Search

Recent discoveries of the purpose and potential of microbial interactions with humans have broad implications for our understanding of metabolism, immunity, the host−microbe genetic interactions. Bioavailability and bioaccessibility of phytonutrients in foods not only enrich microbial diversity in the lower human gastrointestinal tract (GIT) but also direct the functioning of the metagenome of the microbiota. Thus, healthy choices must include foods that contain nutrients that satisfy both the needs of humans and their microbes. Physical activity interventions at a moderate level of intensity have shown positive effects on metabolism and the microbiome, while intense training (>70% VO2max) reduces diversity in the short term. The microbiome of elite endurance athletes is a robust producer of short-chain fatty acids. A lifestyle lacking activity is associated with the development of chronic disease, and experimental conditions simulating weightlessness in humans demonstrate loss of muscle mass occurring in conjunction with a decline in gut short-chain fatty acid (SCFA) production and the microbes that produce them. This review summarizes evidence addressing the relationship between the intestinal microbiome, diet, and physical activity. Data from the studies reviewed suggest that food choices and physical fitness in developed countries promote a resource “curse” dilemma for the microbiome and our health.

Memory and cognitive decline are the product of numerous physiological changes within the aging brain. Multiple theories have focused on the oxidative, calcium, cholinergic, vascular, and inflammation hypotheses of brain aging, with recent evidence suggesting that reductions in insulin signaling may also contribute. Specifically, a reduction in insulin receptor density and mRNA levels has been implicated, however, overcoming these changes remains a challenge. While increasing insulin receptor occupation has been successful in offsetting cognitive decline, alternative molecular approaches should be considered as they could bypass the need for brain insulin delivery. Moreover, this approach may be favorable to test the impact of continued insulin receptor signaling on neuronal function. Here we used hippocampal cultures infected with lentivirus with or without IRβ, a constitutively active, truncated form of the human insulin receptor, to characterize the impact continued insulin receptor signaling on voltage-gated calcium channels. Infected cultures were harvested between DIV 13 and 17 (48 h after infection) for Western blot analysis on pAKT and AKT. These results were complemented with whole-cell patch-clamp recordings of individual pyramidal neurons starting 96 h post-infection. Results indicate that while a significant increase in neuronal pAKT/AKT ratio was seen at the time point tested, effects on voltage-gated calcium channels were not detected. These results suggest that there is a significant difference between constitutively active insulin receptors and the actions of insulin on an intact receptor, highlighting potential alternate mechanisms of neuronal insulin resistance and mode of activation.

The insulin receptor (IR) is a ligand-activated receptor tyrosine kinase that has a key role in metabolism, cellular survival, and proliferation. Progesterone receptor membrane component 1 (PGRMC1) promotes cellular signaling via receptor trafficking and is essential for some elements of tumor growth and metastasis. In the present study, we demonstrate that PGRMC1 coprecipitates with IR. Furthermore, we show that PGRMC1 increases plasma membrane IR levels in multiple cell lines and decreases insulin binding at the cell surface. The findings have therapeutic applications because a small-molecule PGRMC1 ligand, AG205, also decreases plasma membrane IR levels. However, PGRMC1 knockdown via short hairpin RNA expression and AG205 treatment potentiated insulin-mediated phosphorylation of the IR signaling mediator AKT. Finally, PGRMC1 also increased plasma membrane levels of two key glucose transporters, GLUT-4 and GLUT-1. Our data support a role for PGRMC1 maintaining plasma membrane pools of the receptor, modulating IR signaling and function., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)

Background and Objective: To evaluate safety and efficacy of intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) injection (IAI) for the treatment of neovascular polypoidal choroidal vasculopathy (PCV) in a predominantly non-Asian population., Patients and Methods: This was an open-label, prospective, unmasked, nonrandomized clinical trial. Twenty eyes with neovascular PCV received monthly 2.0 mg IAI for 3 months followed by mandatory IAI every 2 months for 12 months., Results: The mean change in ETDRS best-corrected visual acuity from baseline to 1 year was +11 letters in the treatment-naïve group, +5 letters in the treatment non-naïve group, and +9 letters overall. There was an overall mean reduction of 70 µm from baseline central subfield thickness (CST) at 1 year. Patients received a mean of 6.2 mandatory and 0.7 additional IAI injections overall during the course of 1 year. No serious ocular adverse events were reported., Conclusion: At 1 year, neovascular PCV in a predominantly non-Asian population treated with IAI demonstrated favorable visual, anatomic, and safety outcomes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:34-44.]., (Copyright 2017, SLACK Incorporated.)

Background and Objective: To evaluate the safety and efficacy of 0.3 mg ranibizumab (Lucentis; Genentech, South San Francisco, CA) in eyes with persistent diabetic macular edema (DME) after recent, chronic, and frequent bevacizumab (Avastin; Genentech, South San Francisco, CA)., Patients and Methods: Open-label, prospective study of 0.3 mg ranibizumab for eyes with persistent DME after bevacizumab. Thirty eyes randomized to a sustained group or a pro re nata (PRN) dosing group., Results: The mean change in ETDRS best-corrected visual acuity from baseline to 1 year was +6.7 letters in the sustained group, +6.4 letters in the PRN group, and +6.5 letters overall. There was an overall mean reduction of 116 µm from baseline central subfield thickness at 1 year, with -92 µm and -127 µm decreases in the sustained and PRN groups, respectively. Adverse events included two deaths; one patient with multiple cardiopulmonary comorbidities, myocardial infarction, stroke, osteomyelitis; and mild posterior subcapsular cataracts in two eyes., Conclusion: Ranibizumab 0.3 mg demonstrated improved visual and anatomic outcomes in patients with persistent DME following bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1030-1037.]., (Copyright 2016, SLACK Incorporated.)

