Intradialytic parenteral nutrition for patients on hemodialysis: when, how and to whom?

Hemodialysis is associated with high morbidity and mortality rates as well as low quality of life. Altered nutritional status and protein-energy wasting are important indicators of these risks. Maintaining optimal nutritional status in patients with hemodialysis is a critical but sometimes overlooked aspect of care. Nutritional support strategies usually begin with dietary counseling and oral nutritional supplements. Patients may not comply with this advice or oral nutritional supplements, however , or compliance may be affected by other complications of progressive chronic kidney disease. Intradialytic parenteral nutrition (IDPN) may be a possibility in these cases, but lack of knowledge on practical aspects of IDPN delivery are seldom discussed and may represent a barrier. In this review, we, as a consensus panel of clinicians experienced with IDPN, survey existing literature and summarize our views on when to use IDPN, which patients may be best suited for IDPN, and how to effectively deliver and monitor this strategy for nutritional support.

Software-defined optoacoustic tomography.

In this work we present what we believe is the first application of software-defined optoelectronics (SDO) for bidimensional optoacoustic tomography (OAT). The SDO concept refers to optoelectronic systems where the functionality associated with the conditioning and processing of optical and electrical signals are digitally implemented and controlled by software. This paradigm takes advantage of the flexibility of software-defined hardware platforms to develop adaptive instrumentation systems. We implement an OAT system based on a heterodyne interferometer in a Mach-Zehnder configuration and a commercial software-defined radio platform (SDR). Here the SDR serves as a function generator and oscilloscope, while at the same time providing perfect carrier synchronization between its transmitter and receiver in a coherent baseband modulator scheme. This carrier synchronization enables us to have much better phase recovery. We study the performance of the OAT SDO system using different bidimensional phantoms and carry out an analysis of the reconstructed images.

Determination of the thermal boundary conductance of gold nanoparticles in aqueous solution using a method based on nanobubble generation.

We present a method to determine the thermal boundary conductance of gold nanoparticles in aqueous solution. The novel approach consists of two steps: first, measuring photoacoustic signals originated by laser-induced nanobubbles at different energies and, second, fitting the experimental data with a nanobubble generation model developed in a previous work. We used this method on gold nanoparticles with diameters from 10 to 70 nm. Within this range, we obtained values of the thermal boundary conductance between 180 W/m2 K and 225 W/m2 K.

Reducing the capacitance of piezoelectric film sensors.

We present a novel design for large area, wideband, polymer piezoelectric sensor with low capacitance. The large area allows better spatial resolution in applications such as photoacoustic tomography and the reduced capacitance eases the design of fast transimpedance amplifiers. The metalized piezoelectric polymer thin film is segmented into N sections, electrically connected in series. In this way, the total capacitance is reduced by a factor 1/N(2), whereas the mechanical response and the active area of the sensor are not modified. We show the construction details for a two-section sensor, together with the impedance spectroscopy and impulse response experimental results that validate the design.

Laser-induced bubble generation on a gold nanoparticle: A nonsymmetrical description.

The modeling of bubbles initiated by laser-irradiated nanoparticles is of interest for many applications. There is at present no comprehensive physical picture for all the stages of the process. We present an alternative approach with a key assumption: the vapor bubble evolves adjacent to the nanoparticle. To take into account the irreversible evolution, the statistical rate theory was used, thus avoiding the introduction of extra ad hoc parameters. Model results agree well with published data and our measurements. The only free parameter, the thermal boundary conductance, can be obtained by adjusting the model to the experimental data.

Determination of the absolute fluorescence quantum yield of rhodamine 6G with optical and photoacoustic methods--providing the basis for fluorescence quantum yield standards.

To establish the methodical basis for the development and certification of fluorescence quantum yield standards, we determined the fluorescence quantum yield Φ(f) of rhodamine 6G (R6G) with two absolute methods with complementary measurement principles, here optical spectroscopy using an integrating sphere setup and pulsed laser photoacoustic spectroscopy (PAS). For the assessment of aggregation- and reabsorption-induced distortions of measured fluorescence quantum yields and procedures for the reliable consideration of such effects, this systematic comparison was performed in ethanol and in water employing different concentrations of R6G. In addition, the relative and absolute fluorescence quantum yields of these solutions were obtained with a calibrated spectrofluorometer and a commercialized integrating sphere setup. Based upon this systematic comparison, experimental advantages and systematic sources of variation were identified for both methods.

