Showing papers by "Gideon Koren published in 1990"

Flux creep characteristics in high‐temperature superconductors

Abstract: We describe the voltage‐current characteristics of YBa2Cu3O7−δ epitaxial films within the flux creep model in a manner consistent with the resistive transition behavior. The magnitude of the activation energy, and its temperature and magnetic field dependences, are readily derived from the experimentally observed power law characteristics and show a (1−T/Tc)3/2 type of behavior near Tc. The activation energy is a nonlinear function of the current density and it enables the determination of the shape of the flux line potential well.

Femtosecond optical detection of quasiparticle dynamics in high- T c YBa 2 Cu 3 O 7 − δ superconducting thin films

Abstract: Femtosecond dynamics of photogenerated quasiparticles in ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$ superconducting thin films shows, at T\ensuremath{\le}${\mathit{T}}_{\mathit{c}}$, two main electronic processes: (i) quasiparticle avalanche production during hot-carrier thermalization, which takes about 300 fsec; (ii) recombination of quasiparticles to form Cooper pairs, which is completed within 5 psec. In contrastr, nonsuperconducting epitaxial films such as ${\mathrm{PrBa}}_{2}$${\mathrm{Cu}}_{2}$${\mathrm{O}}_{7}$ and ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{6}$ show regular picosecond electronic response.

Systemic exposure to mercaptopurine as a prognostic factor in acute lymphocytic leukemia in children.

Abstract: Background. Despite a success rate of more than 90 percent in inducing remission in children with acute lymphocytic leukemia, 30 to 40 percent of such children relapse. Maintenance therapy during remission usually includes oral mercaptopurine and methotrexate. Recently, wide variability in the bioavailability of oral mercaptopurine has been demonstrated, and there is concern that this may affect the risk of relapse. Methods. To investigate whether lower systemic exposure to mercaptopurine may increase the risk of relapse in acute lymphocytic leukemia, we prospectively studied 23 children receiving maintenance therapy. On the basis of disease features, 11 were classified as being at low risk of relapse, and 12 at standard risk. Those who relapsed (n = 10) did not differ from those who did not in their mean age, hemoglobin level, mean daily dose of mercaptopurine and weekly dose of methotrexate, or the total number of days during which mercaptopurine and methotrexate therapy was interrupted. Result...

All high Tc edge junctions and SQUIDs

Abstract: We present the first observations of superconducting quantum interference in multilevel, all high Tc, lithographically patterned edge junction structures. The current‐voltage characteristics are nonhysteretic and have well‐defined critical currents. The dynamic resistance is independent of current above the critical current. These devices show periodic sensitivity to magnetic fields and low levels of magnetic hysteresis up to temperatures around 60 K.

A Case-Control Study on the Association Between First Trimester Exposure to Lithium and Ebstein's Anomaly

Abstract: Lithium carbonate is considered to be a first-line drug in the management of manic depressive psychosis. According to Food and Drug Administration figures 0.1% of pregnant women are using this medication.1 During the last 2 decades accumulated data have suggested that lithium carbonate may be teratogenic in humans.2 The Danish registry has accumulated over 200 cases, among which there was a 10% occurrence rate of cardiac malformations.3 This rate appears high when compared to the 0.1% risk for such malformations in the general population.2 In particular, the Danish registry reported 8 cases of the rare Ebstein's anomaly which occurs spontaneously in only 1 of every 20,000 births, suggesting a relative risk of 500-fold above that in the general population. However, the information in this registry has been collected by a voluntary reporting system and does not represent systematically collected data. It has been argued that families and physicians caring for malformed babies are more likely to report adverse fetal outcomes to the registry than normal outcomes,4 as was the case with retinoic acid.5 This reporting bias may create a false impression of a teratogen when, in fact, the drug may not be teratogenic. The implication of wrongful incrimination of a drug like lithium may be immense; women may not be optimally treated during conception and pregnancy or, if treated before pregnancy was recognized, they may wish to terminate pregnancy to avoid an increased teratogenic risk. Since our team provides counselling for women in greater Toronto on the safety of drugs and chemicals, we are continuously witnessing both these options being taken by women. To the best of our knowledge no controlled studies have tried to define the teratogenic risk of lithium in humans. In dealing with a rare malformation such as the Ebstein's anomaly, a sample size > 400 women exposed to lithium and a similar group of nonexposed women would have to be collected prospectively in order to detect a 10-fold increased risk with an alpha of 0.05 and power of 0.8. A more realistic approach to try to address this question would therefore be the case-control study where one focuses on the rare event, namely the Ebstein's anomaly, and compares maternal drug exposure in pregnancy of children having this malformation with those of a control group. Because our cardiology division is the tertiary referral center for a population of about 6 million, we have had the rare opportunity to ascertain a large number of cases of Ebstein's anomaly and thus to test the association between first trimester exposure to lithium and this malformation.

