Fee-for-service cancer rehabilitation programs improve health-related quality of life.

BACKGROUND: Rigorously applied exercise interventions undertaken in a research setting result in improved health-related quality of life (hrqol) in cancer survivors, but research to demonstrate effective translation of that research to practice is needed. The objective of the present study was to determine the effect of fee-for-service cancer rehabilitation programs in the community on hrqol and on self-reported physical activity and its correlates. METHODS: After enrolment and 17 ± 4 weeks later, new clients (n = 48) to two fee-for-service cancer rehabilitation programs completed the 36-Item Short Form Health Survey (rand-36: rand Corporation, Santa Monica, CA, U.S.A.), the Godin Leisure-Time Exercise Questionnaire, and questions about physical activity correlates. Normal fee-for-service operations were maintained, including a fitness assessment and individualized exercise programs supervised in a group or one-on-one setting, with no minimum attendance required. Fees were associated with the assessment and with each exercise session. RESULTS: Of the 48 participants, 36 (75%) completed both questionnaires. Improvements in the physical functioning, role physical, pain, and energy/fatigue scales on the rand-36 exceeded minimally important differences and were of a magnitude similar to improvements reported in structured, rigorously applied, and free research interventions. Self-reported levels of vigorous-intensity (p = 0.021), but not moderate-intensity (p = 0.831) physical activity increased. The number of perceived barriers to exercise (p = 0.035) and the prevalence of fatigue as a barrier (p = 0.003) decreased. Exercise self-efficacy improved only in participants who attended 11 or more sessions (p = 0.002). Exercise enjoyment did not change (p = 0.629). CONCLUSIONS: Enrolment in fee-for-service cancer rehabilitation programs results in meaningful improvements in hrqol comparable to those reported by research interventions, among other benefits. The fee-for-service model could be an effective model for delivery of exercise to more cancer survivors.

The absence of bicarbonate-stimulated ATPase activity in the plasma membranes of the bicarbonate secreting ox corneal endothelial cells.

Membranes of ox corneal endothelial cells were studied for their surface area by electron microscopical stereology and then separated from homogenates on self forming Percoll gradients. Enzymic analysis of the plasma membrane-enriched fraction failed to demonstrate an ATPase activity which was stimulated by the presence of bicarbonate ions. It is proposed that the well-established bicarbonate secretion of these cells may be coupled to the plasma membrane (Na+ + K+)-ATPase activity by the stoichiometry of Na+/HCO3- close to 1:1.

Local osmotic coupling to the active trans-endothelial bicarbonate flux in the rabbit cornea.

The present experiments investigate HCO3-, Cl- and fluid fluxes across partially destromalised corneas. Although there is no net flux of Cl-, there is a net flux of HCO-3 across the endothelium from stromal side to aqueous side which is accompanied by a flux of water in the same direction. Bulk phase osmosis cannot account for the initiation of the flux of fluid. Local osmotic coupling between ions and water is postulated to occur in the preparation. The exudate is hypertonic to the bathing Ringer solution.

Localization of Na+/K(+)-ATPase in the bovine corneal endothelium.

A mouse monoclonal antibody has been used to localize Na+/K(+)-ATPase in the bovine corneal endothelium. The specificity of the antibody was demonstrated by reaction with a single protein of molecular mass 100 kDa on Western blots and immunoprecipitation of a complex consisting of 100 kDa and 50 kDa subunits. Treatment of the immunoprecipitated antigen with Peptide N-Glycanase F produced no change in the molecular mass of the 100 kDa protein, but resulted in a progressive decrease in the molecular mass of the 50 kDa subunit, to yield a core protein of molecular mass about 33 kDa. The pattern of deglycosylation suggested the presence of three N-linked glycans attached to the 33 kDa protein core. These results were consistent with the antibody being specific for the alpha subunit of the Na+/K(+)-ATPase. Immunocytochemical studies at the light and electron microscopic level demonstrated antibody binding to both the basal and lateral membranes of bovine corneal endothelial cells. This suggested a baso-lateral distribution of Na+/K(+)-ATPase in these cells, rather than the previously proposed lateral membrane-only distribution.

