Serous borderline tumor of the ovary with isolated cardiophrenic lymph node spread at diagnosis.

•Serous borderline tumor outside of the peritoneal cavity is rare.•Involvement of cardiophrenic lymph nodes with serous borderline tumor can occur.•Preoperative imaging may aid surgical planning even in serous borderline tumor cases.•Sequencing can help confirm a diagnosis of serous borderline tumor at distant sites.

Multivariable analysis of association of beta-blocker use and survival in advanced ovarian cancer.

OBJECTIVE: In this study, we sought to evaluate the relationship between survival and beta blocker use in both the primary and interval debulking setting while adjusting for frequently co-administered medications. METHODS: We performed a retrospective cohort study reviewing charts of women who underwent primary or interval cytoreduction for stage IIIC and IV epithelial ovarian cancer. The exposure of interest was beta-blocker use identified at the time of cytoreduction. The outcomes of interest were PFS and OS. We collected demographic/prognostic variables and information about use of aspirin, metformin, and statins. We used the Kaplan-Meier method and Cox proportional hazards models in survival analyses. RESULTS: 534 women who underwent surgery for stage IIIC or IV ovarian cancer were included in the study. The median age at diagnosis was 64 and 84.8% of women had serous carcinoma. We identified 105 women (19.7%) on a beta-blocker of whom 94 (90%) were on a cardioselective beta-blocker. Additionally, 24 women (4.5%) were on metformin, 91 (17%) on aspirin, and 128 (24%) on a statin. In univariable analysis, beta-blocker users had a median overall survival of 29 months vs 35 months among non-users (hazard ratio HR = 1.52, p = 0.007). After adjustment for important demographic, clinical, and histopathologic factors, as well as use of other common medications, beta-blocker use remain associated with an increased hazard of death (adjusted HR 1.57, p = 0.006). CONCLUSION: In this retrospective study, we found that patients identified as being on a beta-blocker at the time of surgery had worse overall survival and greater risk of death when compared to those patients not on betablockers. Importantly, 90% of patients on beta-blockers were identified as being on a cardioselective beta-blocker.

Diabetes self-management education exposure and glycated haemoglobin levels among Marshallese participants in a randomized controlled study.

AIMS: A randomized control trial (RCT) of diabetes self-management education (DSME), undertaken by a community-based participatory research (CBPR) partnership between the University of Arkansas for Medical Sciences (UAMS) and the Marshallese community in Arkansas. The RCT examined the effect of hours of intervention exposure, with the hypothesis that increased exposure is one reason the Adapted-Family DSME was found to be more effective than the Standard DSME. METHODS: Some 221 Marshallese with type 2 diabetes were randomized to an Adapted-Family DSME group (in-home setting) (n = 110) or a Standard DMSE group (community setting) (n = 111). The Adapted-Family DSME included 10 h of education that covered the core self-care elements recommended by the American Diabetes Association (ADA) and American Association of Diabetes Educators' (AADE) recommendations. The Standard DSME included 10 h of intervention with all ADA and AADE core elements. RESULTS: The number of hours of intervention exposure in the Adapted-Family DSME arm (mean = 8.0; median = 10.0) was significantly higher than the number of hours of intervention received in the Standard DSME arm (mean = 1.5; median = 0.0). As hypothesized, higher exposure was associated with a significant reduction in HbA1c in a model including only study arm and exposure (P = 0.01), and in a model including study arm, exposure, and all demographic variables (P = 0.046). CONCLUSIONS: This finding is consistent with previous reviews that showed increased exposure to DSME produced improved glycaemic control and ≥ 10 h of DSME produces clinically meaningful reductions in HbA1c .

Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies.

OBJECTIVE: Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers. METHODS: This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment. RESULTS: From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5 days (range 0-22 days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44 days (range 9-99). CONCLUSION: Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.

The hHFE gene of browsing and grazing rhinoceroses: a possible site of adaptation to a low-iron diet.