Prevention of unnecessary pregnancy terminations by counselling women on drug, chemical, and radiation exposure during the first trimester

Abstract: As part of a new approach to counselling pregnant women concerned about antenatal exposure to drugs, chemicals, or radiation, we measured their tendency to terminate their pregnancy by using a visual analogue scale (VAS). Analysis of 78 cases where women had less than 50% tendency to continue pregnancy before they were advised by us reveals that 61 decided to continue their pregnancy after the consultation (57 normal, healthy infants, four miscarriages) and 17 terminated. Women who continued their pregnancy significantly changed their tendency after we discussed relevant information with them (from 34.3 +/- 2.5% to 84.5 +/- 3.3%, P less than 0.00001), whereas most of those who eventually terminated pregnancy did not change their tendency to continue pregnancy beyond the 50% mark (from 24.8 +/- 5.4% to 45.1 +/- 9.8%) (P greater than 0.1). Only two of the women who terminated their pregnancy were exposed to teratogenic drugs; however, in most other cases, other obvious reasons, unrelated to the exposure in question, were identified by the women as leading reasons for termination. An appropriate intervention in early pregnancy can prevent unnecessary pregnancy terminations by correcting misinformation and thereby decreasing the unrealistically high perception of risk by women exposed to nonteratogens.

Morphine excretion in breast milk and resultant exposure of a nursing infant.

Abstract: We report the case of an infant who was breastfed while his mother was receiving low doses of morphine. Morphine concentration in his serum was in the analgesic range (4 ng/ml), while concentrations in the milk varied substantially in three samples collected within 2 hours (10, 100, 12 ng/ml). The calculated dose that the infant must have received to achieve the observed serum concentration had to be between 0.8 to 12% of maternal dose, based on reference literature values of clearance and bioavailability. The current perception that maternal morphine exposure is safe for the breastfed infant is based on 50 year old data which were determined by an analytical method 1000 fold less sensitive than the present HPLC, thus leading to a likely erroneous conclusion.

Administration of measles, mumps, and rubella virus vaccine (live) to egg-allergic children.

Abstract: DURING the first year of life, egg allergy is one of the most common food allergies in atopic children. 1 Since the attenuated measles and mumps components of the measles, mumps, and rubella (MMR) virus vaccine (live) are grown in cell cultures of chick embryos, concerns have been raised regarding the safety of administering the MMR vaccine to eggallergic children. Initially, it was believed that egg-allergic children could safely receive the vaccine. 2,3 However, it has since become apparent that reactions to the MMR vaccine can occur in egg-allergic individuals. 4 The American Academy of Pediatrics recommends that "persons with a history of anaphylactic reactions (eg, urticaria, swelling of the mouth and throat, wheezing, laryngospasm, hypotension, or shock) following egg ingestion should not be vaccinated until they have been skin-tested." 5 Because of the effectiveness of vaccines in preventive medicine, ways of safely administering vaccine grown in avian embryos to

Maternal Ginseng Use Associated With Neonatal Androgenization

Abstract: To the Editor.— The termginsengrefers to any of 22 different plants, usually of the genusPanax, used as a tonic and restorative. It is estimated that 5 million people in North America consume ginseng regularly1because of its purported antifatigue, immunologic, and hormonal qualities. No reproductive studies are available to address its safety during pregnancy. We report apparent androgenic effects in a male infant whose mother consumed large amounts of pure ginseng throughout pregnancy and early lactation. Report of a Case.— A 30-year-old white nurse, gravida 3, para 2 (one miscarriage), contacted the Motherisk Program in Toronto, Ontario, to inquire whether her self-medication with pure Siberian ginseng (650-mg tablets twice daily, Jamieson Natural Sources, Toronto) was safe while breast-feeding her 2-week-old neonate. She had been taking the ginseng, purchased from a health store, for irritability and mood swings for 1 1/2 years, including the 9 months of

Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis

Abstract: In order to assess the interaction between methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAID), we studied the pharmacokinetics of oral MTX alone and in the presence of the usually prescribed NSAID in 7 children with chronic arthritis The NSAID studied included tolmetin, indomethacin, naproxen, and aspirin Six patients were treated with multiple NSAID The mean MTX elimination half-life was prolonged when NSAID were coadministered (17 +/- 05 vs 12 +/- 01 h; p = 003) However, neither the apparent MTX clearance (CI) (106 +/- 55 vs 131 +/- 35 l/h; p = 019), the area under the serum MTX concentration-time curve (Auc) (21 +/- 10 vs 15 +/- 06 mumol/l/h; p = 008) or the apparent volume of distribution (Vd) (230 +/- 62 vs 219 +/- 64 l; p = 053) was significantly altered by the administration of NSAID Although the differences between the mean Cl and Auc were not statistically significant, a wide variation in the impact of NSAID on MTX Cl was observed In 6 of 7 patients, the Auc increased during NSAID administration from 19 to 140% This degree of increase may be clinically significant in some individuals It is consequently recommended to closely monitor patients who are receiving MTX and NSAID for MTX toxicity until these results can be verified in a larger population

Vancomycin-Induced Red Man Syndrome

Abstract: A total of 11 cases of red man syndrome collected among 650 children who had received vancomycin in our hospital between 1986 and 1988 (estimated prevalence 16%) were retrospectively analyzed These 11 children were compared with 11 age-matched children who received vancomycin in whom red man syndrome did not develop Of the patients with red man syndrome, 73%, and of the patients with no reaction, 454% received vancomycin for penicillin-resistant Staphylococcus epidermidis-positive cultures, or because of history of penicillin allergy No difference was observed in the dose per kilogram given to both groups (129 +/- 35 mg/kg per dose in those with red man syndrome vs 123 +/- 69 mg/kg per dose in control children The duration (mean +/- standard deviation) of vancomycin infusion was 459 +/- 167 minutes (range 10 to 90 minutes) in patients with red man syndrome and 545 +/- 76 minutes (range 45 to 65 minutes) in the control group (P = 07) In the 5 children with red man syndrome rechallenged with vancomycin, slower infusion rates prevented or reduced the syndrome, which emphasized the fact that the rate of administration is the important determinant of red man syndrome in susceptible cases Clinically, the syndrome developed at the end of the infusion in most patients, but appeared as early as 15 minutes after initiation of the infusion It was mostly manifested as a flushed, erythematous rash on the face, neck, and around the ears Less frequently, the rash was distributed all over the body Pruritus was usually localized to the upper trunk but was also generalized (2 of 11 children)(ABSTRACT TRUNCATED AT 250 WORDS)

Drug-induced aplastic anemia: pathogenesis and clinical aspects.

Abstract: Drug-induced aplastic anemia is one of the few life-threatening reactions to drugs. Although the majority of reported cases have been associated with chloramphenicol, many drugs have the potential to be toxic to the bone marrow. There are two distinct types of toxicity with differing pathogenic mechanisms--a dose-related reversible marrow aplasia and a dose-independent idiosyncratic aplasia with a high mortality. These two forms of marrow suppression may be difficult to distinguish. The pathogenesis of idiosyncratic marrow aplasia is not well understood. Various studies have demonstrated biochemical, immune, pharmacokinetic, and genetic defects that could affect hematopoietic stem cells. The clinical significance of the reported experimental findings is not established. The prognosis of drug-induced aplastic anemia is similar to that of idiopathic aplastic anemia. Patients with this condition respond to bone marrow transplantation or immunosuppressive therapy in a manner similar to patients with idiopathic marrow aplasia. Many questions regarding drug-induced aplastic anemia remain to be answered; little progress has been made in the last decade.

Determination of Gestational Cocaine Exposure by Hair Analysis

Abstract: Drug self-reports are often unreliable and standard blood and urine tests detect only recent cocaine use Since cocaine is deposited in hair, we have applied a radioimmunoassay to hair extract to detect past cocaine use Hair from 16 adult users was positive for benzoylecgonine, in the presence of negative findings from urine screening tests Benzoylecgonine in admitted heavy users averaged 8775 ng/g of hair (range, 640 to 29 089 ng/g of hair), whereas in occasional users it averaged 624 ng/g of hair (range, 32 to 1210 ng/g of hair) Benzoylecgonine was not detected in hair of 21 adults who reported no use of cocaine ever and whose urine samples were negative for the metabolite Neonatal hair from seven infants whose mothers were known cocaine users averaged 5430 ng of benzoylecgonine per gram of hair (range, 200 to 27500 ng/g of hair) Hair from two infants 25 and 35 months of age averaged 6050 ng of benzoylecgonine per gram of hair However, values were negative for infants 1 year and older, corresponding to loss of fetal hair in the few months after birth Because studies reporting reproductive risks of cocaine compare exposed and nonexposed groups, validation of drug-free status of control subjects is extremely important Hair analysis may remedy the disadvantages of currently used methods and may identify intrauterine exposure to cocaine in babies when a maternal drug history is not available or of doubtful truthfulness (JAMA 1989;262:3328-3330)

Home-based palliative care for children--Part 2: The benefits of an established program.

