RESUMO
INTRODUCTION: Nivolumab is a fully human programmed death control immune point 1 immune checkpoint inhibitor antibody which promotes antitumor immunity. Cutaneous toxicity associated with nivolumab, immune system related, could be linked to a more durable response in patients with squamous cell lung cancer. CASE REPORT: We present the case of a 62-year-old male diagnosed with metastatic squamous cell lung cancer, who was treated with nivolumab after cytotoxic chemotherapy. After treatment discontinuation, due to grade 2 cutaneous toxicity, the patient is maintaining with durable partial response for more than one year with close follow-up. MANAGEMENT AND OUTCOME: Cumulative doses of nivolumab could cause immunological toxicities that may prolong survival of these patients even after discontinuation of treatment. DISCUSSION: Nivolumab was approved by European Medicines Agency (EMA), as second-line therapeutic, for the treatment of squamous cell lung cancer, showing a median of 9.23 months of overall survival. The development of immune-related skin toxicities has been associated with greater clinical benefit in patients with lung cancer. When cutaneous toxicity forces to nivolumab suspension, in certain cases, the option of not starting again and closely following up the patient may appear reasonable, even though there are no survival data in this context. Suspension of treatment with close monitoring of these patients until progression may be an alternative, since immune-related skin toxicities could be related to a greater clinical benefit and a durable response to nivolumab.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversosRESUMO
AIM: To quantify the effect of two single-file reciprocating root canal preparation systems on Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament (PDL). METHODOLOGY: Forty PDL samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 20 of these premolars were divided equally in two groups, and then, root canals were prepared using one of two different single-file systems: WaveOne and Reciproc. Ten premolars were prepared with hand files and served as a positive control group. The remaining 10 premolars where extracted without treatment and served as a negative control group. All PDL samples were processed, and SP and CGRP were measured by radioimmunoassay. RESULTS: Greater SP and CGRP expression were found in the hand instrumentation group (1.220 pmol SP and 0.084 pmol CGRP per mg of PDL), followed by the WaveOne group (0.908 pmol SP and 0.046 pmol CGRP per mg of PDL) and the Reciproc group (0.511 pmol SP and 0.022 pmol CGRP per mg of PDL). The lower SP and CGRP values were associated with the intact control group (0.453 pmol SP and 0.018 pmol CGRP per mg of PDL). The Kruskal-Wallis test revealed significant differences between groups (P < 0.001). Post hoc Tukey HSD tests revealed significant differences in SP and CGRP expression between intact teeth in the control group and all the other groups (P < 0.001) except with the Reciproc group (P = 0.165 and P = 0.42 for SP and CGRP, respectively). Hand instrumentation was associated with significant differences with all the other groups (P < 0.001). Differences between the WaveOne and Reciproc groups were also significant (P < 0.001). CONCLUSION: Substance P and CGRP expression in PDL cells increased when teeth were prepared with WaveOne as well as with hand instrumentation. Reciproc maintained SP and CGRP levels in line with the negative control group.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/análise , Neurotransmissores/análise , Ligamento Periodontal/metabolismo , Preparo de Canal Radicular/instrumentação , Substância P/análise , Adolescente , Adulto , Dente Pré-Molar/cirurgia , Desenho de Equipamento , Humanos , Preparo de Canal Radicular/métodos , Adulto JovemRESUMO
OBJECTIVE: Adjustable suture procedures allow addressing the unpredictability of some postoperative results in strabismus surgery. The purpose of the study was to compare the effectiveness of adjustable and non-adjustable suture in the treatment of horizontal strabismus in children and adults. METHODS: Prospective study including patients undergoing strabismus surgery to correct horizontal strabismus with fixed hanging suture (non-adjustable suture group) and adjustable suture. Visual acuity, amblyopia, deviation, oblique muscle involvement, previous surgeries, nystagmus, need for adjustment, and complications were recorded. The variables were recorded in the immediate postoperative period, at one week and at 3 and 6 months. RESULTS: 186 patients were included: 157 (84.4%) with adjustable suture and 29 (15.6%) with non-adjustable suture, of which 119 were children and 67 were adults. Postoperatively, 19 children (16.0%) and 19 adults (28.4%) required adjustment (p = 0.044). Of 157 patients with adjustable suture, it was adjusted in 20% (32/157). Success after adjustment was higher for adjustable suture (91.72% vs 79.31%; p = 0.043) and remained for 6 months (p < 0.05). Previous surgery (p = 0.004) and exotropia (p = 0.018) correlated with the need for adjustment. CONCLUSIONS: 20% of patients with horizontal strabismus can benefit from a postoperative adjustment to improve the surgical result. The adjustable suture was shown to be superior to the fixed hanging suture and is an excellent surgical option, both in children and adults.
