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Competing Interests: Declaration of Competing Interest The authors whose names are listed above certify that they have no business affiliations with or involvement in the Corbett Targeted Coin Test or financial interest in the subject matter or materials discussed in this manuscript.

Identifying marine trematode parasites in host tissue can be complicated when there is limited morphological differentiation between species infecting the same host species. This poses a challenge for regular surveys of the parasite communities in species of socio-economic and ecological importance. Our study focused on identifying digenean trematode species infecting the marine bivalve Cerastoderma edule across Europe by comparing morphological and molecular species identification methods. Cockles were sampled from ten locations to observe the trematode parasites under a stereomicroscope (morphological identification) and to isolate individuals for phylogenetic analyses using two gene markers, the small sub-unit ribosomal (18S) RNA gene (SSU rDNA) and the mitochondrial cytochrome c oxidase subunit 1 (cox1). For the first time, we compared both morphological identification and phylogenetic analyses for each of the 13 originally identified species. First, we identified a group of five species for which morphological identification matched molecular results ( Bucephalus minimus , Monorchis parvus , Renicola parvicaudatus , Psilostomum brevicolle , Himasthla interrupta ). Second, we identified a group of six species for which molecular results revealed either misidentifications or cryptic diversity ( Gymnophallus choledochus , Diphterostomum brusinae , Curtuteria arguinae , Himasthla quissetensis , H. elongata , H . continua ). Third, our analyses showed that all sequences of two expected species, Gymnophallus minutus and G. fossarum , matched between the two, strongly suggesting that only G. minutus is present in the studied area. Our study clearly demonstrates that molecular tools are necessary to validate the trematode species composition. However, with 17 distinct genetic lineages detected, some of which are not fully identified, future studies are needed to clarify the identity and status (regular vs. accidental infection) of some of these cryptic trematode species., Competing Interests: None., (© 2024 The Authors.)

For rural women veterans, significant barriers exist in accessing high-quality, multicomponent behavioral pain self-management interventions. As such, a telehealth behavioral pain self-management intervention designed specifically for rural-dwelling women veterans with chronic pain was piloted for this study. This mixed methods, single-arm preliminary study examined the feasibility and acceptability of this intervention and completed a responder analysis. Participants completed surveys before and 1-month following the intervention, and they completed a qualitative interview following the intervention. About one quarter (24%) of potentially eligible participants who were sent a letter about the study consented to participate ( N = 44). All participants identified as female and were rural dwelling, with mean age of 56 years (range = 34-80), and the majority of the sample (81%) self-identified as White and non-Hispanic or Latino. Average baseline scores on the Pain, Enjoyment of Life, and General Activity three-item scale (PEG-3) measure indicated severe pain and functional interference ( M PEG-3 total = 6.88, SD = 1.62). Of the 44 participants who consented, 70% completed the intervention. About half of treatment completers (47%, 14/30) were deemed responders, reporting ≥ 30% reduction on their PEG-3 total scores. On the Global Impression of Change scale, 87% reported improvement. Study completers indicated that the telehealth platform facilitated their engagement and that they perceived the intervention to be beneficial and credible. Qualitative data emphasized themes of connection with other women veterans who experienced chronic pain while perceiving a retained sense of individual identity. These preliminary data support feasibly of this intervention for rural-dwelling women veterans with chronic pain. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Despite being high health care utilizers, many women Veterans perceive their pain condition to be poorly understood by their providers, which can be a strong demotivator for seeking care. We set out to understand the priorities rural-dwelling women Veterans have for using health care for their chronic pain, and interviewed participants about their experiences with (and priorities for seeking) health care for their chronic pain. Self-Determination Theory identifies three sources of motivation (autonomy, competence, relatedness), all of which were represented through two themes that reflect rural women Veterans' rationale for decision-making to obtain health care for chronic pain: role of trust and competing priorities. Women described their priorities for chronic pain management in terms of their competing priorities for work, education, and supporting their family, but most expressed a desire to function in their daily life and relationships. Second, women discussed the role of trust in their provider as a source of motivation, and the role of patient-provider communication skills and gender played in establishing trust. Rural women Veterans often discussed core values that stemmed from facets of their identity (e.g. gender, military training, ethnicity) that also influenced their decision-making. Our findings provide insight for how providers may use Motivational Interviewing and discuss chronic pain treatment options so that rural-dwelling women Veterans feel autonomous, competent, and understood in their decision-making about their chronic pain. We also discuss importance of acknowledging the effects of disenfranchising talk and perpetuating gendered stereotypes related to chronic pain and theoretical implications of this work.

WHO has determined a public health emergency of international concern (PHEIC) seven times, and beyond this nomenclature declared COVID-19 to be a pandemic. Under the International Health Regulations (IHR), and through their operationalisation in the joint external evaluation (JEE), governments are urged to create suitable legislation to be able to enact a response to a public health emergency. Whether the pandemic declaration had a greater effect than a PHEIC in encouraging goverments to act, however, remains conjecture, as there is no systemic analysis of what each term means in practice and whether either has meaningful legal implications at the national level. We undertook a legal scoping review to assess the utilisation of PHEIC and pandemic language within national legislation in 28 WHO member states. Data were collected from national websites, JEE reviews, COVID Analysis and Mapping of Policies Tool, Natlex, and Oxford Compendium of National Legal Responses to COVID-19. We found that only 16% of countries have any reference to the PHEIC in national legislation and 37·5% of countries reference the term pandemic. This finding paints a weakened picture of the IHR and PHEIC mechanisms. Having such legalese enshrined in legislation might enhance the interaction between WHO determining a PHEIC or declaring a pandemic and resulting action to mitigate transnational spread of disease and enhance health security. Given the ongoing negotiations at WHO in relation to the amendments to the IHR and creation of the pandemic accord, both of which deal with this declaratory power of the PHEIC and pandemic language, negotiators should understand the possible implications of any changes to these proclamations at the national level and for global health security., Competing Interests: Declaration of interests CW sat on the International Health Regulations Review Commitee for amendments to the IHR and reports consultant fees from WHO, unrelated to this research. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney's active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks., (© 2024. The Author(s).)

Low nephron endowment at birth is a risk factor for chronic kidney disease. The prevalence of this condition is increasing due to higher survival rates of preterm infants and children with multi- organ birth defect syndromes that affect the kidney and urinary tract. We created a mouse model of congenital low nephron number due to deletion of Mta2 in nephron progenitor cells. Mta2 is a core component of the Nucleosome Remodeling and Deacetylase (NuRD) chromatin remodeling complex. These mice developed albuminuria at 4 weeks of age followed by focal segmental glomerulosclerosis (FSGS) at 8 weeks, with progressive kidney injury and fibrosis. Our studies reveal that altered mitochondrial metabolism in the post-natal period leads to accumulation of neutral lipids in glomeruli at 4 weeks of age followed by reduced mitochondrial oxygen consumption. We found that NuRD cooperated with Zbtb7a/7b to regulate a large number of metabolic genes required for fatty acid oxidation and oxidative phosphorylation. Analysis of human kidney tissue also supported a role for reduced mitochondrial lipid metabolism and ZBTB7A/7B in FSGS and CKD. We propose that an inability to meet the physiological and metabolic demands of post-natal somatic growth of the kidney promotes the transition to CKD in the setting of glomerular hypertrophy due to low nephron endowment.

