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The superior self-regulation and attention-regulation abilities of securely attached children have been repeatedly demonstrated. However, the mechanisms that allow securely attached children to exhibit higher levels of attention focus than insecurely attached (anxious-ambivalent and anxious-avoidant) children need to be explored. One possible mechanism that has been hypothesized to play a role in focusing attention is self-touch. Previous research has shown that 10-year-old children exhibit more bilateral self-touch (i.e., both hands are simultaneously moving onto each other or on the body, and both hands are in contact with each other or with the body), but not lateral self-touch (i.e., one hand is moving on the other hand or on the body, and the hand is in contact with the other hand or with the body), when they focus attention on a task. Because bilateral coordination is still developing during childhood, we expected that lateral self-touch, instead of bilateral self-touch, may be associated with attention focus for toddlers. The objectives of the present study were to examine whether securely attached toddlers exhibit more self-touch, particularly lateral self-touch, while they focus on a task than while they do not focus on a task. We expected to find that the association between lateral self-touch and attention focus is not as strong for insecurely attached toddlers. Data from forty-nine mother-child dyads were employed for analyses. The attachment classification of the children was determined using the Strange Situation. The duration of attention focus and self-touch behavior during a reading task were coded. An association between lateral self-touch and attention focus was found for children of all attachment classifications. This association was particularly strong for securely attached children. We discuss the possibility that securely attached toddlers may use lateral self-touch to regulate attention.

Background As a result of the COVID-19 pandemic, some governments have mandated that residential care providers rapidly return children and youth to family. Objective The goal of the present study was to better understand the scope and characteristics of rapid return, and to provide data-informed recommendations for service providers working with this population. Participants and setting Representatives from 67 non-government organizations (NGOs) providing residential care that were government-mandated to rapidly return children and youth to family completed a brief online survey. They collectively serve 12,494 children in 14 nations. Methods Using a mixed methods design, results examined 1) characteristics of the rapid return mandate, 2) preparation received by children and families, 3) support services provided since the return, and 4) primary concerns for children and families. Results Data revealed that rapid return was characterized by compressed timelines that did not allow for adequate child and family assessment and preparation. However, all respondents indicated they believed at least some families would be able to remain intact safely with appropriate support. Primary concerns for children and families related to unresolved antecedents to separation, lack of economic capacity, limited monitoring, and lack of access to education. Conclusions Based on the findings, 9 recommendations were made for service providers working with children and families that have been rapidly reunified as a result of the COVID-19 pandemic.

Background: High-flow nasal cannula (HFNC) is a well-established respiratory support device in high-income countries, but to our knowledge, its use in sub-Saharan Africa has not been reported. This...

Background Almost one million prematurely born infants die annually from respiratory insufficiency, predominantly in countries with limited access to respiratory support for neonates. The primary hypothesis tested in the present study was that a modified device for bubble nasal continuous positive airway pressure (Bn-CPAP) would provide lower work of spontaneous breathing, estimated by esophageal pressure-rate products. Methods Infants born

Maternal mental state language is thought to influence children's mental state language and sociocognitive understanding (e.g., theory of mind), but the mechanism is unclear. The current study examined the longitudinal development of mental state language in mother-child interactions. The methodology included assessments of the child and/or mother-child dyad at six time points between 12 to 52 months of the child's age. Measures determined child's attachment style and language abilities, and mental state language used by mother and child during a block-building task. Results showed that (a) mental state talk, including belief and desire language, increased over time; (b) there were differences between the type of mental state words used by the mother in insecure versus secure dyads; (c) there were differences in patterns of mental state words used in both mothers and children in insecure versus secure dyads; and (d) attachment appeared to exert a consistent influence over time.

Background Interventions that improve cognitive function in Alzheimer's disease are urgently required. Aims To assess whether a novel cognitive training paradigm based on ‘chunking’ improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027). Method Thirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted. Results Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls. Conclusions Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease.

Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis.

Children who have experienced early adversities are at risk for behavioral problems and trauma symptoms. Using a two-group, pre–post intervention design, the authors evaluated the effectiveness of an online parent training for Trust-Based Relational Intervention, a trauma-informed, attachment-based intervention, in reducing behavioral problems and trauma symptoms in at-risk adopted children. Children of parents in the treatment group (n = 48) demonstrated significant decreases in behavioral problems and trauma symptoms after intervention. Scores for children in a matched-sample control group did not change. Findings suggest this intervention can effectively reduce behavioral problems and trauma symptoms in children with histories of adversities.

The objective of this work was to determine the effect of androgen deprivation therapy (ADT) on rates of bone mineral density (BMD) loss in men with prostate cancer. It was a prospective study comparing men receiving ADT to age matched controls for 2 y. Subjects received a history, physical exam, bone mineral density measurement, and laboratory evaluation every 6 months. Thirty-nine subjects receiving continuous ADT for prostate cancer (subjects) were compared to 39 age-matched controls not receiving ADT (controls). Twenty-three subjects and 30 controls completed the study through 24 months. Men in the ADT group demonstrated greater rates of bone mineral density loss than men in the control group at every site except the lumbar spine. Twenty-four month per cent of bone mineral density loss is presented as mean+/-standard error (s.e.). At the distal forearm, the ADT group value was -9.4%+/-1.0% and -4.4%+/-0.3% for controls (P

Vesicoureteric reflux (VUR) and renal scarring are commonly found in children with urinary tract infection (UTI). The prevalence of VUR and scarring may vary between racial groups. There are no published data on the prevalence of VUR and scarring in Chinese children with UTI. A retrospective, single-institution study was made of Hong Kong Chinese children aged less than 5 years with a documented UTI investigated by both micturating cystourethrography and dimercaptosuccinic acid scintigraphy. VUR was identified in 39% of 93 Chinese children with UTI. Renal scarring was present in 28% of boys, which is comparable with published data on Western children. Scarring appears to be less common in Chinese girls with UTI (11%) than in Western girls (30-38% from published data), and its severity is poorly related to VUR grade. There is a significant dependency relationship between grade of VUR and degree of scarring in Chinese boys (p0.05). In conclusion, renal scarring appears to be relatively uncommon in Chinese girls. The correlation between grade of VUR and degree of scarring in Chinese boys suggests a relationship, but provides no evidence about the direction of causation.