Assuntos
Procedimentos Cirúrgicos Oftalmológicos , Estrabismo , Adulto , Criança , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Estrabismo/cirurgia , Técnicas de Sutura , SuturasRESUMO
OBJECTIVE: Evaluation of the effectiveness of a standard dose of cefalozin 2 grams for surgical site infection (SSI) prevention in obese patients compared to non-obese patients. There is no still controversy surrounding which is the best dosage of this antibiotic in obese patients for surgical prophylaxis. METHODS: Retrospective review of men who received prophylactic cefazolin between January 1st, 2019 and June 30th, 2019 in a traumatology department of a university hospital. Patients were stratified into 2 groups: obese (≥ 100 kg and body mass index (BMI)> 30 kg / m2) and non-obese. Patients without a 90 days follow-up after surgery and/or with an active infection at the time of surgery and/or treated with immunosuppressants were excluded. Demographic data, height, real weight, smoking, diabetes, concomitant use of immunosuppressants, surgery data and presence of infection until day 90 were collected. RESULTS: A total of 57 patients underwent traumatic surgery with prophylactic cefazolin, 26 non-obese and 23 obese, were studied. Both groups presented statistically significant differences in weight, BMI and post-surgery use of cefazolin. No significant differences were observed in the other variables. Two obese (8.7%) and two non-obese (7.7%) patients developed SSIs after 63 days post-surgery on average, following the difference between the groups being statistically non-significant. CONCLUSIONS: This study shows that there is no significant difference in SSI with a standard prophylactic dose of two grams of cefazolin between obese and non-obese patients.
Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Cefazolina/administração & dosagem , Obesidade/metabolismo , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Índice de Massa Corporal , Peso Corporal , Cefazolina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
We present a first case of Staphylococcus cohnii endocarditis in an 80-year-old patient with a history of valve regurgitation. Endocarditis by this organism has not been reported previously. The patient declined treatment and died a few days later. When present, S. cohnii endocarditis has a poor prognosis as a result of associated comorbidities and the infection itself.
RESUMO
Since the publication of the 2008 guidelines on the diagnosis and treatment of diverticular disease of the colon by the Asociación Mexicana de Gastroenterología, significant advances have been made in the knowledge of that disease. A systematic review of articles published in the medical literature from January 2008 to July 2018 was carried out to revise and update the 2008 guidelines and provide new evidence-based recommendations. All high-quality articles in Spanish and English published within that time frame were included. The final versions of the 43 statements accepted in the three rounds of voting, utilizing the Delphi method, were written, and the quality of evidence and strength of the recommendations were established for each statement, utilizing the GRADE system. The present consensus contains new data on the definition, classification, epidemiology, pathophysiology, and risk factors of diverticular disease of the colon. Special emphasis is given to the usefulness of computed tomography and colonoscopy, as well as to the endoscopic methods for controlling bleeding. Outpatient treatment of uncomplicated diverticulitis is discussed, as well as the role of rifaximin and mesalazine in the management of complicated acute diverticulitis. Both its minimally invasive alternatives and surgical options are described, stressing their indications, limitations, and contraindications. The new statements provide guidelines based on updated scientific evidence. Each statement is discussed, and its quality of evidence and the strength of the recommendation are presented.