Determination of the photoluminescence quantum yield of diluted dye solutions in highly scattering media by pulsed photoacoustic spectroscopy.

A pulsed photoacoustic system is used to determine the fluorescence quantum yield of diluted dye solutions in highly scattering media. In order to show its accuracy, the quantum yield of Rhodamine 6G in water and ethanol was calculated. The chemical Fuchsin was utilized as a dye reference because the entire excitation energy is converted into nonradiative relaxation processes. The scattering coefficient of the samples was incremented by using spherical silica particles of different sizes and concentrations. The determined mean values in the studied scattering optical density range (0-3 cm(-1)) were 0.95 for ethanol and 0.96 for water. These measurements are in excellent agreement with the best literature values.

Simple synchronic detection at audio frequencies through a PC sound card.

We present a simple personal computer based, synchronic detection system that emulates a lock-in amplifier at audio frequencies. The inputs of the sound card are used to acquire two sets of samples: the one to be measured, previously preamplified, and the reference. From the last one, two "quasiorthogonal" signals are derived to perform dual-phase detection. The procedure is fast and compares favorably with a benchtop lock-in amplifier. In the band from 100 Hz to 20 kHz we obtained average amplitude and phase errors below 1% and 0.1 degrees, respectively.

Evaluation of the impact of a pharmaceutical care program in children with asthma.

The objective of this study was to evaluate the impact of a pharmaceutical care program on children with asthma. A comprehensive asthma education and monitoring program that includes basic asthma knowledge, symptoms and exacerbation evaluation, pharmacotherapy assessment including inhaler technique, and quality of life measurements was developed and applied in an outpatient paediatric clinic of the Catholic University of Chile. All patients with moderate asthma scheduled for outpatient visits with their internist over a 1-year period were referred for pharmacist intervention. Patients (aged 7-17) with moderate asthma attending the clinic were allocated to the intervention (group A) or control group (group B). Intervention patients were educated on their disease, pharmacotherapy, self-management, and inhalation techniques. The group B were children with their regular treatment for asthma but without pharmaceutical intervention. A paediatric asthma quality of life questionnaire (PAQLQ) was applied to both groups at 0, 2, and 9 weeks to assess the quality of life. Spirometry was done at the beginning and at the completion of the 9-week study. Beta-agonists used by each patient were also recorded. Eleven children (10.0+/-0.7 years) were included in the pharmaceutical care program, and ten children (9.9+/-0.6 years) in group B. For the individual domains of activities (A), emotions (E), and symptoms (S) there was a significant improvement in the children who received pharmaceutical care in comparison with those who did not receive it. The scores of group B did not change during the 9 weeks of follow-up. There were no significant changes in spirometric values in either group.

Allopurinol encapsulated in polycyanoacrylate nanoparticles as potential lysosomatropic carrier: preparation and trypanocidal activity.

The activity of allopurinol-loaded polyethylcyanoacrylate nanoparticles against Trypanosoma cruzi was compared to that of free allopurinol using in vitro cultures of epimastigotes. Ethylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process, and formulations containing different concentrations of allopurinol, polyethylcyanoacrylate and surfactants were investigated and analyzed in size and amount of drug entrapped. The nanoparticles obtained were less than 200 nm in size, as measured by electron microscopy and cytometry. The peak amount of allopurinol entrapped in the nanoparticles was 62.8+/-1.9 microg mg(-1) of nanoparticles using 400 microl of polyethylcyanoacrylate, 200 microl of surfactant (Tween 20) and 20 mg of allopurinol in 50 ml of polymerization medium and the association efficiency was 100.7%. After 6 h of incubation at pH 7.4 the release of allopurinol from the nanoparticles was 7.4%, while at pH 1.2 only 3.1% was released after 4-6 h (t=42.8, P<0.0001). The in vitro studies, using cultures of T. cruzi epimastigotes, demonstrated considerable increases in the trypanocidal activity of the allopurinol-loaded nanoparticles in comparison with a standard solution of allopurinol (91.5 vs. 45.9%) at an allopurinol concentration of 16.7 microg ml(-1). In addition, it was shown that the unloaded nanoparticles, by mechanisms not completely elucidated, had a trypanocidal activity similar to that of standard solutions of allopurinol. To study cytotoxicity, increasing concentrations of unloaded nanoparticles were incubated on vero-line cell cultures. The concentration that killed 50% cells was 200 microg ml(-1), four times higher than that necessary to kill 50% of T. cruzi. It is concluded that the polyethylcyanoacrylate nanoparticles constitute a good carrier of drugs against the T. cruzi. The allopurinol loaded-nanoparticles significantly increased the trypanocidal activity in comparison to the free drug.