Aim: To generate a landscape of the current knowledge in the interventional management and outcomes of purulent skin and soft tissue infections., Design: This study is a scoping review., Methods: Electronic searches were undertaken using CINAHL, Medline, Cochrane Library, British Nursing Index, Science Direct, the National Health Service knowledge and library hub, ClinicalTrials.gov, and MedNar. The population, concept, context framework, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews were utilised, supporting a rigorous appraisal and synthesis of literature. Data Sources . The initial search and synthesis of literature were completed in January 2022 with repeat searches completed in March 2022 and July 2023. There were no imposed chronological parameters placed on the returned literature., Results: Nineteen papers were reviewed. Incision and drainage with primary closure, needle aspiration, loop drainage, catheter drainage, and suction drainage are viable adjuncts or alternatives to the traditional surgical management of skin and soft tissue abscesses., Conclusion: Despite the empirically favourable alternatives to the incision and drainage technique demonstrated, this does not appear to be driving a change in clinical practice. Future research must now look to mixed and qualitative evidence to understand the causative mechanisms of incision and drainage and its ritualistic practice. Implications . Ritual surgical practices must be challenged if nurses are to improve the treatment and management of this patient group. This will lead to further practice innovation. Impact : This study explored the challenges posed to patients, clinicians, nurses, and stakeholders, resulting from the ritualistic practice of the incision and drainage technique in purulent skin or soft tissue abscesses. Empirically and holistically viable alternatives were identified, impacting all identified entities and recommending a wider holistic study. Reporting Method . Adherence to EQUATOR guidance was achieved through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Liam Stout et al.)

Purpose: This qualitative analysis of interviews with surgical patients who received a brief perioperative psychological intervention, in conjunction with standard medical perioperative care, elucidates patient perspectives on the use of pain self-management skills in relation to postoperative analgesics., Design: This study is a secondary analysis of qualitative data from a randomized controlled trial., Methods: Participants (N = 21) were rural-dwelling United States Military Veterans from a mixed surgical sample who were randomized to receive a manual-based, telephone-based Perioperative Pain Self-management intervention consisting of a total of four pre- and postoperative contacts. Semi-structured qualitative interviews elicited participant feedback on the cognitive-behavioral intervention. Data was analyzed by two qualitative experts using MAXQDA software. Key word analyses focused on mention of analgesics in interviews., Findings: Interviews revealed a dominant theme of ambivalence towards postoperative use of opioids. An additional theme concerned the varied ways acquiring pain self-management skills impacted postoperative opioid (and non-opioid analgesic) consumption. Participants reported that employment of pain self-management strategies reduced reliance on pharmacology for pain relief, prolonged the time between doses, took the "edge off" pain, and increased pain management self-efficacy., Conclusions: Perioperative patient education may benefit from inclusion of teaching non-pharmacologic pain self-management skills and collaborative planning with patients regarding how to use these skills in conjunction with opioid and non-opioid analgesics. Perianesthesia nurses may be in a critical position to provide interdisciplinary postoperative patient education that may optimize postoperative pain management while minimizing risks associated with prolonged opioid use., (Published by Elsevier Inc.)

Infection by parasites with complex life cycles such as trematodes depends on many environmental factors which may result in a time-lag between host biomass fluctuations and parasite density in hosts. A cockle (marine bivalve, second intermediate host) population and its associated parasite community were monitored over 15 years. A time-shift correlation analysis suggests that trematode abundance in cockles responds to cockle biomass after a long delay (8 year time-lag). Thus, these parasites can sustainably support a deficit of their intermediate host., (Copyright © 2023 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Competing InterestsThe authors have no competing interests to declare that are relevant to the content of this article.

Background: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported., Objective: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia., Design: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505)., Setting: 46 U.S. and Canadian hospitals., Participants: Patients aged 50 years or older undergoing hip fracture surgery., Intervention: Spinal or general anesthesia., Measurements: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care., Results: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups., Limitation: Missing outcome data and multiple outcomes assessed., Conclusion: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia., Primary Funding Source: Patient-Centered Outcomes Research Institute .

Background: A previous single-center survey of trauma and general surgery faculty demonstrated perceived positive impact of trauma and surgical subspecialty service-based advanced practice providers (SB APPs). The aim of this multicenter survey was to further validate these findings., Methods: Faculty surgeons on teams that employ SB APPs at 8 academic centers completed an electronic survey querying perception about advanced practice provider (APP) competency and impact., Results: Respondents agreed that SB APPs decrease workload (88%), length of stay (72%), contribute to continuity (92%), facilitate care coordination (87%), enhance patient satisfaction (88%), and contribute to best practice/safe patient care (83%). Fewer agreed that APPs contribute to resident education (50%) and quality improvement (QI)/research (36%). Although 93% acknowledged variability in the APP level of function, 91% reported trusting their clinical judgment., Conclusion: This study supports the perception that SB APPs have a positive impact on patient care and quality indicators. Areas for potential improvement include APP contribution to resident education and research/QI initiatives.

Background: Understanding the mechanisms that regulate hair cell (HC) differentiation in the organ of Corti (OC) is essential to designing genetic therapies for hearing loss due to HC loss or damage. We have previously identified Fibroblast Growth Factor 20 (FGF20) as having a key role in HC and supporting cell differentiation in the mouse OC. To investigate the genetic landscape regulated by FGF20 signaling in OC progenitors, we employ Translating Ribosome Affinity Purification combined with Next Generation RNA Sequencing (TRAPseq) in the Fgf20 lineage., Results: We show that TRAPseq targeting OC progenitors effectively enriched for RNA from this rare cell population. TRAPseq identified differentially expressed genes (DEGs) downstream of FGF20, including Etv4, Etv5, Etv1, Dusp6, Hey1, Hey2, Heyl, Tectb, Fat3, Cpxm2, Sall1, Sall3, and cell cycle regulators such as Cdc20. Analysis of Cdc20 conditional-null mice identified decreased cochlea length, while analysis of Sall1-null and Sall1-ΔZn2-10 mice, which harbor a mutation that causes Townes-Brocks syndrome, identified a decrease in outer hair cell number., Conclusions: We present two datasets: genes with enriched expression in OC progenitors, and DEGs downstream of FGF20 in the embryonic day 14.5 cochlea. We validate select DEGs via in situ hybridization and in vivo functional studies in mice., (© 2020 Wiley Periodicals LLC.)

