Isavuconazole-tacrolimus drug-drug interactions in HSCT patients.

OBJECTIVES: Because tacrolimus has a narrow therapeutic window and exhibits both intraindividual and interindividual variability, we attempted to establish the percentage of calcineurin inhibitor (CNI) dose reduction to prevent toxicity and ensure stem cell engraftment when using this immunosuppressant with the antifungal isavuconazole (ISA). By calculating the tacrolimus concentration/dose (C/D) ratio, we expected to demonstrate the magnitude of change in the C/D ratio from baseline after ISA administration. METHODS: We evaluated the interaction between ISA, a new triazole antifungal used in prophylaxis for invasive fungal infections, and the CNI class of immunosuppressive drugs, specifically tacrolimus, in 11 blood samples from HSCT recipients. RESULTS: The mean tacrolimus C/D ratio increased 1.44-fold from baseline 48 h after ISA administration (P = 0.001). CONCLUSIONS: Although further investigation is needed, the results of this study suggest that a reduction of 18% in tacrolimus may be recommended.

[Causes and factors associated with reconciliation errors in medical and surgical services]. / Causas y factores asociados a los errores de conciliación en servicios médicos y quirúrgicos.

OBJECTIVE: The objective of this study was to determine the main causes of errors of medication reconciliation at hospital admission in medical and surgical department and establish factors associated with medication reconciliation errors. MATERIAL AND METHOD: Cross-sectional study. We included all patients admitted to two services and two surgical for a month. To determine the presence of error reconciliation, the pharmacist compared the medication history interview by the order physician. The factors associated with errors were identified by multivariate logistic regression analysis. RESULTS: 221 patients were included, of which 58.4% had at least one error reconciliation. We detected 629 discrepancies, 339 (53.9%) reconciliation errors. The incidence of errors in medical services was 24.3% and in the surgical services 43.0% (p <0.001) in both groups being most prevalent error of omission (46.2% and 50.8%). Regarding factors associated, the equation determines that patients older than 65 years, polymedicated and taking oral antidiabetic are more likely to have an error with a sensibility of 75.2% and a specificity of 68.5%. CONCLUSION: There is a high rate of error reconciliation in medical and surgical patients, which confirms the need to implement a strategy to reduce these errors. Given the difficulty of applying the process to all patients, the strategy must be directed to patients who are at increased risk of error.

Objetivo: Determinar las principales causas de errores de conciliacion de la medicacion al ingreso hospitalario tanto en los servicios medicos, como en los quirurgicos y que factores se asocian a dichos errores de conciliacion. Material y método: Estudio observacional transversal. Se incluyeron todos los pacientes que ingresaron en dos servicios medicos y dos quirurgicos durante un mes. Para determinar la presencia de error de conciliacion se cotejo la historia realizada por el farmaceutico con la del medico prescriptor. Los factores asociados a los errores se identificaron mediante un analisis de regresion logistica multivariante. Resultados: Se incluyeron 221 pacientes, de los cuales el 58.4% presentaron al menos un error de conciliacion. Se detectaron un total de 629 discrepancias, 339 (53.9%) errores de conciliacion. La incidencia de errores en los servicios medicos fue del 24.3% y en los quirurgicos del 43.0% (p.

Arsenic and fluoride co-exposure affects the expression of apoptotic and inflammatory genes and proteins in mononuclear cells from children.

