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Objective Port-wine birthmark (PWB) is a common occurrence in the newborn, and general pediatricians, dermatologists, and ophthalmologists are often called on to make an assessment of risk for Sturge-Weber syndrome (SWS) due to workforce shortages in pediatric neurologists and MRI’s low sensitivity for SWS brain involvement in infants. We therefore aimed to develop a quantitative EEG (qEEG) approach to safely screen young infants with PWB for SWS risk and optimal timing of diagnostic MRI. Methods Forty-eight infants (prior to first birthday) underwent EEG recording. Signal processing methods compared voltage between left and right sides using a previously defined pipeline and diagnostic threshold. In this test sample, we compared sensitivity/specificity of the qEEG metric against MRI performed after the first birthday. We also used likelihood ratio testing to determine whether qEEG adds incremental information beyond topographical extent of PWB, another risk marker of brain involvement. Results qEEG helped predict SWS risk in the first year of life (p = 0.031), with a sensitivity of 50% and a specificity of 81%. It added about 40% incremental information beyond PWB extent alone (p = 0.042). Conclusion qEEG adds information to risk prediction in infants with facial PWB. Significance qEEG can be used to help determine whether to obtain an MRI in the first year of life. The data collected can assist in developing a predictive model risk calculator that incorporates both PWB extent and qEEG results, which can be validated and then employed in the community.

Objective:To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome.Methods:We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist–Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity.Results:Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale.Conclusions:Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome.Classification of evidence:This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect.

Functional connectivity differences between children with autism spectrum disorder (ASD) and typically developing children have been described in multiple datasets. However, few studies examine the task-related changes in connectivity in disorder-relevant behavioral paradigms. In this paper, we examined the task-related changes in functional connectivity using EEG and a movement-based paradigm that has behavioral relevance to ASD. Resting-state studies motivated our hypothesis that children with ASD would show a decreased magnitude of functional connectivity during the performance of a motor-control task. Contrary to our initial hypothesis, however, we observed that task-related modulation of functional connectivity in children with ASD was in the direction opposite to that of TDs. The task-related connectivity changes were correlated with clinical symptom scores. Our results suggest that children with ASD may have differences in cortical segregation/integration during the performance of a task, and that part of the differences in connectivity modulation may serve as a compensatory mechanism. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Decreased connectivity between brain regions is thought to cause the symptoms of autism. Because most of our knowledge comes from data in which children are at rest, we do not know how connectivity changes directly lead to autistic behaviors, such as impaired gestures. When typically developing children produced complex movements, connectivity decreased between brain regions. In children with autism, connectivity increased. It may be that behavior-related changes in brain connectivity are more important than absolute differences in connectivity in autism.

In this study, we aim to automate the sleep stage scoring process of overnight polysomnography (PSG) data while adhering to expert-based rules. We developed a sleep stage scoring algorithm utilizing the generalized linear modelling (GLM) framework and extracted features from electroencephalogram (EEG), electromyography (EMG) and electrooculogram (EOG) signals based on predefined rules of the American Academy of Sleep Medicine (AASM) Manual for Scoring Sleep. Specifically, features were computed in 30-s epochs in the time and frequency domains of the signals and were then used to model the probability of an epoch being in each of five sleep stages: N3, N2, N1, REM or Wake. Finally, each epoch was assigned to a sleep stage based on model predictions. The algorithm was trained and tested on PSG data from 38 healthy individuals with no reported sleep disturbances. The overall scoring accuracy reached on the test set was 81.50 ± 1.14% (Cohen's kappa, κ = 0.73 ± 0.02 ). The test set results were highly comparable to the training set, indicating robustness of the algorithm. Furthermore, our algorithm was compared to three well-known commercialized sleep-staging tools and achieved higher accuracies than all of them. Our results suggest that automatic classification is highly consistent with visual scoring. We conclude that our algorithm can reproduce the judgement of a scoring expert and is also highly interpretable. This tool can assist visual scorers to speed up their process (from hours to minutes) and provides a method for a more robust, quantitative, reproducible and cost-effective PSG evaluation, supporting assessment of sleep and sleep disorders.