Assuntos
Doenças do Colo/terapia , Doenças Diverticulares/terapia , Consenso , Técnica Delphi , Diverticulite/terapia , Guias como Assunto , Humanos , MéxicoRESUMO
The use of proliferative signal inhibitors (PSIs) in immunosuppression-related malignancies opens new roads for increasing the survival and quality of life in patients with solid organ transplantation. A 56-year-old female recipient of a living donor renal allograft (1990), who was immunosuppressed with cyclosporine (CsA; Neoral), azathioprine, and steroids, did initially well with acceptable renal function. During the last 5 years she required local therapy due to posterior vaginal lip human papillomavirus (HPV) lesions. In 2000, she discontinued azathioprine and the CsA doses were reduced to 100 mg daily. The local lesion showed a good response to reduced immunosuppression. In February 2005, the lesion reappeared and a biopsy showed malignancy. Local surgery was performed and CsA was replaced by everolimus (EVL; Certican). Two months after treatment initiation, the patient developed cough, dyspnea, and low-grade fever. Chest X-ray showed a lesion at the base of the left lung compatible with pneumonitis. After fiberbronchoscopy a diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was obtained. She was treated with increased doses of oral steroids. EVL was never discontinued. The radiological lesion disappeared and the malignancy is currently in remission. In summary, a case of gynecological cancer in a renal transplant recipient was treated by surgical removal. After 1 year of immunosuppression with EVL, no recurrence has been observed. The adverse event (BOOP) was probably related to the PSI treatment and was controlled with an increased dose of steroids without discontinuing EVL.
Assuntos
Transplante de Rim/imunologia , Sirolimo/análogos & derivados , Corticosteroides/uso terapêutico , Azatioprina/uso terapêutico , Pneumonia em Organização Criptogênica/tratamento farmacológico , Ciclosporina/uso terapêutico , Everolimo , Feminino , Humanos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Doenças Renais Policísticas/cirurgia , Complicações Pós-Operatórias , Sirolimo/uso terapêutico , Neoplasias Vaginais/cirurgiaRESUMO
Patients with delayed graft function (DGF) are at risk of increased incidence for acute rejection episodes (ARE). Mycophenolate mofetil or induction therapy has produced a reduction in ARE incidence. An open, prospective, 3-month trial was performed in a group of Argentinian renal transplant recipients. We recruited 46 patients, 71.7% men, aged 41.7 +/- 13.8 years; including 36 (78.3%) recipients of cadaveric donors (CD) who were aged 43.4 +/- 15.5 years with a cold ischemia time of 19.4 hours +/- 5.4 minutes, and 10 (27.7%) recipients of living donors (LD) aged 37.8 +/- 12.9 years. HLA mismatches >or= 3 were observed in 58.4% of CD and in 7% of LD. All patients received two doses of basiliximab (20 mg each, days 0 and 4), cyclosporine microemulsion (CsA-ME) monitored by the second-hour concentrations (C2), enteric-coated mycophenolate sodium (EC-MPS; 720 mg twice a day, and steroids. A 58% incidence of DGF was observed. At the end of the third month the incidence of biopsy-proven ARE was 15%, with a median serum creatinine of was 1.54 +/- 0.42 mg/dL, including three grafts lost. Two patients died. No patient required EC-MPS dose discontinuation but 20% of patients required dose adjustments. The absence of discontinuations and the low incidence of dose adjustments of EC-MPS in this high-risk de novo population provided support of a suitable tolerability profile for this EC-MPS, and the possibility to impact efficacy results.
Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Ácido Micofenólico/uso terapêutico , Adulto , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Emulsões , Feminino , Humanos , Imunossupressores/administração & dosagem , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Comprimidos com Revestimento EntéricoRESUMO
UNLABELLED: Monitoring of cyclosporine (microemulsion CsA) at 2 hours post-dose (C2), a measure of absorption and exposure, appears superior to trough (C0) monitoring for prediction of rejection risk. The purpose of this study was to determine whether C2 was cost-effective compared to C0 in Argentina. METHODS: A predictive decision model was adapted to Argentina to predict costs associated with C0 and C2 measurements in the first year after transplantation. Patients were treated with microemulsion CsA, steroids and azathioprine or MMF. Parameter estimates for the C0 strategy were based on event rates observed in published clinical trials. The model was adapted to Argentinean health system through local protocols and expert opinions; costs were valued in Argentinean pesos and converted to US dollars (1 USD = 2.85 ARS). RESULTS: Incidence of acute rejection was predicted to be 25.0% at 1-year among patients monitored by C0 and 18.0% by C2. Graft survival was predicted to be 1.4% lower in the C0 group. No important differences were identified in co-morbidity, C0 and C2 monitoring costs, and in ambulatory-based adverse events between C0 and C2 cohorts. The model predicted an average cost per patient of $16,269 for C0 and $16,343 for C2 testing (year 1). Sensitivity analyses indicated that the average daily dose of microemulsion CsA was the most important parameter leading to the incremental cost per patient. CONCLUSIONS: C2 is expected to provide a potentially important reduction in the risk of acute rejection without increasing the estimated cost of care in the first year post-transplant.
Assuntos
Ciclosporina/sangue , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/imunologia , Doença Aguda , Argentina , Azatioprina/uso terapêutico , Custos e Análise de Custo , Ciclosporina/economia , Ciclosporina/farmacocinética , Ciclosporina/uso terapêutico , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Emulsões , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/sangue , Imunossupressores/economia , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Fatores de TempoRESUMO
Interactions between the kringle 4 (K4) domain of human plasminogen (Pgn) and segments of the N-terminal Glu1-Lys77 peptide (NTP) have been investigated via 1H-NMR at 500 MHz. NTP peptide stretches devoid of Lys residues but carrying an internal Arg residue show negligible affinity toward K4 (equilibrium association constant Ka < 0.05 mM(-1)). In contrast, while most fragments containing an internal Lys residue exhibit affinities comparable to that shown by the blocked Lys derivative Nalpha-acetyl-L-lysine-methyl ester (Ka approximately 0.2 mM(-1), peptides encompassing Lys50O consistently show higher Ka values. Among the investigated linear peptides, Nalpha-acetyl-Ala-Phe-Tyr-His-Ser-Ser-Lys5O-Glu-Gln-NH2 (AcAFYHSK5OEQ-NH2) exhibits the strongest interaction with K4 (Ka approximately 1.4 mM(-1)), followed by AcYHSK50EQ-NH2 (Ka approximately 0.9 mM(-1)). Relative to the wild-type sequence, mutated hexapeptides exhibit lesser affinity for K4. When a Lys50 --> Ser mutation was introduced (==> AcYHSS50EQ-NH2), binding was abolished. The Ile27-lle56 construct (L-NTP) contains the Lys50 site within a loop constrained by two cystine bridges. The propensity of recombinant Pgn K1 (rK1) and K2 (rK2) modules, and of Pgn fragments encompassing the intact K4 and K5 domains, for binding L-NTP, was investigated. We find that L-NTP interacts with rK1, rK2, K4, and K5-all lysine-binding kringles-in a fashion that closely mimics what has been observed for the Glul-HSer57 N-terminal fragment of Pgn (CB-NTP). Thus, both the constellation of kringle lysine binding site (LBS) aromatic residues that are perturbed upon complexation of L-NTP and magnitudes of kringle-L-NTP binding affinities (rK1, Ka approximately 4.3 mM(-1); rK2, Ka approximately 3.7 mM(-1; K4, Ka approximately 6.4 mM(1); and K5, Ka approximately 2.1 mM(-1)) are essentially the same as for the corresponding kringle-CB-NTP pairs. Molecular modeling studies suggest that the Glu39-Lys50 stretch in NTP generates an area that complements, both topologically and electrostatically, the solvent-exposed kringle LBS surface.