Cardiac complications following surgery can be devastating especially if it is unrecognized. We present a case of a stress-induced cardiomyopathy that occurred in postoperative period following a robotic radical cystectomy and urinary diversion. While most cases of stress-induced cardiomyopathy, also known as Takotsubo cardiomyopathy, are transient and with little to no long term clinical effects, a small number of patients can develop severe complications. This has not been reported in urologic literature and the unique characteristics of this cardiac condition are reviewed.

Objective: Circulating tumor cells (CTCs) have known prognostic implications in metastatic castration-resistant prostate cancer, but little is known regarding its utility in biochemical recurrence (BR) of prostate cancer. The primary objectives were to determine whether CTCs are measurable in patients with BR and whether it can reliably predict prostate-specific antigen (PSA) increase and PSA doubling times (PSADTs)., Methods: BR was identified in patients after prostatectomy or radiation or both, with a PSA increase of ≥ 0.2 for prior prostatectomy or > 2 mg/dL increase for post-nadir in prior radiotherapy. CTCs were enumerated at baseline at the time of study entry using the CellSearch (Janssen Diagnostics, Raritan, NJ) test., Results: The median age for all 36 patients accrued was 69.5 years (range, 51-91) with a median PSA of 1.65 ng/mL (range, 0.2-65.8). Gleason scores ranged from 5 to 9 (median, 7). The majority had prostatectomy (n = 25), external beam radiotherapy (n = 9), CyberKnife (Accuray, Sunnyvale, CA) (n = 1), and combined radiohormonal therapy (n = 1). PSADT ranged from 0.35 to 55 months, with a median of 7.43 months. The incidence of positive CTCs was 8.3% (3 patients), of whom 2 had biopsy-proven bony lesions on presenting with equivocal scans and PSADTs of 2.27 and 3.08 months, respectively. The third CTC-positive patient had a PSADT of 4.99 months., Conclusions: Obtaining CTCs in unselected patients presenting with BR has a relatively low yield. However, obtaining a positive CTC raises the suspicion of the presence of metastatic disease and may have utility for longitudinal follow-ups of patients with BR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter analysis revealed that 382 out of 1,188 genes contained cis-acting AR-binding sequences. Chromatin immunoprecipitation confirmed STAT1, RHOA, ITGB5, MAPKAPK2, CSNK2A,1 and PIK3CB genes as novel AR targets in PCa disparities. Moreover, functional screens revealed that androgen-stimulated AR binding and upregulation of RHOA, ITGB5, and PIK3CB genes were associated with increased invasive activity of AA PCa cells, as siRNA-mediated knockdown of each gene caused a loss of androgen-stimulated invasion. In summation, our findings demonstrate that transcriptional changes have preferentially occurred in multiple signaling pathways converging ("transcriptional convergence") on AR signaling, thereby contributing to AR-target gene activation and PCa aggressiveness in AAs.

Background and Purpose: Complications after robot-assisted prostatectomy are widely reported and varied. Our goal was to determine the incidence of surgical complications resulting from robot-assisted laparoscopic radical prostatectomy (RALP) during the initial phase of a new robotics program that was developed by two surgeons without laparoscopic or robotic fellowship training. A secondary goal was to see if experience changed the incidence of complications with this technology., Patients and Methods: A prospectively maintained database was used to evaluate the first 1000 consecutive patients who were treated with RALP from January 2004 to June 2009. The database was reviewed for evidence of complications in the perioperative period. All patients underwent robot-assisted laparoscopic radical prostatectomy by two surgeons. Complications were confirmed and supplemented by retrospectively reviewing the departmental morbidity and mortality reports, as well as the hospital records. The Clavien classification system, a standardized and validated scale for complication reporting, was applied to all events. The complication rate was determined per 100 patients treated and tested with logistic regression for a relationship with surgeon experience., Results: Ninety-seven (9.7%) patients experienced a total of 116 complications; 81 patients experienced a single complication and 16 patients experienced ≥2 complications. The majority of complications (71%) were either grade I or II. The complication rate decreased with experience when the first 500 cases were compared with the latter 500 cases (P=0.007). All the data were reviewed retrospectively. Involvement of residents/fellows increased as primary surgeon experience improved., Conclusions: Complications after RALP are most commonly minor, requiring expectant or medical management only, even during the initiation of a RALP program. The complication rate improved significantly during the study period.

Every year, thousands of children are admitted to pediatric intensive care for treatment. Many of these admissions are for acute injuries, but children with chronic illnesses requiring repeated hospitalization are also on the rise. Hospitalization of a child is extremely stressful for both the patient and family. Historically, intensive care units had restrictive visitation hours and did not allow for sibling visitation or multiple family members. Parents and family members were not encouraged to participate in care when at the bedside. As the shift toward family-centered care continues, many hospitals are now changing visitation policies to allow for active family involvement in patient care. Parents are now encouraged to participate in care. Intensive care units are modifying layouts of the unit to facilitate visitors and provide sleeping spaces for parents when available. Families are considered part of the team instead of visitors, and are included in the decision making process. The purpose of this article is to promote discussion of family-centered care in the pediatric intensive care unit.

The aim of this study is to explore the use of pathologically confirmed capsular incision and denudation as a measure of adequacy of extirpation following robot-assisted laparoscopic prostatectomy (RALP). All patients who underwent RALP at the George Washington University Medical Center during the first 2 years of inception of the robotic prostatectomy program were included. All pathologic specimens were reviewed by a single pathologist. One hundred twenty-eight men who underwent RALP during the first 2 years were identified. Sixty-four patients underwent RALP during the first year (group 1) and all pathologic specimens were reviewed retrospectively. Sixty-four patients underwent RALP during the second year (group 2) after revision of our operative technique and all pathologic specimens were reviewed prospectively. Of patients in group 1, 18 (28%) had a positive surgical margin (PSM), and 18 (28%) with negative surgical margins were found to have capsular incision or denudation. In group 1, 32 (50%) patients had evidence of iatrogenic capsular violation. Group 2 consisted of 13 (20%) patients with a PSM and 9 (14%) margin-negative patients with capsular incision or denudation. Group 2 had a total of 22 (34%) patients with evidence of iatrogenic capsular violation. Overall reduction in positive margins was not statistically significant between the groups. Improvement in capsular incision/denudation rate and overall capsular violation between the two groups was statistically significant (P < 0.03 and <0.0055). Surgical margin status alone underestimates the overall quality of surgical resection after RALP because not all capsular violations result in a PSM. Surgeon-guided pathologic review in addition to intraoperative experience may improve oncologic success during the RALP learning curve.

