ABSTRACT
BACKGROUND: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. METHODS: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. RESULTS: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. CONCLUSIONS: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.
Subject(s)
Depression , Depressive Disorder, Major , Humans , Heart Rate/physiology , Depressive Disorder, Major/drug therapy , Antidepressive Agents/therapeutic use , BiomarkersABSTRACT
BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.
Subject(s)
General Surgery , Surgical Procedures, Operative , Adult , Aged , Benchmarking , Cohort Studies , Emergencies , Female , Hospital Mortality , Humans , Middle Aged , Postoperative Complications , Prospective Studies , Quality Improvement , Retrospective StudiesABSTRACT
OBJECTIVE: To assess the clinical usefulness of 68Ga-PSMA PET/CT studies in patients with occult biochemical recurrence of prostate carcinoma, with negative or inconclusive radiologic and 18â¯F-Choline PET/CT imaging studies. MATERIAL AND METHODS: Retrospective descriptive study. The first 14 patients with a history of prostate carcinoma, treated with curative intent and presenting suspicion of biochemical recurrence with low PSA values (<3â¯ng/mL) were selected. Imaging studies, prostate ultrasound, pelvic CT and/or MRI were negative, and all of them had a negative or inconclusive 18F-Choline PET/CT. All patients were referred to 68 Ga-PSMA-11 PET/CT. PROTOCOL: Dose 2.2â¯Mâ¯Bq/kg. 20â¯mg furosemide at start. PET/CT images from skull base to proximal third of thighs at 60â¯min, and late images at 3â¯h if needed. RESULTS: The 68 Ga-PSMA-11 PET/CT was able to localize the occult biochemical recurrence in 9 of the 14 patients (64.2%), and it affected the therapeutic attitude in all of them. Four patients (28.5%) obtained a negative or inconclusive 68 Ga-PSMA-11 PET/CT and continued under vigilant approach with PSA controls and imaging studies according to the clinical guidelines. These patients had the lowest PSA values (less than 1â¯ng/mL). One of the 68 Ga-PSMA-11 PET/CT studies was inconclusive, reporting the presence of a doubtful right iliac adenopathy. CONCLUSION: 68 Ga-PSMA-11 PET/CT allows an early diagnosis, with low PSA values, of occult biochemical recurrence of prostate carcinoma, even in patients with negative 18â¯F-Choline PET/CT.
Subject(s)
Carcinoma , Prostatic Neoplasms , Choline , Gallium Isotopes , Gallium Radioisotopes , Humans , Male , Positron Emission Tomography Computed Tomography , Prostate , Prostatic Neoplasms/diagnostic imaging , Retrospective StudiesABSTRACT
Objetivo: Valorar la utilidad de los estudios 68Ga-PSMA PET/TC en la práctica clínica de los pacientes con recidiva bioquímica oculta de carcinoma de próstata, con estudios de imagen radiológicos y 18F-Colina PET/TC negativos o no concluyentes.Material y métodosobservacional retrospectivo y de exactitud diagnóstica. Se seleccionaron los primeros 14 pacientes con antecedentes de carcinoma de próstata, tratados con intención curativa y que presentaban sospecha de recidiva bioquímica con valores bajos de antígeno prostático específico (PSA) (< 3 ng/mL). Los estudios de imagen, ecografía prostática, tomografía computarizada (TC) y/o resonancia magnética (RM) pélvica eran negativos, y todos ellos tenían un 18F-Colina PET/TC negativo o no concluyente. Se derivó a todos los pacientes para realizarse un 68Ga-PSMA-11 PET/TC. Protocolo: Dosis 2,2 MBq/kg, 20 mg de furosemida en el minuto 0. Imágenes PET/TC desde calota craneal hasta el tercio proximal de muslos a los 60 min, e imágenes tardías a las tres horas, si precisara.ResultadosEn nueve de los 14 pacientes (64,2%) el 68Ga-PSMA-11 PET/TC consiguió localizar la recidiva bioquímica oculta, y en todos ellos hubo cambios en la actitud terapéutica. En cuatro de los 14 pacientes (28,5%) el 68Ga-PSMA-11 PET/TC resultó negativo o no concluyente, se prosiguió con la actitud vigilante con controles de PSA y estudios de imagen, según los protocolos habituales. Estos pacientes presentaban los valores más bajos de PSA (inferiores a 1 ng/mL). Uno de los estudios 68Ga-PSMA-11 PET/TC fue no concluyente, informándose la presencia de una dudosa adenopatía iliaca derecha. (AU)