Aims/hypothesis. Diabetes-induced activation of protein kinase C has been associated with the development of vascular complications. Elevated de novo diacylglycerol synthesis has been postulated to underlie this protein kinase C activation. Diabetes also increases the circulating concentrations of non-esterified fatty acids, which are immediate precursors of diacylglycerol through the de novo pathway. We hypothesized that increased fatty acids contribute to de novo diacylglycerol synthesis and activation of protein kinase C in vascular cells. Methods. Primary cultures of porcine carotid smooth muscle cells were exposed to fatty acids, bound to albumin in physiologic ratios. Diacylglycerol and triacylglycerol were measured in extracts of these cells. Protein kinase C activation was measured as membrane translocation with isoform-specific antibodies. Results. Saturated fatty acids caused considerable accumulation of diacylglycerol through de novo synthesis. Unsaturated fatty acids increased triacylglycerol, but not diacylglycerol. Platelet-derived growth factor activated the α, ɛ and ζ protein kinase C isoforms. Activation of the α and ζ isoforms was amplified by oleate pretreatment but inhibited by palmitate. In the absence of growth factor stimulation, neither palmitate nor oleate had any effect on the membrane/cytosol distribution of any protein kinase C isoform. Conclusion/interpretation. Saturated fatty acids elicited de novo diacylglycerol synthesis in vascular smooth muscle cells without activating protein kinase C. Effects of fatty acids on protein kinase C activation by platelet-derived growth factor did not correlate with the effects on de novo diacylglycerol synthesis. These results indicate that de novo diacylglycerol synthesis is, by itself, insufficient to activate protein kinase C. [Diabetologia (2000) 43: 1136–1143]

Summary Respiratory and sleep disturbances may be important causes of morbidity in Steele-Richardson-Olszewski syndrome but the frequency and character of nocturnal abnormalities remains uncertain. A prospective study of 11 patients with Steele-Richardson-Olszewski syndrome and age-matched control subjects was undertaken using clinical assessments, a structured sleep questionnaire, spirometry, static maximum inspiratory and expiratory pressures and nocturnal oximetry. The mean age of the Steele-Richardson-Olszewski syndrome patients was 63.2 (52-70) years and mean disease duration was 4.0 (2-6) years. There was moderate to severe motor disability in nine and mild to moderate dementia in eight. In the patients with Steele-Richardson-Olszewski syndrome the following abnormalities contributed to sleep disturbances significantly more frequently than in normal controls: depression, dysphagia, frequent nocturnal awakenings (usually associated with urinary frequency), immobility in bed, difficulty with transfers, impaired dressing and feeding. There was profound impairment of voluntary respiratory control whilst automatic and limbic control were well maintained. Nocturnal respiratory abnormalities were not present even in the most severely disabled. In Steele-Richardson-Olszewski syndrome sleep abnormalities are common; they relate to the cognitive, pseudobulbar and extrapyramidal disturbances and may therefore be amenable to symptomatic control.

A prospective electrophysiological study of phrenic nerve was performed in 59 subjects undergoing open-heart surgery. The nerve was stimulated percutaneously at the neck and the diaphragmatic response was recorded with surface electrodes placed over the 8th intercostal space. The latency, amplitude, duration and area of the evoked response were measured before and after the operation. Post-operatively no response was elicited in 2 patients bilaterally, in 5 from the left and in 2 from the right. Comparison of the post-operative with the pre-operative group values in the remaining subjects showed that the amplitude and area of the left phrenic were lower in the post-operative study, indicating that some of the nerve fibres were not conducting. There were no statistically significant differences between pre and post-operative values of latency or duration on the left or any of the parameters on the right. Our findings suggest that the amplitude and area of the diaphragmatic response are more sensitive than latency in detecting phrenic nerve paresis associated with open-heart surgery.

Three siblings presented with a progressive neurological disorder beginning in the third decade of life and characterised by palatal myoclonus, nystagmus, bulbar weakness and spastic tetraparesis. There was no evidence of intellectual deterioration or seizures. CT scan showed marked brainstem atrophy in two patients and basal ganglia calcification in one. MRI scan in one showed high signal in the brainstem and periventricular region and cerebral biopsy in this patient showed myelin loss and the presence of Rosenthal fibres. A similar disease affected the siblings' mother, maternal aunt and two of the aunt's daughters, suggesting an autosomal dominant mode of transmission of what appears to be a unique genetic disorder.

To examine the anatomic spread of caudal local anesthetic solution in children aged 1-7 years.To determine whether incremental increases in the volume of caudal injections of 0.5, 0.75, and 1.0 ml·kg(-1) result in reliable (90%) and potentially clinically significant increases in the number of vertebral segments reached.Caudal block is one of the most frequently performed pediatric regional analgesic techniques. Traditional formulae suggest that changes in the volume of caudal injectate in the range 0.5-1.0 ml·kg(-1) would have clinically useful effects.In a single blind design, 45 children aged 1-7 years undergoing caudal block received one of the three predetermined volumes (0.5, 0.75, and 1 ml·kg(-1) ) of local anesthetic solution containing radio-opaque contrast under controlled conditions. Following X-ray examination, the anatomic spread of the block was reported by a radiologist blinded to the volume of solution received.There were 15 children in each group, and they were similar in terms of age, height, and weight. Spread was observed between the 5th lumbar (L5) and 12th thoracic (T12) vertebral levels. A volume of 1 ml·kg(-1) results in a small but significantly greater spread of solution than 0.5 ml·kg(-1) (P0.05), but there was no difference between 0.5 and 0.75 ml or between 0.75 and 1.0 ml. No volume reliably reached a level higher than the second lumbar vertebra (L2).Incrementally increasing the volume of injectate between 0.5 and 1.0 results in a modest increase in the spread of the caudal solution. It is unlikely that volumes of1 ml will reliably reach a vertebral level that is higher than L2.