Abstract: Thirty-four patients have been admitted to our palliative care program since its institution in March 1986. Five were unsuitable and were withdrawn soon after admission. Of the remainder, 22 (75.9%) had central nervous system (CNS) tumors, 5 (17.2%) had myelomeningocoele, 1 (3.45%) had an arteriovenous (AV) malformation, and 1 (3.45%) had a storage disease. Twenty-five (86.2%) have since died and 17 (68%) of these have died at home. In comparison with a similar group of 30 patients studied in a feasibility study prior to the institution of our program, patients admitted to our palliative care program were hospitalized for significantly fewer days during the terminal phase of their illness (p less than 0.05) and a significantly higher proportion died at home (p less than 0.001). Following a survey of the parents of 14 children diagnosed with CNS tumors who died while under our care, we determined that the overall level of satisfaction with the program was high compared to care provided prior to admission to the program (p less than 0.01). Components of the program deemed most satisfactory were (1) being able to care for the child at home (p less than 0.01), (2) having access to a palliative care nurse (p less than 0.05), and (3) having access to a pediatric clinical pharmacologist (p less than 0.05). The most troublesome symptoms occurring in this group of patients were pain, gastrointestinal symptoms, and seizures. Most problems were adequately managed by the parents under the supervision of the team. Eighty percent of the terminal care for these patients was provided at home.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of deferoxamine pharmacokinetics between asymptomatic thalassemic children and those exhibiting severe neurotoxicity.

Abstract: The data suggest that deferoxamine induced neurotoxicity is dose-dependant and cannot be attributed to accumulation of the drug caused bu slower clearance rates.

Diurnal variation in the pharmacokinetics and myelotoxicity of mercaptopurine in children with acute lymphocytic leukemia.

Abstract: During their maintenance therapy, children with acute lymphoblastic leukemia are treated with a daily dose of mercaptopurine for several years. A recent retrospective analysis has suggested that administration of the drug in the evening results in a better prognosis. We compared the disposition pharmacokinetics of mercaptopurine administered in the morning vs in the evening in 13 children with acute lymphoblastic leukemia. Elimination half-life of mercaptopurine was significantly longer in the evening than during the day (423 +/- 142 minutes vs 176 +/- 22 minutes, mean +/- SEM). The area under the concentration-time curve (AUC0-infinity) was significantly larger in the evening (24,713 +/- 3536 ng/mL per minute vs 17,120 +/- 1474 ng/mL per minute). These differences were even more pronounced when comparing the area under the curve of the postdistributive phase (AUC300 min-infinity, 7724 +/- 2955 ng/mL per minute in the evening vs 2597 +/- 712 ng/mL per minute during the day). In a second study, 12 children with acute lymphoblastic leukemia receiving mercaptopurine in the morning had their medication administration switched to the evening. Within 2 weeks there was a sharp fall in peripheral white blood cell counts in all patients (from 4.1 x 10(9)/L to 2.2 x 10(9)/L) mainly due to a drop in polymorphonuclear lymphocytes (from 2.78 x 10(9)/L to 1.05 x 10(9)/L). We conclude that the diurnal variations of mercaptopurine disposition result in clinically important myelotoxicity of the drug.

Simple measurement of captopril in plasma by high-performance liquid chromatography with ultraviolet detection.

Abstract: Captopril is an orally active inhibitor of angiotensin-converting enzyme. A rapid, accurate, and sensitive high-performance chromatography (HPLC) method is described for measuring plasma concentrations of captopril. Captopril was stabilized by forming an adduct with p-bromophenacyl bromide. This adduct was measured by HPLC using a C-18 reverse-phase column and monitoring the column effluent by ultraviolet absorption at 260 nm. The method proved to be linear in the clinical range of 10-1,000 ng/ml. The plasma levels of captopril in a young patient given a small oral dose were determined by this method.