Adverse drug reactions (ADRs) in patients with HIV infection. A prospective study.

AIM: A prospective drug surveillance method was used to monitor 50 ambulatory patients with HIV infection, who were controlled in the Sexual Transmission Disease Service at Dr. Sotero del Río Hospital (Santiago, Chile). The aim of this work was to characterize and study the frequency, characteristics, and associated factors of the ADRs in HIV-infected patients. PATIENTS AND METHODS: Patients were interrogated once or twice a month by a clinical pharmacist, who consigned data concerning the drug prescribed by the physician, drug-related signs and symptoms, and the laboratory's parameters as renal, hepatic, hematological function, and biochemical test. The ADR probability was assessed for an algorithm. RESULTS: The frequency of adverse drug reactions found in the group of patients studied was 32.0%. The dermatological, hepatic, and hematological systems were the most affected by adverse drug reactions. Trimethroprim-sulfamethoxazole and zidovudine were the drugs mainly associated with ADRs. Patients with lymphocytes CD4+ count of 200 or less, presented a higher frequency of ADRs. 48.5% of ADRs were classified as probable. Severe reactions were found in 18.5% of the patients, and moderate in 70.4%. 50% of patients with ADRs needed the withdrawal of the implicated drug, and an 18.5% dose decreased. 63% of the ADRs were dose-independent. CONCLUSION: There was a higher frequency of ADRs in those patients with multiple-drug therapy, but the frequency of ADR was not associated with age, gender, or hematological test.

Adverse drug reactions (ADRs) in hospitalized pediatric patients. A prospective study.

The aim of this study was to determine the frequency and the characteristics of ADRs in 219 hospitalized pediatric patients, using an intensive and prospective drug surveillance method. The frequency of ADRs in these patients was 13.7%. The systems most commonly affected were the gastrointestinal (32.5%), the central nervous (20.0%), and the metabolic systems (17.5%). Asparaginase, methotrexate, phenytoin, phenobarbital, erythromycin, and salbutamol were probably the drugs associated with the ADRs. According to causality, 54.2% of the ADRs were regarded as probable, and 32.2% as possible. The majority of the ADRs were moderate (51.2%), 27.9% were severe. The main treatment of the ADRs was the withdrawal of the suspected drugs. The length of the stay in the hospital and the total number of drugs given to the patients influenced significantly the frequency of ADRs. 93% of the ADRs were dose-dependent.

Characterization and trypanocidal activity of nifurtimox-containing and empty nanoparticles of polyethylcyanoacrylates.

The aim of this study was to evaluate the utility of nanoparticles of polyalkylcyanoacrylate as a targeted delivery system for nifurtimox against Trypanosoma cruzi, responsible for Chagas' disease. Ethylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process and formulations containing different concentrations of nifurtimox, polyethylcyanoacrylates and surfactants were investigated and analysed for size and drug content. The nanoparticles obtained were less than 200 nm in size, as measured by electron microscopy and cytometry. The peak percentage of nifurtimox uptake into the nanoparticles was 33.4% for use of 500 microL polyethylcyanoacrylate, 200 microL surfactant (Tween 20) and 10 mg nifurtimox in 50 mL polymerization medium. The highest release of nifurtimox from the nanoparticles was 65.4% after 6-h incubation at pH 7.4. In-vitro studies using cultures of T. cruzi epimastigotes revealed considerably increased trypanocidal activity compared with a standard solution of nifurtimox. Studies of cell cultures previously infected with metacyclic forms of the parasite showed that only 2-h treatment with solutions of 0.001% of the nanoparticle suspension reduced parasitism by 87-94% both when the nanoparticles were loaded with nifurtimox and when unloaded. Electron-microscopic examination revealed processes of degeneration and lysis, suggesting apoptotic processes, in intracellular amastigotes and free amastigotes treated with the nanoparticles. It was demonstrated that unloaded nanoparticles, by mechanisms not completely elucidated, have trypanocide activity similar to that of a standard solution of nifurtimox. It is concluded that the nanoparticles loaded with nifurtimox constitutes a good carrier of the drug against T. cruzi. The loaded-nanoparticles significantly increase trypanocidal activity.

Hepatic kinetics of SCP-1 (N-[alpha-(1,2-benzisothiazol-3(2H)-ona-1, 1-dioxide-2-yl)-acetyl]-p-aminophenol) compared with acetaminophen in isolated rat liver.

