Looking back at PCPT: looking forward to new paradigms in prostate cancer screening and prevention

OBJECTIVES: Provide a critical summary of the latest interpretation of findings from the Prostate Cancer Prevention Trial (PCPT). METHODS: Findings from PCPT and recently published post-hoc analyses are reviewed. RESULTS: PCPT demonstrated that finasteride can reduce the prevalence of prostate cancer, permitted the first large-scale assessment of the performance characteristics of prostate-specific antigen for prostate cancer screening, and identified new-onset erectile dysfunction as an early predictor of cardiovascular events. CONCLUSIONS: PCPT has and will continue to yield valuable information regarding future strategies for prostate cancer prevention and detection, benign prostatic hyperplasia, and other matters of public health importance.     

Surface contaminants inhibit osseointegration in a novel murine model

Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization procedures and affect osseointegration. The goals of this study were to develop a murine model of osseointegration in order to determine whether removing surface contaminants enhances osseointegration. To develop the murine model, titanium alloy implants were implanted into a unicortical pilot hole in the mid-diaphysis of the femur and osseointegration was measured over a five week time course. Histology, backscatter scanning electron microscopy and X-ray energy dispersive spectroscopy showed areas of bone in intimate physical contact with the implant, confirming osseointegration. Histomorphometric quantification of bone-to-implant contact and peri-implant bone and biomechanical pullout quantification of ultimate force, stiffness and work to failure increased significantly over time, also demonstrating successful osseointegration. We also found that a rigorous cleaning procedure significantly enhances bone-to-implant contact and biomechanical pullout measures by two-fold compared with implants that were autoclaved, as recommended by the manufacturer. The most likely interpretation of these results is that surface contaminants inhibit osseointegration. The results of this study justify the need for the development of better detection and removal techniques for contaminants on orthopedic implants and other medical devices.     

Differences in morphology and contractility of the bulbospongiosus and pubococcygeus muscles in nulliparous and multiparous rabbits

In women, birth trauma can result in altered anatomy of supporting structures of the pelvic floor and in the development of urinary incontinence. The goal of this study was to investigate the association between parturition and the morphology and function of perineal and pelvic muscles in the female rabbit. In ten nulliparous and ten multiparous same-age females, we investigated morphological, histological (n = 5 females/group), and contractile characteristics (n = 5 females/group) of the perineal bulbospongiosus (Bsm) and the pelvic pubococcygeus (Pcm) muscles. Bsm and Pcm muscles of multiparous females were significantly lighter, they had a smaller cross-sectional fiber area, and developed significantly lower twitch and tetanic tension force in response to electrical stimulation than muscles of nulliparous females. In female rabbits, multiparity is associated with potentially pathological changes in the morphological and functional characteristics of these perineal and pelvic muscles, possibly as a result of stretching during parturition.     

Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state.

Tumor necrosis factor (TNF)-alpha causes insulin resistance on glucose uptake in fetal brown adipocytes. We explored the hypothesis that some effects of TNF-alpha could be mediated by the generation of ceramide, given that TNF-alpha treatment induced the production of ceramide in these primary cells. A short-chain ceramide analog, C2-ceramide, completely precluded insulin-stimulated glucose uptake and insulin-induced GLUT4 translocation to plasma membrane, as determined by Western blot or immunofluorescent localization of GLUT4. These effects were not produced in the presence of a biologically inactive ceramide analog, C2-dihydroceramide. Analysis of the phosphatidylinositol (PI) 3-kinase signaling pathway indicated that C2-ceramide precluded insulin stimulation of Akt kinase activity, but not of PI-3 kinase or protein kinase C-zeta activity. C2-ceramide completely abolished insulin-stimulated Akt/protein kinase B phosphorylation on regulatory residues Thr 308 and Ser 473, as did TNF-alpha, and inhibited insulin-induced mobility shift in Akt1 and Akt2 separated in PAGE. Moreover, C2-ceramide seemed to activate a protein phosphatase (PP) involved in dephosphorylating Akt because 1) PP2A activity was increased in C2-ceramide- and TNF-alpha-treated cells, 2) treatment with okadaic acid concomitantly with C2-ceramide completely restored Akt phosphorylation by insulin, and 3) transient transfection of a constitutively active form of Akt did not restore Akt activity. Our results indicate that ceramide produced by TNF-alpha induces insulin resistance in brown adipocytes by maintaining Akt in an inactive dephosphorylated state.     

Neurovascular injuries in acetabular reconstruction cage surgery: an anatomical study

Acetabular reconstruction cages are indicated for severe combined segmental and cavitary acetabular bone defects. The purpose of this study was to evaluate the implications of screw placement and drill plunge and the potential insult to anatomical structures when implanting acetabular reconstruction cages. A segmental cavitary defect was reamed into the acetabulum and a cage was implanted in each of the 10 hemipelvises. The relative course of the superior gluteal neurovascular bundle was mapped to assess dissection intervals. When cage screws were placed at least 15 mm longer than needed, 13% and 20% of screws of the superior flange and anterior rim hit the femoral nerve, respectively, and approximately 60% of the screws placed in the posterior rim endangered the obturator nerve. A "safe zone" for screw size may be a 15- and 25-mm screw for the superior flange and posterior rim, respectively.     

