Showing papers by "Hospital for Sick Children published in 2000"

Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD)

Abstract: A recent study demonstrated that treatment of hyperactive mice with psychostimulants and serotonergic agents produced a calming effect that was dependent on serotonergic neurotransmission and was not associated with any changes in extracellular dopamine levels.1 The complex interaction between the serotonergic and dopaminergic neurotransmitter systems suggests that a balance between the two systems may be necessary for mediating hyperactive behaviour. Defects in serotonin system genes, therefore, may disrupt normal brain serotonin function causing an imbalance between these neurotransmitter systems leading to the development of attention deficit hyperactivity disorder (ADHD). Using the transmission disequilibrium test (TDT), the current study assesses for linkage disequilibrium between polymorphisms in the serotonin HTR2A receptor gene and ADHD. One hundred and fifteen families with a total of 143 children diagnosed with ADHD (DSM-IV) were genotyped for the His452Tyr and the T102C polymorphisms in the serotonin HTR2A receptor gene. TDT analysis revealed a preferential transmission of the 452Tyr allele to the affected offspring (P = 0.03), suggesting linkage disequilibrium of this polymorphism with ADHD. This may open a new door in ADHD molecular genetics research, expanding the existing view of a catecholaminergic hypothesis to include a serotonergic hypothesis and should help elucidate the complex interplay among the neurotransmitter systems in the etiology of ADHD.

Effect of premedication guidelines and leukoreduction on the rate of febrile nonhaemolytic platelet transfusion reactions.

Abstract: Platelet transfusion reactions were prospectively studied in haematology/oncology patients at five university teaching hospitals over three consecutive summers. The initial summer study provided baseline information on the use of premedications and the rate of platelet transfusion reactions (fever, chills, rigors and hives). Most (73%) platelet recipients were premedicated and 30% (95% CI 28-33%) of transfusions were complicated by reactions. The second study followed implementation of guidelines for premedicating platelet transfusions. Despite a marked reduction in premedication (50%), there was little change in the platelet transfusion reaction rate, 26% (95% CI 24-29%), or the type of reactions. The third study followed implementation of prestorage platelet leukoreduction while maintaining the premedication guidelines. The reaction rate decreased to 19% (95% CI 17-22%). For nonleukoreduced platelets, there was a statistically significant association between the platelet age and reaction rate (P = 0.04). For leukoreduced platelets, there was no statistically significant association between platelet age and reaction rate (P = 0.5). Plasma reduction of nonleukoreduced platelet products also reduced the reaction rate. These prospective studies document a high rate of platelet transfusion reactions in haematology/oncology patients and indicate premedication use can be reduced without increasing the reaction rate. Prestorage leukoreduction and/or plasma reduction of platelet products reduces but does not eliminate febrile nonhemolytic platelet transfusion reactions.

How High-Functioning Children with Autism Understand Real and Deceptive Emotion

Abstract: Autism is associated with problems in understanding and expressing emotion. We compared the ability of eight high- functioning children with autism (i.e. those with IQ scores ≥ 70) and eight age- and gender-matched controls with similar oral language development, to understand the facial expression of real and deceptive emotion. Children with autism had limited understanding of socially derived emotion. Although they could relate emotions to standard facial expressions, they were less able than controls to indicate the real emotions story characters feel, the deceptive emotions they express in the face, or the social reasons prompting a deceptive facial expression. For high- function children with autism, facial expressions may function as lexical codes but not as forms of social communication that modify beliefs.

Localized drug delivery using crosslinked gelatin gels containing liposomes: Factors influencing liposome stability and drug release

Abstract: We describe a drug-delivery vehicle that combines the sustained release properties of liposomes with the structural advantages of crosslinked gelatin gels that can be implanted directly or coated onto medical devices. Liposome inclusion in gelatin gels does not compromise thermal stability nor does it interfere with the resiliency of gels to tensile force. However, electron spin resonance analysis of sequestered DPPC liposomes revealed a slight depression (ca. 1.0 degrees C) of the gel-to-fluid phase transition relative to liposomes in suspension. The level of liposome release from gels was determined by liposome concentration, liposome size, and the presence of poly(ethylene oxide) chains in the gel matrix or in the liposome membrane. Both neutral and charged liposomes displayed relatively high affinities for poly(ethylene glycol)gelatin gels, with only 10-15% release of initially sequestered liposomes while liposomes in which poly(ethylene glycol) was included within the membrane were not as well retained (approximately 65% release). The in vitro efflux of ciprofloxacin from liposomal gels immersed in serum was nearly complete after 24 h compared to 38% release of liposomal chlorhexidine after 6 days. The serum-induced destabilization of liposomal ciprofloxacin depended on the accessibility of serum components to gels as partly immersed gels retained approximately 50% of their load of drug after 24 h. In vivo experiments using a catheterized rabbit model of urinary tract infection revealed the absence of viable Escherichia coli on coated catheter surfaces in seven out of nine cases while all untreated catheter surfaces examined (n = 7) were contaminated.

