Drug Challenge Tests With General Anesthetics: Predictive Value of Skin Tests.

BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.

Sequential combined therapy with omalizumab and rituximab: a new approach to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disease, and a significant percentage of AD patients have severe forms. Inflammation based on type 2 helper T cells (T(H)2), autoantibodies, and CD8+ T cells could play a relevant role in this disease. When the patient requires systemic immunosuppressors for disease control, side effects are frequent. We propose a sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti-immunoglobulin [Ig] E) and rituximab (anti-CD20), which might induce clinical benefit with few side effects in selected individuals with AD. METHODS: We report 6 cases of severe AD refractory to conventional therapy. The patients underwent sequential switch therapy with omalizumab and rituximab. Clinical response was assessed by means of the decrease in body surface affected. Immunological parameters and side effects were also monitored. RESULTS: Four patients received omalizumab before a high-dose cycle of rituximab. In the case of recurrences, either low-dose cycles of rituximab or omalizumab were administered. A long-term clinical benefit was observed in 3 out of 4 patients. Two patients first received high-dose rituximab followed by either low-dose rituximab or omalizumab, and one of them achieved a response at 17 months. No severe side effects were recorded. Serum IgE level and B-cell counts decreased with therapy, the latter returning to baseline levels 10 to 11 months after treatment. Specific antibody responses remained protective during the study. CONCLUSIONS: With our proposed switch therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel strategy targets different arms of the immune response and might be a good alternative for patients with severe AD.

Assay of acetylcholinesterase activity by potentiometric monitoring of acetylcholine.

An acetylcholine-selective electrode based on a plasticized polymeric membrane has been developed. The electrode exhibited good selectivity for acetylcholine (ACh) over choline and some common ions, low drift, and a fast response to ACh. The response was linear over an ACh concentration range of 1×10(-6) to 1×10(-3) M with a slope of 59.1±0.1 and a detection limit of 1.5×10(-7)±1.2×10(-8) M. The electrode was used to monitor enzymatic ACh hydrolysis catalyzed by acetylcholinesterase (AChE) at different substrate and enzyme concentrations. A kinetic data analysis permitted the determination of the Michaelis-Menten constant of the enzymatic hydrolysis and AChE activity in the range of 2×10(-5) to 3.8×10(-1)U ml(-1).

Ion transfer through solvent polymeric membranes driven by an exponential current flux.

General analytical equations which govern ion transfer through liquid membranes with one and two polarized interfaces driven by an exponential current flux are derived. Expressions for the transient and stationary E-t, dt/dE-E and dI/dE-E curves are obtained, and the evolution from transient to steady behaviour has been analyzed in depth. We have also shown mathematically that the voltammetric and stationary chronopotentiometric I(N)-E curves are identical (with E being the applied potential for voltammetric techniques and the measured potential for chronopotentiometric techniques), and hence, their derivatives provide identical information.

Voltammetric behaviour and square-wave voltammetric determination of the potent antioxidant and anticarcinogenic agent ellagic acid in foodstuffs.

The voltammetric behaviour of ellagic acid (EA) is investigated by cyclic, differential pulse and square-wave voltammetry (CV, DPV and SWV, respectively). Based on the anodic oxidation peak at approximately 0.42V in acetic/acetate buffer (pH 5.5) a robust and a highly reliable square-wave voltammetric method is presented for the determination of EA. The oxidation peak current was linearly dependent on the concentration of EA in the range of 1.0×10(-7)-1.5×10(-6)mol/L (r=0.9997), with a detection limit of 1.0×10(-8)mol/L (S/N=3) and a quantification limit of 3.4×10(-8)mol/L (S/N=10), good reproducibility and a satisfactory level of selectivity towards others polyphenols. The proposed method was applied to the determination of free and total EA in fruits, nuts and juices with good analytical results being obtained.

Ewe's diet during gestation and lactation affects ready-to-eat meat from light lambs.

