The effects of caffeine on bone mineral density and fracture risk.

Caffeine is a regular part of the diet of many adults (coffee, tea, soft drinks, and energy drinks). Multiple molecular effects of caffeine suggest that it may promote bone loss. Given the extensive consumption of caffeine worldwide, any impact of caffeine consumption on bone strength and/or density would have large population health implications. The most well-established pharmacological effect of caffeine is non-specific antagonism of adenosine receptors. Adenosine regulates bone metabolism in a complex manner, with in vitro studies suggesting that direct stimulation of adenosine A2A and A2B receptors induces bone formation by activating osteoblasts and suppressing osteoclast differentiation and function. Thus, competitive inhibition of adenosine A2 receptors by caffeine may inhibit bone formation and promote bone resorption. However, antagonism of adenosine A1 receptors may have opposing effects. Caffeine has also been suggested to affect bone through derangement of calcium metabolism, alteration of vitamin D responses, and other mechanisms. In clinical and population-based studies, the impact of caffeine consumption on bone metabolism offers a mixed picture, with some but not all studies suggesting a potential link between caffeine intake and reduced bone mineral density or increased fracture risk. Differences in methodology, selected populations, and duration/timing of the studies may account for study outcome discrepancies. The in vitro effects of caffeine on cells involved in bone metabolism suggest that caffeine intake may promote osteoporosis, and some but not all clinical studies support a modest adverse caffeine impact. Herein, we describe the basic biology of caffeine as it pertains to bone, review the clinical literature to date, and consider the implications of the current data on clinical practice and future studies.

Muscle-building supplement use and increased risk of testicular germ cell cancer in men from Connecticut and Massachusetts.

BACKGROUND: No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk. METHODS: We conducted a population-based case-control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts. RESULTS: The odds ratio (OR) for ever use of MBSs in relation to risk of TGCC was significantly elevated (OR=1.65, 95% confidence interval (CI): 1.11-2.46). The associations were significantly stronger among early users, men with more types of MBSs used, and longer periods of use. CONCLUSIONS: MBS use is a potentially modifiable risk factor that may be associated with TGCC.

Micro-finite element analysis applied to high-resolution MRI reveals improved bone mechanical competence in the distal femur of female pre-professional dancers.

UNLABELLED: Micro-finite element analysis applied to high-resolution (0.234-mm length scale) MRI reveals greater whole and cancellous bone stiffness, but not greater cortical bone stiffness, in the distal femur of female dancers compared to controls. Greater whole bone stiffness appears to be mediated by cancellous, rather than cortical bone adaptation. INTRODUCTION: The purpose of this study was to compare bone mechanical competence (stiffness) in the distal femur of female dancers compared to healthy, relatively inactive female controls. METHODS: This study had institutional review board approval. We recruited nine female modern dancers (25.7±5.8 years, 1.63±0.06 m, 57.1±4.6 kg) and ten relatively inactive, healthy female controls matched for age, height, and weight (32.1±4.8 years, 1.6±0.04 m, 55.8±5.9 kg). We scanned the distal femur using a 7-T MRI scanner and a three-dimensional fast low-angle shot sequence (TR/TE=31 ms/5.1 ms, 0.234 mm×0.234 mm×1 mm, 80 slices). We applied micro-finite element analysis to 10-mm-thick volumes of interest at the distal femoral diaphysis, metaphysis, and epiphysis to compute stiffness and cross-sectional area of whole, cortical, and cancellous bone, as well as cortical thickness. We applied two-tailed t-tests and ANCOVA to compare groups. RESULTS: Dancers demonstrated greater whole and cancellous bone stiffness and cross-sectional area at all locations (p<0.05). Cortical bone stiffness, cross-sectional area, and thickness did not differ between groups (>0.08). At all locations, the percent of intact whole bone stiffness for cortical bone alone was lower in dancers (p<0.05). Adjustment for cancellous bone cross-sectional area eliminated significant differences in whole bone stiffness between groups (p>0.07), but adjustment for cortical bone cross-sectional area did not (p<0.03). CONCLUSIONS: Modern dancers have greater whole and cancellous bone stiffness in the distal femur compared to controls. Elevated whole bone stiffness in dancers may be mediated via cancellous, rather than cortical bone adaptation.

Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis.

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6S271), with a maximum lod score of 2.2 occurring near D6S274, located in 6p22. However, we obtained a lod score of -2 at D6S296, the locus found by others to provide the greatest linkage evidence. At D6S274, we report a positive lod score as do Straub et al. (individually non-significant). A combined total lod of 3.6-4.0 suggests the possibility of a susceptibility locus in this region. However, methodological differences between our studies makes a firm conclusion difficult.