Measuring population health: correlates of the Health Utilities Index among English and French Canadians.

Abstract: This study used cross-sectional data from the 1994/95 National Population Health Survey (NPHS) in Canada. The objective of the study was to examine the relationship between several established correlates of health status in the general population and the Health Utilities Index (HUI), a multi-dimensional, preference-based measure of health status. Analyses were carried out separately for the English-speaking (n = 9,853) and French-speaking (n = 1,519) respondents. The index correlated strongly with self-ratings of health status and functional disability and varied as expected according to age, sex, and income. Subjects classified to different categories of chronic conditions reported different levels of health, as predicted. The HUI was also associated with the use of drugs and recent history of hospitalization. No major differences in the findings were observed between the two cultural groups. The results should be treated with caution due to the cross-sectional design and other methodological limitations of the study.

Type II Citrullinemia (Citrin Deficiency): A Mysterious Disease caused by a Defect of Calcium-Binding Mitochondrial Carrier Protein

Abstract: Citrullinemia (OMIM 215700) (McKusick, 1998) is an autosomal recessive disease that is caused by a deficiency of argininosuccinate synthetase (ASS; EC 6.3.4.5). The clinical, biochemical and molecular aspects of citrullinemia have been reviewed elsewhere (Walser, 1983; Saheki et al., 1987a; McKusick, 1998). So far, we have analyzed almost 200 patients with citrullinemia in our laboratory and have classified them into three types according to enzyme abnormality and into two forms according to pathogenesis (Figure 1) (Saheki et al., 1981, 1985a, 1987a, b; Kobayashi et al., 1993, 1999). The first form is the classical form (CTLN1) found in most patients with neonatal/infantile-onset citrullinemia (type I and type III), first described by (1962); the second form is the adult-onset type II citrullinemia (CTLN2) caused by a liver-specific ASS deficiency. In CTLN1, the enzyme defect is found in all tissues and cells in which ASS is expressed (Saheki et al., 1980, 1981, 1982, 1983a, 1985a, b, 1987a, b). To date, we have identified 36 mutations in the ASS gene located on chromosome 9q34 and have clarified the pathogenesis of most CTLN1 patients at the molecular level (Kobayashi et al., 1987, 1990, 1991, 1994, 1995a; Kakinoki et al., 1997).

The Art, Science, and Technology of Pharmaceutical Compounding

Abstract: The Art Science And Technology The Art, Science, and Technology of Pharmaceutical Compounding presents in a logical and progressive format all the information that pharmacists and student pharmacists need to understand the purpose and processes of compounding. Author Loyd V. Allen Jr., the preeminent expert, covers basic guidelines, economic and technical factors that compounding pharmacists must consider, and all aspects of good manufacturing practices for compounded medications.

Storage conditions of avulsed teeth affect the phenotype of cultured human periodontal ligament cells.

Abstract: After severe injury to the periodontal ligament (PL), the phenotypes of cells recolonizing root surfaces influence the extent and type of repair processes. In teeth that are replanted following avulsion injury, recolonization of the PL space by osteogenic cells instead of by PL fibroblasts may favor bone formation (i.e. ankylosis) instead of PL regeneration. We consider here that recolonization processes depend in part on the storage conditions of the teeth following avulsion. We used an in vitro cell culture model to assess the effect of storage conditions on immunohistochemical staining of several marker proteins that are expressed by osteogenic cells (osteopontin and alkaline phosphatase) and fibroblasts (alpha-smooth muscle actin, type III and XII collagens). Prior to cell culture, extracted human premolar teeth were stored in air ("dry") or in alpha-MEM ("wet") for either 30 or 120 min as surrogate conditions for the variations of extra-alveolar tooth storage that may occur following avulsion. Collagenase/trypsin-digested suspensions of PL cells were prepared from the tissue adherent to the extracted root surface. Passage #2 or #3 cultures were immunostained and examined by fluorescence microscopy. For type XII collagen, cells from wet samples displayed perinuclear staining while cells from 30-min dry samples showed only isolated foci. The staining for 120-min dry samples was weak and non-specific. alpha-Smooth muscle actin was not incorporated into stress fibers in wet samples, whereas dry samples demonstrated prominent stress fibers stained for alpha-smooth muscle actin. Detached cytoplasmic fragments resembling cell processes that stained for alpha-smooth muscle actin were abundant in dry samples, indicating the presence of highly contractile cells. The staining for osteopontin was mainly perinuclear but was more intense in dry samples. The focal adhesion pattern of osteopontin staining in 120-min dry samples resembled that of migrating osteogenic cells. The pattern of staining did not vary for type III collagen or alkaline phosphatase, although staining for alkaline phosphatase was more intense in samples stored under dry conditions. We conclude that prolonged extra-alveolar dry storage favors increased in vitro growth of contractile cells expressing osteogenic cell markers while storage in cell culture medium favors growth of cells with the classical phenotype of PL fibroblasts.