Chromatin-remodeling complexes play critical roles in establishing gene expression patterns in response to developmental signals. How these epigenetic regulators determine the fate of progenitor cells during development of specific organs is not well understood. We found that genetic deletion of Brg1 (Smarca4), the core enzymatic protein in SWI/SNF, in nephron progenitor cells leads to severe renal hypoplasia. Nephron progenitor cells were depleted in Six2-Cre, Brg1 flx/flx mice due to reduced cell proliferation. This defect in self-renewal, together with impaired differentiation resulted in a profound nephron deficit in Brg1 mutant kidneys. Sall1, a transcription factor that is required for expansion and maintenance of nephron progenitors, associates with SWI/SNF. Brg1 and Sall1 bind promoters of many progenitor cell genes and regulate expression of key targets that promote their proliferation., (Published by Elsevier Inc.)

Fibrosis is a final common pathway for many causes of progressive chronic kidney disease (CKD). Arginine-glycine-aspartic acid (RGD)-binding integrins are important mediators of the pro-fibrotic response by activating latent TGF-β at sites of injury and by providing myofibroblasts information about the composition and stiffness of the extracellular matrix. Therefore, blockade of RGD-binding integrins may have therapeutic potential for CKD. To test this idea, we used small-molecule peptidomimetics that potently inhibit a subset of RGD-binding integrins in a murine model of kidney fibrosis. Acute kidney injury leading to fibrosis was induced by administration of aristolochic acid. Continuous subcutaneous administration of CWHM-12, an RGD integrin antagonist, for 28 days improved kidney function as measured by serum creatinine. CWHM-12 significantly reduced Collagen 1 (Col1a1) mRNA expression and scar collagen deposition in the kidney. Protein and gene expression markers of activated myofibroblasts, a major source of extracellular matrix deposition in kidney fibrosis, were diminished by treatment. RNA sequencing revealed that inhibition of RGD integrins influenced multiple pathways that determine the outcome of the response to injury and of repair processes. A second RGD integrin antagonist, CWHM-680, administered once daily by oral gavage was also effective in ameliorating fibrosis. We conclude that targeting RGD integrins with such small-molecule antagonists is a promising therapeutic approach in fibrotic kidney disease., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Major advances in the field of pediatric oncology have resulted from rigorous, prospective clinical oncology research trials. Optimizing access for all children and adolescents to clinical research trials is an important goal. Barriers to clinical trial enrollment are numerous, involving the health care system, research infrastructure, access to care, providers, and participants. The perspectives of pediatric oncologists may provide insight into the barriers of clinical trial enrollment for this unique population., Methods and Materials: We conducted qualitative structured interviews over two months of pediatric oncologists in a community-based clinical network as part of a quality improvement project aimed at increasing enrollment rates at St. Jude Affiliate Clinics. We assessed barriers and facilitators to clinical trial opportunities for racial and ethnic minority pediatric participants. In the same fiscal year of the interviews, we tracked clinical trial enrollment by race and ethnicity of the participant over 12 months., Results: The major barriers to clinical trial enrollment for pediatric cancer minority participants included language discordance, travel difficulties, and complex trial designs. In contrast, the major facilitators included building trust with participants and their parents, and education on the merits of clinical research studies. We did not observe any disparities in clinical trial enrollment among the racial and ethnic minority participants of the clinical trials conducted across our network of pediatric oncology clinics., Conclusions: Identifying barriers and facilitators may improve clinical trial enrollment for underrepresented participant groups., (© 2019 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Background: Introduced in 1970, the Swan-Ganz catheter (SGC) soon became widely used because of its unique usefulness in managing intensive care patients. Unfortunately, SGC usage was complicated by pulmonary artery rupture (PAR) with a 50% mortality rate that led to a near banning of the SCG in the late 1980s. Increasing knowledge and decreasing incidence of SGC-related PARs (SGPARs) led to the current feeling that the present SGPAR incidence is now low enough to tolerate given the lives saved by SGC usage. However, an important unknown is that, to our knowledge, pathologists have never published a comprehensive microscopic description of a SGPAR., Case Report: A 73-year-old woman with moderate pulmonary hypertension died from a SGPAR soon after single SGC measurements of right ventricular and pulmonary capillary wedge pressures. By using what we thought to be an appropriate method of dissection, we did a complete microscopic step section study of the 1.6 cm SGPAR revealing 12 relatively uniform longitudinal tears (one perforating) consistent with an overinflated SGC balloon or a weakened arterial wall., Literature Review: A MEDLINE search of 38 consecutive SGPARs from 2014 to 1980 found 52 cases in 38 papers. Analysis revealed that all 46 SGPARs suitable for study came from large institutions, and confirmed that elderly women were more likely to have SGPARs than elderly men., Conclusions: More and better data are needed before fully informed decisions can be made regarding future SGC usage., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Positive patient identification is pivotal to several steps of the transfusion process; it is integral to ensuring that the correct blood is given to the correct patient. If patient misidentification occurs, this has potentially fatal consequences for patients. Historically patient involvement in healthcare has focused on clinical decision making, where the patient, having been provided with medical information, is encouraged to become involved in the decisions related to their individualised treatment. This article explores the aspects of patient contribution to patient safety relating to positive patient identification in transfusion. When involving patients in their care, however, clinicians must recognise the diversity of patients and the capacity of the patient to be involved. It must not be assumed that all patients will be willing or indeed able to participate. Additionally, clinicians' attitudes to patient involvement in patient safety can determine whether cultural change is successful.

Within Scottish hospitals transfusion education is mandatory for all staff involved in the process of transfusion. Currently two modes of delivery exist, face-to-face and e-learning. The researcher,a transfusion practitioner, wished to evaluate the perceptions of registered nurses within her local children's hospital to the transfusion education available. The aim of the evaluation was to ascertain whether there were perceived benefits, whether expectations were met and whether nurses perceived that there were any barriers to undertaking the education. Both quantitative and qualitative data were obtained by means of a questionnaire; all registered nurses in the hospital were invited to participate. The study indicates a high level of compliance with mandatory transfusion education and suggests both satisfaction and perceived benefits with transfusion education among those who responded. Some barriers were highlighted, but it was noted that these were not exclusive to transfusion education and in the current challenging environment with conflicting priorities on time, resolution may be complex.

The rhizosphere in terrestrial systems is the region of soil surrounding plant roots where there is increased microbial activity; in aquatic plants, this definition may be less clear because of diffusion of nutrients in water, but there is still a zone of influence by plant roots in this environment [1]. Within that zone chemical conditions differ from those of the surrounding environment as a consequence of a range of processes that were induced either directly by the activity of plant roots or by the activity of rhizosphere microflora. Recently, there are a number of new studies related to rhizospheres of aquatic plants and specifically their increased potential for remediation of contaminants, especially remediation of metals through aquatic plant-microbial interaction., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Vertebroplasty is commonly used to treat painful, osteoporotic vertebral compression fractures., Methods: In this multicenter trial, we randomly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement (control group). The primary outcomes were scores on the modified Roland-Morris Disability Questionnaire (RDQ) (on a scale of 0 to 23, with higher scores indicating greater disability) and patients' ratings of average pain intensity during the preceding 24 hours at 1 month (on a scale of 0 to 10, with higher scores indicating more severe pain). Patients were allowed to cross over to the other study group after 1 month., Results: All patients underwent the assigned intervention (68 vertebroplasties and 63 simulated procedures). The baseline characteristics were similar in the two groups. At 1 month, there was no significant difference between the vertebroplasty group and the control group in either the RDQ score (difference, 0.7; 95% confidence interval [CI], -1.3 to 2.8; P=0.49) or the pain rating (difference, 0.7; 95% CI, -0.3 to 1.7; P=0.19). Both groups had immediate improvement in disability and pain scores after the intervention. Although the two groups did not differ significantly on any secondary outcome measure at 1 month, there was a trend toward a higher rate of clinically meaningful improvement in pain (a 30% decrease from baseline) in the vertebroplasty group (64% vs. 48%, P=0.06). At 3 months, there was a higher crossover rate in the control group than in the vertebroplasty group (51% vs. 13%, P<0.001) [corrected]. There was one serious adverse event in each group., Conclusions: Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group. (ClinicalTrials.gov number, NCT00068822.), (2009 Massachusetts Medical Society)