Humans may be exposed to arsenic (As) and fluoride (F) through water consumption. However, the interaction between these two elements and gene expression in apoptosis or inflammatory processes in children has not been thoroughly investigated. Herein, the expression of cIAP-1, XIAP, TNF-α, ENA-78, survivin, CD25, and CD40 was evaluated by RT-PCR. Additionally, the surface expression of CD25, CD40, and CD40L on peripheral blood mononuclear cells was analyzed by flow cytometry, and TNF-α was measured by Western blotting. This study examined 72 children aged 6-12 years who were chronically exposed to As (154.2µg/L) and F (5.3mg/L) in drinking water and in food cooked with the same water. The urine concentrations of As (6.9-122.4µg/L) were positively correlated with the urine concentrations of F (1.0-8.8mg/L) (r(2)=0.413, p<0.0001). The CD25 gene expression levels and urine concentrations of As and F were negatively correlated, though the CD40 expression levels were negatively correlated only with the As concentration. Age and height influenced the expression of cIAP-1, whereas XIAP expression was correlated only with age. Additionally, there was a lower percentage of CD25- and CD40-positive cells in the group of 6- to 8-year-old children exposed to the highest concentrations of both As and F when compared to the 9- to 12-year-old group (CD25: 0.7±0.8 vs. 1.1±0.9, p<0.0014; CD40: 16.0±7.0 vs. 21.8±5.8, p<0.0003). PHA-stimulated lymphocytes did not show any changes in the induction of CD25, CD69, or CD95. In summary, high concentrations of As and F alter the expression patterns of CD25 and CD40 at both the genetic and protein levels. These changes could decrease immune responses in children exposed to As and F.

SHBG levels are associated with bone loss and vertebral fractures in patients with prostate cancer.

SUMMARY: Fractures are increased among prostate cancer patients. No data have been reported in patients with prostate cancer about the relation between serum sex hormone-binding globulin (SHBG) and bone metabolism. We found that SHBG levels were inversely related to bone mass and vertebral fractures in this population. INTRODUCTION: Fractures are increased among prostate cancer patients, especially those on androgen deprivation therapy (ADT), but few data are available on the role of SHBG in their bone status. Our objective was to analyze the relation between serum SHBG and bone metabolism in prostate cancer patients. METHODS: This is a cross-sectional study including 91 subjects with prostate cancer (54 % with ADT). We measured serum levels of SHBG and sex steroids, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and prevalent radiographic vertebral fractures. RESULTS: SHBG levels were inversely related to BMD (femoral neck: r = -0.299, p = 0.00; total hip: r = -0.259, p = 0.019). Subjects with osteoporosis had higher SHBG concentrations than patients without osteoporosis (60.97 ± 39.56 vs 44.45 ± 23.32 nmol/l, p = 0.022). Patients with SHBG levels in the first quartile (>57.6 nmol/l) had an odds ratio (OR) for osteoporosis of 2.59 (95 % CI, 1.30-5.12; p = 0.009) compared with patients with lower SHBG levels. In patients with SHBG >57.6 nmol/l, the OR for vertebral fractures was 2.34 (95 % CI, 1.15-4.78; p = 0.034). The calculated OR was higher after adjustment for age (OR, 5.16; 95 % CI, 1.09-24.49; p = 0.039), estrogens (OR, 6.45; 95 % CI, 1.44-28.95; p = 0.023), and androgens (OR, 5.51; 95 % CI, 1.36-22.37; p = 0.017). CONCLUSIONS: In prostate cancer patients, SHBG levels were inversely related to bone mass and vertebral fractures. Determination of the serum SHBG level may constitute a useful and straightforward marker for predicting the severity of osteoporosis in these patients.

Effect of arsenic on regulatory T cells.

INTRODUCTION: Arsenic (As) affects the function and survival of lymphocytes, and some arsenic compounds exert a relevant antineoplastic effect. We have explored the effect of As on T regulatory cells. RESULTS AND DISCUSSION: In vitro experiments with peripheral blood mononuclear cells from healthy subjects showed that low concentrations of As tended to increase the number of natural T regulatory (nTreg) lymphocytes, whereas concentrations >5.0 muM had an opposite effect. Furthermore, rats exposed to As showed redistribution of nTreg cells, and As administration to rats with experimental allergic encephalomyelitis increased the levels of nTreg cells in spleen and diminished the severity of this condition. On the other hand, in 47 apparently healthy subjects chronically exposed to As, we found significant inverse correlation between urinary As levels and the number and function of nTreg lymphocytes. Although most of these individuals showed enhanced levels of apoptotic lymphocytes in peripheral blood, with a diminution of mitochondrial membrane potential, no significant correlation between these parameters and urinary As was detected. CONCLUSION: Our data indicate that As seems to have a relevant and complex effect on nTreg cells.