Assuntos
Kringles/fisiologia , Lisina/metabolismo , Fragmentos de Peptídeos/química , Plasminogênio/química , Sequência de Aminoácidos , Sítios de Ligação/fisiologia , Simulação por Computador , Brometo de Cianogênio/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica/fisiologia , Conformação Proteica , Homologia de Sequência de AminoácidosRESUMO
The Glu1-Val79 N-terminal peptide (NTP) domain of human plasminogen (Pgn) is followed by a tandem array of five kringle (K) structures of approximately 9 kDa each. K1, K2, K4, and K5 contain each a lysine-binding site (LBS). Pgn was cleaved with CNBr and the Glul-HSer57 N-terminal fragment (CB-NTP) isolated. In addition, the Ile27-Ile56 peptide (L-NTP) that spans the doubly S-S bridged loop segment of NTP was synthesized. Pgn kringles were generated either by proteolytic fragmentation of Pgn (K4, K5) or via recombinant gene expression (rK1, rK2, and rK3). Interactions of CB-NTP with each of the Pgn kringles were monitored by 1H-NMR at 500 MHz and values for the equilibrium association constants (Ka) determined: rK1, Ka approximately 4.6 mM(-1); rK2, Ka approximately 3.3 mM(-1); K4, Ka approximately 6.2 mM-'; K5, K, 2.3 mM(-1). Thus, the lysine-binding kringles interact with CB-NTP more strongly than with Nalpha-acetyl-L-lysine methyl ester (Ka < 0.6 mM(-l), which reveals specificity for the NTP. In contrast, CB-NTP does not measurably interact with rK3. which is devoid of a LBS. CB-NTP and L-NTP 1H-NMR spectra were assigned and interproton distances estimated from 1H-1H Overhauser (NOESY) experiments. Structures of L-NTP and the Glul-Ile27 segment of CB-NTP were computed via restrained dynamic simulated annealing/energy minimization (SA/EM) protocols. Conformational models of CB-NTP were generated by joining the two (sub)structures followed by a round of constrained SA/EM. Helical turns are indicated for segments 6-9, 12-16, 28-30, and 45-48. Within the Cys34-Cys42 loop of L-NTP, the structure of the Glu-Glu-Asp-Glu-Glu39 segment appears to be relatively less defined, as is the case for the stretch containing Lys5O within the Cys42-Cys54 segment, consistent with the latter possibly interacting with kringle domains in intact Glul-Pgn. Overall, the CB-NTP and L-NTP fragments are of low regular secondary structure content-as indicated by UV-CD spectra- and exhibit fast amide 1H-2H exchange in 2H2O, suggestive of high flexibility.
Assuntos
Kringles/fisiologia , Conformação Molecular , Fragmentos de Peptídeos/química , Plasminogênio/química , Sequência de Aminoácidos , Brometo de Cianogênio/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Fragmentos de Peptídeos/fisiologia , Estrutura Secundária de ProteínaRESUMO
Metabolic studies on insect allatostatins have suggested that the dipeptide Leu-Tyr may be a target for endopeptidases. In order to increase resistance to degradation, methyleneamino psi [CH2NH] and ketomethylene psi [COCH2] peptide bond surrogates have been introduced at the position Leu3-Tyr4 of the allatostatin Asp-Arg-Leu-Tyr-Ser-Phe-Gly-Leu-amide (BLAST-2), and Leu3-Phe4 of [Phe4]BLAST-2, respectively. Assays of inhibition of juvenile hormone (JH) synthesis in vitro by corpora allata from the cockroach Blattella germanica showed that both analogues were similarly active to the respective model peptides. The methyleneamino analogue was further tested in vivo as an inhibitor of JH synthesis, and in vivo and in vitro as an inhibitor of vitellogenin production by the fat body of B. germanica. The analogue was less active than BLAST-2 when tested in vitro, but more active than it when tested in vivo.
