Peripherally inserted central venous catheters: factors affecting patient satisfaction

OBJECTIVE: We studied factors that affect satisfaction of patients who have undergone placement of peripherally inserted central venous catheters (PICCs) by interventional radiologists and patients' willingness to undergo placement of future PICCs. SUBJECTS AND METHODS: This longitudinal prospective consecutive cohort study included 85 patients referred for PICC placement. A record was made of catheter type, time taken for placement, patient age, and possible complications. Follow-up was obtained by telephone interview to determine the effect of site of placement in the arm, residence time of catheter, additional complications, and interference with activities of daily living on patient willingness to undergo future PICC placement at the same site. Logistic regression analysis was used to determine factors statistically predictive of patient willingness to undergo placement of future PICCs. RESULTS: Patients having PICCs placed above the elbow were more often satisfied (55 of 61 respondents) with catheter location than patients having placements at the elbow (three of 17 respondents). Patient willingness to undergo future PICC placement was strongly related to catheter location (p < .0001) and interference with activities of daily living (p < .0001). Catheter type, residence time, time taken for the placement, age, and complications were not associated with patient willingness to undergo future PICC placement. CONCLUSION: PICC placement above the elbow is more acceptable to patients than placement at the elbow. PICC placement above the elbow and patients' perception of less interference by the PICC with activities of daily living are positively related to patient willingness to undergo future PICC placement.     

Ratings of perceived exertion (RPE) during cycling exercises at constant power output

The purpose of the present investigation was to study the overall rating of perceived exertion (RPEov) according to the 6-20 scale proposed by Borg (1970) and muscular RPE (RPEmu) in exercises at constant load. The relationship between RPE and heart rate for three different loads was studied during exhausting exercises in 10 participants. Whether the drift of RPE during a 20 min exercise at constant load could be an index of the endurance time during long-lasting exercises at constant load was also investigated. At 1-week intervals, the participants performed cycling exercises up to exhaustion at 60, 73, and 86% maximal aerobic power (MAP) measured during an incremental test. Heart rate, RPEov, RPEmu and exhaustion time (tlim) were measured. The upward shift of the HRmax-RPE regressions was significant between 86, 73 and 60% MAP (p < 0.001) for RPEov and RPEmu. This result suggests that the equation HR = 10 x RPE proposed by Borg (1973) for incremental exercise is not valid for long-lasting exercise at constant load until exhaustion because the heart rate corresponding to a given RPE depends on load and time. Mean RPE increased linearly with time up to exhaustion. Unexpectedly, the relationships between RPEmu or RPEov and percentage of exhaustion time were similar for exercises at 60 and 73% MAP although the exhaustion times were very different (79.40 +/- 30.64 min versus 36.19 +/- 15.99 min, respectively) (p < 0.001). Consequently, it is likely that RPE was a subjective estimation of the hardness of exercise rather than the intensity of exercise. The RPE pattern at the beginning of long-lasting exercises at constant load (60 and 73% MAP) cannot be considered as a sensitive predictor of the point of self-imposed exhaustion for individuals. Indeed, the errors in the estimation of exhaustion time from extrapolation of RPE at the beginning of exercise were very large. Moreover, at 60% MAP, a steady-state in RPE was observed during 20 min in five subjects whose tlim were not longer than tlim of the other subjects. In addition, the data of the present study indicate that RPEmu could be more useful than RPEov in cycling.     

Automated three-dimensional US frame positioning computed from elevational speckle decorrelation

For ultrasonographic B-scan images collected by means of a handheld transducer moving in the elevational direction, frame spacings are computed with a speckle-decorrelation algorithm, without additional positioning hardware. Fully developed speckle volumes are automatically segmented and spacing computed from the decorrelation curves. Position accuracy is within 10% for phantoms and 15% for breast studies. The algorithm provides image-based registration, which allows accurate three-dimensional volume rendering.     

Mapping of B epitopes in GRA4, a dense granule antigen of Toxoplasma gondii and protection studies using recombinant proteins administered by the oral route

GRA4, a dense granule protein of Toxoplasma gondii elicits both mucosal and systemic immune responses following oral infection of mice with cysts. We studied the antigenicity and immunogenicity of truncated and soluble forms of GRA4 expressed as glutathione S-transferase fusion proteins in Escherichia coli. Protein C (amino-acids 297-345) was particularly well recognized by serum IgG antibodies, milk IgA antibodies and intestinal IgA antibodies from T. gondii infected mice and by serum IgG antibodies from T. gondii infected humans and T. gondii infected sheep. One major B epitope was localized within the last 11 C-terminal residues of GRA4. A second epitope, recognized with lower frequency, was mapped within the region 318-334. In contrast, the N domain of GRA4 (amino acids 25-276) was poorly recognized. Oral immunization of C57BL/6 mice with N, C or NC (amino acids 25-276 fused to 297-345) in association with cholera toxin induced a significant production of serum anti-GRA4 IgG antibodies but a weak and inconsistent intestinal anti-GRA4 IgG antibody response and afforded partial resistance to oral infection with T. gondii. These results provide new molecular and immunological understanding of GRA4 and indicate that it is a potential candidate for oral vaccination against T. gondii.     