Lead exposure among mothers and their newborns in Toronto

Abstract: Recent studies have suggested that a fetal blood lead level of 0.48 mumol/L (much lower than 1.21 mumol/L, which is the level previously believed to be toxic to the developing brain) may impair brain development permanently. We measured the maternal and umbilical cord blood levels of lead and free erythrocyte protoporphyrin (FEP) among 95 consecutive mother-infant pairs to determine whether neonates in Toronto are in the high-risk group. There was a significant correlation between the maternal and the cord blood lead levels (r = 0.59, p less than 0.0001). Most (99%) of the infants had cord blood lead levels below 0.34 mumol/L; in 11 cases the levels were below the detection limit of 0.01 mumol/L. The cord blood FEP levels were higher than the maternal levels. The US Centers for Disease Control, Atlanta, currently finds acceptable a blood FEP level of 0.62 mumol/L among children up to 10 years of age; however, this is not applicable to newborns since their higher FEP levels apparently reflect immature heme synthesis and increased erythrocyte volume rather than lead poisoning. Our data suggest that living in Toronto does not impose increased teratogenic risk from intrauterine exposure to lead; however, residents in high-risk areas should be followed up.

YBaCuO input coils with low Tc and high Tc SQUIDs

Abstract: We have efficiently coupled single‐level YBaCuO (YBCO) input coils to superconducting quantum interference devices (SQUIDs) using coils and SQUIDs made on separate substrates and sandwiched together. At 4.2 K, the coupling efficiency α to a low noise Nb‐based SQUID was ∼0.76, with no increase in flux noise. At 77 K, the coupling efficiency of a YBCO coil to a TlBaCaCuO SQUID was ∼0.81. The magnetic field sensitivity of the coupled high Tc SQUID at 77 K was 9 pT/√Hz at 1000 Hz, a five times improvement compared to the bare SQUID.

Respiratory response and pharmacokinetics of intravenous salbutamol in infants with bronchopulmonary dysplasia.

Abstract: The effects of iv salbutamol on respiratory mechanics were studied in six infants with bronchopulmonary dysplasia. Salbutamol was infused at a dose of 30 micrograms/kg over 30 min in five infants; a sixth infant received 66.7 micrograms/kg over 4 min. Salbutamol caused improvement in total respiratory system compliance and in airflow resistance. There was no correlation between salbutamol serum concentration and pulmonary function. Elimination half-time appears to be dictated in these infants more by the distribution volume (Vd) than by clearance (Cl). The area under concentration-time curve of salbutamol correlated inversely to the change in heart rate (HR). There was a significant positive correlation between Vd and percent HR change. These data provide evidence that preterm infants have measurable activity of bronchiolar beta 2 receptor responsive to salbutamol.

Clinical course and pharmacokinetics following a massive overdose of amphotericin B in a neonate.

Abstract: Amphotericin is the drug of choice for the treatment of fungal infections in infants and children When used in the recommended doses, amphotericin therapy is associated with high rates of adverse effects, including nephrotoxicity, hepatotoxicity, decrease in white blood cells, platelets and hemoglobin, chills, fever and even death (1) We report a case involving a neonate who was exposed to a 50 fold overdose of Amphotericin over a three day period

Home-based palliative care for children--Part 1: The institution of a program.

Abstract: To assess the necessity and feasibility of introducing a home-based palliative care program for children admitted to our neurosurgical unit and diagnosed as being terminally ill, we conducted an analysis of all such patients admitted to our unit over an 18-month period. Of a total of 30 patients, 22 (73.4%) had central nervous system tumors, 6 (20.0%) had myelomeningocele/hydrocephalus, and 2 (6.6%) had arteriovenous malformations. The mean duration +/- SEM of hospitalized days prior to death and the proportion of time spent hospitalized during the terminal phase of illness were 28.8 +/- 4.77 and 0.327 respectively, for the 23 patients who died and on whom adequate data were available. Sixteen (70.6%) of these 23 patients died in hospital. Nine (30.0%) of the total group of patients were studied prospectively during the last 6 months of this study to determine the extent of their symptoms and to ascertain whether it would be feasible for them to be managed at home. The most troublesome symptoms in this subgroup were feeding difficulties, gastrointestinal symptoms, breathing difficulty, and seizures. These symptoms were managed either by (a) medications administered orally or by feeding tube or rectally, or by (b) noninvasive procedures carried out by a nurse under the direction of the admitting neurosurgeon. This study suggests that prolonged hospitalization for children diagnosed as being terminally ill can be avoided by introducing a home-based palliative program with involvement from a nurse and a physician familiar with drug therapy for terminally ill children.