Background and Purpose: Multiple case series of vertebroplasty outcomes have been published, though no large, placebo controlled trial has yet been performed. Our aim was to report baseline characteristics for the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of vertebroplasty., Materials and Methods: We compared baseline demographics, pain scores, and scores on the modified Roland-Morris Disability Scale (RMDS), a back pain-specific metric, between 2 groups. One group included subjects enrolled at the lead INVEST site (n = 27 to date). The second group consisted of eligible patients seen concurrently at the lead INVEST site, who declined enrollment (n = 70). Comparisons were made by using 2-sample t tests., Results: Mean ages were similar between groups, averaging approximately 74 years among study participants and 77 years among nonenrolled eligible patients (P = .17). Approximately 75% of subjects were female in both groups. RMDS scores of enrolled patients at the lead site (18.0 +/- 4.2) were not statistically different from those of eligible nonenrolled patients at the lead site (18.6 +/- 3.6, P = .49). Pain scores in the enrolled subjects were measured as "average intensity over the prior 24 hours" with mean scores of 7.6 +/- 2.1 among enrolled patients at the lead site. Pain scores in eligible nonenrolled patients were measured as "pain at rest," with mean score of 3.4 +/- 3.3, and "pain with activity," with mean score of 8.5 +/- 2.0., Conclusions: Patient demographics among subjects enrolled in the INVEST are similar to those in a cohort of eligible nonenrolled patients. Back pain-specific disability was similar between subjects enrolled in the INVEST study and eligible nonenrolled patients at the lead site.

This two-part unit focuses on monitoring patients who have blood transfusions. The first part emphasised the importance of visual observations and monitoring patients' vital signs to ensure rapid action should there be any adverse effects. This second part describes the physiology behind the signs and symptoms of a blood transfusion reaction.

This two-part unit explores the monitoring of patients receiving a blood transfusion. This first part outlines the importance of making careful checks before the transfusion, as well as that of monitoring a patient receiving a transfusion.

Background: The treatment of painful osteoporotic vertebral compression fractures has historically been limited to several weeks of bed rest, anti-inflammatory and analgesic medications, calcitonin injections, or external bracing. Percutaneous vertebroplasty (the injection of bone cement into the fractured vertebral body) is a relatively new procedure used to treat these fractures. There is increasing interest to examine the efficacy and safety of percutaneous vertebroplasty and to study the possibility of a placebo effect or whether the pain relief is from local anesthetics placed directly on the bone during the vertebroplasty procedure., Methods/designs: Our goal is to test the hypothesis that patients with painful osteoporotic vertebral compression fractures who undergo vertebroplasty have less disability and pain at 1 month than patients who undergo a control intervention. The control intervention is placement of local anesthesia near the fracture, without placement of cement. One hundred sixty-six patients with painful osteoporotic vertebral compression fractures will be recruited over 5 years from US and foreign sites performing the vertebroplasty procedure. We will exclude patients with malignant tumor deposit (multiple myeloma), tumor mass or tumor extension into the epidural space at the level of the fracture. We will randomly assign participants to receive either vertebroplasty or the control intervention. Subjects will complete a battery of validated, standardized measures of pain, functional disability, and health related quality of life at baseline and at post-randomization time points (days 1, 2, 3, and 14, and months 1, 3, 6, and 12). Both subjects and research interviewers performing the follow-up assessments will be blinded to the randomization assignment. Subjects will have a clinic visit at months 1 and 12. Spine X-rays will be obtained at the end of the study (month 12) to determine subsequent fracture rates. Our co-primary outcomes are the modified Roland score and pain numerical rating scale at 1 month., Discussion: Although extensively utilized throughout North America for palliation of pain, vertebroplasty still has not undergone rigorous study. The study outlined above represents the first randomized, controlled study that can account for a placebo effect in the setting of vertebroplasty., Trial Registration: Current Controlled Trials ISRCTN81871888.

The development of extra efferent vessels (EEV) is a little-known feature of diabetic glomerulopathy. The only previous large study [Min W, Yamanaka N. Three-dimensional analysis of increased vasculature around the glomerular vascular pole in diabetic nephropathy. Virchows Archiv A Pathol Anat 1993; 423:201-7] known to us found that up to 5 EEV per glomerulus (glom) each drained a separate lobule. Most EEV connected to the second- and third-order branches of the afferent arteriole (AA), and drained into peritubular capillaries. Although not so stated, the illustrations suggested that some EEV could be shunts, and thus detrimental to glom function, and possibly glom health. There was no correlation between the unquantitated presence of increased EEV at the vascular pole (VP) and the severity of the major diabetic glomerular (glom) lesions. The authors opined that efferent arteriole (EA) stenosis by insudative lesions (IL) stimulated the formation of EEV. To confirm and extend these findings, we have repeated the study in 18 diabetic cases with mild to severe, but not end-stage, diffuse and nodular lesions (DL and NL), 8 controls, and the 2 normal traumatic nephrectomy cases. Up to 18 EEV per glom were found in diabetic cases along with occasional EEV in controls. EEV contained muscle and were almost identical to the EA in structure. Nearly all EEV connected with efferent glom capillaries at the VP, where they exited the glom through apparently preexisting gaps in the Bowman's capsule and/or glomerular capillary basement membranes (BCBM/GCBM). The EA exited through a similar gap, so the exit of EEV was accomplished without altering the anatomical relationships between the exiting vessels and the components of the VP thought to be important in the control of glom outflow. The largest number of EEV occurred in long-standing T2DM cases with mild to moderate DL and NL. Complete photographic glom reconstructions revealed numerous anastomoses among efferent glom capillaries in normal and diabetic gloms with mild to moderate DL and NL. No disproportionately dilated EEV were seen. The findings just cited confirm that EEV are common and surprisingly numerous in diabetic gloms. They suggest that EEV formation served to preserve glom function, and that EEV could neither shunt nor restrict glom outflow locally. In our opinion, the formation of EEV represents a significant, possibly hemodynamically induced, remodeling of the glom that should be added to the list of changes that occur in diabetes. It is hypothesized that EEV develop because of increased glom inflow, and that the latter may be attributable to AA muscle damage that impairs its contractile ability.

