A comprehensive histopathological evaluation of vascular medial fibrosis: insights into the pathophysiology of arterial stiffening.

Objective: Medial vascular fibrosis contributes to arterial stiffening and reduced compliance, increasing the risk of cardiovascular events. We undertook the first comprehensive histopathologic study of medium-to-large caliber blood vessels (carotid, coronary, dorsalis pedis, internal mammary, iliac, mesenteric, pulmonary, and renal arteries) in 100 autopsy subjects to characterize medial fibrosis in relation to cardiovascular risk factors.

Methods And Results: Masson Trichrome staining of vascular tissue microarrays (TMAs) was digitally analyzed to determine the percent fibrosis (% collagen) of over 700 vascular segments.

An anatomical study of external carotid artery vascular territories in face and midface flaps for transplantation.

Background: The technical success of facial composite tissue allotransplantation demands full understanding of superficial and deep perfusion for reliable microvascular transfer. Candidates with composite midface defects require an appreciation of the circulatory patterns to design a composite midface allotransplant.

Methods: External carotid vascular territories were evaluated in 10 cadavers to determine the reliability of facial soft-tissue flaps based on a single vascular pedicle.

Salvage transplantation for allograft failure using fludarabine and alemtuzumab as conditioning regimen.

Graft failure after allogeneic blood or marrow transplantation, although generally uncommon, can be a devastating complication. This report includes the outcome of nine patients who received a salvage transplant for failure to engraft after one (n=8) or 2 (n=1) prior transplants. Eight patients received allografts from the original donor.

Microsurgical reconstruction of posttraumatic high-energy maxillary defects: establishing the effectiveness of early reconstruction.

Background: Posttraumatic, high-energy defects of the midface can be challenging to reconstruct because they involve extensive composite tissue loss and result in significant permanent functional and cosmetic deformity. These injuries require replacement of the bony framework, external soft tissue, and intraoral mucosa. Local skin flaps and nonvascularized bone grafts have been used for reconstruction, but bony resorption and the associated soft-tissue collapse limit long-term viability.

Glucose-6-phosphate dehydrogenase deficiency: an etiology for idiopathic priapism?

Introduction: Efforts to identify the health risk associations for priapism may reveal pathophysiologic mechanisms for the disorder and suggest a scientifically rational approach for correcting it.

Aim: We describe a clinical presentation of idiopathic recurrent priapism in a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency and consider a possible nitric oxide (NO)-dependent mechanistic basis from which the medical condition causes priapism.

Methods: The case report profiled a 35-year-old African-American man with G6PD deficiency who presented with a rapid progression of recurrent priapism episodes.

Key Methodological Issues in Sexual Medicine Research.

The field of research in sexual medicine has grown dramatically in the past decade to a point where we now have a substantial armamentarium of pharmacologic and psychological interventions available for the treatment of sexual dysfunctions in men. Concomitantly, numerous new compounds are in advanced stages of clinical development to expand the spectrum of treatment options for women's sexual dysfunctions as well. We believe we have reached a point in our overall research agenda where it may be useful to reappraise certain aspects of our clinical research methodology.

Sex and the pathogenesis of cerebral palsy.

Cerebral palsy (CP) and related developmental disorders are more common in males than in females, but the reasons for this disparity are uncertain. Males born very preterm also appear to be more vulnerable to white matter injury and intraventricular hemorrhage than females. Experimental studies in adult animals and data from adult patients with stroke indicate that sex hormones such as estrogens provide protection against hypoxic-ischemic injury, and the neonatal brain is also influenced by these hormones.

Lifetime weight patterns in male physicians: the effects of cohort and selective survival.

Objective: The natural history of lifetime weight change is not well understood because of conflicting evidence from cross-sectional and longitudinal studies. Cross-sectional analyses find that adult weight is highest at approximately 60 years of age and lower thereafter. Longitudinal analyses have not found this pattern.

Meeting report: exploiting the tumor microenvironment for therapeutics.

Recent progress in understanding the role of the tumor microenvironment in cancer progression was the subject of the 2nd International Tumor Metabolism Summit entitled "Exploiting the Tumor Microenvironment for Therapeutics," a meeting held at Palazzo Ducale in Genoa, Italy, October 7 to 8, 2005. One of the major conceptual advances in oncology over the last decade has been the appreciation that all major aspects of cancer biology are influenced by the tumor microenvironment. Two important means by which cancer cells adapt to their microenvironment are by reprogramming cellular glucose/energy metabolism to use pathways that generate ATP in the absence of O(2) and by stimulating angiogenesis to increase O(2) delivery.

Demyelination and remyelination after spinal cord injury.

Since the discovery in the 1960s that remyelination can occur in the damaged central nervous system (CNS) (Bunge et al. 1961), there has been much progress in understanding the cellular and molecular biology of oligodendroglia and the factors that regulate their propagation, migration, differentiation, maturation, and ability to myelinate nerve axons. More recently, greater understanding of disease states and the role of oligodendrocytes in remyelination have sparked tremendous interest in this once obscure field.

The nitric oxide signaling pathway in the penis.

