Environmental toxicants and autism spectrum disorders: a systematic review.

Although the involvement of genetic abnormalities in autism spectrum disorders (ASD) is well-accepted, recent studies point to an equal contribution by environmental factors, particularly environmental toxicants. However, these toxicant-related studies in ASD have not been systematically reviewed to date. Therefore, we compiled publications investigating potential associations between environmental toxicants and ASD and arranged these publications into the following three categories: (a) studies examining estimated toxicant exposures in the environment during the preconceptional, gestational and early childhood periods; (b) studies investigating biomarkers of toxicants; and (c) studies examining potential genetic susceptibilities to toxicants. A literature search of nine electronic scientific databases through November 2013 was performed. In the first category examining ASD risk and estimated toxicant exposures in the environment, the majority of studies (34/37; 92%) reported an association. Most of these studies were retrospective case-control, ecological or prospective cohort studies, although a few had weaker study designs (for example, case reports or series). Toxicants implicated in ASD included pesticides, phthalates, polychlorinated biphenyls (PCBs), solvents, toxic waste sites, air pollutants and heavy metals, with the strongest evidence found for air pollutants and pesticides. Gestational exposure to methylmercury (through fish exposure, one study) and childhood exposure to pollutants in water supplies (two studies) were not found to be associated with ASD risk. In the second category of studies investigating biomarkers of toxicants and ASD, a large number was dedicated to examining heavy metals. Such studies demonstrated mixed findings, with only 19 of 40 (47%) case-control studies reporting higher concentrations of heavy metals in blood, urine, hair, brain or teeth of children with ASD compared with controls. Other biomarker studies reported that solvent, phthalate and pesticide levels were associated with ASD, whereas PCB studies were mixed. Seven studies reported a relationship between autism severity and heavy metal biomarkers, suggesting evidence of a dose-effect relationship. Overall, the evidence linking biomarkers of toxicants with ASD (the second category) was weaker compared with the evidence associating estimated exposures to toxicants in the environment and ASD risk (the first category) because many of the biomarker studies contained small sample sizes and the relationships between biomarkers and ASD were inconsistent across studies. Regarding the third category of studies investigating potential genetic susceptibilities to toxicants, 10 unique studies examined polymorphisms in genes associated with increased susceptibilities to toxicants, with 8 studies reporting that such polymorphisms were more common in ASD individuals (or their mothers, 1 study) compared with controls (one study examined multiple polymorphisms). Genes implicated in these studies included paraoxonase (PON1, three of five studies), glutathione S-transferase (GSTM1 and GSTP1, three of four studies), δ-aminolevulinic acid dehydratase (one study), SLC11A3 (one study) and the metal regulatory transcription factor 1 (one of two studies). Notably, many of the reviewed studies had significant limitations, including lack of replication, limited sample sizes, retrospective design, recall and publication biases, inadequate matching of cases and controls, and the use of nonstandard tools to diagnose ASD. The findings of this review suggest that the etiology of ASD may involve, at least in a subset of children, complex interactions between genetic factors and certain environmental toxicants that may act synergistically or in parallel during critical periods of neurodevelopment, in a manner that increases the likelihood of developing ASD. Because of the limitations of many of the reviewed studies, additional high-quality epidemiological studies concerning environmental toxicants and ASD are warranted to confirm and clarify many of these findings.

Potential amelioration of morbidity in patients with chromosomal anomalies: relevance to Bardet-Biedl syndrome.

Given the genetic basis of their disease, children with major chromosomal abnormalities including Bardet-Biedl syndrome (BBS) are generally considered to have a guarded prognosis with persistence or progression of disease manifestations. Although various therapeutic interventions are commonly used to control signs and symptoms of illness, parents of BBS children are usually cautioned against hoping for sustained improvement. A case of a 21-month-old girl, diagnosed with BBS, manifesting signs of worsening visual impairment, obesity, irascible and disordered behaviour, as well as developmental delay, is presented. After initial evaluation suggested specific biochemical deficiencies, nutritional status correction was undertaken and the patient's signs and symptoms subsequently resolved over the course of several months. To the authors' knowledge, this is the first case report of sustained resolution of all disease manifestations in the face of previously deteriorating health in a young child with this major chromosomal abnormality. It appears that biochemical imbalances and insufficiencies resulting from abnormal metabolism and excretion are potentially amenable to extraordinary dietary supplementation, with partial or complete resolution of clinical abnormalities. It is recommended that all children with chromosomal abnormalities have biochemical and nutritional status evaluation with correction of disordered biochemistry as is possible.

Human detoxification of perfluorinated compounds.