Objective: To assess the clinical usefulness of 68Ga-PSMA PET/CT studies in patients with occult biochemical recurrence of prostate carcinoma, with negative or inconclusive radiologic and 18F-Choline PET/CT imaging studies.Material and methodsRetrospective observational and diagnostic accuracy. The first 14 patients with a history of prostate carcinoma, treated with curative intent and presenting suspicion of biochemical recurrence with low PSA values (< 3 ng/ml) were selected. Imaging studies, prostate ultrasound, pelvic CT and/or MRI were negative, and all of them had a negative or inconclusive 18F-Choline PET/CT.All patients were referred to 68Ga-PSMA-11 PET/CT. Protocol: Dose 2.2 MBq/kg. 20 mg furosemide at start. PET/CT images from skull base to proximal third of thighs at 60 min, and late images at 3 hours if needed.ResultsThe 68Ga-PSMA-11 PET/CT was able to localize the occult biochemical recurrence in 9 of the 14 patients (64.2%), and it affected the therapeutic attitude in all of them.Four patients (28.5%) obtained a negative or inconclusive 68Ga-PSMA-11 PET/CT and continued under vigilant approach with PSA controls and imaging studies according to the clinical guidelines. These patients had the lowest PSA values (less than 1 ng/ml).One of the 68Ga-PSMA-11 PET/CT studies was inconclusive, reporting the presence of a doubtful right iliac adenopathy. (AU)
Subject(s)
Humans , Carcinoma , Gallium Isotopes , Gallium Radioisotopes , Prostate , Prostatic Neoplasms/diagnostic imaging , Choline , Positron-Emission Tomography , Retrospective StudiesABSTRACT
INTRODUCTION: The clinical diagnosis aims to identify the degree of affectation of the psycho-physical state of the patient as a guide to therapeutic intervention. In stress, the lack of a measurement tool based on a reference makes it difficult to quantitatively assess this degree of affectation. AIM: To define and perform a primary assessment of a standard reference in order to measure acute emotional stress from the markers identified as indicators of the degree. SUBJECTS AND METHODS: Psychometric tests and biochemical variables are, in general, the most accepted stress measurements by the scientific community. Each one of them probably responds to different and complementary processes related to the reaction to a stress stimulus. The reference that is proposed is a weighted mean of these indicators by assigning them relative weights in accordance with a principal components analysis. RESULTS: An experimental study was conducted on 40 healthy young people subjected to the psychosocial stress stimulus of the Trier Social Stress Test in order to perform a primary assessment and consistency check of the proposed reference. The proposed scale clearly differentiates between the induced relax and stress states. CONCLUSIONS: Accepting the subjectivity of the definition and the lack of a subsequent validation with new experimental data, the proposed standard differentiates between a relax state and an emotional stress state triggered by a moderate stress stimulus, as it is the Trier Social Stress Test. The scale is robust. Although the variations in the percentage composition slightly affect the score, but they do not affect the valid differentiation between states.
TITLE: Aproximacion a una escala de referencia de estres emocional agudo.Introduccion. El diagnostico clinico persigue identificar el grado de afectacion del estado psicofisico del paciente como orientacion hacia la intervencion terapeutica. En el estres, la falta de un instrumento de medicion por comparacion con una referencia dificulta la valoracion cuantitativa del nivel de afectacion. Objetivo. Definir y hacer una primera validacion de un patron de referencia para la medida del estres emocional agudo a partir de marcadores identificados como indicadores del nivel. Sujetos y metodos. En general, las medidas mas solidas y aceptadas de estres por la comunidad cientifica son los test psicometricos y las variables bioquimicas. Cada uno de ellos responde probablemente a procesos distintos y complementarios de la reaccion frente a un estimulo estresante. La referencia que se propone es una media ponderada de estos indicadores, asignandoles pesos relativos de acuerdo con un analisis de componentes principales. Resultados. Para una primera aproximacion y verificacion de coherencia de la referencia propuesta, se ha utilizado un estudio experimental con una muestra de 40 jovenes sanos sometidos al estimulo estresante psicosocial del Trier Social Stress Test. La escala propuesta diferencia netamente entre los dos estados con distintos niveles de estres inducido. Conclusiones. Aceptando la subjetividad de la definicion, y a falta de una validacion posterior con nuevos datos experimentales, el patron propuesto diferencia entre un estado de relax y uno de estres emocional generados con un estimulo estresante moderado, como es el Trier Social Stress Test. La escala es robusta, ya que variaciones en la composicion porcentual repercuten ligeramente en la puntuacion, pero no en la diferenciacion valida entre estados.
