Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p.

A heterogeneous group of neurological disorders known as the spinocerebellar ataxias (SCA) are characterized by degeneration of the cerebellum, spinal cord and brainstem. We describe linkage analysis in four unusual SCA families revealing a distinct disease locus on chromosome 3p14-21.1. The disease in these families is distinguished from other forms of SCA by concomitant retinal degeneration. Initial visual problems leading to blindness, disabling ataxia and anticipation are seen in all kindreds. The anticipation in these families suggests a dynamic mutation at this locus. Eventual molecular characterization of this disease may provide valuable insights into the processes of both neural and retinal degeneration.

Stakeholder Assessment of Evidence-Based Guideline Dissemination and Implementation in a Dental Group Practice.

OBJECTIVE: This evaluation captures the perspectives of multiple stakeholders within a salaried dental care delivery organization (dentists, dental assistants, dental hygienists, and dental management) on the implementation of a pit-and-fissure sealant guideline in the Kaiser Permanente Dental Program. Also assessed is the role of formal processes and structures in providing a framework for guideline implementation. METHODS: We collected qualitative data through field observations, stakeholder interviews (n = 6), and focus groups (30 participants in 5 focus groups). Field observation notes captured summaries of conversations and other activities. Interviews and focus groups were recorded and transcribed. We analyzed transcripts and field notes using a template analysis with NVivo 12 software to identify themes related to the existing implementation process of clinical guidelines and stakeholder perspectives on the strengths and weaknesses of this process. RESULTS: Stakeholders perceived 2 main barriers for achieving implementation of the pit-and-fissure sealant guideline: 1) shortcomings in the implementation infrastructure resulting in lack of clarity about the roles and responsibilities in the guideline implementation process and lack of effective mechanisms to disseminate guideline content and 2) resource constraints, such as limited human, space, and material resources. Perceived opportunities for the dissemination and implementation of guidelines included recognition of the importance of guidelines in dental practice and well-functioning workflows within dental specialties. CONCLUSION: Our research points to the importance of developing and maintaining an infrastructure to ensure standardized, predictable mechanisms for implementation of guidelines and thereby promoting practice change. While addressing resource constraints may not be possible in all circumstances, an important step for improving guideline implementation-wherever feasible-would be the development of a robust implementation infrastructure that captures and delineates roles and responsibilities of different clinical actors in the guideline implementation process. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by health care leadership and administrators to understand possible reasons for a lack of guideline implementation and provide suggestions for establishing sustainable infrastructure to promote the adoption of clinical guidelines in salaried dental clinics.

Towards a Role for Clinical Pathology Diagnostics for Childhood Maltreatment.

Recent reports from the Center for Disease Control and Kaiser Permanente demonstrate that early life adverse experience leads to morbidity and mortality in adulthood. To date there are no objective tests that help care-givers or local child protective services make informed decisions for children with a history of abuse, neglect or trauma. This is the first report from a new group of trans-disciplinary investigators describing a new approach to identify the biological impact of childhood maltreatment using clinical pathology testing. Such new quantitative measurements will be useful to identify children at risk for poor mental and physical health outcomes and to follow response to interventions.

The effects of orally active enkephalinase inhibitors on morphine withdrawal syndrome.

Considerable evidence has accumulated to suggest that intracerebroventricular administration of enkephalinase inhibitors, which do not penetrate the blood-brain barrier, significantly attenuates opioid withdrawal syndrome. Therefore, the aim of this study was to examine the effect of intraperitoneal (i.p.) administration of orally active enkephalinase inhibitors, acetorphan (2.5-20 mg kg-1) and SCH 34826 (15-120 mg kg-1). These drugs significantly decreased the severity of the naloxone precipitated withdrawal syndrome in morphine dependent rats and mice. It therefore appears that these orally active enkephalinase inhibitors are promising tools in studying modulation of opioid dependence phenomena.

The social network characteristics of fibromyalgia patients compared with healthy controls.

