The Combination of Exercise and Respiratory Training Improves Respiratory Muscle Function in Pulmonary Hypertension

Purpose

Increased dyspnea and reduced exercise capacity in pulmonary arterial hypertension (PAH) can be partly attributed to impaired respiratory muscle function. This prospective study was designed to assess the impact of exercise and respiratory training on respiratory muscle strength and 6-min walking distance (6MWD) in PAH patients.

Methods

Patients with invasively confirmed PAH underwent 3 weeks of in-hospital exercise and respiratory training, which was continued at home for another 12 weeks. Medication remained constant during the study period. Blinded observers assessed efficacy parameters at baseline (I) and after 3 (II) and 15 weeks (III). Respiratory muscle function was assessed by twitch mouth pressure (TwPmo) during nonvolitional supramaximal magnetic phrenic nerve stimulation.

Results

Seven PAH patients (4 women; mean pulmonary artery pressure 45 ± 11 mmHg, median WHO functional class 3.1 ± 0.4, idiopathic/associated PAH n = 5/2) were included. The training program was feasible and well tolerated by all patients with excellent compliance. TwPmo was I: 0.86 ± 0.37 kPa, II: 1.04 ± 0.29 kPa, and III: 1.27 ± 0.44 kPa, respectively. 6MWD was I: 417 ± 51 m, II: 509 ± 39 m, and III: 498 ± 39 m, respectively. Both TwPmo (+0.41 ± 0.34 kPa, +56 ± 39 %) and 6MWD (+81 ± 30 m, +20 ± 9 %) increased significantly in the period between baseline and the final assessment (pairwise comparison: p = 0.012/<0.001; RM-ANOVA considering I, II, III: p = 0.037/<0.001).

Conclusions

Exercise and respiratory training as an adjunct to medical therapy may be effective in patients with PAH to improve respiratory muscle strength and exercise capacity. Future, randomized, controlled trials should be carried out to further investigate these findings.     

High rates of long-lasting remissions after 5-day bendamustine chemotherapy cycles in pre-treated low-grade non-Hodgkin's-lymphomas

PURPOSE: Since continuous relapse rates are characteristic for advanced low-grade non-Hodgkin's lymphomas (NHL), their treatment remains a problem. Previous phase II studies showed that bendamustine induced high remission rates in pre-treated low-grade NHL. To further examine its efficacy and side effects, bendamustine has been studied in a large number of patients with pre-treated low-grade NHL. Follow-up time was 3-8 years. METHODS: From 1993 to 1998, 102 patients with pre-treated low-grade NHL [histologic subtypes: CLL n=15, immunocytic n=46, multiple myeloma (MM) n=25, others n=16] received a median of four (range 1-11) 5-day cycles of daily 60 mg/m(2) bendamustine as salvage chemotherapy. Bendamustine was given in short i.v. infusions mainly at intervals of 4-6 weeks. RESULTS: Partial and complete remissions were observed in 76.5% and disease stabilization in 19.6% of the patients. Only 3.9% showed progressive disease. Median duration of response was 39 months for the NHL patients and 17 months for the MM patients. Median survival time was 32 months for the CLL patients, 31.5 months for the NHL patients and 17.5 months for the MM patients. Non-haematological side effects consisted mainly in reversible reduction of performance status, loss of appetite, and nausea/vomiting and diarrhoea, which were of WHO grade III/IV in less than 5% of patients. Haematological toxicities of WHO grade III/IV have been observed in 6.9%, 11.8%, and 24.5% of patients for hemoglobin, thrombocytes, and leukocytes, respectively. Alopecia did not occur. Febrile episodes or bacterial as well as viral, particularly opportunistic, infections were not observed, although bendamustine induced profound and long-lasting lymphocytopenias, including CD4+-, CD8+-, CD19+-, B-lymphocytes, and NK-cells. CONCLUSIONS: Bendamustine proved to be very effective in pre-treated low-grade NHL patients by inducing high rates of long-lasting remissions. Bendamustine combines the pharmacological properties of an alkylating agent with those of a purine analogue and showed no cross-resistance to chlorambucil, melphalan, cyclophosphamide, mitoxantrone, and other anthracyclines. The myelosuppressive toxicities were dose limiting, and the non-haematological side effects were moderate.     

