[Effects of a Phone-Based Follow-Up Care After Inpatient Rehabilitation for Breast Cancer Patients - A Randomized Controlled Trial]. / Effekte der telefonischen Nachsorge in der onkologischen Rehabilitation nach Brustkrebs ­ Ergebnisse einer randomisierten Studie.

Background Benefit and long-term effects of rehabilitation and psychoeducational interventions after cancer therapy are still controversial discussed. Aim of the study was to evaluate feasibility and effects of a telephone-based follow-up intervention after oncological rehabilitation. Methods 172 breast cancer patients (age 27-54 years) were randomized after inpatient rehabilitation to a telephone-based intervention (phone calls every 4 weeks over 6 months) or control group. Patients were evaluated by standardized questionnaire (e. g. IRES-24, HADS, LZI, emotional thermometer, questionnaire "return to work") at T1 (start of rehabilitation), T2 (end of rehabilitation) and T3 (6 months after rehabilitation). Results 2-way-ANOVAs were performed to evaluate long-term effects. Main effects of IRES-24 and HADS were significant depending on time (IRES-24 F(2,116)=40.49, p<0.01 and HADS F(2,117)=31.50, p<0.01; (F(2,11 6)=31.19, p<0.01) but no significant differences between the intervention and control group were seen. Conclusions Telephone-based follow-up care is feasible with high patient acceptance. However an improvement of therapeutic effects in the intervention group were not be detected by IRES-24 and HADS questionnaire. Potential explanations may be the low "dosage" (duration/quantity of phone calls) of the intervention or the fact that in the last years multimodal treatment interventions were established in German rehabilitation centers leading to a so-called "ceiling effect" without significant effects of additional follow-up interventions.

Synthesis of diamidopyrrolyl molybdenum complexes relevant to reduction of dinitrogen to ammonia.

A potentially useful trianionic ligand for the reduction of dinitrogen catalytically by molybdenum complexes is one in which one of the arms in a [(RNCH(2)CH(2))(3)N](3-) ligand is replaced by a 2-mesitylpyrrolyl-alpha-methyl arm, that is, [(RNCH(2)CH(2))(2)NCH(2)(2-MesitylPyrrolyl)](3-) (R = C(6)F(5), 3,5-Me(2)C(6)H(3), or 3,5-t-Bu(2)C(6)H(3)). Compounds have been prepared that contain the ligand in which R = C(6)F(5) ([C(6)F(5)N)(2)Pyr](3-)); they include [(C(6)F(5)N)(2)Pyr]Mo(NMe(2)), [(C(6)F(5)N)(2)Pyr]MoCl, [(C(6)F(5)N)(2)Pyr]MoOTf, and [(C(6)F(5)N)(2)Pyr]MoN. Compounds that contain the ligand in which R = 3,5-t-Bu(2)C(6)H(3) ([Ar(t-Bu)N)(2)Pyr](3-)) include {[(Ar(t-Bu)N)(2)Pyr]Mo(N(2))}Na(15-crown-5), {[(Ar(t-Bu)N)(2)Pyr]Mo(N(2))}[NBu(4)], [(Ar(t-Bu)N)(2)Pyr]Mo(N(2)) (nu(NN) = 2012 cm(-1) in C(6)D(6)), {[(Ar(t-Bu)N)(2)Pyr]Mo(NH(3))}BPh(4), and [(Ar(t-Bu)N)(2)Pyr]Mo(CO). X-ray studies are reported for [(C(6)F(5)N)(2)Pyr]Mo(NMe(2)), [(C(6)F(5)N)(2)Pyr]MoCl, and [(Ar(t-Bu)N)(2)Pyr]MoN. The [(Ar(t-Bu)N)(2)Pyr]Mo(N(2))(0/-) reversible couple is found at -1.96 V (in PhF versus Cp(2)Fe(+/0)), but the [(Ar(t-Bu)N)(2)Pyr]Mo(N(2))(+/0) couple is irreversible. Reduction of {[(Ar(t-Bu)N)(2)Pyr]Mo(NH(3))}BPh(4) under Ar at approximately -1.68 V at a scan rate of 900 mV/s is not reversible. Ammonia in [(Ar(t-Bu)N)(2)Pyr]Mo(NH(3)) can be substituted for dinitrogen in about 2 h if 10 equiv of BPh(3) are present to trap the ammonia that is released. [(Ar(t-Bu)N)(2)Pyr]Mo-N=NH is a key intermediate in the proposed catalytic reduction of dinitrogen that could not be prepared. Dinitrogen exchange studies in [(Ar(t-Bu)N)(2)Pyr]Mo(N(2)) suggest that steric hindrance by the ligand may be insufficient to protect decomposition of [(Ar(t-Bu)N)(2)Pyr]Mo-N=NH through a variety of pathways. Three attempts to reduce dinitrogen catalytically with [(Ar(t-Bu)N)(2)Pyr]Mo(N) as a "catalyst" yielded an average of 1.02 +/- 0.12 equiv of NH(3).