Determination of pathways for sodium movement across corneal endothelial cell derived plasma membrane vesicles.

A bovine corneal endothelial cell plasma membrane vesicle preparation was used to investigate passive Na+ transport across the plasma membrane of these cells. Sodium accumulation rate into the vesicle was not dependent on the presence of HCO3- or a HCO3- gradient, but was stimulated by a trans-vesicle pH gradient. Amiloride, furosemide and DIDS all reduced the rate of Na+ accumulation. The data indicate the presence of at least two independent pathways for passive sodium movement across the vesicle: the first probably via a Na+/H+ exchanger and the second a furosemide inhibitable Na+ entry mechanism. No evidence was found for direct Na(+)-HCO3- coupled transport.

Determination of Na+/Cl-, Na+/HCO3- and Na+/K+/2Cl- co-transporter activity in corneal endothelial cell plasma membrane vesicles.

Corneal endothelial cell derived plasma membrane vesicles were used to investigate the presence of Na+/Cl-, Na+/HCO3- and Na+/K+/2Cl- co-transporter activity in the plasma membranes of these cells. Na+/H+ exchange was blocked by the presence of 1 mM amiloride in all determinations. The rate of accumulation of Na+ in the presence of chloride or bicarbonate was not significantly different from its accumulation in the presence of acetate, thiocyanate or gluconate. The addition of K+ to Na+ plus Cl- did not stimulate Na+ accumulation into the vesicles. The present work provides no evidence for Na+/K+/2Cl-, Na+/Cl- or Na+/HCO3- co-transport in corneal endothelial cell plasma membrane vesicles.

Neutron and X-ray scattering by ox corneal stroma differentially loaded with bound anions.

Ox corneas at near physiological hydration were subjected to two variables: the amount of chloride ions bound to them and exposure of various mixtures of H(2)O/D(2)O as solvent. The preparations were then exposed to a neutron beam and the contrast match points, at which the collagen fibrils of the corneal stroma most nearly matched the scattering density of the various H(2)O/D(2)O mixtures, were measured. In both cases of high and low bound chloride, the contrast match points of the collagen fibril were equal, indicating that there were no significant changes in the water of electrostriction at the fibril surface when chloride ions bind to the stroma. The data suggest that the ligands which bind anions to corneal stroma are not located at the collagen fibril surface. When the chloride binding ligands were extracted from the corneal stroma there were significant changes in the structure of the fibrils. We suggest that the chloride binding ligands may be located within the collagen fibril.

Two pathways for electrogenic bicarbonate ion movement across the rabbit corneal endothelium.

Amiloride (0.5 mM) inhibited the rate of entry of Na+ into corneal endothelial cells by more than half ((0.76 +/- 0.10) to (0.21 +/- 0.10) microEq cm(-2)h(-1)). The same concentration of amiloride caused only minimal disturbance to corneal hydration control by the endothelium (range 0-12%). Amiloride (0.5 mM) and acetazolamide (1 mM) reversibly inhibited trans-endothelial short circuit current by about a half. Their combined effect was not additive. Acetazolamide (1 mM) reduced net HCO3- flux across the short-circuited endothelium by about the same amount ((0.50 +/- 0.11) microEq cm(-2)h(-1)) that amiloride (0.5 mM) reduced Na+ entry into the cells ((0.55 +/- 0.14) microEq cm(-2)h(-1)). Low concentrations of amiloride (10 microM) had little effect on the transport characteristics of the endothelium, indicating that Na+ entry into the endothelial cells under physiological conditions is not primarily through Na+ channels. The data are consistent with an Na+/H+ exchanger acting in tandem with carbonic anhydrase through a pathway which could have a regulatory role on endothelial transport via its effect on Na+ re-entry. Residual trans-endothelial HCO3- transport, apparently unaffected by amiloride or acetazolamide inhibition, is calculated to be of sufficient magnitude to maintain corneal hydration.

The ordering of corneal collagen fibrils with increasing ionic strength.

