Comparing histological data from different brains: Sources of error and strategies for minimizing them

The recent development of brain atlases with computer graphics templates, and of huge databases of neurohistochemical data on the internet, has forced a systematic re-examination of errors associated with comparing histological features between adjacent sections of the same brain, between brains treated in the same way, and between brains from groups treated in different ways. The long-term goal is to compare as accurately as possible a broad array of data from experimental brains within the framework of reference atlases. Main sources of error, each of which ideally should be measured and minimized, include intrinsic biological variation, linear and nonlinear distortion of histological sections, plane of section differences between each brain, section alignment problems, and sampling errors. These variables are discussed, along with approaches to error estimation and minimization in terms of a specific example—the distribution of neuroendocrine neurons in the rat paraventricular nucleus. Based on the strategy developed here, the main conclusion is that the best long-term solution is a high-resolution 3D computer graphics model of the brain that can be sliced in any plane and used as the framework for quantitative neuroanatomy, databases, knowledge management systems, and structure–function modeling. However, any approach to the automatic annotation of neuroanatomical data—relating its spatial distribution to a reference atlas—should deal systematically with these sources of error, which reduce localization reliability.     

Tooth movement and cytokines in gingival crevicular fluid and whole blood in growing and adult subjects.

INTRODUCTION: Tooth movement has been studied largely with respect to the force required for tipping when pressure distribution varies along the length of the periodontal ligament. But important factors for effective canine translation include the nature and magnitude of applied stress and the patient's cell biology. The purpose of this research was to test 3 hypotheses: (1) the velocity of tooth translation (v(t)) is related to applied stress and growth status, (2) a threshold of stress accounts for the lag phase, and (3) v(t) is correlated with the ratio (AI) of 2 cytokines (IL-1beta, IL-1RA) measured in gingival crevicular fluid (GCF) and stimulated whole blood (SWB). METHODS: Continuous maxillary canine retraction stresses of 13 kPa and 4, 26, or 52 kPa were applied bilaterally in 6 growing and 4 adult subjects for 84 days. Dental models and GCF samples were collected at 1- to 14-day intervals. Cytokines were measured in GCF and SWB cell cultures. RESULTS: V(t) was positively related to stress and was higher in growing subjects (P = .001). It was also related to AI(GCF) in growers (R2= 0.56) and nongrowers (R2= 0.72). Canines moved with 52 kPa showed a lag phase, and postlag phase AI(GCF) was twice that of lag phase AI(GCF). Mean v(t) and associated AI(GCF) during the postlag phase were nearly double the values for canines moved with 13 and 26 kPa. SWB production of cytokines was dose-dependent. For growing subjects, SWB IL-1RA was correlated with v(t) (R = 0.70-0.72), and AI(SWB) and IL-1beta concentrations were correlated with AI(GCF) (R = 0.73-0.78). CONCLUSIONS: V(t) varied with growth status and stresses < or = 52 kPa; stresses of < 52 kPa showed no lag phase; and equivalent stresses yielded subject-dependent differences in v(t), which correlated with cytokines in GCF and SWB.     

Nonabsorbable marker and single, random stool samples used for measuring intestinal absorption of macronutrients in infants and children

To measure intestinal absorption by using a single, random stool sample, polyethylene glycol (PEG), 1 g/d, and a constant diet were given to healthy infants, with a constant PEG-to-macronutrient ratio. After 10 d equilibration, apparent intestinal absorption of macronutrients was estimated from a standard 3-d metabolic balance and compared with that estimated by using the ratio of PEG to macronutrients in a single random sample of feces. Correlation coefficients for this comparison were 0.649, 0.715, and 0.924 for nitrogen, carbohydrate, and fat, respectively. Additionally, apparent intestinal absorptions estimated from two separate consecutive 3-d metabolic-balance studies were compared, showing correlation coefficients of 0.106, 0.653, and 0.463 for nitrogen, carbohydrate, and fat, respectively. The random sample-marker technique appears to be acceptable for measuring apparent absorption of macronutrients and is at least as accurate as a standard 3-d metabolic-balance study.     

Relative effects of diarrhea, fever, and dietary energy intake on weight gain in rural Bangladeshi children

Quantitative studies of morbidity, food intake, and somatic growth were done prospectively during 14 mo for 70 children aged 5-18 mo in two Bangladeshi villages. When random-effect regression models were used, monthly changes in weight were inversely related to proportions of days in the month with fever and diarrhea and positively related to energy intake per kilogram body weight. Interestingly, weight changes did not vary with age in this interval. Estimates indicate that increasing energy intakes to the recommended World Health Organization level would have a significantly greater effect on weight gain than would the elimination of diarrhea and fever. With energy at recommended intake and diarrhea and fever prevalence as found in US children, weight gain is predicted to be near that of the international reference population. Therefore, interventions aimed at improving dietary intake may be as important as infection-control programs for improving growth of children in poor developing nations.     

Potential aripiprazole-mediated extrapyramidal symptoms in an adult with developmental disabilities.

