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7789173
The human gonadotropin-releasing hormone receptor gene (GNRHR) maps to chromosome band 4q13.
A cDNA representing the high-affinity gonadotropin-releasing hormone (GnRH) receptor has been molecularly cloned from the human pituitary gland, a breast tumor cell line (MCF 7), and an ovarian tumor. The nucleotide sequence of this cDNA was determined, and its expression in various human tumors and tumor cell lines was demonstrated. In this study, we localized the gene encoding the GnRH receptor to human chromosome 4, using polymerase chain reaction (PCR) analysis of genomic DNA from human x hamster somatic cell hybrids. The gene was sublocalized to chromosome band 4q13 using fluorescence in situ hybridization with the GnRH receptor gene (GNRHR).
7789172
Chromosome painting analysis of early oogenesis in human trisomy 18.
We have used chromosome 18-specific painting probes to analyze early stages of oogenesis in two human trisomy 18 fetuses. At leptotene, a diffuse, nonlinear chromosomal fluorescence was detected as one (27%), two (42%), or three (31%) signals in 534 cells. The variation in size of these signals implies the possibility of associations between homologs prior to zygotene. At pachytene, about 75% (339/453) of the cells had a trivalent configuration, and almost half of these cells exhibited almost complete triple synapses. Approximately 24% of the pachytene cells demonstrated a bivalent:univalent configuration, and 1% exhibited complete asynapsis. Our data imply that triple synapses may be a regular feature of meiosis involving multivalents.
7789171
Sequence of mouse Odf1 cDNA and its chromosomal localization: extension of the linkage group between human chromosome 8 and mouse chromosome 15.
The mouse cDNA encoding the major protein of the outer dense fibers in sperm tails was isolated by reverse transcription of testicular RNA and amplification with sequence-specific primers. Sequencing of a genomic clone obtained by inverse PCR yielded the 5' untranslated region. The transcription starting point was verified by primer extension. The putative proteins encoded by Odf1 in mouse and by ODF1 in rat and man are very similar. A total of 15 amino acids in the C-terminal region were deleted in the mouse protein, compared with the rat protein. Through in situ hybridization to metaphase chromosomes, the Odf1 gene was localized to mouse chromosome 15 region B2-C. The chromosomal localization of the Odf1 gene extends the hitherto known linkage group consisting of MYC (Myc), PVT1 (Pvt1), GPT (Gpt), and TG (Tg) common to human chromosome 8 and mouse chromosome 15 in the proximal direction of both chromosomes. The linkage group now extends from band q24 to band q22 of human chromosome 8 and from region D2-E to region B2-C of mouse chromosome 15.
7789170
The human S-adenosylmethionine decarboxylase gene: nucleotide sequence of a pseudogene and chromosomal localization of the active gene (AMD1) and the pseudogene (AMD2).
S-adenosylmethionine decarboxylase (AdoMet-DC) is a key enzyme in polyamine biosynthesis. The human genome contains at least two loci for the AdoMetDC gene (AMD), one of which (AMD1) has previously been mapped to chromosome 6 and the other (AMD2) to the X chromosome. The locus on chromosome 6 is the transcriptionally active gene. We now report characterization of the AMD2 locus (GenBank Accession No. U02035) on the X chromosome, which contains sequences that cross-hybridize with human AdoMetDC cDNA. This DNA lacks all of the introns present in AMD1 and has numerous mutations in the protein-coding region. Its overall nucleotide sequence identity with AdoMetDC cDNA is about 90%. AMD2 is therefore a processed pseudogene, which, because of multiple mutations, cannot be translated to an active AdoMetDC enzyme, even if it were transcribed. Chromosomal loci for human AMD sequences were determined by in situ hybridization to metaphase chromosomes, with genomic DNAs from the active gene and the pseudogene loci as probes. AMD1 was localized to chromosome region 6q21-->q22 and AMD2 to band Xq28.
7789169
Partial nucleotide sequence and chromosomal localization of a bovine zinc finger gene ZNF164.
A clone carrying an open reading frame coding for a novel zinc finger protein of the Krüppel family was isolated from a bovine genomic library and designated ZNF 164 (zinc finger protein 164). Partial sequencing revealed that it contained at least 13 zinc finger motifs preceded by a lysine-rich region of 60 amino acids. The ZNF164 protein shared approximately 60% similarity with several zinc finger proteins but did not appear to be orthologous with a previously identified gene. Using fluorescence in situ hybridization, the ZNF164 gene was mapped to bovine chromosome band 17q24.
7789168
Sequence identity locates CEBPD and FGFR1 to mapped human loci within proximal 8p.
The gene loci for human CEBPD (CCAAT enhancer binding protein, delta chain) and FGFR1 (fibroblast growth factor receptor) have been identified within two genetically mapped cosmids by sequence homology between rare cutter site regions and data base sequences for these loci. Cell hybrid and fluorescence in situ hybridization mapping places both of these loci within the chromosome region 8p11.2-->p11.1.
7789167
Assignment of alpha 1-acid glycoprotein gene (ORM1) to swine chromosome region 1q210-->q212 by fluorescence in situ hybridization.
The porcine gene for alpha 1-acid glycoprotein (ORM1) was localized to chromosome region 1q210-->q212 by fluorescence in situ hybridization. From this result and published gene mapping data, it was concluded that the syntenic group comprised of ORM1, IFNA1, and GRP78 in the human genome is also conserved in the pig.
7789166
Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridisation.
The three loci NRAS, NGFB, and CD2 map to human chromosome band 1p13. Using fluorescence in situ hybridisation (FISH) to simultaneously DAPI-banded metaphase chromosomes, we have further refined the localisation of these three genes to specific subbands. NRAS localises to subband 1p13.2 and CD2 and NGFB to 1p13.1. Also, with the use of multicolour FISH, we have determined the order and orientation of the three loci in relation to the centromere. The order is cen-CD2-NGFB-NRAS.
7789156
The epidemiology of measles: thirty years of vaccination.
Measles is a highly infectious disease which has a major impact on child survival, particularly in developing countries. The importance of understanding the epidemiology of this disease is underlined by its ability to change rapidly in the face of increasing immunization coverage. Much is still to be learned about measles epidemiology and the best strategies for administering measles vaccines, as well as about the biological mechanisms of action of measles vaccines. However, it is clear that tremendous progress can be made in preventing death and disease from measles with existing knowledge about the disease, and by using the presently available vaccines and applying well tried methods of treating cases. Research in the coming decade may provide improved strategies and more effective vaccines for use in immunization programmes.
7789155
Immune responses during measles virus infection.
The characteristic disease features of measles--fever and rash--are associated with the immune response to infection and are coincident with virus clearance. MV-specific antibody and CD4 and CD8 T cell responses are generated and contribute to virus clearance and protection from reinfection. During this same phase of immune activation immunologic abnormalities are also apparent. There is a generalized suppression of cellular immune responses that may contribute to increased susceptibility to other infections. Autoimmune disease may appear in the form of acute disseminated encephalomyelitis. If virus-specific immune responses are inadequate infection may progress with pulmonary or CNS manifestations, but without a rash. The pathogenesis of the rare disease SSPE, that occurs many years after primary infection is not clear, but immune responses show increased antibody to measles and cellular immune responses similar to those seen after uncomplicated infection.
7789150
Borna disease--neuropathology and pathogenesis.
Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspicuously absent. In the course of persistent infection of the rat, an elective, focal degeneration ensues that involves the dentate gyrus, retina, and, less frequently, the magnocellular part of the hippocampus. The cytopathic destruction of the dentate gyrus is the likely anatomical substrate of learning deficiencies and behavioral changes, prominent features of chronic infection. Later in infection, more diffuse and random degeneration of neurons can be found. In all species infected, viral antigens are produced in excess and fill all neuronal processes. Beside neurons, glial cells are infected as well. The agent spreads in the nervous system axonally and transsynaptically (transneuronally). The type of neurotransmitter receptors in the synapse and their interaction with viral proteins may modulate the spread of infection (Gosztonyi et al. 1994). Virus particles have not been visualized in the brain in any phase of the disease. During persistent infection of the rat, production of viral proteins has a phasic character. Some rats survive acute infection and develop an obesity syndrome. The anatomical basis of this syndrome is not fully clarified; inflammatory destruction of the infundibular region, vacuolar degeneration of the paraventricular nucleus of the hypothalamus and severe, progressive involution of the hippocampal formation most probably play an important role in the production of this neuroendocrine syndrome. In the acute disease, inflammatory reaction can severely aggravate virus-induced cytopathology, but cannot be the sole cause of the neurological disease, since infection with high passage virus can lead to a similarly severe disease in the absence of inflammatory changes.
7789139
Statistical design of the Child and Adolescent Trial for Cardiovascular Health (CATCH): implications of cluster randomization.
This paper describes some statistical considerations for the Child and Adolescent Trial for Cardiovascular Health (CATCH), a large-scale community health trial sponsored by the National Heart, Lung, and Blood Institute. The trial involves randomization of entire schools rather than individual students to the experimental arms. The paper discussed the implications of this form of randomization for the design and analysis of the trial. The power calculations and analysis plan for the trial are presented in detail. The handling of outmigrating and immigrating students is also discussed.
7789140
Data quality assurance, monitoring, and reporting.
In conclusion, the quality assurance and monitoring program is an integral and continuing part of study operations. A system must be devised and implemented by the coordinating center investigators, with the endorsement of the study leadership and support of the field site and resource center personnel. Proactive mechanisms for promoting high-quality data acquisition and reporting must be implemented. Data quality monitoring must address the entire process by which the data are gathered, transmitted, stored, and analyzed. Data quality should be monitored continually, with summary reports prepared and distributed to the study leadership. Appropriate training and certification enhance data quality, and site visits allow data collection and storage processes to be observed directly. The quality assurance and monitoring system must be documented. It should be flexible enough so that new means of quality assurance or monitoring can be added when necessary during the course of the study. At the completion of the study, quality monitoring results should be summarized in a final report regarding the level of quality achieved by the study investigators and personnel. Finally, for a quality assurance and monitoring program to be successful, the coordinating center investigators and personnel must provide prompt feedback and suggestions for corrective action whenever a data quality problem is discovered. This need can be met only when the coordinating center staff understand data quality goals and are up to date with all phases of data management and reporting. Delays in initiating any stage of data management and quality monitoring may result in uncorrectable data problems. Thus, knowledgeable and efficient coordinating center personnel are essential to achieving good data quality studywide.
7789138
Requirements for controlled clinical trials of preoperative cardiovascular risk reduction.