It is widely accepted that nitric oxide plays an important role in the biology of the penis, serving most familiarly as the agent responsible for penile erection. Early investigation in the field led to the identification of the signaling function of the molecule in the penis which yields corporal smooth muscle relaxation fundamental for the erectile response. Ongoing study of this molecule and its signaling pathway in erectile tissue has served to revise and clarify its importance.

Teaching children with attention deficit hyperactivity disorder (ADHD) and autistic disorder (AD) how to swallow pills.

One barrier to medication adherence in pediatric populations is difficulty swallowing pills. Some children may not have prerequisite skills for pill swallowing, while others may have developed conditioned anxiety from repeated negative experiences. Eight children with attention deficit hyperactivity disorder or autistic disorder participated in behavioral training to increase cooperation with pill swallowing.

Clinical utility of proPSA and "benign" PSA when percent free PSA is less than 15%.

Objectives: To investigate the clinical utility of the subforms of free prostate-specific antigen (PSA), namely proPSA and "benign" PSA (BPSA), to improve cancer detection when the percent free PSA level is less than 15%. Percent free PSA, while maintaining sensitivity, has greatly improved the specificity of PSA for the early detection of prostate cancer. A low percent free PSA value indicates a greater risk of cancer, but only 30% to 50% of men with percent free PSA levels of less than 15% actually have cancer at biopsy.

Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma.

In the setting of inactivated DNA damage-sensitive checkpoints, critically shortened telomeres promote chromosomal instability and the types of widespread cytogenetic alterations that characterize most human carcinomas. Using a direct telomere fluorescence in situ hybridization technique, we analyzed 114 invasive breast carcinomas, 29 carcinoma in situ lesions, 10 benign proliferative lesions, and different normal epithelial components of the male and female breast. We found marked telomere shortening in the majority (52.

Phase I study of docosahexaenoic acid-paclitaxel: a taxane-fatty acid conjugate with a unique pharmacology and toxicity profile.

Purpose: Docosahexaenoic acid (DHA)-paclitaxel, a novel conjugate formed by covalently linking the natural fatty acid DHA to paclitaxel, was designed as a prodrug targeting intratumoral activation. This Phase I trial examined its toxicity and pharmacokinetics (PKs).

Experimental Design: Patients with advanced refractory solid tumors received a 2-h i.

Educational neuroimaging: a proposed neuropsychological application of near-infrared spectroscopy (nIRS).

Objective: To provide a description of an emerging neuroimaging methodology, near-infrared spectroscopy (nIRS), and a potential educational application of the unique aspects of this technology.

Summary: nIRS is documented for its potential as a personal, portable, brain imaging system that may prove useful for cerebral monitoring in applied settings such as home, school, and work. The basis of nIRS brain imaging is reviewed, with summary descriptions of optical and neurovascular issues as well as a brief comparison to other brain imaging methodologies.

Increased laparoscopic experience does not lead to improved results with acute cholecystitis.

Background: As laparoscopic experience increases, ever more challenging cases are attempted. Enlarged surgeon experience, along with better technology, has been lauded as improving outcomes. The purpose of this study is to see if this applies to the management of acute cholecystitis.

Contribution of pneumolysin and autolysin to the pathogenesis of experimental pneumococcal endophthalmitis.

Purpose: To determine the contribution of pneumolysin and autolysin, two putative pneumococcal virulence proteins, to the pathogenesis of Streptococcus pneumoniae endophthalmitis.

Methods: Endophthalmitis was established in Lewis rats by intravitreal injection of pneumococcal strains at an inoculum of 10 organisms. The virulence of three closely related type 2 S.

Effects of celecoxib and rofecoxib on blood pressure and edema in patients > or =65 years of age with systemic hypertension and osteoarthritis.

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), including the cyclooxygenase-2 (COX-2) specific inhibitors, with antihypertensive medication is common practice for many patients with arthritis. This study evaluated the effects of celecoxib 200 mg/day and rofecoxib 25 mg/day on blood pressure (BP) and edema in a 6-week, randomized, parallel-group, double-blind study in patients > or =65 years of age with osteoarthritis who were treated with fixed antihypertensive regimens. One thousand ninety-two patients received study medication (celecoxib, n = 549; rofecoxib, n = 543).

Preoperative therapy in breast cancer: lessons from the treatment of locally advanced disease.

The greater use of screening has changed the stage distribution of breast cancer, and an increasing number of patients are diagnosed with earlier stages of the disease. Still, locally advanced breast cancer (LABC) remains a major clinical problem in the United States and a common presentation in many parts of the world. There is no standard definition of LABC.

Endothelial nitric oxide synthase protein expression, localization, and activity in the penis of the alloxan-induced diabetic rat.

Purpose: To explore the possible relevance of endothelial nitric oxide synthase (eNOS) in the pathophysiology of erectile dysfunction (ED) associated with diabetes mellitus, we compared the catalytic activity, protein expression, and cellular localization of eNOS with those of neuronal nitric oxide synthase (nNOS) in the penis of rats with alloxan-induced diabetes.

Materials And Methods: Adult male Sprague-Dawley rats were given alloxan or vehicle only and monitored weekly by Dextrostix for confirmation of glucosuria. Tail-flick immersion and penile reflex testing were used to evaluate sensory neuropathy and ED, respectively.