Acetone leaf extracts of Combretaceae species Combretum imberbe Wawra, Combretum nelsonii Duemmer, Combretum albopunctatum Suesseng, and Terminalia sericea Burch ex DC and a mixture of asiatic acid and arjunolic acid isolated from C. nelsonii were tested for antifungal activity against Candida albicans, Cryptococcus neoformans, Microsporum canis, and Sporothrix schenckii on wounds of immunocompromised Wistar rats. The therapeutic agents were selected based on low MIC values ranging 0.02-2.5 mg/mL and low toxicity (LC50) ranging 75.7-168.6 microg/mL. Seven circular, full-thickness wounds were made on the back skin of 24 Wistar rats, under general anesthetic and using an aseptic technique. Rats were infected with different fungal pathogens in groups of six. The treatments were administered topically using 20% concentrations of each extract in aqueous cream. Amphotericin B was used as positive control. Erythema, exudate, crust formation, swelling, and ulceration were used to determine the wound healing process. Throughout the experiment, body temperature, measured using a subcutaneous probe, and weight of the rats were found to be within normal ranges. Epithelial closure in all rats occurred by 17 days. There was no significant difference in contraction of the lesion areas treated with different extracts. The variability in erythema at each lesion in rats infected with different fungal pathogens differed with treatments; the lesion without treatment took a longer time to heal in all cases. Exudate formation was observed until day 12 in rats infected with C. albicans and day 8 in rats infected with C. neoformans. In lesions infected with M. canis and S. schenckii, exudate formation was observed until day 10. The treated group presented a rigid, dark, and thick crust formation after day 3 until day 15. During histopathological evaluations, scant fungi were noted in all the wounds, indicating that infection had occurred but had generally cleared. The antifungal potential of crude extracts of selected plants and a mixture of asiatic acid and arjunolic acid on the wounds of immunocompromised rats was confirmed. The extracts of these plants may possibly be further developed into drugs for topical treatment of fungally infected wounds.

Objective.To investigate the marked increase noted over an 8-month period in the number ofLegionella pneumophilaisolates recovered from bronchoalveolar lavage fluid specimens obtained during bronchoscopy in our healthcare system.Setting.Bronchoscopy suite that serves a 580-bed tertiary care center and a large, multisite, faculty practice plan with approximately 2 million outpatient visits per year.Methods.Cultures of environmental specimens from the bronchoscopy suite were performed, including samples from the air and water filters, bronchoscopes, and the ice machine, with the aim of identifyingLegionellaspecies. Specimens were filtered and acid-treated and then inoculated on buffered charcoal yeast extract agar. Serogrouping was performed on all isolates recovered from patient and environmental samples.Results.AUL. pneumophilaisolates recovered from patients were serogroup 8, a serogroup that is not usually recovered in our facility. An epidemiologic investigation of the bronchoscopy suite revealed the ice machine to be contaminated withL. pneumophilaserogroup 8. Patients were exposed to the organism as a result of a recently adopted practice in the bronchoscopy suite that involved directly immersing uncapped syringes of sterile saline in contaminated ice baths during the procedures. At least 1 patient was ill as a result of the pseudo-outbreak. Molecular typing of isolates recovered from patient and environmental samples revealed that the isolates were indistinguishable.Conclusions.Extensive cleaning of the ice machine and replacement of the machine's water filter ended the pseudo-outbreak. This episode emphasizes the importance of using aseptic technique when performing invasive procedures, such as bronchoscopies. It also demonstrates the importance of reviewing procedures in all patient areas to ensure compliance with facility policies for providing a safe patient environment.

1. Efferent discharges were recorded from inspiratory and expiratory intercostal nerve filaments (T2-T10) in artificially ventilated, anaesthetized or decerebrate rabbits with or without vagotomy. 2. Hypocapnic apnoea was used to study the fractional end-tidal CO2 (FET,CO2)-dependent tonic discharges of the expiratory motoneurones, the FET,CO2 threshold for rhythm generation and the FET,CO2 response curve of both inspiratory and expiratory burst activity. 3. Incremental doses of morphine (e.g. 1 mg kg-1 I.V.) produced slowing of the respiratory rhythm due to prolongation of the expiratory duration and an elevation of the FET,CO2 threshold for rhythm generation. Eventually apnoea supervened with associated tonic firing of the expiratory motoneurones. At the elevated levels of FET,CO2 bursts of inspiratory activity, with concomitant phasic inhibition of the tonic expiratory activity, could occur either spontaneously or following sensory stimulation. The peak integrated activities of these bursts were closely similar to the values obtained for corresponding levels of FET,CO2 before the administration of morphine. 4. Tonic expiratory activity responded to increased levels of FET,CO2, as it had during hypocapnic apnoea prior to morphine, by an increased discharge frequency of single units or recruitment of new units. 5. All of these effects of morphine were immediately reversed by naloxone (100 micrograms kg-1). 6. Naloxone (greater than 100 micrograms kg-1), without pre-treatment with morphine, led to an increase in respiratory frequency due to a shortening of the expiratory duration and a dose-dependent reduction in the FET,CO2 threshold for rhythm generation. There was little alteration either in the inspiratory response to FET,CO2 during rhythm or in the FET,CO2 response of the expiratory output whether expressed as tonic activity during hypocapnic apnoea or phasic activity following the onset of rhythm. 7. Thus opiates act upon the mechanisms of rhythm generation without depressing the FET,CO2 drive as expressed either as phasic or tonic activation of the motoneurones.

A high-NaCl diet induces renal medullary cyclooxygenase (COX)2 expression, and selective intramedullary infusion of a COX2 inhibitor increases blood pressure in rats on a high-salt diet. The present study characterized the specific prostanoid contributing to the antihypertensive effect of COX2. C57BL/6J mice placed on a high-NaCl diet exhibited increased medullary COX2 and microsomal prostaglandin E synthase1 (mPGES1) expression as determined by immunoblot and real-time PCR. Cytosolic prostaglandin E synthase and prostacyclin synthase were not induced by the high-salt diet. Immunofluorescence showed mPGES1 in collecting ducts and interstitial cells. High salt increased renal medullary PGE2as determined by gas chromatography/negative ion chemical ionization mass spectrometry. The effect of direct intramedullary PGE2infusion was examined in anesthetized uninephrectomized mice. Intramedullary PGE2infusion (10 ng/h) increased urine volume (from 3.3 ± 0.6 to 9.5 ± 1.6 μl/min) and urine sodium excretion (0.11 ± 0.02 to 0.32 ± 0.05 μeq/min). To determine which E-prostanoid (EP) receptor(s) mediated PGE2- dependent natriuresis, EP-selective prostanoids were infused. The EP2agonist butaprost produced natriuresis (from 0.06 ± 0.02 to 0.32 ± 0.05 μeq/min). The natriuretic effect of intramedullary PGE2or butaprost was abolished in EP2-deficient mice, which exhibit NaCl-dependent hypertension. In conclusion, a high-salt diet increases renal medullary COX2 and mPGES1 expression, and increases renal medullary PGE2synthesis. Renal medullary PGE2promotes renal sodium excretion via the EP2 receptor, thereby maintaining normotension in the setting of high salt intake.