Abdominal incision defect following AAA-surgery (AIDA): 2-year results of prophylactic onlay-mesh augmentation in a multicentre, double-blind, randomised controlled trial.

The reported incidence of incisional hernia following repair of abdominal aortic aneurysm (AAA) via midline laparotomy is up to 69%. This prospective, multicenter, double-blind, randomised controlled trial was conducted at eleven hospitals in Germany. Patients aged 18 years or older undergoing elective AAA-repair via midline incision were randomly assigned using a computer-generated randomisation sequence to one of three groups for fascial closure: with long-term absorbable suture (MonoPlus®, group I), long-term absorbable suture and onlay mesh reinforcement (group II) or extra long-term absorbable suture (MonoMax®, group III). The primary endpoint was the incidence of incisional hernia within 24 months of follow-up, analysed by intention to treat. Physicians conducting the postoperative visits and the patients were blinded. Between February 2011 and July 2013, 104 patients (69.8 ± 7.7 years) were randomised, 99 of them received a study intervention. The rate of incisional hernia within 24 months was not significantly reduced with onlay mesh augmentation compared to primary suture (p = 0.290). Furthermore, the rate of incisional hernia did not differ significantly between fascial closure with slow and extra long-term absorbable suture (p = 0.111). Serious adverse events related to study intervention occurred in five patients (5.1%) from treatment groups II and III. Wound healing disorders were more frequently seen after onlay mesh implantation on the day of discharge (p = 0.010) and three (p = 0.009) and six (p = 0.023) months postoperatively. The existing evidence on prophylactic mesh augmentation in patients undergoing AAA-repair via midline laparotomy probably needs critical review. As the implementation of new RCTs is considered difficult due to the increasing number of endovascular AAA treated, registry studies could help to collect and evaluate data in cases of open AAA-repair. Comparisons between prophylactic mesh implantation and the small bite technique are also required. Trial registration: ClinicalTrials.gov Identifier: NCT01353443. Funding Sources: Aesculap AG, Tuttlingen, Germany.

Non-destructive and quantitative imaging of a nano-structured microchip by ptychographic hard X-ray scanning microscopy.

We used hard X-ray scanning microscopy with ptychographic coherent diffraction contrast to image a front-end processed passivated microchip fabricated in 80 nm technology. No sample preparation was needed to image buried interconnects and contact layers with a spatial resolution of slightly better than 40 nm. The phase shift in the sample is obtained quantitatively. With the additional knowledge of the elemental composition determined in parallel by X-ray fluorescence mapping, quantitative information about specific nanostructures is obtained. A significant enhancement in signal-to-noise ratio and spatial resolution is achieved compared to conventional hard X-ray scanning microscopy.

Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease.

Previous studies support a role for intestinal epithelial cells (IEC) as antigen-presenting cells in mucosal immune responses. T cells activated by IEC are CD8+, suppressor in function, and dependent upon CD8-associated p56lck activation. A 180-kD glycoprotein (gp180) recognized by mAbs B9 and L12 has been identified and shown to be important in CD8+ T cell activation by IEC. Since IEC derived from patients with inflammatory bowel disease (IBD) are incapable of activating CD8+ T cells, we asked whether this correlated with gp180 expression. While frozen sections of normal bowel revealed bright gp180 staining on all IEC, both inflamed and uninflamed ulcerative colitis (UC) specimens showed patchy staining. In Crohn's disease (CD), staining was faint to absent. Flow cytometry confirmed immunohistochemical data. The staining patterns correlated with the ability of IEC to activate CD8-associated p56lck. Normal IEC induced phosphorylation of p56lck in CD8alpha but not CD4+ transfectants. In contrast, both UC and CD IEC activated CD4 and, to a much lesser extent, CD8-associated p56lck. Thus, gp180 expression by IBD IEC appears to be altered, and correlates with a functional alteration of lck activation. This defect may reflect a more proximal event in the pathogenesis of IBD.

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

BACKGROUND: In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. METHODS: Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml-1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. RESULTS: At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. CONCLUSIONS: EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Fibroblast growth factor 4 transfection of MCF-7 cells produces cell lines that are tumorigenic and metastatic in ovariectomized or tamoxifen-treated athymic nude mice.

