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8043278
Ca2+ accumulations in dendrites of neocortical pyramidal neurons: an apical band and evidence for two functional compartments.
Apical dendrites constitute a prominent feature of the microcircuitry in the neocortex, yet their function is poorly understood. Using fura-2 imaging of layer 5 pyramidal neurons from slices of rat somatosensory cortex, we have investigated the Ca2+ influx into dendrites under intracellular, antidromic, synaptic, and receptor-agonist stimulation. We find three spatial patterns of Ca2+ accumulations: an apical band in the apical dendrite approximately 500 microns from the soma, an accumulation restricted to the basal dendrites, soma, and proximal apical dendrite, and a combination of both of these. We show that the apical band can be activated antidromically and synaptically and that, under blocked Na+ and K+ conductances, it generates Ca2+ spikes. Thus, the apical band may serve as a dendritic trigger zone for regenerative Ca2+ spikes or as a current amplifier for distal synaptic events. Our results suggest that the distal apical dendrite should be considered a separate functional compartment from the rest of the cell.
8043277
Reevaluation of Ca2+ channel types and their modulation in bullfrog sympathetic neurons.
With 90 mM Ba2+, the main Ca2+ current in frog sympathetic neurons peaks near +30 mV and is blocked by omega-conotoxin GVIA (omega-CgTx). It is modulated by norepinephrine (NE) in a voltage-dependent manner via a membrane-delimited mechanism. Surprisingly, a different current dominates at more negative voltages (-30 to +10 mV). That novel current is not sensitive to selective blockers of L- or N-type channels (respectively, dihydropyridines or omega-CgTx) and is inhibited weakly if at all by NE. It is selectively inactivated at -40 mV and is selectively blocked by Ni2+, whereas Cd2+ is slightly more potent against the main current. The novel current is associated with a 19 pS channel (0.6 pA at 0 mV). This channel may have been misidentified as the single-channel correlate of the whole-cell N-type Ca2+ current in some previous studies.
8043276
The low affinity NGF receptor, p75, can collaborate with each of the Trks to potentiate functional responses to the neurotrophins.
NGF and the other neurotrophins all bind to the low affinity NGF receptor (LNGFR). Although early studies suggested that the LNGFR was absolutely required for the formation of a functional neurotrophin receptor, current evidence indicates that the Trk family of receptor tyrosine kinases, in the absence of the LNGFR, can directly bind to and mediate responses to the neurotrophins. Here we describe a functional approach, in fibroblasts, designed to assay for the ability of the LNGFR to potentiate Trk-mediated responses to the neurotrophins. We report that although collaboration between the LNGFR and the Trks could be detected in this system, a truncated form of the LNGFR displayed a much more dramatic ability to interact functionally with each of the Trks, potentiating masked autocrine loops as well as responses to limiting amounts of exogenously provided neurotrophins.
8043275
Depolarization-transcription signals in skeletal muscle use calcium flux through L channels, but bypass the sarcoplasmic reticulum.
Membrane depolarization inactivates acetylcholine receptor (AChR) genes in skeletal muscle. We have studied this process in C2C12 cells, focusing on the role of calcium. Cytoplasmic calcium was monitored with fluo-3, and the activity of receptor genes was measured with a sensitive transcript elongation assay. Removal of extracellular calcium or blockage of L-type calcium channels disrupts signaling, even when release of calcium from the sarcoplasmic reticulum (SR) is not impeded, whereas L channel agonists induce signaling without membrane depolarization or release of calcium from intracellular stores. Activators of calcium release from the SR do not inhibit AChR genes, either in C2C12 or in chicken skeletal muscle in vivo. It appears that calcium ions do not act as messengers between sarcolemma and nucleus but target a sensor near their port of entry where they initiate a signal that bypasses the SR.
8043274
Developmental alteration in GABAA receptor structure and physiological properties in cultured cerebellar granule neurons.
Although we now have extensive knowledge about the GABAA receptor subunits determining benzodiazepine modulation of channel function, little is known about subunits influencing other modulatory sites on the GABAA receptor-chloride channel complex. We have identified a developmental change in subunit composition of the GABAA receptor in cultured cerebellar granule neurons that eliminates benzodiazepine-mediated enhancement of GABA responses and alters modulation by a substituted gamma-butyrolactone. Based on data from sequential PCR experiments, we mimicked the functional properties of early and mature receptors with heterologous expression of specific subunit combinations. This report describes one of the most extensive cell- and site-specific developmental changes for an ion channel seen to date.
8043273
Domain-specific activation of neuronal migration and neurite outgrowth-promoting activities of laminin.
The ECM glycoprotein laminin has profound and varied actions on neurons in vitro. Little is known about how laminin's multiple domains and receptor-binding sites interact in determining its overall effects. Here, it is shown that laminin's ability to promote migration of olfactory epithelium neuronal cells maps to distal long arm domain E8 and is mediated by alpha 6 beta 1 integrin. Surprisingly, treatment of laminin with antibodies against its short arms (domains E1' or P1') uncovered a new neuronal migration-promoting activity, mediated by a beta 1 integrin other than alpha 6 beta 1. Laminin treated with anti-short arm antibodies also promoted beta 1 integrin-dependent neurite outgrowth from late embryonic retinal neurons, which are normally unresponsive to laminin. These "antibody-induced" migration and neurite outgrowth activities mapped to laminin's distal long arm, far from the site(s) of antibody binding. Evidence is presented that the induced activities are not actually cryptic in laminin, but are suppressed by an activity that is located in laminin's P1' domain and that may be lacking in the laminin homolog merosin.
8043272
The involvement of the small GTP-binding protein Rab5a in neuronal endocytosis.
Rab5a is a small GTPase that regulates fusion of endocytic vesicles to early endosomes. We investigated whether Rab5a is involved in early endocytic traffic in both the axonal and the somatodendritic domains of polarized neurons. Using immunofluorescence, endogenous Rab5a was detected in axons and dendrites. Its localization in axons strongly overlapped that of the synaptic vesicle protein synaptophysin. Indeed, Rab5a co-immunoisolated with synaptophysin-containing vesicles, and antibodies against Rab5a labeled synaptic vesicle-like structures in nerve terminals. The functional association of Rab5a with dendritic and axonal early endosomes was assayed by electron microscopy after overexpression of wild-type and mutant Rab5a in cultured hippocampal neurons. This induced the formation of abnormal endosomes in both the somatodendritic and the axonal domains. These results show a role for Rab5a in axonal and dendritic endocytosis, and the presence of Rab5a on synaptic vesicles indicates that the axonal endosomes participate in the biogenesis of these vesicles.
8043271
Dystroglycan binds nerve and muscle agrin.
Neurally released agrin is thought to cluster acetylcholine receptors (AChRs) and other synaptic proteins in the postsynaptic membrane during synaptogenesis at the neuromuscular junction. We have examined the binding of nerve and muscle agrins, which have dramatically different abilities to cluster AChRs, to the membrane proteins of Torpedo electric organ and C2 myotubes. Both bound with approximately nanomolar affinity to a single component identified as alpha-dystroglycan: agrin binding was blocked by antibodies to alpha-dystroglycan, and agrin bound to purified alpha-dystroglycan. Dystroglycan was altered in two genetic variants of C2 muscle cells that fail to form spontaneous clusters of AChRs and that show a diminished response to agrin. Antibodies that blocked alpha-dystroglycan binding, however, failed to block the clustering of AChRs by neural agrin. Although alpha-dystroglycan is the major agrin-binding protein in Torpedo and myotube membranes, its physiological role is unclear.
8043269
The psychophysical power law and unilateral spatial neglect.
The relationship between objective measures and subjective experiences of sensory stimuli is described by a power law, psi = K phi beta, in which psi represents the psychological value and phi the physical value. The constant (K) and the exponent (beta) are empirically derived. This relationship is often assumed to correspond to properties of peripheral receptor sensory transduction. Patients with left-sided spatial neglect tend to bisect lines to the right of the objective midline. Line bisection bias was used as the dependent variable in how a patient with neglect and five normal subjects bisected lines of varying lengths. Analyzing these data as a power function accounted for over 99% of the variance in five different experimental conditions. The normal exponent matched the value expected from traditional psychophysical experiments of line length estimation, whereas the patient's exponent was diminished. The patient's data provide evidence for central nervous system participation in computations underlying psychophysical relationships. The notion that attentional and perceptual processes are closely linked was supported by the influence of attentional cuing on the power functions obtained in normal subjects. The descriptive precision of the power function uncovered qualitative variability in how normal subjects allocate attention across different spatial reference frames and demonstrated that this patient had a quantitative defect in directing attention across an allosteric reference frame, but a qualitative defect in directing attention across a viewer/environment reference frame.
8043268
Procedural and declarative memory: a developmental study.
Measures of procedural and declarative memory were administered to 88 children forming two groups, aged 8 and 12. Two measures of priming, Gollin Figures and Degraded Words, were compared to declarative measures of recall. Strong support for a developmental dissociation between priming tasks and declarative memory was found. Both age groups showed a similar amount of priming facilitation, yet a significant age effect was observed for the declarative recall tasks. Current findings demonstrate that the level of procedural memory performance stabilizes during a period of development when declarative memory continues to improve.
8043267
Hemispheric differences in image generation and use in the haptic modality.
Forty adults and 40 children, all right-handed, were presented with either of two series of six nonsense shapes to palpate: Those who were divided into sections by grid lines and thus provided categorical information or those who provided a whole shape and coordinate information that could be processed globally. Subjects were given an Input condition where they formed a mental representation of the shape while palpating the unseen tactual stimulus with either hand, followed by an Evaluation condition in which they attempted to solve the task by generating and using the previously stored image. Evaluation response times showed that the left hemisphere was significantly faster at generating images from categorically stored information. Neither hemisphere had an advantage when generating an image from globally stored information.
8043266
Human corpus callosum: a stable mathematical model of regional neuroanatomy.
The functional utility of regional parameters of the corpus callosum (CC) derived from factor analysis has been demonstrated in the rat and the human. In this study, we have utilized factor analysis to compare CC structure between two independent groups of human subjects. Tracings of the CC were taken from the midsagittal MRIs of two human samples consisting of 103 healthy volunteers and 146 neurological patients. CCs were digitized and factor analyses were performed on 99 widths, area, axis length, and perimeter. The factor structures of these two data sets were highly congruent except that one factor analysis yielded a seven-factor solution, whereas the factor analysis of the other subject population gave six factors. Further study determined that the six-factor structure could be attributed to the presence of non-consistent right-handed males whose wider CCs in the isthmus region biased the correlations. When CC parameters of consistent and non-consistent right-handed subjects were standardized, a seven-factor structure resulted. Reproducibility of the factor structure indicates that there are shared neuroanatomical characteristics of CC morphology among two disparate populations of humans in spite of variability in CC size due to sex, age, hand preference, and hand consistency.
8043265
English and Hebrew letter report by English- and Hebrew-reading subjects: evidence for stimulus control, not hemispheric asymmetry.
Three experiments were conducted using tachistoscopic circular displays of English and/or Hebrew letters that were equidistant from a fixation point. It was found that: (1) Irrespective of native language, English or Hebrew, subjects initiate their reports of English letters from the upper left quadrant and of Hebrew letters from the upper right quadrant of the display. In addition, subsequent letter reports come mostly from the same quadrant. (2) Although Experiments 1 and 2 indicated that direction of reporting might be a function of display language, Experiment 3 provided data to show that direction of reporting was a function of the position of the first response and not the display letter language that engaged that response, nor the display language of adjacent letters. It was suggested that the typical asymmetries reported in the literature, such as right visual field superiority for word stimuli, are the result of a particular set of stimulus conditions (e.g., hemifield presentations) and response requirements (e.g., reaction time and correct recognition). When stimulus conditions and response requirements are made compatible with previously overlearned behaviors, the potential influences of cerebral asymmetries are overshadowed by external stimulus control.
8043264
Less attention and more perception in cued line bisection.
Two experiments tested whether bias in cued line bisection resulted from perceptual grouping or attentional factors. Before trying to bisect a line, subjects had to report two lateralized letters. These cues were either equally spaced (Experiment 1) or asymmetrically spaced (Experiment 2) with respect to the line. No effect of order of cue-report on performance was found, arguing against the role of attentional factors. Bisection was systematically biased toward the closer-spaced cue. These findings in normal subjects suggest that cuing effects are due to perceptual rather than attentional factors.
8043263
Letter matching within and between the disconnected hemispheres.
Three patients with complete cerebral commissurotomy from the California series were given two letter-matching tasks, one requiring physical identity and the other requiring nominal identity. The pairs of letters were presented unilaterally to each disconnected hemisphere or bilaterally, with each hemisphere receiving one of the letters to be compared. The disconnected hemispheres of all three patients showed good performance in the unilateral conditions, even when visual field and response hand were crossed. The crossed visual field-hand conditions resulted in both slower and less accurate responses. Only N.G. was able to cross-compare letters in the bilateral condition and only for physical identity. The results qualify previous reports that higher-level information can transfer subcallosally while visual information cannot.
