocyte subset levels and average relative lymphocyte subset levels of patients undergoing surgery for colorectal cancer fell within normal ranges. CONCLUSIONS: These findings suggest that this sample of patients undergoing surgery has one essential element of an intact immune system--normal levels of lymphocyte subsets. IMPLICATIONS FOR NURSING PRACTICE: There is no indication preoperatively that this population is at a higher risk for infection or delayed wound healing. However, there may be other times in the illness trajectory when the immune system does become compromised, and these values prior to surgery will serve as a baseline to identify changes in patients' immune status over time. Further longitudinal studies are necessary.


Asunto(s)
Neoplasias Colorrectales/inmunología , Linfocitos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Femenino , Citometría de Flujo , Humanos , Subgrupos Linfocitarios , Masculino , Persona de Mediana Edad , Fenotipo , Estrés Psicológico/inmunología
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