Contribution of anthocyanin fraction to the antioxidant properties of wine.

The wine is a beverage with an important antioxidant efficiency which is attributed to their bioactives compounds, especially polyphenols. The anthocyanins are the main phenolic compounds of red wine and its consumption has been partially related with the "French Paradox". The aim of the present work was to evaluate the contribution of the anthocyanins to the antioxidant properties of red wines. So, total antioxidant capacity (TAC), hydroxyl and superoxide scavenger activity and lipid peroxidation of 80 Spanish red wines and their anthocyanins fractions have been assessed for ABTS, DPPH, DMPD, and FRAP methods, hydroxyl radical (HRSA), superoxide radical scavenger activity (SRSA) and ABAP-lipid peroxidation (ABAP-LP). The results showed that free anthocyanins fraction are main responsible of the total antioxidant capacity of red wines correlated with electron transference processes. In similar way, free anthocyanins are the maximum responsible of HRSA scavenger activity of red wines, contributing less extensively to their SRSA capacity or to their protective action on lipid peroxidation. Furthermore, simple anthocyanins exert a low action in TAC process involved with proton transference. Glycosilated and methoxylic anthocyanins as malvidin-3-glucoside, seem to be the type of anthocyanins with higher participation on the antioxidant effect of red wine.

[Treatment of cutaneous T-cell lymphoma with retinoid receptor X-selective ligands: endocrine and metabolic disorders]. / Tratamiento del linfoma cutáneo de células T con ligandos selectivos del receptor retinoide X: alteraciones endocrinológicas y metabólicas.

The retinoid X receptor-selective ligands has been used for advanced stages of cutaneous T-cell lymphoma refractory to previous systemic therapy, being bexarotene the first drug in this group approved in Europe. Multiple drug-related adverse events has been reported such as endocrine-metabolic disorders. We report 2 patients with cutaneous T-cell lymphoma, treated with bexarotene, that developed central hypothyroidism and dislipidaemia inmediately after the begining of this treatment. We also showed the successfully treatment response of these alterations and the total clinical remission after discontinuing the drug.

Dosimetry of small electron fields shaped by lead.

Electron radiotherapy fields are commonly used to treat superficial cancers. Field shaping can be achieved by placing lead on the patient surface to minimise the dose to surrounding areas. However, significant dosimetry changes under high density material edges for electron fields have been reported in the literature. This project evaluated the dosimetry of small dimension electron fields shaped with lead placed on the surface. Comparisons were made between circular lead cutouts placed on the skin and low melting point alloy cutouts placed in an applicator. Depth doses, profiles and output factors were measured using a diode detector in a water phantom. Film was also used to determine surface dose delivered when the lead cutouts were placed on the surface. Minimal differences were observed between the different setups for the depth dose curves, although significant differences were seen in the penumbra and the surface doses. The penumbra is smaller for the lead cutouts placed on the surface, however, significant dose increases at the edge of the field were observed for larger fields and energies; this may result in undesirable clinical effects.

[Literature review on the stability of diluted mixtures of cytostatic agents]. / Revisión bibliográfica de la estabilidad de las mezclas diluidas de citostáticos.

