Liver disease as new work in the context of protocolised primary care - do GPs have a role? A qualitative interview study.

BACKGROUND: Liver disease is common, but not part of routine chronic disease management in primary care. AIM: The aim of this study was to explore the challenges of implementing pathways of care for liver disease within existing highly protocolised structures in primary care. METHOD: Semi-structured interviews with 20 health professionals working in primary care. Interviews were informed by normalisation process theory (NPT) and boundary theory. Data were subject to thematic analysis. RESULTS: Three themes were identified relating to chronic disease work; definitions; need and worth, and roles. Participants identified that understanding and value of roles within chronic disease management were pre-defined by targets imposed on them as part of national incentives schemes. Structural boundaries constrained professional autonomy and the potential to influence this area of primary care management, including taking on new work. CONCLUSION: The inability to influence care decisions blurs occupational boundaries and goes to the core of what it means to be a professional. Unless liver disease sits within this target-based system, it is unlikely to become part of routine work in primary care.

Prevalence and aetiology of juvenile skeletal fluorosis in the south-west of the Hai district, Tanzania--a community-based prevalence and case-control study.

INTRODUCTION: Fluorosis is endemic throughout the East African Rift valley, including parts of Tanzania. The aim of the study was to identify all cases of deforming juvenile skeletal fluorosis (JSF) in a northern Tanzanian village and to document the extent of dental fluorosis (DF). METHODS: Door-to-door prevalence survey of all residents of the village. Residents were assessed for the presence of DF and JSF. Those with JSF and randomly selected controls from the same age range were further assessed for possible JSF risk factors. RESULTS: The village had a population of 1435. DF was endemic within the population, being present in 911 (75.5%; 95% CI, 73.0-77.9) of dentate individuals who were examined (n = 1207). JSF was present in 56 of 1263 people examined, giving a prevalence of 4.4% (95% CI, 3.3-5.6) and was more common in males. Low body mass index, drinking predominantly well water 3 years previously, not being weaned on bananas, the use of fluoride salts in cooking during childhood and drinking more cups of tea per day were independent predictors of JSF. CONCLUSIONS: Juvenile skeletal fluorosis is a common and preventable public health problem. Providing clean, low-fluoride, piped water to affected communities is of obvious health benefit.

Cold storage of 'cryohydrocytosis' red cells: the osmotic susceptibility of the cold-stored erythrocyte.

'Cryohydrocytosis' is an unusual human haemolytic anaemia of the 'hereditary stomatocytosis' group, in which the red cell membrane is abnormally permeable to Na and K+ at both body and (even more prominently) refrigerator temperatures. If whole cryohydrocytosis blood is anticoagulated in heparin or EDTA and stored on ice overnight, about 50% of the cells will lyse. Citrate phosphate dextrose adenine (CPDa) anticoagulant, empirically verified as an optimal anticoagulant for storage of normal blood before transfusion, very markedly ameliorated this overnight lysis, suggesting that these cells might form an informative model in which cold storage of the red cell could be studied in a short time scale. Accordingly, we conducted studies of ion flux, cell swelling and lysis in different media used historically for blood preservation and compared the experimental data with an 'integrated red cell model', which seeks mathematically to model the osmotic behaviour of red cells under different conditions. Upon experiment, lysis in these cells was reduced by additives that could be regarded as impermeant extracellular solutes (citrate, mannitol) and by low pH, but not by those agents that are regarded as protecting the cell against energy depletion or oxidation (adenine, glucose, nicotinic acid). The protective effects of these extracellular additives were all reproduced by the computer simulation, confirming the validity of this model, although the effect of pH could be simulated only semi-quantitatively, possibly because Na+ permeability itself depends on pH.

ATP-dependent vesiculation in red cell membranes from different hereditary stomatocytosis variants.

The hereditary stomatocytoses are a group of dominant haemolytic anaemias that show two main features: invaginated, 'stomatocytic' morphology; and a membrane leak to the univalent cations Na and K. A patient with the most severe variant of these conditions was reported to show a defect in an in vitro process of ATP-dependent endocytic vesiculation (ADEV), which is found in normal red cells. We have examined this endocytosis process in 11 leaky red cell pedigrees available to us in the UK. ADEV in broken membranes was absent only in the two most severely affected, 'overhydrated' pedigrees studied, both of which showed a deficiency in the membrane raft protein, stomatin. The process was present, although typically diminished by about 10-20% compared with normal red cells, in all others. The cross-linker dimethyl adipimate (DMA), which could correct the cation leak in some of these patients, also corrected the ADEV defect in the same patients. In those patients in whom DMA had no effect on the ion leak, ADEV was not absent. In normal cells, this process of vesiculation was inhibited by inhibitors of membrane 'raft' function, by an antistomatin antibody and by vanadate and N-ethyl maleimide, but not by inhibitors of a number of kinases. These data highlight the heterogeneity of these conditions. A mechanism is discussed by which a defect in raft-based endocytosis could lead to the exaggerated surface exposure of an ion channel, which could then function constitutively, i.e. 'leak'.

Four new cases of stomatin-deficient hereditary stomatocytosis syndrome: association of the stomatin-deficient cryohydrocytosis variant with neurological dysfunction.

This report concerns congenitally Na(+)-K(+) leaky red cells of the 'hereditary stomatocytosis' class. Three new isolated cases and one new pedigree are described, and one previously reported case is expanded. In all cases, Western blotting of red cell membranes revealed a deficiency in the 32 kDa membrane protein, stomatin. All showed pronounced cation leaks at 37 degrees C with markedly abnormal intracellular Na(+) and K(+) concentrations, like all other such stomatin-deficient cases. Consistent with recent findings in two previously described British pedigrees, immunocytochemistry demonstrated that the deficiency of stomatin was not complete. On typical blood films, some red cells showed positive stomatin immunoreactivity, while most were negative, although in one case only a minority were negative. All platelets and neutrophils were stomatin positive. The cases differed markedly between themselves with regard to the temperature dependence of the passive leak to K(+). Three showed a simple monotonic temperature dependence, while two showed a minimum at around 20-25 degrees C, such that the cells were extremely leaky at 0 degrees C, giving the phenotype known as 'cryohydrocytosis'. These patients are the only two known cases of stomatin-deficient cryohydrocytosis. Both showed a congenital syndrome of mental retardation, seizures, cataracts and massive hepatosplenomegaly, probably defining a new haemato-neurological syndrome.