Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection.

Extreme-drug-resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. New methods to prevent and treat such infections are a critical unmet medical need. To conduct a rational vaccine discovery program, OmpA was identified as the primary target of humoral immune response after intravenous infection by A.

The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial.

Objectives: Host iron availability is fundamental to mucormycosis pathogenesis. The combination of liposomal amphotericin B (LAmB) and deferasirox iron chelation therapy synergistically improved survival in diabetic mice with mucormycosis. To determine the safety of combination deferasirox plus LAmB therapy for mucormycosis, a multicentred, placebo-controlled, double-blinded clinical trial was conducted.

Design of clinical trials of antibacterial agents for community-acquired bacterial pneumonia.

Standards for the conduct of clinical trials of antibacterial agents for community-acquired bacterial pneumonia (CABP) have changed dramatically in recent years. A draft guidance from the US FDA on the conduct of such trials was issued in March 2009. However, the guidance has already faced substantial criticism during the open public comment period, resulting in uncertainty regarding the appropriate design of such studies from a regulatory perspective.

Vaccines for invasive fungal infections.

Morbidity and mortality from invasive fungal infections remain unacceptably high despite availability of new antifungal agents, underscoring the need for more effective preventative strategies. Due to our enhanced understanding of the host defense and pathogenetic mechanisms that lead to invasive fungal infections, it should be feasible to develop vaccines targeting these infections. A common immunological theme across many vaccine candidates for invasive fungal infections has been the need to activate a cell-based, pro-inflammatory, Th1 or Th17 immune response to improve phagocytic killing of the fungi.

The high affinity iron permease is a key virulence factor required for Rhizopus oryzae pathogenesis.

Rhizopus oryzae is the most common cause of mucormycosis, an angioinvasive fungal infection that causes more then 50% mortality rate despite first-line therapy. Clinical and animal model data clearly demonstrate that the presence of elevated available serum iron predisposes the host to mucormycosis. The high affinity iron permease gene (FTR1) is required for R.

Coronary distensibility index measured by computed tomography is associated with the severity of coronary artery disease.

Background: Atherosclerotic changes within the coronary artery wall can affect vessel distensibility.

Objective: This study evaluated the relationship between the coronary distensibility index (CDI) and the severity of coronary artery disease (CAD) measured by computed tomographic angiography (CTA).

Methods: One hundred thirteen subjects, age 63 +/- 10 years, 32% women, who underwent coronary artery calcium (CAC) scanning and CTA, were studied.

Divergent frequencies of IGF-I receptor-expressing blood lymphocytes in monozygotic twin pairs discordant for Graves' disease: evidence for a phenotypic signature ascribable to nongenetic factors.

Context: Graves' disease (GD) is an autoimmune process of the thyroid and orbital connective tissues. The fraction of T and B cells expressing IGF-I receptor (IGF-IR) is increased in GD. It is a potentially important autoantigen in GD.

Role of caspase 2 in apoptotic signaling in primate and murine germ cells.

This study investigates the role of caspase 2 in apoptotic signaling of nonhuman primate male germ cells triggered by mild testicular hyperthermia, testosterone (T(e)) implants, or by combined interventions. Mean incidence of germ cell apoptosis increased significantly by Day 3 in the heat (H(e)) alone group and by Day 8 in the Te alone group but peaked at Day 3 in H(e) + T(e) group. We found activation of caspase 2 in both germ cells and Sertoli cells after induction of apoptosis.

The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America.

The ongoing explosion of antibiotic-resistant infections continues to plague global and US health care. Meanwhile, an equally alarming decline has occurred in the research and development of new antibiotics to deal with the threat. In response to this microbial "perfect storm," in 2001, the federal Interagency Task Force on Antimicrobial Resistance released the "Action Plan to Combat Antimicrobial Resistance; Part 1: Domestic" to strengthen the response in the United States.

Baseline HIV type 1 coreceptor tropism predicts disease progression.

Background: Human immunodeficiency virus type 1 (HIV-1) coreceptor tropism, the ability of the virus to enter cells via CCR5 or CXCR4, is a viral characteristic mediated by the envelope gene. The impact of coreceptor tropism on the natural history of HIV-1 infection has not been fully explored.

Methods: Coreceptor tropism was measured using a recombinant virus single-cycle assay on plasma specimens obtained at baseline from 126 children and adolescents in the Hemophilia Growth and Development Study cohort who were enrolled from 1989 through 1990 and underwent follow-up through 1997.

Nosocomial fungal infections: epidemiology, diagnosis, and treatment.

Invasive fungal infections are increasingly common in the nosocomial setting. Furthermore, because risk factors for these infections continue to increase in frequency, it is likely that nosocomial fungal infections will continue to increase in frequency in the coming decades. The predominant nosocomial fungal pathogens include Candida spp.