There has been no proven method thus far to accelerate the clearance of potentially toxic perfluorinated compounds (PFCs) in humans. PFCs are a family of commonly used synthetic compounds with many applications, including repelling oil and stains on furniture, clothing, carpets and food packaging, as well as in the manufacturing of polytetrafluoroethylene - a non-stick surfacing often used in cookware (e.g. Teflon(r)). Some PFCs remain persistent within the environment due to their inherent chemical stability, and are very slowly eliminated from the human body due, in part, to enterohepatic recirculation. Exposure to PFCs is widespread and some subpopulations, living in proximity to or working in fluorochemical manufacturing plants, are highly contaminated. PFC bioaccumulation has become an increasing public health concern as emerging evidence suggests reproductive toxicity, neurotoxicity and hepatotoxicity, and some PFCs are considered to be likely human carcinogens. A case history is presented where an individual with high concentrations of PFCs in serum provided: (1) sweat samples after use of a sauna; and (2) stool samples before and after oral administration of each of two bile acid sequestrants - cholestyramine (CSM) and saponin compounds (SPCs). Stool samples before and after use of a cation-exchange zeolite compound were also examined. PFCs found in serum were not detected in substantial quantities in sweat or in stool prior to treatment. Minimal amounts of perfluorooctanoic acid, but no other PFCs, were detected in stool after SPC use; minimal amounts of perfluorooctanesulfonate, but no other PFCs, were detected in stool after zeolite use. All PFC congeners found in serum were detected in stool after CSM use. Serum levels of all PFCs subsequently declined after regular use of CSM. Further study is required but this report suggests that CSM therapy may facilitate gastrointestinal elimination of some PFCs from the human body.

Addressing vitamin D deficiency in Canada: a public health innovation whose time has come.

There is disturbing evidence of widespread vitamin D deficiency in many population groups, particularly within nations at high latitude. Numerous recent studies in the scientific literature associate vitamin D deficiency with a colossal increase in morbidity and mortality. Since Canada is at higher latitude, this review assesses the vitamin D status within the Canadian population. This review was prepared by assessing available medical and scientific literature from Medline, as well as by reviewing several books and conference proceedings. A standard 25(OH)D level of 75-80nmol/l or more was used to indicate vitamin D sufficiency. Between 70% and 97% of Canadians demonstrate vitamin D insufficiency. Furthermore, studies assessing 25(OH)D levels of vitamin D at 25-40nmol/l reveal that many Canadians have profoundly deficient levels. Repletion of vitamin D3 with 2000IU/day for those not receiving judicious sun exposure and those with no contra-indications would likely achieve normalized levels in more than 93% of patients, without risk of toxicity. Explicit directives regarding vitamin D assessment and management are urgently required.

Medical practice and community health care in the 21st century: a time of change.

The contemporary model of evidence-based medicine has not effectively addressed the ubiquitous public health dilemma of escalating chronic illness, and is being challenged by pervasive dissatisfaction among both patients and caregivers. Several recent reports highlight the disturbing problem of deteriorating morale within the medical community, while unprecedented numbers of discontented patients are turning to assorted unconventional therapies in search of help. Although doctor shortages, overwork, increasing regulation and myriad other challenges add to ever-increasing stress, many medical professionals no longer find medicine to be a rewarding vocation and feel ineffective in their work. Recent research, however, highlights innovative clinical strategies using principles from emerging fields, such as molecular medicine and epigenetics, which offer promising outcomes for many chronically ill patients. In this paper, an investigative and aetiologically based approach to clinical practice is presented; a strategy that has resulted in physical and mental health restoration for many patients. Community health applications incorporating disease prevention and health promotion are also discussed.

Time for an oil check: the role of essential omega-3 fatty acids in maternal and pediatric health.

Deficiency of omega-3 fatty acids (omega3FAs) is an often unrecognized determinant of clinical disease; the adequate availability of these essential nutrients may prevent affliction or facilitate health restoration in some pregnant women and developing offspring. The human organism requires specific nutrients in order to carry out the molecular processes within cells and tissues and it is well established that omega3FAs are essential lipids necessary for various physiological functions. Accordingly, to achieve optimal health for patients, care givers should be familiar with clinical aspects of nutritional science, including the assessment of nutritional status and judicious use of nutrient supplementation. In view of the mounting evidence implicating omega3FA deficiency as a determinant of various maternal and pediatric afflictions, physicians should consider recommending purified fish oil supplementation during pregnancy and lactation. Furthermore, omega3FA supplementation may be indicated in selected pediatric situations to promote optimal health among children.

Dismembering the ethical physician.

Physicians may experience ethical distress when they are caught in difficult clinical situations that demand ethical decision making, particularly when their preferred action may contravene the expectations of patients and established authorities. When principled and competent doctors succumb to patient wishes or establishment guidelines and participate in actions they perceive to be ethically inappropriate, or agree to refrain from interventions they believe to be in the best interests of patients, individual professional integrity may be diminished, and ethical reliability is potentially compromised. In a climate of ever-proliferating ethical quandaries, it is essential for the medical community, health institutions, and governing bodies to pursue a judicious tension between the indispensable regulation of physicians necessary to maintain professional standards and preserve public safety, and the support for "freedom of conscience" that principled physicians require to practise medicine in keeping with their personal ethical orientation.

Primary prevention of sexually transmitted disease: applying the ABC strategy.

