Dispersal, habitat differences, and comparative phylogeography of Southeast Asian seahorses (Syngnathidae: Hippocampus).

Four distinct phylogeographical patterns across Southeast Asia were observed for four species of seahorse (genus Hippocampus) with differing ecologies. For all species, genetic differentiation (based on cytochrome b sequence comparisons) was significantly associated with sample site (Phi(ST) = 0.190-0.810, P < 0.0001) and with geographical distance (Mantel's r = 0.37-0.59, P < 0.019). Geographic locations of genetic breaks were inconsistent across species in 7/10 comparisons, although some similarities across species were also observed. The two shallow-water species (Hippocampus barbouri and Hippocampus kuda) have colonized the Sunda Shelf to a lesser degree than the two deeper-water species (Hippocampus spinosissimus and Hippocampus trimaculatus). In all species the presence of geographically restricted haplotypes in the Philippines could indicate past population fragmentation and/or long-distance colonization. A nested clade analysis (NCA) revealed that long-distance colonization and/or fragmentation were likely the dominant forces that structure populations of the two shallow-water species, whereas range expansion and restricted dispersal with isolation by distance were proportionally more important in the history of the two deeper-water species. H. trimaculatus has the most widespread haplotypes [average clade distance (D(c)) of nonsingleton haplotypes = 1169 km], indicating potentially high dispersal capabilities, whereas H. barbouri has the least widespread haplotypes (average D(c) = 67 km) indicating potentially lower dispersal capabilities. Pleistocene separation of marine basins and postglacial flooding of the Sunda Shelf are extrinsic factors likely to have contributed to the phylogeographical structure observed, whereas differences among the species appear to reflect their individual ecologies.

A holistic model for moving toward excellence in chaotic times.

BACKGROUND: Staff development experts in a tertiary-care hospital were searching for a holistic approach to facilitating improved outcomes. METHOD: Staff development experts, clinical nurse specialists, and clinical managers developed a model that provides a framework for educators to integrate their energies with those of other leaders in order to create a holistic approach to the goal of achieving excellence. RESULTS: The model that is proposed links strategies for change with outcome evaluation. CONCLUSIONS: The model provides a conceptual lens that helps nurse leaders focus on organizational assessment, strategies to improve the work environment, and the evaluation of outcomes. The model is useful for guiding practice as well as research.

Inhibition of murine Lewis lung carcinoma metastases by combined chemotherapy and intranasal THF-gamma 2 immunotherapy.

Previous research in our laboratories has shown that the immunoregulatory octapeptide, THF-gamma 2, potentiates the efficacy of anticancer chemotherapy in experimental animal models of local plasmacytoma and repairs drug-induced defects in immunocompetence. The highly metastatic, murine D122 lung carcinoma model has been shown to be useful for evaluating the efficacy of experimental antimetastatic therapeutic modalities. The goal of the present study was to determine whether intranasal thymic humoral factor-gamma 2 (THF-gamma 2) immunotherapy, after a single dose of chemotherapy, could inhibit the development of lung metastases, restore immunocompetence, and increase survival in syngeneic C57BL/6 mice bearing highly metastatic Lewis lung carcinoma (D122) solid footpad tumors. Relative to untreated mice and those receiving chemotherapy alone, mice receiving combined chemoimmunotherapy showed the following significant differences: (a) decreased lung metastatic load as assessed by lung weight, (b) prolonged survival time, (c) massive infiltration of lymphoid cells in the lungs, and (d) restoration of impaired immune parameters to normal values in melphalan-treated mice. THF-gamma 2 prevented tumor emboli from colonizing the target tissue, probably by inducing expansion of the lymphoid cell compartment. When used as an adjunct to anticancer chemotherapy, intranasal THF-gamma 2 immunotherapy is a simple and safe treatment modality that seems to be promising for inhibiting lung metastases.

Thymic humoral factor-gamma 2 (THF-gamma 2) immunotherapy reduces the metastatic load and restores immunocompetence in 3LL tumor-bearing mice receiving anticancer chemotherapy.

In mice bearing immunogenic tumors, adding thymic humoral factor-gamma 2 (THF-gamma 2)1 immunotherapy as an adjunct to anticancer chemotherapeutic regimens not only potentiates the antitumor activity of each drug but also repairs tumor/chemotherapy-induced damage to T-cell populations and functions. The Lewis lung carcinoma (3LL) is a weakly immunogenic, highly metastatic tumor in C57BL/6 mice. To investigate whether the immunoregulatory octapeptide is also effective against a tumor that does not elicit an antitumor immune response, we assessed the effect of combination THF-gamma 2 immunotherapy and chemotherapy in 3LL-bearing mice. The results indicate that THF-gamma 2 combined with either Melphalan or 5-Fluorouracil was more effective in reducing metastatic load than either chemotherapeutic drug alone and was characterized by massive infiltration of lymphatic cells. The combined chemoimmunotherapy treatment also prolonged the survival time in all treated animals and repaired T-cell defects and impaired in vitro cellular immune response parameters, induced either by the tumor or by chemotherapy. THF-gamma 2 immunotherapy reversed the decrease in the number of bone-marrow myeloid colonies (GM-CFU) induced by chemotherapy treatment of tumor-bearing mice, supporting the hypothesis that THF-gamma 2 directly stimulates the proliferation of myeloid stem cells. The overall results imply, that when administered as an adjunct to chemotherapy, THF-gamma 2 immunotherapy is equally effective against immunogenic and nonimmunogenic tumors.