The hepatic disposition of a new analgesic, SCP-1, a derivative of acetaminophen, was studied in the isolated perfused rat liver using a recirculating system. The aim of this study was to compare the kinetic parameters of this molecule with those of acetaminophen. Sprague-Dawley rat (230-330 g) livers were perfused for 2 h with 250 ml Krebs-Henseleit bicarbonate buffer containing SCP-1 or acetaminophen, 0.07 mmol l(-1) (n=4), 0.28 mmol l(-1) (n=4), and 0.8 mmol l(-1) (n=4) (approximately one, four and ten times the therapeutic doses in man, respectively). Perfusate samples were collected from the efflux at various times. The SCP-1 and acetaminophen perfusate concentrations were assayed by a HPLC method. Pharmacokinetic analysis was carried out using a computer program. There were significant differences between the hepatic kinetics of SCP-1 and those of acetaminophen. Thus, SCP-1 elimination half-life (mean 14.8+/-10.0 min) was shorter than that of the acetaminophen (186.1+/-27.7 min) (t=11.6, P=0.0001). While the half-life of SCP-1 increases with concentration, the half-life of acetaminophen remains constant as the concentration increases. The hepatic clearance was higher for SCP-1 than acetaminophen (mean 19.01+/-14.5 ml min(-1) vs. 1.29+/-0.08 ml min(-1), respectively) (t=2.44, P<0.05), and it behaved according to dose-dependent kinetics. The SCP-1 extraction ratio was higher (mean 0.63+/-0.49) than for acetaminophen (0.04+/-0.01) (t=2.41, P<0.05) and this parameter tended to decrease as the perfusate concentrations of SCP-1 increased. It was concluded that the hepatic kinetics of SCP-1 behaved according to dose-dependent kinetics, and statistically significant differences were found between pharmacokinetics parameters of both drugs studied.

Pharmacokinetics of ketorolac in children after abdominal surgery.

The pharmacokinetics of 2 doses of intravenous ketorolac (0.5 and 0.9 mg x kg-1) were studied in 14 children (age 2-8 years). A single dose of the drug was injected into the dorsum vein of one hand. Blood samples were collected at regular time intervals for 6 hours. Serum ketorolac concentrations were assayed using a high pressure liquid chromatography method. Pharmacokinetic values were estimated by a nonlinear computer program. The distribution volume (Vdarea), the total clearance (Cltotal), and elimination half-life (t1/2 beta) were similar in both groups of children who either received 0.5 or 0.9 mg x kg-1 of ketorolac. The estimated geometric mean Vdarea, Cltotal, and t1/2 beta ratios (95% CI in parentheses) for 0.9 mg x kg-1:0.5 mg x kg-1 were 1.24 (0.82, 1.50), 1.14 (0.88, 1.23), and 1.083 (0.40, 1.81), respectively. The pharmacokinetic parameters found in this study are different from those found by other authors in adult subjects.

Pharmacokinetics and hepatotoxicity of diclofenac using an isolated perfused rat liver.

Pharmacokinetics and hepatotoxicity of diclofenac was studied in a recirculating model of isolated perfused rat liver. Ten male Sprague-Dawley rat (weighing 230-330 g) livers were perfused for 2 h with 250 mL Krebs-Henseleit bicarbonate buffer that contained 10.75 mg (group A, n = 5) and 1.075 mg (group B, n = 5) of diclofenac (approximately 100 and 10 times the therapeutic dose in man, respectively). Samples were collected from the efflux at regular time intervals for the determination of diclofenac concentrations by a high performance liquid chromatography (HPLC) method. Pharmacokinetic analyses were carried out using a computer program. To establish viability of the liver and toxicity of the drug, enzyme activity measurements of lactate dehydrogenase (LDH), aspartate aminotransferase (SGOT) and piruvate aminotransferase (SGPT) were performed by a spectrophotometric method. Oxygen consumption was also recorded during the entire perfusion period. Both groups presented bicompartmental kinetics. Concentration profiles showed that group B had a better metabolizing capacity, reflected in a 85.54 +/- 37.05 min half-life, a 0.52 +/- 0.19 mL min-1 g-1 liver clearance and a 0.517 +/- 0.188 extraction ratio, compared to group A, which presented a 123.95 +/- 88.13 min half-life, a 0.1164 +/- 0.067 mL min-1 g-1 liver clearance (P < 0.002) and a 0.116 +/- 0.680 extraction ratio (P < 0.002). LDH activity showed a significant increase in group A at 90 min in comparison with the control group, while in group B this increase was significantly higher at 10 min (P < 0.004). The aminotransferase levels did not show a significant increase. According to these results, diclofenac would not have a direct hepatotoxic effect, even at doses 100 times higher than therapeutic ones.