Maternal grazing may benefit the fatty acid (FA) profile of lamb meat, although any improvement in terms of healthier polyunsaturated FAs (PUFA) may be impaired during subsequent culinary treatments. The objective was to assess the effects of a grass-based ewe diet on the FA profile of the ready-to-eat meat from grain-fed Segureña light lamb. The FA were determined in raw, grilled (G), Sous Vide (SV) cooked and cooked/hot-held (H) lamb leg patties resulting from two maternal rearing systems: grazing (Mediterranean trees, shrubs, herbs, stubble and fallow) or indoors (cereal grain and lucerne pellets). The grass-based ewe diet increased (P < 0.05) levels of n-3 PUFA and total linoleic conjugated acid (CLA), and decreased those of n-6 long chain PUFA and saturated FA (SFA) in the patties from all treatments. These changes in FA slightly increased (P < 0.05) the PUFA/SFA ratio and decreased (P < 0.05) the n-6/n-3 ratio in the raw (from 8.7 to 6.3), SV (from 8.8 to 6.2), G (from 9.0 to 6.3), SV + H (from 8.2 to 6.3) and G + H (from 9.3 to 6.4) patties, improving the atherogenic, thrombogenic and saturation indexes. The effects of the ewe's diet on lamb FA remained unaltered after successive culinary treatments, including aerobically mincing, cooking at an internal temperature of 72 °C and H at 65 °C for 4 h. Heating induced a partial degradation of meat PUFA but also favoured the loss of high saturated melted fat. Both facts balanced the PUFA/SFA ratio in cooked lamb despite the gradual formation of oxidised secondary lipids to the detriment of FA. Grilling or SV cooking did not affect the remaining levels of undegraded FA in the freshly cooked lamb, although SV improved the results obtained for the cooked/H lamb. Maternal diets based on grass result in a healthier ready-to-eat lamb.

Effects of sous vide vs grilling methods on lamb meat colour and lipid stability during cooking and heated display.

The present study compared the effect of grilling (150 °C until 72 °C core temperature) and sous-vide (SV) cooking (75 °C for 35 min in a water bath under vacuum) on lamb patties immediately after cooking and after 4 h display at 65 °C. Both methods produced patties with similar (P > 0.05) weight loss, and moisture and fat contents. SV-cooking prevented (P < 0.05) the formation of thiobarbituric acid reactive substances (TBARS) and oxysterols compared to grilled patties, which showed a larger proportion of highly peroxidisable polyunsaturated fatty acids. Heated display induced dehydration, surface darkening and a reduction in the hexanal/3-methylbutanal ratio, suggesting the progression of Maillard reactions. Moreover, TBARS and some lipid oxidation-derived volatiles increased (P < 0.001), while cooked-meat aroma compounds were reduced (P < 0.001). SV-cooking inhibited (P < 0.05) the formation of malondialdehyde, and 7α- and 7ß-hydroxycholesterol, and lowered the cholesterol oxidation ratio during heated display. Overall, SV-cooking may be considered a healthier way of cooking when lamb meat is to be kept warm for considerable periods before consumption.

Differential pulse voltammetry for ion transfer at liquid membranes with two polarized interfaces.

A simple analytical expression for the response of the double-pulse technique differential pulse voltammetry (DPV) corresponding to ion transfer processes in systems with two liquid/liquid polarizable interfaces has been deduced. This expression predicts lower and wider curves than those obtained with a membrane system with a single polarizable interface. Moreover, the peak potential of these systems is shifted 13 mV from the half-wave membrane potential. We have applied this expression to study the ion transfer of drugs with different pharmacological activities (verapamil, clomipramine, tacrine, and imipramine), at a solvent polymeric membrane ion sensor.

Design and performance evaluation of a coplanar multimodality scanner for rodent imaging.

This work reports on the development and performance evaluation of the VrPET/CT, a new multimodality scanner with coplanar geometry for in vivo rodent imaging. The scanner design is based on a partial-ring PET system and a small-animal CT assembled on a rotatory gantry without axial displacement between the geometric centers of both fields of view (FOV). We report on the PET system performance based on the NEMA NU-4 protocol; the performance characteristics of the CT component are not included herein. The accuracy of inter-modality alignment and the imaging capability of the whole system are also evaluated on phantom and animal studies. Tangential spatial resolution of PET images ranged between 1.56 mm at the center of the FOV and 2.46 at a radial offset of 3.5 cm. The radial resolution varies from 1.48 mm to 1.88 mm, and the axial resolution from 2.34 mm to 3.38 mm for the same positions. The energy resolution was 16.5% on average for the entire system. The absolute coincidence sensitivity is 2.2% for a 100-700 keV energy window with a 3.8 ns coincident window. The scatter fraction values for the same settings were 11.45% for a mouse-sized phantom and 23.26% for a rat-sized phantom. The peak noise equivalent count rates were also evaluated for those phantoms obtaining 70.8 kcps at 0.66 MBq/cc and 31.5 kcps at 0.11 MBq/cc, respectively. The accuracy of inter-modality alignment is below half the PET resolution, and the image quality of biological specimens agrees with measured performance parameters. The assessment presented in this study shows that the VrPET/CT system is a good performance small-animal imager, while the cost derived from a partial ring detection system is substantially reduced as compared with a full-ring PET tomograph.

