The effect of hair pigment on the incorporation of fatty acid ethyl esters (FAEE).

AIMS: The objective of the current study was to determine whether FAEE incorporation is affected by hair pigmentation. METHODS: Black hooded LE rats were injected intraperitoneally daily with ethanol. Prior to dosing, black and white patches of fur were shaved and analyzed for baseline levels of FAEE using an adapted extraction procedure and GCMS method. Once the shaved 'patches' had grown back they were re-sampled along with hair outside the 'patches', referred to as 'no patch' hair, and tested for post-treatment FAEE levels in the same manner. Blood was also sampled for pharmacokinetic analysis of ethanol. RESULTS: Total FAEE levels were significantly higher in post-treatment hair (black and white) compared to baseline (pre-treatment) levels. Total FAEE levels were also significantly higher in post-treatment 'patch' hair (black and white) compared to 'no patch' hair. No significant differences were found between post-treatment black and white hair. The FAEE profiles were similar between black and white hair, with FAEE levels being highest for ethyl myristate, followed by ethyl stearate, palmitate, and then oleate. CONCLUSION: FAEE incorporation into hair does not appear to be affected by hair pigment, which is in congruence with what is known about the chemistry of drug-melanin interactions. This is important in avoiding potential bias and discrimination in the interpretation of alcohol abuse based on hair color.

Meta-analysis of the differences in the time to onset of action between rocuronium and vecuronium.

1. The aim of the present study was to conduct a meta-analysis of the magnitude of differences in the onset of action (T(max)) between rocuronium and vecuronium. 2. A search was made in PubMed, EMBASE Drugs and Pharmacology, Cochrane Controlled Trials Register and Cochrane Database on Systematic Reviews. Studies comparing the T(max) at the adductor policies between rocuronium and vecuronium administered as an intravenous bolus were included in the study. Twenty-nine effect sizes obtained from 21 studies were included. 3. The result of the meta-analysis of differences was -57.9 s (95% confidence interval -71.4 to -44.3 s), favouring rocuronium over vecuronium. The smallest difference in T(max) between these neuromuscular-blocking agents was observed in children (-19.1 s). The difference in T(max) between rocuronium and vecuronium in female patients was -38.7 s. The difference in T(max) between rocuronium and vecuronium measured by electromyography was approximately 50% shorter than that determined by acceleromyography or mechanomyography. In a subanalysis between rocuronium 600 mg/kg versus vecuronium 100 mg/kg, the difference in T(max) between them was very similar to that obtained in the general meta-analysis. 4. According to subanalyses of patient age and sex, drug dose and neuromuscular monitoring systems, the T(max) of rocuronium was approximately 20-70 s faster than that of vecuronium.

Cyclophosphamide hypersensitivity in a leukemic child.

Although hypersensitivity reactions to chemotherapeutic drugs have rarely been reported, they may occur with any of these agents. A Mexican native 44-kg 13-year-old boy suffering from acute lymphoblastic leukemia (ALL) received chemotherapy for 7 years. Three years later, a recurrence of ALL was detected in his right testicle. The patient was scheduled to receive 12 weekly cycles of 50 mg/kg of cyclophosphamide (CPM) as a 1-hour intravenous infusion. The patient did not have any history of drug allergies or any other type of ADR. Immediately after the fourth cycle of CPM, the patient developed itchy, maculopapular rash, sweating, respiratory distress, and anxiety. According to the algorithm developed by Naranjo et al, the ADR was classified as probably secondary to CPM. Skin tests were negative to hypersensitivity to CPM, and a new cycle of CPM was administered. However, the patient developed a similar hypersensitivity reaction to CPM. After an analysis of the clinical course of the ADR and the need to continue the chemotherapeutic treatment with CPM, we decided to desensitize the patient to this drug. Total duration of the procedure was 5 hours and was performed on only 1 occasion. The program of 12 cycles of chemotherapy was successfully completed without any sign or symptom of hypersensitivity to CPM. In conclusion, we have reported a case of hypersensitivity to CPM who was successfully desensitized to CPM.

Dose minimization study of oxytocin in early labor in sows: uterine activity and fetal outcome.

Two hundred sows were randomly assigned to intramuscularly receive 0.9% NaCl (group 1) or oxytocin 0.083, 0.11 or 0.17 IU/kg (groups 2, 3 and 4, respectively) immediately after the expulsion of the first piglet. The overall duration of labor was decreased in a dose-dependent relationship. Time interval between piglets was decreased approximately 5 min in groups 3 and 4 while sows in these groups exhibited approximately 10-20 contractions x 10 births more than controls (P<0.005). Duration and intensity of uterine contractions also showed a positive dose-response relationship. As an indicative of fetal distress, approximately 2.5 times more meconium-stained piglets were born to sows receiving the higher doses of oxytocin, but in the lowest dose significantly decreased. Oxytocin 0.083 IU/kg significant decreased the mortality rate of piglets [OR 0.49 (95%CI, 0.26-0.92)]. In conclusion, we recommend the intramuscular administration of the lowest possible dose of oxytocin, which still decreases the duration of labor in sows.

