Theory of mind, causal attribution and paranoia in Asperger syndrome.

Theory of mind (ToM) deficits are central to autistic spectrum disorders, including Asperger syndrome. Research in psychotic disorders has developed a cognitive model of paranoid delusions involving abnormal causal attributions for negative events. Possible aetiologies of these include deficits in social reasoning, specifically ToM. The present study investigated this attributional model of paranoia in Asperger syndrome. Participants diagnosed with Asperger syndrome scored significantly higher on a measure of paranoia and lower on a measure of ToM, compared with the control group. They did not differ in self-concept and causal attributions, contrary to the attributional model of paranoia. A regression analysis highlighted private self-consciousness as the only predictor of paranoia. The theoretical and clinical implications of these findings are discussed.

Memory dysfunction in multiple sclerosis corresponds to juxtacortical lesion load on fast fluid-attenuated inversion-recovery MR images.

BACKGROUND AND PURPOSE: MR imaging is a sensitive diagnostic tool and paraclinical marker of disease activity and prognosis in multiple sclerosis (MS), yet the role of MR imaging of MS is controversial. The aim of this study was to describe the relationship between cognitive function and MS lesion size and position, as shown on comparative images from conventional spin-echo (CSE) and fast fluid-attenuated inversion-recovery (fast FLAIR) MR studies. METHODS: CSE and fast FLAIR sequences consisted of 40 noncontiguous, 3-mm-thick axial sections matched for geometric position in 18 patients with relapsing-remitting MS. Lesions were scored for size, anatomic position, and their comparative appearance on CSE and fast FLAIR images. The neuropsychological assessment tested general psychological performance, memory, and frontal lobe executive function. RESULTS: Fast FLAIR images showed significantly more small (146 versus six) and medium-sized (18 versus four) juxtacortical lesions than did CSE sequences. Small juxtacortical lesions displayed only on fast FLAIR images had a distinctive appearance, suggestive of small areas of perivascular inflammation. The number of these lesions corresponded to reduced performance on the fifth and delayed trials of the Rey Auditory Verbal Learning memory function test. CONCLUSION: Fast FLAIR images show small lesions at the juxtacortical boundary that are not seen on CSE studies. The presence of such lesions correlates with impaired retention of information in memory tasks, which is characteristic of cognitive problems in patients with MS.

Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour.

RATIONALE: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. OBJECTIVES AND METHODS: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the alpha(1)/alpha(2 )agonist, clonidine (1.5 microg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. RESULTS: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. CONCLUSIONS: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms.

We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers, chronic opiate abusers, and patients with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC. We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT) activity using a tryptophan-depleting amino acid drink in normal volunteers. Chronic amphetamine abusers showed suboptimal decisions (correlated with years of abuse), and deliberated for significantly longer before making their choices. The opiate abusers exhibited only the second of these behavioral changes. Importantly, both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC. Qualitatively, the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse, consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers. Overall, these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC. These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine (DA) projections.

Primary cutaneous neuroendocrine (Merkel cell or trabecular carcinoma) tumour of the skin: a radioresponsive tumour.

Four patients with primary neuroendocrine carcinoma of the skin (Merkel cell or trabecular carcinoma) are reported to document their response to radiotheraphy. In three patients there was complete response following radiation treatment, with no local recurrence, whilst the other patient died later with distant metastases. In one patient, post-operative irradiation after excision of an involved local node prevented the growth of further tumour in this nodal group but the unirradiated primary site recurred after initial wide local excision only. This rare tumour appears to be radioresponsive, and although more clinical data are required, we would advocate a wider study of radiotherapy to the primary lesion after biopsy or excision biopsy, in association with prophylactic nodal irradiation. These tumours occur predominantly in elderly people in whom the avoidance of extensive surgery is particularly desirable.

Malignant lymphoma with eosinophilia of the gastrointestinal tract.

