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PubMed2003

Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary.

Ovarian follicular development, follicle selection, and the process of ovulation remain poorly understood in most species. Throughout reproductive life, follicle fate is balanced between growth and apoptosis. These opposing forces are controlled by numerous endocrine, paracrine, and autocrine factors, including the ligands represented by the transforming growth factor beta (TGFbeta) superfamily. TGFbeta, activin, inhibin, bone morphometric protein (BMP), and growth differentiation factor 9 (GDF-9) are present in the ovary of many animals; however, no comprehensive analysis of the localization of each ligand or its receptors and intracellular signaling molecules during folliculogenesis has been done. The domestic cat is an ideal model for studying ovarian follicle dynamics due to an abundance of all follicle populations, including primordial stage, and the amount of readily available tissue following routine animal spaying. Additionally, knowledge of the factors involved in feline follicular development could make an important impact on in vitro maturation/in vitro fertilization (IVM/IVF) success for endangered feline species. Thus, the presence and position of TGFbeta superfamily members within the feline ovary have been evaluated in all stages of follicular development by immunolocalization. The cat inhibin alpha subunit protein is present in all follicle stages but increases in intensity within the mural granulosa cells in large antral follicles. The inhibin betaA and betaB subunit proteins, in addition to the activin type I (ActRIB) and activin type II receptor (ActRIIB), are produced in primordial and primary follicle granulosa cells. Additionally, inhibin betaA subunit is detected in the theca cells from secondary through large antral follicle size classes. GDF-9 is restricted to the oocyte of preantral and antral follicles, whereas the type II BMP receptor (BMP-RII) protein is predominantly localized to primordial- and primary-stage follicles. TGFbeta1, 2, and 3 ligand immunoreactivity is observed in both small and large follicles, whereas the TGFbeta type II receptor (TGFbeta RII) is detected in the oocyte and granulosa cells of antral follicles. The intracellular signaling proteins Smad2 and Smad4 are present in the granulosa cell cytoplasm of all follicle size classes. Smad3 is detected in the granulosa cell nucleus, the oocyte, and the theca cell nucleus of all follicle size classes. These data suggest that the complete activin signal transduction pathway is present in small follicles and that large follicles primarily produce the inhibins. Our data also suggest that TGFbeta ligands and receptors are colocalized to large antral follicles. Taken together, the ligands, receptors, and signaling proteins for the TGFbeta superfamily are present at distinct points throughout feline folliculogenesis, suggesting discrete roles for each of these ligands during follicle maturation.

Activins↗
PubMed2000

Posttranscriptional regulation of human leukocyte antigen G during human extravillous cytotrophoblast differentiation.

Human maternal tolerance to a semiallogenic fetus may be maintained, in part, by the unusual expression pattern of antigen-presenting molecules in placental trophoblast cells. Extravillous cytotrophoblast (EVC) cells, which invade the maternal decidua, express high levels of human leukocyte antigen G (HLA-G), a nonclassical, major histocompatibility complex (MHC) class I molecule. HLA-G transcripts have been detected in tumors and other tissues, yet protein accumulation is rare. We show that, within EVC cells themselves, the mRNA is more broadly expressed than the protein. Specifically, accumulation of HLA-G protein was markedly delayed during EVC cell differentiation. To elucidate this mechanism, we performed a comprehensive analysis comparing the expression of HLA-G and proteins essential for MHC class I expression at the cell surface. The transporter for antigen processing proteins TAP1 and TAP2, as well as tapasin and beta(2)-microglobulin, appeared to be coordinately expressed throughout EVC cell columns. Strikingly, they all accumulated well in advance of the HLA-G protein but concurrently with its mRNA. A similar delay in the accumulation of the HLA-G protein was observed in vitro, using cultures of chorionic villi. We conclude that posttranscriptional regulation of HLA-G is fundamental to EVC cell development and is achieved independently of the peptide loading system. This represents a novel mechanism of MHC class I regulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Epidermal growth factor-like ligands and erbB genes in the peri-implantation rabbit uterus and blastocyst.