[Adverse drug reactions among hospitalized elderly patients. Prospective study]. / Reacciones adversas a medicamentos en pacientes geriátricos hospitalizados. Estudio prospectivo.

BACKGROUND: It is not clear if old age is a risk factor for adverse drug reactions. AIM: To study the incidence of adverse drug reactions and the effect of age in patients admitted to an Internal Medicine Service in an university hospital. PATIENTS AND METHODS: Two hundred one patients, hospitalized at the Clinical Hospital of the Catholic University, were studied. These patients were followed using a prospective pharmacological surveillance method. For statistical purposes, patients aged 65 years old or older were compared with those younger than 65 years old. RESULTS: Patients over 65 years old had a 33% incidence of adverse drug reactions, mainly involving cardiovascular system and provoking metabolic disturbances. Younger subjects had a 24% incidence of adverse drug reactions, mainly involving the gastrointestinal system and the skin. Sixteen percent of adverse drug reactions were classified as severe and there was a direct relationship between its frequency and the number of drugs prescribed, the hospitalization length and the presence of renal failure. Younger patients with adverse drug reactions had lower serum albumin levels than those without adverse reactions. This relationship was not observed in older patients. CONCLUSIONS: The frequency of adverse drug reactions in hospitalized patients, is related to the number of drugs prescribed and the length of hospitalization.

Pharmacokinetics of lysine clonixinate in children in postoperative care.

The pharmacokinetics of 2 doses of intravenous lysine clonixinate (4 and 6 mg x kg-1) were studied in 10 children (age 4-10 years) under postoperative care. A single dose of the drug was injected in a forearm vein. Blood samples were collected at regular intervals for 3 hours. Serum clonixin concentrations (expressed as clonixin) were analyzed using a high pressure liquid chromatography method. Pharmacokinetic values were estimated by a nonlinear computer program. The distribution volume was similar in both groups of children (1.288 +/- 0.829 1 and 1. 139 +/- 0.667 1, respectively). There were no differences between the values of total plasma clearance and the administered doses (0.026 +/- 0.017 ml x min-1 and 0.017 +/- 0.008 ml x min-1, t = 1.07, p = 0.76). The elimination half-life was longer in children who received 6 mg x kg-1 (44.26 +/- 6.34 min vs 38.63 +/- 10.93 min) but this difference was not statistically significant (t = 0.99, p < 0.34). The pharmacokinetic parameters calculated in these children were different from those found by other authors in adults and experimental animals.

Pharmacokinetics of vancomycin in patients with severely impaired renal function.

The pharmacokinetics of 1 g dose of intravenous vancomycin was studied in 8 patients with severe renal failure. Serum vancomycin levels were determined by fluorescence polarization immunoassay. After single dose of vancomycin peak concentrations ranged from 37.8 microg.ml-1 to 109.3 microg.ml-1 (mean 64.9 +/- 21.7 microg.ml-1). Vancomycin trough concentration 168h after administration of the antibiotic ranged from 2.23 microg.ml-1 to 11.42 microg.ml-1 (mean 6.55 +/- 2.8 microg.ml-1). The data were analyzed using a PCNONLINE computer program, and in all patients a triexponential model described how concentrations decreased in time. Three-compartment parameters obtained from the 8 patients were t1/2 alpha = 0.312 +/- 0.242 h, t1/2 beta 6.012 +/- 5.36 h, and t1/2 gamma = 131.0 +/- 46.7 h. Vd = 0.158 +/- 0.121 1.kg-1, Vdss = 0.920 +/- 0.248 1.kg-1 and total Cl = 0.10 +/- 0.049 1.h-1 per kg of weight. Between 1.5% and 21.2% of the administered vancomycin dose was eliminated during hemodialysis. The dialysis clearance of vancomycin ranged from 50.6 ml.min-1 to 76.8 ml.min-1 (average: 62.4 +/- 10.4 ml.min-1. However, after dialysis plasma concentrations returned to pre-dialysis values. In accordance to our kinetic study 1 g of vancomycin given every 7 days is adequate treatment for methicillin-resistant Staphylococcus aureus infections in patients with severe renal failure whose creatinine clearance is lower than 10 ml.min-1.