RESUMO
Disruption of the perception of taste can have severe consequences on general health. Although evidence suggests that the oral microbiota plays a role in taste perception, little is known about this possible influence. In this scoping review, the influence of oral microbiota on taste perception was studied. Current scientific literature is heterogeneous in study methods and study populations, which impedes comparison of results. Although the findings of this review provide insufficient evidence to confirm the influence of oral microbiota on taste perception, some results show a relationship between taste perception and specific microorganisms. Several factors play a role in taste perception, including tongue coating, use of medication, advanced age, and decreased salivary flow rate, and when these factors are present, it is important to be alert to possible changes in taste. Large-scale studies, in which the multifactorial etiology of taste perception is addressed, are needed to clarify the role of the oral microbiota on taste perception.
Assuntos
Microbiota , Percepção Gustatória , Humanos , Paladar , Lacunas de EvidênciasRESUMO
Acquisition and establishment of the oral microbiota occur in a dynamic process over various stages and involve close and continuous interactions with the host and its environment. In the present review, we discuss the stages of this process in chronological order. We start with the prenatal period and address the following questions: 'Is the fetus exposed to maternal microbiota during pregnancy?' and 'If so, what is the potential role of this exposure?' We comment on recent reports of finding bacterial DNA in placenta during pregnancies, and provide current views on the potential functions of prenatal microbial encounters. Next, we discuss the physiological adaptations that take place in the newborn during the birth process and the effect of this phase of life on the acquisition of the oral microbiota. Is it really just exposure to maternal vaginal microbes that results in the difference between vaginally and Cesarian section-born infants? Then, we review the postnatal phase, in which we focus on transmission of microbes, the intraoral niche specificity, the effects of the host behavior and environment, as well as the role of genetic background of the host on shaping the oral microbial ecosystem. We discuss the changes in oral microbiota during the transition from deciduous to permanent dentition and during puberty. We also address the finite knowledge on colonization of the oral cavity by microbes other than the bacterial component. Finally, we identify the main outstanding questions that limit our understanding of the acquisition and establishment of a healthy microbiome at an individual level.
Assuntos
Microbiota , Bactérias , Feminino , Humanos , Recém-Nascido , Boca , GravidezRESUMO
Transmission of oral microbiota from mother to infant is a highly relevant and, so far, understudied topic due to lack of mainstream high-throughput methods for the assessment of bacterial diversity at a strain level. In their recent article in mBio, S. Kageyama, M. Furuta, T. Takeshita, J. Ma, et al. (mBio 13:e03452-21, 2021, https://doi.org/10.1128/mbio.03452-21) evaluated oral microbial transmission from mothers to their infants by using full-length analysis of the 16S rRNA gene and demonstrated the applicability of this method for assessment of transmission of oral bacteria at the single-nucleotide-difference level. By analyzing different metadata of the mother-infant pairs, they discovered that the presence of maternal oral bacteria was higher in formula-fed infants compared to infants who were breastfed or received mixed feeding. This interesting finding suggests that breastfeeding may prevent early maturation of infant's oral microbiome. The physiological role of this phenomenon still needs to be elucidated.
Assuntos
Aleitamento Materno , Microbiota , Bactérias/genética , Feminino , Hábitos , Humanos , Lactente , Mães , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: To assess the available scientific evidence regarding the placental microbial composition of a healthy pregnancy, the quality of this evidence, and the potential relation between placental and oral microbiome. MATERIALS AND METHODS: Data sources: MEDLINE and EMBASE up to August 1, 2019. STUDY ELIGIBILITY CRITERIA: Human subjects; healthy women; term deliveries; healthy normal birth weight; assessment of microorganisms (bacteria) in placental tissue; full research papers in English. The quality of the included studies was assessed by a modified Joanna Briggs Institute checklist for analytical cross-sectional studies. RESULTS: 57 studies passed the inclusion criteria. Of these, 33 had a high risk of quality bias (e.g., insufficient infection control, lack of negative controls, poor description of the healthy cases). The remaining 24 studies had a low (N = 12) to moderate (N = 12) risk of bias and were selected for in-depth analysis. Of these 24 studies, 22 reported microorganisms in placental tissues, where Lactobacillus (11 studies), Ureaplasma (7), Fusobacterium (7), Staphylococcus (7), Prevotella (6) and Streptococcus (6) were among the most frequently identified genera. Methylobacterium (4), Propionibacterium (3), Pseudomonas (3) and Escherichia (2), among others, although frequently reported in placental samples, were often reported as contaminants in studies that used negative controls. CONCLUSIONS: The results support the existence of a low biomass placental microbiota in healthy pregnancies. Some of the microbial taxa found in the placenta might have an oral origin. The high risk of quality bias for the majority of the included studies indicates that the results of individual papers should be interpreted with caution.
