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At least 829 records · Page 46Linked to original sources
PubMed2003

Evolving hypopituitarism following cranial irradiation.

Increasing survival after treatment for childhood cancer in recent years has left many patients with long-term sequelae. Following cranial irradiation, changes in hypothalamic-pituitary function evolve over several years and multiple hormone deficiencies are frequently found. In the present study we describe a boy whose initial presentation with a cerebral tumour included central precocious puberty. He was followed for more than 15 years and sequentially developed deficiencies of growth hormone, thyroid-stimulating hormone, gonadotrophins and adrenocorticotropic hormone after high-dose cranial irradiation. Long-term endocrine follow up of such children is essential for the early diagnosis and optimal management of hormone deficiencies.

Astrocytoma↗
PubMed2003

Evolving strategies for surgical management of patients with severe left ventricular dysfunction.

As a result of an increasing population with advanced congestive heart failure and the lack of growth in cardiac transplantation, surgical treatments for heart failure have been re-examined. These therapies represent the evolution of well-known operations such as coronary bypass surgery and valve surgeries, and the more novel left ventricular reconstruction and operations aimed at inhibiting left ventricular remodeling. When performed by surgeons with experience in this evolving speciality within cardiovascular surgery, surgery for advanced heart failure is a treatment of choice for many patients.

Journal Article↗
PubMed1999

Impaired glucocorticoid receptor function evolves in aberrant physiological responses to bacterial endotoxin.

The consequences of glucocorticoid receptor (GR) dysfunction for neuroimmunoendocrine responses to an inflammatory challenge were studied in transgenic mice expressing antisense RNA directed against the GR [GR-impaired (GR-i) mice]. Mice were implanted intraperitoneally with a biotelemetry transmitter to monitor body temperature and locomotion. GR-i mice showed decreased locomotion and body temperature during the dark phase of the diurnal cycle. Intraperitoneal administration of saline caused a rapid increase in body temperature in control mice, which was terminated within 90 min. In GR-i mice, however, body temperature remained elevated for about 6 h. Intraperitoneal injection of endotoxin (10 micrograms/mouse) produced a biphasic fever in control mice. However, in endotoxin-injected GR-i mice, body temperature was not significantly different from their saline-injected controls during the first 6 h. Body temperature then increased and remained elevated during the night period. Both strains showed hypolocomotion after endotoxin. In a second experiment, mice were injected intraperitoneally with saline or endotoxin and killed after 1, 3, 6 or 24 h. In GR-i mice, endotoxin caused an augmented rise in plasma ACTH, but not in corticosterone levels. The endotoxin-induced increase in serum levels of interleukin-1 beta and interleukin-6 was not different between the strains. However, whereas in control mice tumour necrosis factor-alpha levels were below detection at the time points studied, substantial levels of this cytokine were found in the serum of GR-i mice 1 h after endotoxin administration. It may be concluded that life-long impairment of GR evolves in aberrant physiological and humoral responses to an acute inflammatory challenge. These findings expand our understanding about the neuroendocrine and physiological disturbances associated with stress-related disorders.

Adrenocorticotropic Hormone↗
PubMed2001

An ischemic stroke during intravenous recombinant tissue plasminogen activator infusion for evolving myocardial infarction.

A 56-year-old man without a previous history of stroke received intravenous recombinant tissue plasminogen activator (tPA) for an evolving myocardial infarction. During the infusion, the patient developed aphasia and right hemiparesis. The CT and MRI confirmed an ischemic stroke without evidence of hemorrhage. Although the cerebral hemorrhage after tPA infusion is relatively more common, in rare cases, tPA infusion may result in fragmentation of a cardiac thrombus resulting in an ischemic cerebral stroke.

Brain Ischemia↗
PubMedDate not supplied

Vertebrate dentitions at the origin of jaws: when and how pattern evolved.