Outcome of non-variceal acute upper gastrointestinal bleeding in patients with antithrombotic therapy.

AIM: To determine the influence of antithrombotic therapy upon the course of non-variceal upper gastrointestinal bleeding (UGB). METHODS: A cohort study was made of consecutive patients admitted to hospital with non-variceal UGB. Three cohorts were defined: patients receiving vitamin K antagonists (AC); patients with antiplatelet treatment (AP), and patients with neither of these treatments (noACAP) as control group. Outcome was assessed by: (a) number of days in hospital; (b) mortality rate; (c) need for urgent surgery, and (d) rebleeding. The measure of the association between antithrombotic therapy and the course of UGB was adjusted for confounders (age, sex, comorbidity, and the use of NSAIDs and PPIs at the time of UGB presentation). RESULTS: A total of 392 consecutive patients were included: 43 were AC, 107 AP, and 242 noACAP patients. There were no significant differences among groups in terms of rebleeding (AC 11.6%, AP 7.5%, NoACAP 9.1%), the need for urgent surgery (AC 2.3%, AP 1.9%, NoACAP 1.2%) or mortality rate (AC 4.7%, AP 5.6%, NoACAP 5.8%). The number of days in hospital was greater in the AC cohort (4.81 more days; 95% CI 2.83-6.79, p < 0.001). After adjusting for age and comorbidity, the increase in days in hospital among the AC patients was 3.24 days (95% CI 1.22-5.26). CONCLUSIONS: Neither anticoagulation nor antiplatelet treatment exerts an influence upon the course of non-variceal UGB. Nevertheless, anticoagulation is associated with a longer hospital stay. This is partially explained by the older age and increased comorbidity of the patients subjected to such treatment.

Risk factors for early renal graft thrombosis: a case-controlled study in grafts from the same donor.

Renal graft thrombosis is an important cause of early graft loss. In a case-controlled analysis including only thrombosed kidneys and their counterparts from the same donors, we found that the right kidney as opposed to the left kidney was the only risk factor for early graft vascular thrombosis. No other recipient, donor, or perioperative factor was significantly associated with the complication. Our findings suggested that implantation of a right kidney might be followed by prophylactic anticoagulant or antiaggregant therapy.

[Recurrence of p-ANCA positive vasculitis with lung hemorrhage in a patient on hemodialysis]. / Recidiva de vasculitis p-ANCA positiva con hemorragia pulmonar en paciente en hemodiálisis.

Relapses of p-ANCA vasculitis during chronic dialysis treatment are infrequent. We report a patient with a pulmonary-renal syndrome and p-ANCA vasculitis who relapsed one year after starting hemodialysis treatment. Treatment with steroids and cyclosphosphamide successfully controlled the relapse, though cyclophosphamide had to be discontinued because of leucopenia. Clinical features of renal vasculitis, relapse after dialysis, the usefulness of ANCA titles as possible predictors and therapeutic options are discussed.

[A clinical study of adult autoimmune hepatitis in Valencia, Spain]. / Estudio clínico de la hepatitis autoinmune del adulto en Valencia.

OBJECTIVE: the clinical phenotype of autoimmune hepatitis (AIH) varies among geographical areas. The aim of this study is to determine the salient features of AIH in adult patients from the province of Valencia, Spain. MATERIAL AND METHODS: eighty-one patients with AIH attended to in eight acute-care hospitals between 1994 and 2003. New patients diagnosed with AIH during year 2003 were evaluated prospectively. Data from patients currently attending follow-up visits and diagnosed before 2003 were collected retrospectively. RESULTS: a total of 94% of patients were females. Forty-three percent were asymptomatic, 27% had acute hepatitis, and 30% had chronic hepatitis. Type 1 AIH was diagnosed in 90% of cases. Type 2 AIH was more frequent in younger patients, and presented with an acute pattern. One third of patients had cirrhosis at onset. Patients with cirrhosis were older than 60 years more frequently. Immunosuppressants were given to 57 patients, with complete or partial remission in 87.7%. There were no significant differences in response to immunosuppression according to presentation pattern or AIH subtype. CONCLUSIONS: AIH in Valencia was predominantly diagnosed in asymptomatic women. Most cases were type 1, and in 25% of patients another autoimmune disease coexisted. At the time of diagnosis one third of patients had cirrhosis, particularly those over 60 years.

Maternal grazing on stubble and Mediterranean shrubland improves meat lipid profile in light lambs fed on concentrates.