8043261
Apperceptive visual agnosia: a case study.
A man with an infarction of his inferior temporal and occipital association cortex bilaterally, which spared primary visual cortex, had impaired visual recognition of objects, faces, colors, words, and gestures. Analysis of visual function indicated that the recognition failures resulted from an agnosia, rather than elemental visual impairment. Whereas his impairment of gesture recognition appeared to be related to an associative agnosia, his inability to recognize objects was related to an apperceptive agnosia. There may be four subtypes of apperceptive agnosia: one where the internal object representations or structural descriptions are impaired, another where an adequate percept cannot be derived, a third where the internal referent and percept are dissociated, and a fourth where both levels are impaired. Our patient demonstrated a failure to relate individual elements to the whole, a failure to integrate multiple elements, and a reliance on global perception. He had normal object imagery. These results suggest that, whereas internal representations were intact, he was unable to form adequate perceptual representations.
8043262
The effect of repeated prime-target presentation in manipulating attention-induced priming in persons with dementia of the Alzheimer's type.
The present experiment manipulated attention-induced semantic priming in seven persons with dementia of the Alzheimer's type (DAT) and 16 healthy aged controls in a word-nonword lexical decision task by means of repeated prime-target presentations. The experimental paradigm allowed for the simultaneous comparison of automatic processing and attention-induced strategic processing. The results showed that both the healthy aged subjects and the subjects with DAT demonstrated semantic facilitation in the automatic processing of information. The two groups differed, however, on the attention-induced component of the task. The control subjects consciously generated a strategic response bias favoring the real word targets and thus used their processing of the prime to induce an expectancy about the following target. The DAT subjects showed no such attention-dependent expectancy, a deficit which is most probably related to the general cognitive impairments which are a hallmark of the disease.
8043259
Fibronectin during CAPD-related peritonitis: no indications for intraperitoneal production.
Fibronectin is a 440-kD MW glycoprotein involved in opsonization and adhesion of cells to collagen. We examined 13 episodes of peritonitis on 8 consecutive days from the start and once after recovery (control). Fibronectin clearance was compared to that of marker proteins for peritoneal transport. Increased dialysate fibronectin levels were observed on the first peritonitis day. They declined during recovery. Serum levels were stable during peritonitis. All protein clearances, including fibronectin, were increased during the acute phase and decreased during recovery. The clearance of fibronectin showed a time course similar to that of the marker proteins. It was in the range between IgG (150 kD) and alpha 2-macroglobulin (820 kD), thus as expected on the basis of its molecular weight. We conclude that elevated dialysate fibronectin levels observed during peritonitis are due to increased transperitoneal transport and not to local synthesis. This augmented transport results from increments in both effective surface area and intrinsic permeability of the peritoneum.
8043260
Dialyzer reprocessing using heat. Scientific and technical considerations.
Reprocessing of used dialyzers with chemical disinfectants is practiced commonly in the United States and in some areas of Western Europe. Concern over residual toxic or allergenic agents has encouraged the search for other practical methods to disinfect or sterilize used hemodialyzers. The use of moist heat has been proposed as an attractive alternative to chemical disinfection, as the effectiveness of moist heat in inactivating microorganisms is well established and, inherently, should be less toxic than chemical means. However, despite the initial appeal of heat reprocessing, validation and maintenance procedures necessary to ensure a reproducible heat cycle are likely to be burdensome with the currently available hardware. This paper discusses the potential requirements for and barriers to implementation of a dialyzer reprocessing system using heat.
8043258
Enhanced coagulation and fibrinolysis during treatment with recombinant human erythropoietin in patients undergoing chronic hemodialysis.
Twenty-two patients on regular hemodialysis treatment suffering from renal anemia were treated with intravenous recombinant human erythropoietin (rhEPO) for more than 8 weeks. Before and 4 and 8 weeks after the start of rhEPO administration, we measured prothrombin time, activated partial thromboplastin time, fibrinogen (FBG), antithrombin III activity (ATIII), plasminogen activity (PLG), alpha 2-plasmin inhibitor activity (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (alpha 2 PIC), and cross-linked fibrin degradation products (XL-FDP) in citrated plasma to determine whether rhEPO treatment enhances coagulation and fibrinolytic activity. The pretreatment values of FBG, alpha 2 PIC, and XL-FDP were significantly higher than the normal control values. The pretreatment values of ATIII, PLG, and alpha 2 PI were significantly lower than the normal control values. Platelet count and FBG were significantly increased 4 and 8 weeks after treatment with rhE-PO. The prothrombin time was significantly shortened 8 weeks after rhEPO treatment, but the activated partial thromboplastin time did not change. PLG was significantly decreased 4 and 8 weeks after rhEPO treatment, and ATIII and alpha 2 PI were significantly decreased 8 weeks after rhEPO treatment. alpha 2 PIC was significantly increased 8 weeks after rhEPO treatment, and XL-FDP was significantly increased 4 and 8 weeks after rhEPO treatment. These data suggest that in patients on regular hemodialysis treatment coagulation and fibrinolysis are already enhanced before the start of rhEPO treatment and that rhEPO administration further enhances these disorders.
8043257
Monodisperse magnetic polymer particles. New biochemical and biomedical applications.
The method of activated swelling of polymer particles developed by the authors allows the preparation of monodisperse spherical beads of predictable size from 1 to 100 microns in diameter. The polymer particles may be prepared from a number of different monomeric materials and with various morphologies including macroporous structures. The porous beads form the basis for magnetizable monodisperse polymer particles which have magnetic iron oxides distributed as small grains all through the volume of the beads. The magnetic particles are being used extensively for selective cell separation and for immunomagnetic separation within microbiology and molecular biology. A review of recent work within these fields is given. New methods for positive cell separation are announced.
8043255
Outcomes research in medical rehabilitation. A primer and introduction to a series.
This article presents basic findings, concepts and methods in medical outcomes research. Epidemiologic outcomes research begins with the daily life of patients or populations and searches for antecedents. Clinical outcomes research begins with an intervention and examines effects. Both are needed. Issues and methodologies in medical rehabilitation outcomes research are examined, and topics for the forth-coming series are sketched. Medical rehabilitation can make substantial advances in understanding its effectiveness in the near future if it will undertake the needed comparative outcomes research.
8043254
Ethical issues of treating patients with AIDS in a rehabilitation setting.
Human Immunodeficiency Virus (HIV) is frightening and fatal. The great fear of acquiring HIV magnifies ethical issues concerning patients and health care workers. Practitioners in the field of rehabilitation medicine will become increasingly aware of these issues, because at least 50% of patients with HIV-related illnesses develop neurological disorders. Many will need physical, emotional, social, psychological or vocational restoration. This article explores some of the ethical issues related to Acquired Immune Deficiency Syndrome (AIDS) rehabilitation, including confidentiality, risk of exposure to infected patients or infected health care workers, treatment of patients and the rights of patients and health care workers.
8043253
Rehabilitation of eosinophilic fasciitis. A case report.
Eosinophilic fasciitis (EF), first described in 1974, is characterized by the sudden onset of painful swelling with induration of the soft tissues and peripheral eosinophilia, often after an episode of intense physical exertion. It rapidly progresses to joint contractures because of inflammation and fibrosis of the fascia. Of the 200 cases reported in the medical literature, most have responded positively to a prolonged course of oral prednisone. Although complete recovery is possible, more frequently signs and symptoms of EF persist. There were no detailed descriptions found in the literature of any rehabilitative interventions in this disease. This case study describes the methods used in a successful, comprehensive rehabilitation treatment of a 21-yr-old man admitted to the Palo Alto VA Medical Center rehabilitation program 8 mo after the onset of symptoms. Previous medication therapy included prednisone and methotrexate. The patient underwent 2 mo of inpatient rehabilitation, which consisted of upper and lower extremity nerve blocks, serial splinting, application of physical modalities, massage, stretching and strengthening exercises and interdisciplinary pain management. Significant improvement was made in the range of motion in all extremities, strength, hand function, level of pain, gait and endurance. Aggressive therapy did not increase eosinophilia. In fact the eosinophil count returned to normal by the time of discharge. A detailed review of the patient's rehabilitation program is presented.
8043252
Intracranial venous thrombosis in a patient with multiple sclerosis. A case report and review of contraceptive alternatives in patients with disabilities.
Intracranial thrombosis is a rare complication of oral contraceptive use. A case is presented of a 35-yr-old woman with multiple sclerosis who took oral contraceptives and, subsequently, experienced intracranial transverse and sigmoid sinus thromboses and, later, deep venous thrombosis of the calf. A review of the relationship between oral contraceptives and venous thrombosis is presented. In addition, the diagnostic work-up and treatment options for intracranial venous thrombosis are discussed, and appropriate birth control alternatives for disabled patients, that is, diaphragm, sponges, condoms and levonorgestrel, are reviewed.
8043251
Return to work for patients with traumatic brain injury. Analysis of costs.
This brief report describes staff time commitment and program cost outcomes for a return to work program of supported employment for persons with brain injuries. The mean cost of providing services was $10,198 for the first year of service (median, $6,942). Clients achieved job stabilization after an average of 18 wk of time-limited job coaching services, during which they received mean intervention time of 245.7 h (median, 219) at a cost of $7,789. A mean of 2.24 h/wk of extended services intervention was required to maintain clients in employment for the remainder of the first year of service, at a mean weekly cost of $71.01. Results are compared with findings reported in a previous study using a smaller sample.
8043250
Tardy effect of neurogenic muscular atrophy by magnetic stimulation.
The influence of pulsed magnetic stimulation on denervated muscles was investigated in this study. Of 24 rats divided into three groups for experiment, 8 rats served as control; 16 rats with bilaterally severed sciatic nerves were divided into two groups for different modes of stimulation. Magnetic stimulation with a high power output that induced an intensive contraction of muscle was applied at one side-denervated gastrocnemius muscle for 1 mo in a group of rats; electric stimulation with high intensity at 6 Hz frequency and 1-ms pulse duration served as a contrast in the other group. Muscular weight, volume, fiber diameter and percentage of fiber types were measured after the experiment. A significant retardation of weight loss in denervated muscles via magnetic stimulation (P < 0.05) was confirmed by observed results. Type II fiber atrophy was retarded in denervated muscles by magnetic stimulation as well as in denervated muscles via electric stimulation. Magnetic stimulation, used as a method that induces muscular activity, was verified in this study as being capable of retarding denervated muscular atrophy. Its benefits of painless stimulation as well as deeply activated muscular contraction could be expected to function as a new model for rehabilitation of paralyzed muscles.
8043249
Correlation of motor control in the supine position and assistive device used for ambulation in chronic incomplete spinal cord-injured persons.
Neurocontrol of movement after spinal cord injury (SCI) is often spared, but few studies have investigated the chronic incomplete SCI patient. Multichannel surface electromyography (SEMG) can describe characteristics of neurocontrol during a series of volitional and reflex events. The relationship of these neurocontrol characteristics to clinical function is incompletely described. This study, retrospectively, evaluated the relationship between neurocontrol patterns evoked by lower limb movement in the supine position and the assistive device used for ambulation in chronic, incomplete SCI persons. The records of 15 neurologically healthy (9 male, 6 female) and 36 incomplete SCI persons (27 male, 9 female) (C2-T10) were used. SEMG was recorded from both quadriceps, adductors, hamstrings, anterior tibialis and triceps surae muscles and displayed on a stripchart for analysis. SEMG patterns of activity recorded in the supine position during volitional, unilateral, multijoint (hip and knee flexion and extension) movement attempts were characterized, divided into seven groups and compared with the subjects' self-selected ambulation device (independent, cane, crutches, walker or nonambulatory). The neurocontrol patterns recorded in the supine position correlated well with the SCI subjects ambulatory assistive device. Marked decreases in motor unit output and/or loss of motor organization were found in the nonambulatory group. Coactivation of proximal muscles, poor timing of muscle activity and radiation of activity into contralateral muscles were also noted in subjects who required a walker or crutches. To a lesser degree, abnormal motor patterns were also noted in subjects who ambulated with a cane or independently.
8043248
French survey of postpolio sequelae. Risk factors study and medical social outcome.
For 10 yr, numerous studies have been conducted to try to explain the further deterioration of the sequelae from a previous, acute poliomyelitis. The different etiologic hypotheses, which have been put forward, have not been confirmed yet. A retrospective study has been completed by mailed questionnaires sent to 360 patients previously affected by acute polio; 248 polio survivors replied. Deterioration, as functional loss especially during walking and exertion, was reported by 77% of our respondents. Among the newly affected cases, 60% have given up or slowed down their socio-professional activities because of these new problems with their health. These functional losses, reported by patients, have been statistically related to several factors: the aging process, weight gain, female predominance and the involvement of abdominal muscles at a previously acute polio stage. The recently affected population has the same degree of disability (measured through the "Functional Independence Measure" (translated in French and self-administered)) as the nonaffected one. This fact suggests that the problems that are being experienced may be partly subjective.
