Norepinephrine and dopamine metabolites and educational variables in boys with attention deficit disorder and hyperactivity

The present study evaluated the biochemical measures of urinary homovanillic acid (HVA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in relation to functioning on selected psychoeducational tests in a group of boys with attention deficit disorder and hyperactivity. The Wechsler Intelligence Scale for Children-Revised (WISC-R), the Wide Range Achievement Test (WRAT), and the Peabody Picture Vocabulary Test were administered to 28 hyperactive and 23 control subjects. The findings suggest subtle differences in psychoeducational test performance in relation to specific levels of homovanillic acid and MHPG.     

Dysphagia Referrals to a District General Hospital Gastroenterology Unit: Hard to Swallow

The aim of our study was to audit dysphagia referrals received by a specialist gastroenterology unit during an entire year. We used a prospective audit carried out over a 12- month period at the District General Hospital gastroenterology unit. The audit included 396 consecutive patients who were referred with swallowing difficulties. We found that 60 referrals (15.2%) were inaccurate and the patients had no swallowing problem. Of the 336 patients with genuine dysphagia, only 29 (8.6%) were new cancer cases. The large majority of subjects had benign disease mostly related to acid reflux. Weight loss was significantly associated with malignancy but also occurred in one third of patients with reflux alone. The temporal pattern of dysphagia was not significantly predictive of cancer. All the cancer patients were above the age of 50 years. Although patients were in general assessed rapidly after hospital referral, the productivity, in terms of early tumor diagnosis, was extremely low. We conclude that there is a substantial rate of inaccurate referrals of dysphagia patients. Most true cases of swallowing difficulty relate to benign disease. Even the devotion of considerable resources to the early diagnosis of esophago gastric malignancy in an attempt to conform with best practice guidelines results in a very low success rate in terms of the detection of potentially curable tumors.     

Direct drug susceptibility testing of Mycobacterium tuberculosis for rapid detection of multidrug resistance using the Bactec MGIT 960 system: a multicenter study

Conventional indirect drug susceptibility testing of Mycobacterium tuberculosis with liquid medium is well established and offers time-saving and reliable results. This multicenter study was carried out to evaluate if drug susceptibility testing (DST) can be successfully carried out directly from processed smear-positive specimens (direct DST) and if this approach could offer substantial time savings. Sputum specimens were digested, decontaminated, and concentrated by the laboratory routine procedure and were inoculated in Bactec MGIT 960 as well as Lowenstein-Jensen (LJ) medium for primary isolation. All the processed specimens which were acid-fast bacterium (AFB) smear positive were used for setting up direct DST for isoniazid (INH) and rifampin (RIF). After the antimicrobial mixture of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin (PANTA) was added, the tubes were entered in the MGIT 960 instrument using the 21-day protocol (Bactec 960 pyrazinamide [PZA] protocol). Results obtained by direct DST were compared with those obtained by indirect DST to establish accuracy and time savings by this approach. Of a total of 360 AFB smear-positive sputum specimens set up for direct DST at four sites in three different countries, 307 (85%) specimens yielded reportable results. Average reporting time for direct DST was 11 days (range, 10 to 12 days). The average time savings by direct DST compared to indirect DST, which included time to isolate a culture and perform DST, was 8 days (range, 6 to 9 days). When results of direct DST were compared with those of indirect DST, there was 95.1% concordance with INH and 96.1% with rifampin. These findings indicate that direct DST with the Bactec MGIT 960 system offers further time savings and is a quick method to reliably detect multidrug resistance (MDR) cases.     

Brain, skull, and cerebrospinal fluid volumes in adult posttraumatic stress disorder

Children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) exhibit smaller intracranial tissue volume than controls. Linear relationships have also been observed between intracranial tissue volume and the age of maltreatment onset. The authors explored associations among adult PTSD, early trauma, and cerebral volumes in 99 combat veterans. A bone-based estimate of cranial volume was developed to adjust for variation in body size. Posttraumatic stress disorder was not associated with smaller cerebral tissue volume, but rather with smaller cerebrospinal fluid (CSF) and cranial volumes. These findings co-occurred with expected effects of alcoholism and aging on cerebral tissue and CSF volumes. The results point to early developmental divergences between groups with and without PTSD following adult trauma.     