Subject(s)
Severity of Illness Index , Stress, Psychological/diagnosis , Biomarkers , Electrodiagnosis , Female , Glycopeptides/blood , Humans , Hydrocortisone/blood , Male , Principal Component Analysis , Prolactin/blood , Psychological Tests , Psychometrics , Reference Standards , Relaxation , Stress, Psychological/blood , Stress, Psychological/physiopathology , Stress, Psychological/psychologyABSTRACT
Sixteen Murciano-Granadina dairy goats, provided with wireless rumen sensors for pH and temperature, were used to assess the rumen environment variations produced by extreme forage to concentrate diets (experiment 1) and climatic conditions (experiment 2). To avoid the interference of feed intake, goats were fed at maintenance level. Rumen sensors were inserted by surgery and programmed to collect and store rumen pH and temperature every 30min. In experiment 1, 8 dry goats (38.6±2.3kg of body weight) in tiestalls were divided into 2 groups and fed at maintenance level with 2 diets varying in forage-to-concentrate ratio [high forage (HF) 70:30; low forage (LF) 30:70] according to a crossover design. Diets were offered once daily for 4h and tap water (4 L, 9.8±0.4°C) was offered for only 30min at 6h after feeding. Rectal temperatures were recorded 3 times during the day. Rumen pH fell immediately after feeding, reaching a nadir depending on the diet (HF=6.35±0.07 at 11h after feeding; LF=6.07±0.07 at 6h after feeding) and being on average greater (0.31±0.06) in HF than LF goats. No diet effects were detected in rectal (38.2±0.1°C) and ruminal (38.9±0.1°C) mean temperatures, which were positively correlated. Rumen temperature dramatically changed by feeding (1.4±0.1°C) and drinking (-3.4±0.1°C), and 2h were necessary to return to the fasting value (38.2±0.1°C). In experiment 2, 8 dry goats (43.9±1.0kg of body weight) were kept in metabolic cages, fed a 50:50 diet and exposed to 2 climatic conditions following a crossover design. Conditions were thermoneutral (TN; 20 to 23°C day-night) and heat stress (HS; 12-h day at 37°C and 12-h night at 30°C). Humidity (40±5%) and photoperiod (light-dark, 12-12h) were similar. Goats were fed at maintenance level, the feed being offered once daily and water at ambient temperature was freely available. Intake, rectal temperature, and respiratory rate were recorded 3 times daily. Despite no differing in dry matter intake, rumen pH was lower in HS than in TN goats (-0.12±0.04). On the contrary, rumen temperature (0.3±0.1°C), rectal temperature (0.4±0.1°C), respiratory rate (77±5 breaths/min), and water intake (3.2±0.7 L/d) had a greater increase in HS than TN, which might indicate an altered microbial fermentation under high temperature conditions. In conclusion, wireless bolus sensors proved to be a useful tool to monitor rumen pH and temperature as affected by different feeding and climatic conditions.
Subject(s)
Diet/veterinary , Goats/physiology , Hot Temperature , Rumen/physiology , Telemetry/veterinary , Wireless Technology , Animal Husbandry , Animals , Female , Telemetry/methodsABSTRACT
This paper presents a study performed in 25 young healthy subjects measuring the evolution of heart rate variability (HRV) indices during emotional stress. Acute emotional stress was generated with a modified version of Trier Social Stress Test (TSST). The TSST comprises several tasks which include a memory test, anticipation of stress, public exposition, and an arithmetic task. Each task has different demanding conditions, carrying subjects' emotional stress to different states. An autogenic relaxation was done before TSST. Significant differences in HRV indices were observed in the arithmetic and memory task with respect to the relaxation stage. In particular during the arithmetic task, mean heart rate increased 22% (p-value <0.00001) the power in the very low frequency band increased 47% (p-value <0.00001 and normalized power in the low frequency (LF) band increased 19% (p-value <0.04). These results support a sympathetic activation during these tasks.