Although controlled clinical trials have had a major impact in many areas of cardiovascular disease management, they have had little influence on preoperative cardiac risk reduction. Over the past 2 years, we have conducted the Reduction of Cardiac Operative Risk (RCOR) Trial, a pilot study designed to determine enrollment and event rates for a definitive trial evaluating a strategy to reduce cardiac risk associated with noncardiac surgery. This experience indicates that a successful, definitive trial will require recognition of the multiple questions to be answered, accurate identification of the study population, a large sample size, cooperation between internists, surgeons, and anesthesiologists, and strategies to minimize cost. The high costs and difficulties of such a trial are likely to be outweighed by the enormous benefit of identifying the proper strategy for the use of the expensive testing methods that are currently employed.
7789135
Design and analysis of multiarm clinical trials with survival endpoints.
The clinical trials literature has paid relatively little attention to the design and analysis of K-sample trials with survival endpoints where K is 3 or greater. Following the least-significant-difference approach proposed by Makuch and Simon [1], we derive sample size formulas by working with the logrank test and proportional hazards model directly. This approach ensures the type I error rate to be the nominal value when the global null hypothesis is true. For power considerations, planning the study based on the least favorable alternative is recommended. The resulting sample size requirements are presented in graphic form for K = 3 and 4. Assuming that there is a control group and considering only the alternative that the survival of the experimental treatments is at least as good as that of the control group, power investigations indicate that the proposed strategy has good power for detecting the difference between the control and the best treatment. The "overall power," defined as the chance of the global test and subsequent pairwise comparisons all being correct, is good when all treatments are similar to either the control or the best treatment. Overall power is poor when the hazards are more evenly spread out between the control and the best group because the sample size is inadequate to detect such differences.
7789133
PC program for assessing the relationship between rate of change and initial value.
A menu-driven PC program implementing Blomqvist's [J. Am. Stat. Assn. 72, 746-749, 1977] method for assessing the relationship between rate of change and initial value is described, illustrated and made available. It is shown that the naive approach to this problem--computing the correlation between the initial value and either the amount or rate of change--results in a negatively biased estimator. The extent of this bias can be dramatic and may lead investigators to conclude that a negative correlation is present when none exists; or that there is no correlation when in fact the correlation is positive. Blomqvist's (maximum likelihood) estimator avoids this bias, and is obtained by a transformation of the naive estimator.
7789134
Computer acquisition, analysis and presentation of results from a Cobas Bio analyser.
Two computer programs for Macintosh computers have been developed in the LabVIEW programming language to perform data acquisition, analyses and presentation of results originating from a Cobas Bio analysing machine. One program is very flexible in its human interface, and is intended for research use. The program allows the results to be combined in a variety of ways, and allows the user to generate graphs to highlight the results. The other program is intended for routinely follow-up of analyses of proteases. It only allows the user to follow strict instructions, and only limited flexibility is built-in.
7789131
Improvements in accuracy and reproducibility of quantitative clotting factor assays by use of a novel approach for modeling reference curves.
A method for creating a reference model in the quantitative assay of specific clotting factor activities is described. This method incorporates the use of a piecewise function with two component polynomials. This function allows more accurate representation of the global coagulation reaction, a sequential activation of multiple serine protease enzymes and cofactors, leading to improvements over traditional methods in range, accuracy, precision and robustness in reported activity levels. Clotting factor assay results using this method are compared with traditional and other candidate methods.
7789132
Model analysis of time duration in a medication order entry system with attention to do-medication orders.
To investigate the relative time length needed for a medication computer order entry in comparison with the handwritten prescription system, we made a model, focusing our attention on the "do-medication order entry function." In the model analysis, we conducted a statistical analysis using the Nagoya University Hospital Information System. From the results and our model, if the time needed to make one (drug) item medication order entry is less than 1.9-3.0 times the time needed for handwriting one item prescription, computer order entry is faster on average.
7789130
Real-time multichannel abdominal fetal ECG monitor using digital signal coprocessor.
A real-time multichannel fetal ECG monitor based on a personal computer (PC) and a MOTOROLA DSP56001 Digital Signal CoProcessor (DSP) is introduced. The DSP board is plugged into the PC, which functions as a HOST computer. An analog 8 Leads Interface and Analog to Digital circuits module is connected to the DSP through a synchronous, optical-isolated communication channel. The fetal ECG detection is based on a cross-correlation technique. An averaged maternal ECG waveform is generated using a cross-correlation alignment procedure and a user-defined template. The fetal ECG signals present in the maternal waveform is suppressed during the averaging procedure, since both are uncorrelated. The average maternal ECG waveform is then subtracted from the abdominal real time signals, and maternal-free fetal ECGs signals are obtained, including fetal QRS complexes that coincide with maternal ones. Using the abdominal ECGs signals after subtraction, an averaged fetal waveform is generated. The maternal and the fetal heart rate are calculated during the process. The algorithm described above can be performed in real time on up to eight abdominal ECG traces by the DSP, and the desired results are passed to the HOST PC, to be stored and displayed. Electrodes positioning procedures for detecting the fetal QRS complexes with the best signal to noise ratio are not needed. Using the multichannel system, the user can select the best channel for fetal QRS detection, and accurate results for the heart rate signal are obtained. Averaged fetal waveforms are obtained from all the leads.
7789128
Connectionist networks in auditory system modeling.
Understanding how complex sounds, such as speech, are processed and eventually perceived in the brain is essential for building more effective speech processors. The echolocating bat provides an animal model for complex-sound processing of identified stimulus features at higher levels of the auditory pathway. In this paper, we present the use of connectionist models for modeling cortical neurons that play a key role in our auditory system model of a species of FM bat, Myotis lucifugus. The influence of network related parameters on modeling accuracy is presented, and the response of these models is explained in a behavioral context.
7789129
Minimization of EOG artefacts from corrupted EEG signals using a neural network approach.
In this paper, we propose a neural network (NN) approach to the enhancement of EEG signals in the presence of EOG artefacts. We recast the EEG enhancement problem into the optimization framework by developing an appropriate cost function. The cost function is nothing but the energy in the enhanced EEG signal obtained through a nonlinear filter formulation, unlike the conventionally-used linear filter formulation. The minimization property of feedback-type neural networks is exploited to solve this problem. An analysis has been performed to characterize the stationary points of the suggested energy function. The hardware set-up of the developed neural network has also been derived. The optimum nonlinear filter coefficients obtained from this minimization algorithm are used to estimate the EOG artefact which is then subtracted from the corrupted EEG signal, sample by sample, to get the artefact minimized signal. The time plots as the LP spectrum show that the proposed method is very effective. Thus the power and efficacy of the NN approach have been exploited for the purpose of minimizing EOG artefacts from corrupted EEG signals.
7789127
Use of neural networks as medical diagnosis expert systems.
A major bottleneck in building expert systems is the process of acquiring the required knowledge in the form of production rules. A novel class of neural networks is proposed to articulate the knowledge it learned from a set of examples. It provides an appealing solution to the problem of knowledge acquisition. After training, the knowledge embedded in the numerical weights of trained neural networks can be easily extracted and represented in the form of production rules. The approach is demonstrated by an example of a hypothesis regarding the pathophysiology of diabetes.
7789125
Around-the-clock mobile psychiatric crisis intervention: another effective alternative to psychiatric hospitalization.
This retrospective study evaluates the effect of the addition of a mobile psychiatrist to a 24-hour crisis intervention team, on the number of admissions, to the local state and private hospitals, of residents of the team's catchment area. During the Program period, the psychiatrist was available at the site of the crisis to provide immediate psychiatric treatment. The number of admissions to the hospitals during the Program period was then compared to those of the corresponding periods of the two previous years and of the year after, by means of a time series statistical analysis. When the on-site services of a psychiatrist were added to the mobile crisis intervention program a sharp decrease in state hospital admissions took place, without any increase in private hospital admissions. This decrease was followed by a definite rebound, after the on-site services of the psychiatrist were terminated, and throughout the following year.
7789124
Living with chronic mental illness: understanding the role of work.
This paper is based upon an exploratory study designed to examine the role of work within the lives of those with severe, persistent mental illness (SPMI). In-depth, open ended interviews were conducted with a small number of consumers (n = 10) who attend a clubhouse for those with SPMI where emphasis is placed upon preparation for work. Given that little is known about how work impinges upon or enriches the lives of consumers we asked consumers about their experience of mental illness and work throughout their life trajectories. This paper describes these work experiences, the effect of mental illness and treatment compliance upon their ability to work, and the relationship of work to stress. We found that in general some kind of meaningful activity was important to these consumers, but many had found work experiences to be stressful and were cautious about their subsequent abilities to sustain meaningful employment. We suggest that subsequent research needs to examine the nature of the work environment, and that work environments may be usefully distinguished in terms of level of expressed emotion.
7789123
Innovative programming in a community service center.
A Community Center in a downtown urban area offers comprehensive services that provide continuity and choice to homeless and poor people. Emphasis is on outreach, through a Day Treatment Program for severely, persistently mentally ill homeless, a mobile outreach team, and neighborhood services, and/or employment, including a restaurant and Employment Reintegration Program. The Center is an example of how professionals, community and business leaders, and citizens can unite to assist clients and how programs can evolve from clients' requests and participation in services. The Center's programming can be followed in any community in this health care reform era.
7789122
Housing choice and community success for individuals with serious and persistent mental illness.
Consumer choice is a central principle of psychosocial rehabilitation and supported housing approaches. This study assessed level of housing choice and the relationship of choice to community success in supported housing demonstration projects in five states. Assessment of level of choice about housing revealed very limited housing options and a high degree of influence from service providers over housing choice. Despite few options, most respondents liked their housing option(s) and felt they had enough information to make a good housing decision. The relationship of choice to community success over time demonstrated that choice was positively related to housing satisfaction, residential stability, and psychological well-being. Discussion focuses on implications of the findings for mental health services and public policy.
7789121
The relationship of service individualization to client functioning in programs for severely mentally ill persons.
A measure of service individualization, derived from the goals in clients' treatment plans, was developed and used to evaluate this treatment process variable for 141 severely mentally ill persons served by three psychosocial rehabilitation programs. Relatively few of the 364 goals reviewed were highly individualized. Level of service individualization was inversely related to clients' functional skills, residential independence, level of education, and a primary diagnosis of an affective disorder, but positively related to a diagnosis of schizophrenia or another psychotic disorder. The goal individualization measure differentiated both between programs and among staff members, even after controlling for differences on client variables.
7789120
Mental health case management: characteristics, job function, and occupational stress.