Background: In certain forms of severe heart failure there is sufficient improvement in cardiac function during ventricular assist device (VAD) support to allow removal of the device. However, it is critical to know whether there is sustained recovery of the heart and long-term patient survival if VAD bridging to recovery is to be considered over the option of transplantation., Methods: To determine long-term outcome of survivors of VAD bridge-to-recovery procedures, we retrospectively evaluated 22 patients with non-ischemic heart failure successfully weaned from the Thoratec left ventricular assist device (LVAD) or biventricular assist device (BVAD) after recovery of ventricular function at 14 medical centers. All patients were in imminent risk of dying and were selected for VAD support using standard bridge-to-transplant requirements. There were 12 females and 10 males with an average age of 32 (range, 12-49). The etiologies were 12 with myocarditis, 7 with cardiomyopathies (4 post-partum [PPCM], 1 viral [VCM], and 2 idiopathic [IDCM]), and 3 with a combination of myocarditis and cardiomyopathy. BVADs were used in 13 patients and isolated LVADs in 9 patients, for an average duration of 57 days (range, 11-190 days), before return of ventricular function and successful weaning from the device. Post-VAD survival was compared with 43 VAD bridge-to-transplant patients with the same etiologies who underwent cardiac transplantation instead of device weaning., Results: Nineteen of the 22 patients are currently alive. Three patients required heart transplantation, 1 within 1 day, 2 at 12 and 13 months post-weaning, and 2 died at 2.5 and 6 months. The remaining 17 patients are alive with their native hearts after an average of 3.2 years (range, 1.2-10 years). The actuarial survival of native hearts (transplant-free survival) post-VAD support is 86% at 1 year and 77% at 5 years, which was not significantly different (p = 0.94) from that of post-VAD transplanted patients, also at 86% and 77%, respectively., Conclusions: Long-term survival for bridge-to-recovery with VADs for acute cardiomyopathies and myocarditis is equivalent to that for cardiac transplantation. Recovery of the native heart, which can take weeks to months of VAD support, is the most desirable clinical outcome and should be actively sought, with transplantation used only after recovery of ventricular function has been ruled out.

Background: Screening pretransplantation recipient sera for percent panel reactive antibodies (%PRA) by an anti-human globulin (AHG) assay may identify recipients who are at risk for graft rejection or development of posttransplantation coronary artery disease. However, the pretransplantation AHG-%PRA does not always correlate with the occurrence of graft rejection or coronary artery disease., Methods: We compared the predictive capacity of the AHG-%PRA with that of an enzyme-linked immunoassay (EIA)-based PRA assay that identifies immunoglobulin G bound to soluble human leukocyte antigen (sHLA) class I molecules from pooled platelets of 240 random donors (sHLA-EIA), and that of an EIA-based assay that detects immunoglobulin G anti-HLA class I antibodies bound to sHLA derived from individual HLA-typed cell cultures (PRA-STAT). The pretransplantation sera from 130 cardiac allograft recipients were comparatively tested and results evaluated., Results: Although AHG-%PRA- and sHLA-EIA-determined PRA results were comparable, neither assay discriminated potential recipients at risk for rejection or coronary artery disease. However, cardiac allograft recipients with pretransplantation PRA-STAT sera > 10% were at risk for (1) graft rejection (77% vs 56%, p < .05); (2) more rejections/recipient (1.9 vs 1.0, p < .02); (3) graft rejection within 30 days (92% vs 38%, p < .001); or (4) development of coronary artery disease (48% vs 23%, p < .05) than recipients with pretransplantation PRA-STAT sera < 10%., Conclusions: PRA-STAT analysis of pretransplantation sera from potential cardiac allograft recipients may be more clinically informative about HLA alloimmunity and a better predictor of adverse clinical events than either AHG-%PRA- or sHLA-EIA-determined PRA.

Transitional cell carcinoma of the upper urinary tract with inferior vena cava tumor thrombus is an unusual entity. We report the 16th such case and review the previous cases in the world literature. Preoperative diagnosis was correct in only 5 of the cases. This type of condition can be easily presumed to be renal cell carcinoma. Fifteen of the cases were managed with radical nephrectomy; 8 patients were managed with partial or complete resection of the vena cava due to adherence of the tumor thrombus to the vessel wall. Overall outcome was poor, with short postoperative survival. Correct preoperative diagnosis, although difficult, could allow more complete preoperative planning or appropriate nonoperative management.

Testis cancer affects 2-3 men per every 100,000 in the United States, making it the most common solid tumor of men in the 20-35-year-old age range. Since the average age of active duty military personnel is included in the age range of those at greatest risk for germ cell testis cancer, it is of pertinent clinical importance to physicians who treat these young patients. The National Naval Medical Center has been using cisplatin-based protocols since the time of their introduction. This study reviews the success of treating these patients and examines the treatment failures.