Assuntos
Fusobacterium/fisiologia , Lactobacillus/fisiologia , Microbiota/genética , Placenta/microbiologia , Gravidez , RNA Ribossômico 16S/genética , Ureaplasma/fisiologia , Adulto , Animais , Feminino , Voluntários Saudáveis , HumanosRESUMO
OBJECTIVES: Large longitudinal cohort studies in infants are needed to understand oral microbiome maturation in relation to general health. The logistics of such studies are complex and costs involved high. Methods like home sampling by caretakers might be a solution to these issues. This study aimed to evaluate feasibility of home sampling by caretakers and to assess which oral niche provides the most reliable sample. METHODS: In this cross-sectional study 30 mothers and their infants aged 2-15 months participated. Swabs of the tongue, buccal mucosa, saliva, and dental plaque of the mother and the infant were collected by the mother after watching an instruction video. Thereafter, the trained researcher repeated the sample collection. Variations on the sampling protocol were listed. Bacterial DNA was quantified and microbial composition was assessed using 16S rDNA amplicon sequencing. RESULTS: None of the sampled niches appeared to be unfeasible based on interviews and observed variations on protocol. No significant differences in bacterial DNA concentration between operators (mother and researcher) were found. In infant's saliva, Shannon diversity of samples collected by the researcher was significantly higher than those collected by mothers (p = 0.0009) and the bacterial composition was influenced by variations on sampling protocol (p = 0.01). CONCLUSIONS: Home sampling by caretakers is a feasible method for oral sample collection in infants and mothers. Oral samples collected by mothers resemble samples collected by a trained researcher, with the tongue sample being the most similar and saliva the least. CLINICAL SIGNIFICANCE: Home sampling can simplify longitudinal oral microbiota collection.
Assuntos
Microbiota , Mães , Estudos Transversais , Feminino , Humanos , Lactente , Estudos Longitudinais , RNA Ribossômico 16S/genética , SalivaRESUMO
Transmission of malaria depends on the successful development of the sexual stages of the parasite within the midgut of the mosquito vector. The differentiation process leading to the production of the sexual stages is delineated by several developmental switches. Arresting the progression through this sexual differentiation pathway would effectively block the spread of the disease. The successful development of such transmission-blocking agents is hampered by the lack of a detailed understanding of the program of gene expression that governs sexual differentiation of the parasite. Here we describe the isolation and functional characterization of the Plasmodium falciparum pfs16 and pfs25 promoters, whose activation marks the developmental switches executed during the sexual differentiation process. We have studied the differential activation of the pfs16 and pfs25 promoters during intraerythrocytic development by transfection of P. falciparum and during gametogenesis and early sporogonic development by transfection of the related malarial parasite P. gallinaceum. Our data indicate that the promoter of the pfs16 gene is activated at the onset of gametocytogenesis, while the activity of the pfs25 promoter is induced following the transition to the mosquito vector. Both promoters have unusual DNA compositions and are extremely A/T rich. We have identified the regions in the pfs16 and pfs25 promoters that are essential for high transcriptional activity. Furthermore, we have identified a DNA-binding protein, termed PAF-1, which activates pfs25 transcription in the mosquito midgut. The data presented here shed the first light on the details of processes of gene regulation in the important human pathogen P. falciparum.
