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Quality of life in patients receiving treatment for gynecologic malignancies: special considerations for patient care.

Advances in the treatment of gynecologic cancer have extended the duration of survival of many patients. However, these patients frequently experience a variety of treatment- and disease-related side effects that diminish their quality of life (QOL) during and after treatment; among these are pain, nausea and vomiting, anemia, fatigue, peripheral neuropathy, emotional distress, and sexual dysfunction. Given the gains in survival time, patient care is being expanded to include enhancement or preservation of QOL in addition to early diagnosis and disease treatment, thus treating the whole person. In parallel with this evolution in cancer care, supportive measures are being increasingly recognized as crucial to effective patient management. This paper reviews some of the potential causes of diminished QOL in gynecologic cancer patients and basic treatment strategies for their control, with a focus on short-term QOL issues. It is important that clinicians monitor QOL during the course of the disease and its treatment, utilize procedures and therapeutic agents that take patient preferences and QOL into account, and proactively prevent and treat relevant symptoms.

Antineoplastic Agents↗

Expansion of the consultation-liaison psychiatry paradigm at a university medical center: integration of diversified clinical and funding models.

The perspective of the contemporary Consultation-Liason Service (CLS) psychiatrist is increasingly one of consultant to medical and surgical colleagues in models other than inpatient medical and surgical units. Simultaneously, the need for a clinically and educationally robust inpatient CLS persists despite funding pressures. The University of California, Davis Medical Center Department of Psychiatry has made use of creative organizational and financial models to accomplish the inpatient CLS clinical and educational missions in a fiscally responsible manner. In addition, the department has in recent years expanded the delivery of psychiatry consultation-liaison clinical and educational services to other models of care delivery, broadening the role and influence of the CLS. Several of the initiatives described in this paper parallel an overall evolution of the practice of consultation-liaison psychiatry in response to managed care influences and other systems pressures. This consultation-liaison paradigm expansion with diversified sources of funding support facilitates the development of consultation-liaison psychiatry along additional clinical, administrative, research, and educational dimensions. Other university medical centers may consider adaptation of some of the initiatives described here to their institutions.

Academic Medical Centers↗

[Jargon of the neonatal intensive care unit].

Jargon, the specialized vocabulary and idioms, is frequently used by people of the same work or profession. The neonatal intensive care unit (NICU) makes no exception to this. As a matter of fact, NICU is one place where jargon is constantly developing in parallel with the evolution of techniques and treatments. The use of jargon within the NICU is very practical for those who work in these units. However, this jargon is frequently used by neonatologists in medical reports or other kinds of communication with unspecialized physicians. Even if part of the specialized vocabulary can be decoded by physicians not working in the NICU, they do not always know the exact place that these techniques or treatments have in the management of their patients. The aim of this article is to describe the most frequent jargon terms used in the French NICU and to give up-to-date information on the importance of the techniques or treatments that they describe.

Humans↗

Molecular phylogeny of Lysimachia (Myrsinaceae) based on chloroplast trnL-F and nuclear ribosomal ITS sequences.

Both nuclear ribosomal ITS and chloroplast trnL-F sequences were acquired for 57 species (accessions) of Lysimachia and its close relatives, and were analyzed together with sequences retrieved from databases. The results of phylogenetic analyses based on these data (separately or combined) show that Lysimachia is paraphyletic, with the monotypic genus Glaux nested deeply inside. Previous suggestions that Anagallis and Trientalis could be ingroups of Lysimachia were not corroborated by our results. The molecular phylogenies do not support the current infrageneric divisions of Lysimachia. Subgenus Lysimachia contains at least five independent lineages. The Hawaii endemic subgenus Lysimachiopsis was shown to group with subgenera Palladia and Heterostylandra, instead of subgenus Idiophyton as previously suggested. The two North American representatives of Lysimachia, subgenus Seleucia and section Verticillatae of subgenus Lysimachia are group together as the most basal clade of the genus. Parallel and independent evolutions were inferred for morphological characters that were previously used as diagnostic criteria. Molecular phylogenies do not offer clear inferences on the overall historical biogeography of Lysimachia, but Southeast Asia origins of several clades, including the Hawaiian endemic clade and the Iberian Lysimachia ephemerum are strongly supported.

Cell Nucleus↗

Thermal hysteresis proteins.