Assuntos
Baratas/fisiologia , Hormônios Juvenis/biossíntese , Neuropeptídeos/farmacologia , Oligopeptídeos/farmacologia , Vitelogeninas/biossíntese , Fatores Etários , Animais , Corpo Adiposo/fisiologia , Feminino , Técnicas In Vitro , Neuropeptídeos/metabolismo , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/químicaRESUMO
OBJECTIVE: We have previously reported a correlation between the starting number of embryos for multifetal pregnancy reduction (MFPR) and discordance in size during the first trimester. Here we evaluated the correlation between the degree of discordance and length of gestation in the remaining fetuses. DESIGN: Observational clinical series. SETTING: Academic medical center with a single physician who performs a large number of MFPRs. PATIENT(S): Analysis of 252 consecutive MFPRs from a 2.5-year period (1996-1998). INTERVENTION(S): MFPR for patients with multifetal pregnancies. MAIN OUTCOME MEASURE(S): We evaluated the correlation between the degree of discordance in embryo size, as measured by the greatest difference in crown-rump length (CRL) (delta max), and the length of gestation. RESULT(S): Embryo size discordance was related to length of gestation of the remaining fetuses after MFPR. Of 72 patients with a delta max >5 mm, the rate of severe premature birth (delivery at <28 weeks' gestation) was 9.7%, compared with 1.7% for patients with a delta max <5 mm (P<.01). Of patients with severe premature birth, 70% had delta max >5 mm, compared with less than 30% in patients who delivered after 28 weeks (P<.05). CONCLUSION(S): Variations in embryo growth patterns in multifetal pregnancies may be observed even in the first trimester, which may be predictive of late pregnancy outcomes. With a delta max > or =5 mm, there is a significant increase in the risk of severe premature birth (delivery at <28 weeks).
Assuntos
Embrião de Mamíferos/anatomia & histologia , Trabalho de Parto Prematuro/diagnóstico , Redução de Gravidez Multifetal , Estatura Cabeça-Cóccix , Feminino , Idade Gestacional , Humanos , Gravidez , Gravidez MúltiplaRESUMO
BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the influence of valve size and left ventricular (LV) mass on long-term LV diastolic reserve in patients subjected to aortic valve replacement for stenosis. METHODS: Seventy-four patients (33 women, 41 men; mean age 64 years) after aortic valve replacement with 40 pericardial bioprostheses and 34 bileaflet mechanical prostheses were studied. All valves were of nominal size 19, 21 or 23 mm. The patients were studied by Doppler echocardiography, at rest and during peak effort, between 12 and 47 months after valve replacement. RESULTS: All patients achieved significantly increased heart rate, blood pressure and cardiac output in response to effort. Effort also significantly modified transvalvular pressure drops and valve areas. The mean diastolic reserve was 29.3 ml, and mean stroke volume reserve 23.2 ml; in neither case were there any significant differences between valve types, or among valve sizes. CONCLUSION: At about one year after surgery, the diastolic reserve of patients subjected to aortic valve replacement on account of stenosis was considerable, and independent of valve size. Despite the persistence of LV hypertrophy after valve replacement, LV diastolic function during effort was similar to that of the normal heart.
Assuntos
Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Bioprótese , Implante de Prótese de Valva Cardíaca/instrumentação , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/cirurgia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Fatores Etários , Idoso , Estenose da Valva Aórtica/diagnóstico por imagem , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Ecocardiografia Doppler , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Espanha/epidemiologiaRESUMO
BACKGROUND: A direct relationship between serum bile acids (SBA) and hepatic and hepatobiliary dysfunction has been demonstrated. However, there is little evidence that SBA are related to renal insufficiency. In a previous study, we showed that hemodialysis patients with advanced chronic renal failure (ACRF) have an increase of SBA in predialysis and a decrease in postdialysis. Consequently, it was assumed that the restoration of renal function in transplanted patients might decrease SBA levels. AIM OF THIS STUDY: Transplanted patients receiving cyclosporine A (CyA) were studied by monitoring CyA and SBA levels to determine if a probable relationship exists between renal function, CyA treatment and SBA levels. SUBJECTS. MATERIALS AND METHODS: SBA levels were determined in 15 recently transplanted patients receiving CyA for 18 months and longer. In addition, 22 renal patients transplanted not less than 6 years ago were also included in the study and were characterized as the stable group. Five patients from this group received mycophenolate or azathioprine instead of CyA as immunosuppressant. In addition to SBA and CyA, creatinine, cholesterol, y-GT, viral markers and triglycerides were also determined in all patients. RESULTS: A significant and constant increase in SBA levels was observed in the recently transplanted group. However, after 18 months, SBA levels gradually decreased to those of patients considered stable under CyA treatment. In both recently transplanted and stable patients who received CyA, SBA values remained higher than normal, but stable patients under mycophenolate or azathioprine treatment showed no such increase. CONCLUSIONS: In recently transplanted patients, in patients studied for 18 months post transplant and in stable patients receiving CyA, the increase of SBA levels might be related to CyA treatment. This effect might be attributed to its cholestatic effect and also to a modification in uptake, metabolism, synthesis and excretion of SBA in the hepatocyte. These conclusions are supported by the results obtained in stable transplanted patients without CyA treatment showing normal SBA levels.