Variable designs of clinical trials of neuromuscular blocking agents: an example of studies comparing rocuronium and vecuronium.

BACKGROUND: Published clinical trials on neuromuscular blocking (NMB) agents are being reported with large variations in their protocols and conflictiing results may emerge from these differences. Because they have been compared in several clinical trials, the study was focused on rocuronium and vecuronium in order to evaluate whether these NMB agents were compared under homogeneous conditions. MATERIAL/ METHOD: A search was made in PubMed, Embase Drugs and Pharmacology, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews. Studies on the neuromuscular response at the adductor pollicis to an i.v. bolus dose of rocuronium or vecuronium in humans were included. Quality of all reports was assessed by means of the 3-item Jadad et al. scale. Twenty-five studies met our inclusion criteria and all were retrieved. RESULTS: Randomization was performed in 21 (80.8%) studies. Blinding procedure for drug administration was mentioned in only one study without clarifying the procedure. Induction was most commonly performed with thiopental, followed by propofol. Two studies were performed in children and two in elderly patients. Withdrawals or dropouts were not mentioned in any paper. Electromyography and mechanomyography were the most common monitoring procedures. The time to maximal response, the maximum effect and the time to reach 25% recovery of neuromuscular function were the most used pharmacodynamic parameters. CONCLUSIONS: Clinical trials on neuromuscular blocking agents, e.g. vecuronium versus rocuronium, are being performed with large variability and without following established guidelines.

Elimination kinetics of ethanol in pregnant women.

To evaluate the pharmacokinetics of ethanol in the early second trimester of pregnancy, ethanol concentrations simultaneously measured in the maternal blood (EtOH-MB) and in the amniotic fluid (EtOH-AF) of six pregnant women were obtained from a previous study in which a single ethanol dose of 300mgkg(-1) body weight was administered orally. For maternal blood ethanol concentration, the kinetic equation was: [Formula: see text] where k(12) and k(21) are, respectively, the rate constant of ethanol transfer from either the central compartment to the peripheral compartment or vice versa; V(max)(EtOH)is the maximal velocity for ethanol oxidation; and K(m)(EtOH) is the concentration at which half of the maximal rate of ethanol elimination is reached. The maximum concentration of EtOH in AF was 60% lower than in MB (P=0.36). However, the AUC(0-3.5h) in AF was only 16% lower than the value for MB (P=0.059). The k(12) (0.20 =/- 0.26 h(-1)) was almost twice faster than k(21) (0, h(-1)). The V(max)(EtOH) was 237.6 +/- 71.5 microgml(-1)h(-1) and K(m)(EtOH) was 3.7 +/- 4.7 microgml(-1). Our results imply that in the early second trimester, ethanol metabolism is fast. However, ethanol clearance from the AF is slower than ethanol clearance in MB. This process is widely variable, and our findings may partially explain the wide variability of ethanol's toxic effects on the fetus.

[Adverse reactions to immunotherapy in pediatric patients]. / Reacciones adversas a la inmunoterapia en pacientes pediátricos.

BACKGROUND: Specific immunotherapy involves administration of allergenic extract in order to reach clinical tolerance of the causal allergens in patients with allergic conditions. When administered, it can provoke side effects. OBJECTIVE: To identify systemic reactions after specific immunotherapy administration. MATERIAL AND METHODS: A retrospective trial from January 1996 to December 2000. We reviewed patients' files with an allergic disease diagnosis that received immunotherapy. We looked for adverse reactions at 20 minutes and immunotherapy sheets report. The results were analyzed by central and dispersion trends. RESULTS: Annual average was of 1,168 applications, 51 (23%) had an adverse reaction. Average age was of 9.5 +/- 2.2 years. 76.5% were male. 125 (5.7%) patients abandoned the treatment and 2,025 (94.3%) continued it. The frequency of intermittent mild asthma/allergic rhinitis was of 51%, persistent moderate asthma/allergic rhinitis, 9.8, and allergic rhinitis, 9.8%. The most common allergen was Dermatophagoides (80.4%). The most frequent reactions were a wheal (64.7%) and exacerbation of clinic baseline (25.5%). CONCLUSIONS: Percentage of patients with an immunotherapy immediate reaction was of 2.3% according to literature reports (2.1%).

[Quality of life in children with allergic rhinitis before and after being treated with specific immunotherapy (cases and controls)]. / Calidad de vida en niños con rinitis alérgica antes y después de ser tratados con inmunoterapia específica (casos y controles).