Extreme environments present a wealth of biochemical adaptations. Thermal hysteresis proteins (THPs) have been found in vertebrates, invertebrates, plants, bacteria and fungi and are able to depress the freezing point of water (in the presence of ice crystals) in a non-colligative manner by binding to the surface of nascent ice crystals. The THPs comprise a disparate group of proteins with a variety of tertiary structures and often no common sequence similarities or structural motifs. Different THPs bind to different faces of the ice crystal, and no single mechanism has been proposed to account for THP ice binding affinity and specificity. Experimentally THPs have been used in the cryopreservation of tissues and cells and to induce cold tolerance in freeze susceptible organisms. THPs represent a remarkable example of parallel and convergent evolution with different proteins being adapted for an anti-freeze role.

Adaptation, Biological↗

Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneous allergic drug reactions.

BACKGROUND: In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T cells may play a relevant role. T cells related to skin immune responses express the cutaneous lymphocyte-associated antigen (CLA), the skin-homing receptor. METHODS: We studied the expression of the CLA in peripheral blood T cells from nine subjects with exanthematous reactions induced by beta-lactams (4), phenytoin (2), propyphenazone (1), spiramycin plus metronidazol (1), and captopril plus tiazide (1). The cutaneous symptoms appeared at least 6 h after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and 1 month later (T2). HLA-DR activation marker expression was also evaluated at T1. In four patients, it was necessary to readminister the culprit drug to establish a causal relationship, and sequential estimation of the markers was performed. Two control groups were included: healthy controls and subjects exposed to the culprit drugs with good tolerance. Values were compared by nonparametric statistics. RESULTS: The expression of circulating CLA + T cells at T1 was increased compared to healthy controls (median = 20.4 vs 9.4) (P < 0.001), and the patients also expressed increased levels of HLA-DR (median = 3.8) (P < 0.005). Comparison between T1 and T2 (median = 11.2) also showed differences in levels of CLA+ T cells (P < 0.01). The patients re-exposed to the culprit drug showed an increase followed by a decrease of circulating CLA+ T cells (P < 0.05) and CLA+ HLA-DR+ (P < 0.05) paralleling the symptoms. CONCLUSIONS: These data support the immunologic nature of delayed skin reactions to drugs, and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiologic mechanisms.

Adult↗

Efferent axons in the avian auditory nerve.

The sensory hair cells of the inner ear receive both afferent and efferent innervation. The efferent supply to the auditory organ has evolved in birds and mammals into a separate complex system, with several types of neurons of largely unknown function. In this study, the efferent axons in four different species of birds (chicken, starling, barn owl and emu) were examined anatomically. Total numbers of efferents supplying the cochlear duct (auditory basilar papilla and the vestibular lagenar macula) were determined; separate estimates of the efferents to the lagenar macula only were also derived and subtracted. The numbers for auditory efferents thus varied between 120 (chicken) and 1068 (barn owl). Considering the much larger numbers of hair cells in the basilar papilla, each efferent is predicted to branch extensively. However, pronounced species-specific differences as well as regional differences along the tonotopic gradient of the basilar papilla were documented. Myelinated and unmyelinated axons were found, with mean diameters of about 1 microm and about 0.5 microm, respectively. This suggests two basic populations of efferents, however, they did not appear to be distinguished sharply. Evidence is presented that some efferents lose their myelination at the transition from central oligodendrocyte to peripheral Schwann cell myelin. Finally, a comparison of the four bird species evaluated suggests that the efferent population with smaller, unmyelinated axons is the phylogenetically more primitive one. A new population probably arose in parallel with the evolution and differentiation of the specialized hair-cell type it innervates, the short hair cell.

Acetylcholinesterase↗

Financing the treatment of chronic pain: models for risk-sharing among pain medicine physicians, health care payers, and consumers.

Chronic pain patients are among a growing group of medically underserved Americans. Despite increasing public awareness about pain and widespread legislative activity that is focusing on the needs of pain patients, there remain significant roadblocks in bringing the expertise of Pain Medicine specialists to these unfortunate people. This paper explores how the managed care revolution has impacted the practice of Pain Medicine in the United States. The dissolution of many prominent multi-disciplinary pain treatment centers has been paralleled by the evolution of pain management as an area of interest by several competing medical specialty societies. Despite this fragmentation, the American Academy of Pain Medicine continues to grow and to promote the needs of Pain Medicine specialists and their patients. The advantages and disadvantages of various practice patterns for Pain Medicine specialists is explored against a backdrop of discussions about: (1) the problems currently faced by chronic pain patients; (2) the role of organized Pain Medicine in helping patients to access and finance care; and (3) the future of American health care and the new responsibilities that will bring to physicians. Finally, we have some specific recommendations for pain medicine specialists about: (1) sharing risk; (2) exerting individual leadership; and (3) simplifying one's professional life in the new health care environment, that we hope will enable them to continue caring for as many chronic pain patients as possible. It is opined that the development of sophisticated regional specialty networks is the best model to accomplish this task in the future.