Background: Viral infections, particularly those caused by cytomegalovirus, are a major cause of postoperative morbidity and mortality in heart transplant recipients. These infections have classically been diagnosed by history, physical examination, peripheral viral cultures, and serologic studies. These methods are often time-consuming and lack sensitivity. Positive viral cultures from the heart are rarely obtained, and viral myocarditis and acute cellular rejection are unable to be differentiated histologically. We have therefore used the polymerse chain reaction to diagnose possible viral infection in pediatric heart transplant recipients with findings consistent with acute unexplained rejection., Methods: Polymerase chain reaction was used as an aid to diagnose cytomegalovirus infection of cardiac tissue obtained by right ventricular endomyocardial biopsy and follow its long-term course. In addition, polymerase chain reaction was used to diagnose infection of the heart by other viruses in patients with clinical and histologic evidence of rejection, especially those with unexplained late rejection or chronic rejection. Polymerase chain reaction primers were designed to amplify nucleic acid sequences from cytomegalovirus, parvovirus, adenovirus, herpes simplex virus, Epstein-Barr virus, and the RNA viruses of the Enterovirus family., Results: Forty patients underwent serial right ventricular endomyocardial biopsy (129 samples) for rejection surveillance with positive results obtained in 41 samples (32%) from 21 patients. Viral genome amplified included cytomegalovirus in 16 samples, adenovirus in 14, enterovirus in 6, parvovirus in 3, and herpes simplex virus in 2. In 13 of the 21 patients positive for viral genome (62%), endomyocardial biopsy histologic scores were consistent with multifocal moderate to severe rejection (Internal Society for Heart and Lung Transplantation scores of 3A or greater)., Conclusions: Polymerase chain reactions may be used as a rapid and sensitive method to evaluate postoperative viral infections in heart transplant recipients, especially in those with late-onset rejection or chronic rejection. Polymerase chain reaction may also be useful in the serial analysis of cytomegalovirus status in transplant recipients. The use of multiple viral primers improves the diagnostic evaluation of these patients and may lead to a better understanding of the epidemiologic characteristics of posttransplantation viral infections and the cause of late or chronic rejection.

This article investigates the relationship between three types of measures obtained from consumer surveys: satisfaction, health status, and report of systems performance. Analyses demonstrate that patient reports of the quality of processes of care or system performance (such as receiving results of tests or receiving conflicting information from staff members) are significantly related to satisfaction independently of perception of health status. Since dissatisfaction is known to be associated with disenrollment, patient reports of system performance are of great interest to health plans.

Controversy exists regarding the clinical significance of a pathological stage T0 (pT0) specimen found at cystectomy or after repeat transurethral resection for transitional cell carcinoma of the bladder. Many investigators cite this subpopulation of patients as a reason to consider more conservative management, based on the premise that the patient may have benefited from the original transurethral resection. However, we questioned whether outcome would be improved in stage pT0 cancer patients or whether outcome in stage pT0 cases would parallel that noted when the original stage was equivalent to the final pathological stage. To test this hypothesis, we examined the survival advantage occasioned by a stage pT0 finding in 66 of 433 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. Of the 433 patients studied 54 had clinical stage Tis or Ta, 166 clinical stage T1 and 213 clinical stage T2 disease. Within each of the 3 clinical groups (clinical stage Tis/Ta, clinical stage T1 and clinical stage T2) Kaplan-Meier survival projections were generated comparing patients with stage pT0 disease to those whose pathological stage was identical to the original clinical stage. Among the 54 clinical stage Tis/Ta cancer patients 11 with stage pT0 and 24 with stage pTis/pTa had survival projections of 90% of 5 years. Of 166 patients with clinical stage T1 disease 32 with stage pT0 and 78 with stage pT1 tumor had survival projections of 75% at 5 years. Among 213 patients with clinical stage T2 cancer 23 with stage pT0 and 71 with stage pT2 disease had survival projections of 68% at 5 years. The data suggest that a stage pT0 cystectomy specimen does not confer a survival advantage over that noted from the initiating population in which the final pathological stage and initial clinical stage are equivalent. A patient with a stage pT0 specimen functions, by survival analysis, in a manner similar to one with the stated clinical stage.

Background: Studies have demonstrated conclusively that the stage and grade of transitional cell tumors at presentation are major determinants of survival for those with the disease in the bladder and prostate. The authors initiated a review of 531 patients with transitional cell carcinoma of the bladder and prostate treated with radical cystectomy between 1969 and 1990 to identify other clinical features predictive of cancer-specific survival., Materials and Methods: Inpatient and clinical medical records were analyzed for age, race, gender, clinical T stage, medical history, and presenting symptoms and signs, and admission laboratory values were correlated with the patient's cancer-specific outcome. Both univariate and multivariate analyses of the various clinical factors were performed to identify variables predictive of cancer-specific survival., Results: Univariate analysis indicated that clinical T classification, preoperative hemoglobin, tumor grade, irritative voiding symptoms, age, preoperative creatinine, obstructive hydronephrosis on preoperative excretory urography, a history of bladder tumors or nephrouretectomy for transitional cell cancer, prior urinary tract infections, prior pelvic irradiation, and obstructive symptoms were all predictive of poor cancer-specific survival. Multivariate analysis demonstrated that higher clinical T classification (T2, T3a, T3b, T4 versus Ta, Tis, T1) (P < 0.001), increasing age (< 65 years versus > or = 65 years) (P < 0.001), the presence of irritative voiding symptoms (P = 0.01), higher tumor grade, lower preoperative hemoglobin level (< or = 12 gm/dl versus > 12 gm/dl) (P < 0.001), higher preoperative creatinine level (> or = 1.5 mg/dl versus < 1.5 mg/dl) (P = 0.002), a history of nephroureterectomy for transitional cell cancer (P = 0.016), and a history of pelvic irradiation (P = 0.002) were all predictive of poor cancer-specific survival., Conclusions: Although clinical T classification and tumor grade remain the best predictors of survival in patients with transitional cell carcinoma of the bladder or prostate, clinical variables such as age, preoperative creatinine and hemoglobin levels, a history of nephroureterectomy or pelvic irradiation, and irritative voiding symptoms at presentation may provide additional prognostic information independent of tumor grade and stage.