Although case management is an important component of treatment for persons with major mental illnesses, little is known about who works in case management, what functions are performed and how much occupational stress case managers experience. Mental health care managers (CM's) throughout the state of Oregon (N = 216) completed an inventory of case management functions and the job dissatisfaction and occupational stress scales of the Medical Personnel Stress Survey-Revised. The average expected tenure for a CM was 11 years, although one fifth expect to be a CM for four years or less. CM's spend 36% of their time performing administrative tasks, 20% in therapy, 17% with skills training, and 18% in case coordination tasks. CM level of education was associated with a different distribution of effort across case management functions. Greater job dissatisfaction was associated with specialized training, larger case load size and greater intention to leave the position. Consumer CM's demonstrated equivalent levels of job satisfaction as their non-consumer colleagues. The relevance of the project's findings for human resource management are discussed.
7789118
[Technical medicine in ancient comedy].
The texts of Greek comedy offer a panoramic vision of the evolution of medicine between the fifth and the third centuries. They provide an excellent way to understand the prejudices and the bases of technical medicine and its relationship with popular medicine. Comedy also shows us a vivid portrait of the physician and his position in Greek society.
7789117
Notes on the syntax of Celsus.
This paper discusses five remarkable syntactic features of the language of Celsus' De medicina: praedicativa, the anaphoric pronoun is, instructive expressions, word order, and complex noun phrases. It is shown that these features should not be explained as 'vulgarisms', but as functional linguistic characteristics that are appropriate to the subject matter of the text and the requirements of scientific and technical exposition.
7789115
The embarrassment of imperfection: Galen's assessment of Hippocrates' linguistic merits.
In antiquity the 'higher' study of medicine shared with many other disciplines a pronounced philological character. Galen both exploited this 'philological paradigm' and underwent its influence. He exploited it in that it enabled him to invest the Corpus Hippocraticum with a dignity comparable to that of Homer only. But his philological instrumentarium, originally designed for the study of literary texts, also forced him to pose and answer certain questions that shed no light whatsoever on the informational content of Hippocrates' writings, questions about Hippocrates' language and style. Galen disentangles himself from the ensuing embarrassment by claiming that Hippocrates' style was ideal for the specific didactic genre he was involved in. This special style necessitates a reassessment of customary grammatical and rhetorical values: correctness recedes into the background, clarity and brevity become the predominant virtues of style.
7789116
Structure and style in the Hippocratic treatise Prorrheticon 2.
Bearing in mind both the capacity of man and his limits, the author of Prorrheticon 2 states his opposition to irrational prognoses and brings forward the sêmeia as the only basis for a correct prognostic. He does so by enhancing his statements by means of structure (ring-composition, psychological structure of recurrence) and style: in this field he uses several devices aimed to attract the reader's attention, putting together colloquial and high-level expressions. In this paper a similar stylistic technique is intended in order to illustrate the points of the Greek author.
7789114
Science as text, science as history: Galen on metaphor.
This paper addresses three related questions: (1) What is Galen's theory of metaphor, and why is metaphor so important to him? (2) What is the place of metaphor in Galen's general theory of the language of science? (3) What is the relation of his theory of metaphor to his views on the historical dimension of language and to the historicity of science?
7789113
Dialectic and science: Galen, Herophilus and Aristotle on phenomena.
This paper examines the nature of Galen's argument in the De placitis Hippocratis et Platonis, books 2-3, concerned with the location of the psychic functions within the body. To this question Galen applies a coherent set of methodological principles, integrating Aristotelian dialectic and scientific demonstration based on anatomical experiments. Galen disagrees with Aristotle in that he relegates the endoxa from the realm of dialectic to that of rhetoric. His attitude is marked by a distinctive emphasis on perceptible phenomena as the starting point for scientific inquiry. This and other features can be traced back to the Hellenistic scientist Herophilus.
7789112
Alexander of Aphrodisias on medicine as a stochastic art.
Medical practice in antiquity was conspicuous for its failures, which seriously challenged medicine's status as an art. Ancient philosophers and doctors tried to explain how a whole group of arts including medicine, the so-called stochastic arts, was characterised by the fact that even the most competent exercise of the art could not guarantee a successful outcome. This paper focuses on Alexander of Aphrodisias' (second century AD) explanation and compares it to some other ancient views, in particular to Galen's. The central feature of Alexander's suggestion is a distinction between the end of an art and its function. In the case of medicine end and function do not coincide; for the end is to heal the patient, whereas the function consists solely in doing artfully what is possible to attain the end.
7789111
[The epistemology of Erasistrate and Hellenistic technology].
Erasistratus tried to build a coherent system of medicine founded on anatomical discoveries from which both physiology and pathology could be consistently derived. In this system, the so-called logôi theôrêta are not merely theoretical constructions, but models (and/or metaphors) transferred to medicine from the two branches of contemporary Hellenistic technology, artillery and pneumatics. However, this system could not stand to the criticism of Empiricist medicine, both because of its oversimplification of pathology and therapy and because of its exceedingly heavy epistemological requirements.
7789110
Aristotle on 'distinguished physicians' and on the medical significance of dreams.
This article studies the way in which Aristotle deals with the view-attributed by him to the 'distinguished physicians'-that dreams may be significant as clues for imminent diseases of the body of the dreamer. Aristotle is thinking of philosophically minded physicians (such as the author of De victu) who base their practice on principles derived from the study of nature in general and who take into account the constitution of the whole body. He accepts their view, but justifies it with his own theory of sleep and dreams; however, his attempt to incorporate the medical view into his own account brings him into conflict with his own presupposition that dreams are not actual perceptions, but experiences of the remnants of perceptions received during the waking state.
7789109
Medicine and the Lyceum.
Although Aristotle reveals a far higher degree of empirical observation than does Plato, he is fundamentally in agreement with him that the first principles of medicine should be drawn from philosophy. Like Plato, he adopts the four element theory, but prefers a system correlating 'elements' with binary combinations of opposites. It is argued that his biological and medical interests have influenced this general theory. It is also suggested that Diocles influenced considerably the development of anatomy and physiology within the Lyceum. Because of doctrinal affinities between Praxagoras and Diocles it has been maintained that the Lyceum exercised a dominant influence upon the subsequent history of Greek medicine; but caution must be enjoined.
7789108
[Non-Hippocratic references in Plato's dialogues].
Plato's references to contemporary medicine are of a twofold nature. They initially concern Hippocratic medicine, first as an epistemological model in opposition with sophistic arguments, secondly as an instrument to define 'political art'. But in the later dialogues, Plato's references to medicine appear to evolve into a 'non-Hippocratic', magical type. This second type of reference-mostly in the Laws-is no longer metaphorical or analogical: it serves to determine the procedures that must be followed by the Law-Giver to establish a theocratic order.
7789107
[Intelligent man and medicine].
In this article, three definitions of the ideal of the pepaideumenos (learned man) are examined in their mutual relations. In the pseudo-Platonic dialogue Amatores, the culture of the pepaideumenos is conceived as exhaustive as regards content, whereas it is attributed a merely 'formal' character in Plato's Charmides. However, on the theoretical level both solutions appear to be unsatisfactory. Aristotle's proposal is more convincing. He considers the pepaideumenos as the man who is able to assess the technicians' preparation adequately, since he knows the endoxa either with reference to knowledge as a whole or to individual technai. In all three cases, the example of the iatrikê (medicine) is the means to test the validity of the proposed resolutions.
7789106
Athumia and philanthrôpia. Social reactions to plagues in late antiquity and early Byzantine society.
Thucydides' description of the plague at Athens stands as a paradigm that influenced eyewitness accounts throughout Greek and Byzantine history. Christian authors in Late Antiquity use his dark picture as heathen background against which they highlight Christian virtues of charity and mercy. The descriptions of the Justinianic plague of AD 542 rely on Thucydides not only stylistically but also in substance, as the early Byzantine society reacts like the people of ancient Athens rather than early Christian communities.
7789105
Tatian's 'rejection' of medicine in the second century.
The question why Tatian, often misrepresented as an opponent of medicine per se, chose to condemn only pharmacology, has never been directly raised. His conviction that pharmakeia was a demonic lure can only be explained in the context of both popular and medical attitudes toward drugs. The basic meaning of pharmaka ranges from sorcery to poison to medicinal drugs. Some people regarded them as categorically similar to substances used by brute beasts to cure themselves, a minority of physicians refused to administer them at all, whereas many revered them as virtually divine, 'hands of the gods'. Hence, in Tatian's view, they were spiritually dangerous for Christians.
7789103
[Anatomia sacra. Religiously motivated interventions on human or animal bodies].
Controlled surgery in the interior of human or animal bodies in classical antiquity was allowed only under certain circumstances. Bloody animal sacrifice and its rules for the interpretation of entrails as well as the rare examples of 'ritual anatomy' presented a religious framework for the opening of bodies. Greek mythology provided several examples of medical operations, for example, the Caesarean section, transplantations and plastic surgery. Great cultic significance was given to organ votives or reproductions of human inner organs which were offered in temples ex voto or with request for their curing. The anatomical knowledge transported along with these offerings represents a separate tradition different from the state of anatomical knowledge found in medical literature of the period.
7789104
The healing event in Graeco-Roman folk-medicine.
The inexplicit character of Graeco-Roman folk-medicine, together with the distorted and haphazard nature of our evidence, has led to easy denigration of its aims and methods. Analysis of the structure of the healing event, especially its spoken component, the charm, provides some insight into tacit beliefs about illness, and into the skills through which folk-practitioners won reputations for competence. Just as in school medicine, the basic aim is acquisition of the authority to intervene: correct diagnosis, drawing upon folk-categories, is followed by the reassertion of order through setting the present contingency into the context of a natural law or regularity, drawing upon the stock of shared knowledge.
7789100
Variations in DNA subtype, antifungal susceptibility, and slime production among clinical isolates of Candida parapsilosis.
Candida parapsilosis is an important nosocomial pathogen that can proliferate in high concentrations of glucose and form biofilms on prosthetic materials. We investigated the genotypic diversity, slime production, and antifungal susceptibility among 60 isolates of C. parapsilosis from 44 patients and 10 patient care providers from five different medical centers. Molecular typing was performed using macrorestriction digest profiles with BssHII followed by pulsed-field gel electrophoresis (REAG) and by electrophoretic karyotyping (EK). Slime production was evaluated by growing the organisms in Sabouraud broth with 8% glucose and examining the walls of the tubes for the presence of an adherent slime layer. Antifungal susceptibility to amphotericin B, 5-fluorocytosine, fluconazole, and itraconazole was determined using National Committee for Clinical Laboratory Standards proposed standard methods. Overall 28 different DNA types were identified by REAG and EK methods. MIC90 values ranged from 0.12 microgram/ml for itraconazole to 1.0 microgram/ml for fluconazole and amphotericin B. Sixty-five percent of the isolates produced slime: 37% were moderately to strongly positive, 28% were weakly positive, and 35% were negative. Overall, 83% of blood and catheter isolates were slime positive versus 53% of isolates from all other sites (P < 0.05). These data underscore the genetic diversity and susceptibility of C. parapsilosis to antifungal agents. Slime production may be important in enabling C. parapsilosis to cause catheter-related bloodstream infections.