FVB/NJ mice frequently are used as transgenic hosts, but the suitability of this genetic background for transgenic and congenic models of systemic autoimmunity have not been reported. In this study, FVB/NJ mice were evaluated for the presence of serum autoantibodies and autoimmune kidney pathology. Previously unreported albuminuria was observed in aged female FVB/NJ mice; however, serum autoantibody testing, light microscopic evaluation of differentially stained renal sections, and evaluation of renal sections for immunoglobulin deposits revealed that the albuminuria was not of autoimmune etiology. Anecdotally, multiple characteristics of the FVB/NJ strain, including albuminuria, cholesterolemia, mild podocyte foot process effacement in aged female FVB/NJ kidneys and predisposition to enhanced Th2 immune responses, is reminiscent of human minimal change nephrotic syndrome (MCNS). We propose that mapping of genetic polymorphisms that are responsible for these traits in FVB/NJ mice may lead to increased understanding of mild nephrotic syndromes including MCNS and other proteinurias.

The frontotemporal lobar degenerations (FTLDs) are a group of disorders in which the clinical picture is not necessarily predictive of the underlying neuropathology. The FTLD with ubiquitin-only-immunoreactive neuronal changes (FTLD-U) subtype is pathologically characterized by ubiquitin-positive, tau and alpha-synuclein-negative neuronal cytoplasmic inclusions in the frontotemporal cortex and hippocampal dentate fascia. When similar pathological changes are accompanied by histological features of motor neuron disease (MND), the term FTLD-MND is used. The latter pathological changes may be found in patients with or without clinical evidence of MND. We retrospectively reviewed the clinical details of three patients with a rapidly progressive, levodopa-unresponsive bradykinetic-rigid syndrome and frontal cognitive impairment. A diagnosis of progressive supranuclear palsy (PSP) had been considered in all three cases at initial presentation. Two of the cases fulfilled clinical diagnostic criteria for PSP, which was the final clinical diagnosis during life. Pathological analysis showed typical histological appearances of FTLD-MND in two cases and of FTLD-U in one case. Semi-quantitative analysis of pathological load seemed to correlate with the clinical phenotype. FTLD-U or FTLD-MND should be considered in the differential diagnosis of progressive frontal dementia with an akinetic rigid syndrome and supranuclear gaze palsy or Steele-Richardson-Olszewski disease.

If sex is naturally selected as a way to combat parasites, then sexual selection for disease resistance might increase the overall strength of selection for outcrossing. In the present study, we compared how two forms of mate choice affect the evolutionary stability of outcrossing in simultaneous hermaphrodites. In the first form, individuals preferred to mate with uninfected individuals (condition-dependent choice). In the second form, individuals preferred to mate with individuals that shared the least number of alleles in common at disease-resistance loci. The comparisons were made using individual-based computer simulations in which we varied parasite virulence, parasite transmission rate, and the rate of deleterious mutation at 500 viability loci. We found that alleles controlling both forms of mate choice spread when rare, but their effects on the evolutionary stability of sex were markedly different. Surprisingly, condition-dependent choice for uninfected mates had little effect on the evolutionary stability of sexual reproduction. In contrast, active choice for mates having different alleles at disease-resistance loci had a pronounced positive effect, especially under low rates of deleterious mutation. Based on these results, we suggest that mate choice that increases the genetic diversity of offspring can spread when rare in a randomly mating population, and, as an indirect consequence, increase the range of conditions under which sexual reproduction is evolutionarily stable.

The discovery that hypocretins are involved in narcolepsy, a disorder associated with excessive daytime sleepiness, cataplexy, and unusually rapid transitions to rapid eye movement sleep, opens a new field of investigation in the area of disorders of sleep and activation. Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) (also called orexin-A and orexin-B) are newly discovered neuropeptides processed from a common precursor. Hypocretin containing cells are located exclusively in the lateral hypothalamus, with widespread projections within the central nervous system. The role of the hypocretin system in other disorders causing excessive daytime sleepiness is more uncertain. This study reports the findings of a prospective study measuring cerebrospinal fluid concentrations of hypocretin-1 and hypocretin-2 in HLA DQB1*0602 positive narcolepsy with cataplexy, monosymptomatic narcolepsy, and primary hypersomnia. The results confirmed the previous observations, that hcrt-1 is deficient in narcolepsy and for the first time report very low levels of hcrt-1 in primary hypersomnia. It is also reported for the first time that there is a generalised defect in hcrt-2 transmission in all three of these clinical entities compared with controls.

OBJECTIVE--To assess the extent and severity of respiratory insufficiency associated with severe rheumatoid atlantoaxial dislocation and its relation to compression of the neuraxis. METHODS--Twelve patients with severe atlantoaxial dislocation due to rheumatoid disease were studied. Detailed clinical, CT myelography and respiratory assessment including nocturnal oximetry, were performed on all patients. RESULTS--All patients were severely disabled by their underlying disease but none had symptoms of hypoventilation. All the patients with C1 compression had myelopathic features. Those with medullary deformation (moulding and/or stretch) had abnormal noctural oximetry whilst no significant desaturations were seen in the remaining patients. Post-operative studies showed resolution of noctural desaturations. CONCLUSION--This study suggests that clinically unsuspected respiratory insufficiency may be common in patients with severe medullary compression associated with rheumatoid atlantoaxial dislocation. It emphasises the importance of careful respiratory monitoring including nocturnal oxygen saturation in patients with major atlantoxial dislocation due to rheumatoid disease.

