Pituitary as a Source of HCG: Residual Levels After Bilateral Testicular Tumor Removal.

Context: Challenging clinical scenario in which elevated β-human chorionic gonadotropin (HCG, subsequently termed HCG) levels suggested occult tumor metastases after removal of bilateral testicular cancers and metastases from them and as well as after chemotherapy.

Case Report: A 22-year-old male, post excision of bilateral testicular tumors, who had no imaging or clinical evidence of residual tumor but an elevated HCG raising the question of the presence and location of occult tumor metastases. Clinical Questions.

Aromatase expression in atypical ductal hyperplasia in women.

Purpose: To determine the levels of aromatase in atypical ductal hyperplasia (ADH) lesions, tissue surrounding the ADH, and in dense and non-dense normal breast tissue. We postulated that excess aromatase in breast tissue might, through production of increased estrogen, drive the carcinogenic process. Estrogens and their metabolites are thought to contribute to the development of breast cancer through estrogen receptor-mediated mechanisms and genotoxic effects of estrogen metabolites.

Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy.

The Women's Health Initiative studies and others have suggested that menopausal hormone therapy may enhance the risk of new cardiovascular (CV) events in older women and diminish the development of coronary atherosclerosis in younger women. The underlying mechanisms to explain these findings are encapsulated in the term "Timing Hypothesis." Extensive pathophysiologic studies have provided mechanistic evidence for the dichotomous effects of estrogen on coronary artery vasculature.

A Review on Functional Electrical Stimulation Cycle Ergometer Exercise for Spinal Cord Injured Patients.

The purpose of this collective review on functional electrical stimulation (FES) cycle ergometer training is to describe the pathologic effects of spinal cord injury (SCI) and the structure and function of the FES cycle ergometers, which reverse the devastating systemic and life-threatening effects of SCI. The pathophysiologic consequences of SCI include diminished cardiopulmonary and circulatory function as well as lower extremity muscle atrophy and bone mass reduction. Clinical studies have demonstrated that the two FES cycle ergometers offer promise in reversing these devastating consequences of SCI, which can shorten patients' lives.

A Review on Functional Electrical Stimulation for a Dropped Foot.

The purpose of this collective review is to study the techniques, usage, methods, and clinical results of functional electrical stimulation applied to the peroneal nerve in the treatment of dropped foot. When stimulation is applied through surface electrodes, clinical reports have documented the therapeutic and orthotic benefits of functional electrical stimulation. Clinical trials are now being undertaken in which implantable electrodes are being used to stimulate the peroneal nerve in patients with dropped foot.

Career Advancement: Meeting the Challenges Confronting the Next Generation of Endocrinologists and Endocrine Researchers.

Context: Challenges and opportunities face the next generation (Next-Gen) of endocrine researchers and clinicians, the lifeblood of the field of endocrinology for the future. A symposium jointly sponsored by The Endocrine Society and the Endocrine Society of Australia was convened to discuss approaches to addressing the present and future Next-Gen needs.

Evidence Acquisition: Data collection by literature review, assessment of previously completed questionnaires, commissioning of a new questionnaire, and summarization of symposium discussions were studied.

Celebrating 75 years of oestradiol.

Oestrogens exert important effects on the reproductive as well as many other organ systems in both men and women. The history of the discovery of oestrogens, the mechanisms of their synthesis, and their therapeutic applications are very important components of the fabric of endocrinology. These aspects provide the rationale for highlighting several key components of this story.

The Adult Calfactant in Acute Respiratory Distress Syndrome Trial.

Background: Surfactant has been shown to be dysfunctional in ARDS, and exogenous surfactant has proven effective in many forms of neonatal and pediatric acute lung injury (ALI). In view of the positive results of our studies in children along with evidence that surfactant-associated protein B containing pharmaceutical surfactants might be more effective, we designed a multiinstitutional, randomized, controlled, and masked trial of calfactant, a calf lung surfactant, in adults and children with ALI/ARDS due to direct lung injury.

Methods: Adult subjects within 48 h of initiation of mechanical ventilation for direct ARDS were randomized to receive up to three interventions with instilled calfactant vs air placebo.

Estrogen metabolites and breast cancer.

Epidemiologic studies link several factors related to estrogen production in women to an increased risk of breast cancer. These include early menarche, late menopause, obesity, use of post-menopausal hormone therapy, and plasma estradiol levels. Two possible mechanisms have been proposed to explain the increased risk: (1) estrogen receptor (ER) mediated stimulation of breast cell proliferation with a concomitant enhanced rate of mutations and (2) metabolism of estradiol to genotoxic metabolites with a resulting increase in DNA mutations.

Competency in menopause management: whither goest the internist?

Background: After publication of the Women's Health Initiative study in 2002, use of menopausal hormone therapy (HT) has declined by nearly 80% worldwide and internists now play only a limited role in menopause management. Over the past decade, new data have increased our knowledge of the multiple effects and mechanisms of HT.

Methods: Existing literature was reviewed.

The lack of specificity of tracheal aspirates in the diagnosis of pulmonary infection in intubated children.

