Phenotypic variation and detection of carrier status in the partial androgen insensitivity syndrome

The partial androgen insensitivity syndrome occurs in 46,XY subjects with phenotypes ranging from perineoscrotal hypospadias with cryptorchidism and micropenis (mild undervirilisation) to clitoromegaly and partial labial fusion (marked undervirilisation). Within an affected family, wide variation in the degree of genital ambiguity between individuals can be seen. Two cousins of a previously reported subject who had severe genital ambiguity and partial androgen insensitivity were investigated. Neither of the cousins had genital abnormalities as marked as the index case, who also had qualitatively abnormal androgen binding and two mutations of the androgen receptor gene. Despite marked phenotypic differences between the index case and his cousins, similar androgen binding and the same androgen receptor mutations were shown in the cousins. Furthermore, one of the androgen receptor gene mutations has been shown in the mother and sister of one of the boys indicating that they are carriers. Thus phenotypic variation in families affected by partial androgen insensitivity is dependent on factors other than abnormalities of the androgen receptor gene alone. Although carrier status in partial androgen insensitivity can be determined, the severity of genital abnormalities in an affected offspring cannot be reliably predicted.     

Pharmacotherapy of alcoholism: gaps in knowledge and opportunities for research

During the past decade, renewed interest in medications to prevent relapse in alcoholics has yielded a number of promising candidates. Although two of these medications, naltrexone and acamprosate, are currently in clinical use in a number of countries, overall, their effectiveness appears to be limited. Disulfiram, the deterrent medication that was approved 50 years ago for the treatment of alcoholism, has not consistently been shown to be efficacious. However, since inadequate dosing and other modifiable factors may limit its deterrent effects, the identification of a more potent metabolite of disulfiram appears to warrant further evaluation. Studies of serotonergic agonists for treatment of alcoholism have also yielded inconsistent results. There is evidence, however, that subgroups of alcoholics may respond well to such medications, suggesting that treatment matching may enhance their efficacy. In addition, nalmefene, a compound with effects similar to naltrexone, as well as a sustained release formulation of naltrexone, may enhance the beneficial effects of opioid antagonist therapy. Despite these developments, much remains to be learned about the pharmacotherapy of alcoholism. The ongoing development and evaluation of novel medications should be given a high priority. However, such basic issues as the optimal dosing strategy and duration of treatment for existing therapies are not known. Similarly, combination therapy, involving either multiple medications or the combination of medication with specific psychotherapies, has not been well studied. The utility of specific pharmacotherapies in women, different ethnic/racial groups, adolescent and geriatric patients, and individuals with co-morbid alcohol and drug use disorders (including nicotine dependence) is also largely unknown, as is the appropriateness of medication therapy for treatment of early problem drinkers. The ultimate aim of these efforts is the development of algorithms for the pharmacological treatment of heavy drinking, which incorporate the characteristics of the patient and of pharmacological and psychosocial treatments with demonstrated efficacy. Although a general framework for such an effort currently exists, much detail is needed before it will be of widespread clinical value.     

Drinking to cope: a comparison of questionnaire and electronic diary reports

OBJECTIVE: The purpose of this article is to assess the correspondence between questionnaire reports of dispositional drinking to cope (DTC) and different indices of daily DTC in a sample of nondependent heavy drinkers. METHOD: Data from electronic diary (ED) records of interpersonal problems, negative affect, coping and drinking were used to examine how questionnaire reports of dispositional DTC corresponded to ED reports of daily DTC and to within-person associations among ED reports of negative affect, interpersonal problems and drinking. In the current study, 98 community-residing heavy drinkers using EDs recorded moods, interpersonal problems, coping attempts, desire to drink and drinking for 21 consecutive days. RESULTS: The findings demonstrate correspondence between questionnaire reports of dispositional DTC and (1) ED reports of daily DTC, (2) intensity of negative mood associated with daily drinking initiation and (3) some between-person differences in within-day prediction of drinking and desire to drink from mood and interpersonal problem ratings. Those reporting higher dispositional DTC were somewhat more likely to drink in response to some negative moods and less likely to drink in response to some positive moods than those reporting relatively lower dispositional DTC, but these findings were mixed. CONCLUSIONS: Questionnaire reports of dispositional DTC are at best inconsistently linked to observed within-person associations among daily moods, interpersonal problems and drinking even among heavy drinkers.     

Practical population group assignment with selected informative markers: characteristics and properties of Bayesian clustering via STRUCTURE

Population stratification, which is caused by population genetic substructure (PGS), is a critical issue for the design and interpretation of genetic association studies. Methods to address this problem have been devised, but little is known at this point about practical genotyping requirements for resolving PGS based on different marker characteristics. In this report, we seek to (1) identify a small, practical marker set to differentiate African Americans (AAs) from European Americans (EAs), and (2) assess the impact of marker efficiency and sample size on clustering individuals into subgroups by the methods of STRUCTURE (Pritchard et al., [2000a] Genetics 155:945-959). A panel of 37 markers was genotyped for 865 individuals (640 EAs and 225 AAs) from the Northeastern United States. Among EAs, the assignment accuracy reached >99% using only the 4 most efficient markers. Among AAs, the assignment accuracy exceeded 95% when using the 6 most informative markers. Smaller sample size increased the variance in population differentiation, rather than degrading the results consistently. We conclude that the use of marker-efficiency measures for marker selection yielded a relatively small set of STR markers that were effective at differentiating EA and AA populations. The number of markers required is much lower than has been suggested in previous studies.     

