Are there cognitive subtypes in adult attention deficit/hyperactivity disorder?

There has been increasing knowledge of the treatment, diagnosis, and demographics of adults with residual attention deficit/hyperactivity disorder (ADHD). However, less is known about the neuropsychological functioning in adults with residual ADHD. In comparing the clinical neuropsychological test performance of a group of adult clinic patients with residual ADHD (N = 30) with that of normal controls (N = 10), we found the patients performed worse on the Trail Making Test, a visual continuous performance test, and the "Brown-Peterson" Auditory Consonant Trigrams Test, but not on any other neuropsychological measures. This pattern indicated a deficit in the area of executive control type functioning, a functional deficit that could be linked to dysregulation of frontal lobe brain systems. Of equal interest was that patients diagnosed with ADHD/hyperactive impulsive type (ADHD+) and patients diagnosed with ADHD/inattentive type (ADHD-) had different types of executive system deficits. ADHD+ was associated with relative deficiency on the Wisconsin Card Sorting Test. ADHD- was associated with relative deficiency on the "Brown-Peterson" Auditory Consonant Trigrams Test, a measure of working memory, as well as less olfactory identification on a smell identification test. The data are discussed in terms of recent localization theories of frontal lobe function. The preliminary data suggest that the different cognitive weaknesses of ADD subtypes may be linked to dysregulation of separate frontal brain regions and/or neurotransmitter systems.     

RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs

RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has an atypical pair of "EF hands" that bind calcium and a diacylglycerol (DAG)-binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was associated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were absent when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation.     

Differences between completers and early dropouts from 2 HIV intervention trials: a health belief approach to understanding prevention program attrition

OBJECTIVES: The purpose of this study was to identify factors predicting program attrition among participants in human immunodeficiency virus (HIV) risk reduction trials. METHODS: Participants were gay/bisexual men and severely mentally ill adults recruited to take part in HIV risk reduction small-group interventions. Program completers were compared with participants who were assessed at baseline but then failed to attend any sessions. The health belief model provided a framework for selection of possible predictors of program attrition. RESULTS: Younger age was associated with early dropout in both samples. Other predictors among gay/bisexual men included involvement in an exclusive sexual relationship, minority ethnicity, injection drug use, and higher perceived severity of AIDS. Severely mentally ill dropouts were less knowledgeable about safer sex methods and more likely to hold positive outcome expectancies for condom use. CONCLUSIONS: Evaluation of intervention effectiveness among vulnerable population segments is threatened if there is selective attrition. Better methods are needed to attract and maintain participation in HIV prevention programs. Alternatively, wider application of "intention to treat" analysis of intervention outcomes is recommended to minimize selection bias due to program dropout.     

Detection and characterization of the electron paramagnetic resonance-silent glutathionyl-5,5-dimethyl-1-pyrroline N-oxide adduct derived from redox cycling of phenoxyl radicals in model systems and HL-60 cells

Rapidly growing knowledge about the nature and behaviour of breast cancer has led to many treatment modalities. Consequently, the possibilities of individualizing the treatment of breast cancer increase. The major tool for the determination of an optimal treatment plan is the estimation of the extent of the disease: in other words, staging. As a consequence, together with the expected result of the treatment, the stage of the disease gives information on the prognosis of the patient. Current staging systems insufficiently describe the clinically important features of breast cancer with respect to management and outcome: local and regional extent, invasiveness, aggressiveness, the state of dissemination, and the effectiveness of different treatment modalities. For staging of the local and regional extent, histology plays a prominent role and should be incorporated in future staging systems. Histological workup therefore needs standardisation. Histological parameters as tumour size, grade, nodal status, and vascular invasion are also the most important prognostic factors. Many so-called biological prognostic factors are related to the invasiveness and aggressiveness (metastatic potential) of the tumour, and therefore to the prognosis of the patient. However, these factors do not necessarily predict the effectiveness of certain systemic treatments. Only if the biological foundation of a prognostic factor is completely clarified can treatment be based on this knowledge, and the factor will become a predictor for the treatment effect. Many "biological" prognostic factors do not fulfil this main criterion and are therefore not useful for clinical decision making. A clinically useful staging system covers three primary aims: (1) to guide locoregional treatment, (2) to prognosticate the chance of survival, and (3) to indicate who needs what kind of adjuvant treatment. For the conception of a new staging system the following steps should be taken: standardization of all aspects of histology, identification of regional nodal involvement, and validation of prognostic factors with respect to their predictive value to treatment outcome.     