7789101
Illness and cures in the Greek propitiatory inscriptions and dedications of Lydia and Phrygia.
The propitiatory inscriptions of Lydia and Phrygia (of the second and third centuries AD) manifest the belief that illness is a divine punishment for a sin (usually for a religious offence); cure can thus be achieved through expiation. Although scientific medicine was not unknown, the high costs of doctors, the belief in the omnipotence of gods, and the attribution of illness to divine intervention led the villagers to the local sanctuaries, where they received instructions by means of dreams and oracles. Some priests had medical experience, but they usually practised a 'religious healing' (incantations, purifications, sacrifices, the ritual transfer of the sin and the illness to animals).
7789097
Cross-resistance analysis for DU-6859a, a new fluoroquinolone, compared to six structurally similar compounds (ciprofloxacin, clinafloxacin, fleroxacin, levofloxacin, ofloxacin, and sparfloxacin).
Emerging resistance to the current fluoroquinolones has encouraged synthesis of new compounds in this class. We have evaluated the activity of DU-6859a, a novel halogenated quinolone, against a panel of 300 bacteria, relative to the activity of ciprofloxacin, clinafloxacin, fleroxacin, levofloxacin, ofloxacin, and sparfloxacin. DU-6859a was the most active of the fluoroquinolones studied and retains potentially useful activity against 80% of isolates resistant (minimum inhibitory concentration, > or = 4 micrograms/ml) to ciprofloxacin. Continued clinical investigation of DU-6859a and similar new quinolones is urged.
7789098
Comparison of one-day versus two-day incubation of urine cultures.
The value of incubating urine cultures for 1 versus 2 days was evaluated prospectively for 1526 consecutive specimens. A total of 507 cultures (33.2%) were positive after 1 day; 41 (2.7%) showed different results after 2 days. Only yeasts and corynebacteria were detected more often with longer incubation. Patient charts were available for review from 27 of 41 late positives; in only three instances (11.1%) was action taken by physicians based on these results.
7789096
In vitro antimicrobial susceptibility of glycopeptide-resistant enterococci.
The results of susceptibility testing of 48 phenotyped strains of glycopeptide antibiotic-resistant enterococci are reported. Minimum inhibitory and bactericidal concentrations (MICs and MBCs) were determined for 27 vanA, 17 vanB, and 4 vanC strains. Antibiotics exhibiting the greatest activity included novobiocin (MIC90 = 8 micrograms/ml and MBC90 = 32 micrograms/ml), ramoplanin (MIC90 = 2 micrograms/ml and MBC90 = 4 micrograms/ml), and the streptogramin RP59500 (MIC90 = 4 micrograms/ml and MBC90 = 32 micrograms/ml). These antibiotics warrant further investigation as potentially useful agents, either alone or in combination, for treating enterococcal infections.
7789095
Multicenter in vitro comparative study of fluoroquinolones against 25,129 gram-positive and gram-negative clinical isolates.
In vitro activities of fleroxacin, ciprofloxacin, ofloxacin, and lomefloxacin were evaluated against 25,129 fresh bacterial isolates from 51 US hospital or medical center laboratories, beginning in October of 1990. Susceptibility rates were > or = 85% against most species of Gram-negative bacteria. Notable exceptions were Pseudomonas, Acinetobacter, Xanthomonas, and Providencia. The study drugs displayed similar activity against most Gram-negative species. At least 90% of oxacillin-susceptible staphylococci were susceptible but, of oxacillin-resistant strains, only approximately 60% of Staphylococcus epidermidis and 25% of Staphylococcus aureus were susceptible to the quinolones tested. Staphylococcus saprophyticus strains were less susceptible to fleroxacin (42%) than to the other compounds (79%-97%). Ofloxacin and ciprofloxacin were more active against streptococci, and none of the compounds demonstrated appreciable activity against enterococci. Thus, the spectra of activity of fluoroquinolones illustrate that they remain effective agents for the treatment of many types of infections caused by Gram-negative pathogens.
7789093
Comparison of three commercially available monoclonal antibodies directed against pp65 antigen for cytomegalovirus antigenemia assay.
A total of 102 blood samples were used in a prospective parallel and blind study to evaluate three commercially available anti-pp65 monoclonal antibodies for cytomegalovirus antigenemia assay, at the dilutions recommended by their manufacturers. Cytomegalovirus was detected in 42 samples (41.2%), by either culture (32 samples; 76.2% of positive samples) or antigenemia (38 samples; 90.6%). Of the antigenemia-positive samples, 37 were detected by Monofluo kit CMV, which showed statistically significant differences when compared with the other reagents (Biosoft 1C3 and Clonab C10/C11), in either positivity rates (P < 0.004) or positive cell counts (P < 0.001). This reagent also gave better results in fluorescence quality than 1C3 and C10/C11. However, technical differences were not reflected in the clinical relevance of the antigenemia results.
7789094
Susceptibility of ciprofloxacin-resistant staphylococci and enterococci to clinafloxacin.
Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis obtained from the Ann Arbor Veterans Affairs Medical Center within the last decade were tested for susceptibility to ciprofloxacin and clinafloxacin. For MRSA isolates, the minimum inhibitory concentrations (MICs) of ciprofloxacin were several fold higher than those noted with clinafloxacin. Prior to the introduction of the fluoroquinolones (1984-1985), all MRSA isolates were susceptible to ciprofloxacin and clinafloxacin. By 1993, virtually all MRSA isolates were resistant to ciprofloxacin and a 50-fold increase in the MIC50 and MIC90 for clinafloxacin was seen. In 1985-1986, most enterococcal isolates were susceptible to ciprofloxacin and clinafloxacin. By 1993, one-third of all enterococci were resistant to both ciprofloxacin and clinafloxacin. Fluoroquinolone resistance developed more quickly in enterococci that demonstrated high-level gentamicin resistance. Thus, cross-resistance between clinafloxacin and ciprofloxacin was seen; however, the lower MICs of clinafloxacin for MRSA may allow the use of this drug for some MRSA infections.
7789092
Recovery of Coccidioides immitis from blood and abscess fluid using the BacT/alert system.
We report the recovery of Coccidioides immitis from the blood and abscess fluid of two separate patients by using two automated blood culture systems. In the first case, an aspirate from a neck abscess containing C. immitis spherules was serially diluted and inoculated into liquid media used by the BacT/Alert and the Bactec NR660 blood culture systems. BacT/Alert bottles inoculated with 10(5), 10(4), 10(3), 10(2), 10 and two spherules produced a positive signal at 19, 24, 35, 42, 57, and 62 h postinoculation, respectively. Bactec NR660 bottles containing > 10(2) shperules and 10 spherules produced a positive signal after approximately 72 and 96 h of incubation, respectively. In the second case, a blood specimen incubated in BacT/Alert blood culture both was signaled positive after 82 h of incubation. No organisms were detected by Gram stain of the broth, but C. immitis grew after blind subculture. Our observations demonstrate that these rapid blood culture systems are capable of supporting growth of C. immitis. To our knowledge, this report is the first to detect C. immitis by these blood culture systems.
7789091
Development, characterization, and initial evaluations of S1. A new chromogenic cephalosporin for beta-lactamase detection.
A novel, chromogenic cephalosporin reagent (S1) for beta-lactamase testing was produced that shares physicochemical characteristics with nitrocefin (formerly 87/312). S1 and nitrocefin in a disk-testing format for beta-lactamase performed at 100% agreement for detecting enzyme-producing isolates of Bacteroides fragilis group, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Staphylococcus aureus, and selected Enterobacteriaceae. The time required to achieve an initial color change or a strong positive reaction was comparable for both chromogenic reagents for all organisms except the Gram-positive species. S1 reaction times were approximately 50% faster than nitrocefin for beta-lactamase-positive enterococci and S. aureus. These results from the developmental studies and a commercially prepared disk lot indicate that S1 is a promising beta-lactamase disk test reagent with the ability to detect all significant enzyme-producing species strains, some significantly earlier than the nitrocefin disk method.
7789090
Phonological recoding and self-teaching: sine qua non of reading acquisition.
The self-teaching hypothesis proposes that phonological recoding functions as a self-teaching mechanism enabling the learner to independently acquire an autonomous orthographic lexicon. Successful decoding encounters with novel letter strings provide opportunities to learn word-specific print-to-meaning connections. Although it may not play a central role in skilled word recognition, phonological recoding, by virtue of its self-teaching function, is regarded as critical to successful reading acquisition. This paper elaborates the self-teaching hypothesis proposed by Jorm and Share (1983), and reviews relevant evidence. Key features of phonological recoding include an item-based rather than stage-based role in development, the progressive "lexicalization" of the process of recoding, and the importance of phonological awareness and contextual information in resolving decoding ambiguity. Although phonological skills have been shown to be primary in reading acquisition, orthographic processing appears to be an important but secondary source of individual differences. This implies an asymmetrical pattern of dissociations in both developmental and acquired reading disorders. Strong relationships between word recognition, basic phonological processing abilities and phonemic awareness are also consistent with the self-teaching notion. Finally, it is noted that current models of word recognition (both PDP and dual-route) fail to address the quintessential problem of reading acquisition-independent generation of target pronunciations for novel orthographic strings.
7789089
Soar and the case for unified theories of cognition.
Despite the potential importance to cognitive psychology of unified theories no attempt has been made to assess concretely the methodological problems that such theorising produces. This paper addresses this issue of unified theorising, and in particular the arguments for unified theories put forward by Newell (1990). Close examination of these arguments reveals that Newell's approach does not adequately counter the difficulties which beset the grand theories of the 1930s, nor the problems of irrelevant specification which arise in modern computational psychological work. These difficulties do not prevent the development of unified theories, but they do pose serious problems, problems which it is argued can only be met by rigorous empirical testing together with extreme methodological sensitivity. The methodological concerns lead us to examine Soar, perhaps the most well-developed unified theory, from methodological, computational, and empirical perspectives. Our conclusions are that, whilst Soar represents an impressive body of research, its methodological foundations are insecure, it is ill specified as a computational/psychological theory, and under empirical testing it does not stand up to close scrutiny as a unified theory. The Soar research programme as it currently stands thus fails to meet the necessary methodological demands imposed by unified theorising.