Previous research has demonstrated distinct neural correlates for maintenance of abstract, relational versus concrete, sensory information in working memory (WM). Storage of spatial relations in WM results in suppression of posterior sensory regions, which suggests that sensory information is task-irrelevant when relational representations are maintained in WM. However, the neural mechanisms by which abstract representations are derived from sensory information remain unclear. Here, using electroencephalography, we investigated the role of alpha oscillations in deriving spatial relations from a sensory stimulus and maintaining them in WM. Participants encoded two locations into WM, then after an initial maintenance period, a cue indicated whether to convert the spatial information to another sensory representation or to a relational representation. Results revealed that alpha power increased over posterior electrodes when sensory information was converted to a relational representation, but not when the information was converted to another sensory representation. Further, alpha phase synchrony between posterior and frontal regions increased for relational compared to sensory trials during the maintenance period. These results demonstrate that maintaining spatial relations and locations in WM rely on distinct neural oscillatory patterns.

Objective: We sought to examine the prevalence of EEG abnormalities in Smith-Lemli-Opitz syndrome (SLOS) as well as the relationship between interictal epileptiform discharges (IEDs) and within-subject variations in attentional symptom severity. Methods: In the context of a clinical trial for SLOS, we performed cross-sectional and repeated-measure observational studies of the relationship between EEG findings and cognitive/behavioral factors on 23 children (aged 4–17 years). EEGs were reviewed for clinical abnormalities, including IEDs, by readers blinded to participants9 behavioral symptoms. Between-group differences in baseline characteristics of participants with and without IEDs were analyzed. Within-subject analyses examined the association between the presence of IEDs and changes in attention-deficit/hyperactivity disorder (ADHD) symptoms. Results: Of 85 EEGs, 43 (51%) were abnormal, predominantly because of IEDs. Only one subject had documented clinical seizures. IEDs clustered in 13 subjects (57%), whereas 9 subjects (39%) had EEGs consistently free of IEDs. While there were no significant group differences in sex, age, intellectual disability, language level, or baseline ADHD symptoms, autistic symptoms tended to be more prevalent in the “IED” group (according to Autism Diagnostic Observation Schedule–2 criteria). Within individuals, the presence of IEDs on a particular EEG predicted, on average, a 27% increase in ADHD symptom severity. Conclusions: Epileptiform discharges are common in SLOS, despite a relatively low prevalence of epilepsy. Fluctuations in the presence of epileptiform discharges within individual children with a developmental disability syndrome may be associated with fluctuations in ADHD symptomatology, even in the absence of clinical seizures.

Attention can modulate processing of visual input according to task-relevant features, even as early as approximately 100 ms after stimulus presentation. In the present study, event-related potential and behavioral data revealed that inhibition of distractor features, rather than activation of target features, is the primary driver of early feature-based selection in human observers. This discovery of inhibition consistent with task goals during early visual processing suggests that inhibition plays a much larger role at an earlier stage of target selection than previously recognized. It also highlights the importance of understanding the role of inhibition (in addition to activation) in attention.

Geschildert wird der Weg des Autors auf Basis der manuellen Medizin in die osteopathische Medizin in einer Zeit, als diese nur in limitierten Moglichkeiten und durch das Engagement einzelner Manualmediziner in Deutschland moglich war. Ein Modell fur Verkettungssyndrome wird anhand der Arbeiten von M. Forte mit dessen Definitionen von Kompensation, Adaptation und Dekompensation vorgestellt. Darauf aufbauend werden Uberlegungen zur Wirkweise der osteopathischen Medizin angestellt und diese in den Kontext der gegenwartigen kontroversen Diskussion um osteopathische Verfahren und osteopathische Medizin gestellt.