OBJECTIVE: To assess structural social network characteristics and perceived loneliness in fibromyalgia syndrome (FMS) patients and healthy controls. METHODS: A cross-sectional, retrospective, case-control design was employed using a structured interview and a self-report questionnaire. We studied 25 female FMS patients and 25 matched healthy female controls. RESULTS: FMS patients had statistically significantly (P < 0.05) more intimate friends (mean 4.5) and more health care providers (mean 1.5) than did controls (2.3 and 0.0, respectively). The FMS patients more often initiated the contact with family members (mean 2.1) than did controls (mean 0.8). FMS patients did not perceive themselves as lonelier than controls perceived themselves. While there was a significant negative correlation between loneliness and social network variables among the controls, this relationship was not significant among the FMS patients. Among the patients, there was a strong correlation between the total social network size and the number of intimate friends, whereas in controls, the mean number of acquaintances was strongly correlated with the total network size. CONCLUSION: Compared to healthy controls, the social networks of FMS patients presented more linkages with intimate friends, family members, and health care providers. The lack of correlation between loneliness and social network variables for FMS patients is not what might be expected from social support theory. The assessment of structural social network characteristics along with social support variables may add to our understanding of the social functioning of FMS patients.

The prevention of stimulant misuse.

The term 'stimulant' refers to a class of drugs that increase psychophysiological arousal. From the viewpoint of prevention, it is more useful to look primarily at the social consequences and functions of stimulants. Every society has a documented use of stimulants. When planning interventions the dynamics of use must be placed in the foreground. Stimulant epidemics, like problematic stimulant users, have a natural tendency to burn themselves out. Different types of stimulants may differ in their origins, but their epidemiological consequences and use functions tend to be similar. Implications for prevention can be drawn from the characteristics of stimulant use epidemics. Users at risk for socially unacceptable patterns should be targeted for prevention efforts. Mass media campaigns that single out stimulants should be avoided. Much of the harm associated with stimulants is a consequence of life-styles characterized by polydrug use and unhealthy practices. Prevention should be timed to the appropriate period of the epidemic. Interventions useful at period 1 will not work at period 2. The recommendations of the WHO Advisory Group on the Adverse Effects of Cocaine and Coca provide a good model for primary, secondary and tertiary prevention for all forms of stimulant misuse. Stimulant prevention must be creative in finding ways of encouraging the movements of the drug to the periphery of users' lives.

The pleasure dome with caves of ice. Cerebral lateralization, creativity, and the drug experience.

The drug experience is not a phenomenon of isolated interest to the neurosciences. The investigation of the phases of the drug experience can tell us much about the process of stimulating and losing creativity. This paper aimed to present a human model of creativity and the drug experience to complement the existing animal models. It remains for future research to reject or confirm the hypotheses sketched here. The exploration of these hypotheses would give us better insight into the control mechanisms determining the delicate process of creating functional forms that link words and images to feelings (for example, art). The examination of the drug experience from the point of view of cerebral lateralization provides a better understanding of how the quest for art may be tied up with the consequences of self-destruction. As Luria has noted, the gnostic disturbances associated with damages of the right hemisphere are "the remarkable absence of perception of the patient of his own defects; . . . such patients have unimpaired speech but they lack the precise analysis of the direct flow of information about their own body." Perhaps this was intuitively known by Coleridge, who in 1803 had already passed into the maintenance phase and wrote the fragment "Reality's Dark Dream": I know 'tis but a dream, yet feel more anguish Than if 'twere truth. It has been often so: Must I die under it? Is no one near? Will no one hear these stifled groans and wake me?

Risk contexts and risk behaviors in the Euregion Maas-Rhein: the Boule de Neige intervention for AIDS prevention among drug users.

Using targeted sampling, self-reported data of 1,767 drug users in the Euregion Maas-Rhein were collected over 3 years. Forty-two percent of the injection drug users shared syringes with sexual partners and 47.8% with friends. Eighty-one percent of the total sample had sexual contact in the last 6 months, half of whom with one person and half with two or more. Significant predictors of high-risk drug use were injecting in the presence of others, injection onset before the age of 20, female gender, and not living in The Netherlands. Participation in needle exchange or methadone programs and sufficient knowledge of risk factors was not significantly related to a reduction of high-risk drug use behavior. High-risk sexual behavior was found to be related to male gender, under the age of 30 and to multiple sexual partners. We conclude that in a social context where needle exchange, methadone programs, and sufficient knowledge of risk factors among the drug user population exist, AIDS prevention can be improved through behavioral skills training and developing specific interventions that target the peer group environments, rituals, partner relationships, and lifestyles of drug users.