Molecular cloning of the partial cDNA coding sequences of the four erbB receptors and the epidermal growth factor (EGF)-like ligands EGF, transforming growth factor alpha (TGF), and heparin-binding EGF (HB-EGF) has provided the basis for a comprehensive analysis of the spatiotemporal expression pattern of the EGF receptor/ligand system during the peri-implantation period in the rabbit. Employing nonradioactive in situ hybridization and immunolocalization, we observed differential expression of erbB1-erbB3 within the trophectoderm of the blastocyst. ErbB1 was strongly expressed in the cytotrophoblast but was downregulated upon syncytium formation. ErbB3 was a product of both the cyto- and syncytiotrophoblast. Despite the expression of erbB2 mRNA, the trophectoderm was devoid of immunoreactive ErbB2. ErbB4 gene activity was exclusively detected in the trophoblast at midpregnancy. The luminal and glandular epithelium and stroma of the nonpregnant, pseudopregnant, and pregnant rabbit uterus at Day 6 of gestation also expressed ErbB1-ErbB3. In the peri-implantation period, gene activities of erbB1-erbB3 were upregulated upon decidualization. At the site of implantation, uterine luminal epithelial cells apposing the preimplantation blastocyst displayed a distinct membrane immunolocalization of ErbB2, identifying the uterine epithelium as target for EGF, TGFalpha, and HB-EGF derived from both the embryonic trophectoderm and the uterine epithelium. In the luminal epithelium at the antimesometrial uterine site, HB-EGF gene activity was upregulated at the time of blastocyst attachment, but this upregulation was not reflected in an increase in immunoreactive HB-EGF. The detection of tyrosine phosphorylated ErbB2 in the rabbit placenta indicated the presence of a functional ErbB/EGF-like system in the pregnant rabbit uterus. This study provides strong evidence for a role of the ErbB/EGF-like system in embryo/maternal interactions during the peri-implantation period in the rabbit.

Animals↗
PubMed2002

Redistribution of Ca2+ among cytosol and organella during stimulation of bovine chromaffin cells.

Recent results indicate that Ca2+ transport by organella contributes to shaping Ca2+ signals and exocytosis in adrenal chromaffin cells. Therefore, accurate measurements of [Ca2+] inside cytoplasmic organella are essential for a comprehensive analysis of the Ca2+ redistribution that follows cell stimulation. Here we have studied changes in Ca2+ inside the endoplasmic reticulum, mitochondria, and nucleus by imaging aequorins targeted to these compartments in cells stimulated by brief depolarizing pulses with high K+ solutions. We find that Ca2+ entry through voltage-gated Ca2+ channels generates subplasmalemmal high [Ca2+]c domains adequate for triggering exocytosis. A smaller increase of [Ca2+]c is produced in the cell core, which is adequate for recruitment of the reserve pool of secretory vesicles to the plasma membrane. Most of the Ca2+ load is taken up by a mitochondrial pool, M1, closer to the plasma membrane; the increase of [Ca2+]M stimulates respiration in these mitochondria, providing local support for the exocytotic process. Relaxation of the [Ca2+]c transient is due to Ca2+ extrusion through the plasma membrane. At this stage, mitochondria release Ca2+ to the cytosol through the Na+/Ca2+ exchanger, thus maintaining [Ca2+]c discretely increased, especially at core regions of the cell, for periods that outlast the duration of the stimulus.

Aequorin↗
PubMed2003

Divergent effects of GM-CSF and TGFbeta1 on bone marrow-derived macrophage arginase-1 activity, MCP-1 expression, and matrix metalloproteinase-12: a potential role during arteriogenesis.

