Eradication of 'ooHelicobacter pylori'ox : an objective assessment of current therapies

The purpose of the present review was to determine objectively the optimal treatment for the eradication of H. pylori amongst the currently used regimens. A comprehensive literature search provided a data-base relating to the following treatments: dual therapy with an anti-secretory drug plus either amoxycillin or clarithromycin; standard triple therapy, with or without additional anti-secretory drugs; proton pump inhibitor triple therapy; and H₂-receptor antagonist triple therapy. Emphasis was placed on intention-to-treat analyses of eradication rates using all of the available evidence. The criteria used to select the optimal treatment were efficacy (eradication rates), frequency of side-effects, simplicity of the regimen (number of tablets per day and duration of treatment) and cost. The analysis showed that proton pump inhibitor triple therapy (that is, a proton pump inhibitor plus any two of amoxycillin, clarithromycin or a nitroimidazole) was the preferred treatment for the eradication of H. pylori . In particular, the 1-week, low-dose regimen with omeprazole plus clarithromycin plus tinidazole produced the highest eradication rates (>90%) with the lowest frequency of side-effects and at only modest cost.     

APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Regulation of major histocompatibility complex (MHC) products in fresh and cultured human fetal pancreata aged 9–16 gestational weeks by gamma-interferon

Immunological data on the human fetal pancreas (HFP) are mainly confined to its constitutive expression of the MHC antigens. However, cytokines, such as gamma-interferon (g-IFN), released by lymphocytes during immune reactions, can induce or upregulate the expression of MHC products in allografts and alter their immunological behaviour. We investigated the effects of g-IFN on fresh and cultured HFPs aged 9–16 gestational weeks (gw). Following g-IFN stimulation of fresh HFPs, there was class I hyperexpression by the ductal cells, and some of the ductal, endothelial and islet cells also became class II⁺. Conventional tissue culture (5% CO₂ in air at 37°C) reduced the number of interstitial class II⁺ cells within the HFP after 1 week but was associated with de novo class I expression by some of the ductal cells. Remarkably, the changes in major histocompatibility complex (MHC) antigen expression by the ductal cells occurred earlier and were markedly enhanced when the HFPs were cultured beforehand. The number of interstitial class II⁺ cells in fresh and cultured HFPs was not influenced by g-IFN. The significance of these observations with regard to clinical HFP transplantation is discussed.     

Acute intermittent porphyria and mental illness – a family study

All cases of acute intermittent porphyria (AIP) are believed to be caused by a mutation in the gene encoding for porphobilinogen deaminase, a rate-limiting enzyme in the haem synthetic pathway. This gene has been mapped to the long arm of chromosome 11, a region of the genome that has recently attracted considerable attention as a possible location for genes implicated in major mental disorder. This study was designed to show whether major mental illness co-segregated with acute intermittent porphyria in families where the two conditions are found. The study also investigated the relation between clinical mental symptoms and biochemical parameters of acute intermittent porphyria. The case records of 344 consecutive patients admitted to the Porphyrias Research Group in the Western Infirmary in Glasgow between 1950 and 1988 with acute intermittent porphyria were examined for evidence of psychiatric contact. Of 16 individuals identified, 12 were available for the study. Forty relatives of these 12 probands, including 9 who were asymptomatic carriers of AIP, were interviewed for lifetime history of mental illness and current symptoms. Comparisons were made between 4 groups of patients based on urinary porphyrin levels and erythrocyte enzyme activity; 1) manifest acute intermittent porphyria, 2) latent acute intermittent porphyria, 3) normal relatives and 4) total acute intermittent porphyria (latent and manifest combined). No association was found between AIP and schizophrenia or manic-depressive illness. Only one patient with schizophrenia was found in the sample of 344 case notes, and in 2 families bipolar illness was found but did not segregate with acute intermittent porphyria. The commonest psychiatric diagnosis in patients was generalized anxiety. In the total AIP group (latent and manifest), compared with normals, the rating scale measures of anxiety were significantly correlated with the level of porphyrin metabolites in the urine at the time of rating. This was true even in subjects with latent AIP, who were not at the time of testing aware that they were asymptomatic carriers of the illness. AIP should be considered in the differential diagnosis of generalized anxiety disorder.     

Relationship of knee joint proprioception to pain and disability in individuals with knee osteoarthritis.