Visual stimulus comparisons across the vertical meridian are faster and more accurate than those restricted to a single hemifield (the bilateral field advantage). We set out to investigate the cerebral mechanisms underlying this effect using functional magnetic resonance imaging. Seven normal volunteers were presented pairs of shape stimuli bilaterally across the vertical meridian and unilaterally within a single hemifield. We found a network of additional areas activated in the unilateral condition over the bilateral condition which have been related to working memory in previous studies. The results suggest different processing strategies with different temporal characteristics in the bilateral and unilateral conditions, providing a novel explanation for the bilateral field advantage.

Involvement of the inferior vena cava (IVC) by hepatic tumors, although uncommon, is considered to be unresectable by standard surgical techniques. Recent advances in hepatic surgery have made combined hepatic and vena caval resection possible. The purpose of this study is to describe the surgical techniques and early results of combined resection of the liver and IVC. From 1997 to 2000, 11 patients underwent resection of the IVC along with four to seven liver segments. Resections were carried out for hepatocellular carcinoma (four); colorectal metastases (four); and hepatoblastoma, gastrointestinal stromal tumor metastases, and squamous cell carcinoma in one patient each. Ex vivo procedures were performed twice, and total vascular isolation was used in the nine other cases. The IVC was reconstructed with ringed Gore-Tex tube graft (five), primarily (five), or with Gore-Tex patches (one). There were two early deaths: one from liver failure at 3 weeks and one from sepsis secondary to a perforated segment of small bowel 4 months postresection. One patient with a gastrointestinal stromal tumor died at 32 months of recurrent tumor and one patient with hepatocellular carcinoma is alive with recurrent tumor at 16 months. The remaining patients are alive and disease free with follow-up ranging from 3 to 40 months without evidence of IVC occlusion. Combined resection of the liver and IVC is a formidable undertaking with substantial surgical risk. However, this aggressive surgical approach offers a chance for cure in patients with tumors involving the IVC that would otherwise have a dismal prognosis.

Kwashiorkor is the edematous form of protein-energy malnutrition. It is associated with extreme poverty in developing countries and with chronic malabsorptive conditions such as cystic fibrosis in developed countries. Rare cases of kwashiorkor in affluent countries unrelated to chronic illness have been reported. We present 12 cases of kwashiorkor unrelated to chronic illness seen over 9 years by pediatric dermatologists throughout the United States, and discuss common causative themes in this easily preventable condition.Twelve children were diagnosed as having kwashiorkor in 7 tertiary referral centers throughout the United States. The diagnoses were based on the characteristic rash and the overall clinical presentation. The rash consisted of an erosive, crusting, desquamating dermatitis sometimes with classic "pasted-on" scale-the so-called flaky paint sign. Most cases were due to nutritional ignorance, perceived milk intolerance, or food faddism. Half of the cases were the result of a deliberate deviation to a protein-deficient diet because of a perceived intolerance of formula or milk. Financial and social stresses were a factor in only 2 cases, and in both cases social chaos was more of a factor than an absolute lack of financial resources. Misleading dietary histories and the presence of edema masking growth failure obscured the clinical picture in some cases.Physicians should consider the diagnosis of kwashiorkor in children with perceived milk allergies resulting in frequent dietary manipulations, in children following fad or unorthodox diets, or in children living in homes with significant social chaos. The presence of edema and "flaky paint" dermatitis should prompt a careful dietary investigation.

Summary Two patients with sarcoidosis and glomerular mesangial proliferative lesions are described. Although a causative relationship between sarcoidosis and glomerulonephritis has been suggested, critical review of the literature fails to confirm this.

Intact or inactivated donor lymphoid cells have been found to downregulate the alloimmune response in a number of experimental models. We conducted a randomized, prospective, double blind, and placebo-controlled trial to determine whether heat-treated donor spleen cells would affect early rejection after liver transplantation. Donor spleen was obtained during organ procurement for 40 patients undergoing liver transplantation. All patients were treated with cyclosporine, azathioprine and steroids. The patients were randomized after surgery to receive either heat-treated (45 degrees C for 1 h) spleen cells or placebo. Patients underwent protocol biopsies at 1 wk, 4 and 12 months, or as needed. Biopsies were reviewed in a blind fashion and scored according to the Banff consensus criteria. Randomization resulted in 19 patients in the spleen cell group and 21 in the placebo group. One-yr graft survival was 94 and 100%, respectively. Early rejection was more frequent in the spleen cell group (61 vs. 35%, p, not significant). The histopathological rejection activity index at 7 d was also higher for the patients in the spleen cell group: 39% of spleen cell treated patients had a score of 4 or higher as opposed to 5% in the placebo group (p0.01). The mean score was 2.9 +/- 2.8 for the spleen cell group versus 1.3 + 1.7 for the placebo group (p = 0.034). It is concluded that heat-treated donor spleen cells given within 24 h after liver transplantation were not clinically beneficial and increased the intensity of rejection in 7-d protocol liver biopsies.

As a direct or indirect result of antiphospholipid antibody production, subjective laboratory interpretation, and false positive results, the common serologic tests for syphilis have been inherently inaccurate diagnostic tests in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases. We assessed the diagnostic accuracy of syphilis testing in patients with SLE and other autoimmune diseases using the treponemal Western blot (TWB) as the gold standard.A prospective cohort study carried out at a tertiary care medical center. We studied 107 patients with autoimmune disease, 50 with at least one positive serologic test for syphilis and 57 disease matched controls. Prior to enrollment all eligible patients underwent a clinical assessment performed by at least 2 rheumatologists to confirm a diagnosis of rheumatic disease. All subjects underwent serologic testing, in blinded fashion, for syphilis using the rapid plasma reagin test (RPR), Venereal Disease Research Laboratory test (VDRL), fluorescent treponemal antibody absorption test (FTA-ABS), and the TWB.Eighty-seven percent of the patients studied were female, the mean age was 46.5 years, and the most common diagnosis at the time of enrollment was SLE. Using the TWB as the gold standard diagnostic test for syphilis, the sensitivity, specificity, and positive predictive values for each syphilis test were calculated. The sensitivity and specificity for the RPR in patients with rheumatic disease was 62.5% (95% confidence interval 24.5 to 91.5%) and 91.9% (95% CI 84.2 to 96.2%), respectively. The sensitivity and specificity for the VDRL were 37.5% (95% CI 8.5 to 75.5%) and 89.9% (95% CI 81.8 to 94.8%), respectively. Confirmatory syphilis testing using the FTA-ABS showed a sensitivity of 100% (95% CI 68.6 to 100%) and a specificity of 67.7% (95% CI 57.4 to 76.5%). Eight patients tested positive for syphilis by Western blotting. For the FTA-ABS test, there was a significantly higher number of false positive results (n = 32) compared to false negative results (n = 0), p0.0005.The FTA-ABS is not an accurate confirmatory test for syphilis in patients with SLE and other autoimmune diseases. While a negative FTA-ABS may exclude syphilis infection in the majority of cases, a positive FTA-ABS test result cannot assuredly confirm syphilis infection in this population. Western blotting is an accurate confirmatory test for syphilis and may be necessary to unequivocally discern the immunological response of syphilis from that of an underlying autoimmune disease.