Granulocyte/macrophage-colony stimulating factor (GM-CSF) and transforming growth factor (TGF)beta1 induce arteriogenesis in a nonischemic model of femoral artery ligation. Moreover, clinical trials demonstrated an improved collateralization after injection of bone marrow cells. In the present study, the expression of arteriogenic factors in bone marrow-derived macrophages (BMDM) was measured to verify the potential of these cells to influence collateral artery growth. GM-CSF induced in BMDM the expression of monocyte chemoattractive protein (MCP)-1, matrix-metalloproteinase (MMP)-12, and arginase-1-the latter also showing a remarkable increase in activity. During in vivo induced arteriogenesis, the accumulation rate of macrophages around proliferating collaterals was significantly increased. We also show that MCP-1 is found to be mainly expressed in the media of the vessel wall, MMP-12 in macrophages of the adventitia, and arginase at both locations. This study provides for the first time a comprehensive analysis of GM-CSF/TGFbeta1-regulated arteriogenic factors in BMDM and supports the hypothesis that arteriogenesis is a multistage mechanism, including monocyte/macrophage adhesion and transmigration, pro-arteriogenic cytokine expression, degradation of connective tissue, and collagen synthesis regulation. Selective modulation of these mechanisms as well as cell-based therapies supplying arteriogenic factors in vivo point toward new strategies to influence collateral artery growth.

Animals↗
PubMed2003

An updated view of the national anesthesia personnel shortfall.

UNLABELLED: Reports of anesthesia personnel shortages in 2001 led to the first comprehensive analysis of labor supply and demand for anesthesiologists since 1993. We now update this analysis and forecast, incorporating newly available data about residency composition, American Board of Anesthesiology and Certified Registered Nurse Anesthetist certification, the 2002 residency match, surgical facilities, and the US physician workforce. In addition, US residency programs were surveyed; national health care utilization and economic data were reviewed. Adjusted for the new information, our model still shows an anesthesiologist shortfall in 2002, projected to continue through 2005. We now estimate a current shortage of 1100-3800 anesthesiologists in 2002, on the basis of past service demand growth assumptions of 2%-3%, respectively. By 2005 this number is expected to be 500-3900, depending on a future service demand growth of 1.5%-2%, respectively. To avoid a surplus of anesthesiologists in 2006-2010, our model suggests that the number of graduates should level out at 1600 yearly, with a 1.5% service demand growth. To forecast the anesthesia personnel market more accurately, thereby helping supply match demand, substantially better quantification of future demand for anesthesia services is needed. If sustained growth in service demand >1.5% is likely, entry into the specialty should be encouraged beyond the current level. IMPLICATIONS: With updates from training programs, surgical activity, and other sources, our previously described model estimates a continuing shortfall of 1000-3800 anesthesiologists in 2002 and 500-3900 in 2005, assuming that service demand growth is 1.5% or 2% annually. If service growth >1.5% is likely, entry into the specialty should be encouraged beyond current levels.

Accreditation↗
PubMed1994

Current management of carcinoma of the breast.

OBJECTIVE: An in-depth retrospective review of the multidisciplinary approach to the management of carcinoma of the breast was done. The author reviewed previous trials and treatment from the past to the present. The indications and contraindications of surgical procedures, radiation therapy, systemic chemotherapy, and hormonal therapy are discussed. SUMMARY BACKGROUND DATA: Carcinoma of the breast is one of the most common malignancies treated by the practicing general or oncologic surgeon. The disease is best treated using a multidisciplinary approach, combining the efforts of surgery, radiation therapy, and systemic treatments. Understanding the indications and contraindications for each of these modalities will provide the practicing surgeon the most up-to-date algorithms for the management of his/her patient. CONCLUSIONS: The author provides a comprehensive analysis of the multidisciplinary approach to the management of carcinoma of the breast. It emphasizes the results of previous trials and discusses future controversies and areas for study.

Breast Neoplasms↗
PubMed2001

Implications of 2,457 consecutive surgical infections entering year 2000.