The fixed stromal charge of bovine corneas, osmotically clamped at physiological hydration, was altered by regulating the amount of chloride ions bound to the matrix. We measured the local fibrillar collagen order using X-ray diffraction methods. As the bound anions increased up to physiological values, the local fibrillar order increased to an optimal value. The coherence distance (t) approximately doubles to a maximum value (409 nm) from 10 mM NaCl to 154 mM NaCl. This then slowly decreased as the bathing solution increased to 1000 mM. In contrast the diameter of the collagen fibrils were minimal at physiological NaCl.

Structural changes in alpha-crystallin and whole eye lens during heating, observed by low-angle X-ray diffraction.

Whole eye lens and alpha-crystallin gels and solutions were investigated using X-ray scattering techniques at temperatures ranging from 20 degrees C to 70 degrees C. In whole lens isolated in phosphate-buffered saline, the spacing of the dominant X-ray reflection seen with low-angle scattering was constant from 20 degrees C to 45 degrees C but increased at 50 degrees C from 15.2 nm to 16.5 nm. At room temperature, the small-angle X-ray diffraction pattern of the intact lens was very similar to the pattern of alpha-crystallin gels at near-physiological concentration (approximately 300 mg/ml), so it is reasonable to assume that the alpha-crystallin pattern dominates the pattern of the intact lens. Our results therefore indicate that in whole lens alpha-crystallin is capable of maintaining its structural properties over a wide range of temperature. This property would be useful in providing protection for other lens proteins super-aggregating. In the alpha-crystallin gels, a moderate increase in both the spacing and intensity of the reflection was observed from 20 degrees C to 45 degrees C, followed by an accelerated increase from 45 degrees C to 70 degrees C. Upon cooling, this effect was found to be irreversible over 11 hours. Qualitatively similar results were observed for alpha-crystallin solutions at a variety of lower concentrations.

Thienyl and thiazolyl acyclic analogues of 5-deazatetrahydrofolic acid.

Analogues of N-[4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]amino] benzoyl]-L-glutamic acid (5-DACTHF), in which the phenylene group is replaced by either a thienoyl or a thiazolyl group were synthesized. These compounds were prepared by reductive amination of suitably protected pyrimidinylpropionaldehyde with the aminoaroyl glutamates. These glutamates were in turn synthesized from the corresponding nitroaroyl carboxylic acids by condensation with protected glutamic acid followed by catalytic reduction. The compounds were tested as inhibitors of methotrexate uptake as a measure of binding to the reduced folate transport system, as inhibitors of glycinamide ribonucleotide transformylase, as substrates for folylpolyglutamate synthetase, and as inhibitors of tumor cell growth in cell culture. The thiophene analogue was found to be equal in activity to 5-DACTHF in the MCF-7 cell growth inhibition assay while the thiazole analogue was 9-fold more active. Indeed this thiazole was over 4 times more active in the MCF-7 cell line than the clinically investigated compound 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).

Synthesis and biological activity of open-chain analogues of 5,6,7,8-tetrahydrofolic acid--potential antitumor agents.

This study describes the synthesis and in vitro antitumor activity of inhibitors of purine de novo biosynthesis that are analogues of N-[4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl) propyl]amino]benzoyl-L-glutamic acid (5-DACTHF). Benzene ring substituted analogues were synthesized from a protected pyrimidinyl propionaldehyde and a substituted benzoyl glutamate moiety by a key reductive amination step. Pyrimidine and linking chain substituted analogues were built up stepwise from p-aminobenzoic acid or analogues. The compounds were tested as inhibitors of methotrexate uptake as a measure of binding to the reduced folate transport system, as inhibitors of glycinamide ribonucleotide transformylase, as substrates for folylpolyglutamate synthetase, and as inhibitors of tumor cell growth in cell culture. With the exception of 2'-F substituent, the ring-substituted analogues are less active than the parent compound. Replacement of the 10-nitrogen by carbon, sulfur, or oxygen produced less than 2-fold changes to biological activity in vitro. A four-atom linking chain and an amino group at the 2-position on the pyrimidine ring are important for good activity.

No transplacental passage of standard heparin or an enzymatically depolymerized low molecular weight heparin.

