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Showing papers by "Gideon Koren published in 1997"


Journal ArticleDOI
TL;DR: Circum circumcised infants showed a stronger pain response to subsequent routine vaccination than uncircumcised infants, and preoperative treatment with Emla attenuated the painresponse to vaccination.

1,099 citations


Journal ArticleDOI
TL;DR: In utero exposure to either tricyclic antidepressant drugs or fluoxetine does not affect global IQ, language development, or behavioral development in preschool children.
Abstract: Background Many women of reproductive age have depression, necessitating therapy with either a tricyclic antidepressant drug or a drug, such as fluoxetine, that inhibits the reuptake of serotonin. Whether these drugs affect fetal neurodevelopment is not known. Methods We studied the children of 80 mothers who had received a tricyclic antidepressant drug during pregnancy, 55 children whose mothers had received fluoxetine during pregnancy, and 84 children whose mothers had not been exposed during pregnancy to any agent known to affect the fetus adversely. The children's global IQ and language development were assessed between 16 and 86 months of postnatal age by age-appropriate Bayley Scales of Infant Development or the McCarthy Scales of Children's Abilities (for IQ) and the Reynell Developmental Language Scales. Results The mean (±SD) global IQ scores were 118±17 in the children of mothers who received a tricyclic antidepressant drug, 117±17 in those whose mothers received fluoxetine, and 115±14 in those ...

523 citations


Journal ArticleDOI
TL;DR: The dynamic physiological changes that occur in the maternal-placental-fetal unit during pregnancy influence the pharmacokinetic processes of drug absorption, distribution and elimination, as well as the fetal exposure to the drugs taken by the mother.
Abstract: The dynamic physiological changes that occur in the maternal-placental-fetal unit during pregnancy influence the pharmacokinetic processes of drug absorption, distribution and elimination. Pregnancy-induced maternal physiological changes may affect gastrointestinal function and hence drug absorption rates. Ventilatory changes may influence the pulmonary absorption of inhaled drugs. As the glomerular filtration rate usually increases during pregnancy, renal drug elimination is generally enhanced, whereas hepatic drug metabolism may increase, decrease or remain unchanged. A mean increase of 8L in total body water alters drug distribution and results in decreased peak serum concentrations of many drugs. Decreased steady-state concentrations have been documented for many agents as a result of their increased clearance. Pregnancy-related hypoalbuminaemia, leading to decreased protein binding, results in increased free drug fraction. However, as more free drug is available for either hepatic biotransformation or renal excretion, the overall effect is an unaltered free drug concentration. Since the free drug concentration is responsible for drug effects, the above mentioned changes are probably of no clinical relevance. The placental and fetal capacity to metabolise drugs together with physiological factors, such as differences acid-base equilibrium of the mother versus the fetus, determine the fetal exposure to the drugs taken by the mother. As most drugs are excreted into the milk by passive diffusion, the drug concentration in milk is directly proportional to the corresponding concentration in maternal plasma. The milk to plasma (M : P) ratio, which compares milk with maternal plasma drug concentrations, serves as an index of the extent of drug excretion in the milk. For most drugs the amount ingested by the infant rarely attains therapeutic levels.

284 citations


Journal ArticleDOI
TL;DR: This analysis indicates that H1 blockers used mainly for morning sickness during the first trimester do not increase the teratogenic risk in humans and may, in fact, be associated with a protective effect.
Abstract: To determine the relative risk for major malformations associated with antihistamine (H1 blockers) exposure in the first trimester of pregnancy, a literature search of all studies examining the association between antihistamines and major malformations for the period 1960 to 1991 was conducted, followed by meta-analysis. Odds ratio was calculated using the Mantel-Haenszel method. Twenty-four controlled studies met the inclusion criteria with more than 200,000 participating women. The summary odds ratio of major malformations associated with antihistamines taken during the first trimester was 0.76 (95% CI: 0.60-0.94). This analysis indicates that H1 blockers used mainly for morning sickness during the first trimester do not increase the teratogenic risk in humans and may, in fact, be associated with a protective effect. More study is needed to verify the possibility that by preventing vomiting, antihistamines may ensure better metabolic conditions to the fetus and thus may reduce some birth defects. Alternatively, it is possible that pregnancies characterized by vomiting are associated with better outcome due to other reasons, such as hormonal status or placental function. Women suffering from morning sickness which is not controlled by nonpharmacological methods can safely use antihistamines.

