Management of labour and delivery in congenitally corrected transposition of great arteries.

A descriptive case report of the labour and delivery management of a 28-year-old woman who presented with congenitally corrected transposition of great arteries, dextrocardia, systemic ventricular dysfunction and junctional tachycardia. Patients with congenitally corrected transposition have a thin-walled morphological right ventricle as the systemic circulatory pump. The stress of increased cardiac output can lead to congestive heart failure, systemic atrioventricular valve regurgitation and arrhythmias. We used minimally invasive continuous cardiac output monitoring, fluid balance optimization and good maternal pain control to prevent decompensation and achieve vaginal delivery with a good maternal and neonatal outcome.

The role of hope in psychotherapy with older adults.

The positive impact of psychotherapy upon the mental health problems of older people is increasingly accepted. However little attention has been paid to the role of hope in working therapeutically with older adults. Three relevant bodies of literature, namely adult psychotherapy, hope in older adulthood, and coping with chronic and terminal illness, provide a starting point for examining the therapeutic uses of hope. However, it is argued that these literatures cannot provide a sufficiently comprehensive conceptualisation of hope in psychotherapy with elders. Firstly, it is considered that hope in therapy is directly affected by key experiences of ageing, namely: facing physical and/or cognitive deterioration and facing death. Also, these three bodies of literature have tended to dichotomise hope as either beneficial and adaptive or dysfunctional and maladaptive. A developmental perspective is used to critique this dichotomy and a clinical framework is provided which examines the role and utility of hope in older adult psychotherapy from a more integrated viewpoint embedded in the client's life history. The framework is comprised of three types of 'hope work': 'facilitating realistic hope,' 'the work of despair' and 'surviving not thriving'. Suggestions are made about how this work may be carried out and with whom.

Cefaclor uptake by the proton-dependent dipeptide transport carrier of human intestinal Caco-2 cells and comparison to cephalexin uptake.

The human Caco-2 cell line spontaneously differentiates in culture to epithelial cells possessing intestinal enterocytic-like properties. These cells possess a proton-dependent dipeptide transport carrier that mediates the uptake of the cephalosporin antibiotic cephalexin (Dantzig, A.H. and Bergin, L. (1990) Biochim. Biophys. Acta 1027, 211-217). In the present study, the uptake of cefaclor was examined and found to be sodium-independent, proton-dependent, and energy-dependent. The initial rate of D-[3-phenyl-3H]cefaclor uptake was measured over a wide concentration range; uptake was mediated by a single saturable transport carrier with a Km of 7.6 mM and a Vmax of 7.6 nmol/min per mg protein and by a non-saturable component. Uptake was inhibited by dipeptides but not amino acids. The carrier showed a preference for the L-isomer. The effect of the presence of a 5-fold excess of other beta-lactam antibiotics was examined on the initial rates of 1 mM cefaclor and 1 mM cephalexin uptake. Uptake rates were inhibited by the orally absorbed antibiotics, cefadroxil, cefaclor, loracarbef, and cephradine and less so by the parenteral agents tested. The initial uptake rates of both D-[9-14C]cephalexin and D-[3-phenyl-3H]cefaclor were competitively inhibited by cephalexin, cefaclor, and loracarbef with Ki values of 9.2-13.2, 10.7-6.2, and 7.7-6.4 mM, respectively. Taken together, these data suggest that a single proton-dependent dipeptide transport carrier mediates the uptake of these orally absorbed antibiotics into Caco-2 cells, and provide further support for the use of Caco-2 cells as a cellular model for the study of the intestinal proton-dependent dipeptide transporter.

Uptake of the cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2.

The transport of the orally absorbed cephalosporin, cephalexin, was examined in the human epithelial cell line, Caco-2 that possesses intestinal enterocyte-like properties when cultured. In sodium-free buffer, the cells accumulated 1 mM D-[9-14C]cephalexin against a concentration gradient and obtained a distribution ratio of 3.5 within 180 min. Drug uptake was maximal when the extracellular pH was 6.0. Uptake was reduced by metabolic inhibitors and by protonophores indicating that uptake was energy- and proton-dependent. Kinetic analysis of the concentration dependence of the rate of cephalexin uptake showed that a non-saturable component (Kd of 0.18 +/- 0.01 nmol/min per mg protein per mM) and a transport system with a Km of 7.5 +/- 2.8 mM and a Vmax of 6.5 +/- 0.9 nmol/min per mg protein were responsible for drug uptake. Uptake was competitively inhibited by dipeptides. The transport carrier exhibited stereospecificity for the L-isomer of cephalexin. Drug uptake was not affected by the presence of amino acids, organic anions, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid or 4,4'-diisothiocyano-2,2'-disulfonic stilbene. Therefore, Caco-2 cells take up cephalexin by a proton-dependent dipeptide transport carrier that closely resembles the transporter present in the intestine. Caco-2 cells represent a cellular model for future studies of the dipeptide transporter.

Carrier-mediated uptake of cephalexin in human intestinal cells.

A transport carrier for cephalexin, a cephalosporin antibiotic, was identified in a human intestinal cell line, HT-29. Uptake via the carrier was inhibited by dipeptides, phe-gly, gly-pro, carnosine, and cefaclor, a close drug analog. Uptake was unaffected by the presence of amino acids. The pH optimum for uptake was 6.2. Drug uptake was not dependent on the presence of sodium and was insensitive to metabolic inhibitors. The efflux of cephalexin was stimulated by extracellular carnosine, indicating counter-transport. Taken together, drug uptake is mediated by a dipeptide transport carrier and not by an amino acid transport carrier. This is the first demonstration of the carrier in an established cell line.

Isolation of methylcholanthrene-"initiated" C3H/10T1/2 cells by inhibiting neoplastic progression with retinyl acetate.

A clone of 3-methylcholanthrene-treated 10T1/2 cells has been isolated which possesses basic characteristics expected of "initiated" cells. In the presence of retinyl acetate, this clone exhibits contact inhibited growth control and is morphologically indistinguishable from the parental 10T1/2 cell line. Removal of retinyl acetate in vitro results in neoplastic transformation after a latent period of 3 weeks. The classical 10T1/2 transformation system was reconstructed by coculturing normal and "initiated" 10T1/2 cells formed either Type II or Type III foci after a latent period of 3-4 weeks, and an additional 22% formed Type I foci. Treatment of "initiated" 10T/2 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate accelerated the formation of transformed foci in the coculture system by reducing the length of the latent period to less than 3 weeks. Injection of 10(6) "initiated" cells/mouse s.c. into nude mice resulted in the appearance of progressively growing fibrosarcomas after a latent period of 5-7 weeks. Dietary supplementation with 4-hydroxyphenyl-retinamide prevented tumor formation; after drug withdrawal, tumors developed in all surviving mice after 6 weeks. We believe this cell line possesses all characteristics expected of "initiated" cells. With this new cell line, designated INIT/10T1/2, we can now study the early biochemical changes in growth control mechanisms resulting in neoplastic transformation and the mechanism(s) of chemoprevention of cancer by vitamin A.