Assuntos
DNA de Protozoário/genética , DNA de Protozoário/isolamento & purificação , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/genética , Regiões Promotoras Genéticas , Animais , Sequência de Bases , Sítios de Ligação/genética , Mapeamento Cromossômico , Culicidae/parasitologia , Primers do DNA/genética , DNA de Protozoário/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genes de Protozoários , Humanos , Insetos Vetores/parasitologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Masculino , Dados de Sequência Molecular , Plasmodium falciparum/patogenicidade , Diferenciação Sexual/genética , Fatores de Transcrição/metabolismo , TransfecçãoRESUMO
With the aid of a binary plasmid in vivo testsystem it was demonstrated that the single-stranded DNA binding protein encoded by gene V of bacteriophage M13 not only regulates the synthesis of its cognate DNA replication proteins at the level of translation, but also of the assembly proteins and the coat proteins encoded by genes I and II, respectively. Furthermore, gene V protein functions as a translational autoregulator of its own synthesis. Comparison of the mRNA levels of genes I and X in the presence and absence of wild-type gene V protein indicated that gene V protein augments the physical stability of these mRNAs. The expression of the Escherichia coli beta-galactosidase gene and of a gene X mutant containing a deletion in the nontranslated mRNA leader sequence was not influenced by gene V protein, lending support to the conclusion that gene V protein exerts its regulatory effect via a specific nucleotide sequence in the leader sequences of the respective M13 mRNAs. We conclude that gene V protein functions as a master regulatory protein of the expression and replication of the M13 genome.
Assuntos
Bacteriófagos/genética , Genes Virais , Biossíntese de Proteínas , RNA Mensageiro/genética , Proteínas Virais/genética , Autorradiografia , Sequência de Bases , Western Blotting , Proteínas de Ligação a DNA/genética , Eletroforese em Gel de Poliacrilamida , Escherichia coli/enzimologia , Regulação Viral da Expressão Gênica , Dados de Sequência Molecular , Mutação , Plasmídeos , RNA Viral/genética , Homologia de Sequência do Ácido Nucleico , Proteínas Virais/biossíntese , beta-Galactosidase/genéticaRESUMO
A mutant of bacteriophage M13 was prepared in which a cysteine residue was introduced at position 25 of the major coat protein. The mutant coat protein was spin-labeled with a nitroxide derivative of maleimide and incorporated at different lipid-to-protein (L/P) ratios in DOPC or DOPG. The rotational dynamics of the reconstituted mutant coat protein was studied using EPR and saturation transfer (ST) EPR techniques. The spectra are indicative for an anisotropic motion of the maleimide spin label with a high order parameter (S = 0.94). This is interpreted as a wobbling motion of the spin label with a correlation time of about 10(-6) to 10(-5) s within a cone, and a rotation of the spin label about its long molecular axis with a correlation time of about l0(-7) s. The wobbling motion is found to correspond generally to the overall rotational motion of a coat protein monomer about the normal to the bilayer. This motion is found to be sensitive to the temperature and L/P ratio. The high value of the order parameter implies that the spin label experiences a strong squeezing effect by its local environment, that reduces the amplitude of the wobbling motion. This squeezing effect is suggested to arise from a turn structure in the coat protein from Gly23 to Glu20.