174 citations


Journal ArticleDOI
TL;DR: The use of hydroxyzine and cetirizine does not appear to be associated with increased teratogenic risk, and there were no significant differences found in the pregnancy outcome: rate of livebirths, spontaneous or therapeutic abortion, or stillbirth.
Abstract: Background Hydroxyzine has been used for many years for the treatment of allergic symptoms. Cetirizine, an active metabolite of hydroxyzine, has become very popular for the treatment of allergy symptoms because of its efficacy without the sedating effects of the parent compound. Little is known about the safety of hydroxyzine use during pregnancy, and there are no published reports on the effects of cetirizine on pregnancy outcome. Objective To determine whether hydroxyzine and cetirizine are associated with any increased risk of malformations in humans. Methods All pregnant women counseled by the Motherisk Program in Toronto on the use of hydroxyzine or cetirizine during their pregnancies were enrolled in a prospective, controlled, observational study. The control group consisted of pregnant women matched for age, smoking, and alcohol consumption who were counseled for non-teratogenic drug. Results One hundred twenty women were followed after exposure to either hydroxyzine or cetirizine during pregnancy. Of these, 53 were exposed to hydroxyzine during organogenesis and 39 to cetirizine. There were no significant differences found between the hydroxyzine groups and the control groups in the pregnancy outcome: rate of livebirths, spontaneous or therapeutic abortion, or stillbirth. There was also no difference in the rates of major or minor anomalies, mean birth weight, mode of delivery, gestational age, or presence of neonatal distress. Conclusions The use of hydroxyzine and cetirizine does not appear to be associated with increased teratogenic risk.

108 citations


Journal ArticleDOI
TL;DR: High forehead, frontal bossing, malar hypoplasia, epicanthus and micrognathia were associated with untreated epilepsy, as well as with DPH and CBZ treatment, and increased rates of hypertelorism were detected among DPH-exposed offspring.
Abstract: Our objective was to evaluate the patterns of malformations in children exposed in utero to phenytoin (DPH) and carbamazepine (CBZ) monotherapy, and to compare them prospectively with matched mother-child pairs exposed to nonteratogens, and to separate the effects of antiepileptic drugs (AEDs) from those of epilepsy by collecting groups of untreated epileptics and those treated with DPH and CBZ for conditions other than epilepsy. This was a prospective, controlled, and blinded observational study. Thirty-six mother-child pairs exposed to CBZ monotherapy, 34 pairs exposed to DPH monotherapy, and 9 nonmedicated epileptic women and their children were compared with matched mother-child pairs exposed to nonteratogens. The control mothers were matched for maternal age, time of consultation, obstetric history, and socioeconomic status (SES). One main outcome measures a "blinded" morphological assessment of the offspring. We found that minor anomalies were significantly more common among children of epileptics on either drug (P = 0.01) and among DPH-treated nonepileptic offspring (P = 0.03). Among epileptics, the relative risk for minor anomalies following DPH (2.1) was similar to that after exposure to either DPH (P = 0.006) or CBZ (P = 0.01). Increased rates of hypertelorism were detected among DPH-exposed offspring. High forehead, frontal bossing, malar hypoplasia, epicanthus and micrognathia were associated with untreated epilepsy, as well as with DPH and CBZ treatment.