INTRODUCTION: Patterns and predictors of recovery from encephalitis are poorly understood. METHODS: This study examined functional status and reviewed charts of all children who presented to a pediatric inpatient rehabilitation facility with encephalitis between 1996 and 2010. Functional status at admission and discharge from inpatient rehabilitation was evaluated using the Functional Independence Measure for Children (WeeFIM) Self-care, Mobility, Cognitive, and Total Developmental Functional Quotient scores (DFQ, % of age-appropriate function). Charts were reviewed to characterize key clinical features and findings. RESULTS: Of the 13 children identified, the mean age was 9 years (range 5–16) with 54% males. Mean WeeFIM Total DFQ at admission was 37 (range: 15–90) and at discharge was 64 (range: 16–96). Average change in WeeFIM Total DFQ from admission to discharge was 26.7 (range 0–55, p< 0.001). WeeFIM domain scores improved between admission and discharge (Self-Care: p< 0.001, Cognition: p< 0.01, Mobility: p< 0.001). Eleven children displayed significant impairments in functional skills, defined as DFQ of 85, at discharge. Key clinical features and findings were diverse and not related to functional outcome. CONCLUSIONS: Results suggest that significant functional improvement in children with encephalitis occurs during inpatient rehabilitation. Further research is necessary to identify predictors of outcome in children with encephalitis.

Several years ago, a colleague in the developmental clinic asked me to tell him what I thought about a brain mapping EEG report brought in by a parent. The report made a number of bold pronouncements about the child's brain function, such as, “Decreased current in the fusiform gyrus indicates face-processing difficulties.” From my research using EEG to study the pathophysiology of developmental disabilities, I knew that making even a single conclusion about group data took years of painstaking development of cognitive experiments and obsessive analysis of the data using a variety of signal-processing techniques. The notion that automatic software could validly produce several conclusions from a few minutes' worth of spontaneous EEG data seemed far-fetched.

There is considerable lay discussion that children with Attention-Deficit/Hyperactivity Disorder (ADHD) have increased difficult with multitasking, but there are few experimental data. In the current study, we examine the simultaneous processing of two stimulus-response tasks using the psychological refractory period (PRP) effect. We hypothesized that children with ADHD would show a greater PRP effect, suggesting a prolonged “bottleneck” in stimulus-response processing. A total of 19 school-aged children with ADHD showed a prolonged PRP effect compared with 25 control children, suggesting a higher cognitive cost in ADHD for multi-tasking.

Aware of parental reports of academic variability, we investigated month-to-month fluctuations in cognitive abilities and EEG status by repeated measures testing in six children with benign epilepsy with central-temporal spikes (BECTS). All showed greater than normal test-retest variability. Daytime EEG abnormalities were also variable. Short-term fluctuations in cognitive function appear common in children with BECTS, potentially impacting academic performance.

Internal action models refer to sensory-motor programs that form the brain basis for a wide range of skilled behavior and for understanding others’ actions. Development of these action models, particularly those reliant on visual cues from the external world, depends on connectivity between distant brain regions. Studies of children with autism reveal anomalous patterns of motor learning and impaired execution of skilled motor gestures. These findings robustly correlate with measures of social and communicative function, suggesting that anomalous action model formation may contribute to impaired development of social and communicative (as well as motor) capacity in autism. Examination of the pattern of behavioral findings, as well as convergent data from neuroimaging techniques, further suggests that autism-associated action model formation may be related to abnormalities in neural connectivity, particularly decreased function of long-range connections. This line of study can lead to important advances in understanding the neural basis of autism and, more critically, can be used to guide effective therapies targeted at improving social, communicative, and motor function.