8043247
Lidocaine injection versus dry needling to myofascial trigger point. The importance of the local twitch response.
This study was designed to investigate the effects of injection with a local anesthetic agent or dry needling into a myofascial trigger point (TrP) of the upper trapezius muscle in 58 patients. Trigger point injections with 0.5% lidocaine were given to 26 patients (Group I), and dry needling was performed on TrPs in 15 patients (Group II). Local twitch responses (LTRs) were elicited during multiple needle insertions in both Groups I and II. In another 17 patients, no LTR was elicited during TrP injection with lidocaine (9 patients, group Ia) or dry needling (8 patients, group IIa). Improvement was assessed by measuring the subjective pain intensity, the pain threshold of the TrP and the range of motion of the cervical spine. Significant improvement occurred immediately after injection into the patients in both group I and group II. In Groups Ia and Ib, there was little change in pain, tenderness or tightness after injection. Within 2-8 h after injection or dry needling, soreness (different from patients' original myofascial pain) developed in 42% of the patients in group I and in 100% of the patients in group II. Patients treated with dry needling had postinjection soreness of significantly greater intensity and longer duration than those treated with lidocaine injection. The author concludes that it is essential to elicit LTRs during injection to obtain an immediately desirable effect. TrP injection with 0.5% lidocaine is recommended, because it reduces the intensity and duration of postinjection soreness compared with that produced by dry needling.
8043246
Structured research training in residency training programs. The impact on the level of resident research activity.
A survey was conducted to construct a profile of structured resident research training and experience in physiatric residency training programs. Resident research activity was quantified, and factors that may influence the level of resident research activity were examined. Questionnaires were sent to all 72 residency training program directors, of which 87% responded. To construct the profile of structured training and experience in research that currently exists, descriptive analyses were applied to the survey responses. Resident research activity was quantified according to projects per resident per year over the last 3 yr. Resident research activity was assigned to level I activity (> or = 0.25 projects/resident/year) or level II activity (< 0.25 projects/resident/year). This point of discrimination was chosen because it represents one project per resident per 4-yr graduate medical education cycle. Nonparametric, univariate analyses were used to evaluate the impact of each characteristic in the research training profile on resident research activity. The following characteristics were found to be statistically significant (P < 0.05): (1) the use of mentors outside of the physical medicine and rehabilitation department; (2) the provision of guidelines to residents for choosing a mentor; (3) the provision of responsibility guidelines to mentors; (4) the presence of a classroom curriculum. Mentorship outside of the department, however, had a negative impact on resident research activity, although the other three characteristics had positive impacts. A multivariate analysis using stepwise logistic regression was applied to further determine the capacity of each characteristic to predict independently the level of resident research activity. Only one characteristic simultaneously and independently remained significant (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
8043245
Rehabilitation resident academic productivity. Report on 1993 graduates.
A survey was designed to explore the relationship among elective time (ET), residency research requirement (RR), mandatory research rotation (MR), and academic productivity for the 1993 graduating residency class. Sixty-seven of the 75 rehabilitation residency program directors listed in the 1993 Directory of Graduate Medical Education Programs responded (89% response rate). Data from 60 programs, representing 283 graduating residents, were analyzed (80% usable response rate). A resident was operationally defined as "active" if that individual submitted either articles (SART) for publication or abstracts (SABS) for oral/poster presentation during the training years; residents with accepted articles (AART) and/or abstracts (AABS) were defined as "productive." Odds ratios and chi 2 statistics were calculated for each study risk variable (ET, RR, MR) and the corresponding outcome variables (SART, SABS, AART, AABS). One hundred and fifty-nine residents (56%) submitted abstracts; 86 (30%) submitted articles; of these residents, 134 (47%) and 54 (19%) had their work accepted, respectively. Research was required by 26/60 (43%) programs. Research elective time was available in 41/60 (68%) programs; only 44/203 (22%) residents used this time for research. Residents who had research required had a 1.9 times greater likelihood of submitting both abstracts (P < 0.008) and articles (P < 0.014). No other study relationship was found to be significant. The study results suggest that implementing a research requirement in the residency training curriculum may lead to an increase in resident research activity.
8043244
Methods used in the evaluation of clinical competency of physical medicine and rehabilitation residents.
A 17-item questionnaire was designed to determine how physical medicine and rehabilitation (PM&R) training directors assess their residents' clinical competency. A response rate of 83% (62/75) was obtained. Seventy-nine percent (49/62) have a written resident supervision policy, and 73% (45/62) have a written resident probation policy. Ninety-four percent (58/62) believe that their system of evaluating residents' clinical competency is effective, although many commented that it could be improved. 76% (47/62) of the residency training directors made the final decision regarding residents' clinical competency. Fifty-two percent (32/62) have a departmental written examination, and 23% (14/62) have formal oral examinations. Eighteen percent (11/62) use an objective structured clinical examination (OSCE), 8% (5/62) use standardized patients and 3% (2/62) use videotaped patient encounters. Forty percent (25/62) use medical record audits. Fifty percent of the programs have rated at least one resident unsatisfactory during a clinical rotation in the past 3 yr, and 11% (7/62) have reported to the American Board of Physical Medicine and Rehabilitation that the overall clinical evaluation of one resident was unsatisfactory in the past 3 yr. Forty-seven percent (29/62) of the programs have asked at least one resident to leave their program in the past 3 yr. The OSCE is emerging as the state-of-the-art method for assessing clinical skills, although it is expensive. The measurement of clinical competency is important in the certification and recertification process, and our specialty needs better methods to assess these performance skills.
8043242
An unusual C-4a hydroxylated decahydroquinolone.
The crystal structure and the relative stereochemistry of the four asymmetric centers of an unusual C-4a hydroxylated decahydroquinolone, phenyl 1,2 alpha,3,4,-4a alpha,5 beta,6,7,8,8a alpha-decahydro-4a-hydroxy-4-oxo-2-propyl-5-vinylquinoline-1 -carboxylate, C21H27NO4, are reported. The H and OH groups at the ring juncture are cis to each other as are the two H atoms alpha to the N atom. The vinyl and OH groups are also cis to each other. The N atom is sp2 hybridized.
8043241
Sodium lanthanum(III) sulfate monohydrate, NaLa(SO4)2.H2O.
The structure of NaLaIII(SO4)2.H2O consists of distorted Na-O6 octahedra, La-O9 complexes in the form of distorted tricapped trigonal prisms, and slightly irregular tetrahedral sulfate ions. All bond distances fall within normal limits. The sulfate ions manifest rigid-body behavior but this is not the case for either of the cation complexes. The single water molecule is modelled as having O-atom disorder but an ordered H atom. Hydrogen bonds involve only sulfate O atoms as acceptors. The absolute structure has been determined.
8043232
Characteristics of individuals using different HIV/AIDS counseling and testing programs.
To describe clinically important differences in the characteristics of subjects using three distinct HIV counseling and testing settings: scheduled confidential, scheduled anonymous, and confidential walk-in. An HIV risk-assessment questionnaire was given to individuals prior to receiving HIV-antibody testing and counseling. Demographic and behavioral data was analyzed for each of the three counseling and testing settings. Walk-in clinic subjects reported fewer high-risk sexual activities and other risk behaviors than subjects from the other two testing settings. They also included more individuals who were health-care workers and victims of sexual assault. The three distinct HIV counseling and testing settings each attracted populations with varying degrees of potential for HIV transmission. The results emphasize the importance of maintaining multiple approaches to HIV counseling and testing in order to reach increasingly diverse at-risk populations.
8043231
Risk factors for HIV-1 infection in adults in a rural Ugandan community: a case-control study.
To study in depth sexual history and sexual behaviour variables as risk factors for HIV-1 infection in a rural Ugandan population. Following a socioeconomic and serological survey of a rural population in Masaka District, south-west Uganda, 233 randomly selected HIV-1-positive cases and 233 negative controls matched on age and village of residence, were invited in October 1990 to participate in a case-control study. A total of 132 cases and 161 controls attended for in-depth investigation including an interview about sexual behaviour. The factor most strongly associated with increased risk of infection was a greater number of lifetime sexual partners, with odds ratios (OR) of 2.1 and 4.9 for those reporting 4-10 and 11 or more partners, respectively, compared with those reporting less than four partners. Having only one sexual partner did not provide complete protection, a total of seven (one male, six female) subjects reporting only one sexual partner were HIV-1-positive. Other significant factors were a history of genital ulcers [OR, 2.9; 95% confidence intervals (CI), 1.0-9.1) and not being a Muslim (OR, 5.4; 95% CI, 1.8-16.5) suggesting a possible protective effect of circumcision. There was a suggestion that those who married within the last 7 years (OR, 2.4; 95% CI, 0.9-6.1) and men exposed to menstrual blood (OR, 5.7; 95% CI, 0.7-49.8) were at an increased risk of HIV-1 infection. These results confirm the predominant role of sexual behaviour in the HIV-1 epidemic. Of particular concern is the observation of HIV-1 infection among those reporting only one partner. Where HIV-1 infection is widely distributed in the general population, risk reduction strategies should, in addition to the promotion of partner reduction, place strong emphasis on safe-sex techniques.
8043230
Risk behaviour and HIV prevalence in international travellers.
To assess risk factors for infection and to determine HIV prevalence in a sample of international travellers. A cross-sectional survey of new patients attending a hospital outpatient clinic, and self-completion of an anonymous questionnaire on sexual behaviour prior to and during travel. Urine samples were tested for the presence of antibodies to HIV. The Hospital for Tropical Diseases, London, UK. All new patients over a 6-month period. Of 782 people approached, 757 (97%) agreed to participate: 141 (18.6%) had had new sexual partners during their most recent trip abroad. Almost two-thirds of those having sex abroad did not use condoms on every occasion with a new partner, and 5.7% contracted a sexually transmitted disease (STD) during their most recent trip; 26% of men from World Health Organization Pattern I countries who had new sexual partners abroad paid for sex. Sixteen out of 731 (2.2%) participants were HIV-antibody-positive. HIV positivity was associated with being born in east, central or southern Africa, having symptoms of an STD since arriving in the United Kingdom and being treated for an STD since arrival. The rates of unsafe sex and payment for sex abroad reported by these international travellers indicate the potential for contracting and transmitting STD, including HIV, in both their foreign and domestic sexual partnerships. With the increasing HIV incidence in Asia (the most common destination for UK travellers after sub-Saharan Africa), the number of cases of HIV contracted abroad may rise in the future.
8043229
Evaluation of a targeted AIDS prevention intervention to increase condom use among prostitutes in Ghana.
To assess the short- and long-term impact of a 6-month pilot intervention program on condom use among prostitutes in Accra, Ghana. The 4-year prospective study follows-up cohorts enrolled in the intervention in 1987 and 1988, comparing condom use in 1991 with that among a comparison group not enrolled in the intervention. The community-based intervention was initiated in Accra, Ghana in 1987. Self-identified female prostitutes who volunteered participation. The educational intervention used local health workers to train and support selected prostitutes to be health educators and condom distributors to their peers. Self-reported condom use with clients. Reported condom use increased dramatically between 1987 and 1988 during the first 6 months of the intervention. In 1991, after 3 years of program relapse, 107 (43%) of the 248 women who had enrolled in 1987 or 1988 were still in prostitution and located for interview. Their level of condom use in 1991 was higher than pre-enrollment but similar to use among prostitutes never enrolled. Sixty-four per cent of those followed-up reported always using condoms with clients in 1991. These 'always users' were more likely to have maintained informal contact with project staff, know that HIV can be transmitted by healthy clients, and report that clients frequently initiate condom use. Findings support the development of long-range educational strategies that recognize the career longevity of prostitutes, available channels for informal program diffusion, individual changes in condom use over time, and the role of clients in condom negotiation.
8043227
HIV seroconversion in intravenous drug users in San Francisco, 1985-1990.
To examine the HIV seroconversion rate, risk factors for seroconversion, and changes in risk behavior over time in intravenous drug users (IVDU) in San Francisco, 1985-1990. Observational study. All methadone maintenance and 21-day methadone detoxification programs in San Francisco. A total of 2351 heterosexual IVDU, of whom 681 were seronegative at first visit and seen at least twice ('repeaters'). HIV seroconversion rates, risk factors for seroconversion, and changes in behavior. The HIV seroconversion rate in repeaters was 1.9% per person-year (ppy) of follow-up [2.1% in women versus 1.7% in men (not significant); 4% in African Americans versus 1% in whites (P = 0.006); 3.9% ppy in the first third of the study, 1.2% in the second (P = 0.007), and 1.9% in the last (not significant)]. Risk factors for seroconversion were five or more sexual partners per year [hazard ratio (HR) = 2.6; P = 0.02], use of shooting gallery ever (HR = 2.9; P = 0.02), and less than 1 year (lifetime) in methadone maintenance (HR = 2.7; P = 0.02). Self-reported intravenous cocaine use fell from 33 to 15% over 5 years, shooting gallery use fell from 19 to 6%, and the proportion with five or more sexual partners fell from 25 to 10%. Bleach use rose to 75% of needle-sharers. The 1985-1990 HIV seroconversion rate in IVDU (1.9% ppy) was comparable to that in San Francisco cohorts of homosexual men (1.4% ppy). A decline in HIV seroconversion coincided with changes in risk behavior. Stable attendance of methadone maintenance was highly protective: the seroconversion rate in subjects with 1 year or more in methadone was 12% ppy.
