How a multidisciplinary vascular access care program enables implementation of the DOQI guidelines. Part I.

This comprehensive, proactive, multidisciplinary team approach to access management has enabled the achievement of center-specific best-demonstrated clinical practiCes for vascular access care. It has also resulted in significant cost savings to the health care delivery process. It has not been an easy task; if it were, access care outcomes would be better nationally than they are today. The VACP approach to vascular access care improvement employs four key implementation principles that ensure the success of Gambro's program and form the infrastructure supporting any successful team approach to care. These core processes, known as the four "C's, include: 1. Commitment, 2. Continuous Quality Improvement, 3. Core Competency, and 4. Communication.

Lessons learned. Implementing a vascular access quality improvement program. Part II.

Implementing a CQI program for vascular access can seem an overwhelming task. It encompasses many areas that are not in the nephrologists' or dialysis facilities' control. However, involving the right multidisciplinary team members in the process and aligning the goals and objectives creates an environment conducive to success. Ongoing communication is critical. Everyone needs to be a part of the change process.

Activated T cells enter rat lymph nodes and Peyer's patches via high endothelial venules: survival by tissue-specific proliferation and preferential exit of CD8+ T cell progeny.

Activated T cells reach the lymph nodes via afferent lymphatics but it is unknown to what extent they also enter them directly via high endothelial venules (HEV). Little is known about the mechanism mediating the proliferation of activated T cells within lymphoid tissues in vivo or the subsequent fate of the progeny. Therefore, we stimulated rat T cells via TCR and CD28 in vitro and after injection identified them in the blood and the HEV of lymphoid organs at several time points. In addition, the proliferation of these cells was studied after entering different lymphoid organs. Our results show that, firstly, activated T cells continuously enter lymph nodes and Peyer's patches directly via HEV. Second, they proliferate within lymphoid organs, the rate significantly depending on the microenvironment. Third, mainly CD8+ progeny are able to leave the tissues and re-enter the blood. Thus, the distribution of activated T cells circulating through the body can be regulated during entry, but also within the tissue by influencing their proliferation and subsequent release.

Treatment of erectile dysfunction with sildenafil.

OBJECTIVES: To determine the efficacy of sildenafil for the treatment of erectile dysfunction (ED) in a clinical practice setting; to evaluate the correlation between patient and partner perceptions of treatment outcomes; and to assess the relation between the severity of ED and response to treatment. METHODS: Among the first 100 men to receive sildenafil in a urology practice setting, 74 (mean + SD age 64+/-11 years) completed a validated sexual function questionnaire (International Index of Erectile Function [IIEF]) before and after a 4 to 6-week treatment period. A modified version of the same questionnaire was independently completed by partners. ED was categorized into a severity class of I to IV. RESULTS: Sildenafil treatment improved erections by 71% to 95%, according to responses in key IIEF questions 3 and 4. Overall, 57 (77%) of 74 patients desired to continue treatment after the test period. Patient score on the IIEF was correlated with partner score on the modified questionnaire before and after treatment (r = 0.67 to 0.81, P <0.01). IIEF scores were reflected in a simple severity classification system. Men with the best preservation of erections (severity class I) exhibited the best responses to sildenafil, whereas men with no erections (severity class IV) were much less likely to respond to the drug and desire continuation of treatment (P <0.01). Patients with a radical prostatectomy were relatively refractory to sildenafil, except for 2 of 5 who had undergone a nerve-sparing operation. CONCLUSIONS: In clinical practice, sildenafil is an effective treatment of ED, according to partner-validated questionnaire responses; and the results of treatment are predictable with an ED severity classification system.

Butyltin compounds in sediment and fish from the Polish Coast of the Baltic Sea.

Concentrations of mono- (MBT), di- (DBT), and tri-(TBT) butyltin compounds were measured in eggs, liver, and muscle of nine species of fish from four regions of the Baltic Sea - the Firth of Vistula, the Gulf of Gdansk, Puck Bay, and the mouth of the Vistula River. The overall concentration ranges among all the fish sampled from the four sites were: < 7 to 79 ng/g for MBT, 6 to 1100 ng/g for DBT, 7 to 3600 ng/g for TBT, and 16 to 4800 ng/g for total BTs, on a wet wt basis. The highest concentration of total BTs was found in herring liver from the Firth of Vistula (4800 ng/g, wet wt) and in roach muscle from Puck Bay (3300 ng/g, wet wt), while the least concentration was found in burbot eggs and liver from the Vistula River (39 and 32 ng/g, wet wt, respectively). TBT was the major form of BTs present in most samples analyzed. Sediment samples collected from shipyards in the Gulf of Gdansk contained butyltin concentrations ranging from 1.2 to 46 microg/g (dry wt) for MBT, 2.0 to 42 microg/g for DBT, and 2.6 to 40 microg/g for TBT. As with the fish, the majority of the BTs in sediment were present as TBT, which suggested recent exposure of the aquatic environment of the region to TBT.

Optimization of post-column photolysis and electrochemical detection for the liquid chromatographic determination of 3-nitro-L-tyrosine.

