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 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.

Cardiovascular actions of the venom from the Irukandji (Carukia barnesi) jellyfish: Effects in human, rat and guinea-pig tissues in vitro and in pigs in vivo

1. We have investigated the cardiovascular pharmacology of the crude venom extract (CVE) from the potentially lethal, very small carybdeid jellyfish Carukia barnesi, in rat, guinea-pig and human isolated tissues and anaesthetized piglets. 2. In rat and guinea-pig isolated right atria, CVE (0.1-10 mu g/mL) caused tachycardia in the presence of atropine (I mu mol/L), a response almost completely abolished by pretreatment with tetrodotoxin (TTX; 0.1 mu mol/L). In paced left atria from guinea-pig or rat, CVE (0.1-3 mu g/mL) caused a positive inotropic response in the presence of atropine (1 mu mol/L). 3. In rat mesenteric small arteries, CVE (0.1-30 mu g/mL) caused concentration-dependent contractions that were unaffected by 0.1 mu mol/L TTX, 0.3 mu mol/L prazosin or 0.1 mu mol/L co-conotoxin GVIA. 4. Neither the rat right atria tachycardic response nor the contraction of rat mesenteric arteries to CVE were affected by the presence of box jellyfish (Chironex fleckeri) antivenom (92.6 units/mL). 5. In human isolated driven right atrial trabeculae muscle strips, CVE (10 mu g/mL) tended to cause an initial fall, followed by a more sustained increase, in contractile force. In the presence of atropine (I mu mol/L), CVE only caused a positive inotropic response. In separate experiments in the, presence of propranolol (0.2 mu mol/L), the negative inotropic effect of CVE was enhanced, whereas the positive inotropic response was markedly decreased. 6. In anaesthetized piglets, CVE (67 mu g/kg, i.v.) caused sustained tachycardia and systemic and pulmonary hypertension. Venous blood samples demonstrated a marked elevation in circulating levels of noradrenaline and adrenaline. 7. We conclude that C. barnesi venom may contain a neural sodium channel activator (blocked by TTX) that, in isolated atrial tissue (and in vivo), causes the release of transmitter (and circulating) catecholamines. The venom may also contain a 'direct' vasoconstrictor component. These observations explain, at least in part, the clinical features of the potentially deadly Irukandji syndrome.

Periodontitis and rheumatoid arthritis: A review

Periodontitis and rheumatoid arthritis (RA) appear to share many pathologic features. In this review, the common pathologic mechanisms of these two common chronic conditions are explored. Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and RA. While this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to experience more significant periodontal problems compared to their non-RA counterparts, and vice versa. A case is made that these two diseases could be very closely related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of such dysfunction is still unknown. Nonetheless, there is accruing evidence to support the notion that both conditions manifest as a result of an imbalance between proinflammatory and anti-inflammatory cytokines. As a result, new treatment strategies are expected to emerge for both diseases that may target the inhibition of proinflammatory cytokines and destructive proteases. The clinical implications of the current data dictate that patients with RA should be carefully screened for their periodontal status.

Adjustment in mothers of children with Asperger syndrome: An application of the double ABCX model of family adjustment

The present study examined the applicability of the double ABCX model of family adjustment in explaining maternal adjustment to caring for a child diagnosed with Asperger syndrome. Forty-seven mothers completed questionnaires at a university clinic while their children were participating in an anxiety intervention. The children were aged between 10 and 12 years. Results of correlations showed that each of the model components was related to one or more domains of maternal adjustment in the direction predicted, with the exception of problem-focused coping. Hierarchical regression analyses demonstrated that, after controlling for the effects of relevant demographics, stressor severity, pile-up of demands and coping were related to adjustment. Findings indicate the utility of the double ABCX model in guiding research into parental adjustment when caring for a child with Asperger syndrome. Limitations of the study and clinical implications are discussed.