8043223
Novel oral drug formulations. Their potential in modulating adverse effects.
The rationale for specialised oral formulations of drugs include prolongation of effect for increased patient convenience and reduction of adverse effects through lowered peak plasma concentrations. Local and systemic adverse effects due to high concentrations of drug can be minimised by the use of controlled release delivery systems. Local effects in the gastrointestinal (GI) tract from the release of irritant drug molecules can also be reduced, but the gastric damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is only partially relieved by formulation approaches because of the involvement of systemic factors in the aetiology of GI adverse events. The advantages for each drug class must be examined. Newer dosage forms include: (i) osmotic pumps and zero order kinetics systems to control the release rate of the drug; (ii) bioadhesive systems and gastric retention devices to control GI transit; (iii) bioerodible hydrogels; (iv) molecular carrier systems (e.g. cyclodextrin-encapsulated drugs) to modulate local toxicity in the GI tract; (v) externally activated systems; and (vi) colloidal systems such as liposomes and microspheres. There is evidence for improved tolerability for a variety of drugs administered in novel delivery systems. However, the evidence for improved tolerability is complicated by the potential bias in adverse reaction reporting systems, and a lack of studies directly comparing conventional and modified release preparations. The technology now available to produce delivery systems which not only release drugs in a controlled and predetermined fashion, but which can also target to regions of the GI tract such as the colon, should allow greater control of therapy and potentially might minimise patient variables. However, the problem of variable GI transit times still eludes solution. Systems which rely on time to release drug might be more vulnerable to patient-to-patient variability than those which respond to local environments. The effect of food intake is more apparent on single-unit, nondisintegrating dosage forms, although of course none so far are immune from influence. The risk of new adverse effects resulting from such positional therapy with novel delivery devices must be considered. Understanding the mechanisms of induction of individual adverse effects can lead to advances in modes of delivery to decrease the potential for adverse reactions and events while maintaining therapeutic efficacy. Increased compliance can led to increased therapeutic control and hence safety. Each system has to be considered on its merits. No generalisations can be made, although invariably the modulation of high peak plasma concentrations diminishes adverse effects due to rapid absorption.
8043228
Impact of AIDS on premature mortality in Amsterdam, 1982-1992.
To study the impact of AIDS on premature mortality in the city of Amsterdam (1982-1992). We combined aggregated data from the Netherlands Central Bureau for Statistics with data from the municipal death and population registry and data from the Amsterdam AIDS surveillance system to calculate age standardized mortality rates for men aged 15-64 years and 25-54 years and working years of potential life lost before 65 years (WYPLL). AIDS was the leading cause of death for men aged 25-54 years in Amsterdam from 1990 onwards, and the third leading cause of death for men aged 15-64 years in 1991. In this larger age group AIDS will probably become the leading cause of death in the coming years. In 1991, AIDS was already the leading cause of WYPLL before 65 years for men in the 15-64 age group. Without AIDS, there would have been a decrease in premature WYPLL from 1982 onwards; however, because of AIDS the number of WYPLL is increasing again. AIDS has had a significant impact on the pattern of premature mortality in Amsterdam in the period 1982-1992. Its impact will probably increase over the next few years.
8043226
Trends in sexual behaviour and the incidence of sexually transmitted diseases and HIV among drug-using prostitutes, Amsterdam 1986-1992.
To determine trends in commercial sexual risk behaviour among drug-using prostitutes in Amsterdam after local and national prevention campaigns began in 1987. A subgroup of 281 drug-using prostitutes was selected from a comprehensive, open cohort study of drug users in Amsterdam. Cross-sectional (at intake) and within-person trends in sexual behaviour were evaluated. Person-time analysis was used to determine trends in incidence of sexually transmitted disease (STD). From 1986 to 1992, 'always' use of condoms in the 6 months preceding intake increased from 21 to 58% (P < 0.001) and the number of commercial contacts declined from 84 to 64 per month (P = 0.06). Consequently, the mean number of unprotected commercial contacts declined from 26 to nine per month (P < 0.001). Temporal trends within individual prostitutes from visits 1 to 8 (mean interval between visits, 4 months) showed a somewhat larger risk reduction than the cross-sectional trends. From 1989 to 1992, the STD incidence declined from 61 to 40 episodes per 100 person-years (P = 0.06). Prostitutes residing in Amsterdam for shorter time periods reported more STD and a relatively small core group reported the majority of STD episodes. At intake, when < 10% of all participants knew their HIV serostatus, HIV-positive prostitutes reported significantly lower levels of condom use and more STD than HIV-negatives, while, after learning their serostatus, levels of condom use and the STD-incidence were comparable. Prevalent and incident HIV infections were not observed among non-injecting prostitutes. Drug-using prostitutes have reduced sexual risk behaviour. There is evidence for the effectiveness of HIV testing and counseling. At present, new infections among clients of drug-using prostitutes are expected to occur, although not on a large scale. Since the incidence of STD continues to be high, it is important to monitor the spread of HIV among heterosexuals, including prostitutes and their clients, closely.
8043225
Heparin specifically inhibits binding of V3 loop antibodies to HIV-1 gp120, an effect potentiated by CD4 binding.
To investigate the binding of the sulphated polysaccharides, dextran sulphate and heparin, to CD4 and gp120 in order to examine the anti-HIV mechanisms of these compounds. In order to study the molecular mechanisms involved, the binding of sulphated polysaccharides to recombinant (r) sCD4 and gp120 was investigated in solid-phase binding studies that employed various monoclonal antibodies directed against known epitopes on these proteins, including the V3 loop of gp120. The ability of sulphated polysaccharides to inhibit both the binding of gp120 to CD4 and the binding of the monoclonal antibodies was investigated by enzyme-linked immunosorbent assays. It was demonstrated that dextran sulphate inhibits gp120-sCD4 binding at concentrations of 100 micrograms/ml, whereas heparin has no effect. Heparin does, however, block the binding to rgp120 of monoclonal antibodies recognizing epitopes in the V3 loop. Clinical low molecular weight heparin preparations are as active as unfractionated heparin in this regard. Pre-incubation of gp120 with excess sCD4 increases the potency of heparin in blocking the binding of V3 loop monoclonals severalfold. The modes of action of heparin and dextran sulphate differ. Dextran sulphate both inhibits CD4-gp120 binding and binds to the V3 loop of gp120. However, heparin is more selective and appears to function only by interfering with events involving the V3 loop that occur prior to HIV fusion with the plasma membrane.
8043222
A risk-benefit assessment of conventional versus intensive insulin therapy.
Some retrospective nonrandomised or cross-sectional studies have shown that higher blood glucose levels are associated with more pronounced microvascular complications in patients with insulin-dependent diabetes mellitus (IDDM). The prospective randomised studies had, until recently, been less definitive. Intensified treatment, and thus lower blood glucose levels, has led to an initial worsening of retinopathy, but this tendency towards more advanced retinopathy has been transient. Albuminuria and manifest neuropathy have been retarded to some extent. Today, 2 long term randomised studies, the Stockholm study and the Diabetes Control and Complications Trial (DCCT), have proven that a lowering of mean blood glucose levels, measured as a lower glycosylated haemoglobin (HbA1c) value, retards or halts retinopathy, nephropathy and peripheral neuropathy. Intensified treatment, whether performed with multiple injections or insulin pumps, leads to some weight gain and a 3-fold increase in the frequency of severe hypoglycaemic episodes. Hypoglycaemia did not cause long term reduced cognitive function in either study, but was unpleasant to the patients. A great majority of patients in the Stockholm study stated that their well-being had increased while participating in the study. The Stockholm programme required 35 minutes extra per patient per month, and a physician and a nurse could tutor 400 patients. This would bring a significant reduction of serious complications and a gain in terms of patient discomfort and cost. A programme of intensified treatment for IDDM is generally indicated and is possible to carry out.
8043200
[Hemotherapy and transfusional Chagas' disease in Brazil].
With the increased presence of Chagas' disease in urban areas and the rising importance of transfusional transmission of Trypanosoma cruzi, a proper and realistic approach to hemotherapeutic treatment has become crucial in Brazil. Bringing together data from various institutions, this study analyzed hemotherapy and the problem of transfusional Chagas' disease in 850 Brazilian municipalities from 1988 to 1989. It was found that some type of hemotherapy was practiced in 68.8% of these municipalities at the time, this practice being qualitatively and quantitatively proportional to the population size of the municipality. The official blood bank system supplied the blood used in 13% of these services. In relation to prevention of the main diseases transmissible by transfusion, prior screening of donors was carried out by 75.2% of the services for syphilis, 65.4% for hepatitis, 53.8% for AIDS, and 66.9% for Chagas' disease. These percentages vary by region and by size of the municipality. The majority of donors are classified as voluntary, with only 2% categorized as paid donors. In the case of Chagas' disease, most services used only one serologic technique to screen donors, most commonly hemagglutination or immunofluorescence, while only 10.3% of services had previous experience with chemoprophylaxis using gentian violet. The proportion of potential donors with positive serology for anti-Trypanosoma cruzi antibodies was around 1%. These data were confirmed by information from blood banks and Brazilian hemotherapy professionals.
8043199
[The decentralization and municipalization of health services in Säo Paulo, Brazil].
The health system in Brazil has undergone profound changes since the 1980s. In the state of São Paulo, the processes of decentralization to the municipio and regional levels, as well as integration of health services, began in 1983. This study describes the strategies adopted by the Ministry of Health of the state of São Paulo to implement these processes and create 65 regional health offices, and discusses the role of these offices in the new unified health system. It is concluded that decentralization has resulted in increased local government participation in financing the health system, that production of medical and community health services has grown, and that health indicators have improved.
8043198
Non-AP-1 tumor promoter 12-O-tetradecanoylphorbol-13-acetate-responsive sequences in the human ornithine decarboxylase gene.
To define the mechanisms of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transcription of the ornithine decarboxylase (ODC) gene, we isolated a genomic clone (hODC41B) of ODC from a human leukocyte genomic DNA library. The restriction endonuclease map, in comparison with the previously published sequences of the human ODC gene, indicated that hODC41B contained a 15.7-kb sequence that extended from the sixth exon to about 10 kb upstream of the ODC gene. A 2.5-kb genomic fragment containing the 5' flanking region and the first exon was subcloned and sequenced. Sequence analysis revealed multiple putative promoter/enhancer elements (a TATA box, a CAAT box, 17 GC boxes, and a cAMP-responsive element) but no consensus AP-1 sequences (TGAGTCA) in the 2.5-kb 5' flanking region. However, three AP-1 sequences were located in introns 3, 5, and 11. We constructed a series of chimeric genes containing part of the first exon and increasingly longer 5' flanking sequences of the ODC gene fused to either bacterial chloramphenicol acetyltransferase (CAT) or luciferase reporter genes. TPA inducibility was determined by transient transfection and measurement of CAT or luciferase expression in HeLa cells. The induction of CAT activity by TPA decreased with decreasing lengths of the 5' flanking sequences up to nt -82. The TPA induction from the construct -72 ODC CAT was threefold to sevenfold, and the TPA inducibility of the same fragment was about ninefold to 30-fold with the luciferase reporter gene. Further deletion analysis revealed TPA-responsive sequences in ODC nt -42 to +54. Gel mobility shift assays using alpha-32P-end labeled ODC nt -42 to +60 revealed that nt -42 to +60 specifically bound HeLa cell nuclear proteins. HeLa cell nuclear protein binding to ODC nt -42 to +60 could not be completely competed by AP-1-, AP-2-, AP-3-, or SP1-responsive sequences.
8043197
The role of 12 cDNA-expressed human, rodent, and rabbit cytochromes P450 in the metabolism of benzo[a]pyrene and benzo[a]pyrene trans-7,8-dihydrodiol.