Which drugs are contraindicated during breastfeeding? Practice guidelines.

Abstract: QUESTION: Many breastfeeding mothers are concerned about taking medications that might affect their babies. Are there any guidelines on which drugs are safe? ANSWER: Only a few drugs pose a clinically significant risk to breastfed babies. In general, antineoplastics, drugs of abuse, some anticonvulsants, ergot alkaloids, and radiopharmaceuticals should not be taken, and levels of amiodarone, cyclosporine, and lithium should be monitored.

Critical appraisal of drug therapy for nausea and vomiting of pregnancy: II. Efficacy and safety of diclectin (doxylamine-B6).

Abstract: Nausea and vomiting of pregnancy is the most common condition in pregnancy and affects up to 80% of all pregnant women. There are a large number of pharmacological agents that are effective for the treatment of nausea and vomiting associated with conditions such as motion sickness and gastrointestinal conditions; however, their use in pregnancy is limited by the lack of sufficient data on their potential teratogenic effects. The efficacy of the delayed-release combination of doxylamine and pyridoxine (Bendectin, Diclectin) has been shown in several randomized, controlled trials. The present review aims to refute the unsubstantiated beliefs that Diclectin is unsafe when used in the treatment of nausea and vomiting of pregnancy.

Occupational exposure to inhaled anesthetic. Is it a concern for pregnant women

Abstract: QUESTION: Two of my pregnant patients are exposed to inhaled anesthetic on the job. One is an anesthetist, and the other is a veterinarian. They have both expressed concern about this exposure. How should I advise them? ANSWER: Occupational exposure to waste anesthetic gas is not associated with increased risk of major malformations. Risk of spontaneous abortion might be slightly increased, however. This risk can be reduced, if not eliminated, by good gas scavenging systems.

Nosocomial transmission of tuberculosis (TB) associated with care of an infant with peritoneal TB.

Abstract: Nosocomial transmission of tuberculosis (TB) after exposure to infected peritoneal fluid has not been described. We report the exposure of 111 healthcare workers to infected dialysate from an infant with TB peritonitis. Two (5%) of 39 primary-care nurses, but no doctors or environmental service workers, had apparent tuberculin skin test conversions, raising the concern that patients with peritoneal TB may be a source for nosocomial transmission of TB.

Caffeine during pregnancy? In moderation.

Abstract: QUESTION: Many of my female patients, those who plan pregnancy or have conceived, are afraid of any intake of caffeine. This often makes their lives miserable during pregnancy. Is this justified scientifically? ANSWER: Motherisk's recent meta-analysis suggests that the risks for miscarriage and fetal growth retardation increase only with daily doses of caffeine above 150 mg/d, equivalent to six typical cups of coffee a day. It is possible that some of this presumed risk is due to confounders, such as cigarette smoking.

Longitudinal change in the treatment of nausea and vomiting of pregnancy in Ontario.