'Then I just showed her my arms . . .' Bodily sensations in moments of alienation related to self-injurious behaviour. A hermeneutic phenomenological study.

People committing self-injurious behaviour are often perceived as difficult patients; confronted with unhelpful reactions from nurses, the patients find themselves left alone in their distress. A connection between self-injurious behaviour and feelings of alienation is suggested in the literature. Alienation is described as a state in which the self is perceived as strange, machinelike and not in contact with its emotional and physical needs. On one hand, complex neuro-biological processes are seen as responsible for this; on the other hand, alienation is seen as a means of self-protection when one is exposed to a threatening or traumatic situation. Nursing interventions focus on the nurse-patient relationship and on the handling of self-injuries, but they tend to ignore the client's previous experience. Proceeding from the assumption that patients committing self-injurious behaviour are the experts on their own harm, the purpose of the present study is to get insight into their 'lived experience' and to contribute to the understanding of this vulnerable group. Adopting a hermeneutic phenomenological research perspective, methods of participant observation and qualitative interviewing were chosen to generate data. The database consists of 99 observational sequences, five interviews and a set of email texts written by a self-injuring woman. A thematic analysis as described by Van Manen was done. The main findings are that alienation is experienced in several stages, that nurses can detect early signs of an impending loss of control, and that self-injurious behaviour is an effective strategy to end a painful experience of alienation. Self-injurious behaviour is appropriately understood as a form of 'self-care'.

Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo.

The tumor-suppressor gene PTEN encodes a multifunctional phosphatase that is mutated in a variety of human cancers. PTEN inhibits the phosphatidylinositol 3-kinase pathway and downstream functions, including activation of Akt/protein kinase B (PKB), cell survival, and cell proliferation in tumor cells carrying mutant- or deletion-type PTEN. In such tumor cells, enforced expression of PTEN decreases cell proliferation through cell-cycle arrest at G1 phase accompanied, in some cases, by induction of apoptosis. More recently, the tumor-suppressive effect of PTEN has been reported in ovarian and thyroid tumors that are wild type for PTEN. In the present study, we examined the tumor-suppressive effect of PTEN in human colorectal cancer cells that are wild type for PTEN. Adenoviral-mediated transfer of PTEN (Ad-PTEN) suppressed cell growth and induced apoptosis significantly in colorectal cancer cells (DLD-1, HT29, and SW480) carrying wtPTEN than in normal colon fibroblast cells (CCD-18Co) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) and cell-cycle arrest at the G2/M phase, but not the G1 phase. Furthermore, treatment of human colorectal tumor xenografts (HT-29, and SW480) with Ad-PTEN resulted in significant (P=0.01) suppression of tumor growth. These results indicate that Ad-PTEN exerts its tumor-suppressive effect on colorectal cancer cells through inhibition of cell-cycle progression and induction of cell death. Thus Ad-PTEN may be a potential therapeutic for treatment of colorectal cancers.

Catalytic asymmetric ring-opening metathesis/cross metathesis (AROM/CM) reactions. Mechanism and application to enantioselective synthesis of functionalized cyclopentanes.

Studies regarding the first examples of catalytic asymmetric ring-opening metathesis (AROM) reactions are detailed. This enantioselective cleavage of norbornyl alkenes is followed by an intermolecular cross metathesis with a terminal olefin partner; judicious selection of olefin is required so that oligomerization and dimerization side products are avoided. Results outlined herein suggest that the presence of suitably positioned heteroatom substituents may be critical to reaction efficiency. Mo-catalyzed tandem AROM/CM affords functionalized cyclopentyl dienes in >98% ee and >98% trans olefin selectivity; both secondary and tertiary ether products can be obtained. The examples provided include the catalytic synthesis of an optically pure cyclopentyl epoxide and dimethyl acetal. Mechanistic studies suggest that it is the more substituted benzylidene or silylated alkylidenes that are involved in the catalytic process (vs the corresponding Mo-methylidenes). Although electron rich benzylidenes react more efficiently, the derived electron poor Mo complexes promote AROM/CM transformations as well; alkylidenes that bear a boron substituent are unreactive.

Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy.