Journal Article↗

The value of idiosyncratic markers and changes to conserved tRNA sequences from the mitochondrial genome of hard ticks (Acari: Ixodida: Ixodidae) for phylogenetic inference.

Idiosyncratic markers are features of genes and genomes that are so unusual that it is unlikely that they evolved more than once in a lineage of organisms. Here we explore further the potential of idiosyncratic markers and changes to typically conserved tRNA sequences for phylogenetic inference. Hard ticks were chosen as the model group because their phylogeny has been studied extensively. Fifty-eight candidate markers from hard ticks (family Ixodidae) and 22 markers from the subfamily Rhipicephalinae sensu lato were mapped onto phylogenies of these groups. Two of the most interesting markers, features of the secondary structure of two different tRNAs, gave strong support to the hypothesis that species of the Prostriata (Ixodes spp.) are monophyletic. Previous analyses of genes and morphology did not strongly support this relationship, instead suggesting that the Prostriata is paraphyletic with respect to the Metastriata (the rest of the hard ticks). Parallel or convergent evolution was not found in the arrangements of mitochondrial genes in ticks nor were there any reversals to the ancestral arthropod character state. Many of the markers identified were phylogenetically informative, whereas others should be informative with study of additional taxa. Idiosyncratic markers and changes to typically conserved nucleotides in tRNAs that are phylogenetically informative were common in this data set, and thus these types of markers might be found in other organisms.

Animals↗

Pathophysiology of language switching and mixing in an early bilingual child with subcortical aphasia.

Acquired aphasia after circumscribed vascular subcortical lesions has not been reported in bilingual children. We report clinical and neuroimaging findings in an early bilingual boy who incurred equally severe transcortical sensory aphasia in his first language (L1) and second language (L2) after a posterior left thalamic hemorrhage. Following recurrent bleeding of the lesion the aphasic symptoms substantially aggravated. Spontaneous pathological language switching and mixing were found in both languages. Remission of these phenomena was reflected on brain perfusion SPECT revealing improved perfusion in the left frontal lobe and left caudate nucleus. The parallelism between the evolution of language symptoms and the SPECT findings may demonstrate that a subcortical left frontal lobe circuity is crucially involved in language switching and mixing.

Adolescent↗

The effect of chloramphenicol on deoxyribonucleic acid synthesis and the development of resistance to ultraviolet irradiation in E. coli infected with bacteriophage T2.

To elucidate the role of protein synthesis in DNA formation, E. coli R2 infected with phage T2 was studied as a model, employing chloramphenicol to inhibit protein synthesis. The following results were obtained. 1. Chloramphenicol inhibited protein synthesis but not synthesis of nucleic acids in uninfected bacteria. 2. Studies of the effect of chloramphenicol on phage maturation indicated a delay of 2 minutes between time of addition and cessation of phage growth. 3. The increase of DNA in phage-infected bacteria was completely suppressed by the addition of chloramphenicol within 2 minutes following infection. Addition at later times showed progressively less inhibitory action depending upon the time interval, and addition after the 10th or 12th minute showed no appreciable effect on DNA synthesis despite the cessation of intracellular phage formation and protein synthesis. 4. When chloramphenicol was added to infected cells the increase of resistance to UV stopped within 2 minutes, whether or not DNA synthesis continued. Thus evolution of resistance paralleled the rate of DNA synthesis achieved, but not the amount of DNA accumulated. 5. We conclude that in infected bacteria, protein synthesis is necessary to initiate DNA synthesis but is not essential for its continuation. The resistance to UV that characterizes infected cells near the midpoint of the latent period is not due to accumulation of DNA, but depends on some chloramphenicol-sensitive process (probably protein synthesis) completed at about the time the rate of DNA synthesis becomes maximal.

Bacteriophage T4↗

Mass spectrometry technologies for proteomics.