Analysis and characterization of antiviral drug-resistant cytomegalovirus isolates from solid organ transplant recipients

The development of cytomegalovirus (CMV) disease and subsequent emergence of drug-resistant strains was examined in a large group of solid organ transplant recipients; drug-resistant CMV was detected in a total of 30 transplant recipients (20 lung, 5 kidney, 4 heart, and 1 liver). Drug resistance was confirmed both phenotypically and genotypically. The sequences of drug-resistant CMV strains from the same patient differed from drug-susceptible baseline sequences only at single sites previously confirmed to confer drug resistance. At least 1 isolate from each patient had a mutation in the UL97 phosphotransferase coding sequence. Mutations in the DNA polymerase gene were found in 6 of 38 sequenced strains. Lung transplant recipients had the highest incidence of drug-resistant virus: of the 30 patients, 28 were CMV-seronegative transplant recipients of CMV-seropositive organs, which strongly supports the premise that drug resistance is most prevalent in that transplant population.     

Polycystic ovary syndrome in the pediatric population

Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinical phenotypes but different underlying pathophysiological processes. However, hyperandrogenism remains the syndrome's clinical hallmark. The clinical manifestations of PCOS often emerge during childhood or in the peripubertal years, suggesting that the syndrome is influenced by fetal programming and/or early postnatal events. However, given that the full clinical spectrum of PCOS does not typically appear until puberty, a "two-hit" hypothesis has been proposed: (1) a girl develops hyperandrogenism via one or more of many different potential mechanisms; (2) the preexisting hyperandrogenism subsequently disturbs the hypothalamic–pituitary–ovarian axis, resulting in ovulatory dysfunction and sustained hyperandrogenism. No consensus guidelines exist regarding the diagnosis and management of PCOS in the pediatric population; however, because the syndrome is a diagnosis of exclusion, the clinical evaluation of girls suspected of having PCOS is aimed at excluding other causes of androgen excess and menstrual dysfunction. For the syndrome's management, emphasis is placed on lifestyle and symptom-directed treatment.     

Bile salts: natural detergents for the prevention of sexually transmitted diseases

The development of new, safe, topical microbicides for intravaginal use for the prevention of sexually transmitted diseases is imperative. Previous studies have suggested that bile salts may inhibit human immunodeficiency virus infection; however, their activities against other sexually transmitted pathogens have not been reported. To further explore the potential role of bile salts in preventing sexually transmitted diseases, we examined the in vitro activities and cytotoxicities of select bile salts against Chlamydia trachomatis, herpes simplex virus (types 1 and 2), Neisseria gonorrhoeae, and human immunodeficiency virus in comparison to those of nonoxynol-9 and benzalkonium chloride using both primary cells and cell lines derived from the human female genital tract. We found that taurolithocholic acid 3-sulfate and a combination of glycocholic acid and taurolithocholic acid 3-sulfate showed excellent activity against all of the pathogens assayed. Moreover, taurolithocholic acid 3-sulfate alone or in combination was less cytotoxic than nonoxynol-9 and benzalkonium chloride. Thus, taurolithocholic acid 3-sulfate alone or in combination warrants further evaluation as a candidate topical microbicidal agent.     

Hypofractionated stereotactic radiotherapy (hfSRT) after tumour resection of a single brain metastasis: report of a single-centre individualized treatment approach

Purpose

Standard treatment of single brain metastases so far is tumour resection in combination with postoperative whole-brain radiotherapy or stereotactic radiosurgery. Here, we report retrospectively our first experience with postoperative hypofractionated stereotactic radiotherapy (hfSRT) to the resection cavity in order to replace upfront WBRT with respect to treatment efficacy and safety.

Methods

Between March 2006 and October 2011, 33 patients with a single newly diagnosed intracranial metastasis were treated with hfSRT following microsurgical resection. Fractionation concepts were 10?×?4?Gy (n?=?22), 7?×?5?Gy (n?=?7) and 5?×?6?Gy (n?=?4). Planning target volume enclosed the tumour resection cavity with a safety margin of 4?mm.

Results

No patient demonstrated toxicity grade 2 or higher. Actuarial median overall survival summed up to 20.2?months, and 12-month survival was 64?%. Actuarial mean local brain control was 30.6?months, median distant brain control 12.4?months and intracranial control 8.8?months, respectively. Actuarial 1-year rates of local, distant brain and intracranial control were 71, 57 and 43?%. Salvage whole-brain radiotherapy due to recurrent brain metastases was performed in 13 patients (39?%).