Purpose: The purpose of this research was to investigate the relationship between glutathione S-transferase (GST) polymorphisms and survival, and chemotherapy-related toxicity in 278 glioma patients., Experimental Design: We determined genetic variants for GSTM1, GSTT1, and GSTP1 enzymes by PCR and restriction fragment length polymorphisms. We conducted Kaplan-Meier and Cox-proportional hazard analyses to examine whether the GST polymorphisms are related to overall survival, and logistic regression analysis to explore whether the GST polymorphisms are associated with toxicity., Results: For patients with anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma (n = 78), patients with GSTP1*A/*A-M1 null genotype survived longer than did the rest of the group (median survival "not achieved," and 41 months, respectively; P = 0.06). Among patients treated with nitrosoureas (n = 108), those with GSTP1*A/*A and GSTM1 null genotype were 5.7 times (95% confidence interval, 0.9-37.4) more likely to experience an adverse event secondary to chemotherapy, compared with the others., Conclusions: In patients with anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma, combination of germ-line GSTP1*A/*A and GSTM1 null genotype confers a survival advantage. Patients with this genotype also have an increased risk of adverse events secondary to chemotherapy that primarily comprised nitrosourea alkylating agents.

To examine the nature and extent of personality dysfunction related to somatization, the authors administered the Structured Interview for DSM-IV Personality and the NEO Five-Factor Inventory to a series of somatizing and nonsomatizing patients in a general medicine clinic. A greater percentage of somatizers met criteria for one or more DSM-IV personality disorders, especially obsessive-compulsive disorder, than did control patients. Somatizers also differed from control patients with respect to self-defeating, depressive, and negativistic personality traits and scored higher on the dimension of neuroticism and lower on the dimension of agreeableness. In addition, initial and facultative somatizers showed more personality pathology than true somatizers. These findings suggest that certain personality disorders and traits contribute to somatization by way of increased symptom reporting and care-seeking behavior.

Objectives: to determine IL-1alpha and IL-1beta levels in patients with bacterial cystitis, microscopic hematuria, and gravid females relative to a control group of normal subjects., Methods: enzyme immunoassays were used to measure concomitantly urinary IL-1alpha and IL-1beta in clean catch urine samples from normal subjects (n = 31) and study patients (n = 46). All normal subjects and patients underwent urinalysis, urine culture, and urine creatinine level determination. Since the IL-1alpha assay was developed for serum, the utility of the assay for urine specimens was unknown. The key parameters of urine collection, processing and sample storage for IL-1alpha were evaluated in detail., Results: mean values +/- SEM (pg/mg) for IL-1alpha/ Cr and IL-1beta/Cr were control group (0.25 +/- 0.10 and 0.17 +/- 0.06), bacterial cystitis (9.97 +/- 1.15 and 42.45 +/- 1.86), and microscopic hematuria (2.81 +/- 0.65 and 2.82 +/- 0.70). Differences in cytokine levels between the control group and patients with either bacterial cystitis or microscopic hematuria were statistically significant for both IL-1alpha/Cr (P < 0.026; P < 0.007, respectively) and IL-1beta /Cr (P < 0.0004; P < 0.014, respectively). IL-1beta/Cr correlates better with pyuria than IL-1alpha/ Cr (P = 0.02 vs P = 0.44). In gravid females, only IL-1alpha was significantly elevated relative to non-pregnant females (IL-1beta elevation approached statistical significance). Gravid females with positive urine cultures could not be distinguished from those with negative cultures based on either interleukin (P > 0.05)., Conclusions: Significant elevations of IL-1alpha and IL-1beta occur in patients with bacterial cystitis and microscopic hematuria. Correlation between pyuria and cytokine elevation was stronger for IL-1beta than for IL-1alpha. Changes in IL-1alpha may reflect changes in the bladder epithelium rather than in the inflammatory leukocytes. The ability of IL-1alpha and IL-1beta to serve as markers for bacterial cystitis in gravid females is diminished due to high basal levels during pregnancy.

Purpose: We challenge the requirement for routine placement of a nephrostomy tube following percutaneous renal surgery., Materials and Methods: A total of 50 patients underwent tubeless percutaneous renal procedures consisting of nephrolithotripsy, endopyelotomy, and stone extraction plus endopyelotomy performed during the same setting. In the initial 30 patients a Double-J* stent and a Councill nephrostomy tube were placed at the end of the procedure. The Councill catheter was removed 2 to 3 hours postoperatively. The subsequent 20 patients received only a Double-J stent with no Councill catheter. This study group was compared to a control group of 50 age, sex and procedure matched patients who had previously undergone standard percutaneous renal procedures with routine placement of postoperative nephrostomy tubes. The incidence of complications, analgesia requirements, length of hospitalization, interval to return to normal activities and cost of treatment were compared between the 2 groups., Results: All 50 tubeless percutaneous procedures were performed successfully without significant complications. In the initial 15 patients postoperative renal ultrasound demonstrated no urinoma. Hospitalization was 0.6 days for the study group and 4.6 days for the controls (p = 0.0001). Average parenteral or intramuscular analgesia requirements were 11.58 and 36.06 mg. morphine sulfate, respectively (p = 0.0001), with patients requiring oral analgesia for 5.9 and 11.7 days, respectively (p = 0.0001). Patients in the study group returned to normal activities within 17.85 days versus 26.6 days for the controls (p = 0.0004). The costs of the procedures were $1,638 and $3,750 (129% greater), respectively, for a cost saving of $2,112 per case., Conclusions: Tubeless percutaneous renal surgery is a safe procedure and offers numerous advantages over routine placement of a nephrostomy tube. The hospitalization, analgesia requirements, return to normal activities as well as cost are significantly less with this new technique.

The major changes in pancreatic islet function during pregnancy and after exposure to lactogens are an increase in beta-cell proliferation and enhanced insulin secretion. In this study we examined INS-1 cells as a potential model for further inquiry into PRL signaling in beta-cells. Proliferation of beta-cells, insulin secretion, and quantitative immunocytochemical analysis of STAT5 translocation were studied. PRL treatment of INS-1 cells resulted in a 2- to 4-fold increase in cell proliferation compared to that in the control group. In contrast, there was no effect of PRL treatment on HIT cell proliferation and only a very small effect on RIN cell proliferation. A significant effect on INS-1 cell proliferation was observed at 10 ng/ml and reached a maximum at 200 ng/ml. PRL treatment resulted in enhanced insulin secretion from INS-1 cells. There was a time-dependent increase in insulin secretion, which when corrected for cell number was 1.5-fold greater in the PRL-treated cells. The effects of PRL on cell division and insulin secretion were glucose dependent. The presence of the JAK family of tyrosine kinases and the transcription factor STAT5 in INS-1 cells was examined by immunocytochemical techniques. Although all members of the JAK family of kinases were detected, the staining intensity of JAK-2 was noticeably more intense. Initial studies of STAT5 translocation were performed using PRL-dependent Nb2 lymphoma cells, in which PRL treatment resulted in a nearly complete translocation of cytoplasmic STAT5 to the nucleus. Under control conditions there was a near-equal fluorescence intensity of STAT5 staining in the nucleus and cytoplasm of INS-1 cells. PRL treatment resulted in a time-dependent increase in STAT5 staining in the nucleus, with a corresponding decrease in the cytoplasm. The STAT5 staining intensity in the nucleus remained elevated for the duration of PRL treatment. This effect was reversible upon removal of PRL from the medium. Besides PRL, both GH and FBS induced a similar translocation of STAT5 to the nucleus. Although present in RIN cells, no detectable changes in STAT5 were observed in RIN cells after exposure to PRL, GH, or FBS. INS-1 cells should provide a good model for further inquiry into the intracellular signaling pathways used by PRL and how these events alter islet function.