OBJECTIVE: To assess the demographics and characteristics of infections in surgical patients to define areas that deserve emphasis in surgical education. SUMMARY BACKGROUND DATA: As a result of evolving technology and diseases, the complexity of diagnosing and treating infections has increased during the past three decades for all patients, including those treated primarily by surgeons. No comprehensive analysis of these conditions in a single surgical cohort has been recently published. METHODS: The authors conducted a prospective, observational study of all infections occurring on the general and trauma surgery services at a single university hospital during a 3.5-year period. RESULTS: The authors identified 2,457 infections: 608 community-acquired, 1,053 occurring on the wards, and 796 occurring in the intensive care unit. Although dependent on patient location, the most common sites were abdomen, lung, and wound; the most common isolates were Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans; and the most commonly used antibiotics were ciprofloxacin, vancomycin, and metronidazole. The overall death rate was 13%, ranging from 5% after community-acquired infections to 25% after infections acquired in the intensive care unit. CONCLUSIONS: Most infections treated by surgeons are hospital-acquired. Infections with gram-positive cocci and fungi are common, with pulmonary infections becoming more common. Fluoroquinolones have become important therapeutic agents. Depending on the type of practice, these data should be helpful to direct educational efforts so that surgeons can remain knowledgeable and active in the nonsurgical care of their patients.

Abdomen↗
PubMed2004

The response of the failing heart to chronic mechanical unloading.

PURPOSE OF REVIEW: The authors present a comprehensive analysis of the evidence in support of improvements at the cellular, structural, and hemodynamic levels after left ventricular assist device support. RECENT FINDINGS: The use of left ventricular assist devices as a strategy to bridge patients to cardiac transplantation and, more recently, as a form of destination therapy has provided a great opportunity to study failing myocardium at various time points. Specifically, myocardial samples can be obtained from patients at the time of left ventricular assist device implantation and again at explant, thereby allowing comparisons between paired samples of failing myocardium obtained before and after mechanical unloading. SUMMARY: A body of knowledge has been generated that illustrates the ability of the myocardium to "heal." This information may give us better insight into cellular and molecular mechanisms of heart failure and potential new therapies for patients with end-stage heart failure.

Dystrophin↗
PubMed2001

Upper extremity peripheral nerve anatomy: current concepts and applications.

The nerve anatomy of the upper extremity is studied constantly through surgical findings, electrodiagnostic studies, and cadaveric dissections. Although it is recognized that the anatomy is not changing rapidly, knowledge of the anatomic relationships and their significance is increasing. The purpose of the current study is to provide a comprehensive analysis of the nerve anatomy of the upper extremity to include innervation patterns, critical landmarks, and clinical applications, with particular focus on recent contributions in the literature.

Arm↗
PubMed2002

Long-term followup of proximal femoral allografts.

Between 1972 and 1999, the orthopaedic service at the authors' institution treated 137 patients with proximal femoral bone lesions by resection and reconstruction with frozen allografts from cadavers. The data were entered into a computer program allowing a comprehensive analysis. Thirty-eight patients had proximal femoral osteoarticular allografts, 69 had allograft-endoprosthesis composites, 22 had intercalary allografts, and eight had an allograft arthrodesis. There were 74 complications in 54 of the 137 patients with allografts, which included 26 allograft fractures (19%), 15 infections (11%), and 20 nonunions (15%). The overall success rate for the patients with these procedures was 103 of 137 (75%) at a mean followup of 7.9 years +/- 5.6 years. If the eight patients with tumor recurrences (surgical failures rather than allograft failures) are not included, the success rate is 103 of 129 (80%). Eighty-three of these patients (55%) without any allograft complications who have been treated and followed up for at least 2 years had a 92% success rate. It is concluded that although allograft reconstruction after resection of the proximal femur for patients with aggressive or malignant tumors has a high complication rate, approximately 80% of the patients have a successful outcome.

Adolescent↗
PubMed2000

Stochastic effects of environmental radiation exposure in populations living near the Mayak Industrial Association: preliminary report on study of cancer morbidity.