When rhinoceros species that are browsers in the wild are fed in captivity they become iron overloaded. Presumably, their iron-absorptive mechanisms have evolved to become highly efficient. In humans, mutations of the HFE gene cause increased iron absorption. To determine whether the HFE gene of rhinoceroses has undergone mutation as an adaptive mechanism to improve iron absorption from iron-poor diets, we have sequenced the entire coding region of the HFE genes of four species of rhinoceros. Two of these were browsing species and two were grazing species. Although the HFE gene has been well preserved across species, numerous nucleotide differences were found between rhinoceros and human or mouse, some of which changed deduced amino acids. Of these mutations, only one found in the black rhinoceros appears to be a viable candidate mutation that might adversely affect HFE function. This mutation, S88T, is in a highly conserved region that is involved in the interaction between transferrin receptor and HFE.

Processing prescription drug information under different conditions of presentation.

OBJECTIVES: The purpose of this study was to investigate individuals' processing of prescription drug information under different conditions of presentation. DESIGN: Videotapes and written materials were used to develop 12 different conditions of presentation and data were collected via a mailed survey methodology. Controlling for respondent age, we studied respondents' perceptions of cognitive effort required to process the information, information overload, and evaluative response to the information. Also, we documented and studied the number of questions reported after exposure to the information. SUBJECTS: Study materials were mailed to 624 volunteers living in the United States, of which 477 (76.4%) returned completed data forms. RESULTS AND CONCLUSIONS: The results suggest there is a balance between the need for information at a level sufficient for individuals to make decisions and the need for information that will not overload individuals as they cognitively process it.

Antipsychotic medications and the elderly: effects on cognition and implications for use.

Despite being frequently prescribed in the elderly, antipsychotic medications are commonly associated with adverse effects in this population, including sedative, orthostatic and extrapyramidal adverse effects. Growing evidence suggests that antipsychotics can also cause deleterious cognitive effects in some elderly patients. Preclinical and growing clinical evidence indicates that inhibitory effects on dopaminergic, cholinergic and histaminergic neurochemical systems may account for antipsychotic-associated cognitive impairment in the elderly. A review of published reports of the cognitive effects of antipsychotics in the elderly suggests that newer antipsychotic medications may possess a more favourable cognitive profile than that of traditional agents in this population. The cognitive effect that a specific antipsychotic will have in the elderly, however, is likely better predicted by considering the pharmacodynamic action of an individual agent in combination with the pathophysiology of the condition being treated. Agents with relatively weak dopamine inhibiting effects (e.g. clozapine and quetiapine), for example, would theoretically have a cognitive profile superior to that of agents with higher degrees of dopaminergic inhibition (all traditional agents, risperidone, olanzapine and ziprasidone) when used for conditions associated with diminished dopamine function (e.g. idiopathic Parkinson's disease). Drugs with weak anticholinergic effects (high-potency traditional agents, risperidone, quetiapine and ziprasidone) would theoretically be less likely to cause cognitive impairment than agents with high degrees of cholinergic receptor blocking actions (clozapine and olanzapine) when treating patients with impaired cholinergic function (e.g. Alzheimer's disease). Cholinergic agonist effects of clozapine and olanzapine may, however, mitigate potential adverse cognitive effects associated with the cholinergic blocking actions of these agents. Large, rigorous trials comparing the cognitive effects of antipsychotics with diverse pharmacodynamic actions are lacking in the elderly and are needed.

Salmonella pathogenicity island 1-independent induction of apoptosis in infected macrophages by Salmonella enterica serotype typhimurium.

