Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: a comparative diagnostic and clinical utility study.

Laboratory diagnosis and clinical management of inpatients with diarrhoea is complex and time consuming. Tests are often requested sequentially and undertaken in different laboratories. This causes prolonged unnecessary presumptive isolation of patients, because most cases are non-infectious. A molecular multiplex test (Luminex(®) Gastrointestinal Pathogen Panel (GPP)) was compared with conventional testing over 8 months to determine diagnostic accuracy, turnaround times, laboratory costs, use of isolation facilities and user acceptability. A total of 262 (12%) patients had a pathogen detected by conventional methods compared with 483 (22.1%) by GPP. Most additional cases were detected in patients developing symptoms in the first 4 days of admission. Additional cases were detected because of presumed improved diagnostic sensitivity but also because clinicians had not requested the correct pathogen. Turnaround time (41.8 h) was faster than bacterial culture (66.5 h) and parasite investigation (66.5 h) but slower than conventional testing for Clostridium difficile (17.3 h) and viruses (27 h). The test could allow simplified requesting by clinicians and a consolidated laboratory workflow, reducing the overall number of specimens received by the laboratory. A total of 154 isolation days were saved at an estimated cost of £30 800. Consumables and labour were estimated at £150 641 compared with £63 431 for conventional testing. Multiplex molecular testing using a panel of targets allowed enhanced detection and a consolidated laboratory workflow. This is likely to be of greater benefit to cases that present within the first 4 days of hospital admission.

Serum anticholinergic activity, white matter hyperintensities, and cognitive performance.

The authors investigated whether the cognitive impairments associated with white matter hyperintensities (WMH) in normal elderly subjects are exacerbated by any anticholinergic medications being taken by the subjects. Results showed serum anticholinergic activity (SAA) and WMH volume to have a synergistic interaction such that the cognitive decrements associated with increasing WMH volume were greatest in those older individuals in the highest quartile of the SAA distribution.

Metachromatic leucodystrophy: a newly identified mutation in arylsulphatase A, D281Y, found as a compound heterozygote with I179L in an adult onset case.

The majority of mutations identified in patients with Metachromatic leucodystrophy are unique to individual families. We report here a new mutation in the arylsulphatase A gene (D281Y) identified in a patient with late-onset Metachromatic leucodystrophy. This mutation was inherited in cis with the common pseudo-deficiency allele and in trans with the previously described I179S (250100.0008) mutation which complicated the enzymatic diagnosis of this condition. Sequence comparison shows D281 to be highly conserved amongst the arylsulphatases. The clinical features of this patient which are predominantly of a slowly progressive psychiatric and intellectual deterioration rather than rapid neurological impairment are typical of I179S compound heterozygotes.

Instantiation of semantic categories in sentence comprehension by Alzheimer patients.

This study examined whether Alzheimer patients can make elaborative inferences based on the semantic context provided by a sentence. More specifically, if presented with the name of a category in a sentence do they, like normals, infer (instantiate) the particular member of that category most appropriate to the meaning of the sentence (e.g., if a sentence mentions a container of juice, do they infer it is a bottle). Patients were presented with a sentence containing the name of a concrete category. The sense of the sentence was consistent with a low-dominant member of that category. Patients were then shown drawings of four members of that category and asked to select the one appropriate to the sentence. They were later asked to name the drawings. If semantic information is degraded in Alzheimer patients for those objects Alzheimer patients cannot name (as has been claimed), then AD patients should be unable to carry out the type of elaborative semantic inference required to instantiate. Results showed that Alzheimer patients were highly accurate at instantiating even objects they could not name. This is consistent with a relative preservation of semantic knowledge about concrete objects in Alzheimer patients.

Cognitive and motor slowing in Alzheimer's disease and geriatric depression.

While response slowing on psychological tasks is a symptom of both depression and Alzheimer's disease (AD), the underlying mechanisms may be quite different: a slowing of cognitive processing in AD and a motor retardation in depression. This hypothesis was tested by examining the rate at which participants performed a simple cognitive operation: subvocal pronunciation. Participants were shown words of between one and three syllables and were asked to decide whether each word ended in a particular sound. This task required participants to transform the written word into its phonological representation, an operation thought to involve subvocal pronunciation. Decision time rose linearly with the number of syllables in all three subject groups. The linear function of the AD patients had a significantly greater slope, indicating a slower rate of subvocal pronunciation, whereas the slope was the same for the normal old and depressed. Both the depressed and AD patients had a higher intercept than the normal old, suggesting a sensorimotor slowing. After treatment, the intercept of the linear function for depressed patients fell, but there was no change in the slope. Thus, this study suggests that AD produces a slowing in both cognitive and motor processes, whereas depression results solely in a motor retardation.

