Schroeder, Darrell R.

Key pointsCommon single nucleotide polymorphisms in the beta‐2 adrenoceptor (ADRB2) gene influence cardiovascular function, but they exist in combinations (haplotypes), so it is crucial to characterize the haplotypes to improve the functional predictive power of ADRB2 gene variation.Dietary sodium affects ADRB2 function.In a large randomized cross‐over phenotyping trial that administered low, normal and high dietary sodium, we determined the interactions between ADRB2 haplotype, receptor density on lymphocytes, cardiovascular haemodynamics during stress manoeuvres, forearm blood flow vasodilator responsiveness and dietary sodium.Healthy young adults were recruited based on the homozygous haplotypes of the ADRB2 gene: Arg16+Gln27, the rare Gly16+Gln27 and Gly16+Glu27.Independent of dietary sodium, the Gly16+Glu27 haplotype had the greatest ADRB2 density and Arg16+Gln27 had the least, suggesting that ADRB2 haplotype influences ADRB2 protein expression, yet the haemodynamic consequences appear modest in healthy humans, necessitating larger trials that explore variation in multiple candidate genes.AbstractDietary sodium affects function of the beta‐2 adrenoceptor (ADRB2). We tested the hypothesis that haplotype variation in the ADRB2 gene would influence the cardiovascular and regional vasodilator responses to sympathoexcitatory manoeuvres following low, normal and high sodium diets, and ADRB2‐mediated forearm vasodilation in the high sodium condition. Seventy‐one healthy young adults were grouped by double homozygous haplotypes: Arg16+Gln27 (n = 31), the rare Gly16+Gln27 (n = 10) and Gly16+Glu27 (n = 30). Using a randomized cross‐over design, subjects were studied following 5 days of controlled low, normal and high sodium with 1 month or longer between diets (and low hormone phase of the menstrual cycle). All three visits utilized ECG and finger plethysmography for haemodynamic measures, and the high sodium visit included a brachial arterial catheter for forearm vasodilator responses to isoprenaline with plethysmography. Lymphocytes were sampled forex vivoanalysis of ADRB2 density and binding conformation. We found a main effect of haplotype on ADRB2 density (P = 0.03) with the Gly16+Glu27 haplotype having the greatest density (low, normal, high sodium: 12.9 ± 0.9, 13.5 ± 0.9 and 13.6 ± 0.8 fmol mg−1protein, respectively) and Arg16+Gln27 having the least (9.3 ± 0.6, 10.1 ± 0.5 and 10.3 ± 0.6 fmol mg−1protein, respectively), but there were no sodium or haplotype effects on receptor binding conformation. In the mental stress trial, there was a main effect of haplotype on cardiac output (P = 0.04), as Arg16+Gln27 had the lowest responses. Handgrip and forearm vasodilation yielded no haplotype differences, and no correlations were present for ADRB2 density and haemodynamics. Our findings support cell‐based evidence that ADRB2 haplotype influences ADRB2 protein expression independent of dietary sodium, yet the haemodynamic consequences appear modest in healthy humans.

BackgroundAllogeneic blood transfusion induces immunosuppression, and concern has been raised that it may increase propensity for cancer recurrence; however, these effects have not been confirmed. We examined the association of perioperative transfusion of allogeneic blood long‐term oncologic outcomes in patients with prostate cancer who underwent prostatectomy.Study Design and MethodsWe reviewed medical records of patients who underwent radical prostatectomy between 1991 and 2005 and received allogeneic nonleukoreduced blood. Each transfused patient was matched to two controls who did not receive blood: matching included age, surgical year, prostate‐specific antigen level, pathologic tumor stages, pathologic Gleason scores, and anesthetic type. Primary outcome was systemic tumor progression, with secondary outcomes of prostate cancer death and all‐cause mortality. Stratified proportional hazards regression analysis was used to assess differences in outcomes between the transfused and nontransfused group.ResultsA total of 379 prostatectomy patients who were transfused and 758 nontransfused controls were followed for 9.4 and 10.2 years (median), respectively. In a multivariable analysis that took into account the matched study design and adjusted for positive surgical margins and adjuvant therapies, the use of allogeneic blood was not associated with systemic tumor progression (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.39‐1.99; p = 0.76), prostate cancer–specific death (HR, 1.69; 95% CI, 0.44 to 6.48; p = 0.44), or all‐cause death (HR, 1.20; 95% CI, 0.87 to 1.67; p = 0.27).ConclusionsWhen adjusted for clinicopathologic and procedural variables transfusion of allogeneic blood was not associated with systemic tumor progression and survival outcomes.