7789086
[A case of a patient with multiple primary neoplasms: ileal leiomyosarcoma and bronchial carcinoid].
Small bowel leiomyosarcoma and lung carcinoid are uncommon neoplasms, and the association of these two neoplasms has never been reported in the literature. In the present article we report the case of a man who developed carcinoid of the lung three years after being operated for leiomyosarcoma of the small intestine. The short time elapsed between the two diagnoses adds further interest to this case.
7789085
[Uremic encephalopathy and oligo-elements].
The author reports the probable pathogenetic connexions between oligo-elements and uremic encephalopathy. Acquired data concerning this rare pathology of the CNS are reported as well as those of more doubtful scientific validity. The behavior of the neuro-psychic sphere and the symptomatology deriving from both deficit and excess of Al, As, Mg, Cr, Mn, Se, etc. are subject to special attention. The result of these changes is a complex of syndromes that are difficult to identify, also because uremia is beset by a large number of complications which more or less directly involve the central and peripheral nervous system.
7789083
[Treatment of chronic obliterative arteriopathy of the legs in the second Fontaine's stage. Personal experience with a buflomedil-pentoxifylline-defibrotide combination].
The authors provide evidence for the efficacy of the buflomedil-pentoxifylline-defibrotide combination for treatment of lower limb chronic obstructive arterial disease, Fontain stage II. Improvement of walking autonomy obtained with these agents ranged from 50 to 100% in 29 of 36 patients (relative frequency = 0.80).
7789084
[C0Q10 in the prevention and treatment of primary osteoporosis. Preliminary data].
Preliminary data are reported of an as yet uncompleted clinical study aimed at evaluating the therapeutic efficacy of C0Q10 for primary osteoporosis. In spite of the small number of subjects treated (only 5) the results obtained are evidence of the efficacy of this agent which had never before been used in the therapy of osteoporosis. The possible mechanisms of action C0Q10 are discussed in the light of an original interpretation of the etiopathogenesis of this very complex bone disease. Details of the study will be reported once the trial has been completed.
7789082
[Lamotrigine: first experience in Italy].
LTG, lamotrigine is a new antiepileptic agent chemically unrelated to any established drugs in use. The safety and the efficacy of LTG (564.5 +/- 74.4) mg/day was evaluated as add-on therapy (plus CBZ) in a placebo controlled study of 34 patients with refractory partial complex and/or partial secondary generalized seizures. The incidence of adverse effects of the drug is low and the unwanted effects are reversible. The long half-life and lack of effect on other AEDs will render LTG an easily dosable addiction to a patient's existing regimen. Reduction in the total number seizures was recorded in 61.4% of patients. We conclude that LTG is an effective AED for treatment of therapy-resistant partial seizure.
7789081
[The use of colchicine in the treatment of alcoholic liver fibrosis in the elderly. Report of 80 cases].
Having briefly analyzed the metabolism of ethanol in elderly subjects and the evidence of great resistance of the senile liver to alcohol-induced damage, the Author describes histological, clinical, biohumoral features of fibrosis and the necessary therapeutic measures. Eighty clinical cases of hepatic fibrosis are also illustrated, studied and observed during five years.
7789079
[Toxicology of reproduction and development. Pregnancy and periods of risks from drugs].
The authors discuss the possibilities of drug interference with the reproductive system and especially during various stages of pregnancy: from the sequence of neurochemical events that condition the release of pituitary gonadotrophines at the level of the central nervous system to late events that may occur during development. After listing the periods of risk, drug-induced changes in the conceptus are illustrated on the basis of data registered in the literature. In this context, it is stressed that the dysmorphogenic effect is limited to the period of differentiation and organogenesis whereas it is becoming more and more obvious that drugs may also have variable effects on other stages of pregnancy where frequently they have specific pharmacodynamic actions on the fetus. The knowledge of these effects may be useful in order to avoid untoward actions on pregnancy or on embryo, fetus, neonate or postnatal development, but may also create a basis for in utero drug treatments of fetal pathologies.
7789080
[Cystic fibrosis of the pancreas. Historical notes, sweat test, and neonatal screening].
Chronologic milestones in cystic fibrosis (CF) are reported. The value of the sweat test and the most recent advances on neonatal CF screening are described.
7789077
Candida chorioretinitis in meningococcal meningitis.
A case of Candida chorioretinitis in a patient suffering from meningococcal meningitis, admitted to the Infectious Disease Department of Frosinone Hospital, Italy, is reported. Five days after the onset of meningitis during antibiotic and cortisone treatment the patient experienced oropharyngeal candidiasis, ocular pain and blurring of vision; two days later positive scotoma appeared. Ophthalmoscopic examination revealed probable Candida chorioretinitis. Treatment with intravenous fluconazole at high doses was employed with complete recovery of the right eye, while visual acuity of the left eye was 2/10. The use of long-term fluconazole at the doses reported, commonly employed in the treatment of systemic mycoses, improves prognosis.
7789076
[Individual arterial pressure variability in newborn infants, adults, and the elderly].
The complexity of the cardiovascular function is related to a wide interindividual variability (VA) that changes with age. The aim of our study was to investigate the spontaneous blood pressure (BP) VA in 3 groups of 20 healthy subjects (S) each, 10 M and 10 F: Group I newborns 24 hours old; Group II 30-40 yrs; Group III 70-80 yrs. Each S underwent BP monitoring in a comfortable condition for 15'. Our data show an increase, with age, of both the average systolic and diastolic BP, paralleled by a simultaneous decrease of their standard deviations. Furthermore, the three distributions show a reasonably gaussian behaviour (maximum absolute value of the skewness was 0.21). These results emphasize the age-dependent reduction in functional flexibility of the cardiovascular system. A major pool of subjects is required to confirm our preliminary data.
7789073
[Diphosphonates in the treatment of osteoporosis and in the prevention of associated fractures].
Diphosphonates are capable to increase vertebral bone mineral mass in postmenopausal osteoporosis. Because the risk of fractures is related to the reduction of bone mass, the positive effect of diphosphonates most probably produced a decrease in fracture rate. At present these drugs represent a rational option for the treatment of postmenopausal osteoporosis.
7789074
[High resolution computerized tomography in cystic fibrosis. Clinico-radiologic correlations in 25 patients].
Twenty five patients with a clinical and radiological diagnosis of cystic fibrosis underwent high resolution Computed Tomography (HRCT) with the aim to study pulmonary parenchymal localization of disease. Both patients with initial pulmonary alterations and patients in a more advanced phase of the disease were studied. HRCT proved an excellent method for detecting very early lesions such as bronchiolar ectasia and bronchiolar obstruction by mucous accumulation. Moreover, HRCT proved to be very useful in detecting centrolobular and panlobular parenchymal lesions, with diagnostic information on axial and peripheral interlobular connective tissue. HRCT provided a better spatial definition of bronchiectasia and subpleural air if compared to conventional radiology. It also allowed for correct diagnosis of pneumothorax and detection of pleural fibrosis as a result of iatrogenic complications.
7789072
[Role of polychemoembolization in the treatment of primary and secondary tumors of the liver].
Unresectable primary hepatocellular carcinoma (HC) and liver metastases (LM) of abdominal tumors (AT) in progression after systemic chemotherapy (CT) have a poor prognosis and few therapeutic options. From 12/91 to 10/93 we treated 20 patients (PTS) 11 men and 9 women, with HC (10) and AT (10) with the following PCE: percutaneous placement of intraarterial hepatic catheter, superselective embolization with lipiodol (5 cc), infusion, mixed with lipiodol, of epirubicine 40 mg/m2, 5-fluorouracil 700 mg/m2, mitomycin-C 10 mg/m2 in 30'. After infusion, the arterial tree was embolized with Ivalon until an almost complete slowing of arterial blood-flow, every 5-6 weeks (W). After a median follow-up of 28 W a total of 35 courses had been administered to 20 PTS. Median (M) age was 69 years. M PS was 2. Okuda stage in HC PTS: 1 stage I, 9 stage II. in 10 HC PTS, positive for hepatitis B virus, CT and b-IFN had failed, while 10 AT PTS (5 colorectal, 2 gastric, 1 uterine, 1 larynx, 1 choledochus) had progressed, after, at least, 2 CT regimens, and had only LM. Median time from the diagnosis of LM in AT PTS was 32 W (12-68). liver enzyme elevation and LDH elevation were 3 times baseline values, 4 PTS had fever for 6 days, 3 PTS had ileus for 3 days. No myelosuppression was observed. M alpha-fetoprotein value decreased from 468 ng/ml, to 56 ng/ml after PCE.(ABSTRACT TRUNCATED AT 250 WORDS)
7789067
Cauda equina syndrome in ankylosing spondylitis: a case report and review of the literature.
The cauda equina syndrome (CES) is an infrequently recognised and poorly understood complication of ankylosing spondylitis (AS). We report a case of CES with enlarged caudal sac and multiple posterior arachnoid diverticula eroding the laminae and spinous processes of the lumbosacral vertebrae in a patient with long-standing AS. The diagnosis was established using computerised tomography (CT) and magnetic resonance imaging (MRI).
7789066
Asplenism and systemic lupus erythematosus.
Although functional hyposplenism, secondary to Fc-receptor blockage by circulating immune complexes saturation, has been described in systemic lupus erythematosus (SLE), only few cases of complete asplenism have been reported. We observed a 60-year-old woman with congenital asplenism who presented with active SLE. The course and the clinical characteristics of such patients are reviewed and the relationship between the asplenic state and initiation and severity of SLE are discussed. These patients are at high risk for fatal pneumococcemia and pneumococcal vaccine is recommended even if long term results are still conflicting.
7789065
Adult polyomyositis/dermatomyositis associated with acute myeloid leukemia. A case report.
Reports of PM/DM associated with haematologic disorders are rare. We describe a 62-year-old man suffering from PM/DM who developed acute myeloid leukemia. The possible paraneoplastic nature of PM/DM in this patient is discussed.
7789064
Campylobacter jejuni arthritis in secondary amyloidosis.
We describe a case of infectious arthritis caused by C. jejuni which developed after C. jejuni enteritis in a patient with rheumatoid arthritis and hypogammaglobulinaemia. Extraintestinal infections of this enteropathogen are rare, but in patients with hypogammaglobulinaemia C. jejuni bacteriaemia is relatively common. The present patient suffered from hypogammaglobulinaemia due to a nephrotic syndrome in secondary amyloidosis. C. jejuni infection must be considered in patients with hypogammaglobulinaemia and arthritis.