Assuntos
Proteínas do Capsídeo , Capsídeo/química , Bicamadas Lipídicas/química , Proteínas de Membrana/química , Fosfolipídeos/química , Capsídeo/genética , Espectroscopia de Ressonância de Spin Eletrônica , Proteínas de Membrana/genética , Modelos Moleculares , Mutação , Conformação Proteica , Marcadores de SpinRESUMO
BACKGROUND: The exact time point at which the first endomyocardial biopsy could be safely performed after the heart transplantation has not been systematically studied. In an attempt to determine this time point in our population, the number and severity of acute rejection episodes in the first eight weeks after the heart transplantation were assessed in 91 patients who underwent the procedure at St Paul's Hospital, Vancouver between September 1996 and December 2002. METHODS AND RESULTS: For the purpose of our analysis, acute rejection was defined as the grade > or =2 according the International Society for Heart and Lung Transplantation (ISHLT). Three hundred and sixty two endomyocardial biopsies were performed in 87 patients surviving to the first biopsy from one to eight weeks after the heart transplantation. In 85 patients who received induction immunosuppressive therapy, 13 episodes of acute rejection were identified. In two patients who did not receive the induction therapy, three episodes of acute rejection occurred. Acute rejection grade ISHLT 3 was found in 2 patients who did not receive induction therapy and in three patients who did. ISHLT grade 4 rejection occurred at weeks 5 and 7 in two patients who received induction therapy. Only one patient who received induction therapy had acute rejection within the first three weeks after the heart transplantation. CONCLUSIONS: Our analysis reveals that the frequency of acute rejection within the first eight weeks after the heart transplantation using induction therapy is low in this cohort, suggesting that the first routine endomyocardial biopsy could be delayed until the week four post-transplant.
Assuntos
Biópsia por Agulha , Endocárdio/patologia , Transplante de Coração , Miocárdio/patologia , Adulto , Idoso , Rejeição de Enxerto/diagnóstico , Humanos , Pessoa de Meia-IdadeRESUMO
The gene encoding the gametocyte/gamete-specific membrane protein Pfs48/45 of Plasmodium falciparum has been cloned. The Pfs48/45 gene is a non-interrupted, single copy gene that codes for a hydrophobic, non-repetitive protein of 448 amino acid residues containing a putative signal peptide at the N-terminus, a hydrophobic C-terminus and 7 potential N-glycosylation sites. Antibodies directed against a Pfs48/45-glutathione-S-transferase fusion protein reacted with both the 45-kDa and 48-kDa proteins of gametocytes. When Pfs48/45 is expressed in the baculovirus-insect cell system the recombinant Pfs48/45 protein is targeted and exposed to the insect cell surface in such a configuration that it is recognized by transmission-blocking anti-45/48-kDa monoclonal antibodies.
Assuntos
Antígenos de Protozoários/genética , Glicoproteínas de Membrana/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Antígenos de Protozoários/imunologia , Sequência de Bases , Northern Blotting , Western Blotting , Clonagem Molecular , DNA de Protozoário , Imunofluorescência , Dados de Sequência Molecular , Plasmodium falciparum/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologiaRESUMO
BACKGROUND: Inhibitors of cyclosporine metabolism are commonly co-administered with cyclosporine in transplant recipients. The aim of this study was to compare cyclosporine pharmacokinetics using the conventional formulation (Sandimmune) and after switching to the microemulsion (Neoral) formulation, in stable heart transplant recipients receiving various cyclosporine metabolic inhibitors. METHODS: Steady-state blood concentration-time profiles of Sandimmune were studied in 47 transplant recipients receiving either cyclosporine alone (Group A, n = 11) or in combination with diltiazem (120 mg/day, Group B, n = 11), ketoconazole (200 mg/day, Group C, n = 13), or both ketoconazole and diltiazem (200 and 120 mg/day, respectively, Group D, n = 12), and restudied 1 week after switching to Neoral. RESULTS: Neoral resulted in more rapid cyclosporine absorption as judged by the shorter absorption half-lives in all groups (p < 0.05). The mean percentage increase in the values of area-under-the-concentration-time curve was 42% and 37.5% higher for Neoral compared with Sandimmune for Groups A and B, respectively, but only 5.4% higher for Group C and 9.5% higher for Group D. The mean morning trough concentration of cyclosporine was not significantly different after administration of Neoral compared with Sandimmune in any of the groups studied (179 vs. 167 microg/liter for Group A; 171 vs. 147 microg/liter for Group B; 189 vs. 194 microg/liter for Group C; and 181 vs 201 microg/liter for Group D). Neoral did not alter serum concentrations of sodium, potassium, creatinine, and urea in any of the study groups. CONCLUSIONS: The faster absorption and improved bioavailability of cyclosporine (around 40%) with Neoral compared with Sandimmune was not seen in patients receiving ketoconazole, where in fact cyclosporine bioavailability was already maximal. Mean morning trough levels of cyclosporine did not reflect the improvement in bioavailability seen in patients switching from Sandimmune to Neoral. Cyclosporine dose adjustment may be needed when switching from Sandimmune to Neoral for patients not receiving sparing agents or who receive diltiazem, but trough levels cannot necessarily be relied upon to determine the degree of adjustment needed. For patientson ketoconazole, the absorption profile is already optimized and no dosage alteration seems necessary.