BACKGROUND: The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the anti-tumor efficacy of Ad-mda7 in a broad spectrum of cancer lines. MATERIALS AND METHODS: Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis). RESULTS: Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers. CONCLUSIONS: The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.

Synthesis of triamidoamine ligands of the type (ArylNHCH(2)CH(2))(3)N and molybdenum and tungsten complexes that contain an [ArylNCH(2)CH(2))(3)N]3- ligand.

Aryl bromides react with (H(2)NCH(2)CH(2))(3)N in a reaction catalyzed by Pd(2)(dba)(3) in the presence of BINAP and NaO-t-Bu to give the arylated derivatives (ArylNHCH(2)CH(2))(3)N [Aryl = C(6)H(5) (1a), 4-FC(6)H(4) (1b), 4-t-BuC(6)H(4) (1c), 3,5-Me(2)C(6)H(3) (1d), 3,5-Ph(2)C(6)H(3) (1e), 3,5-(4-t-BuC(6)H(4))(2)C(6)H(3) (1f), 2-MeC(6)H(4) (1g), 2,4,6-Me(3)C(6)H(2) (1h)]. Reactions between (ArNHCH(2)CH(2))(3)N (Ar = C(6)H(5), 4-FC(6)H(4), 3,5-Me(2)C(6)H(3), and 3,5-Ph(2)C(6)H(3)) and Mo(NMe(2))(4) in toluene at 70 degrees C lead to [(ArNHCH(2)CH(2))(3)N]Mo(NMe(2)) complexes in yields ranging from 64 to 96%. Dimethylamido species (Ar = 4-FC(6)H(4), 3,5-Me(2)C(6)H(3)) could be converted into paramagnetic [(ArNHCH(2)CH(2))(3)N]MoCl species by treating them with 2,6-lutidinium chloride in tetrahydrofuran (THF). The "direct reaction" between 1a-f and MoCl(4)(THF)(2) in THF followed by 3 equiv of MeMgCl yielded [(ArNHCH(2)CH(2))(3)N]MoCl species (3a-f) in high yield. If 4 equiv of LiMe instead of MeMgCl are employed in the direct reaction, then [(ArNHCH(2)CH(2))(3)N]MoMe species are formed. Tungsten species, [(ArNHCH(2)CH(2))(3)N]WCl, could be prepared by analogous "direct" methods. Cyclic voltammetric studies reveal that MoCl complexes become more difficult to reduce as the electron donating ability of the [ArylNCH(2)CH(2))(3)N]3- ligand increases, and the reductions become less reversible, consistent with ready loss of chloride from ([(ArNHCH(2)CH(2))(3)N]MoCl)(-). Tungsten complexes are more difficult to reduce, and reductions are irreversible on the CV time scale.

Synthesis, structure, and electrochemical studies of molybdenum and tungsten dinitrogen, diazenido, and hydrazido complexes that contain aryl-substituted triamidoamine ligands.

One-electron reduction of [ArN(3)N]MoCl complexes (Ar = C(6)H(5), 4-FC(6)H(4), 4-t-BuC(6)H(4), 3,5-Me(2)C(6)H(3)) yields complexes of the type [ArN(3)N]Mo-N=N-Mo[ArN(3)N], while two-electron reduction yields ([ArN(3)N]Mo-N=N)(-) derivatives (Ar = C(6)H(5), 4-FC(6)H(4), 4-t-BuC(6)H(4), 3,5-Me(2)C(6)H(3), 3,5-Ph(2)C(6)H(3), and 3,5-(4-t-BuC(6)H(4))(2)C(6)H(3)). Compounds that were crystallographically characterized include ([t-BuC(6)H(4)N(3)N]Mo)(2)(N(2)), Na(THF)(6)([PhN(3)N]Mo-N=N)(2)Na(THF)(3), [t-BuC(6)H(4)N(3)N]Mo-N=N-Na(15-crown-5), and ([Ph(2)C(6)H(3)N(3)N]MoNN)(2)Mg(DME)(2). Compounds of the type [ArN(3)N]Mo-N=N-Mo[ArN(3)N] do not appear to form when Ar = 3,5-Ph(2)C(6)H(3) or 3,5-(4-t-BuC(6)H(4))(2)C(6)H(3), presumably for steric reasons. Treatment of diazenido complexes (e.g., [ArN(3)N]Mo-N=N-Na(THF)(x)) with electrophiles such as Me(3)SiCl or MeOTf yielded [ArN(3)N]Mo-N=NR complexes (R = SiMe(3) or Me). These species react further to yield ([ArN(3)N]Mo-N=NMe(2))(+) species in the presence of methylating agents. Addition of anionic methyl reagents to ([ArN(3)N]Mo-N=NMe(2))(+) species yielded [ArN(3)N]Mo(N=NMe(2))(Me) complexes. Reduction of [4-t-BuC(6)H(4)N(3)N]WCl under dinitrogen leads to a rare ([t-BuC(6)H(4)N(3)N]W)(2)(N(2)) species that can be oxidized by two electrons to give a stable dication (as its BPh(4)(-) salt). Reduction of hydrazido species leads to formation of Mo=N in low yields, and only dimethylamine could be identified among the many products. Electrochemical studies revealed expected trends in oxidation and reduction potentials, but also provided evidence for stable neutral dinitrogen complexes of the type [ArN(3)N]Mo(N(2)) when Ar is a relatively bulky terphenyl substituent.