New evidence shows that teeth evolved with a greater degree of independence from jaws than previously considered. Pharyngeal denticles occur in jawless fish and also in early gnathostomes and precede jaw teeth in phylogeny. Many of these denticles form joined polarized sets on each branchial arch; these resemble whorl-shaped tooth sets on the jaws of stem and crown gnathostomes and are proposed as homologous units. Therefore, the source of patterning of these pharyngeal denticle and tooth sets is conserved from jawless conditions. It is proposed that developmental regulatory systems, responsible for all such tooth patterns on the jaws, are co-opted from the pharyngeal region and not from the skin as classically understood. This strongly implicates embryonic endoderm as opposed to ectoderm in the genetic control of dentition patterning. New interpretations of ontogenetic data on patterning dentitions of extant sharks are proposed, together with those of osteichthyan fish. Two entirely fossil groups, placoderms and acanthodians, at the base of gnathostome phylogeny are reassessed on the basis of a new model. It is concluded that within stem group and crown group gnathostomes several different strategies, unique to each taxon, were adopted to produce different developmental models of dentition patterning from pharyngeal denticles. One shared developmental pattern is that of initiation from primordial tooth sites, independently in each dentate zone of the jaws. The new model is proposed as a framework for data on evolutionary developmental genetics.

Animals↗
PubMed2003

Conceptualization and measurement of health-related quality of life: comments on an evolving field.

This article summarizes personal views on the rapidly evolving field of functional health assessment and comments on their implications for advances in assessment methods used in rehabilitation medicine. Topics of strategic importance included (1). a new formulation of the structure of health status designed to distinguish role participation from the physical and mental components of health for purposes of international studies; (2). applications of item response theory that offer advantages in constructing better functional health measures and cross-calibrating their underlying metrics; (3). computerized dynamic assessment technology, well proven in education and psychology, which may lead to more practical assessments and more precise score estimates across a wide range of functional health levels; and (4). intellectual property issues involved in standardizing and promoting readily available assessment tools, ensuring their scientific validity, and achieving the best possible partnership between the scientific community and those developing commercial applications. Promising results from preliminary attempts to standardize and improve the metrics of functional health assessment constitute grounds for optimism regarding their potential usefulness in rehabilitation medicine. Someday, all tools used to measure each functional health concept, including the best single-item measure and the most precise computerized dynamic health assessment, will be scored on the same metric and their results will be directly comparable. To achieve this goal in rehabilitation medicine, we have much work to do.

Activities of Daily Living↗
PubMed2000

Ductal carcinoma in situ (DCIS) of the breast: evolving perspectives.

Ductal carcinoma in situ (DCIS) of the breast is an early, localized stage of carcinoma in the process of multistep breast carcinogenesis. The incidence of DCIS is increasing, mainly due to screening mammography, which results in diagnosing the disease in an increasing proportion of asymptomatic patients. Consequently, clinicians are being confronted with growing numbers of women who present with DCIS of the breast; thus, the concepts of managing such patients are assuming greater importance. The most common presentation is calcifications on mammography. DCIS is a biologically and morphologically heterogeneous disease. If left untreated, a significant proportion of these tumours will evolve into invasive cancer. However, when appropriately treated, the prognosis of DCIS is excellent. Optimal management of DCIS remains controversial. The goal in the treatment of patients with DCIS is to control local disease and prevent subsequent development of invasive cancer. For several decades, total mastectomy was the treatment of choice for DCIS and it should still be considered the standard of care, to which more conservative forms of treatment must be compared. Mastectomy is associated with a risk for chest wall recurrence of approximately 1%. Axillary lymph node dissection is not routinely recommended in the management of DCIS. However, mastectomy probably represents overtreatment in a substantial number of patients, especially those with small, mammographically detected lesions. Local excision alone has been suggested in carefully selected patients, whilst the rest of the patients undergoing breast-conservation surgery should be treated with breast irradiation. There is evidence that breast-conservation therapy is an effective option in the management of selected patients with DCIS. The use of radiotherapy after lumpectomy significantly decreases the rate of recurrence. Nuclear grade, presence of comedo necrosis, and margin involvement are the most commonly used predictors of the likelihood of recurrence. There is no role for adjuvant chemotherapy in the management of this disease. The role of tamoxifen in the treatment of DCIS is not clearly defined; tamoxifen should be given only in patients enrolled in clinical trials. Following breast-conservation therapy, about 50% of the tumours recur as invasive cancer. Most patients with recurrent disease can be treated effectively, usually by salvage mastectomy, but also in selected cases by breast-conservation therapy.

Biopsy↗
PubMed1996

Chronic esophagitis evolving to verrucous squamous cell carcinoma: possible role of exogenous chemical carcinogens.