To evaluate cortical auditory function, including speech recognition, in children with benign rolandic epilepsy (BRE).Fourteen children, seven patients with BRE and seven matched controls, underwent audiometric and behavioral testing, simultaneous EEG recordings, and auditory-evoked potential recordings with speech and tones. Speech recognition was tested under multiple listening conditions.All participants demonstrated normal speech recognition abilities in quiet, as well as normal peripheral and subcortical auditory function. BRE patients performed significantly worse than controls when speech recognition was tested under adverse listening conditions, including background noise. Five BRE patients who were impaired on two or more tests had centrotemporal spiking on awake EEG. There were no significant group differences in the latency or amplitude of early N100 cortical responses to speech or tones. Conversely, the mismatch negativity, a preattentive index of cortical processing that is elicited passively, was absent or prolonged for speech, but not tones, in BRE patients as compared to controls.Children with BRE demonstrated specific speech recognition impairments. Our evoked potential findings indicate that these behavioral impairments reflect dysfunction of nonprimary auditory cortex and cannot be attributed solely to attention difficulties. A possible association between auditory impairments and centrotemporal spiking (1/min) on awake EEG was identified. The pattern of speech recognition impairments observed is a known risk factor for academic difficulties in school-age children. Our results underscore the importance of comprehensive auditory testing, using behavioral and electrophysiological measures, in children with BRE.

Disorders of attention or learning commonly accompany neurodevelopmental disorders. The evaluation and diagnosis of these disorders is complex and does not always follow techniques used for typically developing children. These disorders are often underappreciated and inadequately addressed because they are overshadowed by the neurodevelopmental disorder. Nevertheless, failure to recognize, diagnose, and manage these disorders may result in unsuccessful community integration.

To ascertain whether there are differences in the histopathological appearance of tendinopathic Achilles and patellar tendons.In males, we studied biopsies from tendinopathic Achilles (N = 28; average age 34.1 yr) and patellar tendons (N = 28; average age 32.1), Achilles tendons (N = 21; average age 61.8 yr) from deceased patients with no known tendon pathology, and patellar tendons (N = 15; average age 28.3) from patients undergoing anterior cruciate ligament reconstruction. Hematoxylineosin stained slides were interpreted using a semiquantitative grading scale (0: normal to 3: maximally abnormal) for fiber structure, fiber arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, and hyalinization. All slides were assessed blindly twice, the agreement between two readings ranging from 0.170 to 0.750 (kappa statistics).The highest mean score of tendinopathic Achilles tendons was not significantly different from that of tendinopathic patellar tendons (11.6 +/- 5 and 10.4 +/- 3, respectively). The ability to differentiate between an Achilles tendon and a patellar tendon was low.Tendinopathic Achilles and patellar tendons show a similar histological picture. It was not possible to identify whether a specimen had been harvested from an Achilles or a patellar tendon on the basis of histological examination. The general pattern of degeneration was common to both tendinopathic Achilles and patellar tendons. A common, as yet unidentified, etiopathological mechanism may have acted on both these tendon populations.

In this study we show that the characteristics of non-Hodgkin lymphoma (NHL) tumors in female Naval Medical Research Institute (NMRI, USA) mice fed mistletoe lectin (ML)-containing diets were different from those in mice fed control diet. The non-Hodgkin lymphoma tumor was originally established from a spontaneous tumor which developed in the inguinal region of a male mouse. Mice (five animals per group) were fed a lactalbumin (LA)-based control diet or a diet which provided up to 10mg lectin per day. At the highest daily intake (10mg lectin) the degree of mitotic activity in tumors was reduced by 75% and the nuclear area had diminished by 21%. The overall level of lymphocyte infiltration (CD3 positive cells) in tumors from mistletoe lectin fed mice was increased by a factor of two. Other morphological studies showed a high incidence of apoptotic bodies in non-Hodgkin lymphoma tumors obtained from mice fed mistletoe lectin diets. The feeding of such diets thus produced several identifiable changes in the morphology of non-Hodgkin lymphoma tumors. These were consistent with the observed reduction in tumor mass. In 4/15 mice fed a mistletoe lectin diet for 11 days there was no longer evidence of viable tumor. The results show that this lectin exerts powerful anti-tumor effects when provided by the oral route.