Objectives: The purpose of this study was to test the hypothesis that transvalvular left ventricular assistance would support the circulation in patients with cardiogenic shock secondary to acute myocardial infarction and allow recovery of function in patients with a reversibly damaged (stunned) left ventricle., Background: Cardiogenic shock occurs in 7.5% of patients presenting with acute myocardial infarction, resulting in survival of only 20%. Despite the use of aggressive interventional therapy in patients with shock secondary to anterior myocardial infarction, survival remains as low as 33%., Methods: We studied 11 patients with acute myocardial infarction and cardiogenic shock, as defined by a cardiac index < 2 liters/min per m2, pulmonary capillary wedge pressure > 18 mm Hg and systolic blood pressure < 90 mm Hg during positive inotropic therapy. Patients were 57 +/- 13 years old (mean +/- SD) and had a mean left ventricular ejection fraction of 25 +/- 11%, mean arterial pressure of 69 +/- 13 mm Hg and mean cardiac index of 1.6 +/- 0.4 liters/min per m2 on admission to the study., Results: During the 1st 24 h of left ventricular assistance, pulmonary capillary wedge pressure decreased from 26 +/- 4 to 16 +/- 4 mm Hg (p = 0.01), cardiac index increased from 1.6 +/- 0.4 to 2.4 +/- 0.4 liters/min per m2, and the dopamine hydrochloride dose decreased from 51 +/- 92 to 18 +/- 12 micrograms/kg body weight per min. In survivors, cardiac index improved to 3.2 +/- 0.5 liters/min per m2 (p = 0.01), and left ventricular ejection fraction improved to 34 +/- 5% (p < 0.05). The overall survival in the study group was 4 (36%) of 11 patients (95% confidence interval [CI] 8% to 65%), and 4 (66%) of 6 patients (95% CI 29% to 100%) with a Q wave anterior myocardial infarction survived., Conclusions: Transvalvular left ventricular support during cardiogenic shock complicating acute myocardial infarction is feasible and results in significant hemodynamic and functional improvement.

Background: The rarity of testis tumor in black patients has made the study of a large series difficult. Much of the epidemiologic and clinical information regarding this neoplasm in this population is in dispute, including data on incidence, prognosis, histologic distribution, age and stage at presentation, and side distribution., Methods: A retrospective review of 66 blacks with testicular tumors from seven military medical centers was performed., Results: Similar results were found for blacks with testis tumor to those of the general testis cancer population regarding prognosis, side distribution, and age of onset for nonseminoma and interstitial tumors. There is a slight increase in the expected number of interstitial tumors in blacks, but the distribution between seminoma and nonseminoma is similar to the general population. The mean age of presentation for seminoma in blacks was younger than that of the general testis cancer population. For testis tumor treated at the same institution, there was an increased delay of diagnosis in blacks compared with whites. The number of new cases of testicular cancer between 1979 and 1991 at one major center was increased for whites but not for blacks. The availability of cisplatin-based combination chemotherapy has resulted in an improved prognosis for blacks, as has already been demonstrated for white populations., Conclusions: Testis tumor in blacks behaves similarly to testis tumor in the general population except that in blacks there are more interstitial tumors and the mean age of presentation for seminoma is younger. Further, there is an increased delay in diagnosis for blacks compared with whites, but the incidence of this tumor in this population does not appear to be increasing. Cisplatin-based chemotherapy has significantly improved survival in this population.

Between January 1969 and January 1990, 531 patients underwent bilateral pelvic lymph node dissection and radical cystectomy for the management of transitional cell carcinoma of the bladder. Of these procedures 220 were performed for clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either high grade or recalcitrant to transurethral resection and/or intravesical chemotherapy. This subgroup of patients was studied to evaluate the outcome of recurrent or chemotherapy resistant superficial transitional cell carcinoma of the bladder after radical cystectomy. The operative mortality rate for the group was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate was 5.9%. The 5-year cancer-specific survival rates for patients with pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%, 80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%, 92%, 66% and 62%, respectively. A total of 74 patients received preoperative radiation therapy (2,000 rad) but they had no better 5-year cancer-specific survival rates than did nonirradiated patients. Transurethral resection and/or preoperative radiation therapy resulted in a pathological status of T0 in 43 patients but this did not confer a survival advantage. Although bladder preservation is preferable, low operative mortality and pelvic recurrence rates, as well as new methods of continent urinary diversion continue to make radical cystectomy the definitive form of therapy for patients with superficial disease recalcitrant to transurethral therapy.

The impact of medical care on the quality and length of life of the population has been poorly documented. The rapid growth of evidence of efficacy of therapy for individual medical conditions now offers the opportunity to create an inventory of benefits. A method for creating such an inventory is described, as is its application to a selection of condition-treatment pairs, chosen for their high incidence of prevalence, their serious outcomes, and the demonstrated efficacy of their treatment. An aggregate effect of medical care on life expectancy is found to be roughly five years during this century, with a further potential of two years. Although there is no overall index of quality of life analogous to life expectancy, our inventory demonstrates the enormous burden of pain, suffering, and dysfunction that afflicts the population for which medical care can provide a large measure of relief.