BACKGROUND & AIMS: A patient exposed to aerosolized lye and ingested kerosene was followed up for 16 years with chronic esophagitis before developing verrucous esophageal squamous carcinoma. The aim of this study was to elucidate the pathogenesis of the carcinoma. METHODS: Multiple biopsy specimens were graded according to the severity of esophagitis and dysplasia. Molecular biological techniques and immunocytological assay were used to look for human papillomavirus infection, p53 mutations, loss of heterozygosity for TP53 and chromosome 8 markers, and ras mutations. RESULTS: Morphological features of the chronic esophagitis in this patient were similar to the precancerous lesions from high-risk areas for esophageal squamous cancer and the precancerous lesions induced in rats by N-methyl-N-nitrosoaniline. Gastroesophageal acid reflux and human papillomavirus infection were ruled out. No loss of heterozygosity of p53 or for chromosome 8 markers was found. Mutations of the ras oncogene were not identified. By immunocytological assay overexpression of p53 was identified only in the invasive portion of the carcinoma. CONCLUSIONS: In this patient, verrucous squamous carcinoma evolved from chronic esophagitis, squamous papillary hyperplasia, and dysplasia. Although exogenous carcinogens may have been important, they probably did not act by causing loss of heterozygosity or ras mutations. p53 overexpression occurred late.

Aerosols↗
PubMed2004

Wegener's granulomatosis: evolving concepts in treatment.

Wegener's granulomatosis (WG), the most common of the pulmonary granulomatous vasculitides, typically involves the upper respiratory tract, lower respiratory tract (bronchi and lung), and kidney, with varying degrees of disseminated vasculitis. Major histological features include a necrotizing vasculitis involving small vessels, extensive "geographic" necrosis, and granulomatous inflammation. Clinical manifestations of WG are protean; virtually any organ can be involved. Further, the spectrum and severity of the disease is heterogeneous, ranging from indolent disease involving only one site to fulminant, multiorgan vasculitis leading to death. The pathogenesis of WG has not been elucidated, but both cellular and humoral components are involved. Circulating antineutrophil cytoplasmic antibodies (cANCA) likely play a role in the pathogenesis and often correlate with activity of the disease. Treatment strategies are evolving. Cyclophosphamide (CYC) plus corticosteroids (CS) is the mainstay of therapy for generalized, multisystemic WG. Historically, the combination of CYC plus CS was used for a minimum of 12 months, but concern about late toxicities associated with CYC has led to novel treatment approaches. Currently, short-course (3-6 months) induction treatment with CYC plus CS, followed by maintenance therapy with less toxic agents (e.g., methotrexate, azathioprine) is recommended. Further, recent studies suggest that methotrexate combined with CS may be adequate for limited, non-life threatening WG. The role of other immunomodulatory agents (including trimethoprim-sulfamethoxazole) is also explored.

Journal Article↗
PubMed2006

Evolving immunosuppressive regimens for lung transplant recipients.

In organ transplantation, the key tenet remains the maintenance of graft function through the induction of allograft tolerance. Immunosuppression has been the mainstay of therapy to maintain graft function and induce tolerance. Immunosuppression for lung transplant and indeed all solid organ transplantation has greatly evolved in the past decade. Although calcineurin inhibitors, corticosteroids, and azathioprine remain the foundation of immunosuppression in lung transplantation, the arsenal of effective immunosuppression is ever expanding to include biological agents and newer drugs that are directed against increasingly specific targets of the immune cascade. This review examines the characteristics of both traditional and new pharmacological agents, describes a patient-centered approach to their use following lung transplantation, and discusses the controversies surrounding immunosuppression in the lung transplant recipient.

Graft Rejection↗
PubMed1994

Initial clinical results of myocardial revascularization with the internal mammary artery for evolving myocardial infarction.

In 25 patients undergoing emergency revascularization for an evolving myocardial infarction, the internal mammary artery (IMA) was used as graft. To bridge the time needed for harvesting the IMA, the left ventricle was totally decompressed by means of the extracorporeal circulation. Cardioplegia was delivered retrogradely, in order to achieve a good distribution in the jeopardized area. One patient died postoperatively, and eight patients showed a postoperative myocardial infarction. These initial results suggest that, with an adapted operative strategy, the IMA can be used as graft even in emergency revascularization.

Aged↗
PubMed2004

Evolving complex dynamics in electronic models of genetic networks.