Subject(s)
Emotions , Heart Rate/physiology , Stress, Psychological/diagnosis , Adolescent , Adult , Algorithms , Electrocardiography , Electrophysiology , Female , Humans , Male , Signal Processing, Computer-Assisted , Stress, Psychological/physiopathology , Young AdultABSTRACT
A total of 83 lactating dairy ewes (Manchega, n=48; Lacaune, n=35) were used in 2 consecutive experiments for assessing the ability of infrared thermography (IRT) to detect intramammary infections (IMI) by measuring udder skin temperatures (UST). In experiment 1, ewes were milked twice daily and IRT pictures of the udder were taken before and after milking at 46 and 56d in milk (DIM). Milk yield was 1.46 ± 0.04 L/d, on average. Detection of IMI was done using standard bacterial culture by udder half at 15, 34, and 64 DIM. Twenty-two ewes were classified as having IMI in at least one udder half, the others being healthy (142 healthy and 24 IMI halves, respectively). Four IMI halves had clinical mastitis. No UST differences were detected by IMI and udder side, being 32.94 ± 0.04°C on average. Nevertheless, differences in UST were detected for breed (Lacaune - Manchega=0.35 ± 0.08°C), milking process moment (after - before=0.13 ± 0.11°C), and milking schedule (p.m. - a.m.=0.79 ± 0.07°C). The UST increased linearly with ambient temperature (r=0.88). In experiment 2, the UST response to an Escherichia coli O55:B5 endotoxin challenge (5 µg/udder half) was studied in 9 healthy Lacaune ewes milked once daily in late lactation (0.58 ± 0.03 L/d; 155 ± 26 DIM). Ewes were allocated into 3 balanced groups of 3 ewes to which treatments were applied by udder half after milking. Treatments were (1) control (C00, both udder halves untreated), (2) half udder treated (T10 and C01, one udder half infused with endotoxin and the other untreated, respectively), and (3) treated udder halves (T11, both udder halves infused with endotoxin). Body (vaginal) temperature and UST, milk yield, and milk composition changes were monitored by udder half at different time intervals (2 to 72 h). First local and systemic signs of IMI were observed at 4 and 6h postchallenge, respectively. For all treatments, UST increased after the challenge, peaking at 6h in T 0055 (which differed from that in C00, C01, and T10), and decreased thereafter without differences by treatment. Vaginal temperature and milk somatic cell count increased by 6h postchallenge, whereas lactose content decreased, in the endotoxin-infused udder halves. Effects of endotoxin on lactose and somatic cell count values were detectable in the infused udder halves until 72 h. In conclusion, despite the accuracy of the camera (± 0.15°C) and the moderate standard errors of the mean obtained for UST measures (± 0.05 to 0.24°C), we were unable to discriminate between healthy and infected (subclinically or clinically) udder halves in dairy ewes.
Subject(s)
Lactation , Mammary Glands, Animal/physiopathology , Mastitis/diagnosis , Sheep/microbiology , Thermography/methods , Animals , Cell Count , Endotoxins/isolation & purification , Escherichia coli/isolation & purification , Female , Mammary Glands, Animal/microbiology , Mastitis/microbiology , Mastitis/veterinary , Milk/chemistry , Milk/microbiology , TemperatureABSTRACT
OBJECTIVE: Renal transplantation is the most successful therapy to improve survival and quality of life for patients with end-stage renal disease. Living donors have been used as an alternative to reduce the stay on the waiting list. Laparoscopic living donor nephrectomy has become the standard procedure for renal transplantation. Minimally invasive surgery involves less postoperative pain with less analgesic requirements allowing shorter hospital stay for the donor. MATERIAL AND METHODS: We retrospectively analyzed demographic and intraoperative data and surgical complications for 46 patients who underwent laparoscopic living donor nephrectomy between March 2001 and March 2011. RESULTS: Mean donor age was 41 years. Mean operative time was 170 ± 45 minutes. The average cold ischemic time was 40 minutes and warm ischemic time was 26 minutes. Twenty-one patients were donors for pediatric receptors. Fourty patients underwent left laparoscopic nephrectomy, the other 6 patients underwent right laparoscopic nephrectomy due to vascular anatomic variant. Right laparoscopic nephrectomy was converted in 1 case (2.2%) due to renal vein laceration without donor morbidity and without compromise of graft function. Renal function at the second day post donor nephrectomy was measured using serum creatinine averaged 1.2 mg/dL with a mean increase of 0.4 mg/dL from baseline, with normalization after 30 days. No patient required blood transfusion, and there were no immediate surgical complications, infections, or mortality. One patient developed an incisional hernia in relation to the site of kidney removal. The mean hospital stay was 5 ± 1 days. CONCLUSIONS: Laparoscopic nephrectomy in our experience is a safe technique without postoperative morbidity or mortality. It is associated with low levels of pain, early discharge and early return to physical activity and work, good sense of aesthetic results, and long-term graft function comparable to traditional nephrectomy and cadaveric grafts.