Lesions of the gastrointestinal tract with massive tissue eosinophilia may present a difficult diagnostic problem. In a series of 250 gastrointestinal lymphomas drawn from the files of St Bartholomew's and St Mark's Hospitals there were 28 cases of a lymphoma with distinctive histological features, characterized by a massive tissue eosinophilia. Two of these tumours were present in the stomach and 26 in the small intestine. Eight of the latter were associated with coeliac disease. On low power examination a zoning phenomenon was regularly seen and fissuring ulceration, with perforation and fistula formation, was a common finding. The tumour cells were large and pleomorphic with irregular nuclear morphology and prominent nucleoli. Eosinophils were the predominant inflammatory cell associated with the lymphoma but plasma cells, epithelioid histiocytes and small lymphocytes were also present. Vascular changes were prominent. Involved lymph nodes showed gross expansion of the paracortex by tumour. Immunohistochemical studies showed that this lymphoma was probably of T-cell origin.

Cytokeratin and laminin immunostaining in the diagnosis of cutaneous neuro-endocrine (Merkel cell) tumours.

Nine cutaneous neuro-endocrine tumours have been immunostained with monoclonal antibodies to low molecular weight cytokeratin (CAM 5.2) and neurofilament. Polyclonal antisera to neurone-specific enolase, calcitonin and laminin were also used. All nine cases showed paranuclear, dot-like positive staining with CAM 5.2 and diffuse cytoplasmic staining for neurone-specific enolase. Neurofilament and calcitonin immunoreactivity could not be demonstrated. All tumours were negative for laminin immunoreactivity. The limitations of staining for neurone-specific enolase are discussed and the value of CAM 5.2 in the differential diagnosis of cutaneous neuro-endocrine tumours is emphasized. The histogenetic implications of the absence of laminin staining are considered.

Prospective study of colitis in infancy and early childhood.

Ten of a total of 106 children with chronic inflammatory bowel disease seen between 1973 and 1983 were aged 3 years or less (9%). These are the subject of this study. Colonoscopy and biopsy revealed ulcerative colitis in two, Crohn's disease in two, cow's milk-induced colitis in two, and colitis of indeterminate type in four. The children were followed up and reassessed 2 years post-treatment. The four children with ulcerative colitis and Crohn's disease were asymptomatic 6 months after treatment with sulfasalazine and/or prednisolone. The two breast-fed infants with allergic colitis who were treated with cow's milk-free diet in baby and mother showed clinical, endoscopic, and histological resolution. One of the remaining four children with indeterminate colitis is well and off all treatment, and two are well with minimal symptoms and taking sulfasalazine. One child continued to have frequent relapses and subsequently had subtotal colectomy performed with clinical improvement. Histopathology showed features suggestive of intestinal Behcet's disease. The present study shows that colonoscopy and mucosal biopsy allow a firm diagnosis to be established in 60% of cases of this selected group of very young children. In our experience colitis in infancy and early childhood appears to be a heterogeneous group of conditions. An initial assessment of indeterminate colitis should be followed with multiple mucosal biopsies to attempt further categorization.

Eosinophilic infiltrates of the gastrointestinal tract.

There are two lesions which are often confused despite their quite distinct clinical and pathological differences: the inflammatory fibroid polyp and eosinophilic gastroenteritis. Other eosinophilic lesions likely to be encountered in the gut also pose problems of differential diagnosis.

Histological diagnosis of chronic inflammatory bowel disease in childhood.

One hundred and four children were initially assessed by clinical, radiological, and endoscopic criteria as chronic inflammatory bowel disease. All were assessed independently using precise histological diagnostic criteria. Fifty eight patients were diagnosed as Crohn's disease, 25 as ulcerative colitis, 15 remained provisionally categorised as indeterminate colitis and six proved to be normal. Diagnostic granulomas were found in 36% of endoscopic biopsies from the 58 children with Crohn's disease. This appears to be an underestimate as only four of 14 children with granulomatous Crohn's disease operated on had granulomas on endoscopic biopsy. This study shows that there is a spectrum of histological appearances in endoscopic biopsies in chronic inflammatory bowel disease in childhood ranging from definite Crohn's disease to definite ulcerative colitis with indeterminate features in between. Accurate histological diagnosis of chronic inflammatory bowel disease is dependent upon either multiple endoscopic biopsies or assessment of a surgically resected specimen.