Analysis of autoantibody epitopes on steroid 21-hydroxylase using a panel of monoclonal antibodies

A panel of five mouse monoclonal antibodies (MAbs) to human recombinant steroid 21-hydroxylase (21-OH) were produced, characterized, and used to study the interaction of 21-OH autoantibodies (AAbs) with different epitopes on human 21-OH. AAbs in patients with isolated autoimmune Addison's disease, autoimmune polyglandular syndromes types I and II, and 21-OH antibody-positive patients without overt Addison's disease (25 patients in total) were studied. Four MAbs were IgG1 subclass, one was IgG2a, and all had kappa light chains. The affinities of four of the antibodies were in the range 2.0 x 10(8) M(-1) to 7.0 x 10(8) M(-1), and the affinity of the other was 2.3 x 10(7) M(-1) 21-OH MAbs did not cross-react with 17alpha-hydroxylase (17alpha-OH)) or P450 side chain cleavage enzyme. Studies using a series of 21-OH fragments allowed the identification of short stretches of amino acids (AA) that were involved in forming the MAb binding sites. AA 391-405, defined as epitope region (ER) 1, were found to be important for binding of M21-OH1 and M21-OH2, AA 406-411 (ER2) were important for M21-OH3 and M21-OH4 binding, and AA 335-339 (ER3) for M21-OH5 binding. In addition, MAb Fab or F(ab')2 fragments were used to study 21-OH AAb epitopes in competition experiments. These investigations demonstrated that 21-OH AAbs recognize similar epitopes to the MAbs, with ER2 and ER3 being part of two distinct major epitopes, and ER 1 being part of a minor epitope. Mixtures of M21-OH antibody Fab or F(ab')2 fragments caused almost complete inhibition (80%-95%) of AAb binding in 24 out of 25 sera, and in the case of the remaining serum, the effect was marked but incomplete (67% inhibition). There were no major differences between the binding characteristics of AAbs from patients with different forms of autoimmune adrenal disease. All five 21-OH MAbs reacted with human adrenal tissue in an immunofluorescence test, but only M21-OH1 and M21-OH2 reacted with bovine adrenal tissue in these experiments. None of the MAbs reacted with human ovarian tissue in an immunofluorescence test. Overall, these studies indicate that 21-OH AAbs bind to at least three different epitopes in the C-terminal part of 21-OH, and two of these epitopes appear to be human 21-OH specific.     

Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-alpha knockout mice

Testicular androgens are integral components of the hormonal feedback loops that regulate circulating levels of LHbeta and FSH. The sites of feedback include hypothalamic areas regulating GnRH neurons and pituitary gonadotropes. To better define the roles of androgen receptor (AR), estrogen receptor-alpha (ERalpha), and estrogen receptor-beta (ERbeta) in mediating feedback effects of sex steroids on reproductive neuroendocrine function, we have determined the effects of castration and steroid replacement therapy on hypothalamic GnRH content, pituitary LHbeta and FSHbeta messenger RNA (mRNA) levels, and serum gonadotropins in male wild-type (WT) and estrogen receptor-alpha knockout (ERKO) mice. Hypothalami from intact WT and ERKO males contained similar amounts of GnRH, whereas castration significantly reduced GnRH contents in both genotypes. Replacement therapy with estradiol (E2), testosterone (T), or dihydrotestosterone (DHT) restored hypothalamic GnRH content in castrated (CAST) WT mice; only the androgens were effective in CAST ERKOs. Analyses of pituitary function revealed that LHbeta mRNA and serum LHbeta levels in intact ERKOs were 2-fold higher than those in intact WT males. Castration increased levels of LHbeta mRNA (1.5- to 2-fold) and serum LHbeta (4- to 5-fold) in both genotypes. Both E2 and T treatments significantly suppressed LHbeta mRNA and serum LH levels in CAST WT males. However, E2 was completely ineffective, and T was only partially effective in suppressing these two indexes in the CAST ERKO males. DHT treatments stimulated a 50% increase in LHbeta mRNA and serum LH levels in WT males, whereas serum LH was significantly suppressed in DHT-treated ERKO males. Although the pituitaries from intact ERKO males contained similar amounts of FSHbeta mRNA, serum FSH levels were 20% higher than those in the intact WT males. Castration increased FSHbeta mRNA levels only in WT males, but significantly increased serum FSH levels in both genotypes. Both E2 and T treatments significantly suppressed serum FSH in CAST WT males, whereas only E2 suppressed FSHbeta mRNA. DHT treatments of CAST WT mice stimulated a small increase in serum FSH, but failed to alter FSHbeta mRNA levels. None of the steroid treatments exerted any significant effect on FSHbeta mRNA or serum FSH levels in CAST ERKOs. These data suggest that hypothalamic GnRH contents can be maintained solely through AR signaling pathways. However, normal regulation of gonadotrope function requires aromatization of T and activation of ERalpha signaling pathways in the gonadotrope. In addition, serum FSH levels in male ERKOs appear to be regulated largely by nonsteroidal testicular factors such as inhibin. Finally, these data suggest that hypothalamic ERbeta may not be involved in mediating the negative feedback effects of T on serum LH and FSH in male mice.     