PIP: A 3-year (1992-94) prospective study of 1767 drug users from the Euregion Maas-Rhein evaluated a peer counseling intervention for reducing risk behaviors associated with HIV transmission. The HIV prevalence among drug users in this diverse Dutch, German, and Belgian area ranges from 10% to 30%. Duties of the paid peer counselors included promotion of HIV risk reduction in drug use and sexual behavior; administration of questionnaires; distribution of educational materials, condoms, and clean needles; identification of hidden subgroups in the target population; and the development of prevention materials. 50% of those reached by peer counselors had no prior contact with drug abuse services. Although drug users claimed syringes and condoms were readily available, high-risk drug and sexual behaviors were widespread. 52% were injecting drugs and 24.4% had traded drugs for sex. Condoms were used by 24.8% during sexual contacts with a main partner and by 73.5% during sex with casual partners. 47.8% of injecting drug users had shared their syringes with friends. Condom use was significantly higher among drug users residing in South Limburg, women, those over 30 years of age, and those with multiple sex partners. These findings suggest that existing HIV risk-reduction interventions such as methadone treatment and needle exchange may not be sufficient. More emphasis must be placed on personal skills training (e.g., assertiveness training) and peer-driven, lifestyle-oriented processes.

The Addiction Severity Index: reliability and validity in a Dutch addict population.

In order to meet the need for a multidimensional diagnostic instrument in the field of drug addiction in The Netherlands, the Addiction Severity Index (ASI) has been applied to a sample of Dutch drug addicts. In this article the usefulness and psychometric characteristics of the Dutch version of the ASI are discussed. Overall, there was no evidence of a general relationship between the ASI ratings of problem severity. The severity ratings showed good concurrent validity, and subscales of selected items in each problem area of the ASI were demonstrated to have good internal consistency reliability. Regression analysis indicated that the ASI items accounted for a considerable proportion of the variance in the severity ratings, indicating a strong relationship between "subjective" rating and "objective" data. On the basis of the general concept of the ASI and the satisfactory psychometric characteristics, implementation of the instrument in The Netherlands is advocated.

Prevalence of psychopathology in drug-addicted Dutch.

In Dutch samples of treated heroin addicts, high prevalences of a heterogeneous psychiatric co-morbidity can be found with regard to Diagnostic and Statistical Manual (third edition) (DSM-III) classifications, Zung Depression Inventory, and sum scores of a 90-item Symptom Checklist (SCL-90). A high-threshold (N = 87) and a low-threshold (N = 116) program are compared with regard to psychopathology and severity of psychopathology. A consecutive admissions design was used. More than 50% of the respondents suffered from a lifetime DSM-III Axis I disorder (70% with antisocial personality disorder included), and 40% were still suffering from one of the disorders in the year preceding the interview. Schizophrenia was diagnosed five times as much as in normal population samples (5%). The most frequently diagnosed disorders were recurrent major depression, phobic disorders, alcohol abuse and dependence, dysthymic disorder, and antisocial personality disorder. The prevalences of DSM-III disorders, the total number of symptoms, and the score on the Zung Depression Inventory and 90-item Symptom Checklist were all significantly higher in treatment-seeking drug addicts entering the high-threshold program. Within each program, three clinically meaningful subgroups can be distinguished: one group with DSM-III Axis I lifetime or current psychopathology and/or antisocial personality disorder, one with antisocial personality disorder only, and one with neither DSM-III psychopathology nor antisocial personality disorder. Possibly, self-selection results in patients with more serious conditions entering more treatment-oriented facilities. Odds ratios show that schizophrenia and mood disorders and especially associated on a lifetime and current basis.

What works in drug abuse epidemiology in Europe.

This paper discusses what works and what does not work in drug abuse epidemiology in Europe. Given the tradition in European countries of defining the drug abuse problem in terms of social and medical interventions, epidemiological research is also tied to these interventions, and consequently to community-based research. What seems not to work, and what is generally suspect are grand legal designs to solve the drug problem. Promising initiatives are going towards a compromise between a relaxation of legal sanctions but a tendency away from legalization. What is recommended is striving towards a more analytic and multidisciplinary epidemiology that can help society critically evaluate the truth-value of its moral prerogatives.

Drug sharing and HIV transmission risks: the practice of frontloading in the Dutch injecting drug user population.

Injecting drug users may now be the largest group at risk for contracting HIV, mainly through the sharing of drug injection equipment (including lending, borrowing, and renting). This article presents the results of an ongoing ethnographic study into the drug-taking rituals of heroin addicts. A possible additional route of HIV contamination is presented, namely the ritual sharing of drugs through a practice termed "frontloading," which is embedded in a broader pattern of the sharing of resources among addicts. It is hypothesized that in the Netherlands this practice may be responsible for a substantial proportion of HIV spread among injecting drug users.