Conclusion

Postoperative hfSRT appears to be a feasible treatment option in patients with a single newly diagnosed brain metastasis. Replacing the standard postoperative whole-brain radiotherapy necessitates compliant patients and regular MRI follow-up analysis.     

Universal mapping probes and the origin of human chromosome 3.

Universal mapping probes (UMPs) are defined as short segments of human DNA that are useful for physical and genetic mapping in a wide variety of mammals. The most useful UMPs contain a conserved DNA sequence immediately adjoined to a highly polymorphic CA repeat. The conserved region determines physical gene location, whereas the CA repeat facilitates genetic mapping. Both the CA repeat and its neighboring sequence are highly conserved in evolution. This permits molecular, cytogenetic, and genetic mapping of UMPs throughout mammalia. UMPs are significant because they make genetic information cumulative among well-studied species and because they transfer such information from "map rich" organisms to those that are "map poor." As a demonstration of the utility of UMPs, comparative maps between human chromosome 3 (HSA3) and the rat genome have been constructed. HSA3 is defined by at least 12 syntenic clusters located on seven different rat chromosomes. These data, together with previous comparative mapping information between human, mouse, and bovine genomes, allow us to propose a distinct evolutionary pathway that connects HSA3 with the chromosomes of rodents, artiodactyls, and primates. The model predicts a parsimonious phylogenetic tree, is readily testable, and will be of considerable use for determining the pathways of mammalian evolution.     

Selective targeting of human lymphokine-activated killer cells by CD3 monoclonal antibody against the interferon-inducible high-affinity Fc gamma RI receptor (CD64) on autologous acute myeloid leukemic blast cells

The potential of the CD3 monoclonal antibody (MoAb) OKT3 to selectively target lymphokine-activated killer (LAK) cells and T-cell clones in vitro against autologous tumor cells was studied using material from patients with acute leukemias (19 acute myeloid leukemias [AML], and 3 acute lymphoblastic leukemias [ALL]). Cytotoxicity mediated by patient LAK cells against AML blasts, but not against ALL cells and autologous Epstein-Barr virus-transformed B cells, was enhanced 1.5-fold to 9.3- fold by OKT3 in all AML patients studied. The following findings suggest that the major target molecule on AML cells for OKT3-coated LAK cells is the high-affinity Fc receptor for IgG (Fc gamma RI; CD64): (1) susceptibility to killing by OKT3-coated effector LAK cells segregated with target cell expression of CD64; (2) preincubation of AML blasts with monomeric OKT3 (murine IgG2a), the Fc portion of which is known to have preferential binding affinity to CD64, resulted in lysis by autologous T cells that were not spontaneously cytotoxic; (3) OKT3- dependent increase in lysis of primary and relapsed AML cells by autologous T-cell clones correlated with the amount of target cell expression of CD64; (4) anti-leukemic cytotoxicity of OKT3-coated T cells could partially be inhibited by monomeric human Ig, the natural ligand of CD64; and (5) expression of CD64 (Fc gamma RI) on fresh AML cells could be increased by interferon-gamma (IFN-gamma) and IFN-alpha translating into further enhancement of lysis by autologous OKT3-coated LAK cells. Nonmalignant CD34+ cells sorted from peripheral blood were found to lack expression of CD64 and hence were not affected by OKT3- triggered T-cell targeting, as detected by colony formation assays. In conclusion, the in vitro data presented provide a rationale for the combined clinical use of recombinant interleukin-2, IFN-gamma, and low doses of CD3 MoAb to eliminate AML cells while sparing nonmalignant hematopoietic progenitor cells, for example, in the setting of purging procedures for autologous bone marrow transplantation.     

Content analysis of helping group interactions: Toward a developmental perspective

Age comparative content anaylses were carried out for eleven support-discussion groups. Comparisons of six groups of elderly persons and five groups of college youth revealed that the older more frequently discuss bodily changes, family relations, significant others and external sources of self respect. The young were more concerned with physical vulnerabilities. The elderly were more likely to discuss matters in terms of the past. The results are considered in the light of a life stage developmental conception of group behavior which could have implications for helping interventions.