We studied biopsies from the Achilles tendons of patients undergoing open repair for a subcutaneous rupture of their Achilles tendons (27 men, 11 women; mean age, 45.3 13.8 years) and specimens of Achilles tendons from persons with no known tendon ailments (43 men, 3 women; mean age, 64.2 9.7 years). Histologic examination was performed using stained slides that were interpreted using a semiquantitative grading scale assessing fiber structure and arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, hyalinization, and glycosaminoglycan. We gave up to three marks for each of these variables, with 0 being normal and 3 being maximally abnormal. All the histology slides were assessed twice in a blinded manner; the agreement between two readings ranged from 0.56 to 0.87 (kappa statistics). The score of ruptured tendons was significantly greater than the average score of control tendons (20.5 3.6 versus 6.5 2.1), and there was significantly higher degeneration in the ruptured tendons. Nonruptured Achilles tendons, even at an advanced age, and ruptured Achilles tendons are clearly part of two distinct populations. Using these staining techniques, light microscopic degeneration is not a feature of tendons from healthy, older persons.

The historical account of the rise and fall of Nosema locustae as a biological control agent of grasshoppers has substantial implications for the successful development and implementation of biological control of migratory locusts in Africa. The potential of N. locustae was ultimately not sufficient to overcome a set of impediments, including: efficacy (the rate and extent of mortality were relatively low), target specificity (not all pest species were susceptible), formulation (wheat bran bait excluded feeding by some pests), cost (the price of the formulated product was excessive), storage (the organism lacked long-term stability), complex application (the pathogen and its carrier had to be applied during a narrow set of environmental and logistical parameters) and production (the use of an in vivo production system made high-volume production difficult). Some of the most significant limitations that led to the failure of N. locustae have been overcome by work on other pathogens, including the problems of formulation, storage, efficacy and production. However, at least four relevant lessons can be derived from the N. locustae story and applied to ongoing work with biological control of migratory locusts. First, the erratic population dynamics of acridids necessitates that the production, storage and distribution of an augmentative biological control agent will be driven by a boom-and-bust cycle. Second, the immense spatial scale and low unit value of the resources (rangelands) being protected create a unique set of logistical challenges. Third, the control of acridids involves the management of a native insect pest embedded within complex, native ecosystems, which suggests that our interventions should be undertaken with a great deal of caution, monitoring and, ultimately, humility. Fourth, although pathogens can be used as ‘bio-insecticides’, biological control requires education of end-users regarding a more sophisticated approach to pest management.

A child with Sturge-Weber syndrome and a left occipital leptomeningeal angioma developed focal seizures at 6 years of age that responded initially to oxcarbazepine. After 7 months of seizure freedom, the patient developed typical myoclonic-astatic seizures associated with generalized electrographic discharges, which worsened as oxcarbazepine was increased. The seizures and electroencephalogram improved dramatically in 3 weeks as the oxcarbazepine was withdrawn and valproic acid was initiated. This case demonstrates the importance of recognizing that children with epilepsy due to focal lesions can develop secondary bilateral synchrony that can be aggravated by medications that are effective for partial seizures. In such cases, treatment with a broad-spectrum antiepileptic may be advantageous.

The cytochrome P450 superfamily of enzymes play a central part in the metabolism of carcinogens and anti-cancer drugs. The expression, cellular localisation, and distribution of different forms of P450 and the functionally associated enzymes epoxide hydrolase and glutathione S-transferases have been investigated in oesophageal cancer and non-neoplastic oesophageal tissue using immunohistochemistry. Expression of the different enzymes was confined to epithelial cells in both non-neoplastic samples and tumour samples except the CYP3A was also identified in mast cells and glutathione S-transferase pi was present in chronic inflammatory cells. CYP1A was present in a small percentage of non-neoplastic samples but both CYP2C and CYP3A were absent. Epoxide hydrolase was present in half of the non-neoplastic samples and the different classes of glutathione S-transferase were present in a low number of samples. In carcinomas CYP1A, CYP3A, epoxide hydrolase, and glutathione S-transferase pi were expressed in at least 60% of samples. The expression of glutathione S-transferases alpha and mu were significantly less in adenocarcinoma compared with squamous carcinoma.

