Ocular abnormalities in chronic schizophrenia: clinical implications

Objective: As part of a randomised double-blind study of a new atypical antipsychotic we sought to determine both the levels of visual acuity and the occurrence of toxic side-effects in a group of patients treated for many years on a variety of antipsychotics. Method: Twenty-three inpatients with a DSM-III-R diagnosis of chronic schizophrenia from two separate hospital locations who met the criteria for the double-blind trial were examined for ocular abnormalities at both baseline and at trial completion. Results: At baseline a high prevalence of abnormalities was identified: 19 patients (82.6%) were found to have one or more ocular abnormalities, including lens opacities/cataracts and corneal pigmentation; three patients, with delusions related to the sun, were noted to have solar burns; a high proportion (almost 70%) of patients had untreated visual acuity problems. No further changes were observed at the follow-up examinations. Conclusions: The possible causes of ocular disturbance in schizophrenia and the reasons for the relatively high ocular morbidity in this group are thought to result from both illness-related factors and the effects of antipsychotic medication. Causality is confounded by a number of issues such as the high prevalence of smoking, poor general health and the variety of antipsychotic medications used in the treatment of psychosis as well as substance abuse. The clinical implications are considered in this paper in relation to the move towards community-based psychiatric services.

Mechanical effects on the skeleton: Are there clinical implications?

The basic morphology of the skeleton is determined genetically, but its final mass and architecture are modulated by adaptive mechanisms sensitive to mechanical factors. When subjected to loading, the ability of bones to resist fracture depends on their mass, material properties, geometry and tissue quality. The contribution of altered bone geometry to fracture risk is unappreciated by clinical assessment using absorptiometry because it fails to distinguish geometry and density. For example, for the same bone area and density, small increases in the diaphyseal radius effect a disproportionate influence on torsional strength of bone. Mechanical factors are clinically relevant because of their ability to influence growth, modeling and remodeling activities that can maximize, or maintain, the determinants of fracture resistance. Mechanical loads, greater than those habitually encountered by the skeleton, effect adaptations in cortical and cancellous bone, reduce the rate of bone turnover, and activate new bone formation on cortical and trabecular surfaces. In doing so, they increase bone strength by beneficial adaptations in the geometric dimensions and material properties of the tissue. There is no direct evidence to demonstrate anti-fracture efficacy for mechanical loading, but the geometric alterations engendered undoubtedly increase the structural properties of bone as an organ, increasing the resistance to fracture. Like all interventions, issues of safety also arise. Physical activities involving high strain rates, heavy lifting or impact loading may be detrimental to the joints, leading to osteoarthritis; may stimulate fatigue damage leading with some to stress fractures; or may interact pharmaceutical interventions to increase the rate of microdamage within cortical or trabecular bone.

Enterohepatic circulation - Physiological, pharmacokinetic and clinical implications

Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.

The pathophysiology of 'brain shrinkage' in alcoholics - Structural and molecular changes and clinical implications

This article represents a symposium of the 2004 ISBRA Congress held in Mannheim. The presentations were: Review of the neuropathological and neurochemical changes seen in alcohol-related ' brain shrinkage ' by Clive Harper; In Vivo Detection of Macrostructural and Microstructural Markers of Brain Integrity in Human Alcoholism and a Rodent Model of Alcoholism by Adolf Pfefferbaum, Elfar Adalsteinsson and Edith Sullivan; Gene and Protein Changes in the Brains of Alcoholics with ' Brain Shrinkage ' by Joanne Lewohl and Peter Dodd; Cross sectional and longitudinal MR spectroscopy studies of chronic adult alcoholics by Michael Taylor; Brain Atrophy Associated with Impairment on a Simulated Gambling Task in Long-Term Abstinent Alcoholics by George Fein and Bennett Landman.

Proprioceptive neuromuscular facilitation stretching - Mechanisms and clinical implications