Assuntos
Ciclosporina/farmacocinética , Transplante de Coração , Imunossupressores/farmacocinética , Cetoconazol/farmacocinética , Bloqueadores dos Canais de Cálcio/farmacocinética , Ciclosporina/sangue , Diltiazem/farmacocinética , Interações Medicamentosas , Feminino , Humanos , Imunossupressores/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
From 1983 to 1991, 27 women with peripartum cardiomyopathy were considered for heart transplantation. Of 27 patients, 11 (41%) improved with medical therapy, 10 (37%) underwent transplantation, and six (22%) died. Results in the 10 patients with peripartum cardiomyopathy who underwent transplantation were compared with results in 39 women who underwent transplantation for dilated cardiomyopathy (idiopathic, Adriamycin, valvular, or familial) to determine whether there were differences in survival, rejection, or infection rates. The two groups were, by chance, well matched for number of pregnancies, peak panel reactivity, and cross-match. Mean time from delivery to transplantation was 24 weeks (range 2 to 188 weeks), and this time did not correlate with rejection rates. The linearized rate of rejection from 0 to 3 months was 30% higher in the group with peripartum cardiomyopathy (3.4 +/- 0.7 vs 2.6 +/- 0.3 episodes/100 patient days; p = 0.05). The mean postoperative day to first rejection was day 26 for peripartum cardiomyopathy and day 28 for women with dilated cardiomyopathy. Rejection requiring cytolytic therapy occurred in 40% of women with peripartum cardiomyopathy and 21% of the comparison group (difference not significant). Linearized (treated) infection rates were 1.8 +/- 0.5 for the group with peripartum cardiomyopathy versus 1.5 +/- 0.2 episodes/100 patient days for others (p = 0.05). Actuarial survival was excellent in both groups with 88% and 86% 2-year survival rates, respectively. In conclusion, women who undergo transplantation for peripartum cardiomyopathy have a 30% higher rate of early rejection than do those who undergo transplantation for idiopathic cardiomyopathy and tend to have a greater need for cytolytic therapy. Infection rates are consequently higher.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cardiomiopatias/cirurgia , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Complicações Pós-Operatórias/imunologia , Transtornos Puerperais/cirurgia , Análise Atuarial , Adulto , Anticorpos/análise , Cardiomiopatias/imunologia , Cardiomiopatias/mortalidade , Cardiomiopatia Dilatada/imunologia , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/cirurgia , Doença das Coronárias/imunologia , Doença das Coronárias/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/mortalidade , Antígenos HLA/imunologia , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Transplante de Coração/mortalidade , Hemodinâmica/fisiologia , Humanos , Terapia de Imunossupressão , Pessoa de Meia-Idade , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Complicações Pós-Operatórias/mortalidade , Transtornos Puerperais/imunologia , Transtornos Puerperais/mortalidade , Taxa de SobrevidaRESUMO
Prior studies of cardiac transplant recipients have shown that pravastatin reduces 12-month rejection and mortality after cardiac transplantation and simvastatin reduces 4-year mortality, low-density lipoprotein (LDL) cholesterol levels, and intimal thickening. In a 12-month observational study, cardiac transplant recipients received open-label pravastatin 40 mg (n = 42) or simvastatin 20 mg daily (n = 45) on an alternating basis from the time of transplantation. Lipid levels, safety, and post-transplant outcomes were compared. We found no significant differences in total LDL or high-density lipoprotein cholesterol, triglycerides, linearized infection or rejection rates, liver function tests, or immunosuppressant dosages between groups at 1, 3, 6, or 12 months. Rhabdomyolysis or myositis occurred only in patients on simvastatin (n = 6, 13.3%) with no episodes for patients on pravastatin (p = 0. 032). Survival at 12 months on an actual treatment basis was 97.6% for patients on pravastatin and 83.7% for those on simvastatin (p = 0.078). Immunosuppression-related deaths occurred in only 2.4% (1 patient) on pravastatin vs 15.6% (n = 7) on simvastatin (p = 0.06). Pravastatin and simvastatin resulted in comparable lipid profiles. Pravastatin use was however free from the high rates of rhabdomyolysis and myositis seen with simvastatin use. Pravastatin was additionally associated with a trend toward superior survival, attributable to fewer immunosuppression-related deaths. For safety and pharmacokinetic reasons, pravastatin should be considered the statin of choice after heart transplantation.