The Mayak Industrial Association, located in the South Ural Mountains, began operation in 1948 and was the first Russian site for the production and separation of plutonium. During the early days of operation, technological failures resulted in the release of large amounts of radioactive waste into the Techa River. Residents who lived in villages on the banks of the Techa and Iset Rivers were exposed to varying levels of radioactivity. The objective of this study is to assess stochastic (carcinogenic) effects in populations exposed to offsite releases of radioactive materials from the Mayak nuclear facility in Russia. Subjects of the present study are those individuals who lived during the period January 1950 through December 1960 in any of the exposed villages along the Techa River in Chelyabinsk Oblast. Death certificates and cancer incidence data have been routinely collected in the past from a five-rayon catchment area of Chelyabinsk Oblast. The registry of exposed residents along the Techa River assembled and maintained by the Urals Research Center for Radiation Medicine for the past 40 y is the basis for identifying study subjects for this project. Specific study objectives are to evaluate the incidence of cancer among current and former residents of Chelyabinsk Oblast who are in the exposed Techa River cohort; integrate results from the dose-reconstruction study to estimate doses for risk assessment; and develop a structure for maintaining continued follow-up of the cohort for cancer incidence. In the earlier part of our collaborative effort, the focus has been to enhance the cancer morbidity registry by updating it with cancer cases diagnosed through 1997, to conduct a series of validation procedures to ensure completeness and accuracy of the registry, and to reduce the numbers of subjects lost to follow-up. A feasibility study to determine cancer morbidity in migrants from the catchment area has been proposed. Our preliminary analyses of cancer morbidity underscore the importance of examining both cancer mortality and cancer morbidity in conducting a comprehensive analysis of the occurrence of cancer in this important cohort.

Age Distribution↗
PubMed2002

Characterization of electromagnetic interference of medical devices in the hospital due to cell phones.

Concern over electromagnetic interference with medical devices due to cell phone emissions has stemmed from anecdotal reports and unpublished observations of hospital staff. In an effort to characterize electromagnetic interference concerns, representative medical devices from four large teaching hospitals were exposed to standard North American and European communication signal emissions. Of 33 medical devices tested, only 4 showed disruption of critical function due to cell phone emissions at a distance of 25 cm or greater. Although other cases of electromagnetic interference were observed, these were not critically disruptive and mainly occurred when the transmitters were at full power and placed 5 cm or closer to the medical device. Overall, no cell phone signal was exempt from producing electromagnetic interference effects. While sensitive medical devices were often affected by more than one signal type, the effects were not entirely predictable based upon the results of other signals or related medical device units or models. Because a comprehensive analysis of all medical devices in all possible electromagnetic environments was not performed, the data presented here are only intended to provide a general idea of the magnitude of electromagnetic interference effects that might be encountered in a hospital environment, as well as a standard protocol for clinical engineering groups to perform ad hoc electromagnetic interference surveys and methods to manage and/or eliminate electromagnetic interference with appropriate system engineering design including supplementary communication infrastructure, medical device shielding and positioning, and appropriate cell phone user guidelines.

Electrocardiography↗
PubMed1987

Ecological effects of home-based, school-based, and community-based training of parents of children with learning and behavior problems.

A federally funded three year project to train parents of children with learning and behavior problems is discussed in terms of its ecological impact on parents, their children, their children's teachers, and on the community at large. The design of the project including the home intervention component, the school-based support group component, and the community component is briefly detailed. A comprehensive analysis of data on the effects of the various parent training components on parent, teacher and student perceptions of each other, as well as on student achievement, attendance and self-concept measures are reported. Overall, the data demonstrate the success of the project and support the ecological premise that making changes in one system surrounding a troubled child causes resultant changes in other systems surrounding the child.

Child↗
PubMed1994

Analyzing the content of physicians' medical practices.