Proprioceptive neuromuscular facilitation (PNF) stretching techniques are commonly used in the athletic and clinical environments to enhance both active and passive range of motion (ROM) with a view to optimising motor performance and rehabilitation. PNF stretching is positioned in the literature as the most effective stretching technique when the aim is to increase ROM, particularly in respect to short-term changes in ROM. With due consideration of the heterogeneity across the applied PNF stretching research, a summary of the findings suggests that an 'active' PNF stretching technique achieves the greatest gains in ROM, e.g. utilising a shortening contraction of the opposing muscle to place the target muscle on stretch, followed by a static contraction of the target muscle. The inclusion of a shortening contraction of the opposing muscle appears to have the greatest impact on enhancing ROM. When including a static contraction of the target muscle, this needs to be held for approximately 3 seconds at no more than 20% of a maximum voluntary contraction. The greatest changes in ROM generally occur after the first repetition and in order to achieve more lasting changes in ROM, PNF stretching needs to be performed once or twice per week. The superior changes in ROM that PNF stretching often produces compared with other stretching techniques has traditionally been attributed to autogenic and/or reciprocal inhibition, although the literature does not support this hypothesis. Instead, and in the absence of a biomechanical explanation, the contemporary view proposes that PNF stretching influences the point at which stretch is perceived or tolerated. The mechanism(s) underpinning the change in stretch perception or tolerance are not known, although pain modulation has been suggested.

The role of parental anxiety in the treatment of childhood anxiety

Sixty-seven children aged 7 to 14 who met diagnostic criteria for an anxiety disorder were assigned to conditions according to parental anxiety level. Within these conditions, children were randomly assigned to I of 2 treatments: child-focused cognitive-behavioral therapy (CBT) or child-focused CBT plus parental anxiety management (CBT + PAM). At posttreatment, results indicated that within the child-anxiety-only condition, 82% of the children in the CBT condition no longer met criteria for an anxiety disorder compared with 80% in the CBT + PAM condition. Within the child + parental anxiety condition, 39% in the CBT condition no longer met criteria compared with 77% in the CBT + PAM condition. At follow-up, these differences were maintained, with some weakening over time. Results were not consistent across outcome measures. The interpretation and potential clinical implications of these findings are discussed.

Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific Region

Background-The importance of serum triglyceride levels as a risk factor for cardiovascular diseases is uncertain. Methods and Results-We performed an individual participant data meta-analysis of prospective studies conducted in the Asia-Pacific region. Cox models were applied to the combined data from 26 studies to estimate the overall and region-, sex-, and age-specific hazard ratios for major cardiovascular diseases by fifths of triglyceride values. During 796 671 person-years of follow-up among 96 224 individuals, 670 and 667 deaths as a result of coronary heart disease (CHD) and stroke, respectively, were recorded. After adjustment for major cardiovascular risk factors, participants grouped in the highest fifth of triglyceride levels had a 70% (95% CI, 47 to 96) greater risk of CHD death, an 80% (95% CI, 49 to 119) higher risk of fatal or nonfatal CHD, and a 50% (95% CI, 29% to 76%) increased risk of fatal or nonfatal stroke compared with those belonging to the lowest fifth. The association between triglycerides and CHD death was similar across subgroups defined by ethnicity, age, and sex. Conclusions-Serum triglycerides are an important and independent predictor of CHD and stroke risk in the Asia-Pacific region. These results may have clinical implications for cardiovascular risk prediction and the use of lipid-lowering therapy.

Speech disorder in preschool children exposed to Cantonese and English

Speech disorder in monolingual Cantonese- or English-speaking children has been well described in the literature. There appear to be no reports, however, that describe speech-disordered children who have been exposed to both languages. Here we report on the error patterns of two preschool speech-disordered children who were learning two languages. Both children's first language was Cantonese, but they were also exposed to English through the media and child care. Their disorders were of unknown aetiology. The following questions were asked of the data: (a) Do bilingual children, suspected of having speech problems, make errors in Cantonese and English that reflect delay or disorder when compared with normative data on monolingual speech development in each language? (b) How does the children's speech differ from other bilingual children from the same language learning background? (c) Are the children's speech difficulties apparent in both languages? (d) Is the pattern of errors the same in both languages or do language-specific processes operate? The results bear on theories of acquisition, disorder and bilingualism; they also have clinical implications for speech-language pathologists whose caseloads include bilingual preschool children.

Well-formedness judgment: A comparison of offline and online performance in Broca's aphasics