Up-to-date, evidence-based consensus protocols are an increasingly incorporated tool in health care. These protocols, clinical pathways, etc., represent a major support of health-care quality, namely scientific-technical quality. Compliance with these protocols by all team members guarantees that all patients be provided with an adequate level of health-care quality in the light of current knowledge and using available means. This principle of uniformity and quality in health care is essential for all, no matter the level of health care delivered or the activity being developed. In the Pharmacy Department and, more specifically, in the Unit of Cytostatic Agent Reconstitution and Dosing, knowledge and consensus on stability conditions and timing for diluted mixtures are essential to reach area-related quality standards. From literature references that are most relevant to or most widely used by in-hospital pharmacy departments, we designed a documented stabilities protocol to be used as a tool to: Augment preparation quality by including a documented expiry date within labels, optimize management on the basis of scientific criteria for mixtures not administered to patients and returned to the Pharmacy Department and design alternatives to hospitalization and outpatient delivery programs to improve end-user satisfaction and, therefore, health-care quality.

Z score prediction model for assessment of bone mineral content in pediatric diseases.

The objective of this study was to develop an anthropometry-based prediction model for the assessment of bone mineral content (BMC) in children. Dual-energy X-ray absorptiometry (DXA) was used to measure whole-body BMC in a heterogeneous cohort of 982 healthy children, aged 5-18 years, from three ethnic groups (407 European- American [EA], 285 black, and 290 Mexican-American [MA]). The best model was based on log transformations of BMC and height, adjusted for age, gender, and ethnicity. The mean +/- SD for the measured/predicted in ratio was 1.000 +/- 0.017 for the calibration population. The model was verified in a second independent group of 588 healthy children (measured/predicted In ratio = 1.000 +/- 0.018). For clinical use, the ratio values were converted to a standardized Z score scale. The whole-body BMC status of 106 children with various diseases (42 cystic fibrosis [CF], 29 juvenile dermatomyositis [JDM], 15 liver disease [LD], 6 Rett syndrome [RS], and 14 human immunodeficiency virus [HIV]) was evaluated. Thirty-nine patients had Z scores less than -1.5, which suggest low bone mineral mass. Furthermore, 22 of these patients had severe abnormalities as indicated by Z scores less than -2.5. These preliminary findings indicate that the prediction model should prove useful in determining potential bone mineral deficits in individual pediatric patients.

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise developed treatment schedule for advanced head-and-neck cancer.

PURPOSE: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. METHODS AND MATERIALS: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m(2) of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. RESULTS: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. CONCLUSIONS: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions.

Effects of the angiotensinogen gene M235T and A(-6)G variants on blood pressure and other vascular risk factors in a Spanish population.

Angiotensinogen (AGT) gene polymorphism has shown significant differences in the allelic frequencies between hypertensive and normotensive subjects. This allele frequency varies among ethnic groups. There are still some controversies related to the 235T-variant as a marker for essential hypertension. As part of an extensive case-control study carried out in a Spanish population, we selected the 237 subjects with a diagnosis of essential hypertension according to the established criteria. A group of 242 normotensives matched for age and gender was used as control. Smoking habits, a previous diabetes and hypertension medical history, body mass index (BMI) and blood pressure (BP) values were recorded. Glucose, plasma creatinine, lipid profile with Lp(a), homocysteine and microalbuminuria were measured. Angiotensinogen M235T-gene polymorphism was determined by polymerase chain reaction (PCR) from genomic DNA. A(-6)G polymorphism was determined by mutagenically separated PCR (MS-PCR). BP values, BMI and microalbuminuria were significantly higher in hypertensive subjects; 31.6% of hypertensives and 40.1% normotensives were active smokers. M235T-genotype frequencies were not different in the hypertensive and normotensive population. Similarly, homocigotic AA predominate in the hypertensives but without statistical significance. The association of 235T-genotype or the changes in the promoter activity due to A(-6) substitution with essential hypertension was not confirmed in the multivariate regression analyses. Only a previous family history of hypertension and BMI were significantly associated with hypertension. Journal of Human Hypertension (2000) 14, 789-793

[Sporadic familial meningiomas]. / Meningiomas familiares esporádicos.