AIMS--To examine the distribution of PAI-1 antigen in normal and cirrhotic liver and liver with metastases. METHODS--Sections of normal and cirrhotic liver and liver with metastases were stained using the alkaline phosphatase antialkaline phosphatase (APAAP) technique and monoclonal antibody specific for plasminogen activator inhibitor (PAI-1). RESULTS--PAI-1 antigen was identified as discrete granules in the cytoplasm of hepatocytes in normal liver, particularly around portal tracts and central veins of the liver lobule. In cirrhotic liver a striking reduction of PAI-1 antigen was noted. In liver with metastases increased amounts of PAI-1 antigen were concentrated in hepatocytes around the margins of malignant deposits. CONCLUSIONS--Cirrhotic liver contains considerably less PAI-1 antigen than does normal liver, despite raised plasma concentrations of PAI-1. This may reflect release of hepatic PAI-1 into the circulation or decreased clearance of PAI-1 from the plasma. Secondary malignant deposits in the liver seem to stimulate production of PAI-1 in adjacent hepatocytes. This may influence the invasive process and may contribute to the thrombotic tendency associated with malignancy.

Many mutagenic nitroso compounds are also diabetogenic. Betel-nut (Areca catechu) chewing populations have an increased incidence of foregut cancers related to betel-nut nitrosamines which suggests that betel consumption could be diabetogenic. Young adult CD1 mice with a low spontaneous incidence of diabetes were fed betel nut in standard feed for 2–6 days. Single point (90 min) intra-peritoneal glucose tolerance tests were used to follow glucose tolerance up to 6 months of age. Glucose intolerance was defined as over 3 SD above mean control values. Glucose intolerance was found in 3 of 51 male and 4 of 33 female adult mice which were fed the betel diet (p

The cytochrome P450, epoxide hydrolase, and glutathione S-transferase enzyme families play an important part in the metabolism of many carcinogens and anti-cancer drugs. The expression of two forms of cytochrome P450 (P450 1A and P450 3A), epoxide hydrolase and of the alpha, mu, and pi forms of glutathione S-transferase in normal colon, colonic adenomas, and adenocarcinoma of the colon were studied by immunohistochemistry. This allowed the precise cellular site and distribution of each enzyme to be determined. Expression of all the xenobiotic metabolising enzymes studied was almost wholly confined to the epithelial cells, whether in normal, adenoma or carcinoma samples, except that cytochrome P450 3A was also identified in mast cells and glutathione S-transferase pi was also present in chronic inflammatory cells. Cytochrome P450 was present in only a small proportion of normal colon samples, whereas epoxide hydrolase and glutathione S-transferase mu were identified in about half, and glutathione S-transferase alpha and pi in most normal samples. By contrast all the enzyme forms studied were expressed in virtually all adenomas and in over half the carcinomas. These results suggest that cytochrome P450 1A and cytochrome P450 3A are more specific markers of colonic neoplasia than epoxide hydrolase or glutathione S-transferases alpha, mu, and pi.

AIMS: To study the localisation and distribution of albumin mRNA in normal liver and hepatocellular carcinoma by in situ hybridisation with an oligonucleotide probe. METHODS: A 51 base oligonucleotide was synthesised from a sequence at the 5' end of the human albumin gene and the probe was labelled at its 3' end with digoxigenin 11-dUTP. Formalin fixed, wax embedded sections of liver biopsy specimens were used to study the localisation and distribution of albumin mRNA. After in situ hybridisation the bound probe was visualised using a digoxigenin antibody conjugated with alkaline phosphatase. RESULTS: In normal liver albumin mRNA was detected in hepatocytes and no positive signal was observed in biliary epithelium, vascular endothelium, or Kupffer cells. In 75% (9/12) of the hepatocellular carcinomas studied a positive hybridisation signal was observed in tumour cells. CONCLUSIONS: Albumin mRNA can be detected in sections of formalin fixed, wax embedded liver, a digoxigenin labelled probe is ideally suited for in situ hybridisation of liver because there is no background from the detection system. The identification of albumin mRNA may be a useful marker of hepatocellular carcinoma, and the demonstration of albumin mRNA by in situ hybridisation overcomes the potential background problem associated with albumin immunohistochemistry.