Subject(s)
Kidney Transplantation/methods , Laparoscopy , Living Donors , Nephrectomy/methods , Adult , Biomarkers/blood , Chile , Cold Ischemia , Creatinine/blood , Female , Humans , Kidney Transplantation/adverse effects , Laparoscopy/adverse effects , Length of Stay , Male , Nephrectomy/adverse effects , Retrospective Studies , Time Factors , Treatment Outcome , Warm IschemiaABSTRACT
Apoptosis modulation is a procedure amply utilized by intracellular pathogens to favour the outcome of the infection. Nevertheless, the role of apoptosis during infection with Mycobacterium tuberculosis, the causative agent of human tuberculosis, is subject of an intense debate and still remains unclear. In this work, we describe that apoptosis induction in host cells is clearly restricted to virulent M. tuberculosis strains, and is associated with the capacity of the mycobacteria to secrete the 6 kDa early secreted antigenic target ESAT-6 bothunder in vitro and in vivo conditions. Remarkably, only apoptosis-inducing strains are able to propagate infection into new cells, suggesting that apoptosis is used by M. tuberculosis as a colonization mechanism. Finally, we demonstrate that in vitro modulation of apoptosis affects mycobacterial cell-to-cell spread capacity, establishing an unambiguous relationship between apoptosis and propagation of M. tuberculosis. Our data further indicate that BCG and MTBVAC vaccines are inefficient in inducing apoptosis and colonizing new cells, correlating with the strong attenuation profile of these strains previously observed in vitro and in vivo.
Subject(s)
Antigens, Bacterial/metabolism , Apoptosis/immunology , Bacterial Proteins/metabolism , Homeodomain Proteins/metabolism , Mycobacterium tuberculosis/metabolism , Tuberculosis/transmission , Animals , Antigens, Bacterial/genetics , BCG Vaccine/immunology , Bacterial Proteins/genetics , Female , Green Fluorescent Proteins , Humans , Macrophages/microbiology , Mice , Mice, Inbred C57BL , Mycobacterium tuberculosis/pathogenicitySubject(s)
Adenocarcinoma/secondary , Carbon Radioisotopes , Choline , Multimodal Imaging , Penile Neoplasms/secondary , Positron-Emission Tomography , Prostatic Neoplasms/diagnostic imaging , Radiopharmaceuticals , Tomography, X-Ray Computed , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Agents, Hormonal/therapeutic use , Combined Modality Therapy , Humans , Male , Middle Aged , Neoplasm Staging , Penile Neoplasms/diagnostic imaging , Prognosis , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapyABSTRACT
Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Graft Rejection/prevention & control , Graft Survival/drug effects , Immunity, Humoral/drug effects , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Receptors, Interleukin-2/antagonists & inhibitors , Recombinant Fusion Proteins/administration & dosage , Acute Disease , Adult , Basiliximab , Chile , Communicable Diseases/etiology , Female , Graft Rejection/immunology , Graft Rejection/mortality , HLA Antigens/immunology , Humans , Isoantibodies/blood , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Kidney Transplantation/mortality , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: HLA Matchmaker is a computer algorithm developed to evaluate donor/receptor compatibility comparing sequences of polymorphic aminoacids (eplets) present in human leukocyte antigen (HLA) molecules. The aim of this study was to evaluate the predictive value of HLA Matchmaker for patient and graft survival, graft survival free of rejection, and the presence of anti HLA antibodies. METHODS: Using this program, 62 of 173 kidney transplant patients, were retrospectively analyzed. HLA-I loci eplet mismatch value (EMM) was determined and correlated with graft survival, graft survival free of rejection, and the presence of anti HLA-I antibodies. EMM was compared with the traditional HLA antigen mismatch value (MM) in terms of the presence of anti HLA-I antibodies. RESULTS: Graft survival and graft survival free of rejection showed no statistical differences (P-value .975 and .365, respectively) while comparing patients with less or more than 10 HLA-I EMM. Patients with > or =6 HLA-B EMM had an odds ratio (OR) of 5.6 (95% confidence interval [CI], 0.47-66.45) of presenting anti HLA-I antibodies, with a sensitivity of 80% and specificity of 58.3%. For > or =2 HLA-B MM, the OR was 2.58 (95% CI, 0.46-14.5), with a sensitivity of 40% and specificity of 75%. CONCLUSION: Even though in our study population compatibility by HLA Matchmaker did not correlate with graft survival or rejection-free graft survival, it showed a better sensitivity than traditional HLA antigen matching for the presence of anti HLA-I antibodies. HLA Matchmaker is a promising tool in predicting the appearance of anti-HLA antibodies.
