Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons.

The ability to detect environmental cold serves as an important survival tool. The sodium channels NaV1.8 and NaV1.9, as well as the TRP channel Trpm8, have been shown to contribute to cold sensation in mice. Surprisingly, transcriptional profiling shows that NaV1.8/NaV1.9 and Trpm8 are expressed in nonoverlapping neuronal populations. Here we have used in vivo GCaMP3 imaging to identify cold-sensing populations of sensory neurons in live mice. We find that ∼80% of neurons responsive to cold down to 1 °C do not express NaV1.8, and that the genetic deletion of NaV1.8 does not affect the relative number, distribution, or maximal response of cold-sensitive neurons. Furthermore, the deletion of NaV1.8 had no observable effect on transient cold-induced (≥5 °C) behaviors in mice, as measured by the cold-plantar, cold-plate (5 and 10 °C), or acetone tests. In contrast, nocifensive-like behavior to extreme cold-plate stimulation (-5 °C) was completely absent in mice lacking NaV1.8. Fluorescence-activated cell sorting (FACS) and subsequent microarray analysis of sensory neurons activated at 4 °C identified an enriched repertoire of ion channels, which include the Trp channel Trpm8 and potassium channel Kcnk9, that are potentially required for cold sensing above freezing temperatures in mouse DRG neurons. These data demonstrate the complexity of cold-sensing mechanisms in mouse sensory neurons, revealing a principal role for NaV1.8-negative neurons in sensing both innocuous and acute noxious cooling down to 1 °C, while NaV1.8-positive neurons are likely responsible for the transduction of prolonged extreme cold temperatures, where tissue damage causes pan-nociceptor activation.

The medical review officer.

The role and responsibilities of the medical review officer are considered in relation to drug testing in the workplace. Knowledge of substance abuse disorders, pharmacology and toxicology, laboratory techniques for screening and confirmation, forensic collection techniques, and the relevant rules and regulations that govern drug testing is essential. The means for detecting adulterated urine samples are offered, and a procedure for the management of urine-testing results is provided.

Diagnosis and treatment of adolescent substance abuse.

Robert L. DuPont, M.D., the founding director of the National Institute on Drug Abuse and former president of the American Council for Drug Education, made the following comments regarding this monograph: In terms of thinking about treatment, there are several principles that underlie all successful approaches: (1) First is the use of education. They tell drug-dependent youth and their families what is wrong and what to do about the problem. This is in dramatic contrast to the traditional psychotherapy approach, which relies on such techniques as "Tell me what you think." (2) Successful programs insist on drug-free living without compromise. (3) They involve the family actively in the treatment, reinforcing the health of the family rather than focusing on its pathology. Often this is done in family groups. (4) They have substantial duration and intensity. They are not brief or casual. (5) They reinforce prosocial, community-based values and lifestyles (love, duty, hard work, caring for others, etc.). (6) They have structure--a beginning, a middle, and an end (or "steps" or "stages"). Treatment of drug use will vary depending on stage of involvement, community resources, and desired goals of therapy. The bottom line in the evaluation of any treatment plan is its long-range effectiveness in reaching desired goals. What seems least conservative in therapy may, in fact, be the most conservative if less rigorous approaches lead to failure or delay of recovery.

An approach to the problem of teenage pregnancy.

Sex education continues to gain prominence as a critical factor in current challenges to the nation's public health. Adolescent pregnancy, with its frequently adverse consequences for the health and well-being of both mother and child, has reached unprecedented levels in the United States, and AIDS now threatens society in its entirety. Despite awareness that effective sex education is essential to combatting these problems, current debates, focused on the content and timing of sex education provided in the schools, are shortsighted. As currently practiced in this country, sex education curriculums convey the wrong message and are targeted to the wrong audience. In emphasizing the provision of data to youth, we ignore the fact that parental guidance and direction are more often helpful than data and options. Yet we fail to provide parents and others who comprise the traditional systems of child care and nurturance with the information they require to assume responsibility for the safe and healthy development of children and youth. Understanding the reasons for the failure of conventional sex education provides a foundation for developing a more effective approach to preventing adolescent pregnancy. Defining an effective message and targeting information to the appropriate audience are necessary to effect a significant reduction in premature sexual behavior among adolescents.

Patterns of alcohol and drug use among adolescents.

Trends and patterns in adolescent use of alcohol and other drugs over the past two decades are described. The pediatrician's role in preventing and treating drug use is also discussed.

Children of alcoholics.

One of every eight American children is the child of a parent who has a past or present drinking problem. Children of alcoholic parents are at great risk. They are significantly more likely to develop addiction problems and a variety of mental health disorders. They live in homes with high levels of stress. Poor communication, permissiveness, undersocialization, neglect, and violence are common and can be truly devastating. Because of the stigma and denial associated with chemical dependency, these children often suffer in silence, unidentified and unassisted.

Prevention of adolescent smoking and drug use.

Smoking drinking, and the use of psychoactive substances are prevalent among adolescents. Significant morbidity and mortality are related to this use. Initiation to these substances occurs at ages younger than ever before. The pediatrician can and should play a major role in reversing the epidemic of adolescent substance abuse. The "5As for Action" provide a strategy with which pediatricians can exert influence on youngsters, parents, and the community in preventing drug abuse in this age group.

Alcohol abuse, other drug abuse, and mental disorders in medical practice. Prevalence, costs, recognition, and treatment.

Millions of Americans suffer and die of alcohol abuse, other drug abuse, and mental disorders that go undiagnosed and untreated. Studies showing that up to 19% of the US adult population have these disorders also have found that only one fifth of those affected have sought help for them in the previous six months. Many of these persons have disorders that are treatable with modern medications and therapy. Because more than half of all persons with these disorders obtain all of their care from the general medical sector, a great potential exists in primary care for prevention, detection, treatment, and referral of these patients. Primary care physicians, however, have not been very successful at diagnosing and treating substance abuse and mental disorders because of inadequate training, patients' attitudes, and the constraints of the health care system. Recommendations to improve this situation include continued research, improved physician education, and increased emphasis on care of these disorders by organized medicine. Although tobacco use is also a major health problem, data relating to nicotine addiction were not included in this report.

Drug abuse in adolescents. When to intervene, how to help.

Abuse of alcohol and other drugs by adolescents is a major societal problem. For many adolescents, drug use signals departure from childhood and acceptance by peers. Diagnosis is often difficult and depends on a high index of suspicion and an understanding of the typical clinical and psychological course of drug use. Family involvement in treatment is vital and directly affects recovery rates of adolescent drug abusers. An effective treatment program insists on abstinence, and peer group involvement is extremely valuable. Careful follow-up is essential to prevent or detect relapse.

Drugs, drinking, and adolescence.

Despite mounting evidence to the contrary, most physicians do not want to believe that a drug epidemic involving children from all socioeconomic classes across the country is in progress. Prevention efforts are hindered by massive denial at all levels--societal, medical, and parental. Reasons for this denial are many; among them are misconceptions about the risks of experimentation and effectiveness of drug treatment programs, and a tendency to view drug abuse as a moral rather than a health problem. The use of alcohol and other drugs is closely related to rising mortality in older adolescents, for whom the leading causes of death are accidents, suicide, and homicide. The leading causes of disability in this age range are chemical dependency and impairments related to accidents. Chemical dependency, which has trapped millions of children, is best regarded as a progressive, contagious disease that causes serious problems for young people, their families, and society. Pediatricians, well skilled in preventive medicine, must address more seriously this epidemic killer and disabler of young people whose care has been entrusted to them.