0na eg rcarmitimcaal tfieca tcuorem opfr ethhee nospieornat iodneafli cdietf i(nAitiCoDn )o ft hthaet frequently co-occurs with Broca’s aphasia is above-chance performance on well-formedness judgment tasks for many syntactic constructions, but impaired performance where syntactic binding of traces to their antecedents occurs. However, the methodologies used to establish this aspect of the performance profile of the ACD have been predominantly offline. Offline well-formedness tasks entail extralinguistic processing (e.g. perception, attention, short-term memory, conscious reflection) in varying amounts and the influence of such processes on parsing mechanisms is yet to be fully established. In order to (a) further understand the role of extra-linguistic processing on parsing, and (b) gain a more direct insight into the online nature of parsing in Broca’s aphasia, 8 subjects underwent a series of wellformedness judgment investigations using both offline and online test batteries. The sentence types and error types used were motivated by three current theories about the nature of the ACD, namely, the Trace-Based Account (Grodzinsky, 2000), the Mapping Hypothesis (Linebarger et al., 1983) and Capacity proposals (e.g. Frazier & Friederici, 1991). The results from the present investigation speak directly to the three aforementioned theories and also demonstrate the important role that extralinguistic processing plays during offline assessment. The clinical implications of the different outcomes from the offline vs. online tasks are also discussed.

Diagnosis and management of unusual dental abscesses in children

Although the majority of dental abscesses in children originate from dental caries or trauma, a few are associated with unusual conditions which challenge diagnosis and management. Recent research findings have shed light on these unusual entities and greatly improved understanding of their clinical implications. These conditions include developmental abnormalities such as dens invaginatus in which there is an invagination of dental tissues into the pulp chamber and dens evaginatus in which a tubercle containing pulp is found on the external surface of a tooth crown. In addition, inherited conditions which show abnormal dentine such as dentine dysplasia, dentinogenesis imperfecta, and osteogenesis imperfecta predispose the dentition to abscess formation. Furthermore, 'spontaneous' dental abscesses are frequently encountered in familial hypophosphataemia, also known as vitamin D-resistant rickets, in which there is hypomineralization of dentine and enlargement of the pulp. In addition to developmental conditions, there are also acquired conditions which may cause unusual dental abscesses,. These include pre-eruptive intracoronal resorption which was previously known as 'pre-eruptive caries' or the 'fluoride bomb'. In addition, some undiagnosed infections associated with developing teeth are now thought to be the mandibular infected buccal cysts which originate from infection of the developing dental follicles. In the present paper, these relatively unknown entities Which cause unusual abscesses in children are reviewed with the aim of updating the general practitioner in their diagnosis and management.

EMA analysis of tongue function in children with dysarthria following traumatic brain injury

Primary objective : To investigate the speed and accuracy of tongue movements exhibited by a sample of children with dysarthria following severe traumatic brain injury (TBI) during speech using electromagnetic articulography (EMA). Methods and procedures : Four children, aged between 12.75-17.17 years with dysarthria following TBI, were assessed using the AG-100 electromagnetic articulography system (Carstens Medizinelektronik). The movement trajectories of receiver coils affixed to each child's tongue were examined during consonant productions, together with a range of quantitative kinematic parameters. The children's results were individually compared against the mean values obtained by a group of eight control children (mean age of 14.67 years, SD 1.60). Main outcomes and results : All four TBI children were perceived to exhibit reduced rates of speech and increased word durations. Objective EMA analysis revealed that two of the TBI children exhibited significantly longer consonant durations compared to the control group, resulting from different underlying mechanisms relating to speed generation capabilities and distances travelled. The other two TBI children did not exhibit increased initial consonant movement durations, suggesting that the vowels and/or final consonants may have been contributing to the increased word durations. Conclusions and clinical implications : The finding of different underlying articulatory kinematic profiles has important implications for the treatment of speech rate disturbances in children with dysarthria following TBI.

The relationship between the mismatch negativity (MMN) and psycholinguistic models of spoken word processing

Background: The results from previous studies have indicated that a pre-attentive component of the event-related potential (ERP), the mismatch negativity (MMN), may be an objective measure of the automatic auditory processing of phonemes and words. Aims: This article reviews the relationship between the MMN data and psycholinguistic models of spoken word processing, in order to determine whether the MMN may be used to objectively pinpoint spoken word processing deficits in individuals with aphasia. Main Contribution: This article outlines the ways in which the MMN data support psycholinguistic models currently used in the clinical management of aphasic individuals. Furthermore, the cell assembly model of the neurophysiological mechanisms underlying spoken word processing is discussed in relation to the MMN and psycholinguistic models. Conclusions: The MMN data support current theoretical psycholinguistic and neurophysiological models of spoken word processing. Future MMN studies that include normal and aphasic populations will further elucidate the role that the MMN may play in the clinical management of aphasic individuals.

Cervical Cancer Control, Priorities and New Directions

Cervical cancer is caused by infection with a range of high risk oncogenic human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than I in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, Screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.(1) The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference. (C) 2003 Wiley-Liss, Inc.