7789063
A case of Werner's syndrome associated with systemic lupus erythematosus.
The case of a 40-year-old woman with Werner's syndrome associated with systemic lupus erythematosus (SLE) is reported. The patient exhibited short stature, slender extremities, thinned hair, high-pitched voice, cataracts, ulceration of the fingers, and mental retardation. Malar erythema, photosensitivity, and proteinuria had been noted since age 34. The serum contained high titers of antibodies to dsDNA, Sm, nRNP, and SS-A/Ro. The simultaneous presence of Werner's syndrome and SLE could be a coincidental occurrence of the two diseases, although it might be due to an abnormality in replication or degeneration of DNA leading to the development of both diseases.
7789061
Anticardiolipin antibodies in the polymyalgia rheumatica-temporal arteritis syndromes.
A series of seven patients with the polymyalgia rheumatica-temporal arteritis (PMR-TA) complex is presented, each of whom during the clinical course demonstrated the presence of anticardiolipin antibodies (ACLs). Presenting symptoms consisted of proximal myalgias and stiffness characteristic of PMR in five patients and of visual symptoms and headache suspicious for TA in two patients. Two of the five PMR patients later developed jaw claudication characteristic of TA. Six of the seven cases demonstrated clinical evidence of a vasculopathic process such as a cerebrovascular infarct or a vasculitic syndrome. Previous studies have suggested an association between ACLs and PMR-TA, and this series of patients appears to provide more supporting evidence. Even patients who only manifested PMR symptoms without suggestion of accompanying TA developed vascular complications. An increasing range of symptoms have been recognized in association with ACLs, and the vasculitic syndromes of PMR-TA should be included as a possible association. While this series together with previous studies may suggest that the presence of ACLs in patients with PMR-TA symptoms may serve as a marker for the development of vascular complications, larger longitudinal studies will be necessary in the future.
7789062
Cogan's syndrome: a new possible complication of antiphospholipid antibodies?
A 55-year-old woman with a six-year history of Sjögren's syndrome (SS) and the positivity of IgG and IgM antiphospholipid antibodies (aPL) developed a sudden onset of sensorineural hearing loss associated with vertigo. This suggested the presence of an atypical Cogan's syndrome (CS), which might be a focal, neurological complication of aPL.
7789060
Long-term performance in vitro and in vivo of dual-energy X-ray absorptiometry.
Dual-energy X-ray absorptiometry (DXA) is actually considered as one of the most appropriate techniques for measuring bone mineral content (BMC) and bone mineral density (BMD). An anthropomorphic phantom and a 25-year-old girl were repeatedly measured, 160 times and 50 times respectively, over an 18-month period to investigate performance in vitro and in vivo of a commercial DXA equipment (HOLOGIC QDR 1000). DXA is a highly accurate technique, the BMC and BMD determinations only overestimated the exact value of the phantom by 0.20% and 0.51% respectively. In vivo long-term (18 months) reproducibility of BMD of the spine is characterized by an interassay coefficient of variation (CVt) of 0.8% while, for the different regions of interest of the hip, BMD CVt varies from 1.1% (total zone) to 5.3% (Ward's triangle). In the subject tested, BMD sensitivity for changes of 2.2% at the lumbar spine and 3% at the hip were recorded.
7789059
Risk factors for the development of acute disseminated intravascular coagulation in patients with systemic lupus erythematosus.
Since acute disseminated intravascular coagulation (DIC) often contributes to a fatal outcome in patients with systemic lupus erythematosus (SLE), prediction of its development is important to prevent the occurrence of such an event. To analyze the risk factor(s) contributing to the development of acute DIC in SLE, we carried out a retrospective study of a series of 129 SLE patients, eight of whom developed DIC during the course of this disease, to assess which of the easily assessable parameters, present at the time of first medical examination, were of predictive significance. The important individual variables, determined by univariate analysis, were male sex, leukopenia, and infection. These factors were placed in a multivariate logistic regression model, and only one factor, infection at first medical examination, was found to have predictive significance for the development of acute DIC in SLE patients. The prevention and control of infection in SLE patients might have implications for preventing the development of acute DIC.
7789058
Characterization of systemic lupus erythematosus in patients in U.A.E.
Twenty-eight SLE patients (Arabs and Asians) in the UAE were studied in this report. The F:M ratio was markedly high; 27:1 in the group as a whole and 21:1 among Arabs. Local patients (Emirians) developed the disease at an earlier age compared to their expatriate Arab compatriots. Arthropathy occurred in 86% and nephropathy in 43% of cases. Next in frequency were leucopenia, mucocutaneous manifestations and serositis. Apart from lupus headache, the other neuro-psychiatric LE were uncommon or not encountered. Anti-cardiolipin syndrome, Sneddon's syndrome, shrunken lung syndrome, sicca complex, thyrotoxicosis and myasthenia gravis were also present in this small group of patients. Their presence reflects the marked heterogeneity displayed by the disease irrespective of the number of cases involved. An unusually high prevalence of anti ds (DNA) antibodies (92.5%) as compared to ANF (82.5%) was detected (P = NS). Anti-Sm antibody occurred in 30% of cases particularly in those patients with lymphadenopathy and fever. There was a relative paucity in the prevalence of anti RNP, Ro and La antibodies in this group. Differences with and similarities to previous reports concerning other populations are also presented.
7789057
Multidisciplinary approach to fibromyalgia. A pilot study.
The aim of the study was to instruct a group of fibromyalgia patients how to solve problems related to activities of daily life. Sixteen female fibromyalgia patients completed a ten week multidisciplinary program, consisting of a cognitive and an exercise part. After ten weeks a reduction in general pain intensity (p < 0.05) was found. At six months follow-up sensory (somatic) pain intensity was reduced compared to baseline recordings (p = 0.05). All patients had made adjustments to their everyday life after ten weeks. Eight patients reported that they regularly practised relaxation techniques, and seven patients had undertaken dietary changes. Thus, the study shows that adjustment of activities in daily living may reduce pain in patients with fibromyalgia. Controlled studies are needed in the future.
7789056
Left ventricular wall motion abnormalities in 80 patients with systemic sclerosis.
Segmental analysis of left ventricular wall motion was performed in 80 patients with systemic sclerosis by echocardiography. Half of the cases showed normal wall motion. Eighteen of the 57 patients with limited cutaneous systemic sclerosis (31.6%) exhibited hypokinetic wall motion abnormalities, while five of the 23 cases with diffuse cutaneous systemic sclerosis (21.7%) had similar findings. The three cases showing akinesis also belonged to the limited scleroderma subgroup. Our findings show that hypokinetic wall motion abnormalities can be detected in a remarkably high proportion of cases with limited cutaneous systemic sclerosis.
7789055
Effect of oestrogen replacement on bone metabolism and cytokines in surgical menopause.
The effect of oestrogen replacement on bone metabolism and serum cytokine levels (IL1,IL6) was investigated in surgical menopause. The study included 40 female subjects; 10 healthy premenopausal women underwent total hysterectomy without oophorectomy. Thirty healthy premenopausal women underwent total hysterectomy with bilateral oophorectomy. They were randomly divided into 3 groups of 10 subjects. The first group received natural estradiol (0.05 mg/day) for 6 months; the second group received natural estradiol (0.05 mg/day) and medroxyprogesteron acetate (10 mg/day) for 6 months, the third group received no therapy. Calcium-phosphorus metabolism, inflammatory indices, serum IL1 and IL6 levels were tested before and 6 months after surgery in all patients. A significant increase in serum alkaline phosphatase, urinary cross-links, serum PTH and IL1-IL6 was observed in the untreated women with total hysterectomy and oophorectomy. No significant variation in any of the parameters considered was observed in patients treated with oestrogen, in those treated with oestrogens and medroxyprogesteron nor in patients without oophorectomy. These results in human "in vivo" confirm that ovarian steroids play an important role in regulating the production of IL1 and IL6 which could regulate bone resorption.
7789054
The diagnosis value of beta 2-microglobulin and immunoglobulins in primary Sjögren's syndrome.
Salivary and serum concentrations of beta 2-microglobulin, salivary levels of the immunoglobulins, and salivary flow (as measured by a gravimetric method) were assessed in 34 patients and 11 controls. Of the 34 study patients, 16 had a primary form of Sjögren's syndrome (pSS) and 18 had sicca syndrome. The salivary and serum concentrations of beta 2-microglobulin and salivary levels of IgA and IgG were much higher in the patients with pSS than in controls or those with sicca syndrome (p < 0.001). Similarly, the salivary IgM levels of patients with pSS were higher (although at a lower degree of statistical significance) as compared to those of patients with sicca syndrome (p < 0.01) or controls (p < 0.05). No correlation was observed among the salivary flow and the salivary IgG and IgM levels, while there was a negative relationship (p < 0.01 with salivary IgA levels in all 45 patients considered as a whole. In 12 patients with pSS, the coefficient of correlation between the salivary gland biopsy focus score and the salivary (but not serum) concentration of beta 2-microglobulin was highly significant (p < 0.001). A similar relationship was observed with the IgG (p < 0.001) and IgM (p < 0.05) levels, but not IgA. In the diagnosis of pSS, the salivary IgA level demonstrates high sensitivity and low specificity. In contrast, serum and salivary concentrations of beta 2-microglobulin, salivary IgG, and to a lesser degree, salivary IgM have high specificity and positive predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)
7789053
Medical, physical and psychological status related to early rheumatoid arthritis.
As part of an international European research project, a longitudinal study was started by the end of 1990 in the northern part of The Netherlands. The study concentrated on recently diagnosed RA patients (N = 292), i.e., incident cases up to four years. According to the duration of the disease, five groups of patients had been formed. The early influence of rheumatoid arthritis on medical parameters, on functional status, on physical condition and on psychological well-being was evaluated. From the results, an overall statistically significant pattern related to the duration of the disease could not be distinguished. However, patients recently diagnosed did face activity restrictions, a decline in physical condition and social functioning. On medical parameters this deterioration is less profound. Furthermore, across and within the five patient groups, it seems that males and females respond differently to the influence of early RA. Based on cross-sectional data from the five onset cohorts, the present findings do not significantly suggest a steady worsening in medical, physical and psychological condition.
7789052
Sensitivity versus specificity of phonoarthrography as an indicator for cartilage degeneration.