The potent carcinogen benzo[a]pyrene (B[a]P) and its metabolite B[a]P trans-7,8-dihydrodiol (7,8-diol) require metabolic activation by the microsomal cytochrome P450s (P450s) to exert several adverse biological effects, including binding to DNA, toxicity, mutagenicity, and carcinogenicity. In the study reported here, we defined the role of each of 12 individual cDNA-expressed cytochrome P450s in the metabolism of B[a]P and 7,8-diol. Human P450s 1A1 and 1A2 were expressed in the absence or presence of epoxide hydrolase (EH) in a human lymphoblastoid cell line, and six human and five rodent and rabbit P450s were expressed from cDNA with vaccinia virus vectors in the hepatoma cell line Hep G2. B[a]P metabolism resulted in nine metabolites (three diols, three quinones, and three phenols), which were separated, identified, and quantitated by high-pressure liquid chromatography. In the human lymphoblastoid cells, human 1A1 metabolized B[a]P at a rate 4.5 times greater than that for 1A2. EH was shown to be directly involved in B[a]P activation, since increasing the amount of EH resulted in less 7-hydroxybenzo[a]pyrene and more 7,8-diol formation. Of the human P450s expressed with the vaccinia virus vectors in Hep G2 cells, 1A2 and 2C9 showed the highest activity and 2B6 showed moderate activity for B[a]P metabolism. Mouse 1A1 had activity 40 times higher than any human, rabbit, or rodent P450s, indicating the potential pitfalls of extrapolating P450 activity across species. Metabolism of the 7,8-diol resulted in six metabolites (four tetrols and two triols). In the lymphoblastoid cells, human 1A1 was shown to be 4.2 times more active than 1A2 for 7,8-diol metabolism. Among human P450s expressed from vaccinia virus, 1A2, 2E1, and 2C9 gave the highest activity, and 2C8 and 3A4 showed moderate activity for 7,8-diol metabolism to the diol epoxides. Again, mouse 1A1 was much more active than any other P450. These studies, in which we determined the capacity of individual P450 in the metabolism and activation of B[a]P and 7,8-diol, may thus lead to a better understanding of how P450s control the detoxification and activation of polycyclic aromatic hydrocarbons.
8043196
Transforming growth factor-alpha expression in peritoneal macrophages elicited from SENCAR and B6C3F1 mice: responses to lipopolysaccharide and 12-O-tetradecanoylphorbol-13-acetate.
Recent findings in our laboratory indicated that peritoneal macrophages (MPs) elicited from phorbol ester-sensitive SENCAR mice generated significant amounts of superoxide when stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro; negligible responses were observed for MPs derived from relatively resistant B6C3F1 mice. We hypothesized a similar strain-dependent secretion of transforming growth factor-alpha (TGF-alpha) by TPA-stimulated MPs. TGF-alpha secreted by MPs was quantitated by competitive enzyme-linked immunosorbent assay. After 72 h (maximal secretion), for MPs derived from B6C3F1 mice, in vitro exposure to 10 microgram/mL lipopolysaccharide (LPS; non-lipid-A-detoxified) resulted in maximal induction (708 pg/mL), in vivo exposure to intraperitoneally (i.p.) administered TPA (2 micrograms/mouse) alone resulted in a minimal response (32 pg/mL), and prior in vivo exposure to TPA significantly inhibited (more than 90% suppression) the LPS-stimulated MP response in culture (i.e., to 62 pg/mL). Although significant amounts of TGF-alpha could be detected in both SENCAR- and B6C3F1-derived MPs (i.e., approximately 2-3 ng/5 x 10(6) cells), SENCAR MPs did not secrete TGF-alpha in response to either TPA or LPS. In addition, the use of the semiquantitative reverse transcription-polymerase chain reaction to detect TGF-alpha-specific mRNA did not support the strain dependency observed for LPS-stimulated TGF-alpha secretion, i.e., detectable transcripts were observed in MP RNA derived from both strains. In conclusion, although TPA itself demonstrated negligible effects on TGF-alpha expression in murine MPs, prior in vivo exposure inhibited LPS-stimulated transcriptional activation and intracellular TGF-alpha production. The negligible TGF-alpha secretion determined for LPS-stimulated SENCAR-derived MPs suggested the possibility of a strain-specific defect in the posttranslational processing of the proTGF-alpha molecule.
8043195
Cellular control of human papillomavirus oncogene transcription.
Specific types of human papillomaviruses (HPVs) are closely associated with the development of cervical cancer. The transforming ability of these high-risk HPV types depends on the expression of the viral E6 and E7 oncogenes. It is therefore of particular interest to elucidate the molecular mechanisms that result in the activation of E6/E7 expression during HPV-associated tumorigenesis. Recently, much progress has been made in characterizing the proteins involved in the regulation of HPV oncogene transcription. This review describes the functional significance of cellular factors involved in the transcriptional control of the E6/E7 promoter for the two most common HPV types associated with cervical cancer, HPV16 and HPV18. In addition, we discuss regulatory pathways that may contribute to the epithelial cells specificity of E6/E7 transcription. The definition of the factors that regulate HPV oncogene transcription could provide new insights into the molecular mechanisms activating viral oncogene expression during cervical carcinogenesis and forms an experimental basis for investigating the specific biochemical pathways that contribute to HPV-associated malignant cell transformation.
8043192
When is a pressure ulcer not a pressure ulcer? ... external pressure versus internal pressure.
This case study presents a nontraditional explanation for recurring and difficult to heal pressure ulcers: internal pressure rather than external pressure. The authors are hopeful that this discussion will assist colleagues in recognizing this alternative diagnosis.
8043187
Clinical study: the relationship between patient perceived risk and actual risk for the development of pressure ulcers.
The purpose of this study was to determine the relationship between the risk perceived by a patient and that patient's actual risk for the development of pressure ulcers. The nonprobability convenience sample consisted of 20 caucasian individuals who had suffered traumatic spinal cord injuries and were all living in noninstitutional settings. Perceived risk was measured using Gosnell's Risk Assessment Tool, rewritten for self-administration. Actual risk was measured using a skin assessment tool developed by the investigator. The data obtained on perceived risk and on actual risk was analyzed using frequency distributions and Spearman's Rank Order Correlations. The majority of subjects in this study (85%) were determined to be at risk for pressure ulcer development. No significant relationship between the client perceived risk and the actual risk for the development of pressure ulcers was discovered. Significant relationships were discovered between nine of the factor pairs (p = 0.05), two of which were marginally significant. The pairs, in order of significance from greatest to least, were moisture/circulation, circulation/color, perceived mobility/circulation (the only intertool pair to achieve significance), sensation/circulation, color/Total Actual Risk score, continence/Total Actual Risk score, activity/Total Perceived Risk score, circulation/Total Actual Risk score, and sensation/Total Actual Risk score. The overall conclusion is that the self-perception of risk by the subjects in this study was representative of their true potential for pressure ulcer development.
8043185
Developing care plans for psychosocial nursing diagnoses.
In 1992, the Nursing Department Documentation Committee at Spaulding Rehabilitation Hospital decided to revise the process of and forms for documenting nursing diagnoses. A sub-committee developed a format for standardized nursing care plans and piloted its use on two patient care units. The unit nursing staffs selected a number of common nursing diagnoses and, using the new format, developed standardized nursing care plans for them. After refining the process based on this pilot, the development of care plans was extended to all patient care units. A collaborative partnership was then formed between interested Primary Nurses, the Psychiatric Clinical Nurse Specialist and the Nursing Practice Coordinator to focus on developing psychosocially-oriented care plans as well as physically-oriented plans. Although psychosocial diagnoses are less frequently identified in the assessment process and included in nursing care planning, they are still very important for providing comprehensive care. This article describes the process of developing and implementing psychosocial care plans. This article also describes the components of the standardized nursing care plans developed for four psychosocial nursing diagnoses.
8043178
Measuring tissue interface pressures of two support surfaces used in the operating room.
Patients undergoing surgery are often overlooked for the prevention of pressure ulcers. Anesthetized patients are at very high risk for pressure injury due to forced immobility which occurs during surgery. This risk has been reported to be higher for patients undergoing vascular surgery. Few studies have been conducted which examine the tissue interface pressure of the conventional operating table pad and products available to reduce pressure for patients undergoing surgery. Several cases of pressure injury in patients undergoing vascular surgery led to this study.
8043175
Direct HPLC separation of enantiomers of main moguisteine metabolite: comparison of different stationary phases.
Moguisteine is a new non-narcotic antitussive agent. The molecule contains a chiral centre, which is maintained in the metabolite structure. The unchanged drug is not found in the plasma of treated animals or humans. The main moguisteine metabolite, M1, is the free racemic acid generated by hydrolysis of the ethyl-ester group of moguisteine. HPLC separation of M1 enantiomers was attempted using various chiral stationary phases. Separation of the enantiomers was achieved with alpha-1-AGP and beta-cyclodextrin columns, which showed similar enantioselectivity and good resolution. However, the routine application of alpha-1-AGP columns turned out to be difficult, due to the limiting low flow rate which displayed baseline problems and progressive loss of resolution. beta-Cyclodextrin columns showed greater efficiency than alpha-1-AGP columns, as the former allows reproducible separation and can easily be applied to biological sample analysis in pharmacokinetic studies.
8043174
Synthesis and anticancer activity of new phenyl-ring substituted 4-morpholino-1-phenylthio-2-butanones [Mannich bases].
The preparation of phenyl-ring substituted 4-morpholino-1-phenylthio-2-butanones 4a-e is described. These compounds were evaluated against P-388 leukemia and human cancer rhinopharynx KB cells in vitro; some compounds were found to exhibit activity against these cell lines.
8043173
Synthesis and antibacterial properties of 7 beta-[2-(5-substituted-or unsubstituted-2-furyl)acetamido]cephalosporanic acid derivatives.
Several new 7 beta-[2-(5-substituted or unsubstituted-2-furyl) acetamido]cephalosporanic acid derivatives with various hydrophilic groups on the triazole at the C-3 position of the cephem nucleus were synthetised. The antimicrobial activity of the prepared compounds was tested.
8043172
Trifluoromethylcontaining sulfanilamides. I. Synthesis and in vitro antibacterial activity.
In a wider research directed to improve pharmacological profiles of known anti-infective agents by introducing fluorine or trifluoromethyl groups, some sulfanilamides trifluoromethylsubstituted on N1 ring, were synthesized and examined for their in vitro activity against gram-positive and gram-negative bacteria. Two N1-trifluoromethylphenyl-sulfanilamides, 1 and 4, exhibited MIC values, against all tested bacteria, similar or lower than those of the "classical" sulfanilamides, assayed in comparison. The new sulfanilamide 4 appears to be the more interesting: in fact, the presence of p-aminobenzoic acid (PABA) in culture medium did not influence its MIC values and no synergy was observed with trimethoprim, suggesting mechanism of action different from that of known sulfanilamides.
8043171
Structure-activity relationships in thienodiazepine and benzodiazepine derivatives.
The structural and electronic characteristics as well as the anticonvulsant properties and benzodiazepine receptor binding of thieno[3,4-b][1,4]diazepine and 1,5-benzodiazepine derivatives are compared and discussed. The data obtained suggest that the electronic rather than the structural properties appear mainly responsible for the variant degree of anticonvulsant activity exhibited by the tested compounds.
8043170
N(6)-substituted 2-phenyl-9-benzyl-8-azaadenines. Affinity for adenosine A1 and A2 receptors. A comparison with 2-N-butyl analogous derivatives. V.
The title compounds were prepared to evaluate their affinity towards adenosine A1 and A2 receptors. Some 2-phenyl-N(6)-substituted-8-azadenines showed good binding properties and good A1 selectivity. The biological results allow us to confirm the presence in A1 receptors of a third lipophilic pocket, able to receive the substituent on N(9), and to evince increased affinity when a phenyl group on C(2) substitutes an n-butyl group. These affinity differences between analogous 2-n-butyl and 2-phenyl derivatives indicate that they arrange themselves within A1 receptors in a similar manner and suggest that this receptor is able to arrange 8-azaadenines, bearing three lipophilic substituents, in two different ways.
8043168
1,2,3-Triazole[4,5-d]pyridazines--II. New derivatives tested on adenosine receptors.
This paper reports the synthesis and biological evaluation towards A1 and A2 adenosine receptors of new 1,2,3-triazole[4,5-d]pyridazines bearing lipophilic substituents in the 1 position. Some 1-benzyl-4-substituted amino derivatives were prepared and the cyclohexylamino-, anilino- and p-toluidino- derivatives showed an interesting moderately selective activity on the A1 receptor.
8043167
Constituents of euphorbiaceae 12. Comm. (1). Isolation and structure elucidation of four new cerebrosides from Euphorbia biglandulosa Desf.
Four new cerebrosides 4-6 were isolated from the latex of Euphorbia biglandulosa Desf. and their structures determined. Normal and reverse-phase flash chromatography was effective for the isolation of the cerebrosides, and FAB-MS spectrometry, 1H-NMR, 13C-NMR, DQF-COSY and HMQC experiments and chemical reactions were useful in elucidating their structure. EI-MS of the dimethyl disulfide derivatives of the long chain bases and glucosphingoside-heptaacetates was decisive for the determination of the double bond position on the long chain parts.
8043166
QSAR study on H3-receptor affinity of benzothiazole derivatives of thioperamide.