In the late 1980s, the advent of soft ionization techniques capable of generating stable gas phase ions from thermally unstable biomolecules, namely matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), laid the way for the development of a set of powerful alternatives to the traditional Edman chemistry for the structural characterization of peptides and proteins. The rapid protein identification capabilities that, coupled with two-dimensional gel electrophoresis, provided insights into all sorts of biological systems since the dawn of proteomics and have been exploited in the last few years for the development of more powerful and automatable gel-free strategies, mainly based on multidimensional chromatographic separations of peptides from proteolytic digests. In parallel to the evolution of ion sources, mass analysers and scan modes, the invention of new elegant biochemical strategies to fractionate or simplify highly complex mixtures, or to introduce isotopic labels in peptides in a variety of ways now makes also possible large-scale, high-coverage quantitative studies in a wide dynamic range. In this review, we provide the fundamental concepts of mass spectrometry (MS) and describe the technological progress of MS-based proteomics since its earliest days. Representative literature examples of their true power, either when employed as exploratory or as targeted techniques, is provided as well.

Mass Spectrometry↗

Phylogenetic--evolutionary approaches to bioinformatics.

Phylogenies of organisms are essential to investigating a range of evolutionary questions of interest to researchers in the field of bioinformatics. Phylogenies not only help to define how to study many evolutionary questions, they must also be taken into account when conducting statistical analyses. Here it is shown how phylogenies can be used to investigate variability along the sites of a gene, reconstruct ancestral states of ancient genes and proteins, identify and characterise events of parallel and convergent evolution, find events of gene duplication, analyse predictions from molecular clocks, seek evidence for correlated changes among different parts of the same gene or genome, and test theories of molecular evolution. A table of statistical and phylogenetic methods is presented.

Animals↗

Mutations in human DNA polymerase eta motif II alter bypass of DNA lesions.

Human DNA polymerase eta (hPol eta) is one of the newly identified Y-family of DNA polymerases. These polymerases synthesize past template lesions that are postulated to block replication fork progression. hPol eta accurately bypasses UV-associated cis-syn cyclobutane thymine dimers in vitro and contributes to normal resistance to sunlight-induced skin cancer. We describe here mutational analysis of motif II, a highly conserved sequence, recently reported to reside in the fingers domain and to form part of the active site in Y-family DNA polymerases. We used a yeast-based complementation system to isolate biologically active mutants created by random sequence mutagenesis, synthesized the mutant proteins in vitro and assessed their ability to bypass thymine dimers. The mutability of motif II in 210 active mutants has parallels with natural evolution and identifies Tyr52 and Ala54 as prime candidates for involvement in catalytic activity or bypass. We describe the ability of hPol eta S62G, a mutant polymerase with enhanced activity, to bypass five other site-specific lesions. Our results may serve as a prototype for studying other members of the Y-family DNA polymerases.

Amino Acid Sequence↗

Sequence of Abeta-protein deposition in the human medial temporal lobe.

The deposition of Abeta protein (Abeta) and the development of neurofibrillary changes are important histopathological hallmarks of Alzheimer disease (AD). In this study, the medial temporal lobe serves as a model for the changes in the anatomical distribution pattern of different types of Abeta-deposits occurring in the course of AD, as well as for the relationship between the development of Abeta-deposition and that of neurofibrillary pathology. In the first of 4 phases of beta-amyloidosis, diffuse non-neuritic plaques are deposited in the basal temporal neocortex. The same plaque type appears in the second phase within the external entorhinal layers pre-beta and pre-gamma, and fleecy amyloid deposits occur in the internal entorhinal layers pri-alpha, pri-beta, pri-gamma, and in CA1. In the third phase, Abeta-deposits emerge in the molecular layer of the fascia dentata, and band-like Abeta-deposits occur in the subpial portion of the molecular layer of both the entorhinal region and the temporal neocortex. In addition, confluent lake-like Abeta-deposits appear in the parvopyramidal layer of the presubicular region. The fourth phase is characterized by diffuse and core-only plaques in CA4. Diffuse plaques evolve sporadically in the external entorhinal layer pre-alpha. Parallel to the evolution of beta-amyloidosis as represented by the 4 phases, neuritic plaques gradually make their appearance in the temporal neocortex, entorhinal region, CA1, the molecular layer of the fascia dentata, and CA4. A prerequisite for their development is the presence of Abeta and the presence of neurofibrillary tangles in neurons targeting the regions where neuritic plaques evolve. Each of the different types of Abeta-deposits, including neuritic plaques, plays a specific role in the distinct developmental sequence as represented by the 4 phases so that the medial temporal lobe inexorably becomes involved to an ever greater extent. The step-for-step involvement of connected anatomical subfields highlights the importance of the entorhino-hippocampal pathways for the expansion of beta-amyloidosis. The 4 phases in the evolution of beta-amyloidosis correlate significantly with the stages of the neurofibrillary pathology proposed by Braak and Braak.