Objectives: Ventilator-associated pneumonia is the first or second most commonly diagnosed nosocomial infection in the PICU. Centers for Disease Control diagnostic criteria include clinical signs or symptoms in conjunction with a "positive" tracheal aspirate, defined as more than 10 colony-forming units/mL of bacteria on quantitative culture and/or more than 25 polymorphonuclear neutrophils per low-power field on Gram stain. We hypothesized that tracheal aspirate cultures and Gram stains would not correlate with clinical signs and symptoms and would therefore not distinguish between colonization and infection.

The relationship of fluid administration to outcome in the pediatric calfactant in acute respiratory distress syndrome trial.

Objectives: Adult studies have demonstrated the relationship between fluid overload and poor outcomes in acute lung injury/acute respiratory distress syndrome. The approach of pediatric intensivists to fluid management in acute lung injury/acute respiratory distress syndrome and its effect on outcomes is less clear. In a post hoc analysis of our Calfactant in Acute Respiratory Distress Syndrome trial, we examined the relationship of fluid balance to in-hospital outcomes in subjects with acute lung injury/acute respiratory distress syndrome.

Menopausal hormone therapy and breast cancer.

Observational and randomized controlled trial data have extensively examined the relationship between menopausal hormone therapy (MHT) and risk of developing breast cancer. A highly influential study from the Women's Health Initiative (WHI) in 2002 reported that a MHT regimen of conjugated equine estrogens and medroxyprogesterone acetate increased the risk of breast cancer by 26%. Later reports from the WHI indicated that a MHT regimen with conjugated equine estrogens alone decreased the risk of breast cancer by 23%.

Pediatric calfactant in acute respiratory distress syndrome trial.

Rationale: Our previous studies in children with acute lung injury/acute respiratory distress syndrome demonstrated improved outcomes with exogenous surfactant (calfactant) administration. Sample sizes in those studies were small, however, and the subject populations heterogeneous, thus making recommendations tenuous.

Objective: To investigate the efficacy of surfactant administration in a larger, more homogenous population of children with lung injury/acute respiratory distress syndrome due to direct lung injury.

Hypopituitarism after stereotactic radiosurgery for pituitary adenomas.

Background: Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS)-induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking.

Objective: We investigated the outcomes of SRS for pituitary adenoma patients with regard to newly developed hypopituitarism.

Methods: This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006.

Hemorrhage risk of cerebral arteriovenous malformations before and during the latency period after GAMMA knife radiosurgery.

Background And Purpose: To evaluate the hemorrhage rates of cerebral arteriovenous malformations (AVM) and the risk factors of hemorrhage before and after Gamma Knife radiosurgery (GKS).

Methods: The annual hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Characteristics of patients and AVM related to hemorrhagic or nonhemorrhagic presentation were evaluated by logistic regression.

Clinical review: Effect of endocrine therapies on bone in breast cancer patients.

Context: Two common strategies are used to treat estrogen receptor-positive breast cancer in women: tamoxifen to inhibit estrogen action, and aromatase inhibitors (AIs) to block estrogen biosynthesis. Recent data suggest that AIs are more effective than tamoxifen in the adjuvant and advanced disease settings and are now being more commonly used. Tamoxifen, as a selective estrogen receptor modulator, exerts estrogenic effects to preserve bone, whereas the AIs profoundly lower estrogen levels and cause bone loss.

Estrogen stimulation of cell migration involves multiple signaling pathway interactions.

Hormone-dependent breast cancers respond to inhibitors of estrogen synthesis or action with tumor regression and with a reduction of new metastases. The mechanisms underlying the effects of estrogen on metastasis likely differ from those on tumor regression. Cell migration is a key first step in the metastatic process.

Repeat γ knife surgery for incompletely obliterated cerebral arteriovenous malformations.

Objective: The causes of failure after an initial Gamma procedure were studied, along with imaging and clinical outcomes, in a series of 140 patients with cerebral arteriovenous malformations (AVMs) treated with repeat Gamma Knife surgery (GKS).

Methods: Causes of initial treatment failure included inaccurate nidus definition in 14 patients, failure to fill part of the nidus as a result of hemodynamic factors in 16, recanalization of embolized AVM compartments in 6, and suboptimal dose (<20 Gy) in 23. Nineteen patients had repeat GKS for subtotal obliteration of AVMs.

Physiology and pharmacology of myocardial preconditioning and postconditioning.

Perioperative myocardial ischemia and infarction are not only major sources of morbidity and mortality in patients undergoing surgery but also important causes of prolonged hospital stay and resource utilization. Ischemic and pharmacological preconditioning and postconditioning have been known for more than 2 decades to provide protection against myocardial ischemia and reperfusion and limit myocardial infarct size in many experimental animal models, as well as in clinical studies. This article reviews the physiology and pharmacology of ischemic and drug-induced preconditioning and postconditioning of the myocardium with special emphasis on the mechanisms by which volatile anesthetics provide myocardial protection.

Estrogen mediation of breast tumor formation involves estrogen receptor-dependent, as well as independent, genotoxic effects.

Long-term exposure to estrogens influences the development of breast cancer in women, but the precise mechanisms involved are not clearly defined. Our working hypothesis is that estrogen modulates this process by two separate processes. One involves the binding of estradiol to estrogen receptor (ER) alpha with stimulation of cell proliferation.