Potentiation of myeloid colony-formation in bone marrow of intact and neonatally thymectomized mice by the thymic hormone THF-gamma 2.

The effect of the thymic hormone THF-gamma 2 on committed stem cells of bone marrow (BM) origin was determined using the myeloid progenitor cell clonal assay. Preincubation of normal BM cells with THF-gamma 2 for 1 hour or 18 hours caused a 2- to 6-fold increase in the number of myeloid colonies in the presence of suboptimal concentrations of colony-stimulating factor (CSF). The optimal dose of THF-gamma 2 causing this enhancement was in the range of 25 to 100 ng/mL. THF-gamma 2 was not able to replace CSF as an inducer in these experiments. THF-gamma 2 neither induced IL-6 activity upon 24-hour incubation with bone marrow cells nor enhanced LPS-induced IL-6 secretion by bone marrow cells in vitro. Neonatal thymectomy (NTx) of Balb/c mice caused a decrease in myeloid progenitors, which was repaired by serial injections of THF-gamma 2. The repair of the stem cell compartment in the bone marrow correlated with an increased percentage of Thy1+ cells in the spleen of THF-gamma 2-treated NTx mice. These findings indicate that THF-gamma 2 is able to regulate committed stem cell functions in the bone marrow of immune-deprived NTx and of normal mice.

A synthetic thymic hormone, THF-gamma 2, repairs immunodeficiency of mice cured of plasmacytoma by melphalan.

BALB/c mice cured of large MOPC-315 plasmacytomas by melphalan remain deficient in their spleen T-cell functions. This was manifested by impairment of the allogeneic and the antibody responses in vitro to SRBC and in decreased numbers of T-cells including their subsets CD4 and CD8. IL-2 production and specific cytotoxicity against MOPC-315 tumor cells were, on the other hand, maintained. Treatment of these cured mice by in-vivo administration of THF-gamma 2, an octapeptide from calf thymus, repaired these deficits. This was evidenced by in vitro tests with spleen cells which manifested an increased allogeneic response and elevated generation of primary antibody response, restoration of T-cell subpopulations to normal and an enhanced IL-2 production above normal levels. The potential use of THF-gamma 2 as supportive therapy in cancer treatment is suggested.

Ketoprofen versus indomethacin in patients with rheumatoid arthritis: a multicenter double blind comparative study.

Oral ketoprofen (200-300 mg/day) and indomethacin (100-150 mg/day) were compared in a 12-week double blind study involving 140 patients with rheumatoid arthritis. The treatments were generally equally effective in most assessments, producing highly significant (p less than 0.01) improvements from baseline values within one week. Only isolated statistically significant differences (p less than 0.05) were detected between the 2 treatments: ketoprofen had a more pronounced effect than indomethacin in functional class (Weeks 1 and 12), swollen joint score (Week 1), and patients' global assessments (Week 12); indomethacin was significantly superior in improving grip strength at Week 4. The clinical significance of these statistically established differences may be questioned. The incidence of side effects, primarily gastrointestinal and neurologic, was also comparable in the 2 treatments.

Immunologic alterations in MRL/lpr mice after chronic dimethyl sulfoxide administration.

Dimethyl sulfoxide (DMSO) in 1 and 2% concentration was added to the drinking water of 30-100 day MRL/lpr mice. In comparison to control mice, the DMSO treated mice had a 78% increase in their response to exogenous IL-2 and a 64% increase in production of IL-2. Con A stimulated cells had a net help effect in the untreated mice, which was suppressed from 82-26% after DMSO treatment. There was no marked change in Thy 1.2, Lyt 1 and Lyt 2 percentages after treatment. The anti-DNA decreased from 29.0 +/- 17.0% to 13.2 +/- 7.8% after DMSO treatment. We conclude that chronic DMSO administration to MRL/lpr mice can induce immunologic alterations with possible clinical implications.

Treatment of rheumatoid arthritis with levamisole. A controlled trial.

Levamisole, an anthelminthic agent with immunostimulatory properties, was used in a double-blind, controlled therapeutic trial in rheumatoid arthritis. Patients received either levamisole 100 mg 4 days a week, or placebo, for a period of 4 months. Significant improvement in the treated group, as compared with the control group, was found in the number of tender and swollen joints, grip strength, range of joint motion, sedimentation rate, and C-reactive protein. On double-blind global evaluation by the examining physicians, 9 of 14 patients on levamisole and none of 13 on placebo were considered to have improved. Adverse effects did not differ in frequency between the two groups except for mild alteration in taste, which was more common with levamisole.

Association of renal papillary necrosis and ankylosing spondylitis.

Three patients with ankylosing spondylitis developed renal papillary necrosis. All had received prostaglandin synthetase inhibitors including phenylbutazone, indomethacin, or ibuprofen. One patient had sickle trait. These drugs are not commonly associated with papillary necrosis in man, but may adversely effect renal medullary blood flow. An underlying renal vascular abnormality related to ankylosing spondylitis is also considered. Patients with ankylosing spondylitis who are taking prostaglandin synthetase inhibitors should be routinely screened for hematuria.