Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

Outcomes in patients with interrupted aortic arch and associated anomalies: a 20-year experience.

OBJECTIVE: The surgical results for the repair of interrupted aortic arch (IAA) have evolved in recent years. We report our results for staged repair of this complex congenital malformation. METHODS: Sixty-five patients (mean age, 16.9+/-41.7 days) were diagnosed with IAA and referred for surgical therapy. The surgical management strategy at our institution between 1982 and 2005 has been one-stage complete repair (n=13) or staged repair (n=52) in selected patients. Non-complex patients (group I, n=51) had a ventricular septal defect (87%), aortopulmonary window (8%), and left ventricular outflow tract obstruction (27%). Group II (n=14) were patients with Taussig-Bing double outlet right ventricle (n=6) or truncus arteriosus (n=8). Method of staged repair of IAA was to transect and turn down the left carotid artery and anastomosis it to the descending aorta (n=41) or graft interposition (n=2) combined with a pulmonary artery (PA) banding followed in a few months by delayed ventricular septal defect (VSD) closure and PA de-banding. RESULTS: There were 5 early and 10 late deaths. The actuarial survival including early mortality was 92% at 1 year, 81% at 5 years, and 76% at 10 and 15 years. There was an 81% 15-year survival for children in group I compared with a 54% for children in group II (p<0.001). Risk factors for increased mortality by univariate analysis were as follows: (1) primary aortic anastomosis (p=0.03), (2) presence of complex anomalies (p=0.05), and (3) initial IAA repair performed before 1994 (p=0.05). Actuarial freedom from any type of aortic reoperation or intervention was 86% at 1 year, 69% at 5 years, and 60% at 10 and 15 years. Univariate and multivariate analyses identified no tested variables as risk factors for reoperation. The majority (86%) was in New York Heart Association (NYHA) class I, and 14% remained in NYHA class II. During the postoperative course there were no neurologic deficits, seizures, and growth disturbances in any patient. CONCLUSION: Staged repair of IAA using a left carotid artery turn down can be safely applied in IAA patients with and without other intracardiac anomalies with good results. Use of the left carotid artery for arch reconstruction did not result in any detectable neurological events or growth disturbances later in life. Associated anomalies played an important role in outcomes. The long-term probability for reoperation and/or reintervention remains high regardless of operative technique.     

Restoring and preserving trust in biomedical research.

Recent media depictions of the dangers of biomedical research have fueled public and regulatory scrutiny of academic research institutions. The authors argue that if these institutions are to preserve the trust that the public has historically bestowed upon them, they must go beyond mere compliance with regulatory mandates. Several steps are suggested that institutions can take to strengthen and supplement ongoing compliance efforts, steps the authors believe will bolster the public's confidence in the integrity of academic research institutions. These steps grow out of the authors' analysis of three key components of institutional trustworthiness: (1) shared goals between research institutions and the communities they serve, (2) robust institutional oversight of research activities, and (3) training programs that build professional character. The authors' recommendations include the use of research advisory councils to assure the public that research goals reflect community interests, more collaborative relationships between institutional review boards and members of investigative teams, and educational programs that emphasize the importance of professional integrity in biomedical research. These efforts will help preserve public confidence that an institution's research priorities are appropriate and that the research it conducts is ethical. Preserving this public trust is central to the long-term success of biomedical research and the institutions in which such research takes place.     

Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS)

1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.

2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.

3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.     

True conversive hallucinations

A case of true conversive hallucinations in a 19-year-old female soldier is described. This phenomenon is rare and should be distinguished from psychotic or dissociative states.     

Perceived control of asthma and quality of life among adults with asthma.

BACKGROUND: Perceived control of certain chronic conditions influences health status outcomes. OBJECTIVE: To explore the impact of perceived control of asthma on asthma-specific and generic health status outcomes among adults with asthma. Perceived control was defined as individuals' perceptions of their ability to deal with asthma and its exacerbations. METHODS: Data were drawn from the baseline and first two followups of a longitudinal study of adults with asthma surveyed by telephone at 18-month intervals. An 11-item questionnaire (Perceived Control of Asthma Questionnaire [PCAQ]) was developed and validated. RESULTS: The PCAQ demonstrated high internal consistency (Cronbach's alpha = 0.79). Greater perceived control was associated with less severe asthma, greater asthma self-efficacy, lower perceived asthma severity, lower perceived danger from asthma, and greater perceived usefulness of asthma medicines. Greater perceived control was significantly associated with better asthma-specific quality of life concurrently and 18 and 36 months later, after controlling for demographics, smoking, and severity of asthma. Greater perceived control as also significantly associated with generic mental health outcomes concurrently and 18 and 36 months later, after controlling for covariates. Perceived control was associated with physical function concurrently and 18 months later, but not 36 months later. CONCLUSIONS: The PCAQ is a reliable and valid measure of perceived control of asthma. Perceived control of asthma was associated with both asthma-specific and generic health status outcomes, concurrently and predictively. If perceived control could be modified, better outcomes, particularly better psychologic outcomes, might be achieved for individuals with asthma.