Tryptophan depletion in normal volunteers produces selective impairments in learning and memory.

The amino-acid L-tryptophan is essential in the synthesis of brain serotonin, and its depletion can lead to a widespread reduction in central serotonergic activity. A placebo-controlled cross-over within-subjects design (n = 12) examined the effects of tryptophan depletion on human cognitive performance. A low-tryptophan (low-TRP) drink successfully reduced the levels of plasma and total free tryptophan. Computerized tests of memory, learning and executive function revealed selective and non-sedative impairments on cognitive performance following the active drink. Specifically, low-TRP impaired learning as seen in tests of visual discrimination and paired associates. Furthermore, low-TRP lengthened thinking times during the Tower of London planning task, but only in subjects already familiar with the task, suggesting a retrieval deficit. No evidence was found for an effect of the low-TRP drink on measures sensitive to frontal lobe dysfunction, supporting instead a specific role for the serotonergic system in the processes of memory and learning not directly implicated in frontal lobe function.

Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion on focused attention and attentional search.

As the catecholamines have long been implicated in attentional processes, the present investigation compared the effects of the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (CLO), the benzodiazepine diazepam (DZP), the D1/D2 antagonist haloperidol (HAL) and a low-tryptophan drink (Lo-TRP) on performance of tests of selective attention with distractors in four groups of young, healthy volunteers. Using a placebo-controlled, cross-over design, selective and dissociable effects on performance were found with each pharmacological manipulation. Specifically, CLO acted to broaden the focus of attention, HAL generally slowed reaction times during attentional search, and DZP and Lo-TRP produced differential effects on stimulus-response compatibility during attentional search. Furthermore, these results underline the usefulness of employing a single test with several neurochemical manipulations, allowing for a comprehensive analysis of the neurochemical basis of attention.

Hemicorporectomy for intractable decubitus ulcers.

A hemicorporectomy was successfully employed for control of intractable decubitus ulcers, osteomyelitis, and low-grade epidermoid cancer in a 55-year-old man marked reduction in pulmonary functions. Strict attention to postoperative fluid balance was associated with a smooth convalescence. The operation may be more applicable to paraplegic patients with intractable pelvic decubiti than to those with advanced pelvic tumors. In view of the increased number of paraplegics who may be at risk for developing this problem, more frequent consideration of the procedure seems warranted.

Zebra technique for "de-epithelialization" of dermal pedicles.

The zebra technique for "de-epithelialization" is a rapid and controllable one for creating a dermal pedicle in plastic surgery procedures.

Fine tuning of the skin edges in the closure of surgical wounds. Controlling inversion and eversion with the path of the needle--the right stitch at the right time.

A primary objective in closure of surgical wounds is accurate apposition of epithelial edges in a manner that will return the tissues to as near normal a condition as possible. This article describes types of suture techniques that enable the surgeon to control the tendency of wound edges to either invert or evert. Accurate approximations and esthetically pleasing results are reached by using the appropriate pass of the needle and path of the suture to control tendencies to inversion and eversion.

Quantitative optics: the control of perspective in comparative photography.

Although angle of view is only one of several factors that influence the reliability with which judgments can be made in comparing one photograph with another, application of this concept in taking photographs of patients will permit the surgeon, no matter what camera equipment is used, to achieve a high degree of standardization in preoperative and postoperative photographs.

Wandering in dementia: a longitudinal study.

OBJECTIVE: This article analyzes the natural history of wandering behavior throughout the course of dementia. DESIGN: Prospective, 10-year, longitudinal study of wandering behavior in dementia, with autopsy follow-up. SETTING: Participants with dementia, living at home with a carer. All lived in Oxfordshire, UK. PARTICIPANTS: Eighty-six people with dementia who were living at home with a carer and who were able to walk unaided at entry to study. MEASURES: At 4-monthly intervals, the carers were interviewed using the Present Behavioural Examination to assess wandering behavior in detail; participants with dementia were assessed cognitively. Nine types of "wandering" behavior were distinguished. RESULTS: Changes in wandering behavior were not generally related to gender, age, or time since onset of dementia. Onset of different types of wandering behavior showed some relationship with cognitive state. Various forms of increased walking first appeared during moderate dementia, each type typically persisting for 1 to 2 years. Late dementia was characterized by decreased walking and immobility. CONCLUSIONS: Wandering behavior in dementia can cause great problems for carers. There are different causes for such changes, some of which are related to cognitive ability, for example increased confusion results in ineffectual "pottering" and getting lost. Increased walking at night corresponds with disruption of diurnal rhythm.

Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology.

OBJECTIVES: To assess olfactory function of patients with dementia. Odour detection ability is impaired in clinical Parkinson's disease. Evidence of impaired detection in patients with clinically diagnosed Alzheimer's disease is inconsistent. No studies of olfaction have been neuropathologically validated. METHODS: The olfactory function of 92 patients with dementia and 94 controls was assessed using a simple bedside test as part of the Oxford Project To Investigate Memory and Ageing (OPTIMA). Neuropathological assessment was made of cortical Lewy bodies and substantia nigra (SN) cell counts and of Alzheimer's disease in all 92 patients, 22 of whom had SN Lewy bodies and 43 of whom had only Alzheimer's disease. RESULTS: Patients with Lewy bodies were more likely to be anosmic than those with Alzheimer's disease or controls. Patients with Alzheimer's disease were not more likely to be anosmic than controls. Nor was anosmia associated with degree of neurofibrillary tangles, as assessed by Braak stage. Among subjects with Lewy bodies, overall cortical Lewy body scores and Lewy body density in the cingulate were higher in those who were anosmic. Consensus clinical criteria for dementia with Lewy bodies had a sensitivity of 64% and specificity of 89%. In the absence of definite Alzheimer's disease, the criteria had sensitivity of 100%. In patients with definite Alzheimer's disease, anosmia was slightly more sensitive (55%) than the consensus criteria (33%). However, the addition of anosmia to the consensus criteria did not improve their overall performance. CONCLUSION: Dementia with Lewy bodies is associated with impaired odour detection. Misdiagnosis may have accounted for some previous reports of impaired odour detection in Alzheimer's disease. Simple but more sensitive tests of anosmia are required if they are to be clinically useful in identifying patients with dementia with Lewy bodies.

Dementia with Lewy bodies: a pure case.

A pure case of autopsy-confirmed dementia with Lewy bodies (DLB) is described. The patient presented with distinctive verbal fluency deficits in the context of mild language impairment, intact recognition memory, and impaired paragraph recall. Neuroimaging (CT and SPECT) showed progressive medial temporal lobe atrophy. Neuropathology revealed Lewy bodies, degeneration in the substantia nigra, nucleus basalis of Meynert (Nakano & Hirano, 1984), and locus ceruleus, but no pathology characteristic of Alzheimer's disease. It is in this sense that the case is "pure" DLB. Early neuropsychological diagnosis of DLB is essential (Salmon et al., 1996) given the potentially fatal hazard of neuroleptics (McKeith et al., 1992) and the difficulties associated with clinical neurological diagnoses (Litvan et al., 1998).