106 citations


Journal ArticleDOI
TL;DR: Therapeutic drug monitoring in the newborn infant is necessary because dose requirements differ greatly from those for older children, and the small blood volume of neonates makes them sensitive to iatrogenic blood loss.
Abstract: Therapeutic drug monitoring in the newborn infant is necessary because dose requirements differ greatly from those for older children. These differences stem from major changes in kinetic disposition at the absorption, distribution, and elimination phases. The small blood volume of neonates makes them sensitive to iatrogenic blood loss. Similarly, the small size of these patients means that medication errors frequently lead to morbidity and even mortality. The clinical laboratory must set up strict, high-standard, carefully updated guidelines to ensure the safety of infants who need drug therapy at this very vulnerable phase of their lives.

100 citations


Journal ArticleDOI
TL;DR: Unexpectedly low cyclosporine levels are strongly suggestive of noncompliance, whereas other variables, including prediction by physicians and nurses intimately involved in the care, were not reflective of non compliance.
Abstract: Inadequate compliance with prescribed medication regimens in children is complex and poorly understood. We measured the extent and pattern of noncompliance with cyclosporine in our adolescent renal transplant population and attempted to determine factors associated with poor compliance. After informed consent, each patient was provided cyclosporine capsules in a medication bottle equipped with an electronic monitoring device (MEMS-4) in the lid. Of the 24 patients eligible, 19 patients (8 female, 11 male) completed the study. Four (21%) patients took less than 80% of the prescribed cyclosporine doses. Five (26%) patients took drug holidays involving ≥3 consecutive doses. There was a trend towards improved compliance with the evening dose (88.5% vs. 93.4%, P = 0.09) and a downward trend in compliance over the course of the study (P = 0.17). None of the variables tested were found to be associated with noncompliance. Experienced physicians and nurses were able to identify 2 of the 4 individuals who were identified by MEMS as noncompliant. Additionally, 2 of the 4 noncompliant patients demonstrated low cyclosporine trough levels (<50 ng/ml). Noncompliance with cyclosporine regimens occurs commonly in adolescent renal transplant recipients. Unexpectedly low cyclosporine levels are strongly suggestive of noncompliance, whereas other variables, including prediction by physicians and nurses intimately involved in the care, were not reflective of noncompliance.

94 citations


Journal Article
TL;DR: Pregnant women who report binge alcohol consumption often report use of cigarettes, cocaine, marijuana and other illicit drugs as well, all of which represent a significant risk to the fetus.
Abstract: OBJECTIVE: To characterize pregnant women who engage in binge drinking and to identify other risk behaviour that these women engage in. DESIGN: Observational study based on retrospective review of records. SETTING: A telephone and outpatient counselling service in Toronto that advises pregnant women about exposure to drugs, chemicals, radiation and infections during pregnancy and lactation. PARTICIPANTS: All pregnant women who sought counselling concerning fetal risk of exposure to binge drinking from 1985 to 1994 as well as those counselled by telephone from 1993 to 1994, and an equal number of control women who sought counselling. OUTCOME MEASURES: Information about binges, demographic factors, history of elective and spontaneous abortion, and use of psychotropic drugs and cigarettes as well as marijuana, cocaine and other illicit drugs. RESULTS: Of the 3800 women seen in the clinic, 119 (3.1%) reported binge drinking during pregnancy; of the 19,991 women counselled by telephone, 153 (0.8%) reported binge drinking during pregnancy. The mean number of drinks per binge was 7.2 (standard deviation 2.5). None of the women was an alcoholic; 83.1% had binged fewer than 10 times during their pregnancy. A large majority (84.0%) of the women had a binge early in the first trimester (before 6 weeks' gestation). In comparison with control women, the women who had engaged in binge drinking were significantly younger (mean 30.0 v. 27.9 years, p < 0.0001) and more likely to be single (12.2% v. 54.6%, p < 0.0001), to be white (69.2% v. 92.9%, p < 0.004), to smoke (19.3% v. 57.1%, p < 0.0001) and to use cocaine (1.1% v. 11.0%, p < 0.0001), marijuana (3.0% v. 19.3%, p < 0.0001) and other illicit drugs (0.7% v. 9.2%, p < 0.0001). CONCLUSIONS: Pregnant women who report binge alcohol consumption often report use of cigarettes, cocaine, marijuana and other illicit drugs as well, all of which represent a significant risk to the fetus. Rigorous efforts should be made to prevent the socially accepted binge consumption of alcohol among young, sexually active women.