Starting from the structure of thioperamide, a known H3-antagonist, a new series of compounds with a benzothiazole nucleus instead of the cyclohexylcarbothioamide moiety was synthesized. Various substituents, selected by experimental design, were introduced in position 6 of the benzothiazole nucleus, in order to change its physico-chemical characteristics. The lipophilicity of the synthesized compounds was measured by means of RP-HPLC, and their H3-receptor affinity was evaluated by competitive binding assays on rat cortex synaptosomes, with the labelled ligand N alpha-[3H]methylhistamine. A QSAR analysis was performed on the experimental data, using also substituent constants taken from the literature. The newly synthesized compounds showed lower H3-affinities than thioperamide; quantitative structure-activity relationships, described by models obtained with PLS and MRA techniques, were observed among benzothiazole derivatives. According to these relationships, any attempt to improve the potency of these compounds should involve the substitution of the benzothiazole moiety with less bulky and/or more flexible structures, which should also be less lipophilic and allow better electronic interactions with the binding site. 1-(Benzothiazol-2-yl)-4-[(1H)-imidazol-4-yl]piperidine represents a limit structure for H3-activity, since it seems impossible to improve its affinity by means of substitution in the studied position of the benzothiazole nucleus, as shown by predictions performed by a PLS model.
8043165
Grading of cystosarcoma phyllodes by texture analysis of tissue architecture.
Conventional histologic grading of cystosarcoma phyllodes of the breast has not been entirely successful in the prognosis of recurrence or metastasis. Our study first developed a tumor grade classification based on computerized texture features and then compared the classification to conventional grading of these tumors. Evaluation of the tissue architecture of histologic sections was obtained by measuring nine texture features on an image analysis system. Forty cases of cystosarcoma phyllodes were studied. Each parameter was calculated on subimages of 128 x 128 pixels. This size resulted from a preliminary study that confirmed that the difference between texture primitives depends on the area of subimages. We also compared our series to a panel of 20 extramammary sarcomas. The results show that tissue architecture evaluated by texture analysis allows good discrimination between benign, borderline and malignant cystosarcoma phyllodes. Furthermore, extramammary sarcomas and malignant cystosarcoma phyllodes were discriminated well in most cases.
8043164
Selection of morphometric features that identify responders and nonresponders in stage IV Wilms' tumors.
Wilms' tumor is the most common renal malignancy of childhood. The use of histologic grade and stage has divided those patients into two main groups, responders and nonresponders, based on the absence or presence of extreme cytologic atypia (anaplasia). Patients with Wilms' tumor who have favorable histology experience excellent cure rates with relatively conservative treatment regimens. However, some patients with a favorable histologic diagnosis die of the disease. Destained hematoxylin and eosin-stained tissue sections were restained stoichiometrically with Feulgen stain, and 100 tumor cells per case were measured on a CAS 200 running CMP software. Using multivariant stepwise discriminant analysis on 13 cases of stage IV, favorable-histology Wilms' tumor, we successfully classified 92% of individuals into their correct prognostic groupings using 10 features of the quantitative morphology of tumor cells, including six Markovian textures. This morphometric technique may identify patients who can benefit from reduced therapy and those who must be treated with the more aggressive, classic therapy regimens.
8043163
Nuclear area and DNA content in tumor and nontumor portions of hepatocellular carcinoma.
The nuclear area and DNA content between tumor and nontumor portions of hepatocellular carcinoma (HCC) were compared. Thirty pairs of imprint smears were made from surgical specimens and stained with a modified Feulgen reaction. Two hundred nuclei were scanned with a microdensitometer at a wavelength of 550 nm. DNA histograms were plotted with lymphocytes as the internal control. Nuclear areas of 200 cells in each case were measured with Minimagiscan image analyzer. Hyperploidy (DNA index > 1.1) was 76.7% and 53.3% in tumor and nontumor portions, respectively. The S-phase fraction value was 7.9 +/- 3.5% (+/- SD) and 4.1 +/- 2.4% in tumor and nontumor portions of HCC (P < .001). The mean nuclear area of the tumor portion was significantly larger than that of its corresponding nontumor portion (232.9 +/- 68.1 vs. 137.6 +/- 15.5 microns2, P < .001). Marked anisonucleosis was found in both the tumor and nontumor portions of HCC. The mean coefficient of variation of mean nuclear areas was 27.8 +/- 10.4% and 22.9 +/- 4.9% in the tumor and nontumor portions, respectively (P < .05). DNA ploidy correlated well with mean nuclear area in the tumor portions (r = .730) but not in the nontumor ones. The results indicate that the three most important cytologic criteria of malignant cells--hyperchromatism, nuclear enlargement and anisonucleosis--are evident in both the tumor and nontumor portions of HCC.
8043162
Measurement by confocal laser scanning microscopy of the volume of epidermal nuclei in thick skin sections.
The mean volume and shape of nuclei assessed in standard tissue sections by means of stereologic and morphometric methods are associated with prognosis in tumors of different sites. Thus, accurate quantification of the volume and shape of cell nuclei can be important for cancer patients and also may be useful for a better understanding of basic cellular events, such as growth and differentiation. Confocal laser scan microscopy (CLSM) makes it possible to obtain image sets consisting of very thin serial optical slices from thick tissue sections. These images can be used with digital image processing to construct a three-dimensional (3-D) model of individual nuclei. We used CLSM to study a 50-micron-thick paraffin section of a skin biopsy. Image processing was applied to the CLSM images to precisely segment epidermal nuclei from the background, and serial two-dimensional (2-D) binary images were created. Alignment of the 2-D images that form the 3-D model of the original nuclei was carefully controlled. The series of 2-D binary images was connected with an algorithm to form the 3-D model of each complete nucleus and organized for the 3-D visualization and analysis using a 3-D volume rendering method. In this way we measured the volume and surface area of 22 intact epidermal nuclei. The mean nuclear volume was 174.7 micron3, the standard deviation of the volume 26.47 micron3, the mean surface area 168.0 micron2 and the standard deviation of the surface area 22.00 micron2.(ABSTRACT TRUNCATED AT 250 WORDS)
8043161
Fluorescence image analysis of plasma cells in monoclonal gammopathies.
The DNA content of plasma cells was estimated by fluorescence image analysis in monoclonal gammopathies. Image analysis provides the possibility of measuring the bone marrow plasma cell population separately from the other myeloid cells. Plasma cells were labeled, identified and then relocated for propidium iodide intensity measurements. Patients with DNA malignancy grade > 0.20 or with DNA index > 1.15 had a poorer survival rate than did patients with a low DNA malignancy grade or DNA index. DNA malignancy grade is based on the variance of DNA values around the normal diploid peak, as proposed by Böcking. Of all the biologic and clinical parameters investigated, the serum beta 2 microglobulin level was the most important prognostic factor for survival in the multivariate regression analysis, and the DNA entropy index provided the most significant additional information.
8043160
Effect of embedding methods versus fixative type on karyometric measures.
The influence of fixation and embedding methods in seven urologic tumor samples was studied karyometrically for 12 preparatory techniques. Routine histologic formalin fixation was compared with Carbowax and Kryofix fixatives. Also, histologic material was studied embedded in paraffin and plastic (GMA) and secondarily in plastic (after paraffin embedding). From the cell suspensions, cytocentrifuge preparations were made (10 minutes, 1,500 rpm). The influence on nuclear light microscopic characteristics for two morphometric and five texture features in Feulgen-stained nuclei was evaluated. Nuclear features were influenced by both fixation and embedding method. The most extensive karyometric differences were found between different embedding techniques. More abnormally shaped tumor cell nuclei tended to occur with plastic (GMA) embedding methods. Plastic embedding proved to be superior to paraffin for all three fixation methods. Reembedding of archival formalin-fixed, paraffin-embedded material in plastic greatly influenced nuclear features, nuclear area in particular. We conclude that nuclear features are particularly influenced by the embedding method applied.
8043159
Bivariate flow cytometric analysis of p53 and DNA content in hepatocellular carcinoma.
Bivariate flow cytometric analysis of p53 protein and DNA content was studied in archival specimens of hepatocellular carcinoma (HCC) from Chinese patients and corresponding benign liver tissues from a series of 51 patients at Sun Yat-sen University of Medical Sciences. Extracted nuclei were stained with the fluoresceinated monoclonal antibody PAb 1801, which recognizes human p53 protein (mutant and wild types). The nuclei were counterstained with the DNA stain propidium iodide. They were measured on an Ortho FC-200 flow cytometer and the data acquired and analyzed with an IBM 386 personal computer using Kusuda's Get Simple and List Simple software. Of the 51 hepatomas studied, 26 (51%) were p53 positive as compared with 4 (16%) of 24 samples of benign liver tissue from the same patients (P < .0257). The S-phase fraction of p53-positive HCC (12.3 +/- 8.8%) (SD) was significantly greater (P < .05) than for p53-negative HCC (7.4 +/- 7.2%). p53 Expression did not correlate with age, sex, alpha-fetoprotein, hepatitis B surface antigen, tumor size, tumor grade or survival rate. List Simple software permitted analysis of each specimen together with its isotype control (IgG1) on the same cytogram so that p53 expression could be determined separately for the diploid and aneuploid populations of aneuploid tumors and for tumor cells of diploid tumors in the various phases of the cell cycle. Since p53 (PAb 1801) expression can withstand formalin fixation and pepsin treatment of paraffin-embedded tissues, flow cytometric analysis of archival specimens is feasible, and clinical correlations such as these may be carried out in retrospective studies of other tumors.
8043158
Image analysis of Feulgen-stained transformed NIH 3T3 cells differing in p21 expression and ras-induced metastatic ability.
Nuclear phenotypes of clonal and polyclonal T24 H-ras-transformed NIH 3T3 cells differing in p21 expression and experimental metastatic ability were studied in Feulgen-stained preparations by image analysis. The objective was to determine if these cells varied in their degree of chromatin condensation, as previously reported with cell transformation, or in any other chromatin texture property highlighted by image analysis parameters. The majority of nuclei in all of these ras-transformed cells exhibited increased levels of chromatin condensation, independent of ras levels or metastatic properties. This chromatin texture characteristic was assumed to be related to the transformed phenotype. No significant changes in chromatin supraorganization that could be correlated directly with ras levels or metastatic ability were found, with the exception of an increased frequency of a relatively rare phenotype in highly metastatic cells. This phenotype was characterized by an extreme contrast in packing state between condensed and noncondensed chromatin. It is suggested that ras transformation results in alterations in chromatin structure but that there is not a simple relationship between ras p21 expression levels or ras-induced metastatic ability and the degree of these changes.
8043157
Prostatic intraepithelial neoplasia. Development of a Bayesian belief network for diagnosis and grading.
The diagnosis and grading of prostatic intraepithelial neoplasia (PIN) are affected by uncertainties that arise from the fact that almost all our knowledge of PIN histopathology is not expressed in numeric form but rather in descriptive linguistic terms, words and concepts. A Bayesian belief network (BBN) was used to reduce the problem of uncertainty in diagnostic clue assessment while considering the dependencies between elements in the reasoning sequence. A shallow network was developed with an open-tree topology, with a root node containing the diagnostic alternatives and seven first-level descendant nodes for the diagnostic clues. One of these nodes was based on tissue architecture and the others on cell features. The results obtained with prototypes of relative likelihood ratios showed that beliefs for the diagnostic alternatives are very high. The network can grade and differentiate PIN lesions from other prostate lesions with certainty. A number of diagnostic clues greater than seven did not significantly improve network performance, whereas a reduced number of clues resulted in decreased beliefs. A BBN for PIN diagnosis and grading offers a descriptive classifier that is readily implemented and allows the use of linguistic, fuzzy variables. A BBN allows the accumulation of evidence presented by diagnostic clues, each offering only weak evidence.
8043156
The influence of drinking on physiological tremor and reaction time.
Tremor is an invisible mechanical vibration observed on parts of the body. It is classified into physiological and pathological tremors. It was reported that an oral dose of alcohol could decrease the amplitude of pathological tremor. Usually, drunken level is estimated by the alcohol concentration in expiration. But, physiological tremor can be used to estimate drunken level easily. In this paper, power spectrum of the physiological tremor of index finger and some reaction time of the pedal operations of imitated car driving were measured every 15 minutes for 3 hours under drinking and non-drinking conditions. Subjects were 10 males aged 20 to 25 years. Under drinking condition, the total power values of tremor from 15 to 180 minutes after drinking were smaller than that of before drinking. It is clear that the influence of drinking could be estimated by the total power of the physiological tremor, even when the significant difference of the influence of drinking on reaction time was not found.
8043155
[Study on the aging influence on the recognizability for colored targets--black and color].
Recently spaces for the aged have become more wide spread as the population of them has increased. Most of the spaces, however, are originally provided for the young and, accordingly, can not be considered preferable environments for the aged. From this point of view, the authors aimed at the visual environments for the aged and carried out experimental research on the influences that aging gives to recognizability for colored targets, for the purpose of providing a preferable visual environment for the aged. The results show that the recognizability for colored targets declines drastically from about fifty years old, as just as the recognizability for uncolored targets. Moreover, the results show that, although the recognizability of the young is considerably influenced by differences of the illuminance and color of the target surfaces, aging made the recognizability less influencable by these differences.
8043153
Effects of wearing compression stockings on cardiovascular responses.