Subject(s)
Graft Survival/immunology , HLA Antigens/immunology , Kidney Transplantation/physiology , Adult , Cadaver , Female , Graft Rejection/epidemiology , Graft Rejection/immunology , HLA-D Antigens/immunology , Histocompatibility Antigens Class I/immunology , Histocompatibility Testing , Humans , Kidney Diseases/classification , Kidney Diseases/surgery , Kidney Transplantation/immunology , Living Donors , Male , Middle Aged , Polymerase Chain Reaction , Retrospective Studies , Tissue DonorsABSTRACT
Alemtuzumab (ALT), a humanized monoclonal anti-CD52 antibody, was introduced in solid organ transplantation as an induction agent. ALT associated with anticalcineurins has provided a low incidence of acute rejection episodes (ARE) and potential tolerogenic properties. We analyzed the clinical outcomes and effects on peripheral Treg of renal transplant recipients treated with ALT. Six-month data on kidney alone or kidney combined with pancreas or liver patients treated with ALT and tacrolimus (TAC) in standard doses were compared with those on renal transplant recipients of similar demography who were not treated with ALT. We evaluated patient and graft survivals, ARE incidence, hematological parameters, renal function, adverse events, and CD4+CD25+FoxP3+ T cells in peripheral blood. Demographics of recipients, donors, and transplants were similar in both groups. Mean HLA mismatch was slightly greater among ALT-treated patients (3.5 vs 2.5). No combined transplantation was performed in the ALT-untreated group. Patient and graft survivals were 100% without rejection or serious infections in both groups. ALT-treated recipients showed anemia and leukopenia in 3 patients as well as severe lymphopenia in 5 recipients, who partially recovered on day 90. Final mean plasma creatinine was 1.4 mg/dL, while calculated creatinine clearance was approximately 65 mL/min in both groups. Mean Treg cell percentage was higher among ALT-treated recipients than the comparative group or healthy controls (P < .05). In conclusion, renal transplantation results obtained using ALT with rigorous immunosuppressive therapy were excellent; serious adverse events and acute rejection were absent. The effect of the increased proportion of Treg cells must be evaluated with longer observation.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Neoplasm/therapeutic use , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Alemtuzumab , Antibodies, Monoclonal, Humanized , Antigens, CD/immunology , Antigens, Neoplasm/immunology , Autoantibodies/blood , CD4 Lymphocyte Count , CD52 Antigen , Female , Glycoproteins/immunology , Graft Rejection/epidemiology , Graft Survival/drug effects , Graft Survival/immunology , HLA Antigens/immunology , Humans , Kidney Diseases/classification , Kidney Diseases/surgery , Liver Transplantation/immunology , Male , Middle Aged , Pancreas Transplantation/immunology , Tacrolimus/therapeutic use , Treatment OutcomeABSTRACT
Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.
Subject(s)
Liver Transplantation/physiology , Adolescent , Cadaver , Child , Child, Preschool , Female , Follow-Up Studies , Graft Survival , Humans , Infant , Kidney Diseases/surgery , Liver Transplantation/mortality , Living Donors , Male , Reoperation , Retrospective Studies , Survival Analysis , Time Factors , Tissue DonorsABSTRACT
It is commonly accepted that electrical impedance provides relevant information about the physiological condition of living tissues. Currently, impedance measurements are performed with relatively large electrodes not suitable for studies in small animals due to their poor spatial resolution and to the damage that they cause to the tissue. A minimally invasive needle shaped probe for electrical impedance measurements of living tissues is presented in this paper. This micro-probe consists of four square platinum electrodes (300 microm x 300 microm) on a silicon substrate (9 mm x 0.6 mm x 0.5 mm) and has been fabricated by using standard Si microelectronic techniques. The electrodes are not equally spaced in order to optimise the signal strength and the spatial resolution. Characterisation data obtained indicate that these probes provide high spatial resolution (measurement radius <4 mm) with a useful wide frequency band going from 100 Hz to 100 kHz. A series of in vivo experiments in rat kidneys subjected to ischemia was performed to demonstrate the feasibility of the probes and the measurement system. The impedance modulus and phase were measured at 1 kHz since this frequency is sufficiently low to permit the study of the extracellular medium. The extracellular pH and K+ were also simultaneously measured by using commercial miniaturised Ion Selective Electrodes. The induced ischemia period (45 min) resulted in significant changes of all measured parameters (Delta/Z/ approximately 65%; DeltapH approximately 0.8; DeltaK+ approximately 30 mM).