70 citations


Journal ArticleDOI
TL;DR: In most cases accidental electric shock occurring during day-to-day life during pregnancy does not pose a major fetal risk.

56 citations


Journal ArticleDOI
TL;DR: There is very little evidence regarding the efficacy of different pharmacological therapy regimens to treat NAS and more studies are required to produce the evidence needed to allow a rational choice between treatment modalities of NAS and thus to ensure optimal care of the neonates suffering from this condition.
Abstract: Objective: To systematically and critically analyse and summarise the published evidence for the rational choice of pharmacologic treatment of the neonatal abstinence syndrome (NAS), a frequently observed condition in neonates born to mothers who are dependent on physically addicting drugs. Design: Studies comparing different pharmacological agents for the treatment of NAS were identified utilising MEDLINE® and additionally the references cited in pertinent articles. The identified studies were critically analysed regarding their study designs and outcome measures. The reported data for the comparative efficacy of the drugs were summarised and evaluated. Results: Fourteen studies were identified, most of them comparing treatment of NAS with phenobarbital, paregoric or diazepam. However, none of these studies was conducted in a double-blind fashion. Frequently, treatment allocations were not properly randomised. Prenatal drug exposure varied and was often not sufficiently verified. Outcome measures and their evaluations differed widely. Due to the different study objectives and flaws in study design, a combined analysis of the published data in the form of a meta-analysis was not deemed possible. When attempting to compare efficacy, diazepam appears to be less efficacious in treating NAS than phenobarbital or paregoric. The relative efficacy of paregoric and phenobarbital appears to depend upon the antenatal exposure of the neonate and on the outcome measure of the study. Only two studies evaluate the efficacy of pure opioids, none of them in direct comparison to paregoric. It remains questionable whether paregoric, which contains the central stimulant camphor and a large amount of alcohol, should be the opioid of choice for the treatment of NAS. Conclusion: Most published studies were conducted prior to the development of clinical epidemiology and modern study design and thus yielded only very limited comparative data on the benefits of different treatment protocols. There is very little evidence regarding the efficacy of different pharmacological therapy regimens to treat NAS. More studies are required to produce the evidence needed to allow a rational choice between treatment modalities of NAS and thus to ensure optimal care of the neonates suffering from this condition.

Journal ArticleDOI
TL;DR: Individualized oral BU dosing is individualized in 10 children to target an area under the curve of BU (BU AUC) of 900–1400 μ M/min based on BU AUC0–∞ calculated from nine serum BU concentrations performed after a BU test dose of 40 mg/m2.
Abstract: An improved limited sampling method for individualised busulphan dosing in bone marrow transplantation in children


Journal ArticleDOI
TL;DR: Citric acid-stimulated saliva constitutes a convenient alternative for TDM of carbamazepine and phenytoin therapy in pediatric patients and of phenobarbital in children > or = 8 years of age.
Abstract: Summary:Studies performed in the research setting suggested that saliva instead of blood may be used for therapeutic drug monitoring (TDM) of anticonvulsants in children. This is an attractive alternative because its collection is painless, and simpler and cheaper than blood drawing. Citric acid sti

Journal ArticleDOI
TL;DR: Two children developed multiorgan dysfunction with disseminated intravascular coagulation 9 days after lamotrigine was added to their antiepileptic therapy, which included valproic acid, suggesting that this adverse reaction may involve muscular tissue.
Abstract: Two children developed multiorgan dysfunction with disseminated intravascular coagulation 9 days after lamotrigine was added to their antiepileptic therapy, which included valproic acid. During the episodes, rhabdomyolysis was detected in one of them, while being seizure-free, suggesting that this adverse reaction may involve muscular tissue.