Proprioception plays an integral role in neuromotor control of the knee joint and deficits in knee joint proprioception are well documented in individuals with knee osteoarthritis (OA). However, the functional relevance of these deficits is not clear. This cross-sectional study evaluated the relationship between knee joint proprioception and pain and disability in a large cohort of individuals with knee OA. Two hundred and twenty participants (145 F, 75 M) with symptomatic knee OA were recruited from the community. Five non-weight bearing active tests with ipsilateral limb matching responses were performed at 20 degrees and 40 degrees flexion to measure knee joint position sense. Pain and disability were assessed by self-reported questionnaires and objective measures of balance and gait. Results showed little association between knee joint position sense variables and measures of pain and disability (r values <0.24, most p>0.05). When comparing participants with the worst and best joint position sense, no significant differences in pain and disability could be found (p>0.05). While our study design does not allow causality to be established, these results suggest that deficits in joint position sense may be due to factors other than pain and that deficits are not large enough to impact upon disability.     

Prediction of liability to orofacial clefting using genetic and craniofacial data from parents.

BACKGROUND: Cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) are separate clinical entities and for both polygenic multifactorial aetiology has been proposed. Parents of children with orofacial clefting have been shown to have distinctive differences in their facial shape when compared to matched controls. OBJECTIVE: To test the hypothesis that genetic and morphometric factors predispose to orofacial clefting and that these markers differ for CL(P) and CP. Methods-Polymorphisms at the transforming growth factor alpha (TGFalpha) locus in 83 parents of children with nonsyndromic orofacial clefts were analysed, and their craniofacial morphology was assessed using lateral cephalometry. RESULTS: Parents of children with CL(P) and CP showed an increased frequency of the TGFalpha/TaqI C2 allele (RR=4.10, p=0.009) relative to the comparison group. Also the TGFalpha/BamHI A1 allele was more prevalent in the CP parents. MULTIVARIATE STATISTICAL ANALYSIS: Using stepwise logistic regression analysis the TGFalpha/TaqI C2 polymorphism provides the best model for liability to orofacial clefting. To determine the type of clefting a model involving interaction between the parental TGFalpha/BamHI and TGFalpha/RsaI genotypes showed the best fit. Using genotype only to predict the clefting defect in the children according to parental genotype, 68.3% could be correctly classified. By adding information on craniofacial measurements in the parents, 76% of CP and 94% of CL(P) parents could be correctly classified. CONCLUSIONS: This study provides a model for prediction of liability to orofacial clefting. These findings suggest that different molecular aberrations at the TGFalpha locus may modify the risk for CP and CL(P).     

Theory and practice in the occupational therapy guidelines for client-centred practice

A model for occupational therapy has evolved and has come to be referred to as the "Guidelines" model or the Canadian Occupational Performance model. This paper attempts to reformulate information relating to the Guidelines model, to support its use as a conceptual model and a model of practice. Both the conceptual model and model of practice are described in terms of their domain of concern, underlying values and assumptions, concepts and principles. The conceptual model provides a means of understanding occupational performance, while the model of practice offers a way of understanding the relationship between occupational therapy interventions and occupational performance. Both models are evaluated relative to nine criteria derived from the literature. The conceptual model is found to be largely consistent, supportable, comprehensive and useful. The model of practice, however, proves more problematic, with technical, structural and conceptual variances. The paper is intended as a stimulus for discussion and study of this central model of Canadian occupational therapy.     

Coping with community reintegration after severe brain injury: a description of stresses and coping strategies

A basic qualitative approach was used to describe the stresses and coping strategies of 11 adults with severe brain injury during a critical period of reintegrating into a new community. Subjects identified nine problems as stressful. The stresses conform to a theoretical model of community integration, consisting of four factors: social support, independent living, occupation, and a general integration factor. These stresses identified by subjects may be used in the development of a new measure of stress for persons with brain injury. Subjects used eight coping strategies to deal with these stresses. The coping strategies represent a sampling of three major types of coping: problem-focused, perceptionfocused, and emotion-focused. The findings show that subjects made more use of problem-focused coping strategies than any other type of coping, suggesting that persons with brain injury have awareness of the problems they face and the ability to assert some control over eliminating or managing these problems. The stresses and coping strategies are consistent with existing studies involving persons with brain injury. However, significant differences in some coping strategies reported in this study change how some forms of coping are thought about. The findings delineate the need for professionals to assist persons with brain injury develop more positive, adaptive coping strategies.