Elevated Serum Cytokines and Trichomonas vaginalis Serology at Diagnosis Are Not Associated With Higher Gleason Grade or Lethal Prostate Cancer

Background

Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.

Nursing time to program and assess deep brain stimulators in movement disorder patients.

The use of deep brain stimulation (DBS) to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia is increasing. Although some published literature describes the methods for DBS programming, the time and nursing requirements to run a DBS surgical program have not been examined previously. For this study, we prospectively recorded the time required for both assessments and programming of the DBS from the preoperative period to 1 year after surgery in a variety of patients. Results showed that the mean total time spent programming the stimulator and assessing these patients ranged from 18.0-36.2 hours per patient. It took twice as long to program the stimulator in patients with Parkinson's disease as it did in patients with essential tremor or dystonia. When setting up a program for movement disorders surgery, nursing time spent on patient assessment and programming should be considered in the workload.     

Excitation and desensitization of mouse rod photoreceptors in vivo following bright adapting light

Electroretinographic (ERG) methods were used to determine response properties of mouse rod photoreceptors in vivo following adapting illumination that produced a significant extent of rhodopsin bleaching. Bleaching levels prevailing at ∼10 min and ∼20 min after the adapting exposure were on average 14% and 9%, respectively, based on the analysis of visual cycle retinoids in the eye tissues. Recovery of the rod response to the adapting light was monitored by analysing the ERG a -wave response to a bright probe flash presented at varying times during dark adaptation. A paired-flash procedure, in which the probe flash was presented at defined times after a weak test flash of fixed strength, was used to determine sensitivity of the rod response to the test flash. Recovery of the response to the adapting light was 80% complete at 13.5 ± 3.0 min (mean ± s.d .; n = 7) after adapting light offset. The adapting light caused prolonged desensitization of the weak-flash response derived from paired-flash data. By comparison with results obtained in the absence of the adapting exposure, desensitization determined with a test-probe interval of 80 ms was ∼fourfold after 5 min of dark adaptation and ∼twofold after 20 min. The results indicate, for mouse rods in vivo , that the time scale for recovery of weak-flash sensitivity substantially exceeds that for the recovery of circulating current following significant rhodopsin bleaching. The lingering desensitization may reflect a reduced efficiency of signal transmission in the phototransduction cascade distinct from that due to residual excitation.     

Insulinemic and Inflammatory Dietary Patterns and Risk of Prostate Cancer

BackgroundHyperinsulinemia and inflammation are inter-related pathways that link diet with the risk of several chronic diseases. Evidence suggests that these pathways may also increase prostate cancer risk.ObjectiveTo determine whether hyperinsulinemic diet and inflammatory diet are associated with prostate cancer incidence and mortality.Design, setting, and participantsWe prospectively followed 41 209 men in the Health Professionals Follow-up Study (1986–2014). Scores for two validated dietary patterns were calculated from food frequency questionnaires at baseline and updated every 4 yr.Outcome measurements and statistical analysisTotal, advanced, and lethal prostate cancer outcomes were assessed. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for associations between two empirical hypothesis-oriented dietary patterns—empirical dietary index for hyperinsulinemia and empirical dietary inflammatory pattern—and prostate cancer risk estimated using Cox proportional hazard regression.Results and limitationsDuring 28 yr of follow-up, 5929 incident cases of total prostate cancer, including 1019 advanced and 667 fatal, were documented. In multivariable-adjusted models, there was a 7% higher risk of advanced prostate cancer (HR: 1.07; 95% CI: 1.01–1.15) and a 9% higher risk of fatal prostate cancer (HR: 1.09; 95% CI: 1.00–1.18) per standard deviation (SD) increase in the hyperinsulinemic diet. When stratified by age, the hyperinsulinemic diet was associated with only earlier-onset aggressive prostate cancer (men under 65 yr), with per SD HRs of 1.20 (95% CI: 1.06–1.35) for advanced, 1.22 (1.04–1.42) for fatal, and 1.20 (1.04–1.38) for lethal. The inflammatory diet was not associated with prostate cancer risk in the overall study population, but was associated with earlier-onset lethal prostate cancer (per SD increase HR: 1.16; 95% CI: 1.00–1.35).ConclusionsHyperinsulinemia and inflammation may be potential mechanisms linking dietary patterns with the risk of aggressive prostate cancer, particularly earlier-onset disease.Patient summaryAvoiding inflammatory and hyperinsulinemic dietary patterns may be beneficial for the prevention of clinically relevant prostate cancer, especially among younger men.     

A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer.

PURPOSE: To define the toxicities, pharmacodynamics, and clinical activity of the proteasome inhibitor, PS-341 (bortezomib), in patients with advanced malignancies. PATIENTS AND METHODS: Twenty-eight patients (14 male and 14 female) received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity necessitated dose omissions on this schedule, 16 additional patients (12 male and 4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of 20S proteasome activity in peripheral blood mononuclear cells (PBMC) and accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated as pharmacodynamic markers of PS-341 activity. RESULTS: The most common toxicity was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6 mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a patient in schedule I. Grade > or =3 toxicities for schedule I were constipation, fatigue, myalgia, and sensory neuropathy. Grade > or =3 toxicities for schedule II were dehydration resulting from diarrhea, nausea and vomiting, fatigue, hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both schedules. Reversible dose-dependent decreases in 20S proteasome activity in PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75% at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in tumor samples after treatment with PS-341. A patient with multiple myeloma had a partial response. CONCLUSION: PS-341 given 1.5 mg/m2 twice weekly for 2 of every 3 weeks is well tolerated and should be further studied.     

Comparison of coronary stenting versus conventional balloon angioplasty on five-year mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Little is known about the influence of stenting versus balloon angioplasty on long-term outcomes (particularly mortality) after primary percutaneous coronary intervention (PCI). We evaluated 2,087 patients with ST-elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction (PAMI) trials in the United States, who underwent primary PCI. The main outcome was all-cause mortality at 5 years, obtained through the National Death Index. Of the 2,087 patients, stenting was performed in 692 (33%). The absolute difference in the hospital (2.2% vs 3.3%), 1-year (3.3% vs 5.2%), and 5-year (10% vs 13%) mortality rates favored patients receiving a stent versus conventional balloon therapy, with the difference increasing with time. A multivariate Cox model identified stent use (vs balloon alone) as an independent correlate of lower 5-year mortality (hazard ratio 0.60, 95% confidence interval 0.42 to 0.85). The absolute reduction in mortality was greatest in the highest risk group. In conclusion, compared with balloon angioplasty, stenting during primary PCI not only resulted in better angiographic and short-term outcomes, but also in a sustained beneficial effect on mortality at 5 years. These data support the routine use of coronary stenting in most patients undergoing primary PCI, when feasible.