Chemotherapy of diffuse malignant mesothelioma. Phase II trials of single-agent 5-fluorouracil and adriamycin.

Twenty consecutive patients with a confirmed diagnosis of diffuse malignant mesothelioma of the pleura or peritoneum, previously untreated with chemotherapy, were studied in a Phase II trial of single-agent 5-fluorouracil. One partial response of 24 months was seen. Eleven patients were treated with single-agent Adriamycin (doxorubicin) after progression on 5-fluorouracil, and one partial response of 34 months was seen. It is concluded that 5-fluorouracil has only minimal activity in diffuse malignant mesothelioma. Preliminary data suggest that Adriamycin has little activity as a second-line agent.

Varied light and scanning electron microscopic appearances of barium sulphate in smears and histological sections.

The various light and scanning electron microscopic appearances of barium sulphate in smears and in histopathological lesions in sections are illustrated. One type of barium sulphate (E-Z-HD) includes much larger, bright birefringent particles and has very different appearances from other widely used types. Such larger particles in sections were not originally suspected to be barium sulphate and were identified only by energy dispersive x ray analysis in a scanning electron microscope. This form of barium sulphate is used for double contrast upper gastrointestinal radiography, and is not thought to have been responsible for the lesions in which it has been observed by us.

Chronic inflammatory bowel disease in childhood.

The diagnosis of Crohn's disease in childhood has been facilitated by the use of fibreoptic endoscopy with biopsies, complemented by double-contrast radiology. Clinical suspicion leads initially to several relevant blood tests. These are followed by endoscopy and multiple colonic biopsies or barium follow-through studies depending on whether large-bowel or small-bowel disease is suspected. The present approach to diagnosis is based on corroborative investigative techniques-endoscopy, radiology, and histology, The availability of paediatric colonoscopes of small diameter should make it possible for paediatricians to perform limited examinations, but when more extensive endoscopy is indicated the child should be referred to special centres.

Squamous carcinoma of the colorectum and its genesis.

A case of pure aquamous carcinoma of the rectum is presented, and the literature reviewed. Squamous carcinomas of the colorectum are rare tumours which have clinicopathological features in common with adenocarcinomas. Evidence is presented to support the proposal that most tumours of the large intestine that consist partly or completely of squamous elements arise from areas of squamous differentiation in pre-existing adenomas. The pathogenesis of squamous carcinoma and adenosquamous carcinoma appears to be similar to that of adenocarcinoma.

Chlamydia, cytomegalovirus, and Yersinia in inflammatory bowel disease.

The relationship of three infectious agents, Chlamydia, cytomegalovirus, and Yersinia enterocolitica, to the aetiology, clinical course, and diagnosis of Crohn's disease was studied. There was no evidence of chlamydial infection in Crohn's disease and no indication either that cytomegalovirus alters the outcome of acute attacks or that infection with Y. enterocolitica is being misdiagnosed as Crohn's disease.

Colonic lymphoma complicating ulcerative colitis.

Colonic lymphoma is a rare complication of ulcerative colitis. Two cases are described in patients who had had ulcerative colitis for 12 and 22 years respectively. Both patients presented with a recent change in their symptoms, which had become increasingly severe and which had not remitted with customary treatment for ulcerative colitis. Physical and haematological examinations revealed no evidence of generalized lymphoma, though barium enema studies indicated the sites of the lymphomatous lesions superimposed on chronic ulcerative colitis which were confirmed at operation and biopsy.