A new post-column photolysis technology has been developed based on the use of a low pressure, low temperature UV lamp and TiO2 coated knitted reaction coil. As a test case the developed technique was used for the determination of 3-nitro-L-tyrosine by liquid chromatography with electrochemical detection. Different photolysis lamps and reactor tubing lengths were evaluated in terms of their effect on the separation efficiency and/or photolysis efficiency. A detection limit of 0.5 nM (10 fmol) for 3-nitro-L-tyrosine was achieved under optimized conditions, with a linear correlation coefficient of R2 = 0.9898 over a concentration range of 2-100 microM. Pre-injection photolysis of 3-nitro-L-tyrosine indicated that dihydroxyphenylalanine is the main photolysis product. In general, use of the photoreactor prior to liquid chromatography is an excellent method for exploring photodegradation products of an analyte in conjunction with the full range of available liquid chromatography detectors.

Refolding of serine proteinases.

Bovine trypsinogen and chymotrypsinogen were successfully refolded as the mixed disulfide of glutathione using cysteine as the disulfide interchange catalyst. The native structures were regenerated with yields of 40%-50% at pH 8.6 and 4 degrees C, and the half-time for the refolding was approximately 60-75 min. We then refolded threonine-neochymotrypsinogen, which is a two-chain structure held together by disulfide bonds and produced on cleavage of Tyr 146-Thr 147 in native chymotrypsinogen [Duda CT, Light A, J Biol Chem 257 9866-9871, 1982]. Neochymotrypsinogen was denatured and fully reduced, and the thiols were converted to the mixed disulfide of glutathione. The two polypeptide fragments, representing the amino- and carboxyl-terminal domains, were separated on Sephadex G-75. Mixtures of the polypeptide fragments varying in the ratio of their concentration from 1:5 to 5:1 were refolded with yields of 21-28%. The lack of dependence on the concentration of either fragment and the relatively high yields suggest independent folding of the amino- and carboxyl-terminal domains. When the globular structures of the domains formed, they then interacted with one another and produced the native intermolecular disulfide bridge and the proper geometry of the active site.

Refolding of bovine threonine-neochymotrypsinogen.

The mixed disulfide derivative of fully reduced neochymotrypsinogen was refolded at pH 9.2 and 4 degrees C with 4 mM cysteine as the disulfide interchange catalyst. The yield of regenerated neochymotrypsinogen was 25%; the corresponding yield of refolded chymotrypsinogen was 50%. The refolded neochymotrypsinogen exhibited the characteristics of the native molecule as determined from polyacrylamide gel electrophoresis and the enzymatic properties of the activated zymogen. The rate of refolding of neochymotrypsinogen was approximately the same as that found for chymotrypsinogen. These studies show that two separate fully reduced polypeptide chains were capable of refolding, associating with one another, and regenerating a native structure with full biological activity.

Effects of gamma irradiation on chromatin activity of sugar beet tissue.

Chromatin-associated RNA polymerase activity increases during washing of sugar beet tissue to a maximum by 20 hours. This increase was inhibited by dosages of gamma irradiation between 50 and 400 krad. Template availability, as measured by saturating levels of added Escherichia coli RNA polymerase, also increased with washing and was inhibited, although to a lesser extent, by the above irradiation dosages. Neither endogenous polymerase activity nor template availability was affected by high dosages (300 krad) in unwashed tissue. Exposure of tissue to irradiation (300 krad) at different times during a 20-hour washing period severely inhibited the development of RNA polymerase activity during the early stages of washing. The inhibition of template availability, however, was independent of time of irradiation. The data presented are discussed in relation to the mechanisms involved in the inhibitory effects of gamma irradiation on RNA production and subsequent protein synthesis.

Chromatin- and nuclei-directed ribonucleic Acid synthesis in sugar beet root.

The synthesis of RNA by chromatin-bound RNA polymerase prepared from sugar beet (Beta vulgaris) root tissue is completely dependent on the presence of a divalent metal (Mg(2+) or Mn(2+)) and the presence of four ribonucleoside triphosphates. Accumulation of labeled acid-insoluble product is inhibited by the addition of RNase and actinomycin D to the reaction. When beet root slices are washed for 25 hours, chromatin-associated RNA polymerase activity increases 7-fold over that of unwashed tissue. This enzyme activity declines with further washing. DNA template availability, as measured by saturating levels of added Escherichia coli RNA polymerase, was also found to follow a pattern similar to that for RNA polymerase. Nearest neighbor frequencies of the RNA synthesized by chromatin isolated from unwashed and washed tissue are different.Washing tissue in solutions of gibberellic acid and auxin enhances template availability of the isolated chromatin. Experiments with isolated nuclei indicate an effect of these hormones on RNA synthesis.

Increased ribonucleic Acid polymerase activity associated with chromatin from internodes of dwarf pea plants treated with gibberellic Acid.

Gibberellic acid increases the level of RNA polymerase associated with chromatin isolated from expanding internodes of light-grown, dwarf pea plants (Pisum sativum L.), without a detectable increase in the amount of DNA template available.