BACKGROUND: Rhinitis is the most frequent allergic disease in children. Symptoms may affect importantly life quality. Measures to avoid allergens when possible and the use of drugs are an important part of the treatment; however, specific immunotherapy is the only treatment altering the natural course of the disease. OBJECTIVE: To assess if specific immunotherapy improves life quality in children with allergic rhinitis. MATERIAL AND METHODS: Patients who attended to the allergy department during August and September 2002, and who fulfilled the inclusion criteria, were included. Two groups of treatment were formed: group A received specific immunotherapy with standardized allergenic extracts, from IPI ASAC Mexico. They started with a concentration of 0.07 bioequivalent units (BEU), with twice-a-week-application with increases of 10 (0.7, 7 and 80 BEU) each seven weeks up to maintenance dose of 700 BEU at six months. Group B only was given pharmacological treatment. Paediatric Rhinoconjunctivitis Quality of Life Questionnaires, specific to children with allergic rhinoconjunctivitis, validated for its use in Spanish in Mexican children by the department of Clinical Epidemiology and Biostatistics of Mc Master University, were applied to all patients. RESULTS: Twenty-seven patients were included in each group, 14 males, adjusted for age with a correlation coefficient (r2) = 0.9799. In both groups, mean age was of 11 years 6 months (group A: 7 to 16 years, group B: 7 to 17 years). Eighteen (44.4%) and fifteen patients (33.3%), of groups A and B respectively, had persistent mild rhinitis, and 9 (55.6%) and 12 cases (66.7%) of groups A and B, respectively, had moderate persistent rhinitis. All of them were sensitized to domiciliary allergens. As to life quality a high odds ratio (OR) was found when assessing patients six months after treatment, especially in nasal symptoms such as pruritus (OR = 6.8) and obstruction (OR = 5.9). Also for practical symptoms the OR was high: carving eyes and nose (OR = 7), blowing the nose (OR = 4.8) and carrying disposable tissues (OR = 4.7). OR for other symptoms was as follows: thirst and throatitch, OR = 4; irritability, OR = 6.2, and ocular pruritus, OR = 3.1. Patients without immunotherapy were likely to use more drugs (OR = 6.4) than those receiving immunotherapy. CONCLUSION: We did not find controlled studies on life quality with the use of immunotherapy in children. In this study, specific immunotherapy was found to improve life quality in children with allergic rhinoconjunctivitis, especially in nasal symptoms, such as pruritus and obstruction, as well as in practical symptoms. These results are similar to those by Fell, who found that 92% patients referred an improvement of nasal symptoms, a better labor performance and a lesser use of drugs after four months of using immunotherapy.

Mathematical analysis of a pharmacodynamic model without plasma concentrations to extend its applicability.

Using a mathematical approach, we analyzed the behavior of the PD model originally described by Bragg et al. The effect was dose-dependent modified until a maximum value (E(max)) was reached. Further increments in dose prolonged the E(max), but the recovery phase did not increase beyond a calculable asymptope. In the absence of plasma concentrations, it was impossible to distinguish the rate of plasma equilibration with the effect compartment (k(e0)) from the rate of drug elimination (k(e1)). Variations on the sigmoidicity affected both the onset and offset of drug effect. Sigmoidicity and the slowest rate constant had identical effects on the spontaneous reversion of the effect, as judged by the recovery index. The IR(50), the index of potency, merely shifted the dose-response relationship to the left or right. Changes in IR(50) were compensated for by making the same proportional changes in dose.

[Allergen sensitization and asthma in children from 1 to 3 years of age]. / Sensibilización con alergenos y asma en niños de uno a tres años de edad.

BACKGROUND: Asthma is a multifactorial disease. Children with atopy history could be sensitized with indoor and food allergens from early stages of the life and this predispose to develop asthma. Controversy exists about the factors that increase or decrease the risk of disease, such as breast feeding, early weaning, smoking exposition, immunizations. OBJECTIVE: To determine if these risk factors and inhaled and food allergen sensitization predispose to asthma development. METHODS: A case-control study was performed. Cases (1 to 3 year-old 74 children) with asthma and control (74 healthy age-matched children) were included, r2 = 0.90. Skin-prick test (SPT) was performed by using indoor and food allergens. Test was considered positive if skin reaction was equal or higher than 3 mm. The results were compared by means of the x2 test. A logistic regression analysis was performed for obtaining odds ratio (OR) (95% confidence interval for each factor). RESULTS: Out of the SPT carried out with aero-allergens, 23 (31%) were positive in the two groups. Regarding the food, 27 cases (36.4%) and 15 controls (20.2%) were positive (x2 = 4.7); p < 0.05, OR = 2.2, IC 95% (1.6-3.1). Atopy was positive in 50 (67.5%) cases and 39 (52.7%) of the controls (x2 = 3.4); p < 0.05, OR 1.8 (1.3 to 2.5). The weaning before the first three months of life was positive in 44 (59.4%) of the cases against 15 (20.2%) of the controls (x2 = 23.7) p < 0.05 with a OR 5.7 (4.9 at 6.6). CONCLUSIONS: We found a probability 2.2 times higher for developing asthma when children were sensitive to at least one food. We also reported that 100% of our sensitized cases with food had received breast feeding during the first four months of life, which is similar to results of other authors where the breast feeding during an intermediate time (one to six months) does not protect against allergic disease. Early introduction of solid food (before the three months of age) was the main factor increasing probability for developing asthma. In our study, atopy almost duplicated this probability.