INTRODUCTION: Meningiomas are primary tumours of the central nervous system. Usually they are sporadic. The occurrence in more than one member of a family is unusual. Up till now this coincidence had been related with type 2 neurofibromatosis. In this paper we comment on two siblings who did not fulfil neurofibromatosis diagnostic criteria as an example of sporadic familial meningiomas. CLINICAL CASES: Two siblings (a 79 years old female and a 77 years old male) were diagnosed of a meningioma in an interval of two years, with surprising clinical and neuroimaging similarities. In sporadic meningiomas, abnormalities in the long arm of chromosome 22 have been found. Type 2 neurofibromatosis causative gene has also been found in this chromosome. Meningiomas are quite often found in this entity, and therefore, this gene was implicated as a main factor in the genesis of an important number of meningiomas. However, several studies have not found an association between these tumours and the locus for neurofibromatosis, leading to think that there may be other genes that may influence on meningiomas development.

Photon buildup in orthovoltage X-ray beams.

Orthovoltage x-ray beams exhibit the characteristic of depth dose buildup which is not well described in the literature. The principal reason for this phenomenon is the increase in dose deposited due to electrons set in motion by secondary (Compton) scattered photons within the phantom, as depth is increased until longitudinal equilibrium is reached. This happens within a few millimetres of the surface and has been demonstrated both experimentally and by Monte Carlo methods. The Monte Carlo technique also enabled description of a second order primary dose buildup effect (due to longitudinal electronic disequilibrium) that would be impossible to detect with conventional detectors due to the short range of the electrons. The magnitude of buildup was observed to alter with various combinations of beam parameters. Variations will also occur with detectors used to measure buildup. It is recommended that radiation oncology departments assess this effect in the context of their clinical data in current use to ensure that there are not doses higher than prescribed being applied a few millimetres below the skin surface, especially if data was collected with a thin windowed, parallel plate ionisation chamber and/or that coarse steps for depth dose data collection were used along the beam central axis.

An independent check method of radiotherapy computer plan derived monitor units.

With the increasing complexity of radiotherapy computer treatment planning systems (CTPS), verification of the treatments is an important component of a quality assurance program. The radiation dose delivered to a patient is based on treatment machine monitor units (MUs) that are calculated either using data tables or within the CTPS. An independent method for checking radiotherapy MU calculations is proposed. This method involves calculating the dose at a point (usually ICRU reference point) using the derived MUs and independently measured treatment data and comparing to the dose at the same point as predicted by the CTPS. A program was developed using Microsoft Excel to assist in performing this check. The program contains the beam data and various correction factors and calculates the dose after input of the treatment setup parameters. This independent method is used to check all radiotherapy treatment fields at Liverpool Hospital and has found a number of significant errors in the planning process and in the CTPS calculations.

Chemotherapy as a part of each treatment fraction in a twice-a-day hyperfractionated schedule: a new chemoradiotherapy approach for advanced head and neck cancer.

BACKGROUND: Using chemotherapy as a part of each treatment fraction remains unexplored. This study integrates the concomitant administration of carboplatin with hyperfractionated irradiation by optimizing chemopotentiation through carboplatin administration with each irradiation fraction. METHODS: From February 1993 to August 1996, 52 patients with advanced head and neck cancer were treated on a twice-a-day chemoradiotherapy schedule. Each fraction consisted of 115 cGy preceded by 5 mg/m2 of carboplatin. Treatment was given 5 days a week up to total doses of 350 mg/m2 of carboplatin + 8050 cGy in 7 weeks. RESULTS: All (100%) of patients tolerated the treatment (83% as scheduled). Acute and late toxicities were moderate. Rates of 96% complete response (CR) and 4% partial response (PR) were achieved. At 52 months, local control and cause-specific survival rates are 72% and 59%, respectively. Nodal control rate is 95%. CONCLUSION: These results show potential for improvement upon hyperfractionated radiotherapy alone and compare favorably with those of most reported trials.

Increasing incidence of childhood class V lupus nephritis.