Assuntos
Doença das Coronárias/prevenção & controle , Transplante de Coração , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Cuidados Pós-Operatórios/métodos , Pravastatina/uso terapêutico , Sinvastatina/uso terapêutico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença das Coronárias/sangue , Doença das Coronárias/mortalidade , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/mortalidade , Transplante de Coração/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Segurança , Taxa de Sobrevida , Resultado do Tratamento , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologiaRESUMO
In an effort to reduce the level of presensitization in patients on our heart and lung transplant waiting list, ten patients with random panel reactivity above 10% on monthly screening for durations of 2 to 59 months were given low-dose azathioprine (25 to 75 mg/day) for 1 to 22 months. All patients had positive T-cell panel reactivity (10% to 70%) against specific (n = 6), multi-specific (n = 1), or undefined (n = 3) HLA loci, and four additional patients had positive B-cell panel reactivity (5% to 40%). No effect of azathioprine on panel reactivity was seen in four of ten patients (40%), whereas a significant and sustained reduction in panel reactivity occurred in six patients (60%), all within 2 months of commencing azathioprine. All nonresponders had antibodies with class I (A locus) specificity, whereas all six responders had multi-specific or undefined antibody specificities. A formal trial of low-dose azathioprine in presensitized recipients is warranted.
Assuntos
Soro Antilinfocitário/imunologia , Azatioprina/administração & dosagem , Transplante de Coração/imunologia , Imunossupressores/administração & dosagem , Transplante de Pulmão/imunologia , Adulto , Soro Antilinfocitário/análise , Linfócitos B/imunologia , Feminino , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Linfócitos T/imunologiaRESUMO
BACKGROUND: To determine the influence of HLA mismatching on rejection after cardiothoracic organ transplantation, we analyzed results in 243 recipients. METHODS: There were 183 heart, 25 heart-lung, and 35 single lung recipients, all receiving triple-drug immunosuppression with anti-thymocyte globulin induction. Zero, one, and two mismatches occurred by chance at each locus in between 0% to 9%, 26% to 35%, and 47% to 70% of recipients, respectively. RESULTS: In heart recipients, compared with a two mismatch, a zero mismatch was associated with a lower linearized rejection rate in the first 6 months. A zero B locus mismatch was likewise associated with less rejection in month 1, and DR zero mismatch with reduced rejection in the first 3 months. Steroid withdrawal was more successful in those with zero mismatch at any locus. In heart-lung recipients linearized rejection was significantly lower in those with lesser degrees of A and DR locus mismatching, and after single-lung transplantation linearized rejection was significantly lower with lesser degrees of A and B locus mismatching from 3 to 6 months only. Actuarial survival did not differ for any organ with any degree of mismatch at any locus. CONCLUSIONS: HLA mismatching affects rejection, but the effect is limited to the early postoperative period for heart and heart-lung recipients. Lower grades of mismatch increase the likelihood of successful steroid withdrawal for heart recipients. The chance occurrence of no mismatch at any locus is rare, making prospective matching infeasible. HLA mismatching identifies patients at higher risk of rejection. The best use of this information may be to guide early immunosuppression, limiting prospective matching to retransplants or with presensitized recipients.