Journal ArticleDOI
TL;DR: The objective was to evaluate the effect of clobazam on the apparent clearance of other antiepileptic drugs at steady state, and to determine the factors that determine the plasma levels of cl obazam and its active metabolite N-desmethylclobrazam.
Abstract: Clobazam is a 1,5-benzodiazepine effective in antiepileptic therapy of children and adults. Presently it is mainly used as adjuvant therapy for intractable seizures. Our objective was to evaluate the effect of clobazam on the apparent clearance of other antiepileptic drugs at steady state, and to determine the factors that determine the plasma levels of clobazam and its active metabolite N-desmethylclobazam. Patients were 74 children with intractable seizures who received treatment with clobazam at our institution as part of the Canadian Cooperative Clobazam Study Group during the years 1987 to 1991. Serum concentrations of clobazam, N-desmethylclobazam, and of concomitant antiepileptic drugs were monitored and prospectively collected. The effect of clobazam treatment on the apparent clearance steady state of the other antiepileptic drugs was determined by statistical comparison of the clearances of each drug before and after initiation of clobazam treatment using Wilcoxon's signed rank test. The effects ...

Journal Article
TL;DR: The data suggest that propafenone is an inhibitor of P-glycoprotein, whereas 5-OHP is a possible substrate, which is consistent with the hypothesis that the digoxin-propafen one interaction results from the inhibition of the renal tubular transport of digoxin by propafinone and its metabolites.
Abstract: When propafenone is given with digoxin, digoxin serum concentrations increase. Although the digoxin-propafenone interaction is well known clinically, the mechanism by which propafenone interferes with digoxin elimination is unclear. To test the hypothesis that propafenone or one or both of its two major metabolites, 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP), inhibit the P-glycoprotein-mediated net renal tubular secretion of digoxin, we examined the transport of digoxin and the well-studied P-glycoprotein substrate vinblastine across confluent Madin-Darby canine kidney cell monolayers in the absence and presence of propafenone, 5-OHP and NDPP. Propafenone and its two major metabolites significantly inhibit the secretory flux of digoxin and vinblastine (propafenone > 5-OHP ≫ NDPP). Despite decreases in net transport, cellular digoxin accumulation did not decrease, suggesting that neither propafenone nor its metabolites prohibited digoxin from entering the cells at the basolateral side. NDPP, but not 5-OHP, was detected after 48 hr of incubation of the cells with propafenone alone. When the cells were incubated with propafenone or 5-OHP, apical accumulation of 5-OHP, but neither propafenone nor NDPP, against a concentration gradient was observed. These findings are consistent with the hypothesis that the digoxin-propafenone interaction results from the inhibition of the renal tubular transport of digoxin by propafenone and its metabolites. Our data suggest that propafenone is an inhibitor of P-glycoprotein, whereas 5-OHP is a possible substrate.

Journal ArticleDOI
TL;DR: It was concluded that, in a rhesus monkey model, chronic cocaine exposure throughout pregnancy had no significant effect on maternal outcome, but did significantly affect infant outcome as assessed in this investigation.

Journal ArticleDOI
TL;DR: Home-based palliative care appeared to be an effective program for many children with a variety of terminal illnesses after adequate supports for the child and family had been established.
Abstract: This retrospective chart review presents the patient characteristics and utilization of the home-based palliative care program at The Hospital for Sick Children in Toronto. A total of 126 children dying from a broad spectrum of diseases was admitted during the period 1986-1994, referred from neurosurgery, genetic/metabolic, neurology, neonatology, nephrology, cardiology, general pediatrics, general surgery, and pulmonology. At the time of review, 15 patients remained alive and 18 had been discharged from the program. Mean age at the time of referral was 4.8 +/- 0.51 years and mean age at death was 5.3 +/- 0.55 years. The mean number of days in hospital was 26.5 +/- 14.6 while days spent at home averaged 98.4 +/- 15.2; thus 80% of the children's remaining time was spent at home. The average number of parent-team contacts was 3.5 +/- 0.9 by pager and 24.0 +/- 2.9 by telephone. Of the 93 patients who died in the program, 53% died at home, 18% died in community hospitals, and 29% died in a tertiary care facility. Analgesic medications were administered to 54% of the patients; 56% of these then required opioid analgesia for pain and symptom management. Home-based palliative care appeared to be an effective program for many children with a variety of terminal illnesses after adequate supports for the child and family had been established.