A retrospective review was performed on all patients with stage D1 prostate cancer treated at Duke University Medical Center between 1975 and 1989. A total of 156 patients underwent staging pelvic lymph-node dissection for clinically organ-confined prostate cancer (stage A or B) but were found to have disease metastatic to the pelvic lymph nodes (stage D1). Of this population, 42 patients also underwent radical prostatectomy (group 1), leaving 114 who did not have their prostate removed (group 2). The median cancer-specific survival was 11.2 years for group 1 versus 5.8 years for group 2 (P = 0.005). In patients with one or two positive lymph nodes the median cancer-specific survival was 10.2 years for group 1 versus 5.9 years for group 2 (P = 0.015). There was no difference in survival if three or more lymph nodes were positive. Adjuvant treatment with immediate androgen deprivation and/or postoperative radiation therapy failed to improve the survival experience. The incidence of local problems, including stricture formation, bleeding, or regrowth of cancer requiring dilation or surgical intervention (transurethral prostatectomy) averaged 9.5% in group 1 and 24.6% in group 2. These data show that patients with limited node-positive disease selected for radical prostatectomy experience a survival advantage over those denied such therapy and that this advantage is independent of adjunctive therapy.

This introduction and the three essays that follow examine ambulatory cardiac monitoring for specific clinical indications. They also examine the ways in which evidence from the literature may be synthesized through the framework of decision analysis to guide its appropriate use and identify areas in which more research is needed. The essays discuss ambulatory cardiac monitoring for evaluation of syncope in the elderly; detection of silent ischemia after a myocardial infarction; and selection of antiarrhythmic drugs for malignant ventricular arrhythmias.

Given a group of individuals presenting with syncope, the use of the standard diagnostic maneuvers will yield a diagnosis for approximately half. Promising new diagnostic tests offer the prospect of more efficient diagnostic pathways and treatments and demonstrate the need for better clinical trials before they are adopted.

We developed a self-administered patient questionnaire that asks for data concerning the time to receive services (access to care), communication between providers (coordination of care), and follow up after tests and treatment (continuity of care). From these data, we construct rates of performance about the clinical management systems that support provision of these services. Rates of system performance are calculated for indicators using patients' responses to survey questions. These indicators add the number of patients reporting a problem of those patients who have encountered a particular clinical management system. Information derived from 3000 patient questionnaires is matched with data abstracted from health care medical records. The sensitivity and specificity of patient reports are being evaluated for all indicators classified as gold standards for medical records. Indicators considered gold standard items for patient reports are matched for agreement with any information contained in the medical record. Also, patient characteristics associated with accurate reporting is to be assessed using multivariate logistic regression models.

Background: A recent consensus conference on bladder carcinoma highlighted the need for pathologic predictors of outcome for patients with transitional cell carcinoma of the bladder. This review was undertaken to determine the pathologic features predictive of cancer-specific survival after a radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder and prostate., Methods: Between 1969 and 1990, 531 patients with transitional cell carcinoma of the bladder and prostate were treated with radical cystectomy at the Duke University Medical Center. Records and pathologic specimens were analyzed and correlated with outcome. Both univariate and multivariate analyses of the pathologic staging were performed to identify variables predictive of cancer-specific survival., Results: Univariate analysis indicated that pathologic tumor (pT) stage, positive nodes, positive surgical margins, prostatic stromal involvement, grade, age, ureteral involvement, squamous cell carcinoma, and squamous cell differentiation in the specimen all were predictive of poor cancer-specific survival. Carcinoma in situ (CIS) in the specimen was not an adverse prognostic indicator. Multivariate analysis demonstrated that the pT stage, nodal involvement, positive surgical margins, patient's age at surgery, and loss of histologic differentiation were predictive of poor cancer-specific survival. CIS was found again not to have a negative influence on cancer-specific survival., Conclusions: If any of these features are noted in the final pathologic specimen, patients should be considered for some form of additional postoperative treatment such as chemotherapy or radiation therapy in an attempt to improve their chances for cancer-free survival. These factors will become more important in selecting which patients should be placed in developing adjuvant clinical trials.

Current bias would conclude that elevation of serum prostate specific antigen (PSA) after radical prostatectomy infers failure of the procedure. Since April 1987 preoperative and postoperative serum PSA levels have been obtained on 226 patients who underwent radical perineal prostatectomy for presumed organ confined prostate cancer (stage T1-2N0M0). Clinical failure as defined by elevation of serum acid phosphatase, biopsy proved local recurrence or evidence of malignant disease on bone scan has occurred in 3.9% of the patients with organ confined, 7.0% with specimen confined and 13.2% with margin positive disease. However, when a PSA elevation of greater than 0.5 ng./ml. was used as an indicator of failure the failure rate became 9.8% for the organ confined group, 39.4% for the specimen confined group and 66.0% for margin positive group. Of the patients who failed clinically the interval from initial elevation of postoperative PSA to clinical detection of failure ranged from 2 to 28 months (median 16). Among the patients with an elevated postoperative PSA level but who have not clinically failed followup ranged from 4 to 46 months (median 23). A total of 11 patients had no evidence of failure at greater than 36 months despite the elevated postoperative serum PSA level. These PSA elevations in patients who undergo supposed curative therapy are distressing. However, at this time the majority of these patients have not failed. In the clinically cured patient biochemical evidence of failure may not be sufficient to change the treatment course.

Background: Prostate-specific antigen (PSA) is an important marker for adenocarcinoma of the prostate and is of clinical utility in assessment of residual carcinoma after radical prostatectomy. Although elevated postoperative serum PSA levels have been linked to pathologic stage in radical prostatectomy specimens, limited data are available on the relationship of postoperative PSA levels to margin positivity, intraglandular tumor extent, and histologic grade., Methods: Initial postoperative serum PSA levels were related to pathologic features of 90 radical prostatectomy specimens with adenocarcinoma of the prostate. Logistic regression analysis was used to stratify pathologic stage, percentage intraglandular carcinoma, histologic grade, and margin positivity as predictors of elevated initial postoperative PSA levels., Results: Pathologic stage, percentage carcinoma, and margin positivity were nearly equivalent in strength of prediction, whereas Gleason histologic grade was a significant but less reliable predictor of elevated initial postoperative PSA levels. Thirty-one of 51 (60.8%) patients with extension of carcinoma outside the prostate gland had an elevated initial postoperative PSA level, whereas only 5 of 39 (12.8%) patients with organ-confined carcinoma had an elevated postoperative PSA level. Intraglandular tumor extent greater than 10% was associated with a greater likelihood of an elevated postoperative PSA level. Additional predictive capacity was obtained with concurrent use of pathologic stage and percentage carcinoma or margin positivity in multivariate analysis., Conclusions: In radical prostatectomy specimens, pathologic stage, intraglandular carcinoma extent, and margin positivity are particularly important morphologic parameters because they are predictive of residual carcinoma that is detected early, as judged by an elevated initial postoperative serum PSA level.