In 21 women who had an abortion by hysterotomy between the 15th and 23rd week of pregnancy, the possibility that unfragmented heparin or low molecular weight heparin (LMWH) passed the placental barrier to the foetus was studied. Laboratory analyses included amidolytic assays of factor Xa inhibitory activity (XaI), antithrombin III (ATIII) and a direct measurement of heparin-like substances in plasma with a competitive binding assay. The ATIII concentration in foetal plasma was about 20% of that in normal human plasma and varied considerably between individuals (2-27%). The XaI activity did not differ between the two treated groups, but the mean XaI activity of the combined groups differed from zero (P less than 0.05). If the XaI activity was corrected for the ATIII concentration, the heparin activities no longer differed significantly from zero. As the concentration of heparin-like substances were above the detection limit (0.35 microgram/ml) in 6/16 analysable samples of foetal plasma, a further 15 women who had not received any heparin were included as controls. In 12/14 analysable foetal plasmas heparin-like substances in concentrations above 0.35 micrograms/ml could be detected. Determination of heparin activity in foetal plasma is thus difficult due to the influence of endogenous ATIII on heparin assays. In conclusion, this study did not demonstrate any evidence for the passage of heparin or LMWH across the placental barrier. No differences were detected whether unfragmented heparin or LMWH had been given to the mothers. Our results also indicate the presence of an endogenous glycosaminoglycan in foetal plasma.

The movement of sodium across short-circuited rabbit corneal endothelium.

Unidirectional sodium and bicarbonate ion fluxes were measured under short-circuit conditions across rabbit corneal endothelium. A net flux of bicarbonate was measured, direction tears to lens, however no net flux of sodium was measured. From these experiments it seems that the inequality between electrically measured short-circuit current and net trans-endothelial bicarbonate ion flux cannot be bridged by any supposed net sodium flux.

Bicarbonate and the trans-endothelial short circuit current of human cornea.

Experiments were performed in vitro, to determine the effect of bicarbonate ion concentration on human cornea endothelial potential difference, short circuit current and resistance. Decreasing the bicarbonate concentration resulted in a reversible and parallel fall in potential differences and short circuit current, whereas resistance remained unchanged. The results demonstrate that bicarbonate is a necessary component of the mechanisms that generate trans-endothelial short circuit current. Similarities between data derived from rabbit, ox and human suggest that a common underlying bicarbonate dependent mechanism is operating in these species.

The effect of bicarbonate ion concentration on trans-endothelial short circuit current in ox corneas.

Experiments were performed in vitro, to determine the effect of bicarbonate ion concentration on bovine cornea endothelial potential difference, short circuit current and resistance. Corneas were perfused with Ringer solutions containing 36, 12, 6, 3, 0 mM NaHCO3. Endothelial potential difference, short circuit current and resistance were measured at each concentration. Decreasing the bicarbonate concentration resulted in a reversible and parallel fall in potential difference and short circuit current, whereas resistance remained unchanged. The results demonstrate that bicarbonate is a necessary component of the mechanisms that generate trans-endothelial short circuit current.

Evidence for keratin proteins in normal and abnormal human meibomian fluids.

Hyperkeratinization of meibomian glands has been postulated to cause gland dysfunction. Recent investigations on rabbits show that keratin proteins are indeed present in the meibomian fluids of these animals. In this report we present our findings on the presence of these water-insoluble proteins in human meibomian secretions. 6 anti-cytokeratin antibodies, CK8, 18, 19, CK7, CK8, CK14, CK19 and AE1/AE3 were used against the keratin proteins expressed from the human meibomian fluids. Using the immunoblotting (dot blot) technique, abnormal waxy meibomian fluids obtained from subjects diagnosed to have meibomian gland dysfunction (MGD) were compared to normal clear meibomian fluids. The results show that keratins are present in a higher concentration (10%) in the abnormal human meibomian excreta as compared to the normals. Even though the presence of protein markers for keratinization in the abnormal meibomian excreta were not shown, the increased presence of keratin proteins in the abnormal meibomian fluids suggests that, in MGD patients, hyperkeratinization of ductal epithelium may have taken place. More keratin proteins (possibly those of higher molecular weights) were produced in addition to the keratin proteins normally produced by the duct epithelium. The increased amount of keratin proteins in the abnormal meibomian fluids may be explained by the susceptibility of duct epithelium to undergo the process of hyperkeratinization as postulated by other researchers.