The enteric pathogen Salmonella enterica serotype Typhimurium induces apoptosis in infected macrophages. This process is rapid, specific, and depends on the type III protein secretion system encoded within Salmonella pathogenicity island 1 (SPI1). Here, we demonstrate that serotype Typhimurium can activate programmed macrophage cell death independently of SPI1. SPI1 independent induction of apoptosis in infected macrophages is observed as early as 12 to 13 h postinfection, even in the absence of intracellular bacterial replication. Delayed activation of programmed macrophage cell death is not observed with serotype Typhimurium strains mutated in ompR or SPI2. Even though SPI2 mutants have a defect in intracellular proliferation, our results indicate that long-term intracellular survival and growth are not required for delayed macrophage killing per se, since Salmonella mutants that are severely defective in intracellular growth still induce delayed apoptosis. Inactivation of genes required for either rapid or delayed induction of apoptosis results in a conditional noncytotoxic phenotype, whereas simultaneous inactivation of genes required for both rapid and delayed induction of apoptosis renders serotype Typhimurium noncytotoxic under all conditions tested. Our hypothesis is that differential activation of programmed macrophage cell death by serotype Typhimurium occurs under discrete physiological conditions at distinct locations within an infected host.

Salmonella SsrB activates a global regulon of horizontally acquired genes.

Salmonella enterica is a bacterial pathogen of humans that can proliferate within epithelial cells as well as professional phagocytes of the immune system. This ability requires an S. enterica specific locus termed Salmonella pathogenicity island 2 (SPI-2). SPI-2 encodes a type III secretion system that injects effectors encoded within the island into host cell cytosol to promote virulence. SsrAB is a two-component regulator encoded within SPI-2 that was assumed to activate SPI-2 genes exclusively. Here, it is shown that SsrB in fact activates a global regulon. At least 10 genes outside SPI-2 are SsrB regulated within epithelial and macrophage cells. Nine of these 10 SsrB-regulated genes outside SPI-2 reside within previously undescribed regions of the Salmonella genome. Most share no sequence homology with current database entries. However, one is remarkably homologous to human glucosyl ceramidase, an enzyme involved in the ceramide signalling pathway. The SsrB regulon is modulated by the two-component regulatory systems PhoP/PhoQ and OmpR/EnvZ, and is upregulated in the intracellular microenvironment.

The influence of sulfate-reducing bacteria colonization of 2 different bioresorbable barrier membranes for GTR. An 18-month case-controlled microbiologic and clinical study.

The purpose of the present microbiologic and case-controlled clinical study was to examine the colonization of 2 different resorbable barrier membranes by sulfate-reducing bacteria (SRB). The barrier membranes tested were Guidor matrix barrier and Resolut regenerative material. Ten patients exhibiting 3 Class II furcation defects and 7 intrabony defects were included in the study. The probing depth and the clinical attachment level at 4 surfaces per tooth were taken at the beginning of the study. Microbiologic samples were taken from the experimental sites and from the approximal sites of the adjacent teeth. Both types of resorbable membranes were positive for SRB colonization. The detection of SRB in 2 of 7 intrabony defects and in all defects with furcation involvement before the membrane placement indicated that these organisms are a common inhabitant of sites showing periodontal destruction and are associated with guided tissue regeneration (GTR). According to the clinical criteria for healing tendencies used in this study, the GTR procedures were less successful in the presence of SRB. There were no significant clinical effects of different resorbable membrane materials or membrane layout on attachment level changes for either the intrabony defect or furcation groups after 18 months. There were no statistical differences for sites that became exposed to SRB when compared to sites that remained unexposed after 18 months. The numeric significance of SRB in relation to the total microbial count needs to be determined to gain insight into the ecologic role of membrane resorption rates.

Primary Mycobacterium avium complex infections correlate with lowered cellular immune reactivity in Matschie's tree kangaroos (Dendrolagus matschiei).

The National Zoological Park has maintained a breeding colony of Matschie's tree kangaroos (Dendrolagus matschiei) since 1975 with a documented history and continued prevalence of Mycobacterium avium complex (MAC) infections. No evidence of immunosuppressive retrovirus infections or loss of heterozygosity that may have led to an immune dysfunction in these animals was found. Isolates of MAC organisms from affected tree kangaroos and from their environment had no common restriction fragment DNA types. Cellular immune reactivity in apparently healthy tree kangaroos was 3- to 6-fold lower than in humans and other marsupial and eutherian mammals, as determined by lymphocyte proliferative assays. Thus, while MAC infections are typically opportunistic in humans and other mammals, tree kangaroos commonly develop primary progressive disease with MAC from random sources. Comparative information derived from this study should benefit both the endangered tree kangaroo and humans with immunosuppressive disorders that lead to mycobacterial infections.