In an attempt to update the idea of recording knee sounds, 400 osteoarthritic (OA) knees, 100 knees from a young age group (18-31 years) and 100 knees from an age-matching group (45-60 years) were recorded by a computerized device using a special program that enabled the conversion of sounds--recorded in a fixed lapse of time--to waves which were then analysed in terms of frequency/second and average amplitude. Radiological grading was done for all groups in order to compare both parameters. Reproducibility of the recordings for each knee was confirmed statistically. Phonoarthrography was found to be 100% sensitive for radiological changes and for clinically felt crepitus, simultaneously diagnosing early OA in 32.5% of subjects with no radiological changes and in 7.5% of subjects with no clinically felt crepitus. From the work it can be deduced that computerized phonoarthrography can diagnose early cases of OA and is excellent for assessing and following up cases. It may be regarded as an indicator for cartilage degeneration.
7789051
n-Butyrate mediation of ganglioside expression of human and murine cancer cells demonstrates relative cell specificity.
1. n-Butyrate, a short chain fatty acid produced by colonic fermentation, induces differentiation in human neoplastic cell lines, and reduces expression in vitro of a sialyltransferase that glycosylates N-linked glycoproteins in hepatoblastoma cells. Gangliosides are amphipathic, sialylated glycosphingolipids that undergo profound changes in many transformed cells and may protect neoplastic cells from host immune surveillance. Colonic mucosal cells are exposed to luminal short-chain fatty acid concentrations of up to 80 mmol/l, and there is some evidence that short-chain fatty acids may alter ganglioside expression in colon cancer cells. 2. Because of the importance of gangliosides in cancer pathogenesis, we investigated the effects of n-butyrate on ganglioside expression of colonic (human and murine) and non-colonic cancer cells. 3. Three separate colon cancer cell lines (LS174T, T84 and MCA-38), when butyrate treated, demonstrated striking amplification of specific individual gangliosides. However, the total lipid-bound sialic acid content of gangliosides of butyrate-treated LS174T cells diminished. In contrast to earlier reports, n-butyrate did not mediate expression of all gangliosides and specifically did not mediate expression of GM3. This effect persisted even after removal of butyrate. 4. In contrast, exposure of extracolonic cells to butyrate, including cervical cancer (HeLa) and laryngeal cancer (HEp-2) cell lines in this study and hepatoblastoma cells (Hep G2) in our previous work, caused no detectable changes in ganglioside expression. 5. In conclusion, our results indicate a relative tissue specificity of butyrate-mediated alterations in ganglioside expression that is not universal but is limited to specific gangliosides.
7789050
Demonstration of hypomethylation of proteins in the brain of pigs (but not in rats) associated with chronic vitamin B12 inactivation.
1. Pigs treated with nitrous oxide for periods of 1, 2 and 4 months demonstrated markedly reduced levels of methionine synthase and concomitant reduction in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, the methylation ratio, at all time intervals. 2. Both 'O' and 'N' methylations were significantly reduced in pigs after 4 months in nitrous oxide but not after shorter periods. 3. Hypomethylation correlated with the development of clinical ataxia, but was absent when the pigs were clinically normal. It also only occurred when the S-adenosylmethionine level fell. 4. Rats maintained in nitrous oxide for 4 months showed a marked reduction of methionine synthase but no reduction in the methylation ratio or in brain hypomethylation. None of the rats became clinically ataxic. 5. Using an exogenous protein as a methyl group acceptor, it was demonstrated in an in vitro assay that the methyltransferase enzymes responsible for brain 'O' and 'N' methylation were not affected per se by nitrous oxide treatment. 6. It is concluded that reduction of the methylation ratio in the brain of pigs as a consequence of methionine synthase inhibition leads to brain hypomethylation. This hypomethylation could affect critical components of nerve tissue, inducing the vacuolar myelopathic changes seen in the spinal cord of these animals, which mimic those of subacute combined degeneration in man.
7789049
Relationship between plasma volume, carotid baroreceptor sensitivity and orthostatic tolerance.
1. Studies were carried out on 43 otherwise healthy patients referred for investigation for attacks of syncope of unknown cause and on six healthy volunteers. 2. Plasma volume was determined by Evans Blue dye dilution and blood volume was estimated using haematocrit. Carotid baroreceptor sensitivity was determined from the changes in pulse interval in response to subatmospheric pressures applied to the neck overlying the carotid sinuses, and orthostatic tolerance was assessed as the time to presyncope in a test of head-up tilt, followed by the addition of graded lower body suction. 3. Eight patients and one volunteer fainted during head-up tilt alone, 23 patients and two volunteers fainted during tilt with lower body suction at -20 mmHg and 12 patients and three volunteers either fainted during suction at -40 mmHg or tolerated the entire procedure. 4. Although plasma and blood volumes were higher in males than females, the values normalized for either body weight or for calculated lean body mass were not different between male and female patients and asymptomatic volunteers. The subjects showing the greatest resistance to syncope were found to have significantly larger plasma and blood volumes (P < 0.0001) and significantly smaller baroreceptor sensitivities (P < 0.0002) than those who fainted earlier.(ABSTRACT TRUNCATED AT 250 WORDS)
7789048
Is voluntary control of breathing impaired in patients with chronic obstructive pulmonary disease?
1. To assess whether voluntary control of breathing is impaired in patients with chronic obstructive pulmonary disease, a group of such patients performed a tracking task, requiring volitional control of respiratory muscles. 2. Eight patients (mean age 60 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 31%) took part in the study. Five of the seven patients in whom blood gas measurements were made were mildly hypoxaemic (PaO2 = 53-71 mmHg), and one of these was hypercapnic (PaCO2 = 55 mmHg). Each subject performed a compensatory ventilatory tracking task using a tracking system which comprised a fixed target displayed on a monitor screen and a cursor moving in a line bisecting the target. The position of the cursor was perturbed by a forcing function and patients were required to keep the cursor on the target by breathing in and out of a spirometer. 3. To allow for any non-specific deficiency in motor control, patients performed a similar manual tracking task, using their dominant arm to move a joystick. As a control group, 11 healthy subjects (mean age 58 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 77%) underwent an identical experimental protocol. 4. Motor control performances were measured in terms of the error between the target position and the subject's positioning of the cursor. Indices of performance were the root mean square of the error and the averages of the zero errors (i.e. end expiration/arm movement towards the trunk) and the peak errors (i.e. end inspiration/arm movement from the trunk).(ABSTRACT TRUNCATED AT 250 WORDS)
7789047
Effects of inhaled nebulized morphine on ventilation and breathlessness during exercise in healthy man.
1. Nebulized inhaled morphine has been reported to increase exercise endurance in patients with chronic lung disease and to relieve dyspnoea in patients with malignant disease. Potential mechanisms include a central effect occurring after systemic drug absorption or a local action mediated by receptors in the lung. 2. The ventilatory effects of nebulized morphine (10 and 25 mg) were therefore compared with those of intravenous morphine (1.0 and 2.5 mg) and placebo in a double-blind study involving 12 young healthy males. Submaximal cycle ergometry with respiratory gas analysis was performed 15 min after drug administration and breathlessness assessed using a linear visual analogue scale. 3. Neither dose of inhaled morphine had statistically significant effects on spirometry, heart rate, ventilation, respiratory gases or breathlessness at any level of exercise. The slopes and intercepts of the lines relating ventilation to breathlessness were also unaffected. 4. Intravenous morphine 2.5 mg reduced breathlessness slightly at the highest equivalent workload [mean (least significant range) 33 mm (26-40 mm)] compared with placebo [41 mm (34-48 mm), P < 0.05] but had no other significant effects. 5. These results do not support the hypothesis that intrapulmonary opiate receptors modulate the sensation of breathlessness in healthy man. The possibility that inhaled morphine may affect breathlessness caused by other factors, such as disease, has not been excluded.
7789046
Sympathoadrenal responses to bronchoconstriction in asthma: an invasive and kinetic study of plasma catecholamines.
1. Bronchoconstriction does not seem to be a stimulus for sympathoadrenal activation, as judged by venous plasma concentrations of noradrenaline, adrenaline or neuropeptide Y-like immunoreactivity. However, venous measurements have methodological drawbacks. In the present study arterial and mixed venous (pulmonary arterial) levels of these variables were determined before and after histamine-induced bronchoconstriction in non-medicated asthmatic subjects. In addition, noradrenaline kinetics in plasma (isotope dilution) and the pulmonary overflows of noradrenaline and neuropeptide Y-like immunoreactivity were determined. 2. Histamine inhalation induced bronchoconstriction; forced expiratory volume in ls decreased by 38.7% +/- 4.1% (SE) and arterial PO2 by 3.0 +/- 0.9 kPa. This acute bronchoconstriction induced significant elevations of arterial and mixed venous plasma noradrenaline from < or = 1.18 nmol/l to > or = 1.40 nmol/l. The clearance of NA from plasma increased marginally. Thus, the arterial plasma NA response was due to increased spillover of noradrenaline to plasma (from 1.80 +/- 0.18 to 2.52 +/- 0.36 mmol min-1/m2 at maximal bronchoconstriction, with a subsequent further increase). There were no elevations of adrenaline or neuropeptide Y-like immunoreactivity in arterial plasma. 3. No sympathetic activation could be demonstrated in the lungs (pulmonary noradrenaline or neuropeptide Y-like immunoreactivity overflow), and no alterations in pulmonary vascular resistance or cardiac output were observed. Neither arterial nor mixed venous plasma concentrations of adrenaline were influenced by bronchoconstriction. 4. Acute bronchoconstriction thus leads to peripheral sympathetic activation (possibly due to the increased work of breathing) which does not involve the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
7789045
Investigation of the mechanism of beta 2-agonist-induced activation of the renin-angiotensin system.
1. We have previously described activation of the renin-angiotensin system in asthma, and also by high-dose nebulized beta 2-agonists. In this study we sought to determine the mechanism responsible. 2. The influence of the angiotensin-converting enzyme inhibitor, lisinopril, on the response of the renin-angiotensin system and serum potassium to nebulized salbutamol was investigated in a randomized, double-blind, crossover study in eight healthy volunteers using a factorial block design. On study days, subjects received lisinopril 20 mg orally or identical placebo tablets followed 3 h later by nebulized salbutamol or placebo inhalation; plasma renin, angiotensin II, serum angiotensin-converting enzyme and potassium were measured at intervals for 120 min after inhalation. 3. Following salbutamol, plasma renin and angiotensin II concentrations were increased significantly compared with placebo [mean (SEM) plasma renin of 61.7 (15.6) mu-units/ml and angiotensin II of 17.7 (5.4) pg/mol 15 min after salbutamol, P < 0.05 versus placebo]. Baseline plasma renin concentrations were increased [160.1 (20.6) mu-units/ml] and baseline plasma angiotensin II concentrations were reduced [1.4 (0.1) pg/ml] by lisinopril, P < 0.05 versus placebo in each case. Inhibition of angiotensin-converting enzyme completely inhibited this salbutamol-induced rise in plasma angiotensin II [mean (SEM) plasma angiotensin II of 1.5 (0.4) pg/ml 15 min after salbutamol, P < 0.05 versus placebo] but had no effect on the changes in plasma renin concentrations after the beta 2-agonist [mean (SEM) plasma renin of 198.4 (18.9) mu-units/ml 15 min after salbutamol].(ABSTRACT TRUNCATED AT 250 WORDS)
7789044
Comparison of intraperitoneal and subcutaneous insulin administration on insulin sensitivity and serum lipids in type I diabetic patients on continuous ambulatory peritoneal dialysis treatment.