Immediate and short-term benefit of multilesion coronary angioplasty: influence of degree of revascularization

The safety and short-term therapeutic benefit of multilesion percutaneous transluminal coronary angioplasty was assessed in 135 patients, 66 of whom had a minimum of 6 months of follow-up study. Primary success, defined as successful dilation of the most critical lesion or all lesions attempted without major in-hospital complications was obtained in 117 (87%) of the 135 patients. Cardiac complications associated with the procedure were uncommon; prolonged angina occurred in 5% and myocardial infarction in 3%; emergency coronary bypass surgery was performed in 4% of the patients. There were no deaths. Complete revascularization was achieved in 46% of the 117 patients with a primary success. Of the 66 patients eligible for 6 month follow-up, 80% had an uncomplicated course and required no further procedures. Clinical improvement by at least one angina functional class was observed in 90% of the patients. Cardiac events such as the need for a second revascularization procedure were significantly more common in patients who had incomplete versus complete revascularization (35 versus 9%; p = 0.018). Repeat coronary angiography performed an average of 5 months after angioplasty revealed restenosis in 18 of 22 symptomatic patients and 3 of 9 asymptomatic patients. Restenosis occurred at the site of a single dilation in 12 patients, at two sites in 8 patients and at three sites in 1 patient. Thus, multilesion coronary angioplasty is an important therapeutic option for selected patients with multivessel disease and can be performed with relatively low risk. Improvement in angina status can be expected even in patients who have incomplete revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evolution of the extraglottic airway: a review of its history, applications, and practical tips for success

The development of the laryngeal mask airway in 1981 was an important first step toward widespread use and acceptance of the extraglottic airway (EGA). The term extraglottic is used in this review to encompass those airways that do not violate the larynx, in addition to those with a supraglottic position. Although the term extraglottic may be broad and include airways such as tracheostomy tubes, the term supraglottic does not describe a large number of devices with subglottic components and is too narrow for a discussion of modern devices. EGAs have flourished in practice, and now a wide variety of devices are available for an ever-expanding array of applications. In this review we attempt to clarify the current state of EGA devices new and old, and to illustrate their use in numerous settings. Particular attention is paid to the use of EGAs in special situations such as obstetric, pediatric, prehospital, and nontraditional "out of the operating room" settings. The role of the EGA in difficult airway management is discussed. EGA devices have saved countless lives because they facilitate ventilation when facemask ventilation and tracheal intubation were not possible. Traditionally, difficult airway management focused on successful tracheal intubation. The EGA has allowed a paradigm shift, changing the emphasis of difficult airway management from tracheal intubation to ventilation and oxygenation. EGA devices have proved to be useful adjuncts to tracheal intubation; in particular, the combination of EGA devices and fiberoptic guidance is a powerful technique for difficult airway management. Despite their utility, EGAs do have disadvantages. For example, they typically do not provide the same protection from pulmonary aspiration of regurgitated gastric material as a cuffed tracheal tube. The risk of aspiration of gastric contents persists despite advances in EGA design that have sought to address the issue. The association between excessive EGA cuff pressure and potential morbidity is becoming increasingly recognized. The widespread success and adoption of the EGA into clinical practice has revolutionized airway management and anesthetic care. Although the role of EGAs is well established, the user must know each device's particular strengths and limitations and understand that limited data are available for guidance until a new device has been well studied.     

Healthcare disparities in Asians and Pacific Islanders with hepatocellular cancer

BackgroundHawaii has the highest incidence of hepatocellular cancer (HCC) in the United States and the largest proportion of Asians and Pacific Islanders. HCC studies generally combine these groups into 1 ethnicity, and we sought to examine differences between Asian and Pacific Islander subpopulations.MethodsDemographic, clinical, and treatment data for 617 patients with HCC (420 Asians, 114 whites, and 83 Pacific Islanders) were reviewed. Main outcome measures included HCC screening and liver transplantation.ResultsAsian and Pacific Islander subgroups had significantly more immigrants, and age was different between groups. Compared with whites, Pacific Islanders and Filipinos had less HCC screening and liver transplantation procedures, fewer met Milan criteria, and a smaller proportion of those with Milan criteria actually underwent transplantation.ConclusionsThere were significant differences in risk factors, clinical presentation, treatment, and access to care among Asian, Pacific Islander, and white patients with HCC. Future HCC studies may benefit from differentiating subgroups within Asian and Pacific Islander populations to better focus these efforts.     

Pancreatic Adenocarcinoma: Complete Tumor Extirpation Improves Survival Benefit Despite Larger Tumors for Patients Who Undergo Distal Pancreatectomy and Splenectomy

Introduction  

Patients with pancreatic adenocarcinoma have poor survival. Presumably, tumors in the body or tail of the pancreas, due to paucity of symptoms, present later than patients with tumors in the head of the pancreas. This study was undertaken to determine if tumors amenable to complete extirpation by distal pancreatectomy/splenectomy have worse survival when compared to their proximal counterparts.