Successful antiestrogen treatment in patients with tamoxifen-responsive breast tumors is often followed by an outgrowth of tumors cells that are antiestrogen resistant, implying that estrogen-dependent tumors can become estrogen-independent. In an effect to mimic this progression, we have transfected fibroblast growth factor 4 into MCF-7 cells, a human breast carcinoma cell line that is estrogen-dependent for growth in nude mice. This transfection results in cell lines that form progressively growing, metastatic tumors when injected s.c. into untreated or tamoxifen-treated ovariectomized nude mice. In contrast to the parental cell line, growth of transfected cells in ovariectomized nude mice is stimulated by tamoxifen treatment and inhibited by estrogen treatment of the mice. Parental MCF-7 cells were transfected with an expression vector for beta-galactosidase, conferring the ability to convert the chromogenic substrate, 5-bromo-4-chloro-3-indoyl-beta-galactoside, to a blue color and allowing the detection of their presence within tumors developing after coinoculation with fibroblast growth factor 4-transfected cells. The fibroblast growth factor 4-transfected cells could support growth and metastasis of the beta-galactosidase-expressing parental cell line when both lines were coinjected into the same site in untreated or tamoxifen-treated, ovariectomized mice. These data suggest a possible role for fibroblast growth factors in the progression of breast tumors to an estrogen-independent, antiestrogen-resistant, metastatic phenotype. They also support a role for paracrine factors in mixed populations of tumor cells of differing states of malignant progression.

Intensive outpatient adjuvant therapy for breast cancer: results of dose escalation and quality of life.

PURPOSE: A dose-escalation study was conducted to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cyclophosphamide (CY) in combination with granulocyte colony-stimulating factor (G-CSF0 and doxorubicin (DOX) given every 2 weeks for eight cycles as outpatient adjuvant therapy for node-positive breast cancer. A pilot study to assess quality of life (QOL) was performed. PATIENTS AND METHODS: From March 1991 to April 1993, 19 patients were entered. Patients received escalating doses of CY intravenously (i.v.) (1,000 mg/m2, 1,500 mg/m2, 2,000 mg/m2, or 2,500 mg/m2) with DOX 40 mg/m2, G-CSF 10 micrograms/kg/d on days 2 to 12, and mesna, every 2 weeks for eight cycles. QOL was measured by the Profile of Mood States (POMS), the Psychosocial Adjustment to Illness Scale-Self Report (PAIS-SR), and a 27-item QOL scale. RESULTS: The CY dose of 2,500 mg/m2 every 2 weeks elicited toxicities that required dose reductions secondary to a combination of thrombocytopenia, hematuria, and anemia that required transfusion. The dose of 2,000 mg/m2 resulted in an acceptable toxicity profile. Ninety-two percent of cycles at the 2,000-mg/m2 dose were delivered on schedule and 77% without hospitalization. QOL assessments indicated high levels of distress measured by POMS in 47%, poor overall quality of life in 40%, and significant problems with physical symptoms in less than 27% of all patients for any given cycle. CONCLUSION: A dose of CY at 2,000 mg/m2 can be administered every 2 weeks with DOX and G-CSF for eight cycles in the outpatient setting with manageable toxicity. The majority of women described levels of physical symptoms and emotional distress as tolerable during treatment.

Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.

PURPOSE: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. PATIENTS AND METHODS: Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. RESULTS: Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] >/= 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD >/= 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E(1)), estradiol (E(2)), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E(1) and E(2) levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. CONCLUSION: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.

Scanning electronmicroscopy of experimental anencephaly development.

The scanning electronmicroscope was used to study the development of anencephaly in an experimental model. Anencephaly was produced consistently, using vitamin A as the teratogen. Embryos destined to become anencephalic displayed failure of opposing sides of the rostral neural tube to fuse. Subsequently, the neural folds of the experimental embryos progressively curved laterally away from the midline, whereas the neutral folds of the control embryos fused in the midline by day 12. The anlage of the choroid plexus could be identified on the surface of the everting brain folds as early as gestational day 13. Thus, the abnormal eversion of the neural tube occurred before development of the choroid plexus. This study supports the view that anencephaly ultimately results from neural tube nonclosure.

Clinical trials in acute musculoskeletal injury states. An analysis of methodology.

Therapeutic evaluation of nonsteroidal anti-inflammatory drugs in the treatment of acute musculoskeletal diseases and injuries requires the use of adequate models for clinical trials. The objective of a short-term pain study is to determine whether a new treatment is effective and how it compares with a standard or reference drug for the indication being evaluated. Among the requirements for the pain model study are proper protocols and adequate, homogeneous patient populations. Problems in establishing the model include difficulty in finding adequate numbers of patients, inappropriate sites, patient resistance, and varying conditions of natural recovery. Suggestions are presented for conducting these studies: relying on global pain relief scores, keeping a home diary that is simple and objective, and extending the initial observation period in the office to generate single-dose data in a controlled environment. Sports medicine models are useful in allowing investigators the necessary numbers of patients and providing data that meaningfully address pharmacologic treatment for acute musculoskeletal disorders.

Crystal deposition disease. Diagnosis by electron microscopy.