Insulin-degrading enzyme (IDE) has been implicated in the intracellular degradation of insulin in insulin target cells. Knowledge of the existence of this enzyme in the intestine will be beneficial to the achievement of clinical oral efficacy of insulin. A comparative study was conducted with rat intestine, human colon adenocarcinoma (Caco-2) cells, and human ileum. Confocal microscopy analysis using the anti-IDE antibody showed that IDE was localized in the mucosal cells of rat and human intestines, as well as in Caco-2 cells. Immunostaining of this enzyme was homogeneous throughout the cell excluding nucleus, indicating a typical cytosolic distribution in rat and human enterocytes and in Caco-2 cells.

During pregnancy, islets undergo a number of up-regulatory changes to meet the increased need for insulin. One of the most important changes is an increase in glucose-stimulated insulin secretion with a reduction in the glucose-stimulated threshold. Similarly, placental lactogen and PRL induce the same changes in islets as pregnancy. In this study, we examined the effects of pregnancy and PRL treatment of islets in vitro on insulin secretion; glucokinase and hexokinase activities; glucokinase, hexokinase, and glucose transporter 2 protein levels; and rates of glucose utilization and oxidation. Glucokinase activity was 4.9 +/- 0.4 pmol glucose/ng DNA.h in control islets and was significantly increased by 50% in islets on day 15 of pregnancy and by 60% on day 20 of pregnancy. Hexokinase activity was 11.7 +/- 0.9 pmol glucose/ng DNA.h in control islets and was increased by 20% in islets on day 15 of pregnancy and by 90% on day 20 of pregnancy. In the in vitro studies, glucokinase activity was 7.4 +/- 0.89 pmol glucose/ng DNA.h in control islets. PRL treatment of islets in vitro increased glucokinase activity by 60%, an effect similar to that observed in the pregnancy islets. In contrast, hexokinase activity was nearly undetectable in cultured islets, whether control or PRL treated. Quantitative Western blot analysis of glucokinase and hexokinase was performed using equivalent number of protein per lane for all experimental groups. On a protein equivalency basis, glucokinase expression levels were the same in control islets on days 15 and 20 of pregnancy. Likewise, hexokinase levels were not different between control islets and islets on days 15 and 20 of pregnancy. Similarly, Western blot analysis of cultured islets indicated that there were not effect of PRL on glucokinase or hexokinase levels. However, when enzyme levels were normalized on the basis of DNA, the levels of expression appeared to be commensurate with their activities. In cultured islets, the very low level of hexokinase activity corresponded to the low level of hexokinase detected by Western blots. Glucose transporter 2, as determined by Western blot quantification, was increased 2-fold in pregnancy islets on day 15 and increased by 45% in pregnancy islets on day 20. Similar results were observed in cultured islets where glucose transporter 2 was increased 2-fold in PRL-treated islets. Islet glucose utilization and oxidation rates on day 15 of pregnancy were significantly greater than those in control islets at all glucose concentrations examined. This enhanced glucose sensitivity resulted in a shift of the glucose utilization and oxidation response curves to the left. Comparable results were obtained from islets on day 20 of pregnancy. PRL treatment of islets in vitro resulted in the same changes in glucose utilization and oxidation rates that were observed during pregnancy. These results demonstrate changes in glucokinase, hexokinase, and glucose transporter 2 levels and glucose metabolism that occur as islets adapt to an increased need for insulin secretion during pregnancy. The results also indicate that these same changes can be induced by PRL treatment of islets in vitro. This provides further evidence that the long term adaptive changes that occur under the normoglycemic conditions of pregnancy are mediated by lactogen-regulated events.

Objectives: Dimethyl sulfoxide (DMSO), an agent that provides symptomatic relief in patients with interstitial cystitis (IC) works via an unknown mechanism. We investigated whether DMSO acts as a chemical stimulant of mast cell degranulation., Methods: A radioimmunoassay (RIA) specific for histamine was used to test this hypothesis. Twelve women with strictly diagnosed IC were treated with intravesical instillations of DMSO. Treatments were repeated at varying intervals, and each patient received three to six treatments. Urine histamine levels were measured before and after each intravesical instillation of DMSO. Dilutional effects of DMSO were corrected for by conversion of urine histamine concentration to urine histamine:creatinine ratio., Results: The RIA was unaffected by the addition of DMSO to urine. No consistent change in the urine histamine:creatinine ratio following DMSO instillation was found. Trend analysis revealed no trend in the histamine:creatinine ratio with time., Conclusions: The relief of symptoms reported in 50% to 77% of patients treated with intravesical DMSO is not related to detectable mast cell release of histamine. Other mechanisms of action must be investigated to explain the beneficial effect of this agent.

Lactogenic hormones, PRL and placental lactogen, are important regulators of insulin secretion and islet beta-cell proliferation. In this study we examined the presence of PRL receptor immunoreactivity in pancreatic islets of Langerhans using PRL receptor monoclonal antibodies provided by Dr. Paul Kelly. Studies were performed using islets isolated from neonatal, adult, and day 14 pregnant rats. The islets were examined by immunohistochemistry and laser scanning confocal microscopy. In neonatal rat islets, PRL receptors were observed in beta- and alpha-cells, but not in delta-cells. Among islet beta- and alpha-cells there was heterogeneity of cellular staining for PRL receptors. A small portion of the cells was intensely stained for PRL receptors. However, the majority of the cells had a much lower level of staining intensity, suggesting that most islet cells have a low level of PRL receptors. In general, alpha-cells were more uniformly stained than beta-cells. Similar results were obtained with adult rat islets, in which, again, there was a large range of staining intensity and many cells with low levels of PRL receptor. Rats on day 14 of pregnancy had an increased level of islet PRL receptor expression compared with age-matched control animals. There was also a decrease in cellular heterogeneity for PRL receptors, with nearly all cells having a uniformly high level of PRL receptor expression. JAK2, the tyrosine kinase associated with PRL receptors, was examined in Nb2 cells and islets. JAK2 immunoreactivity was detected at the cell membrane in very low levels in Nb2 cells. It was also found in numerous vesicular structures in the cytoplasm, where it colocalized with PRL receptors. A prominent feature of all cells was the presence of JAK2 in the nucleus, but not the nucleolus. In islets, JAK2 immunoreactivity was similarly observed in the nucleus of nearly all cells. However, the vesicular cytoplasmic location of JAK2 was less frequently observed and did not colocalize with PRL receptors. For comparison, JAK2 immunoreactivity was examined in several other tissues where it was detected in fibroblasts (endomysial and endoneurial cells), smooth muscle cells, and ganglion cells in the pancreas. JAK2 was notably absent from pancreas acinar cells, hepatocytes, skeletal muscle cells, and Schwann cells. This study demonstrates the presence of PRL receptors in islet beta- and alpha-cells, but not delta-cells. There was an increase in PRL receptor expression in islets during pregnancy, which is commensurate with the up-regulation of islet function. In addition, JAK2 immunoreactivity was detected in most islet cells and Nb2 node cells.

