Does an oral analgesic protocol improve pain control for patients with cancer? An intergroup study coordinated by the Eastern Cooperative Oncology Group

BACKGROUND: Cancer pain is highly prevalent and commonly undertreated. This study was designed to determine whether dissemination of a clinical protocol for pain management would improve outcomes in community oncology practices. PATIENTS AND METHODS: A pain management protocol was developed based on accepted guidelines. After baseline assessment, oncology practices were randomly assigned to 'analgesic protocol' (AP) sites, where oncologists implemented the guidelines in a group of lung or prostate cancer patients, or to 'physician discretion' (PD) sites, where customary treatment was continued. Patients treated on protocol and a comparison group of patients with pain due to breast cancer or myeloma were monitored for change in pain using the Brief Pain Inventory, and for change in other symptoms or mood. RESULTS: The protocol terminated early because of poor accrual. We compared groups using proportions of patients who had no or mild pain at follow-up. Although measures of protocol adherence did not suggest the occurrence of major practice change, the proportion of lung or prostate cancer patients with no or mild pain increased significantly from baseline for those treated at AP sites compared with those treated at PD sites. There was no significant difference between the breast and myeloma patients treated at AP sites versus those treated at PD sites. CONCLUSION: A protocol for cancer pain management can improve pain control. Diffusion of these benefits to other patients was not confirmed. Given the small sample size, these findings require confirmation in a larger trial.     

Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury.

In response to traumatic brain injury (TBI), neurons initiate neuroplastic processes through the activation of intracellular signaling pathways. However, the molecular mechanisms underlying neuroplasticity after TBI are poorly understood. To study this, we utilized the fluid-percussion brain injury (FPI) model to investigate alterations in the mammalian target of rapamycin (mTOR) signaling pathways in response to TBI. Mammalian target of rapamycin stimulates mRNA translation through phosphorylation of eukaryotic initiation factor 4E binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via dendritic protein synthesis. Rats received sham surgery or moderate parasagittal FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h, 24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR, p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in the ipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI, whereas total protein levels were unchanged. Using confocal microscopy to localize these changes, we found that rpS6 phosphorylation was increased in the parietal cortex and all subregions of the hippocampus. In accordance with these results, eIF4E, a key, rate-limiting mRNA translation factor, was also phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15 mins after TBI. Together, these results suggest that changes in mRNA translation may be one mechanism that neurons use to respond to trauma and may contribute to the neuroplastic changes observed after TBI.     

Differential control of mesangial cell proliferation by interferon-gamma.

Rat mesangial cells were shown to be sensitive to recombinant interferon-gamma (IFN-gamma). IFN-gamma reduced thymidine uptake by these cells and inhibited cell proliferation. Incubation of the cells with 1000 U/ml IFN-gamma decreased thymidine uptake by up to 64% and cell numbers were decreased by 17%. The effects of IFN-gamma were dose and time dependent and were partially reversible by the anti-IFN-gamma monoclonal antibody DB-1. This lymphokine did not reduce incorporation of RNA and protein precursors however. Measurements of 3H-uridine and 3H-leucine incorporation indicated significant increases in RNA and protein synthesis (37% and 45%, respectively) on a per cell basis. The mitogenic effects of IL-1 and platelet-derived growth factor (PDGF) were also susceptible to IFN-gamma-mediated inhibition but the mitogenic response to epidermal growth factor (EGF) was much less sensitive. We conclude that while IFN-gamma may act to modulate the mitogenic signals provided by some factors such as IL-1 and PDGF, the response to EGF appears to be unaffected.     

Gallbladder dyskinesia in chronic acalculous cholecystitis

To test the hypothesis that there is an early stage of cholesterol gallstone formation in man characterized by symptoms of chronic cholecystitis, poor gallbladder emptying, and biliary cholesterol crystals, we studied cholecystokinin-stimulated gallbladder emptying by DISIDA scintigraphy and examined bile for cholesterol crystals in symptomatic patients with normal oral cholecystography and gallbladder sonography. Of 36 patients studied, 16 had biliary cholesterol crystals; their mean 30-min gallbladder ejection fraction was 25.9±14.8%. Among the 20 patients without crystals, the mean ejection fraction was 60.3±23.3%. Fifteen patients, 11 with crystals and four without, had cholecystectomy because of persistent symptoms. All with crystals preoperatively and three without had chronic cholecystitis histologically. One patient without crystals had normal histology. We conclude that poor gallbladder contractility, well-established as an etiologic factor in animal models of cholesterol cholelithiasis, is now linked to acalculous cholecystitis, an early stage of human cholesterol cholelithiasis.     

Radionuclide venography vs Tc-99m-RBC equilibrium angiography: A comparative paired study

Combined direct injection venography (DIV) and equilibrium angiography (EA) were performed in 13 patients, by injecting in vitro labeled ^99mTc autologous RBC, via pedal veins, and imaging the first pass and the equilibrium phase. This paired comparative study of DIV with EA shows that DIV has advantages over EA because it provides selective information on the deep venous system from the calves to the inferior vena cava. DIV provides information on the flow dynamics and the high contrast first pass images provide better definition of non filling venous segments as well as visualization of collaterals. When using ^99mTc-MAA, lung perfusion can also be imaged. DIV is recommended as the procedure of choice for the diagnosis of DVT and EA should be employed only when pedal vein injection is not possible.