Abstract: BACKGROUND: Health problems associated with untreated nausea and vomiting of pregnancy (NVP) include maternal weight loss, dehydration, and electrolyte and acid-base disturbances. Negative social consequences include the deterioration of domestic, social and occupational function of the affected women. In 1994 it was documented that most physicians in Ontario tended not to treat women with NVP pharmacologically. PURPOSE: To investigate the longitudinal change in therapeutic practice of physicians, with respect to the treatment of NVP. SUBJECTS AND METHODS: A questionnaire was distributed to a randomly selected sample of physicians that included community-based family physicians, hospital-based family physicians, obstetricians and physicians who called the Motherisk Program for information. The participants were questioned about their choices in the pharmacological treatment of NVP. The data from the survey were compared with those from a previously published survey conducted in 1994. RESULTS: In 1999, 90.2% of physicians surveyed reported to have used pharmacological means to treat NVP. In 1999, 95% of the physicians surveyed reported to have prescribed doxylamine succinate-pyridoxine hydrochloric acid (Diclectin), and 11% prescribed dimenhydrinate (Gravol) to treat NVP. These results are significantly different from those found in 1994 (90% prescribed Gravol as the first choice). CONCLUSIONS: In 1999, temporally related to various educational efforts, physicians offered treatment for NVP more readily, including the drug recommended by the regulatory agency. These changes may explain in part the recently documented decrease in hospitalizations due to NVP in Canada.

Human mapping databases.

Abstract: This unit concentrates on the data contained within two human genome databasesGDB (Genome Database) and OMIM (Online Mendelian Inheritance in Man)and includes discussion of different methods for submitting and accessing data. An understanding of electronic mail, FTP, and the use of a World Wide Web (WWW) navigational tool such as Netscape or Internet Explorer is a prerequisite for utilizing the information in this unit.

Controversies in antenatal corticosteroid treatment.

Abstract: QUESTION: I am following up a former preterm infant, born at 29 weeks' gestation after premature labour. This infant had a relatively benign hospital course and when discharged was not thought to have any complications of prematurity. Despite this, at 1 year old his neurologic examination is abnormal: head circumference is on the 3rd percentile for age (weight on the 25th percentile), and he has increased tone in his lower legs and a moderate developmental delay. His discharge letter indicated that he was exposed antenatally to many doses of dexamethasone. Could this have adversely influenced his neurologic outcome? ANSWER: Antenatal steroids are proven therapy for preventing respiratory distress syndrome and decrease both morbidity and mortality associated with prematurity. Use of multiple doses of antenatal steroids might adversely affect neurologic outcome. There is insufficient evidence to support routine use of multiple doses of antenatal steroids when delivery of a preterm infant is anticipated.

Sturge-Weber syndrome.

Abstract: I have no intention of going into the difficult question of the pathology of port-wine mark. The point to which I wish to call particular attention is the probable relationship between the mark and...

Can we use metronidazole during pregnancy and breastfeeding? Putting an end to the controversy.

Abstract: QUESTION: Two of my patients have been diagnosed with giardiasis, and I would like to treat them with the drug of choice for this infection, metronidazole (Flagyl). One of them is 6 weeks pregnant and the other is breastfeeding a 2-month-old infant, and I have received conflicting information about the safety of this drug during pregnancy and breastfeeding. What should I do? ANSWER: Although metronidazole has been on the market for almost 40 years, its use remains controversial during pregnancy and breastfeeding. Recent evidence has shown, however, that this drug is not associated with adverse effects during either pregnancy or breastfeeding.

Zopiclone use during pregnancy.

Abstract: QUESTION: One of my patients, whom I had treated with a 2-week course of zopiclone for insomnia, conceived while using the medication. She is concerned. How should I advise her? ANSWER: Based on available, albeit limited, evidence, zopiclone does not appear to be a major human teratogen.

Human serum induces apoptosis of xenogenic cardiomyocytes in vivo and in vitro.

Abstract: Discordant xenotransplantation is complicated by delayed xenograft rejection (DXR). Previous studies have demonstrated that anti-apoptotic genes are protective against DXR. This study examines the hypothesis that apoptosis plays a role in human anti-xenograft responses. C57BL/6 mice and NOD SCID mice were given a single intravenous injection of either a lethal dose (LD, survival 0.05) alter the percentage apoptosis. The addition of 20 mM Gal-alpha-1,3-Gal to SLD 18 h significantly (P < 0.05) reduced percentage apoptosis to levels comparable to saline treated control animals. In vitro using mouse and pig cardiomyocytes demonstrated parallel results as in vivo experiments. Human serum induces apoptosis of cardiomyocytes in immunocompetent and immunoincompetent mice in vivo, as well as mouse and pig cardiomyocytes in vitro. Further, this apoptotic response can be inhibited by the addition of Gal-alpha-1,3-Gal without affecting the capacity of the serum to cause HAR. These results demonstrate that a putative human serum factor induces a delayed apoptotic injury of xenograft tissues, and supports the hypothesis that apoptosis may be an important mediator of DXR.

Varicella virus vaccine before pregnancy. Important breakthrough in protecting fetuses.