Predictive genetic test decisions for Huntington's disease: Elucidating the test/no-test dichotomy

Predictive genetic testing for serious, mature-onset genetic illness represents a unique context in health decision making. This article presents findings from an exploratory qualitative Australian-based study into the decision making of individuals at risk for Huntington's disease (HD) with regard to predictive genetic testing. Sixteen in-depth interviews were conducted with a range of at-risk individuals. Data analysis revealed four discrete decision-making positions rather than a 'to test' or not to test' dichotomy. A conceptual dimension of (non-)openness and (non-)engagement characterized the various decisions. Processes of decision making and a concept of 'test readiness' were identified. Findings from this research, while not generalizable, are discussed in relation to theoretical frameworks and stage models of health decision making, as well as possible clinical implications.

Nephron number, hypertension, renal disease, and renal failure

Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension. The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or multihit models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility. Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the Barker hypothesis, which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9). The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.

Stem cells in the periodontal ligament

The ability to identify and manipulate stem cells has been a significant advancement in regenerative medicine and has contributed to the development of tissue engineering-based clinical therapies. Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques such as tissue engineering need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. One of the critical requirements for a tissue engineering approach is the delivery of ex vivo expanded progenitor populations or the mobilization of endogenous progenitor cells capable of proliferating and differentiating into the required tissues. By definition, stem cells fulfill these requirements and the recent identification of stem cells within the periodontal ligament represents a significant development in the progress toward predictable periodontal regeneration. In order to explore the importance of stem cells in periodontal wound healing and regeneration, this review will examine contemporary concepts in stem cell biology, the role of periodontal ligament progenitor cells in the regenerative process, recent developments in identifying periodontal stem cells and the clinical implications of these findings.

Uroscopic rainbow: modern matula medicine

Visual inspection of a patient's urine has long been used by physicians, with colour recognised as having important clinical implications. In this review the authors will revisit this ancient pastime with relevance to contemporary medical practice.

Lifetime suicide risk in major depression: sex and age determinants

Background: Recent work has demonstrated that the lifetime suicide risk for patients with DSM IV Major Depression cannot mathematically approximate the accepted figure of 15%. Gender and age significantly affect both the prevalence of major depression and suicide risk, Methods: Gender and age stratified calculations were made on the entire population of the USA in 1994 using a mathematical algorithm. Sex specific corrections for under-reporting were incorporated into the design. Results: The lifetime suicide risks for men and women were 7% and 1%, respectively. The combined risk was 3.4%. The male:female ratio for suicide risk in major depression was 10:1 for youths under 25, and 5.6:1 for adults. Conclusions: Suicide in major depression is predominantly a male problem, although complacency towards female sufferers is to be avoided. Diagnosis of major depression is of limited help in predicting suicide risk compared to case specific factors. The male experience of depression that leads to suicide is often not identified as a legitimate medical complaint by either sufferers or professionals. Increasing help-accessing by males is a priority. Clinical implications: Patients with a history of hospitalisation; comorbidity, especially for substance abuse; and who are male, require greater vigilance for suicide risk. It may be that for males che threshold for diagnosing and treating major depression needs to be lowered. Limitations: This research is based on a mathematical algorithm to approximate a life-long longitudinal study that identifies community cases of depression. Our findings therefore rely on the validity of the statistics used. Extrapolation is limited to populations with an actual suicide rate of 17/100,000 or less and a lifetime prevalence of major depression of 17% or more. (C) 1999 Elsevier Science B.V. All rights reserved.

Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies

Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published methods for the determination of free drug concentrations by HPLC-MS. The development of atmospheric pressure ionisation sources, together with on-line microdialysis or on-line equilibrium dialysis and column switching techniques have reduced sample run times and increased assay efficiency. The availability of such methods will aid in drug development and the clinical use of certain drugs, including anti-convulsants, anti-arrhythmics, immunosuppressants, local anaesthetics, anti-fungals and protease inhibitors. The history of free drug measurement and an overview of the current HPLC-MS applications for these drugs are discussed. Immunosuppressant drugs are used as an example for the application of HPLC-MS in the measurement of drug pharmacodynamics. Potential biomarkers of immunosuppression that could be measured by HPLC-MS include purine nucleoside/nucleotides, drug-protein complexes and phosphorylated peptides. At the proteomic level, two-dimensional gel electrophoresis combined with matrix-assisted laser desorption/ionisation time-of-flight (TOF) MS is a powerful tool for identifying proteins involved in the response to inflammatory mediators. (C) 2003 Elsevier Science B.V. All rights reserved.