Catalytic asymmetric olefin metathesis.

This paper provides a survey of the first examples of efficient catalytic enantioselective olefin metathesis reactions. Mo-catalyzed asymmetric ring-closing (ARCM) and ring-opening (AROM) reactions allow access to myriad optically enriched compounds that are otherwise difficult to access.

The market made them do it. Participants in the Medicare Choices project say they're nudging out the insurance middleman--and insuring their own survival. Panel discussion.

Medicare is experimenting again. This time HCFA wants to figure out ways to expand managed care options for the elderly. Under the Medicare Choices Demonstration Project, hospitals and health systems are developing and testing alternatives to standard Medicare HMOs. Dick Davidson, president of the American Hospital Association, sees these pilot programs as the precursors to provider-sponsored organizations building up a base of knowledge about what it means to manage risk. The AHA recently convened a meeting of organizations involved in the demonstration project and asked Hospitals & Health Networks executive editor Alden Solovy to lead a panel discussion on the lessons being learned.

[Physical complaints, stress and quality of life of oncologic patients. Effects and patient assessment in inpatient rehabilitation]. / Beschwerden, Belastung sowie Lebenszufriedenheit onkologischer Patienten. Effekte und Patienteneinschätzungen stationärer Rehabilitation.

AIM: To what extent do cancer patients use an inpatient aftercare programme and how is its effect been estimated by them? How is the progress of "general physical complaints", "psychosocial stress" and "satisfaction with life" in some cases over a period of up to eight months? PATIENTS AND METHODS: To 201 patients with breast or intestinal cancer respectively, who were going to be or had already been admitted to an inpatient aftercare, standardised and unstandardized questionnaire were presented to be filled out at 4 or 5 different dates before and during the programme as well as 3 and 6 months later. RESULTS: Many patients tried to take part in the aftercare programme actively. Even 6 months later 95.6% estimated it as being "successful" and 70% said that there had been a lasting positive effect after the treatment. The "general physical complaints" and "psychosocial stress" grew significantly less during the inpatient aftercare programme and "satisfaction with life" improved. After the treatment these effects were declining again. CONCLUSIONS: The results indicate that many patients, who participate in an inpatient aftercare programme, profit by it directly. As the positive effects partially get lost during the following months, the patients should be prepared more intensely for the time after dismission with its higher level of strain and should get an especially attentive ambulant care at home.

Processivity of the gene 41 DNA helicase at the bacteriophage T4 DNA replication fork.

The gene 41 protein is the DNA helicase associated with the bacteriophage T4 DNA replication fork. This protein is a major component of the primosome, being essential for coordinated leading and lagging strand DNA synthesis. Models suggest that such DNA helicases are loaded only onto DNA at origins of replication, and that they remain with the ensuing replication fork until replication is terminated. To test this idea, we have measured the extent of processivity of the 41 protein in the context of an in vitro DNA replication system composed of eight purified proteins (the gene 43, 44/62, 45, 32, 41, 59, and 61 proteins). After starting DNA replication in the presence of these proteins, we diluted the 41 helicase enough to prevent any association of new helicase molecules and analyzed the replication products. We measured an association half-life of 11 min, revealing that the 41 protein is processive enough to finish replicating the entire 169-kilobase T4 genome at the observed replication rate of approximately 400 nucleotides/s. This processivity of the 41 protein does not require the 59 protein, the protein that catalyzes 41 protein assembly onto 32 protein-covered single-stranded DNA. The stability we measure for the 41 protein as part of the replication fork is greater than estimated for it alone on single-stranded DNA. We suggest that the 41 protein interacts with the polymerase holoenzyme at the fork, both stabilizing the other protein components and being stabilized thereby.

[Moral action in nursing]. / Zum moralischen Handeln in der Pflege.

