Effect of hyperbaric oxygen therapy on amphotericin-B induced acute renal failure in rats.

AIM: Acute renal injury may occur after amphotericin B (AmB) administration. The hypothesized injury mechanism is renal vasoconstriction and direct toxic damage. Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischemic events but not for acute renal failure (ARF). The aim of this study was to investigate the role of HBO therapy in AmB induced ARF. METHODS: ARF was induced in 41 Sprague-Dawley rats by a single dose of 75 mg/kg AmB. The rats were randomly divided into two groups; one group was treated with daily HBO for 3 consecutive days. The control group received no HBO treatment. Parameters of renal function were taken on the 5th day after AmB administration. RESULTS: Forty-one rats were treated with AmB, 21 received HBO and 20 served as controls. Body weight loss following the administration of AmB was 13.5+14.7% in the HBO treated rats, as opposed to 24.6+5% in the control group (P=0.004). Serum creatinine and urea were 0.49+0.13 mg/dL and 200.63+87.82 mg/dL in the treatment group and 0.70+0.22 mg/dL and 368.01+169.35 mg/dL, respectively in the control (P=0.001). CONCLUSION: In this model of AmB-induced ARF, HBO treatment alleviated renal injury as reflected by changes in serum creatinine and urea levels.

Factors associated with empyema in children with community acquired pneumonia.

AIM: Empyema is a potential complication of community acquired pneumonia but factors predicting this complication are lacking. METHODS: A retrospective study of all previously healthy pediatric patients admitted between January 2007 and July 2009 with CAP. Patients with non-lobar pneumonia, RSV bronchiolitis, underlying chronic disease, or hospital-acquired pneumonia were excluded. Preadmission, clinical characteristics on admission, and outcome were compared between patients with and without empyema. Management strategies in patients with empyema were also compared. RESULTS: Overall 356 patients were included. Median age was 3.8 ± 3.54 years and 60.7% were males. A total of 43 patients (12%) were diagnosed with empyema. The development of empyema was independently associated, on multivariate analysis, with older age, female gender and antibiotic therapy prior to admission, and with dyspnea, thrombocytopenia and involvement of more than one lobe on chest radiograph on admission. Patients who developed empyema had a longer and more complicated course. Hypoxemia on admission was significantly less frequent in patients with empyema who were treated with antibiotic therapy alone, compared to those treated with chest tube or video-assisted thoracoscopic surgery. CONCLUSION: Early identification of dyspnea and thrombocytopenia in patients with community acquired pneumonia could alert physicians on the potential development of empyema. Antibiotic therapy alone may be sufficient in patients with empyema who are mildly hypoxemic on admission.

Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure.

WHAT IS KNOWN AND OBJECTIVE: Carvedilol is the standard of care for heart failure (HF) patients. Carvedilol is partially metabolized by the highly polymorphic enzyme, CYP2D6. To reach an effective dose while avoiding adverse drug reactions (ADRs), testing of CYP2D6 genotype prior to carvedilol initiation may be considered. The objectives of this study were to determine CYP2D6 metabolic genotypes in an Israeli cohort of HF patients and to investigate the relationship between genotype, carvedilol dose and number of ADRs to determine the importance of CYP2D6 genotyping prior to treatment initiation. METHODS: Ninety-three patients with HF on carvedilol were CYP2D6 genotyped and classified as poor (PM), intermediate (IM), extensive (EM) or ultrarapid (UM) metabolizers. Carvedilol dose and ADRs were calculated and correlated with genotype using linear regression statistic analysis. RESULTS AND DISCUSSION: The distribution of the CYP2D6 phenotype in the Israeli population with HF is similar to the European general population. There were no significant differences of carvedilol dose and number of ADRs among genotype groups. Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose changes. WHAT IS NEW AND CONCLUSION: Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose during therapy for patients with HF. The Israeli CYP2D6 phenotype distribution in HF patients was consistent with the frequency in the general European population.

Strategy for increasing detection rates of drug and alcohol abuse in paediatric emergency departments.

AIM: To determine whether implementation of criteria for performing a toxicology screen and increasing staff awareness improve detection of substance abuse among adolescents presenting to the emergency department. METHODS: Patients 12 to 18 years of age presenting to one of three emergency departments in Israel were included in a prospective cohort study. In the 'study' hospital, a set of criteria for urine toxicology screen and measurements of ethanol serum level were implemented. No specific interventions were implemented in the two other hospitals. The main outcome measure was the rate of substance abuse detection. RESULTS: The number of adolescents seen in the participating centres was 3200 at the study hospital, and 3493 and 2792 at the two other hospitals. High blood ethanol concentrations were found in 49 patients at the study hospital compared with 30 and 19 patients at the two other hospitals (p < 0.001). Illicit drugs were detected in 13, 4 and 1 patients, respectively (p = 0.002). CONCLUSIONS: Introducing structured guidelines for ordering toxicological screening increases the detection of alcohol and drug of abuse among adolescents presenting to paediatric emergency departments.