Concentrates-fed lamb meat is often associated with an unfavourable lipid profile (high levels of saturated and/or n-6 polyunsaturated fatty acids; SFA and PUFA). For this reason, Spanish sheep producers from Mediterranean areas are turning to traditional grazing by ewes to obtain healthier lamb meat. The objective of this research was to determine the effects of maternal grazing on the fatty acid (FA) composition of weaned lamb meat. The ewes (Segureña breed) were allocated to two different rearing systems during pregnancy (5 months) and lactation (45 days): (i) feeding indoors on barley grain and lucerne pellets; (ii) grazing on cereal stubble, fallow land and seasonal pastures consisting of Mediterranean shrubs, herbs and trees. Two groups of 20 autumn and spring lambs were sampled. The lambs were weaned at 13.1±0.9 kg and 45.0±4.1 days age and fed on grain-based concentrates until they reached 24.8±2.1 kg live weight (light lambs slaughtered at 98.3±3.6 days of age). The FA content was determined in the intramuscular loin fat by gas chromatography using a flame ionization detector. The ewe diet did not affect the levels of the main lamb FAs (C18:1c+t, C16:0 and C18:2c), and so did not provide any additional reduction in fat saturation. Saturated fatty acids represented around 40% of total FAs determined in the meat. Ewe grazing acted as an n-3 PUFA-promoting diet, providing a lamb meat with a lower n-6/n-3 ratio. Spring lamb meat had higher proportions of n-3 PUFA (C18:3n-3, C20:5, C22:5 and C22:6) and conjugated linoleic acid (C18:2c9t11+c11t9) to the detriment of the n-6 PUFAs (C20:4, C20:2 and C22:4), while autumn lamb meat also had higher levels of C18:3n-3 and C18:3n-6, and lower level of C20:4, which points to little seasonal differences. The n-6/n-3 ratio achieved by ewe grazing fell from 8.2 to 4.1 (Spring) and from 7.6 to 5.5 (Autumn), values which are close to those recommended in human diet for good cardiovascular health. These n-6/n-3 reductions were associated with lower levels of total PUFA and C20:4n-6. Our research concluded that grazing on stubble and Mediterranean shrubland by ewes, a sustainable rearing practice involving local agro resources, contributed to obtaining weaned lamb meat with a more favourable lipid profile and so can be recommended to sheep farmers.

A Mediterranean age-comorbidity prognostic index for survival in dialysis populations.

BACKGROUND: The most widely used prognostic indices for estimation of survival, including for dialysis patients, were described by Charlson, and an adaptation was proposed by Hemmelgarn for dialysis patients. We present the first age-comorbidity prognostic index (ACPI) designed in a Mediterranean incident dialysis population and examine its concordance with other prognostic indices. METHODS: Incident dialysis patients were scored in relation to age and 11 diseases. Cox regression analysis was performed to construct multiple regression models, and diseases with a hazard ratio (HR) higher than 1.2 were included in the index. The impact of age was assessed by including it in a separate multivariate model. Scores were categorized in 3 levels of risk: low (0-1 points), medium (2-4 points) and high levels (5 or more points). The probability of survival of each group was calculated according to the Kaplan-Meier method, and receiver operating characteristic (ROC) curves were plotted to examine the concordance with other prognostic indices. RESULTS: A cohort of 304 patients on hemodialysis (80%) and peritoneal dialysis was analyzed. Global mortality rate was 31% (93/304). The mean score was 4.41 +/- 2.84. Diseases that received the highest scores were ischemic heart disease (IHD) with chronic heart failure (CHF), and malignancies of less than 5 years of evolution. With regard to age, the maximum score was received by patients over 60 years old. The probability of survival at 3 years was 89%, 77% and 54% for low-, medium- and high-risk groups, respectively (log-rank test, 19; p=0.0001). The ROC curves showed similar areas for our index (0.749), the Charlson index (0.758) and Hemmelgarn index (0.708), but our index scored higher than Charlson in older patients, IHD with CHF, CHF, peripheral vascular disease and systemic diseases. CONCLUSIONS: Although prospective external validation of this new index is required, this index adequately estimates the probability of survival at 3 years. The prognostic power of ACPI is similar to that of the Charlson index; however, relevant differences were found, concerning the weight of factors age, cardiovascular diseases and myocardial dysfunction. In end-stage renal disease we recommend estimating survival by indices established in incident dialysis patients, due to the particular comorbid conditions of this population.

Mycophenolate mofetil levels in stable kidney transplant recipients.