OBJECTIVE: Class V lupus nephritis (LN) is reported to occur in 0-23% of patients with LN. To better characterize pediatric LN, we determined at a single center (1) the relative frequency of Class V LN on first and serial biopsies, (2) the frequency of transformation between LN classes on serial biopsies, (3) types of treatment received and outcome to date of different classes of LN. METHODS: All pediatric renal biopsies from 1985 to the present performed for diagnosis and classification of suspected LN were reviewed. Biopsy results were grouped into 2-3 year time intervals to assess trends in the distribution of WHO class diagnoses over time. RESULTS: Sixty patients underwent 97 renal biopsies. Class V LN was present in 28% (17/60) of patients on first biopsy, and in 37% (22/60) on most recent biopsy. Class V LN on first biopsy increased from 17% (8/46) before 1995 to 64% (9/14) after 1995 (p < 0.001). Age at presentation, age at biopsy, time to biopsy, and types of treatment did not differ before and after 1995. Transformation to Class V LN occurred in 19% (5/27) of patients having repeat biopsies. No transformation from Class V LN occurred on repeat biopsy. Renal outcome was available in 48 patients with followup of 4.7 +/- 3.2 years for Class V LN, and 5.2 +/- 2.4 years for non-Class V LN. Five percent (1/20) of Class V LN patients had renal dysfunction or had died compared to 21% (6/28) of non-Class V LN patients (p = NS). CONCLUSION: We found (1) a greater frequency of Class V LN than has been reported, (2) a recent increase in the incidence of Class V LN at our institution, (3) frequent transformation between classes on serial biopsies, and (4) no regression of Class V lesions in patients who had repeat biopsies.

[Influence of the necessity of transfusion in anemia on the prognosis of ENT cancer in the protocol with concurrent hyperfractionation of carboplatin and irradiation]. / Influencia de la necesidad de transfusión por anemia sobre el pronóstico del cáncer O.R.L. en un protocolo con hiperfraccionamiento concurrente de carboplatino e irradiación.

Because of the determinant role of hemoglobin level in blood to the response of treatment (viewpoint admitted whether for irradiation or chemotherapic agents) the AA. have lead an analysis of a group of 36 patients suffering an advanced head and neck cancer (18 months mid-follow up and 30 months maximum) which underwent a program of concomitant radio-chemotherapy hyperfraccionated with carboplatin (the cytostatic) as part of each therapeutic fraction. The results in patients being transfused with an erytrocyte concentrate were compared with those from patients not having had any transfusion. The purpose of this study was the assessment of which are the influence on the prognostic of ENT-cancer resulting of the compulsory necessity of transfunding erytrocyte concentrates aroused by serious anemia presenting during the development of the schedule treatment. In brief, in that kind of patients needing transfusions of red blood cells concentrates because of serious anemia during the treatment (17% of the totality treated) were recorded 50% local failures, 33% metastases and only 17% of the totality were free of neoplasma at the end of the follow-up fixed. Instead between patients not having had transfusions (for treating anemia) the differences registered were 20% failures of loco-regional control and 13% metastases, whereas 67% were free of tumor at the end of the study. The conclusion drawn out is: the important influence on the prognostic of these tumors, when in the course of the scheduled treatment, appear severe anemia making the transfusions compulsory.

[Cystic fibrosis: nutritional aspects and recommendations]. / Fibrosis quística: aspectos y recomendaciones nutricionales.

Given the high numbers of nutritional supplements and enteral diets which are supplied for patients suffering from cystic fibrosis, by the departments of hospital pharmacy, the present study aims to review which are the characteristics of this disease which determine the appearance of malnutrition in these patients. Also, their nutritional treatment has been reviewed. On one hand, considering the general dietary measures, keeping in mind the composition of the diets, their characteristics according to age, and the supplementation with vitamins and with pancreatic enzymes. On the other hand, there is a review of the special dietary measures which should be applied in case of failure to thrive of the child, which goes from the modification of the oral diet, to the administration of parenteral nutrition.