The safety of macrolides during lactation.

BACKGROUND: Infantile exposure to macrolides has been associated with hypertrophic pyloric stenosis causing projectile vomiting, dehydration, electrolyte abnormalities, and in rare cases death possibly via macrolide interaction with gastric motilin receptors. Large population-based cohorts have suggested that exposure to macrolides via breastmilk may be associated with pyloric stenosis. METHODS: In this prospective, controlled observational study designed to assess the safety of macrolides during lactation, we followed infants whose mothers contacted our Drug Consultation Center at the Assaf Harofeh Medical Center (Zerrifin, Israel) inquiring about safety of macrolides during lactation and compared them to a cohort of infants exposed to amoxicillin during breastfeeding. RESULTS: Fifty-five infants exposed to macrolide antibiotics were compared to a control cohort of 36 infants exposed to amoxicillin via lactation. The infants in the macrolide group were all exposed to erythromycin and the newer macrolides: azithromycin, clarithromycin, and roxithromycin. The rate of adverse reactions the infant experienced while being exposed to both antibiotics was comparable. Seven (12.7%) infants in the macrolide group experienced adverse reactions versus three infants (8.3%) in the amoxicillin group (odds ratio = 1.6, 95% confidence interval, 0.38-6.65, p = 0.73). The adverse reactions in the infants exposed to macrolides were rash, diarrhea, loss of appetite, and somnolence, whereas the infants exposed to amoxicillin experienced rashes and somnolence. Factors such as gestational age, age and weight at exposure, maternal age, or type of macrolide were not associated with the infant's adverse reaction in multivariate regression analysis. CONCLUSIONS: Rates and types of minor adverse reactions in breastfed infants exposed to a macrolide or amoxicillin in breastmilk were comparable. Macrolide exposure during breastfeeding was not associated with pyloric stenosis, although larger prospective studies are required to confirm our observation.

The stethoscope as a vector of infectious diseases in the paediatric division.

AIM: Nosocomial infections are of great concern in hospital settings, and even more so in the paediatric ward. Health professionals and their medical equipment have long been known to act as vectors of infectious diseases. This study aimed at evaluating the presence of bacterial pathogens on the stethoscopes of medical personnel in the paediatric division. METHODS: Forty-three stethoscopes belonging to senior physicians, residents, interns and medical students at the paediatric ward were sampled. Bacterial cultures and antibiotic sensitivity testing were carried out. RESULTS: All but six bacterial cultures were positive (85.7%). Staphylococcal species were the most common contaminants (47.5%). One case of methicillin-resistant Staphylococcus aureus was encountered. Gram-negative organisms were isolated in nine different samples (21%) including one case of Acinetobacter baumannii in the neonatal intensive care unit. CONCLUSION: Most stethoscopes harbour potential pathogens. The isolation of Gram-negative organisms pose a real risk of spreading potentially serious infections, especially in the setting of intensive care departments. Apparently, the current recommendations of regular disinfection of stethoscopes are not carried out by health personnel that participated in the study.

[The risks of combining medicine and herbal remedies].

The risks of using herbal remedies, considered 'natural', should not be disregarded, as some have serious side effects and some interact with and influence conventional medical therapeutics. The effect may be pharmacokinetic by altering absorption or metabolism, and may be pharmacodynamic, by changing the final effect of the drug. St. John's wort, for example, an antidepressant herbal remedy, may pharmacodynamically interact with specific serotonin reuptake inhibitors (SSRI's), causing a serotonin syndrome. St. Johns wort also causes serious pharmacokinetic interactions by activating the cytochrome CYP3A4, dangerously decreasing blood levels of cyclosporin, warfarin, and theophylline, and reducing the efficacy of contraceptive pills and AIDS therapy. The article presents a review of a number of herbal remedies, commonly used in Israel, that have documented drug interactions, providing details of common indications, adverse reactions and drug interactions of each herbal remedy. Physicians should recognize the fact that patients use herbal remedies, purchased directly at pharmacies or health stores, and be aware of the potential interactions of these remedies with conventional drugs.

How much acetaminophen do paediatricians prescribe? A survey among Israeli paediatricians.