For many large physician groups, about 75% of all revenues come from capitation contracts. These groups may reduce the variable expenses of patient care by conducting medical outcome studies. Physician groups will obtain the most benefit for their limited research dollars by focusing outcomes research on prevalent medical conditions. The purpose of this study is to provide a comprehensive analysis of the content of physicians' medical practices. We found that 21 diagnostic clusters defined 70% or more of the episodes treated by primary care physicians. For specialists, no more than eight diagnostic clusters were needed to define the majority of their practices. Outcomes research should initially focus on abdominal pain, acute lower respiratory infections, cataracts, cholelithiasis, congestive heart failure, diabetes mellitus, external abdominal hernias, ischemic heart disease, low back pain, maternity care, menstrual disorders, otitis media, peptic diseases, prostate cancer, psychotic episodes, renal calculi, seizure disorders, and thyroid diseases.

Algorithms↗
PubMed1982

Multidimensional problems and findings in developmentally disabled children.

The background factors, problems, findings, and recommendations emerging from the interdisciplinary evaluation of 301 children referred to the Duke Developmental Evaluation Center for assessment of suspected development disabilities are analyzed. The perspective on developmental disabilities gained from utilization of a problem-oriented clinical record and a functional rather than a categorical approach is discussed. Particular attention is directed toward the frequency of findings in various dimensions of functioning and the implications arising from this comprehensive analysis for the roles of pediatricians, parents, and teachers in case management.

Adolescent↗
PubMed1993

Determinants of children's health care use: an investigation of psychosocial factors.

Factors related to the amount of health care used by 5- to 11-year-old children in a health maintenance organization (HMO) were investigated using a comprehensive multivariate model that assessed the contribution of child health need, mental health, and social functioning; maternal mental health, social support and health care utilization; and family functioning and life events. Mothers reported on the 450 participating children. Health care visits for a two-year retrospective period were obtained from the computerized encounter system. Child health need and maternal patterns of health care use were powerful predictors of the overall amount of health care used, and these factors discriminated high users from low users of care. Family conflict was associated with a higher volume of care, while children's depressive symptoms and non-white race were related to lower use. Maternal social support, mental health, and life events were not predictive of use in either full multivariate model. Enabling factors were held relatively constant by participation of all families in a prepaid HMO. The multiple regression model explained 33% of the variance in use, slightly more than in previous studies of children's health care use. When included in a comprehensive analysis, child and family psychosocial characteristics help to explain children's health care use beyond what is possible using simple health and illness variables. The implications of these findings in the development of further research and to the practice of routine pediatric care are discussed.

Adult↗
PubMed2000

Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up.

BACKGROUND: Several disorders have been attributed to measles-mumps-rubella (MMR) vaccination during the past decade. The aim of this prospective follow-up study was to identify serious adverse events causally related to MMR vaccination. METHODS: When the MMR vaccination program was launched in Finland in 1982, a countrywide surveillance system was set up to detect serious adverse events associated with MMR. To obtain detailed case histories vaccinees' clinical charts were reviewed. Serum samples were analyzed to trace concurrent infections. SETTING: All hospitals and health centers in Finland from 1982 through 1996. RESULTS: Immunization of 1.8 million individuals and consumption of almost 3 million vaccine doses by the end of 1996 gave rise to 173 potentially serious reactions claimed to have been caused by MMR vaccination. In all, 77 neurologic, 73 allergic and 22 miscellaneous reactions and 1 death were reported, febrile seizure being the most common event. However, 45% of these events proved to be probably caused or contributed by some other factor, giving an incidence of serious adverse events with possible or indeterminate causal relation with MMR vaccination of 5.3 per 100,000 vaccinees or 3.2 per 100,000 vaccine doses. CONCLUSIONS: Causality between immunization and a subsequent untoward event cannot be estimated solely on the basis of a temporal relation. Comprehensive analysis of the reported adverse reactions established that serious events causally related to MMR vaccine are rare and greatly outweighed by the risks of natural MMR diseases.

Adolescent↗