The identification of exported proteins with gene fusions to invasin.

Exported proteins are integral to understanding the biology of bacterial organisms. They have special significance in pathogenesis research because they can mediate critical interactions between pathogens and eukaryotic cell surfaces. Further, they frequently serve as targets for vaccines and diagnostic tests. The commonly used genetic assays for identifying exported proteins use fusions to alkaline phosphatase or beta-lactamase. These systems are not ideal for identifying outer membrane proteins because they identify a large number of inner membrane proteins as well. We addressed this problem by developing a gene fusion system that preferentially identifies proteins that contain cleavable signal sequences and are released from the inner membrane. This system selects fusions that restore outer membrane localization to an amino terminal-truncated Yersinia pseudotuberculosis invasin derivative. In the present study, a variety of Salmonella typhimurium proteins that localize beyond the inner membrane were identified with gene fusions to this invasin derivative. Previously undescribed proteins identified include ones that share homology with components of fimbrial operons, multiple drug resistance efflux pumps and a haemolysin. All of the positive clones analysed contain cleavable signal sequences. Moreover, over 40% of the genes identified encode putative outer membrane proteins. This system has several features that may make it especially useful in the study of genetically intractable organisms.

Skeletal muscle histology and biochemistry of an elite sprinter, the African cheetah.

To establish a skeletal muscle profile for elite sprinters, we obtained muscle biopsy samples from the vastus lateralis, gastrocnemius and soleus of African cheetahs (Acinonyx jubatus). Muscle ultrastructure was characterized by the fiber type composition and mitochondrial volume density of each sample. Maximum enzyme activity, myoglobin content and mixed fiber metabolite content were used to assess the major biochemical pathways. The results demonstrate a preponderance of fast-twitch fibers in the locomotor muscles of cheetahs; 83% of the total number of fibers examined in the vastus lateralis and nearly 61% of the gastrocnemius were comprised of fast-twitch fibers. The total mitochondrial volume density of the limb muscles ranged from 2.0 to 3.9% for two wild cheetahs. Enzyme activities reflected the sprinting capability of the cheetah. Maximum activities for pyruvate kinase and lactate dehydrogenase in the vastus lateralis were 1519.00 +/- 203.60 and 1929.25 +/- 482.35 mumol min-1.g wet wt-1, respectively, and indicated a high capacity for glycolysis. This study demonstrates that the locomotor muscles of cheetahs are poised for anaerobically based exercise. Fiber type composition, mitochondrial content and glycolytic enzyme capacities in the locomotor muscles of these sprinting cats are at the extreme range of values for other sprinters bred or trained for this activity including greyhounds, thoroughbred horses and elite human athletes.

Human microvascular endothelial tissue culture cell model for studying pathogenesis of Brazilian purpuric fever.