Quinacrine noncompetitive inhibitor binding site localized on the Torpedo acetylcholine receptor in the open state

Open-channel blockers of the nicotinic acetylcholine receptor (nAcChR) are widely thought to act sterically by entering and "plugging" the open channel of the nAcChR. However, quinacrine, a fluorescent open-channel blocker, has been recently shown to bind to the nAcChR at a site near the lipid bilayer while the receptor is in a closed, desensitized state, suggesting that at least one open-channel blocker might act allosterically outside the channel [Valenzuela et al. (1992) J. Biol. Chem. 267, 8238]. To determine whether or not quinacrine also binds near the lipid bilayer when the receptor is in an open state, a short-range lipophilic quencher (5-doxylstearate, 5-SA) was used to assess the proximity of the nAcChR-bound quinacrine to the lipid bilayer while the receptor was transiently open by an agonist. Initial experiments using a stopped-flow instrument established the conditions required to monitor a portion of the changes in quinacrine fluorescence associated with its binding to the receptor in the open state. 5-SA (80 microM) reduced the amplitude of the rapid agonist-induced change in quinacrine emission to 44% +/- 12% of the control value, indicating that the quinacrine was binding to a site proximal to the membrane-partitioned 5-SA. Control experiments established that 5-SA had no effect on the ability of the receptor to undergo agonist-induced conformational changes, suggesting that little, if any, 5-SA distributed into the channel lumen and perturbed the functional activity of the receptor. Together, the results indicate that quinacrine binds to a site on the open receptor that is in contact with the lipid bilayer and not in the channel lumen.     

Cervical pain and proprioceptive sensitivity

With the intent of estimating the proprioceptive sensitivity of the cervical rachis, the Authors subjected 17 healthy volunteers and 20 patients suffering from various cervical disorders to a clinical head positioning test, which was previously experimented upon by several french Authors was modified under certain aspects by our equipe. The test, consists in flexion and extension of the head after maximal rotations to the left and right, then repositioning the head at the starting point "0" which corresponds to the crossing point of two orthogonal axis of a target. The positions are marked on the target by a laser beam situated on the helmet worn by the subject undergoing testing. The results obtained corresponding to the errors committed regarding point "0", permit us to confirm the reliability of the test and significant definitions between the control group and the patients suffering from cervical disorders.     

The whistle and the rattle: the design of sound producing muscles

Vertebrate sound producing muscles often operate at frequencies exceeding 100 Hz, making them the fastest vertebrate muscles. Like other vertebrate muscle, these sonic muscles are "synchronous," necessitating that calcium be released and resequestered by the sarcoplasmic reticulum during each contraction cycle. Thus to operate at such high frequencies, vertebrate sonic muscles require extreme adaptations. We have found that to generate the "boatwhistle" mating call (approximately 200 Hz), the swimbladder muscle fibers of toadfish have evolved (i) a large and very fast calcium transient, (ii) a fast crossbridge detachment rate, and (iii) probably a fast kinetic off-rate of Ca2+ from troponin. The fibers of the shaker muscle of rattlesnakes have independently evolved similar traits, permitting tail rattling at approximately 90 Hz.     

The effect of urinary tract reconstruction on neurologically impaired women previously treated with an indwelling urethral catheter

PURPOSE: We investigated the changes in sexuality and quality of life that evolve after lower urinary tract reconstruction in neurologically impaired women previously treated with an indwelling urethral catheter. MATERIALS AND METHODS: A total of 18 neurologically impaired women treated with an indwelling urethral catheter underwent bladder reconstruction. Pubovaginal sling urethral compression was required to restore perineal dryness in 13 patients and was the only operation required in conjunction with intermittent catheterization in 3. Eight patients underwent ileocystostomy, that is creation of a "bladder chimney," and 4 underwent augmentation cystoplasty with creation of a continent catheterizable stoma. In 3 patients ileocystoplasty alone with intermittent urethral catheterization was performed. All patients were followed 6 to 40 months (mean 18) after reconstructive surgery using a 9-part questionnaire to score numerically the effect of surgical reconstruction on sexuality and quality of life issues. RESULTS: On a scale of 0 (worst) to 5 (best) mean score for self-esteem improved from 1 preoperatively to 4 postoperatively, self-image from 1 to 4, sexual desire from 2 to 4 and ability to cope with disability from 1 to 4, respectively. In 4 of the 15 women who were sexually active preoperatively the frequency of sexual intercourse doubled from a mean of 3 to 6 times per month, respectively, and all 4 women reported improved sexual satisfaction. All 13 patients with pelvic pain and 5 with symptoms of autonomic dysreflexia noticed significant improvement if not complete resolution of the symptoms. CONCLUSIONS: Neurogenic lower urinary tract dysfunction treated with an indwelling urethral catheter is detrimental to sexuality and quality of life in neurologically impaired women. Urinary tract reconstruction restores not only quality of life but also sexuality by improving self-image, self-esteem and the ability to cope. Indwelling catheterization as a method of long-term urinary treatment should be avoided in women.