1. The metabolic effects of intraperitoneal and subcutaneous insulin delivery were compared in a cross-over manner in six C-peptide-negative diabetic patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Each treatment period lasted at least 3 months. Hyperinsulinaemic euglycaemic clamp was performed and glucose turnover assessed using [3-(3)H]glucose as a tracer. 2. During intraperitoneal delivery the daily insulin dose was 2.4 times higher than during subcutaneous administration and glycaemic control was significantly better (HbA1c 7.63% +/- 0.46% and 9.52% +/- 0.51% during intraperitoneal and subcutaneous insulin respectively, P < 0.01). The number of hypoglycaemic episodes was lower during intraperitoneal insulin than during subcutaneous therapy. 3. Intraperitoneal insulin resulted in an enhanced glucose disposal rate (P < 0.01) and reduced fasting hepatic glucose production (P < 0.01). High-density lipoprotein-cholesterol decreased and the ratio of low-density lipoprotein/high-density lipoprotein-cholesterol increased significantly (P < 0.05) during intraperitoneal insulin delivery. 4. The results suggest that intraperitoneal insulin, while resulting in better glycaemic control and improved insulin sensitivity than subcutaneous insulin, increases serum triacylglycerol and total cholesterol and reduces high-density lipoprotein-cholesterol, possibly via a direct effect on the liver.
7789043
Selective enhancement of alpha 2-adrenoceptor-mediated vasoconstriction in insulin-dependent diabetic patients with microalbuminuria.
1. Microalbuminuria, the earliest clinical marker of microvascular disease, is an important predictor of early death in insulin-dependent diabetes, and abnormal vascular reactivity may contribute to microvascular disease. We have previously found that vasoconstrictive responses to noradrenaline are exaggerated in insulin-dependent diabetic patients with microalbuminuria as compared with both normoalbuminuric insulin-dependent diabetic patients and non-diabetic control subjects. 2. To determine whether this is due to increased sensitivity at alpha 1- or alpha 2-adrenergic receptors, we compared vascular responses to the alpha 1-adrenergic agonist phenylephrine and the alpha 2-adrenergic agonist clonidine. 3. We studied 15 insulin-dependent diabetic patients with microalbuminuria, 15 insulin-dependent diabetic patients with normal urinary albumin excretion and 14 non-diabetic subjects. Vascular constrictive responses were measured in dorsal hand veins. 4. No difference in vasoreactivity to phenylephrine was demonstrated between any of the three groups. However, enhanced vascular responsitivity to clonidine at infusion rates of 16-2048 ng/min (analysis of variance, P < 0.001) was found in insulin-dependent diabetic patients with microalbuminuria as compared with both non-diabetic control subjects and normoalbuminuric insulin-dependent diabetic patients. There were no significant differences between the dose-response curves of the diabetic group with normal urinary albumin excretion and the non-diabetic group. 5. Vasoconstriction mediated by alpha 2-adrenergic receptors is therefore enhanced in normotensive insulin-dependent diabetic patients with microalbuminuria. If also present at the level of the peripheral resistance arterioles or the efferent glomerular arterioles, this could lead to systemic and intraglomerular hypertension, factors which may contribute to the development of diabetic nephropathy.
7789042
Participation of endogenous atrial natriuretic peptide in the regulation of urinary protein excretion in experimental diabetic rats.
1. In order to determine whether atrial natriuretic peptide might play a role in the development of glomerular hyperfiltration in diabetes mellitus, we examined the effects of administration of glucose, albumin, atrial natriuretic peptide and an atrial natriuretic peptide receptor antagonist on renal function in rats with streptozotocin-induced diabetes mellitus and vehicle-treated control rats. 2. Four weeks after treatment, rats with diabetes mellitus had a higher mean plasma atrial natriuretic peptide concentration than controls [152 +/- 5 (SE) versus 115 +/- 6 pg/ml, P < 0.01] and a higher glomerular filtration rate (3.3 +/- 0.1 versus 2.7 +/- 0.2 ml min-1 kg-1, P < 0.05). 3. Infusion of albumin or glucose caused significant increases in atrial pressure, plasma atrial natriuretic peptide concentration and urinary excretion of sodium and protein in both groups of rats. 4. Increasing plasma atrial natriuretic peptide concentration by 60% via atrial natriuretic peptide infusion increased urinary excretion of sodium and protein in both control rats and rats with diabetic mellitus. 5. Administration of the atrial natriuretic peptide receptor antagonist HS-142-1 to diabetic rats resulted in diminished urinary excretion of both sodium (-61 +/- 14%, P < 0.02) and protein (-51 +/- 17%, P < 0.05). These changes were associated with a significant reduction in glomerular filtration rate (-32 +/- 11%, P < 0.05) and urinary cGMP excretion (-40 +/- 14%, P < 0.05). No significant effects of HS-42-1 on renal function were observed in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
7789041
Metabolic acidosis is a potent stimulus for cellular inorganic phosphate generation in uraemia.
1. During metabolic acidosis, significant fluxes of inorganic phosphate (Pi) may occur from cellular to extracellular fluid. In this study Pi was measured in erythrocytes of uraemic patients before and after haemodialysis and was related to their plasma pH (acidosis), plasma Pi (hyperphosphataemia) and cellular organic phosphate concentrations. 2. Before dialysis, the ratio of cellular to extracellular Pi concentration correlated inversely with plasma pH, increasing 2.5-fold as pH fell from 7.4 to 7.2. 3. An increase in cellular Pi similar to that seen in the patients was observed within 90 min of adding acid to normal erythrocytes in vitro. 4. The total Pi content of the cell suspension increased 25% on decreasing plasma pH from 7.4 to 7.2, largely as a result of generation of Pi from 2,3-bisphosphoglycerate in the cells. This was accompanied by net efflux of Pi into plasma. 5. In addition, the increase in the steady-state cellular Pi concentration on adding a constant extracellular Pi load was 50% greater at pH 7.2 than at 7.4, implying that alterations in the regulation of the transmembrane Pi gradient also contribute to the rise in cellular Pi observed at low pH. 6. At normal plasma Pi concentration (1 mM), glycolytic flux (lactate production) was inhibited by 20% when pH was lowered from 7.4 to 7.2. However, this inhibition was blocked when cellular Pi was increased by adding Pi to the plasma in vitro. 7. Metabolic acidosis is therefore a potent stimulus for Pi generation in erythrocytes, and this Pi may serve to stimulate glycolysis which is normally inhibited by low pH.
7789040
Combined intestinal trefoil factor and epidermal growth factor is prophylactic against indomethacin-induced gastric damage in the rat.
1. The availability of recombinant epidermal growth factor provides a potentially exciting development for the treatment of gastrointestinal ulceration. However, because of its potent mitogenic activity, there is a need for strategies which reduce the dose required. Intestinal trefoil factor stimulates mucosal healing without increasing proliferation. Studies were undertaken to examine the biological effects of rat intestinal trefoil factor and/or human epidermal growth factor upon gastrointestinal epithelial cell functions pertinent to mucosal protection, using two wounding models. 2. The study of epithelial restitution in vitro demonstrated a marked synergistic effect on the rate of migration of the wound edge when intestinal trefoil factor was used in combination with epidermal growth factor. There was no increased cellular proliferation due to the addition of intestinal trefoil factor to the cells when given alone, or to the stimulatory effect of cells treated with epidermal growth factor. In the rat model of gastric ulceration, the presence of both epidermal growth factor and intestinal trefoil factor protected against the development of indomethacin-induced gastric lesions. 3. We conclude that combination therapy of epidermal growth factor with intestinal trefoil factor could provide a more potent, safer approach to the treatment of human gastrointestinal ulceration.
7789038
The influence of trans fatty acids on health: a report from the Danish Nutrition Council.
Trans fatty acids constitute 0-30% of the fat in Danish margarines, most in industry and bakery margarines and usually less in table margarine. The trans fatty acids make margarines more solid at room temperature and therefore provide an economical storage advantage. In British and U.S. reports from 1984-1989, the trans fatty acids were more or less acquitted of unhealthy effects. During the last 5-6 years, however, a series of new studies has been published regarding both the connection between the consumption of trans fatty acids and the occurrence of coronary heart disease and the impact on the lipoprotein level in plasma. Studies suggest that the consumption of trans fatty acids from margarine is equally, or perhaps more, responsible for the development of arteriosclerosis than saturated fatty acids. In addition, it is now clear that both the fetus and the breast-fed baby are exposed to trans fatty acids in relation to the mother's consumption. A couple of recent studies suggest a possible restrictive influence of the trans fatty acids on the weight of the fetus. The average consumption of trans fatty acids from margarine in Denmark in 1991 was approximately 2.5 g/day per person. For about 150,000 adult Danes, the consumption is assumed to be more than 5 g/day per person. On this basis, the Danish Nutrition Council recommend that the consumption of trans fatty acids is reduced as much as possible. This can be done by reducing the fat content in food and by reducing the trans fatty acid content in all Danish margarine products to 5% or less. Thereafter, the group of adult Danes, including pregnant and breast-feeding women, with a large consumption of margarine and margarine-containing products, will on average only consume 2 g of vegetable trans fatty acids/day. This corresponds to the consumption in the low-risk groups in the above-mentioned epidemiological studies. In addition, the Danish Nutrition Council encourage the producers of margarines to make products that can be marketed as 'free of trans fatty acids'.
7789032
Case report: a variant of the subclavian steal syndrome. Demonstration by duplex Doppler imaging.
The subclavian steal syndrome results from occlusion of the proximal subclavian or innominate artery which causes reversal of blood flow in the ipsilateral vertebral artery. We describe a case where a further occlusion of the ipsilateral common carotid artery (CCA) resulted in an intermittent reversal of flow in the ipsilateral external carotid artery (ECA), to siphon blood up the internal carotid artery (ICA) and down the ipsilateral vertebral artery.