Ordinary differential equations are often used to model the dynamics and interactions in genetic networks. In one particularly simple class of models, the model genes control the production rates of products of other genes by a logical function, resulting in piecewise linear differential equations. In this article, we construct and analyze an electronic circuit that models this class of piecewise linear equations. This circuit combines CMOS logic and RC circuits to model the logical control of the increase and decay of protein concentrations in genetic networks. We use these electronic networks to study the evolution of limit cycle dynamics. By mutating the truth tables giving the logical functions for these networks, we evolve the networks to obtain limit cycle oscillations of desired period. We also investigate the fitness landscapes of our networks to determine the optimal mutation rate for evolution.

Biological Evolution↗
PubMed2006

A new time evolving Gaussian series representation of the imaginary time propagator.

Frantsuzov and Mandelshtam [J. Chem. Phys. 121, 9247 (2004)] have recently demonstrated that a time evolving Gaussian approximation (TEGA) to the imaginary time propagator exp(-betaH) is useful for numerical computations of anharmonically coupled systems with many degrees of freedom. In this paper we derive a new exact series representation for the imaginary time propagator whose leading order term is the TEGA. One can thus use the TEGA not only as an approximation but also to obtain the exact imaginary time propagator. We also show how the TEGA may be generalized to provide a family of TEGA's. Finally, we find that the equations of motion governing the evolution of the center and width of the Gaussian may be thought of as introducing a quantum friction term to the classical evolution equations.

Journal Article↗
PubMed2003

Evolving trends in risk profiles and causes of death after heart transplantation: a ten-year multi-institutional study.

BACKGROUND: As therapeutic options evolve for advanced heart failure, the appropriate role for cardiac transplantation will require survival analyses that reflect changing trends in causes of death and patient and institutional risk profiles. Results from multi-institutional studies could be used to monitor progress in individual centers. METHODS: Between 1990 and 1999, 7290 patients undergoing cardiac transplantation in 42 institutions entered a formal outcomes study. Changing survival, causes of death, and patient risk profiles were analyzed. Multivariable risk-factor equations were applied to a single institution (300 primary heart transplants) to examine differences in risk-adjusted expected versus observed actuarial outcomes over time. RESULTS: Overall survival in the 42 institutions improved during the decade (P =.02). One- and 3-year cardiac transplant research database survival was as follows: era 1 (1990-1992), 84% and 76%, respectively; era 2 (1993-1995), 85% and 79%, respectively; and era 3 (1996-1999), 85% and 79%, respectively. Causes of death changed over time. Pretransplantation risk profiles increased over time (P =.0001), with increases in reoperations, devices, diabetes, severely ill recipients, pulmonary vascular resistance, sensitization, ischemic times, donor age, and donor inotropic support. Three-year actuarial survival in a single institution was 3% less than risk-adjusted predicted survival in era 1, 1% higher than predicted in era 2, and 7% higher than predicted in era 3. CONCLUSIONS: Survival after cardiac transplantation is gradually improving, despite increasing risk profiles. Further improvement requires periodic re-evaluation of risk profiles and causes of death to target areas of surveillance, therapy, and research. By using these methods, progress at individual institutions can be assessed in a time-related, risk-adjusted manner that also reflects changing institutional experience, expertise, or both.

Cause of Death↗
PubMed1986

Should coronary artery bypass be delayed following successful direct coronary artery streptokinase thrombolysis during evolving myocardial infarction?

The effect of deferring immediate coronary artery bypass was evaluated in two groups of similar patients having successful direct coronary artery thrombolysis with streptokinase in the treatment of evolving myocardial infarction. Within 6 hours of onset of myocardial infarction, 140 patients underwent immediate cardiac catheterization and infusion of intracoronary streptokinase up to 500,000 units. Of those patients having restoration of orthograde coronary blood flow coupled with immediate evidence of myocardial salvage, 31 patients (group I) had immediate coronary artery bypass and 34 patients (group II) had coronary artery bypass deferred. Group I had no hemorrhagic, hemodynamic, or new cardiac complications. There were no deaths, reinfarction, recurrence of angina, or loss of salvaged myocardium at restudy. In group II, 11 of 34 patients had early reinfarction (p less than 0.01 vs. group I), 16 of 34 patients had recurrent angina (p less than 0.01 vs. group I) and two deaths occurred from cardiac causes. Subsequent coronary bypass was needed in 16 patients. All restudied reinfarction patients lost restored myocardium. We concluded that immediate coronary artery bypass is safe after acute myocardial infarction and coronary artery thrombolysis with streptokinase, delay of coronary artery bypass leads to an unacceptable incidence of reinfarction and recurrent severe angina, and early coronary artery bypass is needed to ensure success of thrombolysis.

