Environmental covariates: effects on the power of sib-pair linkage methods

The effect of inclusion of environmental risk factors on the power of sib-pair linkage methods was tested for a qualitative trait. It was found that inclusion of an environmental variable did not increase the power of the Haseman-Elston (H-E) sib-pair nonparametric linkage analysis test. However, a significant increase in power was observed for both the H-E and affected-sib-pair tests, even in small samples, when persons unexposed to the environmental risk factor were coded as unknown.     

Induction of stress proteins in rat cardiac myocytes by antimony.

The effects of nonlethal concentrations of potassium antimonyl tartrate (PAT) were examined in cultured neonatal rat cardiac myocytes. PAT (5, 10 microM) significantly increased cellular reduced glutathione (GSH) and heme oxygenase activity after 18 h. GSH levels and heme oxygenase activity were increased 2.5- and 5.4-fold, respectively, by 10 microM PAT after 18 h. In addition, total cytochrome P450 levels were decreased by PAT after an 18-h exposure. PAT exposures were associated with the induction of specific stress proteins. Nonlethal concentrations of PAT produced a dose-dependent increase in HO-1, HSP70, and HSP25/27 protein levels but did not increase HSP60 levels. Pretreatment of cardiac myocytes with low concentrations of PAT (0.5-10 microM) protected against a subsequent lethal concentration of PAT (200 microM). This protection was blocked if cells were treated with the protein synthesis inhibitor cycloheximide. Results demonstrate that low concentrations of PAT increase GSH levels and stress protein synthesis, which may be responsible for the protection that low-level PAT exposure offers against the subsequent toxicity of higher concentrations of PAT.     

In vivo comparison of copper blood-pool agents: potential radiopharmaceuticals for use with copper-62

Two techniques for labeling of albumin with copper-67 (67Cu) and 62Cu were investigated; one using the native Cu(II) binding site of the protein and the other employing a bifunctional chelate, 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane- N,N'N",N"'-tetraacetic acid (Br-benzyl-TETA or BAT), conjugated to the protein. Rat biodistribution experiments with 67Cu demonstrated retention of i.v. 67Cu-benzyl-TETA-albumin in the blood pool identical to co-injected 125I-albumin. By contrast, i.v. administration of either [67Cu]-Cu-acetate or [67Cu]-Cu-acetate pre-mixed with albumin results in relatively rapid clearance of blood-pool radioactivity as the tracer is excreted into the urine. The 62Cu-benzyl-TETA-albumin radiopharmaceutical was obtained in ca. 17% radiochemical yield (end of synthesis, without decay correction) following a procedure that can be completed in 15-18 min. In PET experiments with a baboon, myocardial blood volume images with 62Cu-benzyl-TETA-albumin were identical to those obtained with C15O. Use of the 62Cu-benzyl-TETA-albumin image for blood-pool subtraction of a 62Cu-PTSM myocardial perfusion image is illustrated. Copper-62-benzyl-TETA-HSA should be a useful, generator-produced radiotracer for the detection of the vascular pool at PET facilities without cyclotrons.     

Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission.

PURPOSE: The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. PATIENTS AND METHODS: The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen-identical related (n = 103), or matched unrelated (n = 118) donor. RESULTS: Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P =.014) or who relapsed (P <.001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P =.052), and Philadelphia chromosome-positive patients had no poorer outcome than Philadelphia chromosome-negative patients. Total-body irradiation-based conditioning improved DFS in comparison with busulfan (P =.041). CONCLUSION: Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.     

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

Aprotinin improves pulmonary function during reperfusion in an isolated lung model

BACKGROUND: We hypothesized that the use of aprotinin would ameliorate the reperfusion injury observed after lung transplantation because of a reduction in the inflammatory response. METHODS: We used an isolated, whole blood-perfused, ventilated rabbit lung model to study the effects of aprotinin during reperfusion. The control animals (group A, n = 8) underwent lung harvest after pulmonary arterial prostaglandin E1 injection and Euro-Collins preservation flush before saline storage for 18 hours at 4 degrees C. The experimental groups received either a low dose (3,000 KIU/mL; group B, n = 8) or a high dose (10,000 KIU/mL; group C, n = 8) of aprotinin added to the pulmonary flush before storage. Each lung was reperfused at 37 degrees C at a rate of 60 mL/min. RESULTS: The arterial partial pressure of oxygen values of group B (low-dose aprotinin) were significantly higher than those of group A (control) after 10 minutes of reperfusion (69.19 +/- 5.69 mm Hg versus 264.30 +/- 48.59 mm Hg, respectively, p = 0.001). Similar results were recorded at 20 and at 30 minutes of reperfusion. Similarly, after 10 minutes of reperfusion, the differences between groups A and C were 69.19 +/- 5.69 mm Hg versus 235.91 +/- 28.63 mm Hg, respectively (p = 0.001). CONCLUSIONS: The addition of aprotinin to the Euro-Collins pulmonary flush significantly improves arterial oxygenation in the early reperfusion period. The enhanced oxygenation suggests that aprotinin may offer protection against early reperfusion injury.     

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.     

Immunosuppressive effects of peritoneal fluids from ovarian cancer patients

Peritoneal fluid samples from 42 patients with ovarian carcinomas were tested for their suppressive effects on in vitro responses of normal lymphocytes. Suppression was detected both in a natural killer cell assay against K562 cells and in an assay measuring phytohemagglutinin-induced lymphoproliferation. There was no correlation between the level of immunosuppression and the 1-year survival. The greatest suppression was seen in radically operated patients and in patients with normal amounts of peritoneal fluid. Complete suppression was also seen in two patients operated for benign diseases. The results indicate that immunosuppression is not restricted to malignant ascites, but may be a normal function of the peritoneal fluid.     

Seawater activated TiO2 photocatalyst for degradation of organic compounds

The world's oceans are polluted by a continuous inflow of plastic. Plastic fragments finally into microplastic, which can be taken up, for example by plankton, and subsequently by the entire ocean food web. An approach to reduce plastic pollution constitutes the accelerated microplastic degradation in marine environments. TiO₂ (anatase) is commonly used as an oxidative photocatalyst and well known to catalyze the degradation of organic compounds upon UV irradiation.In this study, a selective activation of TiO₂ (anatase) particles encapsulated by Ca- or Sr-polyphosphate is presented. The TiO₂ polyphosphate core-shell particles are envisaged as additives in plastic products. The highly concentrated cations from seawater, viz. Na⁺ and Mg²⁺, displace the Ca²⁺ or Sr²⁺ cations from the polyphosphate shell. As a result, the polyphosphate coating dissolves and thus the photocatalytically active TiO₂ core is released. The stability of the TiO₂ polyphosphate particles in potable water and the seawater activated disintegration of methylene blue, methyl methacrylate, terephtalic acid, and poly(vinyl alcohol) was shown. It has been demonstrated, that the sweetwater stable polyphosphate coating degrades in the presence of seawater, which could be monitored by the activation of the TiO₂ (anatase) photocatalyst.     

Velocity discrimination in the cat

After considerable training (over 2 years) we measured the just noticeable differences (JNDs) in velocity as a function of reference velocity in three cats. The velocity discrimination curve plotting JNDs in velocity, expressed as Weber fractions as a function of reference velocity is U-shaped with optimal performance at reference speeds between 25 and 60 degrees/sec. The discrimination curve changed little with a tenfold change in slit width. Compared to the human velocity discrimination curve determined with the same test apparatus, the feline curve is narrower and shifted towards faster velocities and larger Weber fractions. These results support our specific linking hypothesis between velocity tuned cells as observed in cortical areas 17 and 18 of the cat, and velocity discrimination.