Escalating rates of sexually transmitted disease (STD) in many areas of the world necessitate a re-evaluation of current public health STD preventive programmes. Pervasive long term sequelae for many STD afflicted people and the emerging threat, caused by the HIV/AIDS pandemic, to some national infrastructures, suggests that ongoing initiatives focusing primarily on risk reduction through barrier protection have not met their desired objective. Recent strategies to promote non-coital sexual involvement as a means of achieving STD reduction fail to address the transmission of infection that may occur through alternative non-intercourse sexual activities. The demonstrated success of the innovative, comprehensive ABC strategy shows that while risk reduction and treatment of existing infection remain important, the promotion of optimal health may be achieved more effectively through broad based comprehensive and adaptable programmes that include an emphasis on risk avoidance through delayed sexual debut and partner reduction.

Orgasm without organisms: science or propaganda?

The worldwide epidemic of sexually transmitted diseases (STDs) presents a major public health challenge to medical practitioners and educators as they seek to implement preventive educational strategies in the adolescent population. The serious consequences of many STDs and the insufficient impact of condom promotion in this high-risk group have led to increasing recognition that sexual intercourse is medically unwise for young adolescents. As a result of this recognition, some educators have proposed that adolescent sexuality education focus on the explicit teaching of noncoital sexual activities, sometimes called outercourse. This paper explores the emergence of this educational strategy, the assertion that noncoital sexual activities will positively impact the rising incidence of STDs and unplanned pregnancy in teenagers, and the hypothetical benefits of adolescent noncoital sex.

Public attitudes toward the right to die.

OBJECTIVE: To determine public attitudes toward the right to die, euthanasia and related end-of-life decisions. DESIGN: Mail survey based on telephone numbers randomly selected by computer. SETTING: Edmonton. PARTICIPANTS: Of 1347 computer-generated, randomly selected telephone numbers called between February and June 1992, 902 individuals were reached, and 500 eligible contacts (55%) agreed to fill out the mailed questionnaire based on 12 vignettes involving end-of-life decisions. A total of 356 usable questionnaires (71%) were subsequently returned. MAIN OUTCOME MEASURES: Attitudes toward end-of-life decisions including withdrawal of life support, euthanasia, chronic suffering and the right to die, living wills and family involvement in decision making for incompetent individuals. Comments and demographic data were also solicited. RESULTS: Of the respondents 84% supported a family's right to withdraw life support from a patient in a persistent coma, and 90% supported a mentally competent patient's right to request that life support be withdrawn. Active euthanasia was supported by 65% for only patients experiencing severe pain and terminal illness. There was marked opposition to euthanasia for patients in other circumstances, such as an elderly disabled person who feels he or she is a burden on relatives (opposed by 65%), a patient with chronic depression resistant to treatment (by 75%) or an elderly person no longer satisfied with life and who has various minor physical ailments (by 83%). In all, 63% of the respondents felt that legalization of euthanasia for terminal illnesses would lead to euthanasia for many other, unsupported reasons, and 34% supported legislation to prohibit euthanasia in all situations. CONCLUSIONS: Public support for the right to die varies depending on the circumstances of the patient. The single most significant factor determining attitudes was the level of religious activity. The family's wishes were an important factor in end-of-life decisions for patients unable to communicate their desires. Both the general public and physicians should be primary participants in determining legislation regarding the right to die.

Public attitudes in Edmonton toward assisted reproductive technology.

OBJECTIVE: To determine public attitudes toward the use and possible limitations of assisted reproductive technology (ART). DESIGN: Mail survey based on telephone numbers selected at random by computer. SETTING: Edmonton. PARTICIPANTS: A total of 602 Edmonton residents aged 16 years or more (57% of eligible subjects) reached by telephone agreed to participate. Completed questionnaires were received from 455 subjects (76%). MAIN OUTCOME MEASURES: Attitudes toward egg donation, sperm donation, selective fetal reduction, embryo freezing and experimentation, and surrogacy, as determined through responses to five cases. Comments and demographic data were also solicited. MAIN RESULTS: Overall, 66% and 63% respectively of the respondents would donate an egg or sperm to a sibling; the corresponding rates for donation to a stranger were 41% and 44%. Selective fetal reduction was supported by 47% of the respondents, although only 24% would support fetal reduction to eliminate fetuses of an undesired sex. Most (64%) thought that live embryo freezing should be permitted by law. A total of 74% agreed with surrogacy if done for medical reasons, but 85% opposed its use for reasons of convenience. Overall, 72% of the respondents thought that ART should be regulated. A total of 58% felt that physicians should be primarily responsible for determining the allowable limits of this technology, and 38% felt that the public should be primarily responsible. Only 21% agreed with public funding of ART. Religious affiliation strongly influenced attitudes toward ART. CONCLUSIONS: Public support for ART varies depending on the circumstances of its use. Education is needed to make the general community aware of the various aspects of ART. The results of this survey should help physicians and governing bodies make informed decisions about the future directions of ART in Canada.