OBJECTIVE--To audit the accuracy and impact on the frequency of operation of fine needle aspiration cytology of isolated thyroid swellings. DESIGN--Prospective analysis over six years of cytological predictions compared with histological findings. SETTING--Thyroid clinic serving the Grampian region. PATIENTS--395 Consecutive patients presenting with an isolated thyroid swelling, 307 of whom underwent surgical excision. Analysis was confined to a subgroup of 283 patients with satisfactory aspirates who were operated on. RESULTS--The positive predictive value of aspiration cytology for detecting malignant disease was 100% and the sensitivity 83%. The sensitivity for the detection of neoplasia (frank malignancy together with follicular adenomas) was 76%. The specificity was 58% and the overall accuracy 69%. Recalculation of data in previous papers with strict criteria showed the accuracy of aspiration cytology to be variable and lower than is widely accepted. Since the introduction of aspiration cytology 21% fewer operations for isolated thyroid swellings have been performed. CONCLUSIONS--As a basis of selection for surgical excision of isolated thyroid swellings according to prediction of neoplasia fine needle aspiration cytology is less reliable than is widely accepted. It is an adjunct to management rather than a definitive test, and negative cytological results do not exclude neoplastic disease. Further study should take account of the implications of repeated clinic attendances for review and aspiration as these may culminate in delayed surgical treatment.

The potential value of DNA aneuploidy, in distinguishing benign from malignant follicular thyroid neoplasms, was studied. The nuclear DNA content of 65 follicular thyroid neoplasms (52 adenomas and 13 carcinomas) was determined by flow cytometric analysis of paraffin embedded material; in 58 cases preparations were technically satisfactory. In 22 follicular neoplasms DNA analysis was also performed on fresh material obtained by fine needle aspiration of surgical specimens. Cell cycle analysis was performed on both fresh and fixed specimens. An aneuploid DNA profile was found on analysis of fixed tissue in eight of 45 (18 per cent) follicular adenomas and four of 13 (31 per cent) follicular carcinomas. DNA aneuploidy was also found in six of the 22 (27 per cent) fresh preparations from follicular adenomas. The frequency of DNA aneuploidy in apparently benign and malignant follicular neoplasms was similar. Follicular thyroid neoplasia are best regarded as a single entity with a low incidence of local and distant spread. All follicular neoplasia are therefore best excised.

In this study we have investigated the expression of a major family of cytochrome P450, cytochrome P450IA, in human breast carcinoma. Two closely related subfamilies (or forms) of cytochrome P450IA, cytochrome P450IA1 and cytochrome P450IA2 have been identified in rat and similar forms occur in man (Ioannides & Parke, 1990). The murine monoclonal antibody RM3 used in this study recognises rat cytochrome P450IA1 and not rat cytochrome P450IA2 and recognises a single band on immunoblots of human liver

Diets containing genetically modified (GM) potatoes expressing the lectin Galanthus nivalis agglutinin (GNA) had variable effects on different parts of the rat gastrointestinal tract. Some effects, such as the proliferation of the gastric mucosa, were mainly due to the expression of the GNA transgene. However, other parts of the construct or the genetic transformation (or both) could also have contributed to the overall biological effects of the GNA-GM potatoes, particularly on the small intestine and caecum.

The preoperative diagnosis of some thyroid neoplasms remains difficult even with the routine use of fine-needle aspiration cytology. The potential of nuclear magnetic resonance imaging (MRI) to discriminate between different thyroid pathologies was explored prospectively and compared with the final pathology in a series of 37 patients. MRI yielded high-quality images of the thyroid swelling but did not provide additional information to differentiate benign from neoplastic lesions. MRI does not contribute to the routine management of thyroid swellings.

By means of incoherent quasielastic neutron scattering experiments on uniaxially oriented n‐C33H68 samples it was possible to give an experimental proof that molecular motion in modification C is composed of rotational and translational components. The analysis of the quasielastic spectra was performed comparing them to theoretical scattering laws, which were calculated on the basis of different models, compatible with the results of former x‐ray, NMR and ir experiments. This procedure leads to the conclusion that translational jumps in the chain direction, the jump distance 1.27 A, and rotational 180° jumps take place independently. At 67 °C the jump rates are: vt = (2.6±0.4) ×108 s−1 and vr= (5±2) ×107 s−1, respectively.