Assuntos
Ácidos e Sais Biliares/sangue , Ciclosporina/sangue , Ciclosporina/farmacologia , Imunossupressores/sangue , Imunossupressores/farmacologia , Transplante de Rim/efeitos adversos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Complicações Pós-Operatórias , Recuperação de Função Fisiológica/fisiologia , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Insuficiência Renal/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Renal/etiologia , Fatores de TempoRESUMO
BACKGROUND: Chronic renal failure (CRF) patients usually suffer from pruritus. The pathophysiology of pruritus is still incompletely understood. SUBJECTS, MATERIALS AND METHODS: In this paper we determined serum total bile acids (STBA) in hemodialysis patients with advanced CRF (ACRF) in order to obtain STBA concentration in predialysis, to assess their probable relation among patients with pruritus and in postdialysis using a polysulfone membrane for dialysis. STBA were determined in 49 ACRF patients with chronic hemodialysis and values were compared to 20 control subjects. Hemodialysis patients were divided in two groups: with and without pruritus. In all these patients, month of renal replacement therapy, diabetic patients, dose of dialysis (Kt/V), viral markers, serum creatinine, serum glucose, aspartate and alanine aminotransferase, alkaline phosphatase, hematocrits and albumin were determined. The intensity of itching among pruritic patients was measured by a score system: mild (M), moderate (MO) and severe (S). RESULTS: No significant differences were found in patients with and without pruritus in months of renal replacement therapy, duration of dialysis or dose of dialysis (Kt/V). STBA were determined in all ACRF patients in predialysis and they showed significant differences compared to controls (p < 0.05), however, no differences were observed in the results obtained when control subjects were compared to ACRF patients without pruritus. Also in predialysis, pruritic patients showed significant differences in STBA compared to patients without pruritus (p < 0.001). STBA concentration showed a significant decrease in postdialysis using a polysulfone membrane in ACRF patients with and without pruritus. Finally, correlation with STBA and itch score of pruritus was significant (p < 0.02). CONCLUSION: Hemodialysis patients with ACRF and pruritus showed an increase of STBA in predialysis and a decrease in postdialysis.
Assuntos
Ácidos e Sais Biliares/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Prurido/etiologia , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Membranas Artificiais , Pessoa de Meia-IdadeRESUMO
The effect of dexamethasone on ethanol-induced hypothermia was investigated in 3.5-month old male Wistar rats (N = 10 animals per group). The animals were pretreated with dexamethasone (2.0 mg/kg, i.p.; volume of injection = 1 ml/kg) 15 min before ethanol administration (2.0, 3.0 and 4.0 g/kg, i.p.; 20% w/v) and the colon temperature was monitored with a digital thermometer 30, 60 and 90 min after ethanol administration. Ethanol treatment produced dose-dependent hypothermia throughout the experiment (-1.84 +/- 0.10, -2.79 +/- 0.09 and -3.79 +/- 0.15 degrees C for 2.0, 3.0 and 4.0 g/kg ethanol, respectively, 30 min after ethanol) but only the effects of 2.0 and 3.0 g/kg ethanol were significantly antagonized (-0.57 +/- 0.09 and -1.25 +/- 0.10, respectively, 30 min after ethanol) by pretreatment with dexamethasone (ANOVA, P < 0.05). These results are in agreement with data from the literature on the rapid antagonism by glucocorticoids of other effects of ethanol. The antagonism was obtained after a short period of time, suggesting that the effect of dexamethasone is different from the classical actions of corticosteroids.