A retrospective review was performed on all 675 patients who underwent radical cystectomy and urinary diversion during 2 decades. Of the patients 197 were treated from 1969 to 1979 (group 1) and 478 were treated from 1980 until 1990 (group 2). The mean age of patients in group 1 was 56.7 years versus 64.2 years in group 2 (p < 0.001). The overall operative mortality rate in both groups was 2.5%. A total of 215 patients (31.9%) experienced postoperative complications (within 30 days of surgery). The morbidity rate was nearly identical between the 2 groups (32.0% for group 1 versus 31.8% for group 2, p = 0.962). Of note, however, there was a decreased incidence of wound infections and wound dehiscence among the patients in group 2 compared to group 1. Long-term complications occurred in 198 of the 675 patients (29.3%). At followup group 1 had a 35.5% incidence of long-term complications versus 26.8% in group 2 (p = 0.022). Most notably there was significant improvement in the incidence of ureteroenteric anastomotic strictures when comparing groups 1 (11.2%) and 2 (5.2%) (p = 0.006).

Persistent perineal pain, unresponsive to antibiotics and analgesia, sufficient to produce an inability to function in any work or social environment is occasionally encountered. A total of 5 such patients underwent total prostatoseminal vesiculectomy: 3 experienced complete relief of the pain and 1 experienced symptomatic relief to the extent that he ranks the residual discomfort as 1 on a scale of 1 to 10. The remaining patient had complete absence of pain for approximately 4 months but thereafter mild, intermittent proximal urethral discomfort developed during voiding. Total prostatoseminal vesiculectomy may be occasionally applicable in the patient disabled by chronic perineal pain. We believe that psychiatric evaluation and concurrence should be a preoperative prerequisite.

Radical prostatectomy is frequently recommended for the treatment of localized adenocarcinoma of the prostate. The use of the perineal versus the retropubic approach is mostly dependent upon the experience of the individual surgeon. This study was performed to evaluate the short-term differences between the 2 operations. Between 1988 and 1989, 173 patients were identified with organ confined prostate cancer (stage A or B) who were treated with radical prostatectomy. Of this total population 122 patients underwent radical perineal prostatectomy (group 1) and 51 patients underwent radical retropubic prostatectomy (group 2). The median estimated blood loss for group 1 was 565 cc and for group 2 it was 2,000 cc (p less than 0.001). Group 1 received a median of 0 units of blood during hospitalization, while group 2 received a median of 3 units of blood (p less than 0.001). The total operative time was slightly shorter for group 1 but the anesthesia time was similar for both patient populations. There was no difference in the incidence of positive surgical margins, and in in-hospital and long-term complication rates between the 2 groups. In light of these significant findings it is our belief that the radical perineal prostatectomy is an excellent approach for the treatment of adenocarcinoma of the prostate.

Prostatic specific antigen (PSA) is considered an antigen unique to benign and malignant prostatic tissue. Recent evidence in the literature has raised serious doubts about the specificity of this antigen. In this study twenty male urethral specimens were evaluated for PSA and prostatic acid phosphatase (PAP) from patients without evidence of prostatic cancer. Eight of these 20 urethral specimens exhibited strong immunostaining for both PSA and PAP, localized in the periurethral glands. Five of the 17 urethral biopsies were positive for both antigens, while all three of the whole mount autopsy specimens stained positive for PSA and PAP. Within the autopsy series, there was heterogenous staining of the periurethral glands within the same specimen. This evidence disproves the fact that PSA and PAP are organ specific as previously described. More than likely any tissue of cloacal origin has potential for staining positive for prostatic specific antigen and prostatic acid phosphatase.

Laparoscopic cholecystectomy has quickly become the treatment of choice by most surgeons for the treatment of gallstone disease. The authors reviewed their first 100 consecutive patients undergoing laparoscopic cholecystectomy at a rural hospital. Twenty-three patients had previous abdominal procedures. The open insufflation technique was used on all patients with previous abdominal operations, with the exception of those who had an appendectomy only. Operative cholangiography was performed routinely and successfully on all patients, with the exception of the first seven because of nonavailability of a cholangiocath. In 54 percent of the first two-thirds of these patients, the operation was completed in less than 1.5 hours. In contrast, 88 percent of the last one-third of the patients were operated on within the same time period. All but 9 of the 100 patients were discharged within 24 hours of their surgery. Laparoscopic cholecystectomy can be performed safely and routinely in the rural hospital setting with results similar to those expected in larger metropolitan centers.

A family is presented in which 4 of 4 (100%) siblings demonstrate vesicoureteral reflux on voiding cystogram. Mechanisms of inheritance are reviewed.

We report the morphologic, immunohistochemical, and electron microscopic characteristics observed in a case of an inverted papilloma that contained neuroendocrine cells resected from the urinary bladder of a 77-year-old woman. Additionally, we evaluated the incidence of neuroendocrine cells in eight cases of inverted papillomas of the urinary bladder obtained from the files of the Armed Forces Institute of Pathology, Washington, DC. To our knowledge, an in-depth study of neuroendocrine cells in this neoplasm and a comparison of the same with neuroendocrine cells observed in other conditions in the lower genitourinary tract have not been previously published, prompting this report.