Assuntos
Rejeição de Enxerto , Antígenos HLA/imunologia , Transplante de Coração , Transplante de Coração-Pulmão , Histocompatibilidade , Transplante de Pulmão , Transplante de Coração/mortalidade , Transplante de Coração-Pulmão/mortalidade , Humanos , Terapia de Imunossupressão , Transplante de Pulmão/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND AND METHODS: We compared outcome measures in twenty single lung transplant recipients: 10 patients received the first lung of a donor pair (group 1), and 10 patients received the second lung (group 2) to determine the feasibility of sequential use, respectively, of donor lungs from the same donor in the same institution. The paired recipients underwent transplantation in the same operating room by the same surgical team. Both groups were well matched for age, gender, pretransplantation symptom class and diagnosis. RESULTS: The ischemic time for group 1 versus group 2 was 164 +/- 53 minutes (mean +/- standard deviation) (range 103 to 250 minutes) versus 377 +/- 53 minutes (range 315 to 445 minutes), respectively, (p < 0.001), but the longer ischemic time for group 2 did not adversely affect time to extubation (10.5 +/- 5.1 hours versus 10.3 +/- 7.6 hours; p = Not significant), early gas exchange (partial pressure of arterial oxygen on a fractional concentration of oxygen in inspired gas of 0.60: 237 +/- 61 versus 267 +/- 88 mm Hg; p = Not significant), length of hospital stay (16 +/- 13 days versus 16 +/- 5 days; p = Not significant), or actuarial one-year survival (80 +/- 12% versus 90 +/- 12%; p = Not significant). However, acute lung rejection (expressed as events/100 days) was more common within the first 3 months in group 1 versus group 2 (2.68 +/- 0.57 versus 1.32 +/- 0.38, respectively; p < 0.01), as were infectious events (2.07 +/- 0.50 versus 0.99 +/- 0.33; p < 0.01). CONCLUSIONS: These data confirm the safety of using the second lung from a donor pair sequentially in the same institution. The longer cold ischemic time for the second lung does not impair demonstrably early graft function and may be associated with a lower perioperative morbidity from acute rejection and subsequent infection. One-year outcome appears favorable for both groups.
Assuntos
Transplante de Pulmão , Doadores de Tecidos , Adolescente , Adulto , Feminino , Rejeição de Enxerto , Humanos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: The aim of this double-blind, placebo-controlled study was to determine whether a prolonged course of low-dose ganciclovir prevented the development of clinical cytomegalovirus disease after heart transplantation. METHODS: Fifty-six consecutive patients were stratified into two groups: cytomegalovirus-positive recipients (n = 40) and cytomegalovirus-negative recipients of organs from cytomegalovirus-positive donors (n = 16). All patients received equine antithymocyte globulin induction for 7 days and maintenance doses of cyclosporine, azathioprine, and prednisolone. Ganciclovir (5 mg/kg intravenously) or matching placebo was given with the premedication, three times weekly for the first 6 weeks after transplantation and for another 2 weeks for each treated rejection episode between 6 and 12 weeks. RESULTS: Ganciclovir prophylaxis reduced the actuarial incidence of cytomegalovirus disease from 71% to 11% in cytomegalovirus-mismatched patients (p < 0.01). Ganciclovir prophylaxis did not reduce the incidence of cytomegalovirus disease in cytomegalovirus-positive recipients (25% in both placebo and ganciclovir groups) but did delay its onset and reduce its morbidity. There were no adverse reactions during ganciclovir administration. Gastritis was the most common clinical manifestation of cytomegalovirus disease. Pneumonitis and myocarditis were seen only in placebo-treated cytomegalovirus-mismatched patients. All patients with clinical cytomegalovirus disease responded to ganciclovir, 10 mg/kg/day for 2 weeks. CONCLUSIONS: Prolonged low-dose ganciclovir prophylaxis after heart transplantation reduces the incidence of cytomegalovirus disease in cytomegalovirus-mismatched patients and reduces the morbidity of cytomegalovirus disease in cytomegalovirus-positive recipients.