Low-level serum anticholinergicity as a source of baseline cognitive heterogeneity in geriatric depressed patients.

Depressed geriatric patients show substantial intersubject variability in cognitive performance, which complicates attempts to evaluate the cognitive effects of depression and of antidepressant therapy. This variability may reflect the multiple medications older patients take, many of which have anticholinergic effects. This study examined whether serum anticholinergicity (SA) explained some of the variability in depressed geriatric patients' memory performance. Before starting antidepressant treatment, 36 elderly depressed subjects were given a verbal learning test. At the same time, a blood sample was taken and analyzed by radioreceptor binding assay to determine their SA level. Nineteen of the subjects had detectable levels (mean = 0.28 pmole atropine equivalent). Subjects with an SA of zero showed significantly better delayed recall than did those with a positive SA level. Thus, even very low SA may produce subtle decrements in memory performance, an area of cognition known to be highly sensitive to anticholinergic effects.

Sentence context influences the interpretation of word meaning by Alzheimer patients.

This study examined whether, in Alzheimer patients, verbal context selectively activates elements of a word's meaning that are relevant to the context. Subjects were shown a sentence ending in a target noun, followed by a question about an attribute of that target. The sentence primed either the attribute in the question, a different attribute, or no attribute. Both normals and AD patients answered the question faster when the target had appeared in a context priming that particular attribute. These results suggest that Alzheimer patients retain knowledge of semantic attributes and that these attributes are susceptible to contextual activation.

Contextual constraint facilitates semantic decisions about object pictures by Alzheimer patients.

Semantic constraints produced by sentence context reduce the time normal adults take to decide whether a given stimulus constitutes a meaningful ending to that sentence. The mechanism responsible for this constraint effect is thought to involve generation of featural restrictions based on context. In the present study, participants heard a sentence whose last word was replaced by an object picture. They decided whether the object formed a sensible ending to that sentence. Contextual constraint present in the sentences greatly influenced decision time: the greater the constraint, the faster the decision. Alzheimer patients were as affected by contextual constraint as were normal adults. The normality of the constraint effect in Alzheimer patients suggests that they can generate featural restrictions and thus retain knowledge of the semantic attributes of objects.

Non-enzymic glycation of fibrous collagen: reaction products of glucose and ribose.

Non-enzymic glycation of collagen involves a series of complex reactions ultimately leading to the formation of intermolecular cross-links resulting in changes in its physical properties. During analysis for the fluorescent cross-link pentosidine we identified the presence of an additional component (Cmpd K) in both glucose and ribose incubations. Cmpd K was formed more quickly than pentosidine in glucose incubations and more slowly than pentosidine in ribose incubations. Cmpd K represented 45% of the total fluorescence compared with 15% for pentosidine in glucose incubations and 25% of the total fluorescence compared with 30% for pentosidine in the ribose incubations. Cmpd K is not an artefact of in vitro incubations, as it was shown to be present in dermal tissue from diabetic patients. Subsequent high-resolution h.p.l.c. analysis of glucose-incubated collagen revealed Cmpd K comprise two components (K1 and K2). Further, a similar analysis of Cmpd K from the ribose incubations revealed two different components (K3 and K4). These differences indicate alternative mechanisms for the reactions of glucose and ribose with collagen. The amounts of these fluorescent components and the pentosidine cross-link determined for both glucose and ribose glycation were found to be far too low (about one pentosidine molecules per 200 collagen molecules after 6 months incubation with glucose) to account for the extensive cross-linking responsible for the changes in physical properties, suggesting that a further additional series of cross-links are formed. We have analysed the non-fluorescent high-molecular-mass components and identified a new component that increases with time of in vitro incubation and is present in the skin of diabetic patients. This component is present in sufficient quantities (estimated at one cross-link per two collagen molecules) to account for the changes in physical properties occurring in vitro.