A prospective investigation of outcomes after hospital discharge for endemic, community-acquired methicillin-resistant and -susceptible Staphylococcus aureus skin infection.

Background: Although community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has become increasingly common, prospective data on outcomes of patients with skin infection remain poorly defined.

Methods: We prospectively observed a cohort of 201 patients discharged after hospitalization for CA-MRSA infection or community-acquired methicillin-susceptible S. aureus (CA-MSSA) infection.

Clinical and epidemiologic characteristics cannot distinguish community-associated methicillin-resistant Staphylococcus aureus infection from methicillin-susceptible S. aureus infection: a prospective investigation.

Background: Community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) infection has become common worldwide. Some researchers have argued that empirical therapy for MRSA should be given only to patients with suspected CA S. aureus infections who have risk factors for acquisition of MRSA.

Influence of body mass index and gender on growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests.

The aim of this study is to assess whether gender and body mass index (BMI) should be considered in developing thresholds to define GH deficiency, using GH responses to GHRH + arginine (ARG) stimulation and insulin tolerance test (ITT). Thirty-nine healthy subjects (19 males, 20 females; ages 21-50 yr) underwent GHRH + ARG, and another 27 subjects (19 males, 8 females; ages 20-49 yr) underwent ITT. Peak GH response was significantly higher (P = 0.

Genetic risks of intracytoplasmic sperm injection in the treatment of male infertility: recommendations for genetic counseling and screening.

Objective: To review the most clinically significant genetic disorders associated with severe oligospermia and azoospermia in males, and to present recommendations for the genetic counseling and screening of infertile males and their partners before undertaking intracytoplasmic sperm injection (ICSI)-assisted reproduction.

Design: The literature on genetic disorders associated with severe oligospermia and azoospermia was reviewed, and the most recent outcome data from surveys of ICSI-derived offspring are presented. Studies related to this topic were identified through MEDLINE.

Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation.

Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-deficient by homologous recombination maintain normal steady-state hematopoiesis but have an alveolar accumulation of surfactant lipids and protein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat PC) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls.

Scintimammography: the complementary role of Tc-99m sestamibi prone breast imaging for the diagnosis of breast carcinoma.

Purpose: To evaluate the complementary role of technetium-99m sestamibi scintimammography in improvement of the sensitivity and specificity of mammography in detection of carcinoma of the breast.

Materials And Methods: At 5 and 60 minutes after intravenous injection of Tc-99m sestamibi, scintimammograms were obtained in 147 women (age range, 18-73 years; mean age, 47.9 years +/- 10.

Evaluation of the CellTrak computer-assisted sperm analysis system in comparison to the Cellsoft system to measure human sperm hyperactivation.

Objective: To measure and compare sperm hyperactivation (HA) and associated motility parameters using the CellTrak (Motion Analysis Corporation, Santa Rosa, CA) and Cellsoft (Cryo Resources, New York, NY) Computer-Assisted Sperm Analysis (CASA) Systems. The accuracy of the CellTrak system also was assessed by repeated measurements of the same sample.

Setting: A university-affiliated tertiary care center.

Acute fatty liver of pregnancy: laparoscopy-assisted diagnosis.

We report a case of fatty infiltration of the liver in a 27-year-old Hispanic woman. She went to an outside hospital in her third trimester of pregnancy with abdominal pain, jaundice, peripheral edema, and diffuse intravascular coagulation. An emergent cesarean section was performed, and she developed symptoms of acute hemorrhagic pancreatitis and altered mental status.

Localization of alveolar surfactant clearance in rabbit lung cells.

Localization of surfactant phospholipid clearance in lung cells was investigated in vivo in rabbits using radiolabeled dipalmitoylphosphatidylcholine (DPPC) and 1,2-dihexa-decyl-sn-glycero-3-phosphocholine (DPPC-ether), a phospholipase A1- and A2-resistant analogue of DPPC. After intratracheal injection of liposomes of the labeled lipids associated with unlabeled surfactant, adult rabbits were killed in groups of three to five at 0, 4, 12, and 24 h with recovery of bronchoalveolar lavages for alveolar macrophages and surfactant. Type II cells and tissue-associated macrophages were isolated on Percoll gradients following elastase and trypsin digestion of the lungs.

Marked suppression of gonadotropins and testosterone by an antagonist analog of gonadotropin-releasing hormone in men.

To study the dose response characteristics of a gonadotropin-releasing hormone (GnRH) antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5,dGlu6 (AA), d-Ala10] GnRH; Nal-Glu), 1.5 or 5.0 mg of Nal-Glu were administered to two groups of five normal men by daily subcutaneous injection for 21 days.