Scheduled Bright Light for Treatment of Insomnia in Older Adults

OBJECTIVES: To determine whether bright light can improve sleep in older individuals with insomnia.
DESIGN: Single-blind, placebo-controlled, 12-week, parallel-group randomized design comparing four treatment groups representing a factorial combination of two lighting conditions and two times of light administration.
SETTING: At-home light treatment; eight office therapy sessions.
PARTICIPANTS: Thirty-six women and fifteen men (aged 63.6±7.1) meeting primary insomnia criteria recruited from the community.
INTERVENTION: A 12-week program of sleep hygiene and exposure to bright (∼4,000 lux) or dim light (∼65 lux) scheduled daily in the morning or evening for 45 minutes.
MEASUREMENTS: Within-group changes were observed for subjective (sleep logs, questionnaires) and objective (actigraphy, polysomnography) sleep measures after morning or evening bright light.
RESULTS: Within-group changes for subjective sleep measures after morning or evening bright light were not significantly different from those observed after exposure to scheduled dim light. Objective sleep changes (actigraphy, polysomnography) after treatment were not significantly different between the bright and dim light groups. Scheduled light exposure was able to shift the circadian phase predictably but was unrelated to changes in objective or subjective sleep measures. A polymorphism in CLOCK predicted morningness but did not moderate the effects of light on sleep. The phase angle between the circadian system (melatonin midpoint) and sleep (darkness) predicted the magnitude of phase delays, but not phase advances, engendered by bright light.
CONCLUSION: Except for one subjective measure, scheduled morning or evening bright light effects were not different from those of scheduled dim light. Thus, support was not found for bright light treatment of older individuals with primary insomnia.     

Changes in the amplitude and timing of the hemodynamic response associated with prepulse inhibition of acoustic startle

Disruption of the early stages of information processing in limbic brain circuits may underlie symptoms of severe neuropsychiatric disorders. Prepulse inhibition of acoustic startle (PPI) is diminished in many of these disorders and may reflect the disruption of this CNS function. PPI is associated with brain activity in many of the same regions in humans as it is in laboratory animals, suggesting that neuroimaging studies in humans may help localize deficits that can then be elucidated in animal models. In this article, we employed a rapid presentation event-related design during continuous EPI BOLD scanning to examine hemodynamic response functions (HRFs) associated with PPI. Fourteen healthy participants listened to 100 pulse alone and 100 prepulse combined with pulse (prepulse-pulse) trials. PPI is the normalized difference in the startle response to the two trial types. Following the prepulse-pulse trials, the amplitudes of the HRFs in auditory cortices and in the anterior insula were increased, while in the cerebellum, thalamus and anterior cingulate, they were decreased, relative to the pulse alone trials. In addition, the timing of the prepulse-pulse responses was delayed in the auditory cortices, anterior insula and cerebellum. Finally, PPI measured outside the scanner was predicted by the difference in BOLD responses between trial types in the anterior insula and in the cerebellum. The results suggest that prepulse inhibition, and by extension early stages of information processing, modulate both the amplitude as well as timing of neural activity.     

Factors in choosing atypical antipsychotics: toward understanding the bases of physicians' prescribing decisions

OBJECTIVE: Off-label prescribing of medications, polypharmacy, and other questionable prescribing practices have led investigators to examine a large VA pharmacy database to determine if physician prescribing decisions appear reasonable. METHOD: The current study addresses the question of physician prescribing of atypical antipsychotics in 34,925 veterans with schizophrenia, using a series of signal detection analyses. RESULTS: These results suggest that only three factors (hospital size, age, and secondary diagnosis) allow classification of patients prescribed atypicals into three groups with frequencies of use of atypicals ranging from 43% to 79%, and that these results are consistent with reasonable clinical practice. CONCLUSIONS: Results of two-stage signal detection analyses are readily interpretable by clinicians and administrators who are faced with the task of evaluating how physicians prescribe medications in clinical practice. Physicians' decisions to prescribe atypical antipsychotics are based on both patient and fiscal considerations. This likely reflects a combination of clinical judgment and institutional guidelines.