A novel technique combining the freeze drying and embedding in glycol methacrylate at low temperature of tissue permitted the histochemical demonstration of a variety of enzymes, showing maintenance of enzyme activity, accurate enzyme localisation without apparent diffusion, and excellent morphological detail. The results obtained with this new approach were superior to standard techniques used for both enzyme histochemical and morphological studies. Moreover, blocks of the embedded tissue were stored for at least one year at room temperature without loss of enzyme activity. This method should find a wide range of applications in histopathology.

The increments in plasma zinc concentrations after an oral dose of elemental zinc (50 mg) as the sulphate were used to assess the intestinal absorption of the metal in 11 patients with dermatitis herpetiformis (DH) before starting a gluten-free diet, 12 patients with newly diagnosed celiac disease (CD), 10 patients known to have CD, and 15 healthy volunteers. The areas under the plasma zinc increment curve plotted against time were determined for 3 (AUC3) and 6 (AUC6) h. The AUC3 in healthy volunteers was 401 +/- 48 mumol 1(-1) 3 h (mean +/- SD); it was reduced in newly diagnosed CD 187 +/- 76 mumol 1(-1) 3 h (p less than 0.001), and in dermatitis herpetiformis 206 +/- 87 mumol 1(-1) 3 h (p less than 0.01); but it was normal in the known CD 396 +/- 204 mumol 1(-1) 3 h, the wide variation reflecting the variable compliance with a previously instituted gluten-free diet. The AUC6 was similarly affected, healthy volunteers 700 +/- 111 mumol 1(-1) 6 h, new CD 380 +/- 169 mumol 1(-1) 6 h (p less than 0.01); dermatitis herpetiformis 471 +/- 107 mumol 1(-1) 6 h (p less than 0.01); known CD 725 +/- 380 mumol 1(-1) 6 h. The AUC3 was more consistently abnormal than conventional tests of small intestinal function. In a prospective study the AUC3 and AUC6 improved and reflected compliance with a gluten-free diet.

The single chain dynamics of polydimethylsiloxane in the melt is studied by means of quasielastic neutron scattering. For this polymer the wave vector range 0.03 A−1≦q≦0.30 A−1 covers the regime of universal modes as well as local diffusive processes. A model is described which incorporates the specific chemical structure of the macromolecule and allows to interpret our data in the full wave vector regime. The only parameter which enters the model, the monomer diffusion constantDm, is found to be (1.2±0.2)·10−5 cm2s−1.

Six patients are described to illustrate the operative management of tubulovillous neoplasms of the duodenum. Pancreaticoduodenectomy is appropriate for associated invasive carcinoma. Transduodenal submucosal excision of tubulovillous neoplasms with resection and reconstruction of the distal bile and pancreatic ducts if necessary is a satisfactory alternative when the neoplasm has not penetrated the muscularis mucosae.

An emended description of Entomophthora erupta and a description of Entomophthora helvetica sp. nov., fungi pathogenic to insects of the family Miridae, are given. Entomophthora erupta usually had 2–5 nuclei per conidium (mean diameter of 3.8 μm), colonized predominantly the abdomen of the host, and sporulated on the dorsal surface of the abdomen of the adult host, usually before death; E. helvetica usually had 8–13 nuclei per conidium (mean diameter of 1.6 μm), colonized the whole interior of the host, killed it in the nymphal stage before sporulation started, and sporulated on all parts of the cadaver. We advocate these features, including the pathobiological manifestations, as important taxonomic criteria at the infrageneric level of the genus Entomophthora sensu stricto.

Summary.— A patient with histologically proven Crohn's disease of the ileum and caecum presented with unusual ulceration of the mouth 3 years after subtotal colectomy. Worsening of bowel symptoms was associated with exacerbation of oral ulceration on several occasions. The areas of ulceration in the mouth were in relation to a sarcoid reaction typical of Crohn's disease.