Adult↗

How uniform are post-graduate training programs in medical oncology in the European Union?

BACKGROUND: Medical oncology is a relatively new discipline whose rapid evolution is not paralleled by advances in the academic curricula. The present study was designed to provide a description of the status of post-graduate training programs in medical oncology in the European Union. RESULTS: Our survey shows that 'some form' of training in medical oncology is available in 10 countries of the European Union, but that there are officially recognized Schools of Specialization in this discipline in only four (Great Britain, Portugal, Republic of Ireland and Spain). Italy and France offer training programs in medical oncology as specific tracks of the School of Specialization in Oncology. A 'special competence' in medical oncology, within the specialty of internal medicine, is issued in 3 additional countries (Denmark, Belgium and the Netherlands). Finally, training in medical oncology is linked to that in haematology in Germany. A wide variation was found among the different European countries regarding the requirements for admission to these training programs. Similarly, the duration of the programs in the various schools ranges between 2 and 6 years and the total number of years from graduation to achievement of the title of specialist ranges from 4 to 9 years. CONCLUSIONS: Our survey discloses a broad heterogeneity of academic attitude regarding medical oncology in the European Union and points to the need for recognition of this discipline as a specific and essential specialization.

Education, Medical, Graduate↗

Possible effect of a sex chromosome on reproductive performance in Columbidae.

In comparison with the reproductive performance of matings within Streptopelia risoria, the species hybrid males, from matings to S. risoria of males of S. chinensis or S. senegalensis, displayed increased infertility, but not an increase of embryo mortality. Previous findings of a high percentage of sperm abnormalities provide a basis that explains in part the infertility of the species hybrid males. The infertility and embryo mortality of both kinds of species hybrid females, the heterogametic sex, was much higher than in the S. risoria X S. risoria matings. The reproductive performance of the backcross females of the first, second and third backcross generations, having either species hybrid or backcross hybrid males as parents, could be divided into two classes, differing significantly either in percentage of infertility or embryo mortality, or in both categories. The backcross females producing the lower reproductive performance presumably carried the X chromosome of the wild parental species. Limited date obtained following a mating between a S. senegalensis female and a S. chinensis male showed a very low percentage of infertility of eggs from two species hybrid females and a backcross female (1/4-S. chinensis), indicating that the adverse effect of changes affecting infertility, presumably on the X-chromosome of these two wild species, towards S. risoria, had occurred in parallel during their evolution. The genetic changes affecting embryo mortality, and particularly the death of the squabs before becoming adults, are located on somatic chromosomes.

Animals↗

Hepatoid adenocarcinoma of the lung: report of a case of an unusual alpha-fetoprotein-producing lung tumor.

We report on a rare tumor of the lung characterized by its morphologic hepatoid features and alpha-fetoprotein production. This unusual neoplasm arose in the left lung of a 36-year-old man in whom clinical and radiologic examinations did not reveal any other tumor. The serum level of alpha-fetoprotein was measured at 6,090 ng/mL and was parallel to the evolution of the tumor. Despite treatment, the patient died 7 months after the diagnosis. The microscopic appearance of the tumor was the same as observed in hepatocarcinoma and hepatoid adenocarcinoma of the ovary or the stomach, with a tubular, papillary, or trabecular pattern. Periodic acid-Schiff-positive hyaline globules were numerous, and tumor cells showed immunohistologic positivity for alpha-fetoprotein and carcinoembryonic antigen. This lung adenocarcinoma was first described by Ishikura et al. in 1990 and was named hepatoid lung adenocarcinoma. Like the rare hepatoid carcinoma of the gallbladder, the pancreas, the ampulla of Vater, the renal pelvis, and the bladder, the exact histogenesis and the prognosis of this type of lung tumor are not yet known.

Adenocarcinoma↗