OBJECTIVE: To describe the current practice of Israeli paediatricians regarding acetaminophen dosing. METHODS: A cross-sectional survey among 200 paediatricians. The paediatricians were questioned of the recommended dose of acetaminophen, and whether they give prescriptions for acetaminophen and instruct their patients how to use it. RESULTS: The response rate was 36%. When asked on the recommended dose of acetaminophen, 30 (42%) physicians gave doses different from the dose recommended by the Israeli formulary. Thirty (42%) of the paediatricians answered that they usually or always give prescriptions for antipyretics. CONCLUSIONS: A large percentage of Israeli paediatricians do not provide parents proper instructions regarding the correct dosing of acetaminophen.

Copper and zinc blood levels among children with nonorganic failure to thrive.

BACKGROUND AND AIMS: Copper and zinc deficiency are commonly reported among children with organic failure to thrive. In contrast, reports on copper and zinc status in children with non-organic failure to thrive are scarce. The goal of this study was to evaluate copper and zinc blood levels and nutritional intake among children with non-organic failure to thrive. METHODS: A study group of 32 children with non-organic failure to thrive were investigated and compared with 32 healthy controls. Each child had copper and zinc blood level measurements. In addition, the study group underwent evaluation of thyroid function, immunoglobulins, endomesial antibodies and xylose test. A dietary questionnaire that included a diet history and a 24-h dietary recall was administered to parents by a dietician. Weight for height, height for age and mean daily intake of calories, protein, copper and zinc were calculated. RESULTS: There were no significant differences between the two groups in either socioeconomic status or caloric, copper or zinc intake. Protein intake was significantly lower in the study group (P<0.0001). Plasma copper levels were within the normal range in both groups (P=0.3). Zinc plasma levels were significantly higher in the study group as compared to controls (P=0.03); however, they remained within the normal range in both groups. CONCLUSIONS: Children with non-organic failure to thrive can maintain plasma copper and zinc levels within normal range and similar to normal controls.

Sore Throat Treatment during Pregnancy : A Prospective, Controlled, Pilot Study.

OBJECTIVE: To determine whether exposure during pregnancy to two types of lozenges used for treatment of sore throat [Kalgaron® (Rafa Laboratories, Jerusalem, Israel) or Strepsils® (Boots Healthcare International, Nottingham, UK)] was associated with an increased risk of malformations, spontaneous abortions or decreased birthweight. DESIGN: Prospective, controlled, observational study. STUDY PARTICIPANTS: The study group included 54 women who received Kalgaron® or Strepsils® during the first trimester of pregnancy. The control group included 54 women exposed to non-teratogenic drugs. RESULTS: The rate of major malformations in the study group (3.84%) did not differ from that of the control group (3.92%) [p = 0.98; relative risk 0.98, 95% confidence interval 0.14 to 6.7]. The rate of minor malformations in the study group (1.92%) did not differ statistically from that of the control group (0%) [p = 0.32]. There were also no statistically significant differences in birthweight, rate of live births and rate of spontaneous abortions among the two groups. CONCLUSIONS: The use of Kalgaron® or Strepsils® during pregnancy was not associated with an increased risk of malformations, spontaneous abortions or decreased birthweight. However, larger studies are needed to confirm the safety of these medications during pregnancy.

Breast-feeding and smoking habits among Israeli women.

BACKGROUND: Many women stop smoking before or during pregnancy, or while breast-feeding (nursing). OBJECTIVES: To assess the relation between breast-feeding and smoking habits. METHODS: A survey was conducted among 920 women attending family health clinics (group 1) and a maternity department (group 2) on their breast-feeding and smoking habits. RESULTS: A total of 156 women (16.95%) smoked during pregnancy. A significant correlation was found between breast-feeding and not smoking after delivery (P = 0.009 in group 1, P = 0.03 in group 2). A higher tendency to nurse was found among women with an uneventful pregnancy, who vaginally delivered a singleton at term weighing 2,500-4000 g, and who received guidance on breast-feeding. CONCLUSION: Professional guidance in favor of breast-feeding is crucial to increase the rate of nursing. Encouraging breast-feeding will probably decrease the rate of cigarette smoking.

Haemophilus influenza type b vaccine in Israel: experience in a paediatric ambulatory clinic.

In Israel, vaccination are the overall responsibility of the government. We were the first in Israel to give the Hib (Haemophilus influenza type b) vaccine to the population, through independent means, without government control. The aim of the study was to follow longitudinally the specific group of children vaccinated in our ambulatory clinic. In this study, 1,497 children between 2 and 52 [mean (SD) 13 (9)] months of age at the time of first vaccination were vaccinated with Hib vaccine. Over the next 7 years, they were followed up by repeated phone calls when parents were asked about hospitalisation and any serious infectious diseases. Of the 1,497, 1,444 were followed during the years 1992 to 1999 and 36 were hospitalised during this time. All blood and cerebrospinal fluid cultures were negative. No proven case of Hib infection could be demonstrated. Despite the small sample size, this study justifies the continued use of the vaccine along with maintaining surveillance for Hib infection.