Two adult Quarter Horse geldings were evaluated for signs of abdominal pain. Both horses had signs of depression and distended small intestines on abdominal palpation per rectum. Abdominal exploratory surgery was performed on both horses. In each instance, small intestine was found to be strangulated by components of the spermatic cord. Both horses were euthanatized because of a poor prognosis. Although not commonly observed, incarceration of intestine by components of the spermatic cord should be considered as a cause of small intestine strangulation in male horses. Early recognition of this condition would have increased these horses' chances of survival.

The prevailing subcutaneous nude rodent tumor xenograft models used for biological and preclinical studies do not optimally reflect some important biological properties of cancer, especially invasion and metastasis. Orthotopic models have been developed to address this need. However, for lung cancer none of the available models are optimal, in that none originate from an orthotopic (bronchial) primary site and exhibit extensive extrathoracic metastasis. Our goal was to develop a consistent rodent model of non-small cell lung cancer with both of these properties. Groups of male Rowett nude rats were given 500 rads of gamma radiation and then endobronchially implanted in the right caudal lobe airway with 50 mg of small NCI-H460 tumor fragments taken from an orthotopic donor tumor. They were then sacrificed at selected post-implantation times and evaluated grossly and histologically for animal weight, primary tumor take and size, and metastatic tumor incidence at multiple sites. At a late time point (32-35 days), consistency of primary tumor size and metastasis was estimated by comparing results from four groups of rats implanted on different occasions. The results showed that the primary tumors grew steadily, reaching four grams by days 32-35. Rats gained weight until days 14 to 21, but then began to show cachexia. High metastatic rates (60%) were seen for mediastinal lymph nodes (by 21 days), and kidney, bone and brain (by 28 days). Mean primary tumor size and the incidences of both regional and systemic metastasis were consistent at 32-35 days in four different groups of six animals. In conclusion, this orthotopic lung cancer model is highly metastatic and consistent in terms of both primary tumor growth and metastatic behavior. It is the only available rodent model of human lung cancer emanating from an endobronchial site and metastasizing to multiple extrapulmonary sites, and should be very useful for both biological and preclinical studies of lung cancer, particularly where studies of antimetastatic activity are of interest, and/or where survival studies are desired.

We performed a prospective infectious natural history study of 21 patients with low-grade lymphoproliferative disorders receiving fludarabine as initial (n = 5) or salvage (n = 16) therapy. 12 (57%) of these patients developed herpes zoster (n = 9), herpes simplex I (n = 1) or herpes simplex II (n = 2) infections at a median of 8 (range 1-17) months following initiation of fludarabine, with 75% of these having completed therapy. All patients with herpes zoster developed severe post-herpetic neuralgia. Factors differentiating patients developing these infections included older age and low serum IgG or IgA. Based upon these prospective data, we conclude that herpes virus infections frequently occur following fludarabine treatment, necessitating aggressive patient education and new prophylactic strategies.

To investigate the effect of ethnicity on clinical and serologic expression in patients with systemic sclerosis (SSc) and anti-DNA topoisomerase I (anti-topo I) antibody.Clinical and serologic features, as well as HLA class II allele frequencies, were compared among 47 North American white, 15 North American black, 43 Japanese, and 12 Choctaw Native American SSc patients with anti-topo I antibody.The frequency of progressive pulmonary interstitial fibrosis was lower, and cumulative survival rates were better in white compared with black and Japanese patients. Sera of white and black patients frequently recognized the portion adjacent to the carboxyl terminus of topo I, sera of Japanese patients preferentially recognized the portion adjacent to the amino terminus of topo I, and sera of Choctaw patients recognized both portions of topo I. Anti-RNA polymerase II and anti-SSA/Ro antibodies were present together with anti-topo I antibody more frequently in sera of Japanese patients than in sera of white patients. The HLA-DRB1 alleles associated with anti-topo I antibody differed; i.e., DRB1*1101-*1104 in whites and blacks, DRB1*1502 in Japanese, and DRB1*1602 in Choctaws. Multivariate analysis showed that ethnic background was an independent determinant affecting development of severe lung disease as well as survival.Clinical and serologic features in SSc patients were strongly influenced by ethnic background. The variability of disease expression in the 4 ethnic groups suggests that multiple factors linked to ethnicity, including genetic and environmental factors, modulate clinical manifestations, disease course, and autoantibody status in SSc.

We conducted a multicenter retrospective study to determine the results of treatment for prostate cancer in solid organ transplant recipients.A retrospective analysis of all patients diagnosed with prostate cancer after organ transplantation at five centers was conducted. Data were obtained by chart review and a multipoint data sheet was used to abstract the data from the patient charts.Eighteen cases of prostate cancer were identified from six institutions. Most (84%) of the cancers were clinically localized at the time of diagnosis. Nine (50%) of 18 patients underwent radical prostatectomy, which was the predominant mode of treatment. Overall survival at a mean follow-up of 32 months was 66%, with a cancer specific mortality of 16%. Mortality was 13% for the 15 patients with localized disease and 33% for the 3 patients with metastatic disease at the time of diagnosis.Most of the patients with prostate cancer being detected after solid organ transplantation were diagnosed with localized disease. Aggressive therapeutic intervention as in the general (nontransplant) population yields good results and should be pursued. Diligent surveillance for prostate cancer in this population using periodic digital rectal examination, serum prostate-specific antigen, and prostate needle biopsy as needed will ensure earlier cancer detection and allow for definitive therapeutic intervention.