Objective: The objective of this investigation was to assess whether a new electronic health (e-health) platform, combining mobile computing and a content management system, could effectively deliver modular and “just-in-time” education to older patients following cardiac surgery. Subjects and Methods: Patients were provided with iPad ® (Apple ® , Cupertino, CA) tablets that delivered educational modules as part of a daily “to do” list in a plan of care. The tablet communicated wirelessly to a dashboard where data were aggregated and displayed for providers. Results: A surgical population of 149 patients with a mean age of 68 years utilized 5,267 of 6,295 (84%) of education modules delivered over a 5.3-day hospitalization. Increased age was not associated with decreased use. Conclusions: We demonstrate that age, hospitalization, and major surgery are not significant barriers to effective patient education if content is highly consumable and relevant to patients' daily care experience. We also show that mobile technology, even if unfamiliar to many older patients, makes this possible. The combination of mobile computing with a content management system allows for dynamic, modular, personalized, and “just-in-time” education in a highly consumable format. This approach presents a means by which patients may become informed participants in new healthcare models.

Abstract We report findings in 70 patients with both diffuse interstitial lung disease and either polymyositis (PM) or dermatomyositis (DM). Initial presentations were most commonly either musculoskeletal (arthralgias, myalgias, and weakness) or pulmonary (cough, dyspnea, and fever) symptoms alone; in only 15 patients (21.4%) did both occur simultaneously. Pulmonary disease usually took the form of acute to subacute antibiotic-resistant community-acquired pneumonia. Chest radiographs and computed tomography most commonly demonstrated bilateral irregular linear opacities involving the lung bases; occasionally consolidation was present. Jo-1 antibody was present in 19 (38%) of 50 patients tested. Synchronous associated malignancy was present in 4 of 70 patients (5.7%). Surgical lung biopsies disclosed nonspecific interstitial pneumonia (NSIP) in 18 of 22 patients (81.8%), organizing diffuse alveolar damage (DAD) in 2, bronchiolitis obliterans organizing pneumonia (BOOP) in 1, and usual interstitial pneumonia (UIP) in 1. Treatment usually included prednisone in 40–60 mg/d dosages for initial control, followed by lower dose prednisone plus an immunosuppressive agent such as azathioprine or methotrexate for disease suppression. Survival was significantly better than that observed for historical control subjects with idiopathic UIP, and was more consistent with survival previously reported in idiopathic NSIP. There was no difference in survival between Jo-1 positive and Jo-1 negative groups.

Abstract The clinical records of 487 patients seen at Mayo Clinic Rochester (MCR) during 1994 through 1996 who were diagnosed as having idiopathic pulmonary fibrosis of the usual interstitial pneumonia type (IPF/UIP) were reviewed. Computed tomography (CT) had been done in 94.7% of patients and surgical open lung biopsy (OLB) in 20.3%. Median survival was 3.2 yr. We compared survival as a function of treatment program, based on intent to treat at the time of the initial contact within the study window. Treatment advised included colchicine alone in 167, no therapy in 157, prednisone at maintenance dosages alone in 54, colchicine plus prednisone in 71, and other programs in 38. Oxygen therapy was advised in 133 patients. By univariate analysis, worse survival was associated with prednisone therapy compared with no therapy, and with oxygen therapy compared with no oxygen therapy. However, on multivariate analysis, worse survival was associated with older age, male gender, lower diffusing capacity for carbon monoxide (DlCO), lower alveolar volume (Va), and a history of worsening pulmonary function. When adjustment was made for these factors, there was no significant difference in survival between those patients treated with colchicine or prednisone and those on no therapy, and no difference between those on oxygen therapy and those without oxygen.