PURPOSE: A case of extrapyramidal symptoms (EPS) following administration of aripiprazole to a man with developmental disabilities who had never received antipsychotic medications and had no history of movement disorders is presented. SUMMARY: The patient was a 40-year-old male with developmental disabilities. He was nonverbal, profoundly mentally retarded, and diagnosed with obsessive compulsive disorder (OCD) and orthopedic problems. He developed episodic movements possibly consistent with EPS secondary to aripiprazole usage. The patient was antipsychotic naive before initiation of aripiprazole 5 mg daily. Concurrent medications at the time of EPS onset included oxazepam, baclofen, and citalopram. Baclofen and oxazepam were prescribed secondary to right-sided hemiparesis contractures. Aripiprazole, 5 mg daily, was initiated in November 2004 as an augmentation strategy for the diagnosis of OCD. Facial, tongue, and arm movements were first reported approximately five weeks after the initiation of aripiprazole. Initial symptoms resolved after approximately 24 hours. The dosage was increased to 10 mg daily two weeks later. Dystonic episodes continued on an intermittent basis, and the patient presented with lower-lip thrusting and upper-limb athetosis. These movements interfered with the patient's eating, chewing, and holding of utensils. Several of the standard treatment strategies for EPS were used. Initially, diphenhydramine hydrochloride 25 mg was administered orally every six hours. The patient's movements resolved following diphenhydramine administration. Aripiprazole was subsequently discontinued secondary to its lack of efficacy for OCD and the development of a movement disorder. CONCLUSION: A patient with developmental disabilities who had no history of movement disorders developed EPS following initiation of aripiprazole.     

Breast pump adverse events: reports to the food and drug administration.

Breast pumps are medical devices used to express milk and maintain the milk supply. The purpose of this study was to characterize adverse events reported to the United States Food and Drug Administration (FDA) on breast pumps. Thirty-seven adverse event reports on breast pumps were identified from the Manufacturer and User Facility Device Experience database between 1992 and 2003. Four additional reports were found in the Device Experience Network database from 1992 to 1996. The most commonly reported adverse events for electric breast pumps were pain, soreness, or discomfort; the need for medical intervention; and breast tissue damage. Most frequently reported problems for manual breast pumps were breast tissue damage and infection. Contamination of breast milk during pumping was also reported. Breast pump adverse events are likely underreported to the FDA. Reporting adverse events is important for improving the design and manufacture of breast pumps and subsequently decreasing adverse events.     

PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes.

Scintigraphic imaging with (123)I-metaiodobenzylguanidine ((123)I-MIBG) has demonstrated extensive losses of cardiac sympathetic neurons in idiopathic Parkinson's disease (IPD). In contrast, normal cardiac innervation has been observed in (123)I-MIBG studies of multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP). Consequently, it has been hypothesized that cardiac denervation can be used to differentiate IPD from MSA and PSP. We sought to test this hypothesis by mapping the distribution of cardiac sympathetic neurons in patients with IPD, MSA, and PSP by using PET and (11)C-meta-hydroxyephedrine ((11)C-HED). Also, the relationship between cardiac denervation and nigrostriatal denervation was investigated by measuring striatal presynaptic monoaminergic nerve density with PET and (11)C-dihydrotetrabenazine ((11)C-DTBZ). METHODS: (11)C-HED and (11)C-DTBZ scans were obtained for patients with IPD (n = 9), MSA (n = 10), and PSP (n = 8) and for age-matched control subjects (n = 10). Global and regional measurements of (11)C-HED retention were obtained to assess the extent of cardiac sympathetic denervation. (11)C-DTBZ binding was measured in the caudate nucleus, anterior putamen, and posterior putamen. RESULTS: As expected, extensive cardiac denervation was observed in several of the patients with IPD. However, substantial cardiac denervation was also seen in some patients with MSA and PSP. (11)C-DTBZ studies demonstrated striatal denervation in all patients with IPD and in most patients with MSA and PSP. No correlation was found between cardiac (11)C-HED retention and striatal (11)C-DTBZ binding. CONCLUSION: Cardiac sympathetic denervation was found to occur not only in IPD but also in other movement disorders, such as MSA and PSP. This finding implies that scintigraphic detection of cardiac sympathetic denervation cannot be used independently to discriminate IPD from other movement disorders, such as MSA and PSP. Cardiac sympathetic denervation was not correlated with striatal denervation, suggesting that the pathophysiologic processes underlying cardiac denervation and striatal denervation occur independently in patients with parkinsonian syndromes. These findings provide novel information about central and peripheral denervation in patients with neurodegenerative disorders.     

'THOUGH THIS BE MADNESS YET THERE IS METHOD IN'T'1

ABSTRACT Freud's paper on the Schreber Case is considered from a contemporary perspective drawing on the object relations theorists. Some of Winnicott's ideas are used to illustrate how one might understand Schreber's predicament today. Although Freud's views on the role of repressed homosexual longings in the aetiology of Schreber's illness are not endorsed his prescience in the search for meaning in the patient's discourse is applauded.     

Therapeutic potpourri

Many older treatments should not be discarded because of newer modalities. Various dermatologic disorders may be controlled effectively by prescribing these older topical agents.