Assuntos
Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Coração , Complicações Pós-Operatórias/prevenção & controle , Análise Atuarial , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , Método Duplo-Cego , Esquema de Medicação , Feminino , Ganciclovir/administração & dosagem , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/virologia , Fatores de TempoRESUMO
BACKGROUND: The aim of this study was to evaluate the efficacy of inhaled nitric oxide in the prevention and reversal of pulmonary hypertension during and after left ventricular assist device implantation. METHODS: Inhaled nitric oxide (20 ppm) was administered to seven consecutive patients undergoing implantation of a left ventricular assist device at the time of implantation and for the first 24 hours after operation. RESULTS: Withdrawal of inhaled nitric oxide at 24 hours after operation was associated with a significant rise in both the transpulmonary gradient (from 8+/-1 to 14+/-2 mm Hg, p < 0.01) and in pulmonary vascular resistance (from 110+/-19 to 196+/-32 dynes x sec x cm[-5], p < 0.01). In two patients, the rise in pulmonary vascular resistance resulted in a critical fall in left ventricular assist device flow and hemodynamic deterioration, necessitating urgent reinstitution of inhaled nitric oxide. CONCLUSION: The administration of inhaled nitric oxide at the time of left ventricular assist device implantation prevents rises in pulmonary vascular resistance that in some patients result in critical reductions in left ventricular assist device flow. We suggest that inhaled nitric oxide is a useful adjunctive treatment that should be routinely available at the time of left ventricular assist device implantation.
Assuntos
Coração Auxiliar , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/prevenção & controle , Óxido Nítrico/uso terapêutico , Administração por Inalação , Adulto , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
BACKGROUND: The successful use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has prompted our examination of quality of life (QOL) outcomes. The purposes of this study are to describe QOL in patients 1 to 2 weeks after LVAD implantation and to compare QOL in a smaller cohort of patients from before to 1 to 2 weeks after surgery. METHODS: Data were collected from a convenience sample of 81 patients who completed booklets of questionnaires that measure domains of QOL 1 to 2 weeks after LVAD insertion and from 30 of 81 patients who completed booklets at both the pre-implantation and post-implantation periods. Patients completed booklets of 6 to 8 self-reporting instruments, with acceptable reliability and validity. Data were analyzed using descriptive and comparative statistics (chi-square, Mann-Whitney U and Wilcoxon signed ranks tests) with p = 0.01 considered statistically significant. RESULTS: One to 2 weeks after LVAD implantation, patients were quite satisfied with their lives, experienced moderately low amounts of stress, coped well, and perceived themselves as having good health and QOL, low symptom distress, and moderately low functional disability. Patients reported significantly better QOL, more satisfaction with health and functioning, and were significantly less distressed by symptoms from immediately pre-operatively to post-operatively. However, patients reported significantly more self-care disability and more dissatisfaction with socioeconomic areas of life from before to immediately after surgery. Psychological distress was low and did not change with time. CONCLUSION: Given that QOL improved from before to after LVAD implantation, our findings provide a springboard for investigation of the impact of LVADs on long-term QOL outcomes.
Assuntos
Cardiomiopatias/cirurgia , Ventrículos do Coração/cirurgia , Coração Auxiliar , Qualidade de Vida , Adulto , Idoso , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Downstream of the genes for the structural alpha and beta subunits of the periplasmic Desulfovibrio vulgaris (Hildenborough) hydrogenase a DNA fragment was detected with sequence homology to these genes. This fragment was cloned in Escherichia coli and the nucleotide sequence was determined. A gene was detected on the fragment with coding capacity for a 65.8 kDa polypeptide, hyd gamma. The central part of hyd gamma has an unusually high degree of homology with the alpha subunit and the C-terminal part has similarity with the beta subunit. These results strongly suggest that the three genes for hyd gamma and the alpha and beta subunits derive from one common ancestor gene. We succeeded in the identification of the translational product of this gene in E. coli, but were unable to determine the function of hyd gamma after expression in E. coli.