Illegal drug use, alcohol and aggressive crime among Mexican-American and white male arrestees in San Antonio.

This research explores the relationship between use of certain drugs and aggressive crimes among Mexican-American and White male arrestees in San Antonio, Texas, for 1992. This is based on a Drug Use Forecasting (DUF) sample of 534 male arrestees administered a drug urine analysis test and questionnaire by the Department of Justice and the city of San Antonio. Using a four-way asymmetrical analysis, logit-models were tested to examine the relationships between the response variable, the types of crimes charged (nonaggressive versus aggressive) and a set of exploratory variables, ethnicity (White versus Hispanic), drug test results (positive versus negative), and alcohol use (infrequent versus frequent). The logit-analysis allows the specification of a subset of relevant models to be tested for their adequacy of fit. Findings indicate a complex but interpretable pattern between drug use, alcohol use patterns, and aggressive crimes. A surprising finding was that more aggressive crimes were committed by all men testing negative for drugs. Mexican-Americans with frequent alcohol use and testing positive for drugs were twice as likely to commit an aggressive crime (a crime associated with violence) than Whites in the same subgroup. The implication of these findings for prevention strategies aimed at alcohol and other drug users involved in violent behavior is discussed.

Reaching the unreached: targeting hidden IDU populations with clean needles via known user groups.

Needle exchange is a practical and important part of the Dutch prevention strategy to check the spread of HIV among injecting drug users (IDUs). However, needle-exchange programs are often tied to drug treatment programs that only reach a limited number of IDUs. To overcome this limitation, alternative designs are considered and initiated. This article describes a community-based approach to needle exchange that is built on empowerment of, and intense participation by, known IDUs to target unknown IDUs for delivery of clean needles. The needle-exchange patterns of the IDUs participating in this collective scheme are compared to those of other users who exchanged needles on an individual basis. It was found that this approach extended the reach of the program to a great degree and that it was well received in the IDU community. However, the results were negatively influenced by police activities aimed at closing down places where drugs were used and sold. It is concluded that engaging IDUs in peer-group-directed prevention efforts is both feasible and promising.

Management of pain through cerebral activation. An experimental analogue of alexithymia.

The present experiment was designed to explore the relationship between pain, language and cerebral functioning in normal subjects, as an analogue to alexithymia. Left hemisphere cerebral activation, as measured by an EEG-alpha ratio score, was found to be associated with a reported increase in painful sensation during painful stimulation. Right hemisphere activation was found to be associated with a decrease in reported pain. The results were interpreted in terms of the mobilization of fantasy processes, following experimental instructions, which seem to be mediated by right hemisphere activation. Uninstructed subjects, lacking a stable visualization, utilize a left-hemisphere, verbal mode to cope with the pain. It is suggested that left-hemisphere mobilization, and a lack of right-hemisphere processing of painful stimulation may be in part responsible for the alexithymic patients' psychosomatic symptoms.

Lateralized differences associated with semantically varied auditory material.

EEGs were recorded from 13 subjects while they listened to four tape-recorded passages differing in semantic content. The distribution of alpha band power over the two hemispheres, measured at T3/T4, was found to show significant task-dependent shifts. More reality-oriented passages tended to be processed with greater left-hemisphere involvement, while "pleasurable" material showed significant right-hemisphere involvement. Since the differences in laterality were not related to grammatical measures of linguistic complexity, the apparent shifts were attributed to semantic differences between the tasks. Explanation of the results is made in terms of a theory of the metacontrol of cerebral processing.

Changing cocaine smoking rituals in the Dutch heroin addict population.

Recently the use patterns, circumstances and consequences of cocaine have become of interest to both researchers and policy makers in Europe. Currently only a few studies have been conducted of the social epidemiology of cocaine. In this article, focus is placed upon the use of cocaine in one subpopulation, heroin addicts. Based mainly upon ethnographic research conducted in the city of Rotterdam it can be estimated that the prevalence of cocaine use in this population has reached a very high level. The mode of ingesting cocaine parallels that of heroin; Injecting Drug Users inject cocaine-hydrochloride, heroin smokers smoke cocaine base. This cocaine base is mainly processed by users themselves. An exception to this rule of self-processing can be found in the most marginalized addicts who do not have access to the house addresses where both heroin and cocaine-hydrochloride are sold. In this group the selling of 'cooked cocaine', a crack-like product, has occurred. The circumstances and potential consequences of the emergence of 'cooked cocaine' are discussed.