Stone-forming potential of milk or calcium-fortified orange juice in idiopathic hypercalciuric adults.

Milk and orange juice (OJ) fortified with calcium-citrate-malate (CCM; calcium-citrate-malate salt is a coined term to describe a trademarked calcium delivery system found only in Citrus Hill Plus Calcium) were evaluated for their potential to alter urine chemistries and crystallization during the course of an eleven week, crossover study. Six male and six female, non-stone-forming, idiopathic hypercalciuric adults consumed 600 mg per day as beverage calcium for four consecutive weeks. The results show that both milk and CCM-fortified OJ (CCM-OJ) were well tolerated by male and female hypercalciurics since few significant changes occurred in overall urinary chemistry profiles. CCM-OJ did, however, significantly (P less than or equal to 0.05) increase urinary pH relative to milk in both sexes and urinary citrate concentration in women only. Both of these urinary parameters were significantly increased by CCM-OJ in both sexes relative to the basal period. The combined pH and citrate effects are recognized to protect against calcium oxalate stone formation through formation of the soluble calcium citrate salt. These data indicate that either milk or CCM-fortified orange juice can be consumed, at least within the limits tested, as a dietary source of calcium without increasing the risk of stone formation in a calcium-sensitive subpopulation. That the urine chemistries and crystallization of such calcium-sensitive individuals does not significantly change with the consumption of either beverage implies that the urine of normal individuals would be exceedingly unlikely to change as well.     

Building a relationship: communications and relationships between staff and stroke patients on a rehabilitation ward

Communications among staff and patients on a stroke rehabilitation ward form the focus of this article, which reports on some aspects of a larger study using a grounded theory approach. Tape-recorded interviews were transcribed and analysed concurrently according to recommendations for the approach. A main theme entitled building a relationship was identified, and this process was found to occur in a context varying from participative at one end of a continuum to hierarchical at the other. Building a relationship was found to be influenced by role, personal qualities and organizational context. Appropriate relationships between role-holders were subject to negotiation, leading to a resulting congruence or incongruence between participants' expectations of each other and their roles. Personal qualities were brought into play in the process, with patients' views of staff and staff views of patients both being influential. Some of these views seemed to parallel what has been described in earlier literature as ‘the sick role’ and the labelling of patients as ‘good’ or ‘bad’. Responses to personal qualities led to nurses ascribing meaning to patients' behaviour in terms of adjustment to their stroke, giving time to them to help them to adjust, and withdrawal and handing over to other staff if this strategy failed. Organizational context also had an influence on building a relationship, with time constraints being identified particularly by nurses, and the need to fit in the most essential aspects of care. Place was also important, in that nurses were confined to the ward as a work location, whereas other therapists and doctors worked in other places and sometimes had the facility to take patients off the ward to concentrate on therapy. The findings are discussed against the background of related literature and the conclusion is drawn that the crucial role of nurses in rehabilitation is not recognized and valued, and that shortages of resources - especially suitably qualified and trained nursing staff- are a negative influence on building the relationships which are vital to successful rehabilitation.     

Comparative inotropic effect of calcium, endothelin-1, and forskolin on ferret papillary muscles during acidosis

Summary— Acidosis affects multiple steps in the excitation-contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca²⁺ and 3) endothelin-1, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady-state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin-1 was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca²⁺, which was more effective than increasing [Ca²⁺]_i through elevating extracellular Ca²⁺ or the addition of forskolin which increased [Ca²⁺]_i but desensitized the myofilaments to Ca²⁺.     

Shared care: a review of the literature

This review examines broad issues of concern regarding the primary/secondarycare interface. The main purpose was to identify areas of goodpractice which could be adapted for more general use. One ofthe most fundamental aspects identified was communication, whichis discussed in some detail. Also covered are shared prescribingand disease management. The data suggest that the most effectivesystem(s) of shared care has yet to be established. Furtherqualitative and economic evaluations are required, taking intoaccount patient preferences. Although the literature does describecertain practice exemplars, it is clear that inter- and intra-professionalcommunication continues to be a problem. Whilst informationtechnology may provide some of the solutions, it is concludedthat a culture change, which compels health professionals tomake sharing of patient information a much higher priority,is reauired. Keywords. Shared care, seamless care, hospital, general practice, family practice.     

Generation and comparative analysis of approximately 3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7q11.23 implicated in Williams syndrome.

Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a approximately 1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (approximately 300 kb) duplicated blocks of DNA of near-identical sequence. Previously, we showed that the orthologous region of the mouse genome is devoid of such duplicated segments. Here, we extend our studies to include the generation of approximately 3.3 Mb of genomic sequence from the mouse Williams syndrome region, of which just over 1.4 Mb is finished to high accuracy. Comparative analyses of the mouse and human sequences within and immediately flanking the interval commonly deleted in Williams syndrome have facilitated the identification of nine previously unreported genes, provided detailed sequence-based information regarding 30 genes residing in the region, and revealed a number of potentially interesting conserved noncoding sequences. Finally, to facilitate comparative sequence analysis, we implemented several enhancements to the program, including the addition of links from annotated features within a generated percent-identity plot to specific records in public databases. Taken together, the results reported here provide an important comparative sequence resource that should catalyze additional studies of Williams syndrome, including those that aim to characterize genes within the commonly deleted interval and to develop mouse models of the disorder.     

Chaperonin-mediated assembly of wild-type and mutant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli

We developed a bacterial expression system for the human alpha and beta cDNAs of propionyl-CoA carboxylase (PCC). These cDNAs (less the putative mitochondrial matrix targeting presequences) were co-expressed in Escherichia coli on one plasmid vector with each cDNA having its own IPTG-inducible promoter. Only negligible amounts of active PCC were measured despite the presence of both alpha and beta subunits as indicated by Western blot analysis and the almost complete biotinylation of the alpha subunit. Co-expression of this plasmid with a second plasmid vector over-expressing the E. coli chaperonin proteins, groES and groEL, resulted in a several hundred-fold increase in PCC specific activity, to a level comparable with that found in crude human liver extracts. PCC was partially purified on monomeric avidin affinity resin and the presence of both alpha and beta subunits was demonstrated, thereby confirming the assembly of both subunits into an active enzyme. Deficiency of either alpha PCC or beta PCC results in propionic acidemia, an autosomal recessive disorder. We used this expression system to characterize one missense mutation previously described in five Japanese alleles, namely C1283T (Thr428lle) in beta PCC. This mutation, when expressed in E.coli under the same conditions as that of wild-type PCC, had null activity, despite the presence of assembled alpha PCC and beta PCC subunits. This bacterial expression system can be useful for analysis of either alpha PCC or beta PCC mutations. Our findings indicated that the groES and groEL chaperonin proteins were essential for folding and assembly of the human PCC heteromeric subunits.      

Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-κB

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