Humoral and cellular responses were examined among natives and migrants in an area of the Amazon region of Brazil. Rhoptry-associated protein-1 (RAP-1) and RAP-2 expressed in Escherichia coli expression systems, a peptide corresponding to the epitope bound by inhibitory anti-RAP-1 antibodies, and four other RAP-1 and RAP-2 synthetic peptides were used in these studies. Plasma from the native population had greater IgG reactivity to the N-terminal third of RAP-1 than the migrant population; both populations had low levels of IgM to this region of RAP-1. The IgG reactivity to RAP-2 and to the C-terminal third of RAP-1, as well as for all the peptides, including the peptide from the inhibitory domain, were low or absent in both populations. In contrast, there were a high number of subjects with an IgM response to the peptides. Cellular responses were measured by proliferation of peripheral blood mononuclear cells (PBMC) and, in some subjects, by reverse transcription-polymerase chain reaction for interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, and IL-10. Proliferation of PBMC was low when stimulated by recombinant proteins, peptides, or parasite lysate. Both RAP-1 and RAP-2 stimulated cytokine production by donor T cells; IL-2, IL-4, and IFN-gamma RNA transcripts were observed in response to recombinant proteins and parasite lysate, but with no uniform trends. From the observed antibody responses, RAP-1 appears to be more immunogenic than RAP-2.

Transendoscopic pulsed dye laser lithotripsy was effective in the treatment of calcium carbonate urothlithiasis in 2 adult geldings. Perineal urethrotomy provided convenient access for standing transendoscopic lithotripsy and evacuation of a large cystic calculus in one gelding. In the second horse, an obstructive urethral calculus was fragmented and removed by a transurethroscopic approach. Pulsed dye laser lithotriptor is effective in fragmentation of the most common form (calcium carbonate) of uroliths in horses and may be performed in standing horses with reduced surgical invasiveness and trauma to the urinary tract, compared with conventional approaches. The principle disadvantages include cost of the procedure, which is comparable to laparocystotomy, and the time delay required to make arrangements for use of the pulsed dye laser lithotriptor.

There is a strong association between delayed graft function (DGF) and reduced graft survival (GS) of cadaveric renal transplants. This study was performed to identify donor characteristics that might predict adverse outcomes.We reviewed the folders of 509 consecutive organ donors for 586 renal transplant recipients receiving grafts between 1990 and 1995. A uniform immunosuppression protocol was employed.The factors that did not alter the rate of DGF were procurement year, local versus shared organs, donor gender, race, hypotension, serum creatinine level and trend, blood transfusions, and vasopressor use and dose. The factors that did alter the frequency of DGF were cause of death (P=0.0053), donor age (P=0.0017), cold ischemic time (P=0.0009), anastomotic time (P=0.0012), combined cold ischemic time and anastomotic time (P=0.00018), and body mass index (P=0.009). All of the factors with the exception of body mass index were of comparable import when analyzed by multiple logistic regression. One-year GS of patients without DGF was 93.2%, and the GS of those with DGF was 76.6% (P0.0001). However, none of the donor factors correlated with 1-year GS. Seventy-seven donors were the source of paired transplants performed by our program. Sixty percent were concordant for immediate function, 32% were discordant for DGF with equal numbers affecting the first or second graft, and in only 8% did DGF affect both grafts.Donor factors associated with DGF were increased ischemia, donor age, and cause of death. Although there is a close association between DGF and reduced GS, there is no association between these donor factors and GS. This seeming paradox suggests that unknown variables contribute heavily to early graft outcome.

To determine how soon after admission to a medical ICU physicians and nurses decide that attempts at resuscitation are inappropriate and how frequently physicians and nurses disagree about do-not-resuscitate (DNR) decisions.Prospective, opinion survey of care providers.Ten-bed adult medical ICU in a university-affiliated tertiary care referral hospital.Consecutive adult medical ICU admissions.Over 10 months, physicians and nurses were surveyed independently every day regarding their opinions about DNR issues on each patient in the ICU.ICU day when DNR order was deemed appropriate by either physicians or nurses.Of 368 consecutive admissions, 84 (23%) patients were designated DNR during their ICU stay. In 6 of these 84 cases (7%), the responsible nurse did not agree that DNR orders were appropriate. In the remaining 78 patients designated DNR, the median time for physicians to recommend DNR (median, 1 day; range, 0 to 22 days) was not significantly different from the median time for nurses (median, 1 day; range, 0 to 13 days); (p=0.45). For the 284 patients not designated DNR, physicians and nurses both believed DNR was appropriate in 14 cases (5%), but a DNR order was not written five times (2%) because there was not time to do so and nine times (3%) because patient or family did not concur. Physicians and nurses disagreed about a DNR recommendation in 33 of the 284 patients not designated DNR (12%). Physicians were more likely to believe that DNR was appropriate than were nurses (p0.0005), with physicians alone recommending DNR 29 times (10%) and nurses alone favoring DNR in four cases (1%).At our institution, recognition of DNR appropriateness by nurses and physicians occurs over a similar time frame. However, physicians are more likely to recommend DNR in cases of disagreement between nurses and physicians.

Activated B cells express Fas (CD95) and are targets for apoptosis induced by CD4+ Th1 effector cells that kill in a Fas-dependent fashion. We report here that IL-4 reverses the susceptibility to Fas-mediated apoptosis that characterizes CD40-stimulated primary B cells. IL-4-induced Fas resistance is not associated with an alteration in the elevated level of Fas expression produced by CD40 ligand and does not depend on additional receptor-mediated signals. However, IL-4-induced resistance to Th1 cell-mediated cytotoxicity (Th1-CMC) develops more slowly than resistance mediated by surface Ig and is not affected by protein kinase C depletion, unlike anti-Ig-induced Fas resistance. By these two criteria, IL-4-and anti-Ig-induced resistance to Th1-CMC appear to be driven through distinct mechanisms; in keeping with this, suboptimal doses of IL-4 and anti-Ig act in synergy to induce marked protection against Th1-CMC. An important role for IL-4-induced Fas resistance is suggested by the observation that sera from IL-4-overexpressing transgenic mice contain autoreactive Abs.