Subject(s)
Biosensing Techniques/instrumentation , Electric Impedance , Electrodes , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Kidney/physiopathology , Minimally Invasive Surgical Procedures/methods , Needles , Animals , Biosensing Techniques/methods , Equipment Design , Equipment Failure Analysis , Ischemia/complications , Ischemia/diagnosis , Ischemia/physiopathology , Kidney Diseases/etiology , Kidney Function Tests/instrumentation , Kidney Function Tests/methods , Male , Rats , Rats, Wistar , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Microelectrode technology is a promising tool for monitoring kidney ischemia and the changes induced by its therapeutic management. Ischemic preconditioning, that is, brief ischemic periods before sustained ischemia, has been shown to protect several organs, including the kidney, from ischemia-reperfusion injury. We tested whether the effect of preconditioning could be appraised by real-time measurement of parameters representative of tissue hypoxia. METHODS: In a sample of pentobarbital-anesthetized and mechanically ventilated rats, we studied the effect of renal ischemic preconditioning (10-min ischemia and 10-min reflow interval) on subsequent ischemia-reperfusion (45 min and 60 min). Renal tissue electrical impedance, extracellular pH, and potassium concentration [K+] were measured continuously by implanted microelectrodes. RESULTS: Ischemia induced an early, rapid rise in extracellular potassium and impedance module, followed by a phase of slower increase, whereas pH decreased rapidly, reaching a plateau. Preconditioning treatment did not cause significant changes in interstitial pH and [K+] but increased ischemic tissue impedance. During reperfusion, the three variables recovered progressively; however, after a decline, electrical impedance showed a clear postischemic increase. This rise was suppressed by preconditioning. CONCLUSIONS: Real-time measurement of any of the three parameters showed capability for early detection of ischemia. In contrast with findings in myocardial tissue, preconditioning in the kidney did not increase potassium cell loss during ischemia or improve ischemic acidosis or tissue impedance. Electrical impedance increased for a second time during reperfusion, indicating the presence of a postischemic cellular edema; concealing this episode was the most noticeable effect of the preconditioning treatment.
Subject(s)
Ischemic Preconditioning , Kidney Transplantation , Kidney/blood supply , Monitoring, Physiologic/methods , Reperfusion Injury/diagnosis , Acidosis/diagnosis , Animals , Disease Models, Animal , Electric Impedance , Kidney/physiology , Male , Microelectrodes , Potassium/metabolism , Rats , Rats, Wistar , Renal Artery/physiology , Surgical InstrumentsABSTRACT
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Subject(s)
Aged , Female , Humans , Ganciclovir , Treatment Outcome , Rectovaginal Fistula , Anti-Bacterial Agents , Antiviral Agents , Colon , Colitis , Cytomegalovirus Infections , Cytomegalovirus , ImmunocompetenceABSTRACT
Objectives. The goal of this work is to study and develop an electrical integrated system that allows the control of the basic functions (such as micturition, defecation, and erection) by sacral root stimulation in paraplegic patients. Materials and Methods. The system has been implemented using a commercially available Mietec CMOS technology. It is based on an external transceiver unit, which provides data and energy to the implant device through a bi-directional inductive link, and an implantable batteryless module that generates the needed current pulses, according to the orders received from the external unit. To test the electrode-tissue interface and system performance, an impedance measurement circuit has been included. Results. The three independent channel stimulators allow an exhaustive control of the waveform parameters (amplitude, pulse width, frequency) independent of the placement of the external coil respect to the internal device. Conclusion. The architecture of the new stimulator, applied over the sacral roots, can be used to control the voiding of the bladder. The system allows an independent distance programmable stimulation. The impedance measurement circuit implemented allows an easy and systematic performance test.