The diagnosis of gout and pseudogout has traditionally been established by the identification, in synovial fluid, of monosodium urate and calcium pyrophosphate dihydrate crystals with compensated polarizing light microscopy. In this paper the utility of electron microscopy in establishing these diagnosis in two cases, when the conventional means of synovial fluid analysis had failed to do so, is discussed. The application of ultrastructural analysis of synovial fluid increases diagnostic capability in the crystal deposition diseases, and it is recommended for those patients in whom the more usual studies have not established a diagnosis.

Tamoxifen for the reduction in the incidence of breast cancer in women at high risk for breast cancer.

Recent legislation, including the Prescription Drug User Fee Act (1992) and the FDA Modernization Act (FDAMA) (1997), has provided an environment in which new drug applications (NDA) can be efficiently reviewed, resulting in rapid access to new drugs or to new uses for approved drugs by the public. The recent submission of a supplemental NDA for tamoxifen for the reduction in the incidence of breast cancer in women at high risk for breast cancer is an excellent example of the application of this legislation. First, the application received expedited but thorough multidisciplinary and interdivisional review by the FDA. Second, it required collaboration between the manufacturer (AstraZeneca Pharmaceuticals), the National Surgical Adjuvant Breast and Bowel Project (NSABP), the National Cancer Institute (NCI), and the FDA. This process worked well and demonstrated that cooperative group data can be used effectively to support an application. Third, a single large adequate and well-controlled trial was sufficient to support the effectiveness of tamoxifen for this indication. The quantity of evidence required to support approval has been discussed in FDA guidances ("Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products") and is part of FDAMA.

Long-term therapy for the pain of osteoarthritis: a comparison of zomepirac sodium and aspirin.

In this long-term, double-blind, multicenter study, efficacy and safety of zomepirac sodium were compared with those of aspirin for treatment of the chronic pain associated with osteoarthritis in 607 patients, 405 of whom received zomepirac and 202 of whom received aspirin. Final evaluations during one year of treatment showed zomepirac significantly more effective than aspirin for reducing pain at rest (P = 0.02) and average pain (P = 0.04). Moreover, zomepirac was rated better than aspirin in physician global evaluations of overall response to therapy (P = 0.02) and patient evaluations of pain relief (P = 0.03). At the end of the one-year study, patients were permitted to extend double-blind treatment for an additional year. In final evaluations for patients who continued, zomepirac was significantly better than aspirin for relief of pain on motion (P = 0.05) and also in patient global evaluations of therapeutic response (P = 0.02). Side effect profiles during the first year of therapy were generally comparable for zomepirac and aspirin. However, complaints related to the special senses, especially tinnitus and hearing disturbances, were reported more frequently during aspirin therapy, and urogenital side effects were more common during zomepirac therapy. For both drug groups, the overall incidence of side effects was lower in the second year than in the first. This is the first published study to show a nonsteroidal antiinflammatory agent to be more effective than aspirin for the long-term treatment of pain associated with osteoarthritis.

An appraisal of codeine as an analgesic: single-dose analysis.

Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult.

Postsurgical pain: zomepirac sodium, propoxyphene/-acetaminophen combination, and placebo.

Zomepirac sodium, a new, nonnarcotic analgesic agent, was compared with the combination of propoxyphene/acetaminophen in a placebo-controlled, double-blind, single-dose study in 196 hospitalized postsurgical patients with pain severe enough to require a prescription analgesic. Patients received 100 mg zomepirac sodium, 50 mg zomepirac sodium, 100 mg propoxyphene napsylate with 650 mg acetaminophen, or placebo. Total pain relief during the 6-hour observation period showed that 100 mg zomepirac sodium was significantly more effective than the propoxyphene combination. All active drugs were superior to placebo. Percentages of patients requiring remedication before the end of the study were: 77 per cent for placebo, 48 per cent for propoxyphene/acetaminophen, 43 per cent for 50 mg zomepirac sodium, and 29 per cent for 100 mg zomepirac sodium. The numbers of patients reporting side effects were not significantly different among the treatment groups. These results confirm those of other single-dose pain studies which showed 100 mg zomepirac sodium significantly more efficacious than the propoxyphene/acetaminophen combination.

Non-Hodgkin's lymphoma can mimic renal adenocarcinoma with inferior vena caval involvement.

Genitourinary involvement in both Hodgkin's and non-Hodgkin's lymphomas is common and can be confused with other benign and malignant urologic conditions. While lymphoma commonly produces vascular and ureteral encasement, intraluminal vascular involvement is rare. Indeed, there are no previous reports of renal lymphoma with tumor thrombus extending into both the renal vein and inferior vena cava. We describe the first reported case of lymphoma mimicking a Stage IIIA renal adenocarcinoma with tumor thrombus in the renal vein and the inferior vena cava. Renal lymphoma should be considered in the differential diagnosis even when tumor thrombus is present in the renal vein or vena cava.

Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.

PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.