Journal ArticleDOI
TL;DR: In the past two decades, several new noninvasive methods to measure drugs have been tested and implemented in therapeutic drug monitoring and it is hoped that these new techniques will help advance the ability to diagnose and manage infants and young children.

Journal ArticleDOI
TL;DR: Clinical trials are in progress in many centers worldwide that will provide further information on the long-term effectiveness of deferiprone as well as on the incidence of serious adverse effects in patients with iron overload and methods to predict individual susceptibility to these adverse effects and ways of preventing them.


Journal ArticleDOI
TL;DR: It is concluded that exposure to cisapride during pregnancy is not associated with a major increased risk of malformations or spontaneous abortions or with decreased birthweight.
Abstract: The objective of this prospective multicenter study was to determine whether cisapride is associated with increased risk of malformations, spontaneous abortions, or decreased birthweight when used during pregnancy Cases were paired for age, smoking, and alcohol consumption with controls exposed to nonteratogens, as well as with disease-paired controls One hundred and twenty-nine pregnant women were exposed to cisapride during pregnancy, including 88 during the period of fetal organogenesis There were no differences in maternal history, birthweight, gestational age at delivery, and rates of livebirths, spontaneous or therapeutic abortions, fetal distress, and major or minor malformations among groups It is concluded that exposure to cisapride during pregnancy is not associated with a major increased risk of malformations or spontaneous abortions or with decreased birthweight

Journal ArticleDOI
TL;DR: The sensitivity of the hair test was established in validating clinical suspicion of in utero exposure to cocaine in the presence of negative urine test, indicating that when clinical suspicions prompted physicians to test neonatal hair, they identify a subgroup of heavy cocaine users, who are probably at higher perinatal risks.
Abstract: Background: There has been a steady increase in the number of newborns affected by maternal drug use. Cocaine and its metabolites cross the placenta and have been routinely measured

Journal ArticleDOI
TL;DR: Saliva concentrations of morphine cannot be used to predict the plasma concentration of morphine in children or adults, however, the concentration of Morphine in saliva may be used as a qualitative indicator of systemic exposure to morphine in a subject.
Abstract: This study sought to determine whether saliva concentrations of morphine correlate with plasma levels of morphine in pediatric patients receiving morphine analgesia for severe pain, and to evaluate whether the measurement of saliva morphine concentrations would be a useful, noninvasive, clinical tool to diagnose systemic exposure to morphine. Fifteen pediatric patients were enrolled; for the control group, 18 adult volunteers were recruited. Patients received continuous morphine drips to ameliorate pain caused by a sickle cell vasoocclusive crisis (range, 10-40 μg/kg.h). Control subjects were randomized into those receiving acetaminophen with either 8 mg (n = 13) or 30 mg (n = 5) of codeine. All participants fasted at least 2 hours before sample collection. Blood and saliva samples were collected simultaneously. All samples were analyzed by radioimmunoassay for morphine. There was no correlation between saliva and plasma morphine concentrations in either the patients receiving intravenous morphine (r = 0.04, P = 0.89) or in the controls receiving codeine (r = 0.43, P = 0.08). There was no observed difference in the mean counts per minute (CPM) for saliva samples in the pH range 3.96 to 8.06. Saliva concentrations of morphine cannot be used to predict the plasma concentration of morphine in children or adults. However, the concentration of morphine in saliva may be used as a qualitative indicator of systemic exposure to morphine in a subject.