To determine the usefulness of the Bosniak classification of cystic renal masses, the computed tomographic (CT) and ultrasound findings of 16 pathologically proven cystic renal masses were retrospectively reviewed. All imaging studies were reviewed and categorized utilizing the Bosniak classification without knowledge of the final pathologic diagnosis. There were no category I lesions (classical simple cyst), four category II (minimally complicated), seven category III lesions (more complicated), and five category IV lesions (probable malignant). All category II lesions were benign, all category IV lesions were malignant. Of the seven category III lesions, three were benign and four were malignant. We conclude that the Bosniak classification is extremely useful in the management of cystic renal masses.

There is a previously unobserved connection between corporal punishment of public school children and capital punishment of juveniles. Both are barometers of acceptable levels of violent punishment and their elimination is a hallmark of a maturing and decent society. Within a majority of the eighteen states where school authorities most frequently strike children are housed 25 of the nation's 28 juvenile death row inmates. On average, the homicide rates of these jurisdictions are two and a half times greater than those that have abolished both state-sanctioned corporal and capital punishment or limit death sentences to those age eighteen and older at the time of their crime(s). Most of the eighteen state abolitions of corporal punishment occurred in the 1980's. The US Supreme Court has ruled both corporal and capital punishment of juveniles constitutional. Additional state legislative abolition of both is anticipated in the 1990s.

Three postoperative patients with oliguirc renal failure and hypochloremic metabolic alkalosis were treated with hemodialysis using a specailly prepared high-chloride, low-acetate dialysate. This mode of therapy corrected the metabolic abnormalities and was significantly more effective than treatment with commercially available high-acetate dialysate at increasing the serum chloride and hydrogen ion concentration. Furthermore, hemodialysis with high-chloride, low-acetate dialysate corrected the clinical sequelae of hypoventilation, cardiac arrhythmia, and neuromuscular irritability associated with metabolic alkalosis while treating uremia simultaneously.

The tissue adhesive butyl cyanoacrylate was evaluated in the repair of injured porcine kidneys following low-velocity ballistic trauma. This technique was compared to the classic renal repair using chromic suture and a patch of perirenal fat. The repair with butyl cyanoacrylate was less time consuming (four minutes vs. 28 minutes for the controls) and decreased blood loss (67 cc vs. 180 cc for the controls). Ten days post injury the kidneys repaired with tissue adhesive showed minimal intraparenchymal hemorrhage or perirenal bleeding, while two of the four (50%) suture-repaired kidneys showed intrarenal microhemorrhages and one (25%) developed a perirenal hematoma. Perirenal adhesions were noted in both groups. Vital signs, IVP's, creatinine clearance, and serum and urine chemistries were nearly identical in the two groups. The results show that low-velocity ballistic injuries of renal tissue can be repaired effectively and more efficiently with the use of butyl cyanoacrylate when compared to conventional suturing methods.

Family therapy has traditionally centered on the nuclear family and thus has been typically oriented toward urban white middle-class families. A variety of modifications in therapeutic technique has evolved for work with the many modern families whose structure consists of a functional psychosocial family kinship. The authors have developed a formal theoretical framework and model for family therapy that encompasses the total psychosocial network, i.e., the extended kinships of the nuclear family and the functional kin such as friends, neighbors, and associates.

The driving force for active transport of Na+ in the isolated toad bladder, ENa, was measured as the reciprocal slope of the change in conductance with change in short-circuit current after stimulation with antidiuretic hormone. The base-line short-circuit current was altered by change in ambient Na+ concentration or addition of amiloride, maneuvers which alter availability of Na+ at the site of active transport. In the absence of a chemical gradient for Na+ across the bladder, ENa was found to be inversely related to the rate of Na+ transport, a finding incompatible with the simple electrical analogue that has been proposed for the system. The results provide additional support for the view that ENa measured in this way has both energetic and kinetic components.

Many nurses and nursing students live far from the closest campus or health care agency that can provide basic or continuing education. Videoteleconferencing is one way to bridge this distance. As videoteleconferencing technologies become available and cost effective, nurse educators must be knowledgeable about their use. The authors explain telecommunications technologies of videoteleconferencing, identify advantages and disadvantages, and discuss planning, implementation, and evaluation for offering a program by videoteleconference.

Fifty-five patients with extensive-disease small cell bronchogenic carcinoma received three courses of intensive, inpatient, remission induction chemotherapy in (25 patients) or out (30 patients) of protected environment-prophylactic antibiotic (PEPA) units. Chemotherapy consisted of ECHO induction (E = epipodophyllotoxin VP-16-213; C = cyclophosphamide; H = hydroxydaunorubicin; O = Oncovin) and PRIME maintenance (PR = procarbazine; I = ifosfamide; ME = methotrexate). All evaluable patients (22 in the protected environment group and 26 in the control group) had a complete (50 percent in the protected environment group and 54 percent in the control group) or partial (50 percent in the protected environment group and 46 percent in the control group) remission. Median response and survival durations for both treatment groups were similar. The median survival duration of patients with a complete remission favored the protected environment group (16.5 versus 12.67 months; p = 0.20). Two patients (one from each group) are alive and disease-free for more than four years. Myelosuppression was intense and more pronounced in the protected environment group (p less than or equal to 0.01). Infectious complications were less common in patients receiving intravenous prophylactic antibiotics and in those treated with intravenous antibiotics in PEPA units (p less than or equal to 0.04). There were no treatment-related deaths, although treatment might have contributed to the death of three patients in the protected environment group and four in the control group. The administration of intensive ECHO induction chemotherapy to patients with extensive small cell bronchogenic carcinoma produced a high complete remission rate, although there was no significant long-term survival advantage over a program of less intensity. The administration of intravenous prophylactic antibiotics and the use of PEPA units significantly reduced the infectious morbidity of chemotherapy.