Brazilian purpuric fever (BPF) is a fulminant pediatric disease characterized by fever, with rapid progression to purpura, hypotensive shock, and death. All known BPF cases have been caused by three clones of Haemophilus influenzae biogroup aegyptius and have occurred in either Brazil or Australia. Using an immortalized line of human vascular endothelial cells, we developed an in vitro assay that identifies all known BPF-causing H. influenzae biogroup aegyptius strains (R. S. Weyant, F. D. Quinn, E. A. Utt, M. Worley, V. G. George, F. J. Candal, and E. W. Ades, J. Infect. Dis. 169:430-433, 1994). With multiplicities of infection (MOIs) as low as one bacterium per 1,000 tissue culture cells, BPF-associated strains produce a unique cytotoxic effect in which the tissue culture cells detach and aggregate in large floating masses after 48 h of incubation. In this study, using a BPF-associated strain and a non-BPF-associated control, we demonstrated that strains which produce the cytotoxic phenotype were able to replicate intracellularly whereas non-BPF-associated strains, with MOIs of > or = 1,000 did not replicate and did not produce the phenotype. We also showed that this phenotype is not caused by the activity of an endotoxin or the release of some other compound from the bacterial cell, since neither gamma irradiation-killed whole BPF clone bacteria nor bacterial cell fractions at MOIs of > 1,000 produced the cytotoxic effect. Furthermore, bacteria in numbers equal to MOIs of > 1,000 treated with chloramphenicol did not produce the cytotoxic phenotype, suggesting a requirement for bacterial protein synthesis. In addition, viable bacteria separated from the tissue culture monolayer by a 0.2-micron-pore-size membrane also failed to produce the phenotype. The ability of the bacterium to invade, replicate, and produce the phenotype appears to be primarily parasite directed since phagocytosis, pinocytosis, and eukaryotic protein synthesis inhibitors, including cycloheximide, cytochalasin D, and methylamine, had no effect on the ability of the bacterium to invade and cause a cytotoxic response. Understanding the basic mechanisms involved in this tissue-destructive process should enhance our knowledge of the general pathogenesis of BPF.

Human microvascular endothelial cell toxicity caused by Brazilian purpuric fever-associated strains of Haemophilus influenzae biogroup aegyptius.

An in vitro cytotoxicity model that uses an immortalized human microvascular endothelial cell line (HMEC-1) differentiates Brazilian purpuric fever (BPF)-associated Haemophilus influenzae biogroup aegyptius (HAE) strains from non-BPF-associated HAE strains. Toxic strains produced a characteristic HMEC-1 phenotype at an MOI of < 1 bacterium/1000 tissue culture cells (TCC). Nontoxic strains required MOIs of > 1000 bacteria/TCC to produce an observable effect. The cytotoxic phenotype was characterized by the presence of large clumps of HMEC-1 cells, which detached from the monolayer within 48 h of inoculation by HAE cells. The cytotoxic phenotype was observed with 100% of BPF-associated HAE (40/40) and 14% of non-BPF-associated HAE (8/57; P < .001). The ability to study a BPF-associated phenotype in vitro using human microvascular cells should enhance our knowledge of BPF pathogenesis.

A statewide breast cancer screening project.

The cause of breast cancer remains unknown. Because prevention is not an option, early detection is the most viable alternative for decreasing the mortality rates from breast cancer. To promote early detection, the Arkansas Division of the American Cancer Society implemented a project aimed at increasing public awareness. The project used a three-pronged approach: the life-saving benefits of mammography, regular breast examination by a health-care professional, and the importance of regular breast self-examination (BSE). This article focuses on the third prong, BSE. Project members recruited and trained 408 BSE instructors in the MammaCare method of BSE and contacted a total of 87,141 Arkansas women about breast cancer and the importance of early detection. In a follow-up survey of 1,300 women, of the 198 (15%) who returned the surveys, two women reported finding lumps that were diagnosed as cancer.

Comparative study of antipneumocystis agents in rats by using a Pneumocystis carinii-specific DNA probe to quantitate infection.

A repetitive genomic DNA clone (B12-2) that specifically hybridizes to Pneumocystis carinii DNA has been identified. No cross-hybridization to genomic DNA prepared from bacteria, other fungi, protozoa, or mammals was observed. Clone B12-2 is multiply represented in the P. carinii genome. By direct hybridization to DNA prepared from the lungs of immunosuppressed rats, the probe can detect the equivalent of fewer than 1,000 P. carinii organisms. A hybridization assay employing clone B12-2 has been developed to quantitate organism load in the rat model for P. carinii. Application of the assay to track the accumulation of organisms during the immunosuppression regimen as well as to monitor the efficacy of two drug therapies used clinically for the treatment of P. carinii pneumonia is described here. The clone B12-2 hybridization assay for the determination of P. carinii organism load possesses several advantageous features and thus should serve to complement conventional staining and immunohistochemical methods.