Journal ArticleDOI
TL;DR: Investigating the effect of different mixing techniques on the distribution of the components of cyclosporine concentrate for infusion found that thorough mixing of high-dose cyclospora infusions may be important to reduce the possibility of life-threatening anaphylactoid reactions.
Abstract: BACKGROUND:During a Phase I/II trial of high-dose intravenous cyclosporine, a high incidence of anaphylactoid reactions was observed. Epidemiologic investigations revealed that the occurrence of anaphylactoid reactions was significantly associated with improper mixing during preparation of the infusions. It was hypothesized that improper mixing during the preparation of the infusion may have caused initial bolus infusions of the vehicle, Cremophor EL. These inadvertent bolus infusions may have caused the anaphylactoid reactions.OBJECTIVE:To investigate the effect of different mixing techniques on the distribution of the components of cyclosporine concentrate for infusion: cyclosporine, Cremophor EL, and ethanol in the infusions administered to the patients.METHODS:Infusions were prepared in a similar fashion as those administered to study patients enrolled in a high-dose cyclosporine therapy protocol. Samples were collected at defined time points of the infusions. Concentrations of cyclosporine and Cremop...

Journal ArticleDOI
TL;DR: It is necessary to select patients suitable for vaginal or laparoscopic mesh placement for these procedures on the basis of prior history and once they provide informed consent for surgery.
Abstract: Clinical Pharmacology & Therapeutics (1997) 62, 1–5; doi:

Journal ArticleDOI
TL;DR: The data suggest that no clinical or laboratory changes consistent with immunosuppression or immunodeficiency are observed during deferiprone therapy, and immune function in 57 thalassaemia patients is studied.
Abstract: Short-term deferiprone may reduce body iron in some patients with thalassaemia major. Concerns regarding potential immunosuppressive effects of deferiprone have been raised from results of animal studies and case reports in humans. We studied immune function in 57 thalassaemia patients: 36 treated with deferiprone (L1; CP020) and 21 treated with desferrioxamine (DFO). Circulating B lymphocytes were increased in all patient groups. No differences were detected between treatment groups in percentages of circulating lymphocytes, concentrations of IgG, IgM or IgA, specific antibody titres, complement levels, or in vitro lymphocyte proliferation. No clinically important infections were observed in any patient. These data suggest that no clinical or laboratory changes consistent with immuno-suppression or immunodeficiency are observed during deferiprone therapy.

Journal ArticleDOI
TL;DR: In this article, the thickness dependence of the irreversible magnetization in superconducting Y1Ba2Cu3O7−δ films of thickness 350-3000 A was investigated.
Abstract: We report on the thickness dependence of the irreversible magnetization in superconducting Y1Ba2Cu3O7−δ films of thickness 350–3000 A. Our results reveal a nonmonotonous dependence of the persistent current density j on the film thickness, which is interpreted in terms of surface pinning and variations in the surface microstructure. Measurements of the time dependence of j show that under certain conditions relaxation curves of samples of different thickness cross each other, i.e., the sample with initially larger j exhibits after some time a lower j. The crossing point is shifted to shorter times as the temperature is increased. We propose a simple explanation to this effect and discuss its practical implications. Low dose heavy ion irradiation of the films has a modest effect on j and on the rate of its relaxation.

Journal ArticleDOI
TL;DR: It is concluded that saliva can be substituted for serum in monitoring L1 levels, and the pharmacokinetic profiles were similar using serum and saliva monitoring.
Abstract: Deferiprone (L1) is the first clinically available oral iron chelator and it has been proven to be effective for the treatment of transfusional iron overload in thalassemic patients. Because many of these patients have impaired compliance with their medications, effective means of continuous monitoring of compliance are crucial. Saliva drug monitoring has the potential advantage of an easy, noninvasive approach, assuming that it represents serum levels. However, drugs have variable correlations between saliva and serum concentration. We compared serum and saliva levels of L1 at various time points after ingestion of a 75 mg/kg/day dose in nine thalassemic patients. A highly significant correlation between serum-free L1 and saliva levels (r = 0.97, p = 0.0003) was found. Pharmacokinetic profiles were similar using serum and saliva monitoring. We conclude that saliva can be substituted for serum in monitoring L1 levels.