Coronary Artery Bypass↗
PubMed2004

Reconstruction of in vivo time-evolving neuroendocrine dose-response properties unveils admixed deterministic and stochastic elements.

Homeostasis in the intact organism is achieved implicitly by repeated incremental feedback (inhibitory) and feedforward (stimulatory) adjustments enforced via intermittent signal exchange. In separated systems, neurohormone signals act deterministically on target cells via quantifiable effector-response functions. On the other hand, in vivo interglandular signaling dynamics have not been estimable to date. Indeed, experimentally isolating components of an interactive network definitionally disrupts time-sensitive linkages. We implement and validate analytical reconstruction of endogenous effector-response properties via a composite model comprising (i) a deterministic basic feedback and feedforward ensemble structure; (ii) judicious statistical allowance for possible stochastic variability in individual biologically interpretable dose-response properties; and (iii) the sole data requirement of serially observed concentrations of a paired signal (input) and response (output). Application of this analytical strategy to a prototypical neuroendocrine axis in the conscious uninjected horse, sheep, and human (i) illustrates probabilistic estimation of endogenous effector dose-response properties; and (ii) unmasks statistically vivid (2- to 5-fold) random fluctuations in inferred target-gland responsivity within any given pulse train. In conclusion, balanced mathematical formalism allows one to (i) reconstruct deterministic properties of interglandular signaling in the intact mammal and (ii) quantify apparent signal-response variability over short time scales in vivo. The present proof-of-principle experiments introduce a previously undescribed means to estimate time-evolving signal-response relationships without isotope infusion or pathway disruption.

Animals↗
PubMed2003

Structural basis for recognition by an in vitro evolved affibody.

The broad binding repertoire of antibodies has permitted their use in a wide range of applications. However, some uses of antibodies are precluded due to limitations in the efficiency of antibody generation. In vitro evolved binding proteins, selected from combinatorial libraries generated around various alternative structural scaffolds, are promising alternatives to antibodies. We have solved the crystal structure of a complex of an all alpha-helical in vitro selected binding protein (affibody) bound to protein Z, an IgG Fc-binding domain derived from staphylococcal protein A. The structure of the complex reveals an extended and complementary binding surface with similar properties to protein-antibody interactions. The surface region of protein Z recognized by the affibody is strikingly similar to the one used for IgG(1) Fc binding, suggesting that this surface contains potential hot-spots for binding. The implications of the selected affibody binding-mode for its application as a universal binding protein are discussed.

Amino Acid Sequence↗
PubMed2005

Listeria monocytogenes phosphatidylinositol-specific phospholipase C has evolved for virulence by greatly reduced activity on GPI anchors.

Listeria monocytogenes phosphatidylinositol-specific phospholipase C (PI-PLC) plays a critical role in escape of this human pathogen from host cell vacuoles. Unlike classical bacterial PI-PLCs, the L. monocytogenes enzyme has very weak activity on glycosylphosphatidylinositol (GPI)-anchored proteins. Previous crystal structure analysis has revealed that a small beta-strand (Vb) is present in Bacillus cereus PI-PLC and is absent in the enzyme from L. monocytogenes. This Vb beta-strand in B. cereus PI-PLC forms contacts with the glycan linker of GPI anchors, which presumably increases its activity on GPI-anchored proteins. In this study, we show that, of all known bacterial PI-PLCs, those from listeriae are the only ones that lack the beta-strand. Expression by L. monocytogenes of B. cereus PI-PLC, which has strong activity on GPI-anchored proteins, inhibited bacterial escape from a vacuole and cell-to-cell spread, resulting in greatly reduced virulence in mice. Deletion of the Vb beta-strand from B. cereus PI-PLC abolished its ability to cleave GPI-anchored proteins, decreased its inhibitory effects, and increased its virulence in mice. These results strongly suggest that L. monocytogenes PI-PLC has evolved as an important determinant of L. monocytogenes pathogenesis by absence of the Vb beta-strand, thus leading to greatly reduced activity on GPI-anchored proteins.

Amino Acid Sequence↗