Relationships between nurses and families form the foundation of effective nursing practice. This article describes a study of medical-surgical nurses' perceptions of the impact of a Family Systems Nursing Continuing Education Project (FSNP). Four major themes emerged from the study: 1) reduction in family crises during acute hospitalizations; 2) increased efficiency and productivity of discharge planning; 3) increased family involvement in multidisciplinary conferences with nurse-family interactions described as collaborative; and 4) improvement in nursing competence and confidence while caring for families. Implications for clinical practice, continuing education, and research are presented.

L-Arginine:glycine amidinotransferase (transamidinase) occurs at high concentrations in the kidney and the pancreas of rats. The cellular localization of transamidinase was investigated in fetal, neonatal, and adult rat pancreatic tissue using three indicators of the presence of transamidinase: (1) immunofluorescence microscopy, (2) in vitro enzymatic activity measurements on homogenates of whole pancreas and on isolated acinar and islet tissue from adult rats, and (3) ornithine production from perfused adult rat pancreas. The cellular localization of transamidinase was determined in fetal, neonatal, and adult rat pancreas, using a polyclonal guinea pig antibody made against a highly purified preparation of kidney transamidinase. Immunoreactive transamidinase was detected only in the pancreatic acinar cells. The cellular distribution of the immunostaining was compatible with the presence of transamidinase in mitochondria. The transamidinase enzymatic activity of whole pancreatic homogenates was 13.4 +/- 0.7 U/g wet weight (n = 11). In pancreata where islets had been isolated away from the acinar tissue, the transamidinase activity was similar to that of the whole pancreatic homogenates (16.8 +/- 2 U/g wet weight). Any transamidinase activity present in isolated islets was below the sensitivity of the assay. Transamidinase activity in the isolated perfused pancreas was determined by measuring the amount of ornithine released into the perfusate. The transamidinase activity of the perfused pancreas was 16.4 +/- 1.8 U/g pancreas and is an estimate of the physiological production capacity of the enzyme (270 +/- 29 nmol ornithine/min/g pancreas). These results indicate that transamidinase is present at high concentrations in the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological analysis of hormone content and functional assessment of hormone secretion were conducted in beta TC-6 cells, an insulin-secreting cell line derived from transgenic mice expressing the large T-antigen of simian virus 40 (SV40) in pancreatic beta-cells. We observed by immunohistochemistry and confocal microscopy that beta TC-6 cells contain abundant insulin and small amounts of glucagon and somatostatin (SRIF). Glucagon usually co-localized with insulin, whereas cells containing SRIF did not contain insulin or glucagon. Static incubation and perifusion experiments demonstrated that beta TC-6 cells at passage 30-45 secrete insulin in response to glucose. In static incubations, maximal stimulation was achieved for glucose concentrations > 2.8 mmol/l glucose, and the half-maximal effect was observed at 0.5 mmol/l. Maximal stimulation was four times greater than HIT-T15 cells at passage 72-81, although HIT cells had a greater response over their basal levels. The magnitude of the insulin response to glucose in perifusion was 1,734 +/- 384 pmol.l-1. min and was 4.6-fold greater in the presence of 3-isobutyl-1-methylxanthine. Low amounts of glucagon were released in response to amino acids. Epinephrine (EPI), and to a lesser extent SRIF, inhibited phasic glucose-induced insulin secretion. A major portion of these inhibitory effects was mediated by pertussis toxin-sensitive substrates. Immunoblots detected the presence of the G-proteins Gi alpha 2, Gi alpha 3, and Go alpha 2. These results indicate that beta TC-6 cells are a glucose-responsive cell line in which insulin exocytosis is physiologically regulated by EPI and SRIF through Gi/Go-mediated mechanisms.

The transjugular intrahepatic portosystemic shunt has recently become widely used for portal decompression. Shunt stenosis resulting from pseudointimal hyperplasia and hepatic encephalopathy are emerging as important midterm complications of the procedure. Bile extravasation caused by bile duct transection by the stent wires has been suggested as a cause of the pseudo-intimal hyperplasia. The present case report describes a 6 1/2-month-old transjugular intrahepatic portosystemic shunt in which apparent biliary epithelial proliferation had formed large cyst-like spaces within the pseudo-intima at the site of shunt stenosis. We hypothesize that secretory products from these biliary epithelial cells may have contributed to shunt stenosis by creating expansile cysts or by stimulating pseudointimal hyperplasia. In addition, we found a large, recent Zahn's infarct adjacent to the stent. Pseudointimal hyperplasia had extended from the stent wires into the orifices of contiguous small portal and hepatic vein branches. The resulting stenosis of these small veins may have contributed to the Zahn's infarct.

Kidneys from 74 consecutive, primarily non-insulin-dependent diabetics at autopsy and 59 age-, sex, and ethnic group-matched controls were examined qualitatively and semiquantitatively to determine the prevalence and severity of insudative lesions (ILs) and obsolescent glomeruli with (OGcFC) and without (OGsFC) insudative (fibrin cap) lesions. A subset of 25 cases with advanced diabetic changes was examined using serial sections, immunohistochemical stains, and electron microscopy to determine the pathogenesis of ILs and OGcFCs. Insudative lesions consisted of intramural accumulations (hereafter called deposits) of presumably imbibed plasma proteins and lipids within renal arterioles, glomerular capillaries, Bowman's capsule, and proximal convoluted tubules. Insudative lesions in Bowman's capsule are called capsular drop lesions (CDs), in glomerular capillaries they are called fibrin cap lesions (FC), and in afferent and efferent arterioles they are called hyalinized afferent (HA) and hyalinized efferent (HE) arterioles, respectively. All ILs were much more numerous and/or larger in diabetics than in controls. Contrary to previous opinion, CDs and HE arterioles were not specific for diabetes, being present in small numbers in nine (15%) controls. Controls with CD/HE arterioles had far more HA arterioles and focal mesangiolyses (FMs) than those without. Insudative lesions consisted of the well known homogenous eosinophilic deposits (homogenous eosinophilic ILs) and the less familiar foamy, reticulated, and vacuolar deposits (heterogenous lucent ILs). Homogenous eosinophilic ILs were predominant in afferent arterioles and more so in efferent arterioles, and were segregated into globules of varying density with the denser deposits located peripherally. Two types of CDs, which differed sharply in location and composition, were found. The first was mostly homogenous eosinophilic, usually without capsular adhesions and located near the vascular pole close to preglomerular arterioles. The second was mostly heterogenous lucent, located away from the vascular pole, and consistently connected by adhesions to the capillary tuft usually near FMs and/or Kimmelstiel-Wilson (KW) nodules. The latter ILs sometimes extended in continuity along the internal surface of the basement membrane from Bowman's capsule into the proximal convoluted tubule. It was hypothesized that ILs traveled centrifugally through the walls of preglomerular arterioles to form the first type of CD and longitudinally within the walls of afferent arterioles and glomerular capillaries and through adhesions to form the second. Contrary to previous opinion, FCs were consistently intramural. When numerous, FCs were associated with a form of glomerular obsolescence called OGcFC.(ABSTRACT TRUNCATED AT 400 WORDS)