To investigate the effects of wearing compression stockings on cardiovascular responses, the heart rate (HR), cardiac output (Q) measured by CO2 rebreathing method, and oxygen intake were measured at rest in a supine position for 40 min and standing position for 120 min. Six female subjects wore the compression stockings after 20 min of rest at supine position. The oxygen intake and ventilation showed no significant difference between with and without the stockings. Q at standing position was lower than that at supine position by an act of hydrostatic pressure. However this decrease was lower with stockings than that without stockings. The compression stockings used in this study might improve the venous return to the heart. However, the subjects complained of discomfort due to the high clothing pressure. In the second experiment, the authors estimated the minimum pressure required in improving the venous return. The subjects wore the trousers having two bladders inflated by air pressure. The trousers could compress the leg (contain the foot) and thigh individually. From the relationship between air pressure and Q, the estimated minimum pressures were 17 mmHg for the leg and 15 mmHg for the thigh.
8043154
Thermal responses affected by different underwear materials during light exercise and rest in cold.
The purpose of this study was to evaluate the effects of two types of underwear materials on thermophysiological responses during rest and light exercise. Two differently moisture-regaining underwear materials were tested: 100% cotton (COTTON) and 100% acrylic (ORLON). Nine female subjects participated in the experiments at an ambient temperature of -10 degrees C. The experiment comprised a 20-min of rest, a 40-min of walking exercise (6 km/h) and a 40-min of recovery. No significant differences could be found in the average values of core temperature, skin and clothing temperatures, amount of non-evaporated and evaporated sweat or subjective ratings of thermal sensations within the two different underwear ensembles. The amount of sweat accumulated into the underwear was very low (3 +/- 1g) and (5 +/- 3g) (mean +/- SE) in COTTON and ORLON, respectively. In both ensembles moisture was transferred towards outer layers of the clothing where the amount of moisture correlated significantly with the total sweat production. In a heavily sweating individual, however, the properties of COTTON underwear, such as wicking ability and high moisture regain, became apparent (accumulated sweat 71g) compared to ORLON (46g). It is concluded that the underwear materials have no significant influence on the thermophysiological responses or subjective sensations under the conditions studied, especially when the sweat rate is low. On the other hand, in individuals with a higher sweating rate the differences between materials may become evident even during light exercise.
8043152
[A study on the visibility of different floor levels--experiments from a stumbling point of view].
Experiments were conducted to examine the visibility of different floor levels from a stumbling point of view. The test subjects were the elderly and the young, and we compared the difference between the two. We investigated eye movement while they were scanning the different floor levels. The results were as follows: 1) The height of different floor levels and illuminance had an influence on the visibility of different floor levels. Especially, the elderly were easily influenced by them. 2) The eye movements in scanning the different floor levels did not relate to the visibility of them, but were related to the personality of the test subjects. Eye movement patterns of the elderly differed from that of the young. The elderly were scanning mainly the lower part. The eye fixation time of the elderly was longer than that of the young. From the results, it was clarified that there were the difference between the elderly and the young. We could show it by the degree of influence. For example, the influence by the change of environmental condition.
8043151
[A tentative plan of measuring the amount of the stretch of the skin using origin on body surface].
The present study was made to search for the origin on human dorsal surface, which is available for a correct grasp of a change of body surface (skin surface) with human activities and to try to re-evaluate, using the above origin, quantitative skin deformation of human dorsal surface on raising arms. The following results were obtained: 1) X. examination in standing (static) and arm-raising (dynamic) positions revealed a site with inter-positional difference, as zero, in slippage on dorsal median line. This site was supposed to be the origin and was confirmed to be Th10 and Th12. The palpation of the site of, Th10 and Th12 on dorsal median line was thought to be simple and effective in searching for a site with the least bone and skin slippage, thus in presuming the origin. 2) Based upon the origins on dorsal median line and scapular line parallel thereto in sitting position, 5 cm phi-correct circles were stamped up and down, then arm raising action was taken. The utilization of the origin enabled us to determine the length, directional angle, theta, and area, S, of the slippage between correct and distorted circles as obtained by these actions. 3) For arm raising, the skin slipped up and down on median line for lower and higher sites than the origin, respectively, with the angle theta on scapular line indicating the + direction, while and theta appeared greater and smaller for a nearer site to the origin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
8043150
Effect of KRN2391 on canine ventricular arrhythmia models.
1. KRN2391 (3-30 micrograms/kg, i.v.) produced a decrease in mean blood pressure (MBP) with concomitant increase in heart rate (HR) and change in electrocardiogram (ECG) such as the shortening of PP and PQ intervals and the prolongation of QTc and these changes in HR and ECG were attenuated by pretreatment with propranolol (1 mg/kg) in normal dogs. 2. KRN2391 at 30 micrograms/kg induces neither suppression nor aggravation of ventricular arrhythmias caused by adrenaline and digitalis. 3. In two-stage coronary ligation-induced arrhythmia, KRN2391 inhibited arrhythmia at 48 hr. 4. These results suggest that KRN2391 may be effective on arrhythmia related to ischemia. In addition, it is considered that arrhythmia is not induced even by a high dose of KRN2391 in the normal condition.
8043149
Relative rates of nucleotide substitution in the chloroplast genome.
Coding sequences from maize, rice, tobacco, and liverwort chloroplasts are aligned and subjected to relative rate tests. Results of rate tests suggest that coding sequences from maize and rice are evolving with homogeneous rates of nucleotide substitution while coding sequences from the grass lineages (i.e., maize and rice) are evolving at a faster rate than coding sequences from the tobacco chloroplast. Rate tests also suggest that particular loci evolve at significantly faster rates in grass chloroplast genomes than the tobacco chloroplast genome. These loci encode proteins important to RNA polymerase, the H(+)-ATPase complex, and the ribosomal proteins. Much of the variation at these loci can be attributed to differences in nonsynonymous substitution rates. Taken together, these studies suggest that the chloroplast DNA molecular clock varies both between evolutionary lineages and between protein coding loci.
8043104
Pleiotropic function of ArgRIIIp (Arg82p), one of the regulators of arginine metabolism in Saccharomyces cerevisiae. Role in expression of cell-type-specific genes.
ArgRIIIp (Arg82p), together with ArgRIp (Arg80p), ArgRIIp (Arg81p) and Mcm1p, regulates the expression of arginine anabolic and catabolic genes. An argRIII mutant constitutively expresses five anabolic enzymes and is impaired in the induction of the synthesis of two catabolic enzymes. A genomic disruption of the ARGRIII gene not only leads to an argR phenotype, but also prevents cell growth at 37 degrees C. The disrupted strain is sterile especially in an alpha background and transcription of alpha- and a-specific genes (MF alpha 1 and STE2) is strongly reduced. By gel retardation assays we show that the binding of the Mcm1p present in a crude protein extract from an argRIII mutant strain to the P(PAL) sequence is impaired. Sporulation of alpha/a argRIII::URA3 homozygous diploids is also affected. Overexpression of Mcm1p in an argRIII-disrupted strain restores the mating competence of the strain, the ability to form a protein complex with P(PAL) DNA in vitro, and the regulation of arginine metabolism. However, overexpression of Mcm1p does not complement the sporulation deficiency of the argRIII-disrupted strain, nor does it complement its growth defect at 37 degrees C. Western blot analysis indicates that Mcm1p is less abundant in a strain devoid of ArgRIIIp than in wild type.
8043077
You can lead a horse to water....
This case study concerns a girl called Jane whose family, like most members of a rural community, are both friends and patients of the general practitioner. Jane, now aged 13, presented with a common and potentially serious condition of her age group. The management of her recurrent urinary tract infections turned out to be an exercise in frustration because of indifferent follow up.
8043075
Structure and organization of mouse GlcNAc-1-phosphate transferase gene.
The gene encoding UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate transferase (GPT), the enzyme that initiates the pathway for the biosynthesis of asparagine-linked glycoproteins, was isolated and characterized. Southern blot analyses demonstrated a single copy gene for GPT. The gene spans about 7.5 kilobase pairs of DNA and is divided into 9 exons by 8 introns. All the introns are found in the coding region, and most of them occur in segments separating the putative membrane-spanning domains. The exon/intron organization of the gene also correlates with the presence of several highly conserved regions of potential functional importance among yeast, leishmania, hamster, and mouse enzymes. Primer extension and reverse transcription-polymerase chain reaction analyses suggested the presence of several potential transcription start sites, with the closest one being approximately 200 base pairs upstream from the translation initiation codon. The 5'-flanking region lacks a typical TATA box, but is high in GC content and contains two putative Sp1 binding sites (GC boxes), consistent with promoters described for housekeeping genes. The 3'-end reverse transcription-polymerase chain reaction analysis indicated that the first of the two polyadenylation sites was used predominantly, in agreement with a approximately 2.0-kilobase pair GPT message seen on Northern blots of RNA from a wide variety of mouse tissues. This is the first report of cloning of a gene for an enzyme of the dolichol cycle in higher eukaryotes. A novel finding of this study is the observation of a G-->A change between the genomic sequence and nucleotide 280 in the cDNA. This could have important implications as an RNA editing mechanism for regulating the expression of the gene and therefore, protein N-glycosylation. A previous study (11) had shown that the activity of GPT was developmentally regulated in mouse mammary gland, with possible involvement by the hormone prolactin. The availability of the GPT gene with its promoter should facilitate future studies on delineating the mechanism for the hormonal regulation of GPT.
8043076
Extracellular domain of pemphigus vulgaris antigen (desmoglein 3) mediates weak homophilic adhesion.
Pemphigus vulgaris antigen is in the cadherin supergene family. We hypothesized that the extracellular domain of pemphigus vulgaris antigen might mediate homophilic cell adhesion because 1) the originally described cadherins (e.g., E-cadherin) mediate this type of adhesion, 2) pemphigus vulgaris antigen is localized in desmosomes that are cell adhesion junctions, and 3) autoantibodies in pemphigus vulgaris patients cause loss of cell adhesion. To test this hypothesis we used a system developed for E-cadherin that, when transfected into L cells (mouse fibroblasts), has been shown to cause aggregation. Because this aggregation requires the cytoplasmic domain of E-cadherin to bind to catenins, we made a chimeric cDNA construct that encodes the extracellular domain of pemphigus vulgaris antigen and the cytoplasmic domain of E-cadherin. Analysis by immunofluorescence and flow cytometry with pemphigus vulgaris sera indicated that the pemphigus vulgaris antigen extracellular domain of this chimeric molecule (PVEC) was expressed on the cell surface of transiently transfected cells and permanently transfected L-cell clones. Immunoprecipitation of the chimeric molecule from extracts of these clones showed that the E-cadherin cytoplasmic domain bound catenins. Surprisingly, these L-cell clones displayed only slight aggregation compared to an L-cell clone transfected with E-cadherin. This weak aggregation was, however, specific and homophilic, as determined by cell sorting of only PVEC transfectants into aggregates from mixtures of PVEC and neomycin resistance gene transfectants, one of which was labeled with a fluorescent dye. We conclude that the extracellular domain of pemphigus vulgaris antigen mediates weak homophilic adhesion and is not interchangeable in function with the extracellular domain of E-cadherin.
8043072
By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?
To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being close to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18,000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change, lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45,000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.
8043070
A comparison of endoscopic and open carpal tunnel release.
Fifty consecutive open and 50 consecutive endoscopic carpal tunnel releases performed by a single surgeon were compared. The endoscopic technique was safe, effective, and resulted in earlier return to work.
8043069
Surgical treatment of solitary brain metastases: Monmouth County experience.
Our experience in Monmouth County with surgical resection of single brain metastases followed by whole brain radiotherapy confirms the findings of a recent prospective randomized controlled study of this problem and demonstrates that patients treated with surgical resection followed by whole brain radiation live longer and have a better quality of life than those patients treated with radiotherapy alone. Best results are attainable if there is no evidence of disease activity at the primary site or systemically at the time the brain metastasis is diagnosed.
8043068
Complete amino acid sequence of porcine adrenomedullin and cloning of cDNA encoding its precursor.
Porcine adrenomedullin was isolated from adrenal medulla extract and its amino acid sequence was determined. The peptide is identical to human adrenomedullin with a single replacement of Gly for Asn at position 40. The cDNA clone encoding the porcine adrenomedullin precursor was isolated and sequenced. The precursor for adrenomedullin (preproadrenomedullin) is 188 amino acids in length, including the adrenomedullin sequence, followed by a glycine (the amide donor). In addition to adrenomedullin, proadrenomedullin (proAM) contains a candidate for a unique 20-residue peptide, proAM-N20, whose carboxy-terminus may be amidated. By RNA blot analysis, porcine adrenomedullin mRNA was found to be highly expressed in several porcine tissues including lung and kidney as well as adrenal medulla.
8043066
Local effect of serotonin released during coronary angioplasty.