Major motor atrophic patterns in the face and neck: CT evaluation

Cranial nerve deficits from various pathologic processes of the head and neck may result in characteristic patterns of denervation muscular atrophy. Such atrophic patterns may be clues to the location and extent of the lesion, particularly when cranial nerves are involved early in the course of the disease process. Thirty-six patients with computed tomographic (CT) evidence of muscular atrophy secondary to pathologic conditions involving the motor division of cranial nerves were examined. Five characteristic denervation muscular atrophy patterns seen on CT scans were identified. In several patients, identification of the muscular atrophy pattern was the only clue to the presence of a pathologic condition. Recognition of these atrophic patterns can prevent misinterpretation of their CT appearance and direct the CT examination to the course of the compromised cranial nerve from the brainstem to its peripheral innervation.     

Psychosocial group prevention and intervention programs for children and adolescents

Psychosocial group interventions provide a potent venue for promoting children's social competencies, self-regulation, and problem solving in a natural peer group context. Three exemplary prevention and intervention group programs were described that are empirically supported, theoretically rich, and flexible for application in residential care settings. Special considerations are offered for designing and implementing groups with this population.     

Typologies of drug dependence: comparative validity of a multivariate and four univariate models

Data from a longitudinal cohort study were used to directly compare the concurrent and predictive validity of four univariate typologic approaches with a multivariate approach in subtyping drug dependence. The four univariate typologies were based upon: (a) age-of-onset of drug abuse/dependence, (b) presence of drug abuse in first-degree relatives, (c) presence of antisocial personality disorder, and (d) sex. The multivariate typologic approach was based on indices of vulnerability, chronicity, consequences, and psychopathology, yielding the Type A/B dichotomy first demonstrated in alcohol dependence. Subtypes generated from the univariate typologies were then each compared with the multivariate typology on measures of concurrent and predictive validity, and the strength of association was compared statistically. There was evidence of significantly greater concurrent validity of the Type A/B typology compared with the univariate typologies across all the domains of validation (risk, substance use, psychopathology, personality, and overall functioning). The multivariate typology also fared better than the univariate ones in all three domains on which predictive validity was evaluated: substance use, psychopathology, and overall functioning, as well as the degree of change in several composite scores (drug, medical, legal, and psychiatric) and the global psychiatric symptom index. This direct method of comparison seemed to demonstrate the superior validity of the multivariate cluster-analytic approach over the univariate approaches to classifying subjects with drug dependence.     

Respiratory function after repair of congenital diaphragmatic hernia

Respiratory function studies were carried out in 22 infants who had successful repair of diaphragmatic herniae of the Bochdalek type. Thoracic gas volume was initially reduced in only 3 of these, but subsequent studies showed that improvement occurred. There were no consistent abnormalities in either dynamic compliance or mean pulmonary conductance. This is evidence that there is rapid adaptation which compensates for any alteration in the parenchymatous tissue in the lungs or abnormalities in the bronchial tree in infants soon after the repair of congenital diaphragmetic herniae. Further studies are necessary to determine the changes in these lungs with growth.     

Does affect mediate the association between daily events and alcohol use?

OBJECTIVE: We examined the within-person associations among positive and negative daily events, positive and negative affect, desire to drink, and alcohol consumption in a sample of heavy drinkers. METHOD: Forty-six subjects (25 men; mean [SD] age = 47.0 [9.3] years) who were enrolled in an 8-week treatment program for heavy drinkers were studied using a daily diary methodology. RESULTS: Multilevel regression analyses indicated that individuals reported stronger desire to drink and greater consumption on days in which more positive and negative nonwork events occurred. Lower levels of desire to drink and number of drinks were reported on days with more positive work events. Negative work events had a marginal positive association with daily desire to drink. Daily positive and negative affect uniquely predicted greater daily consumption and desire to drink, but only weak evidence was found for their mediating role in the association between daily events and the criterion variables. Several of the within-person associations among affect and the criterion variables varied as a function of number of lifetime symptoms of alcohol dependence and treatment condition. CONCLUSIONS: These findings generally support the dual-process (i.e., tension-reduction and experience-enhancement) motivational model of alcohol consumption. However, the observed associations among events, affect and alcohol-related behavior suggests that these pathways are complex, with each being comprised of affective and cognitive subpathways.     

Percutaneous drainage access: a simplified coaxial technique

We describe an access technique that we have used in 150 nephrostomy and biliary drainage procedures and for access to some abscesses and viscera. The system provides safe coaxial access with a 22-gauge removable hub needle, which then acts as a guide wire and is replaced by an 18-gauge cannula. A major advantage is that only one guide wire is used (0.038-inch) for the entire drainage procedure. No significant complications have occurred to date with this method.