Abstract: QUESTION: Now that the new varicella virus vaccine is available, should I vaccinate all my female patients of reproductive age who do not remember having had chickenpox in childhood? ANSWER: In North America, seven out of 10 women who do not remember having chickenpox in childhood actually had it and are immune. You should test their immunity and, if they are susceptible, vaccinate them. Ensure they are not pregnant at the time of vaccination because the vaccine's safety has not been proven.

Does breastfeeding have an effect on intelligence

Abstract: QUESTION: A young mother under my care is concerned because she has decided not to breastfeed and was told by several people that formula feeding will cause the baby not to be "as smart." Is this based on real science? ANSWER: Studies during the last decade have shown breastfeeding to be associated with higher intelligence in young children. Better controlled and more recent studies have shown that this association is probably not proof of causation, because mothers who decide to breastfeed tend to be better educated and more socioeconomically advantaged than those who decide to use formula. After controlling for these differences, the effect tends to disappear.

Appraisal of drug therapy for nausea and vomiting of pregnancy: I. The placebo effect - methodological and practical considerations.

Abstract: BACKGROUND Despite that nausea and vomiting of pregnancy (NVP) is the most common medical problem during pregnancy, the placebo effect in the treatment of this condition has not been properly evaluated. METHODS Two published randomized, controlled trials comparing the antiemetic effects of vitamin B6 with placebo were analyzed. RESULTS When the severity of nausea or vomiting in the placebo groups at baseline was compared with that at the end of the trials, there was a clear time-dependent placebo effect that peaked between days 4 and 5. The placebo effect appeared to be more pronounced in nausea than in vomiting. CONCLUSIONS There is a clear placebo effect on NVP. The effect appears to be stronger with nausea than with vomiting.

Antenatal phenobarbital for prevention of intraventricular hemorrhage in preterm infants.

Abstract: QUESTION: One of my patients, a 36-year-old, who has had three pregnancies and two live births, delivered her third baby at 32 weeks' gestation. Her first pregnancy was complicated by premature labour, which led to delivery at 30 weeks' gestation. She received antenatal phenobarbital before the first delivery because it was considered proven therapy for preventing intraventricular hemorrhage in preterm infants. I would like to know why it is no longer routinely used. ANSWER: Cumulative results from recent studies have failed to confirm the initial impression of effectiveness of antenatal phenobarbital. It is no longer recommended when preterm delivery is anticipated.

Canada and Japan

Abstract: SIDS is the main cause of postnatal infant death. SIDS occurs characteristically in early infancy and during sleep. The causes and mechanisms of death in SIDS have not been elucidated in SIDS infants. We found subcortical leukomalacia in the cerebral white matter and reactive astrogliosis in the brainstem tegmentum, developmental delay of dendritic spines, increase of substance P, and decrease of catecholaminergic and serotonergic neurons in the respiratory centers of the brainstem. From these results we proposed a chain of events each having the potential to increase the vulnerability of the delicate balance of cardiorespiratory control so that a minor triggering terminal event could produce sudden death. Down syndrome (DS) is caused by trisomy of the DSobligate region in chromosome 21, and is manifested clinically by multiple somatic anomalies, mental retardation and precocious dementia. Our pathological examinations of DS brains revealed poor development of synapses in cortical neurons, atrophy of the dendrites with age and the precocious appearance of senile plaques. The pathogenesis of intellectual disabilities is not clear but the overexpression of genes on the DSobligate region appears to alter dendritic development and set the stage for the later occurrence of Alzheimertype dementia. Recent publications are shown in references 1–24. In addition, K Washiyama, K Watabe, J Satoh, M Mizuguchi and M Yamada worked with Prof. SU Kim and published many papers. A very successful Japanese and Canadian International Workshop on ‘development of synaptic transmission in mental retardation’ was held on 6 and 7 March 1997 in Tokyo, Japan. The symposium was organized with the support of the Ministry of Technical Agency and National Center of Neurology and Psychiatry in order to review the recent progress of neurobiological, neurological and neuroradiological research on development of synaptic transmission in mental retardation. The recent progress of molecular biology and neuroimaging is striking. The proceedings of this workshop were published as ‘Development of synaptic transmission in mental retardation’. Neuropathology 2000; 20, S127–S128

Serving Children with HIV/AIDS in Canadian Public Schools: An Interpretation of the CPA Guidelines for Non-Discriminatory Practice

Abstract: As a result of recent advances in HIVIAIDS treatments, the near future will bring a significantly increased number of children either infected with - or affected by - HIV/AIDS into public schools i...