Serotonin is released after the aggregation of platelets, a phenomenon that may occur after coronary angioplasty. We sought to determine whether serotonin is released into the coronary circulation during coronary angioplasty and to assess whether serotonin can affect coronary-artery tone during angioplasty. Blood samples were drawn from the ascending aorta and the coronary sinus of eight patients scheduled to undergo angioplasty of the left anterior descending or circumflex coronary artery. Samples were obtained before angioplasty and after each balloon dilation. The dimensions of arterial segments distal to the site of dilation were measured angiographically before angioplasty and 5 and 15 minutes after the last dilation in these eight patients and in seven similar patients; the latter group was treated with ketanserin, a serotonin2-receptor antagonist, before angioplasty. Before the eight patients underwent angioplasty, their mean (+/- SE) plasma serotonin level in the aorta was 2.5 +/- 0.7 ng per milliliter and that in the coronary sinus was 2.3 +/- 0.6 ng per milliliter (P = 0.34). The serotonin level in plasma from the coronary sinus rose significantly, to 31.5 +/- 13.5, 17.6 +/- 5.3, and 29.1 +/- 8.1 ng per milliliter after the first, second, and third dilations, respectively (P = 0.014 for the comparison with preoperative levels). In contrast, the serotonin level in plasma from the ascending aorta did not change. The cross-sectional area of the coronary artery was significantly reduced 5 and 15 minutes after the last dilation (from a preoperative value of 3.7 +/- 0.5 mm2 to 2.7 +/- 0.4 mm2 15 minutes after the last dilation; P = 0.011). This vasoconstriction was significantly blunted in the seven patients who received ketanserin (from 3.7 +/- 0.5 mm2 before angioplasty to 3.9 +/- 0.4 mm2 after 15 minutes) (P = 0.017 for comparison with the eight patients who did not receive ketanserin). Serotonin is released into the coronary circulation during angioplasty, and this vasoactive substance may contribute to the occurrence of vasoconstriction distal to the dilated site. The vasoconstriction is attenuated by ketanserin, a serotonin2-receptor antagonist.
8043064
Venipuncture tips for radiologic technologists.
Radiologic technologists may be called upon to perform venipuncture to start intravenous lines to administer contrast media. This article provides advice to facilitate successful venipuncture techniques. It should not be considered a substitute for appropriate training.
8043061
The spectrum of severe rheumatic mitral valve disease in a developing country. Correlations among clinical presentation, surgical pathologic findings, and hemodynamic sequelae.
To describe the demographic, pathologic, and hemodynamic profiles of patients with severe rheumatic mitral valve disease in a developing country and to assess their relation to uncontrolled rheumatic disease activity. Retrospective, cross-sectional, cohort study. Tertiary medical center in Soweto, South Africa. 714 of 737 consecutive black patients, 4 to 73 years old, with pure mitral regurgitation, pure mitral stenosis, or mixed mitral disease who had mitral valve surgery and in whom preoperative and surgical data were concordant. Valve lesions were evaluated on the basis of clinical, echocardiographic, hemodynamic, and surgical pathologic data. Active rheumatic carditis was diagnosed according to clinical evidence for concurrent acute rheumatic fever (Jones criteria), macroscopic appearances at surgery, and histologic findings. 219 patients had pure mitral regurgitation, 275 had pure mitral stenosis, and 220 had mixed lesions. Ongoing rheumatic activity was diagnosed in 106 patients with pure regurgitation (47%) and in only 5 patients with pure stenosis (2%). Pure regurgitation was the most common lesion in the first and second decades; the relative prevalence of pure stenosis increased with age. Purely regurgitant valves had pliable, unscarred leaflets (95%), dilated mitral annuli (95%), elongated chordae tendineae (92%), and anterior leaflet prolapse (81%). In contrast, purely stenotic valves had fused leaflet commissures (100%) and rigid leaflets (38%) but no evidence of prolapse. The spectrum of rheumatic mitral valve disease that is hemodynamically severe in developing countries differs from that currently reported in the United States. Severe, pure rheumatic mitral regurgitation is as prevalent as pure stenosis but has an entirely different time course, surgical anatomy, and relation to disease activity, suggesting a separate pathophysiologic mechanism.
8043059
A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer.
The efficacy of surgery for patients with non-small-cell lung cancer is limited, although recent studies suggest that preoperative chemotherapy may improve survival. We conducted a randomized trial to examine the possible benefit of preoperative chemotherapy and surgery for the treatment of patients with non-small-cell lung cancer. We studied 60 patients (59 men and 1 woman) with stage IIIA non-small-cell lung cancer. The patients were randomly assigned to receive either surgery alone or three courses of chemotherapy (6 mg of mitomycin per square meter of body-surface area, 3 g of ifosfamide per square meter, and 50 mg of cisplatin per square meter) given intravenously at three-week intervals and followed by surgery. All patients received mediastinal radiation after surgery. The resected tumors were evaluated by means of K-ras oncogene analysis and flow cytometry. The median period of survival was 26 months in the patients treated with chemotherapy plus surgery, as compared with 8 months in the patients treated with surgery alone (P < 0.001); the median period of disease-free survival was 20 months in the former group, as compared with 5 months in the latter (P < 0.001). The rate of recurrence was 56 percent in the group treated with chemotherapy plus surgery and 74 percent in the group treated with surgery alone. The prevalence of mutated K-ras oncogenes was 15 percent among the patients receiving preoperative chemotherapy and 42 percent among those treated with surgery alone (P = 0.05). Most of the patients treated with chemotherapy plus surgery had tumors that consisted of diploid cells, whereas the patients treated with surgery alone had tumors with aneuploid cells. Preoperative chemotherapy increases the median survival in patients with non-small-cell lung cancer.
8043058
Bedside chest radiography.
Bedside chest radiography is one of the most frequently performed radiologic examinations, yet it is the examination with the most variation in image quality. The need to improve the quality of this examination has long been recognized, but it is a difficult problem to solve. Critically ill patients must undergo bedside chest radiography almost daily. These examinations are useful 76%-94% of the time. A national survey revealed that there is a wide variation in the methods used to perform bedside chest radiography, indicating that there is no excellent preferred technique. The reduced image quality is due to scatter radiation. The scatter fraction is about 0.95 in the mediastinum and is about 0.66 in the lung. When grids are used, the image quality is improved; acceptance has been slow, however, because the grid is frequently misaligned. Storage phosphor imaging/computed radiography with grids is a technology improvement that almost completely solves this problem. Radiologists should be sure to optimize the current techniques, as well as provide prompt examination reporting.
8043055
Continuous single-layer serosubmucosal anastomosis in the upper gastrointestinal tract.
In a 4-year period, 100 anastomoses in the upper gastrointestinal tract were fashioned using a single serosubmucosal layer of continuous polydioxanone. One patient required revisional surgery because of anastomotic stricture after partial gastrectomy, but there was no other complication related to the anastomosis. This technique is simple, safe, and quick to perform.
8043054
Coma reversal with cerebral dysfunction recovery after repetitive hyperbaric oxygen therapy for severe carbon monoxide poisoning.
The accepted beneficial effects of hyperbaric oxygen (HBO) include a greatly diminished carboxyhemoglobin (COHgb) half-life, enhanced tissue clearance of residual carbon monoxide (CO), reduced cerebral edema, and reversal of cytochrome oxidase inhibition, and prevention of central nervous system lipid peroxidation. Debate regarding the criteria for selection of HBO versus 100% normobaric oxygen therapy continues, and frequently is based solely on the level of COHgb saturation. Patients who manifest signs of serious CO intoxication (unconsciousness, neuropsychiatric symptoms, cardiac or hemodynamic instability) warrant immediate HBO therapy. An unresponsive 33-year-old woman was found in a closed garage, inside her automobile with the ignition on. Her husband admitted to seeing her 6 hours before discovery. 100% normobaric oxygen was administered in the prehospital and emergency department settings. The patient had an initial COHgb saturation of 46.7%, a Glasgow coma score of 3, and was transferred for HBO therapy. Before HBO therapy, the patient remained unresponsive and demonstrated decerebrate posturing and a positive doll's eyes (negative oculocephalic reflex). The electroencephalogram pattern suggested bilateral cerebral dysfunction consistent with a toxic metabolic or hypoxic encephalopathy. The patient underwent HBO therapy at 2.4 ATA for 90 minutes twice a day for 3 consecutive days. On day 7, the patient began to awaken, was weaned from ventilatory support, and was not soon verbalizing appropriately. A Folstein mental status examination showed a score of 26 of 30. Neurological examination demonstrated mild residual left upper extremity weakness and a normal gait. There was no evidence of significant neurological sequelae at 1 month follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
8043052
Relationship of interfacial equilibria to interfacial activation of phospholipase A2.
The equilibrium dissociation constants for the distribution of pig pancreatic phospholipase A2, its competitive inhibitors, and their complexes at the interface of a neutral diluent are determined. The relationship between these parameters and their significance for interfacial catalysis is elaborated in terms of a model based on the relationship between the underlying equilibria. By using a combination of spectroscopic and chemical modification methods, it was possible to determine the equilibrium dissociation constant of an inhibitor bound to the interface (K') or of the inhibitor bound to the enzyme in the aqueous phase (KI) or the interface (KI*). The equilibrium dissociation constant for the free enzyme (Kd) or for the enzyme-inhibitor complex (KdI) from the interface were also obtained. These constants are shown to be thermodynamically related, i.e., K'KdKI* = KIKdI, as predicted on the basis of the cyclic equilibrium scheme (thermodynamic box) describing the distribution of the enzyme and the inhibitor between the aqueous phase and the interface at constant calcium concentration. Results show that (i) calcium is required for the binding of a substrate or inhibitor molecule to the catalytic site; (ii) the effective dissociation constant of the inhibitor-enzyme complex in the aqueous phase is considerably larger than that for the enzyme at the interface, i.e., KI >> effective KI*; (iii) KdI does not depend on the structure of the inhibitor and Kd >> KdI; and (iv) structure-activity correlations suggest that ionic interactions between a ligand and the interfacial recognition site of the enzyme are important for K', which controls the concentration of the bound inhibitor that the enzyme "sees" in the interface. These observations demonstrate that the binding of the enzyme to the interface and the binding of the inhibitor to the active site of the enzyme at the interface are two distinguishable processes. Therefore, binding of a ligand to the active site of the enzyme promotes binding of the enzyme-inhibitor complex to other amphiphiles and the interface with higher affinity. It is suggested that the primary effect of binding the enzyme to the interface is to increase its intrinsic affinity toward the active-site-directed ligands, i.e., the interfacial activation of PLA2 is of K-type.
8043050
Intracranial Wegener's granulomatosis.
We describe an atypical neurologic presentation of Wegener's granulomatosis (WG) with striking meningeal and cerebral involvement, responding to immunosuppressive therapy. WG may cause treatable intracranial complications in the absence of nasal or renal disease and without cerebral angiographic abnormalities, CSF pleocytosis, or a positive assay for antineutrophil cytoplasmic antibodies.
8043048
A cell kinetics model of radiation-induced myelopoiesis: rate coefficient estimates for mouse, rat, sheep, swine, dog, and burro irradiated by photons.
Rate coefficients in the model of cell kinetics and mortality introduced by Jones et al. (Radiat. Res. 128, 258-266, 1991) are estimated using mortality data from 27 animal experiments. Adjustments are made for the six species and three nominal classes of gamma radiation represented in these studies. The model fits most of the mortality data quite well when the rate coefficient representing cellular proliferation is fitted to individual species and each of the other coefficients is given a single value across the entire data set. Results are qualitatively similar to those reported by Morris et al. (Radiat. Res. 128, 267-275, 1991) who estimated the rate coefficients from a limited number of mouse studies involving only 250 kVp X rays. As in the earlier study, estimates here lead to greater cell survival than is observed for marrow cells in the amplification division compartment.
8043047
Trauma in infants less than three months of age.
We evaluated the characteristics of traumatic injury and risk for subsequent trauma in infants less than three months of age (n = 111). Medical records were reviewed at presentation and one year later. Injury was due to abuse/neglect in 28%, whereas 72% were accidentally injured. Falls were the most common mechanism of accidental injury (67%). The percentage of infants with skull fractures was greater in the abuse/neglect group than in the accidental group (7/31 vs 7/80; P < 0.05) with a tendancy toward more diastatic and multiple skull fractures (6/7 vs 2/7) as well as intracranial hemorrhages (3/7 vs 0/7). More infants in the abuse/neglect group suffered extremity fractures (4/31 vs 2/80; P < 0.05). Hospitalization was more frequent (12/31 vs 8/80; P < 0.001), as was social or protective service intervention (25/31 vs 17/80; P < 0.001), in the abuse/neglect group. The two groups showed no difference in the number of previous emergency department (ED) visits; however, the use of the ED declined significantly in the abuse/neglect group following the trauma (0.81 +/- 1.2 vs 1.5 +/- 2.1 visits; P < 0.05). The abuse/neglect group tended to have a greater number of subsequent traumatic injuries than those accidentally injured. Abuse/neglect should be considered in any seriously injured infant less than three months of age because of the likelihood of subsequent trauma.