The usefulness of mycophenolate mofetil (MMF) levels in stable kidney transplant patients is not well known. We measured MMF trough levels in 137 adult kidney recipients with more than 1 year of stable graft function. The MMF dose was adjusted according to hematological or gastrointestinal toxicity, it was 500 mg in 22 (16%) patients; 750 mg in 22 (16%); 1000 mg in 69 (50.5%); 1500 mg in 15 (11%); and 2000 mg in 9 (6.5%). We analyzed the total dose, virgule dose/kg, and MMF levels in relation to efficacy parameters (creatinine, proteinuria) and hematological toxicity (erythrocytes, leukocytes, and platelets) at the time of MMF level determinations and 3 months thereafter. Statistical analyses were performed with SSPS 12.0, including sensitivity and specificity analyses by ROC. Mean MMF levels were 3.68 mg/L (Pc25, 1.6-Pc75, 4.4 mg/L) with significant differences according to dose (P < .001). Trough MMF levels did not have discriminatory capacity in the area under the ROC for anemia, renal failure, or proteinuria at the time of determination or 3 months later. The percentage of patients without proteinuria was high among patients with MMF levels between 1.6 and 4.4 mg/L. The MMF levels were low in patients who had a major increase in creatinine (1.6 vs 3.8 mg/L, P < .05). In stable renal transplant patients the levels of MMF were related to the administered dose, and they are higher than those previously described in patients with less than a year follow-up with a functioning kidney. They did not have discriminatory value at the time of determination or 3 months later. Nevertheless, low MMF levels could help recognize patients at risk of developing chronic nephropathy.

Variability of mycophenolate mofetil trough levels in stable kidney transplant patients.

Great interindividual variability in the pharmacokinetics of mycophenolate mofetil (MMF) exists among kidney transplanted patients. The within-patient variability in stable transplanted patients is not well established. We performed 258 determinations of trough MMF levels in 86 stable transplant patients without hematological or gastrointestinal toxicity after at least year of a functioning kidney and a fixed dose of MMF. We examined the within-patient variability of levels related with clinical factors (age, gender, underlying cause of kidney failure, time since transplant, associated immunosuppression, and MMF dose) and analytical factors (serum creatinine, proteinuria, hemoglobin). Trough MMF levels were 3.6 mg/L, percentile (Pc) 25 1.6 mg/L, Pc 75 4.4 mg/L with intraindividual variability median of 65% (Pc 25 14%, Pc 75 79%). For the data analysis a variation of 14% was chosen, which corresponded to the 25th percentile. We did not observed differences between patients with variation below or above the Pc 25 in age, gender, underling cause of kidney failure, basal MMF levels, and MMF dose. Patients with greater variations showed significantly higher serum creatinine and proteinuria values than the others (1.84 +/- 0.54 vs 1.46 +/- 0.44 mg/dL and 0.45 +/- 0.42 vs 0.19 +/- 0.14 g/L; P < .05). Therefore, great within-patient variability in trough MMF levels was associated with poor kidney function and proteinuria.

High body mass index and posttransplant weight gain are not risk factors for kidney graft and patient outcome.

BACKGROUND: High body mass constitutes a significant risk factor for morbidity and mortality in the general population, but it has been associated with an increased survival among dialysis patients. Its effects on renal transplant outcomes are controversial. The aim of our present work was to investigate the impact of high body mass and posttransplant weight gain on patient and graft outcomes. PATIENTS AND METHODS: One thousand consecutive renal transplant recipients (631 men and 369 women) were included in the study. Their mean age was 42.9 years and the follow-up was at least 2 years. Basal immunosuppression was azathioprine (Aza) and steroids in 196 patients, cyclosporine (CsA) without or with antiproliferative agent in 557, and 239 were presented tacrolimus (Tac). RESULTS: At the time of transplantation the body mass index (BMI) was 23.7 +/- 3.9 kg/m2, namely, <18.5 kg/m2 in 6.3%; 18.5 to 25 in 61.7%; 25 to 30 in 25.4%; and >30 in 6.5%. Pretransplant obesity was associated with old age and female gender. Obese patients experienced a greater risk of delayed graft function (P < .01) and surgical wound complications (P < .01). After 1 year, 299 patients (29.9%) displayed weight gain >10% (mean 8.6% +/- 10.4% or 5.0 +/- 6.1 kg). Patients on Aza showed increased body weight by 11.9% +/- 10.9%; CsA patients by 9.5% +/- 10.3%, and Tac patients by 4.9% +/- 9.1% (P < .001). Univariate and multivariate analysis showed that pretransplant BMI had no effect on graft or patient survival either in the whole group or in the patients treated with CsA or TAC. Posttransplant weight gain above 5% or 10% did not influence graft or patient outcomes. CONCLUSIONS: The new immunosuppressive regimes reduce posttransplant weight gain. Pretransplant high body mass and 1-year posttransplant weight gain were not risk factors for graft or patient survival in our experience.