Cell proliferation and cancer

The discovery that phosphorylation of selected proteins by cyclin-dependent kinases is the engine which makes the cycle run provides a new image of the control of proliferation and of its deregulation. The high conservation of this machinery in the different eukaryotic organisms emphasizes its early origin and its importance for life. It also makes the extrapolation of findings between different species feasible. The control of proliferation relies basically on accelerating and braking mechanisms which act on the engine driving the cycle. This review particularly stresses the importance of checkpoint or tumor suppressor pathways as transduction systems of negative signals which may induce a cycle braking operation. They prevent any important cycle transition, as the initiation of proliferation, that of replication, mitosis, etc., until the DNA and other cellular conditions make such a progression safe. These checkpoint pathways are able to recognize and transduce signals about the adequacy of initiating or continuing proliferation for a cell at a particular time, under a particular set of external and internal conditions. Crucial components of these pathways are proteins encoded by some of the checkpoint genes that evaluate the final balance of mitogenic and antimitogenic pathways reaching them and, if the balance is negative, they prevent temporarily cycle inititation or its progression by inhibiting the corresponding cyclin-dependent kinases. On the other hand, when the balance becomes positive, they allow the activation of the cyclin-dependent kinases. Uncontrolled cell proliferation associated with cancer always depends on the functional abrogation of at least one of the checkpoint pathways. The checkpoint or tumor suppressor protein p53 is one of the proteins in them, and mutations in the gene encoding it are present in more than half of all human tumours. The review touches new pharmacological strategies which have been opened by the discovery of portions of some of the signal transduction cascades involved in the transient brake of cell proliferation. Restoration of checkpoint pathways either prevents further proliferation of cells with damaged genome until repair is over or, alternatively, the dismantling of these checkpoints induce those cells to commit suicide (apoptosis). The fact that both restoration and dismantling of checkpoint pathways sensitive to DNA damage have not disturbing effects on any other proliferating cell with undamaged DNA makes these selective strategies promissing.     

The mannose 6-phosphate/insulin-like growth factor II receptor is a nanomolar affinity receptor for glycosylated human leukemia inhibitory factor

Comparison of the binding properties of non-glycosylated, glycosylated human leukemia inhibitory factor (LIF) and monoclonal antibodies (mAbs) directed at gp190/LIF-receptor beta subunit showed that most of the low affinity (nanomolar) receptors expressed by a variety of cell lines are not due to gp190. These receptors bind glycosylated LIF produced in Chinese hamster ovary cells (CHO LIF) (Kd = 6.9 nM) but not Escherichia coli-derived LIF or CHO LIF treated with endoglycosidase F. CHO LIF binding to these receptors is neither affected by anti-gp190 mAbs nor by anti-gp130 mAbs and is specifically inhibited by low concentrations of mannose 6-phosphate (Man-6-P) (IC50 = 40 microM), suggesting that they could be related to Man-6-P receptors. The identity of this LIF binding component with the Man-6-P/insulin-like growth factor-II receptor (Man-6-P/IGFII-R) was supported by several findings. (i) It has a molecular mass very similar to that of the Man-6-P/IGFII-R (270 kDa); (ii) the complex of LIF cross-linked to this receptor is immunoprecipitated by a polyclonal anti-Man-6-P/IGFII-R antibody; (iii) this antibody inhibits LIF and IGFII binding to the receptor with comparable efficiencies; (iv) soluble Man-6-P/IGFII-R purified from serum binds glycosylated LIF (Kd = 4.3 nM) but not E. coli LIF. The potential role of Man-6-P/IGFII-R in LIF processing and biological activity is discussed.