What ought I to do? is the classic question of moral dilemmas. It is concerned with the field of action in which human beings meet and where moral decisions have to be made in the course of everyday nursing care. Only when nurses discuss their own actual experiences, can they learn to arrive at a competent appropriate rationale and justification for action. With growing self-confidence, the willingness to act increases. Ethics is one of the relevant fields of knowledge. The attempt to create a link between moral action in nursing and ethics, comes to grief when the "myth of life and death" and the "Hypocratic myth" move centre stage. These myths really belong to the medical, not nursing perspective. Several other medical tendencies for generalisation and some in nursing, create barriers to the development of appropriate models for nursing action. It would be bad advice for nursing to present itself as a reservoir of humanitarianism. An appeal to professional conscience is no guarantee that morally defensible decisions will be arrived at. Only continuous examination of their own actions against a framework of sound moral argument can make it more likely that action appropriate to the desired goal can take place.

Saturation of cubic optical nonlinearity in long-chain polyene oligomers.

The scaling of the cubic nonlinearity gamma with chain length in polyenic molecules has received considerable theoretical attention. Earlier experimental investigations have been restricted to oligomers with fewer than 20 double bonds because of problems associated with the synthesis and solubility of conjugated molecules. These synthetic difficulties have been overcome in the present study by the use of modern living polymerization techniques. Solution measurements of gamma as a function of chain length in long-chain (up to 240 double bonds) model polyene oligomers are reported. A saturation of the increase of gamma with chain length is observed, and the onset of this saturation occurs for chain lengths considerably longer than predicted from theory.

Evidence for an imino intermediate in the T4 endonuclease V reaction.

Reductive methylation and site-directed mutagenesis experiments have implicated the N-terminal alpha-amino group of T4 endonuclease V in the glycosylase and abasic lyase activities of the enzyme. NMR studies have confirmed the involvement of the N-terminal alpha-amino group in the inhibition of enzyme activity by reductive methylation. A mechanism accounting for these results predicts that a (imino) covalent enzyme-substrate intermediate is formed between the protein N-terminal alpha-amino group and C1' of the 5'-deoxyribose of the pyrimidine dimer substrate subsequent to (or concomitantly with) the glycosylase step. Experiments to verify the existence of this intermediate indicated that enzyme inhibition by cyanide was substrate-dependent, a result classically interpreted to imply an imino reaction intermediate. In addition, sodium borohydride reduction of the intermediate formed a stable dead-end enzyme-substrate product. This product was formed whether ultraviolet light-irradiated high molecular weight DNA or duplex oligonucleotides containing a defined thymine-thymine cyclobutane dimer were used as substrate. The duplex oligonucleotide substrates demonstrated a well-defined gel shift. This will facilitate high-resolution footprinting of the enzyme on the DNA substrate.

Site-directed mutagenesis of the NH2 terminus of T4 endonuclease V. The position of the alpha NH2 moiety affects catalytic activity.

Reductive methylation of the alpha NH2 moiety of the DNA repair enzyme T4 endonuclease V has been shown previously to eradicate both the N-glycosylase and apyrimidinic/apurinic lyase activities of the enzyme (Schrock, R. D., III, and Lloyd, R. S. (1991) J. Biol. Chem. 266, 17631-17639). The present study uses the technique of site-directed mutagenesis to investigate the important parameters involved in the cleavage mechanism. The prediction was that the addition of an amino acid in the immediate NH2-terminal region of the protein would alter the proximity of the alpha NH2 moiety of Thr2 to its target, thereby severely compromising the enzyme's catalytic activity. However, substitutions in this region generally should be tolerated. To test this hypothesis, three substitutions of the NH2-terminal amino acid were produced: Ser2 (T2S), Val2 (T2V), and Pro2 (T2P). An addition mutant was also produced by adding a glycine between the first and second amino acids of the protein (Thr2-Gly-Arg3) (+Gly). The T2P and +Gly mutants had negligible pyrimidine dimer-specific N-glycosylase activity as well as negligible pyrimidine dimer-specific nicking activity in vitro. Conversely, the T2S enzyme exhibited wild type levels of activity and the T2V exhibited intermediate levels of activity in vitro. Results from ultraviolet (UV) survival studies of the mutant enzymes indicated that the in vivo activities of these enzymes were directly correlated to the enzymes' ability to cleave at pyrimidine dimers in vitro. These results indicate that a critical parameter for the functionality of endonuclease V is the relative distance between the primary alpha NH2 group in the active site of the enzyme and those elements responsible for DNA binding and pyrimidine dimer recognition.