Tamoxifen has been an effective antiestrogen in suppressing breast cancer growth which is estrogen-responsive or dependent. Early studies have provided circumstantial evidence that transforming growth factor-beta (TGF-beta) may be an autocrine mediator of tamoxifen action. Therefore, it is both fundamentally important and clinically relevant to investigate the relationship between tamoxifen and TGF-beta. In this study, we demonstrated that CAMA-1 cells, which are sensitive to tamoxifen inhibition, did not respond to TGF-beta growth inhibition. The type I and II TGF-beta receptors were undetectable by the radio-ligand affinity labeling technique. Despite the presence of a normal TGF-beta type II receptor gene, the mRNA transcript of the gene was undetectable by the extremely sensitive Intron-differential RNA/PCR method. The possibility that the lack of TGF-beta receptors might be intimately linked to the absence of normal retinoblastoma (Rb) gene products, as suggested by previous studies of retinoblastoma cells, was further investigated. The lack of TGF-beta receptor expression was found due to reasons other than the absence, deletion or abnormality of the Rb gene because a normal Rb gene and its hyper- and hypo-phosphorylated protein products were detected in CAMA-1 cells. In conclusion, our results suggest that the TGF-beta system is not obligatory for antiestrogen growth inhibition of CAMA-1 cells.

A 65 year old healthy female developed a small bowel obstruction after laparoscopic unroofing of a large, symptomatic, right renal cyst. After failure of conservative management, exploratory laparotomy revealed a very localized herniation of small intestine at a trocar site as suggested by CT scan. The hernia was reduced at the time of laparotomy and no bowel resection was necessary. The patient had an uneventful recovery. Although uncommon, bowel herniation at the site of trocar insertion should be recognized as part of the possible morbidity of laparoscopic surgery. The mechanism of development of such a complication and possible preventive measures are reviewed. A "preventive" fascial closure technique is suggested.

Kidneys from 74 consecutively autopsied primarily non-insulin-dependent diabetes cases and 59 age-, sex-, and ethnic group-matched controls were examined qualitatively and semiquantitatively to determine whether focal mesangiolyses (FMs), Kimmelstiel-Wilson (KW) nodules, and glomerular capillary microaneurysms (GCMs) were related lesions, to determine their extent and pathogenic sequence, and to look for associations with structural and functional factors. Light microscopic examination of serial sections, immunohistochemical stains, image analysis, and electron microscopy were used. Focal mesangiolyses, KW nodules, and GCMs occurred in 31 of the 74 diabetes cases (27 had FMs, 29 had KW nodules, and nine had GCMs) and were positively correlated with each other semiquantitatively (r = .71, .70, and .68, respectively). Numerous FMs were found, involving 62% and 78% of the glomeruli in the two most severely affected cases. Most FMs were located at the periphery of KW nodules, but de novo FMs were documented in six cases. Glomerular capillary microaneurysms were deemed occasional complications of FMs because they were much less common, and 25 of the 27 GCMs identified were contiguous with FMs. Focal mesangiolyses and GCMs were deemed transient lesions, being absent in end-stage kidneys. Both FMs and KW nodules consisted of a spectrum of lesions. For the sake of clarity they were arbitrarily divided into two types: edematous and proliferative FMs and simple and complicated KW nodules. Their characteristics suggested the following pathogenic sequence: edematous FM-->proliferative FM-->focal nodular mesangial expansion-->simple KW nodule-->recurrent FM-->complicated KW nodule. Complicated nodules were associated with marked alterations in the lobular capillary. The number of mesangial cells was increased in FMs and they were thought to be responsible for increased matrix production. Focal mesangiolyses and KW nodules were positively associated with diabetes, proteinuria, and hyalinization of afferent and efferent arterioles, but were weakly or not associated with hypertension, arcuate and interlobular artery stenosis, hydroenphrosis, acute pyelonephritis, renal arterial atheromatous emboli, glomerular platelet-fibrin thromboemboli, and congestive heart failure.

Induction of indoleamine-2,3-dioxygenase (IDO) by interferon-gamma (IFN-gamma) is thought to be one mechanism underlying IFN-gamma's antineoplastic properties. Since clinical trials with IFN-gamma have yielded variable efficacy in treating cancers of gynecological origin, we tested the effects of IFN-gamma on cell growth and IDO activity in cell lines from seven gynecologic and five breast cancers. At a dose of 250 IU/ml, IFN-gamma suppressed cell growth and induced IDO activity in one cervical (C41), one vulva (A431), one breast (HS578T) and two ovarian (OVCAR-3, CAOV-3) cancer cell lines. Differing inhibition of cell growth, but with no induction of IDO activity, was found with IFN-gamma treatment of the other cell lines.

To elucidate the relationship between epidermal growth factor (EGF)/transforming growth factor (TGF-alpha) and estradiol-17 beta (E) in cell proliferation, we examined their effects on the breast cancer cell line, CAMA-1. While E was able to consistently induce cell proliferation under a variety of experimental conditions, EGF/TGF-alpha was without effect. Despite the presence of the receptor (EGFR) gene, mature EGFR protein and mRNA were not detected by radioreceptor assay, 35S Met-labelling, and the Intron Differential RNA/PCR method under conditions in which cells remain responsive to E. Furthermore, TGF-alpha is not an autocrine factor in CAMA-1 cells. We demonstrated unequivocally that EGF/TGF-alpha interaction with EGFR is not an obligatory event in mediating estrogen-stimulated cell proliferation.

Objective: Immature mammalian oocytes cultured in vitro undergo inadequate cytoplasmic maturation and hence have a limited potential for fertilization. Our primary objective was to determine if the addition of epidermal growth factor (EGF) to the in vitro culture system would have a positive effect on oocyte cytoplasmic maturation., Design: We studied the effect of different EGF concentrations on both denuded and cumulus-enclosed mouse oocytes cultured in vitro., Main Outcome Measures: The percentage of oocytes undergoing germinal vesicle breakdown (GVBD) and polar body one formation over time as a function of EGF concentration was determined., Results: A dose-related positive effect of EGF on both GVBD and polar body one formation over time was observed for mouse oocytes. As well, a similar effect of EGF was seen on immature human oocytes that had not been stimulated with exogenous gonadotropins., Conclusions: The use of EGF may allow for the performance of successful in vitro fertilization procedures using immature human oocytes retrieved during unstimulated cycles.