To assess the effect of white petrolatum vs bacitracin ointment on wound infection incidence, allergic contact dermatitis incidence, and healing characteristics.Randomized, double-blind, prospective trial comparing white petrolatum with bacitracin ointment in postprocedure wound care.A general outpatient dermatology clinic and a tertiary referral advanced surgical procedure clinic at Walter Reed Army Medical Center, Washington, DC.A total of 922 patients who had dermatologic surgery with a total of 1249 wounds.The incidence of infection and allergic contact dermatitis during a follow-up period of 4 weeks. Healing characteristics were secondary outcomes.Of the 922 patients enrolled, 440 in the white petrolatum group and 444 in the bacitracin group were evaluable for clinical response. The 2 treatment groups had comparable baseline characteristics. Thirteen patients developed postprocedure infection (1.5%), 9 (2.0%) in the white petrolatum group vs 4 (0.9%) in the bacitracin group (95% confidence interval for difference, -0.4% to 2.7%; P=.37). Eight infections (1.8%) in the white petrolatum group were due to Staphylococcus aureus vs none in the bacitracin group (P=.004). No patient in the group using white petrolatum developed allergic contact dermatitis vs 4 patients (0.9%) in the group using bacitracin (P=.12). Additionally, there were no clinically significant differences in healing between the treatment groups on day 1 (P=.98), day 7 (P=.86), or day 28 (P=.28) after the procedure.White petrolatum is a safe, effective wound care ointment for ambulatory surgery. In comparison with bacitracin, white petrolatum possesses an equally low infection rate and minimal risk for induction of allergy.

A study to determine reference intervals in normal Asian and non-Asian populations for CD3 (T cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic cells), and for the CD4/CD8 ratio and absolute CD4 lymphocyte count was performed. Coulter Clone/Cytostat reagents were used. The samples were lysed using the Coulter Q-Prep and analyzed on the Coulter Profile II flow cytometer. The Asian population appeared to have a lower mean percentage of CD3 and CD4 cells, a lower CD4/CD8 ratio, and lower absolute CD4 lymphocytes. These findings indicate that race should be a consideration in determining reference intervals for immunophenotyping for CD3, CD4, and CD8.

Mice deficient in complement components C3 (C3 -/-) and C4 (C4 -/-) were found to have a profound defect in their Ab response to a T-dependent Ag (bacteriophage (phi X174). Characterization of the deficient mice demonstrated a diminished level of peanut agglutinin+ germinal centers and a failure in isotype switching despite normal B cell signaling in vitro. The nature of the defect was found to lie at the B cell level, as the T cells were primed in C3- and C4-deficient mice as well as those in wild-type mice. These results, and the finding that the defect could be partly reversed by a 10-fold increase in Ag dose, support the hypothesis that covalent attachment of complement ligands, i.e., C3b and C3d to the Ag-Ab complex, increases its immunogenicity.

We have searched, using a sensitive nested-PCR, for enterovirus RNA in cerebrospinal fluid and post mortem central nervous system (CNS) tissue from patients with previous poliomyelitis with or without late functional deterioration, patients with motor neuron disease (MND), and control patients with other neurological disease or without neurological disease. Enterovirus RNA was detected in patients with previous poliomyelitis and MND, but also in control patients with and without neurological disease. Our results do not provide any evidence that such enterovirus infection is related to late functional deterioration in patients with previous poliomyelitis, which could be attributed to other medical conditions in most instances, and do not support the hypothesis that MND is associated with enterovirus infection of the CNS. Nucleotide sequence analysis of enterovirus RNA sequences detected indicated that enteroviruses detected were of the non-polio type.

F tacheodispersion, a new neurophysiological technique based on F waves, was used to determine the motor nerve conduction velocities in 16 patients with motor neuron disease and 19 patients with sequelae following paralytic poliomyelitis. The findings were compared to two age-matched groups, each consisting of 20 healthy volunteers. In each subject the F wave maximal, minimal, mean conduction velocities and the difference between maximal and minimal velocities of the ulnar and peroneal nerves were calculated. M response distal latency, amplitude and conduction velocity were also measured. There was a statistical significant slowing of one or more of the F wave estimated velocities in the absence of M response abnormalities in 31.3% of nerves in motor neuron disease group and in 27.3% of nerves in the poliomyelitis group; between 6.3% and 37.5%, of the nerves studied showed a significant change in the difference between maximal and minimal conduction velocities. Our results favour the presence of changes of motor fibre conduction properties in some patients with anterior horn diseases.

Potentially preventable adverse drug-drug interactions increase morbidity and financial costs to hospitals and third party payers. This study's purpose is to document the prevalence of potential drug-drug interactions (PDDI) in patients referred to a Physical Medicine and Rehabilitation (PMR) clinic, to identify risk factors associated with PDDI, and to evaluate physicians' ability to correctly identify these PDDI. Current medication lists were obtained by questionnaire and confirmed by chart review for 121 consecutive new patients. The physician-identified PDDI were compared with computer-identified PDDI. Twenty-seven patients (22%; 95% confidence interval, 15-31%) had PDDI. PDDI were associated with number of medications (P = 0.0011) and PMR subspecialty clinic (P = 0.012). Twenty-nine of the 46 computer-identified interactions (63%) were not identified by the physicians, and the physicians falsely identified 28 other drug combinations as PDDI. Potential drug-drug interactions occur at high rates in PMR outpatient populations, and physicians are inadequately prepared to identify these PDDI.

Bancroft has proposed a central arousability system as an androgen-sensitive neurophysiological substrate of sexual desire. The present paper describes the author's explorations of a brain-wave measure, the contingent negative variation (CNV), as a putative index of sexual desire under conditions of sexually-relevant stimulation in paedophilic child sex offenders and in non-offender control men. As a group, the former showed undifferentiated CNV responses to adult and child stimuli, unlike non-paedophilic child sex offenders and controls, who showed larger CNVs to adult than to child stimuli. These results suggest that CNV may be usefully developed as an adjunct to penile plethysmographic (PPG) assessment of deviant sexual interests in offenders. Some possible directions for future research are indicated.