Congenital cytomegalovirus infection. Is there a breakthrough?

QUESTION: My 26-year-old patient is planning her first pregnancy in the coming month. She works in a day-care centre. Recently, two cases of cytomegalovirus (CMV) infection were diagnosed in her class. What tests should she have before and during the pregnancy, and how should I care for her? ANSWER: Cytomegalovirus infection, the most common congenital viral infection in humans, carries high risk of long-term morbidity and mortality. Seronegative mothers of children in day-care centres are at as high risk of acquiring the infection as day-care workers themselves. The immune status of at-risk patients should be evaluated as pregnancy progresses. Evidence of fetal infection does not necessarily mean fetal disease or damage. With a primary-infected fetus, termination of pregnancy might be discussed with the parents.

False-high blood salicylate levels in neonates with hyperbilirubinemia.

Drug assays may yield false-positive results caused by cross-reacting compounds. After finding a serum salicylate concentration of 81 microg/mL by using Trinder's colorimetric method, in a comatose child admitted to the authors' pediatric intensive care unit, in the absence of reported salicylate intake, the authors aimed to compare this situation with the phenomenon involving endogenous digoxin-like substances, which cross-react with the routine assay of digoxin. None of the participants in the study had been exposed to salicylate. Salicylate concentration was measured in all patients using Trinder's colorimetric method and in the second stage of the study also by AxSYM salicylate assay. Salicylate concentration using Trinder's method was 18 +/- 25 (4-81) microg/mL among nine seriously ill children in the pediatric intensive care unit, of whom two children with extensive burns had salicylate levels of 30 and 81 microg/mL, respectively. Salicylate concentrations were 107 +/- 24 (45-143) microg/mL and 60 +/- 25 (28-92) microg/mL, among 18 premature newborns and 18 term newborns, with hyperbilirubinemia, respectively. In the second stage, which involved 22 jaundiced term newborns and cord blood from 21 pregnant women, Trinder's method yielded elevated salicylate blood levels among the hyperbilirubinemic infants: 82 +/- 5 (73-89) microg/mL; however, the AxSYM assay yielded significantly lower blood levels: 2.5 +/- 3.4 (0-10.9) microg/mL (P < 0.0001). Among the pregnant women, salicylate cord blood levels were found to be low-within the limit error of the assay with both assay methods. In conclusion, when salicylate intoxication is suspected, particularly during the neonatal period, it is advisable to measure salicylate levels by immunoassay technology.

Therapeutic drug monitoring of once daily gentamicin in serum and saliva of children.

UNLABELLED: Gentamicin is widely used in paediatric medicine and therapeutic monitoring is mandatory due to the narrow margin of safety. Saliva sampling may be of potential interest, especially in children in whom blood sampling is often difficult. Experience with once daily intravenous administration of aminoglycosides has grown in recent years. Gentamicin levels were measured in serum and saliva of 55 children treated with the drug (5 mg/kg per day), administered intravenously in three different regimens: thrice (n = 19), twice (n = 18), and once daily (n = 18). No correlation was found between serum gentamicin concentrations and saliva levels when the drug was administered twice or thrice daily, however, there was good correlation when the drug was administered once daily (r2 = 0.96, P < 0.0001). CONCLUSION: In children with uncomplicated infections treated with once daily gentamicin, trough concentrations of the drug can be monitored in saliva.

First trimester exposure to cefuroxime: a prospective cohort study.

AIMS: There are no published studies on the safety of cefuroxime use during pregnancy. We therefore investigated prospectively the possible teratogenic effect of intrauterine exposure to cefuroxime. METHODS: One hundred and six women who received cefuroxime during the first trimester of pregnancy were recruited from three teratogen information centres in Israel. Exposed women were paired for age, smoking habits and alcohol consumption with references being exposed to nonteratogenic antibiotics administered for the same indications. RESULTS: Maternal history, birthweight, gestational age at delivery, rates of live births, spontaneous abortions and fetal distress were comparable among the two groups. Rates of major malformations in the cefuroxime group (3.2%) did not differ from references (2%) (P = 0. 61, relative risk = 1.56, 95% confidence interval 0.27-9.15). There was a significantly higher rate of induced abortions among the cefuroxime exposed women as compared to the references (P = 0.04, relative risk = 3.33, 95% confidence interval 0.94-11.77). CONCLUSIONS: Our data may suggest that exposure to cefuroxime during the first trimester is probably not associated with an increased risk for malformations or spontaneous abortions; however, in light of the small sample size and the broad confidence limits, larger studies are needed to confirm these findings.